The 2014 European Inventory on validation of non-formal and informal learning. Prospects and trends on validation in Europe

The European Inventory is a tool produced under the auspices of the European Commission and has been in place since 2004. It presents an overview of the situation regarding validation in European countries. The 2014 Inventory investigates 33 countries through 36 country reports. After describing the political context for the validation of non-formal and informal learning in Europe, namely the European Council Recommendation of December 2012, the article explains the main features of the European Inventory and presents selected findings

A Traditional Diet Is Associated with a Reduced Risk of Eczema and Wheeze in Colombian Children

Background: Diet might influence the risk of allergic diseases. Evidence from developing countries with high prevalence of childhood asthma is scant. Methods: Information on wheeze, rhinitis, and eczema was collected from 3209 children aged 6–7 years in 2005, who were taking part in the International Study on Asthma and Allergy in Children (ISAAC) in Colombia. Intake frequency of twelve food groups was assessed. Associations between each food group and current wheeze, rhino-conjunctivitis, and eczema were investigated with multiple logistic regressions, adjusting for potential confounders. Simes’ procedure was used to test for multiple comparisons. Results: 14.9% of children reported wheeze in the last 12 months, 16% rhino-conjunctivitis, and 22% eczema. Eczema was negatively associated with consumption of fresh fruits and pulses three or more times per week (adjusted Odds ratio (aOR): 0.64; 95% Confidence Interval (CI): 0.49 to 0.83; p value = 0.004; and aOR: 0.62, 95% CI: 0.47 to 0.80; p value < 0.001, respectively). Current wheeze was negatively associated with intake of potatoes (aOR: 0.44, 95% CI: 0.31 to 0.62, p value = 0.005), whilst this outcome was positively associated with consumption of fast food (aOR: 1.76, 95% CI: 1.32 to 2.35, p value = 0.001). These associations remained statistically significant after controlling for multiple comparisons. Conclusions: A traditional diet might have a protective effect against eczema and wheeze in Colombian children, whilst intake of fast foods increases this risk

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

Background In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. Objectives The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action. Methods Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1Δi12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. Results In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1Δi12 mice show increased cardiac hypertrophy and declined contractility. Conclusions The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches

The association between the tumor immune microenvironments and clinical outcome in low-grade, early-stage endometrial cancer patients

Endometrial tumors show substantial heterogeneity in their immune microenvironment. This heterogeneity could be used to improve the accuracy of current outcome prediction tools. We assessed the immune microenvironment of 235 patients diagnosed with low-grade, early-stage endometrial cancer. Multiplex quantitative immunofluorescence was carried out tomeasure CD8, CD68, FOXP3, PD-1,and PD-L1markers, aswell as cytokeratin (CK), on tissuemicroarrays. Clustering results revealed five robust immune response patterns, each associated with specific immune populations, cell phenotypes, and cell spatial clustering.Most samples (69%) belonged to theimmune-desert subtype, characterized by lowimmune cell densities. Tumor-infiltrating lymphocyte (TIL)-rich samples (4%) displayed high CD8+ T-cell infiltration, as well as a high percentage of CD8/PD-1+ cells. Immune-exclusion samples (19%) displayed the lowest CD8+ infiltration combined with high PD-L1 expression levels in CK+ tumor cells. In addition, they demonstrated high tumor cell spatial clustering as well as increased spatial proximity of CD8+/PD-1+ andCK/PD-L1+ cells.FOXP3andmacrophage-rich phenotypes (3%and 4% of total samples) displayed relatively high levels of FOXP3+ regulatory T-cells and CD68+ macrophages, respectively. These phenotypes correlated with clinical outcomes, with immune-exclusion tumors showing an association with tumor relapse. When compared with prediction models built using routine pathological variables, models optimized with immune variables showed increased outcome prediction capacity (AUC = 0.89 versus 0.78) and stratification potential. The improved prediction capacity was independent of mismatch repair protein status and adjuvant radiotherapy treatment. Further, immunofluorescence results could be partially recapitulated using single-marker immunohistochemistry (IHC) performed on whole tissue sections. TIL-rich tumors demonstrated increased CD8+ T-cells by IHC, while immune-exclusion tumors displayed a lack of CD8+ T-cells and frequent expression of PD-L1 in tumor cells. Our results demonstrate the capability of the immune microenvironment to improve standard prediction tools in low-grade, early-stage endometrial carcinomasCEA and IgM were funded by Fundación La Marató de TV3. This project was supported by grants from Partners of Choice Network from AstraZeneca and by the Instituto de Salud Carlos III (ISCIII) (PI17/01723 and PI21/00920), co-financed by the European Regional Development Fund ‘A way to achieve Europe’ (FEDER). We thank Marco Cassano (Lunaphore Technologies) for his help in writing the manuscrip

