Modeling age-specific incidence of colon cancer via niche competition

Cancer development is a multistep process often starting with a single cell in which a number of epigenetic and genetic alterations have accumulated thus transforming it into a tumor cell. The progeny of such a single benign tumor cell expands in the tissue and can at some point progress to malignant tumor cells until a detectable tumor is formed. The dynamics from the early phase of a single cell to a detectable tumor with billions of tumor cells are complex and still not fully resolved, not even for the well-known prototype of multistage carcinogenesis, the adenoma-adenocarcinoma sequence of colorectal cancer. Mathematical models of such carcinogenesis are frequently tested and calibrated based on reported age-specific incidence rates of cancer, but they usually require calibration of four or more parameters due to the wide range of processes these models aim to reflect. We present a cell-based model, which focuses on the competition between wild-type and tumor cells in colonic crypts, with which we are able reproduce epidemiological incidence rates of colon cancer. Additionally, the fraction of cancerous tumors with precancerous lesions predicted by the model agree with clinical estimates. The correspondence between model and reported data suggests that the fate of tumor development is majorly determined by the early phase of tumor growth and progression long before a tumor becomes detectable. Due to the focus on the early phase of tumor development, the model has only a single fit parameter, the time scale set by an effective replacement rate of stem cells in the crypt. We find this effective rate to be considerable smaller than the actual replacement rate, which implies that the time scale is limited by the processes succeeding clonal conversion of crypts.Comment: 28 pages, 13 figure

Phonembewusstheit von angehenden Grundschullehrkräften: Wie gut sind sie auf den schriftsprachlichen Anfangsunterricht vorbereitet?

Die eigene Phonembewusstheit ist ein wichtiger Teil der diagnostischen Kompetenz von Grundschullehrkräften. International ist die Phonembewusstheit von Lehrkräften bereits umfassend untersucht, national besteht dazu noch ein Forschungsdesiderat. Deswegen wurde ein standardisiertes Testverfahren zur Erfassung der Phonembewusstheit entwickelt und bei N = 271 Grundschullehramtsstudierenden des höheren Fachsemesters in Baden-Württemberg und Bayern eingesetzt. Die explizite Phonembewusstheit der Studierenden ist mit 41 % korrekt gelöster Items eher gering. Hauptverantwortlich sind dafür orthografische Interferenzeffekte. Insgesamt überschätzen 73 % ihre Leistung, wobei der Effekt umso stärker auftritt, je geringer die Testleistung ist. Die praktischen Implikationen werden diskutiert

Learning support with digital teaching materials: Interdisciplinary findings and developmental perspectives

Digitalen Medien wird grosses Potenzial für die Lernunterstützung beigemessen, das bislang oft nicht ausgeschöpft wird. Dieser Beitrag gibt einen Einblick in den Forschungsstand zu differenziellen Effekten der Mediengestaltung als Orientierungs- und Entscheidungshilfe zur Auswahl bzw. zur Entwicklung lernförderlicher digitaler Unterrichtsmaterialien. Es werden spezifische Aspekte der Gestaltung von multimedialen, hypermedialen und ludischen Arrangements hinsichtlich des möglichen Einflusses auf die kognitiven Verarbeitungsprozesse beschrieben, Entwicklungsperspektiven aus dem Bereich der Intelligenten Tutoriellen Systeme aufgezeigt und jeweils empirische Befunde dazu berichtet. Dazu werden nach der Kognitiven Theorie des Multimedialen Lernens (1) inhaltsbedingte, (2) sachfremde und (3) lernrelevante kognitive Prozesse unterschieden. Es zeigt sich mit Blick auf die Lernvoraussetzungen, den Lerninhalt und das Lernziel ein komplexes Bedingungsgefüge, bei dem durch gezielte Modifikationen am digitalen Medium das Lernen optimiert werden kann.Digital media is supposed to have great potential for learning support, which has not been fully exploited so far. This article provides an insight into the current state of research on the differential effects of media design: We describe specific aspects of design in multimedia, hypermedia and educational game-based arrangements and report possible influence on the cognitive processing and learning outcomes underpinned by results of empirical research. Additionally, we describe Intelligent Tutoring Systems as a means of optimizing learning processes in these different types of digital media design in the classroom. For this purpose, according to the Cognitive Theory of Multimedia Learning, we differentiate between (1) extraneous, (2) essential and (3) generative cognitive processes. With regard to the prerequisites for learning, the learning content and the learning objective, we show a complex set of conditions, in which learning can be optimized through targeted modifications to the digital medium

