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Objective: The aim was to create pathological changes in mice relevant to human smoke exposure that can be used to further understand the mechanisms and pathology of smoke-induced inflammatory disease. Methods: Mice were exposed to tobacco smoke or lipopolysaccharide (LPS) to generate an inflammatory infiltrate within the lungs. Results: Tobacco smoke exposure over a 4 day period led to neutrophil
The interest for studying server systems subject to cloned requests has recently increased. In this paper we present a model that allows us to equivalently represent a system of servers with cloned requests, as a single server. The model is very general, and we show that no assumptions on either inter-arrival or service time distributions are required, allowing for, e.g., both heterogeneity and de
Interesting approaches to counteract performance variability within cloud datacenters include sending multiple request clones, either immediately or after a specified waiting time. In this paper we present a performance model of cloud applications that utilize the latter concept, known as speculative execution. We study the popular Join-Shortest-Queue load-balancing strategy under the processor sh
In this Rapid Communication we analyze the efficiency of operations based on transferring charge from a quantum dot (QD) to two coupled topological superconductors, which can be used for performing non-Abelian operations on Majorana bound states (MBSs). We develop a method which allows us to describe the full time evolution of the system as the QD energy is manipulated. Using a full counting stati
We use the Twitter-based Hedonometer happiness index to study the link between happiness and gold price changes. We find no significant correlation between the two when we look at correlations across the entire distributions. However, turning to an extreme value theory (EVT) modeling of the tails of the non-normally distributed happiness distribution we find that during particularly depressing day
The azimuthal anisotropy of charged particles produced in sNN=8.16 TeV p+Pb collisions is measured with the ATLAS detector at the LHC. The data correspond to an integrated luminosity of 165 nb - 1 that was collected in 2016. Azimuthal anisotropy coefficients, elliptic v2 and triangular v3, extracted using two-particle correlations with a non-flow template fit procedure, are presented as a function
Hurler syndrome (HS) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Hematopoietic stem cell transplantation (HSCT) results in long-term survival, although with significant residual disease burden. How this residual disease affects the health-related quality of life is unknown. Therefore, we conducted a multicenter cohort study on functional and
Background In patients with GTP-cyclohydrolase deficient dopa-responsive dystonia (DRD) the occurrence of associated non-motor symptoms (NMS) is to be expected. Earlier studies report conflicting results with regard to the nature and severity of NMS. The aim of our study was to investigate the prevalence of psychiatric disorders, sleep problems, fatigue and health-related quality of life (HR-QoL)
BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in 57%, but patients were highly selected for known and likely Mendelian disorders. The aim of our prospect
In recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the “classical” inborn errors of metabolism in catabolic pathways, in which elevated lev
Background: North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and
Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic me
Background: Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis. Methods: In th
In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement diso
We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, we achieve a sen
Objectives: Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Methods: Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 chil
