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Post-secondary institutions are required to complete a variety of quality assurance activities including external program review, a process of inviting external reviewers from outside the institution to provide constructive feedback on all aspects of an academic program. While external program reviews have been completed for decades, there has been little work to ensure that meaningful change occurs as a result. Assessment of outcomes at the department level are limited and research specifically considering external academic program review as a primary quality assurance activity is scant. Each of these limitations is even more significant when considered at the institutional level. From our experience, there is minimal consideration in research or practice to ensure that external review recommendations have an impact on educational planning at the institutional level. To help address this concern, in this paper we describe an approach involving secondary research and thematic document analysis that can be leveraged to enhance institutional decision-making processes by uncovering institutional themes evident across external reviews. We suggest that our approach may be helpful for other higher education institutions striving to make sense of program review recommendations from an institutional perspective.

Beryl Gilroy (1924-2001) is often referred to as one of the first Black primary school headteachers in London, England. Her refusal to continue teaching in schools once she reached her fifties has not been explored in recent publications. Her interest in sound, pedagogy and therapeutic recovery can be revisited retrospectively. She strove to counter racism through the power of communication as a teacher, radio broadcaster, headteacher, therapist and published writer of memoir, novels and children's reading books. The unifying thread in this article interweaves different perspectives on why Beryl Gilroy tried to create colloquial and phonetic speech in her published writings. It is argued that perhaps this was devised to help the reader share in her own reimagining of "poignant veridicality" -- an appreciation of truth as something reached through sonic immersion in valuable and contrasting interpretations and feelings that do not always have to have rational explanations.

External program review is often considered the "gold standard" approach to evaluating academic programs in higher education. Despite the importance of program review, skepticism persists regarding its ability to meaningfully engage faculty and have sustaining impact on program improvement. This paper builds on the academic Program Review Learning Community conceptual model and presents a process for applying a project management facilitation technique that leverages a course structure. The Program Review Course allows for multiple programs to be reviewed concurrently as part of an interdisciplinary cohort. Within the cohort, faculty teams gain access to templates, information sessions, workshops, and discussion forums, with opportunities for engagement both within and across multiple disciplines. Using learning modules, this approach is designed to create efficiency and collaboration in delivering program review tools and customized supports. Utilizing a course structure for program review fits well with a new way to think about program review because successful learning communities are often embedded within institutional structures. Use of this approach is expected to increase clarity and consistency, improve administrative feasibility, provide guidance for those new to program review, promote collegiality within and across programs, and involve team members in the creation of action planning. The authors propose that a course-based approach for conducting program review, with teams of disciplinary faculty joining an interdisciplinary cohort and supported by quality assurance practitioners and educational developers is a novel way to provide structure and academic development while meeting legislative requirements.

Abstract We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5+ cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment. α-LGR5-BiTE treatment was less effective in the pre-B-ALL cancer model yet promoted a twofold reduction in tumour burden. α-LGR5-CAR-T cells also showed specific and potent LGR5+ cancer cell killing in vitro and effective tumour targeting with a fourfold decrease in pre-B-ALL tumour burden relative to controls. Taken together, we show that α-LGR5 can not only be used as a research tool and a biomarker but also provides a versatile building block for a highly effective immune therapeutic portfolio targeting a range of LGR5-expressing cancer cells.

Introduction: Boerhaave syndrome is a rare condition associated with high morbidity and mortality. Prompt intervention greatly improves outcomes, with surgery traditionally being the mainstay of management. Recent advances in therapeutic endoscopy have led to increasing interest in endoluminal vacuum therapy (EVT), a minimally invasive technique, allowing wound debridement and drainage, encouraging granulation tissue formation. EVT has been associated with positive clinical outcomes, including lower mortality rates compared to surgery and stenting for the management of anastomotic leaks, and to a lesser extent, oesophageal perforations. EVT has been adopted into practice across Europe; however, only few cases have been reported from the UK. Case Presentations: We report three cases of Boerhaave syndrome, successfully managed with EVT, using the Eso-SPONGE ® (B.Braun Medical Ltd, Sheffield, UK). EVT involves the placement of a polyurethane sponge into the wound cavity. The cavity is initially assessed, then an overtube is introduced through which the sponge is inserted, and then the overtube is removed. Sponge position is confirmed and adjusted if necessary. The sponge is connected via a trans-nasal drain to continuous negative pressure suction and is changed every 3–5 days. Having been deemed surgically unfit, all 3 patients were referred for EVT. All patients made excellent recovery and were discharged home. Conclusion: EVT is an effective management strategy for surgically unfit Boerhaave syndrome patients. Eso-SPONGE use aided drainage of the septic focus and closure of the defect, leading to complete recovery. Our findings support the existing evidence that EVT is a promising solution for Boerhaave syndrome.

Abstract Background Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare. Methods The CAIDE model was applied to a sub-sample of a large, population-based cohort study (n = 5,360; aged 50–75) and evaluated for the outcomes of all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD) by calculating Akaike’s information criterion (AIC) and the area under the curve (AUC). The improvement of the CAIDE model by PRS and SCD was further examined using the net reclassification improvement (NRI) method and integrated discrimination improvement (IDI). Results During 17 years of follow-up, 410 participants were diagnosed with dementia, including 139 AD and 152 VD diagnoses. Overall, the CAIDE model showed high discriminative ability for all outcomes, reaching AUCs of 0.785, 0.793, and 0.789 for all-cause dementia, AD, and VD, respectively. Adding information on SCD significantly increased NRI for all-cause dementia (4.4%, p = 0.04) and VD (7.7%, p = 0.01). In contrast, prediction models for AD further improved when PRS was added to the model (NRI, 8.4%, p = 0.03). When APOE ε4 carrier status was included (CAIDE Model 2), AUCs increased, but PRS and SCD did not further improve the prediction. Conclusions Unlike PRS, information on SCD can be assessed more efficiently, and thus, the model including SCD can be more easily transferred to the clinical setting. Nevertheless, the two variables seem negligible if APOE ε4 carrier status is available.

BACKGROUND: To analyze the influence of the COVID-19 pandemic on the process of diagnosis and monitoring of drug-resistant pulmonary tuberculosis (TB) cases reported in the state of Paraná, Brazil, from 2015 to 2020. METHODS: Ecological study with quantitative approach. This study was based on diagnosed cases of pulmonary TB reported in the Notifiable Disease Information System in residents of Paraná; as well as through the number of confirmed cases of COVID-19 in the state epidemiological bulletin for the year 2020. The study data were analyzed using descriptive statistics. RESULTS: It was found that, although the number of reported pulmonary TB cases (drug-resistant and general) increased between 2015 and 2019, there was a drop in notification in 2020, the first year of the COVID-19 pandemic. The notification of TB cases was also influenced monthly during the year according to the increase in the number of COVID-19 cases. For cases of drug-resistant pulmonary TB, the provision of diagnostic tests and Directly Observed Treatment decreased by more than half in 2020, especially when compared to 2019. CONCLUSIONS: In view of these findings, the influence of COVID-19 on the diagnosis and monitoring of drug-resistant and general pulmonary TB cases is evident, showing that the pandemic has compromised the advances of recent decades in achieving the goals established for its eradication by 2035.

Abstract Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb’s free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.

Abstract Background Glycolytic flux is regulated by the energy demands of the cell. Upregulated glycolysis in cancer cells may therefore result from increased demand for adenosine triphosphate (ATP), however it is unknown what this extra ATP turnover is used for. We hypothesise that an important contribution to the increased glycolytic flux in cancer cells results from the ATP demand of Na+/K+-ATPase (NKA) due to altered sodium ion homeostasis in cancer cells. Methods Live whole-cell measurements of intracellular sodium [Na+]i were performed in three human breast cancer cells (MDA-MB-231, HCC1954, MCF-7), in murine breast cancer cells (4T1), and control human epithelial cells MCF-10A using triple quantum filtered 23Na nuclear magnetic resonance (NMR) spectroscopy. Glycolytic flux was measured by 2H NMR to monitor conversion of [6,6-2H2]d-glucose to [2H]-labelled l-lactate at baseline and in response to NKA inhibition with ouabain. Intracellular [Na+]i was titrated using isotonic buffers with varying [Na+] and [K+] and introducing an artificial Na+ plasma membrane leak using the ionophore gramicidin-A. Experiments were carried out in parallel with cell viability assays, 1H NMR metabolomics of intracellular and extracellular metabolites, extracellular flux analyses and in vivo measurements in a MDA-MB-231 human-xenograft mouse model using 2-deoxy-2-[18F]fluoroglucose (18F-FDG) positron emission tomography (PET). Results Intracellular [Na+]i was elevated in human and murine breast cancer cells compared to control MCF-10A cells. Acute inhibition of NKA by ouabain resulted in elevated [Na+]i and inhibition of glycolytic flux in all three human cancer cells which are ouabain sensitive, but not in the murine cells which are ouabain resistant. Permeabilization of cell membranes with gramicidin-A led to a titratable increase of [Na+]i in MDA-MB-231 and 4T1 cells and a Na+-dependent increase in glycolytic flux. This was attenuated with ouabain in the human cells but not in the murine cells. 18FDG PET imaging in an MDA-MB-231 human-xenograft mouse model recorded lower 18FDG tumour uptake when treated with ouabain while murine tissue uptake was unaffected. Conclusions Glycolytic flux correlates with Na+-driven NKA activity in breast cancer cells, providing evidence for the ‘centrality of the [Na+]i-NKA nexus’ in the mechanistic basis of the Warburg effect.

