Gathering Validity Evidence for a Simulation-Based Test of Otoscopy Skills.

Objective: Otoscopy is a key clinical examination used by multiple healthcare providers but training and testing of otoscopy skills remain largely uninvestigated. Simulator-based assessment of otoscopy skills exists, but evidence on its validity is scarce. In this study, we explored automated assessment and performance metrics of an otoscopy simulator through collection of validity evidence according to Messick's framework.

Impact of Single-Melamine Tautomerization on the Excitation of Molecular Vibrations in Inelastic Electron Tunneling Spectroscopy.

Vibrational quanta of melamine and its tautomer are analyzed at the single-molecule level on Cu(100) with inelastic electron tunneling spectroscopy. The on-surface tautomerization gives rise to markedly different low-energy vibrational spectra of the isomers, as evidenced by a shift in mode energies and a variation in inelastic cross sections. Spatially resolved spectroscopy reveals the maximum signal strength on an orbital nodal plane, excluding resonant inelastic tunneling as the mechanism underlying the quantum excitations.

Bistability between π-diradical open-shell and closed-shell states in indeno[1,2-a]fluorene.

Indenofluorenes are non-benzenoid conjugated hydrocarbons that have received great interest owing to their unusual electronic structure and potential applications in nonlinear optics and photovoltaics. Here we report the generation of unsubstituted indeno[1,2-a]fluorene on various surfaces by the cleavage of two C-H bonds in 7,12-dihydroindeno[1,2-a]fluorene through voltage pulses applied by the tip of a combined scanning tunnelling microscope and atomic force microscope. On bilayer NaCl on Au(111), indeno[1,2-a]fluorene is in the neutral charge state, but it exhibits charge bistability between neutral and anionic states on the lower-workfunction surfaces of bilayer NaCl on Ag(111) and Cu(111).

From Solution to Surface: Persistence of the Diradical Character of a Diindenoanthracene Derivative on a Metallic Substrate.

Organic diradicals are envisioned as elementary building blocks for designing a new generation of spintronic devices and have been used in constructing prototypical field effect transistors and nonlinear optical devices. Open-shell systems, however, are also reactive, thus requiring design strategies to "protect" their radical character from the environment, especially when they are embedded in solid-state devices. Here, we report the persistence on a metallic surface of the diradical character of a diindeno[,]anthracene (DIAn) core protected by bulky end-groups.

Detecting the spin-polarization of edge states in graphene nanoribbons.

Low dimensional carbon-based materials can show intrinsic magnetism associated to p-electrons in open-shell π-conjugated systems. Chemical design provides atomically precise control of the π-electron cloud, which makes them promising for nanoscale magnetic devices. However, direct verification of their spatially resolved spin-moment remains elusive.

Dynamic Friction Unraveled by Observing an Unexpected Intermediate State in Controlled Molecular Manipulation.

The pervasive phenomenon of friction has been studied at the nanoscale via a controlled manipulation of single atoms and molecules with a metallic tip, which enabled a precise determination of the static friction force necessary to initiate motion. However, little is known about the atomic dynamics during manipulation. Here, we reveal the complete manipulation process of a CO molecule on a Cu(110) surface at low temperatures using a combination of noncontact atomic force microscopy and density functional theory simulations.

Orbital-symmetry effects on magnetic exchange in open-shell nanographenes.

Open-shell nanographenes appear as promising candidates for future applications in spintronics and quantum technologies. A critical aspect to realize this potential is to design and control the magnetic exchange. Here, we reveal the effects of frontier orbital symmetries on the magnetic coupling in diradical nanographenes through scanning probe microscope measurements and different levels of theoretical calculations.

3-D-Printed Models for Temporal Bone Training: A Validity Study.

Objective: 3-D printing offers convenient and low-cost mastoidectomy training; nonetheless, training benefits using 3-D-printed temporal bones remain largely unexplored. In this study, we have collected validity evidence for a low-cost, 3-D-printed temporal bone for mastoidectomy training and established a credible pass/fail score for performance on the model.

Study Design: A prospective educational study gathering validity evidence using Messick's validity framework.

Using population pharmacokinetic analyses of drugs metabolized by CYP2D6 to study the genotype-phenotype translation.

Cytochrome P450 2D6 (CYP2D6) is an important drug-metabolizing enzyme exhibiting extensive interindividual variability predominantly caused by genetic polymorphism. Predicting CYP2D6 function based on genotype may be used to personalize pharmacotherapy, but the process of translating CYP2D6 genotype into predicted phenotype is complex and has suffered from a lack of consensus. The Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group have proposed a standardized translation scheme based on the activity score system aiming to facilitate more consistent CYP2D6 genotype-phenotype translation.

Mach-Zehnder-like interferometry with graphene nanoribbon networks.

We study theoretically electron interference in a Mach-Zehnder-like geometry formed by four zigzag graphene nanoribbons arranged in parallel pairs, one on top of the other, such that they form intersection angles of 60. Depending on the interribbon separation, each intersection can be tuned to act either as an electron beam splitter or as a mirror, enabling tuneable circuitry with interfering pathways. Based on the mean-field Hubbard model and Green's function techniques, we evaluate the electron transport properties of such eight-terminal devices and identify pairs of terminals that are subject to self-interference.

