Implicit and explicit self-esteem as predictors of reactive and proactive aggression in adolescent boys and girls

This study aims at examining gender differences and their association with implicit and explicit self-esteem (SE), and reactive and proactive aggression in adolescents. Hundred and eighteen adolescents (60 boys and 58 girls) performed the Implicit Association Test assessing implicit SE. The Rosenberg Self-Esteem scale was used to measure explicit SE. Reactive and proactive aggression were assessed with the self-report Reactive and Proactive Aggression Scale. Results showed that girls characterized by both low explicit and implicit SE (insecure SE), or by high explicit but low implicit SE (defensive SE), showed more reactive aggression than girls reporting high explicit and implicit SE (secure SE) or low explicit but high implicit SE (anxious SE). In contrast, none of these SE types were associated to reactive aggression in boys. Finally, no significant association was found between the different types of SE and proactive aggression, for both genders

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M.S

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer:A biomarker-enriched phase II study

OBJECTIVE: In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response to this combination treatment.METHODS: This is a phase II, open-label, non-randomized study. Patients with TP53 mutated PROC received carboplatin AUC 5 mg/ ml·min intravenously and adavosertib 225 mg BID orally for 2.5 days in a 21-day cycle. The primary objective is to determine the efficacy and safety of carboplatin and adavosertib. Secondary objectives include progression-free survival (PFS), changes in circulating tumor cells (CTC) and exploration of genomic alterations.RESULTS: Thirty-two patients with a median age of 63 years (39-77 years) were enrolled and received treatment. Twenty-nine patients were evaluable for efficacy. Bone marrow toxicity, nausea and vomiting were the most common adverse events. Twelve patients showed partial response (PR) as best response, resulting in an objective ORR of 41% in the evaluable patients (95% CI: 23%-61%). The median PFS was 5.6 months (95% CI: 3.8-10.3). In patients with tumors harboring CCNE1 amplification, treatment efficacy was slightly but not significantly better.CONCLUSIONS: Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 could be safely combined and showed anti-tumor efficacy in patients with PROC. However, bone marrow toxicity remains a point of concern, since this is the most common reason for dose reductions and dose delays.</p

Comportamiento Organizacional-AH14-202101

El curso de Comportamiento Organizacional realiza el análisis de las organizaciones en diferentes niveles, explora el impacto que tiene el proceso de transformación digital en las organizaciones, profundiza en el análisis de diversos procesos de gestión organizacional en los cuales los protagonistas principales son las personas, resaltando el rol del líder para el desarrollo de dichos procesos, además, aborda el análisis individual en el cual se evalúan y describen los principales factores que constituyen a las personas, así como, aquellos elementos estratégicos que contribuyen al éxito de una organización

Comportamiento Organizacional-AH14-202102

El curso de Comportamiento Organizacional realiza el análisis de las organizaciones en diferentes niveles, explora el impacto que tiene el proceso de transformación digital en estas, profundiza en el análisis de diversos procesos de gestión organizacional en los cuales los protagonistas principales son las personas, resaltando el rol del líder para el desarrollo de dichos procesos, además, aborda el análisis individual en el cual se evalúan y describen los principales factores que constituyen a las personas, así como, aquellos elementos estratégicos que contribuyen al éxito de una organización

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study

OBJECTIVE: In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response to this combination treatment. METHODS: This is a phase II, open-label, non-randomized study. Patients with TP53 mutated PROC received carboplatin AUC 5 mg/ ml·min intravenously and adavosertib 225 mg BID orally for 2.5 days in a 21-day cycle. The primary objective is to determine the efficacy and safety of carboplatin and adavosertib. Secondary objectives include progression-free survival (PFS), changes in circulating tumor cells (CTC) and exploration of genomic alterations. RESULTS: Thirty-two patients with a median age of 63 years (39-77 years) were enrolled and received treatment. Twenty-nine patients were evaluable for efficacy. Bone marrow toxicity, nausea and vomiting were the most common adverse events. Twelve patients showed partial response (PR) as best response, resulting in an objective ORR of 41% in the evaluable patients (95% CI: 23%-61%). The median PFS was 5.6 months (95% CI: 3.8-10.3). In patients with tumors harboring CCNE1 amplification, treatment efficacy was slightly but not significantly better. CONCLUSIONS: Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 could be safely combined and showed anti-tumor efficacy in patients with PROC. However, bone marrow toxicity remains a point of concern, since this is the most common reason for dose reductions and dose delays

Comportamiento Organizacional - AH14 - 202101

Descripción: El curso de Comportamiento Organizacional realiza el análisis de las organizaciones en diferentes niveles, explora el impacto que tiene el proceso de transformación digital en las organizaciones, profundiza en el análisis de diversos procesos de gestión organizacional en los cuales los protagonistas principales son las personas, resaltando el rol del líder para el desarrollo de dichos procesos, además, aborda el análisis individual en el cual se evalúan y describen los principales factores que constituyen a las personas, así como, aquellos elementos estratégicos que contribuyen al éxito de una organización. El curso brinda información actualizada y propuestas aplicativas para el desarrollo de una organización promoviendo un espacio para crear aplicaciones concretas relacionadas a los temas desarrollados. Busca incentivar la investigación, el análisis, la resolución de casos, la elaboración de propuestas y la creatividad por parte del estudiante, con la finalidad de diseñar una propuesta que contribuya al desarrollo organizacional, el cual contenga estrategias y herramientas innovadoras. Propósito: 1El curso de comportamiento organizacional ha sido diseñado con el propósito de permitir al futuro profesional desarrollar sus competencias organizacionales, mediante un adecuado análisis de la organización a todo nivel (individual, procesos de gestión de personas y del liderazgo), así como también promover la creatividad e innovación para crear una propuesta con estrategias y herramientas impactantes enfocadas al desarrollo organizacional considerando las nuevas características de los entornos laborales. El curso contribuye directamente al desarrollo de las competencias de Comunicación Oral (general ¿ UPC) y específica, de Dirección de personas, ambas a un nivel 2