The ability to maintain rhythm is predictive of ADHD diagnosis and profile.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric disorder in the world. Currently, the diagnosis is based mainly on interviews, resulting in uncertainties in the clinical assessment. While some neuropsychological tests are used, their specificity and selectivity are low, and more reliable biomarkers are desirable. Previous research indicates that ADHD is associated with morphological changes in the cerebellum, which is essential for motor ability and timing. Here, we compared 29 children diagnosed with ADHD to 96 age-matched controls on prism adaptation, eyeblink conditioning, and timed motor performance in a finger tapping task. Prism adaptation and timing precision in the finger tapping task, but not performance on eyeblink conditioning, differed between the ADHD and control groups, as well as between children with and without Deficits in Attention, Motor control, and Perception (DAMP) - a more severe form of ADHD. The results suggest finger tapping can be used as a cheap, objective, and unbiased biomarker to complement current diagnostic procedures.

Long-Term Experimental Hyperglycemia Does Not Impair Macrovascular Endothelial Barrier Integrity and Function in vitro.

Hyperglycemia is a hallmark of type 2 diabetes implicated in vascular endothelial dysfunction and cardiovascular complications. Many in vitro studies identified endothelial apoptosis as an early outcome of experimentally modeled hyperglycemia emphasizing cell demise as a significant factor of vascular injury. However, endothelial apoptosis has not been observed in vivo until the late stages of type 2 diabetes. Here, we studied the long-term (up to 4 weeks) effects of high glucose (HG, 30 mM) on human umbilical vein endothelial cells (HUVEC) in vitro. HG did not alter HUVEC monolayer morphology, ROS levels, NO production, and exerted minor effects on the HUVEC apoptosis markers. The barrier responses to various clues were indistinguishable from those by cells cultured in physiological glucose (5 mM). Tackling the key regulators of cytoskeletal contractility and endothelial barrier revealed no differences in the histamine-induced intracellular Ca2+ responses, nor in phosphorylation of myosin regulatory light chain or myosin light chain phosphatase. Altogether, these findings suggest that vascular endothelial cells may well tolerate HG for relatively long exposures and warrant further studies to explore mechanisms involved in vascular damage in advanced type 2 diabetes.

Thermoelectric Signature of Individual Skyrmions.

We experimentally study the thermoelectrical signature of individual skyrmions in chiral Pt/Co/Ru multilayers. Using a combination of controlled nucleation, single skyrmion annihilation, and magnetic field dependent measurements the thermoelectric signature of individual skyrmions is characterized. The observed signature is explained by the anomalous Nernst effect of the skyrmion's spin structure. Possible topological contributions to the observed thermoelectrical signature are discussed. Such thermoelectrical characterization allows for noninvasive detection and counting of skyrmions and enables fundamental studies of topological thermoelectric effects on the nanoscale.

Modal Frustration and Periodicity Breaking in Artificial Spin Ice.

Here, an artificial spin ice lattice is introduced that exhibits unique Ising and non-Ising behavior under specific field switching protocols because of the inclusion of coupled nanomagnets into the unit cell. In the Ising regime, a magnetic switching mechanism that generates a uni- or bimodal distribution of states dependent on the alignment of the field is demonstrated with respect to the lattice unit cell. In addition, a method for generating a plethora of randomly distributed energy states across the lattice, consisting of Ising and Landau states, is investigated through magnetic force microscopy and micromagnetic modeling. It is demonstrated that the dispersed energy distribution across the lattice is a result of the intrinsic design and can be finely tuned through control of the incident angle of a critical field. The present manuscript explores a complex frustrated environment beyond the 16-vertex Ising model for the development of novel logic-based technologies.

Comparison and Validation of Different Magnetic Force Microscopy Calibration Schemes.

