Galvanising Transition and Success for Underrepresented Students: Five Conditions for Enhancing Online Student Engagement

The Australian Universities Accord’s (Department of Education, 2024) focus on expanding underrepresented groups’ access to higher education underscores an on-campus-online paradigm shift, or post-pandemic digital transformation, to address students’ flexibility and accessibility needs. The shift identifies that online student engagement, and students’ learning outcomes, need to be effective and fit for purpose if students are to succeed. Conducted as one phase of a longitudinal project (2017-present), this research investigated the approaches and strategies that could be incorporated to facilitate students’ online engagement. Findings suggest that these strategies could be encapsulated under five key conditions: fashioning a strong teacher presence; crafting an inclusive and safe online learning environment; creating well-structured and interesting content; forging explicit expectation management; and ensuring students have time to engage. This article argues that if educators are purposeful in applying these conditions, employing targeted, specific strategies in their curriculum design and teaching, students’ online engagement, and their learning outcomes, will be enhanced

A Multidimensional Connectomics- and Radiomics-Based Advanced Machine-Learning Framework to Distinguish Radiation Necrosis from True Progression in Brain Metastases

We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as well as 5 clinical and treatment factors. We developed an Integrated Radiomics Informatics System (IRIS) based on an Isomap support vector machine (IsoSVM) model to distinguish TP from RN using leave-one-out cross-validation. Class imbalance was resolved with differential misclassification weighting during model training using the IRIS. In total, 135 lesions in 110 patients were analyzed, including 43 cases (31.9%) of pathologically proven RN and 92 cases (68.1%) of TP. The top-performing connectomics features were three centrality measures of degree, betweenness, and eigenvector centralities. Combining these with the 10 top-performing mpRad features, an optimized IsoSVM model was able to produce a sensitivity of 0.87, specificity of 0.84, AUC-ROC of 0.89 (95% CI: 0.82-0.94), and AUC-PR of 0.94 (95% CI: 0.87-0.97)

Drug Use in Street Sex worKers (DUSSK) study – results of a mixed methods feasibility study of a complex intervention to reduce illicit drug use in drug dependent female sex workers

OBJECTIVES: The majority of female street-based sex workers (SSWs) are dependent on illicit drugs and sell sex to fund their drug use. They typically face multiple traumatic experiences, starting at a young age, which continue through sex work involvement. Their trauma-related symptoms tend to increase when drug use is reduced, hindering sustained reduction. Providing specialist trauma care to address post-traumatic stress disorder (PTSD) alongside drug treatment may therefore improve treatment outcomes. Aims to (1) evaluate recruitment and retention of participants; (2) examine intervention experiences and acceptability; and (3) explore intervention costs using a mixed methods feasibility study. SETTING: Female SSW charity premises in a large UK inner city. PARTICIPANTS: Females aged 18 years or older, who have sold sex on the street and used heroin and/or crack cocaine at least once a week in the last calendar month. INTERVENTION: Female SSW-only drug treatment groups in a female SSW-only setting delivered by female staff. Targeted PTSD screening then treatment of positive diagnoses with eye movement desensitisation and reprocessing (EMDR) therapy by female staff from a specialist National Health Service trauma service. RESULTS: (1) Of 125 contacts, 11 met inclusion criteria and provided informed consent, 4 reached the intervention final stage, (2) service providers said working in collaboration with other services was valuable, the intervention was worthwhile and had a positive influence on participants. Participants viewed recruitment as acceptable and experienced the intervention positively. The unsettled nature of participant's lives was a key attendance barrier. (3) The total cost of the intervention was £11 710, with staff costs dominating. CONCLUSIONS: Recruitment and retention rates reflected study inclusion criteria targeting women with the most complex needs. Two participants received EMDR demonstrating that the three agencies working together was feasible. Staff heavy costs highlight the importance of supporting participant attendance to minimise per participant costs in a future trial

Autosomal Dominant Retinitis Pigmentosa: Absence of the Rhodopsin Proline- Histidine Substitution (codon 23) in Pedigrees from Europe

In exon 1 at codon 23 of the rhodopsin gene, a mutation resulting in a proline-to-histidine substitution has previously been observed in approximately 12% of American autosomal dominant retinitis pigmentosa (ADRP) patients. The region around the site of this mutation in the rhodopsin gene has been amplified and analyzed in affected individuals from 91 European ADRP pedigrees. The codon 23 mutation has been found to be absent in all cases, including a large Irish pedigree in which the disease gene has previously been shown to be closely linked to the rhodopsin locus. This indicates the presence of either allelic or nonallelic heterogeneity in ADRP

The calcium binding protein S100β marks hedgehog-responsive resident vascular stem cells within vascular lesions

A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog-responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100β vSCs in vivo, we identified S100β/ Sca1 cells derived from a S100β non-SMC parent population within lesions that co-localise with smooth muscle α-actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100β/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100β and PTCH1 cells were present in human vessels while S100β cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100β neuroectoderm progenitors in vitro. We conclude that hedgehog-responsive S100β vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis

Estimating the prevalence of food risk increasing behaviours in UK kitchens

© 2017 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Foodborne disease poses a serious threat to public health. In the UK, half a million cases are linked to known pathogens and more than half of all outbreaks are associated with catering establishments. The UK Food Standards Agency (FSA) has initiated the UK Food Hygiene Rating Scheme in which commercial food establishments are inspected and scored with the results made public. In this study we investigate the prevalence of food risk increasing behaviours among chefs, catering students and the public. Given the incentive for respondents to misreport when asked about illegal or illicit behaviours we employed a Randomised Response Technique designed to elicit more accurate prevalence rates of such behaviours. We found 14% of the public not always hand-washing immediately after handling raw meat, poultry or fish; 32% of chefs and catering students had worked within 48 hours of suffering from diarrhoea or vomiting. 22% of the public admitted having served meat “on the turn” and 33% of chefs and catering students admitted working in kitchens where such meat was served; 12% of the public and 16% of chefs and catering students admitted having served chicken at a barbeque when not totally sure it was fully cooked. Chefs in fine-dining establishment were less likely to wash their hands after handling meat and fish and those who worked in award winning restaurants were more likely to have returned to work within 48 hours of suffering from diarrhoea and vomiting. We found no correlation between the price of a meal in an establishment, nor its Food Hygiene Rating Score, and the likelihood of any of the food malpractices occurring

Comparison of Whole Blood and Peripheral Blood Mononuclear Cell Gene Expression for Evaluation of the Perioperative Inflammatory Response in Patients with Advanced Heart Failure

Background: Heart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP) was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC) transcriptomes obtained from patients’ blood samples. Whole blood (WB) samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined. Methods: We collected blood samples from 31 HF patients (57¡15 years old) undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively) (25–75% IQR 7–14 days) and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA) score was used to characterize the severity of MOD into low (# 4 points), intermediate (5–11), and high ($ 12) risk categories correlating with GEP. Results: Results indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO) analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups. Conclusion: GEP analysis of WB has the potential to become a clinical tool for immune-monitoring in patients with MO

Effects of varying case definition on carpal tunnel syndrome prevalence estimates in a pooled cohort

OBJECTIVE: To analyze differences in carpal tunnel syndrome (CTS) prevalence using a combination of electrodiagnostic studies (EDSs) and symptoms using EDS criteria varied across a range of cutpoints and compared with symptoms in both ≥1 and ≥2 median nerve–served digits. DESIGN: Pooled data from 5 prospective cohorts. SETTING: Hand-intensive industrial settings, including manufacturing, assembly, production, service, construction, and health care. PARTICIPANTS: Employed, working-age participants who are able to provide consent and undergo EDS testing (N=3130). INTERVENTIONS: None. MAIN OUTCOME MEASURES: CTS prevalence was estimated while varying the thresholds for median sensory latency, median motor latency, and transcarpal delta latency difference. EDS criteria examined included the following: median sensory latency of 3.3 to 4.1 milliseconds, median motor latency of 4.1 to 4.9 milliseconds, and median-ulnar sensory difference of 0.4 to 1.2 milliseconds. EDS criteria were combined with symptoms in ≥1 or ≥2 median nerve–served digits. EDS criteria from other published studies were applied to allow for comparison. RESULTS: CTS prevalence ranged from 6.3% to 11.7%. CTS prevalence estimates changed most per millisecond of sensory latency compared with motor latency or transcarpal delta. CTS prevalence decreased by 0.9% to 2.0% if the criteria required symptoms in 2 digits instead of 1. CONCLUSIONS: There are meaningful differences in CTS prevalence when different EDS criteria are applied. The digital sensory latency criteria result in the largest variance in prevalence

Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine

Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)-carboxytetramethylrhodamine (TMR).We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability

IntroductionRare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer susceptibility for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD susceptibility, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.MethodsIn a cohort of 8,426 subjects with ASD and 169,804 controls with cognitive assessments, we found that rare coding CNVs and PRS-IQ increased ASD risk, even after adjusting for their effects on cognitive ability.ResultsBottom decile PRS-IQ and CNVs both decreased cognitive ability but had opposing effects on ASD risk. Models combining both classes of variants showed that the effects of rare CNVs and PRS-IQ on ASD risk and cognitive ability were largely additive, further suggesting that susceptibility for ASD is conferred independently from its effects on cognitive ability. Despite imparting mostly additive effects on ASD risk, rare CNVs and PRS-IQ showed opposing effects on core and associated features and developmental history among subjects with ASD.DiscussionOur findings suggest that cognitive ability itself may not be the factor driving the underlying liability for ASD conferred by these two classes of genomic variants. In other words, ASD risk and cognitive ability may be two distinct manifestations of CNVs and PRS-IQ. This study also highlights the challenge of understanding how genetic risk for ASD maps onto its dimensional traits