1,720,959 research outputs found
Nitric Oxide-Mediated Dispersal as an Adjunctive Strategy for the Control of Biofilm-Associated Infection
No full textStructured biofilm aggregates offer an increased tolerance to antimicrobials, providing either a physical barrier to antimicrobial penetration or leading to physiological adaptations amongst biofilm bacteria that may impact on antibiotic efficacy. Consequently, biofilms are causative of a range of chronic infections where the use of antimicrobials rarely eradicates the underlying infection. One feature of the development of microbial biofilm communities is that they often undergo lifecycle changes between aggregated and planktonic modes of growth. This transition between sessile and motile growth modes is referred to as biofilm dispersal. Understanding and controlling the dispersal process is leading to novel adjunctive strategies to disrupt clinically important biofilms. Exogenous nitric oxide (NO) has been shown to regulate, in a dose-dependent manner, biofilm lifecycle dynamics and can induce the disruption of biofilm aggregates. The use of NO therefore offers a potential therapeutic approach to address the challenge of biofilm-associated antimicrobial tolerance. This chapter explores the current and prospective NO therapies and the underpinning mechanisms of NO-mediated biofilm regulation. It also reviews NO-releasing chemistries, prodrugs, and materials for clinical use
Phenotyping of <i>Pseudomonas aeruginosa</i> biofilms in cystic fibrosis patients, biofilm biomarker identification, and understanding the nitric oxide mediated biofilm dispersal response.
No full textColonisation of Pseudomonas aeruginosa (PA) in the airways is associated with persistent morbidity, and increased mortality in cystic fibrosis (CF) patients. Treatment strategies include aggressive antibiotic regimes aimed at eradicating or controlling the infection. However, structured biofilm aggregates offer an increased tolerance to antimicrobials, with eradication treatments failing in 10-40% of patients. Biofilms are largely unculturable, are unable to be diagnosed via culture-based methods. A lack of biomarkers for a biofilm infection escalates this diagnostic issue. Previous studies have explored the relationship of novel nitric oxide (NO) donors as biofilm dispersal agents for potential new antibiofilm therapy to be used in CF. Biofilms formed by CF isolates in vitro were foundto have varied responses to the NO donor sodium nitroprusside (SNP).This study focuses both assessing the biofilm status of CF patients chronically infected with P. aeruginosa undergoing exacerbation and looks to combine the phenotypic biofilm status and proteomic data to identify potential biomarkers for biofilm infection. Secondly the study also aims to further explore the underlying mechanisms of the varied responses of clinical CF P. aeruginosa biofilms to the NO biofilm dispersal signal determining patient suitability for the therapeutic use of NO.Using series of microbiological techniques including fluorescently labelled via in-situ hybridisation (FISH) microscopy, dispersal assays, biofilm culture models, and multi-omics methods, the biofilm status was determined for 62 patients and further assessed for alterations following antibiotic treatment. Sputum samples were processed for proteomic analysis to identify correlations between biofilm status and disease state to seek out potential human protein biomarkers for the presence of a biofilm infection. Histone H4 was observed positively correlate with the disease state, with a decreased abundance post antibiotics suggesting a potential infection marker. Despite showing no correlation to that of the biofilm biomass, histone H4 remains to be of interest for further analysis.An extended panel of 10 PA isolates obtained from the sputum of Cystic fibrosis patients at the University hospital Southampton were assessed for their NO response. Interestingly, three distinct phenotypes were identified: dispersing, no change, and growth promotion. Isolates underwent whole genome sequencing, however, no obvious genetic adaptation to the NO signal was discovered suggesting deeper regulatory mechanisms to be responsible. Analysis of the transcriptomes of isolates with differing responses was unable to confidently identify any regulatory mechanism, but has suggested the roles of numerous elements, raising questions on the involvement of the two-component regulatory system, PhoPQ, reported to play a role in virulence and polymyxin resistance,and flagella in the increased biofilm integrity in response to NO.Overall, this study used biofilm phenotyping to characterise the patient biofilm status by identifying bacterial aggregates in expectorated sputum and highlighted the variability between individual patients, raising questions for personalised approaches to CF treatments. A potential biomarker,histone H4, for the CF disease state and PA biofilm phenotype has been identified as being of interest for further proteomic analysis within an extended patient cohort. Further analysis of the bacterial isolates in the CF culture collection is required for full understanding of the varied NO dispersal response
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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