350 research outputs found
Early career patterns, experiences, and influences: reflections from women engineers in senior roles
Early career experiences provide the foundation for career progression and inform career choices and decisions. For women in the engineering profession, positive early career experiences have been linked to persistence and retention within the profession A recent focus on early careers within engineering has provided insight into early career role types and related competencies, competency and capability gaps experienced by novice engineers, and their perceptions of meaningful engineering work. There is opportunity to diversify and contextualise this understanding by exploring early career experiences of women working within the engineering profession, and by considering the influence of gender on early career experiences and decisions. This paper reports on an empirical investigation of the career experiences of 22 women engineers in senior roles within engineering organisations in the Australian context. Phenomenological and temporal analysis of their career reflections provides evidence of three early career patterns of varied sequence and focus. The influences shaping these career paths are described. By making explicit possible, diverse early career paths, determinants and outcomes, this paper aims to continue to bridge the engineering education-practice gap and to contribute to greater equality, diversity, and inclusion within the profession
Development of depressive symptoms post hip fracture is associated with altered immunosuppressive phenotype in regulatory T and B lymphocytes
Hip fracture is a common physical trauma in older adults that is also associated with a high incidence of new onset depression. The immune system declines with age and is also compromised by physical and psychological stress. This study examined whether hip fracture and depressive symptoms had additive effects upon the aged immune system that might contribute to poor health outcomes after hip fracture. We assessed the frequency of regulatory T cells, Tregs (CD4+ CD25+ Foxp3+) and IL10 production by CD4 T cells, and the frequency and IL10 production by regulatory B cells, Bregs (CD19+ CD24hi CD38hi) in 101 hip fracture patients (81 female) 6 weeks after injury and 43 healthy age-matched controls (28 female). 38 hip fracture patients (37 %) developed depressive symptoms. Hip fracture did not have an effect on circulating Tregs frequency but a significant reduction in the frequency of Bregs was observed in patients who developed depression compared with non-depressed patients (p = 0.001) or healthy controls (p < 0.001). Bregs also showed a significant decline in IL10 production in depressed hip fracture patients compared with controls (p = 0.04) and non-depressed patients (p = 0.01). In contrast, there was an increase in IL10 production by CD4 T cells in hip fracture patients with new onset depression compared to hip fracture patients without depression (p = .04) and healthy controls (p = .02). We conclude that the reduced immunity associated with new onset depression post hip fracture could include a contribution by heightened Tregs function
Depressive symptoms post hip fracture in older adults are associated with phenotypic and functional alterations in T cells
Background Ageing is accompanied by reduced immunity, termed immunesenescence. The immune system does not act in isolation and is sensitive to both psychological and physical stress. Hip fracture is a common physical stressor in older adults with a high incidence of new onset depression, which relates to poorer prognosis. We therefore set out to examine the possible synergistic effects of physical stress (hip fracture) and psychological stress (depressive symptoms) on the aged immune system. Results T cell phenotype and function was assessed in 101 hip fracture patients (81 female) 6 weeks after hip fracture and 43 healthy age-matched controls (26 female). 38 fracture patients had depressive symptoms at 6 weeks. T cell frequency (p = .01) and numbers (p = .003) were both lower in depressed hip fracture patients compared to healthy controls. The frequency of senescent CD28-ve (p = .001), CD57+ve (p = .001), KLRG1+ve (p = .03) CD8 T cells, as well as senescent CD28-ve CD4+ve (p = .01) and CD57+ve CD4+ve (p = .003) T cells were higher in depressed hip fracture patients compared with healthy controls and the frequency of CD28-ve CD8 T cells was also higher when compared to patients with hip fracture alone (p = .01). Additionally, activated CD69+ve (p = .005) and HLADR+ve (p
New-Onset Depression Following Hip Fracture Is Associated With Increased Length of Stay in Hospital and Rehabilitation Centers
This article examines the coincident effects of new-onset depression post hip fracture on length of hospital stay, readmission rates, and incidence of infections in older adults. Participants were 101 hip fracture patients aged 60+ years; 38 developed depressive symptoms following their fracture. Infection rates, readmissions to hospital and rehabilitation units, and length of hospital stay were assessed over the 6 months post hip fracture from hospital and general practitioner notes. Patients who developed depression by Week 6 post fracture were likely to spend more time in hospital/rehabilitation wards (p = .02) and more likely to be discharged to a rehabilitation unit (p < .05). There were no group differences in readmissions or infection rates. New-onset depression coincident with hip fracture in older adults is associated with longer hospital ward stays and greater need for rehabilitation
NK cell immunesenescence is increased by psychological but not physical stress in older adults associated with raised cortisol and reduced perforin expression
NK cell cytotoxicity (NKCC) reduces with age and this has been associated previously with increased mortality. The immune response is also modulated by stress, and here, we assessed the effect of the physical stress of hip fracture and the psychological stress of depression on NKCC in an aged immune system. NKCC was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and in 50 healthy age-matched controls (28 female). Thirty-eight patients were depressed at 6 weeks post-injury, and NKCC was reduced in patients who developed depression compared with non-depressed hip fracture patients (p = 0.004) or controls (p
Estimating cancer distant recurrence rates from administrative datasets: comparison of cancer registry and hospital records.
