Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1–27 weeks. Changes in consensus sequence and resistance mutations were analyzed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored. Targeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative maribavir and ganciclovir resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient. Deep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of 11 subjects and identified resistance mutations earlier than conventional PCR-based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome.
In wall-less Hall thrusters, the ionization of the propellant and the acceleration of the ions occur outside the thruster [S. Mazouffre, S. Tsikata, and J. Vaudolon, in 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference (American Institute of Aeronautics and Astronautics, Cleveland, OH, 2014)]. This reduces interactions between the plasma and the thruster parts as compared to conventional annular and cylindrical Hall thrusters and promises a longer thruster lifetime. With a much simpler design, these non-conventional thrusters are also easier to miniaturize for operation at low power levels of a few hundred watts and lower. In this work, experiments demonstrate that a miniaturized (3 cm diameter) 200 W wall-less thruster is also able to achieve similar voltage utilization, propellant utilization, and current utilization efficiencies as conventional Hall thrusters. Yet, thruster performance of the wall-less thruster is generally lower due to a much larger plume divergence than that in conventional Hall thrusters. This plume divergence is a consequence of ion acceleration in the fringing magnetic field. Thrust and plasma measurements suggest that the thrust generated by the wall-less thruster is due to two components: ion acceleration by the JxB force in the region of the fringing magnetic field radially away from the thruster and by plasma expansion in the diverging magnetic field near the thruster axis.
Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV + haematological clones that are lost on successful treatment.
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