Purpose With the increase of especially hospital-acquired infections, timely and accurate diagnosis of bacterial infections is crucial for effective patient care. Molecular imaging has the potential for specific and sensitive detection of infections. Siderophores are iron-specific chelators recognized by specific bacterial transporters, representing one of few fundamental differences between bacterial and mammalian cells. Replacing iron by gallium-68 without loss of bioactivity is possible allowing molecular imaging by positron emission tomography (PET). Here, we report on the preclinical evaluation of the clinically used siderophore, desferrioxamine-B (Desferal®, DFO-B), radiolabelled with 68 Ga for imaging of bacterial infections. Methods In vitro characterization of [ 68 Ga]Ga-DFO-B included partition coefficient, protein binding and stability determination. Specific uptake of [ 68 Ga]Ga-DFO-B was tested in vitro in different microbial cultures. In vivo biodistribution was studied in healthy mice and dosimetric estimation for human setting performed. PET/CT imaging was carried out in animal infection models, representing the most common pathogens. Results DFO-B was labelled with 68 Ga with high radiochemical purity and displayed hydrophilic properties, low protein binding and high stability in human serum and PBS. The high in vitro uptake of [ 68 Ga]Ga-DFO-B in selected strains of Pseudomonas aeruginosa , Staphylococcus aureus and Streptococcus agalactiae could be blocked with an excess of iron-DFO-B. [ 68 Ga]Ga-DFO-B showed rapid renal excretion and minimal retention in blood and other organs in healthy mice. Estimated human absorbed dose was 0.02 mSv/MBq. PET/CT images of animal infection models displayed high and specific accumulation of [ 68 Ga]Ga-DFO-B in both P. aeruginosa and S. aureus infections with excellent image contrast. No uptake was found in sterile inflammation, heat-inactivated P. aeruginosa or S. aureus and Escherichia coli lacking DFO-B transporters. Conclusion DFO-B can be easily radiolabelled with 68 Ga and displayed suitable in vitro characteristics and excellent pharmacokinetics in mice. The high and specific uptake of [ 68 Ga]Ga-DFO-B by P. aeruginosa and S. aureus was confirmed both in vitro and in vivo, proving the potential of [ 68 Ga]Ga-DFO-B for specific imaging of bacterial infections. As DFO-B is used in clinic for many years and the estimated rad...

Contact between and mutual influences among varieties of standard and non-standard English have always been a central concern in research on World Englishes. In a mobile and globalising world such contacts are by no means restricted to diffusion of features in face-to-face interaction, across contiguous territories in space or up and down the sociolinguistic scale. In order to better represent and understand the complex relationships obtaining between varieties of standard and non-standard English in the contemporary “English language complex” (McArthur 2003: 56; Mesthrie and Bhatt 2008: 1–3), the present paper proposes a new theoretical model, based on language systems theory (de Swaan 2002, 2010). While the model is not designed to supersede existing alternatives, such as the Kachruvian (1982) Circles, it will nevertheless complement them in important ways, chiefly because it is better equipped to handle uses of English in domains beyond the post-colonial nation state. The “World System of Englishes” model was developed in the course of the author’s work on the use of pidgins and creoles in web forums serving the post-colonial West African and Caribbean diasporas. The way Nigerian Pidgin figures in the creation of a globalised digital ethnolinguistic repertoire will hence serve as an illustration of its usefulness.

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Based on the systematic analysis of large amounts of computer-readable text, this book shows how the English language has been changing in the recent past, often in unexpected and previously undocumented ways. The study is based on a group of matching corpora, known as the 'Brown family' of corpora, supplemented by a range of other corpus materials, both written and spoken, drawn mainly from the later twentieth century. Among the matters receiving particular attention are the influence of American English on British English, the role of the press, the 'colloquialization' of written English, and a wide range of grammatical topics, including the modal auxiliaries, progressive, subjunctive, passive, genitive and relative clauses. These subjects build an overall picture of how English grammar is changing, and the linguistic and social factors that are contributing to this process.