Caractérisation de l'endommagement localisé dans les géomatériaux à l'aide des ondes

Nous présentons les résultats de nos premières études sur la détection et caractérisation de la déformation localisée dans des échantillons d'argile à l'aide des ondes ultrasonores. Les vitesses des ondes élastiques (ultrasoniques, sismiques...) sont sensibles aux changements des propriétés élastiques du matériau, leur mesure permet de quantifier l'endommagement induit par la déformation. Par ailleurs, les méthodes de mesure de champs par analyse d'images (stéréophotogrammétrie, corrélation d'image numérique...) sont complémentaires, elles permettent de mesurer un champ de déplacement et de déformation, donc d'identifier la déformation localisée, mais ne fournissent pas d'information sur les évolutions des propriétés mécaniques. Nous présentons les résultats de deux types d'analyse ultrasonore : une méthode appelée «circumferential velocity analysis» (CVA), qui utilise les mesures des vitesses des ondes sur différents chemins radiaux dans un échantillon cylindrique ; et une méthode de « tomographie ultrasonore» en effectuant des mesures de champ de vitesse de propagation des ondes

Off-target stoichiometric binding identified from toxicogenomics explains why some species are more sensitive than others to a widely used neonicotinoid

Neonicotinoids are currently licensed for use in 120 countries, making accurate nontarget species sensitivity predictions critical. Unfortunately, such predictions are fraught with uncertainty, as sensitivity is extrapolated from only a few test species and neonicotinoid sensitivities can differ greatly between closely related taxa. Combining classical toxicology with de novo toxicogenomics could greatly improve sensitivity predictions and identify unexpectedly susceptible species. We show that there is a >30-fold differential species sensitivity (DSS) for the neonicotinoid imidacloprid between five earthworm species, a critical nontarget taxon. This variation could not be explained by differential toxicokinetics. Furthermore, comparing key motif expression in subunit genes of the classical nicotinic acetylcholine receptor (nAChR) target predicts only minor differences in the ligand binding domains (LBDs). In contrast, predicted dissimilarities in LBDs do occur in the highly expressed but nonclassical targets, acetylcholine binding proteins (AChBPs). Critically, the predicted AChBP divergence is capable of explaining DSS. We propose that high expression levels of putative nonsynaptic AChBPs with high imidacloprid affinities reduce imidacloprid binding to critical nAChRs involved in vital synaptic neurotransmission. This study provides a clear example of how pragmatic interrogation of key motif expression in complex multisubunit receptors can predict observed DSS, thereby informing sensitivity predictions for essential nontarget species

Pest categorisation of Acrobasis pirivorella

The European Commission requested EFSA to conduct a pest categorisation of Acrobasis pirivorella (Lepidoptera: Pyralidae), a monophagous moth whose larvae exclusively feed on developing buds, flowers, and fruits of cultivated and wild Pyrus spp. A. pirivorella is a species with reliable methods available for identification. A. pirivorella occurs in north-east Asia only, causing significant damage in cultivated pears. It is regulated in the EU by Council Directive 2000/29/EC where it is listed in Annex IIAI. Within this regulation, plants for planting of Pyrus spp. is a closed pathway. This species has never been reported by Europhyt. Fruits and cut branches of Pyrus spp. are open pathways. Biotic and abiotic conditions are conducive for establishment and spread of A. pirivorella in the EU. Were A. pirivorella to establish, impact on pear production is expected. Considering the criteria within the remit of EFSA to assess its regulatory plant health status, A. pirivorella meets the criteria for consideration as a potential Union quarantine pest (it is absent from the EU, potential pathways exist and its establishment would cause an economic impact). Given that A. pirivorella is not known to occur in the EU, it fails to meet some of the criteria required for regulated non-quarantine pest (RNQP) status

Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research

Incidence and phenotypes of childhood-onset genetic epilepsies:a prospective population-based national cohort

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy

Early developmental changes in the timing of turn-taking: A longitudinal study of mother-infant interaction

To accomplish a smooth transition in conversation from one speaker to the next, a tight coordination of interaction between speakers is required. Recent studies of adult conversation suggest that this close timing of interaction may well be a universal feature of conversation. In the present paper, we set out to assess the development of this close timing of turns in infancy in vocal exchanges between mothers and infants. Previous research has demonstrated an early sensitivity to timing in interactions (e.g. Murray & Trevarthen, 1985). In contrast, less is known about infants’ abilities to produce turns in a timely manner and existing findings are rather patchy. We conducted a longitudinal study of twelve mother-infant dyads in free-play interactions at the ages of 3, 4, 5, 9, 12 and 18 months. Based on existing work and the predictions made by the Interaction Engine Hypothesis (Levinson, 2006), we expected that infants would begin to develop the temporal properties of turn-taking early in infancy but that their timing of turns would slow down at 12 months, which is around the time when infants start to produce their first words. Findings were consistent with our predictions: Infants were relatively fast at timing their turn early in infancy but slowed down towards the end of the first year. Furthermore, the changes observed in infants’ turn-timing skills were not caused by changes in maternal timing, which remained stable across the 3-18 month period. However, the slowing down of turn-timing started somewhat earlier than predicted: at 9 months

Species sensitivity to toxic substances: evolution, ecology and applications

Because it is only possible to test chemicals for effects on a restricted range of species and exposure scenarios, ecotoxicologists are faced with a significant challenge of how to translate the measurements in model species into predictions of impacts for the wider range of species in ecosystems. Because of this challenge, within ecotoxicology there is no more fundamental aspect than to understand the nature of the traits that determine sensitivity. To account for the uncertainties of species extrapolations in risk assessment, “safety factors” or species sensitivity distributions are commonly used. While valuable as pragmatic tools, these approaches have no mechanistic grounding. Here we highlight how mechanistic information that is increasingly available for a range of traits can be used to understand and potentially predict species sensitivity to chemicals. We review current knowledge on how toxicokinetic, toxicodynamic, physiological, and ecological traits contribute to differences in sensitivity. We go on to discuss how this information is being used to make predictions of sensitivity using correlative and trait-based approaches, including comparisons of target receptor orthologs. Finally, we discuss how the emerging knowledge and associated tools can be used to enhance theoretical and applied ecotoxicological research through improvements in mechanistic modeling, predictive ecotoxicology, species sensitivity distribution development, mixture toxicity assessment, chemical design, biotechnology application and mechanistically informed monitoring

Measuring ZnO nanoparticles available concentrations in contaminated soils using the diffusive gradient in thin-films (DGT) technique

This is an accepted manuscript of an article published by Elsevier in Science of the Total Environment on 24/06/2021, available online: https://doi.org/10.1016/j.scitotenv.2021.148654 The accepted version of the publication may differ from the final published version.A major gap in understanding nanomaterials behaviour in the environment is a lack of reliable tools to measure their available concentrations. In this research we use diffusive gradients in thin films (DGT) for measuring concentrations of zinc oxide nanoparticles (ZNO NPs) in soils. Available nanoparticle concentrations were assessed by difference, using paired DGT devices with and without 1000 MWCO dialysis membranes to exclude NPs. We used ZnO because its toxic effects are accelerated through dissolution to Zn2+. Our test soils had different pH and organic matter (OM) contents, which both affect the dissolution rate of ZnO NPs. Woburn (pH≈6.9, OM≈1.8%) and Lufa (pH≈5.9, OM≈4.2%) soils were spiked to a single concentration of 500 mg of ZnO NPs per 1 kg of soil and the available concentrations of ZnO NPs and dissolved zinc were evaluated in 3, 7, 14, 21, 28, 60, 90, 120, 150 and 180 day intervals using DGT. The results showed that the dissolution of ZnO NPs, as well as the available concentrations of both dissolved and nanoparticulate Zn, were much higher in Lufa soil than in Woburn. This work demonstrates that DGT can be used as a simple yet reliable technique for determining concentrations of ZnO NPs in soils and probing its dissolution kinetics