Abstract An important aspect of Space Situational Awareness is to estimate the intent of objects in space. This paper discusses how discriminating features can be obtained from Inverse Synthetic Aperture Radar images of such objects and how these discriminators can be used to recognise the objects or to estimate their intent. If the object is, for example, a satellite of a known type, the scheme proposed is able to recognise it. The ability of the scheme to detect damage to the object is also discussed. The focus is on imagery obtained in the sub‐terahertz band (typically 300 GHz) because of the greater imaging capability given by the diffuse scattering which is observed at these frequencies. The paper also discusses the importance of being able to use images obtained by electromagnetic simulation to be able to train the subsystem which recognises features of the objects and describes a practical scheme for creating these simulations for large objects at these very short wavelengths.

Abstract With the aim of investigating the existence of an integrable elliptic deformation of strings on AdS3 × S3 × T4, we compute the tree-level worldsheet S-matrix of the elliptically-deformed bosonic sigma model on AdS3 × S3 in uniform light-cone gauge. The resulting tree-level S-matrix is compatible with the integrability of the model and has interesting features, including a hidden U(1) symmetry not manifest in the Lagrangian. We find that it cannot be embedded in the known exact integrable R-matrices describing deformations of the undeformed AdS3 × S3 × T4 light-cone gauge S-matrix including fermions. Therefore, we construct embeddings of the deformed 6-d metric in type II supergravity with constant dilaton and homogeneous fluxes. The simplicity of these solutions suggests they are promising candidates to lead to an integrable string sigma model including fermions.

The Work Volition Scale (WVS) is a brief measure of the perceived capacity to make career decisions despite constraints; however, systematic validation of item responses to the scale is still in its infancy. The present article reports on research conducted to investigate the latent structure of WVS, its invariance across gender, and mean differences in work volition across income in a sample of retail workers. A bifactor structure of the WVS accounted for construct-relevant multidimensionality in scores due to the presence of general and specific volition dimensions. Tests of gender invariance revealed the equivalence of item loadings, thresholds, uniquenesses, and factor means. Support was also found for plausible latent mean differences in general volition across income, with retail workers earning high wages reporting greater volition than those earning low wages. Finally, evidence was obtained for theoretically meaningful relations of the general and specific volition dimensions with career control.

Abstract: Comparative single-cell studies of group 3/4 medulloblastomas (MBs) and fetal brain have identified a common hierarchy of glutamatergic-lineage cell types and an apparent cell-of-origin in the rhombic lip. An increased understanding of the genetic regulators of stem-cell maintenance and differentiation in MB would clearly be of therapeutic benefit. There is a significant need for lineage-tracing systems to model MB malignant transformation, progression, and response to therapy. We developed in vivo and in organoid genetic lineage-tracing systems with a single-cell readout. A high-complexity lentiviral library expressing heritable polyadenylated molecular barcodes was transduced into D283 and D425 patient-derived cell lines. Barcoded cells were injected into the brains of immunocompromised mice. Both preimplantation barcoded cultures and the resulting mature tumors were profiled by single-cell RNA-sequencing (scRNA-seq). This captured both endogenous RNA and barcode transcripts. While only minimal barcode clash was detected in the preimplantation cultures, we observed a clonal expansion of barcodes in mature tumors which aligned with phylogenetics analysis of expressed mutations in endogenous RNA. Methods for assessing lineage coupling between transcriptional clusters and inferring their lineage relationship were developed. Ongoing efforts to recover barcodes from tumor sections via spatial transcriptomics will be presented. These studies fill a gap in status quo models of MB which are needed to leverage recent findings derived from single-cell analysis of human tumors.

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

The developmental period of adolescence is a known transitional life phase with unique risk and protective factors that can affect mental wellbeing outcomes. This, in combination with the pressures and demand of elite sport, make young elite athletes an important population in which positive mental wellbeing can be explored. This study aimed to examine the state of wellbeing, informed by positive psychology and the Positive emotions, Engagement, Relationships, Meaning, Accomplishment (PERMA) model of wellbeing, in a cohort of young athletes aged 16–19 years in the Australian setting as part of a model of continuous improvement. The objectives of these aims were to inform the development of a wellbeing curriculum for implementation in the Australian Rules Football talent pathway and to assess whether wellbeing presents differently in young athletes relative to the general school-attending population of that same age. Participants were 608 young Australian footballers participating in the developmental talent pathway during 2020 and 2021. There were 299 young male footballers, and 309 young women footballers who completed data collection. Wellbeing was assessed using the Engagement, Perseverance, Optimism, Connectedness, Happiness Measure of Adolescent Wellbeing (EPOCH) which corresponds to the PERMA model of wellbeing, and total mean scores were reported. Engagement and connectedness were similar for the young men and women athletes. Young men reported higher perseverance, optimism, happiness, and overall wellbeing relative to young women. Wellbeing among young athletes appears similar to the general population, however perseverance may be higher among young athletes. These findings form an important component of the continuous improvement model adopted in the football program in that the results informed the development of a tailored wellbeing curriculum program that is reflective of the wellbeing needs of the young athletes.

Abstract The interaction between multi‐component rare earth element (REE) aqueous solutions and carbonate grains (dolomite, aragonite, and calcite) are studied at hydrothermal conditions (21–210 °C). The effect of ionic radii of five REEs (La, Ce, Pr, Nd, Dy) on solid formation are analyzed using two solution types: equal REE concentrations and concentrations normalized to Post Archean Australian Shale Standard (PAAS). The interaction replaces the host Ca–Mg carbonate grains with a series of REE minerals (lanthanite → kozoite → bastnäsite → cerianite). At 165 °C, equal concentration solutions promote kozoite crystallization, maintaining similar REE ratios in solids and solution. PAAS solutions result in zoned REE‐bearing crystals with heterogeneous elemental distributions and discreet REE phases (e.g., cerianite). Chemical signatures indicate metastable REE‐bearing phases transforming into more stable polymorphs, along with symplectite textures formed by adjacent phase reactions. Overall, experiments highlight the dependence of polymorph selection, crystallization pathway, mineral formation kinetics, and chemical texture on REE concentrations, ionic radii, temperature, time, and host grain solubility.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Abstract Background Depression ranks as the foremost mental health concern among childbearing women. Within low- and middle-income countries (LMICs), between 20 and 25% of women encounter depression during pregnancy or soon after delivery. This condition impacts not only the mothers but also their offspring. Offspring of women suffering from postnatal depression (PND) exhibit suboptimal cognitive development and increased emotional and behavioural issues throughout their growth. This scenario becomes more pronounced in LMICs, where numerous adversities further jeopardise children’s developmental progress. Despite antenatal services providing a pivotal platform to address women’s mental health needs, PND treatment remains inaccessible in many LMICs. The World Health Organization advocates interpersonal psychotherapy (IPT) for treating depression. While research from high-income countries has established the efficacy of IPT and group-IPT (g-IPT) for PND, its effectiveness within the LMIC context and its potential benefits for child development remain uncharted. This study seeks to gauge the potency of g-IPT for women with PND in two LMICs. Methods This multi-site randomised controlled trial is a continuation of two preceding phases—conceptual mapping and a feasibility study executed in Lebanon and Kenya. Insights gleaned from these phases underpin this comprehensive RCT, which contrasts the efficacy and cost-effectiveness of high-quality standard care (HQ-SC) augmented with g-IPT against HQ-SC in isolation. The trial, characterised as an individually randomised superiority assessment, targets women with postnatal depression in Beirut, Lebanon, and Nairobi, Kenya. It aims to determine if culturally tailored g-IPT, administered within community settings in both countries, outperforms HQ-SC in influencing child developmental outcomes, maternal depression, and the quality of the mother–child bond. Discussion The SUMMIT trial, designed with pragmatism, possesses the magnitude to evaluate g-IPT within two LMIC frameworks. It seeks to enlighten policymakers, service commissioners, professionals, and users about g-IPT’s potential to alleviate maternal PND and bolster child developmental outcomes in LMICs. Additionally, the trial will generate valuable data on the clinical and economic merits of high-quality standard care. Trial registration ISRCTN, ISRCTN15154316. Registered on 27 September 2023, https://doi.org/10.1186/ISRCTN15154316