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Objective: Erdheim‐Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome‐wide association study. Methods: After quality controls, a cohort of 255 patients with ECD and 7,471 healthy donors was included in this study. Afterward, a logistic regression followed by in silico functional annotation was performed. Results: A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (P = 2.75 × 10−11; Odds Ratio = 2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease. Conclusion: Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role. [ABSTRACT FROM AUTHOR]

Background: The 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Methods: We explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction. Results: The mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment. Conclusions: Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories. [ABSTRACT FROM AUTHOR]

BACKGROUND: Microplastics are a pervasive contaminant cycling through food webs—leading to concerns regarding exposure and risk to humans. OBJECTIVES: We aimed to quantify and characterize anthropogenic particle contamination (including microplastics) in fish caught for human consumption from the Humber Bay region of Lake Ontario. We related quantities of anthropogenic particles to other factors (e.g., fish size) that may help in understanding accumulation of microplastics in fish. METHODS: A total of 45 samples of six fish species collected from Humber Bay in Lake Ontario near Toronto, Ontario, Canada, were examined for anthropogenic particles in their gastrointestinal (GI) tracts and fillets. Using microscopy and spectroscopy, suspected anthropogenic particles were identified and characterized. RESULTS: We observed anthropogenic particles in the GI tracts and fillets of all species. Individual fish had a mean±standard deviation of 138±231 anthropogenic particles, with a single fish containing up to 1,508 particles. GI tracts had 93±226 particles/fish (9.8±32.6 particles/gram), and fillets had 56±61 particles/fish (0.5±0.8 particles/gram). Based on a consumption rate of 2 servings/week, the average yearly human exposure through the consumption of these fish fillets would be 12,800±18,300 particles. DISCUSSION: Our findings suggest that consumption of recreationally caught freshwater fish can be a pathway for human exposure to microplastics. The elevated number of particles observed in fish from Humber Bay highlights the need for large-scale geographic monitoring, especially near sources of microplastics. Currently, it is unclear what the effects of ingesting microplastics are for humans, but given that recreationally caught freshwater fish are one pathway for human exposure, these data can be incorporated into future human health risk assessment frameworks for microplastics. [ABSTRACT FROM AUTHOR]

In the last few decades, the word 'safety' has become silently but increasingly pervasive in educational policies and debates, gaining a new momentum with the pandemic. Our intention in this article is to problematise what is done in schools in the name of safety by delving into the safety policy discourses of a New Zealand school and the narratives of resistance employed by a group of female Pasifika students during the Covid-19 crisis. This critical ethnographic inquiry explores how safety at schools operates as a mechanism to oppress their fights and reproduce inequalities in an era of apparent 'racism without racists'. [ABSTRACT FROM AUTHOR]

Silicon nanowires (SiNWs) with good extinction performance achieve light capture larger than own cross-section. However, the isotropic response of the polarization angle and the narrow response spectrum of SiNWs limit their application in optoelectronic detectors. In this work, we designed a kind of oblate SiNWs with excellent anisotropic response and wide absorption spectrum, which is suitable for linear polarized light detection. According to the propagation characteristics of electromagnetic waves in the Si material medium, it is found that the induced current presents a vortex flow in the polarization plane of the incident light. Meanwhile, extending the scale of SiNWs in the polarization plane increases the number and mode of induced current to accelerate the attenuation of light in SiNWs for broadens the response spectrum. In addition, this scale extending changes the axial symmetry of SiNWs to achieve anisotropic response. Based on numerical simulation technology, it is obtained that when the incident light wavelength is 420 nm, the light absorption coefficient (Qabs) of oblate SiNWs is 11.42 higher than that of cylindrical SiNWs. The excellent Qabs anisotropy ratio (Qmax/Qmin) of oblate SiNWs can be achieved in the range of 400 nm to 650 nm, of which the maximum value is 74.18. This provides ideas for the design of semiconductor nanowires and their application in photodetectors. [ABSTRACT FROM AUTHOR]

Chew, Teng Keat, BSH23-EP51. Ross, David M, BSH23-PO33, BSH23-PO35. B v b van de Donk, Niels WCJ, BSH23-EP162. van de Wetering, Gijs, BSH23-PO72, BSH23-PO78. van der Poel, Marjolein, BSH23-OR13. Tan, Sui Keat, BSH23-EP51. Peffault de Latour, R, BSH23-PO103. [Extracted from the article]

