Stylised Facts and the Contribution of Simulation to the Economic Analysis of Budgeting

The application of computer simulation as a research method raises two important questions: (1) Does simulation really offer added value over established methods? (2) How can the danger of arbitrariness caused by the extended modelling possibilities be minimised? We present the concept of stylised facts as a methodological basis for approaching these questions systematically. In particular, stylised facts provide a point of reference for a comparative analysis of models intended to explain an observable phenomenon. This is shown with reference to a recent discussion in the "economic analysis of accounting" literature where established methods, i.e. game theory, as well as computer simulations are used: the susceptibility of the "Groves mechanism" to collusion. Initially, we identify six stylised facts on the stability of collusion in empirical studies. These facts serve as a basis for the subsequent comparison of four theoretical models with reference to the above questions: (1) We find that the simulation models of Krapp and Deliano offer added value in comparison to the game theoretical models. They can be related to more stylised facts, achieve a better reproduction and exhibit far greater potential for incorporating yet unaddressed stylised facts. (2) Considered in the light of the stylised facts to which the models can be related, Deliano's simulation model exhibits considerable arbitrariness in model design and lacks information on its robustness. In contrast, Krapp demonstrates that this problem is not inherent to the method. His simulation model methodically extends its game theoretical predecessors, leaving little room for arbitrary model design or questionable parameter calibration. All in all, the stylisedfactsconcept proved to be very useful in dealing with the questions simulation researchers are confronted with. Moreover, a "research landscape" emerges from the derived stylised facts pinpointing issues yet to be addressed.Computer Simulation, Stylised Facts, Methodology, Groves Mechanism, Collusion, Game Theory

Shrinking droplets in electrospray ionization and their influence on chemical equilibria

We investigated how chemical equilibria are affected by the electrospray process, using simultaneous in situ measurements by laser-induced fluorescence (LIF) and phase Doppler anemometry (PDA). The motivation for this study was the increasing number of publications in which electrospray ionization mass spectrometry is used for binding constant determination. The PDA was used to monitor droplet size and velocity, whereas LIF was used to monitor fluorescent analytes within the electrospray droplets. Using acetonitrile as solvent, we found an average initial droplet diameter of 10 µm in the electrospray. The PDA allowed us to follow the evolution of these droplets down to a size of 1 µm. Rhodamine B-sulfonylchloride was used as a fluorescent analyte within the electrospray. By spatially resolved LIF it was possible to probe the dimerization equilibrium of this dye. Measurements at different spray positions showed no influence of the decreasing droplet size on the monomer-dimer equilibrium. However, with the fluorescent dye pair DCM and oxazine 1 it was shown that a concentration increase does occur within electrosprayed droplets, using fluorescence resonance energy transfer as a probe for the average pair distanc

Investigations on the Usefulness of CEACAMs as Potential Imaging Targets for Molecular Imaging Purposes

Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well. In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.Germany. Bundesministerium für Bildung und Forschung (TOMCAT, grant number 01EZ0824

Markers of cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD: An observational study

In dialysis patients, cholesterol-lowering therapy with statins is less effective than in other high-risk patients. This may be explained by a shift from cholesterol synthesis toward cholesterol absorption. In line, markers of cholesterol absorption-such as campesterol-better predict atherosclerotic cardiovascular events than markers of cholesterol synthesis-such as lathosterol-in dialysis patients. To test the association between markers of cholesterol absorption such as campesterol-and markers of cholesterol synthesis-such as lathosterol-against cardiovascular events in non-dialysis CKD patients. Altogether 251 patients those not on lipid-lowering agents were followed annually for the composite endpoint atherosclerotic cardiovascular disease (ASCVD) and all-cause death. During follow-up of 5.2 ± 2.1 years, 61 participants reached the primary endpoint atherosclerotic cardiovascular disease/all-cause death [ASCVD/D], 47 participants suffered from ASCVD, and 46 participants died. In univariate Cox regression analysis, campesterol/lathosterol ratio did not significantly predict ASCVD/D (HR 0.643; 0.358-1.155; 3rd vs. 1st tertile), all-cause death (HR 1.309; 0.604-2.838; 3rd vs. 1st tertile) nor ASCVD (HR 0.589; 0.311-1.118; 3rd vs. 1st tertile). We did not observe a shift from cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD. Campesterol/lathosterol ratio did not predict future ASCVD or all-cause death in non-dialysis CKD