Lernunterstützung mit digitalen Medien in der Grundschule: Theorie und Empirie zur Wirkweise zentraler Funktionen und Gestaltungsmerkmale

Digitale Medien haben großes Potenzial für die Lernunterstützung, das bislang nicht ausgeschöpft wird. Dieser Beitrag gibt einen Einblick zum Forschungsstand: Ausgehend vom Substitution Augmentation Modification Redefinition-Modell werden Funktionen und Gestaltungsmerkmale wie Bild-Text-Kombinationen, Hypermedia und Gamification hinsichtlich der möglichen Wirkung auf die kognitiven Verarbeitungsprozesse beschrieben und empirische Befunde dazu berichtet. Hierzu werden nach der Kognitiven Theorie des multimedialen Lernens (1) inhaltsbedingte, (2) sachfremde und (3) lernrelevante kognitive Prozesse unterschieden. Es zeigt sich mit Blick auf die Lernvoraussetzungen, den Lerninhalt und das Lernziel ein komplexes Bedingungsgefüge, das bei der Nutzung, Entwicklungen und Erforschung lernförderlicher digitaler Medien berücksichtigt werden sollte

Special Issue on the Economics of Security and Privacy: Guest Editors’ Introduction

This editorial introduces the special issue on the economics of security and privacy. The global adoption of the Internet has transformed economies and societies. However, Internet technologies have also resulted in heightened societal concerns about information security and privacy. Insufficient safeguards—actual or perceived—have become a barrier to certain economic activity, and a source of downside risk to growth and sustainability, with possible systemic impact. Scholars have long realized that choices pertaining to security and privacy affect the world in ways that are not captured within the narrow modeling of engineering systems. In essence, these choices are strategic decisions. Thus, the analysis that is performed should incorporate the models and methods developed in economics and, where applicable, in the behavioral sciences

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value<0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP

An assessment of Arctic Ocean freshwater content changes from the 1990s to the 2006-2008 period

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 58 (2011): 173-185, doi:10.1016/j.dsr.2010.12.002.Unprecedented summer-season sampling of the Arctic Ocean during the period 2006−2008 makes possible a quasi-synoptic estimate of liquid freshwater (LFW) inventories in the Arctic Ocean basins. In comparison to observations from 1992−1999, LFW content relative to a salinity of 35 in the layer from the surface to the 34 isohaline increased by 8400 ± 2000 km3 in the Arctic Ocean (water depth greater than 500m). This is close to the annual export of freshwater (liquid and solid) from the Arctic Ocean reported in the literature. Observations and a model simulation show regional variations in LFW were both due to changes in the depth of the lower halocline, often forced by regional wind-induced Ekman pumping, and a mean freshening of the water column above this depth, associated with an increased net sea ice melt and advection of increased amounts of river water from the Siberian shelves. Over the whole Arctic Ocean, changes in the observed mean salinity above the 34 isohaline dominated estimated changes in LFW content; the contribution to LFW change by bounding isohaline depth changes was less than a quarter of the salinity contribution, and non-linear effects due to both factors were negligible.This work was supported by the Co-Operative Project “The North Atlantic as Part of the Earth System: From System Comprehension to Analysis of Regional Impacts” funded by the German Federal Ministry for Education and Research (BMBF) and by the European Union Sixth Framework Programme project DAMOCLES (Developing Arctic Modelling and Observing Capabilities for Long-term Environment Studies), contract number 018509GOCE

Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays

Bose-Einstein Correlations (BEC) of three identical charged pions were studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP. The genuine three-pion correlations, corrected for the Coulomb effect, were separated from the known two-pion correlations by a new subtraction procedure. A significant genuine three-pion BEC enhancement near threshold was observed having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029 (syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041 (syst.). The Coulomb correction was found to increase the \lambda_3 value by \~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of 0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the three-pion sample purity. A relation between the two-pion and the three-pion source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.

Measurement of the Production Rate of Charm Quark Pairs from Gluons in Hadronic Z0Z^{0} Decays

The rate of secondary charm-quark-pair production has been measured in 4.4 million hadronic Z0 decays collected by OPAL. By selecting events with three jets and tagging charmed hadrons in the gluon jet candidate using leptons and charged D* mesons, the average number of secondary charm-quark pairs per hadronic event is found to be (3.20+-0.21+-0.38)x10-2