Correlation between Targeted qPCR Assays and Untargeted DNA Shotgun Metagenomic Sequencing for Assessing the Fecal Microbiota in Dogs

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs

Coumarin anticoagulants and co-trimoxazole: avoid the combination rather than manage the interaction

OBJECTIVE: The objective of our study was to examine the management of the interaction between acenocoumarol or phenprocoumon and several antibiotics by anticoagulation clinics and to compare the consequences of this interaction on users of co-trimoxazole with those for users of other antibiotics. METHODS: A follow-up study was conducted at four anticoagulation clinics in The Netherlands. Data on measurements of the International Normalised Ratio (INR), application of a preventive dose reduction (PDR) of the coumarin anticoagulant, fever and time within or outside the therapeutic INR range were collected. RESULTS: The study cohort consisted of 326 subjects. A PDR was given more often to users of co-trimoxazole PDR than to users of other antibiotics. The PDR in co-trimoxazole users resulted in a significantly reduced risk of both moderate overanticoagulation (INR >4.5) and severe overanticoagulation (INR >6.0) compared with no PDR, with odds ratios (ORs) of 0.06 [95% confidence interval (CI): 0.01-0.51] and 0.09 (95% CI: 0.01-0.92), respectively. In co-trimoxazole users without PDR, the risk of overanticoagulation was significantly increased compared with users of other antibiotics. All co-trimoxazole users spent significantly more time under the therapeutic INR range during the first 6 weeks after the course than users of other antibiotics. CONCLUSION: PDR is effective in preventing overanticoagulation in co-trimoxazole users, but results in a significantly prolonged period of underanticoagulation after the course. Avoidance of concomitant use of co-trimoxazole with acenocoumarol or phenprocoumon seems to be a safer approach than management of the interaction between these drugs

Human Practice. Digital Ecologies. Our Future. : 14. Internationale Tagung Wirtschaftsinformatik (WI 2019) : Tagungsband

Erschienen bei: universi - Universitätsverlag Siegen. - ISBN: 978-3-96182-063-4Aus dem Inhalt: Track 1: Produktion & Cyber-Physische Systeme Requirements and a Meta Model for Exchanging Additive Manufacturing Capacities Service Systems, Smart Service Systems and Cyber- Physical Systems—What’s the difference? Towards a Unified Terminology Developing an Industrial IoT Platform – Trade-off between Horizontal and Vertical Approaches Machine Learning und Complex Event Processing: Effiziente Echtzeitauswertung am Beispiel Smart Factory Sensor retrofit for a coffee machine as condition monitoring and predictive maintenance use case Stakeholder-Analyse zum Einsatz IIoT-basierter Frischeinformationen in der Lebensmittelindustrie Towards a Framework for Predictive Maintenance Strategies in Mechanical Engineering - A Method-Oriented Literature Analysis Development of a matching platform for the requirement-oriented selection of cyber physical systems for SMEs Track 2: Logistic Analytics An Empirical Study of Customers’ Behavioral Intention to Use Ridepooling Services – An Extension of the Technology Acceptance Model Modeling Delay Propagation and Transmission in Railway Networks What is the impact of company specific adjustments on the acceptance and diffusion of logistic standards? Robust Route Planning in Intermodal Urban Traffic Track 3: Unternehmensmodellierung & Informationssystemgestaltung (Enterprise Modelling & Information Systems Design) Work System Modeling Method with Different Levels of Specificity and Rigor for Different Stakeholder Purposes Resolving Inconsistencies in Declarative Process Models based on Culpability Measurement Strategic Analysis in the Realm of Enterprise Modeling – On the Example of Blockchain-Based Initiatives for the Electricity Sector Zwischenbetriebliche Integration in der Möbelbranche: Konfigurationen und Einflussfaktoren Novices’ Quality Perceptions and the Acceptance of Process Modeling Grammars Entwicklung einer Definition für Social Business Objects (SBO) zur Modellierung von Unternehmensinformationen Designing a Reference Model for Digital Product Configurators Terminology for Evolving Design Artifacts Business Role-Object Specification: A Language for Behavior-aware Structural Modeling of Business Objects Generating Smart Glasses-based Information Systems with BPMN4SGA: A BPMN Extension for Smart Glasses Applications Using Blockchain in Peer-to-Peer Carsharing to Build Trust in the Sharing Economy Testing in Big Data: An Architecture Pattern for a Development Environment for Innovative, Integrated and Robust Applications Track 4: Lern- und Wissensmanagement (e-Learning and Knowledge Management) eGovernment Competences revisited – A Literature Review on necessary Competences in a Digitalized Public Sector Say Hello to Your New Automated Tutor – A Structured Literature Review on Pedagogical Conversational Agents Teaching the Digital Transformation of Business Processes: Design of a Simulation Game for Information Systems Education Conceptualizing Immersion for Individual Learning in Virtual Reality Designing a Flipped Classroom Course – a Process Model The Influence of Risk-Taking on Knowledge Exchange and Combination Gamified Feedback durch Avatare im Mobile Learning Alexa, Can You Help Me Solve That Problem? - Understanding the Value of Smart Personal Assistants as Tutors for Complex Problem Tasks Track 5: Data Science & Business Analytics Matching with Bundle Preferences: Tradeoff between Fairness and Truthfulness Applied image recognition: guidelines for using deep learning models in practice Yield Prognosis for the Agrarian Management of Vineyards using Deep Learning for Object Counting Reading Between the Lines of Qualitative Data – How to Detect Hidden Structure Based on Codes Online Auctions with Dual-Threshold Algorithms: An Experimental Study and Practical Evaluation Design Features of Non-Financial Reward Programs for Online Reviews: Evaluation based on Google Maps Data Topic Embeddings – A New Approach to Classify Very Short Documents Based on Predefined Topics Leveraging Unstructured Image Data for Product Quality Improvement Decision Support for Real Estate Investors: Improving Real Estate Valuation with 3D City Models and Points of Interest Knowledge Discovery from CVs: A Topic Modeling Procedure Online Product Descriptions – Boost for your Sales? Entscheidungsunterstützung durch historienbasierte Dienstreihenfolgeplanung mit Pattern A Semi-Automated Approach for Generating Online Review Templates Machine Learning goes Measure Management: Leveraging Anomaly Detection and Parts Search to Improve Product-Cost Optimization Bedeutung von Predictive Analytics für den theoretischen Erkenntnisgewinn in der IS-Forschung Track 6: Digitale Transformation und Dienstleistungen Heuristic Theorizing in Software Development: Deriving Design Principles for Smart Glasses-based Systems Mirroring E-service for Brick and Mortar Retail: An Assessment and Survey Taxonomy of Digital Platforms: A Platform Architecture Perspective Value of Star Players in the Digital Age Local Shopping Platforms – Harnessing Locational Advantages for the Digital Transformation of Local Retail Outlets: A Content Analysis A Socio-Technical Approach to Manage Analytics-as-a-Service – Results of an Action Design Research Project Characterizing Approaches to Digital Transformation: Development of a Taxonomy of Digital Units Expectations vs. Reality – Benefits of Smart Services in the Field of Tension between Industry and Science Innovation Networks and Digital Innovation: How Organizations Use Innovation Networks in a Digitized Environment Characterising Social