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Abstract The specific aim of this study was to assess the faecal shedding of zoonotic enteropathogens by semi-domesticated reindeer (Rangifer tarandus tarandus) to deduce the potential risk to human health through modern reindeer herding. In total, 2,243 faecal samples of reindeer from northern regions of Finland and Norway were examined for potentially enteropathogenic bacteria (Campylobacter species, Enterococcus species, Escherichia coli, Salmonella species and Yersinia species) and parasites (Cryptosporidium species) in accordance with standard procedures. Escherichia coli were isolated in 94.7%, Enterococcus species in 92.9%, Yersinia species in 4.8% of the samples and Campylobacter species in one sample only (0.04%). Analysis for virulence factors in E. coli and Yersinia species revealed no pathogenic strains. Neither Salmonella species nor Cryptosporidium oocysts were detected. The public health risk due to reindeer husbandry concerning zoonotic diseases included in this study has to be considered as very low at present but a putative epidemiological threat may arise when herding conditions are changed with respect to intensification and crowding.

An accurate forecast of flare and coronal mass ejection (CME) initiation requires precise measurements of the magnetic energy buildup and release in the active regions of the solar atmosphere. We designed a new space weather mission that performs such measurements using new optical instruments based on the Hanle and Zeeman effects. The mission consists of two satellites, one orbiting the L1 Lagrangian point (Spacecraft Earth, SCE) and the second in heliocentric orbit at 1AU trailing the Earth by 80° (Spacecraft 80, SC80). Optical instruments measure the vector magnetic field in multiple layers of the solar atmosphere. The orbits of the spacecraft allow for a continuous imaging of nearly 73% of the total solar surface. In-situ plasma instruments detect solar wind conditions at 1AU and ahead of our planet. Earth-directed CMEs can be tracked using the stereoscopic view of the spacecraft and the strategic placement of the SC80 satellite. Forecasting of geoeffective space weather events is possible thanks to an accurate surveillance of the magnetic energy buildup in the Sun, an optical tracking through the interplanetary space, and in-situ measurements of the near-Earth environment.

A combined molecular and cultural method for the detection of the Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium subsp. paratuberculosis was developed and tested with artificially contaminated milk and dairy products. Results indicate that the method can be used for a reliable detection as a basis for first risk assessments. [ABSTRACT FROM AUTHOR]

Understanding and controlling the individual behavior of nanoscopic matter in liquids, the environment in which many such entities are functioning, is both inherently challenging and important to many natural and man-made applications. Here, we transport individual nano-objects, from an assembly in a biological ionic solution, through a nanochannel network and confine them in electrokinetic nanovalves, created by the collaborative effect of an applied ac electric field and a rationally engineered nanotopography, locally amplifying this field. The motion of so-confined fluorescent nano-objects is tracked, and its kinetics provides important information, enabling the determination of their particle diffusion coefficient, hydrodynamic radius, and electrical conductivity, which are elucidated for artificial polystyrene nanospheres and subsequently for sub-100-nm conjugated polymer nanoparticles and adenoviruses. The on-chip, individual nano-object resolution method presented here is a powerful approach to aid research and development in broad application areas such as medicine, chemistry, and biology., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of NRAS ( n = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.

Background: Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT., Methods: We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era., Results: The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7-1.2 years). Patients treated with anti-PD-1 or a combination of anti-CTLA-4/PD-1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti-PD-1, anti-CTLA-4, or a combination of anti-CTLA-4/PD-1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT., Conclusion: In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate whether a microelectromechanical system (MEMS) inertial sensor module is as accurate as fiber-optic gyroscopes when classifying subjects as normal for clinical stance and gait balance tasks., Methods: Data of ten healthy subjects were recorded simultaneously with a fiber-optic gyroscope (FOG) system of SwayStar™ and a MEMS sensor system incorporated in the Valedo® system. Data from a sequence of clinical balance tasks with different angle and angular velocity ranges were assessed. Paired t -tests were performed to determine significant differences between measurement systems. Cohen's kappa test was used to determine the classification of normal balance control between the two sensor systems when comparing the results to a reference database recorded with the FOG system. Potential cross-talk errors in roll and pitch angles when neglecting yaw axis rotations were evaluated by comparing 2D FOG and 3D MEMS recordings., Results: Statistically significant ( α =0.05) differences were found in some balance tasks, for example, "walking eight tandem steps" and various angular measures ( p < 0.03). However, these differences were within a few percent (<2.7%) of the reference values. Tasks with high dynamic velocity ranges showed significant differences ( p =0.002) between 2D FOG and 3D MEMS roll angles but no difference between 2D FOG and 2D MEMS roll angles. An almost perfect agreement could be obtained for both 2D FOG and 2D MEMS ( κ =0.97) and 2D FOG and 3D MEMS measures ( κ =0.87) when comparing measurements of all subjects and tasks., Conclusion: MEMS motion sensors can be used for assessing balance during clinical stance and gait tasks. MEMS provides measurements comparable to values obtained with a highly accurate FOG. When assessing pitch and roll trunk sway measures without accounting for the effect of yaw, it is recommended to use angle and angular velocity measures for stance, and only angular velocity measures for gait because roll and pitch velocity measurements are not influenced by yaw rotations, and angle errors are low for stance., Competing Interests: D. Roetenberg and C. Höller are employees of Hocoma AG producing the Valedo inertial sensors used in this study. J. H. J. Allum is a consultant for the company Balance International Innovation GmbH producing the SwayStar equipment used in this study., (Copyright © 2019 Daniel Roetenberg et al.)