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Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Um zu überprüfen, ob sich die Artenzusammensetzung alpiner Kalk-Magerrasen (Blaugras-Horstseggenrasen, Polsterseggenrasen) im Nationalpark Berchtesgaden während der letzten drei Jahrzehnte geändert hat, wurden Vegetationsaufnahmen aus den 1980er Jahren 2013/14 zum zweiten Mal wiederholt vegetationskundlich erfasst.
Ziel der Arbeit war es, durch den Vergleich der Aufnahmenkollektive Vegetationsveränderungen während der letzten drei Jahrzehnte aufzuzeigen und diese als allogene oder autogene Prozesse zu interpretieren. Dabei wurde insbesondere der Frage nachgegangen, ob anthropogene Stickstoff-Einträge als Hauptursache für mögliche Veränderungen angesehen werden können.
Tatsächlich konnten ausgeprägte floristische Veränderungen im Vergleichszeitraum aufgezeigt werden. So hat sich seit den 1980er Jahre die mittlere Artenzahl sowohl im Polsterseggenrasen als auch im Horstseggenrasen um mehr als 10 Arten pro Aufnahmefläche erhöht. Im Polsterseggenrasen wurde ferner eine signifikante Abnahme der mittleren Kontinentalitätszahlen nachgewiesen.
Die dokumentierten floristischen Veränderungen könnten auf die globale Erwärmung und die damit verbundenen Klimaeffekte zurückzuführen sein. Auch natürlich ablaufende Sukzessionsprozesse könnten die aufgezeigten Änderungen in der Artenzusammensetzung erklären, allerdings ist die Zeitspanne von 30 Jahren zu kurz, als dass eine autogene Sukzession als der Hauptfaktor angesehen werden kann. Denkbar ist aber, dass Sukzessionsprozesse durch die globale Erwärmung heutzutage beschleunigt ablaufen. Stickstoffeinträge oder Landnutzungsänderungen spielen als Erklärungsmodell für die Vegetationsveränderungen dagegen wohl eher eine untergeordnete Rolle.
Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity.
Potentilla heptaphylla gehört in Hessen zu den oft verkannten Arten. Durch Herbarbelege bestätigt sind Vorkommen bei Niederkleen, Münzenberg sowie in Nordhessen um Korbach und Waldeck. Für diese Vorkommen konnte die diploide Chromosomenzahl von 2n = 14 bestätigt werden. Ein Vorkommen im Frankfurter Wald ist erloschen. In Nordhessen wurden außerdem tetraploide Pflanzen festgestellt, bei denen es sich eventuell um Bastarde zwischen Potentilla heptaphylla und P. neumanniana handelt.
Mittels molekulargenetischer Elternschaftsanalyse wurde eine niedrige Rate gemischter Mutterschaften in Bruten der sozial monogamen Tannenmeise nachgewiesen, einer Art, die sich durch hohe Fremdvaterschaftsraten auszeichnet. Gemischte Mutterschaften wurden in vier (= 0,8 %) von 483 Bruten entdeckt und nur für zehn (= 0,3 %) von 3563 erfolgreich genotypisierten Nachkommen wurde die Putativmutter von der genetischen Mutterschaft ausgeschlossen. In Anbetracht dieser sehr niedrigen Rate kann in evolutionsbiologischen Studien der soziale Fortpflanzungserfolg mit dem genetischen Fortpflanzungserfolg für Weibchen der Tannenmeise ohne weiteres gleichgesetzt werden. Die Putativväter wurden ebenfalls in allen Fällen von der genetischen Elternschaft ausgeschlossen, was Quasiparasitismus als Erklärung für gemischte Mutterschaften ausschließt. In einem Fall konnten die Partner eines Brutpaares, das zeitgleich in der Nähe eine eigene Brut aufzog, zweifelsfrei als die genetischen Eltern eines einzelnen Nachkommen identifiziert werden. Mögliche
Ursachen für das Auftreten gemischter Mutterschaften bei der Tannenmeise schließen die Übernahme von
Nistkästen samt begonnenen Gelegen nach dem Tod oder Abwandern der Vorbesitzer und innerartlichen
Brutparasitismus ein.
From 12.12.2010 to 17.12.2010, the Dagstuhl Seminar 10501 "Advances and Applications of Automata on Words and Trees" was held in Schloss Dagstuhl - Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available.
Seminar: 10501 - Advances and Applications of Automata on Words and Trees. The aim of the seminar was to discuss and systematize the recent fast progress in automata theory and to identify important directions for future research. For this, the seminar brought together more than 40 researchers from automata theory and related fields of applications. We had 19 talks of 30 minutes and 5 one-hour lectures leaving ample room for discussions. In the following we describe the topics in more detail.
Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na(+)-dependent [(3)H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.