We thank the NSW Central Cancer Registry and the NSW Department of Health for providing data for this study and the Centre for Health Research Linkage for undertaking the record linkage. This study was supported through an Australian National Health and Medical Research Council Project Grant (No 633223) and the NSW Health BiostatisticalOfficer Training Program (for J Patterson)
Depressive symptoms in hip fracture patients are associated with reduced monocyte superoxide production
Ageing is accompanied by reduced functioning of the immune system, termed immunesenescence which is associated with increased risk of infection and mortality. However the immune system does not operate in isolation and can be modified by many environmental factors, including stress. In this study we determined whether physical stress (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system, specifically on monocyte numbers and function. We assessed immune function in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age matched controls (28 females). Thirty-eight of the hip fracture group were found to be depressed at the 6 week sampling. No differences in peripheral monocyte count, distribution of monocyte subsets or TNFα secretion were observed between hip fracture patients and healthy controls. However we observed significantly reduced superoxide production in response to Escherichia coli in the monocytes of hip fracture patients who developed depressive symptoms compared with non-depressed hip fracture patients (p = 0.002) or healthy controls (p = 0.008) 6 weeks after the fracture which remained decreased 6 months following injury. In previous studies we have shown an effect of depression on neutrophil superoxide generation in hip fracture patients, suggesting a particular susceptibility of this aspect of immune cell function to psychological stress
Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC):can patient stratification be improved in the UK Tayside population? A retrospective cohort study
OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy.METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status.RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS.CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.</p
Advancing Genetic Selection and Behavioral Genomics of Working Dogs Through Collaborative Science
The ancient partnership between people and dogs is struggling to meet modern day needs, with demand exceeding our capacity to safely breed high-performing and healthy dogs. New statistical genetic approaches and genomic technology have the potential to revolutionize dog breeding, by transitioning from problematic phenotypic selection to methods that can preserve genetic diversity while increasing the proportion of successful dogs. To fully utilize this technology will require ultra large datasets, with hundreds of thousands of dogs. Today, dog breeders struggle to apply even the tools available now, stymied by the need for sophisticated data storage infrastructure and expertise in statistical genetics. Here, we review recent advances in animal breeding, and how a new approach to dog breeding would address the needs of working dog breeders today while also providing them with a path to realizing the next generation of technology. We provide a step-by-step guide for dog breeders to start implementing estimated breeding value selection in their programs now, and we describe how genotyping and DNA sequencing data, as it becomes more widely available, can be integrated into this approach. Finally, we call for data sharing among dog breeding programs as a path to achieving a future that can benefit all dogs, and their human partners too
Metastatic breast cancer incidence, site and survival in Australia, 2001-2016: A population-based health record linkage study protocol
Introduction: Advances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients’ survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001– 2002 vs 2006–2007.
Methods and analysis: Population-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001–2002 and 2006–2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women’s demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of- residence and area-level socioeconomic status to examine equity of access to healthcare.
Ethics and dissemination: Research ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals
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