Search

Background: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. Methods: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49–0.96) but not in females (Pinteraction = 0.08). Conclusions: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. Impact: These findings support an importance of immunosurveillance in colorectal cancer.

Supplemental Table 2 shows the associations between pre-selected SNPs and Visit 2 sMICA and sMICB levels (continuous variables) stratified by sex, race, or diabetes status.

Supplemental Table 4 shows the associations of Visit 2 sMICA and sMICB levels (in quartiles) with CRC risk.

Supplemental Table 3 shows the associations between pre-selected SNPs and CRC risk stratified by sex, race, or diabetes status.

Supplemental Table 8 shows the associations of pre-selected SNPs with Visit 2 sMICA and sMICB levels and CRC risk without adjustment for ancestry markers.

Background:The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development.Methods:sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed.Results:Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49–0.96) but not in females (Pinteraction = 0.08).Conclusions:Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males.Impact:These findings support an importance of immunosurveillance in colorectal cancer.

Supplemental Table 1 shows the results from previous studies that found significant associations between the pre-selected SNPs and risk of cancers or autoimmune diseases.

Supplemental Table 7 shows the association of sMICA and sMICB levels (continuous variables) and pre-selected SNPsa with risk of CRC stratified by family history of CRC.

Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables).

Supplemental Table 10 shows that associations between mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables) with CRC risk.

Supplemental Table 6 shows the associations of sMICA and sMICB levels (continuous variables) and pre-selected SNPsb with risk of CRC and subtypes of CRC.

Supplemental table 5 shows the associations between pre-selected SNPs and risk of CRC with and without adjustment for sMICA and sMICB levels.

The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g

Resistance to chemotherapeutic drugs is a major cause of treatment failure in Acute Myeloid Leukemias (AML). To better characterize the mechanisms of chemoresistance, we first identified genes whose expression is dysregulated in AML cells resistant to daunorubicin (DNR) or cytarabine (Ara-C), the main drugs used for the induction therapy. The genes found activated are mostly linked to immune signaling and inflammation. Among them, we identified a strong up-regulation of the NOX2 NAPDH oxidase subunit genes (CYBB, CYBA, NCF1, NCF2, NCF4 and RAC2). The ensuing increase in NADPH oxidase activity, which is particularly strong in DNR-resistant cells, participates in the acquisition and/or maintenance of resistance to DNR. In addition, analyzing gp91phox (CYBB-encoded Nox2 catalytic sub-unit) expression at the surface of leukemic blasts from 74 patients at diagnosis showed that NOX2 is generally more expressed and active in leukemic cells from the FAB M4/M5 subtypes compared to FAB M0-M2 ones. Using a gene expression-based score we demonstrate that high NOX2 subunit genes expression is a marker of adverse prognosis, independent of the cytogenetic-based risk classification, in AML patients.

International audience

Seagrass meadows are globally distributed ecosystems found on coastal shelves, where they typically occupy the intertidal and shallow subtidal zones. Their sensitivity to environmental changes and proximity to human activities puts them at risk of degradation; as highly valuable marine habitats and potent carbon sequestration agents, they are therefore the target of numerous conservation programmes.The presence of seagrass strongly influences both wave and current propagation as well as sediment mobility, affecting the morphodynamics of entire estuarine systems. However, quantifying this influence is difficult, because our knowledge of seagrass cover is limited by its dynamic nature. Sensitivity to environmental factors such as nutrient load, available sunlight (mediated by turbidity) and temperature makes seagrass meadows prone to widespread changes in extent and density. Further degradation may occur stochastically through fishing and aquaculture. Conversely, seasonal cycles of high productivity allow meadows to recover and colonize new grounds through clonal and sexual reproduction. We propose a novel and cost-effective method to monitor seagrass cover in shallow waters across its seasonal and interannual variations. Combining machine learning and simple numerical modelling, we create a dense time-series of seagrass extent using over 100 LandSat scenes covering a 20-year-long period in the Venice Lagoon, Italy. Based on an expert-lead ecological survey (2004), we train one binary Random Forest Classifier in each of 5 environmentally-homogeneous geographical subzones, using spectral reflectance in the blue, green, red and near-infrared bands of the corresponding LandSat scene as recognition features. We then predict seagrass presence probability for LandSat scenes spanning the 1999-2019 period. Such predictions are made unstable by their sensitivity to sediment plumes as well as algal or gelbstoff blooms. Classification is therefore constrained by a simple numerical model that simulates clonal and sexual reproduction, regional die-off and punctual degradation. The model examines the potential areas colonised or degraded with respect to previous scenes, iteratively building stabilised maps of seagrass cover over time.Results are verified using further expert-lead estival surveys of the lagoon (2009, 2010, 2017) and of the inlets of Lido, Malamocco and Chioggia (2006 to 2015), as well as 10 digitised seagrass patches for a subsample of 20 invernal scenes. Accuracy metrics improve on the raw predictions (>80% to >85%), and scene-to-scene variability is reduced(>50% to

