ABSTRACT
People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS. SIGNIFICANCE: By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.
Subject(s)
Cell-Free Nucleic Acids , Li-Fraumeni Syndrome , Humans , Li-Fraumeni Syndrome/diagnosis , Li-Fraumeni Syndrome/genetics , Li-Fraumeni Syndrome/pathology , Tumor Suppressor Protein p53/genetics , Early Detection of Cancer , Cell-Free Nucleic Acids/genetics , Genes, p53 , Germ-Line Mutation , Genetic Predisposition to DiseaseABSTRACT
BACKGROUND: Here we present a revised species checklist for the Brassicaceae, updated from Warwick SI, Francis, A, Al-Shehbaz IA (2006), Brassicaceae: Species checklist and database on CD-ROM, Plant Systematics and Evolution 259: 249â25. This update of the checklist was initiated, based on recent taxonomic and molecular studies on the Brassicaceae that have resulted in new species names, combinations and associated synonyms. NEW INFORMATION: New data have been added indicating tribal affiliations within the family and where type specimens have been designated. In addition, information from many early publications has been checked and added to the database. The database now includes information on 14983 taxa, 4636 of which are currently accepted and divided into 340 genera and 52 tribes. A selected bibliography of recent publications on the Brassicaceae is included.
ABSTRACT
Hybridization between crops and their wild relatives has the potential to introduce novel variation into wild populations. Camelina (Camelina sativa) is a promising oilseed and cultivars with modified seed characteristics and herbicide resistance are in development, prompting a need to evaluate the potential for novel trait introgression into weedy relatives. Little-podded false flax (littlepod; Camelina microcarpa) is a naturalized weed in Canada and the USA. Here we evaluated the hybridization rate between the three cytotypes of littlepod (â) and camelina (â), assessed characteristics of hybrids, and evaluated the fitness of hexaploid littlepod and camelina hybrids in the glasshouse and field. In total we conducted, 1,005 manual crosses with diploid littlepod, 1, 172 crosses with tetraploid littlepod, and 896 crosses with hexaploid littlepod. Hybrids were not produced by the diploids, but were produced by the tetraploids and hexaploids at rates of one hybrid for 2,000 ovules pollinated and 24 hybrids for 25 ovules pollinated, respectively. Hybrids between tetraploid littlepod and camelina showed low pollen fertility and produced a small number of seeds. In the glasshouse, hybrids between hexaploid littlepod and camelina also showed significantly lower pollen fertility and seed production than parental lines, but their seeds showed high viability. A similar pattern was observed in field trials, with hybrids showing earlier flowering, reduced biomass, seed production and seed weight. However, seed produced by the hybrids showed greater viability than that produced by hexaploid littlepod and is potentially the result of a shortened lifecycle. The introgression of lifecycle traits into littlepod populations may facilitate range expansion and contribute to crop gene persistence. Consequently, future work should evaluate the hybridization rate in the field, the fitness of advanced generation backcrosses, and the role of time to maturity in limiting hexaploid littlepod's distribution.
ABSTRACT
En Colombia, son escasos los estudios sobre la asociación de los factores psicosociales y medioambientales con trastornos mentales de mayor prevalencia; tales estudios son necesarios debido al contexto de violencia, inseguridad social e inestabilidad laboral y económica del país. El objetivo de este estudio fue identificar los factores de riesgo psicosociales y ambientales de los trastornos mentales, en los usuarios de servicios de psicología de Colombia. Para ello, se aplicaron el Mini International Neuropsychiatric Interview y un cuestionario de evaluación del Eje IV del DSM-IV-TR, a 490 participantes. Se utilizaron análisis descriptivos y de factores de riesgo. Como factor de riesgo para la depresión, se identificaron los problemas de vivienda, acceso a los servicios de asistencia sanitaria, los relativos al grupo primario, los económicos, del ambiente social y los problemas laborales. Para la ansiedad generalizada se identificaron los problemas económicos y los relativos a la enseñanza. Para los trastornos de pánico, fueron relevantes los problemas relacionados con el ambiente social, y para la fobia social, los problemas de enseñanza, los laborales y el ambiente social.
In Colombia, there are few studies on the association of psychosocial and environmental factors with the most prevalent mental disorders; such studies are important due to the context of violence, social insecurity, and job and economic instability in the country. The objective of this study was to identify the psychosocial and environmental risk factors for mental disorders, in users of psychologicalservices in Colombia. The Mini International Neuropsychiatric Interview and a Questionnaire to evaluate the Axis-IV of the DSM-IV-TR were applied to 490 participants.The analysis comprised descriptive statistics and risk factors. As riskfactors for depression, there were identified housing problems, access to health care services, problems related to the primary group, economics, problems of the social environment, and labor. For generalized anxiety, there were identified economic and education issues. For panic disorders, the risk factors were related to social environment, and for social phobia, the risk factors were problems in education,work and social environment.