Reading Platforms— A Taxonomy-Based Approach to Structure the Field Less Complex than Expected – What Really Drives IT Consulting Value Modularity Canvas – A Framework for Visualizing Potentials of Service Modularity Towards a Conceptualization of Capabilities for Innovating Business Models in the Industrial Internet of Things A Taxonomy of Barriers to Digital Transformation Ambidexterity in Service Innovation Research: A Systematic Literature Review Design and success factors of an online solution for cross-pillar pension information Track 7: IT-Management und -Strategie A Frugal Support Structure for New Software Implementations in SMEs How to Structure a Company-wide Adoption of Big Data Analytics The Changing Roles of Innovation Actors and Organizational Antecedents in the Digital Age Bewertung des Kundennutzens von Chatbots für den Einsatz im Servicedesk Understanding the Benefits of Agile Software Development in Regulated Environments Are Employees Following the Rules? On the Effectiveness of IT Consumerization Policies Agile and Attached: The Impact of Agile Practices on Agile Team Members’ Affective Organisational Commitment The Complexity Trap – Limits of IT Flexibility for Supporting Organizational Agility in Decentralized Organizations Platform Openness: A Systematic Literature Review and Avenues for Future Research Competence, Fashion and the Case of Blockchain The Digital Platform Otto.de: A Case Study of Growth, Complexity, and Generativity Track 8: eHealth & alternde Gesellschaft Security and Privacy of Personal Health Records in Cloud Computing Environments – An Experimental Exploration of the Impact of Storage Solutions and Data Breaches Patientenintegration durch Pfadsysteme Digitalisierung in der Stressprävention – eine qualitative Interviewstudie zu Nutzenpotenzialen User Dynamics in Mental Health Forums – A Sentiment Analysis Perspective Intent and the Use of Wearables in the Workplace – A Model Development Understanding Patient Pathways in the Context of Integrated Health Care Services - Implications from a Scoping Review Understanding the Habitual Use of Wearable Activity Trackers On the Fit in Fitness Apps: Studying the Interaction of Motivational Affordances and Users’ Goal Orientations in Affecting the Benefits Gained Gamification in Health Behavior Change Support Systems - A Synthesis of Unintended Side Effects Investigating the Influence of Information Incongruity on Trust-Relations within Trilateral Healthcare Settings Track 9: Krisen- und Kontinuitätsmanagement Potentiale von IKT beim Ausfall kritischer Infrastrukturen: Erwartungen, Informationsgewinnung und Mediennutzung der Zivilbevölkerung in Deutschland Fake News Perception in Germany: A Representative Study of People’s Attitudes and Approaches to Counteract Disinformation Analyzing the Potential of Graphical Building Information for Fire Emergency Responses: Findings from a Controlled Experiment Track 10: Human-Computer Interaction Towards a Taxonomy of Platforms for Conversational Agent Design Measuring Service Encounter Satisfaction with Customer Service Chatbots using Sentiment Analysis Self-Tracking and Gamification: Analyzing the Interplay of Motivations, Usage and Motivation Fulfillment Erfolgsfaktoren von Augmented-Reality-Applikationen: Analyse von Nutzerrezensionen mit dem Review-Mining-Verfahren Designing Dynamic Decision Support for Electronic Requirements Negotiations Who is Stressed by Using ICTs? A Qualitative Comparison Analysis with the Big Five Personality Traits to Understand Technostress Walking the Middle Path: How Medium Trade-Off Exposure Leads to Higher Consumer Satisfaction in Recommender Agents Theory-Based Affordances of Utilitarian, Hedonic and Dual-Purposed Technologies: A Literature Review Eliciting Customer Preferences for Shopping Companion Apps: A Service Quality Approach The Role of Early User Participation in Discovering Software – A Case Study from the Context of Smart Glasses The Fluidity of the Self-Concept as a Framework to Explain the Motivation to Play Video Games Heart over Heels? An Empirical Analysis of the Relationship between Emotions and Review Helpfulness for Experience and Credence Goods Track 11: Information Security and Information Privacy Unfolding Concerns about Augmented Reality Technologies: A Qualitative Analysis of User Perceptions To (Psychologically) Own Data is to Protect Data: How Psychological Ownership Determines Protective Behavior in a Work and Private Context Understanding Data Protection Regulations from a Data Management Perspective: A Capability-Based Approach to EU-GDPR On the Difficulties of Incentivizing Online Privacy through Transparency: A Qualitative Survey of the German Health Insurance Market What is Your Selfie Worth? A Field Study on Individuals’ Valuation of Personal Data Justification of Mass Surveillance: A Quantitative Study An Exploratory Study of Risk Perception for Data Disclosure to a Network of Firms Track 12: Umweltinformatik und nachhaltiges Wirtschaften Kommunikationsfäden im Nadelöhr – Fachliche Prozessmodellierung der Nachhaltigkeitskommunikation am Kapitalmarkt Potentiale und Herausforderungen der Materialflusskostenrechnung Computing Incentives for User-Based Relocation in Carsharing Sustainability’s Coming Home: Preliminary Design Principles for the Sustainable Smart District Substitution of hazardous chemical substances using Deep Learning and t-SNE A Hierarchy of DSMLs in Support of Product Life-Cycle Assessment A Survey of Smart Energy Services for Private Households Door-to-Door Mobility Integrators as Keystone Organizations of Smart Ecosystems: Resources and Value Co-Creation – A Literature Review Ein Entscheidungsunterstützungssystem zur ökonomischen Bewertung von Mieterstrom auf Basis der Clusteranalyse Discovering Blockchain for Sustainable Product-Service Systems to enhance the Circular Economy Digitale Rückverfolgbarkeit von Lebensmitteln: Eine verbraucherinformatische Studie Umweltbewusstsein durch audiovisuelles Content Marketing? Eine experimentelle Untersuchung zur Konsumentenbewertung nachhaltiger Smartphones Towards Predictive Energy Management in Information Systems: A Research Proposal A Web Browser-Based Application for Processing and Analyzing Material Flow Models using the MFCA Methodology Track 13: Digital Work - Social, mobile, smart On Conversational Agents in Information Systems Research: Analyzing the Past to Guide Future Work The Potential of Augmented Reality for Improving Occupational First Aid Prevent a Vicious Circle! The Role of Organizational IT-Capability in Attracting IT-affine Applicants Good, Bad, or Both? Conceptualization and Measurement of Ambivalent User Attitudes Towards AI A Case Study on Cross-Hierarchical Communication in Digital Work Environments ‘Show Me Your People Skills’ - Employing CEO Branding for Corporate Reputation Management in Social Media A Multiorganisational Study of the Drivers and Barriers of Enterprise Collaboration Systems-Enabled Change The More the Merrier? The Effect of Size of Core Team Subgroups on Success of Open Source Projects The Impact of Anthropomorphic and Functional Chatbot Design Features in Enterprise Collaboration Systems on User Acceptance Digital Feedback for Digital Work? Affordances and Constraints of a Feedback App at InsurCorp The Effect of Marker-less Augmented Reality on Task and Learning Performance Antecedents for Cyberloafing – A Literature Review Internal Crowd Work as a Source of Empowerment - An Empirical Analysis of the Perception of Employees in a Crowdtesting Project Track 14: Geschäftsmodelle und digitales Unternehmertum Dividing the ICO Jungle: Extracting and Evaluating Design Archetypes Capturing Value from Data: Exploring Factors Influencing Revenue Model Design for Data-Driven Services Understanding the Role of Data for Innovating Business Models: A System Dynamics Perspective Business Model Innovation and Stakeholder: Exploring Mechanisms and Outcomes of Value Creation and Destruction Business Models for Internet of Things Platforms: Empirical Development of a Taxonomy and Archetypes Revitalizing established Industrial Companies: State of the Art and Success Principles of Digital Corporate Incubators When 1+1 is Greater than 2: Concurrence of Additional Digital and Established Business Models within Companies Special Track 1: Student Track Investigating Personalized Price Discrimination of Textile-, Electronics- and General Stores in German Online Retail From Facets to a Universal Definition – An Analysis of IoT Usage in Retail Is the Technostress Creators Inventory Still an Up-To-Date Measurement Instrument? Results of a Large-Scale Interview Study Application of Media Synchronicity Theory to Creative Tasks in Virtual Teams Using the Example of Design Thinking TrustyTweet: An Indicator-based Browser-Plugin to Assist Users in Dealing with Fake News on Twitter Application of Process Mining Techniques to Support Maintenance-Related Objectives How Voice Can Change Customer Satisfaction: A Comparative Analysis between E-Commerce and Voice Commerce Business Process Compliance and Blockchain: How Does the Ethereum Blockchain Address Challenges of Business Process Compliance? Improving Business Model Configuration through a Question-based Approach The Influence of Situational Factors and Gamification on Intrinsic Motivation and Learning Evaluation von ITSM-Tools für Integration und Management von Cloud-Diensten am Beispiel von ServiceNow How Software Promotes the Integration of Sustainability in Business Process Management Criteria Catalog for Industrial IoT Platforms from the Perspective of the Machine Tool Industry Special Track 3: Demos & Prototyping Privacy-friendly User Location Tracking with Smart Devices: The BeaT Prototype Application-oriented robotics in nursing homes Augmented Reality for Set-up Processe Mixed Reality for supporting Remote-Meetings Gamification zur Motivationssteigerung von Werkern bei der Betriebsdatenerfassung Automatically Extracting and Analyzing Customer Needs from Twitter: A “Needmining” Prototype GaNEsHA: Opportunities for Sustainable Transportation in Smart Cities TUCANA: A platform for using local processing power of edge devices for building data-driven services Demonstrator zur Beschreibung und Visualisierung einer kritischen Infrastruktur Entwicklung einer alltagsnahen persuasiven App zur Bewegungsmotivation für ältere Nutzerinnen und Nutzer A browser-based modeling tool for studying the learning of conceptual modeling based on a multi-modal data collection approach Exergames & Dementia: An interactive System for People with Dementia and their Care-Network Workshops Workshop Ethics and Morality in Business Informatics (Workshop Ethik und Moral in der Wirtschaftsinformatik – EMoWI’19) Model-Based Compliance in Information Systems - Foundations, Case Description and Data Set of the MobIS-Challenge for Students and Doctoral Candidates Report of the Workshop on Concepts and Methods of Identifying Digital Potentials in Information Management Control of Systemic Risks in Global Networks - A Grand Challenge to Information Systems Research Die Mitarbeiter von morgen - Kompetenzen künftiger Mitarbeiter im Bereich Business Analytics Digitaler Konsum: Herausforderungen und Chancen der Verbraucherinformati

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Vergleichende klinische und immunhistochemische Charakterisierung keratozystischer odontogener Tumoren und Ameloblastome im Hinblck auf das Rezidivverhalten

Hintergrund: Die �Keratozyste� rückt mit der neuen Bezeichnung keratozystischer odontogener Tumor� (KZOT) auch in der Nomenklatur näher an die differentialdiagnostisch relevante Entität der Ameloblastome (A). Fragestellung: Das Rezidivverhalten von KZOT und Ameloblastomen wird vor dem Hintergrund etablierter Therapieverfahren und immunhistochemischer Marker des Zellzyklus und der Migration oder Strukturumbildung in einer retrospektiven Analyse miteinander verglichen. Patienten und Methoden: Klinische und immunhistochemische Untersuchung von 103 Patienten (88 x KZOT, 15 x Ameloblastome) über einen Zeitraum von 22 Jahren. Histologie: In Paraffin eingebettete chirurgische Bioptate wurden in Multiblocktechnik arrangiert und mit den monoklonalen Antikörpern Cyclin D1, Kollagen IV, p16, Cox-2, Laminin-5, Tenascin-C immunhistochemisch gefärbt. Ergebnisse: Altersdurchschnitt: KZOT 47 Jahre (14-80 Jahre), Ameloblastome 41 Jahre (16-79 Jahre). Geschlechtsverteilung: KZOT: m:w=2:1, Ameloblastome: m:w=3:2. Lokalisation: Im Unterkiefer mit Prädilektionsstelle in der Molarenregion und im aufsteigenden Unterkierferast fanden sich 76 KZOT und 12 Ameloblastome, im Oberkiefer 18 KZOT und 3 Ameloblastome. Multiples Auftreten nur bei 5 KZOT-Patienten. Therapie: Bei primären KZOT: 6 x Zystostomie, 48 x Zystektomie, 17 x Zystektomie und Kürettage, 14 x Zystektomie und marginale Ostektomie, 11 x Resektion. Bei Ameloblastomen: 5 x Enukleation, 10 x Resektion. Rezidivrate: Für KZOT ergab sich eine Rezidivrate von 11,7% nach durchschnittlich 5,4 Jahren, dabei 4 Rezidive nach Zystostomie, 6 nach Zystektomie, 3 nach Zystektomie und Kürettage und 2 nach Zystektomie und marginaler Ostektomie. Bei den Ameloblastomen trat kein Rezidiv auf. Immunhistochemie: Sowohl die Zellzyklus assoziierten als auch die extrazellulären Matrixproteine unterschieden bezüglich ihrer Quantität weder KZOT von den Ameloblastomen noch rezidivierende von nicht rezidivierenden KZOT. Schlussfolgerungen: 1. Die KZOT zeigen im eigenen Untersuchungsgut mehr Rezidive als die Ameloblastome. 2. Das höhere Rezidivverhalten der KZOT kann nicht durch die üblichen Marker des Zellzyklus und der Migration oder Strukturmodulation erklärt werden. 3. Die ungünstige Prognose der KZOT im Vergleich zu den Ameloblastomen im eigenen Untersuchungsgut wird durch eine eingeschränkte Radikalität der Therapie und durch das Auftreten charakteristischer Satellitenzysten erklärt

