Gender Differences in the Relationship between Pressure from Schoolwork and Health Complaints: a Three Country Study

Pressure from schoolwork is associated with health complaints in primary and high school students. Girls are more likely to report high levels of pressure and experience frequent health complaints. However, the moderating effect of gender on the relationship between pressure and health complaints has not been fully explored. Logistic regression was used to examine the association between pressure from schoolwork and health complaints for a sample of 11–12 and 13–14-year-olds in Australia (N = 4723), England (N = 2734) and Spain (N = 3743), moderating for gender and controlling for family affluence and teacher support. Across the entire sample, a significant relationship between pressure and frequent health complaints was found (OR = 3.03, p < .001). Among students reporting a lot of pressure, differences between boys and girls in marginal odds of frequent health complaints were greater in Spain than in Australia or England (difference in log odds: Australia 0.426, p = .211; England 0.445, p = .821; Spain 1.044, p < .001). Pressure from schoolwork is an important issue for student mental health. This study suggests that the role of gender in moderating this relationship differs across countries. Differing national approaches to testing and grade repetition, as well as differences in macro-economic and social contexts, especially between Australia and England on the one hand, and Spain on the other, are discussed as possible explanations for these gender differences. More research is needed on how these factors influence boys’ and girls’ perceptions of pressure and stress associated with schoolwork.Australian Research Council y Australian Government LP120100543Australian Research Council y Australian Government DP190100247Australian Research Council and Australian Government LP120100543 DP190100247UK Department of Health 201617Ministerio de Sanidad, Consumo y Bienestar Social de EspañaMCIN/AEI/10.13039/501100011033 RYC-2017-21626Fondo Social Europe

Why do an online Change Laboratory?

This technical submission was created collaboratively, by a group of researchers united by shared interests and experiences in conducting research online using the Change Laboratory methodology. Our current contribution seeks to inform and engage colleagues, setting out a collaborative response to a relatively unsophisticated yet reflexive and timely question: Why do an online Change Laboratory? To us, it seems that this question could be interpreted in multiple ways: why should people become involved in an online Change Laboratory, as discrete from an onsite Change Laboratory; why should people become involved in an online Change Laboratory, as discrete from using other online options; or why should people become involved in any type of research-intervention at all. As individual researcher-interventionists, who meet regularly to share our experiences and interests in online Change Laboratories, we also interpret this question in multiple ways, and we hope that our collaborative response reflects our diversity of thought (a closing section of this paper described how we worked in its production). We seek to encourage colleagues to further explore these and other questions about online Change Laboratories, and we call for others to join us in purposeful conversations to advance the methodology

Understanding child disadvantage from a social determinants perspective

Copyright information: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.Background Child health and developmental inequities exist in all countries. Comprehensive and robust concepts of disadvantage are fundamental to growing an evidence base that can reveal the extent of inequities in childhood, and identify modifiable leverage points for change. We conceptualise and test a multidimensional framework of child disadvantage aligned to a social determinants and bioecological perspective. Methods The Longitudinal Study of Australian Children is a nationally representative sample of two cohorts of Australian children, including the birth cohort of 5107 infants, which commenced in May 2004. The analysis focused on disadvantage indicators collected at age 4–5 years. Confirmatory factor analysis was used to test a theoretically informed model of disadvantage. Concurrent validity was examined through associations with academic performance at 8–9 years. Results The model comprising four latent factors of sociodemographic (10 indicators), geographical environments (three indicators), health conditions (three indicators) and risk factors (14 indicators) was found to provide a better fit for the data than alternative models. Each factor was associated with academic performance, providing evidence of concurrent validity. Conclusion The study provides a theoretically informed and empirically tested framework for operationalising relative child disadvantage. Understanding and addressing inequities will be facilitated by capturing the complexity of children’s experiences of disadvantage across the multiple environments in which their development unfolds

Network analysis of SRC-1 reveals a novel transcription factor hub which regulates endocrine resistant breast cancer.

