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Can Population Modelling Principles be Used to Identify Key PBPK Parameters for Paediatric Clearance Predictions? An Innovative Application of Optimal Design Theory

PurposePhysiologically-based pharmacokinetic (PBPK) models are essential in drug development, but require parameters that are not always obtainable. We developed a methodology to investigate the feasibility and requirements for precise and accurate estimation of PBPK parameters using population modelling of clinical data and illustrate this for two key PBPK parameters for hepatic...

When to reveal what you feel: How emotions towards antagonistic out-group and third party audiences are expressed strategically

In intergroup conflicts, expressed emotions influence how others see and react to those who express them. Here, we investigated whether this in turn implies that emotions may be expressed strategically. We tested whether emotion expression can differ from emotion experience, and whether emotion expression (more than emotion experience) is used to pursue specific goals...

Responsible Cognitive Enhancement: Neuroethical Considerations

Cognitive enhancement is the use of any (legitimate) means to reach one’s personal best cognitive performance. Cognitive enhancement can help delay cognitive decline in the elderly. Along the same lines, training children could speed up the education and reduce the risk of behavioral deviance and pathology. Nonetheless, cognitive enhancement is one of the most widely discussed...

Mass Spectrometry Imaging and Integration with Other Imaging Modalities for Greater Molecular Understanding of Biological Tissues

Over the last two decades, mass spectrometry imaging (MSI) has been increasingly employed to investigate the spatial distribution of a wide variety of molecules in complex biological samples. MSI has demonstrated its potential in numerous applications from drug discovery, disease state evaluation through proteomic and/or metabolomic studies. Significant technological and...

The role of properdin in complement-mediated renal diseases: a new player in complement-inhibiting therapy?

Properdin is known as the only positive regulator of the complement system. Properdin promotes the activity of this defense system by stabilizing its key enzymatic complexes: the complement alternative pathway (AP) convertases. Besides, some studies have indicated a role for properdin as an initiator of complement activity. Though the AP is a powerful activation route of the...

A new method for fine-scale assessments of the average urban Heat island over large areas and the effectiveness of nature-based solutions

People living in cities experience extra heat stress due to the so-called Urban Heat Island (UHI) effect. To gain an insight into the spatial variability of the UHI for the Netherlands, a detailed map (10 m horizontal resolution) has been calculated that shows the summer-averaged daily maximal UHI situation. The map is based on a relationship between the UHI, mean wind speed at...

Virtual patient simulations for cardiology education and research: A CircAdapt perspective

Nowadays cardiac simulations are becoming increasingly sophisticated. This trend, part of the maturing field of computational medicine, has provided medical students and cardiologists alike with a new tool for education and research – their very own virtual “patient”. The CircAdapt biophysical model of the human heart and circulation (www.circadapt.org) allows the creation of a...

Association between use of antidepressants or benzodiazepines and the risk of subsequent fracture among those aged 65+ in the Netherlands

SummaryThis is the first study to examine the association between antidepressant and benzodiazepine use following a MOF and risk of subsequent fracture in those 65+. Using national data, drug use following MOF showed that the 1-year fully adjusted risk of subsequent MOF in those on antidepressants was more than doubled.IntroductionWe evaluated the association between the use of...

How to reach a wider audience with open access publishing: what research universities can learn from universities of applied sciences

In Amsterdam, the libraries of the University of Amsterdam (UvA) and the Amsterdam University of Applied Sciences (AUAS) cooperate closely. In this cooperation, the differences between a research university (i.c. UvA) and a university of applied sciences (i.c. AUAS) become particularly clear when we look at the aim and implementation of open access policies. The open access plan...

QR-patterns: artefacts in multiresolution topology optimization

Recent multiresolution topology optimization (MTO) approaches involve dividing finite elements into several density cells (voxels), thereby allowing a finer design description compared to a traditional FE-mesh-based design field. However, such formulations can generate discontinuous intra-element material distributions resembling QR-patterns. The stiffness of these disconnected...

Changes in bone density and bone turnover in patients with rheumatoid arthritis treated with rituximab, results from an exploratory, prospective study

Data describing the effect of in vivo B cell depletion on general bone loss in patients with rheumatoid arthritis (RA) are limited. Given the pathogenetic role of B cells in RA, it is tempting to speculate that B cell depletion might have a beneficial effect on bone loss. We prospectively investigated the changes in bone mineral density (BMD), bone turnover, inflammation and...

Minimally interrupted novel oral anticoagulant versus uninterrupted vitamin K antagonist during atrial fibrillation ablation

PurposeThe safety and efficacy of a minimally interrupted novel oral anticoagulant (NOAC) strategy at the time of atrial fibrillation (AF) ablation is uncertain. The purpose of this study was to compare rates of bleeding and thromboembolic events between minimally interrupted NOAC and uninterrupted vitamin K antagonist (VKA) in patients undergoing AF ablation.MethodsThis was a...

Action models in inquisitive logic

Information exchange can be viewed as a process of asking questions and answering them. While dynamic epistemic logic traditionally focuses on statements, recent developments have been concerned with ways of incorporating questions. One approach, based on the framework of inquisitive semantics, is inquisitive dynamic epistemic logic (\(\textsf {IDEL}\)). In this system, agents...

How to Continue a Meaningful Judicial Dialogue About EU Law? From the Conditions in the CILFIT Judgment to the Creation of a New European Legal Culture

The aim of this article is to better understand the conditions outlined in the CILFIT judgment and their role in creating a meaningful dialogue about European Union law. For these purposes two distinct views on the relation between language and meaning are utilised, as has been argued for by Ludwig Wittgenstein in his Philosophical Investigations. In the CILFIT judgment both of...

Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values

Neonatologists can use echocardiography for real-time assessment of the hemodynamic state of neonates to support clinical decision-making. There is a large body of evidence showing the shortcomings of conventional echocardiographic indices in neonates. Newer imaging modalities have evolved. Tissue Doppler imaging is a new technique that can provide measurements of myocardial...

Introduction to neonatologist-performed echocardiography

Cardiac ultrasound techniques are increasingly used in the neonatal intensive care unit to guide cardiorespiratory care of the sick newborn. This is the first in a series of eight review articles discussing the current status of “neonatologist-performed echocardiography” (NPE). The aim of this introductory review is to discuss four key elements of NPE. Indications for scanning...

Application of NPE in the assessment of a patent ductus arteriosus

In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term...

Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values

Advances in neonatal cardiac imaging permit a more comprehensive assessment of myocardial performance in neonates that could not be previously obtained with conventional imaging. Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in neonates. Cardiac strain is a measure of tissue...

Methane emissions in the Netherlands: The Groningen field

The Groningen natural gas field in the Netherlands – one of Europe’s major gas fields – deploys a “production cluster” infrastructure with extraction, some processing and storage in a single facility. This region is also the site of intensive agriculture and cattle operations. We present results from a multi-scale measurement campaign of methane emissions, including ground and...