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This study examined the perceptions of educators to determine if they felt that they were adequately prepared to teach in a high poverty school setting. The participants, educators from four school districts, completed a survey based on their perceptions of their own level of self-efficacy and preparedness to work in high poverty schools. The analyses indicated that, overall, educators felt well-prepared with limited supporting evidence to work in high poverty schools in the areas of student learning and engagement, which included curriculum and pedagogy, differentiation, and assessment. Findings further indicated a need for professional learning so educators can best support students in the high poverty setting in terms of problem solving when issues arise in the classroom. The implications for practice suggest that educators need support to ensure a high level of preparedness to work in high-poverty schools, as educators need to have a high level of self-efficacy to positively impact student success. Future research could help pinpoint specific areas of need within student learning and engagement to determine how to best develop professional learning opportunities that are purposeful, collaborative, and sustainable. Additional research should be conducted to determine if teachers' levels of self-efficacy and perceptions of preparedness are correlated to leadership style.

School leaders must make decisions and implement strategies to improve a school climate and student achievement, and it benefits them to understand which areas of school climate have the greatest impact on student achievement. The State of Georgia measures school climate and student achievement with its school accountability measure, the College and Career Ready Performance Index (CCRPI). This study employed a quantitative research design using archival data that was publicly available from CCRPI data for a two year span to examine the relationship between school climate and student achievement statewide in the middle grade sector. Findings revealed that all four components of school climate (i.e., Survey Score, Discipline Score, Safe & Substance-Free Learning Environment Score, and Attendance Score) were significantly related to student achievement. Additionally, the Survey Score and Discipline Score were the most significant predictors of student achievement. These findings provide school leaders with essential information to strategically make decisions involving processes and procedures that impact these areas. Future research is needed to determine whether the relationship between school climate and student achievement is similar for elementary, middle, or high schools. In addition, separating the data into rural, suburban, and urban schools and running similar analyses may also help administrators improve school climate and student achievement.

This systematic review examines the landscape of extracellular vesicle (EV)-related clinical trials to elucidate the field's trends in clinical applications and EV-related methodologies, with an additional focus on the acknowledgement of EV subpopulations. By analysing data from public reporting repositories, we catalogued 471 EV-related clinical trials to date, with indications for over 200 diseases. Diagnostics and companion diagnostics represented the bulk of EV-related clinical trials with cancer being the most frequent application. EV-related therapeutics trials mainly utilized mesenchymal stromal cell (MSC) EVs and were most frequently used for treatment of respiratory illnesses. Ultracentrifugation and RNA-sequencing were the most common isolation and characterization techniques; however, methodology for each was not frequently reported in study records. Most of the reported characterization relied on bulk characterization of EV isolates, with only 11% utilizing EV subpopulations in their experimental design. While this may be connected to a lack of available techniques suitable for clinical implementation, it also highlights the opportunity for use of EV subpopulations to improve translational efforts. As academic research identifies more chemically distinct subpopulations and technologies for their enrichment, we forecast to more refined EV trials in the near future. This review emphasizes the need for meticulous methodological reporting and consideration of EV subpopulations to enhance the translational success of EV-based interventions, pointing towards a paradigm shift in personalized medicine.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

The international human rights framework and United Nations' Agenda 2030 with its Sustainable Development Goals are two closely linked frameworks. Agenda 2030 has galvanized much interest and action within the education sector around Education for Sustainable Development. The human rights framework, with its calls for Human Rights Education, provides a legal imperative for embedding these pedagogies in education. This article argues that for the education sector, unifying actions and embracing the two pedagogies of Education for Sustainable Development and Human Rights Education can form a foundation for a new social contract for education. For these frameworks to meet their potential in education, they must be embedded at both curricular and institutional levels. We will need robust and committed governance at national and institutional levels for these approaches to achieve their transformational potential.

