The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within ...clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
The territory of present-day Vietnam was the cradle of one of the world's earliest civilizations, and one of the first world regions to develop agriculture. We analyzed the mitochondrial DNA (mtDNA) ...complete control region of six ethnic groups and the mitogenomes from Vietnamese in The 1000 Genomes Project (1000G). Genome-wide data from 1000G (~55k SNPs) were also investigated to explore different demographic scenarios. All Vietnamese carry South East Asian (SEA) haplotypes, which show a moderate geographic and ethnic stratification, with the Mong constituting the most distinctive group. Two new mtDNA clades (M7b1a1f1 and F1f1) point to historical gene flow between the Vietnamese and other neighboring countries. Bayesian-based inferences indicate a time-deep and continuous population growth of Vietnamese, although with some exceptions. The dramatic population decrease experienced by the Cham 700 years ago (ya) fits well with the Nam tiến ("southern expansion") southwards from their original heartland in the Red River Delta. Autosomal SNPs consistently point to important historical gene flow within mainland SEA, and add support to a main admixture event occurring between Chinese and a southern Asian ancestral composite (mainly represented by the Malay). This admixture event occurred ~800 ya, again coinciding with the Nam tiến.
Purpose
The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients.
Methods
A case-control study nested within the Grupo Latino ...Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up.
Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0–25%), occasionally (>25%–50%), commonly (˃50%–75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used.
The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models.
Results
A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869–0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522–0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309–2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005–1.064; p = 0.022).
Conclusions
In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The opacities of iron and other mid-Z elements help to regulate the transport of energy in the sun. Recent experiments on the Sandia National Laboratories Z machine have shown large discrepancies ...between the measured and calculated opacities of iron at certain solar conditions. To replicate these opacity measurements a platform is being developed on the National Ignition Facility to measure the opacities of iron and other elements at the same conditions as in the Z experiments. The NIF platform consists of a hohlraum to heat the opacity sample to the desired conditions, a separate backlighter to radiograph the sample, and a spectrometer to give the spectrally resolved opacity. Not only must the opacity be measured but the temperature and density of the sample must also be accurately determined. This platform has now produced its first iron transmission measurements. These measurements will be presented along with plans for future measurements and details on how the measurements will be improved.
X-ray opacity is a crucial factor of all radiation-hydrodynamics calculations, yet it is one of the least validated of the material properties in the simulation codes. Recent opacity experiments at ...the Sandia Z-machine have shown up to factors of two discrepancies between theory and experiment, casting doubt on the validity of the opacity models. Therefore, a new experimental opacity platform is being developed on the National Ignition Facility (NIF) not only to verify the Z-machine experimental results but also to extend the experiments to other temperatures and densities. The first experiments will be directed towards measuring the opacity of iron at a temperature of ∼160eV and an electron density of ∼7 ×1021 cm−3. Preliminary experiments on NIF have demonstrated the ability to create a sufficiently bright point backlighter using an imploding plastic capsule and also a hohlraum that can heat the opacity sample to the desired conditions. The first of these iron opacity experiments is expected to be performed in 2017.
Progress toward NIF opacity measurements Perry, T. S.; Heeter, R. F.; Opachich, Y. P. ...
High energy density physics,
06/2020, Letnik:
35, Številka:
C
Journal Article
Recenzirano
The opacities of iron and other mid-Z elements help to regulate the transport of energy in the sun. Recent experiments on the Sandia National Laboratories Z machine have shown large discrepancies ...between the measured and calculated opacities of iron at certain solar conditions. To replicate these opacity measurements a platform is being developed on the National Ignition Facility to measure the opacities of iron and other elements at the same conditions as in the Z experiments. The NIF platform consists of a hohlraum to heat the opacity sample to the desired conditions, a separate backlighter to radiograph the sample, and a spectrometer to give the spectrally resolved opacity. Not only must the opacity be measured but the temperature and density of the sample must also be accurately determined. This platform has now produced its first iron transmission measurements. These measurements will be presented along with plans for future measurements and details on how the measurements will be improved.
Progress toward NIF opacity measurements Perry, T. S.; Heeter, R. F.; Opachich, Y. P. ...
High energy density physics,
06/2020, Letnik:
35, Številka:
na
Journal Article
Recenzirano
Odprti dostop
The opacities of iron and other mid-Z elements help to regulate the transport of energy in the sun. Recent experiments on the Sandia National Laboratories Z machine have shown large discrepancies ...between the measured and calculated opacities of iron at certain solar conditions. To replicate these opacity measurements a platform is being developed on the National Ignition Facility to measure the opacities of iron and other elements at the same conditions as in the Z experiments. The NIF platform consists of a hohlraum to heat the opacity sample to the desired conditions, a separate backlighter to radiograph the sample, and a spectrometer to give the spectrally resolved opacity. Not only must the opacity be measured but the temperature and density of the sample must also be accurately determined. This platform has now produced its first iron transmission measurements. Overall, these measurements will be presented along with plans for future measurements and details on how the measurements will be improved.
RESUMEN Introducción: El fentanilo de administración transmucosa tiene características específicas que lo convierten en el fármaco adecuado para el tratamiento del dolor irruptivo oncológico (DIO). ...Aunque en España existe un amplio consenso sobre la idoneidad de la administración de fentanilo transmucoso para el DIO, es relevante conocer cómo los oncólogos adecuan su prescripción al paciente y cuáles son los factores determinantes de la elección de las diferentes formas farmacéuticas. Objetivos: El objetivo principal de este proyecto fue identificar y priorizar los atributos que los oncólogos médicos españoles tienen en cuenta cuando valoran las opciones de tratamiento con fentanilo transmucoso en pacientes con DIO. Métodos: Un comité científico realizó una tipificación de 14 atributos relevantes en la prescripción de fentanilo transmucoso para el DIO. Posteriormente se generó un dossier de evidencia científica comparando estos 14 atributos entre los distintos fentanilos transmucosos disponibles, que se compartió con el panel de expertos (115 oncólogos médicos). Tras una exhaustiva revisión del documento, los participantes realizaron una votación online de priorización de los atributos. Resultados: De catorce atributos analizados, siete consiguieron un consenso de ≥ 50 % de los participantes: el inicio de la acción analgésica (84 %), la adecuación del efecto del fentanilo al perfil del episodio de DIO (72 %), la facilidad de uso por los pacientes y cuidadores (69 %), la duración del efecto (58 %), la presencia de mucositis (57 %),la facilidad de titulación de la dosis óptima (57 %) y las presentaciones y dosis disponibles (59 %). Conclusiones: Los atributos más valorados fueron los relativos a la rapidez de acción del tratamiento analgésico y su adaptación al perfil del DIO, algo esperable dadas las características clínicas del episodio de DIO. Como atributos menos valorados aparecen el riesgo de abuso o conductas aberrantes y la presencia de rinitis para su administración, lo que indica que la existencia de estos factores no tiene tanta influencia en la elección del tratamiento para el abordaje del DIO. Estos resultados permitirán a los oncólogos médicos conocer qué atributos deben ser tenidos en cuenta a la hora de personalizar los tratamientos del paciente con DIO con el objetivo de mejorar la adecuación de la analgesia de rescate.
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