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This article examines the accounts of actions undertaken by Early Career Teachers (ECTs) recently graduated from a social justice-oriented Initial Teacher Education (ITE) program and employed in complex school settings with high levels of student diversity, disadvantage, and poverty. The study drew on theories of teacher agency and agency more broadly to examine the workshadowing observations of the teachers' practice in classrooms augmented by their reflective accounts in interviews. The study found that the ECTs' agency, or contextualised social action, can be conceptualised as temporally embedded social engagement directed at addressing their students' cultural, social and academic needs. The teachers drew on past learnings from their ITE program, committed to future-oriented innovations in teaching, and made in-the-present decisions about actions to resolve emergent contingencies such as resource shortages. We argue that these understandings are usefully enhanced by recognising contingency, consciousness, criticality and creativity as additional features of the teachers' deliberative programs of action.

Super bioavailability (SUBA) itraconazole (S-ITZ), which releases drug in the duodenum, and conventional itraconazole (C-ITZ), which releases drug in the stomach, were compared in two pharmacokinetic (PK) studies: a 3-day loading dose study and a 15-day steady-state administration study. These were crossover oral bioequivalence studies performed under fed conditions in healthy adult volunteers. In the loading dose study, C-ITZ (two doses of 100 mg each) and S-ITZ (two doses of 65 mg each) were administered three times daily for 3 days and once on day 4 (n = 15). For the steady-state administration study, C-ITZ (two doses of 100 mg each) and S-ITZ (two doses of 65 mg each) were administered twice daily for 14 days and a last dose was administered 30 min after a meal on day 15 (n = 16). Blood samples collected throughout both studies were analyzed for ITZ and hydroxy-ITZ (OH-ITZ) levels. Least-squares geometric means were used to compare the maximum peak concentration of drug after administration at steady state prior to administration of the subsequent dose (Cmax_ss), the minimum drug level after administration prior to the subsequent dose (Ctrough), and the area under the curve over the dosing interval (AUCtau) of each formulation. The ratios of itraconazole (ITZ) and OH-ITZ for S-ITZ to C-ITZ were between 107% and 118% in both studies for Cmax_ss, Ctrough, and AUCtau, which were within the U.S. FDA-required bioequivalence range of 80% to 125%. At the end of the steady-state administration study, 13 of 16 volunteers obtained higher mean ITZ blood Ctrough levels of >1,000 ng/ml when they were administered S-ITZ (81%) than when they were administered C-ITZ (44%). The study drugs were well tolerated in both studies, with similar adverse events (AEs). All treatment-emergent AEs resolved after study completion. One volunteer receiving C-ITZ discontinued due to a treatment-unrelated AE in the steady-state administration study. No serious AEs were reported. Total, trough, and peak ITZ and OH-ITZ exposures were similar between the two formulations. Therefore, SUBA-ITZ, which has 35% less drug than C-ITZ, was bioequivalent to C-ITZ in healthy adult volunteers and exhibited a safety profile similar to that of C-ITZ.

Improving the quality of education for young people growing up in high poverty and culturally diverse communities is an escalating problem in affluent nations with increasing gaps between the wealthy and the poor. Improving the quality of teachers and improving the quality of teaching are amongst the prominent solutions offered to redress the differences between student academic performances related to socio-economic family circumstances. This article examines the different discourses of "quality" in relation to the preparation of pre-service teachers to work in high poverty schools such as graduates of the National Exceptional Teaching for Disadvantaged Schools pre-service teacher education program. Key tenets of "quality teacher" and "quality teaching" solutions are summarized along with their critiques. An alternative approach starting from a position of social justice is considered. This approach situates the work of teaching within high poverty school communities and considers what pre-service teachers need to understand and learn to do with respect to context.

This article explores how early-career teachers working in high-poverty schools in Australia account for their decision-making during critical classroom incidents. Classroom management solutions are problematized by investigating how two teachers take up particular positions, make decisions, and enact what they believe to be 'quality teaching' in context. Through a combination of interviews and observations of teachers "in situ," we examine what these teachers do, why they do it, what informs their decisions, and how they reflect on their actions. The complexity of teachers' work in schools located in high-poverty areas is highlighted. We argue that both early-career teachers prefer to position themselves within 'pastoral', in contrast to 'disciplinarian', discourses, as part of constituting the school as a site of possibility and teachers who advocate for youth growing up in poverty.

