RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia

RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnos

Impact of comorbid conditions on asthmatic adults and children

Comorbid conditions (comorbidities) can complicate the diagnosis and management of asthma. In different age groups, comorbid conditions can present varying challenges, including diagnostic confusion due to mimicking asthma symptoms, exacerbation of asthma symptoms, therapy for comorbid conditions affecting asthma or therapy for asthma affecting these conditions. This review aims to summarise some common comorbid conditions with asthma, such as rhinitis, vocal cord dysfunction, gastro-oesophageal reflux, psychiatric disorders, obesity and obstructive sleep apnoea, and discuss their prevalence, symptoms, diagnosis and treatment, highlighting any differences in how they impact children and adults. Overall, there is a lack of data on the impact of treating comorbid conditions on asthma outcomes and further studies are needed to guide age-appropriate asthma management in the presence of these conditions.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.A.K. reports personal fees from AstraZeneca, Behring, Boehringer Ingelheim, GlaxoSmithKline, Griffols, Teva, Novartis, Novo Nordisk, Paladdin, Pfizer, Purdue, Sanofi and Trudel, outside the submitted work. D.M.G.H. reports personal fees from AstraZeneca, Chiesi and Pfizer and grants and personal fees from Boehringer Ingelheim, GlaxoSmithKline and Novartis, outside the submitted work. S.J.S. reports fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Propeller Health, Regeneron and Sanofi, outside the submitted work all paid to the University of Colorado School of Medicinepublished version, accepted version, submitted versio

On extremal dependence : some contributions

The usual coefficients of tail dependence are based on exceedances of high values. These extremal events are useful and widely used in literature but an adverse situation may also occur with the upcrossing of a high level. In this context we define upcrossings-tail dependence coefficients and analyze all types of dependence coming out. We will prove that these coefficients are related to multivariate tail dependence coefficients already known in literature. We shall see that the upcrossings-tail dependence coefficients have the interesting feature of congregating both “temporal” and “spatial” dependence. The coefficients of tail dependence can also be applied to stationary sequences and hence measure the tail dependence in time. Results concerning connections with the extremal index and the upcrossings index as well as with local dependence conditions will be stated. Several illustrative examples will be exploited and a small note on inference will be given by presenting estimators derived from the stated results and respective properties.Fundação para a Ciência e a Tecnologia (FCT

Extremes of multivariate ARMAX processes

We define a new multivariate time series model by generalizing the ARMAX process in a multivariate way. We give conditions on stationarity and analyze local dependence and domains of attraction. As a consequence of the obtained results, we derive new multivariate extreme value distributions.We characterize the extremal dependence by computing the multivariate extremal index and bivariate upper tail dependence coefficients. An estimation procedure for the multivariate extremal index is presented. We also address the marginal estimation and propose a new estimator for the ARMAX autoregressive parameter.Fundação para a Ciência e a Tecnologia (FCT