Diagnosis of alpha1-antitrypsin deficiency not just in severe COPD

Alpha1-antitrypsin deficiency (AATD) is a well known genetic risk factor for pulmonary disease and is the most frequent hereditary disease diagnosed in adults. Despite being one of the most common hereditary diseases, AATD remains under-diagnosed because of its variable clinical presentation and the poor knowledge of this disease by physicians. With the aim of identifying clinical differences that could influence early diagnosis, we compared two groups of six AATD Pi*ZZ patients with different lung function severity and clinical expression at diagnosis. On comparing the two groups, we observed a younger mean age at diagnosis and more exacerbations in the severe group, but the percentage of smokers did not statistically differ between the two groups. Our results suggest that AATD continues being a disease suspected on younger patients with a worse lung function. In addition these findings confirm the clinical variability of the disease and that there are still unknown factors that contribute to its development. Therefore, early diagnosis may modify the prognosis of this disease

Credit consulting : anàlisi de l'amortització anticipada de crèdits mitjançant el VAD

El projecte que he dut a terme és la implementació d'una pàgina web orientada a aquells usuaris que necessiten assessorament davant d'un crèdit bancari que ja posseeixen o que vulguin realitzar. Aquesta web financera té com a objectiu donar un cop de mà a tota aquella gent que té demanat un crèdit bancari a interès fixe i vol saber en un moment determinat si és convenient o no amortitzar anticipadament tenint en compte variables com: interès del mercat, penalització deguda a l'anticipació, la fiscalitat en el cas de les empreses, anys que queden per acabar de pagar el crèdit, sistema d'amortització financera utilitzat, etc.El proyecto que he llevado a cabo es la implementación de una página web orientada a aquellos usuarios que necesitan asesoramiento respecto a un crédito bancario que ya poseen o que quieran realizar. Esta web financiera tiene como objetivo servir de ayuda a todo aquel que haya pedido un crédito bancario a interés fijo y quera saber en un momento dado si es conveniente o no amortizarlo anticipadamente teniendo en cuenta variables como: interés del mercado, penalización debida a la anticipación, fiscalidad en el caso de las empresas, años que quedan para acabar de pagar el crédito, sistema de amortización financiera utilizado, etc.Implementation of a financial website aimed at those users who need credit counseling

Spectral network based on component cells under the SOPHIA European project

In the frame of the European project SOPHIA, a spectral network based on component (also called isotypes) cells has been created. Among the members of this project, several spectral sensors based on component cells and collimating tubes, so-called spectroheliometers, were installed in the last years, allowing the collection of minute-resolution spectral data useful for CPV systems characterization across Europe. The use of spectroheliometers has been proved useful to establish the necessary spectral conditions to perform power rating of CPV modules and systems. If enough data in a given period of time is collected, ideally a year, it is possible to characterize spectrally the place where measurements are taken, in the same way that hours of annual irradiation can be estimated using a pyrheliometer

D4.5 Framework development and release

This deliverable presents the nal release of the ExaQUte framework as result of task 4.6 of the project focused on the framework development and optimization. The rst part of the document presents an overview of the dierent parts of the ExaQUte framework providing the links to the repositories where the code of the dierent components can be found as well as the installation and usage guidelines. These repositories will include the nal version of the ExaQUte API and its implementation for the runtimes provided in the project (PyCOMPSs/COMPSs and Quake). The second part of the document presents a performance analysis of the framework by performing strong and weak scaling experiments. In this case, we have focused on the analysis of the new features introduced during the last part of the project to support and optimize the execution of MPI solvers inside the framework. The support for OpenMP was already reported in Deliverable D4.3 [21]. The results of the experiments demonstrate that the proposed framework allow to reach very good scalability for the analysed Monte Carlo problems

Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha1-antitrypsin deficiency

Introduction: COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Materials and methods: peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). Results: the severe and mild COPD-AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Conclusions: despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD-AATD. Nonetheless, our findings warrant further validation in large studies

D5.5 Report on the application of multi-level Monte Carlo to wind engineering

We study the use of multi-level Monte Carlo methods for wind engineering. This report brings together methodological research on uncertainty quantification and work on target applications of the ExaQUte project in wind and civil engineering. First, a multi-level Monte Carlo for the estimation of the conditional value at risk and an adaptive algorithm are presented. Their reliability and performance are shown on the time-average of a non-linear oscillator and on the lift coefficient of an airfoil, with both preset and adaptively refined meshes. Then, we propose an adaptive multi-fidelity Monte Carlo algorithm for turbulent fluid flows where multilevel Monte Carlo methods were found to be inefficient. Its efficiency is studied and demonstrated on the benchmark problem of quantifying the uncertainty on the drag force of a tall building under random turbulent wind conditions. All numerical experiments showcase the open-source software stack of the ExaQUte project for large-scale computing in a distributed environment

D6.5 Report on stochastic optimisation for wind engineering

This report presents the latest methods of optimisation under uncertainties investigated in the ExaQUte project, and their applications to problems related to civil and wind engineering. The measure of risk throughout the report is the conditional value at risk. First, the reference method is presented: the derivation of sensitivities of the risk measure; their accurate computation; and lastly, a practical optimisation algorithm with adaptive statistical estimation. Second, this method is directly applied to a nonlinear relaxation oscillator (FitzHugh–Nagumo model) with numerical experiments to demonstrate its performance. Third, the optimisation method is adapted to the shape optimisation of an airfoil and illustrated by a large-scale experiment on a computing cluster. Finally, the benchmark of the shape optimisation of a tall building under a turbulent flow is presented, followed by an adaptation of the optimisation method. All numerical experiments showcase the open-source software stack of the ExaQUte project for large-scale computing in a distributed environment

D5.3 Report on theoretical work to allow the use of MLMC with adaptive mesh refinement

This documents describes several studies undertaken to assess the applicability of MultiLevel Monte Carlo (MLMC) methods to problems of interest; namely in turbulent fluid flow over civil engineering structures. Several numerical experiments are presented wherein the convergence of quantities of interest with mesh parameters are studied at different Reynolds’ numbers and geometries. It was found that MLMC methods could be used successfully for low Reynolds’ number flows when combined with appropriate Adaptive Mesh Refinement (AMR) strategies. However, the hypotheses for optimal MLMC performance were found to not be satisfied at higher turbulent Reynolds’ numbers despite the use of AMR strategies. Recommendations are made for future research directions based on these studies. A tentative outline for an MLMC algorithm with adapted meshes is made, as well as recommendations for alternatives to MLMC methods for cases where the underlying assumptions for optimal MLMC performance are not satisfied.&nbsp

Dexamethasone Implant for Diabetic Macular Oedema: 1-Year Treatment Outcomes from the Fight Retinal Blindness! Registry

INTRODUCTION Phase III clinical trials of dexamethasone intravitreal implant for diabetic macular oedema (DMO) have reported significant improvements in visual acuity (VA). Studies evaluating the treatment of DMO in routine clinical practice provide data to identify areas that need improvement. This study evaluated 12-month treatment outcomes of dexamethasone implant for DMO in routine clinical practice. METHODS Retrospective data analysis of eyes that started dexamethasone implant for DMO from 1 June 2013 to 30 April 2019 in routine clinical practice tracked in the Fight Retinal Blindness! Registry. RESULTS Of the 4282 eyes (2518 patients) that started DMO treatment in the specified period, 267 (6%) eyes (204 patients) received 454 dexamethasone implant injections. Two-fifths (106 eyes) had received prior treatment for DMO. The mean (95% confidence interval [CI]) VA change at 12 months was 1.8 (- 0.5, 4.2) letters from the mean (standard deviation [SD]) VA of 56.5 (19.8) letters at baseline, with 41% eyes achieving at least 20/40. The mean (95% CI) change in central subfield thickness over 1 year was - 79 (- 104, - 54) µm from a mean (SD) of 459 (120) µm at baseline. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 2 (1, 2) dexamethasone implants. One-tenth of phakic eyes received cataract surgery while 2% had a pressure response requiring anti-glaucoma medications. CONCLUSIONS One-year treatment outcomes of dexamethasone intravitreal implant for DMO in routine clinical practice were inferior to those in the clinical trials perhaps because of fewer treatments in clinical practice