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CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19− (pre)-leukemic cells represent an “early progenitor origin-related” mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19−CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19−CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19−CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19−CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19− relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged., The work in P.M. and C.B.’s Laboratory was supported by the European Research Council (CoG-2014-646903, PoC-2018-811220) and the Spanish Ministry of Economy and Competitiveness (SAF2016-80481R, PID2019-108160RB-I00) (P.M.); the ISCIII (ISCIII/FEDER, PI17/01028 and PI20/00822), the Spanish Association against Cancer (AECC), and the FERO Foundation (C.B.). P.M. and J.M.R. acknowledge the support of ISCIII-RICORS within the Next Generation EU program (Plan de Recuperación, Transformación y Resiliencia). N.E. is supported by Cancer Research UK and a Children and Young People’s Cancer Innovation Award (DRCPGM\100058). A.R. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (216632/Z/19/Z). A.O. was supported by ISCIII (PI19/011183). F.S. was supported by AGAUR/Generalitat de Catalunya (SGR288). The single-cell transcriptomic analysis was supported by MRC Discovery award MRCDA 0816-11 and the MRC WIMM Single Cell Facility and MRC-funded Oxford Consortium for Single-Cell Biology (MR/M00919X/1) provided assistance.

36th European Photovoltaic Solar Energy Conference and Exhibition; 757-763, A study of the optical properties of silicon perovskite tandem solar cells is reported. A 4-terminal (4T) tandem device has been built with 22.3 % efficiency, combining a semitransparent perovskite solar cell (PSC) with a commercially-available Aluminum Back Surface Field (Al-BSF) silicon solar cell from French manufacturer Photowatt. The silicon cell presents a PCE of 18.5% and results in an overall 4T tandem efficiency of 22.3% in combination with a semitransparent perovskite solar cell (PSC) of 16.6%. In order to further increase the device performance, optical losses have to be minimized through the PSC in the near infrared region. However, the optical properties of each layer composing the PSC are not accurately known, and they depend on the exact material composition and process. This work aims to characterize optically each layer of the semitransparent PSC by spectrophotometry, profilometry and ellipsometry measurements, in order to determine their optical indices n and k. In particular, we report for the first time the optical indices of the Cs0.05(MA0.166FA0.833)0.95Pb(Br0.166I0.833)3 triple cation perovskite. Optical modelling based on the transfer matrix method is used to identify the optical losses. These results will allow a precise design of the devices and a quick test of various materials, by predicting their impact on the efficiency of the bottom silicon cell and the tandem cell.

Introduction: Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. Material and methods: All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. Results: A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. Conclusions: The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. (C) 2016 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U. All rights reserved.

International @ ENERGIE+HJO; International audience; None

International @ ENERGIE+HJO; International audience; None

International audience

The Network of Research Infrastructures for European Seismology (NERIES) is European Commission (EC) project whose focus is networking together seismological observatories and research institutes into one integrated European infrastructure that provides access to data and data products for research. Seismological institutes and organizations in European and Mediterranean countries maintain large, geographically distributed data archives, therefore this scenario suggested a design approach based on the concept of an internet service oriented architecture (SOA) to establish a cyberinfrastructure for distributed and heterogeneous data streams and services. Moreover, one of the goals of NERIES is to design and develop a Web portal that acts as the uppermost layer of the infrastructure and provides rendering capabilities for the underlying sets of data. The Web services that are currently being designed and implemented will deliver data that has been adopted to appropriate formats. The parametric information about a seismic event is delivered using a seismology-specific Extensible mark-up Language(XML) format called QuakeML (https://quake.ethz.ch/quakeml), which has been formalized and implemented in coordination with global earthquake-information agencies. Uniform Resource Identifiers (URIs) are used to assign identifiers to (1) seismic-event parameters described by QuakeML, and (2) generic resources, for example, authorities, locations providers, location methods, software adopted, and so on, described by use of a data model constructed with the resource description framework (RDF) and accessible as a service. The European-Mediterranean Seismological Center (EMSC) has implemented a unique event identifier (UNID) that will create the seismic event URI used by the QuakeML data model. Access to data such as broadband waveform, accelerometric data and stations inventories will be also provided through a set of Web services that will wrap the middleware used by the seismological observatory or institute that is supplying the data. Each single application of the portal consists of a Java-based JSR-168-standard portlet (often provided with interactive maps for data discovery). In specific cases, it will be possible to distribute the deployment of the portlets among the data providers, such as seismological agencies, because of the adoption, within the distributed architecture of the NERIES portal of the Web Services for Remote Portlets (WSRP) standard for presentation-oriented web services The purpose of the portal is to provide to the user his own environment where he can surf and retrieve the data of interest, offering a set of shopping carts with storage and management facilities. This approach involves having the user interact with dedicated tools in order to compose personalized datasets that can be downloaded or combined with other information available either through the NERIES network of Web services or through the user‘s own carts. Administrative applications also are provided to perform monitoring tasks such as retrieving service statistics or scheduling submitted data requests. An administrative tool is included that allows the RDF model to be extended, within certain constraints, with new classes and properties.

Bacterial contamination of blood components is an infrequent although potentially fatal event. Bacterial contamination rate of platelet concentrates (PC) varies between 1/900 to 1/2,000 random donor units. However the risk of symptomatic bacteriemias is lower (between 1/2,000 to 1/12,000 random donor units). The organisms most commonly implicated in contaminated PC are gram-positive bacteria such as coagulase negative Staphylococci, Bacillus cereus or Propionibacterium acnes, although gram-negative organisms are also found that generally are associated to a higher mortality. Here, a fatal case of sepsis due to Staphylococcus carnosus associated to transfusion of a contaminated random donor platelet unit is reported.