Att göra kön på ungdomsgårdar : en kvalitativ studie

The purpose of this essay is to describe and analyze how three leisure centers in Örebro county are working with gender issues. Our research questions are: What is Machofabriken? How do leisure centers in Örebro county work with equal treatment? In which way do leisure centers in Örebro county work with Machofabriken’s material? How come the recreation centers in Örebro don’t use Machofabriken’s material to any greater extent? We have focused on masculinity oriented gender projects at three leisure centers. We did semi-structured interviews with three recreation leaders who have all been educated in Machofabriken. The interviews were analyzed based on terms that are central in gender equality and masculinity research. The result demonstrates how they work with gender equality, how they use Machofabriken’s material and their thoughts and opinions about the material.Syftet med denna uppsats är att beskriva och analysera hur tre fritidsgårdar i Örebro kommun arbetar med jämställdhet. Våra frågeställningar är: Vad är Machofabriken? Hur ser jämställdhetsarbetet ut på fritidsgårdar i Örebro kommun? På vilket sätt arbetar fritidsgårdar med Machofabrikens material? Varför används inte Machofabrikens material i någon större utsträckning på fritidsgårdarna i Örebro? Vi har fokuserat på tre fritidsgårdars jämställdhetsarbete, framförallt det riktat mot unga män. Vi har utgått från semistrukturerade intervjuer med tre fritidsledare som alla har gått en utbildning i Machofabriken. Intervjuerna är analyserade utifrån begrepp som är centrala inom jämställdhets- och maskulinitetsforskning. Resultatet visar hur de arbetar med jämställdhet, hur de använder Machofabrikens material och deras tankar och åsikter om materialet

Untersuchungen zu Sequenzvarianten im p12-Gen beim hereditären Pankreaskarzinom

Unter allen Karzinomen rangiert das Pankreaskarzinom in Deutschland bei Männern an fünfter und bei Frauen an sechster Position. Die schlechte Prognose mit einer 5-Jahres-Überlebensrate von etwa 4% resultiert aus einer meist späten Diagnose der Erkrankung mit oft schon bestehenden Metastasen und begrenzten Therapiemöglichkeiten. Das Pankreaskarzinom tritt zum größten Teil sporadisch auf. Jedoch erkranken etwa 3 bis 5% der Pankreaskarzinompatienten mit familiärer Häufung. Es tritt entweder isoliert auf (= familiäres Pankreaskarzinom) oder ist mit so genannten Tumorprädispositionssyndromen assoziiert. Im Gegensatz zu den Tumorprädispositionssyndromen, bei denen Pankreaskarzinome mit den unterschiedlichsten Karzinomen kombiniert auftreten, konnte für das familiäre Pankreaskarzinom bislang keine krankheitsauslösende Mutation und damit eine Genlokalisation identifiziert werden. Eines dieser Tumorprädispositionssyndrome ist das Familial atypical multiple mole melanoma-Syndrom (FAMMM-Syndrom). Verschiedene Mutationen im CDKN2A-Gen (Cyclin dependent kinase 2A) auf dem menschlichen Chromosomenabschnitt 9p21 sind für dieses Tumorsyndrom verantwortlich. Ziel dieser Arbeit war daher, eine 1999 entdeckte alternative Splicevariante des CDKN2A-Genlocus, die ausschließlich in humanen Pankreaszellen exprimiert wird, einerseits auf Mutationen zu untersuchen, die ursächlich für ein familiäres Pankreaskarzinom sein könnten, und andererseits weitere Mutationen zu finden, die Ursache für andere Tumorprädispositionssyndrome sein könnten. Es wurde die genomische DNA von 25 Patienten auf konstitutionelle Mutationen untersucht, die im Rahmen der Deutschen Fallsammlung für familiäres Pankreaskarzinom bereits rekrutiert wurden. Die Ergebnisse aus den Sequenzanalysen zeigten bei einem der 25 untersuchten Indexpatienten in der Gruppe des Pankreaskarzinom-Melanom-Syndroms die nonsense Mutation c.148 C&gt;T (Q50X). Die weiteren 24 untersuchten Patienten zeigten keine Mutationen in der alternativen Splicevariante p12 des CDKN2A-Gens. Bei den untersuchten Mitgliedern der hereditären Pankreassyndrom-Familien konnte in der pankreas-spezifischen Splicevariante p12 des CDKN2A-Gens keine Mutation nachgewiesen werden und damit nicht den Verdacht bestätigen, dass Mutationen in einem pankreas-spezifisch exprimierten Gen zur Entstehung von Tumoren beitragen können. Da bisher keine Screening-Untersuchungen an großen Patientengruppen durchgeführt wurden, war ein weiteres Ziel an 42 Probanden, die in keiner Weise einer der Tumordispositions-Syndrom-Gruppen angehören, eine Untersuchung auf Polymorphismen durchzuführen. Es zeigte sich bei keiner Person eine Veränderung der untersuchten Gensequenz. Die genetischen Untersuchungen des hereditären Pankreaskarzinoms werden durch die relativ niedrigen Fallzahlen beschränkt. Durch die Erforschung des Krankheitsverlaufs, der Pathomechanismen inklusive genetischen Veränderungen von Pankreaskarzinompatienten können Hochrisikopatienten in Früherkennungsprogramme aufgenommen und in frühen Tumorstadien bzw. Vorläuferstadien einer chirurgischen Therapie zugeführt werden, die derzeit die einzig potentiell kurative Maßnahme darstellt. Weiterhin wäre durch die Identifizierung von Gendefekten des Pankreaskarzinoms ein Pankreaskarzinomscreeningprogramm denkbar. Forschungsergebnisse von Vorläuferläsionen und genetischen Mechanismen einer hereditären Tumorerkrankung geben sehr oft auch Aufschluss über das sporadische Karzinom. Aus allen diesen Gründen sind auch in Zukunft weitere Untersuchungen von Pankreaskarzinompatienten und deren Angehörigen in kontrollierten Studien- und Fallsammlungen dringend notwendig

Apprentissage de la médecine de famille et de la relation médecinpatient: témoignages d'étudiants

The five university institutes/units for family medicine in Switzerland are now responsible for teaching family medicine to medical students, particularly through the introductory cleckship in primary care in the 2nd year. During four half-days, the students attend the office of a family doctor and discover the characteristics of family medicine according to the definition of the World Association of Family Doctors (WONCA). This article shows how these training sessions are a profound and enriching learning experience for students. Different skills are presented and are illustrated by extracts from the reports students write at the end of the four half-days