20588 research outputs found
Sort by
Caveolin 1 and 2 enhance the proliferative capacity of BCAM-positive corneal progenitors
Get PDFCaveolin (CAV) 1 and 2 are integral membrane proteins that constitute major components of small membrane pouches termed caveolae. While several functions have been described in other tissues, the roles of CAV1 and CAV2 in the ocular surface have remained unknown. In the current study, we investigated the expression and function of CAV1 and CAV2 in the human cornea. We found CAV1 and CAV2 to be preferentially expressed by proliferative Basal Cell Adhesion Molecule (BCAM)-positive progenitor cells along the entire limbal and corneal basal epithelial layer. Functional gene knockdown studies reveal that BCAM, BCAM co-expressed Laminin α5 (LAMA5) and Laminin α3 (LAMA3) regulate expression of CAV2. Mechanistically, we demonstrate that CAV1 and CAV2 contribute to enhanced BCAM-positive cell proliferation through regulation of Fibroblast Growth Factor Receptor 2 (FGFR2) cell surface expression. In aggregate, our study identifies specific expression of CAV1 and CAV2 in BCAM-positive corneal basal epithelial cells and uncovers a novel CAV1/CAV2-dependent mechanism of corneal progenitor cell proliferation, with potential implications for therapeutic enhancement of corneal regeneration
Determining timeframes to death for imminently dying patients: A retrospective cohort study
Get PDFBackground: Clinicians are frequently asked ‘how long’ questions at end-of-life by patients and those important to them, yet predicting timeframes to death remains uncertain, even in the last weeks and days of life. Patients and families wish to know so they can ask questions, plan, make decisions, have time to visit and say their goodbyes, and have holistic care needs met. Consequently, this necessitates a more accurate assessment of empirical data to better inform prognostication and reduce uncertainty around time until death. The aims of this study were to determine the timeframes for palliative care patients (a) between becoming comatose and death, and (b) between being totally dependent and bedfast, and then comatose, or death, using Australia-modified Karnofsky Performance Status (AKPS) scores. The secondary aim was to determine if covariates predicted timeframes. Method: This is a large retrospective cohort study of 2,438 patients, 18 years and over, cared for as hospice inpatients or by community palliative care services, died between January 2017 and December 2021, and who collectively had 49,842 AKPS data points. An Interval-Censored Cox Proportional Hazards regression model was used. Results: Over 53% (n = 1,306) were comatose (AKPS 10) for longer than one day before death (mean = 2 days, median = 1, SD = 2.0). On average, patients were found to be totally dependent and bedfast (AKPS 20) for 24 days, before progressing to being comatose. A difference in life expectancy was observed at AKPS 20 among people with cancer (mean = 14.4, median = 2, SD = 38.8) and those who did not have cancer (mean = 53.3, median = 5, SD = 157.1). Conclusion: Results provide clinicians with validated data to guide communication when answering ‘how long’ questions at end-of-life. Knowledge of projected time to death can prompt timely conversations while the patient can understand and engage in meaningful conversations. The importance of considering covariates such as location and diagnosis in determining timeframes has been highlighted. Shared decision-making and essential person-centered end-of-life care can be planned
Exploring non-invasive brain stimulation effects on physical outcomes in people with parkinson’s disease: An umbrella evidence mapping review with meta-analyses
Get PDFBackground: Non-invasive brain stimulation (NIBS) is sometimes used alongside medication to alleviate motor symptoms in people with Parkinson’s disease (PD). However, the evidence supporting NIBS’s effectiveness for improving motor function in PD patients is uncertain.
Objective: This umbrella review aims to synthesize recent systematic reviews and meta-analyses that have evaluated the effectiveness of NIBS in improving motor function in people with PD, with a key focus being to examine the quality of the evidence presented. Methods: The review protocol was registered in PROSPERO (CRD42022380544) and conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search strategy was guided by the Population, Intervention, Comparison, and Outcome framework, focusing on individuals with idiopathic PD (Hoehn and Yahr stages 1-4). The review included studies comparing various NIBS techniques (eg, repetitive transcranial magnetic stimulation and transcranial direct current stimulation) to sham or alternative treatments, targeting motor and cognitive regions. Six databases were searched up to June 2024. Methodological quality was assessed using Assessment of Multiple Systematic Reviews 2 (AMSTAR2), and random-effects meta-analyses were performed to pool standardized mean differences (SMDs).
Results: The final analysis included 31 meta-analyses and 10 systematic reviews. Overall, the reviews were rated as moderate quality (54% average for AMSTAR2). NIBS showed a small-to-moderate effect on motor function (Unified Parkinson’s Disease Rating Scale-Section III scores; SMD = −0.80), functional mobility (gait speed and timed-up-and-go; SMD = −0.39), and freezing of gait (SMD = −0.58), but no significant effect on balance.
