Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Aprendizagem experiencial: fortalecendo competências essenciais para uma liderança empresarial abrangente

Today the business context, marked by the growing complexity and volatility of environments and by the uncertainty and ambiguity that characterize numerous aspects of the economic, social, political, environmental and technological reality, presents a constant challenge for business organizations and their leaders in order to address the multiplicity of factors that influence the development of organizations. In this sense, the requirement for comprehensive training stands as a fundamental pillar for the personal and professional development of business leaders, who must constantly adapt and evolve to face emerging challenges and lead their organizations towards competitiveness and sustainability in an environment dynamic and demanding.Hoy el contexto empresarial, marcado por la creciente complejidad y la volatilidad de los entornos y por la incertidumbre y la ambigüedad que caracterizan numerosos aspectos de la realidad económica, social, política, medioambiental y tecnológica, presenta un desafío constante para las organizaciones empresariales y sus líderes en aras de hacer frente a la multiplicidad de factores que influyen en el desenvolvimiento de las organizaciones. En este sentido la exigencia de una formación integral se erige como pilar fundamental para el desarrollo personal y profesional de los líderes empresariales, quienes deben adaptarse y evolucionar constantemente para enfrentar los retos emergentes y conducir a sus organizaciones hacia la competitividad y la sostenibilidad en un entorno dinámico y exigente.Hoje o contexto empresarial, marcado pela crescente complexidade e volatilidade dos ambientes e pela incerteza e ambiguidade que caracterizam numerosos aspectos da realidade económica, social, política, ambiental e tecnológica, apresenta um desafio constante às organizações empresariais e aos seus líderes, a fim de abordar a multiplicidade de fatores que influenciam o desenvolvimento das organizações. Neste sentido, a exigência de uma formação integral constitui-se como um pilar fundamental para o desenvolvimento pessoal e profissional dos líderes empresariais, que devem adaptar-se e evoluir constantemente para enfrentar os desafios emergentes e conduzir as suas organizações rumo à competitividade e sustentabilidade num ambiente dinâmico e exigente

ALSEC: decisiones para incrementar su valor

Texto digital.“La empresa de alimentos Alsec fue elegida por la Asociación Nacional de Empresarios de Colombia (Andi) como la empresa más innovadora del sector en Colombia y como la quinta del país” (Sánchez, 2019, párr. 1). Asimismo, esta pequeña compañía antioqueña compite con multinacionales que manejan presupuestos mucho más grandes (Sánchez, 2019). 56 ALSEC fue fundada por dos ingenieros mecánicos, que nació como una empresa que vendía equipos de secado. Aunque los socios se darían cuenta de que el mercado de estos equipos es limitado porque su duración es superior a los 20 años. Por tal motivo, encontraron que había mayor potencial en la industria alimenticia.Cuarta edició

Incidencia del turismo en la sociedad local y la incorporación de la mujer en la actividad socieconómica y su promoción local: el caso de Guatuso en la Región Huetar Norte de Costa Rica

El Instituto de Estudios Sociales en Población IDESPO, de la Universidad Nacional, forma parte del proyecto “Turismo Sostenible, Desarrollo Local y Cooperación Internacional: Resilencia, Socioecológia y Articulación Transfronterizo en el Río San Juan (Costa Rica-Nicaragua). Dicho proyecto que se lleva a cabo conjuntamente con otras instituciones nacionales e internacionales, tiene como área de estudio la zona ubicada entre las comunidades de Caño Negro y Guatuso en Costa Rica y San Carlos y El Castillo en Nicaragua. La idea con dichos proyectos es aportar conocimiento y facilitar espacios de investigación participativa que permitan proporcionar, fomentar, desarrollar, consolidar e integrar factores socios culturales vinculados al turismo que puedan contribuir al desarrollo socioeconómico sostenible

Incidencia del turismo en la sociedad local y la incorporación de la mujer en la actividad socioeconómica y su promoción local: el caso de Guatuso en la región Huetar Norte de Costa Rica

El Instituto de Estudios Sociales en Población (IDESPO) de la Universidad Nacional, forma parte del Proyecto "Turismo sostenible, desarrollo local y cooperación internacional: resiliencia socioecológica y articulación transfronteriza en el Río San Juan (Costa Rica-Nicaragua)". Dicho proyecto, que se lleva a cabo conjuntamente con otras instituciones nacionales e internacionales, tiene como área de estudio la zona ubicada entre las comunidades de Caño Negro y Guatuso en Costa Rica, y San Carlos y El Castillo en Nicaragua. El objetivo o propósito general del proyecto es: Aportar conocimiento y facilitar espacios de investigación participativa que permitan propiciar, fomentar, desarrollar, consolidar e integrar los factores socio culturales vinculados al turismo que puedan contribuir al desarrollo socioeconómico sostenible, la cohesión social, el fortalecimiento de la resiliencia socioecológica de los ecosistemas y la articulación transfronteriza entre Nicaragua y Costa Rica

Turismo Transfronterizo Costa Rica-Nicaragua2008-2010 (Informe act. 2009) Programa Horizontes Ambientales

Presentación del Informe para el 2009 del proyecto Turismo sostenible, desarrollo local y cooperación internacional: resiliencia socioecológica y articulación transfronteriza en el río San Juan (Costa Rica-Nicaragua)