Contaminant removal efficiency, design parameter in cleanrooms

In cleanrooms worden hoge ventilatievouden gehanteerd. Dit is in lijn met de beschikbare richtlijnen [1]. Normaal gesproken worden de daarvoor benodigde debieten 24/7 gerealiseerd zodat de cleanroom continu op het gewenste niveau presteert. Dit is daarmee een energie-intensieve activiteit. In twee deelonderzoeken is onderzocht wat de mogelijkheden zijn om het ventilatie-energiegebruik van cleanrooms te reduceren, bij een gelijkblijvende prestatie. In dit deelonderzoek is de focus op de efficiency waarmee geventileerd wordt om verontreinigingen af te voeren

Contaminant removal efficiency, design parameter in cleanrooms

In cleanrooms worden hoge ventilatievouden gehanteerd. Dit is in lijn met de beschikbare richtlijnen [1]. Normaal gesproken worden de daarvoor benodigde debieten 24/7 gerealiseerd zodat de cleanroom continu op het gewenste niveau presteert. Dit is daarmee een energie-intensieve activiteit. In twee deelonderzoeken is onderzocht wat de mogelijkheden zijn om het ventilatie-energiegebruik van cleanrooms te reduceren, bij een gelijkblijvende prestatie. In dit deelonderzoek is de focus op de efficiency waarmee geventileerd wordt om verontreinigingen af te voeren

Continental drift: connecting Great Britain and Scandinavia

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Outcome measures in Angelman syndrome

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Aim: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. Methods: The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Results: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Conclusions: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Trial registration: Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075</p

Outcome measures in Angelman syndrome

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Aim: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. Methods: The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Results: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Conclusions: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Trial registration: Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075</p

Towards fixed dosing of tocilizumab in ICU-admitted COVID-19 patients: results of an observational population pharmacokinetic and descriptive pharmacodynamic study

Background and Objective In the randomized controlled trial REMAP-CAP, it was shown that next to dexamethasone, the interleukin (IL)-6 receptor antagonist tocilizumab improves outcome, including survival in intensive care unit (ICU)-admitted coronavirus disease 2019 (COVID)-19 patients. Therefore tocilizumab has been added to many COVID-19 treatment guidelines. Because obesity is a risk factor for the development of severe COVID-19, concerns have been raised about overtreatment, as well as undertreatment, through weight-based dosing of tocilizumab. The currently applied dose of 8 mg/kg is based on the use of this drug for other indications, however it has not formally been investigated for COVID-19. In this study, the pharmacokinetics and pharmacodynamics of tocilizumab were investigated in ICU-admitted COVID-19 patients. Methods This was an open-label, single-centre, observational population pharmacokinetic and descriptive pharmacodynamic evaluation study. Enrolled patients, with polymerase chain reaction-confirmed COVID-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received intravenous tocilizumab 8 mg/kg (maximum 800 mg) within 24 h after admission to the ICU and received dexamethasone 6 mg daily as concomitant therapy. For evaluation of the pharmacokinetics and pharmacodynamics of tocilizumab, all time points from day 0 to 20 days after dose administration were eligible for collection. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetic parameters of tocilizumab in ICU-admitted COVID-19 patients. Covariate analysis was performed to identify potential covariates for dose individualization. For the development of alternative dosing schedules, Monte Carlo simulations using the final model were performed. Results Overall, 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and nonlinear clearance (CL) was developed and validated. Average CL was estimated to be 0.725 L/day, average volume of distribution (V-d) was 4.34 L, maximum elimination rate (V-max) was 4.19 mu g/day, and concentration at which the elimination pathway is half saturated (K-m) was 0.22 mu g/mL. Interindividual variability was identified for CL (18.9%) and V-d (21%). Average area under the concentration versus time curve from time zero to infinity of the first dose (AUC(inf 1st DOSE)) was 938 [+/- 190] mu g/mL*days. All patients had tocilizumab exposure above 1 mu g/mL for at least 15 days. Bodyweight-based dosing increases variability in exposure compared with fixed dosing. Conclusions This study provides evidence to support a fixed dose of tocilizumab 600 mg in COVID-19 patients. Fixed dosing is a safe, logistically attractive, and drug expenses saving alternative compared with the current 8 mg/kg recommendation.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso

Метод интегрирования дифференциальных уравнений динамики электрических машин с вращающимся ротором

Для исследования переходных процессов в электротехнических системах, содержащих статические электромагнитные устройства, включенные в сложные электрические схемы, разработан программный комплекс Colo, функционирующий на основе магнитоэлектрических схем замещения в матричной форме. Главная матрица комплекса Colo содержит коэффициенты при искомых токах или магнитных потоках. Моделирование динамических процессов в электрических машинах с вращающимся ротором связано с интегрированием дифференциальных уравнений, в которые входят произведения искомых величин, поэтому непосредственно эти уравнения не могут решаться в программном комплексе Colo