Medical students must be adept at critical thinking to successfully meet the learning objectives of their preclinical coursework. To encourage student success on assessments, the course director of a first-year medical physiology course emphasized the use of learning objectives that were explicitly aligned with formative assessments in class. The course director introduced the physiology discipline, learning objectives, and evidence-based methods of studying to students on the first day of class. Thereafter, class sessions started with a review of the learning objectives for that session and included active learning opportunities such as retrieval practice. The instructor provided short answer formative assessments aligned with the learning objectives, intended to help the students apply and integrate the concepts. Midsemester, students received a link to an online survey with questions on studying habits, class attendance, and student engagement. After finals, students were invited to participate in focus groups about their class experience. A qualitative researcher moderated focus groups, recorded responses, and analyzed the narrative data. Of 175 students, 95 submitted anonymous online surveys. Student engagement was significantly correlated with in-person class attendance (r = 0.26, T = 2.5, P = 0.01) and the completion of open-ended formative assessments (r = 0.33, T = 3.3, P = 0.001). Focus groups were held via videoconference. From the class, 14 students participated in 4 focus groups; focus group participants were mostly women (11 of 14) and mostly in-class attendees (13 of 14). The students in this sample valued critical thinking but misunderstood expectations on exams and few students used learning objectives to study.

PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Since extracellular vesicles (EVs) have emerged as a promising drug delivery system, diverse methods have been used to load them with active pharmaceutical ingredients (API) in preclinical and clinical studies. However, there is yet to be an engineered EV formulation approved for human use, a barrier driven in part by the intrinsic heterogeneity of EVs. API loading is rarely assessed in the context of single vesicle measurements of physicochemical properties but is likely administered in a heterogeneous fashion to the detriment of a consistent product. Here, we applied a suite of single-particle resolution methods to determine the loading of rhodamine 6G (R6G) surrogate cargo mimicking hydrophilic small molecule drugs across four common API loading methods: sonication, electroporation, freeze-thaw cycling and passive incubation. Loading efficiencies and alterations in the physical properties of EVs were assessed, as well as co-localization with common EV-associated tetraspanins (i.e., CD63, CD81 and CD9) for insight into EV subpopulations. Sonication had the highest loading efficiency, yet significantly decreased particle yield, while electroporation led to the greatest number of loaded API particles, albeit at a lower efficiency. Moreover, results were often inconsistent between repeated runs within a given method, demonstrating the difficulty in developing a rigorous loading method that consistently loaded EVs across their heterogeneous subpopulations. This work highlights the significance of how chosen quantification metrics can impact apparent conclusions and the importance of single-particle characterization of EV loading.

7009 Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed in patients (pts) who had progressive disease (PD). Here, we report outcomes for pts with high-risk genomic features from the FD cohort and retreatment outcomes in pts from the FD cohort and MRD cohort placebo arm. Methods: Pts aged ≤70 y with previously untreated CLL/SLL without restriction on genomic risk factors received 3 cycles of Ibr, then 12 cycles of Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 mg/d orally). On-study retreatment included single-agent Ibr (FD cohort or MRD cohort placebo arm); pts with PD >2 y after end of treatment (EOT) could be retreated with FD Ibr+Ven (FD cohort). Results: In the FD cohort (n=159) with a median follow-up of 61.2 mo (range, 0.8–66.3), 5-y PFS and OS rates (95% CI) were 67% (59–74) and 96% (91–98), respectively. 5-y PFS rates were higher in pts with undetectable MRD at 3 mo after EOT in peripheral blood (83%) or bone marrow (84%) vs those without (48% and 50%, respectively). 5-y PFS rates (95% CI) in pts with genomic risk factors were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), and unmutated IGHV 68% (50–80) (Table). In total, 18 second malignancies occurred in 13 pts (10 events in 8 pts during FD Ibr+Ven, 6 events in 4 pts after EOT and before retreatment, and 2 events in 2 pts during retreatment). Of 202 pts who completed Ibr+Ven (FD cohort, n=159; MRD cohort placebo arm, n=43), 63 have had PD to date; PD occurred >2 y after EOT in 43/63 pts (68%). 32/63 (51%) pts initiated retreatment with Ibr (n=25) or Ibr+Ven (n=7). With a median time on Ibr retreatment of 21.9 mo (range, 0.03–50.4), ORR was 86% in 22 evaluable pts (best response: 1 CR; 1 nodular PR; 17 PR; 2 SD; 1 PD [Richter transformation]). With a median time on Ibr+Ven retreatment of 13.8 mo (range, 3.7–15.1), ORR was 71% in 7 evaluable pts (best response: 1 CR; 4 PR; 1 PR with lymphocytosis; 1 SD). Conclusions: With up to 5.5 y of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS in pts with high-risk genomic features, as well as in the overall population. Ibr-based retreatment provides promising responses in pts needing subsequent therapy after the all-oral FD regimen of Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

Pete Smith,1 David Price,2,3 Richard Harvey,4,5 Andrew Simon Carney,6 Vicky Kritikos,7 Sinthia Z Bosnic-Anticevich,7,8 Louise Christian,9 Derek Skinner,10 Victoria Carter,10 Alice Marie Sybille Durieux3 1Clinical Medicine, Griffith University, Southport, QLD, Australia; 2Observational and Pragmatic Research Institute, Singapore; 3Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK; 4Applied Medical Research Center, University of New South Wales, Sydney, NSW, Australia; 5Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; 6Department of Otolaryngology – Head and Neck Surgery, Flinders University, Adelaide, SA, Australia; 7Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; 8Central Sydney Area Health Service, Sydney, NSW, Australia; 9NostraData, Kew, VIC, Australia; 10Optimum Patient Care, Cambridge, UK Purpose: There is a relative paucity of research regarding medication expenditure associated with multiple-therapy use for rhinitis in Australia. To describe 1) the nature and extent of multiple-therapy use for rhinitis in Australia using data on therapies purchased with prescription or over-the-counter (OTC) and 2) additional costs incurred by multiple-therapy use compared with intranasal corticosteroid (INCS) therapy alone. Patients and methods: A retrospective observational study was carried out using a database containing anonymous pharmacy transaction data available from 20% of pharmacies in Australia that links doctor prescriptions and OTC purchase information. Pharmacy purchases of at least one prescription or OTC rhinitis treatment, with or without additional asthma/chronic obstructive pulmonary disease (COPD) therapy, by patients during 2013 and 2014 were assessed. Results: In total, 4,247,193 prescription and OTC rhinitis treatments were purchased from 909 pharmacies over 24 months. The majority of rhinitis therapy transactions were single-therapy purchases without additional asthma/COPD therapy. Of the single therapies purchased, 73% were oral antihistamines (OAHs) and 15% were INCS therapy. Dual-therapy purchases of INCSs and OAHs accounted for 40% of multiple-therapy purchases. Patients frequently purchased OAHs, nonsteroidal nasal sprays, and eye drops for allergic conjunctivitis alongside INCSs, resulting in higher financial costs (up to AU$21 per treatment episode) compared with INCS monotherapy. Conclusion: This study highlighted the significant burden posed on community pharmacy to address the needs of people with rhinitis symptoms, and the failure to translate the evidence that INCSs are the most effective monotherapy for moderate to severe and/or persistent rhinitis into clinical practice in light of the lack of evidence supporting combination of INCS and OAH therapy. Health care professional engagement, especially at the pharmacy level, will be extremely important if we wish to ensure that the purchase of rhinitis treatment is in accordance with guidelines and that their use is optimal. Keywords: community pharmacy, intranasal corticosteroids, oral antihistamines, over-the-counter, prescription, rhinitis, therapy

John T. McGreevy, Catholicism: A Global History from the French Revolution to Pope Francis (New York: Norton, 2022. Pd. 528. Paperback $22.00. ISBN: 978 1-324-06604-0) Introduction * Stephen Schloesser (Loyola [...]

Students with disabilities continue to experience barriers to accessing tertiary (i.e., postsecondary) education in Australia. Using the principles of Universal Design for Learning (UDL) may help educators proactively address barriers through the design of more accessible and inclusive educational experiences. However, at present, references to UDL appear in only a small number of Australian educational policies and tertiary institute websites, and few tertiary educators use UDL in practice. In this article, we describe how a team of educators, learning designers, accessibility advocates, and people with disabilities from multiple institutions across Australia collaborated to co-create a free, accessible eLearning program to build workforce knowledge and skill in UDL. We first describe how the advisory group was established, how the Knowledge to Action cycle was used to guide the activities of the advisory group, and the evaluation framework that was used to assess the outcomes of the eLearning program. We share potential future activities to raise awareness of UDL and influence policy and practice in local contexts and propose directions for future work in this area.