An Exploratory Pilot Study

While mental health treatments have proven to be effective for a range of mental health problems, there is comparably little research on its effects on personality disorders or difficulty (PD). New dimensional conceptualizations of PD such as the ICD-11 PD model enable the cost- and time-effective dimensional assessment of severity and style of PD. Furthermore, they constitute a promising tool to investigate PD, not only as a treatment endpoint but also as a predictive or influencing factor for mental health treatments. In this study, we investigated the effects in two different mental health treatment settings [online (N = 38); face-to-face and blended [FTF/blended] (N = 35)] on the reduction of maladaptive personality traits as well as the interaction between maladaptive personality patterns and the response on primary endpoints (i.e., mental distress). Results indicate that both treatment settings have comparable within-group effects on the reduction of distress symptoms, while the treatment in the FTF/blended setting seems to have a stronger impact on the reduction of maladaptive traits. Further, reduction of maladaptive trait expressions was a reliable predictor of treatment response in the FTF/blended setting while explaining less variance in the online setting. Beyond the promising findings on the utility of maladaptive trait change as an outcome measure, we discuss possible applications as an information source for treatment decisions

Realizing efficient topological temporal pumping in electrical circuits

Quantized adiabatic transport can occur when a system is slowly modulated over time. In most realizations however, the efficiency of such transport is reduced by unwanted dissipation, back-scattering, and non-adiabatic effects. In this work, we realize a topological adiabatic pump in an electrical circuit network that supports remarkably stable and long-lasting pumping of a voltage signal. We further characterize the topology of our system by deducing the Chern number from the measured edge band structure. To achieve this, the experimental setup makes use of active circuit elements that act as time-variable voltage-controlled inductors.Comment: main (5 pages, 3 figures) plus supplement (8 pages, 4 figures

Simulating hyperbolic space on a circuit board

The Laplace operator encodes the behavior of physical systems at vastly different scales, describing heat flow, fluids, as well as electric, gravitational, and quantum fields. A key input for the Laplace equation is the curvature of space. Here we discuss and experimentally demonstrate that the spectral ordering of Laplacian eigenstates for hyperbolic (negatively curved) and flat two-dimensional spaces has a universally different structure. We use a lattice regularization of hyperbolic space in an electric-circuit network to measure the eigenstates of a ‘hyperbolic drum’, and in a time-resolved experiment we verify signal propagation along the curved geodesics. Our experiments showcase both a versatile platform to emulate hyperbolic lattices in tabletop experiments, and a set of methods to verify the effective hyperbolic metric in this and other platforms. The presented techniques can be utilized to explore novel aspects of both classical and quantum dynamics in negatively curved spaces, and to realise the emerging models of topological hyperbolic matter

Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier

Background: Echovirus (E) 30 (E-30) meningitis is characterized by neuroinflammation involving immune cell pleocytosis at the protective barriers of the central nervous system (CNS). In this context, infection of the blood-cerebrospinal fluid barrier (BCSFB), which has been demonstrated to be involved in enteroviral CNS pathogenesis, may affect the tight junction (TJ) and adherens junction (AJ) function and morphology. Methods: We used an in vitro human choroid plexus epithelial (HIBCPP) cell model to investigate the effect of three clinical outbreak strains (13-311, 13-759, and 14-397) isolated in Germany in 2013, and compared them to E-30 Bastianni. Conducting transepithelial electrical resistance (TEER), paracellular dextran flux measurement, quantitative real-time polymerase chain reaction (qPCR), western blot, and immunofluorescence analysis, we investigated TJ and AJ function and morphology as well as strain-specific E-30 infection patterns. Additionally, transmission electron and focused ion beam microscopy electron microscopy (FIB-SEM) was used to evaluate the mode of leukocyte transmigration. Genome sequencing and phylogenetic analyses were performed to discriminate potential genetic differences among the outbreak strains. Results: We observed a significant strain-dependent decrease in TEER with strains E-30 Bastianni and 13-311, whereas paracellular dextran flux was only affected by E-30 Bastianni. Despite strong similarities among the outbreak strains in replication characteristics and particle distribution, strain 13-311 was the only outbreak isolate revealing comparable disruptive effects on TJ (Zonula Occludens (ZO) 1 and occludin) and AJ (E-cadherin) morphology to E-30 Bastianni. Notwithstanding significant junctional alterations upon E-30 infection, we observed both para- and transcellular leukocyte migration across HIBCPP cells. Complete genome sequencing revealed differences between the strains analyzed, but no explicit correlation with the observed strain-dependent effects on HIBCPP cells was possible. Conclusion: The findings revealed distinct E-30 strain-specific effects on barrier integrity and junctional morphology. Despite E-30-induced barrier alterations leukocyte trafficking did not exclusively occur via the paracellular route

Clinical evaluation of the bed cycling test

Objective: Additionally to the forearm rolling test to detect mild unilateral upper limb dysfunction, the bed cycling test (BCT) for detection of mild to moderate lower limb dysfunction was developed, evaluated and compared to the leg holding test. Methods: In a prospective observer-blinded study, 60 patients with MRI/CT-proven focal cerebral hemisphere lesions and a mild to moderate unilateral paresis of the lower limb (graduated MRC 3-4/5), and 60 control persons with normal imaging were examined and filmed. Nine observers blinded to the diagnosis evaluated these videos. The sensitivity, specificity and the positive and negative predictive values of the clinical tests were analyzed. Results: The observers gave a correct evaluation of BCT in 35.5% of all patients with focal cerebral lesions compared to 26.0% for the leg holding test. On the other hand, observers had false negative results in 29.1% of cases with BCT and 44.7% with leg holding test. In 36.7% of patients, only BCT was pathological while leg holding test was unremarkable. The sensitivity of the combination of both tests was 0.68 (95% CI 0.61-0.75). The BCT is more sensitive (64.3%) than leg holding test (46.2%) while the specificity of leg holding test (85.6%) is higher than of BCT (70.1%) to detect a cerebral lesion affecting the lower limb. The inter-rater variability is high with no differences comparing different types of clinical experience. Conclusions: The BCT is a useful additional clinical bedside test to detect subtle unilateral cerebral lesions. The BCT is easy to perform and can be added to the routine neurological examination

Acute Cerebrovascular Disease in the Young The Stroke in Young Fabry Patients Study

Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results-Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions-Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies

The North Atlantic Waveguide and Downstream Impact Experiment

The North Atlantic Waveguide and Downstream Impact Experiment (NAWDEX) explored the impact of diabatic processes on disturbances of the jet stream and their influence on downstream high-impact weather through the deployment of four research aircraft, each with a sophisticated set of remote sensing and in situ instruments, and coordinated with a suite of ground-based measurements. A total of 49 research flights were performed, including, for the first time, coordinated flights of the four aircraft: the German High Altitude and Long Range Research Aircraft (HALO), the Deutsches Zentrum für Luft- und Raumfahrt (DLR) Dassault Falcon 20, the French Service des Avions Français Instrumentés pour la Recherche en Environnement (SAFIRE) Falcon 20, and the British Facility for Airborne Atmospheric Measurements (FAAM) BAe 146. The observation period from 17 September to 22 October 2016 with frequently occurring extratropical and tropical cyclones was ideal for investigating midlatitude weather over the North Atlantic. NAWDEX featured three sequences of upstream triggers of waveguide disturbances, as well as their dynamic interaction with the jet stream, subsequent development, and eventual downstream weather impact on Europe. Examples are presented to highlight the wealth of phenomena that were sampled, the comprehensive coverage, and the multifaceted nature of the measurements. This unique dataset forms the basis for future case studies and detailed evaluations of weather and climate predictions to improve our understanding of diabatic influences on Rossby waves and the downstream impacts of weather systems affecting Europe

B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4

Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen1. The immunopathology in neuromyelitis optica is largely driven by autoantibodies to AQP42. However, the T cell response that is required for the generation of these anti-AQP4 antibodies is not well understood. Here we show that B cells endogenously express AQP4 in response to activation with anti-CD40 and IL-21 and are able to present their endogenous AQP4 to T cells with an AQP4-specific T cell receptor (TCR). A population of thymic B cells emulates a CD40-stimulated B cell transcriptome, including AQP4 (in mice and humans), and efficiently purges the thymic TCR repertoire of AQP4-reactive clones. Genetic ablation of Aqp4 in B cells rescues AQP4-specific TCRs despite sufficient expression of AQP4 in medullary thymic epithelial cells, and B-cell-conditional AQP4-deficient mice are fully competent to raise AQP4-specific antibodies in productive germinal-centre responses. Thus, the negative selection of AQP4-specific thymocytes is dependent on the expression and presentation of AQP4 by thymic B cells. As AQP4 is expressed in B cells in a CD40-dependent (but not AIRE-dependent) manner, we propose that thymic B cells might tolerize against a group of germinal-centre-associated antigens, including disease-relevant autoantigens such as AQP4. The immune system is tolerized against the neuromyelitis optica autoantigen AQP4 by thymic B cells, which present their endogenous AQP4 to AQP4-reactive thymocytes

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients