Benchmarking eleven biodiversity indicators based on environmental DNA surveys: more diverse functional traits and evolutionary lineages inside marine reserves

To mitigate the ongoing threats to coastal ecosystems, and the biodiversity erosion they are causing, Marine Protected Areas (MPAs) have emerged as powerful and widespread conservation tools. Strictly no-take MPAs, also called marine reserves, undeniably promote fish biomass and density, but it remains unclear how biodiversity responds to protection. Identifying which facets of biodiversity respond to protection is critical for the management of MPAs and the development of relevant conservation strategies towards the achievement of biodiversity targets. We collected 99 environmental DNA (eDNA) samples inside and outside nine marine reserves in the Mediterranean Sea to assess the effect of protection on 11 biodiversity indicators based on fish traits, phylogeny and vulnerability to fishing. We controlled for the effect of environmental heterogeneity (habitat, bathymetry, productivity, temperature, and accessibility) using a Principal Component Analysis, and for spatial autocorrelation due to potential unmeasured factors. We found a positive and significant effect of protection on only 3 out of 11 indicators: functional and phylogenic diversity but also the ratio between demerso-pelagic and benthic species richness. Rather, total fish richness responded significantly and negatively to protection. We did not detect any significant effect of protection on threatened and elasmobranch species richness, probably due to their large home range compared to the size of Mediterranean marine reserves. Synthesis and applications: Our findings highlight the importance of looking beyond the mere number of species to fully depict and understand the effect of marine reserves on biodiversity and evaluate the effectiveness of conservation measures. Rather, we propose a dashboard of three eDNA-based indicators that can provide an early signal of ecosystem deterioration or recovery. eDNA metabarcoding offers a powerful tool to supply site-specific and standardized taxonomic-, phylogenetic- and trait-based biodiversity assessments, in complement to other classical technics, such as visual censuses or video surveys, able to estimate species abundance but also individual life-stage and size

Opérer ou non une lésion atypique du sein ? Prise en compte de l’anxiété dans l’aide à la décision partagée à partir d’une cohorte prospective de 300 patientes

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions "(ABL). Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, p<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.INTRODUCTION: Les dépistages mammaires organisés et individuels se sont accompagnés d’une augmentation de la détection de lésions « frontières » (LF). Récemment, l’étude multicentrique NOMAT a proposé un modèle prédictif du risque de développer un cancer après détection d’une LF afin d’éviter l’exérèse chirurgicale de lésions à « bas risque ». Elle avait également pour objectif de renseigner le vécu psychologique, notamment l’anxiété, afin d’orienter le processus de décision médicale partagée. MATÉRIELS ET MÉTHODES : Trois cents femmes opérées pour une LF du sein ont été incluses entre 2015 et 2018 dans 18 centres français. Les femmes remplissaient avant et après chirurgie des questionnaires évaluant leurs niveaux d’anxiété situationnelle et habituelle (STAI-Etat et Trait) et d’intolérance à l’incertitude, leur perception du risque de développer un cancer et leur satisfaction vis-à-vis de la prise en charge. RÉSULTATS : Cent quatre-vingt-dix-neuf femmes ont complété le STAI-Etat avant et après chirurgie. Globalement, une diminution du niveau d’anxiété (35,4 vs. 42,7, p < 0,001) a été observée. Un tempérament anxieux et une plus grande intolérance à l’incertitude étaient significativement associés à une diminution de l’anxiété (33 % des femmes), tandis qu’un plus jeune âge était associé à une augmentation de l’anxiété (8 % des femmes). CONCLUSION : La chirurgie des LF ne semble s’associer que dans très peu de cas à une augmentation de l’anxiété et ne fait évoluer qu’à la marge la perception du risque de développer un cancer. La prise en compte de la dimension psychologique reste dans tous les cas essentielle dans la décision médicale partagée

Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions

International audienceBackground: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.- methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH

Severe ADAMTS13 Deficiency in Adult Idiopathic Thrombotic Microangiopathies Defines a Subset of Patients Characterized by Various Autoimmune Manifestations, Lower Platelet Count, and Mild Renal Involvement

International audienceThe significance of ADAMTS13 deficiency in adult thrombotic microangiopathy (TMA) remains controversial. In an attempt to define the characteristics of adult TMA with severe ADAMTS13 deficiency, we determined 2 groups of patients on the basis of ADAMTS13 activity (undetectable or detectable). Clinical presentation, laboratory values, autoimmune manifestations, and outcome were compared between the groups. Patients were included retrospectively from 12 centers. All fulfilled the diagnosis criteria of TMA. Patients with a history of transplantation, cancer and chemotherapy, and Centers for Disease Control and Prevention (CDC) stage C human immunodeficiency virus (HIV) infection were not included. Forty-six patients were included. Thirty-one patients had an undetectable ADAMTS13 activity (25%. Severe ADAMTS13 deficiency was associated with a plasmatic inhibitor in 17 cases (55%), suggesting an immune-mediated mechanism. Patients with undetectable ADAMTS13 were more frequently of Afro-Caribbean origin than patients with detectable ADAMTS13 activity (48.4% vs 13.3%, respectively; p = 0.03). As opposed to patients with detectable ADAMTS13 activity, patients with severe ADAMTS13 deficiency displayed various autoimmune manifestations that consisted of nondestructive polyarthritis (4 cases) associated in 1 case with malar rash and extramembranous glomerulonephritis, discoid lupus (3 cases), and autoimmune endocrinopathies, Raynaud phenomenon, and sarcoidosis-like disease (1 case each). In patients with severe ADAMTS13 deficiency, antinuclear antibodies, anti-double-stranded DNA antibodies, and anticardiolipin antibodies were positive in 22 (71%) cases, 3 (9.7%) cases, and 1 (3.2%) case, respectively. One patient fulfilled the criteria for the diagnosis of systemic lupus erythematosus. During follow-up, 1 patient with severe ADAMTS13 deficiency developed antinuclear antibodies, and 3 others developed anti-double-stranded DNA antibodies, in association with neurologic manifestations and anticardiolipin antibodies in 1 case. Patients with severe ADAMTS13 deficiency also had a lower platelet count (12 x 10(9)/L; range, 2-69 x 10(9)/L) and less severe renal failure (estimated glomerular filtration rate: 78 mL/min; range, 9-157 mL/min) than patients with detectable ADAMTS13 activity (49.5 x 10(9)/L; range, 6-103 x 10(9)/L; p = 0.0004, and 15.8 mL/min; range, 5.6-80 mL/min; p < 0.0001, respectively). End-stage renal failure occurred in 1 patient with severe ADAMTS13 deficiency and in 3 patients with detectable ADAMTS13 activity (3.2% vs 21.4%, respectively; p = 0.08). Flare-up and relapse episodes and survival were comparable between the groups. Taken together, these data indicate that adult idiopathic thrombotic thrombocytopenic purpura, as defined by severe ADAMTS13 deficiency, may occur preferentially in a particular ethnic group, and is characterized by severe thrombocytopenia, mild renal involvement, and a wide spectrum of autoimmune manifestations that may be completed during follow-up. Indeed, apparently idiopathic thrombotic thrombocytopenic purpura may be considered a specific autoimmune disease

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old