Disease heterogeneity of adult diabetes based on routine clinical parameters at diagnosis: Results from the German/Austrian DPV registry.

AIMS To cluster adults with diabetes using parameters from real-world clinical care at manifestation. MATERIALS AND METHODS We applied hierarchical clustering using Ward's method to 56,869 adults documented in the Prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, BMI, HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidemia/hyperuricemia), and beta-cell antibody status. Time until use of oral antidiabetic drugs (OAD), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy, or neuropathy were assessed using Kaplan Meier analysis and Cox regression models. RESULTS We identified eight clusters: Four clusters comprised early diabetes onset (median age between 40 and 50 years), but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and relatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. CONCLUSIONS Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available parameters in clinical practice using an automated clustering algorithm which allows both continuous and binary variables. This article is protected by copyright. All rights reserved

PPAR Gamma Activators: Off-Target Against Glioma Cell Migration and Brain Invasion

Today, there is increasing evidence that PPARγ agonists, including thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and invasiveness of glioma cells and other highly migratory tumor entities. However, the mechanism(s) by which PPARγ activators mediate their antimigratory and anti-invasive properties remains elusive. This letter gives a short review on the debate and adds to the current knowledge by applying a PPARγ inactive derivative of the TDZ troglitazone (Rezulin) which potently counteracts experimental glioma progression in a PPARγ independent manner

Best Practices and Recommendations for Crowdsourced QoE - Lessons learned from the Qualinet Task Force Crowdsourcing

Crowdsourcing is a popular approach that outsources tasks via the Internet to a large number of users. Commercial crowdsourcing platforms provide a global pool of users employed for performing short and simple online tasks. For quality assessment of multimedia services and applications, crowdsourcing enables new possibilities by moving the subjective test into the crowd resulting in larger diversity of the test subjects, faster turnover of test campaigns, and reduced costs due to low reimbursement costs of the participants. Further, crowdsourcing allows easily addressing additional features like real-life environments. This white paper summarizes the recommendations and best practices for crowdsourced quality assessment of multimedia applications from the Qualinet Task Force on “Crowdsourcing”. The European Network on Quality of Experience in Multimedia Systems and Services Qualinet (COST Action IC 1003, see www.qualinet.eu) established this task force in 2012 which has more than 30 members. The recommendation paper resulted from the experience in designing, implementing, and conducting crowdsourcing experiments as well as the analysis of the crowdsourced user ratings and context data

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

Influence of the sulphate carrier on a portland cement/calcium aluminate cement system

Mischsysteme aus Weißzement (WZ) und Calciumaluminatzement (CAZ) gehören zu den sogenannten Schnellzementen, welche nach dem Anrühren mit Wasser innerhalb kurzer Zeit abbinden. Einen wesentlichen Einfluss auf das Abbindeverhalten dieser Zemente hat der im WZ enthaltene Sulfatträger. Weißzemente enthalten in der Regel mindestens zwei Arten von Sulfatträgern, deren Verhältnis von Zement zu Zement variiert. Die Rolle des Sulfatträgers im Weißzement wurde von vielen Autoren untersucht und beschrieben. Der Einfluss des Sulfatträgers auf die Hydratation von WZ/CAZ-Mischsystemen ist aber noch wenig erforscht. Die Herstellung und Charakterisierung von Sulfatträgern mit definierter Zusammensetzung bildete den Ausgangspunkt der vorliegenden Untersuchung. Um die Wirkungsweise von verschiedenen Sulfatträgern im WZ/CAZ-System zu studieren wurde Gips bei verschiedenen Temperaturen dehydriert und röntgenographisch charakterisiert. Oberflächenanalysen nach BET-Methode und Lasergranulometrie wurden vollzogen. Neben einer Charakterisierung der physikalischen und chemischen Eigenschaften der verwendeten Zemente war vor allem der Aufbau einer funktionierenden Verfeinerungsroutine für röntgenographische in-situ Untersuchungen von WZ/CAZ-Systemen Inhalt der Arbeit. Daten aus den kinetischen Untersuchungen am Wärmeflusskalorimeter, aus der Porenwasseranalyse, sowie aus rheologischen Untersuchungen ermöglichten eine umfassende Analyse der Hydratationsmechanismen. Die Hydratation in WZ/CAZ-Systemen zeigt eine starke Abhängigkeit von der Art und Menge des eingesetzten Sulfatträgers. Abhängig von der Menge an gut löslichem Sulfatträger sind die Calciumaluminathydratation und die Calicumsilikathydratation beeinflusst. Ein Zementsystem mit einer ausreichender Menge von früh verfügbarem Sulfatträger bedingt eine länger andauernde Ettringitbildung, das Ausbleiben von Monophasenbildung und einen schnelleren Verbrauch des Sulfatträgers. Die Passivierung des C3A ist beendet, sobald sich ein Großteil des im Zement vorhandenen Sulfatträgers aufgelöst hat. Wenn die C3A-Reaktion fortschreitet kommt es zur Ausbildung eines Halbkarbonats. Je mehr Sulfat im System verfügbar ist, desto höher ist die Lösungsrate des Alit. Ab einer bestimmten Sulfatzumischung zu bestehenden WZ/CAZ-Systemen kann somit die Silikatreaktion deutlich beschleunigt werden.Cements consisting of White Cement (WC) and Calcium Aluminate Cement (CAC) belong to the group of rapid hardening cement systems.The sulfate carrier of the WC has a major impact on the hydration of the cement systems. Commercial white cements are Portland cements and contain at least two different sulfate carriers, most commonly Bassanite and Anhydrite II. The role of the sulfate carrier in pure white cement systems was researched by many authors. Never-theless, there is only little literature about the influence of the sulfate carrier on cement mixtures such as the WC/CAC cement system. The synthesis and characterization of sulfate carriers with predefined composition was the first step in this investigation. In order to study the mode of action of the sulfate carriers in a WC/CAC system, pure gypsum was dehydrated at different temperatures and classified by XRD-methods. The specific surface area was determined with BET-methods and the particle size distribution was examined by using laser granulometry. The cements were investigated and their physical and chemical properties were evaluated. To this end it was necessary to develop a proper refinement routine with the Rietveld method for in-situ XRD investigations of the hydrating cement pastes. Results from kinetic investigations from heat flow calorimetry were combined with the results from pore water analysis, XRD and rheological investigations. Consequently, the hydration mechanisms could be described and analyzed. The hydration of WC/CAC systems is connected to the nature and amount of the sulfate carrier present. This has an impact on both the calcium-aluminate-hydration and the calcium-silicate-hydration. It has equally an impact on rheological behavior of the cement pastes. A cement system with a certain amount of available sulfate carrier at the beginning of the hydration process leads to a higher formation rate of ettringite, a hindered formation of monophases and an accelerated dissolution of the sulfate carrier in the cement system. C3A is passivated after the stirring process and reactivated after the majority of the sulfate carrier has dissolved. After sulfate consumption the formation of hemicarbonate starts. The more soluble sulfate carrier is available in the system, the more alite is dissolved within the first 22 hours of hydration. The silicate reaction is strongly accelerated with the addition of a certain amount of the highly soluble sulfate carrier to an existing WC/CAC system