A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia

[EN] To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q-CLLs. In patients with >= 40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) (P<0.0001). In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008). The absence of splenomegaly (P = 0.02), low LDH (P = 0.018) or beta 2M (P = 0.006), and the presence of 11q-L (P = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q-showed mutations and fewer patients with low frequencies of 11q-had mutations among genes examined (50% vs 94.1%, P = 0.023). In summary, CLL patients with <40% of 11q-had a long TFT and OS that could be associated with the presence of fewer mutated genes.European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624

Instructional Changes Adopted for an Engineering Course: Cluster Analysis on Academic Failure

As first-year students come from diverse backgrounds, basic skills should be accessible to everyone as soon as possible. Transferring such skills to these students is challenging, especially in highly technical courses. Ensuring that essential knowledge is acquired quickly promotes the student’s self-esteem and may positively influence failure rates. Metaphors can help do this. Metaphors are used to understand the unknown. This paper shows how we made a turn in student learning at the University of Almeria. Our hypothesis assumed that metaphors accelerate the acquisition of basic knowledge so that other skills built on that foundation are easily learned. With these goals in mind, we changed the way we teach by using metaphors and abstract concepts in a computer organisation course, a technical course in the first year of an information technology engineering degree. Cluster analysis of the data on collective student performance after this methodological change clearly identified two distinct groups. These two groups perfectly matched the before and after scenarios of the use of metaphors. The study was conducted during 11 academic years (2002/2003 to 2012/2013). The 475 observations made during this period illustrate the usefulness of this change in teaching and learning, shifting from a propositional teaching/learning model to a more dynamic model based on metaphors and abstractions. Data covering the whole period showed favourable evolution of student achievement and reduced failure rates, not only in this course, but also in many of the following more advanced courses.The paper is structured in five sections. The first gives an introduction, the second describes the methodology. The third section describes the sample and the study carried out. The fourth section presents the results and, finally, the fifth section discusses the main conclusions

Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population

Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. This study aimed to evaluate the involvement of all genetic variants in pre-miRNAs described so far in relationship to the risk of osteosarcoma. We analyzed a total of 213 genetic variants in 206 pre-miRNAs in two cohorts of osteosarcoma patients (n = 100) and their corresponding controls (n = 256) from Spanish and Slovenian populations, using Goldengate Veracode technology (Illumina). Four polymorphisms in pre-miRNAs at 14q32 miRNA cluster were associated with osteosarcoma risk in the Spanish population (rs12894467, rs61992671, rs58834075 and rs12879262). Pathway enrichment analysis including target genes of these miRNAs pointed out the WNT signaling pathways overrepresented. Moreover, different single nucleotide polymorphism (SNP) effects between the two populations included were observed, suggesting the existence of population differences. In conclusion, 14q32 miRNA cluster seems to be a hotspot for osteosarcoma susceptibility in the Spanish population, but not in the Slovenian, which supports the idea of the existence of population differences in developing this disease.Special thanks to Slovenian Osteosarcoma Study Group for their collaboration in sample collection. The "Slovenian Osteosarcoma Study Group" is conformed by Katja Goricar from the Institute of Biochemistry, Faculty of Medicine of Ljubljana, Viljem Kovac from the Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine of University of Ljubljana, Janez Jazbec from the Institute of Oncology Ljubljana, Janez Lamovec from the Oncology and Hematology Unit, University Children's Hospital, University Medical Centre of Ljubljana and Prof. Vita Dolzan included in the authorship of this article. The authors would like to thank Leire Iparraguirre for her technical assistance with figures. This study was funded by the Basque Government (IT661-13, IT989-16), UPV/EHU (UFI11/35)

Confirmation of involvement of new variants at CDKN2A/B in pediatric acute lymphoblastic leukemia susceptibility in the Spanish population

The locus CDKN2A/B (9p21.3), which comprises the tumor suppressors genes CDKN2A and CDKN2B and the long noncoding RNA (lncRNA) known as ANRIL (or CDKN2B-AS), was associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in several genome wide association studies (GWAS). However, the variants associated in the diverse studies were different. Recently, new and independent SNPs deregulating the locus function were also identified in association with ALL risk. This diversity in the results may be explained because different variants in each population could alter CDKN2A/B locus function through diverse mechanisms. Therefore, the aim of this study was to determine whether the annotated risk variants in the CDKN2A/B locus affect the susceptibility of B cell precursor ALL (B-ALL) in our Spanish population and explore if other SNPs altering additional regulatory mechanisms could be also involved. We analyzed the four SNPs proposed by GWAs and two additional SNPs in miRNA binding sites in 217 pediatric patients with B-ALL and 330 healthy controls. The SNPs rs2811712, rs3731249, rs3217992 and rs2811709 were associated with B-ALL susceptibility in our Spanish population. ALL subtypes analyses showed that rs2811712 was associated with B-hyperdiploid ALL. These results provide evidence for the influence of genetic variants at CDKN2A/B locus with the risk of developing BALL.This study was funded by the Basque Government (IT661-13, IT989-16), UPV/EHU (UFI11/35). AGC was supported by a pre-doctoral grant from the Basque Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Involvement of SNPs in miR-3117 and miR-3689d2 in Childhood Acute Lymphoblastic Leukemia Risk

