Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Overland flow and sediment transport in an agricultural lowland catchments: a focus on tile drain export

International audienceRural landscapes have been extensively modified by human activities in Western Europe since the beginning of the 20th century in order to intensify agricultural production. Cultivated areas often expanded at the expense of grassland and wetlands located in lowland areas (de Groot et al., 2002). Therefore, large modifications were made to the agricultural landscapes: stream redesign, land consolidation, removal of hedges, and installation of tile drainage networks to drain the hydromorphic soils. These changes modified sediment processes and resulted in large morphological alterations (e.g. channel bed incision, deposition of fine sediment, channel bank erosion). Accordingly, these alterations threaten water quality and prevent to meet the requirements of the European directives. Improving water quality requires a clear understanding of the hydrosedimentary dynamics in these lowland cultivated catchments. However, few studies were conducted in drained environments. To fill this research gap, a pilot study was started in cultivated catchment of the Loire River basin, France, where tile drain densities are very high (> 1.5 km/km$^2$). Six hydro-sedimentary monitoring stations were installed in the Louroux catchment (24 km 2). One of them was specifically dedicated to measuring water/sediment fluxes from tile drains. Water level and turbidity were continuously monitored and sediments were sampled during floods and low stage periods. Samples were measured for particle size distribution, and sediment tracing studies are currently being developed to quantify the contribution of potential sources (e.g. surface vs subsurface, lithologies) to river sediment. Hydro-sedimentary fluxes were quantified and modelled for some selected events. The catchment hydrosedimen-tary fluxes and their properties were shown to be impacted by tile drain sediment transport, especially regarding particle size distribution, with the dominant export of very fine particles (< 2 $\mu$m) from tile drains. This study demonstrates that tile drain transport should be included when developing and running hydro-sedimentary models in catchments, and particularly in lowland/wetland environments

Overland flow and sediment transport in agricultural lowland catchments: a focus on tile drain export

International audienceRural landscapes have been extensively modified by human activities in Western Europe since the beginning of the 20th century in order to intensify agricultural production. Cultivated areas often expanded at the expense of grassland and wetlands located in lowland areas (de Groot et al., 2002). Therefore, large modifications were made to the agricultural landscapes: stream redesign, land consolidation, removal of hedges, and installation of tile drainage networks to drain the hydromorphic soils. These changes modified sediment processes and resulted in large morphological alterations (e.g. channel bed incision, deposition of fine sediment, channel bank erosion). Accordingly, these alterations threaten water quality and prevent to meet the requirements of the European directives. Improving water quality requires a clear understanding of the hydrosedimentary dynamics in these lowland cultivated catchments. However, few studies were conducted in drained environments. To fill this research gap, a pilot study was started in cultivated catchment of the Loire River basin, France, where tile drain densities are very high (> 1.5 km/km²). Six hydro-sedimentary monitoring stations were installed in the Louroux catchment (24 km²). One of them was specifically dedicated to measuring water/sediment fluxes from tile drains. Water level and turbidity were continuously monitored and sediments were sampled during floods and low stage periods. Samples were measured for particle size distribution, and sediment tracing studies are currently being developed to quantify the contribution of potential sources (e.g. surface vs subsurface, lithologies) to river sediment. Hydro-sedimentary fluxes were quantified and modelled for some selected events. The catchment hydrosedimentary fluxes and their properties were shown to be impacted by tile drain sediment transport, especially regarding particle size distribution, with the dominant export of very fine particles (< 2 µm) from tile drains. This study demonstrates that tile drain transport should be included when developing and running hydro-sedimentary models in catchments, and particularly in lowland/wetland environments

Study of cognitive, socio-emotional and autistic behavior evolution in children with Autism ant other Pervasive Developmental Disorders benefiting of a structured intervention, Applied Behavior Analysis

International audienceContext. - Recommendations of the Great Health Authority (HAS, 2012) indicate that children with autism and other pervasive developmental disorders have to benefit of scientifically validated behavioral and developmental structured interventions as early as possible, such as for example Applied Behavior Analysis (ABA). In this context, this not randomized and with no controlled group longitudinal study aims at confirming the interest of the behavioral approach ABA intervention for children with autism (n = 10) cared in a Parisian educational establishment dedicated to autism. Objective. - To examine the evolution of both their cognitive and socio-emotional development and autistic behaviors with validated and appropriated tests and scales (PEP 3, BECS, EDEI-R; BSE-R, BFE) proposed three times (T1, T2 and T3) over a period of 20 months and at intervals of 10 months between Tl and T2 and T2 and T3. The children of this study are examined by expert psychologists external to the establishment. Hypothesis. - It is postulated that there is both an increasing in cognitive and socio-emotional development domains and a decreasing in autistic behavior. Moreover, it was hypothesized that the developmental and behavioral progresses are better for youngest children and for these ones who have a best development level at the beginning of the intervention. Participants. - Ten children with autism (n = 8) and other pervasive developmental disorders (n = 2) were included. They were aged from 4 years and 2 months to 11 years and 1 month of age. Diagnosis was carried out with DSM-IV-TR criteria and CARS by specialist practitioners and psychiatrists. Nine children on 10 exhibited a developmental delay and for those who were mentally retarded, the degree of severity of delay was variable (Global Developmental Quotient: from 21 to 57). All these children benefit of ABA method five days a week, which is provided by specially trained educators who were coached and supervised by a psychologist ``BCBA-Board Certified Behavior Analyst''. Results. - The cognitive, socio-emotional and behavioral evolution of these 10 children was overall good over period of 20 months, variable and heterogeneous from one child to another and rather not regular to under -period to another. The autistic symptomatology decreased after 8 months of intervention (between Tl and T2) and after 20 months of intervention (between Tl and T3). Moreover, higher is the developmental age at the beginning of intervention higher is the motor development after 20 months of intervention (between T1 and T3). Discussion. - Focusing on the interest of the ABA intervention, this study permits to confirm that children with autism and intellectual deficiency progress in cognitive and socio-emotional domains and that their autistic symptomatology decrease. (C) 2018 Elsevier Masson SAS. All rights reserved

Quantifying the transfer times of suspended sediment during floods with 7^7Be and 210^{210}Pbxs_{xs} measurements in a drained lowland catchment of central France

International audienceIntensification of agriculture after WWII increased soil erosion and sediment supply to rivers in Northwestern Europe. The Louroux Pond catchment (25 km 2), located in the Loire River basin (central France), is representative of these intensively cultivated environments and subject to severe soil erosion and river siltation. This catchment was equipped with an extensive network of tile drains that were installed after 1945 to produce crops in this former wetland. In order to decrease the deleterious impacts induced by accelerated soil erosion in this region, there is a need to better understand sediment dynamics during flood events. To this end, natural fallout radionuclides were analysed in both sediment sources and suspended matter transiting the river network to quantify the respective proportions of recently eroded vs. resuspended material. Accordingly, 7Be and 210Pbxs concentrations were measured in overland flow and suspended sediment collected in the pond tributaries during a succession of floods that occurred during winter in 2013-2014 and in 2016. The results show that the mean fraction of recently eroded material transiting these rivers increased from 40 ± 20% to 80 ± 20 in 2013-2014, and from 65 ± 20% to 80 ± 20% in 2016. These results demonstrate an initial flush of sediment previously accumulated in the river channel during the first winter floods. Then, the fraction of sediment recently eroded from the hillslopes significantly increased during subsequent events. This research illustrates the added value of combining continuous river monitoring and fallout radionuclide analyses to improve our knowledge of sediment dynamics and to protect soil and water resources in these environments

Accroissement de la contribution des sources d'érosion aux rivières et plans d'eau (1950-2010) : le cas du Louroux (Indre-et-Loire, France)

