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TLE4 is a repressor of the oncogenic activity of TLX3 in T-cell acute lymphoblastic leukemia
No full textT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease originating from the malignant transformation of T-cell progenitors, caused by the accumulation of genetic aberrations. One-fifth of T-ALL patients are characterized by ectopic expression of the homeobox transcription factor TLX3. However, the role of TLX3 in T-ALL remains elusive, partly due to the lack of suitable study models. Strikingly, this TLX3-positive subgroup has a high frequency of FLT3 mutations, predominantly FLT3-ITD, in pediatric cases. To investigate this, we generated ex vivo cultured pro-T cells driven by the co-expression of TLX3 and FLT3-ITD, which conferred IL7 independent growth. This model allowed us to confirm that TLX3 expression and FLT3 signaling cooperate to transform T-cells and induce an oncogenic context. Data from this cell model, combined with gene expression data from TLX3 positive T-ALL cases, revealed a strong downregulation of the transcriptional repressor TLE4. Furthermore, TLE4 showed to have a repressive effect on ex vivo TLX3 T-ALL cell growth, likely caused by a partial reversal of the TLX3 transcriptional profile. In conclusion, we developed a TLX3+FLT3-ITD pro-T cell model and used it to illustrate that TLX3 directly represses TLE4 expression, which is beneficial for the oncogenic function of TLX3
Canagliflozin and iron metabolism in the CREDENCE trial
Full text linkBackground. Studies in patients with heart failure have indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors increase iron use and enhance erythropoiesis. In this post hoc analysis of the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we evaluated the effects of canagliflozin on iron metabolism in patients with chronic kidney disease (CKD) and whether the effects of canagliflozin on hemoglobin and cardiorenal outcomes were modified by iron deficiency. Methods. We measured serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT) and ferritin at baseline and 12 months. The effects of canagliflozin, relative to placebo, on iron markers were assessed with analysis of covariance. Interactions between baseline iron deficiency, defined as TSAT <20%, and the effects of canagliflozin on hemoglobin and cardiorenal outcomes were evaluated with mixed effect models and Cox regression models, respectively. Results. Of 4401 participants randomized in CREDENCE, 2416 (54.9%) had iron markers measured at baseline, of whom 924 (38.2%) were iron deficient. Canagliflozin, compared with placebo, increased TIBC by 2.1% [95% confidence interval (CI) 0.4, 3.8; P = .014] and decreased ferritin by 11.5% (95% CI 7.1, 15.7; P < .001) with no clear effect on serum iron or TSAT. Canagliflozin increased hemoglobin over the trial duration by 7.3 g/L (95% CI 6.2, 8.5; P < .001) and 6.7 g/L (95% CI 5.2, 8.2; P < .001) in patients with and without iron deficiency, respectively (P for interaction = .38). The relative effect of canagliflozin on the primary outcome of doubling of serum creatinine, kidney failure or death due to cardiovascular disease or kidney failure (hazard ratio 0.70, 95% CI 0.56, 0.87) was consistent regardless of iron deficiency (P for interaction = .83), as were effects on other cardiovascular and mortality outcomes (all P for interactions ≥0.10). Conclusion. Iron deficiency is highly prevalent in patients with type 2 diabetes and CKD. Canagliflozin increased TIBC and decreased ferritin in patients with type 2 diabetes and CKD, suggesting increased iron utilization, and improved hemoglobin levels and clinical outcomes regardless of iron deficiency
Patterns of non-prescribed cannabis use among two samples of people who regularly use drugs in Australia, 2014-2024
No full textElectronic vaping products emerged in the late 1990s as an alternative mode of cannabis use. While the rapid increase in nicotine containing vape products has been well documented, there is also some evidence of an increase in cannabis vaping. . Further, evidence from North America suggeststhat preference for cannabis products may be shifting. However, changes in patterns of cannabis use in the Australian context have received comparatively little attention.
This bulletin examines the recent use (2014-2024) of non-prescribed cannabis and/or cannabinoid-related products among two samples of people who regularly use drugs in Australia, including routes of administration and the types of products used
The use of nicotine pouches among people in Australia who regularly consume illicit substances, 2024
Full text linkThere are concerns that nicotine pouches have gained popularity due to their lower cost, ease of concealability, as well as recent laws introducing restrictions to the access of e-cigarettes, however literature on use remains scarce. In 2024, questions on past 6-month use of nicotine pouches, and source of obtainment, were included in the Ecstasy and Related Drugs Reporting System (EDRS) and the Illicit Drug Reporting System (IDRS). This bulletin aims to examine patterns of use and sourcing of nicotine pouches among these two samples of people who regularly use illicit substances
Neutrinos and Loops: Studying Neutrino Mass Models Through Their Quantum Effects
Full text linkThe neutrino mass problem, which refers to the unknown origin of neutrino masses, strongly motivates the need for new physics beyond that of the Standard Model (SM). A given mass model, through quantum effects, generates a rich network of predictions deviating from those of the SM. The enterprising physicist can use these to constrain the model, and—in some cases—resolve experimental anomalies and offer solutions to other unsolved problems.
This thesis is divided into two parts. In the first, I investigate whether high-precision measurements of the cross section of the Higgsstrahlung process e^+ e^- → Zh at a next-generation electron-positron collider can be utilised to probe the Type-I and Type-III Seesaw models. By employing an effective field theory approach, I compare the collider reaches to constraints from electroweak observables, probes of lepton flavour universality, and the existing and prospective bounds from searches for lepton flavour violation. I find that while any appreciable correction to the Higgsstrahlung cross section is already strictly constrained in the Type-I Seesaw model, effects of up to O(10%) are possible within Type-III Seesaw.
In the second part of this thesis I investigate whether a high-scale realisation of the Zee model of neutrino mass can be used to explain the observed baryon abundance of the universe. In this realisation the baryon asymmetry is generated through the CP-violating decay of a new singly-charged scalar with a mass of O(10^12 GeV). I find that the flavour structure of the Zee model forces the scenario to be one of flavoured leptogenesis, which turns out to be too restrictive to produce a sufficient asymmetry. This work is followed up with a discussion of infrared divergences in the Zee model, where I demonstrate how to achieve infrared-finiteness at zero temperature and discuss how this cancellation might be extended to finite temperature
An e-learning program improves low back pain beliefs of physiotherapists: a randomised trial
No full textQuestion: How effective is an e-learning program based on international clinical guidelines in promoting beliefs more aligned with the current evidence for the management of low back pain among physiotherapists? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: 106 physiotherapists who treat patients with low back pain. Interventions: The experimental group received access to an e-learning program, based on recommendations of clinical practice guidelines for the management of low back pain, over a 6-week period. The program consisted of six units, totalling 15 hours, and was offered in a self-instructional and self-paced format. The control group was instructed to continue their activities as usual. Outcome measures: The primary outcome was beliefs about low back pain measured using the Modified Back Beliefs Questionnaire (MBBQ, –50 worst to 50 best). Secondary outcomes included the Back Pain Attitudes Questionnaire (Back-PAQ, –20 worst to 20 best) and agreement with two statements (1: X-rays or scans are necessary to get the best medical care for low back pain; 2: Everyone with low back pain should have spine imaging). Participants were evaluated at baseline and 6 weeks. Results: Out of 53 participants allocated to the e-learning program, two completed only the first unit and one did not complete any units, resulting in an overall adherence rate of 94%. Compared with control, the e-learning program improved the MBBQ (MD 8 points, 95% CI 5 to 10) and the Back-PAQ score (MD 3.1 points, 95% CI 1.8 to 4.3). For the imaging beliefs statements, the e-learning program was able to increase the proportion of participants with beliefs aligned with the current evidence (statement 1: RD 38%, 95% CI 21 to 52; statement 2: RD 17%, 95% CI 7 to 29) compared with the control group. Conclusion: The e-learning program based on recommendations of clinical practice guidelines for the management of low back pain improved physiotherapists’ beliefs about the management of low back pain. Registration: NCT05661968
A Physical-Based Semi-Automatic Algorithm for Post-Tropical Cyclone Identification and Tracking in Australia
Full text linkOf all meteorological events, Tropical Cyclones (TCs) are by far the costliest of natural hazards around the globe. They typically lose their strength quite rapidly once making landfall. Recent studies have revealed that TCs, even degrading below TC strength after landfall, can survive for prolonged periods and still exert a significant impact as Post-Tropical Cyclones (PTCs). However, the widely used TC best track datasets, including the International Best Track Archive for Climate Stewardship, do not consistently track TCs for long enough following landfall to include complete PTC tracks. The absence of tracking limits our understanding of the overall TC-related impacts. In this study, we developed a semi-automatic tracking algorithm using satellite imagery and reanalysis data to extend TC tracks beyond the best track dataset until dissipation overland. Based on all landfalling TCs for the period 1990–2020 in Australia, these TCs can be further tracked overland for an additional 1.6 days on average, with a maximum of 15 days, since the last record in best track datasets. Although the intensity of Australian landfalling TCs has declined over the 30 years, they continue to linger over land for similar durations before dissipation, suggesting an increasing likelihood of favorable land conditions for TCs and PTCs
Exploring discursive patterns in post-lesson mentoring conversations
No full textPost-lesson mentoring conversations are critical for preservice teachers’ professional development. These conversations aim to identify the strengths and weaknesses of their lessons. However, the quality of these conversations is often problematic. This study builds on the theory of learning as discursive achievement to examine different discourse patterns in post-lesson mentoring conversations in Australia. The analysis identified five discourse patterns—evaluative, analytic, justificatory, directive, and normalising—in these conversations. It also revealed the features, proportion, interactions, and flexibility of these discourse patterns. This paper concludes that mentoring conversations should balance evaluation with development talk by using analytic and justificatory discourses
Recommendations for Implementing the INTERACT3 Care Bundle for Intracerebral Hemorrhage in Latin America: Results of a Delphi Method
Full text linkIntroduction: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). Methods: A 3-phase Delphi study allowed a panel of 32 healthcare workers from 14 LAC to sequentially rank statements relevant to 7 domains (training, resources/ infrastructure, patient education, blood pressure, temperature, glycemic control, and anticoagulation reversal). The pre-defined consensus threshold was 75%. Results: A total of 43 statements reached consensus by the third round, with 12 new statements emerging through rounds. The highest-ranked statements in each domain emphasized critical aspects, but successful implementation requires appropriate resourcing. Key priorities were continuous training of all healthcare workers in ICH management, establishing protocols aligned with available resources, and collaborative interdisciplinary care supported by institutional networks. Statements related to anticoagulation reversal had the highest priority. Conclusions: Consensus statements are provided to facilitate integration of the INTERACT3 care bundle to reduce disparities in ICH outcomes in LAC
Play and Protect: Exploring Game-Based Learning for Cyber Safety in Primary Education
Full text linkAs the internet becomes a critical part of everyday life, the danger of cyber threats, especially to children, becomes increasingly significant. Effective education about these risks and how to address them is crucial for staying safe online. There is a wide range of materials on cyber awareness; however, these lack structure and are not tailored to diverse age groups, adding pressure on teachers to independently supplement classroom education. Existing resources sometimes rely on teaching methods that may not always align with children’s developmental needs, limiting their ability to engage, retain, and effectively apply knowledge on the internet. Therefore, this study aims to explore the current need for improving cyber safety awareness education for primary school children and evaluate the effectiveness of a game-based approach for cyber safety awareness among primary school children.
The study followed the instructional design model ADDIE for technology integration. First a needs analysis was conducted with primary school teachers in the Australian Capital Territory (ACT) revealing gaps in current safety education and suggestions for game based design. Consequently, a game was holistically developed and was tested with a sample of school students in Grades 1 to 6 from the ACT. A quasi-experimental design, including pre and post-test semi-structured interviews and a mixed-method approach, were employed for data collection and analysis. Additionally, the research explored parents' perceptions surrounding their confidence and perceptions regarding their children's online activities.
The interactive educational game utilised bright colours, playful sounds, clear dialogue boxes with supplementing audio and simple controls in a free-roaming two-dimensional world, utilising rewards and immediate feedback. Statistical and thematic analyses used to analyse the change in knowledge of children before and after playing the game revealed that the game improved participants' cyber safety awareness and understanding. The findings also revealed a strong parental desire for using interactive games as a tool to help increase their children's cyber safety awareness.
Although the results indicated a positive outlook on games as an effective educational medium, further research is needed for the long-term retention of educational content for children