Protective mechanisms and current clinical evidence of hypothermic oxygenated machine perfusion (HOPE) in preventing post-transplant cholangiopathy

The development of cholangiopathies after liver transplantation impacts on the quality and duration of graft and patient survival, contributing to higher costs as numerous interventions are required to treat strictures and infections at the biliary tree. Prolonged donor warm ischaemia time in combination with additional cold storage are key risk factors for the development of biliary strictures. Based on this, the clinical implementation of dynamic preservation strategies is a current hot topic in the field of donation after circulatory death (DCD) liver transplantation. Despite various retrospective studies reporting promising results, also regarding biliary complications, there are only a few randomised-controlled trials on machine perfusion. Recently, the group from Groningen has published the first randomised-controlled trial on hypothermic oxygenated perfusion (HOPE), demonstrating a significant reduction of symptomatic ischaemic cholangiopathies with the use of a short period of HOPE before DCD liver implantation. The most likely mechanism for this important effect, also shown in several experimental studies, is based on mitochondrial reprogramming under hypothermic aerobic conditions, e.g. exposure to oxygen in the cold, with a controlled and slow metabolism of ischaemically accumulated succinate and simultaneous ATP replenishment. This unique feature prevents mitochondrial oxidative injury and further downstream tissue inflammation. HOPE treatment therefore supports livers by protecting them from ischaemia-reperfusion injury (IRI), and thereby also prevents the development of post-transplant biliary injury. With reduced IRI-associated inflammation, recipients are also protected from activation of the innate immune system, with less acute rejections seen after HOPE

Adult Attachment and Personality as Predictors of Jealousy in Romantic Relationships.

Functional relationships between romantic jealousy and traits, such as neuroticism or adult attachment styles, are well-known. For the first time, we conducted a joint analysis of the Big Five traits and attachment dimensions as predictors of jealousy, which considered gender differences as well as differences in infidelity experiences and relationship status. In 847 participants, path modeling showed that higher neuroticism, lower agreeableness, and lower openness predicted higher romantic jealousy. The attachment dimensions "anxiety" and "depend" partly mediated the effect of neuroticism and fully mediated the effect of agreeableness on romantic jealousy. The direct and indirect relationships did not differ as a function of gender, relationship status, and infidelity experiences. These findings contribute to a better understanding of individual differences in romantic jealousy from a personality perspective

Forecasting in Hierarchical Environments

Forecasting is an important data analysis technique and serves as the basis for business planning in many application areas such as energy, sales and traffic management. The currently employed statistical models already provide very accurate predictions, but the forecasting calculation process is very time consuming. This is especially true since many application domains deal with hierarchically organized data. Forecasting in these environments is especially challenging due to ensuring forecasting consistency between hierarchy levels, which leads to an increased data processing and communication effort. For this purpose, we introduce our novel hierarchical forecasting approach, where we propose to push forecast models to the entities on the lowest hierarch level and reuse these models to efficiently create forecast models on higher hierarchical levels. With that we avoid the time-consuming parameter estimation process and allow an almost instant calculation of forecasts

Learning from connectomics on the fly.

Parallels between invertebrates and vertebrates in nervous system development, organisation and circuits are powerful reasons to use insects to study the mechanistic basis of behaviour. The last few years have seen the generation in Drosophila melanogaster of very large light microscopy data sets, genetic driver lines and tools to report or manipulate neural activity. These resources in conjunction with computational tools are enabling large scale characterisation of neuronal types and their functional properties. These are complemented by 3D electron microscopy, providing synaptic resolution data. A whole brain connectome of the fly larva is approaching completion based on manual reconstruction of electron-microscopy data. An adult whole brain dataset is already publicly available and focussed reconstruction is under way, but its 40× greater volume would require ∼500-5000 person-years of manual labour. Nevertheless rapid technical improvements in imaging and especially automated segmentation will likely deliver a complete adult connectome in the next 5 years. To enhance our understanding of the circuit basis of behaviour, light and electron microscopy outputs must be integrated with functional and physiological information into comprehensive databases. We review presently available data, tools and opportunities in Drosophila. We then consider the limits and potential of future progress and how this may impact neuroscience in rich model systems provided by larger insects and vertebrates

Viability Assessment in Liver Transplantation—What Is the Impact of Dynamic Organ Preservation?

Based on the continuous increase of donor risk, with a majority of organs classified as marginal, quality assessment and prediction of liver function is of utmost importance. This is also caused by the notoriously lack of effective replacement of a failing liver by a device or intensive care treatment. While various parameters of liver function and injury are well-known from clinical practice, the majority of specific tests require prolonged diagnostic time and are more difficult to assess ex situ. In addition, viability assessment of procured organs needs time, because the development of the full picture of cellular injury and the initiation of repair processes depends on metabolic active tissue and reoxygenation with full blood over several hours or days. Measuring injury during cold storage preservation is therefore unlikely to predict the viability after transplantation. In contrast, dynamic organ preservation strategies offer a great opportunity to assess organs before implantation through analysis of recirculating perfusates, bile and perfused liver tissue. Accordingly, several parameters targeting hepatocyte or cholangiocyte function or metabolism have been recently suggested as potential viability tests before organ transplantation. We summarize here a current status of respective machine perfusion tests, and report their clinical relevance

The natverse, a versatile toolbox for combining and analysing neuroanatomical data.