First month prednisone dose predicts prednisone burden during the following 11 months: An observational study from the RELES cohort

Aim: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of =6, the model did not change. Conclusion: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months

Optimizing DDRADseq in non-model species: A Case Study in Eucalyptus dunnii Maiden

Restriction site-associated DNA sequencing (RADseq) and its derived protocols, such as double digest RADseq (ddRADseq), offer a flexible and highly cost-effective strategy for efficient plant genome sampling. This has become one of the most popular genotyping approaches for breeding, conservation, and evolution studies in model and non-model plant species. However, universal protocols do not always adapt well to non-model species. Herein, this study reports the development of an optimized and detailed ddRADseq protocol in Eucalyptus dunnii, a non-model species, which combines different aspects of published methodologies. The initial protocol was established using only two samples by selecting the best combination of enzymes and through optimal size selection and simplifying lab procedures. Both single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) were determined with high accuracy after applying stringent bioinformatics settings and quality filters, with and without a reference genome. To scale it up to 24 samples, we added barcoded adapters. We also applied automatic size selection, and therefore obtained an optimal number of loci, the expected SNP locus density, and genome-wide distribution. Reliability and cross-sequencing platform compatibility were verified through dissimilarity coefficients of 0.05 between replicates. To our knowledge, this optimized ddRADseq protocol will allow users to go from the DNA sample to genotyping data in a highly accessible and reproducible way.Instituto de BiotecnologíaFil: Aguirre, Natalia Cristina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Filippi, Carla Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zaina, Giusi. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Rivas, Juan Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acuña, Cintia Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villalba, Pamela Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Martin Nahuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonzalez, Sergio Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivarola, Maximo Lisandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Maria Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Puebla, Andrea Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morgante, Michele. University of Udine. Department of Agricultural, Food, Environmental and Animal Sciences; ItaliaFil: Hopp, Horacio Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paniego, Norma Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marcucci Poltri, Susana Noemi. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Bacteriemia secundaria a balanitis por pseudomona aeruginosa XDR en paciente con LLC con inmunosupresión severa prolongada

PB-071 Introducción: La neutropenia severa (7- 10 días) es indicación de profilaxis antibiótica en pacientes de alto riesgo para desarrollo de infección según guías de recomendación. En enfermedades con clonalidad linfoide como la leucemia linfática crónica (LLC), se añade frecuentemente el desarrollo de hipogamaglobulinemia, que produce afectación de la inmunidad innata y humoral, aumentando el riesgo infeccioso de base. Caso clínico: Paciente de 70 años con antecedentes de colicitis ulcerosa (CU) y LLC estadío Rai 4 Binet C desde mayo de 2017, con cadena pesada de las inmunoglobulinas y p53 normales, que recibió Ibrutinib durante 20 días en diciembre de 2017, suspendiéndose por múltiples complicaciones infecciosas: NAC, bacteriemia por E. Coli, gripe A y aspergilosis pulmonar invasiva. Ingresa en hematología en abril de 2018 por diarrea, disuria y balanitis prepucial de una semana de evolución. Presenta fiebre en contexto de neutropenia severa y prolongada, con posible foco infeccioso digestivo y/o urinario. Se inicia tratamiento antibiótico empírico y se continúa tratamiento antifúngico previo. Digestivo descarta que la diarrea sea secundaria a brote de CU. Presenta mejoría de cuadro diarreico con empeoramiento de balanitis, documentándose tándose aislamiento de P. aeruginosa XDR en orina y exudado uretral. Se realizó cambio de antibiótico a aztreonam y colistina según antibiograma recogido en Tabla 1. Durante la evolución, se reactiva infección por CMV y se decide inicio de valganciclovir sin evidencia de lesión orgánica o enfermedad por CMV. Se descarta infección fúngica invasiva activa durante la hospitalización. Debido a progresión clínica de adenopatías y aumento de hepatoesplenomegalia, además de neutropenia persistente, secundarios a infiltración por LLC; se decide inicio de quimioterapia con esquema R-Clorambucilo y reinicio de G-CSF (G-CSF inefectivo en ingresos previos). Se descarta transformación de hemopatía de base mediante biopsia de médula ósea. Se produce reducción importante de adenopatías axilares e inguinales con menor respuesta del conglomerado adenopático abdominal. ..

Glomerulonefritis membranoproliferativa paraneoplásica en leucemia linfática crónica: a propósito de un caso

PB-070 Introducción: La leucemia linfática crónica (LLC) es una neoplasia hematológica con alta incidencia en la población general. Sin embargo, la incidencia de afectación extranodal o extramedular secundaria a procesos paraneoplásicos es rara. En las series de casos encontradas en la literatura, la incidencia de afectación sintomática a nivel genitourinario o ginecológico es inferior al 10%, pero en autopsias se ha encontrado infiltración asintomática hasta en un 90% de los casos. La glomerulonefritis membranoproliferativa (GNMP) es la afectación paraneoplásica más frecuentemente encontrada a nivel renal y se presenta generalmente con insuficiencia renal o síndrome nefrótico. Caso clínico: Paciente de 81 años con antecedentes de HTA, dislipemia, fibrilación auricular, HBP e hipoacusia crónica. Ingresa en Nefrología en septiembre de 2018 por insuficiencia renal progresiva desde una creatinina basal de 1.26 mg/dL hasta 2.54 mg/dL, asociado a microhematuria y proteinuria; sin proceso intercurrente ni exposición a nefrotóxicos. Se encuentra asintomático, sin hallazgos patológicos a la exploración física. Se objetiva proteinuria de 7.7 gramos en orina de 24 horas, proteinuria de Bence Jones negativa y hematuria persistente. Así mismo, se objetiva una linfocitosis de 5.8x103/microL. Se completa el estudio etiológico mediante biopsia renal, con el diagnóstico de GNMP. En las pruebas de inmunohistoquímica, se objetiva un infiltrado linfocítico en cápsula renal CD20 positivo, CD23 y CD5 focalmente positivos; compatible con infiltración por LLC. En la citometría de flujo de sangre periférica, se halla un 38, 1% de linfocitos B maduros, siendo un 96% elementos clonales con inmunofenotipo de LLC con coexpresión de CD20, CD19, CD23, CD200 y CD5. En la citogenética se obtiene trisomía del cromosoma 12. Presenta biología molecular no mutada para TP53 y VH. En la serie ósea no se objetivan imágenes osteolíticas. En diciembre de 2018, Nefrología inicia tratamiento con ..

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio

Search for B0→π0π0B^{0}\to \pi^{0}\pi^{0} Decay

We have searched for the charmless hadronic decay of B0 mesons into two neutral pions. Using 9.13fb^-1 taken at the Upsilon(4S) with the CLEO detector, we obtain an improved upper limit for the branching fraction BR(B0-->pi0pi0) < 5.7*10^-6 at the 90% confidence level.Comment: pages postscript, also available through http://w4.lns.cornell.edu/public/CLN