International audienceSoil erosion is recognized as one of the main processes triggering the physical and chemical degradation of water bodies. Although erosive dynamics have been widely described in morphogenic areas, much less is known about this process in lowland agricultural catchments.To address this issue, a multidisciplinary study was carried out at the scale of a small agricultural lowland catchment (Louroux catchment, France, 25 km (2)) to reconstruct the evolution of the soil erosion rates and sources, from the hillslopes to the deposition areas in the water bodies. This study's goal is specifically to understand the impact of changes in land use and agricultural practices after 1950 (field re-design, ditch creation, drainage) on sediment dynamics For this purpose, sediment cores were collected in a medieval pond (870AD) located at the outlet of the catchment. These cores have been dated and used to reconstruct the temporal variations in sediment fluxes over time (from 1954 to 2013). In addition, sediment sources were identified using fallout radionuclide measurements (cesium-137 and beryllium7 / excess lead-210 ratios). These results will contribute to the implementation of effective management measures to reduce the transfer of sediments from the hillslopes to the hydrosystems.14 15 L'érosion des sols est reconnue comme étant l'un des principaux processus à l'origine de la dégradation physico-16 chimique des masses d'eau. Les phénomènes érosifs, largement décrits en contexte morphogène, restent pourtant 17 peu étudiés en contexte de plaine. 18 Pour combler ce manque, une étude pluridisciplinaire a été menée à l'échelle d'un petit bassin versant (25 km²) 19 de plaine agricole drainée pour reconstruire l'évolution des taux et des sources d'érosion, depuis les zones 20 d'accumulation de matière jusqu'aux zones sources. Cette étude vise ainsi à comprendre l'impact des 21 aménagements intervenus dans le bassin après 1950 (remembrements, création de fossés, drainage) sur la 22 dynamique sédimentaire actuelle et passée. 23 À cette fin, des carottages ont été réalisés dans un étang médiéval (870AD) localisé à l'exutoire du bassin versant 24 du Louroux (France). Les carottes ont été datées et ont permis de reconstruire les variations temporelles du flux 25 sédimentaire (de 1954 à 2013), mais aussi de les associer avec les changements d'usage des sols. Par ailleurs, les 26 sources de sédiments ont été identifiées à partir de mesures de radionucléides (césium 137 et rapport béryllium 27 7/plomb 210 en excès). Ces résultats vont permettre de guider la mise en place d'aménagements pour lutter contre 28 le départ de matière sur les versants. 29 MOTS CLEFS : érosion, sédiment, colmatage, archive sédimentaire, traçage 30 31 Increase of erosion source contributions to rivers and lakes (1950-2010): 32 the case of the Louroux Pond (Central France) 33 Soil erosion is recognized as one of the main processes triggering the physical and chemical degradation of water 34 bodies. Although erosive dynamics have been widely described in morphogenic areas, much less is known about 35 this process in lowland agricultural catchments. 36 To address this issue, a multidisciplinary study was carried out at the scale of a small agricultural lowland 37 catchment (Louroux catchment, France, 25 km²) to reconstruct the evolution of the soil erosion rates and sources, 38 from the hillslopes to the deposition areas in the water bodies. This study's goal is specifically to understand the 39 impact of changes in land use and agricultural practices after 1950 (field redesign , ditch creation, drainage) on 40 sediment dynamics 41 For this purpose, sediment cores were collected in a medieval pond (870AD) located at the outlet of the 42 catchment. These cores have been dated and used to reconstruct the temporal variations in sediment fluxes over 43 time (from 1954 to 2013). In addition, sediment sources were identified using fallout radionuclide measurements 44 (cesium-137 and beryllium7 / excess lead-210 ratios). These results will contribute to the implementation of 45 effective management measures to reduce the transfer of sediments from the hillslopes to the hydrosystems. 46 KEY WORDS: erosion, sediment, siltation, lake deposits, sediment fingerprinting 47 48 4

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer