Laser-Supported CD133+ Cell Therapy in Patients with Ischemic Cardiomyopathy: Initial Results from a Prospective Phase I Multicenter Trial

Objectives: This study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy. Methods: Forty-two patients with severe ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) >15% and 3 myocardial segments) determined in the preoperative MRI was inversely correlated with a LVEF increase after laser-supported cell therapy (p = 0.024). Conclusions: This multicenter trial demonstrates that laser-supported CD133+ cell transplantation is safe and feasible in patients with ischemic cardiomyopathy undergoing CABG, and in most cases, it appears to significantly improve the myocardial function. Importantly, our data show that the beneficial effect was significantly related to the extent of transmural delayed enhancement, suggesting that MRI-guided selection of patients is mandatory to ensure the effectiveness of the therapy. Trial Registration: EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN4999863

Molecular Classification of Neuroendocrine Tumors of the Thymus

INTRODUCTION: The WHO classification of pulmonary neuroendocrine tumors (PNETs) is also used to classify thymic NETs (TNETs) into typical and atypical carcinoid (TC and AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), but little is known about the usability of alternative classification systems. METHODS: One hundred seven TNET (22 TC, 51 AC, 28 LCNEC, and 6 SCC) from 103 patients were classified according to the WHO, the European Neuroendocrine Tumor Society, and a grading-related PNET classification. Low coverage whole-genome sequencing and immunohistochemical studies were performed in 63 cases. A copy number instability (CNI) score was applied to compare tumors. Eleven LCNEC were further analyzed using targeted next-generation sequencing. Morphologic classifications were tested against molecular features. RESULTS: Whole-genome sequencing data fell into three clusters: CNIlow, CNIint, and CNIhigh. CNIlow and CNIint comprised not only TC and AC, but also six LCNECs. CNIhigh contained all SCC and nine LCNEC, but also three AC. No morphologic classification was able to predict the CNI cluster. Cases where primary tumors and metastases were available showed progression from low-grade to higher-grade histologies. Analysis of LCNEC revealed a subgroup of intermediate NET G3 tumors that differed from LCNEC by carcinoid morphology, expression of chromogranin, and negativity for enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CONCLUSIONS: TNETs fall into three molecular subgroups that are not reflected by the current WHO classification. Given the large overlap between TC and AC on the one hand, and AC and LCNEC on the other, we propose a morphomolecular grading system, Thy-NET G1-G3, instead of histologic classification for patient stratification and prognostication. peerReviewe

Man against machine reloaded : performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions

Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.Background: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. Materials and methods: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists’ management decisions. Secondary endpoints included the dermatologists’ diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). Results: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866–0.970), respectively. In level I, the dermatologists’ management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists’ management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. Conclusions: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.publishersversionPeer reviewe

Daptomycin as a possible new treatment option for surgical management of Methicillin-Resistant Staphylococcus aureus sternal wound infection after cardiac surgery

We present a case of a 77-year old female who had undergone a coronary artery bypass grafting with an aortic valve replacement and developed three month later a Methicillin-Resistant Staphylococcus aureus (MRSA) sternal wound infection which was successful treated with Daptomycin combined with vacuum-assisted closure (VAC)

The Solenoidal Large Intensity Device (SoLID) for JLab 12 GeV

The Solenoidal Large Intensity Device (SoLID) is a new experimental apparatus planned for Hall A at the Thomas Jefferson National Accelerator Facility (JLab). SoLID will combine large angular and momentum acceptance with the capability to handle very high data rates at high luminosity. With a slate of approved high-impact physics experiments, SoLID will push JLab to a new limit at the QCD intensity frontier that will exploit the full potential of its 12 GeV electron beam. In this paper, we present an overview of the rich physics program that can be realized with SoLID, which encompasses the tomography of the nucleon in 3-D momentum space from Semi-Inclusive Deep Inelastic Scattering (SIDIS), expanding the phase space in the search for new physics and novel hadronic effects in parity-violating DIS (PVDIS), a precision measurement of $J/\psi$ production at threshold that probes the gluon field and its contribution to the proton mass, tomography of the nucleon in combined coordinate and momentum space with deep exclusive reactions, and more. To meet the challenging requirements, the design of SoLID described here takes full advantage of recent progress in detector, data acquisition and computing technologies. In addition, we outline potential experiments beyond the currently approved program and discuss the physics that could be explored should upgrades of CEBAF become a reality in the future.Comment: This white paper for the SoLID program at Jefferson Lab was prepared in part as an input to the 2023 NSAC Long Range Planning exercise. To be submitted to J. Phys.

Der innere Aufbau Periglazialer Landformen

The internal structure of periglacial landforms contains valuable information on past and present environmental conditions. To benefit from this archive, however, an enhanced understanding of subsurface variations is crucial. This enables to assess the influence of the internal structure on prevailing process regimes and to evaluate the sensitivity of different landform units to environmental changes. This thesis investigates structural variations in the subsurface of (i) rock glaciers,(ii) solifluction lobes, (iii) palsas/ lithalsas and (iv) patterned ground, which occur between the different landform types, but also between landform units of the same type. Investigated variables comprise (i) the spatial distribution of permafrost, (ii) ground ice content, (iii) the origin of ground ice, (iv) thickness of the active layer and (v) frost table topography. Multi-dimensional investigations by the geophysical methods Electrical Resistivity Imaging (ERI) and Ground-Penetrating Radar (GPR) were performed in six study areas (a–f): four of them are located in high-alpine environments in Switzerland and two of them are located in the subarctic highlands of Iceland. Additionally, surface and subsurface temperature values were continuously recorded at selected study sites. At one study site, pF-values, representing the matric potential (or water potential), were recorded. From a methodological view, this thesis focuses on the application of quasi-3-D ERI, an approach in which many two-dimensional data sets are combined to create one three-dimensional data set. This permits e.g., a three-dimensional delimitation of subsurface structures and a spatial investigation of the distribution of ground ice. Besides the analysis of field data, this thesis incudes a comparison between inversion models produced with different software products, based on two synthetic data sets. The detection of resistivity structures and reflection patterns provides valuable insights into the internal structure of the investigated landform units: At the high-alpine study site at (a) Piz Nair, a highly variable ice content indicates a complex development of the investigated rock glacier assembly. The local formation of ground ice is attributed to an embedding of surface patches of snow or ice into the subsurface by rockfall. Results of geoelectric monitoring surveys on selected rock glaciers show the influence of seasonal alterations in the internal structure on subsurface meltwater flow. At the study site at (b) Piz Üertsch, results indicate the occurrences of isolated ground ice patches in a significantly larger rock glacier. Detected characteristics of the internal structure enable to reconstruct the development of the rock glacier, in which a temporary override of an adjacent glacier tongue on the rock glacier is considered crucial for the current distribution of ground ice. However, results of this thesis clearly show the absence of buried glacier ice in the subsurface of the rock glacier. Results from a rock glacier near the (c) Las Trais Fluors mountain ridge affirm the existence of a water-permeable frozen layer, which was assumed in previous studies. Furthermore, results show that the rock glacier contains large amounts of rockfall deposits. A joint interpretation of ERI and GPR results from the investigated scree slope at the mountain (d) Blauberg (Furka Pass) reveals characteristic structures in the subsurface, which enable a differentiation between solifluction lobes and pebbly rock glaciers. At the subarctic study site (e) Orravatnsrústir, results show that the internal structure of palsas can be used to deduce their current development stage and to assess past and future developments. Presented results affirm a long history of palsa development at the study site, as assumed in previous studies, but indicate recently changing environmental conditions. The investigated occurrences of patterned ground in the proglacial area of the glacier (f) Hofsjökull are currently not influenced by the detected occurrence of permafrost, according to the presented results. Therefore, a temporary formation of pattered ground is assumed, which is linked to the retreat of the glacier. This thesis shows discrepancies between the internal structure of some of the investigated landform units and the recent environmental conditions. This indicates a delayed adaption and a low sensitivity of the landform units to environmental changes. Findings indicate that the future development of permafrost will be strongly affected by variations in snowfall. Furthermore, the detection of isolated occurrences of ground ice at several study sites contradicts the widely assumed effectivity of balancing heat fluxes to create homogenous subsurface conditions in relatively fine-grained subsurface materials.Der strukturelle Aufbau periglazialer Landformen beinhaltet wertvolle Informationen über vergangene und heutige Umweltbedingungen. Um diese Informationen nutzen zu können, muss jedoch ein vertieftes Verständnis für den Zustand der inneren Struktur und möglicher Variationen entwickelt werden. Dieses Wissen ermöglicht beispielsweise eine Abschätzung des Einflusses der inneren Struktur auf das momentan dominierende Prozess-Regime und eine Beurteilung der Sensitivität gegenüber sich verändernden Umweltbedingungen. Die vorliegende Arbeit untersucht Unterschiede im Aufbau von (i) Blockgletschern, (ii) Solifluktionsloben, (iii) Palsas/ Lithalsas und (iv) Frostmusterböden, die zwischen den Landformtypen, aber auch zwischen einzelnen Einheiten desselben Typs bestehen. Betrachtet werden dabei (i) die räumliche Verbreitung von Permafrost,(ii) der Eisgehalt im Untergrund, (iii) die Entstehung von Untergrundeis, (iv) die Mächtigkeit der Auftauschicht sowie (v) die Formung der Frosttafel. In sechs Untersuchungsgebieten (a–f), davon vier in Hochgebirgsregionen der Schweiz und zwei im subarktischen Hochland Islands, wurden Untersuchungen mittels mehr-dimensionaler geophysikalischer Verfahren, Widerstandsgeoelektrik (ERI) und Bodenradar (GPR), durchgeführt. Zudem wurden an ausgewählten Standorten kontinuierlich Temperaturwerte der Oberfläche und des Untergrunds aufgezeichnet. An einem Standort wurden ergänzend pF-Werte, die die Saugspannung des Porenwassers angeben, aufgezeichnet. Methodischer Schwerpunkt der vorliegenden Arbeit ist die Anwendung von quasi-3-D ERI, einem Ansatz bei dem Datenpunkte mehrerer zweidimensionaler Datensätze zu einem dreidimensionalen Datensatz vereinigt werden. Dies erlaubt beispielsweise eine dreidimensionale Abgrenzung von Untergrundstrukturen und damit eine räumliche Untersuchung der Verbreitung von Untergrundeis. Ergänzend zur Arbeit mit Felddaten enthält die vorliegende Arbeit einen Vergleich zwischen Inversionsmodellen, die auf Basis von zwei identischen, synthetischen Datensätzen mit unterschiedlichen Softwareprodukten generiert wurden. Durch die Detektion von Widerstandsstrukturen und Reflektionsmustern lassen sich wertvolle Erkenntnisse über den strukturellen Aufbau der untersuchten Einheiten gewinnen: Im hochalpinen Untersuchungsgebiet am (a) Piz Nair weisen stark schwankende Eisgehalte auf eine komplexe Entwicklungsgeschichte der untersuchten Blockgletschergruppe hin. Die lokale Entstehung von Untergrundeis wird auf Verschüttungen oberflächlicher Schnee- oder Eisfelder durch Steinschlag zurückgeführt. An einem Blockgletscher der Gruppe wird mittels geoelektrischer Wiederholungsmessungen der saisonale Einfluss der inneren Struktur auf den Schmelzwasserabfluss im Untergrund durch Veränderungen der Permafrosttafel gezeigt. An einem deutlich größeren Blockgletscher im Untersuchungsgebiet am (b) Piz Üertsch zeigen die Ergebnisse dieser Arbeit isolierte Vorkommen von Untergrundeis. Hier kann anhand der inneren Struktur die Entwicklung des Blockgletschers nachvollzogen werden, wobei insbesondere eine zeitweilige Überdeckung des Blockgletschers durch eine benachbarte Gletscherzunge als ausschlaggebend für die lokale Verteilung von Untergrundeis angesehen wird. Die Ergebnisse zeigen, dass kein Gletschereis in den Block gletscher eingebettet wurde. Die vorgestellten Ergebnisse der Untersuchungen an einem Blockgletscher nahe des Bergkamms (c) Las Trais Fluors bestätigen die dort in vorherigen Studien angenommene Wasserdurchlässigkeit der Frosttafel. Zudem zeigt der Aufbau des Blockgletschers das Auftreten großer Mengen von Steinschlagablagerungen. Am untersuchten Schutthang am (d) Blauberg (Furkapass) können durch eine gemeinsame Auswertung der Ergebnisse von ERI und GPR charakteristische Strukturen detektiert werden, durch die sich die dort auftretenden Lobenstrukturen in Solifluktionsloben und Feinmaterial-Blockgletscher (Pebbly Rock Glaciers) unterscheiden lassen. Im subarktischen Untersuchungsgebiet (e) Orravatnsrústir zeigen die Ergebnisse, dass vom strukturellen Aufbau von Palsas auf deren gegenwärtiges Entwicklungsstadium geschlossen werden kann und dass Rückschlüsse auf vergangene und zukünftige Entwicklungen möglich sind. Die vorgestellten Ergebnisse bestätigen die in vorherigen Studien getroffene Annahme einer lange zurückreichenden Entwicklungsgeschichte der Palsas, weisen aber auch auf sich seit kurzem verändernde Umweltbedingungen hin. Die untersuchten Frostmusterböden im Gletschervorfeld des (f) Hofsjökull zeigen gegenwärtig keine Beeinflussung durch Permafrost, obwohl ein rezentes Vorkommen von Permafrost angenommen wird. Daher wird eine temporäre Bildung der untersuchten Oberflächenstrukturen angenommen, die an den Rückzug des Gletschers gebunden ist. Die vorliegende Arbeit zeigt, dass die innere Struktur einiger der untersuchten Landform-Einheiten Diskrepanzen zu den momentanen Umweltbedingungen aufweist. Dies deutet auf eine geringe Sensitivität, beziehungsweise eine verzögerte Anpassung der Landschaftsformung auf sich verändernde Umweltbedingungen hin. Des Weiteren zeigt die vorliegende Arbeit, dass besonders Veränderungen im Schneedeckenauf- und abbau wesentlich zur zukünftigen Entwicklung von Permafrost in den untersuchten Gebieten beitragen werden. Die Beobachtung isolierter Vorkommen von Untergrundeis in mehreren Untersuchungsgebieten steht in Kontrast zur verbreiteten Annahme, dass die ausgleichende Wirkung von Wärmeströmen im Untergrund in feinkörnigem Material besonders stark istPeriglacial environments are facing dramatic changes. Warming air temperatures and strong snow cover variations fundamentally affect landforming processes in this hotspot region of Climate Change. But before we can assess the response of landform development to a changing climate, we need to enhance our understanding of the internal structure of those landforms. Within this study, a broad scope of landform types from alpine and subarctic regions is investigated: rock glaciers, solifluction lobes, palsas and patterned ground. By using the geophysical methods 2-D and 3-D ERI, as well as GPR surveying, structural differences and similarities between landform units of different or the same landform types are highlighted. This enables a reconstruction of their past and a projection of their future development

A Quantitative Graph Model of Social Ontologies by Example of Wikipedia

Mehler A. A Quantitative Graph Model of Social Ontologies by Example of Wikipedia. In: Dehmer M, Emmert-Streib F, Mehler A, eds. Towards an Information Theory of Complex Networks: Statistical Methods and Applications. Boston, Basel: Birkhäuser; In Press

Towards an Information Theory of Complex Networks

For over a decade, complex networks have steadily grown as an important tool across a broad array of academic disciplines, with applications ranging from physics to social media. A tightly organized collection of carefully-selected papers on the subject, Towards an Information Theory of Complex Networks: Statistical Methods and Applications presents theoretical and practical results about information-theoretic and statistical models of complex networks in the natural sciences and humanities. The book's major goal is to advocate and promote a combination of graph-theoretic, information-theoret

Generalized Shortest Paths Trees: A Novel Graph Class Applied to Semiotic Networks

Mehler A. Generalized Shortest Paths Trees: A Novel Graph Class Applied to Semiotic Networks. In: Dehmer M, Emmert-Streib F, eds. Analysis of Complex Networks: From Biology to Linguistics. Weinheim: Wiley-VCH; 2009: 175-220