Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Floods and fidget wheels : a comparative systemic functional analysis of Slessor's 'Five Bell' and Olsen's 'Salute to Five Bells'

22 page(s

Witnessing war : from near and far

This paper presents research conducted as part of a major research project on media bias in the reporting of war, focusing particularly on the most recent war in Iraq (beginning in March 2003). The notion of bias is approached via the notion of “witnessing” – a term which conflates ideas about the external perception and explanation of events (that is, about seeing event first-hand and telling others what one has seen) with ideas about the internal cognizance of such events (that is, about telling the truth as one understands or knows it, whether or not from first-hand perception of the world – as in religious uses of the term). The paper explores a method of modelling the relative physical and semiotic proximity of various “witnesses” to the “on the ground” events of the war, and then considers the various ways that these witnesses are identified, and their perceptions and opinions represented, in news reporting and commentary.18 page(s

Evolution and the system of AGENCY

6 page(s

A Tenorless genre? Forensic generic profiling of workers' compensation dispute resolution discourse

This paper turns genre modelling to the task of exploring critical variation between instances of an emerging genre – the workers’ compensation teleconference. It attempts to tease out the role that such variation plays in the success of that genre in terms of the social process that it was designed to realise, noting however that ‘success’ must be viewed from multiple perspectives. We describe and illustrate a Hasanian GSP approach to genre description, based on collaborative research we undertook with the NSW Workers Compensation Commission (WCC) in Australia. The method proved useful for identifying what kinds of discourse strategies contribute to the successful resolution of disputes at teleconference, and we present preliminary findings which suggest an association between resolution and what we have called the ‘Orient to Process’ phase in the generic structure of these teleconferences, using a semantic network to display the crucial variation within this phase. We also address some pragmatic consequences of training arbitrators to use ‘successful’ discourse strategies in relation to issues of equity for the worker, and some theoretical consequences of adjusting the GSP framework for research on professional discourses.28 page(s

The teleological illusion in linguistic \u27drift\u27: choice and purpose in semantic evolution

Linguistic models of all varieties have invoked the notion of ‘choice’, whether explicitly as in Systemic Functional Linguistics (SFL) or implicitly through various fundamental concepts like ‘paradigm’ and ‘associative axis’, ‘agnation’, or even ‘optional’ versus ‘obligatory transformations’. The idea of choice as ‘meaning potential’ seems congruent also with the experience of language: as Halliday (this volume) has put it: “All human activity involves choice: doing this rather than doing that . . . meaning this rather than meaning that.

The Teleological illusion in linguistic 'drift' : choice and purpose in semantic evolution

19 page(s

Formulation, conversation and therapeutic engagement

Objectives: The aim of this study was to review psychodynamic formulation with respect to the language used and the evidence it provides about variations of clinical purpose. Method: The purpose of the psychodynamic formulation is considered in training and clinical contexts. Three formulations are presented: two written from alternative theoretical perspectives and one designed to be spoken to the patient. Linguistic comparisons are made using these examples, emphasizing differences in grammatical complexity, lexical density ('wordiness') and other qualities. Results: The essential purpose of psychodynamic formulation is to develop an understanding that can be shared in the service of effective care. Significant differences were found between written and spoken versions with greater grammatical complexity and lower lexical density in the spoken form. An intrapsychic theoretical model was more grammatically complex and 'noun-based' compared to an inter-subjective model. Other differences are also described, including the tendency for the intrapsychic account to efface the sense of personal agency. This contributes to the impression of a subject under the influence of 'unseen' forces. Conclusions: The communicability of psychodynamic formulation is essential to its utility in clinical practice.7 page(s

Aspects of extended impregnation kraft cooking for high-yield pulping of hardwood

The long-term trend regarding wood is an increase in price. Because wood contributes to a large part of production costs, the efficient utilisation of wood is greatly desired to reduce production costs for kraft pulp producers. During the 1990s, the development of improved modified kraft cooking began, which led to higher yields. There was also a trend of terminating kraft cooking at a higher kappa number to maximise the overall yield. For hardwood, the defibration point became a critical setback in allowing this termination at a high kappa number. This thesis discusses how this issue has been tackled in the laboratory by using improved modified kraft cooking combined with extended impregnation to enable a decrease in reject content and shift the defibration point towards a higher kappa number for hardwood. This lab concept is referred to as extended impregnation kraft cooking (EIC), and this thesis reveals that EIC cooking efficiently reduces the reject content for both birch and eucalypt. By using EIC cooking, the defibration point was shifted to a kappa number of ca. 30 from ca. 20 using conventional kraft cooking. This study demonstrates the great potential for achieving a higher overall yield for eucalypt by terminating the EIC cooking at a high kappa number, but with the conditions used in this thesis, no improvement in yield was observed for birch.   An important issue is that the termination of kraft cooking at high kappa number increases the demand for extended oxygen delignification to reach a similar kappa number into bleaching, i.e., due to cost and environmental reasons. Extended oxygen delignification was shown to be possible for both birch and eucalypt EIC pulps (i.e., from kappa number 27 to 10) with an acceptable pulp viscosity number.   The other part of this thesis addresses aspects regarding the limitations in oxygen delignification. It has previously been shown in the literature that a high xylan yield of kraft cooking could negatively affect the efficiency of subsequent oxygen delignification. In this work, the increased xylan content in eucalypt kraft pulp within the range of 8–18% had only a marginally negative impact on the oxygen delignification efficiency after correcting for the HexA contribution to the kappa number. It is also desired to extend the oxygen delignification towards lower kappa number, i.e., below kappa number 10 to decrease the bleaching chemical requirement. In this study, the hypothesis that the reduced efficiency of oxygen delignification at low kappa numbers could partly be due to the formation of oxidisable carbohydrate-related structures (i.e., HexA and/or other non-lignin structures) was also tested. No formation was established. On the other hand, a final oxygen delignification stage in the bleaching could be an attractive alternative for reducing yellowing and enhancing brightness; in fact, this has led to the development of a patent (SE 528066).Ved står för en stor del av produktionskostnaderna vid framställning av sulfatmassa. Då vedpriserna har ökat genom åren är ett effektivt utnyttjande av veden önskvärt för att kunna sänka produktionskostnaderna. Under 1990-talet förbättrades den modifierade sulfatkokningen vilket innebar möjlighet till högre massautbyte. För att maximera massautbytet styrdes kokningsprocessen mot ett högre kappatal. Detta har visat sig vara svårare för lövved än för barrved, eftersom defibrerbarhetspunkten utgör ett kritiskt hinder. I denna avhandling har laborationsstudier utförts där förbättrad modifierad sulfatkokning kombinerats med förlängd impregnering för att kunna sänka spethalten och därmed förskjuta defibrerbarhetspunkten mot ett högre kappatal. Detta koncept kallas för extended impregnation kraft cooking (EIC). EIC-kokning visade sig vara en effektiv metod för att minska spethalten hos björk och eukalyptus. Med EIC-kokning kunde defibrerbarhetspunkten höjas från cirka 20 till cirka 30. I denna avhandling klarläggs att det finns stora möjligheter att öka massautbytet för eukalyptus genom att avsluta sulfatkoket vid ett högre kappatal. För björk kunde ingen ökning av massutbytet uppnås genom ovanstående metod.   Vid ett högre kappatal efter sulfatkoket ställs även krav på förlängd syrgasdelignifiering, för att kunna behålla samma kappatal in till blekeriet. Det visade sig vara fullt möjligt att förlänga syrgasdelignifieringen för de EIC-kokade björk- och eukalyptusmassorna (d.v.s. från kappatal 27 till 10) med accepterad massaviskositet.   Den andra delen av avhandlingen tar upp aspekter på syrgasdelignifieringens begränsningar. Tidigare studier har visat att ett högre utbyte av xylan vid sulfatkokning kan vara negativt för syrgasdelignifieringens effektivitet.  I denna studie har det påvisats att en ökad xylanhalt i intervallet 8–18 procent i eukalyptusmassa endast har en marginell negativ inverkan på syrgasdelignifieringens effektivitet efter att kappatalet korrigerats för HexA. Det är önskvärt att förlänga syrgasdelignifieringen till ett lägre kappatal än 10 för att minska förbrukningen av blekkemikalier. I den här studien prövades hypotesen att syrgasdelignifieringens begränsningar vid låga kappatal, under 10, delvis skulle kunna bero på bildning av oxiderbara kolhydratrelaterade strukturer (d.v.s. HexA och/eller andra okända ”non-lignin”-strukturer). Ingen bildning kunde dock observeras. Däremot indikerades att ett syrgassteg i slutet av bleksekvensen skulle kunna vara ett eftersträvansvärt alternativ för minskad eftergulning och ökad ljushet, vilket ledde till ett patent (SE 528066).QC 2012050