In this paper we describe how an improved word prediction implemented on a PDA can make it easier for users to enter text. The resulting predictions are a result of trigrams using POS-tags (Part Of Speech). The first two parts of the trigrams are POS-tagged, and the last part is extended into a ternary tree, using information from the trigrams to narrow the search. With an improved predictions system, the users are more likely to trust the system, find it improves their ability to enter text with less keystrokes. It is also likely that they will to use the prediction feature more actively when they perceive that it is useful to them.
Colistin (COL) is a cationic cyclic peptide that disrupts negatively-charged bacterial cell membranes and frequently serves as an antibiotic of last resort to combat multidrug-resistant Gram-negative bacterial infections. Emergence of the horizontally transferable plasmid-borne mobilized colistin resistance(mcr)determinant and its spread to Gram-negative strains harboring extended-spectrum β-lactamase and carbapenemase resistance genes threatens futility of our chemotherapeutic arsenal. COL is widely regarded to have zero activity againstmcr+patients based on standard antimicrobial susceptibility testing (AST) performed in enriched bacteriological growth media; consequently, the drug is withheld from patients withmcr+infections. However, these standard testing media poorly mimic in vivo physiology and omit host immune factors. Here we report previously unrecognized bactericidal activities of COL againstmcr+isolates ofEscherichia coli(EC),Klebsiella pneumoniae(KP), andSalmonella enterica(SE) in standard tissue culture media containing the physiological buffer bicarbonate. Moreover, COL promoted serum complement deposition on themcr-1+Gram-negative bacterial surface and synergized potently with active human serum in pathogen killing. At COL concentrations readily achievable with standard dosing, the peptide antibiotic killedmcr-1+EC, KP, and SE in freshly isolated human blood proved effective as monotherapy in a murine model ofmcr-1+EC bacteremia. Our results suggest that COL, currently ignored as a treatment option based on traditional AST, may in fact benefit patients withmcr-1+Gram negative infections based on evaluations performed in a more physiologic context. These concepts warrant careful consideration in the clinical microbiology laboratory and for future clinical investigation of their merits in high risk patients with limited therapeutic options.
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