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -11.8 ± 4.3 ml min-1·1.73 m-2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect

Stacking Polymorphism in PtSe2 Drastically Affects Its Electromechanical Properties

PtSe2 is one of the most promising materials for the next generation of piezoresistive sensors. However, the large-scale synthesis of homogeneous thin films with reproducible electromechanical properties is challenging due to polycrystallinity. It is shown that stacking phases other than the 1T phase become thermodynamically available at elevated temperatures that are common during synthesis. It is shown that these phases can make up a significant fraction in a polycrystalline thin film and discuss methods to characterize them, including their Seebeck coefficients. Lastly, their gauge factors, which vary strongly and heavily impact the performance of a nanoelectromechanical device are estimated

Herausforderungen bei der Schätzung von Trends in Schulleistungsstudien. Eine Skalierung der deutschen PISA-Daten

Internationale Schulleistungsstudien wie das Programme for International Student Assessment (PISA) dienen den teilnehmenden Ländern zur Feststellung der Leistungsfähigkeit ihrer Schulsysteme. In PISA wird die Zielpopulation (15-jährige Schülerinnen und Schüler) alle 3 Jahre getestet. Von besonderer Bedeutung sind dabei die Trendinformationen, die für die Zielpopulation ausweisen, ob sich ihre Leistungen gegenüber denen aus früheren Erhebungen verändert haben. Um solche Trends valide interpretieren zu können, sollten die PISA-Erhebungen unter möglichst vergleichbaren Bedingungen durchgeführt und die verwendeten statistischen Verfahren vergleichbar bleiben. In PISA 2015 wurde erstmalig computerbasiert getestet; zuvor mittels Papier-und-Bleistift-Tests. Es wurde das Skalierungsmodell verändert und in den Naturwissenschaften wurden neue Aufgabenformate eingesetzt. Im vorliegenden Beitrag gehen wir anhand der nationalen PISA-Stichproben von 2000 bis 2015 der Frage nach, inwiefern der Wechsel des Testmodus und der Wechsel des Skalierungsmodells die Interpretation der Trendschätzungen beeinflussen. Die Analysen belegen, dass die Veränderung von Papier-und-Bleistift-Tests auf Computertestung die Trendschätzung für Deutschland verzerrt haben könnte. (DIPF/Orig.)International large-scale assessments, for instance, the Programme for International Student Assessment (PISA), are conducted to provide information on the effectiveness of educational systems. In PISA, the target population of 15-year-old students is assessed every 3 years. Trends show whether competencies have changed for the target population between PISA cycles. To ensure valid trend information, it is necessary to keep the test conditions and statistical methods in all PISA cycles as constant as possible. In PISA 2015, however, several changes were established; the test model changed from paper pencil to computer tests, scaling methods were changed, and new types of tasks were used in science. In this article, we investigate the effects of these changes on trend estimation in PISA using German data from all PISA cycles (2000 - 2015). Findings suggest that the change from paper pencil to computer tests could have biased the trend estimation. (DIPF/Orig.

Interaction modulation through arrays of clustered methyl-arginine protein modifications

Systematic analysis of human arginine methylation identifies two distinct signaling modes;either isolated modifications akin to canonical post-translational modification regulation, or clustered arrays within disordered protein sequence. Hundreds of proteins contain these methyl-arginine arrays and are more prone to accumulate mutations and more tightly expression-regulated than dispersed methylation targets. Arginines within an array in the highly methylated RNA-binding protein synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) were experimentally shown to function in concert, providing a tunable protein interaction interface. Quantitative immunoprecipitation assays defined two distinct cumulative binding mechanisms operating across 18 proximal arginine-glycine (RG) motifs in SYNCRIP. Functional binding to the methyltransferase PRMT1 was promoted by continual arginine stretches, whereas interaction with the methyl-binding protein SMN1 was arginine content-dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive modifiable amino acid arrays in low structural complexity regions can provide regulatory platforms, with SYNCRIP as an extreme example how arginine methylation leverages these disordered sequences to mediate cellular interactions

BKV, CMV, and EBV Interactions and their Effect on Graft Function One Year Post-Renal Transplantation: Results from a Large Multi-Centre Study