International audience; By using ZnO thin films doped with Ce, Tb or Eu, deposited via radiofrequency magnetron sputtering, we have developed monochromatic (blue, green and red, respectively) light emitting devices (LEDs). The rare earth ions introduced with doping rates lower than 2% exhibit narrow and intense emission peaks due to electronic transitions in relaxation processes induced after electrical excitation. This study proves zinc oxide to be a good host for these elements, its high conductivity and optical transparency in the visible range being as well exploited as top transparent electrode. After structural characterization of the different doped layers, a device structure with intense electroluminescence is presented, modeled, and electrically and optically characterized. The different emission spectra obtained are compared in a chromatic diagram, providing a reference for future works with similar devices. The results hereby presented demonstrate three operating monochromatic LEDs, as well as a combination of the three species into another one, with a simply-designed structure compatible with current Si technology and demonstrating an integrated red-green-blue emission.

Salt marshes filter pollutants, protect coastlines against storm surges, and sequester carbon, yet are under threat from sea level rise and anthropogenic modification. The sustained existence of the salt marsh ecosystem depends on the topographic evolution of marsh platforms. Quantifying marsh platform topography is vital for improving the management of these valuable landscapes. The determination of platform boundaries currently relies on supervised classification methods requiring near-infrared data to detect vegetation, or demands labour-intensive field surveys and digitisation. We propose a novel, unsupervised method to reproducibly isolate salt marsh scarps and platforms from a digital elevation model (DEM), referred to as Topographic Identification of Platforms (TIP). Field observations and numerical models show that salt marshes mature into subhorizontal platforms delineated by subvertical scarps. Based on this premise, we identify scarps as lines of local maxima on a slope raster, then fill landmasses from the scarps upward, thus isolating mature marsh platforms. We test the TIP method using lidar-derived DEMs from six salt marshes in England with varying tidal ranges and geometries, for which topographic platforms were manually isolated from tidal flats. Agreement between manual and unsupervised classification exceeds 94% for DEM resolutions of 1 m, with all but one site maintaining an accuracy superior to 90% for resolutions up to 3 m. For resolutions of 1 m, platforms detected with the TIP method are comparable in surface area to digitised platforms and have similar elevation distributions. We also find that our method allows for the accurate detection of local block failures as small as 3 times the DEM resolution. Detailed inspection reveals that although tidal creeks were digitised as part of the marsh platform, unsupervised classification categorises them as part of the tidal flat, causing an increase in false negatives and overall platform perimeter. This suggests our method may benefit from combination with existing creek detection algorithms. Fallen blocks and high tidal flat portions, associated with potential pioneer zones, can also lead to differences between our method and supervised mapping. Although pioneer zones prove difficult to classify using a topographic method, we suggest that these transition areas should be considered when analysing erosion and accretion processes, particularly in the case of incipient marsh platforms. Ultimately, we have shown that unsupervised classification of marsh platforms from high-resolution topography is possible and sufficient to monitor and analyse topographic evolution.

International audience

International audience

Retreat and progradation make the edges of salt marsh platforms their most active features. If we have a single topographic snapshot of a marsh, is it possible to tell if some areas have retreated or prograded recently or if they are likely to do so in the future? We explore these questions by characterising marsh edge topography in mega-tidal Moricambe Bay (UK) in 2009, 2013 and 2017. We first map outlines of marsh platform edges based on lidar data and from these we generate transverse topographic profiles of the marsh edge 10 m long and 20 m apart. By associating profiles with individual retreat or progradation events, we find that they produce distinct profiles when grouped by change event, regardless of event magnitude. Progradation profiles have a shallow scarp and low relief that decreases with event magnitude, facilitating more progradation. Conversely, steep-scarped, high-relief retreat profiles dip landward as retreat reveals older platforms. Furthermore, vertical accretion of the marsh edge is controlled by elevation rather than its lateral motion, suggesting an even distribution of deposition that would allow bay infilling were it not limited by the migration of creeks. While we demonstrate that marsh edges can be quantified with currently available DTMs, oblique observations are crucial to fully describe scarps and better inform their sensitivity to wave and current erosion.

High energy, rocky coastlines often feature sandy beaches within headland‐bound embayments. Not all such embayments have beaches however, and beaches in embayments can be removed by storms and may subsequently reform. What dictates the presence or absence of an embayed beach and its resilience to storms? In this paper, we explore the effect of offshore slope and wind conditions on nearshore sediment transport within idealised embayments to give insight into nearshore sediment supplies. We use numerical simulations to show that sand can accumulate near shore if the offshore slope is >0.025 m/m, but only under persistent calm conditions. Our modelling also suggests that if sediment in an embayment with an offshore gradient steeper than 0.025 m/m is removed during a period of persistent stormy conditions, it will be unlikely to return in sub‐decadal timescales. In contrast, sediment located in embayments with shallower gradients can reform swiftly in both calm and stormy conditions. Our findings have wide implications for contemporary coastal engineering in the face of future global climate change, but also for Quaternary environmental reconstruction. Our simple method to predict beach stability based on slope can be used to interpret differing responses of embayments to periods of changing coastal storminess such as the medieval climate anomaly‐little ice age (MCA‐LIA) transition.

Jean-Yves Niemier,1,2 Frédérique Claudot,3,4 Phi Linh Nguyen-Thi,4 Jean-Marie Hubert,5 Hubert Rousselot,2,6 Athanase Benetos,1 Christine Perret-Guillaume1,3 1Department of Geriatric Medicine, CHRU de Nancy, Nancy, France; 2UCOG Lorraine, Nancy, France; 3EA 4360 APEMAC, Faculté de Médecine, Université de Lorraine, Nancy, France; 4PARC, CHRU de Nancy, Nancy, France; 5Spincourt Multidisciplinary MSP, Spincourt, France; 6SISSPO Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France Objective: The objective of this study was to identify changes in the decision-making criteria of general practitioners (GPs) concerning the care of elderly cancer patients after 1year of corrective measures for care practices in the Lorraine region, France. Materials and methods: In 2014, a postal mail questionnaire was sent to all GPs in the Lorraine region. This questionnaire was designed to identify GPs’ decision-making criteria. It was based on the results of a literature review and on existing guidelines. During 1year, corrective measures were implemented to improve practices, especially training sessions for physicians and production of specific tools, including a guide to the accepted ideas in geriatric oncology. In 2015, the same questionnaire was resent to all GPs to compare the answers. Results: In 2014, 430 questionnaires were returned out of 2,048 sent, and in 2015, 378 questionnaires were returned out of 2,066 sent. Our results show for the first time that there exists a significant difference in the overall decision criteria between the two survey periods. This difference mainly concerns criteria related to the cancerous diseases. Physicians tend to consider the principal decision criteria to be less important after the training period. GPs express the importance of accessibility to specialists for additional advice in both 2014 and 2015; the distance between the patient’s home and an adapted care facility and the interval before care begins are viewed as similarly important. Conclusion: Training and information sessions for physicians remain the most important tool for improving care practices. Such training strategies are more effective when carried out at the geographical scale at which the cancer professionals practice, allowing them to exploit their local organizational structure. The analysis of our data makes it possible to further integrate the patient into the care path, which remains a public health issue in terms of cost and organization. Keywords: elderly, cancer, general practitioner, treatment decision-making, care improvement, older people, tumors, physician, management, ethics

