7 research outputs found

    Impact pronostique de la concentration des fragments courts d’ADN libre circulant chez des patients atteints de glioblastome nouvellement diagnostiquĂ©, non rĂ©sĂ©quĂ©

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    Contexte : L’évaluation prĂ©coce de la rĂ©ponse au traitement est un problĂšme rĂ©current pour les patients traitĂ©s pour un glioblastome. La concentration de l’ADN libre circulant (cfDNA), ayant dĂ©montrĂ© un impact pronostique, est influencĂ©e par de nombreux paramĂštres systĂ©miques. Un autre biomarqueur pronostique qui reflĂšte au mieux l’évolution tumoral est nĂ©cessaire. L’objectif de l’étude est d’évaluer l’impact pronostique de la variation de la concentration des fragments courts d’ADN libre circulant chez des patients atteints de glioblastome nouvellement diagnostiquĂ©, non opĂ©rĂ©. MĂ©thodes : Nous avons conduit une Ă©tude ancillaire de l’essai prospectif GLIOPLAK dans laquelle ont Ă©tĂ© sĂ©lectionnĂ© les patients atteint d’un glioblastome histo-molĂ©culaire IDH sauvage selon la classification WHO 2021 CNS5. Les patients ayant eu une rĂ©section partielle ou totale au diagnostic Ă©taient exclus. Tous les patients ont Ă©tĂ© traitĂ©s par radiochimiothĂ©rapie concomitante aprĂšs biopsie diagnostique. Les plasmas Ă©taient collectĂ©s Ă  trois temps : avant (prĂ©-RT) et aprĂšs (post-RT) la radiochimiothĂ©rapie et au moment de la progression tumorale. L’ADN libre circulant (cfDNA) Ă©tait extrait des plasmas Ă  l’aide du kit QIAamp circulating nucleic acid (QiagenÂź) et la concentration des fragments courts d’ADN libre circulant (slDNA), mesurĂ©s aprĂšs Ă©lectrophorĂšse avec l’automate 4200 TapeStation SystemÂź. L’objectif principal Ă©tait d’évaluer l’impact sur la survie de la variation des slDNA pendant la radiochimiothĂ©rapie concomitante. Les objectifs secondaires Ă©taient d’évaluer la corrĂ©lation entre le volume tumoral initial, l’exposition aux corticoĂŻdes et la concentration de slDNA, ainsi que l’impact de la concentration d’ADN libre circulant (cfDNA) sur les donnĂ©es de survie. RĂ©sultats : 38 patients ont Ă©tĂ© inclus dans l’étude ; l’ñge mĂ©dian Ă©tait de 63 ans [55 ;66], 84.2% (n=32) ont un indice de Karnofsky supĂ©rieur Ă  80% Ă  l’inclusion et la survie mĂ©diane est de 13.3 mois [CI 95% 11.5;15.5]. Les fragments courts d’ADN libre circulant (slDNA) Ă©taient dĂ©tectĂ©s pour 69.4% des patients en prĂ©-RT (9.3 ng/mL ±19.9) et dans 83.3% des cas en postRT (8.3 ng/mL ±13.4). La prĂ©sence de slDNA en prĂ©-RT est corrĂ©lĂ©e Ă  une meilleure survie globale : 11.7 mois [9.8-19.6] dans le groupe slDNA(+) versus 8.8 mois [5.5-NA] dans le groupe slDNA(-), HR=0.309 [0.133-0.716], p=0.004. La diminution de la concentration de slDNA entre prĂ© et post-RT est aussi significativement associĂ©e Ă  une meilleure survie en comparaison Ă  une augmentation ou une stabilitĂ© : 13.2 mois [11.4;NA] contre 9.6 mois [6.9;11.5], ou 6.8 mois [4.5; NA], p=0.015. L’exposition aux corticoĂŻdes n'est pas corrĂ©lĂ©e Ă  la concentration de slDNA Ă  l’inclusion ou Ă  sa variation, avec respectivement des coefficients de corrĂ©lation Ă  0.123 et 0.162. En prĂ©-RT, la prĂ©sence de slDNA est indĂ©pendante du volume tumoral initial : volume moyen de 265.0 cm3 ±84.7 dans slDNA(+) contre 237.7 cm3 ±115.7 dans slDNA(-), p=0.492. La concentration de cfDNA n’est pas corrĂ©lĂ©e aux donnĂ©es de survie dans notre Ă©tude. Conclusion : La concentration slDNA est un facteur pronostic indĂ©pendant pour les patients suivis pour un glioblastome non opĂ©rĂ©. Le rĂŽle des slDNA comme biomarqueur, pour adapter le traitement aprĂšs radiochimiothĂ©rapie doit ĂȘtre explorĂ© dans des Ă©tudes dĂ©diĂ©es

    Produktionsassessment 4.0 : Entwicklung eines Reifegradmodells zur Bewertung der Lean Management und Industrie-4.0-Reife von produzierenden Unternehmen