Background BK virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are common after kidney transplantation and associated with increased morbidity and mortality. Although CMV might be a risk factor for BKV and EBV, the effects of combined reactivations remain unknown. The purpose of this study is to ascertain the interaction and effects on graft function of these reactivations. Methods 3715 serum samples from 540 kidney transplant recipients were analysed for viral load by qPCR. Measurements were performed throughout eight visits during the first post-transplantation year. Clinical characteristics, including graft function (GFR), were collected in parallel. Findings BKV had the highest prevalence and viral loads. BKV or CMV viral loads over 10,000 copies·mL−1 led to significant GFR impairment. 57 patients had BKV-CMV combined reactivation, both reactivations were significantly associated (p = 0.005). Combined reactivation was associated with a significant GFR reduction one year post-transplantation of 11.7 mL·min−1·1.73 m−2 (p = 0.02) at relatively low thresholds (BKV > 1000 and CMV > 4000 copies·mL−1). For EBV, a significant association was found with CMV reactivation (p = 0.02), but no GFR reduction was found. Long cold ischaemia times were a further risk factor for high CMV load. Interpretation BKV-CMV combined reactivation has a deep impact on renal function one year post-transplantation and therefore most likely on long-term allograft function, even at low viral loads. Frequent viral monitoring and subsequent interventions for low BKV and/or CMV viraemia levels and/or long cold ischaemia time are recommended. Fund Investigator Initiated Trial; financial support by German Federal Ministry of Education and Research (BMBF).Peer Reviewe

Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction

The task of breast density quantification is becoming increasingly relevant due to its association with breast cancer risk. In this work, a semi-automated and a fully automated tools to assess breast density from full-field digitized mammograms are presented. The first tool is based on a supervised interactive thresholding procedure for segmenting dense from fatty tissue and is used with a twofold goal: for assessing mammographic density(MD) in a more objective and accurate way than via visual-based methods and for labeling the mammograms that are later employed to train the fully automated tool. Although most automated methods rely on supervised approaches based on a global labeling of the mammogram, the proposed method relies on pixel-level labeling, allowing better tissue classification and density measurement on a continuous scale. The fully automated method presented combines a classification scheme based on local features and thresholding operations that improve the performance of the classifier. A dataset of 655 mammograms was used to test the concordance of both approaches in measuring MD. Three expert radiologists measured MD in each of the mammograms using the semi-automated tool (DM-Scan). It was then measured by the fully automated system and the correlation between both methods was computed. The relation between MD and breast cancer was then analyzed using a case-control dataset consisting of 230 mammograms. The Intraclass Correlation Coefficient (ICC) was used to compute reliability among raters and between techniques. The results obtained showed an average ICC = 0.922 among raters when using the semi-automated tool, whilst the average correlation between the semi-automated and automated measures was ICC = 0.838. In the case-control study, the results obtained showed Odds Ratios (OR) of 1.38 and 1.50 per 10% increase in MD when using the semi-automated and fully automated approaches respectively. It can therefore be concluded that the automated and semi-automated MD assessments present a good correlation. Both the methods also found an association between MD and breast cancer risk, which warrants the proposed tools for breast cancer risk prediction and clinical decision making. A full version of the DM-Scan is freely available. (C) 2014 Elsevier Ireland Ltd. All rights reserved.This work was supported by research grants from Gent per Gent Fund (EDEMAC Project); Spain's Health Research Fund (Fondo de Investigacion Santiaria) (PI060386 & FIS PS09/00790); Spanish MICINN grants TIN2009-14205-C04-02 and Consolider-Ingenio 2010: MIPRCV (CSD2007-00018); Spanish Federation of Breast Cancer Patients (Federacion Espanola de Cancer de Mama) (FECMA 485 EPY 1170-10). The English revision of this paper was funded by the Universitat Politecnica de Valencia, Spain.Llobet Azpitarte, R.; Pollán, M.; Antón Guirao, J.; Miranda-García, J.; Casals El Busto, M.; Martinez Gomez, I.; Ruiz Perales, F.... (2014). Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction. Computer Methods and Programs in Biomedicine. 116(2):105-115. https://doi.org/10.1016/j.cmpb.2014.01.021S105115116