Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low-and intermediate-risk prostate cancer patients (Gleason scores 6-7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach

Three-Dimensional Investigation of Free-Edge Effects in Laminate Composites Using X-ray Tomography and Digital Volume Correlation

International audienceLaminate composite materials are widely used for many industrial applications because of their high specific mechanical properties as well as the possibility to adapt the structure properties to its application and loading conditions by optimization of the stacking sequence. It is now well known that the mechanical properties mismatch of adjacent layers having different fibre orientation induces stresses concentrations at interlaminar interfaces in the vicinity of structure edges. Edge effects experimental investigation is generally made through two dimensional measurements, crack initiation detection and characterization using various observation techniques. In this paper, it is proposed to investigate edge effects by coupling 2D and 3D measurements, using X-Ray tomography and kinematic field measurements. A preconditioned Digital Volume Correlation is developped in order to capture the in depth evolution of the residual displacement discontinuity at the ply interfaces. After it has been validated by comparison with the 2D measurements on the surface, the analysis of the 3D fields is carried out

Etude tridimensionnelle des singularités de bord libre dans les composites stratifiés

International audienceLes composites stratifiés sont aujourd'hui très largement utilisés dans le monde industriel. En raison de leur architecture spécifique, des phénomènes singuliers peuvent être induits au voisinage des interfaces interlaminaires et entraîner la rupture précoce par délaminage de certaines séquences d'empile-ment. Les singularités de bords libres résultent d'effets combinés entre un bord libre et des hétérogénéités matériaux. Dans ce problème, les états mécaniques à analyser sont tridimensionnels. Ils pourraient être étudiés numériquement mais le rôle majeur joué par la microstructure est mal connu. Ceci a pour conséquence de rendre l'étude de ces variations délicate à la fois numériquement et expérimentalement. Il parait alors incontournable de mener une analyse expérimentale utilisant des outils de caractérisation et de mesure donnant accès à des données tridimensionnelles

High Prevalence of SXT/R391-Related Integrative and Conjugative Elements Carrying bla CMY-2 in Proteus mirabilis Isolates from Gulls in the South of France

International audienceThe genetic structures involved in the dissemination of blaCMY-2 carried by Proteus mirabilis isolates recovered from different gull species in the South of France were characterized and compared to clinical isolates. blaCMY-2 was identified in P. mirabilis isolates from 27/93 yellow-legged gulls and from 37/65 slender-billed gulls. It was carried by a conjugative SXT/R391-like integrative and conjugative element (ICE) in all avian strains and in 3/7 human strains. Two clinical isolates had the same genetic background as six avian isolates

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease

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Scedosporiosis/lomentosporiosis observational study (SOS): Clinical significance of Scedosporium species identification

International audienceScedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes