A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

Ultrathin and Flat Layer Black Phosphorus Fabricated by Reactive Oxygen and Water Rinse

Ultrathin black phosphorus (BP) is one of the promising two-dimensional (2D) materials for future optoelectronic devices. Its chemical instability in ambient conditions and lack of a bottom-up approach for its synthesis necessitate efficient etching methods that generate BP films of designed thickness with stable and high-quality surfaces. Herein, reporting a photochemical etching method, we demonstrate a controlled layer-by-layer thinning of thick BP films down to a few layers or a single layer and confirm their Raman and photoluminescence characteristics. Ozone molecules generated by O₂ photolysis oxidize BP, forming P₂O₅-like oxides. When the resulting phosphorus oxides are removed by water, the surface of BP with preset thickness is highly flat and self-protective by surface oxygen functional groups. This method provides a fabrication strategy of BP and possibly other 2D semiconductors with band gaps tuned by their thickness

Anomalous Ambipolar Transport of Organic Semiconducting Crystals via Control of Molecular Packing Structures

Organic crystals deposited on 2-dimensional (2D) van der Waals substrates have been widely investigated due to their unprecedented crystal structures and electrical properties. van der Waals interaction between organic molecules and the substrate induces epitaxial growth of high quality organic crystals and their anomalous crystal morphologies. Here, we report on unique ambipolar charge transport of a ???lying-down??? pentacene crystal grown on a 2D hexagonal boron nitride van der Waals substrate. From in-depth analysis on crystal growth behavior and ultraviolet photoemission spectroscopy measurement, it is revealed that the pentacene crystal at the initial growth stage have a lattice-strained packing structure and unique energy band structure with a deep highest occupied molecular orbital level compared to conventional ???standing-up??? crystals. The lattice-strained pentacene few layers enable ambipolar charge transport in field-effect transistors with balanced hole and electron field-effect mobilities. Complementary logic circuits composed of the two identical transistors show clear inverting functionality with a high gain up to 15. The interesting crystal morphology of organic crystals on van der Waals substrates is expected to attract broad attentions on organic/2D interfaces for their electronic applications

Influence of Luminescence Quantum Yield, Surface Coating, and Functionalization of Quantum Dots on the Sensitivity of Time-Resolved FRET Bioassays

In clinical diagnostics, homogeneous time-resolved (TR) FRET immunoassays are used for fast and highly sensitive detection of biomarkers in serum samples. The most common immunoassay format is based on europium chelate or cryptate donors and allophycocyanin acceptors. Replacing europium donors with terbium complexes and the acceptors with QDs offers large photophysical advantages for multiplexed diagnostics, because the Tb-complex can be used as FRET donor for QD acceptors of different colors. Water-soluble and biocompatible QDs are commercially available or can be synthesized in the laboratory using many available recipes from the literature. Apart from the semiconductor material composition, an important aspect of choosing the right QD for TR-FRET assays is the thickness of the QD coating, which will influence the photophysical properties and long-term stability as well as the donor–acceptor distance and FRET efficiency. Here we present a detailed time-resolved spectroscopic study of three different QDs with an emission maximum around 605 nm for their application as FRET acceptors (using a common Tb donor) in TR-bioassays: (i) Invitrogen/Life Technologies Qdot605, (ii) eBioscience eFluorNC605 and iii) ter-polymer stabilized CdSe/CdS/ZnS QDs synthesized in our laboratories. All FRET systems are very stable and possess large Förster distances (7.4–9.1 nm), high FRET efficiencies (0.63–0.80) and low detection limits (0.06–2.0 pM) within the FRET-bioassays. Shapes, sizes and the biotin/QD ratio of the biocompatible QDs could be determined directly in the solution phase bioassays at subnanomolar concentrations. Both commercial amphiphilic polymer/lipid encapsulated QDs and self-made ligand-exchanged QDs provide extremely low detection limits for highly sensitive TR-FRET bioassays