20 research outputs found

    Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance

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    The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications

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

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    Erschienen bei: universi - UniversitĂ€tsverlag 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 fĂŒr 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? EntscheidungsunterstĂŒtzung 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 fĂŒr 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 fĂŒr 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 StressprĂ€vention – 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 KontinuitĂ€tsmanagement 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 KommunikationsfĂ€den 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 EntscheidungsunterstĂŒtzungssystem zur ökonomischen Bewertung von Mieterstrom auf Basis der Clusteranalyse Discovering Blockchain for Sustainable Product-Service Systems to enhance the Circular Economy Digitale RĂŒckverfolgbarkeit 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: GeschĂ€ftsmodelle 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 fĂŒr 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 fĂŒr Ă€ltere 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 kĂŒnftiger Mitarbeiter im Bereich Business Analytics Digitaler Konsum: Herausforderungen und Chancen der Verbraucherinformati

    Therapie und PrÀvention von opportunistischen Infektionen

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    Incidence as well as morbidity and mortality of opportunistic infections (OI) have declined remarkably since the availability of antiretroviral treatment (ART). Nearly half of all persons infected with HIV however do not know their HIV-status, and the diagnosis of an OI may be the first manifestation of their HIV infection. Therefore, knowledge of the presentation of OIs as well as their management should remain an essential part of clinicians' expertise. After starting ART the immune system will improve; in this context OI may be unmasked or the clinical presentation of known OI may worsen. Before starting ART therefore, it is essential to rule out any asymptomatic or latent OI. For the same reason, in the case of a known OI, the start of ART must often be deferred for some weeks after the start of OI treatment. Treatment of OIs is complex and often results in a large pill-burden for the patient with the potential for multiple drug-drug-interactions, particularly once ART has to be started. Many of the OI treatments are also associated with frequent drug side-effects and allergies. OIs can be prevented with specific antimicrobial agents once the CD4 have decreased below a defined threshold. However, the main prevention of OI is the timely recognition of HIV infection and an early start of ART before complications of OI appear.Die Inzidenz sowie auch die MorbiditĂ€t und MortalitĂ€t opportunistischer Infektionen (OI) ist seit der EinfĂŒhrung der kombinierten antiretroviralen Therapie (ART) in den letzten 15 Jahren deutlich gesunken. Weiterhin treten OI aber auf, da 30 – 50 % der HIV-Infizierten ihren HIV-Status nicht kennen, und bei vielen von ihnen eine OI die erste Manifestation der HIV-Erkrankung ist. Bei Erstarken des Immunsystems nach Beginn der ART kann eine OI demaskiert oder in ihrer AusprĂ€gung verschlimmert werden. Entsprechend sollten gezielte AbklĂ€rungen vor ART-Beginn getĂ€tigt werde. In der Regel muss aus demselben Grunde vor Beginn der ART der Behandlungsbeginn der OI abgewartet werden. Gewisse OI lassen sich durch gezielte prĂ€ventive Maßnahmen verhindern, sobald ein CD4-Schwellenwert unterschritten wird. Die wichtigste PrĂ€vention von OI ist aber das frĂŒhzeitige Erkennen einer HIV-Erkrankung und ein entsprechend frĂŒhzeitiger Beginn der ART

    [Vaccinations for immunocompromised hosts – focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia]

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    Personen mit einer HIV-Infektion, nach einer Organ- oder einer hĂ€matologischen Stammzelltransplantation oder mit einer funktionalen oder anatomischen Asplenie sind gegenĂŒber Infektionen anfĂ€lliger. Sie haben eine grössere Komplikationsrate und ein höheres Risiko fĂŒr einen chronifizierten Verlauf. Impfungen wĂ€ren eine ideale primĂ€re PrĂ€ventionsmassnahme, sind aber – durch dieselben Mechanismen des Immundefektes der zu schwereren KrankheitsverlĂ€ufen fĂŒhrt – in ihrer Wirksamkeit vermindert. Die Impfungen sollen daher, wenn immer möglich, vor Beginn der Immunsuppression oder spĂ€ter zum Zeitpunkt der minimalsten Immunsuppression, durchgefĂŒhrt werden. Trotzdem bleibt der Benefit von Impfungen bei immunsupprimierten Personen unbestritten, sofern die Indikationsstellung bezĂŒglich Zeitpunkt und Dosierung (Dosismenge und -anzahl), die zu einem maximalen Ansprechen fĂŒhrt, beachtet wird. Lebendimpfungen sind wegen der Gefahr der unkontrollierten Vermehrung der Impfviren bei schwerer Immunsuppression kontraindiziert. Die Serologie soll unspezifischer gemessen werden, da schwer immunsupprimierte Personen im Falle einer relevanten Exposition durch passive Immunisierung mittels spezifischer oder unspezifischer intravenöser Immunglobuline geschĂŒtzt werden können.Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts – or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters – this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented

    Travellers returning ill from the tropics – a descriptive retrospective study

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    nternational travel continues to increase in frequency. Health care providers need a wide understanding of the spectrum of travel related diseases and their management. This retrospective study analyses the demographic and clinical data of 360 travellers returning from the tropics presenting to an outpatient clinic at a tertiary hospital between 2003 - 2007. The aim of this study was to analyse the frequency of presenting symptoms and diseases in ill returning travellers and to correlate them to the areas visited and the duration and purpose of travel. The main symptoms during travel were diarrhoea (n = 200, 56 %) and fever (n = 124, 34 %). Travellers not visiting friends and relatives but with close contact to the local population were at more than two-fold increased risk of diarrhoea (Odds Ratio [OR] 2.5; 95 % confidence interval [CI] 1.1-6.0, p = 0.03) and fever (OR 2.4; 95 % CI 1.1-5.3; p = 0.02) compared to tourist travellers. Travellers visiting friends and relatives (VFR) were not at increased risk for diarrhoea (OR 0.6; 95 % CI 0.3-1.3; p = 0.17), or fever (OR 1.5; 95 % CI 0.7-3.4; p = 0.28). Thirty-two percent of all travellers (n = 115) were diagnosed with a specific pathogen. Malaria (6 %), giardiasis (6 %) and amebiasis (4 %) were the most frequently detected pathogens. The odds of malaria as a cause of the presenting illness was lower among travellers reporting pre-travel advice. Specific antimicrobial treatment was required in around one third of the patients

    Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study

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    BACKGROUND The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir 350 (P 350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited

    FTLD‐TDP assemblies seed neoaggregates with subtype‐specific features via a prion‐like cascade

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    Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 follows a prion-like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD-TDP-A and FTLD-TDP-C aggregates. Upon inoculation of patient-derived aggregates in cells, FTLD-TDP-A seeds amplify in a template-dependent fashion, triggering neoaggregation more efficiently than those extracted from FTLD-TDP-C patients, correlating with the respective disease progression rates. Neoaggregates are sequentially phosphorylated with N-to-C directionality and with subtype-specific timelines. The resulting FTLD-TDP-A neoaggregates are large and contain densely packed fibrils, reminiscent of the pure compacted fibrils present within cytoplasmic inclusions in postmortem brains. In contrast, FTLD-TDP-C dystrophic neurites show less dense fibrils mixed with cellular components, and their respective neoaggregates are small, amorphous protein accumulations. These cellular seeding models replicate aspects of the patient pathological diversity and will be a useful tool in the quest for subtype-specific therapeutics

    Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013

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    Late presentation (LP) for HIV care across Europe remains a significant issue. We provide a cross-European update from 34 countries on the prevalence and risk factors of LP for 2010-2013. People aged >= 16 presenting for HIV care (earliest of HIV-diagnosis, first clinic visit or cohort enrolment) after 1 January 2010 with available CD4 count within six months of presentation were included. LP was defined as presentation with a CD4 count < 350/mm(3) or an AIDS defining event (at any CD4), in the six months following HIV diagnosis. Logistic regression investigated changes in LP over time. A total of 30,454 people were included. The median CD4 count at presentation was 368/mm(3) (interquartile range (IQR) 193-555/mm(3)), with no change over time (p = 0.70). In 2010, 4,775/10,766 (47.5%) were LP whereas in 2013, 1,642/3,375 (48.7%) were LP (p = 0.63). LP was most common in central Europe (4,791/9,625, 49.8%), followed by northern (5,704/11,692; 48.8%), southern (3,550/7,760; 45.8%) and eastern Europe (541/1,377; 38.3%; p < 0.0001). There was a significant increase in LP in male and female people who inject drugs (PWID) (adjusted odds ratio (aOR)/year later 1.16; 95% confidence interval (CI): 1.02-1.32), and a significant decline in LP in northern Europe (aOR/year later 0.89; 95% CI: 0.85-0.94). Further improvements in effective HIV testing strategies, with a focus on vulnerable groups, are required across the European continent
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