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Objectives: Severe pneumonia may evoke acute lung injury, and sphingosine-1-phosphate is involved in the regulation of vascular permeability and immune responses. However, the role of sphingosine-1-phosphate and the sphingosine-1-phosphate producing sphingosine kinase 1 in pneumonia remains elusive. We examined the role of the sphingosine-1-phosphate system in regulating pulmonary vascular barrier function in bacterial pneumonia. Design: Controlled, in vitro, ex vivo, and in vivo laboratory study. Subjects: Female wild-type and SphK1-deficient mice, 8-10 weeks old. Human postmortem lung tissue, human blood-derived macrophages, and pulmonary microvascular endothelial cells. Interventions: Wild-type and SphK1-deficient mice were infected with Streptococcus pneumoniae. Pulmonary sphingosine-1-phosphate levels, messenger RNA expression, and permeability as well as lung morphology were analyzed. Human blood-derived macrophages and human pulmonary microvascular endothelial cells were infected with S. pneumoniae. Transcellular electrical resistance of human pulmonary microvascular endothelial cell monolayers was examined. Further, permeability of murine isolated perfused lungs was determined following exposition to sphingosine-1-phosphate and pneumolysin. Measurements and Main Results: Following S. pneumoniae infection, murine pulmonary sphingosine-1-phosphate levels and sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 expression were increased. Pneumonia-induced lung hyperpermeability was reduced in SphK1(-/-) mice compared with wild-type mice. Expression of sphingosine kinase 1 in macrophages recruited to inflamed lung areas in pneumonia was observed in murine and human lungs. S. pneumoniae induced the sphingosine kinase 1/sphingosine-1-phosphate system in blood-derived macrophages and enhanced sphingosine-1-phosphate receptor 2 expression in human pulmonary microvascular endothelial cell in vitro. In isolated mouse lungs, pneumolysin-induced hyperpermeability was dose dependently and synergistically increased by sphingosine-1-phosphate. This sphingosine-1-phosphate-induced increase was reduced by inhibition of sphingosine-1-phosphate receptor 2 or its downstream effector Rho-kinase. Conclusions: Our data suggest that targeting the sphingosine kinase 1-/sphingosine-1-phosphate-/sphingosine-1-phosphate receptor 2-signaling pathway in the lung may provide a novel therapeutic perspective in pneumococcal pneumonia for prevention of acute lung injury.
Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
Das prolongierte Weaning von Patienten mit neurologischen oder neurochirurgischen Erkrankungen weist Besonderheiten auf, denen die Deutsche Gesellschaft für Neurorehabilitation e. V. in einer eigenen Leitlinie Rechnung trägt.
Im Hinblick auf Definitionen (z. B. Weaningerfolg und -versagen), Weaningkategorien, Pathophysiologie des Weaningversagens und allgemeine Weaningstrategien wird ausdrücklich auf die aktuelle S2k-Leitlinie der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. verwiesen.
In der neurologisch-neurochirurgischen Frührehabilitation werden Patienten mit zentralen Störungen der Atmungsregulation (z. B. Hirnstammläsionen), des Schluckaktes (neurogene Dysphagien), mit neuromuskulären Problemen (z. B. Critical-illness-Polyneuropathie, Guillain-Barre-Syndrom, Querschnittlähmungen, Myasthenia gravis) und/oder kognitiven Störungen (z. B. Bewusstseins- und Vigilanzstörungen, schwere Kommunikationsstörungen) versorgt, deren Betreuung bei der Entwöhnung von der Beatmung neben intensivmedizinischer Kompetenz auch neurologische bzw. neurochirurgische und neurorehabilitative Expertise erfordert. In Deutschland wird diese Kompetenz in Zentren der neurologisch-neurochirurgischen Frührehabilitation vorgehalten, und zwar als Krankenhausbehandlung.
Der Leitlinie liegt eine systematische Recherche von Leitliniendatenbanken und Medline zugrunde. Unter Moderation durch die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) erfolgte die Konsensfindung mittels nominalen Gruppenprozesses und Delphi-Verfahren.
In der vorliegenden Leitlinie der DGNR wird auf die strukturellen und inhaltlichen Besonderheiten der neurologisch-neurochirurgischen Frührehabilitation sowie vorhandene Studien zum Weaning in Frührehabilitationseinrichtungen eingegangen.
Adressaten der Leitlinie sind Neurologen, Neurochirurgen, Anästhesisten, Palliativmediziner, Logopäden, Intensivpflegekräfte, Ergotherapeuten, Physiotherapeuten und Neuropsychologen. Ferner richtet sich diese Leitlinie zur Information an Fachärzte für Physikalische Medizin und Rehabilitation (PMR), Pneumologen, Internisten, Atmungstherapeuten, den Medizinischen Dienst der Krankenkassen (MDK) und des Spitzenverbands Bund der Krankenkassen e. V. (MDS). Das wesentliche Ziel dieser Leitlinie ist es, den aktuellen Wissensstand zum Thema „Prolongiertes Weaning in der neurologisch-neurochirurgischen Frührehabilitation“ zu vermitteln.
The problem of atmospheric emission from OH molecules is a long standing problem for near-infrared astronomy. PRAXIS is a unique spectrograph which is fed by fibres that remove the OH background and is optimised specifically to benefit from OH-Suppression. The OH suppression is achieved with fibre Bragg gratings, which were tested successfully on the GNOSIS instrument. PRAXIS uses the same fibre Bragg gratings as GNOSIS in its first implementation, and will exploit new, cheaper and more efficient, multicore fibre Bragg gratings in the second implementation. The OH lines are suppressed by a factor of similar to 1000, and the expected increase in the signal-to-noise in the interline regions compared to GNOSIS is a factor of similar to 9 with the GNOSIS gratings and a factor of similar to 17 with the new gratings. PRAXIS will enable the full exploitation of OH suppression for the first time, which was not achieved by GNOSIS (a retrofit to an existing instrument that was not OH-Suppression optimised) due to high thermal emission, low spectrograph transmission and detector noise. PRAXIS has extremely low thermal emission, through the cooling of all significantly emitting parts, including the fore-optics, the fibre Bragg gratings, a long length of fibre, and the fibre slit, and an optical design that minimises leaks of thermal emission from outside the spectrograph. PRAXIS has low detector noise through the use of a Hawaii-2RG detector, and a high throughput through a efficient VPH based spectrograph. PRAXIS will determine the absolute level of the interline continuum and enable observations of individual objects via an IFU. In this paper we give a status update and report on acceptance tests.
Understanding the natural history of model organisms is important for the effective use of their genomic resourses. Arabidopsis lyrata has emerged as a useful plant for studying ecological and evolutionary genetics, based on its extensive natural variation, sequenced genome and close relationship to A. thaliana. We studied genetic diversity across the entire range of European Arabidopsis lyrata ssp. petraea, in order to explore how population history has influenced population structure. We sampled multiple populations from each region, using nuclear and chloroplast genome markers, and combined population genetic and phylogeographic approaches. Within-population diversity is substantial for nuclear allozyme markers (mean P = 0.610, A(e) = 1.580, H-e = 0.277) and significantly partitioned among populations (F- ST = 0.271). The Northern populations have modestly increased inbreeding (F-IS = 0.163 verses F-IS = 0.093), but retain comparable diversity to central European populations. Bottlenecks are common among central and northern Europe populations, indicating recent demographic history as a dominant factor in structuring the European diversity. Although the genetic structure was detected at all geographic scales, two clear differentiated units covering northern and central European areas (F-CT = 0.155) were identified by Bayesian analysis and supported by regional pairwise F-CT calculations. A highly similar geographic pattern was observed from the distribution of chloroplast haplotypes, with the dominant northern haplotypes absent from central Europe. We conclude A. l. petraea's cold-tolerance and preference for disturbed habitats enabled glacial survival between the alpine and Nordic glaciers in central Europe and an additional cryptic refugium. While German populations are probable peri-glacial leftovers, Eastern Austrian populations have diversity patterns possibly compatible with longer-term survival.
Magnetically doped topological insulators enable the quantum anomalous Hall effect (QAHE), which provides quantized edge states for lossless charge-transport applications(1-8). The edge states are hosted by a magnetic energy gap at the Dirac point(2), but hitherto all attempts to observe this gap directly have been unsuccessful. Observing the gap is considered to be essential to overcoming the limitations of the QAHE, which so far occurs only at temperatures that are one to two orders of magnitude below the ferromagnetic Curie temperature, T-C (ref. (8)). Here we use low-temperature photoelectron spectroscopy to unambiguously reveal the magnetic gap of Mn-doped Bi2Te3, which displays ferromagnetic out-of-plane spin texture and opens up only below T-C. Surprisingly, our analysis reveals large gap sizes at 1 kelvin of up to 90 millielectronvolts, which is five times larger than theoretically predicted(9). Using multiscale analysis we show that this enhancement is due to a remarkable structure modification induced by Mn doping: instead of a disordered impurity system, a self-organized alternating sequence of MnBi2Te4 septuple and Bi2Te3 quintuple layers is formed. This enhances the wavefunction overlap and size of the magnetic gap(10). Mn-doped Bi2Se3 (ref. (11)) and Mn-doped Sb2Te3 form similar heterostructures, but for Bi2Se3 only a nonmagnetic gap is formed and the magnetization is in the surface plane. This is explained by the smaller spin-orbit interaction by comparison with Mn-doped Bi2Te3. Our findings provide insights that will be crucial in pushing lossless transport in topological insulators towards room-temperature applications.
Introducing the CTA concept
(2013)
The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.