828 The use of digital platforms in the financial sector requires automated processes in order to collect the large volumes of data which will allow firms to create a shared understanding around rules through technological applications. The UK Financial Conduct Authority launched innovation programmes, i. e. a regulatory sandbox, to assess technologies and expedite the delivery of fintech products. This initiative has been followed by the European Digital Finance Package, which introduced the Pilot Regime for market infrastructure based on distributed ledger technology. Albeit a laudable initiative, the EU sandbox model may face obstacles on account of the different approaches taken by Member States in relieving regulatory requirements which can create a perverse incentive to circumvent prudential rules in the context of risk assessment. This article examines the impact of sandboxes on the operation of digital platforms and considers the extent to which decision-making processes are amenable to digital treatment, and what will be the implications for the quality of regulation and the exercise of judgement by the supervisory authority. It argues that the application of regulatory sandboxes can promote more effective compliance processes, while ensuring transparency and accuracy of enforcement actions. 829 [ABSTRACT FROM AUTHOR]

854 Despite a pandemic, crowdfunding continues to be a growing source of finance for small businesses across the EU. This article discusses nature and business typology of digital platforms that raise funds from the crowd. In the effort to support the ongoing uptake of new technologies in financial services, the first harmonised regime for the intermediation of financial instruments and loans to businesses via digital crowdfunding platforms has recently entered into application and promises to change the landscape of this financial service in the years to come. The new policy framework creates a robust EU-wide license, with requirements that support integration with social media, as well as the progressive creation of pan-European one-stop-shop platforms that offer multiple funding tools. Moreover, the regime also tests new boundaries in investor protection and behavioural finance, with the introduction of a system of warnings, targeted transparency on multiple levels and a conflict-of-interest framework to ensure that the platform acts as a risk neutral gatekeeper. The jury is still out and there are a number of unknowns, as this new framework will have to face the reality of well-established legal and supervisory national obstacles in its implementation. [ABSTRACT FROM AUTHOR]

In the Māori world, people move backwards into the future. The past is on the horizon, we can see it, we know it. The future remains uncertain, we must sharpen our senses and proceed with caution. This article contends that a change of perspective is the most powerful tool to identify multiple ethical implications when conducting research in settings characterized by unfolding processes that weave together human interventions and non-human agency. Walking backwards and based on ethnographic fieldwork in Māori lands, scientific laboratories, research nurseries, and healthy and declining forest in the upper North Island of New Zealand, this paper reflects on the ethical issues that arise from meeting in the field with scientists, Indigenous experts, lethal microorganisms, and giant ancient trees, while also considering the evidence of past multispecies encounters and the uncertainty of future ones. Aware that most of the terrestrial biomass remains outside the field of vision of institutional review boards, this article argues for the adoption of a broader conception of ethics, not as a human construct associated with the production of knowledge, but rather as an essential component of all interdependencies that make life possible on Earth. [ABSTRACT FROM AUTHOR]

Our previously published health economic modelling studies of DNA screening for HBOC, Lynch syndrome20 and familial hypercholesterolaemia21 provide a platform for the consideration of DNA screening in Australia. Our model on DNA screening for familial hypercholesterolaemia genes found similar results.21 Our future modelling will assess the combined benefits and costs of screening for familial cancer genes and familial hypercholesterolaemia genes concurrently in the same test. At $200 per test, savings in prevented cancer treatment outweighed DNA screening costs, projecting DNA screening to be cost-saving for the Australian public health system (for cancer genes alone). Keywords: Genetic counselling; Mass screening; Population health EN Genetic counselling Mass screening Population health 278 280 3 04/05/22 20220401 NES 220401 Australia will take a world-first step towards offering preventive DNA screening through the public health care system In adult-onset genomic conditions, such as hereditary breast and ovarian cancer (HBOC), Lynch syndrome and familial hypercholesterolaemia, certain DNA variants confer high risk of developing future disease.1 DNA screening for these conditions could thereby identify medically actionable genetic risk factors, prompting timely risk management and informed decision making from early adulthood to facilitate early detection or prevention.2 Despite this opportunity, diagnostic rates for these conditions remain low,2-4 limited by restricted access to genetic testing and lack of awareness. [Extracted from the article]