Polygenic factors are estimated to account for an additional 18% of the familial relative risk of breast cancer, with those at the highest level of polygenic risk distribution having a least a ...twofold increased risk of the disease. Polygenic testing promises to revolutionize health services by providing personalized risk assessments to women at high-risk of breast cancer and within population breast screening programs. However, implementation of polygenic testing needs to be considered in light of its current limitations, such as limited risk prediction for women of non-European ancestry. This article aims to provide a comprehensive review of the evidence for polygenic breast cancer risk, including the discovery of variants associated with breast cancer at the genome-wide level of significance and the use of polygenic risk scores to estimate breast cancer risk. We also review the different applications of this technology including testing of women from high-risk breast cancer families with uninformative genetic testing results, as a moderator of monogenic risk, and for population screening programs. Finally, a potential framework for introducing testing for polygenic risk in familial cancer clinics and the potential challenges with implementing this technology in clinical practice are discussed.
Mangrove ecosystems are targeted for many conservation and rehabilitation efforts due to their ability to store large amounts of carbon in their living biomass and soil. Traditional methods to ...monitor above-ground biomass (AGB) rely on on-ground measurements, which are expensive, labour intensive and cover small spatial scales. Structure from Motion and Multi-View Stereo reconstructions from Unmanned Aerial Vehicles imagery (UAV-SfM) have the potential to increase fieldwork efficiency by providing a greater amount of spatial information in less time. However, there is still a need to assess the ability of UAV-SfM to retrieve structural information of mangrove forests, which could pose challenges in areas of high forest complexity and density.
In this study we successfully used UAV-SfM data to estimate height, canopy diameter and AGB of natural and rehabilitated mangrove forests across two regions of the southeastern coast of Australia. We used a variable window filter algorithm to detect trees with an 80% detection rate when considering the top canopy. Individual tree canopy segmentation was performed using a marker-controlled watershed segmentation with two sets of constraining markers: treetops and a minimum height below which a pixel is not considered part of a tree.
Direct comparison with on-ground measurements at the regional level showed no significant difference in tree height and AGB medians when only top canopy was considered. Similarly, median canopy diameters were not significantly different in natural areas of both regions, but significant differences were found in rehabilitated areas. UAV-SfM estimates of AGB were on average 15% lower in natural areas and 10% higher in rehabilitated areas when compared to on-ground measurements and followed a strong linear relationship close to the ideal one-to-one relationship.
Additionally, we performed a cost-benefit analysis of the two methodologies. UAV-SfM methods can save almost AU$ 50,000 per ha when compared to on-ground measurements and become cost-effective (based on total costs) after just 15 days of surveys. The methods described in this study open the possibility for easily repeatable, low-cost UAV-SfM surveys for local managers by providing a faster, more cost-effective approach for monitoring mangrove forests over larger areas than traditional on-ground surveys while maintaining forest inventory data accuracy in both natural and rehabilitated mangrove forests.
•UAV imagery can be used to assess AGB of natural and rehabilitated mangrove forests.•Mangrove tree height and canopy diameter accurately estimated•UAVs are more cost-effective than on-ground surveys (AU$ 50,000 savings per ha).
Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause ...damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.
Polygenic risk scores (PRS) are becoming increasingly available in clinical practice to evaluate cancer risk. However, little is known about health professionals' knowledge, attitudes, and ...expectations of PRS. An online questionnaire was distributed by relevant health professional organisations predominately in Australia, Canada and the US to evaluate health professionals' knowledge, views and expectations of PRS. Eligible participants were health professionals who provide cancer risk assessments. Results from the questionnaire were analysed descriptively and content analysis was undertaken of free‐text responses. In total, 105 health professionals completed the questionnaire (genetic counsellors 84%; oncologists 6%; clinical geneticists 4%; other 7%). Although responses differed between countries, most participants (61%) had discussed PRS with patients, 20% had ordered a test and 14% had returned test results to a patient. Confidence and knowledge around interpreting PRS were low. Although 69% reported that polygenic testing will certainly or likely influence patient care in the future, most felt unprepared for this. If scaled up to the population, 49% expect that general practitioners would have a primary role in the provision of PRS, supported by genetic health professionals. These findings will inform the development of resources to support health professionals offering polygenic testing, currently and in the future.
Genetic counselors have long recognized the challenges of working with adolescents and young adults (AYA) and their families. In 2010, a framework of Youth‐friendly Genetic Counseling was developed ...by an expert reference group with the aim to improve both care for AYAs and the experience of health professionals delivering that care. Subsequently, an education workshop was developed aimed to upskill genetic health professionals in youth‐friendly genetic counseling. The workshop was piloted with genetic counselors in Australia and New Zealand. A purpose designed, pre‐ and post‐workshop survey and post‐workshop focus group was utilized for evaluation. Mean confidence scores increased pre‐ and post‐workshop. Participants also demonstrated increases in knowledge regarding: adolescent development; developmental theory; social factors impacting on health; the needs of young people; practice challenges; youth‐friendly engagement, communication, consent and confidentiality; practice approaches; principles of adolescent healthcare; ethical issues; and available services and resources. Focus group data revealed several themes relating to practice challenges, learning gains, barriers, and enablers to clinical translation and workshop feedback. Results demonstrate utility of the workshop in up‐skilling genetic health professionals in the provision of youth‐friendly genetic counseling. Consideration of adaptation and sustainability, by embedding this theoretical and skills‐based workshop as a module within genetic counseling education, is required to ensure practice competence and the best health outcomes for young people and their families.
The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have ...characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3β loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.
► Isolation and characterization of NKT TCRs interacting with self-lipid-CD1d tetramers ► Crystal structure of autoreactive NKT TCR-CD1d complex ► NKT cell autoreactivity is mediated by CDR3β loop in an antigen-independent manner ► Multiple self-antigens are recognized in a similar fashion by autoreactive NKT TCRs
The use of genomic data in research and genomic information in clinical care is increasing as technologies advance and sequencing costs decrease. Using Rogers' Diffusion of Innovation (DOI) theory as ...a framework we reviewed recent literature examining publics' current knowledge of, attitude to, and motivation towards health-related genomics in clinical and research settings. The population of interest was described as 'publics' to denote the heterogeneity of 'the public'. Eligible studies were published in English between 2016-2022. We retrieved 1657 records, with 278 full-text reviewed against the eligibility criteria and concept definitions. In total, 99 articles were included in the review and descriptive numerical summaries were collated. Knowledge literature was categorized using deductive thematic analysis. For attitude and motivation, literature was coded using an analytic framework developed by the authors. There was wide variability in concept definition and measurement across studies. Overall, there was general positivity about genomics, with high awareness but little familiarity or factual knowledge. Publics had high expectations of genomics and perceived that it could provide them with information for their future. Only a few key attitudes were found to be important as motivators or barriers for participation in genomics; these were related to personal and clinical utility of the information. Context was often missing from studies, decreasing the utility of findings for implementation or public engagement. Future research would benefit by using theory-driven approaches to assess relevant publics' knowledge and attitudes of specific contexts or applications to support genomic implementation and informed decision-making.
To help mitigate the impacts of climate change, many nature-based solutions are being explored. These solutions involve protection and restoration of ecosystems that serve as efficient carbon sinks, ...including vegetated coastal ecosystems (VCEs: tidal marshes, mangrove forests, and seagrass meadows) also known as ‘Blue Carbon’ ecosystems. In fact, many nations are seeking to manage VCEs to help meet their climate change mitigation targets through Nationally Determined Contributions (NDCs). However, incorporation of VCEs into NDCs requires national-scale estimates of contemporary and future blue carbon storage, which has not yet been achieved. Here we address this challenge using machine learning approaches to reliably map (with 62–72% accuracy) soil carbon stocks in VCEs based on geospatial data (topography, geomorphology, climate, and anthropogenic impacts), using Australia as a case study. The resulting maps of soil carbon stocks showed that there is a total of 951 Tg (±65 Tg) of carbon stock within Australian VCEs. Strong relationships between soil carbon stocks and climatic conditions (temperature, rainfall, solar radiation) allowed us to project future changes in carbon storage across all RCP scenarios for the years 2050 and 2090 to determine changes in environmental suitability for soil carbon stocks. Results show that soil carbon stocks in mangrove/tidal marsh ecosystems are likely to predominantly experience declines in carbon stocks under predicted climate change scenarios (19% of ecosystems area is predicted to have an increase in soil carbon stocks, while 38% of ecosystems area is predicted to have a decrease in soil carbon stocks), but a majority of seagrass area is likely to have increased soil carbon stocks (56% increase, 7% decrease). This approach is effective for developing robust national blue carbon inventories and revealing the capacity for blue carbon to help meet NDCs. The resulting spatially-explicit maps can also be used to pinpoint areas for successful blue carbon projects both now and in the future.
