Australian university outcomes: A national study comparing IBDP and non-IBDP students

This study compares the university outcomes of students who completed the International Baccalaureate (IB) Diploma Programme (DP) in Australia compared to non-DP students nationally. The findings are based on population-level data for all students who applied to and entered universities in Australia between 2013 and 2018. To address differences in DP and non-DP student characteristics, the researchers further examined outcomes by groups within the populations that are more alike, for example, by gender and socio-economic status. Across all cohorts, DP students gain offers of university admission, continue to their second year of study, and complete university for all check points examined within the study (4 years, 6 years and 9 years after commencement) at significantly higher rates than non-DP students. Additionally, completing the DP appears to offer an advantage in university completion rates for students from a range of socio-economic backgrounds

Yeast UBL-UBA proteins have partially redundant functions in cell cycle control

BACKGROUND: Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation. There are three UBL-UBA containing proteins in budding yeast: Ddi1, Dsk2 and Rad23, which have been demonstrated to play regulatory roles in targeting ubiquitinated substrates to the proteasome for degradation. An involvement of these proteins in cell cycle related events has also been reported. We tested whether these three proteins act redundantly in the cell cycle. RESULTS: Here we show that the UBL-UBA proteins are partially redundant for cell cycle related roles. RAD23 is redundant with DDI1 and DSK2, but DDI1 and DSK2 are not redundant with each other and the triple deletion shows a synthetic effect, suggesting the existence of at least two roles for RAD23 in cell cycle control. The rad23Δddi1Δdsk2Δ triple deletion strain delays both in G2/M-phase and in mid-anaphase at high temperatures with duplicated spindle pole bodies. Cell cycle progression in the triple deletion strain can only be partially rescued by a rad23 allele lacking the c-terminal UBA domain, suggesting that RAD23 requires its c-terminal UBA domain for full function. In addition to their ability to bind ubiquitin and the proteasome, the UBL-UBA proteins also share the ability to homodimerize. Rad23 and Dsk2 dimerization requires their UBL and/or UBA domains whereas Ddi1 dimerization does not. Here we show that Ddi1 homodimerization is necessary for its cell cycle related functions. CONCLUSION: The three yeast UBL-UBA proteins have partially redundant roles required for progression through mitosis

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a ‘function follows form’ model of differentiation

The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis. These changes in the proteome were followed later in the differentiation time-course by alterations in the expression of proteins involved in cation transport and beta-oxidation. Studying the temporal profile of the H9C2 proteome during differentiation in further detail revealed eight clusters of co-regulated proteins that can be associated with early, late, continuous and transient up- and downregulation. Subsequent reactome pathway analysis based on these eight clusters further corroborated and detailed the results of the GO analysis. Specifically, this analysis confirmed that proteins related to pathways in muscle contraction are upregulated early and transiently, and proteins relevant to extracellular matrix organization are downregulated early. In contrast, upregulation of proteins related to cardiac metabolism occurs at later time points. Finally, independent validation of the proteomics results by immunoblotting confirmed hereto unknown regulators of cardiac structure and ionic metabolism. Our results are consistent with a function follows form' model of differentiation, whereby early and transient alterations of structural proteins enable subsequent changes that are relevant to the characteristic physiology of cardiomyocytes

A randomised controlled trial of cognitive behaviour therapy versus non-directive reflective listening for young people at ultra high risk of developing psychosis:The detection and evaluation of psychological therapy (DEPTh) trial

Background: Intervention trials for young people at ultra high risk (UHR) for psychosis have shown cognitive behaviour therapy (CBT) to have promising effects on treating psychotic symptoms but have not focused on functional outcomes. We hypothesized that compared to an active control, CBT would: (i) reduce the likelihood of, and/or delay, transition to psychosis; (ii) reduce symptom severity while improving social functioning and quality of life, whether or not transition occurred. Method: This was a single-blind randomised controlled trial for young people at UHR for psychosis comparing CBT to an active control condition, Non Directive Reflective Listening (NDRL), both in addition to standard care, with a 6 month treatment phase and 12 months of follow-up. Statistical analysis is based on intention-to-treat and used random effect models to estimate treatment effects common to all time-points. Results: Fifty-seven young people (mean age = 16.5 years) were randomised to CBT (n = 30) or NDRL (n = 27). Rate of transition to psychosis was 5%; the 3 transitions occurred in the CBT condition (baseline, 2 months, 5 months respectively). The NDRL condition resulted in a significantly greater reduction in distress associated with psychotic symptoms compared to CBT (treatment effect = 36.71, standard error = 16.84, p = 0.029). There were no significant treatment effects on frequency and intensity of psychotic symptoms, global, social or role functioning. Conclusion: Our sample was higher functioning, younger and experiencing lower levels of psychotic like experiences than other trials. The significantly better treatment effect of NDRL on distress associated with psychotic symptoms supports the recommendations for a stepped-care model of service delivery. This treatment approach would accommodate the younger UHR population and facilitate timely intervention

Implementation, Evalution and Maintenance of a Social-Emotional Skills Training Program for Children with an Autism Spectrum Disorder in a Specialist School Setting

Socialization difficulties in children with an Autism Spectrum Disorder (ASD) are often associated with peer rejection and impaired academic achievement. Schools might appear to offer an ideal setting for social-emotional skills (SES) instruction. However, common challenges to successful implementation of school-based programs include inadequate staffing and resourcing, and a lack of ASD-specific staff training. This paper describes how barriers to program implementation were overcome in a project evaluating the Secret Agent Society (SAS) SES training intervention within Autism Spectrum Australia (Aspect) specialist classes. Questionnaire data was collected from school staff over a one-year period. Findings supported the effectiveness of the adoption process used, and suggest that SAS was feasible and acceptable to school staff

Genetic stratification of depression in UK Biobank

Depression is a common and clinically heterogeneous mental health disorder that is frequently comorbid with other diseases and conditions. Stratification of depression may align sub-diagnoses more closely with their underling aetiology and provide more tractable targets for research and effective treatment. In the current study, we investigated whether genetic data could be used to identify subgroups within people with depression using the UK Biobank. Examination of cross-locus correlations were used to test for evidence of subgroups using genetic data from seven other complex traits and disorders that were genetically correlated with depression and had sufficient power (>0.6) for detection. We found no evidence for subgroups within depression for schizophrenia, bipolar disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, anorexia nervosa, inflammatory bowel disease or obesity. This suggests that for these traits, genetic correlations with depression were driven by pleiotropic genetic variants carried by everyone rather than by a specific subgroup

Human ISL1+ ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction

The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo. On day 6 of differentiation, HVPs were enriched by depleting cells positive for pluripotency marker TRA-1-60 with magnetic-activated cell sorting (MACS), and 3 million sorted cells were sub-capsularly transplanted onto kidneys of NSG mice where, after 2 months, they formed a 7 mm x 3 mm x 4 mm myocardial patch resembling the ventricular wall. The graft acquired several features of maturation: expression of ventricular marker (MLC2v), desmosomes, appearance of T-tubule-like structures, and electrophysiological action potential signature consistent with maturation, all this in a non-cardiac environment. We further demonstrated that HVPs transplanted into un-injured hearts of NSG mice remain viable for up to 8 months. Moreover, transplantation of 2 million HVPs largely preserved myocardial contractile function following myocardial infarction. Taken together, our study reaffirms the promising idea of using progenitor cells for regenerative therapy.ERC AdG743225Swedish Research Council Distinguished Professor Grant Dnr 541-2013-8351The Knut and Alice Wallenberg Foundation (KAW Dnr 2013.0028)Horizon 2020 research and innovation programme grant agreement No 647714Publishe

Transcriptome dynamics of CD4⁺ T cells during malaria maps gradual transit from effector to memory

The dynamics of CD4⁺ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4⁺ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T_H1) and follicular helper T (T_(FH)) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T_H1 and T_(FH) trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T_(FH) and central memory were revealed, with antimalarials modulating these responses and boosting T_H1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4⁺ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene–gene correlations (http://haquelab.mdhs.unimelb.edu.au/cd4_memory/)

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions

This research is funded by the NIHR Research for Patient Benefit programme (NIHR203568). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Peer reviewe

The role of social identity and self-efficacy in predicting service providers’ use of Stepping Stones Triple P following training

Background: Identifying factors that may contribute to the use of programs following the completion of training by practitioners is of practical and theoretical importance. Aim: This study examined the role of social identity and self-efficacy in contributing to the delivery of an evidence-based parenting program. Methods and Procedures: A sample of 63 multi-disciplinary professionals trained in the Stepping Stones Triple P-Positive Parenting Program, for parents of children with developmental disability, as part of a statewide roll-out were interviewed two years after training. Data on the number of hours of delivery during the 2-year period was analysed along with quantitative data obtained during interviews that assessed professionals’ self-efficacy and social identity as a Stepping Stones professional. Outcomes and Results: Social identity was associated with the use of SSTP in an independent analysis, but the association was no longer significant when other factors were included in a regression model. Self-efficacy predicted the use of SSTP and was found to be a mediator in the relationship between social identity and use of SSTP. Conclusions and Implications: This first investigation into the role of social identity in the implementation of evidence-based parenting programs showed that social identity could play an important role. The role of self-efficacy in predicting program use was further supported in this study and the mediator function of self-efficacy is explored. The practical and theoretical implications of the role of self-efficacy and social identity in the training of professionals are discussed.</p