Quantifizierung der Darmwandvaskularisation mittels Dynamic Contrast Enhanced Ultrasound (DCE–US) zur Beurteilung des Therapieansprechens bei Patienten mit chronisch entzündlichen Darmerkrankungen unter Therapie mit dem anti-TNF-Antikörper Infliximab

Background: The objective of this study was to investigate the use of contrast enhanced ultrasound (DCEUS) as a parameter to monitor the therapy response in people with inflammatory bowel disease undergoing therapy with the anti-TNFa-antibody Infliximab. Therefore, we compared DCEUS with well established examinations like ultrasound, doppler ultrasonography, endoscopy and histology. Methods: Patients with diagnosed inflammatory bowel disease (IBD) and the indication for treatment with the anti-TNFa-antibody Infliximab were examined at timepoints U0-U5 with contrast enhanced ultrasound. At all timepoints the disease-specific activity scores (HBI, Mayo) were ascertained and an ultrasound of the bowel including doppler ultrasonography was performed. At the timepoints U0 (start of therapy) and U5 (end of observation period) there was an endoscopy with sample collection. According to the disease activity (endoscopy, histology, activity score, clinical evaluation) the response to the therapy was calculated and the patients were divided in responder and non-responder. Results: 54 patients with IBD (mean age 44 years, 28 men, 26 women) were included in the study. 35 of them suffered from crohn´s disease and 19 from ulcerative colitis. According to the clinical evaluation, 45 patients were classified into the responder group and 9 patients into the non-responder group. For patients in the responder group a significant change in wall thickness (p=0.001), vascularization (p=0.001) and peak enhancement (p=0.039) could be shown at the timepoint U3 (Therapy week 6). There were no significant changes in the non-responder group. A significant correlation could be shown between the peak enhancement and the vascularization (rsp=0.412; p=0.001) as well as the inflammatory activity according to endoscopy (rsp=0.227; p=0.027) and histology (rsp=0.224; p=0.028). The strongest correlation was shown between the bowel wall thickness and the endoscopy (rsp=0.554; p=0.001). Conclusion: Two months after therapy induction changes in sonographic parameters like wall thickness and vascularization as well as the DCEUS parameter PE indicate a response to therapy. A significant correlation was shown between wall thickness, doppler ultrasonography, peak enhancement and endoscopy as well as histology. The use of perfusion related parameters like peak enhancement enables an early prognosis of the response to therapy. But there were no additional benefits compared to established methods like sonography and doppler ultrasonography.Hintergrund: Ziel der Studie war es das Therapieansprechen von Patienten mit chronisch entzündlichen Darmkrankheiten während einer Therapie mit dem anti-TNFa-Antikörper Infliximab mittels quantifizierender Kontrastmittelsonographie (DCEUS) zu untersuchen. Dabei wurden die klinische Beurteilung durch den behandelnden Arzt, Werte aus B-Bild-/ Dopplersonographie, Endoskopie und Histologie als Vergleichsparameter herangezogen. Methoden: Bei Patienten mit gesicherter CED und der Indikation zur Therapie mit dem anti-TNF-Antikörper Infliximab, erfolgte zu den Untersuchungszeitpunkten U0-U5 die Durchführung von kontrastmittelverstärkten Ultraschalluntersuchungen des Darmes. Zusätzlich wurden zu diesen Zeitpunkten die erkrankungsspezifischen klinischen Aktivitätsscores (Mayo, HBI) erhoben und eine umfassende Darmsonographie (B-Bild-, Dopplersonographie und DCEUS) durchgeführt. Zu den Zeitpunkten U0 (Therapiebeginn) und U5 (Ende des Beobachtungszeitraums) erfolgte zudem die Durchführung einer Endoskopie mit Probengewinnung. Entsprechend der ermittelten Krankheitsaktivität (Endoskopie, Histologie, Aktivitätsscore, klinische Einschätzung) erfolgten die Einschätzung des Therapieansprechens und die Einteilung der Patienten in Responder und Non-Responder. Ergebnisse und Beobachtungen: Es wurden 54 CED-Patienten (Mittleres Alter 44 Jahre, 28 Männer und 26 Frauen) in die Studie eingeschlossen, davon 35 Patienten mit M. Crohn und 19 Patienten mit Colitis ulcerosa. Verwendet man die klinische Einschätzung des Arztes als Einteilungskriterium erfolgte die Klassifikation von 45 Patienten in die Respondergruppe und von 9 Patienten in die Non-Respondergruppe. In der Respondergruppe (n=45) konnte eine signifikante Änderung der Wanddicke (p=0.001), der Vaskularisation (p=0.001) sowie des Peak Enhancements (p=0.039) bereits zum Zeitpunkt U3 (Therapiewoche 6) gezeigt werden. In der Non Respondergruppe (n=9) zeigten sich keine signifikanten Veränderungen der Messparameter. Bei Betrachtung aller Werte konnte zudem eine signifikante Korrelation zwischen dem Peak Enhancement und der im Farbdoppler bestimmten Vaskularisation (rsp=0.412; p=0.001) sowie der endoskopischen (rsp=0.227; p=0.027) und der histologischen (rsp=0.224; p=0.028) Entzündungsaktivität gezeigt werden. Die stärkste Korrelation bestand jedoch für die Darmwanddicke im Ultraschall und der mittels Endoskopie evaluierten Entzündungsaktivität (rsp=0.554; p=0.001). Praktische Schlussfolgerungen: Veränderungen der sonographischen Parameter Darmwanddicke, Darmwandperfusion im Farbdoppler als auch des DCEUS-Parameters PE können innerhalb von 2 Monaten nach Einleitung einer Infliximabtherapie ein erfolgreiches Therapieansprechen zeigen. Zudem konnte für die Wanddicke, den Farbdoppler und für das PE eine signifikante Korrelation zu den endoskopischen als auch histologischen Untersuchungen herausgearbeitet werden. Hierbei lieferte die Wanddicke jedoch die stärkste Korrelation. Die Verwendung perfusionsabhängiger Parameter wie z.B. Peak Enhancement kann somit eine frühzeitige Prognose des Therapieansprechens ermöglichen. Jedoch zeigten sich hierfür auch die bereits etablierten Methoden der B-Bild-Sonographie und der Farbdoppler als geeignet. Ein zusätzlicher Vorteil von DCEUS gegenüber den bereits etablierten Methoden konnte nicht gezeigt werden

Total hip replacement in patients with history of illicit injecting drug use

Background: A history of illicit injecting drug use makes indication of total hip arthroplasty (THA) in patients with end stage hip osteoarthritis difficult, as the risk of infection with colonized strains is multiplied if the patient continues to inject or inhale illicit drugs. Methods: A retrospective survivorship analysis of a consecutive series of 27 THA in patients with a history of illicit drug use was performed. Follow-up evaluation consisted of (1) a WOMAC score, (2) a standardized interview including queries on drug habits and eventual additional medico-surgical treatments of the affected hip, (3) a clinical examination in order to complete a Harris Hip Score, (4) radiological examination and (5) blood tests (blood sedimentation rates and C-reactive protein). Defined endpoints were death, implant revised or awaiting revision for deep infection or any other reason and lost to follow-up or follow-up after at least 2years. Results: Overall, 5- and 10-year implant survival rates with failure for any reason were 61% (CI: 41;81) and 52.3% (CI: 29;76) and for septic reasons 70.6% (CI: 52;89) and 60.5% (CI: 36;85), respectively. Even if at the time of THA all patients and respective health care professionals confirmed abstinence of illicit injecting drug use, five patients reported occasional use. Declared abstinence of less than 1year before THA was associated with higher recurrence rates (p=0.001) and both with higher septic failure rates (p=0.023, p=0.061). Positive serology for human deficiency virus did not increase implant failure rates. Conclusion: We use this unacceptable high failure rate as evidence when counseling patients and their health care professionals about the appropriate treatment of osteoarthritis in patients with a history of illicit drug use. Furthermore, we support the request of hair analysis for drugs documenting abstinence of at least 1year before indicating TH

Automated modelling assistance by integrating heterogeneous information sources

Model-Driven Engineering (MDE) uses models as its main assets in the software development process. The structure of a model is described through a metamodel. Even though modelling and meta-modelling are recurrent activities in MDE and a vast amount of MDE tools exist nowadays, they are tasks typically performed in an unassisted way. Usually, these tools cannot extract useful knowledge available in heterogeneous information sources like XML, RDF, CSV or other models and meta-models. We propose an approach to provide modelling and meta-modelling assistance. The approach gathers heterogeneous information sources in various technological spaces, and represents them uniformly in a common data model. This enables their uniform querying, by means of an extensible mechanism, which can make use of services, e.g., for synonym search and word sense analysis. The query results can then be easily incorporated into the (meta-)model being built. The approach has been realized in the Extremo tool, developed as an Eclipse plugin. Extremo has been validated in the context of two domains { production systems and process modelling { taking into account a large and complex industrial standard for classi cation and product description. Further validation results indicate that the integration of Extremo in various modelling environments can be achieved with low e ort, and that the tool is able to handle information from most existing technological spacesThis work was supported by the Ministry of Education of 1256 Spain (FPU grant FPU13/02698); the Spanish MINECO (TIN2014-52129-R);1257 the R&D programme of the Madrid Region (S2013/ICE-3006); the Austrian 1258 agency for international mobility and cooperation in education, science and re1259 search (OeAD) by funds from the Austrian Federal Ministry of Science, Research 1260 and Economy - BMWFW (ICM-2016-04969

