Unemployment in Europe: Swimming against the Tide of Skill-Biased Technical Progress without Relative Wage Adjustment

The hypothesis that European unemployment is the rigid relative wage mirror-image of increased wage dispersion in the US is explored. The framework is a two sector –manufacturing and services- model with skilled and unskilled labor. A proxy for skill-biased technical progress (SBTP) is constructed from data on total factor productivity (TFP). Econometric analysis of the relationship between SBTP and aggregate unemployment shows that SBTP explains some 50% of the unemployment increase in major European countries since the early 1970s, but it does not explain US unemployment. The hypothesis is robust in that it is not rendered void by inclusion of alternative, mostly macroeconomic, explanatory variables.TBA

Public Ownership and Income Redistribution

The large differences among advanced OECD countries in the shares of workers that are employed by the government can probably only to a small part be explained by factors that are in the center of modern organization theory explanations for public vs. private ownership. This paper explores a new hypothesis for explaining the share of government employment. It is based on asymmetric information about individual worker productivity between the taxman, and workers and their employers. Hence, government employment opens up policy options, not available with only private production. The hypothesis is that government employment is an efficient element of redistribution policy. The mechanism is that the government can, through its employment policy, increase the relative scarcity in the private sector of the workers the government wants to redistribute in favor of. That increases their wages and lowers the need for redistribution through the tax- and transfer systems, which mitigates distortions. One can therefore expect large government employment in countries where the tolerance of inequality is low.Structure and Scope of Government; Optimal non-linear income taxation; public production; production efficiency

Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on mycobacterium tuberculosis

Objectives: the first objective of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee for antimycobacterial susceptibility testing (AMST), launched in 2016, was to set a reference method for determining the MICs of antituberculous agents, since many protocols are used worldwide and a consensus one is needed for the determination of microbiological breakpoints. Methods: during 2017 and 2018, MIC determination protocols were evaluated prospectively in a multicentre study within the four AMST laboratories. MIC results were obtained for isoniazid, levofloxacin and amikacin on the reference strain Mycobacterium tuberculosis H37Rv ATCC 27294. Broth microdilution (BMD) in Middlebrook 7H9 and solid medium dilution (SMD) in Middlebrook 7H10 were performed using two inoculum concentrations. MICs were interpreted with regard to visual and 99% inhibition after 7, 14 or 21 days of incubation for BMD and 21 days for SMD. Results: following the EUCAST reference protocol, intra- and inter-assay agreements were within ±1 MIC dilution for >95% of the observations for the three drugs in both methods. MIC values, presented as MIC mode (range) for BMD and SMD respectively, were: 0.03 (0.015-0.06) mg/L and 0.12 (0.06-0.25) mg/L for isoniazid, 0.25 mg/L (0.25-0.5) and 0.5 mg/L (0.12-0.5) for levofloxacin, and 0.5 mg/L (0.5-1.0) and 0.5 mg/L (0.5-1.0) for amikacin. Conclusions: both SMD and BMD were reproducible and eligible as a reference method for MIC determination of the Mycobacterium tuberculosis complex (MTBC). BMD was finally selected as the EUCAST reference method. From now on it will be used to set epidemiological cut-off values and clinical breakpoints of new and old antituberculous agents

Antimicrobial susceptibility testing of mycobacterium tuberculosis complex isolates - the EUCAST broth microdilution reference method for MIC determination

Scope:Several methods are used worldwide for antibiotic susceptibility testing (AST) for theMycobac-terium tuberculosiscomplex (MTBC). The variability in the results obtained with these methods hamperssetting epidemiological cut-off (ECOFF) values and clinical breakpoints according to EUCAST guidelines.Methods for susceptibility testing and determination of the minimal inhibitory concentrations (MICs)need to be standardized for MTBC isolates for old and new agents. Our objective was to establish astandardized reference method for MIC determination for MTBC.Methods:The EUCAST antimycobacterial susceptibility testing subcommittee (AMST) compared pro-tocols of MIC determination with regard to medium, inoculum preparation, antituberculous agentpreparation, incubation, reading of the results and interpretation.Recommendations:The EUCAST reference method of MIC determination for MTBC is the broth micro-dilution method in Middlebrook 7H9-10% OADC medium. Thefinal inoculum is a 105CFU/mL suspension,obtained from a 10 2dilution of a 0.5 McFarland suspension prepared after vortexing bacterial colonieswith glass beads before suspending them in sterile water. The culture is maintained in a U-shaped 96-well polystyrene microtitre sterile plate with a lid incubated at 36 ±1 C. Reading is done using aninverted mirror as soon as the 1:100 diluted control (i.e. 103CFU/mL suspension) shows visual growth.The MIC, expressed in mg/L, is the lowest concentration that inhibits visual growth.MycobacteriumtuberculosisH37Rv ATCC 27294 is used as the reference strain and its targeted MIC values are within therange 0.03e0.12 for isoniazid, 0.12e0.5 for levofloxacin and 0.25e1 mg/L for amikacin.Conclusions:The EUCAST reference method for MTBC was endorsed by EUCAST after public consultationand will from now on be used to define EUCAST ECOFFs and clinical breakpoints. This reference methodis not primarily intended to be used under routine conditions and the AST methods will need to b

Air temperature conditions in northern Nordaustlandet (NE Svalbard) at the end of World War II

This article presents the results of an investigation into air temperature conditions in northern Nordaustlandet (NE Svalbard) based on meteorological observations made by German soldiers towards the end of World War II (1944/1945) and 4 months after its end. Traditional analysis using mean monthly data was supplemented by a detailed analysis based on daily data: maximum temperature, minimum temperature and diurnal temperature range. The latter kind of data made it possible to study such aspects of climate as the number of “characteristic days” (i.e., the number of days with temperatures exceeding specified thresholds), dayto-day temperature variability, and duration, onset and end dates of thermal seasons. The results from Nordaustlandet for the warmest period of the early 20th century warming period (ETCWP) were compared with temperature conditions both historical (the end part of the Little Ice Age) and contemporary (different sub-periods taken from the years 1981–2017) to estimate the range of warming during the ETCWP. Analysis reveals that the expedition year 1944/1945 in Nordaustlandet was, in the majority of months, the warmest of all analysed periods, that is, both historical and contemporary periods. The study period was markedly warmer than 1981–2010 (mean annual −6.5 vs. −8.4 °C) but colder than the periods 2011–2016 (−5.7 °C) and 2014–2017 (−5.8 °C). The majority of mean monthly air temperatures in the ETCWP lies within two standard deviations of the modern 2014–2017 mean. This means that values of air temperature in the study period lie within the range of recent temperature variability. All other thermal characteristics show changes in accordance with expectations associated with general warming of the Arctic (i.e., a decrease in diurnal temperature range and number of cold days, and an increase in number of warm days). The latter days were most common in the ETCWP

Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid

OBJECTIVES: To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug. METHODS: The Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine the MICs of a phylogenetically diverse collection of 356 Mycobacterium tuberculosis complex (MTBC) strains to establish the epidemiological cut-off value for pretomanid. MICs were correlated with WGS data to study the genetic basis of differences in the susceptibility to pretomanid. RESULTS: We observed ancient differences in the susceptibility to pretomanid among various members of MTBC. Most notably, lineage 1 of M. tuberculosis, which is estimated to account for 28% of tuberculosis cases globally, was less susceptible than lineages 2, 3, 4 and 7 of M. tuberculosis, resulting in a 99th percentile of 2 mg/L for lineage 1 compared with 0.5 mg/L for the remaining M. tuberculosis lineages. Moreover, we observed that higher MICs (≥8 mg/L), which probably confer resistance, had recently evolved independently in six different M. tuberculosis strains. Unlike the aforementioned ancient differences in susceptibility, these recent differences were likely caused by mutations in the known pretomanid resistance genes. CONCLUSIONS: In light of these findings, the provisional critical concentration of 1 mg/L for MGIT set by EMA must be re-evaluated. More broadly, these findings underline the importance of considering the global diversity of MTBC during clinical development of drugs and when defining breakpoints for AST

In vitro activity of new combinations of β-lactam and β-lactamase inhibitors against the Mycobacterium tuberculosis complex

11 págiinas, 3 figuras, 2 tablas. Supplemental Material: Table S1 and Figure S1 (Spectrum01781-23-s0001.docx). Preparation of test concentrations and plate layout BMD. Table S2 (Spectrum01781-23-s0002.xlsx). Raw data of minimum inhibitory concentrations and WGSAs meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the in vitro activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine Mycobacterium tuberculosis complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant. Broth microdilution MICs were determined using the EUCAST reference method. Meropenem and tebipenem were tested individually and in combination with vaborbactam 8 mg/L and clavulanic-acid 2 and 4 mg/L, respectively. Whole-genome sequencing was performed to explore resistance mechanisms. Clavulanic acid lowered the modal tebipenem MIC approximately 16-fold (from 16 to 1 mg/L). The modal meropenem MIC was reduced twofold by vaborbactam compared with an approximately eightfold decrease by clavulanic acid. The only previously described high-confidence carbapenem resistance mutation, crfA T62A, was shared by a subgroup of lineage 4.3.4.1 isolates and did not correlate with elevated MICs. The presence of a β-lactamase inhibitor reduced the MTBC MICs of tebipenem and meropenem. The resulting MIC distribution was lowest for the orally available drugs tebipenem-clavulanic acid. Whether this in vitro activity translates to similar or greater clinical efficacy of tebipenem-clavulanic acid compared with the currently WHO-endorsed meropenem-clavulanic acid requires clinical studies. IMPORTANCE Repurposing of already approved antibiotics, such as β-lactams in combination with β-lactamase inhibitors, may provide new treatment alternatives for drug-resistant tuberculosis. Meropenem-clavulanic acid was more active in vitro compared to meropenem-vaborbactam. Notably, tebipenem-clavulanic acid showed even better activity, raising the potential of an all-oral treatment option. Clinical data are needed to investigate whether the better in vitro activity of tebipenem-clavulanic acid correlates with greater clinical efficacy compared with the currently WHO-endorsed meropenem-clavulanic acid.Swedish Research Council 2019-05 901Peer reviewe

Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acidâ stimulated neutrophils

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142119/1/jlb0976.pd