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Neuderth, Silke ; Schwarz, Betje ; Gerlich, Christian ; Schuler, Michael ; Markus, Miriam ; Bethge, Matthias
Background
Musculoskeletal disorders are one of the most important causes of work disability. Various rehabilitation services and return-to-work programs have been developed in order to reduce sickness absence and increase sustainable return-to-work. As the effects of conventional medical rehabilitation programs on sickness absence duration were shown to be slight, work-related medical rehabilitation programs have been developed and tested. While such studies proved the efficacy of work-related medical rehabilitation compared with conventional medical rehabilitation in well-conducted randomized controlled trials, its effectiveness under real-life conditions has yet to be proved.
Methods/Design
The cohort study will be performed under real-life conditions with two parallel groups. Participants will receive either a conventional or a work-related medical rehabilitation program. Propensity score matching will be used to identify controls that are comparable to treated work-related medical rehabilitation patients. Over a period of three months, about 18,000 insured patients with permission to undergo a musculoskeletal rehabilitation program will be contacted. Of these, 15,000 will receive a conventional and 3,000 a work-related medical rehabilitation. We expect a participation rate of 40 % at baseline. Patients will be aged 18 to 65 years and have chronic musculoskeletal disorders, usually back pain. The control group will receive a conventional medical rehabilitation program without any explicit focus on work, work ability and return to work in diagnostics and therapy. The intervention group will receive a work-related medical rehabilitation program that in addition to common rehabilitation treatments contains 11 to 25 h of work-related treatment modules. Follow-up data will be assessed three and ten months after patients’ discharge from the rehabilitation center. Additionally, department characteristics will be assessed and administrative data records used. The primary outcomes are sick leave duration, stable return to work and subjective work ability. Secondary outcomes cover several dimensions of health, functioning and coping strategies.
Discussion
This study will determine the relative effectiveness of a complex, newly implemented work-related rehabilitation strategy for patients with musculoskeletal disorders.
Motilitätsstörungen des Magen-Darm-Traktes können bei kritisch kranken Patienten auf der Intensivstation zu einem lebensbedrohlichen Krankheitsbild führen. Dabei spielen eine Vielzahl von Pathomechanismen eine Rolle, wobei das Interesse dieser Arbeit den Wirkungen des Tag-Nacht-Hormons Melatonin gilt. Da aus anderen Untersuchungen eine protektive Funktion des Melatonins postuliert werden kann, ist sein Einfluss auf die Peristaltik am Meerschweinchendünndarm untersucht worden. Dabei wurde durch kontinuierliche Perfusion eines Dünndarmsegments im Organbad eine gerichtete Peristaltik induziert. Der Schwellendruck, bei dem eine Kontraktionswelle ausgelöst wurde, als Messparameter herangezogen. Durch Zugabe von Melatonin (in den Konzentrationen: 10 pM, 1nM, 0,1µM und 10 µM) in das Organbad konnte kein Einfluss auf dem Schwellendruck nachgewiesen werden. Auch der Melatoninrezeptorantagonist Luzindol führte zu keiner Änderung des Schwellendruckes. Ein signifikanter Anstieg des Schwellendruckes und damit ein inhibitorischer Einfluss auf die Dünndarmperistaltik konnte lediglich durch den partiellen Agonisten 2Phenylmelatonin nachgewiesen werden. Wesentliche Ergebnisse dieser Arbeit zeigen den Einfluss von Melatonin unter Hypoxiebedingungen des Dünndarmes, bei dem Luzindol den inhibitorischen Effekt auf die Darmperistaltik verstärkt. Die Melatoningabe führt zu keiner protektiven Wirkung auf die Darmperistaltik unter Hypoxiebedingungen. Damit ist zu vermuten, dass der protektive Effekt des Melatonins auf die Darmperistaltik nicht durch seine Eigenschaften als Radikalfänger, sondern über Melatoninrezeptoren vermittelt wird. In den Versuchen mit dem Opioid Fentanyl ist eine signifikante Hemmung der Dünndarmperistalik ebenso unter Blockade des Melatoninrezeptorantagonisten Luzindol festzustellen. Bei Versuchen mit Propofol wurde durch Zugabe von Melatonin oder Melatoninrezeptoragonisten eine Verstärkung der Hemmung der Dünndarmmotilität durch Propofol nachgewiesen. In unseren Versuchen bestätigten wir, dass Midazolam eine hemmende Wirkung auf die Dünndarmperistalik hat. Eine vorherige Zugabe von Melatonin hatte dabei keinen Einfluss auf die hemmende Wirkung von Midazolam, wohingegen Luzindol die Hemmwirkung von Midazolam verstärkte. Somit hat das endogene Melatonin möglicherweise einen protektiven Einfluss, der jedoch durch exogene Zugabe von Melatonin nicht verstärkt wird und nicht nachgeahmt werden kann. Insgesamt zeigen die Untersuchungen, dass Melatonin per se keinen gesicherten Einfluss auf die Peristaltik hat, möglicherweise aber in Wechselwirkung mit Anästhetika.
Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates
(2016)
The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.
Burns, Alan J. ; Goldstein, Allan M. ; Newgreen, Donald F. ; Stamp, Lincon ; Schäfer, Karl-Herbert ; Metzger, Marco ; Hotta, Ryo ; Young, Heather M. ; Andrews, Peter W. ; Thapar, Nikhil ; Belkind-Gerson, Jaime ; Bondurand, Nadege ; Bornstein, Joel C. ; Chan, Wood Yee ; Cheah, Kathryn ; Gershon, Michael D. ; Heuckeroth, Robert O. ; Hofstra, Robert M.W. ; Just, Lothar ; Kapur, Raj P. ; King, Sebastian K. ; McCann, Conor J. ; Nagy, Nandor ; Ngan, Elly ; Obermayr, Florian ; Pachnis, Vassilis ; Pasricha, Pankaj J. ; Sham, Mai Har ; Tam, Paul ; Vanden Berghe, Pieter
Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
Previous research found that men conspicuously consume luxury products to attract a mate and to signal their mate value. However, these studies have yet neglected to investigate the function of male conspicuous consumption in same-sex competition. Given that intersexual selection and intrasexual selection are closely related processes, it stands to reason that a further function of male conspicuous consumption could be to impress and deter same-sex rivals. An 2 (intrasexual competition context vs. control) × 2 (conspicuous luxury vs. inconspicuous nonluxury) between-subjects experimental study conducted with an Amazon Mechanical Turk sample (N = 160) revealed that men reported both higher liking of and an intent to purchase a conspicuous luxury car compared to an inconspicuous nonluxury car due to increased feelings of social status. This effect was stronger in the intrasexual competition than in the control context. An additional perception study using a single-factor between-subjects design (conspicuous luxury vs. inconspicuous nonluxury car) among German men (N = 405) indicated that male participants rated a man who displayed a conspicuous luxury car more as a rival and mate poacher and less as a friend. They further perceived him to be superior on various mate value characteristics (i.e., attractiveness, intelligence, ambition, and status) and rated him as more oriented toward short-term mating. In sum, our findings add to previous research in the field of evolutionary consumer psychology by suggesting that male conspicuous consumption of luxuries may also serve a function in male–male competition.
Diese Arbeit befasst sich mit zeitaufgelösten Prozessen in molekularen Systemen. Dabei wurde sowohl die Wellenpaketdynamik nach Photoanregung betrachtet als auch spektrale Eigenschaften mittels Absorptions- und zweidimensionaler Spektroskopie untersucht.
Zunächst widmet sich die Arbeit der Wellenpaket- und Populationsdynamik in zwei diabatischen, gekoppelten Zuständen. Nach impulsiver Anregung aus dem zu Beginn besetzten Zustand treten in der Populationsdynamik zwei deutlich verschiedene Oszillationen auf. Der langsamer variierende Populationstransfer besitzt die Periodendauer der Vibrationsbewegung und ist auf einen Wechsel der Zustände beim Durchlaufen des Wellenpakets durch die Kreuzungsregion der diabatischen Potentiale zurückzuführen. Die ultraschnelle Komponente mit einer Periodendauer von etwa 4 fs lässt sich als eine Art Rabi-Oszillation beschreiben, die durch die (zeitunabhängige) Kopplung hervorgerufen wird. Sie wurde mit Hilfe von analytischen Berechnungen ausführlich charakterisiert. Damit dieser Prozess auftreten kann müssen mehrere Bedingungen erfüllt werden: Das Wellenpaket muss über die Dauer der Oszillationen annähernd örtlich lokalisiert bleiben; dies ist an den Umkehrpunkten der Wellenpaketsbewegung der Fall. Die Amplitude der Oszillationen in den Populationen ist proportional zum Verhältnis der Kopplung zum Energieabstand der Zustände. Deshalb muss an den stationären Stellen die Kopplung groß im Vergleich zum Energieabstand sein. Die Amplitude der Oszillationen hängt außerdem von dem Populationsverhältnis und den Phasen der Komponenten des Wellenpakets in den beiden Zuständen ab. Die ultraschnellen Oszillationen bleiben auch in mehrdimensionalen Systemen mit unterschiedlichen Vibrationsfrequenzen je Freiheitsgrad erhalten.
Das gleiche Modell wurde benutzt, um Ladungstransferprozesse mittels linearer und 2D-Spektroskopie zu untersuchen. Eine Kopplung an die Umgebung wurde, aufbauend auf einer Quanten-Master-Gleichung in Markov-Näherung, wellenfunktionsbasiert mittels eines Quantum-Jump-Algorithmus mit expliziter Dephasierung beschrieben. Dabei findet mit vorher definierten Wahrscheinlichkeiten zu jedem Zeitschritt einer von drei stochastischen Prozessen statt. Neben kohärenter Propagation können Sprünge in einen anderen Eigenzustand des Systems und Dephasierungen auftreten. Zwei Dissipationsparameter spielen dabei eine Rolle. Dies ist zum einen die Stärke der System-Bad-Kopplung, welche die Gesamtrate der Energierelaxation beschreibt. Weiterhin beeinflusst die Dephasierungskonstante den Verlust kohärenter Phasen ohne Energieänderung. Fallenzustände wurden identifiziert, die durch sehr geringe Sprungraten in niedrigere Zustände charakterisiert sind. Die Langlebigkeit kann durch die Form der Eigenfunktionen erklärt werden, die eine deutlich andere Wahrscheinlichkeitsverteilung als die der Nicht-Fallenzustände besitzen. Dadurch werden die in die Sprungraten eingehenden Matrixelemente klein. Das Absorptionsspektrum zeigt Peaks an der Stelle der Fallenzustände, da nur die Eigenfunktionen der Fallenzustände große Franck-Condon-Faktoren mit der Anfangswellenfunktion besitzen. Verschiedene Kombinationen der Dissipationsparameter führen zu Änderungen der relativen Peakintensitäten und der Peakbreiten.
Die 2D-Spektren des Ladungstransfersystems werden störungstheoretisch über die Polarisation dritter Ordnung berechnet. Sie zeigen viele eng nebeneinander liegende Peaks in einer schachbrettmusterförmigen Anordnung, die sich auf Übergänge unter Mitwirkung der Fallenzustände zurückführen lassen. Höhere System-Bad-Kopplungen führen aufgrund der effizienten Energiedissipation zu einer Verschiebung zu kleineren Energien. Peaks, die mit schneller zerfallenden Fallenzuständen korrespondieren, bleichen schneller aus. Höhere Dephasierungskonstanten resultieren in verbreiterten Peaks. Um den Einfluss der Dissipation genauer zu charakterisieren, wurden gefilterte 2D-Spektren betrachtet. Dazu wurden Ausschnitte der Polarisation dritter Ordnung zu verschiedenen Zeiten fouriertransformiert. Längere Zeiten führen zu einer effektiveren Energierelaxation entlang der entsprechenden Zeitvariablen. Die Entvölkerung der höher liegenden Zustände lässt sich somit zeit- und energieaufgelöst betrachten. Weiterhin wurde gezeigt, dass sich der Zerfall eines einzelnen Peaks mit dem Populationsabfall des damit korrespondierenden Eigenzustandes in Einklang bringen lässt, obwohl die Zuordnung der Peaks im 2D-Spektrum zu Übergängen zwischen definierten Eigenzuständen nicht eindeutig ist.
Mit dem benutzten eindimensionalen Modell können auch Ladungstransferprozesse in organischen gemischtvalenten Verbindungen beschrieben werden. Es wurde die Frage untersucht, welche Prozesse nach einem optisch induzierten Energietransfer in solchen Systemen ablaufen. Experimentelle Daten (aufgenommen im Arbeitskreis von Prof. Lambert) deuten auf eine schnelle interne Konversion (IC) gefolgt von Thermalisierung hin. Um dies theoretisch zu überprüfen, wurden Absorptionsspektren bei verschiedenen Temperaturen berechnet und mit den gemessenen transienten Spektren verglichen. Es findet sich, abhängig von der Stärke der elektronischen Kopplung, eine sehr gute bis gute Übereinstimmung, was die Annahme eines schnellen ICs stützt.
Im letzten Teil der Arbeit wurden vibronische 2D-Spektren von molekularen Aggregaten betrachtet. Dazu wurde die zeitabhängige Schrödingergleichung für ein Monomer-, Dimer- und Trimersystem mit der Multi-Configuration Time-Dependent Hartree-Methode gelöst und die Polarisation nicht-störungstheoretisch berechnet. Der Hamiltonoperator des Trimers umfasst hierbei sieben gekoppelte elektronische Zustände und drei bzw. sechs Vibrationsfreiheitsgrade. Der betrachtete Photonenecho-Beitrag der Polarisation wurde mittels phasencodierter Laserpulse extrahiert. Die resultierenden Spektren sind geometrieabhängig, ein Winkel zwischen den Übergangsdipolmomenten der Monomere von 0° (180°) resultiert in einem H-Aggregat (J-Aggregat). Die Lage und Intensität der Peaks im rein elektronischen Trimer wurde analytisch erläutert. Die Spektren unter Einbeziehung der Vibration zeigen eine ausgeprägte vibronische Struktur. Es wurde gezeigt, wie die Spektren für höhere Aggregationsgrade durch die höhere Dichte an vibronischen Zuständen komplexer werden. Im J-Aggregat ist mit zunehmender Aggregation eine stärkere Rotverschiebung zu sehen. Das Spektrum des H-Aggregats zeigt eine im Vergleich zum J-Aggregat kompliziertere Struktur. Die Verwendung zweier Vibrationsfreiheitsgrade je Monomer führt zu Spektren mit überlappenden Peaks und einer zusätzlichen vibronischen Progression. Der Vergleich von Spektren verschiedener Mischungen von Monomer, Dimer und Trimer, entsprechend einem von Temperatur und Konzentration abhängigen Aggregationsgrad, zeigt den Einfluss dieser experimentellen Faktoren. Schließlich wurden mögliche Ansätze aufgezeigt, anhand der Spektren auf den Aggregationsgrad zu schließen.
Estrecho, E. ; Gao, T. ; Brodbeck, S. ; Kamp, M. ; Schneider, C. ; Höfling, S. ; Truscott, A. G. ; Ostrovskaya, E. A.
Diabolical points (spectral degeneracies) can naturally occur in spectra of two-dimensional quantum systems and classical wave resonators due to simple symmetries. Geometric Berry phase is associated with these spectral degeneracies. Here, we demonstrate a diabolical point and the corresponding Berry phase in the spectrum of hybrid light-matter quasiparticles—exciton-polaritons in semiconductor microcavities. It is well known that sufficiently strong optical pumping can drive exciton-polaritons to quantum degeneracy, whereby they form a macroscopically populated quantum coherent state similar to a Bose-Einstein condensate. By pumping a microcavity with a spatially structured light beam, we create a two-dimensional quantum billiard for the exciton-polariton condensate and demonstrate a diabolical point in the spectrum of the billiard eigenstates. The fully reconfigurable geometry of the potential walls controlled by the optical pump enables a striking experimental visualization of the Berry phase associated with the diabolical point. The Berry phase is observed and measured by direct imaging of the macroscopic exciton-polariton probability densities.
Visual Attention in Flies-Dopamine in the Mushroom Bodies Mediates the After-Effect of Cueing
(2016)
Visual environments may simultaneously comprise stimuli of different significance. Often such stimuli require incompatible responses. Selective visual attention allows an animal to respond exclusively to the stimuli at a certain location in the visual field. In the process of establishing its focus of attention the animal can be influenced by external cues. Here we characterize the behavioral properties and neural mechanism of cueing in the fly Drosophila melanogaster. A cue can be attractive, repulsive or ineffective depending upon (e.g.) its visual properties and location in the visual field. Dopamine signaling in the brain is required to maintain the effect of cueing once the cue has disappeared. Raising or lowering dopamine at the synapse abolishes this after-effect. Specifically, dopamine is necessary and sufficient in the αβ-lobes of the mushroom bodies. Evidence is provided for an involvement of the αβ\(_{posterior}\) Kenyon cells.
A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.