Steroid receptor coactivator 1 (SRC-1) interacts with nuclear receptors and other transcription factors (TFs) to initiate transcriptional networks and regulate downstream genes which enable the cancer cell to evade therapy and metastasise. Here we took a top-down discovery approach to map out the SRC-1 transcriptional network in endocrine resistant breast cancer. First, rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) was employed to uncover new SRC-1 TF partners. Next, RNA sequencing (RNAseq) was undertaken to investigate SRC-1 TF target genes. Molecular and patient-derived xenograft studies confirmed STAT1 as a new SRC-1 TF partner, important in the regulation of a cadre of four SRC-1 transcription targets, NFIA, SMAD2, E2F7 and ASCL1. Extended network analysis identified a downstream 79 gene network, the clinical relevance of which was investigated in RNAseq studies from matched primary and local-recurrence tumours from endocrine resistant patients. We propose that SRC-1 can partner with STAT1 independently of the estrogen receptor to initiate a transcriptional cascade and control regulation of key endocrine resistant genes

Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype

Funder: Breast Cancer Ireland GR 14-0883Abstract: Steroid regulated cancer cells use nuclear receptors and associated regulatory proteins to orchestrate transcriptional networks to drive disease progression. In primary breast cancer, the coactivator AIB1 promotes estrogen receptor (ER) transcriptional activity to enhance cell proliferation. The function of the coactivator in ER+ metastasis however is not established. Here we describe AIB1 as a survival factor, regulator of pro-metastatic transcriptional pathways and a promising actionable target. Genomic alterations and functional expression of AIB1 associated with reduced disease-free survival in patients and enhanced metastatic capacity in novel CDX and PDX ex-vivo models of ER+ metastatic disease. Comparative analysis of the AIB1 interactome with complementary RNAseq characterized AIB1 as a transcriptional repressor. Specifically, we report that AIB1 interacts with MTA2 to form a repressive complex, inhibiting CDH1 (encoding E-cadherin) to promote EMT and drive progression. We further report that pharmacological and genetic inhibition of AIB1 demonstrates significant anti-proliferative activity in patient-derived models establishing AIB1 as a viable strategy to target endocrine resistant metastasis. This work defines a novel role for AIB1 in the regulation of EMT through transcriptional repression in advanced cancer cells with a considerable implication for prognosis and therapeutic interventions

Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype

Funder: Breast Cancer Ireland GR 14-0883Abstract: Steroid regulated cancer cells use nuclear receptors and associated regulatory proteins to orchestrate transcriptional networks to drive disease progression. In primary breast cancer, the coactivator AIB1 promotes estrogen receptor (ER) transcriptional activity to enhance cell proliferation. The function of the coactivator in ER+ metastasis however is not established. Here we describe AIB1 as a survival factor, regulator of pro-metastatic transcriptional pathways and a promising actionable target. Genomic alterations and functional expression of AIB1 associated with reduced disease-free survival in patients and enhanced metastatic capacity in novel CDX and PDX ex-vivo models of ER+ metastatic disease. Comparative analysis of the AIB1 interactome with complementary RNAseq characterized AIB1 as a transcriptional repressor. Specifically, we report that AIB1 interacts with MTA2 to form a repressive complex, inhibiting CDH1 (encoding E-cadherin) to promote EMT and drive progression. We further report that pharmacological and genetic inhibition of AIB1 demonstrates significant anti-proliferative activity in patient-derived models establishing AIB1 as a viable strategy to target endocrine resistant metastasis. This work defines a novel role for AIB1 in the regulation of EMT through transcriptional repression in advanced cancer cells with a considerable implication for prognosis and therapeutic interventions

Australian educational technologies trends 2018

Educational Technologies represent the wide range of digital tools used by teachers for teaching, students for learning, and administrators for managing schools. New tools are continually in development and often repurposed for an educational context from other industries. The following technologies have been considered as the five most significant for schools over the next 5 years, along with cost and professional learning requirements

Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features

The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC’s with born to be bad traits

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707