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Hepatitis B core-related antigen rapid diagnostic test for point-of-care identification of women at high risk of hepatitis B vertical transmission: a multicountry diagnostic accuracy study
No full textInternational audienceBackground Timely administration of the hepatitis B virus (HBV) birth dose vaccine, along with identifying high-risk pregnant individuals for antiviral prophylaxis, is essential for the global elimination of vertical transmission of HBV. However, in resource-limited settings, access to HBV DNA testing is scarce, and accurate rapid tests for HBeAg are lacking. We aimed to assess the diagnostic performance of a newly developed hepatitis B core-related antigen (HBcrAg) rapid diagnostic test (RDT) to identify women who are HBsAg-positive and eligible for antiviral prophylaxis.MethodsIn this multicountry diagnostic accuracy study, we retrospectively validated the HBcrAg-RDT using stored plasma from pregnant women who were HBsAg-positive in cohort studies from Cambodia and Cameroon and prospectively using finger-prick capillary blood from postpartum mothers at rural health centres in Burkina Faso. We estimated the sensitivity and specificity of the HBcrAg-RDT for diagnosing high HBV DNA concentrations (≥200 000 IU/mL) using real-time PCR (rtPCR) as the reference. We compared the diagnostic performance of the HBcrAg-RDT with that of conventional HBeAg assays based on the area under the receiver operating characteristic curve (AUROC).FindingsIn total, plasma samples were available for 1964 participants: 1194 stored plasma samples available for analysis from the Cambodian cohort, 501 stored samples from the Cameroonian cohort, and 269 prospectively collected samples from women in the Burkina Faso cohort. In the pooled population, the mean age was 28•1 years (SD 6•0), and 382 (20•0%) were HBeAg positive. The HBcrAg-RDT showed an overall sensitivity of 93•1% (95% CI 90•5-95•2) and specificity of 94•3% (93•0-95•4). Sensitivity and specificity were 93•4% (90•7-95•5) and 94•4% (92•9-95•6) in the retrospective laboratory-based analyses of samples from Cambodia and Cameroon, and 89•7% (75•8-97•1) and 93•9% (90•0-96•6) in the prospective real-world analysis of samples of HBsAg-positive women from Burkina Faso. The AUROC for HBcrAg-RDT (0•937 [95% CI 0•924-0•950]) in distinguishing high versus low HBV DNA concentrations at the 200 000 IU/mL threshold in the pooled data set was significantly higher than that of HBeAg rapid tests (0•822 [0•798-0•845]; p<0•0001) and similar to laboratory-based HBeAg immunoassays (ELISA and chemiluminescence assay; 0•926 [0•897-0•955]; p=0•72). In Burkina Faso, the median turnaround time for HBV DNA testing was 46 days (IQR 31-72), whereas HBcrAg-RDT provided same-day results for all participants. Interpretation HBcrAg-RDT might offer a practical solution for integrating the prevention of vertical transmission of HBV into decentralised antenatal care in resource-limited settings, enabling timely identification and management of pregnant individuals who are at high risk of transmission. Funding Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Total Foundation, Gilead Sciences, and Japan Society for the Promotion of Science
The Random Matrix-based informative content of correlation matrices in stock markets
No full textInternational audienceStudying and comprehending the eigenvalue distribution of the correlation matrices of stock returns is a powerful tool to delve into the complex structure of financial markets. This paper deals with the analysis of the role of eigenvalues and their associated eigenvectors of correlation matrices within the context of financial markets. We exploit the meaningfulness of Random Matrix Theory with the specific aspect of the Marchenko-Pastur distribution law to separate noise from true signal but with a special focus on giving an interpretation of what mean these signals in the financial context. We empirically show that the highest eigenvalue serves as a proxy of market spillover. Furthermore, based on an analysis of portfolio betas, we prove that the eigenvector associated with this eigenvalue is the market portfolio. These analyses of portfolio betas also reveal that the second and third-highest eigenvalues, and their associated eigenvectors, result in some cases of counter-behavior that makes them suitable to be a safe haven during high-volatility periods. The analysis is performed on a set of indices coming from developed and emerging countries over a time period ranging from 2015 to 2024
Dynamic stochastic optimization for sustainability and management of overconsumption
No full textInternational audienceThis paper deals with an intergenerational utility maximization problem for consuming a naturally exhaustible resource. In this context, we are at odds with the unfair standard procedure of applying a time-dependent factor for discounting the utility and introducing a suitable function for penalizing overconsumption. A finite-time horizon dynamic stochastic optimization problem is presented to achieve the desired target. We provide a closed-form solution to the problem which does not lead forcefully to the classical golden rule outcome of not consuming now to save the future. The theoretical findings are validated through extensive numerical experiments, with a parameter set selected based on empirical data. Such experiments highlight that optimal consumption depends strongly on the natural resource regeneration rate and the initial value of the stock
Gene–Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies
No full textInternational audienceBackground: Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology.Methods: We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings.Results: The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (ORinteraction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype.Conclusion: Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur
Anti-PD1-/PDL1-induced chronic intestinal pseudo-obstruction: three cases treated with vedolizumab after corticosteroid failure with mixed results
No full textInternational audienceImmune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes
Mesures d'instruction in futurum, droit à la preuve et minimisation des données
No full textInternational audienceLa Cour de cassation confirme une solution déjà adoptée (articulation de l’article 145 du Code de procédure civile et du droit à la preuve) tout en y ajoutant le respect du principe de minimisation des données issu du RGPD. Cette exigence de minimisation des données s’harmonise parfaitement avec la jurisprudence classique relative à l’article 145 précité, dont la mise en œuvre ne saurait avoir pour finalité d’autoriser des mesures d’investigation générale sur les agissements d’un possible adversaire
Association Between Breastfeeding and Neurodevelopment at 6 Years of Age in the French PELAGIE Birth Cohort
No full textInternational audienceIntroduction: Breastfeeding has been shown to be associated with improved child cognitive performance, but the causality of this association is still debated because it tends to disappear when accounting for maternal cognitive performance and socioeconomic status. We aimed to explore the relationship between breastfeeding and the cognitive performance of children in the French general population.Methods: From the PELAGIE woman-child cohort, which included pregnant women between 2002 and 2006 in Brittany (France), 286 children were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV) and the Developmental Neuropsychological Assessment (NEPSY) scales at age 6. Associations between breastfeeding and cognitive performance were assessed using multivariable linear regression models adjusted for maternal verbal cognitive performance and education level, familial stimulation and environment (Home Observation for Measurement of the Environment scale), and Rey's Social Deprivation Index (contextual indicator). In addition, we performed structural equation modeling (SEM) to investigate the complex interrelation between these variables.Results: Children who were breastfed for at least 4 months had significantly higher scores on the WISC Verbal Comprehension Index (WISC-VCI) than those who were never breastfed or who were breastfed less than 15 days (βadjusted, 4.95 points; 95% CI, 0.54-9.37). Among the 193 children who were breastfed, the duration of breastfeeding, in particular during the first 4 months, was increasingly associated with the WISC-VCI score. We also observed statistically significant associations between breastfeeding itself or the duration of breastfeeding and better performance on several NEPSY subtests, including visual attention, design copying, arrows, and narrative memory. SEM analysis confirmed these associations. No statistical association was observed between breastfeeding and the WISC Working Memory Index or other NEPSY subtests.Discussion: These data support current national and World Health Organization global 2025 targets of promoting breastfeeding for at least 4 to 6 months
Large mammal population trends in Comoé National Park (1958–2022): Towards understanding their asymmetric decline and recovery in West Africa’s largest savanna park
No full textInternational audienceAfrica’s wildlife decline has received increasing attention, yet underlying reasons have remained opaque. Using generalized additive models of 25 terrestrial and aerial counts, we present West Africa’s first large herbivore population trend series alongside potential drivers. Following Comoé national park’s creation in 1968, large herbivore populations increased till the mid-1980s, but subsequently declined, amplified during Côte d’Ivoire’s political crisis (2002–2011) when active management ceased. Between 2010–2022, populations of roan, hartebeest and waterbuck have quasi-recovered to pre-crisis numbers. The previously dominant kob, common hippopotamus and savanna elephant have remained at c. 10% of their 1970-80s numbers, however. Grasslands declined from 15 to 2% between 1979–2020, negatively impacting kob and common hippopotamus. Since 1962, surrounding human populations and cattle inside the park increased over six-fold, yet the number of rangers only doubled. These developments have resulted in a different wildlife assemblage. Species typical of long-coarse shrub savanna - hartebeest and roan – have reached pre-crisis levels, contrary to kob and common hippopotamus likely because of the reduction of floodplain grasslands and their gregarious distribution rendering them vulnerable to poaching. We recommend increased efforts to understand habitat changes and poaching pressures, prior to re-introducing extinct species. This study highlights the importance but also the challenges of studying large herbivore populations trends alongside drivers of change
