Sur certaines relations entre les intégrales trajectorielles et l'opérateur de translation et son dual dans l'espace de Poisson canonique

We study the relationship between the translation operator, its dual and the pathwise integral on the Poisson space with weak conditions on the processes

An Immune Gene Expression Signature Associated With Development of Human Hepatocellular Carcinoma Identifies Mice That Respond to Chemopreventive Agents

Cirrhosis and chronic inflammation precede development of hepatocellular carcinoma (HCC) in approximately 80% of cases. We investigated immune-related gene expression patterns in liver tissues surrounding early-stage HCCs and chemopreventive agents that might alter these patterns to prevent liver tumorigenesis.We analyzed gene expression profiles of non-tumor liver tissues from 392 patients with early-stage HCC (training set, n=167 and validation set, n=225) and liver tissue from patients with cirrhosis without HCC (n=216, controls) to identify changes in expression of genes that regulate the immune response that could contribute to hepatocarcinogenesis. We defined 172 genes as markers for this deregulated immune response, which we called the immune-mediated cancer field (ICF). We analyzed the expression data of liver tissues from 216 patients with cirrhosis without HCC and investigated the association between this gene expression signature and development of HCC and outcomes of patients (median follow-up 10 years). Human liver tissues were also analyzed by histology. C57BL/6J mice were given a single injection of N-nitrosodiethylamine followed by weekly doses of carbon tetrachloride to induce liver fibrosis and tumorigenesis. Mice were then given orally the multiple tyrosine inhibitor nintedanib or vehicle (controls); liver tissues were collected and histology, transcriptome, and protein analyses were performed. We also analyzed transcriptomes of liver tissues collected from mice on a choline-deficient high-fat diet, which developed chronic liver inflammation and tumors, given orally aspirin and clopidogrel or the anti-inflammatory agent sulindac vs mice on a chow (control) diet.We found the ICF gene expression pattern in 50% of liver tissues from patients with cirrhosis without HCC and in 60% of non-tumor liver tissues from patients with early-stage HCC. The liver tissues with the ICF gene expression pattern had 3 different features: increased numbers of effector T cells; increased expression of genes that suppress the immune response and activation of transforming growth factor beta signaling; or expression of genes that promote inflammation and activation of interferon gamma signaling. Patients with cirrhosis and liver tissues with the immunosuppressive profile (10% of cases) had a higher risk of HCC (hazard ratio, 2.41; 95% 1.21-4.80). Mice with chemically-induced fibrosis or diet-induced steatohepatitis given nintedanib or aspirin and clopidogrel downregulated the ICF gene expression pattern in liver and developed fewer and smaller tumors than mice given vehicle.We identified an immune-related gene expression pattern in liver tissues of patients with early-stage HCC, called the ICF, that associates with risk of HCC development in patients with cirrhosis. Administration of nintedanib or aspirin and clopidogrel to mice with chronic liver inflammation caused loss of this gene expression pattern and developed fewer and smaller liver tumors. Agents that alter immune regulatory gene expression patterns associated with carcinogenesis might be tested as chemopreventive agents in patients with cirrhosis

Non-invasive Geophysical Surveys in Search of the Roman Temple of Augustus Under the Cathedral of Tarragona (Catalonia, Spain): A Case Study

An integrated geophysical survey has been conducted at the Tarragona's Cathedral (Catalonia, NE Spain) with the aim to confirm the potential occurrence of archaeological remains of the Roman Temple dedicated to the Emperor Augustus. Many hypotheses have been proposed about its possible location, the last ones regarding the inner part of the Cathedral, which is one of the most renowned temples of Spain (twelfth century) evolving from Romanesque to Gothic styles. A geophysical project including electrical resistivity tomography (ERT) and ground probing radar (GPR) was planned over 1 year considering the administrative and logistic difficulties of such a project inside a cathedral of religious veneration. Finally, both ERT and GPR have been conducted during a week of intensive overnight surveys that provided detailed information on subsurface existing structures. The ERT method has been applied using different techniques and arrays, ranging from standard Wenner-Schlumberger 2D sections to full 3D electrical imaging with the advanced Maximum Yield Grid array. Electrical resistivity data were recorded extensively, making available many thousands of apparent resistivity data to obtain a complete 3D image after a full inversion. In conclusion, some significant buried structures have been revealed providing conclusive information for archaeologists. GPR results provided additional information about shallowest structures. The geophysical results were clear enough to persuade religious authorities and archaeologists to conduct selected excavations in the most promising areas that confirmed the interpretation of geophysical data. In conclusion, the significant buried structures revealed by geophysical methods under the cathedral were confirmed by archaeological digging as the basement of the impressive Roman Temple that headed the Provincial Forum of Tarraco, seat of the Concilium of Hispania Citerior Province

A la recerca del temple d'August a Tarragona: una experiència entre arqueologia i geofísica

La catedral de Tarragona està enclavada en l'espai més elevat de la ciutat. Els romans ocuparen aquest indret a partir de final del segle III aC i el convertiren en el campament militar des d'on iniciaren, a la Península, les lluites contra els cartaginesos, comandats per Anníbal. Tarraco fou punt d'arribada de les tropes que iniciaren la conquesta d'Iberia. En temps de l'emperador August Tarraco fou elevada a la categoria de capital de la Provincia Hispania Citerior i s'hi inicià una sèrie de transformacions urbanístiques d'acord amb el nou rang. És així que l'historiador Tàcit esmenta que l'any 15 dC una representació de tarraconenses van demanar a Tiberi autorització per aixecar un temple de culte al seu antecessor August, que podia haver estat el primer que se li dedicà fora de Roma. Així ens ho indiquen les fonts clàssiques: in omnes provincias exemplum. Finalment, l'epigrafia ens parla de l'existència del Concilium Prouinciae Hispaniae Citerioris, el màxim òrgan provincial. La major part d'estudis arqueològics que s'han desenvolupat fins ara coincideixen a ubicar el temple augustal a l'acròpolis de la ciutat, l'espai actualment ocupat per la catedral medieval de Tarragona

Quasispecies Spatial Models for RNA Viruses with Different Replication Modes and Infection Strategies

Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along time

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia

Altres ajuts: This project was supported by the Asociación Española Contra el Cáncer, AECC (project ref.: GC16173697BIGA), Obra Social "La Caixa" and by Celgene Spain. A. Gonzalez-Perez is supported by a Ramon y Cajal fellowship (RYC-2013-14554) of the Educational Ministry (Madrid, Spain). This work was also partially supported by FEDER funds from CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain).Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation

Thermal and Optical Characterization of Undoped and Neodymium-Doped Y3ScAl4O12 Ceramics

Y3–3xNd3xSc1Al4O12 (x = 0, 0.01, and 0.02) ceramics were fabricated by sintering at high temperature under vacuum. Unit cell parameter refinement and chemical analysis have been performed. The morphological characterization shows micrograins with no visible defects. The thermal analysis of these ceramics is presented, by measuring the specific heat in the temperature range from 300 to 500 K. Their values at room temperature are in the range 0.81–0.90 J g1–K–1. The thermal conductivity has been determined by two methods: by the experimental measurement of the thermal diffusivity by the photopyroelectric method, and by spectroscopy, evaluating the thermal load. The thermal conductivities are in the range 9.7–6.5 W K–1 m–1 in the temperature interval from 300 to 500 K. The thermooptic coefficients were measured at 632 nm by the dark mode method using a prism coupler, and the obtained values are in the range 12.8–13.3 × 10–6 K–1. The nonlinear refractive index values at 795 nm have been evaluated to calibrate the nonlinear optical response of these materials.This work is supported by the Spanish Government under projects MAT2011-29255-C02-01-02, MAT2013-47395-C4-4-R, and the Catalan Government under project 2014SGR1358. It was also funded by the European Commission under the Seventh Framework Programme, project Cleanspace, FP7-SPACE-2010-1-GA No. 263044

Biomarkers characterization of circulating tumour cells in breast cancer patients

Introduction: Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease. Methods: Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics. Results: Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03). Conclusions: This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted

El barranc de la Boella de la Canonja (Tarragonès) revisitat en la intervenció arqueològica preventiva de l'any 2007

El barranc de la Boella de la Canonja és un jaciment descobert en el primer terç del segle XX. Cinquanta anys després de la seva descoberta, la publicació d'aquest jaciment pels senyors R. Capdevila i S. Vilaseca va permetre actualitzar l'escàs coneixement de la bioestratigrafia del quaternari del Camp de Tarragona (Vilaseca, 1973). Tal com assenyala el mateix S. Vilaseca, la presència de fòssils de mamífers en el barranc va ser donada a conèixer per J. R. Bataller en la memòria explicativa del segon mapa geològic del full 473 de l'IGME corresponent a Tarragona (Bataller, 1935). El mateix S. Vilaseca apunta altres descobertes de mamífers ressenyades en el Camp de Tarragona, com la nota de Faura i Sans sobre un fragment de molar de proboscidi que Harlé determinaria com Elephas meridionalis el mateix any (Faura i Sans, 1920; Harlé, 1920). Aquesta resta va ser enviada per A. Romaní, aleshores director del Museu Balaguer de Vilanova i la Geltrú, a qui li van fer arribar des d'unes pedreres del Port de Tarragona. Els treballs geològics de M. Faura i Sans, J.R. Bataller i S. Vilaseca durant el primer quart del segle XX protagonitzaren el desenvolupament de la geologia, la paleontologia i la prehistòria en el marc del Servei del Mapa de la Mancomunitat de Catalunya

ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe