Individual Pay and Outside Options: Evidence from the Polish Labour Force Survey

Using Polish Labour Force Survey data, we examine whether competition for labour has induced individual pay to depend on outside options, availability and quality of jobs. Exploiting the lack of inter-regional job and worker flows we estimate the elasticity of individual pay, amongst a rich set of individual characteristics, to be approximately -0.1 for local unemployment (job shortages) and + 0.1 for local job reallocation (restructuring). Variations in local labour market conditions explain approximately 50 per cent of the differences in expected individual earnings across regions, while differences in inherited human capital and occupation structures explain the rest.http://deepblue.lib.umich.edu/bitstream/2027.42/39748/3/wp364.pd

Proteomics as the final step in the functional metagenomics study of antimicrobial resistance

peer-reviewedThe majority of clinically applied antimicrobial agents are derived from natural products generated by soil microorganisms and therefore resistance is likely to be ubiquitous in such environments. This is supported by the fact that numerous clinically important resistance mechanisms are encoded within the genomes of such bacteria. Advances in genomic sequencing have enabled the in silico identification of putative resistance genes present in these microorganisms. However, it is not sufficient to rely on the identification of putative resistance genes, we must also determine if the resultant proteins confer a resistant phenotype. This will require an analysis pipeline that extends from the extraction of environmental DNA, to the identification and analysis of potential resistance genes and their resultant proteins and phenotypes. This review focuses on the application of functional metagenomics and proteomics to study antimicrobial resistance in diverse environments.The Alimentary Pharmabiotic Centre is a research centre funded by Science Foundation Ireland (SFI). This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2273 and by FP7 funded CFMATTERS (Cystic Fibrosis Microbiome-determined Antibiotic Therapy Trial in Exacerba- tions: Results Stratified, Grant Agreement no. 603038)

Individual Pay and Outside Options: Evidence from the Polish Labour Force Survey

Using Polish Labour Force Survey data, we examine whether competition for labour has induced individual pay to depend on outside options, availability and quality of jobs. Exploiting the lack of inter-regional job and worker flows we estimate the elasticity of individual pay, amongst a rich set of individual characteristics, to be approximately -0.1 for local unemployment (job shortages) and + 0.1 for local job reallocation (restructuring). Variations in local labour market conditions explain approximately 50 per cent of the differences in expected individual earnings across regions, while differences in inherited human capital and occupation structures explain the rest.

Telithromycin: the first ketolide, the interactions and alterations

Respiratory tract infections are a serious cause ofmorbidity and mortality throughout the world. The most frequent causes of infection are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and atypical pathogens such as Chlamydophila pneumoniae. These infections are treated traditionally with antimicrobial agents, mainly the penicillins and macrolides. However, the incidence ofmacrolide resistance has increased markedly over the past 10 years, particularly in France, Belgium and Italy. Therefore, new compounds like telithromycin, an erythromycin derivative called a ketolide (K), have been developed to overcome this problem.In this study, clinical isolates ofS. pneumoniae, H. influenzae and M. catarrhalis were tested in vitro against a range ofantimicrobial agents, including telithromycin, to investigate the efficacy ofthis new drug. Telithromycin showed excellent activity against S. pneumoniae, including macrolide resistant strains, but its activity was not as high against M. catarrhalis or H. influenzae. For M. catarrhalis the minimum inhibitory concentration (MIC) oftelithromycin was similar to that of the macrolides. With regard to H. influenzae telithromycin had higher activity than erythromycin and clarithromycin.The ermB and mefA/E genes mediate resistance to macrolides in S. pneumoniae in most cases. The ermB gene confers resistance to macrolide, lincosamide and streptogramin B (MLSB) antimicrobial agents by methylation ofpart oftheir ii ribosomal binding site. The mefA/E gene mediates efflux of 14- and 15-membered macrolides. Recent investigations have also implicated mutations in the 23S rRNA site ofMLSbK interactions with macrolide and, in certain cases, ketolide resistance. Alterations oftwo ribosomal proteins L4 and L22 have also been associated with increased MLSBK MICs and resistance.In this study in vitro mutants were generated from three S. pneumoniae strains, 02J1095 (ermB positive), 02J1175 {mefA/E positive) and NCTC 13593 (MLSBK sensitive), on telithromycin. The MICs ofthe final generation mutants of each parent were increased in comparison to the parent but only the mutants from the macrolide resistant parents, 02J1095 and 02J1175, were telithromycin resistant. In order to ascertain the mechanism used by these telithromycin resistant mutants to achieve resistance, the ermB gene and upstream region, the mefA/E gene, the 23 S rRNA genes encoding domains II and V and the L4 and L22 riboprotein genes were amplified by PCR and sequenced. No alterations were located in any ofthe genes of the 02J1175 mutants investigated. No changes were present in the ermB genes or upstream regions, the 23 S rRNA genes or the L4 or L22 riboprotein genes ofthe 02J1095 mutants except J III 8. J III 8 had a telithromycin MIC of>32mg/L and was a second-generation mutant of 02J1095. In this strain two mutations were present. The first was a 94K to Q94 amino acid mutation in the L22 riboprotein. The second was a 208 base pair deletion in the upstream region ofthe ermB gene containing the control peptide and one oftwo ribosome-binding sites. This region controls the expression ofthe ermB gene and hence methylase production. These mutations either alone or together were not present in any other mutant. They have not been described previously in S. pneumoniae. These mutations, while novel, do not alone explain the development oftelithromycin resistance in S. pneumoniae. They do however; give an insight into how telithromycin interacts with the ribosome and the potential mechanisms clinical isolates may develop when telithromycin is introduced into the community

Doripenem: A new carbapenem antibiotic a review of comparative antimicrobial and bactericidal activities

Doripenem is a new parental 1-β-methyl carbapenem which, unlike imipenem, does not require the addition of cilastatin on administration because of the protection afforded to doripenem by the 1-β-methyl component. It combines the in vitro activities of imipenem and ertapenem against gram-positive bacteria with the in vitro activity of meropenem against gram-negative bacteria. It has excellent bactericidal activity against Streptococcus neumoniae. Carbapenem resistant mutants were selected with less frequency and lower minimum inhibitory concentrations (MICs) after exposure to doripenem than to imipenem or meropenem. High concentration levels of doripenem may be achieved in plasma. The half life of doripenem is higher than imipenem or meropenem. This new antibiotic has excellent in vitro activity and pharmacological properties. but how it may best be utilized still needs to be determined

Investigating antibiotic resistance in non-clinical environments

There have been many calls for more information about the natural resistome and these have also highlighted the importance of understanding the soil resistome in the preservation of antibiotics for the treatment of infections. However, to date there have been few studies which have investigated the culturable soil resistome, which highlights the difficulties faced by microbiologists in designing these experiments to produce meaningful data. The World Health Organization definition of resistance is the most fitting to non-clinical environmental studies: antimicrobial resistance is resistance of a microorganism to an antimicrobial medicine to which it was previously sensitive. The ideal investigation of non-clinical environments for antibiotic resistance of clinical relevance would be using standardized guidelines and breakpoints. This review outlines different definitions and methodologies used to understand antibiotic resistance and suggests how this can be performed outside of the clinical environment

Molecular characterization of carbapenem-resistant Acinetobacter species in an Irish university hospital: predominance of Acinetobacter genomic species 3

A 30 month prospective study of Acinetobacter species encountered in the Central Pathology Laboratory of St James's Hospital, Dublin, Ireland, was conducted to investigate the prevalence and molecular epidemiology of carbapenem resistance in such isolates. Acinetobacter genomic species 3 (AG3) was found to be the predominant Acinetobacter species (45/114, 39 %) in our institution. A total of 11 % of all Acinetobacter species (12/114) and 22 % of AG3 isolates (10/45) were carbapenem resistant. Carbapenem resistance was mediated by Ambler class D beta-lactamase OXA-23 in all 12 isolates, with insertion sequence ISAba1 found upstream of bla(OXA-23). ISAba1 was also found upstream of bla(ADC-25), which encodes the enzyme AmpC, in an Acinetobacter baumannii isolate, and upstream of the aminoglycoside-acetyltransferase-encoding gene aacC2 in three AG3 isolates. Inter-species plasmidic transfer was most likely involved in the emergence and spread of bla(OXA-23) among the Acinetobacter isolates within our institution. The emergence of carbapenem resistance was associated not only with prior carbapenem use but also with the use of other antimicrobial agents, most notably beta-lactam/beta-lactamase-inhibitor combinations. The study demonstrated the emerging trend of carbapenem resistance in the wider context of the Acinetobacter genus, and reiterated the paramount importance of the prudent use of antimicrobial agents, stringent infection control measures and resistance surveillance of pathogens

Detection and molecular characterisation of plasmidic AmpC b-lactamases in Klebsiella pneumoniae isolates from a tertiary-care hospital in Dublin, Ireland

This study determined the types of AmpC enzymes produced by Klebsiella pneumoniae isolates resistant to third-generation cephalosporins and the clonality of these isolates. The presence of AmpC enzymes was identified by cephalosporin-cloxacillin synergy tests. Genes encoding AmpC enzymes were characterised by PCR and sequencing. Pulsed-field gel electrophoresis (PFGE) was used to type the isolates. Fifteen K. pneumoniae isolates were positive for bla(AmpC), 13 were positive for bla(ACC-1) and two were positive for bla(DHA-1). Production of the DHA-1 enzyme was inducible. The ampR gene was identified upstream of the bla(DHA-1) gene. PFGE demonstrated the polyclonal origin of the isolates carrying bla(ACC-1)