Crossflow : A framework for distributed mining of software repositories

Large-scale software repository mining typically requires substantial storage and computational resources, and often involves a large number of calls to (rate-limited) APIs such as those of GitHub and StackOverflow. This creates a growing need for distributed execution of repository mining programs to which remote collaborators can contribute computational and storage resources, as well as API quotas (ideally without sharing API access tokens or credentials). In this paper we introduce Crossflow, a novel framework for building distributed repository mining programs. We demonstrate how Crossflow can delegate mining jobs to remote workers and cache their results, and how workers can implement advanced behaviour such as load balancing and rejecting jobs they cannot perform (e.g. due to lack of space, credentials for a specific API)

UML-based Cloud Application Modeling with Libraries, Profiles, and Templates

Recently, several cloud modeling approaches have emerged. They address the diversity of cloud environments by introducing a considerable set of modeling concepts in terms of novel domain-specific languages. At the same time, general-purpose languages, such as UML, provide modeling concepts to represent software, platform and infrastructure artifacts from different viewpoints where the deployment view is of particular relevance for specifying the distribution of application components on the targeted cloud environments. However, the generic nature of UML’s deployment language calls for a cloud-specific extension to capture the plethora of cloud provider offerings at the modeling level. In this paper, we propose the Cloud Application Modeling Language (CAML) to facilitate expressing cloud-based deployments directly in UML, which is especially beneficial for migration scenarios where reverse-engineered UML models are tailored towards a selected cloud environment. We discuss CAML’s realization as a UML internal language that is based on a model library for expressing deployment topologies and a set of profiles for wiring them with cloud provider offerings. Finally, we report on the use of UML templates to contribute application deployments as reusable blueprints and identify conceptual mappings between CAML and the recently standardized TOSCA.European Commission ICT Policy Support Programme 31785

XMLText: From XML Schema to Xtext

A multitude of Domain-Specific Languages (DSLs) have been implemented with XML Schemas. While such DSLs are well adopted and flexible, they miss modern DSL editor functionality. Moreover, since XML is primarily designed as a machine-processible format, artifacts defined with XMLbased DSLs lack comprehensibility and, therefore, maintainability. In order to tackle these shortcomings, we propose a bridge between the XML Schema Definition (XSD) language and text-based metamodeling languages. This bridge exploits existing seams between the technical spaces XMLware, modelware, and grammarware as well as closes identified gaps. The resulting approach is able to generate Xtextbased editors from XSDs providing powerful editor functionality, customization options for the textual concrete syntax style, and round-trip transformations enabling the exchange of data between the involved technical spaces. We evaluate our approach by a case study on TOSCA, which is an XML-based standard for defining Cloud deployments. The results show that our approach enables bridging XMLware with modelware and grammarware in several ways going beyond existing approaches and allows the automated generation of editors that are at least equivalent to editors manually built for XML-based languages.European Commission ICT Policy Support Programme 31785

Reusable textual styles for domain-specific modeling languages

Domain-specific languages enable concise and precise formalization of domain concepts and promote direct employment by domain experts. Therefore, syntactic constructs are introduced to empower users to associate concepts and relationships with visual textual symbols. Model-based language engineering facilitates the description of concepts and relationships in an abstract manner. However, concrete representations are commonly attached to abstract domain representations, such as annotations in metamodels, or directly encoded into language grammar and thus introduce redundancy between metamodel elements and grammar elements. In this work we propose an approach that enables autonomous development and maintenance of domain concepts and textual language notations in a distinctive and metamodel-agnostic manner by employing style models containing grammar rule templates and injection-based property selection. We provide an implementation and showcase the proposed notationspecification language in a comparison with state of the art practices during the creation of notations for an executable domain-specific modeling language based on the Eclipse Modeling Framework and Xtext