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    Angesichts des breiten Angebotsspektrums neuer Technologien und der Vielzahl verschieden verwendeter Begriffe rund um Industrie 4.0, stehen Unternehmen nicht selten orientierungslos vor der Herausforderung, individuelle Umsetzungsstrategien abzuleiten. Das vorliegende Reifegradmodell ermöglicht die Erfassung bereits im Produktionssystem implementierter Lean Management-Prinzipien und gibt praktikable Antworten auf die evolutionĂ€ren Visionen, indem es realisierbare und individuelle Migrationspfade in Richtung Industrie 4.0 fĂŒr Unternehmen aufzeigt.Production assessment 4.0 – development of a maturity model to assess the Lean Management and Industrie 4.0 maturity of manufacturing companies. Facing the huge range of new technologies and the variety of different terms used around Industrie 4.0 companies are often disoriented towards the challenge of developing a customized implementation strategy. The maturity model enables the evaluation of implemented lean management principles in the production system and accesses the evolutionary visions by creating feasible as well as individual migration paths for companies

    Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients

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    Background: Liquid biopsy application is still challenging in glioblastoma patients and the usefulness of short-length DNA (slDNA) fragments is not established. The aim was to investigate slDNA concentration as a prognostic marker in unresected glioblastoma patients. Methods: Patients with unresected glioblastoma and treated by radiochemotherapy (RT/TMZ) were included. Plasmas were prospectively collected at three times: before (pre-) RT, after (post-) RT and at the time of progression. Primary objective was to investigate the impact on survival of slDNA concentration [slDNA] variation during RT/TMZ. Secondary objectives were to explore the association between tumor volume, corticosteroid exposition and [slDNA]; and the impact of slDNA detection at pre-RT on survival. Results: Thirty-six patients were analyzed: 11 patients (30.6 %) experienced [slDNA] decrease during RT/TMZ, 22 patients (61.1 %) experienced increase and 3 patients (8.3 %) had stability. Decrease of [slDNA] during RT/TMZ was associated with better outcome compared to increase or stability: median OS, since end of RT, of 13.2 months [11.4 - NA] vs 10.1 months [7.8 - 12.6] and 6.8 months [4.5 - NA], p = 0.015, respectively. slDNA detection at pre-RT time was associated with improved OS: 11.7 months in the slDNA(+) group versus 8.8 months in the slDNA(-) group, p = 0.004. [slDNA] was not associated with corticosteroids exposition or tumor volume. No influence on survival was observed for both whole cfDNA concentration or slDNA peak size. Conclusion: [slDNA] decrease during radiochemotherapy phase is a favorable prognostic marker on OS for unresected glioblastoma patients. Larger and independent cohorts are now required. Trial registration: ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=

    SPHERE/ZIMPOL high resolution polarimetric imager

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    International audienceContext. The SPHERE “planet finder” is an extreme adaptive optics (AO) instrument for high resolution and high contrast observations at the Very Large Telescope (VLT). We describe the Zurich Imaging Polarimeter (ZIMPOL), the visual focal plane subsystem of SPHERE, which pushes the limits of current AO systems to shorter wavelengths, higher spatial resolution, and much improved polarimetric performance.Aims. We present a detailed characterization of SPHERE/ZIMPOL which should be useful for an optimal planning of observations and for improving the data reduction and calibration. We aim to provide new benchmarks for the performance of high contrast instruments, in particular for polarimetric differential imaging.Methods. We have analyzed SPHERE/ZIMPOL point spread functions (PSFs) and measure the normalized peak surface brightness, the encircled energy, and the full width half maximum (FWHM) for different wavelengths, atmospheric conditions, star brightness, and instrument modes. Coronagraphic images are described and the peak flux attenuation and the off-axis flux transmission are determined. Simultaneous images of the coronagraphic focal plane and the pupil plane are analyzed and the suppression of the diffraction rings by the pupil stop is investigated. We compared the performance at small separation for different coronagraphs with tests for the binary α Hyi with a separation of 92 mas and a contrast of Δm ≈ 6m. For the polarimetric mode we made the instrument calibrations using zero polarization and high polarization standard stars and here we give a recipe for the absolute calibration of polarimetric data. The data show small ( 100, and the suppression of the diffracted light improves the contrast performance by a factor of approximately two in the separation range 0.06″−0.20″. The polarimetric sensitivity is Δp < 0.01% and the polarization zero point can be calibrated to better than Δp ≈ 0.1%. The contrast limits for differential polarimetric imaging for the 400 s I-band data of R Aqr at a separation of ρ = 0.86″ are for the surface brightness contrast SBpol( ρ)−mstar ≈ 8m arcsec−2 and for the point source contrast mpol( ρ)−mstar ≈ 15m and much lower limits are achievable with deeper observations.Conclusions. SPHERE/ZIMPOL achieves imaging performances in the visual range with unprecedented characteristics, in particular very high spatial resolution and very high polarimetric contrast. This instrument opens up many new research opportunities for the detailed investigation of circumstellar dust, in scattered and therefore polarized light, for the investigation of faint companions, and for the mapping of circumstellar Hα emission
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