Embedded point of care randomisation for evaluating comparative effectiveness questions: PROSPECTOR-critical care feasibility study protocol

INTRODUCTION: Many routinely administered treatments lack evidence as to their effectiveness. When treatments lack evidence, patients receive varying care based on the preferences of clinicians. Standard randomised controlled trials are unsuited to comparisons of different routine treatment strategies, and there remains little economic incentive for change.Integrating clinical trial infrastructure into electronic health record systems offers the potential for routine treatment comparisons at scale, through reduced trial costs. To date, embedded trials have automated data collection, participant identification and eligibility screening, but randomisation and consent remain manual and therefore costly tasks.This study will investigate the feasibility of using computer prompts to allow flexible randomisation at the point of clinical decision making. It will compare the effectiveness of two prompt designs through the lens of a candidate research question-comparing liberal or restrictive magnesium supplementation practices for critical care patients. It will also explore the acceptability of two consent models for conducting comparative effectiveness research. METHODS AND ANALYSIS: We will conduct a single centre, mixed-methods feasibility study, aiming to recruit 50 patients undergoing elective surgery requiring postoperative critical care admission. Participants will be randomised to either 'Nudge' or 'Preference' designs of electronic point-of-care randomisation prompt, and liberal or restrictive magnesium supplementation.We will judge feasibility through a combination of study outcomes. The primary outcome will be the proportion of prompts displayed resulting in successful randomisation events (compliance with the allocated magnesium strategy). Secondary outcomes will evaluate the acceptability of both prompt designs to clinicians and ascertain the acceptability of pre-emptive and opt-out consent models to patients. ETHICS AND DISSEMINATION: This study was approved by Riverside Research Ethics Committee (Ref: 21/LO/0785) and will be published on completion. TRIAL REGISTRATION NUMBER: NCT05149820

How customers ‘learn’ to work for retailers

The purpose of this paper is to investigate how learning style affects the performance of the ‘working’ customer in one self-service context – retail Self Check-Out Tills (SCOT). For the purposes of this paper, we have adopted the UK term Self Check-Out Tills (SCOT), also known as ‘self-service registers’ in other countries, to describe this form of self-service in retail stores). The study uses qualitative and quantitative data collected from users of retail SCOT. Initial exploratory factor analysis of 232 SCOT users revealed significant differences in learning styles. Three categories emerged: ‘regular reassurance’, ‘motivated practice’ and ‘cautious discovery’. Customers adopting different learning styles varied in their perceptions of ability and enjoyment with SCOT, and in their capability of helping other customers with SCOT. The demographic make-up of customers adopting the different learning styles was also shown to vary. Previously, little has been done to identify the specific training needs of working customers. This research begins to address this knowledge gap

SNAP-2 EPICCS: the second Sprint National Anaesthesia Project-EPIdemiology of Critical Care after Surgery: protocol for an international observational cohort study.

INTRODUCTION: The admission of high-risk patients to critical care after surgery is a recommended standard of care. Nevertheless, poor compliance against this recommendation has been repeatedly demonstrated in large epidemiological studies. It is unclear whether this is due to reasons of capacity, equipoise, poor quality clinical care or because hospitals are working creatively to create capacity for augmented care on normal surgical wards. The EPIdemiology of Critical Care after Surgery study aims to address these uncertainties. METHODS AND ANALYSIS: One-week observational cohort study in the UK and Australasia. All patients undergoing inpatient (overnight stay) surgery will be included. All will have prospective data collection on risk factors, surgical procedure and postoperative outcomes including the primary outcome of morbidity (measured using the Postoperative Morbidity Survey on day 7 after surgery) and secondary outcomes including length of stay and mortality. Data will also be collected on critical care referral and admission, surgical cancellations and critical care occupancy. The epidemiology of patient characteristics, processes and outcomes will be described. Inferential techniques (multilevel multivariable regression, propensity score matching and instrumental variable analysis) will be used to evaluate the relationship between critical care admission and postoperative outcome. ETHICS AND DISSEMINATION: The study has received ethical approval from the National Research Ethics Service in the UK and equivalent in Australasia. The collection of patient identifiable data without prior consent has been approved by the Confidentiality Advisory Group (England and Wales) and the Public Privacy and Patient Benefit Panel (Scotland). In these countries, patient identifiable data will be used to link prospectively collected data with national registers of death and inpatient administrative data. The study findings will be disseminated using a multimedia approach with the support of our lay collaborators, to patients, public, policy-makers, clinical and academic audiences

The rsmS (ybaM) mutation causes bypass suppression of the RsmAB post-transcriptional virulence regulation system in enterobacterial phytopathogens.

Plant cell wall degrading enzymes (PCWDEs) are the primary virulence determinants of soft rotting bacteria such as the potato pathogen, Pectobacterium atrosepticum. The regulation of secondary metabolite (Rsm) system controls production of PCWDEs in response to changing nutrient conditions. This work identified a new suppressor of an rsmB mutation - ECA1172 or rsmS (rsmB suppressor). Mutants defective in rsmB (encoding a small regulatory RNA), show reduced elaboration of the quorum sensing molecule (N-3-oxohexanoyl-homoserine lactone; OHHL) and PCWDEs. However, OHHL and PCWDE production were partially restored in an rsmB, rsmS double mutant. Single rsmS mutants, overproduced PCWDEs and OHHL relative to wild type P. atrosepticum and exhibited hypervirulence in potato. RsmS overproduction also resulted in increased PCWDEs and OHHL. Homology searches revealed rsmS conservation across pathogens such as Escherichia coli (ybaM), Dickeya solani, Klebsiella pneumoniae and Shigella flexneri. An rsmS mutant of Pectobacterium carotovorum ATCC39048 showed bypass of rsmB-dependent repression of PCWDEs and OHHL production. P. carotovorum ATCC39048 produces the β-lactam antibiotic, 1-carbapen-2-em-3-carboxylic acid (a carbapenem). Production of the antibiotic was repressed in an rsmB mutant but partially restored in an rsmB, rsmS double mutant. This work highlights the importance of RsmS, as a conserved pleiotropic regulator of virulence and antibiotic biosynthesis.James Hutton Institut

The polaroid image as photo-object

This article is part of a larger project on the cultural history of Polaroid photography and draws on research done at the Polaroid Corporate archive at Harvard and at the Polaroid company itself. It identifies two cultural practices engendered by Polaroid photography, which, at the point of its extinction, has briefly flared into visibility again. It argues that these practices are mistaken as novel but are in fact rediscoveries of practices that stretch back as many as five decades. The first section identifies Polaroid image-making as a photographic equivalent of what Tom Gunning calls the ‘cinema of attractions’. That is, the emphasis in its use is on the display of photographic technologies rather than the resultant image. Equally, the common practice, in both fine art and vernacular circles, of making composite pictures with Polaroid prints, draws attention from image content and redirects it to the photo as object

NESC Peer-Review of the Flight Rationale for Expected Debris Report

Since the loss of Columbia on February 1, 2003, the Space Shuttle Program (SSP) has significantly improved the understanding of launch and ascent debris, implemented hardware modifications to reduce debris, and conducted tests and analyses to understand the risks associated with expected debris. The STS-114 flight rationale for expected debris relies on a combination of all three of these factors. A number of design improvements have been implemented to reduce debris at the source. The External Tank (ET) thermal protection system (TPS) foam has been redesigned and/or process improvements have been implemented in the following locations: the bipod closeout, the first ten feet of the liquid hydrogen (LH2) tank protuberance air load (PAL) ramp, and the LH2 tank-to-intertank flange closeout. In addition, the forward bipod ramp has been eliminated and heaters have been installed on the bipod fittings and the liquid oxygen (LO2) feedline forward bellows to prevent ice formation. The Solid Rocket Booster (SRB) bolt catcher has been redesigned. The Orbiter reaction control system (RCS) thruster cover "butcher paper" has been replaced with a material that sheds at a low velocity. Finally, the pad area has been cleaned to reduce debris during lift-off

The spectra and energies of classical double radio lobes

We compare two temporal properties of classical double radio sources: i) radiative lifetimes of synchrotron-emitting particles and ii) dynamical source ages. We discuss how these can be quite discrepant from one another, rendering use of the traditional spectral ageing method inappropriate: we contend that spectral ages give meaningful estimates of dynamical ages only when these ages are << 10^7 years. In juxtaposing the fleeting radiative lifetimes with source ages which are significantly longer, a refinement of the paradigm for radio source evolution is required. The changing spectra along lobes are explained, not predominantly by synchrotron ageing but, by gentle gradients in a magnetic field mediated by a low-gamma matrix which illuminates an energy-distribution of particles, controlled largely by classical synchrotron loss in the high magnetic field of the hotspot. The energy in the particles is an order of magnitude higher than that inferred from the minimum-energy estimate, implying that the jet-power is of the same order as the accretion luminosity produced by the quasar central engine. This refined paradigm points to a resolution of the findings of Rudnick et al (1994) and Katz-Stone & Rudnick (1994) that both the Jaffe-Perola and Kardashev-Pacholczyk model spectra are invariably poor descriptions of the curved spectral shape of lobe emission, and indeed that for Cygnus A all regions of the lobes are characterised by a `universal spectrum'. [abridged]Comment: LaTeX, 4 figures. To appear in A

How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?

BACKGROUND: Falls affect approximately one third of community-dwelling older adults each year and have serious health and social consequences. Fear of falling (FOF) (lack of confidence in maintaining balance during normal activities) affects many older adults, irrespective of whether they have actually experienced falls. Both falls and fear of falls may result in restrictions of physical activity, which in turn have health consequences. To date the relation between (i) falls and (ii) fear of falling with physical activity have not been investigated using objectively measured activity data which permits examination of different intensities of activity and sedentary behaviour. METHODS: Cross-sectional study of 1680 men aged 71-92 years recruited from primary care practices who were part of an on-going population-based cohort. Men reported falls history in previous 12 months, FOF, health status and demographic characteristics. Men wore a GT3x accelerometer over the hip for 7 days. RESULTS: Among the 12% of men who had recurrent falls, daily activity levels were lower than among non-fallers; 942 (95% CI 503, 1381) fewer steps/day, 12(95% CI 2, 22) minutes less in light activity, 10(95% CI 5, 15) minutes less in moderate to vigorous PA [MVPA] and 22(95% CI 9, 35) minutes more in sedentary behaviour. 16% (n = 254) of men reported FOF, of whom 52% (n = 133) had fallen in the past year. Physical activity deficits were even greater in the men who reported that they were fearful of falling than in men who had fallen. Men who were fearful of falling took 1766(95% CI 1391, 2142) fewer steps/day than men who were not fearful, and spent 27(95% CI 18, 36) minutes less in light PA, 18(95% CI 13, 22) minutes less in MVPA, and 45(95% CI 34, 56) minutes more in sedentary behaviour. The significant differences in activity levels between (i) fallers and non-fallers and (ii) men who were fearful of falling or not fearful, were mediated by similar variables; lower exercise self-efficacy, fewer excursions from home and more mobility difficulties. CONCLUSIONS: Falls and in particular fear of falling are important barriers to older people gaining health benefits of walking and MVPA. Future studies should assess the longitudinal associations between falls and physical activity

IL4Rα signaling abrogates hypoxic neutrophil survival and limits acute lung injury responses <i>in vivo</i>

Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood.  Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1a (hypoxia-inducible factor-1a)mediated neutrophil adaptation, resulting in resolution of lung injury.  Methods: Neutrophil activation of IL4Ra (IL-4 receptor a) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4.  Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1a-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis.  Conclusions: We describe an important interaction whereby IL4Ra-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury