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AbstractObjectivesTo determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes.DesignMulticentre, parallel, cluster randomised controlled trial.SettingLong term care homes in the UK, registered to care for older people or those with dementia.Participants1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care.InterventionsGuide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care.Main outcome measuresPrimary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation.ResultsMean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively.ConclusionsThe GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency.Trial registrationISRCTN34353836.

Acute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance of establishing new experimental models, the present investigation evaluated the modulation of APPs following inflammatory stimulus by the inoculation of Aeromonas hydrophila in tilapias. Fish were sampled 6 and 24 hours post-infection. Tilapias presented increase of positive APPs such as ceruloplasmin, haptoglobin, alpha-2-macroglobulin and complement C3, as well as decrease of negative APPs such as albumin and transferrin. The protein response of tilapias during the course of bacterial infection showed correlation with the kinetics of cellular accumulation in the inflamed focus with significant increase of granulocytes, thrombocytes, lymphocytes and macrophages. However, granulocytes were the predominant cells, associated with increment in the reactive oxygen species (ROS) production. Showing responses similar to those observed in humans, the modulation of APPs and the kinetics of cellular accumulation in the exudate demonstrate the feasibility of this alternative experimental model for advances and studies to understand changes in pathophysiological mechanisms of acute inflammatory reaction due to bacterial infection.

The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Background Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals. Methods A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian ( n  = 20) and New Zealand ( n  = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qualitative component will consist of semi-structured interviews with three to five key emergency department and paediatric inpatient medical and nursing staff per site (total n  = 78-130). Factors that may have contributed to sustaining outcomes and/or interventions will be explored and mapped to an established sustainability framework. Discussion This study will improve our understanding of the sustainability of evidence-based bronchiolitis management in infants. Results will also advance implementation science research by informing future de-implementation strategies to reduce low-value practices and sustain practice change in paediatric acute care. Trial registration Australian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

The growth in atmospheric methane (CH4) concentrations over the past 2 decades has shown large variability on a timescale of several years. Prior to 1999 the globally averaged CH4 concentration was increasing at a rate of 6.0 ppb yr−1, but during a stagnation period from 1999 to 2006 this growth rate slowed to 0.6 ppb yr−1. From 2007 to 2009 the growth rate again increased to 4.9 ppb yr−1. These changes in growth rate are usually ascribed to variations in CH4 emissions. We have used a 3-D global chemical transport model, driven by meteorological reanalyses and variations in global mean hydroxyl (OH) concentrations derived from CH3CCl3 observations from two independent networks, to investigate these CH4 growth variations. The model shows that between 1999 and 2006 changes in the CH4 atmospheric loss contributed significantly to the suppression in global CH4 concentrations relative to the pre-1999 trend. The largest factor in this is relatively small variations in global mean OH on a timescale of a few years, with minor contributions of atmospheric transport of CH4 to its sink region and of atmospheric temperature. Although changes in emissions may be important during the stagnation period, these results imply a smaller variation is required to explain the observed CH4 trends. The contribution of OH variations to the renewed CH4 growth after 2007 cannot be determined with data currently available.

Assessments, understood as tools for tracking what and how well students have learned, play a critical role in the classroom. Developing Assessments for the Next Generation Science Standards develops an approach to science assessment to meet the vision of science education for the future as it has been elaborated in A Framework for K-12 Science Education (Framework) and Next Generation Science Standards (NGSS). These documents are brand new and the changes they call for are barely under way, but the new assessments will be needed as soon as states and districts begin the process of implementing the NGSS and changing their approach to science education. The new Framework and the NGSS are designed to guide educators in significantly altering the way K-12 science is taught. The Framework is aimed at making science education more closely resemble the way scientists actually work and think, and making instruction reflect research on learning that demonstrates the importance of building coherent understandings over time. It structures science education around three dimensions - the practices through which scientists and engineers do their work, the key crosscutting concepts that cut across disciplines, and the core ideas of the disciplines - and argues that they should be interwoven in every aspect of science education, building in sophistication as students progress through grades K-12. Developing Assessments for the Next Generation Science Standards recommends strategies for developing assessments that yield valid measures of student proficiency in science as described in the new Framework . This report reviews recent and current work in science assessment to determine which aspects of the Framework's vision can be assessed with available techniques and what additional research and development will be needed to support an assessment system that fully meets that vision. The report offers a systems approach to science assessment, in which a range of assessment strategies are designed to answer different kinds of questions with appropriate degrees of specificity and provide results that complement one another. Developing Assessments for the Next Generation Science Standards makes the case that a science assessment system that meets the Framework's vision should consist of assessments designed to support classroom instruction, assessments designed to monitor science learning on a broader scale, and indicators designed to track opportunity to learn. New standards for science education make clear that new modes of assessment designed to measure the integrated learning they promote are essential. The recommendations of this report will be key to making sure that the dramatic changes in curriculum and instruction signaled by Framework and the NGSS reduce inequities in science education and raise the level of science education for all students.

