SummaryBackgroundTuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks.MethodsIn a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit–variable-number tandem-repeat data.FindingsWe sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3–0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p<0·0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters.InterpretationWhole-genome sequencing can delineate outbreaks of tuberculosis and allows inference about direction of transmission between cases. The technique could identify super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatment of infectious patients and their contacts.FundingMedical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.

This article demonstrates the differences in EWDI that exist between European countries with implications for both research and policy. Many deaths may be avoidable as environmental, social and personal factors are known to contribute to winter mortality. We now need to work to better understand the causes of inter-country differences.

We have studied the transport properties of a high quality one-dimensional constriction formed in an undoped GaAs/Al x Ga 1Ϫx As heterostructure and therefore largely free of the random potential of ionized donors. We induce an electron gas electrostatically and are able to vary the sheet carrier density (n 2D ) by a factor of at least seven. The constriction shows resonance-free integer conductance plateaus and the additional ''0.7 structure,'' a plateaulike feature, the conductance of which decreases from about 0.80 towards 0.5 ϫ2e 2 /h at low and high n 2D . This low value is unaffected by a high in-plane magnetic field, supporting previous evidence and theories that the breaking of the spin degeneracy at high fields persists in some form, even at zero field. The height of the feature generally seen at a conductance of about 0.85ϫ2e 2 /h at high dc bias also varies, and we show that this is in reasonable agreement with a simple relation linking the conductances of the two features. We use a source-drain bias to study the spin splitting of the lowest one-dimensional subbands, and find a spin gap that is independent of n 2D for the first subband. We discuss possible reasons for the splitting, and show how various models for the 0.7 structure can be applied in the finite bias regime.

Fabrication of high-quality two-dimensional electron gases by overgrowth of focused-ion-beam-doped Al x Ga 1x As Appl.High magnetic field studies of two-dimensional electron gas in a GaN/GaAlN heterostructure: Mechanisms of parallel conduction Formation of a two-dimensional electron gas in an inverted undoped heterostructure with a shallow channel depth J. Appl. Phys. 87, 952 (2000)

We discuss quantization of the conductance in short, ultraclean one-dimensional quantum wires of a design where an electron gas is induced electrostatically. Two-level sets of gates allow independent control of electron density in the constriction and in the reservoirs, thus varying the conductance G as a function of the bias on the gates G(Vtg,Vsg). Up to 12 clean well-resolved conductance G(Vsg) plateaus confirm the high quality of the constriction. The experimental curves are modeled using three-dimensional self-consistent calculations in the Thomas–Fermi approximation of the electrostatic potential of the constriction and solution of the two-dimensional problem of electron transport in the calculated potential. Our calculations are in qualitative agreement with the experiment.