Narrating arguments and argumenting narratives: a study in the homes of young children from different social groups

En este estudio se analizan secuencias interaccionales en las que narración y argumentación se entrelazan en el discurso de niños de dos grupos sociales -medio (NSM) y bajo (NSB)- en sus intercambios cotidianos en el hogar. La mayoría de los estudios sobre la producción discursiva infantil han atendido a cada forma discursiva por separado, sin embargo, en la interacción natural las formas discursivas se entrelazan en función de los roles y objetivos de los participantes (Adam, 1999). En el estudio que se reporta se atiende al modo en el que argumentación y narración se imbrincan considerando diferencias según el grupo social y los participantes -adultos y niños- que interactúan con el niño. Se identificaron 43 secuencias -21 en NSB y 22 en NSM- en un corpus de 468 horas de audio-grabación en el hogar de 39 niños. Las secuencias fueron categorizadas empleando el Método Comparativo Constante (Glaser & Strauss, 1967). Los resultados mostraron dos formas en las que narrativa y argumentación se entretejían: 1) la narración cumplía la función de Evidencia factual, se insertaba en la disputa y funcionaba como una estrategia argumentativa, 2) el interlocutor producía un Cuestionamiento de los hechos, ponía en duda los hechos narrados por el niño dando de este modo lugar a la disputa. Se encontró que los dos grupos sociales entrecruzan narración y argumentación de forma similar. Sin embargo, cuando el interlocutor era un adulto se producían mayor proporción de secuencias de cuestionamiento de los hechos que cuando el interlocutor era otro niño.In the present study, interactional sequences are analyzed in which narration and argumentation are intertwined in the speech of children from two social groups - middle (NSM) and low (NSB) - in their daily interactions at home. Most studies on children’s discursive production have dealt with each discursive form separately, however, in natural interaction the discursive forms are intertwined depending on the roles and objectives of the participants (Adam, 1999). In the study that is reported, attention is paid to the way in which argumentation and narration are intertwined considering differences according to the social group and the participants - adults and children - who interact with the child. 43 sequences -21 in NSB and 22 in NSM- were identified in a corpus of 468 hours of audio recording in the home of 39 children. The sequences were categorized using the Constant Comparative Method (Glaser and Strauss, 1967). The results showed two ways in which narrative and argumentation were intertwined: 1) the narrative fulfilled the function of “Factual Evidence”: it was inserted into the dispute and functioned as an argumentative strategy, 2) the interlocutor produced a “Questioning of the facts”: he questioned the facts narrated by the child, thus giving rise to the dispute. The two social groups were found to intertwine narrative and argumentation in a similar way. However, when the interlocutor was an adult, a higher proportion of questioning sequences occurred than when the interlocutor was another child.Fil: Alam, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Rosemberg, Celia Renata. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Lewinsky, Viviana. Universidad de Buenos Aires. Facultad de Filosofia y Letras. Instituto de Investigación en Ciencias de la Educación; ArgentinaFil: Shiro, Marta. Universidad Central de Venezuela; VenezuelaFil: Arrué, Josefina. No especifíca

Structural, electrical and photocatalytic properties of iron-containing soda-lime aluminosilicate glass and glass-ceramics

The structure and electrical conductivity of iron-containing soda-lime alumino-silicate glass-ceramic system were investigated and used for the degradation of methylene blue (MB) solution. Mössbauer isomer shifts were decreased from 0.26 and 0.25 to 0.14 and 0.12 mm s-1 with increasing basicity from 0.75 to 1.50 revealing the cleavage in network structure due to the incorporation of Ca2+ ions. By increasing basicity from 0.75 to 1.50, the electrical conductivity was increased from (2.2 × 10-12 to 2.2 × 10-8 Ω -1 cm-1 ). More increase in basicity to 1.75 decreased the conductivity to 6.5× 10-9 Ω -1 cm-1 . The electrical conductivity is ionic in nature and was correlated to the microstructure of the samples. The first-order rate constant (k) for the MB degradation was enhanced from 0.09 × 10-1 to 1.15 × 10−1 min−1 with increasing basicity from 0.75 to 1.50, having a good correlation with microstructure and electrical conductivity

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Paradigm shift in heart failure treatment: are cardiologists ready to use gliflozins?

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment

A new educational program in heart failure drug development: the Brescia international master program

: Despite recent advances in chronic heart failure treatment, prognosis of acute heart failure patients remains poor with a heart failure rehospitalization rate or death reaching approximately 25% during the first 6 months after discharge. In addition, about half of these patients have preserved ejection fraction for which there are no evidence-based therapies. Disappointing results from heart failure clinical trials over the past 20 years emphasize the need for developing novel approaches and pathways for testing new heart failure drugs and devices. Indeed, many trials are being conducted without matching the mechanism and action of the drug with the clinical event. The implementation of these novel approaches should be coupled with the training of a new generation of heart failure physicians and scientists in the art and science of clinical trials. Currently, drug development is led by opinion leaders and experts who, despite their huge personal experience, were never trained systematically on drug development. The aim of this article is to propose a training program of \u27drug development in Heart Failure\u27. A physician attending this course would have to be trained with a major emphasis on heart failure pathophysiology to better match mechanisms of death and rehospitalization with mechanism of action of the drug. Applicants will have to prove their qualifications and special interest in heart failure drug development before enrollment. This article should serve as a roadmap on how to apply emerging general principles in an innovative drug-development-in-heart-failure-process as well as the introduction of a new educational and mentorship program focusing on younger generations of researchers

Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018)

PURPOSE To evaluate the addition of ofranergene obadenovec (ofra-vec, VB-111), a novel gene-based anticancer targeted therapy, to once a week paclitaxel in patients with recurrent platinum-resistant ovarian cancer (PROC). METHODS This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655 ) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression. The dual primary end points were overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review. RESULTS Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS. In the ofra-vec arm, the HR in CA-125 responders compared with that in nonresponders for PFS was 0.2428 (CI, 0.1642 to 0.3588), and for OS, the HR was 0.3343 (CI, 0.2134 to 0.5238). Safety profile was characterized by common transient flu–like symptoms such as fever and chills. CONCLUSION The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for PFS and OS in patients with PROC treated with paclitaxel

ENIGMA CHEK2gether Project : a comprehensive study identifies functionally impaired CHEK2 germline missense variants associated with increased breast cancer risk

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1–CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case–control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)–like (N = 226). We then examined their association with breast cancer risk in the case–control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35–3.41), 1.57 (95% CI, 1.41–1.75), and 1.19 (95% CI, 1.08–1.31), respectively. The meta-analysis of population-specific datasets showed similar results. Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers