151 research outputs found

    Beaurieux, Cury-lès-Chaudardes – La Plaine (zone 3)

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    Identifiant de l'opération archéologique : 9252 Date de l'opération : 2007 (FP) Le rapport de fouille n’étant pas encore réalisé, cette notice constitue une présentation préliminaire. Le site repéré en 2004 lors d’un diagnostic dirigé par Frédéric Gransar (Inrap), se trouve à 35 km à l’est de Soissons sur une terrasse de la rive droite de l’Aisne. D’un point de vue archéologique, le gisement se localise dans un environnement très riche, en face notamment du village rubané de Cuiry-lès-Chaudar..

    Le bâtiment monumental de Beaurieux « La Plaine » : bâtiment unique ou évolution terminale du modèle danubien ?

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    Le bâtiment monumental de Beaurieux « La Plaine » se trouve au sein d’une nécropole monumentale qui comprend deux à trois monuments funéraires appartenant à la culture du Cerny (4 700-4 300 av. notre ère), un monument funéraire du Michelsberg ancien (4 700-4 300 av. notre ère) ainsi que quatre sépultures allant du Michelsberg ancien au Michelsberg récent (4 000-3 500 av. notre ère). Ce bâtiment a déjà fait l’objet d’une présentation, c’est pourquoi nous n’en rappellerons ici que les principau..

    Cuiry-lès-Chaudardes, Beaurieux – La Plaine (zone 2 sud)

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    Identifiant de l'opération archéologique : 8960 Date de l'opération : 2006 (MH) L'intervention archéologique réalisée en 2006 précède l’exploitation de 92 000 m² d’une carrière de granulats réalisée par la Compagnie des Sablières de la Seine. Le diagnostic (Gransar, Baillieu et Naze, 2004) suggérait la présence possible d’une enceinte Cerny ou d’un monument funéraire. La prescription a porté sur l’ensemble de la parcelle avec une surveillance archéologique des 5 ha, mais la fouille de seuleme..

    The multinational second Diabetes, Attitudes, Wishes and Needs study: results of the French survey

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    International audienceAIM:The second Diabetes, Attitudes, Wishes and Needs (DAWN2â„¢) multinational cross-sectional study was aimed at generating insights to facilitate innovative efforts by people with diabetes (PWD), family members (FMs), and health care professionals (HCPs) to improve self-management and psychosocial support in diabetes. Here, the French data from the DAWN2â„¢ study are described.METHODS:In France, 500 PWD (80 with type 1 diabetes [T1] and 420 with type 2 diabetes [T2]), 120 FMs, and 288 HCPs were recruited. The questionnaires assessed the impact of diabetes on quality of life and mood, self-management, attitudes/beliefs, and care/support.RESULTS:Diabetes negatively impacted the emotional well-being of 59% of people with T1 versus 45% of people with T2 (P<0.05) and about half of FMs. A high level of distress was felt by about half of PWD and FMs. About half of HCPs reported assessing depression in their patients. Sixty-two percent of FMs considered managing diabetes to be a burden. Hypoglycemia was a source of concern for 64% of people with T1 and 73% of FMs of insulin users. About two-thirds of non-insulin-medicated people with T2 agreed to start insulin if prescribed, while half of HCPs preferred to delay insulin initiation. A discrepancy between HCPs' perceptions of their interactions with their patients and PWD's recollection of these interactions with regard to patients' personal needs and distress was also observed.CONCLUSION:While distress remains under-assessed by HCPs, the negative impact of diabetes on the lives of PWD and FMs clearly induces distress on both groups. These findings provide new understanding of barriers precluding optimal management of diabetes. Developing strategies to overcome these barriers is now warranted

    Le gisement paléolithique multistratifié « les Bossats » à Ormesson (Seine-et-Marne, France) : palethnographie ou pâle ethnographie ? Une synthèse des huit premières années de fouille (2009-2016)

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    editorial reviewedÀ l'évidence, ces vingt dernières années ont vu en France, notamment, se développer en parallèle deux nouvelles façons de traiter le Paléolithique supérieur ancien qui ne sont pas antagonistes d'ailleurs. L'une consiste en une reprise des stratigraphies anciennes dans le Centre et le Sud-Ouest de la France plus spécifiquement et est associée à une meilleure redéfinition des entités culturelles par l'analyse détaillée des différentes composantes des systèmes techniques. L'autre s'efforce d'appliquer à cette période la démarche palethnographique, inféodée historiquement au Magdalénien du Bassin parisien. Il est vrai que peu de gisements autorisaient ce type d'approche, en raison d'une surface fouillée insuffisante ou d'un état de conservation médiocre, mais même lorsque les découvertes s'y prêtaient, le manque de temps et d'investissement freinait également toute velléité d'une étude approfondie des sites en question, qui aurait alors débouché sur une lecture palethnographique des lieux et des artefacts. À l'issue d'un PCR mené entre 1999 et 2005, nous pouvions ainsi légitimement nous demander si nous étions capables de jouer les ethnologues du passé pour le Paléolithique supérieur ancien dans le Bassin parisien. Les sites identifiés dans le cadre de ce programme de recherche étaient certes nombreux mais représentés surtout par des découvertes de surface, ils ne garantissaient pas un niveau d'analyse digne de ce qui a pu se faire depuis plus de 50 ans à Pincevent ou à Étiolles par exemple (Bodu et al., 2013). Il aura fallu attendre la découverte fortuite du gisement de plein-air d'Ormesson « les Bossats » (Seine-et-Marne, près de Nemours) au début des années 2000 pour que cette question trouve une réponse positive. Concernant, au départ, presqu'exclusivement des vestiges lithiques et osseux attribués au Gravettien, les premières fouilles menées en 2009 permirent d'identifier rapidement un second niveau d'occupation, d'attribution moustérienne. Les campagnes suivantes amenèrent à la découverte de cinq autres niveaux d'occupation paléolithiques, inégaux tant pour la surface couverte que pour l'état de conservation : un second niveau moustérien résultant vraisemblablement de palimpsestes, un ensemble châtelperronien, un autre solutréen, un quatrième badegoulien et enfin entre Châtelperronien et Gravettien, un foyer isolé sans vestiges archéologiques associés. Cette stratigraphie paléolithique de plein-air dilatée est le témoignage d'une forte occupation du lieu pendant près de 30 000 ans, ce qui s'explique notamment par la configuration particulière de la vallée à cet endroit. À la diversité chronologique des occupations préhistoriques répond une diversité des comportements économiques et techniques au sein des différentes sphères d'activités mais également des habitudes spatiales différentes. À l'issue des huit premières années de fouille (2009-2016), le site d'Ormesson « les Bossats » permet ainsi de développer une approche détaillée des comportements techniques, économiques, spatiaux de groupes culturels distincts ayant vécu durant 30 000 ans dans un cadre géomorphologique et plus globalement naturel, relativement identique. Dépassant le jeu de mot facile « palethnographie ou pâle ethnographie ? » à Ormesson « les Bossats », nous proposons ici quelques éléments de réponse

    The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

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    International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

    Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

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    Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

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    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

    Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

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    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat
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