L'Impacte ambiental dels abocadors de residus assimilables als urbans. Mètodes de detecció i correcció

Després d'una introducció dedicada a centrar 1'exposició en l'impacte ambiental dels abocadors de residus industrials assimilables als urbans, es descriuen diversos métodes de detecció, control, prevenció i correcció dels diversos tipus d'impacte sobre el paisatge, l'atmosfera i les aigües, i també dels impactes deguts a incidents (incendis). Es descriu també un mètode poc conegut de seguiment de l l'activitat interna dels abocadors

Study for the numerical resolution of the Navier-Stokes equations using the Fractional Step Method

Consolidar i ampliar els coneixements en termodinàmica, transferència de calor, dinàmica de fluids computacional, aerodinàmica, etc., així com la seva aplicació a sistemes tèrmics i fluídics concrets, millorant l’eficiència energètica. La metodologia bàsica de l’estudi serà la simulació numèrica de les fenomenologies de dinàmica de fluids i transferència de calor i massa presents. Es proposaran casos de referència per verificar el codi desenvolupat i les solucions numèriques obtingudes. Sempre que sigui adient, es validaran els models matemàtics en base a la contrastació dels resultats amb dades experimentals o de simulacions avançades obtingudes pel CTTC (www.cttc.upc.edu) o per altres investigadors. En una segona fase, i en base a les eines desenvolupades per l’estudiant, es desenvoluparà l'aplicació al disseny en àmbits concrets. A títol d’exemple mencionarem: aerodinàmica, energia eòlica, energia solar d’alta temperatura (CSP), sistemes actius i passius d’aprofitament de l’energia solar (arquitectura bioclimàtica), acumulació d’energia, refrigeració per compressió de vapor o per absorció, bescanviadors de calor, refrigeració de components elèctrics i electrònics, ventilació, climatització i aire condicionat (HVAC), etc. El títol final del TFG es decidirà en funció de la línia concreta escollida entre l’estudiant i el professor tutor.    This work is denominated Study for the numerical resolution of the Navier-Stokes equations using the Fractional Step Method. It is divided into 7 Chapters and 1 Annex. Chapter 1 presents the objectives, scope, requirements and background of the work and, additionally, the state of the art. Chapter 2 is dedicated to the introduction to numerical methods, while Chapter 3 covers the analysis of conduction heat transfer in solids. Chapter 4 covers different resolution methodologies of the Convection-Diffusion equation. An introduction to the numerical resolution of the Navier-Stokes equations through the Fractional Step Method is presented in Chapter 5. Finally, the environmental impact and some conclusions are presented in Chapter 6 and 7, respectively. In addition, one annex is presented. It includes additional graphs and the own developed computational codes

Reaprofitament i emmagatzematge de l'excedent elèctric produït a la planta fotovoltaica del Campus Sud en forma d’hidrogen

Aquest projecte de fi de grau és un estudi de viabilitat del reaprofitament i emmagatzematge en forma d’hidrogen de l’excedent elèctric teòric generat a la planta fotovoltaica projectada pel Campus Sud de la Universitat Politècnica de Catalunya. Mitjançant les dades de consum elèctric recollides pels informes SIRENA dels darrers anys als edificis de la UPC i la projecció de generació de la instal·lació fotovoltaica dissenyada, es pretén determinar la viabilitat energètica i econòmica de la introducció de l’hidrogen com a vector energètic al campus. El principi de funcionament de la proposta es basa en l’emmagatzematge d’energia en forma d’hidrogen, obtingut a través de l’electròlisi de l’aigua corrent, per al seu futur ús. L’energia utilitzada en el procés, s’obtindrà de l’excedent elèctric produït per les plaques fotovoltaiques com a alternativa a la venta d’aquest excedent a la xarxa. L’estudi ha partit de les dades simulades per a la planta de generació projectada a l’edifici de FME (Facultat de Matemàtiques i Estadística), per a una posterior distribució a altres escoles del Campus Sud. Un cop obtingudes les corbes de generació horàries de la instal·lació, s’ha fet un anàlisi energètic i econòmic amb l’objectiu de determinar la viabilitat de l’hidrogen com a vector energètic de abastir la demanda de consum del campus en diferents escenaris.Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminan

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Choosing Variant Interpretation Tools for Clinical Applications: Context Matters

Pathogenicity predictors are computational tools that classify genetic variants as benign or pathogenic; this is currently a major challenge in genomic medicine. With more than fifty such predictors available, selecting the most suitable tool for clinical applications like genetic screening, molecular diagnostics, and companion diagnostics has become increasingly challenging. To address this issue, we have developed a cost-based framework that naturally considers the various components of the problem. This framework encodes clinical scenarios using a minimal set of parameters and treats pathogenicity predictors as rejection classifiers, a common practice in clinical applications where low-confidence predictions are routinely rejected. We illustrate our approach in four examples where we compare different numbers of pathogenicity predictors for missense variants. Our results show that no single predictor is optimal for all clinical scenarios and that considering rejection yields a different perspective on classifiers

