The ALADIN Interactive Sky Atlas

The Aladin interactive sky atlas, developed at CDS, is a service providing simultaneous access to digitized images of the sky, astronomical catalogues, and databases. The driving motivation is to facilitate direct, visual comparison of observational data at any wavelength with images of the optical sky, and with reference catalogues. The set of available sky images consists of the STScI Digitized Sky Surveys, completed with high resolution images of crowded regions scanned at the MAMA facility in Paris. A Java WWW interface to the system is available at: http://aladin.u-strasbg.fr/Comment: 8 pages, 3 Postscript figures; to be published in A&

Kevoree Modeling Framework (KMF): Efficient modeling techniques for runtime use

The creation of Domain Specific Languages(DSL) counts as one of the main goals in the field of Model-Driven Software Engineering (MDSE). The main purpose of these DSLs is to facilitate the manipulation of domain specific concepts, by providing developers with specific tools for their domain of expertise. A natural approach to create DSLs is to reuse existing modeling standards and tools. In this area, the Eclipse Modeling Framework (EMF) has rapidly become the defacto standard in the MDSE for building Domain Specific Languages (DSL) and tools based on generative techniques. However, the use of EMF generated tools in domains like Internet of Things (IoT), Cloud Computing or Models@Runtime reaches several limitations. In this paper, we identify several properties the generated tools must comply with to be usable in other domains than desktop-based software systems. We then challenge EMF on these properties and describe our approach to overcome the limitations. Our approach, implemented in the Kevoree Modeling Framework (KMF), is finally evaluated according to the identified properties and compared to EMF.Comment: ISBN 978-2-87971-131-7; N° TR-SnT-2014-11 (2014

Renal Angiomyolipoma Associated with Inferior Vena Cava Thrombus

A 57-year-old woman was found to have an inferior vena cava involvement of a known sinusal angiomyolipoma incompletely resected three years beforehand. Intravascular extension into the IVC of angiomyolipoma has rarely been reported. We present a new case and reconsider the literature about this uncommon complication of a benign renal tumor

Novel Assays For Immunotherapy Product Characterisation And Potency Measurement

The use of adoptive T-cell therapy for the treatment of haematological cancers and solid tumours is one of the fastest growing areas in the cell and gene therapy field, with oncology targets accounting for approximately 40% of all cell therapy clinical trials currently being performed. A significant number of these immunotherapies use genetic modifications of T-cells using viral vectors to engineer their specificity or enhance their function. Examples of these products include gene modified T-cells expressing Chimeric Antigen Receptors (CAR) which direct specificity against cancer cell surface markers, or engineered T-cell receptors (TCR) which can target intracellular proteins through the presentation of their fragments on the cell surface by HLA molecules. Various strategies are applied for the manufacture of gene modified immunotherapies but the use of patient cells as a starting material and the use of viruses to deliver the CAR or TCR construct can lead to variability in terms of transduction efficiency, CAR/TCR expression and product potency. Characterisation is therefore critical both during manufacture to maintain consistency, and post manufacture to ensure sufficient function. Strategies for the characterisation of gene modified immunotherapies are continually evolving. However, a number of the methods commonly used for measurement of viral transduction and potency are complex, semi-quantitative, require complex pre-labelling of cells or are based on the detection of surrogate markers. In this paper we demonstrate two novel approaches for the characterisation of a gene modified TCR immunotherapy product targeting the Wilms-tumour 1 (WT1) protein. WT1 expression has been demonstrated to be elevated in haematological malignancies such as acute myeloid leukaemia (AML) chronic myeloid leukaemia (CML) and myelodysplastic syndrome (MDS). The first approach uses single cell analysis to directly measure viral copy number integration into the genome and the expression of the WT1-TCR mRNA following transduction. This assay offers advantages over currently used techniques. From a safety perspective it provides high level characterisation of viral integration which can be used to optimise the manufacture process to control the number of integration events within the genome. It also offers a method to optimise the amount of virus used during manufacture which could have a significant positive impact on the cost of goods for product manufacture. Single cell mRNA analysis offers a direct functional measurement of TCR expression following viral transduction which overcomes the limitations of available antibodies specific for the antigen recognised by the TCR. The second approach demonstrated in this paper is for a novel potency assay which uses impedance spectroscopy to give a label free, real time measurement of cell killing by the WT1-TCR gene modified T-cells. This has many advantages over commonly used alternative methods such as the chromium-51 killing assay or surrogate assays looking at the stimulation of cytokine release. Firstly it is label free and does not require pre-loading of the target cells with a radioactive isotopes or other detection labels which can interfere with the assay readout. Secondly it can be performed with established cell lines which can act as antigen presenting cells reducing the assay variability associated with the use of primary cells. Thirdly, the impedance assay provides real time data showing the kinetics of the killing response rather than just a single end-point measurement. These new assays are a valuable addition to the repertoire of techniques which can be applied to characterise immunotherapy products and while this paper demonstrates their use with a gene modified TCR products they are equally as applicable for CAR T-cell therapies and for measuring lentiviral based immunotherapy products

Theoretical study of optical properties of anti phase domains in GaP

International audienceIII-V/Si heterostructures are currently investigated for silicon photonics and solar energy conversion. In particular, dilute nitride alloy GaAsPN grown on a GaP/Si platform exhibits lattice match with Si and an optimal band gap configuration for tandem solar cell devices. However, monolithic "coherent" growth of the GaP thin layer on Si suffers from the nucleation of extended structural defects, which can hamper device operation as well as the GaP/Si interface level and through their propagation inside the overall heterostructure. However, the effect of such structural defects on optical and transport properties is actually not well understood in details. In this letter, we investigate the anti phase domains defect (also called inversion domains) by means of ab initio calculations giving insights into the alteration of optical and transport properties of GaP due to the defective GaP/Si interface

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma

BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy

Improving proton therapy by metal-containing nanoparticles:Nanoscale insights

The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/mu m) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (&gt;2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.</p

Mapping of transrectal ultrasonographic prostate biopsies: quality control and learning curve assessment by image processing

Objective: Mapping of transrectal ultrasonographic (TRUS) prostate biopsies is of fundamental importance for either diagnostic purposes or the management and treatment of prostate cancer, but the localization of the cores seems inaccurate. Our objective was to evaluate the capacities of an operator to plan transrectal prostate biopsies under 2-dimensional TRUS guidance using a registration algorithm to represent the localization of biopsies in a reference 3-dimensional ultrasonographic volume. Methods: Thirty-two patients underwent a series of 12 prostate biopsies under local anesthesia performed by 1 operator using a TRUS probe combined with specific third-party software to verify that the biopsies were indeed conducted within the planned targets. RESULTS: The operator reached 71% of the planned targets with substantial variability that depended on their localization (100% success rate for targets in the middle and right parasagittal parts versus 53% for targets in the left lateral base). Feedback from this system after each series of biopsies enabled the operator to significantly improve his dexterity over the course of time (first 16 patients: median score, 7 of 10 and cumulated median biopsy length in targets of 90 mm; last 16 patients, median score, 9 of 10 and a cumulated median length of 121 mm; P = .046). Conclusions: In addition to being a useful tool to improve the distribution of prostate biopsies, the potential of this system is above all the preparation of a detailed "map" of each patient showing biopsy zones without substantial changes in routine clinical practices

Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial.

INTRODUCTION: Septic shock is the subgroup of patients with sepsis, which presents as vasopressor dependence, an elevated blood lactate concentration and is associated with a mortality of at least 30%. Expression of the triggering receptor expressed on myeloid cells 1 (TREM-1) pathway, measured using a serum biomarker of pathway activation (soluble TREM-1, sTREM-1) has been associated with outcome in septic shock. Preclinical and early phase patient data suggest that therapeutic modulation of this pathway may improve survival. METHODS AND ANALYSIS: Efficacy, Safety and Tolerability of Nangibotide in Patients with Septic Shock is a phase IIb randomised controlled trial that will take place in up to 50 centres in seven countries and recruit 450 patients with septic shock to receive either placebo or one of two doses of nangibotide, a novel regulator of the TREM-1 pathway. The primary outcome will be the impact of nangibotide therapy on the change in Sequential Organ Failure Assessment score from a baseline determined before initiation of study drug therapy. This will be assessed first in the patients with an elevated sTREM-1 level and then in the study population as a whole. In addition to safety, secondary outcomes of the study will include efficacy of nangibotide in relation to sTREM-1 levels in terms of organ function, mortality and long-term morbidity. This study will also facilitate the development of a novel platform for the measurement of sTREM-1 at the point of care. ETHICS AND DISSEMINATION: The study has been approved by the responsible ethics committees/institutional review boards in all study countries: Belgium: Universitair Ziekenhuis Antwerpen, France: CPP Ile de France II, Denmark: Region Hovedstaden, Spain: ethics committee from Valld'Hebron Hospital, Barcelona, Finland: Tukija, Ireland: St. James' Hospital (SJH) / Tallaght University Hospital (TUH) Joint Research Ethics Committee, USA: Lifespan, Providence TRIAL REGISTRATION NUMBERS: EudraCT Number: 2018-004827-36 and NCT04055909