Fractional Langevin equation

We investigate fractional Brownian motion with a microscopic random-matrix model and introduce a fractional Langevin equation. We use the latter to study both sub- and superdiffusion of a free particle coupled to a fractal heat bath. We further compare fractional Brownian motion with the fractal time process. The respective mean-square displacements of these two forms of anomalous diffusion exhibit the same power-law behavior. Here we show that their lowest moments are actually all identical, except the second moment of the velocity. This provides a simple criterion which enables to distinguish these two non-Markovian processes.Comment: 4 page

Minimal residual disease assessment in B-cell precursor acute lymphoblastic leukemia by semi-automated identification of normal hematopoietic cells:A EuroFlow study

Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, data-analysis remains mainly expert-dependent. In this study, we designed and validated an Automated Gating &amp; Identification (AGI) tool for MRD analysis in BCP-ALL patients using the two tubes of the EuroFlow 8-color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow-up samples from 174 BCP-ALL patients, stained with the EuroFlow BCP-ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra-expert concordance (100%) and good inter-expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP-ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.</p

Language, Life, Limits

Motivated by the desire to facilitate the implementation of interactive proof systems with rich sets of proof rules, we present a uniform system of rule schemata to generate proof rules for different styles of logical calculi. The system requires only one schema for each logical operator to generate introduction and elimination rules in natural deduction and sequent calculus style. In addition, the system supports program extraction from proofs by generating realizers for the proof rules automatically

Pharmacokinetics of anidulafungin in critically ill intensive care unit patients with suspected or proven invasive fungal infections

Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0-24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg·h·liter-1, a median daily trough concentration (C24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (Cmax) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters·h-1. Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0-24 of 82.7 (IQR, 73.0 to 129.5) mg·h·liter-1, a median minimum concentration of drug in serum (Cmin) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median Cmax of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters·h-1. The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.)

Experience With IVDR Implementation in Three Diagnostic Laboratories: Messages to EU Health Institutions, Diagnostic Healthcare Payers, and Authorities

Regulation (EU) 2017/746 on in vitro diagnostic medical devices1 (IVDR) has been implemented with the aim to safeguard the quality of diagnostic tests in the EU, for example, by requiring robust proof of safety and performance. The IVDR is a product regulation mainly aimed at industry manufacturing and marketing medical devices. While IVDR-compliant diagnostic tests should predominantly be supplied by manufacturers, health institutions have the possibility of manufacturing and using in-house devices (IH-IVDs), provided they meet the Article 5(5) conditions and relevant general safety and performance requirements in Annex I. This “health institution exemption” concerns, for example, their quality management system (QMS), risk management, performance evaluation, and justification of IH-IVD use.2 The first significant task for diagnostic laboratories at health institutions, compliance with Annex I, has been applicable since May 2022, whereas other implementation timelines are shifted based on the December 2021 amendment of the IVDR.3,