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Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether th

Stochastic differential mixed-effects models

Stochastic differential equations have been shown useful in describing random continuous time processes. Biomedical experiments often imply repeated measurements on a series of experimental units and differences between units can be represented by incorporating random effects into the model. When both system noise and random effects are considered, stochastic differential mixed-effects models ensu

Phase I, Randomized, Double-Blind, Placebo-Controlled, Multiple Intravenous, Dose-Ascending Study of Sirukumab in Cutaneous or Systemic Lupus Erythematosus

ObjectiveWe undertook a 2-part, phase I, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab, a human anti-interleukin-6 monoclonal antibody, in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE). MethodsIn part A, patients with histologically confirmed CLE were randomized to 4 infusi

Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study

Background Trials of imatinib have provided evidence of activity in adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (ALL), but the drug's role when given with multidrug chemotherapy to children is unknown. This study assesses the safety and efficacy of oral imatinib in association with a Berlin-Frankfurt-Munster intensive chemotherapy regimen and allo geneic stem-cell tr

Differences in outcomes of oesophageal and gastric cancer surgery across Europe

Background: In several European countries, centralization of oesophagogastric cancer surgery has been realized and clinical audits initiated. The present study was designed to evaluate differences in resection rates, outcomes and annual hospital volumes between these countries, and to analyse the relationship between hospital volume and outcomes. Methods: National data were obtained from cancer re

Birth-jump processes and application to forest fire spotting

Birth-jump models are designed to describe population models for which growth and spatial spread cannot be decoupled. A birth-jump model is a nonlinear integro-differential equation. We present two different derivations of this equation, one based on a random walk approach and the other based on a two-compartmental reaction-diffusion model. In the case that the redistribution kernels are highly co

Cognitive and semiotic determinants of sign order in gestural and pictorial event representations

The way people order signs in non-verbal event representations of events has been a topic of extensive research in recent decades, with conflicting findings. Based on a literature review, we distinguish the following factors that have been argued to influence sign order: (a) diagrammatic iconicity, (b) manipulation vs. construction events, (c) reversibility, (d) most common word order of L1, (e) t

Necrorobotics: The Ethics of Resurrecting the Dead

By drawing from recent progress in AI, this chapter scrutinises implications of a specific imaginary of automated futures: the possible resurrection of the dead. Necrorobotics is proposed as a field of critical studies on the use of data and design based on one specific dead individual in order to “resurrect” that individual. That is, to mimic or create some level of robotic agency for the sake of

Risk Factors for Heart Failure among Pan-European Childhood Cancer Survivors : A PanCareSurFup and ProCardio Cohort and Nested Case-Control Study

PURPOSE Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines.METHODSThis study includes the PanCareSurFup and ProCa

Intersection of Longest Paths in a Graph

In 1966, Gallai asked whether every connected graph has a vertex that is common to all its longest paths. The answer to this question is negative. We prove that the answer is positive for outerplanar graphs. Another related question was raised in 1995 at the British Combinatorial Conference: Do any three longest paths in a connected graph have a vertex in common? We prove that, in a connected grap

Accurate Prediction of Persistent Upper Extremity Impairment in Patients With Ischemic Stroke

Objective: To develop a simple and effective risk score for predicting which stroke patients will have persistent impairment of upper extremity motor function at 90 days. Design: Post hoc analysis of clinical trial patients hospitalized with acute ischemic stroke who were followed for 90 days to determine functional outcome. Setting: Patient were hospitalized at facilities across the United States

The neurological and neuropsychiatric spectrum of adults with late-treated phenylketonuria

Introduction: Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of p

Intratunical injection of autologous adipose stromal vascular fraction reduces collagen III expression in a rat model of chronic penile fibrosis

Previous studies have shown that the injection of adipose stem cells and stromal vascular fraction(SVF) into the tunica albuginea (TA) during the inflammatory phase in a rat model of Peyronie’s disease(PD) prevented the development of TA fibrosis. Our aim was to investigate whether local injection of SVF can reduce established fibrosis in a rat model of chronic phase of PD. Eighteen-male 12-wk-old

Myoclonus in childhood-onset neurogenetic disorders : The importance of early identification and treatment

Background In clinical practice, myoclonus in childhood-onset neurogenetic disorders frequently remains unrecognized, because it is often overshadowed by other neurological features. Since treatment can lead to significant functional improvement, accurate phenotyping is essential. To demonstrate the importance of early identification and treatment, we report on four patients with various childhood

A clinical diagnostic algorithm for early onset cerebellar ataxia

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype–phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebe

An integrated transcriptomic- and proteomic-based approach to evaluate the human skin sensitization potential of glyphosate and its commercial agrochemical formulations

We investigated the skin sensitization hazard of glyphosate, the surfactant polyethylated tallow amine (POEA) and two commercial glyphosate-containing formulations using different omics-technologies based on a human dendritic cell (DC)-like cell line. First, the GARD™skin assay, investigating changes in the expression of 200 transcripts upon cell exposure to xenobiotics, was used for skin sensitiz