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Numerous studies have shown that microRNAs (miRNAs) could play a role in this disease. Nowadays, more than 2500 miRNAs have been described, that regulate more than 50% of genes, including those involved in B-cell maturation, differentiation and proliferation. Genetic variants in miRNAs can alter their own levels or function, affecting their target gene expression, and then, may affect ALL risk. Therefore, the aim of this study was to determine the role of miRNA genetic variants in B-ALL susceptibility. We analyzed all variants in pre-miRNAs (MAF > 1%) in two independent cohorts from Spain and Slovenia and inferred their functional effect by in silico analysis. SNPs rs12402181 in miR-3117 and rs62571442 in miR-3689d2 were associated with ALL risk in both cohorts, possibly through their effect on MAPK signalling pathway. These SNPs could be novel markers for ALL susceptibility

Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

PURPOSE: Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure. METHODS: The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients. RESULTS: The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes. CONCLUSION: Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates

Personal resources and their relationship to job crafting and burnout: a challenge for male nurses as a minority group

The heavy workload and pressure to which nurses are subjected leads to an increase in stress-related problems, such as burnout. Personal resources, such as job crafting, proactive personality, self-efficacy and regulatory focus are fundamental in palliating negative effects in the work environment and reducing quitting by male nurses. The objective of this study was to analyze individual differences, with attention to proactive personality, regulatory approach and general self-efficacy in job crafting, and to determine the predictive power of these variables for burnout in nurses. The sample was made up of 643 nurses. After correlation and descriptive analyses, multiple linear regression models were computed to find out the possible predictor role of the individual variables on burnout. The results showed that job crafting, proactive personality, general self-efficacy and the promotion regulatory focus were associated with a decrease in burnout in nurses. Similarly, the predictive models for each of the factors in burnout in all cases included the increase in structural resources dimension of job crafting as the variable with the most weight. Furthermore, self-efficacy, increase in job crafting social resources and proactive personality were mediators in this relationship for personal impact, social climate and job dissatisfaction factors of burnout. These findings are significant for improving performance of nurses and increasing their retention, which could be especially significant among male nurses

Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.This work was partially supported by the Instituto de Salud Carlos III-Cofinanciación con fondos FEDER (PI080568, PS0901897 and PI13/00111), the Gerencia Regional de Salud, Junta de Castilla y León (GRS202/A08 and GRS 702/A/11), the Spanish Myeloma Network Program (RD06/0020/0006) and the Asociación Española Contra el Cáncer (AECC, GCB120981SAN).Peer Reviewe

Guía de Recursos de Evaluación en Convivencia Escolar

La guía recoge una recopilación de recursos que facilita la selección de un instrumento de evaluación adecuado, que permite recoger los datos propios de una investigación. Con tal compendio de instrumentos, el alumno podrá seleccionar aquellos que más se adecúen a los objetivos planteados para su Trabajo Fin de Máster. Todo ello, basándose en el análisis y conocimiento pormenorizado de todas las opciones disponibles en cada caso. Así, los contenidos de la guía suponen una ventaja con respecto al proceso de búsqueda y selección de instrumentos utilizado tradicionalmente, al que el alumno dedica un tiempo y esfuerzo que resta a otras etapas importantes de la investigación y elaboración de su Trabajo Fin de Máster, Trabajo Fin de Grado u otros proyectos de investigación

Inteligencia emocional y salud en el envejecimiento: beneficios del programa PECI-PM

El entrenamiento de la inteligencia emocional en personas mayores, ha demostrado su efectividad en la mejora de la calidad de vida. El objetivo es analizar los beneficios en salud, de un programa de estimulación cognitiva e inteligencia emocional para personas mayores (PECI-PM). La muestra estuvo formada por 28 alumnos de la Universidad de Mayores de Almería, que completaron la primera fase del PECI-PM. Para la evaluación (pre-post) de la salud, se aplicó la versión española del SF-36. Los resultados mostraron puntuaciones significativamente más elevadas, tras la intervención, en las dimensiones de salud: Función Social, Dolor Corporal, Vitalidad y Función Social. La primera implementación del PECI-PM, revela efectos positivos del entrenamiento emocional sobre la percepción de la salud, en personas mayores.  El entrenamiento de la inteligencia emocional en personas mayores, ha demostrado su efectividad en la mejora de la calidad de vida. El objetivo es analizar los beneficios en salud, de un programa de estimulación cognitiva e inteligencia emocional para personas mayores (PECI-PM). La muestra estuvo formada por 28 alumnos de la Universidad de Mayores de Almería, que completaron la primera fase del PECI-PM. Para la evaluación (pre-post) de la salud, se aplicó la versión española del SF-36. Los resultados mostraron puntuaciones significativamente más elevadas, tras la intervención, en las dimensiones de salud: Función Social, Dolor Corporal, Vitalidad y Función Social. La primera implementación del PECI-PM, revela efectos positivos del entrenamiento emocional sobre la percepción de la salud, en personas mayores