Problematizing Complexities and Pedagogy in Teacher Education Programs: Enacting Knowledge in a Narrative Inquiry Teacher Education Discourse Community

This article describes how a cross-Canada cohort of teacher educators identified the benefits of participating in a narrative inquiry teacher education discourse community. The community enables conscious dialogue regarding the legitimacy of teacher knowledge, identification of personal and professional issues within educational contexts, and connections between local issues and global trends. Three themes are explored: (1) development of a non-hierarchical community, (2) unravelling of complexities in light of external pressures, and (3) personal ethical responses to current challenges. Teacher educator knowledge is deepened by providing a relational venue to attend to educational reform and programmatic complexity by grounding practices in collaborative experience

Probing Evolutionary Repeatability: Neutral and Double Changes and the Predictability of Evolutionary Adaptation

The question of how organisms adapt is among the most fundamental in evolutionary biology. Two recent studies investigated the evolution of Escherichia coli in response to challenge with the antibiotic cefotaxime. Studying five mutations in the beta-lactamase gene that together confer significant antibiotic resistance, the authors showed a complex fitness landscape that greatly constrained the identity and order of intermediates leading from the initial wildtype genotype to the final resistant genotype. Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection. I further explore these data in several ways.Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629. Allowing multiple simultaneous mutations also greatly increases the number of accessible pathways. Allowing a single case of double mutation to occur along a pathway increases the number of pathways from 27 to 259, and allowing arbitrarily many pairs of simultaneous changes increases the number of possible pathways by more than 100 fold, to 4800. I introduce the metric 'repeatability,' the probability that two random trials will proceed via the exact same pathway. In general, I find that while the total number of accessible pathways is dramatically affected by allowing neutral or double mutations, the overall evolutionary repeatability is generally much less affected.These results probe the conceivable pathways available to evolution. Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α

BACKGROUND & AIMS: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres. METHODS: All seven centres agreed a standardised data set and data characterising clinical, demographic and emergency hospital admissions were collected retrospectively for the time periods 3, 6 and 12 months before and following initiation of rifaximin-α. Admission rates and hospital length of stay before and during therapy were compared. Costs of admissions and drug acquisition were estimated using published sources. Multivariate analyses were carried out to assess the relative impact of various factors on hospital length of stay. RESULTS: Data were available from 326 patients. Following the commencement of rifaximin, the total hospital length of stay reduced by an estimated 31-53%, equating to a reduction in inpatient costs of between £4858 and £6607 per year. Taking into account drug costs of £3379 for 1-year treatment with rifaximin-α, there was an estimated annual mean saving of £1480-£3228 per patient. CONCLUSIONS: Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving

Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme

Objective: Serogroup W and Y invasive meningococcal disease increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) invasive meningococcal disease, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, the vaccine coverage in the eligible school cohorts aged 14 to 19 years was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage. Methods: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15 to 19 years, using two cross-sectional studies: 2014 to 2015 “UKMenCar4” and 2018 “Be on the TEAM” (ISRCTN75858406). Results: A total of 10 625 participants preimplementation and 13 434 postimplementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2.03 to 0.71% (OR 0.34 [95% CI 0.27–0.44], p < 0.001). Carriage of genogroup B meningococci did not change (1.26% vs 1.23% [95% CI 0.77–1.22], p = 0.80) and genogroup C remained rare (n = 7/10 625 vs 17/13 488, p = 0.135). The proportion of serogroup positive isolates (i.e. those expressing capsule) decreased for genogroup W by 53.8% (95% CI –5.0 to 79.8, p = 0.016) and for genogroup Y by 30.1% (95% CI 8.9–46·3, p = 0.0025). Discussion: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection

A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways

Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM. The causal mutation was identified as a missense change, L972P, in the Nischarin (NISCH) gene. edison mice develop a serous or granulocytic effusion, increasingly macrophage and neutrophil rich with age, along with a thickened, inflamed mucoperiosteum. We also identified a second hypomorphic allele, V33A, with only modest increases in auditory thresholds and reduced incidence of OM. NISCH interacts with several proteins, including ITGA5 that is thought to have a role in modulating VEGF-induced angiogenesis and vascularization. We identified a significant genetic interaction between Nisch and Itga5; mice heterozygous for Itga5-null and homozygous for edison mutations display a significantly increased penetrance and severity of chronic OM. In order to understand the pathological mechanisms underlying the OM phenotype, we studied interacting partners to NISCH along with downstream signalling molecules in the middle ear epithelia of edison mouse. Our analysis implicates PAK1 and RAC1, and downstream signalling in LIMK1 and NF-κB pathways in the development of chronic OM

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

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

Information Literacy—Is It Worth the Investment?

Many academic libraries have extensive information literacy programs. Often a lot of staff time is dedicated to the creation and delivery of these programs making them a big investment of resources. There is also a cost associated with opportunities forgone. If resources are to be maximised there needs to be a careful analysis of staff costs in relation to student benefits. Librarians at Central Queensland University analysed the costs associated with the creation and delivery of one information literacy program within the Faculty of Education and Creative Arts. The intention was to use an embedded approach and link the information literacy skills and concepts with the content so that students would learn sections of content by accessing and using information sources. Costs, along with evaluative data from all stakeholders, were instrumental in planning the future development of the program