Casting a wider tax net: Experimental evidence from Costa Rica

The majority of firms in developing countries are informal, and encouraging them to register for taxation is challenging. We argue that non-filing of taxes among registered firms constitutes an important intermediate form of informality, which can be tackled cost-effectively. Using a randomized experiment in Costa Rica, we show that credible enforcement emails increased the tax payment rate (amount) by 3.4 p.p. (US$ 15) among previously nonfiling firms. Highlighting third-party reports of a firm’s transactions further increased compliance. The effect persisted in the medium term, and treated firms became more likely to report transactions with other firms, facilitating future tax enforcement

Surface Based Modelling of Ground Motion Areas in Lower Saxony

Systematic investigations have shown subsidence in almost 30% of the land area in Lower Saxony. It is essential to model these variations of the Earth surface especially to update the spatial reference system. Since the geodetic observations result in discrete points, it is necessary to mathematically model these measurements to have a continues surface. This enables the user to do predictions at any position. This is challenging especially because these types of measurements usually result in non-uniformly distributed data. There are different approaches to deal with this problem, here the stochastic method of Kriging and the deterministic method of Multilevel B-Splines are implemented to model ground motion. This paper investigates the ground motion of specific areas in Lower Saxony through the cooperation of Landesamt für Geoinformation und Landesvermessung Niedersachsen (LGLN) and Geodetic Institute of Hannover. For this investigation, a time series of measurements from leveling, Global Navigation Satellite System (GNSS) observations and height changes that are acquired by Persistent Scatterer Interferometry (PSI) technique are taken into consideration. Evaluation of the results show not only good performance and promising results from both the approaches, but also compatibility between the approximated surface from both of them

Comprehensive Meta-Analysis of Safety and Efficacy of Bivalirudin Versus Heparin With or Without Routine Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome

AbstractObjectivesThe aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS).BackgroundBivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear.MethodsA total of 13 randomized, controlled trials involving 24,605 patients were included.ResultsThere was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly.ConclusionsOverall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

Daten der Landesvermessung zur räumlichen Interpolation von Bodenbewegungen

Zur Bereitstellung eines einheitlichen integrierten Raumbezugs ist das Aktualitätsgebot der Festpunktfelder ein wesentliches Qualitätsmerkmal. Vorhandene Veränderungen der Erdoberfläche bewirken eine stetige Verringerung der Aktualität des amtlichen Raumbezugs, da sich die aktuell gemessenen und berechneten Koordinaten von den im Nachweis geführten Koordinaten zunehmend unterscheiden. Zur genauen Abgrenzung der Einflussbereiche von Bodenbewegungen werden daher alle verfügbaren Daten des LGLN für den Aufbau eines niedersächsischen Bodenbewegungsdienstes aufbereitet und auf Veränderungen der Lage- und Höhenkomponenten analysiert. Eine weitere wichtige Säule zum Aufbau dieses Dienstes bilden PSI-Analysen, da mit dieser Technik der Fernerkundung auch Bewegungen außerhalb der linien- und punktförmigen geodätischen Netze erfasst werden können. Die gesammelten numerischen Bewegungsinformationen werden zunächst gebietsweise zur grafischen Visualisierung unter Verwendung eines erweiterten Kriging-Ansatzes zu einem Bodenbewegungsmodell kombiniert. Auf Grundlage derart geschätzter Bewegungsmodelle können Erhaltungsmaßnahmen sowie Wiederholungsmessungen im amtlichen Bezugsrahmen bedarfsorientiert angepasst und durchgeführt werden, wodurch die Aktualität des Raumbezugs gesteigert wird. Perspektivisch können die modellierten Geschwindigkeiten auch zur Berechnung von zusätzlichen Korrekturdaten des SAPOS-Dienstes HEPS dienen. Mithilfe von bereitgestellten örtlichen und zeitlichen Transformationsparametern könnten lokale Anpassungen der Liegenschaftsvermessungen in Bodenbewegungsgebieten für den Nutzer entfallen

Regional Ground Movement Detection by Analysis and Modeling PSI Observations

Any changes to the Earth’s surface should be monitored in order to maintain and update the spatial reference system. To establish a global model of ground movements for a large area, it is important to have consistent and reliable measurements. However, in dealing with mass data, outliers may occur and robust analysis of data is indispensable. In particular, this paper will analyse Synthetic Aperture Radar (SAR) data for detecting the regional ground movements (RGM) in the area of Hanover, Germany. The relevant data sets have been provided by the Federal Institute for Geo-sciences and Natural Resources (BGR) for the period of 2014 to 2018. In this paper, we propose a data adoptive outlier detection algorithm to preprocess the observations. The algorithm is tested with different reference data sets and as a binary classifier performs with 0.99 accuracy and obtains a 0.95 F1-score in detecting the outliers. The RGMs that are observed as height velocities are mathematically modeled as a surface based on a hierarchical B-splines (HB-splines) method. For the approximated surface, a 95% confidence interval is estimated based on a bootstrapping approach. In the end, the user is enabled to predict RGM at any point and is provided with a measure of quality for the prediction

Comprehensive Meta-Analysis of Safety and Efficacy of Bivalirudin Versus Heparin With or Without Routine Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome

OBJECTIVES The aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS). BACKGROUND Bivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear. METHODS A total of 13 randomized, controlled trials involving 24,605 patients were included. RESULTS There was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (<= 24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly. CONCLUSIONS Overall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI. (C) 2015 by the American College of Cardiology Foundation

Towards a harmonized approach for food authenticity marker validation and accreditation

Recent publications in the field of food authentication have reported using analytical methods which measure changes in sample composition. These changes can be due to a variety of causes such as the presence of adulterants, different production methods, or varying geographical origins of food. While the increasing use of marker-based approaches is beneficial in combating food fraud, there is a pressing need to adopt a harmonized approach for validating these markers. In this article, we make recommendations for harmonized terminologies and general definitions related to food authenticity markers. First, we propose the terms “primary” and “secondary” markers to distinguish between direct and indirect authentication. The terms “single” and “dual” authenticity markers, and authentic “profiles” and “fingerprints” are suggested to distinguish between the number of analytical targets used. We also recommend that the terms: “threshold”, “binary”, and “interval” markers are applied depending on how they discriminate authentic from non-authentic samples. Second, we advocate for harmonization in marker discovery approaches. A summary of the main analytical techniques, published guidelines, data repositories and data analysis approaches is presented for various marker classes while also stating their applicability and limitations. Finally, we propose guidelines for the analytical community concerning marker validation. In our view, the validation of the authentication method should include the following steps: 1) applicability statement; 2) experimental design; 3) marker selection and analysis; 4) analytical method validation; 5) method release; 6) method monitoring. Implementing these approaches will represent a significant step towards establishing a wide range of fully validated and accredited methodologies that can be applied effectively in food authenticity monitoring and control programs

Comparative efficacy and safety of anticoagulant strategies for acute coronary syndromes: Comprehensive network meta-analysis of 42 randomised trials involving 117,353 patients

International guidelines differ in strengths of recommendation for anticoagulation strategies in acute coronary syndromes (ACS). We performed a comprehensive network meta-analysis (NMA) of randomised controlled trials (RCTs) to investigate the comparative efficacy and safety of parenteral anticoagulants in ACS. MEDLINE, Cochrane, EM-BASE, Google Scholar, major cardiology websites, and abstracts/presentations were searched. Six treatments were identified: 1) unfractionated heparin (UFH) + glycoprotein IIb/IIIa inhibitor (GPI) [UFH+ GPI], 2) UFH +/- GPI, 3) bivalirudin, 4) low-molecular-weight heparins (LMWHs), 5) otamixaban, and 6) fondaparinux. Prespecified out-comes (death, myocardial infarction [MI], revascularisation, major bleeding [MB], minor bleeding, and stent thrombosis [ST]) were evaluated up to 30 days. Forty-two RCTs involving 117,353 patients were included. No significant differences in mortality rates were found among strategies. Compared to UFH+GPI, bivalirudin reduced the odds of MB but increased the odds of ST and MI. LMWHs vs bivalirudin reduced MI risk at the price of MB excess. UFH +/- GPI significantly increased the odds of MI vs LMWHs, of ST vs UFH+GPI, and of MB vs bivalirudin. Reduced ST risk with otamixaban vs UFH +/- GPI and vs bivalirudin was offset by a marked 2.5- to four-fold MB excess. Fondaparinux showed an intermediate profile. Results for ST-segment elevation MI were consistent with the overall findings. Early anticoagulant strategies for ACS differ in efficacy and safety, with UFH+ GPI and LMWHs reducing ischaemic but increasing bleeding risk, and bivalirudin reducing MB but increases MI and ST. The findings support individualised therapy based on patients' bleeding and ischaemic risks

Regulation of cAMP-dependent Protein Kinases: THE HUMAN PROTEIN KINASE X (PrKX) REVEALS THE ROLE OF THE CATALYTIC SUBUNIT αH-αI LOOP*

cAMP-dependent protein kinases are reversibly complexed with any of the four isoforms of regulatory (R) subunits, which contain either a substrate or a pseudosubstrate autoinhibitory domain. The human protein kinase X (PrKX) is an exemption as it is inhibited only by pseudosubstrate inhibitors, i.e. RIα or RIβ but not by substrate inhibitors RIIα or RIIβ. Detailed examination of the capacity of five PrKX-like kinases ranging from human to protozoa (Trypanosoma brucei) to form holoenzymes with human R subunits in living cells shows that this preference for pseudosubstrate inhibitors is evolutionarily conserved. To elucidate the molecular basis of this inhibitory pattern, we applied bioluminescence resonance energy transfer and surface plasmon resonance in combination with site-directed mutagenesis. We observed that the conserved αH-αI loop residue Arg-283 in PrKX is crucial for its RI over RII preference, as a R283L mutant was able to form a holoenzyme complex with wild type RII subunits. Changing the corresponding αH-αI loop residue in PKA Cα (L277R), significantly destabilized holoenzyme complexes in vitro, as cAMP-mediated holoenzyme activation was facilitated by a factor of 2–4, and lead to a decreased affinity of the mutant C subunit for R subunits, significantly affecting RII containing holoenzymes