The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa

Background. The Beijing genotype of M. tuberculosis is a virulent strain that is disseminating worldwide and has a strong association with drug resistance. In the Western Cape of South Africa, epidemiological studies have identified the R220 cluster of the Beijing genotype as a major contributor to a recent outbreak of drug-resistant tuberculosis. Although the outbreak is considered to be due to clonal transmission, the relationship among drug resistant isolates has not yet been established. Results. To better understand the evolution of drug resistance among these strains, 14 drug-resistant clinical isolates of the Beijing genotype were sequenced by whole-genome sequencing, including eight from R220 and six from a more ancestral Beijing cluster, R86, for comparison. While each cluster shares a distinct resistance mutation for isoniazid, mapping of other drug-resistance mutations onto a phylogenetic tree constructed from single nucleotide polymorphisms shows that resistance mutations to many drugs have arisen multiple times independently within each cluster of isolates. Thus, drug resistance among these isolates appears to be acquired, not clonally derived. This observation suggests that, although the Beijing genotype as a whole might have selective advantages enabling its rapid dissemination, the XDR isolates are relatively less fit and do not propagate well. Although it has been hypothesized that the increased frequency of drug resistance in some Beijing lineages might be caused by a mutator phenotype, no significant shift in synonymous substitution patterns is observed in the genomes. Conclusion. While MDR-TB is spreading by transmission in the Western Cape, our data suggests that further drug resistance (i.e. XDR-TB) at this stage is acquired.Peer Reviewe

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Genomic and functional analyses of mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.

CAPRISA, 2016.Abstract available in PDF file

Wear of different materials for total hip replacement under adverse stop-dwell-start in vitro wear simulation conditions

Hip simulation is a common technique for pre-clinical evaluation of wear performance of total hip arthroplasty. Standard techniques replicate kinematics of walking patterns of a typical patient. Attention has focussed in developing simulations of other typical patient daily activities to improve accuracy of wear predictions. A method for simulating stop-dwell-start motion during patient walking and the effect on 36-mm metal-on-metal total hip arthroplasty was previously presented by the authors. This study sought to extend the previous work to look at the effect of these conditions on ceramic-on-ceramic, metal-on-polyethylene and ceramic-on-polyethylene bearings. Two stop-dwell-start protocols were used: one reproducing average patient movement patterns and one examining more severe conditions. For all materials tested, no significant increase in wear was observed under average stop-dwell-start conditions, suggesting the bearing types tested are robust to this type of activity. A significant increase in wear was observed for metal-on-metal, metal-on-polyethylene and ceramic-on-polyethylene bearings under severe stop-dwell-start conditions, this was attributed to depletion of lubricant in the bearing during the dwell period. A greater relative increase in wear was observed for metal-on-metal bearings compared with metal-on-polyethylene and ceramic-on-polyethylene bearings. This may be explained by the contributions of the different lubrication mechanisms in each bearing type. Wear of ceramic-on-ceramic was very low in all tests, suggesting normal measurement variation was masking any effect of the adverse conditions. It was not possible to determine any effect of the different activities. These results emphasise the importance of exploring adverse patient activity simulations. The increase in wear rate associated with an adverse activity such as seen in stop-dwell-start motion, has to be considered in the context of the frequency of the adverse activity cycle relative to other activities such as standard continuous walking, to determine the impact on the total wear in a given time period