BackgroundIn 2017, the PREDICT (Paediatric Research in Emergency Departments International Collaborative) network conducted a cluster randomised controlled trial (cRCT) at 26 Australian and New Zealand hospitals to improve bronchiolitis care. Findings demonstrated that targeted interventions significantly improved adherence with five evidence-based low-value bronchiolitis practices (no chest radiography, salbutamol, glucocorticoids, antibiotics and epinephrine) in the first 24 hours of hospitalisation (adjusted risk difference, 14.1%; 95% CI: 6.5% to 21.7%; p<0.001). During the intervention year (2017), intervention hospital (n=13) compliance was 85.1% (95% CI: 82.6% to 89.7%). This study aimed to determine if improvements in bronchiolitis management were sustained at intervention hospitals 2 years post-trial completion.MethodsInternational, multicentre follow-up study of hospitals in Australia and New Zealand that participated in a cRCT of de-implementation of low-value bronchiolitis practices, 1 year (2018) and 2 years (2019) post-trial completion, obtained retrospectively from medical audits. Sustainability was defined a priori as no more than a <7% decrease to any level of improvement in adherence for all five low-value practices (composite outcome) from the cRCT intervention year.ResultsOf the 26 hospitals, 11 intervention and 10 control hospitals agreed to participate in the follow-up study. Data were collected on 3299 infants with bronchiolitis 1 year (intervention and control hospitals) and 1689 infants 2 years post-trial (intervention hospitals). Adherence with no use of the five low-value practices 2 years post-trial completion was 80.9% (adjusted predicted adherence, 80.8%, 95% CI: 77.4% to 84.2%; estimated risk difference from cRCT outcome −3.9%, 95% CI: −8.6% to 0.8%) at intervention hospitals, fulfilling the a priori definition of sustainability.DiscussionTargeted interventions, delivered over one bronchiolitis season, resulted in sustained improvements in bronchiolitis management in infants 2 years later. This follow-up study provides evidence for sustainability in de-implementing low-value care in bronchiolitis management.Trial registration detailsAustralian and New Zealand Clinical Trials Registry No: ACTRN12621001287820.

The effect of Nb on the properties and microstructure of two novel powder metallurgy (P/M) Ni-based superalloys was evaluated, and the results critically compared with the Rolls-Royce alloy RR1000. The Nb-containing alloy was found to exhibit improved tensile and creep properties as well as superior oxidation resistance compared with both RR1000 and the Nb-free variant tested. The beneficial effect of Nb on the tensile and creep properties was due to the microstructures obtained following the post-solution heat treatments, which led to a higher γ′ volume fraction and a finer tertiary γ′ distribution. In addition, an increase in the anti-phase-boundary energy of the γ′ phase is also expected with the addition of Nb, further contributing to the strength of the material. However, these modifications in the γ′ distribution detrimentally affect the dwell fatigue crack-growth behavior of the material, although this behavior can be improved through modified heat treatments. The oxidation resistance of the Nb-containing alloy was also enhanced as Nb is believed to accelerate the formation of a defect-free Cr2O3 scale. Overall, both developmental alloys, with and without the addition of Nb, were found to exhibit superior properties than RR1000.