We combine sea level records and repeat lidar surveys at 8 sites in the United Kingdom and the United States to explore controls on marsh accretion. We compare marsh elevations relative to sea level as well as lidar-derived marsh accretion rates to simple 0-dimensional settling simulations in order to explore constraints on suspended sediment concentration and particle size.We find that the marsh platforms examined occupy a narrow range of elevations in the upper tidal frame, situated between Mean High Tide $MHT$ and the Observed Highest High Tide $OHHT$. Under sinusoidal tidal forcing, common in marsh accretion models, marshes at these elevations are never inundated, highlighting the inadequacy of sinusoidal forcing in numerical models of salt marshes.Forcing the model with year-long tidal records, deposition rates follow hyperbolic contour lines when expressed as a function of sediment concentration and median grain size.We also observe that when using a median sediment grain size $D_{50} = 50 \ \mu m$ and sediment concentrations derived from satellite data, modeled deposition rates are much lower than when using field data.We find that the deposition of coarse, concentrated sediment is necessary for platforms in the upper tidal frame to withstand sea level rise, suggesting a strong dependance on infrequent high-deposition events.This is particularly true for marshes that are very high in the tidal frame, making accretion increasingly storm-driven as marsh platforms gain elevation.Finally, we reflect on the capacity of marshes to regenerate after erosion events within a context of changing sediment supply conditions.

Background: Several bacterial taxa that are consistently enriched in the gut microbiome of CRC cases are also found in the oral cavity. They exhibit phenotypic traits such as adherence to host epithelial cells, mucus degradation, and biofilm formation, which promote bacterial survival in the colon and may play a role in both oral disease and colorectal carcinogenesis by stimulating an inflammatory response. We evaluated the effect of a 6-week aspirin intervention on the relative abundance of oral bacterial taxa in a randomized placebo-controlled trial. Methods: Fifty healthy subjects, 50-75 years old, were randomized to receive either aspirin (N=30) or placebo (N=20) for 6 weeks. Oral samples were collected at baseline and after treatment (6 weeks) and amplicon sequencing of the V4 region of the 16S rRNA gene was done using Illumina MiSeq technology. The data were analyzed using the standard DADA2 workflow. We used linear regression analysis, PERMANOVA, and negative binomial regressions (DESeq2 package) to assess the association between intervention assignment (aspirin vs. placebo) and α-diversity, β-diversity, and fold change in specific taxa, after adjustment for age, gender, and BMI at baseline and postintervention. Intervention assignment was hypothesized to influence the following bacterial taxa a priori: Fusobacterium, Porphyromonas, Prevotella, Gemella, Neisseria, Streptococcus, Haemophilus, Campylobacter, Veillonella, Actinomyces based on previous studies. We estimated the association between aspirin use and the changes in the relative abundance of the specified taxa from pre- to post-treatment (baseline to week 6) using a mixed-effect regression model (lme4 package) with a binomial distribution in which the log of odds ratio (β estimate) for the interaction term compared aspirin to placebo intervention for post- versus pretreatment. Results: Aspirin treatment was not associated with α- or β- diversity at baseline or postintervention. However, the change in relative abundance of 8 out of the 10 prespecified taxa over time differed between the aspirin and placebo groups. In the aspirin group, there were greater increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and greater decreases in the relative abundance of Prevotella, Veillonella, Fusobacterium, and Porphyromonas. Conclusions: These preliminary findings suggest that aspirin may change the relative abundance of oral taxa associated with oral dysbiosis or CRC. Further studies are needed to understand the impact that the duration and dosage of the aspirin intervention may have on the oral microbiome. Citation Format: Guillaume C. Chinedu, Christopher M. Staley, Ryan T. Demmer, Shaukat Aasma, Tim R. Church, Anna E. Prizment. Effects of aspirin intervention on health and disease-associated oral bacterial taxa [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A04.

Salt marshes filter pollutants, protect coastlines against storm surges, and sequester carbon, yet are under threat from sea level rise and anthropogenic modification. The sustained existence of the salt marsh ecosystem depends on the topographic evolution of marsh platforms. Quantifying marsh platform topography is vital for improving the management of these valuable landscapes. The determination of platform boundaries currently relies on supervised classification methods requiring near-infrared data to detect vegetation, or demands labour-intensive field surveys and digitisation. We propose a novel, unsupervised method to reproducibly isolate salt marsh scarps and platforms from a digital elevation model (DEM), referred to as Topographic Identification of Platforms (TIP). Field observations and numerical models show that salt marshes mature into subhorizontal platforms delineated by subvertical scarps. Based on this premise, we identify scarps as lines of local maxima on a slope raster, then fill landmasses from the scarps upward, thus isolating mature marsh platforms. We test the TIP method using lidar-derived DEMs from six salt marshes in England with varying tidal ranges and geometries, for which topographic platforms were manually isolated from tidal flats. Agreement between manual and unsupervised classification exceeds 94% for DEM resolutions of 1 m, with all but one site maintaining an accuracy superior to 90% for resolutions up to 3 m. For resolutions of 1 m, platforms detected with the TIP method are comparable in surface area to digitised platforms and have similar elevation distributions. We also find that our method allows for the accurate detection of local block failures as small as 3 times the DEM resolution. Detailed inspection reveals that although tidal creeks were digitised as part of the marsh platform, unsupervised classification categorises them as part of the tidal flat, causing an increase in false negatives and overall platform perimeter. This suggests our method may benefit from combination with existing creek detection algorithms. Fallen blocks and high tidal flat portions, associated with potential pioneer zones, can also lead to differences between our method and supervised mapping. Although pioneer zones prove difficult to classify using a topographic method, we suggest that these transition areas should be considered when analysing erosion and accretion processes, particularly in the case of incipient marsh platforms. Ultimately, we have shown that unsupervised classification of marsh platforms from high-resolution topography is possible and sufficient to monitor and analyse topographic evolution., Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 936

This article gives a brief outline of the life of Sergio Salbany (1941–2005) and of his mathematical career, coupled with his social outreach and political activity in South Africa until 1980, in Zimbabwe 1981–1992, in Botswana 1993–1997, and finally again in South Africa 1997–2005. We include a list of his mathematical publications. Salbany was best known for his research in the area of asymmetric topology, comprising topics such as bitopological spaces, quasi-uniform spaces, ordered spaces and quasi-pseudometric spaces. His publications in this area were essentially the first that explicitly described the functors that served to clarify the structure and aims of the then novel theory.

7th Shelf-Life International Meeting (SLIM), Italian Sci Grp Food Packaging, Vimercate, ITALY, 21-23 octobre 2015; Food shelf life is mainly related to the dynamic of mass transfer in the food / packaging system. For instance, microbial safety of fresh products in Modified Atmosphere Packaging (MAP) implies to take into account the dynamic of O2 and CO2 exchanges in the system and its effect on microbial growth. Fresh fruits and vegetable decay is related to respiration rate that could be minimized using packaging material with the suitablepermeation properties. We developed mathematical models of gas transfer (permeation through packaging and solubilisation/diffusion within food) coupled with models of food shelf life such as predictive microbiology or respiration. These mechanistic models, once validated, and connected to dedicated food and packaging databases, could be used as a Decision Support Tool (DST) in order to optimize the storage conditions of the product orto identify the packaging material the most suitable for the product.

Let T : QU 0 → Top 0 denote the usual forgetful functor from the category of quasi-uniform T 0 -spaces to that of the topological T 0 -spaces. We regard the bicompletion reflector as a (pointed) endofunctor K : QU 0 → QU 0 . For any section F : Top 0 → QU 0 of T we consider the (pointed) endofunctor R = T K F : Top 0 → Top 0 . The T -section F is called upper bicompletion-true (briefly, upper K-true ) if the quasi-uniform space KFX is finer than FRX for every X in Top 0 . An important known characterisation is that F is upper K -true iff the canonical embedding X → R X is an epimorphism in Top 0 for every X in Top 0 . We show that this result admits a simple, purely categorical formulation and proof, independent of the setting of quasi-uniform and topological spaces. We thus mention a few other settings where the result is applicable. Returning then to the setting T : QU 0 → Top 0 , we prove: Any T -section F is upper K -true iff for all X the bitopology of KFX equals that of FRX ; and iff the join topology of KFX equals the strong topology (also called the b - or Skula topology) of RX .

In this paper we propose a review of the model called MVHR (Multi-Vibrational Hydrogen Release) dealing with Si-H bond physics and allowing explaining the complex physics of gate oxide breakdown. A large amount of effect as polarization, gate bias, temperature, and oxide thickness impacts are well explained by this physical model. In addition the model predicts some process related effects such as poly doping and oxide nitridation impact. The application of this model to high-K metal gate stack is discussed and a complete description of physical degradation in high-K stack is provided. A large amount of gate stack is studied as gate material (TiN, TaC, Poly), gate oxide (SiON, HfSiON, HfO2, HfZrO2). Hence the reliability limit of the SiON gate oxide will be predicted and guideline will be provided for metal gate dielectrics lifetime extrapolation.

Let Top 0 be the category of topological T 0-spaces, QU 0 the category of quasi-uniform T 0-spaces, T : QU 0 → Top 0 the usual forgetful functor and K : QU 0 → QU 0 the bicompletion reflector with unit k : 1 → K. Any T-section F : Top 0 → QU 0 is called K-true if KF = FTKF, and upper (lower) K-true if KF is finer (coarser) than FTKF. The literature considers important T-sections F that enjoy all three, or just one, or none of these properties. It is known that T(K,k)F is well-pointed if and only if F is upper K-true. We prove the surprising fact that T(K,k)F is the reflection to Fix(TkF) whenever it is idempotent. We also prove a new characterization of upper K-trueness. We construct examples to set apart some natural cases. In particular we present an upper K-true F for which T(K,k)F is not idempotent, and a K-true F for which the coarsest associated T-preserving coreflector in QU 0 is not stable under K.

We show that there exists at least a proper class of functorial approach structures, i.e., right inverses to the forgetful functor T : AP→ Top (where AP denotes the topological construct of approach spaces and contractions as introduced by R. Lowen). There is however a great difference in nature of these functorial approach structures when compared to the quasi-uniform paradigm which has been extensively studied by the first author: whereas it is well-known from [2] that a large class of epireflective subcategories of Top0 can be “parametrized” using the interaction of functorial quasi-uniformities with the quasi-uniform bicompletion, we show that using functorial approach structures together with the approach bicompletion developed in [10], only Top0 itself can be retrieved in this way.

It is proved that the quasi-proximity space induced by the bicompletion of a quasi-uniform T0-space X is a subspace of the quasi-proximity space induced by the Samuel bicompactification of X. The result is then used to establish that the locally finite covering quasi-uniformity defined on the category Top0 of topological T0-spaces and continuous maps is not lower K-true (in the sense of Brummer). It is also shown that a functorial quasi-uniformity F on Top0 is upper K-true if and only if FX is bicomplete whenever X is sober.

International audience; PurposeWe present the validation data of the French version of a new quality of life questionnaire, specifically developed for use with older adults (> 60 years old): the WHOQOL-OLD module. This questionnaire, which contains 24 items in six domains, is a complementary module of the WHOQOL-BREF quality of life questionnaire. It was internationally developed by a World Health Organization (WHO) group.MethodsThe first development and pilot studies led to a first questionnaire applied in field studies in 20 centers all over the world. They were done in 5566 subjects and allowed the validation of the final form of the WHOQOL-OLD questionnaire. For its French version, 281 subjects, with a mean age of 74 years, were recruited in three centers (Paris, Nancy and Geneva).ResultsThe results of the psychometric properties of the questionnaire, particularly the multitrait analysis, are compatible with the assumptions underlying the construction of scores. Otherwise, scores present a sufficient accuracy to use this instrument in group comparisons.ConclusionThe WHOQOL-OLD questionnaire can be used in older people in health services, clinical research and epidemiologic studies.; ProposCet article présente le développement et les premières données de validation de la version française d’un nouveau questionnaire de mesure de la santé perçue ou de la qualité de vie des personnes âgées (> 60 ans) : le module WHOQOL-OLD. Ce questionnaire, mis au point dans le cadre d’un projet international sous l’égide de l’OMS avec le soutien de l’Union européenne, est destiné à compléter le questionnaire de qualité de vie générique WHOQOL-BREF. Il comporte 24 questions regroupées en six dimensions.MéthodesLe développement initial du questionnaire et les études pilotes réalisées ont conduit à un premier questionnaire qui a fait l’objet d’études de terrain dans 20 centres répartis dans le monde entier. Elles ont concerné 5566 personnes et permis la validation du WHOQOL-OLD dans sa version finale. En ce qui concerne la version française, 281 sujets, d’âge moyen 74 ans, ont été recrutés par trois centres (Paris, Nancy et Genève).RésultatsLes résultats de l’analyse des propriétés psychométriques du questionnaire, notamment l’analyse multitrait, sont compatibles avec les hypothèses sous-jacentes à la construction des scores. Par ailleurs, les scores présentent une précision suffisante pour utiliser cet instrument dans les comparaisons de groupes.ConclusionAu total, le questionnaire WHOQOL-OLD peut être utilisé auprès des personnes âgées dans les études de service de santé, la recherche clinique et les études épidémiologiques.

International audience; Calcium phosphate materials are widely used as bone substitutes because of their properties close to those of the mineral phase of bones. Nevertheless, after several months, calcium phosphate-based materials release particles that may be phagocytosed by monocytes, leading to an inflammatory reaction. Strontium is well known to counteract the osteoporosis process, but little is known about its effect on inflammatory processes. The purpose of this work was to study the effect of biphasic calcium phosphate (BCP) particles substituted with strontium on the inflammatory reaction. Human primary monocytes stimulated or not by lipopolysaccharide (LPS) were exposed to BCP particles containing strontium for 6 and 24 h. Inflammatory mediators (cytokines and matrix metalloproteinases (MMPs)) production was then quantified by ELISA and zymography. We observed that the presence of strontium had few effects on unstimulated cells, but it decreased the production of pro-inflammatory cytokines and the chemokine interleukin 8 in LPS-stimulated cell-conditioned medium. This work suggests for the first time that strontium may be involved in the control of inflammatory processes following BCP phagocytosis by human monocytes.

This paper deals with certain concrete functors between topological categories in the sense of H. Herrlich. In particular we consider those functors which are sections of forgetful functors between two such categories, and we represent them as composite of a left adjoint section followed by a concrete bireflection. We give sufficient conditions for such functors to be uniquely determined by their restrictions to the respective quotient-reflective full subcategories of T 0 objects in the sense of Th. Marny [Th. Marny, On epireflective subcategories of topological categories, General Topology Appl. 10 (1979) 175–181], and we give an example to show how the uniqueness may fail. We also address the question of commutation between the forgetful functor and its sections with the T 0 reflectors.

Pulse wave velocity (PWV) and pulse pressure amplification (PPA) are independent predictors of cardiovascular risk, mainly in the elderly. The aim of the current research was to determine the influence of PPA and PWV, both manifestations of arterial stiffness, on heart disease in the elderly.The study population consisted of 1042 participants (814 women) aged 80 years and over who participated in the PARTAGE study. Carotid-femoral PWV was determined in order to assess aortic stiffness. Central aortic blood pressure values and central pulse wave analysis were obtained using the calibration method applied on the common carotid artery by a PulsePen tonometer. Amplification phenomenon was expressed as PPA, that is, the percentage of increase of pulse pressure in the brachial artery relative to central pulse pressure. Heart disease was defined as presence of heart failure, ischemic heart disease or atrial fibrillation.PPA was significantly lower in patients with heart disease, independently of the presence of hypertension, diabetes or both. Heart disease was present in 61.8% of participants with PPA less than 10%, in 46.2% of participants with PPA between 10 and 20% (P0.01), in 42.6% of participants with PPA between 20 and 30% (P0.005) and in 32.5% of participants with PPA more than 30% (P0.001). PWV, on the contrary, was not influenced by the presence of heart disease (12.3 ± 4.0 vs. 13.5 ± 4.6 m/s) but significantly increased in presence of hypertension (14.4 ± 5.0 m/s, P0.001) or diabetes (16.1 ± 5.1 m/s, P0.001).In the very elderly, low brachial/aortic PPA is associated with higher prevalence of heart disease.

Jury : C. Darcel, Y. Grohens, V. Langlois, F. Burel, S. Guillaume, J.-F. Carpentier

Synchrotron single-crystal diffraction data show that sodium transforms from the oP8 structure to an incommensurate host-guest composite structure above 125 GPa in which the guest component is nearly ``melted.'' At 147 GPa, the correlation length between the guest chains is only $28(3)\phantom{\rule{0.3em}{0ex}}\text{\AA{}}$, or approximately six times the chain spacing. This configuration shows a wide range of stability from above 125 GPa to at least 155 GPa and 550 K. The transition to this phase is accompanied by a marked decrease in optical reflectivity. Electronic band-structure calculations are used to interpret this change.

International audience; Objectives: Strontium is known to induce a positive bone balance but its specific pathway is still unknown. The purpose of this study is to test if Srsubstituted sol-gel HA could keep the osteogenic properties of strontium and so could enhance osteoformation, and if a specific pathway could be involved in that effect. Materials and Methods: Primary osteoblastic cells obtained from bone explants were used to study their proliferation when HA, Sr-substituted HA (HA5%), and Strontium chloride (5 x 10-5M ClSr2) were added to the culture medium at 3 culture times: 7, 14 and 21 days. PCR arrays and Cytokine Antibody Arrays were performed to detect differences in the RNA production and cytokines production. Non parametric stratified permutation tests were performed to check the significance of difference observed. p=0.05 level was used. Results: Proliferation: Strontium demonstrated a statistically significant increase of the osteoblastic cells replication without any changes in cells viability. Real time PCR demonstrated that osteoblastic cells were influenced by strontium which gave them an osteogenetic phenotype and modifications in expression of SMADs and TGFβ Receptors 1 and 2 tend to prove that strontium influences the TGFβ pathways. Osteoblasts produced 20 of the 42 cytokines that arrays could detect. Few showed differences in their expression after strontium treatment. GRO and MCP-1 production were modified in the osteogenic way. Conclusions: Strontium showed a high capacity to influence the bone balance to the osteogenesis by increasing the expression of constitutive proteins of bone RNAs and downregulating factors implicated in the initiation of osteoclastogenisis or the recruitment of osteoclasts. Those properties were kept when it was incorporated in sol-gel HA and the TGFβ pathway could be involved. In that way, HA acts as a drug delivery system.

International audience; Objectives: Hydroxyapatite (HA) is widely used as implant or coating biomaterial in affected bones or prosthesis metal parts. The release of HA particles mounts an inflammatory response and if uncontrolled, could result in implant loss. We have recently shown that HA particles induce the activation of human polymorphonuclear cells (PMNs) and increase secretion of their inflammatory mediators. A study by our group showed that zinc-substituted HA particles have the capacity to modulate the expression of cytokines by monocytes. The purpose of this work is to determine the effect of zinc on HA-mediated acute inflammation. Materials and Methods: PMNs (from healthy adult volunteers) were cultured in the absence or presence of HA powders, substituted or not with zinc ions. Conditioned media were used for IL-8 measurement (ELISA), gelatin zymmography and Boyden chamber chemotaxis assay. PMNs total mRNAs were extracted for IL-8 mRNA measurement (RT-PCR). Results: IL-8 concentration measurement showed a 45% decrease when PMNs were in contact with HA containing 5% Zn (HA5%) compared with HA alone. Such decrease in protein levels was associated with 47.5% decrease in IL-8 mRNAs as confirmed by RT-PCR. Gelatin zymography analysis shows that HA-activated PMNs increased MMP-9 secretion whereas HA 5%- activated cells exhibit a basal level of gelatinase B secretion. Moreover, Boyden chamber chemotaxis results show that HA5%-activated PMNs supernatants are less chemotactic than HA-activated PMNs supernatants. Conclusions: Our data show that HA5% has the capability to decrease the expression and secretion of inflammatory mediators such as IL-8 and MMP-9, leading to reduced neutrophil influx at the inflammation site. Studies are underway to investigate the underlying mechanism(s) of zinc substituted HA (e.g., signal transduction) in the processes. Data from these studies will help gain new insights into PMN's role in HA-associated inflammation surrounding prosthesis.

National audience

International audience

* INRA, Documentation, Domaine St Paul, Site Agroparc, 84914 Avignon cedex 9 Diffusion du document : INRA, Documentation, Domaine St Paul, Site Agroparc, 84914 Avignon cedex 9