Acute respiratory distress syndrome : prevention and early recognition

Acute respiratory distress syndrome (ARDS) is common in critically ill patients admitted to intensive care units (ICU). ARDS results in increased use of critical care resources and healthcare costs, yet the overall mortality associated with these conditions remains high. Research focusing on preventing ARDS and identifying patients at risk of developing ARDS is necessary to develop strategies to alter the clinical course and progression of the disease. To date, few strategies have shown clear benefits. One of the most important obstacles to preventive interventions is the difficulty of identifying patients likely to develop ARDS. Identifying patients at risk and implementing prevention strategies in this group are key factors in preventing ARDS. This review will discuss early identification of at-risk patients and the current prevention strategies

Acute respiratory distress syndrome: prevention and early recognition

Acute respiratory distress syndrome (ARDS) is common in critically ill patients admitted to intensive care units (ICU). ARDS results in increased use of critical care resources and healthcare costs, yet the overall mortality associated with these conditions remains high. Research focusing on preventing ARDS and identifying patients at risk of developing ARDS is necessary to develop strategies to alter the clinical course and progression of the disease. To date, few strategies have shown clear benefits. One of the most important obstacles to preventive interventions is the difficulty of identifying patients likely to develop ARDS. Identifying patients at risk and implementing prevention strategies in this group are key factors in preventing ARDS. This review will discuss early identification of at-risk patients and the current prevention strategies

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Variables psicológicas implicadas en la actitud e iniciativa emprendedora

Identificar variables individuales relacionadas con la iniciativa emprendedora y el fomento de competencias transversales relacionadas con la misma, supone un desafío en la investigación actual sobre emprendimiento. El proyecto titulado Variables psicológicas implicadas en la actitud e iniciativa emprendedora, realizado bajo el programa Innova Docencia promovido por el Vicerrectorado de Calidad de la UCM en la convocatoria 2016-2017, ha tenido por objetivo analizar y evaluar variables psicológicas relacionadas con emprendimiento que presentan una muestra de estudiantes de la Universidad Complutense de Madrid. En dicho estudio han participado 1222 estudiantes de la UCM correspondientes a 27 titulaciones: 14 de Grado, 2 de Dobles Grados, y 11 de Máster. El 28,6% de la muestra fueron hombres y el 71% fueron mujeres. La media de edad fue de 20,43 años. El equipo investigador estuvo compuesto por 40 personas: 25 PDI de la UCM, 2 PAS, 8 alumnos y alumnas, 1 técnico, y 4 PDI de las universidades de Castilla-La Mancha (UCLM), UNED, Carlos III de Madrid (UC3M), y Alcalá de Henares (UAH). El PDI de la UCM correspondía a las siguientes facultades: Psicología (7), Ciencias de la Documentación (3), Ciencias Económicas y Empresariales (6), Ciencias Políticas y Sociología (3), Comercio (1), Trabajo Social (1), Ciencias Biológicas (2), Informática (1), y Bellas Artes (1). Un equipo UCM perteneciente a 9 facultades, que representó a 13 departamentos y a todas las áreas de conocimiento. La metodología empleada consistió en un cuestionario que evaluaba los siguientes aspectos: datos sociodemográficos, actitud emprendedora, y las variables psicológicas: personalidad, inteligencia emocional, resolución de problemas y tolerancia a la ambigüedad. Se optó por instrumentos estandarizados, con buenas características psicométricas de fiabilidad y validez que permitieran obtener resultados robustos, con amplia evidencia empírica y que evaluaban adecuadamente variables que la literatura ha relacionado con la actitud e iniciativa emprendedora. Además todos ellos se han utilizado en investigaciones relacionadas con emprendimiento, lo que aumentó la validez externa. Se ha analizado la iniciativa emprendedora desde el punto de vista de los estudiantes y también teniendo en cuenta variables del entorno familiar y personal. Los resultados nos muestran que son las variables psicológicas de extraversión, reparación emocional y estrategias de resolución de problemas las que predicen la iniciativa emprendedora. Los estudiante que compaginan estudios y trabajo tienen una mayor iniciativa emprendedora, y aquellos cuyos padres y/o pareja desarrollan su actividad laboral como autónomos. Se presentan datos por titulación académica, sexo, actividad laboral de los padres y compaginar estudios y trabajo. Se muestran datos de todas las variables psicológicas por titulación académica, y una comparativa de dichas variables entre los universitarios, un grupo de estudiantes de Formación Profesional (FP) y una muestra de emprendedores reales. Los resultados obtenidos son relevantes para tomar decisiones orientadas a la mejora de la actitud, iniciativa y comportamiento emprendedor. Permitirán el diseño y ejecución de actividades académicas para sensibilizar a los estudiantes en la cultura emprendedora, y formar en competencias transversales, cada vez más demandadas, para mejorar la empleabilidad y competitividad como claves para el crecimiento de nuestra sociedad

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Funder: Ludwig Center at HarvardFunder: National Cancer Institute: K22CA193848Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266Abstract: Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer