72 research outputs found
Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient
Background: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX.
Methods: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients.
Results: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients.
Conclusion: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient’s performance status and comorbidities
Imaging features of fibrolamellar hepatocellular carcinoma in gadoxetic acid-enhanced MRI
Background: Fibrolamellar hepatocellular carcinoma (FLC) is a rare malignancy occurring in young patients without cirrhosis. Objectives of our study were to analyze contrast material uptake in hepatobiliary phase imaging (HBP) in gadoxetic acid-enhanced liver MRI in patients with FLC and to characterize imaging features in sequence techniques other than HBP.
Methods: In this retrospective study on histology-proven FLC, contrast material uptake in HBP was quantitatively assessed by calculating the corrected FLC enhancement index (CEI) using mean signal intensities of FLC and lumbar muscle on pre-contrast imaging and HBP, respectively. Moreover, enhancement patterns in dynamic contrast-enhanced MRI and relative signal intensities compared with background liver parenchyma were determined by two radiologists in consensus for HBP, diffusion-weighted imaging using high b-values (DWI), and T2 and T1 weighted pre-contrast imaging.
Results: In 6 of 13 patients with FLC gadoxetic acid-enhanced liver MRI was available. The CEI suggested presence of HBP contrast material uptake in all FLCs. A mean CEI of 1.35 indicated FLC signal increase of 35% in HBP compared with pre-contrast imaging. All FLCs were hypointense in HBP compared with background liver parenchyma. Three of 6 FLCs had arterial hyperenhancement and venous wash-out. In DWI and T2 weighted imaging, 5 of 6 FLCs were hyperintense. In T1 weighted imaging, 5 of 6 FLCs were hypointense.
Conclusion: Hepatobiliary uptake of gadoxetic acid was quantitatively measurable in all FLCs investigated in our study. The observation of hypointensity of FLCs in HBP compared with background liver parenchyma emphasizes the role of gadoxetic acid-enhanced liver MRI for non-invasive diagnosis of FLC and its importance in the diagnostic work-up of indeterminate liver lesions
A Plan for a Long-Term, Automated, Broadband Seismic Monitoring Network on the Global Seafloor
Establishing an extensive and highly durable, long‐term, seafloor network of autonomous broadband seismic stations to complement the land‐based Global Seismographic Network has been a goal of seismologists for decades. Seismic signals, chiefly the vibrations from earthquakes but also signals generated by storms and other environmental processes, have been processed from land‐based seismic stations to build intriguing but incomplete images of the Earth’s interior. Seismologists have mapped structures such as tectonic plates and other crustal remnants sinking deep into the mantle to obtain information on their chemical composition and physical state; but resolution of these structures from land stations is not globally uniform. Because the global surface is two‐thirds ocean, increasing the number of seismic stations located in the oceans is critical for better resolution of the Earth’s interior and tectonic structures. A recommendation for a long‐term seafloor seismic station pilot experiment is presented here. The overarching instrumentation goal of a pilot experiment is performance that will lead to the installation of a large number of long‐term autonomous ocean‐bottom seismic stations. The payoff of a network of stations separated from one another by a few hundred kilometers under the global oceans would be greatly refined resolution of the Earth’s interior at all depths. A second prime result would be enriched understanding of large‐earthquake rupture processes in both oceanic and continental plates. The experiment would take advantage of newly available technologies such as robotic wave gliders that put an affordable autonomous prototype within reach. These technologies would allow data to be relayed to satellites from seismometers that are deployed on the seafloor with long‐lasting, rechargeable batteries. Two regions are presented as promising arenas for such a prototype seafloor seismic station. One site is the central North Atlantic Ocean, and the other high‐interest locale is the central South Pacific Ocean
A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial
BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18 )F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. METHODS/DESIGN: The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18 )F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18 )F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT200811021020; EudraCT 20090132792
Live well, die well – an international cohort study on experiences, concerns and preferences of patients in the last phase of life: the research protocol of the iLIVE study
Introduction Adequately addressing the needs of patients at the end of life and their relatives is pivotal in preventing unnecessary suffering and optimising their quality of life. The purpose of the iLIVE study is to contribute to high-quality personalised care at the end of life in different countries and cultures, by investigating the experiences, concerns, preferences and use of care of terminally ill patients and their families. Methods and analysis The iLIVE study is an international cohort study in which patients with an estimated life expectancy of 6 months or less are followed up until they die. In total, 2200 patients will be included in 11 countries, that is, 200 per country. In addition, one relative per patient is invited to participate. All participants will be asked to fill in a questionnaire, at baseline and after 4 weeks. If a patient dies within 6 months of follow-up, the relative will be asked to fill in a post-bereavement questionnaire. Healthcare use in the last week of life will be evaluated as well; healthcare staff who attended the patient will be asked to fill in a brief questionnaire to evaluate the care that was provided. Qualitative interviews will be conducted with patients, relatives and healthcare professionals in all countries to gain more in-depth insights. Ethics and dissemination The cohort study has been approved by ethics committees and the institutional review boards (IRBs) of participating institutes in all countries. Results will be disseminated through the project website, publications in scientific journals and at conferences. Within the project, there will be a working group focusing on enhancing the engagement of the community at large with the reality of death and dying. Trial registration number NCT04271085
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
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions
Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.
Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD
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