Corruption Epidemics

When estimating the determinants of perceived corruption, economists assumed that there is full independence across countries. In the presence of peer-group or learning effects through cross-border economic activity (such as trade or labor migration), this assumption might be violated. We provide evidence that this is the case. Using a cross-section of 123 economies for the year 2000, we illustrate that corruption in one country spills over to adjacent economies. This finding implies that institutional changes reducing corruption in one country lead to smaller but qualitatively similar effects in neighboring countries

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes : A multicenter prospective observational trial

Background: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. Methods: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. Results: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. Conclusion: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during singlelung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. Registration of Clinical Trial: DRKS-ID DRKS00014788 (www.drks.de)

Sandy soils in silty loess:The loess system of Matmata (Tunisia)

International audienceThe purpose of this study is to better understand the system of Quaternary loess-palaeosol sequences (LPS) of the Matmata region in southern Tunisia. Results from a combination of predominantly classical methods (grain size and mineral analysis, CaCO3- content estimation, environmental magnetism) indicate strong soil formation phases during which the conditions of sedimentation changed drastically. The heavy mineral analysis underlines northwest, west and southwest provenances of the loessic material. Furthermore, we discuss the process of soil formation in LPS and explain why these soils are very sandy in comparison to the loess units. During phases of soil formation, the northwestern sediment transport path was blocked while sandy material was blown dominantly from the southwestern Grand Erg. Therefore, we present a conceptual model including a provenance analysis of the loessic material that support and improve earlier results of Coudé-Gaussen and collaborators.Dans cette étude, nous présentons un modèle conceptuel pour une meilleure compréhension du système de séquences de loess paléosol (LPS) dans la région de Matmata située dans le sud de la Tunisie. Les résultats d'une combinaison de méthodes principalement classiques (analyse granulométrique, analyse minéralogique, détermination de la teneur en CaCO3, magnétisme environnemental) indiquent des phases de formation importante de sols au cours desquelles les conditions de sédimentation ont fondamentalement changé. L'analyse des minéraux lourds met en évidence une origine nord-ouest, ouest et sud-ouest du matériel loessique. En outre, nous discutons la nature de la formation des sols et expliquons pourquoi ces sols sont si sableux par rapport aux unités de loess. Pendant les phases de formation des sols, le trajet des sédiments en provenance du nord-ouest a été bloqué alors que les matériaux sableux pouvaient encore être soufflés à partir du Grand Erg au sud-ouest. Notre modèle conceptuel de la provenance du lœss à Matmata soutient et précise les conclusions de Coudé-Gaussen et collaborateurs

Osteoblastic Response in Patients with Non-small Cell Lung Cancer with Activating EGFR Mutations and Bone Metastases during Treatment with EGFR Kinase Inhibitors

© 2010International Association for the Study of Lung Cance

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy

GRB Light Curves in the Relativistic Turbulence Model

Randomly oriented relativistic emitters in a relativistically expanding shell provides an alternative to internal shocks as a mechanism for producing GRBs' variable light curves with efficient conversion of energy to radiation. In this model the relativistic outflow is broken into small emitters moving relativistically in the outflow's rest frame. Variability arises because an observer sees an emitter only when its velocity points towards him so that only a small fraction of the emitters are seen by a given observer. Models with significant relativistic random motions require converting and maintaining a large fraction of the overall energy into these motions. While it is not clear how this is achieved, we explore here, using two toy models, the constraints on parameters required to produce light curves comparable to the observations. We find that a tight relation between the size of the emitters and the bulk and random Lorentz factors is needed and that the random Lorentz factor determines the variability. While both models successfully produce the observed variability there are several inconsistencies with other properties of the light curves. Most of which, but not all, might be resolved if the central engine is active for a long time producing a number of shells, resembling to some extent the internal shocks model.Comment: Significantly revised with a discussion of additional models. Accepted for publication in APJ

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ

Benchmarking of Mutation Diagnostics in Clinical Lung Cancer Specimens

Treatment of EGFR-mutant non-small cell lung cancer patients with the tyrosine kinase inhibitors erlotinib or gefitinib results in high response rates and prolonged progression-free survival. Despite the development of sensitive mutation detection approaches, a thorough validation of these in a clinical setting has so far been lacking. We performed, in a clinical setting, a systematic validation of dideoxy ‘Sanger’ sequencing and pyrosequencing against massively parallel sequencing as one of the most sensitive mutation detection technologies available. Mutational annotation of clinical lung tumor samples revealed that of all patients with a confirmed response to EGFR inhibition, only massively parallel sequencing detected all relevant mutations. By contrast, dideoxy sequencing missed four responders and pyrosequencing missed two responders, indicating a dramatic lack of sensitivity of dideoxy sequencing, which is widely applied for this purpose. Furthermore, precise quantification of mutant alleles revealed a low correlation (r2 = 0.27) of histopathological estimates of tumor content and frequency of mutant alleles, thereby questioning the use of histopathology for stratification of specimens for individual analytical procedures. Our results suggest that enhanced analytical sensitivity is critically required to correctly identify patients responding to EGFR inhibition. More broadly, our results emphasize the need for thorough evaluation of all mutation detection approaches against massively parallel sequencing as a prerequisite for any clinical implementation

Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer