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The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
Background Heart failure (HF) is a complex, chronic condition that is associated with debilitating symptoms, all of which necessitate close follow-up by health care providers. Lack of disease monitoring may result in increased mortality and more frequent hospital readmissions for decompensated HF. Remote patient management (RPM) in this patient population may help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a manifestation of HF decompensation. Objective The objective of the present article is to describe the design of a new trial investigating the impact of RPM on unplanned cardiovascular hospitalisations and mortality in HF patients. Methods The TIM-HF2 trial is designed as a prospective, randomised, controlled, parallel group, open (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. Eligible patients with HF are randomised (1:1) to either RPM + usual care or to usual care only and are followed for 12 months. The primary outcome is the percentage of days lost due to unplanned cardiovascular hospitalisations or all-cause death. The main secondary outcomes are all-cause and cardiovascular mortality. Conclusion The TIM-HF2 trial will provide important prospective data on the potential beneficial effect of telemedical monitoring and RPM on unplanned cardiovascular hospitalisations and mortality in HF patients.
Contemporary drought impact assessments have been constrained due to data availability, leading to an incomplete representation of impact trends. To address this, we present a novel method for the comprehensive and near-real-time monitoring of drought socio-economic impacts based on media reports. We tested its application using the case of the exceptional 2018/19 German drought. By employing text mining techniques, 4839 impact statements were identified, relating to livestock, agriculture, forestry, fires, recreation, energy and transport sectors. An accuracy of 95.6% was obtained for their automatic classification. Furthermore, high levels of performance in terms of spatial and temporal precision were found when validating our results against independent data (e.g. soil moisture, average precipitation, population interest in droughts, crop yield and forest fire statistics). The findings highlight the applicability of media data for rapidly and accurately monitoring the propagation of drought consequences over time and space. We anticipate our method to be used as a starting point for an impact-based early warning system.
Aims: 1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic neurons. Extrapolations of data obtained using MPTP-based parkinsonism models to human disease are common; however, the precise mechanism by which MPTP is converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium (MPP+), has not been fully elucidated. In this study, we aimed to address two unanswered questions related to MPTP toxicology: (1) Why are MPTP-converting astrocytes largely spared from toxicity? (2) How does MPP+ reach the extracellular space? Results: In MPTP-treated astrocytes, we discovered that the membrane-impermeable MPP+, which is generally assumed to be formed inside astrocytes, is almost exclusively detected outside of these cells. Instead of a transporter-mediated export, we found that the intermediate, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), and/or its uncharged conjugate base passively diffused across cell membranes and that MPP+ was formed predominately by the extracellular oxidation of MPDP+ into MPP+. This nonenzymatic extracellular conversion of MPDP+ was promoted by O-2, a more alkaline pH, and dopamine autoxidation products. Innovation and Conclusion: Our data indicate that MPTP metabolism is compartmentalized between intracellular and extracellular environments, explain the absence of toxicity in MPTP-converting astrocytes, and provide a rationale for the preferential formation of MPP+ in the extracellular space. The mechanism of transporter-independent extracellular MPP+ formation described here indicates that extracellular genesis of MPP+ from MPDP is a necessary prerequisite for the selective uptake of this toxin by catecholaminergic neurons.