Choosing Variant Interpretation Tools for Clinical Applications: Context Matters

Clinical variant interpretation; Healthcare costs; Pathogenicity predictionInterpretación de variantes clínicas; Costes sanitarios; Predicción de patogenicidadInterpretació de variants clíniques; Despeses sanitàries; Predicció de patogenicitatPathogenicity predictors are computational tools that classify genetic variants as benign or pathogenic; this is currently a major challenge in genomic medicine. With more than fifty such predictors available, selecting the most suitable tool for clinical applications like genetic screening, molecular diagnostics, and companion diagnostics has become increasingly challenging. To address this issue, we have developed a cost-based framework that naturally considers the various components of the problem. This framework encodes clinical scenarios using a minimal set of parameters and treats pathogenicity predictors as rejection classifiers, a common practice in clinical applications where low-confidence predictions are routinely rejected. We illustrate our approach in four examples where we compare different numbers of pathogenicity predictors for missense variants. Our results show that no single predictor is optimal for all clinical scenarios and that considering rejection yields a different perspective on classifiers.This work was supported by research grants SAF2016-80255-R from the Spanish Ministerio de Economía y Competitividad (MINECO), PID2019-111217RB-I00 and TED2021-130342B-I00 from the Spanish Ministerio de Ciencia e Innovación, and by the European Regional Development Fund (ERDF) through the Interreg program POCTEFA (Pirepred, EFA086/15)

Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?

Síndromes de càncer; Panell genètic; Proves genètiquesSíndromes de cáncer; Panel de genes; Prueba genéticaCancer syndromes; Gene panel; Genetic testingImportance Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations. Objective To determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel. Patients and methods A cohort of 1023 unrelated patients with suspicion of hereditary cancer was screened using a validated panel including up to 135 genes associated with hereditary cancer and phakomatoses. Results Thirteen (1.37%) patients harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 5.7% (13/226) of patients with pathogenic mutations. Most (10/13) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene. Conclusions and relevance Genetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.Contract grant sponsor: Supported by the Carlos III National Health Institute and Ministerio de Educación y Ciencia funded by FEDER funds–a way to build Europe (PI16/00563, PI16/01363, SAF2015-68016-R and CIBERONC); the Government of Catalonia (Pla estratègic de recerca i innovació en salut (PERIS), 2017SGR1282 and 2017SGR496); and the scientific foundation Asociación Española Contra el Cáncer

BARD1 Pathogenic Variants Are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

BARD1; Càncer hereditari de mama i ovari; Risc moderat de càncerBARD1; Cáncer de mama y ovario hereditario; Riesgo de cáncer moderadoBARD1; Hereditary breast and ovarian cancer; Moderate cancer riskOnly a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10–6.48; p = 1.16 × 10−5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10–7.70; p = 5.45 × 10−5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77–18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.Contract grant sponsor: Supported by the Carlos III National Health Institute funded by FEDER funds—a way to build Europe—(PI19/00553; PI16/00563; PI16/01898; PI16/11363; PI15/00355; PI12/02585; SAF2015-68016-R and CIBERONC); the Government of Catalonia (Pla estratègic de recerca i innovació en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496); and CERCA Programa/Generalitat de Catalunya for institutional support. GCAT is supported by Acción de Dinamización del ISCIII-MINECO (ADE 10/00026), by the Ministry of Health of the Generalitat of Catalunya and by Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529) and GCAT Cession Research Project PI-2018-09 GCAT_CM

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1

BackgroundGermline variants affecting the proofreading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a specific mutational spectrum. In addition to the implementation of multiple pieces of evidence for the classification of gene variants, POLE and POLD1 variant classification is particularly challenging given that non-disruptive variants affecting the proofreading activity of the corresponding polymerase are the ones associated with cancer. In response to an evident need in the field, we have developed gene-specific variant classification recommendations, based on the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) criteria, for the assessment of non-disruptive variants located in the sequence coding for the exonuclease domain of the polymerases.MethodsA training set of 23 variants considered pathogenic or benign was used to define the usability and strength of the ACMG/AMP criteria. Population frequencies, computational predictions, co-segregation data, phenotypic and tumor data, and functional results, among other features, were considered.ResultsGene-specific variant classification recommendations for non-disruptive variants located in the exonuclease domain of POLE and POLD1 were defined. The resulting recommendations were applied to 128 exonuclease domain variants reported in the literature and/or public databases. A total of 17 variants were classified as pathogenic or likely pathogenic, and 17 as benign or likely benign.ConclusionsOur recommendations, with room for improvement in the coming years as more information become available on carrier families, tumor molecular characteristics and functional assays, are intended to serve the clinical and scientific communities and help improve diagnostic performance, avoiding variant misclassifications

CNVfilteR: an R/bioconductor package to identify false positives produced by germline NGS CNV detection tools.

Germline copy-number variants (CNVs) are relevant mutations for multiple genetics fields, such as the study of hereditary diseases. However, available benchmarks show that all next-generation sequencing (NGS) CNV calling tools produce false positives. We developed CNVfilteR, an R package that uses the single nucleotide variant calls usually obtained in germline NGS pipelines to identify those false positives. The package can detect both false deletions and false duplications. We evaluated CNVfilteR performance on callsets generated by 13 CNV calling tools on 3 whole-genome sequencing and 541 panel samples, showing a decrease of up to 44.8% in false positives and consistent F1-score increase. Using CNVfilteR to detect false-positive calls can improve the overall performance of existing CNV calling pipelines. Availability: CNVfilteR is released under Artistic-2.0 License. Source code and documentation are freely available at Bioconductor (http://www.bioconductor.org/packages/CNVfilteR). Supplementary information: Supplementary data are available at Bioinformatics online