The future of consumer electronics depends on the capability to reliably fabricate nanostructures with given physical properties. Therefore, techniques to characterize materials and devices with nanoscale resolution are crucial. Among these is magnetic force microscopy (MFM), which transduces the magnetic force between the sample and a magnetic oscillating probe into a phase shift, enabling the locally resolved study of magnetic field patterns down to 10 nm. Here, the progress done toward making quantitative MFM a common tool in nanocharacterization laboratories is shown. The reliability and ease of use of the calibration method based on a magnetic reference sample, with a calculable stray field, and a deconvolution algorithm is demonstrated. This is achieved by comparing two calibration approaches combined with numerical modeling as a quantitative link: measuring the probe's effect on the voltage signal when scanning above a nanosized graphene Hall sensor, and recording the MFM phase shift signal when the probe scans across magnetic fields produced by metallic microcoils. Furthermore, in the case of the deconvolution algorithm, it is shown how it can be applied using the open-source software package Gwyddion. The estimated magnetic dipole approximation for the most common probes currently in the market is also reported.

Imaging Bulk and Edge Transport near the Dirac Point in Graphene Moiré Superlattices.

Van der Waals structures formed by aligning monolayer graphene with insulating layers of hexagonal boron nitride exhibit a moiré superlattice that is expected to break sublattice symmetry. Despite an energy gap of several tens of millielectronvolts opening in the Dirac spectrum, electrical resistivity remains lower than expected at low temperature and varies between devices. While subgap states are likely to play a role in this behavior, their precise nature is unclear. We present a scanning gate microscopy study of moiré superlattice devices with comparable activation energy but with different charge disorder levels. In the device with higher charge impurity (∼1010 cm-2) and lower resistivity (∼10 kΩ) at the Dirac point we observe current flow along the graphene edges. Combined with simulations, our measurements suggest that enhanced edge doping is responsible for this effect. In addition, a device with low charge impurity (∼109 cm-2) and higher resistivity (∼100 kΩ) shows subgap states in the bulk, consistent with the absence of shunting by edge currents.

Design of peptidase-resistant peptide inhibitors of myosin light chain kinase.

Myosin light chain kinase (MLCK) is a key regulator of various forms of cell motility including smooth muscle contraction, cell migration, cytokinesis, receptor capping, secretion, etc. Inhibition of MLCK activity in endothelial and epithelial monolayers using cell-permeant peptide Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys (PIK, Peptide Inhibitor of Kinase) allows protecting the barrier capacity, suggesting a potential medical use of PIK. However, low stability of L-PIK in a biological milieu prompts for development of more stable L-PIK analogues for use as experimental tools in basic and drug-oriented biomedical research. Previously, we designed PIK1, H-(Nα Me)Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 , that was 2.5-fold more resistant to peptidases in human plasma in vitro than L-PIK and equal to it as MLCK inhibitor. In order to further enhance proteolytic stability of PIK inhibitor, we designed the set of six site-protected peptides based on L-PIK and PIK1 degradation patterns in human plasma as revealed by 1 H-NMR analysis. Implemented modifications increased half-live of the PIK-related peptides in plasma about 10-fold, and these compounds retained 25-100% of L-PIK inhibitory activity toward MLCK in vitro. Based on stability and functional activity ranking, PIK2, H-(Nα Me)Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-D-Arg-Lys-NH2 , was identified as the most stable and effective L-PIK analogue. PIK2 was able to decrease myosin light chain phosphorylation in endothelial cells stimulated with thrombin, and this effect correlated with the inhibition by PIK2 of thrombin-induced endothelial hyperpermeability in vitro. Therefore, PIK2 could be used as novel alternative to other cell-permeant inhibitors of MLCK in cell culture-based and in vivo studies where MLCK catalytic activity inhibition is required. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Classification of Magnetic Nanoparticle Systems--Synthesis, Standardization and Analysis Methods in the NanoMag Project.

This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical) susceptometry and magnetorelaxometry and the size parameters are determined from electron microscopy and dynamic light scattering. Using these methods, we also show that the nanocrystal size and particle morphology determines the dynamic magnetic properties for both single- and multi-core particles. The presented results are obtained from the four year EU NMP FP7 project, NanoMag, which is focused on standardization of analysis methods for magnetic nanoparticles.

Express optical analysis of epitaxial graphene on SiC: impact of morphology on quantum transport.

We show that inspection with an optical microscope allows surprisingly simple and accurate identification of single and multilayer graphene domains in epitaxial graphene on silicon carbide (SiC/G) and is informative about nanoscopic details of the SiC topography, making it ideal for rapid and noninvasive quality control of as-grown SiC/G. As an illustration of the power of the method, we apply it to demonstrate the correlations between graphene morphology and its electronic properties by quantum magneto-transport.

Psychometric properties of the Opening Minds Stigma Scale for Health Care Providers in 32 European countries - A bifactor ESEM representation.

Aims: To measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe. Materials and methods: The OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures. Results: A total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042-0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of 'attitude,' 'disclosure and help-seeking,' and 'social distance' could be treated as a single dimension of stigma. Among the specific factors, the 'disclosure and help-seeking' factor explained a considerable unique proportion of variance in the observed scores. Conclusion: This international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak.

Attitudes of psychiatrists towards people with mental illness: a cross-sectional, multicentre study of stigma in 32 European countries.

Background: Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce. Methods: A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978). Findings: A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = -0.92, 95% confidence interval (CI) = -1.68 to -0.15, p = 0.019), receiving medical treatment for a mental illness (d = -0.88, 95% CI = -1.71 to -0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = -0.68, 95% CI = -1.14 to -0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = -0.98, 95% CI = -1.26 to -0.70, p < 0.001), providing psychotherapy to patients (d = -1.14, 95% CI = -1.63 to -0.65 p < 0.001), and being open to (d = -1.69, 95% CI = -2.53 to -0.85, p < 0.001) and actively participating in (d = -0.94, 95% CI = -1.45 to -0.42, p < 0.001) case discussion, supervision, or Balint groups. Interpretation: Our study highlights the importance of psychotherapy training, supervision, case discussions and Balint groups in reducing the stigmatising attitudes of psychiatrists toward patients. As the findings represent cross-national predictors, Europe-wide policy interventions, national psychiatric education systems and the management of psychiatric institutions should take these findings into consideration. Funding: National Youth Talent Award (Ministry of Human Resources, Hungary, (NTP-NFTÖ-20-B-0134). All authors received no funding for their contribution.

Mapping of local electrical properties in epitaxial graphene using electrostatic force microscopy.

Local electrical characterization of epitaxial graphene grown on 4H-SiC(0001) using electrostatic force microscopy (EFM) in ambient conditions and at elevated temperatures is presented. EFM provides a straightforward identification of graphene with different numbers of layers on the substrate where topographical determination is hindered by adsorbates. Novel EFM spectroscopy has been developed measuring the EFM phase as a function of the electrical DC bias, establishing a rigorous way to distinguish graphene domains and facilitating optimization of EFM imaging.

Keto-enol tautomerism of curcumin in the preparation of nanobiocomposites with fumed silica.

The tautomerism of curcumin (Cur) in water-ethanol solutions in the presence of fumed silica was studied by UV-visible spectroscopy. The results showed that the enol tautomer exists at an ethanol concentration in solution >50%, and with an increase in the water content, the tautomeric equilibrium shifts towards the formation of the keto tautomer. Quantum-chemical calculations (solvation model SM 5.42/6-31G (d), GAMESSPLUS) of various curcumin isomers confirmed that the existence of curcumin keto tautomer in aqueous solution is more thermodynamically favorable. The ratio of keto and enol forms also depends on the dielectric constant of water-ethanol solutions: at ε < 45, only the enol form of curcumin exists, while at ε > 45, the relative amount of the keto tautomer increases in proportion to the dielectric constant. Curcumin tautomers adsorb on fumed silica in different ways. At a low curcumin concentration in the initial solutions (<1.5 × 10-4 M), only the enol tautomer forms a monolayer on the sorbent surface, apparently due to its planar structure. The keto tautomer, characterized by a bent structure, begins to adsorb only at a concentration of Cur > 1.5 × 10-4 M, being a component of molecular aggregates with coplanar geometry.

Defect-induced monopole injection and manipulation in artificial spin ice.

Lithographically defined arrays of nanomagnets are well placed for application in areas such as probabilistic computing or reconfigurable magnonics due to their emergent collective dynamics and writable magnetic order. Among them are artificial spin ice (ASI), which are arrays of binary in-plane macrospins exhibiting geometric frustration at the vertex interfaces. Macrospin flips in the arrays create topologically protected magnetic charges, or emergent monopoles, which are bound to an antimonopole to conserve charge. In the absence of controllable pinning, it is difficult to manipulate individual monopoles in the array without also influencing other monopole excitations or the counter-monopole charge. Here, we tailor the local magnetic order of a classic ASI lattice by introducing a ferromagnetic defect with shape anisotropy into the array. This creates monopole injection sites at nucleation fields below the critical lattice switching field. Once formed, the high energy monopoles are fixed to the defect site and may controllably propagate through the lattice under stimulation. Defect programing of bound monopoles within the array allows fine control of the pathways of inverted macrospins. Such control is a necessary prerequisite for the realization of functional devices, e. g. reconfigurable waveguide in nanomagnonic applications.

Local thermoelectric response from a single Néel domain wall.

Spatially resolved thermoelectric detection of magnetic systems provides a unique platform for the investigation of spintronic and spin caloritronic effects. Hitherto, these investigations have been resolution-limited, confining analysis of the thermoelectric response to regions where the magnetization is uniform or collinear at length scales comparable to the domain size. Here, we investigate the thermoelectric response from a single trapped domain wall using a heated scanning probe. Following this approach, we unambiguously resolve the domain wall due to its local thermoelectric response. Combining analytical and thermal micromagnetic modeling, we conclude that the measured thermoelectric signature is unique to that of a domain wall with a Néel-like character. Our approach is highly sensitive to the plane of domain wall rotation, which permits the distinct identification of Bloch or Néel walls at the nanoscale and could pave the way for the identification and characterization of a range of noncollinear spin textures through their thermoelectric signatures.

Distinguishing Local Demagnetization Contribution to the Magnetization Process in Multisegmented Nanowires.

Cylindrical magnetic nanowires are promising materials that have the potential to be used in a wide range of applications. The versatility of these nanostructures is based on the tunability of their magnetic properties, which is achieved by appropriately selecting their composition and morphology. In addition, stochastic behavior has attracted attention in the development of neuromorphic devices relying on probabilistic magnetization switching. Here, we present a study of the magnetization reversal process in multisegmented CoNi/Cu nanowires. Nonstandard 2D magnetic maps, recorded under an in-plane magnetic field, produce datasets that correlate with magnetoresistance measurements and micromagnetic simulations. From this process, the contribution of the individual segments to the demagnetization process can be distinguished. The results show that the magnetization reversal in these nanowires does not occur through a single Barkhausen jump, but rather by multistep switching, as individual CoNi segments in the NW undergo a magnetization reversal. The existence of vortex states is confirmed by their footprint in the magnetoresistance and 2D MFM maps. In addition, the stochasticity of the magnetization reversal is analysed. On the one hand, we observe different switching fields among the segments due to a slight variation in geometrical parameters or magnetic anisotropy. On the other hand, the stochasticity is observed in a series of repetitions of the magnetization reversal processes for the same NW under the same conditions.

Interfacial ferroelectricity in marginally twisted 2D semiconductors.

Twisted heterostructures of two-dimensional crystals offer almost unlimited scope for the design of new metamaterials. Here we demonstrate a room temperature ferroelectric semiconductor that is assembled using mono- or few-layer MoS2. These van der Waals heterostructures feature broken inversion symmetry, which, together with the asymmetry of atomic arrangement at the interface of two 2D crystals, enables ferroelectric domains with alternating out-of-plane polarization arranged into a twist-controlled network. The last can be moved by applying out-of-plane electrical fields, as visualized in situ using channelling contrast electron microscopy. The observed interfacial charge transfer, movement of domain walls and their bending rigidity agree well with theoretical calculations. Furthermore, we demonstrate proof-of-principle field-effect transistors, where the channel resistance exhibits a pronounced hysteresis governed by pinning of ferroelectric domain walls. Our results show a potential avenue towards room temperature electronic and optoelectronic semiconductor devices with built-in ferroelectric memory functions.

Research by Psychiatric Trainees and Early Career Psychiatrists-Results of a Survey From 34 Countries in Europe.

Clinical psychiatric practice should be intricately linked with research work. Although psychiatric trainees and early career psychiatrists (ECPs) are in the frontline of clinical services, little is known about how much access they have to research opportunities. A semi-structured questionnaire of 35 questions-exploring research goals achieved, facilitators and barriers as well as personal context-was sent to psychiatric trainees and ECPs across Europe. The survey was disseminated through the local committees of the main professional psychiatric societies in Europe. A total of 258 individuals working in 34 European countries participated. The majority (69.8%) were psychiatric trainees within training in adult psychiatry. Most participants (69.0%) were highly interested in research, but faced major obstacles toward their research activities, such as lack of time and funding. They were highly satisfied with mentoring and publishing papers. Only half of the participants, however, had already published a scientific article, and only a few have been able to contribute to randomized clinical trials (20.9%). A large proportion of participants (87.2%) reported to conduct research after or during a mixture of working hours and after working hours. Only one tenth ever received a grant for their work. These findings highlight that the key barriers for the performance of research are lack of time and funding. Psychiatric trainees and ECPs are motivated to perform research but need support and regular opportunities.

Training the trainers: Finding new educational opportunities in the virtual world.

The COVID-19 pandemic has disrupted scientific gatherings and conferences, opening up opportunities for virtual learning platforms. Realizing the potential of online academic exchanges, the World Psychiatric Association (WPA) also developed virtual avenues and information systems for capacity building of mental health professionals across the world. Among its first such initiatives, the WPA organized a virtual Train the Trainers workshop, where 123 psychiatrists, psychiatric trainees, and educators from 45 countries participated. The innovative and interactive workshop allowed participants to get to know each other, exchange educational and professional experiences, and ask questions or receive advice from experts. Keynote speakers, including WPA President Prof. Afzal Javed and Prof. Norman Sartorius, stressed upon the importance of finding innovative solutions in psychiatry training and the need to improve teaching and training in the field of psychiatry, especially in the provision of leadership and communication skills. Online training methods can provide easy access to academics and students while reducing the organizational and logistical costs. They have the potential to improve educational equality and allow the voice of the underprivileged scientists to be heard across the globe. The devastating impact on access to mental health services during COVID-19 underscores the urgent need for online training, particularly in countries where the ratio of psychiatrists to patients is inadequate and doctors concentrate more on treatment than on research and education. Virtual educational interventions could prove incredibly useful in the future just as they are being successfully utilized in local and regional contexts during the pandemic.

Psychiatry training in 42 European countries: A comparative analysis.

Psychiatry qualifications are automatically recognized among European Union (EU) countries despite differences in national training programs. A widening gap between the number of psychiatrists, their competencies and the growing burden of mental illnesses in Europe has renewed calls for international standardization of training. Comprehensive information about training programs is missing, which limits thorough comparisons and undermines development of an actionable strategy to improve and harmonize psychiatry training. This study describes and compares the existing postgraduate psychiatry programs in 42 countries in the European region. Representatives of national psychiatry associations completed a semi-structured, 58-item questionnaire. Training structure and working conditions of each country were compared with population needs calculated by the World Health Organization to determine the European mean and contrasted among pre-2004 and post-2004 EU members and countries with unrecognized qualifications. Differences were tested with nonparametric (Wilcoxon) and parametric (Anova) tests. Median training duration was 60 months, significantly shorter in countries with unrecognized qualifications (48 months, χ²16.5, p < 0.001). In 80% of the countries, placement in a non-psychiatric specialty such as neurology or internal medicine was mandatory. Only 17 countries (40%) stipulated a one-month rotation in substance abuse and 11 (26%) in old-age psychiatry. The overall deficit of training versus population need was 22% for substance abuse and 15% for old-age psychiatry. Salaries were significantly higher in pre-2004 EU members (χ²22.9, p < 0.001) with the highest in Switzerland (€5,000). Significant variations in curricula, training structure and salaries exist in Europe. Harmonization of training standards could offer significant benefits for improving mental healthcare.