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Goujon et al thank Catherine Hill for her comments on their recent study on the association between residential proximity to viticultural areas and childhood acute leukemia risk in mainland France. However, they believe she has misunderstood certain aspects of their study.

Background: Pesticide exposures are suspected of being a risk factor for several childhood cancers, particularly acute leukemia (AL). Most of the evidence is based on self-reported parental domestic use of pesticides, but some studies have also addressed associations with agricultural use of pesticides near the place of residence. Objectives: The objective of the study was to evaluate the risk of AL in children living close to vines, a crop subject to intensive pesticide use. Methods: Data were drawn from the national registry-based GEOCAP study. We included all of the AL cases under the age of 15 years diagnosed in 2006-2013 (n = 3,711) and 40,196 contemporary controls representative of the childhood population in France. The proximity of the vines (probability of presence within 200, 500, and 1,000 m) and the viticulture density (area devoted to vines within 1,000 m) were evaluated around the geo-coded addresses in a geographic information system combining three national land use maps. Logistic regression models were used to estimate odds ratios (ORs) for all AL and for the lymphoblastic (ALL) and myeloid (AML) subtypes. Heterogeneity between regions was studied by stratified analyses. Sensitivity analyses were carried out to take into account, in particular, geocoding uncertainty, density of other crops and potential demographic and environmental confounders. Results: In all, about 10% of the controls lived within 1 km of vines. While no evidence of association between proximity to vines and AL was found, viticulture density was positively associated with ALL [OR = 1.05 (1.00-1.09) for a 10% increase in density], with a statistically significant heterogeneity across regions. No association with AML was observed. The results remained stable in all the sensitivity analyses. Conclusion: We evidenced a slight increase in the risk of ALL in children living in areas with high viticulture density. This finding supports the hypothesis that environmental exposure to pesticides may be associated with childhood ALL.

African swine fever (ASF) is an emerging disease currently spreading at the interface between wild boar and pig farms in Europe and Asia. Current disease control regulations, which involve massive culling with significant economic and animal welfare costs, need to be improved. Modelling enables relevant control measures to be explored, but conducting the exercise during an epidemic is extremely difficult. Modelling challenges enhance modellers' ability to provide timely advice to policy makers, improve their readiness when facing emerging threats, and promote international collaborations. The ASF-Challenge, which ran between August 2020 and January 2021, was the first modelling challenge in animal health. In this paper, we describe the objectives and rules of the challenge. We then demonstrate the mechanistic multi-host model that was used to mimic as accurately as possible an ASF-like epidemic, provide a detailed explanation of the surveillance and intervention strategies that generated the synthetic data, and describe the different management strategies that were assessed by the competing modelling teams. We then outline the different technical steps of the challenge as well as its environment. Finally, we synthesize the lessons we learnt along the way to guide future modelling challenges in animal health. Competing Interest Statement The authors have declared no competing interest.

WHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption. Using a mouse model harboring a WHIM Syndrome-linked gain-of-function CXCR4 mutation and bone marrow samples from WHIM patients, the authors show that proper CXCR4 signaling termination is essential for bone tissue homeostasis.

In France, the presence of marine microalgae of the genus Ostreopsis has been identified repeatedly on the Mediterranean coast for several years, whereas on the French Basque coasts its presence is much more recent. In the summers of 2021 and 2022, major Ostreopsis flowering episodes were reported on the Basque coast, resulting in several hundred cases of intoxication among holidaymakers and residents. The main route of human exposure is inhalation of aerosols, although it is not yet known whether the agents responsible for poisoning are Ostreopsis cells, cell debris, known toxins produced by Ostreopsis, or other as yet unidentified compounds. Other routes of exposure (dermal contact, eye contact, ingestion of contaminated water or seafood) are also possible. Poisoning is manifested through various signs and symptoms, occurring within 48 hours of exposure (Neurosensory and neurological, respiratory, dermal and digestive). This document presents the opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), established from the work of its WATER and ERCA Expert Committees. ANSES received a request from the Directorate General for Health (DGS) and the Directorate General for Food (DGAL) to update knowledge about Ostreopsis that had been reported in the Agency's opinions from 2007 and 2008 (ANSES, 2007 and 2008), and draw up specific recommendations for managing Ostreopsis proliferation on the Basque coast. The literature review conducted as part of this expert appraisal revealed that knowledge about the genus Ostreopsis (diversity, biology, ecology, toxins produced) is still too fragmentary to characterise the hazard and risk to human health. Nevertheless to help local authorities affected by Ostreopsis blooms, Agency proposes a surveillance and quality monitoring strategy based on collaboration between site managers and the regional health agencies (ARSs), applicable to sites currently subject to bathing water quality monitoring and water sports sites that meet the conditions below.