S-ketamine bij de pijnbehandeling van ernstige orale mucositis door chemotherapie bij kinderen.

Item does not contain fulltex

Microstructural and seismic properties of the upper mantle underneath a rifted continental terrane (Baja California): An example of sub-crustal mechanical asthenosphere?

The Gulf of California rift is a young and active plate boundary that links the San Andreas strike-slip fault system in California to the oceanic spreading system of the East Pacific Rise. The xenolith bearing lavas of the San Quintin volcanic area provide lower crust and upper mantle samples from beneath Baja California peninsula. The microstructures, crystallographic preferred orientations (CPO) and petrology of the San Quintin xenoliths suggest that the continental lithosphere in this region has undergone several stages of deformation, recrystallisation and melt–rock interaction. Melt–rock interactions have led to enrichment in olivine while fine-grained microstructures suggest intense deformation in an active shear zone in the shallow upper mantle. In this study we highlight the effect of the fine-grained mylonitic shear zone development in the upper mantle as an important process of weakening of continental lithosphere. The results of the microstructural study show a reduction in CPO strength with increasing grain size reduction. Most CPOs are consistent with dominant slip on the {0kl}[100] system. As a consequence, corresponding seismic anisotropies decrease for both P- and S-waves with increasing grain size reduction. The shallow crystallographic fabric can be related to active shear zones, which accommodate the relative motion between the Northern Baja terrane and the Pacific plate. Estimates of the strain rate, stress and viscosity indicate that the shallow mantle beneath Northern Baja is thermally and chemically lithospheric but mechanically has similar viscosity as the asthenosphere. The Northern Baja terrane is an interesting case of continental crust lying directly on low viscosity upper mantle

Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing

BACKGROUND: The substantial technological advancements in next-generation sequencing (NGS), combined with dropping costs, have allowed for a swift diffusion of NGS applications in clinical settings. Although several commercial parties report to have broken the $1000 barrier for sequencing an entire human genome, a valid cost overview for NGS is currently lacking. This study provides a complete, transparent and up-to-date overview of the total costs of different NGS applications. METHODS: Cost calculations for targeted gene panels (TGP), whole exome sequencing (WES) and whole genome sequencing (WGS) were based on the Illumina NextSeq500, HiSeq4000, and HiSeqX5 platforms, respectively. To anticipate future developments, sensitivity analyses are performed. RESULTS: Per-sample costs were euro1669 for WGS, euro 792 for WES and euro333 for TGP. To reach the coveted$1000 genome, not only is the long-term and efficient use of the sequencing equipment needed, but also large reductions in capital costs and especially consumable costs are also required. CONCLUSIONS: WES and TGP are considerably lower-cost alternatives to WGS. However, this does not imply that these NGS approaches should be preferred in clinical practice, since this should be based on the tradeoff between costs and the expected clinical utility of the approach chosen. The results of the present study contribute to the evaluation of such tradeoffs

Long-read technologies identify a hidden inverted duplication in a family with choroideremia

Contains fulltext : 244033.pdf (Publisher’s version ) (Open Access

Evaluación de hemerotecas de prensa digital: indicadores y ejemplos de buenas prácticas

La gran mayoría de los diarios digitales facilitan el acceso a la información retrospectiva mediante servicios de hemerotecas o archivos de prensa, un producto de notable interés para bibliotecas y otros servicios de información. El objetivo de este estudio es determinar cuáles son los indicadores fundamentales para la evaluación de hemerotecas digitales y, además, señalar ejemplos de buenas prácticas en España para cada uno de ellos. Se propone una relación de veintisiete indicadores agrupados en cuatro grandes apartados (aspectos generales, contenidos, sistema de consulta, y presentación de resultados), se describe cada uno de ellos y se incluye algún ejemplo de buena aplicación. Metodológicamente, se ha partido de la revisión de la bibliografía especializada en evaluación de recursos web, bases de datos y hemerotecas digitales, así como del análisis de hemerotecas de diarios de España y Catalunya. La utilización de estos indicadores puede ser de utilidad para que bibliotecas y otros servicios de información puedan orientar a sus usuarios en la consulta retrospectiva de información de prensa

Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications

BACKGROUND: Approximately two third of patients with a rare genetic disease remain undiagnosed after exome sequencing (ES). As part of our post-test counseling procedures, patients without a conclusive diagnosis are advised to recontact their referring clinician to discuss new diagnostic opportunities in due time. We performed a systematic study of genetically undiagnosed patients 5 years after their initial negative ES report to determine the efficiency of diverse reanalysis strategies. METHODS: We revisited a cohort of 150 pediatric neurology patients originally enrolled at Radboud University Medical Center, of whom 103 initially remained genetically undiagnosed. We monitored uptake of physician-initiated routine clinical and/or genetic re-evaluation (ad hoc re-evaluation) and performed systematic reanalysis, including ES-based resequencing, of all genetically undiagnosed patients (systematic re-evaluation). RESULTS: Ad hoc re-evaluation was initiated for 45 of 103 patients and yielded 18 diagnoses (including 1 non-genetic). Subsequent systematic re-evaluation identified another 14 diagnoses, increasing the diagnostic yield in our cohort from 31% (47/150) to 53% (79/150). New genetic diagnoses were established by reclassification of previously identified variants (10%, 3/31), reanalysis with enhanced bioinformatic pipelines (19%, 6/31), improved coverage after resequencing (29%, 9/31), and new disease-gene associations (42%, 13/31). Crucially, our systematic study also showed that 11 of the 14 further conclusive genetic diagnoses were made in patients without a genetic diagnosis that did not recontact their referring clinician. CONCLUSIONS: We find that upon re-evaluation of undiagnosed patients, both reanalysis of existing ES data as well as resequencing strategies are needed to identify additional genetic diagnoses. Importantly, not all patients are routinely re-evaluated in clinical care, prolonging their diagnostic trajectory, unless systematic reanalysis is facilitated. We have translated our observations into considerations for systematic and ad hoc reanalysis in routine genetic care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-022-01069-z