MAINTENANCE HORMONAL TREATMENT IMPROVES PROGRESSION FREE SURVIVAL AFTER A FIRST LINE CHEMOTHERAPY IN PATIENTS WITH METASTATIC BREAST CANCER

The present study was conducted in patients with metastatic breast cancer. Its aim was to identify the factors which influence progression -free survival (PFS) and overall survival (OS) after the first line of chemotherapy in patients with positive tumour hormone receptor status. The patients with early disease progression during first-line chemotherapy were not included. In total, 560 patients who achieved a stable disease or a response to first-line chemotherapy were studied. The factors identified to improve the duration of PFS or OS in multivariate analysis were: number of metastatic sites (p = .01; p = .01), metastatic sites (p = .02; p = .04), Disease free interval (p = .001; p < .0001), previous hormonal therapy (p = .03; p = ns), response to first line chemotherapy (p < .0001; p = 0.0001) and an administration of maintenance hormonal therapy (p < .0001; p = .001). The major impact obtained by maintenance hormonal treatment after first-line chemotherapy in this study seems to indicate that this strategy should be recommended in patients with an ER or PgR positive tumour

Key-Recovery Attacks on Full Kravatte

This paper presents a cryptanalysis of full Kravatte, an instantiation of the Farfalle construction of a pseudorandom function (PRF) with variable input and output length. This new construction, proposed by Bertoni et al., introduces an efficiently parallelizable and extremely versatile building block for the design of symmetric mechanisms, e.g. message authentication codes or stream ciphers. It relies on a set of permutations and on so-called rolling functions: it can be split into a compression layer followed by a two-step expansion layer. The key is expanded and used to mask the inputs and outputs of the construction. Kravatte instantiates Farfalle using linear rolling functions and permutations obtained by iterating the Keccak round function. We develop in this paper several attacks against this PRF, based on three different attack strategies that bypass part of the construction and target a reduced number of permutation rounds. A higher order differential distinguisher exploits the possibility to build an affine space of values in the cipher state after the compression layer. An algebraic meet-in-the-middle attack can be mounted on the second step of the expansion layer. Finally, due to the linearity of the rolling function and the low algebraic degree of the Keccak round function, a linear recurrence distinguisher can be found on intermediate states of the second step of the expansion layer. All the attacks rely on the ability to invert a small number of the final rounds of the construction. In particular, the last two rounds of the construction together with the final masking by the key can be algebraically inverted, which allows to recover the key. The complexities of the devised attacks, applied to the Kravatte specifications published on the IACR ePrint in July 2017, or the strengthened version of Kravatte recently presented at ECC 2017, are far below the security claimed

Do submesoscale frontal processes ventilate the oxygen minimum zone off Peru?

The Peruvian upwelling system encompasses the most intense and shallowest oxygen minimum zone (OMZ) in the ocean. This system shows pronounced submesoscale activity like filaments and fronts. We carried out glider-based observations off Peru during austral summer 2013 to investigate whether submesoscale frontal processes ventilate the Peruvian OMZ. We present observational evidence for the subduction of highly oxygenated surface water in a submesoscale cold filament. The subduction event ventilates the oxycline but does not reach OMZ core waters. In a regional submesoscale-permitting model we study the pathways of newly upwelled water. About 50% of upwelled virtual floats are subducted below the mixed layer within 5 days emphasizing a hitherto unrecognized importance of subduction for the ventilation of the Peruvian oxycline

Timescales of Quartz Crystallization and the Longevity of the Bishop Giant Magma Body

Supereruptions violently transfer huge amounts (100 s–1000 s km3) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ∼760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500–3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies

Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie

In prion diseases, PrPc, a widely expressed protein, is transformed into a pathogenic form called PrPSc, which is in itself infectious. Antibodies directed against PrPc have been shown to inhibit PrPc to PrPSc conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrPc makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs). Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrPc. Frequencies of PrP-specific IFNγ-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3+ T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrPSc replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses

Impact de la sarcopénie sur la sévérité de la pancréatite aiguë

Background: Nutritional status influences the prognosis of many diseases. While obesity is known to be a risk factor for severe acute pancreatitis (SAP), little evidence exists on the influence of sarcopenia. The aim of this study was to evaluate the influence of sarcopenia on the occurrence of SAP and to determine the performances of anthropometric indices in order to predict severe forms. Method: We conducted a single-centre retrospective study at Caen University Hospital between January 2014 and December 2017. Sarcopenia was assessed by measuring the psoas muscle area (PMA) on a CT scan performed during hospitalization to obtain the PMA/BMI ratio. Indexed to body surface area, we obtained a ratio called Sarcopancreatic Index (SI) which was independent of gender differences in measurement. SAP was defined by the presence of infected necrotizing pancreatitis or persistent organ failure. Results: On the 503 patients included in our analysis, 73 (14.5%) had SAP. SI was independently associated with the occurrence of SAP (OR=1.455 CI [1.028-2.061]; p=0.0346), as were visual analogue scale, creatinine and albumin. Based on these parameters, we created a score named Sarcopenia Severity Index (SSI). The SSI had an area under the ROC curve at 0,84, which was comparable to Ranson score (0.87) and superior to BMI or SI alone in predicting SAP.Conclusion: Sarcopenia appears to be associated with the occurrence of PAS. Its assessment should be considered to predict more efficiently the occurrence of a severe form of acute pancreatitis.Introduction : l’état nutritionnel influence le pronostic de nombreuses pathologies. S’il est établi que l’obésité est un facteur de risque de pancréatite aiguë sévère (PAS), peu de données existent quant à l’influence de la sarcopénie. L’objectif de ce travail était d’évaluer l’influence de la sarcopénie sur la survenue d’une PAS et de mesurer les performances d’indices anthropométriques pour prédire ces formes sévères. Méthode : nous avons conduit une étude rétrospective monocentrique au CHU de Caen entre janvier 2014 et décembre 2017. La sarcopénie a été évaluée par mesure de l’aire des muscles psoas (AP) sur un scanner réalisé durant l’hospitalisation afin d’obtenir le rapport AP/IMC. Rapporté à la surface corporelle, on obtenait un indice nommé Indice Sarcopancréatique (IS) qui s’affranchissait des différences de mesure entre sexes. La PAS était définie par la présence d’une infection de coulées de nécrose ou d’une défaillance d’organe persistante. Résultats : sur les 503 malades inclus dans notre analyse, 73 (14,5 %) ont présenté une PAS. L’IS était indépendamment associé à la survenue d’une PAS (OR = 1,455 IC [1,028-2,061] ; p = 0,0346), de même que l’Échelle Visuelle Analogique, la créatininémie et l’albuminémie. À partir de ces variables, nous avons construit un score nommé Sarcopenia Severity Index (SSI). Le SSI présentait une aire sous la courbe ROC à 0,84 comparable à celle du score de Ranson (0,87) et supérieure à l’IMC ou à l’IS isolé pour prédire un épisode de PAS. Conclusion : la sarcopénie semble être associée à la survenue d’une PAS. Son évaluation pourrait être un élément à considérer pour prédire plus efficacement la survenue d’une forme sévère de PA

Capital, travail et entreprise numérique

International audienc