This paper provides three case studies of initiatives developed to improve educational opportunities in vulnerable urban communities. The cities in the three countries involved, Australia, the United States, and Spain, are different in many ways; however, each has persistent and entrenched inequalities between the educational opportunities and outcomes of historically marginalised students and their mainstream counterparts. Here, we focus on conceptualising and describing urban examples of poverty from three different countries, and reporting on programs and strategies aimed at enhancing the quality of teaching in schools in high-poverty areas. By providing and comparing the three cases, we aim to contribute to broader understandings of poverty in three locations and how teachers and schools in high-poverty urban settings can re-think their practices.

This paper describes the aims, origins and principles of the "Australian National Exceptional Teaching for Disadvantaged Schools" programme and reflects on findings from its first eight years. As a well-established, mainstream university-based initial teacher-education programme designed to prepare social justice teachers for low socio-economic or high-poverty schools, NETDS has had significant impact on recruiting and retaining high-performing teachers in the schools that need them most. In this paper we discuss how it works, but also outline some of the complexities that arose in trying to design a teacher-education programme with equity at the centre and some of the changes we made along the way.

In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post hoc analysis of 368 patients aimed to explore treatment heterogeneity through unsupervised learning. All available clinical variables at baseline were used as input. Treatment heterogeneity was assessed using latent class analysis (LCA), Ward's hierarchical clustering (HC) and the adjudication to previously described clinical sepsis phenotypes. The primary outcome was 28-day mortality. For LCA, a 2-class latent model was deemed most suitable. In the LCA model, 82 (22%) patients were assigned to class 1 and 286 (78%) to class 2. Class 1 was defined by more severely ill patients with significantly higher mortality. In an adjusted logistic regression, no heterogeneity of treatment effect (HTE) between classes was observed (p = 0.998). For HC, no significant classes were found (p = 0.669). Using the previously described clinical sepsis subtypes, 41 patients (11%) were adjudicated subtype alpha (α), 17 (5%) beta (β), 112 (30%) delta (δ) and 198 (54%) gamma (γ). HTE was observed between clinical subtypes (p = 0.001) with improved 28-day mortality after treatment with vilobelimab for the δ subtype (OR = 0.17, 95% CI 0.07–0.40, p < 0.001). No signal for harm of treatment with vilobelimab was observed in any class or clinical subtype. Overall, treatment effect with vilobelimab was consistent across different classes and subtypes, except for the δ subtype, suggesting potential additional benefit for the most severely ill patients. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the working lives of three Australian teachers in the hardest-to-staff schools as they tell their stories of how teacher attrition has impacted them and others. Drawing on Zavelevsky & Shapira-Lishchinsky's ecological framework (2020) we analyse their work-stories to better understand issues impacting the teaching workforce in a time of extreme teaching shortages. Part of a larger study on teachers who remain in hard-to-staff schools, here we focus not only on the challenges facing the education workforce but also on the insights that may lead to better strategies to retain teachers in the schools that need them most. [ABSTRACT FROM AUTHOR]

Background: Vilobelimab, a complement 5a (C5a)-specific monoclonal antibody, reduced mortality in critically ill COVID-19 patients in a phase 3 multicentre, randomized, double-blind, placebo-controlled study. As part of the study, vilobelimab concentrations and C5a levels as well as antidrug antibodies (ADAs) to vilobelimab were analysed. Results: From Oct 1, 2020 to Oct 4, 2021, 368 invasively mechanically ventilated COVID-19 patients were randomized: 177 patients were randomly assigned to receive vilobelimab while 191 patients received placebo. Pharmacokinetic sampling was only performed at sites in Western Europe. Blood samples for vilobelimab measurements were available for 93 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. On day 8, after three infusions, mean vilobelimab (trough) concentrations ranged from 21,799.3 to 302,972.1 ng/mL (geometric mean 137,881.3 ng/mL). Blood samples for C5a measurements were available for 94 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. At screening, C5a levels were highly elevated and comparable between groups. In the vilobelimab group, median C5a levels were 118.3 ng/mL [IQR 71.2–168.2 ng/mL] and in the placebo group, median C5a levels were 104.6 ng/mL [IQR 77.5–156.6 ng/mL]. By day 8, median C5a levels were reduced by 87% in the vilobelimab group (median 14.5 ng/mL [IQR 9.5–21.0 ng/mL], p < 0.001) versus an 11% increase in the placebo group (median 119.2 ng/mL [IQR 85.9–152.1 ng/mL]). Beyond day 8, though plasma sampling was sparse, C5a levels did not reach screening levels in the vilobelimab group while C5a levels remained elevated in the placebo group. Treatment-emergent ADAs were observed in one patient in the vilobelimab group at hospital discharge on day 40 and in one patient in the placebo group at hospital discharge on day 25. Conclusions: This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trialregistration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420 [ABSTRACT FROM AUTHOR]

It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acuterespiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence. [ABSTRACT FROM AUTHOR]