Bones pràctiques per a adolescents vulnerables. Educar a les Unitats d'Escolarització Compartida

[cat] Amb la consolidació d’un sistema educatiu comprensiu i obligatori fins als setze anys es fa evident el desencaix entre un grup d’adolescents i l’institut, entre l’escola i joves que abans de fer setze anys diuen no a l’aprenentatge. Es tracta de nois i noies que no queden integrats a les institucions educatives però tampoc ho fan en cercles socials, culturals i comunitaris. Així, si bé les manifestacions més visibles d’aquesta problemàtica al instituts han estat la transgressió de la norma, l’absentisme i el baix rendiment acadèmic per part d’aquets nois, és tracta d’un col·lectiu que, per sobre de tot, comparteix una condició de vulnerabilitat que es tradueix en itineraris biogràfics marcats per l’adversitat i en vivències limitades pels pocs recursos socials, econòmics i culturals amb què compten els seus entorns. Davant aquesta realitat, la investigació que presentem té la finalitat última d’aportar un sistema pedagògic que ajudi a posar en marxa pràctiques que facin possible la reconnexió i integració d’aquests adolescents al sistema. Per fer-ho, hem optat per una investigació qualitativa de tall etnogràfic. Ens hem nodrit de dues fonts principals: el treball de camp i les fonts bibliogràfiques. Per una banda, durant un any i mig, hem fet observació participant a tres Unitats d’Escolarització Compartida (UEC). És tracta de recursos educatius que donen resposta als adolescents que són expulsats dels instituts per temes de comportament essencialment però que encara estan en edat d’escolarització obligatòria. L’observació a tres UEC – Cruïlla, Cancuní i Esclat – ens ha permès recollir informació relativa a activitats que aconsegueixen una transformació substantiva sobre aquests joves. La segona font d’informació ha estat la revisió d’experiències dutes a terme en un passat i en l’actualitat que ens han permès visualitzar mecanismes pedagògics efectius amb aquesta població. Tot plegat, i a través d’un procés d’anàlisi qualitatiu, ha resultat en l’elaboració de disset relats etnogràfics sobre bones pràctiques educatives, 17 mapes conceptuals corresponents a les pràctiques descrites i un sistema pedagògic on s’ofereix una classificació de bones pràctiques per adolescents vulnerables segons les finalitats educatives que persegueixen, tot desenvolupant el sentit educatiu i els trets educatius principals de cada agrupació establerta.[eng] With the consolidation of a comprehensive and compulsory educational system up to the age of sixteen, it is evident that there is a distance between a group of adolescents and the institute, between the school and young people who, before turning sixteen, say “no” to learning. These are boys and girls that are not integrated into educational institutions but nor do in social, cultural and community circles. Thus, although the most visible manifestations of this problem in the institutes have been the transgression of the norm, the absenteeism and the low academic achievements, we are talking about a group of guys that share a vulnerability condition. This translates to biographical itineraries marked by adversity and in experiences limited by the few social, economic and cultural resources that are in their environments. In view of this situation, the research we present has the ultimate purpose of providing a pedagogical system that helps to put into practice activities that make it possible to reconnect and integrate these teens into the system. To do this, we have opted for a qualitative ethnographic investigation. We have been fed by two main sources: field work and bibliographic sources. On the one hand, for a year and a half, we have made an observation participating in three Units of Shared Schooling (UEC). It is educational resources that respond to adolescents who are expelled from the institutes, due to behavioral issues essentially, but are still under mandatory schooling. The observation in three UEC - Cruïlla, Cancuní and Esclat - has allowed us to collect information related to activities that achieve a substantive transformation on these young people. The second source of information has been the revision of experiences carried out in the past and at present that have allowed us to visualize effective pedagogical mechanisms with this population. All in all, and through a qualitative analysis process, it has resulted in the elaboration of seventeen ethnographic reports on good educational practices, seventeen conceptual maps corresponding to the described practices and a pedagogical system for vulnerable adolescents conformed by good practices that have been organized according to the educational aims they pursue

El aprendizaje-servicio como práctica inclusiva

This article primarily focuses on the implementation of service-learning in centres that work with adolescents at risk of social exclusion. Specifically, the paper relates part of a project developed over three years at four centres: the Shared Schooling Unit (UEC, by its Spanish initials) in Esclat; the UEC in Cruïlla, the Saó-Prat Foundation and the Adsis Foundation. The main issues discussed are the benefits of service-learning for social inclusion, the development of service-learning at one of the centre that had never before attempted this methodology and the factors that enabled the introduction of service-learning in all four centres. The article concludes with five reflections that seek to help guide the implementation and subsequent roll-out of service-learning in other centres that work with highly vulnerable adolescents.El artículo se centra de manera prioritaria en la implementación del aprendizaje-servicio en entidades que trabajan con adolescentes en riesgo de exclusión social. En concreto recoge parte de la experiencia realizada durante tres años en cuatro entidades: la Unidad de Escolaridad Compartida (UEC) Esclat, La UEC Cruïlla, La Fundación Saó-Prat y la Fundación Adsis. Los principales aspectos que se desarrollan son la aportación del aprendizaje-servicio a los procesos de inclusión social, el relato sobre el desarrollo del aprendizaje servicio en una de las entidades pioneras en el tema y los factores facilitadores en la introducción del aprendizaje servicio con este colectivo. El artículo finaliza con cinco reflexiones que pretenden ayudar a la implementación y posterior generalización de la metodología en entornos que trabajan con adolescentes en situación de alta vulnerabilidad

Introducción ¿Cómo difundir el aprendizaje servicio?

IntroductionEl monográfico presenta la experiencia de innovación educativa que ha supuesto el aprendizaje-servicio en Catalunya

Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response

Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells

Mutanome and expression of immune response genes in microsatellite stable colon cancer

The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis

Colon-specific eQTL analysis to inform on functional SNPs

BACKGROUND: Genome-wide association studies on colorectal cancer have identified more than 60 susceptibility loci, but for most of them there is no clear knowledge of functionality or the underlying gene responsible for the risk modification. Expression quantitative trail loci (eQTL) may provide functional information for such single nucleotide polymorphisms (SNPs). METHODS: We have performed detailed eQTL analysis specific for colon tissue on a series of 97 colon tumours, their paired adjacent normal mucosa and 47 colon mucosa samples donated by healthy individuals. R package MatrixEQTL was used to search for genome-wide cis-eQTL and trans-eQTL fitting linear models adjusted for age, gender and tissue type to rank transformed expression data. RESULTS: The cis-eQTL analyses has revealed 29,073 SNP-gene associations with permutation-adjusted P-values < 0.01. These correspond to 363 unique genes. The trans-eQTL analysis identified 10,665 significant SNP-gene associations, most of them in the same chromosome, further than 1 Mb of the gene. We provide a web tool to search for specific SNPs or genes. The tool calculates Pearson or Spearman correlation, and allows to select tissue type for analysis. Data and plots can be exported. CONCLUSIONS: This resource should be useful to prioritise SNPs for further functional studies and to identify relevant genes behind identified loci

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component

Background: Somatic copy number aberrations (CNA) are common acquired changes in cancer cells playing an important role in the progression of colon cancer (CRC). This study aimed to perform a characterization of CNA and their impact in gene expression.Methods: CNA were inferred from SNP array data in a series of 99 CRC. CNA events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes. All analyses were adjusted for the quantity of stroma in each sample, that was inferred from gene expression data.Results: High heterogeneity among samples was observed, the proportion of altered genome ranged between 0.04 and 26.6%. Recurrent CNA regions with gains were frequent in chromosomes 7p, 8q, 13q, and 20 while 8p, 17p, and 18 cumulated loses. A significant positive correlation was observed between the number of somatic mutations and total CNA (Spearman r=0.42, P=0.006). Approximately 37% of genes located in CNA regions changed their level of expression, and the average partial correlation (adjusted for stromal content) with copy number was 0.54 (inter-quartile range 0.20 to 0.81). Altered genes showed enrichment in pathways relevant for colorectal cancer. Tumours classified as CMS2 and CMS4 by the consensus molecular subtyping showed higher frequency of CNA. Loses of one small region in 1p36.33, with gene CDK11B, were associated with poor prognosis. More than 66% of the recurrent CNA were validated in the TCGA data when analysed with the same procedure. Also 79% of the genes with altered expression in our data were validated in the TCGA.Conclusion: Though CNA are frequent events in MSS CRC, few focal recurrent regions were found. These aberrations have strong effects on gene expression and contribute to deregulate relevant cancer pathways. Due to the diploid nature of stromal cells, it is important to consider the purity of tumour samples to accurately calculate CNA events in CRC

Grupo de Trabalho de Arqueobotânica e Zooarqueologia : resultados da primeira reunião

Resultados da primeira reunião geral de investigadores das áreas científicas da Arqueobotânica e Zooarqueologia a trabalhar em Portugal, realizada em Outubro de 2014, no Museu Nacional de Arqueologia (Lisboa). Identificando um conjunto de dificuldades comuns às duas disciplinas, os presentes decidiram criar um grupo de trabalho informal para fomentar o diálogo profissional e com as instituições universitárias, a tutela (administração central e regional), as empresas e a comunidade arqueológica em geral.Results of the first general meeting of researchers in the fields of Archaeobotany and Zooarchaeology working in Portugal, which took place in October 2014 at the National Museum of Archaeology in Lisbon. Having identified a set of difficulties in common, participants at the meeting decided to set up an informal work group to encourage dialogue among professionals and with universities, central and regional authorities, companies and the archaeological community at large

Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients

Fanconi anemia (FA) is caused by biallelic mutations in FA genes. Monoallelic mutations in five of these genes (BRCA1, BRCA2, PALB2, BRIP1 and RAD51C) increase the susceptibility to breast/ovarian cancer and are used in clinical diagnostics as bona-fide hereditary cancer genes. Increasing evidence suggests that monoallelic mutations in other FA genes could predispose to tumor development, especially breast cancer. The objective of this study is to assess the mutational spectrum of 14 additional FA genes (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCP, FANCQ, FANCR and FANCU) in a cohort of hereditary cancer patients, to compare with local cancer-free controls as well as GnomAD. A total of 1021 hereditary cancer patients and 194 controls were analyzed using our next generation custom sequencing panel. We identified 35 pathogenic variants in eight genes. A significant association with the risk of breast cancer/breast and ovarian cancer was found for carriers of FANCA mutations (odds ratio (OR) = 3.14 95% confidence interval (CI) 1.4-6.17, p = 0.003). Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk

Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine

Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. We present the generation and characterization of five distinct MPNST orthoxenograft models for preclinical testing and personalized medicine. Four of the models are patient-derived tumor xenografts (PDTX), two independent MPNSTs from the same NF1 patient and two from different sporadic patients. The fifth model is an orthoxenograft derived from an NF1-related MPNST cell line. All MPNST orthoxenografts were generated by tumor implantation, or cell line injection, next to the sciatic nerve of nude mice, and were perpetuated by 7-10 mouse-to-mouse passages. The models reliably recapitulate the histopathological properties of their parental primary tumors. They also mimic distal dissemination properties in mice. Human stroma was rapidly lost after MPNST engraftment and replaced by murine stroma, which facilitated genomic tumor characterization. Compatible with an origin in a catastrophic event and subsequent genome stabilization, MPNST contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Mutational frequency and type of somatic point mutations were highly variable among the different MPNSTs modeled, but very consistent when comparing primary tumors with matched orthoxenografts generated. Unsupervised cluster analysis and principal component analysis (PCA) using an MPNST expression signature of ~1,000 genes grouped together all primary tumor-orthoxenograft pairs. Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines. Following standardization and extensive characterization and validation, the orthoxenograft models were used for initial preclinical drug testing. Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth. The development of genomically well-characterized preclinical models for MPNST allowed the evaluation of novel therapeutic strategies for personalized medicine