Conclusion: NIBS offers small-to-moderate benefits for motor symptoms and functional movement in PD, though it does not significantly impact balance. Practitioners should consider the variety of techniques and treatment parameters before application
Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health
Get PDFINTRODUCTION: Melanopsin is a photopigment with roles in mediating sleep and circadian-related processes, which are often disrupted in Alzheimer\u27s disease (AD). Melanopsin also impacts cognition and synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, and markers of brain health. METHODS: Linear regression analyses examined the relationship of single-nucleotide polymorphisms (SNPs) within the melanopsin gene (OPN4), with cortical amyloid beta (Aβ), cognition, brain volumes, and self-reported sleep traits in cognitively unimpaired older adults. Further analyses assessed whether sleep traits x OPN4 SNP interactions were associated with markers of brain health. RESULTS: OPN4 SNPs rs2355009 and rs3740334 were associated with attention and processing speed and ventricular volume and language, respectively. Furthermore, rs3740334 and rs1079610 showed significant interactions with sleep traits in association with language. DISCUSSION: This study shows associations of OPN4 genetic variants with markers of brain health, and suggests that these variants interact with sleep to exacerbate cognitive effects. Highlights: The relationships between melanopsin gene (OPN4) variants and markers of brain health were examined cross-sectionally in cognitively unimpaired older individuals. Variation within OPN4is associated with differences in cognition and ventricular volume. rs2355009 and rs3740334 show small–moderate associations with differences in attention and processing speed. Further to this, rs2355009 and rs3740334 were associated with ventricular volumes and language performance, respectively. The interactions between rs3740334 and rs1079610 and sleep traits also showed small–moderate associations with differences in language performance
Implementing a nurse-enabled, integrated, shared-care model involving specialists and general practitioners in early breast cancer post-treatment follow-up (EMINENT): A single-centre, open-label, phase 2, parallel-group, pilot, randomised, controlled trial
Get PDFBackground: Current models of post-treatment cancer care rely heavily on hospital-based, medical specialists and do not sufficiently leverage primary care. Many breast cancer survivors face ongoing unmet needs that may benefit from a multidisciplinary, shared-care approach. We aimed to evaluate the feasibility and preliminary effectiveness of implementing nurse-enabled, shared-follow-up care between the acute and primary care setting for early-stage breast cancer. Methods: In this single-centre, open-label, phase II, pilot, randomised, controlled trial, individuals diagnosed with breast cancer (Stage 0–III) were randomised 1:1 to either usual care or intervention, which includes a 1) Specialist Nurse Consultation to co-develop a survivorship care plan (SCP), 2) Pharmacist Consultation, 3) Case Conference with General Practitioner (GP), and 4) shared follow-up care arrangements. Feasibility and effectiveness outcome measures, including health-related quality of life (primary outcome), physical activity and nutrition, patient experience, and financial toxicity were collected at baseline, and at 3-, 6-, and 12-months, with health service utilisation data at 24-months. Bivariate and multivariable, intention-to-treat analyses were conducted. This trial is registered at Anzctr.org.au (ACTRN12619001594112). Findings: From 3rd December 2019 to 13th April 2021, 61 participants were randomised (intervention n = 29; usual care n = 32); mean age 62.9 standard deviation (SD) = 10.9 years. The intervention was feasible with 100% completion rates across all elements of the specialist nurse consultation and GP case conference. Evaluation of the 28 SCPs indicated the top three goals were exercise (n = 23), diet (n = 12) and mental well-being (n = 11). All care goals can be supported by GPs. No differences were observed between groups for health-related quality of life and the other effectiveness outcomes measures listed above at all timepoints (P \u3e 0.05 for all). There were significantly fewer average post-treatment radiation oncology appointments per patient in the intervention group compared to the control group (0.69 versus 1.27, P = 0.013) at 24-months. Number of unplanned hospital presentations at 24-months were low across both intervention (n = 7) and control (n = 4) groups. Interpretation: Nurse-enabled, shared-care arrangements for women with early-stage breast cancer is feasible, and is as safe as specialist-led model of care. It may provide a more sustainable model of care in a longer term. GPs can meet the survivorship care needs identified breast cancer survivors. This trial can inform a large, pragmatic, hybrid effectiveness-implementation trial. Funding: Metro South Health Research Support Scheme Project Grant
Mathematical practices (commonly used by mathematicians) in mathematics teachers’ solutions to algebraic problems
Get PDFA teacher of mathematics knows mathematics as a teacher and as a mathematician. Whilst the existing research on teacher knowledge contributes to our understanding of the ways of knowing mathematics as a teacher, little is known about ways of knowing mathematics as a mathematician. Guided by the conceptual framework of mathematical practices (MPs) (commonly used by mathematicians), this case study aimed to contribute to fill this gap. The study examined solutions generated by two secondary teachers of mathematics to a set of algebraic problems to determine which MPs are apparent, or not, in the teachers’ work. Data were content analyzed deductively. Findings reveal that both teachers consistently demonstrated three practices: seeking to find patterns; creating models for mathematical ideas; and using symbolic representations of ideas, whilst two practices: using precise definitions of objects; and having fine distinctions about language were less present in either teacher solutions. More high-level practices such as characterizing objects based on structure and using logical arguments as sources of conviction were manifested in routine problems but absent in nonroutine problems. It is anticipated that teacher training experiences and curriculum contexts have influences on teachers’ MPs in doing mathematics
Meso-damage characterization of chemically corroded rocks under unloading confinement conditions
Get PDFCharacterizing meso-damage and understanding its correlation with macroscopic mechanical responses of rocks under coupled chemical-mechanical (C-M) conditions are crucial for the stability analysis and safety design of underground constructions in chemically corrosive environments. This research proposes a model to quantify coupled C-M meso-damage of rocks, utilizing geochemical surface reaction theory, statistical mechanics, thermodynamic principles, and novel principals proposed in this study, termed Random Energy Release Rate (RERR) and Effective Chemical Damage (ECD). To achieve this goal, a multiscale experimental investigation, including Nuclear Magnetic Resonance (NMR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), pH and ion chromatography analysis, triaxial compression and unloading confinement tests, is employed to examine meso-damage evolution and its linkage with the macro-mechanical responses of limestone under coupled C-M conditions. Based on the experimental investigations, the ECD model is introduced to differentiate chemical damage into effective and apparent categories. Then RERR is proposed to characterize the heterogeneity of damage. Utilizing ECD, along with RERR, the coupled C-M meso-damage model is finally proposed and validated with experimental data. Results show that the evolution of coupled C-M damage follows an S-shaped curve with four stages; Confining pressure limits ECD and C-M damage development, while ECD accelerates C-M damage; As dual-pore geo-media, RERR predominantly originate from the crack-like pores, and ECD is closely tied to crack-like pore closure and rock skeleton flexibility
Reimagining higher education: Navigating the challenges of Generative AI adoption
Get PDFThe proliferation of generative artificial intelligence (GenAI) has disrupted academic institutions across the world, presenting transformative challenges for decision makers, and leading to questions around existing methods and practices within higher education (HE). The widespread adoption of GenAI tools and processes highlights an ongoing change to existing perceptions of the role of humans and machines. Academics have expressed concerns relating to: academic integrity, undermining critical thinking, lowering of academic standards and the threat to existing academic models. This study presents a mixed methods approach to developing valuable insight to the key underlying challenges impacting GenAI adoption within HE. The results highlight many of the key challenges impacting decision makers in the formation of policy and strategic direction. The findings identify significant interdependencies between the key underlying challenges associated with GenAI adoption in HE. We further discuss the implications in the findings of the high levels of driving power of the factors: (i) perceived risks from Large Language Model training and learning; (ii) the reliability of GenAI outputs in the context of impact on creativity and decision making; (iii) the impact from poor levels of GenAI platform regulation. We posit this research as offering new insight and perspective on the changing landscape of HE through the widespread adoption of GenAI
The important role of pollinators in sustainability education
Get PDFIn this chapter we illustrate some of the ways the education sector can play a key role, not just in educating and activating students as advocates for and agents of sustainability but also in motivating and mobilising communities towards a sustainability agenda. Initially in this chapter it was important to look back and identify how important bees have been through the ages, noting that humans identified very early on that bees could enhance their lives. We then outline some of the contributions a focus on bees can make to sustainability education. One important contribution includes fostering a balanced perspective on bees; acknowledging any dangers and affective responses; and, more importantly, fostering a sense of connection and interdependence with bees. Another important contribution is developing capabilities as citizens as leaders in support of sustainability. Finally in this contribution we provide some examples of how educational settings have an important role in developing knowledge and motivating and empowering learners of all ages to take action for sustainability
Top management green commitment and employee in-role green performance: An emerging economy study
Get PDFThis study examines how and when top management green commitment influences in-role employee green performance, by investigating the mediating role of employee green passion and employee green commitment, and the moderating role of adverse working conditions. Based on a two-wave survey of 397 hotel employees in an emerging economy, Vietnam, the results show that top management green commitment, directly and indirectly, influences in-role employee green performance through employee green passion and employee green commitment. Additionally, the indirect effect of management green commitment on employee in-role green performance through employee green commitment has a stronger effect than through employees’ green passion. Furthermore, adverse working conditions constitute a boundary condition that mitigates the effects of top management green commitment, employee green passion, and employee green commitment on employee in-role green performance. The study extends environmental sustainability literature on the top management green commitment-employee in-role green performance relationship by explicating dual mediation effects and moderation effects, and offers practical strategies for enhancing employee in-role green performance