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•Vegetated coastal ecosystems store significant amounts of ‘blue carbon’.•Environmental and anthropogenic conditions explain the variation in blue carbon.•Spatially explicit maps of blue carbon stocks are developed at a national scale.•Climate projections are used to assess future suitability for blue carbon.•The results help to pinpoint current and future locations for blue carbon projects.
Monitoring of intertidal reefs is traditionally undertaken by on-ground survey methods which have assisted in understanding these complex habitats; however, often only a small spatial footprint of ...the reef is observed. Recent developments in unmanned aerial vehicles (UAVs) provide new opportunities for monitoring broad scale coastal ecosystems through the ability to capture centimetre resolution imagery and topographic data not possible with conventional approaches. This study compares UAV remote sensing of intertidal reefs to traditional on-ground monitoring surveys, and investigates the role of UAV derived geomorphological variables in explaining observed intertidal algal and invertebrate assemblages. A multirotor UAV was used to capture <1 cm resolution data from intertidal reefs, with on-ground quadrat surveys of intertidal biotic data for comparison. UAV surveys provided reliable estimates of dominant canopy-forming algae, however, understorey species were obscured and often underestimated. UAV derived geomorphic variables showed elevation and distance to seaward reef edge explained 19.7% and 15.9% of the variation in algal and invertebrate assemblage structure respectively. The findings of this study demonstrate benefits of low-cost UAVs for intertidal monitoring through rapid data collection, full coverage census, identification of dominant canopy habitat and generation of geomorphic derivatives for explaining biological variation.
Background
Despite healthcare professionals (HCP) endorsing the clinical utility of pharmacogenomics testing, use in clinical practice is limited.
Aims
To assess HCP' perceptions of pharmacogenomic ...testing and identify barriers to implementation.
Methods
HCP involved in prescribing decisions at three hospitals in Sydney, Australia, were invited to participate. The online survey assessed perceptions of pharmacogenomic testing, including: (i) demographic and practice variables; (ii) use, knowledge and confidence; (iii) perceived benefits; (iv) barriers to implementation; and (v) operational and/or system changes and personnel required to implement on site.
Results
HCP were predominantly medical practitioners (75/107) and pharmacists (25/107). HCP perceived pharmacogenomic testing was beneficial to identify reasons for drug intolerance (85/95) and risk of side‐effects (86/95). Although testing was considered relevant to their practice (79/100), few HCP (23/100) reported past or intended future use (26/100). Few HCP reported confidence in their ability to identify indications for pharmacogenomic testing (14/107), order tests (19/106) and communicate results with patients (16/107). Lack of clinical practice guidelines (62/79) and knowledge (54/77) were identified as major barriers to implementation of pharmacogenomics. Comprehensive reimbursement for testing and clinical practice guidelines, alongside models‐of‐care involving multidisciplinary teams and local clinical champions were suggested as strategies to facilitate implementation of pharmacogenomic testing into practice.
Conclusions
Pharmacogenomic testing was considered important to guide drug selection and dosing decisions. However, limited knowledge, low confidence and an absence of guidelines impede the use of pharmacogenomic testing. Establishment of local resources including multidisciplinary models‐of‐care was suggested to facilitate implementation of pharmacogenomics.
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