692 research outputs found

    Archaeological Geophysical Prospection in Peatland Environments: case studies and suggestions for future practice

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    Peatland environments, in contrast to β€˜dry-land’ sites, preserve organic material, including anthropogenic objects, because they are anaerobic, and are therefore of great importance to archaeology. Peat also preserves macro- and micro- paleoenvironmental evidence and is the primary resource for understanding past climates and ecology. Archaeological sites often lie within or at the base of wet, deep, homogenous peat rendering them invisible to surface observers. As a result, they most often c..

    Identification of dfrA14 in two distinct plasmids conferring trimethoprim resistance in Actinobacillus pleuropneumoniae

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    OBJECTIVES: The objective of this study was to determine the distribution and genetic basis of trimethoprim resistance in Actinobacillus pleuropneumoniae isolates from pigs in England. METHODS: Clinical isolates collected between 1998 and 2011 were tested for resistance to trimethoprim and sulphonamide. The genetic basis of trimethoprim resistance was determined by shotgun WGS analysis and the subsequent isolation and sequencing of plasmids. RESULTS: A total of 16 (out of 106) A. pleuropneumoniae isolates were resistant to both trimethoprim (MIC >32 mg/L) and sulfisoxazole (MIC β‰₯256 mg/L), and a further 32 were resistant only to sulfisoxazole (MIC β‰₯256 mg/L). Genome sequence data for the trimethoprim-resistant isolates revealed the presence of the dfrA14 dihydrofolate reductase gene. The distribution of plasmid sequences in multiple contigs suggested the presence of two distinct dfrA14-containing plasmids in different isolates, which was confirmed by plasmid isolation and sequencing. Both plasmids encoded mobilization genes, the sulphonamide resistance gene sul2, as well as dfrA14 inserted into strA, a streptomycin-resistance-associated gene, although the gene order differed between the two plasmids. One of the plasmids further encoded the strB streptomycin-resistance-associated gene. CONCLUSIONS: This is the first description of mobilizable plasmids conferring trimethoprim resistance in A. pleuropneumoniae and, to our knowledge, the first report of dfrA14 in any member of the Pasteurellaceae. The identification of dfrA14 conferring trimethoprim resistance in A. pleuropneumoniae isolates will facilitate PCR screens for resistance to this important antimicrobial

    The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation

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    We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains

    Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis

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    Background: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. Methodology/Principal Findings: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, ,40% of the ,2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three ,90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. Conclusions/Significance: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance

    Winter 2022–23 influenza vaccine effectiveness against influenza-related hospitalised aLRTD: A test-negative, case-control study

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    Influenza activity in the UK started early during the winter 2022-23 season, with most surveillance systems reporting high levels of hospitalisation, intensive care unit influenza admission and GP influenza-like illness (ILI) consultation rates. Laboratory confirmed positivity rates were comparable to those seen pre-pandemic, between the end of November 2022 and the end of January 2023, exceeding 25% as they did during the 2019-2020 season [1,2]. Annual vaccination against influenza is recommended in the UK to eligible higher-risk groups: adults β‰₯65 years(y); children and adults in at-risk groups (including during pregnancy); and, pre-school, primary and secondary school-aged children[3]. However, in 2022-23 the offer of seasonal influenza immunisation was extended to healthy 50-64y olds[4]. The vaccines used were quadrivalent, containing one influenza A(H1N1) virus, one influenza A(H3N2) virus, one influenza B/Victoria lineage virus, and one influenza B/Yamagata lineage virus[5]. Public health measures aiming to reduce the transmission of SARS-CoV-2 had affected the transmission of respiratory viruses like influenza during the previous two seasons, with the 22-23 season being the first one where social mixing returned to pre-pandemic levels. Systematic monitoring of the effectiveness of the seasonal flu vaccine (VE) is a public health priority as influenza activity returns to pre-pandemic levels

    Clinically important associations of pleurodesis success in malignant pleural effusion: Analysis of the TIME1 data set

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    Background and Objective: Chemical pleurodesis is performed for patients with MPE with a published success rate of around 80%. It has been postulated that inflammation is key in achieving successful pleural symphysis, as evidenced by higher amounts of pain or detected inflammatory response. Patients with mesothelioma are postulated to have a lower rate of successful pleurodesis due to lack of normal pleural tissue enabling an inflammatory response. Methods: The TIME1 trial data set, in which pleurodesis success and pain were co‐primary outcome measures, was used to address a number of these assumptions. Pain score, systemic inflammatory parameters as a marker of pleural inflammation and cancer type were analysed in relation to pleurodesis success. Results: In total, 285 patients were included with an overall success rate of 81.4%. There was a significantly higher rise in CRP in the Pleurodesis Success group compared with the Pleurodesis Failure group (mean difference: 19.2, 95% CI of the difference: 6.2–32.0, P = 0.004) but no significant change in WCC. There was no significant difference in pain scores or analgesia requirements between the groups. Patients with mesothelioma had a lower rate of pleurodesis success than non‐mesothelioma patients (73.3% vs 84.9%, Ο‡2 = 5.1, P = 0.023). Conclusion: Change in CRP during pleurodesis is associated with successful pleurodesis but higher levels of pain are not associated. Patients with mesothelioma appear less likely to undergo successful pleurodesis than patients with other malignancies, but there is still a significant rise in systemic inflammatory markers. The mechanisms of these findings are unclear but warrant further investigation
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