To analyse neuron data at scale, neuroscientists expend substantial effort reading documentation, installing dependencies and moving between analysis and visualisation environments. To facilitate this, we have developed a suite of interoperable open-source R packages called the natverse. The natverse allows users to read local and remote data, perform popular analyses including visualisation and clustering and graph-theoretic analysis of neuronal branching. Unlike most tools, the natverse enables comparison across many neurons of morphology and connectivity after imaging or co-registration within a common template space. The natverse also enables transformations between different template spaces and imaging modalities. We demonstrate tools that integrate the vast majority of Drosophila neuroanatomical light microscopy and electron microscopy connectomic datasets. The natverse is an easy-to-use environment for neuroscientists to solve complex, large-scale analysis challenges as well as an open platform to create new code and packages to share with the community

The natverse, a versatile toolbox for combining and analysing neuroanatomical data.

To analyse neuron data at scale, neuroscientists expend substantial effort reading documentation, installing dependencies and moving between analysis and visualisation environments. To facilitate this, we have developed a suite of interoperable open-source R packages called the natverse. The natverse allows users to read local and remote data, perform popular analyses including visualisation and clustering and graph-theoretic analysis of neuronal branching. Unlike most tools, the natverse enables comparison across many neurons of morphology and connectivity after imaging or co-registration within a common template space. The natverse also enables transformations between different template spaces and imaging modalities. We demonstrate tools that integrate the vast majority of Drosophila neuroanatomical light microscopy and electron microscopy connectomic datasets. The natverse is an easy-to-use environment for neuroscientists to solve complex, large-scale analysis challenges as well as an open platform to create new code and packages to share with the community

Impact of percutaneous mitral valve repair using the MitraClip™ system on ventricular arrhythmias and ICD therapies

Transcatheter edge-to-edge repair (TEER) using the MitraClip™ device has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high or prohibitive surgical risk. Only limited information regarding the impact of TEER on ventricular arrhythmias (VA) has been reported. The aim of the present study was to assess the impact of TEER using the MitraClip(TM) device on the burden of VA and ICD (Implantable Cardioverter Defibrillator) therapies. Among 600 MitraClip(TM) implantations performed in our clinic between September 2009 and October 2018, we identified 86 patients with successful TEER and an active implantable cardiac device (pacemaker, ICD, CRT-P/D (Cardiac Resynchronization Therapy-Pacemaker/Defibrillator)) eligible for retrospective VA analyses. These patients presented with mainly functional MR (81.4%) and severely reduced left ventricular ejection fraction (mean LVEF 22.1% ± 10.3%). The observation period comprised 456 ± 313 days before and 424 ± 287 days after TEER. The burden of ventricular arrhythmias (sustained ventricular tachycardia (sVT) and ventricular fibrillation (VF)) was significantly reduced after TEER (0.85 ± 3.47 vs. 0.43 ± 2.03 events per patient per month, p = 0.01). Furthermore, the rate of ICD therapies (anti-tachycardia pacing (ATP) and ICD shock) decreased significantly after MitraClip(TM) implantation (1.0 ± 3.87 vs. 0.32 ± 1.41, p = 0.014). However, reduction of VA burden did not result in improved two-year survival in this patient cohort with severely reduced LVEF. Mitral valve TEER using the MitraClip™ device was associated with a significant reduction of ventricular arrhythmias and ICD therapies

Improvement of tensile shear strength and wood failure percentage of 1C PUR bonded wooden joints at wet stage by means of DMF priming

Tensile shear tests according to EN 302-1 for load-bearing timber structures were performed on European beech wood (Fagus sylvatica L.) and Douglas fir [Pseudotsuga menziesii (Mirb.) Franco] bonded by means of a one-component polyurethane adhesive (1C PUR). Results reveal a substantial loss of tensile shear strength (TSS) and wood failure percentage (WFP) at the wet stage compared to the dry stage. As can be seen from microscopic images, this is accompanied by a loss of adhesion at the boundary layer. Therefore, the aim of this work was to find a priming fluid that improves the load transmission between adhesive and adherend at the wet stage without introducing formaldehyde into the gluing process. A substantial improvement of TSS and WFP was achieved by means of the hygroscopic organic solvent N,N-dimethylformamide (DMF). In addition, contact angle measurements were carried out, revealing that DMF heavily enhances the wettability of the joining surface. Furthermore, it was attempted to integrate the outcomes into the swelling strain model stated by Frihart in 2009. By way of comparison a hydroxymethylated resorcinol coupling agent, a mixture of diphenylmethane-4,4′-diisocyanate isomers and water were also tested as priming fluids. The data confirm that TSS and WFP of 1C PUR bonded wooden joints do not correlate, whilst WFP is mostly not normally (at wet stage often bimodally) distributed

Safety Evaluation of a Medical Congress Held During the COVID-19 Pandemic-A Prospective Cohort

Objectives: During the COVID-19 pandemic, few scientific congresses have been held on-site. We prospectively evaluated the safety concept of the congress of the Swiss Societies of Infectious Diseases and Hospital Hygiene. Methods: The congress was held in Geneva (Switzerland) while local COVID-19 incidence (with SARS-CoV-2 wild type circulating) was 65/100,000 population (September 2020). A rigorous safety concept was implemented. Congress attendees filled out a questionnaire to assess risk perception, exposures, symptoms and diagnoses of SARS-CoV-2 before, during and after the congress. Dried blood spots were taken on-site and 4 weeks later to detect SARS-CoV-2 seroconversions. Results: Of 365 congress attendees, 196 (54%) either answered the questionnaire (N = 150) or provided baseline and follow-up blood samples (N = 168). None of the participants reported a positive PCR in the 2 weeks after the congress. Five of 168 (3%) participants were seropositive at follow-up, all of which had already been positive at baseline. Conclusion: Findings indicate that congresses with a rigorous safety concept may take place, even in areas with moderately-high COVID-19 activity. Whether this holds true in vaccinated populations and with more transmissible viral variants circulating remains unclear