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Considering Clinical Implementation of Polygenic Scores in Hereditary Cancer Risk Assessment: Recipients’ Perspectives on Influencing Factors and Strategies
No full textBACKGROUND: Polygenic scores (PGS) capture a proportion of the genomic liability for cancer in unselected and high-risk cohorts, with meaningful application in improving risk-stratified screening and management. However, there are significant evidence gaps regarding future clinical implementation. Despite being key interest-holders, recipient views are underrepresented. The objective of this study was to explore recipients' views on the clinical implementation of PGS for hereditary cancer risk assessment in Australian cancer genetics clinics. METHODS: Three video-conferenced focus groups were conducted with recipients who had been given their breast and ovarian cancer PGS through the PRiMo trial. Nominal Group Technique was used to enable evaluation of implementation determinants and strategies, and priority setting. Descriptive and deductive content analyses were conducted utilising the Consolidated Framework for Implementation Research and the Expert Recommendations for Implementing Change compilation of facilitative strategies. RESULTS: Participants (N = 10) were female, with an average age of 36 years (range 18-70 years). Of these, 50% (N = 5) experienced a change in their hereditary cancer risk assessment due to their PGS. Participants prioritised the positive value and impact of PGS, and the behavioural characteristics of recipients, notably their knowledge and expectations of PGS and cancer genetics clinics, as major determinants of implementation success. Implementation strategies that prepared and supported recipients to access, engage, and use PGS were emphasised, with a focus on a clear results report, educational resources, in-clinic resources, and delivery of ongoing good clinical follow-up. CONCLUSION: Evidence-based strategies should be deployed to address recipients' priority barriers to the clinical implementation of PGS for hereditary cancer risk assessment. Centralising recipient voices in implementation design will improve effectiveness and success
Evaluation of the Ergomechanic Markerless Motion Capture System for Lower Body Kinematics During Standing, Squatting, and Walking
No full textMarkerless motion capture (MMC) shows promise for examining human movement across many domains because of its nonintrusive nature and negligible per-subject setup time. However, published MMC systems typically require specific hardware. This validation study compared lower-body joint kinematics from Ergomechanic, a hardware-agnostic pose model-based MMC system, to an established marker-based motion capture (MBMC) system. Static trial data from eighteen people were used to register MMC keypoints within a widely used musculoskeletal model. The registered model was used to calculate joint kinematics for static pose, squatting, and walking trials. A novel perturbation analysis estimated the contributions to differences in MBMC and MMC approaches to measurement disparities. Very good (0.87-1.0) correlations between the systems were calculated for ankle, knee, and hip flexion-extension angles. Good (0.70-0.86) correlations were found for hip external-internal and abduction-adduction. Pelvis and lumbar spine angles had a wider range of correlation results (-0.06 to 0.95), likely due to the few MMC keypoints in these body regions. Relative contributions from the perturbation analysis were (i) 75% from variations in MMC data relative to MBMC; (ii) 8% because MMC keypoints (26) < MBMC markers (67); and (iii) 3% from differences in musculoskeletal model scaling. These results validate Ergomechanic for leg kinematics during standing, walking, and squatting. Further, they suggest system improvements for pelvis and torso kinematics and provide new insights into the sources of known differences between MMC and MBMC measurements
The effect of shear stress on bovine lactoferrin
No full textBovine lactoferrin is a multi-functional glycoprotein susceptible to environmental changes which can alter its structure and functionality. This paper explores the impact of shear stress on this protein in the presence of an air interface. Lactoferrin remained stable in 10 mM buffer when sheared at 4000 s−1 for 1h, while aggregate size increased from 13 to 405 nm in de-ionized water. The thermal stability of this latter sample also declined, with solution turbidity increasing after heating for 10 min at 80oC. This increased protein association could be related to higher surface hydrophobicity in de-ionized water. The iron-binding capacity of lactoferrin did not vary with shear stress but was notably higher in de-ionized water at pH 5.5 and buffer at pH 7. The study also compared UV absorbance, the Bradford Assay, and an Index of Refraction sensor for measuring protein concentration in turbid solutions, with the sensor proving the most effective
How Can We Better Assist Caregivers With Understanding and Addressing the Cognitive Health Needs of People With Psychotic Disorders?
No full textCognitive impairment is a prominent feature of psychosis-spectrum disorders that impedes functional recovery. Globally, clinical guidelines recommend that evidence-based treatments, including cognitive remediation and cognitive compensation, are offered to people with psychosis with cognitive impairment. Clinical guidelines also recommend that, where possible, family is involved in the mental health treatment of their loved ones more broadly. Nevertheless, there is little guidance on how to assist family members with understanding and addressing the cognitive health needs of people with psychotic disorders. This is despite a demonstrable relationship between this symptom domain and caregiver burden as well as a clear need for greater professional supports from the perspectives of consumers and carers. In this article, we highlight the impact of cognitive impairment in psychosis on caregiver outcomes and argue the need to increase efforts to promote knowledge about cognitive health among caregivers via cognition-specific psychoeducation and/or more active involvement in cognitive rehabilitation. We showcase some of the existing cognition-specific resources that are available to caregivers and propose areas in need of future research. We conclude this article by presenting several practical recommendations for how clinical teams can advance their support of family members caring for loved ones with psychosis and cognitive impairment when it is clinically appropriate to do so and the consumer their caregiving network are agreeable
Potential viral influence on sulfur metabolism in acid sulfate soils
No full textAcid sulfate soils cover extensive areas across the globe and pose profound ecological and economic challenges. While microbial activities associated with sulfur metabolisms primarily mediate the formation process of acid sulfate soils, the potential impact of viruses, known for their roles in infecting microorganisms or encoding auxiliary metabolic genes (AMGs), remains largely unexplored. Here, we characterized the community and biogeochemical impacts of viruses in unoxidized acid sulfate soils (hypersulfidic soils, pH 6.5–7.3) and oxidized acid sulfate soils (sulfuric soils, pH < 3.3) using paired viromes and total metagenomes. Our results revealed higher diversity and distinct composition of viral communities in hypersulfidic soils compared to sulfuric soils. In hypersulfidic soils, we identified 30 times more virus-encoded AMGs and observed an average abundance 6.6 times higher than in sulfuric soils. Particularly, the identification of AMGs associated with assimilatory and dissimilatory sulfate reduction, organosulfur compound degradation, organic matter degradation, and electron transfer implied the potential role of viruses in influencing sulfur cycling and the formation of sulfidic materials in Hypersulfidic soils. The virus-host predictions linked seven lysogenic and 55 lytic vOTUs to sulfate-reducing and sulfur-oxidizing microorganisms in both soils, suggesting that viruses play a role in sulfur cycling through host infection. Altogether, our findings highlight the potential roles of viruses in influencing sulfur cycling processes in acid sulfate soils
What doesn't kill you makes you stronger: Using plant traits to inform species selection for naturalistic plantings in hotter and drier climates
No full textUrban plantings can improve the liveability of cities, but wide-scale implementation can be deterred by maintenance costs. Naturalistic plantings are low-maintenance and are being used to provide multiple ecosystem services and amenity in cities worldwide. In hotter and drier climates, naturalistic plantings could take inspiration from natural shrubland communities to tolerate summer droughts and remain low maintenance. The Woody Meadow Project proposes using diverse plantings of small trees and shrubs maintained by coppicing (hard pruning every 2 years) to create dense canopies to suppress weeds and promote flowering. Therefore, Woody Meadow species should resprout vigorously after coppicing, but coppicing response remains poorly understood. Leveraging on research into resprouting after natural disturbances such as fire, we investigated whether plant traits, starch reserves, and habitat water availability influence resprouting success and vigour after coppicing. We evaluated 77 Australian woody species in a common garden experiment and related coppicing response to pre-coppiced traits and storage reserves and their habitat water availability based on species occurrences (Atlas of Living Australia) and their climates (WorldClim). Most (88 %) species resprouted after coppicing, suggesting that most Australian woody species are suitable for Woody Meadows. However, we could not predict resprouting success after coppicing with pre-coppiced traits and habitat water availability. Nonetheless, greater species diversity could minimise impacts of poorer resprouters on planting success. Greater resprouting vigour was observed for species with greater pre-coppiced basal area, height, total biomass, and starch pool (i.e., greater pre-coppiced plant size), indicating that larger-sized plant species will maintain weed suppression and visual appeal in Woody Meadows after coppicing
Why did the Big Four get so large? Evidence from Australia
No full textAbstract
We use a long time-series from Australia to shed light on economic factors that led to audit market concentration and the Big N. We show that increases in the size of a small number of public companies was an important factor that led to large audit firms and market concentration. We also show that emerging Big N firms made sunk cost investments, including in the ability to provide industry expertise and non-audit services, which allowed them to retain clients, differentiate, and grow. These changes occurred around the time the profession lifted restrictions on advertising, which helped facilitate differentiation, and that larger, more complex clients switched to emerging Big N firms while smaller clients switched to non-Big N firms. We do not find that increases in audit market concentration reduced competition; our results instead suggest the audit market became more competitive over time
Bridging patterns and practice: Cultivating shared understanding in health professions education
No full textBridging theory and practice in health professions education requires fostering shared understanding of concepts, recognising how context, experience, identity, and systems influence their enactment, and ensuring multi‐level support
Spatial variation of short birth interval in the Asia-Pacific region
No full textBackground: Most countries in the Asia-Pacific region experience high rates of adverse maternal and child health outcomes, including maternal and child mortality. A significant proportion of these adverse outcomes are related to short birth intervals (SBI), which the World Health Organization defines as <33 months between two subsequent live births. Understanding the country-specific geographical variation of SBI in the Asia-Pacific region will enable the implementation of targeted interventions in higher-risk areas. Therefore, we aimed to explore the spatial variation of SBI across the Asia-Pacific region. Methods: We used data from Demographic and Health Surveys (DHS) of eight countries in the Asia-Pacific region: Bangladesh, Cambodia, India, Myanmar, Nepal, Pakistan, Philippines, and Timor-Leste, as these countries have location data available (i.e., latitude/longitude) along with the standard DHS data. The degree of spatial autocorrelation was identified using Global Moran's I statistics, and the degree of clustering of SBI was measured using Getis-Ord General G statistics. Getis-Ord Gi* was used to identify SBI hot spots. Results: The prevalence of SBI in the Asia-Pacific region varied from 21.3 % in Bangladesh to 60.7 % in Pakistan. SBI hot spots were identified in Bangladesh, India, Myanmar, Nepal, Pakistan, the Philippines, and Timor-Leste. Conclusion: This study revealed significant spatial variation in SBI across the Asia-Pacific region, with hotspots in several countries. These findings highlight the importance of bolstering targeted family planning services and raising awareness around optimal birth intervals. Statement of significance: Problem or Issue - SBI is associated with an increased risk of adverse maternal and child health outcomes such as gestational diabetes and maternal anemia, preterm birth and low birth weight. What is already known? - Previous studies have investigated spatial variations in SBI within specific countries in the Asia-Pacific region. However, they do not provide data on broader geographical areas across the region. What this paper adds? - Using nationally representative data, our study conducted a comprehensive spatial analysis of SBI in eight Asia-Pacific countries. The findings reveal wide-ranging geographical variations in SBI, helping policymakers implement targeted interventions and prioritise high-risk areas