The bidirectional association between atrial fibrillation and myocardial infarction.

Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI) and vice versa. This bidirectional association relies on shared risk factors as well as on several direct and indirect mechanisms, including inflammation, atrial ischaemia, left ventricular remodelling, myocardial oxygen supply-demand mismatch and coronary artery embolism, through which one condition can predispose to the other. Patients with both AF and MI are at greater risk of stroke, heart failure and death than patients with only one of the conditions.

Does ethnicity impact CYP2D6 genotype-phenotype relationships?

Polymorphism of the CYP2D6 gene leads to substantial interindividual variability in CYP2D6 enzyme activity. Despite improvements in prediction of CYP2D6 activity based on genotype information, large interindividual variability within CYP2D6 genotypes remains and ethnicity could be a contributing factor. The aim of this study was to investigate interethnic differences in CYP2D6 activity using clinical datasets of three CYP2D6 substrates: (i) brexpiprazole (N = 476), (ii) tedatioxetine (N = 500), and (iii) vortioxetine (N = 1073).

Five-year changes in alcohol intake and risk of atrial fibrillation: a Danish cohort study.

Aims: Alcohol intake is a well-established risk factor for atrial fibrillation (AF). However, evidence on the effects of changes in alcohol intake to primary AF prevention is sparse. The aim of this study was to examine the association between 5-year changes in alcohol intake and the risk of incident AF.

Estimating the In Vivo Function of CYP2D6 Alleles through Population Pharmacokinetic Modeling of Brexpiprazole.

Accurate prediction of CYP2D6 phenotype from genotype information is important to support safe and efficacious pharmacotherapy with CYP2D6 substrates. To facilitate accurate CYP2D6 genotype-phenotype translation, there remains a need to investigate the enzyme activity associated with individual CYP2D6 alleles using large clinical data sets. This study aimed to quantify and compare the in vivo function of different CYP2D6 alleles through population pharmacokinetic (PopPK) modeling of brexpiprazole using data from 13 clinical studies.

Carbon-based nanostructures as a versatile platform for tunable-magnetism.

Emergence of-magnetism in open-shell nanographenes has been theoretically predicted decades ago but their experimental characterization was elusive due to the strong chemical reactivity that makes their synthesis and stabilization difficult. In recent years, on-surface synthesis under vacuum conditions has provided unprecedented opportunities for atomically precise engineering of nanographenes, which in combination with scanning probe techniques have led to a substantial progress in our capabilities to realize localized electron spin states and to control electron spin interactions at the atomic scale. Here we review the essential concepts and the remarkable advances in the last few years, and outline the versatility of carbon-based-magnetic materials as an interesting platform for applications in spintronics and quantum technologies.

Spin-Polarizing Electron Beam Splitter from Crossed Graphene Nanoribbons.

Junctions composed of two crossed graphene nanoribbons (GNRs) have been theoretically proposed as electron beam splitters where incoming electron waves in one GNR can be split coherently into propagating waves in two outgoing terminals with nearly equal amplitude and zero back-scattering. Here we scrutinize this effect for devices composed of narrow zigzag GNRs taking explicitly into account the role of Coulomb repulsion that leads to spin-polarized edge states within mean-field theory. We show that the beam-splitting effect survives the opening of the well-known correlation gap and, more strikingly, that a spin-dependent scattering potential emerges which spin polarizes the transmitted electrons in the two outputs.

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com).

The G213D variant in Nav1.5 alters sodium current and causes an arrhythmogenic phenotype resulting in a multifocal ectopic Purkinje-related premature contraction phenotype in human-induced pluripotent stem cell-derived cardiomyocytes.

Aims: Variants in SCN5A encoding Nav1.5 are associated with cardiac arrhythmias. We aimed to determine the mechanism by which c.

Association Between CYP2D6 Metabolizer Status and Vortioxetine Exposure and Treatment Switching: A Retrospective, Naturalistic Cohort Study Using Therapeutic Drug Monitoring Data From 640 Patients.

Purpose: The antidepressant vortioxetine is mainly metabolized by the polymorphic enzyme CYP2D6. The aim of this study was to investigate the absolute serum concentrations of vortioxetine and frequency of switching to an alternative antidepressant in relation to CYP2D6 genotype in a naturalistic patient population.

Methods: The analyses included data from 640 CYP2D6 -genotyped patients treated with vortioxetine from a Norwegian therapeutic drug monitoring database.

Outcome after out-of-hospital cardiac arrest in patients with ischaemic and non-ischaemic heart disease: A Danish tertiary-center cohort study.

Background: Mortality following out-of-hospital cardiac arrest (OHCA) is high, and studies on return to work show varying results. It remains uncertain whether mortality and return to work differs between patients with ischaemic heart disease (IHD) and non-ischaemic heart disease (non-IHD).

Aim: To investigate all-cause mortality, cardiac death, and return to work among patients admitted after OHCA with IHD and non-IHD.