Adult Hyalomma marginatum tick positive for Rickettsia aeschlimannii in Austria, October 2018

We report on a non-indigenous adult Hyalomma marginatum tick in Austria carrying the human pathogenic Rickettsia aeschlimannii; presumably introduced as a nymph via migratory birds and completed the moulting within the same year. It was negative for Crimean-Congo haemorrhagic fever virus, but the finding of R. aeschlimannii represents a potential threat for humans due to its zoonotic character. Awareness of invasive tick species and carried pathogens should be improved in central and northern Europe

Radiative impact of an extreme Arctic biomass-burning event

The aim of the presented study was to investigate the impact on the radiation budget of a biomass-burning plume, transported from Alaska to the High Arctic region of Ny-Ålesund, Svalbard, in early July 2015. Since the mean aerosol optical depth increased by the factor of 10 above the average summer background values, this large aerosol load event is considered particularly exceptional in the last 25 years. In situ data with hygroscopic growth equations, as well as remote sensing measurements as inputs to radiative transfer models, were used, in order to estimate biases associated with (i) hygroscopicity, (ii) variability of single-scattering albedo profiles, and (iii) plane-parallel closure of the modelled atmosphere. A chemical weather model with satellite-derived biomass-burning emissions was applied to interpret the transport and transformation pathways. The provided MODTRAN radiative transfer model (RTM) simulations for the smoke event (14:00 9 July–11:30 11 July) resulted in a mean aerosol direct radiative forcing at the levels of −78.9 and −47.0 W m ^-2 at the surface and at the top of the atmosphere, respectively, for the mean value of aerosol optical depth equal to 0.64 at 550 nm. This corresponded to the average clear-sky direct radiative forcing of −43.3 W/m ^2, estimated by radiometer and model simulations at the surface. Ultimately, uncertainty associated with the plane-parallel atmosphere approximation altered results by about 2 W m^−2. Furthermore, model-derived aerosol direct radiative forcing efficiency reached on average −126 W m^−2/τ550 and −71 W^m−2/τ550 at the surface and at the top of the atmosphere, respectively. The heating rate, estimated at up to 1.8 K day^−1 inside the biomass-burning plume, implied vertical mixing with turbulent kinetic energy of 0.3 m^2s^−

Radiative impact of an extreme Arctic biomass-burning event

The aim of the presented study was to investigate the impact on the radiation budget of a biomass-burning plume, transported from Alaska to the High Arctic region of Ny-Ålesund, Svalbard, in early July 2015. Since the mean aerosol optical depth increased by the factor of 10 above the average summer background values, this large aerosol load event is considered particularly exceptional in the last 25 years. In situ data with hygroscopic growth equations, as well as remote sensing measurements as inputs to radiative transfer models, were used, in order to estimate biases associated with (i) hygroscopicity, (ii) variability of single-scattering albedo profiles, and (iii) plane-parallel closure of the modelled atmosphere. A chemical weather model with satellite-derived biomass-burning emissions was applied to interpret the transport and transformation pathways. The provided MODTRAN radiative transfer model (RTM) simulations for the smoke event (14:00 9 July–11:30 11 July) resulted in a mean aerosol direct radiative forcing at the levels of −78.9 and −47.0 W m−2 at the surface and at the top of the atmosphere, respectively, for the mean value of aerosol optical depth equal to 0.64 at 550 nm. This corresponded to the average clear-sky direct radiative forcing of −43.3 W m−2, estimated by radiometer and model simulations at the surface. Ultimately, uncertainty associated with the plane-parallel atmosphere approximation altered results by about 2 W m−2. Furthermore, model-derived aerosol direct radiative forcing efficiency reached on average −126 W m−2∕τ550 and −71 W m−2∕τ550 at the surface and at the top of the atmosphere, respectively. The heating rate, estimated at up to 1.8 K day−1 inside the biomass-burning plume, implied vertical mixing with turbulent kinetic energy of 0.3 m2 s−2

Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer

The generation of antitumour immunity depends on the nature of dendritic cell (DC)–tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013