Transmission of multidrug-resistant tuberculosis in the UK: a cross-sectional molecular and epidemiological study of clustering and contact tracing

BACKGROUND: Between 2000 and 2012 the number of multidrug-resistant (MDR) tuberculosis cases in the UK increased from 28 per year to 81 per year. We investigated the proportion of MDR tuberculosis cases arising from transmission in the UK and associated risk factors. METHOD: We identified patients with MDR tuberculosis notified in England, Wales, and Northern Ireland between Jan 1, 2004, and Dec 31, 2007, by linking national laboratory and surveillance data. Data for laboratory isolates, including drug sensitivities and 24-mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing were obtained routinely from the National Tuberculosis Reference laboratories as part of national tuberculosis surveillance. We investigated clusters of cases with indistinguishable MIRU-VNTR profiles to identify epidemiological links. We calculated transmission using the n-1 method and established associated risk factors by logistic regression. We also assessed the likelihood of transmission to additional secondary active tuberculosis cases, identified through conventional contact tracing. FINDINGS: 204 patients were diagnosed with MDR tuberculosis in the study period; 189 (92·6%) had an MIRU-VNTR profile. We identified 12 clusters containing 40 individuals and 149 unique strains. The proportion of cases attributable to recent transmission, on the basis of molecular data, was 15% (40 cases clustered-12 clusters/189 with a strain type). The proportion of cases attributable to recent transmission (ie, transmission within the UK) after adjustment for epidemiological links was 8·5% (22 cases with epidemiological links-six clusters/189 cases with a strain type). Being UK born (odds ratio 4·81; 95% CI 2·03-11·36, p=0·0005) and illicit drug use (4·75; 1·19-18·96, p=0·026) were significantly associated with clustering. The most common transmission setting was the household but 21 of 22 of epidemiological links were missed by conventional contact tracing. 13 secondary active tuberculosis cases identified by conventional contact tracing were mostly contacts of patients with MDR tuberculosis from countries of high tuberculosis burden. 11 (85%) of 13 shared the same country of birth as the index case, of whom ten did not share a strain type or drug resistance pattern. INTERPRETATION: Transmission of MDR tuberculosis in the UK is low and associated with being UK born or illicit drug use. MIRU-VNTR typing with cluster investigation was more successful at identifying transmission events than conventional contact tracing. Individuals with tuberculosis who have had contact with a known MDR tuberculosis source case from a country of high tuberculosis burden should have drug-sensitivity testing on isolates to ensure appropriate treatment is given. FUNDING: Public Health England

Temperate southern Australian coastal waters are characterised by surprisingly high rates of nitrogen fixation and diversity of diazotrophs

Biological dinitrogen (N2) fixation is one mechanism by which specific microorganisms (diazotrophs) can ameliorate nitrogen (N) limitation. Historically, rates of N2 fixation were believed to be limited outside of the low nutrient tropical and subtropical open ocean; however, emerging evidence suggests that N2 fixation is also a significant process within temperate coastal waters. Using a combination of amplicon sequencing, targeting the nitrogenase reductase gene (nifH), quantitative nifH PCR, and 15N2 stable isotope tracer experiments, we investigated spatial patterns of diazotroph assemblage structure and N2 fixation rates within the temperate coastal waters of southern Australia during Austral autumn and summer. Relative to previous studies in open ocean environments, including tropical northern Australia, and tropical and temperate estuaries, our results indicate that high rates of N2 fixation (10–64 nmol L−1 d−1) can occur within the large inverse estuary Spencer Gulf, while comparatively low rates of N2 fixation (2 nmol L−1 d−1) were observed in the adjacent continental shelf waters. Across the dataset, low concentrations of NO3/NO2 were significantly correlated with the highest N2 fixation rates, suggesting that N2 fixation could be an important source of new N in the region as dissolved inorganic N concentrations are typically limiting. Overall, the underlying diazotrophic community was dominated by nifH sequences from Cluster 1 unicellular cyanobacteria of the UCYN-A clade, as well as non-cyanobacterial diazotrophs related to Pseudomonas stutzeri, and Cluster 3 sulfate-reducing deltaproteobacteria. Diazotroph community composition was significantly influenced by salinity and SiO4 concentrations, reflecting the transition from UCYN-A-dominated assemblages in the continental shelf waters, to Cluster 3-dominated assemblages in the hypersaline waters of the inverse estuary. Diverse, transitional diazotrophic communities, comprised of a mixture of UCYN-A and putative heterotrophic bacteria, were observed at the mouth and southern edge of Spencer Gulf, where the highest N2 fixation rates were observed. In contrast to observations in other environments, no seasonal patterns in N2 fixation rates and diazotroph community structure were apparent. Collectively, our findings are consistent with the emerging view that N2 fixation within temperate coastal waters is a previously overlooked dynamic and potentially important component of the marine N cycle

Brachiaria species influence nitrate transport in soil by modifying soil structure with their root system

Leaching of nitrate from fertilisers diminishes nitrogen use efficiency (the portion of nitrogen used by a plant) and is a major source of agricultural pollution. To improve nitrogen capture, grasses such as brachiaria are increasingly used, especially in South America and Africa, as a cover crop, either via intercropping or in rotation. However, the complex interactions between soil structure, nitrogen and the root systems of maize and different species of forage grasses remain poorly understood. This study explored how soil structure modification by the roots of maize (Zea maize), palisade grass (Brachiaria brizantha cv. Marandu) and ruzigrass (Brachiaria ruziziensis) affected nitrate leaching and retention, measured via chemical breakthrough curves. All plants were found to increase the rate of nitrate transport suggesting root systems increase the tendency for preferential flow. The greater density of fine roots produced by palisade grass, subtly decreased nitrate leaching potential through increased complexity of the soil pore network assessed with X-ray Computed Tomography. A dominance of larger roots in ruzigrass and maize increased nitrate loss through enhanced solute flow bypassing the soil matrix. These results suggest palisade grass could be a more efficient nitrate catch crop than ruzigrass (the most extensively used currently in countries such as Brazil) due to retardation in solute flow associated with the fine root system and the complex pore network

Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1

Acknowledgements This work was supported by grants from the Wellcome Trust (200855/Z/16/Z) to MFN and the BBSRC (BB/V010107/1) to MFN and BV. The authors thank Innes Jarmson for the generation of adeno-associated viruses.Peer reviewedPublisher PD

Water-wax behaviour in porous silica at low temperature Fischer-Tropsch conditions

© 2018 Water is a major product of Fischer-Tropsch synthesis, and hence the behaviour of water within Fischer-Tropsch synthesis catalysts and its potential influence on catalyst rate and selectivity are questions of long-standing interest. The present work applies three different magnetic resonance techniques to study how water interacts with a model wax, n-octacosane, within the pore space of a porous silica of mean pore size ∼18 nm. 1H magnetic resonance spectroscopy, spin-lattice relaxation time and pulsed-field gradient measurements were performed at 195 °C, and for water pressure in the range 3–13.6 bar, conditions relevant to low temperature Fischer-Tropsch synthesis. The uptake of water within this system is shown to be very similar to that observed for capillary condensation of water within the empty pore space of the same porous silica under the same experimental conditions; suggesting that capillary condensation of water within the wax-saturated pores is occurring. The behaviour of water is characterised by two regimes. At low water relative pressures of ∼0.3 ≤ P/P0 ≤ ∼0.8 water moves into the pore space, displacing wax from the pore surface and existing as a water-rich layer between the pore surface and an oil-rich phase in the centre of the pore; the strong interaction with the pore surface is evidenced by the short nuclear spin relaxation time values of water at the lowest pressures which then increase slightly as multi-layer adsorption at the pore surface occurs with increase in pressure. In the water relative pressure range ∼0.8 ≤ P/P0 ≤ ∼0.97, condensation of water within the pores is observed, characterised by increases in both spin-lattice relaxation time and molecular diffusivity. Analysis of the data suggests that as much as ∼40% of the pore surface is occupied by condensed water after condensation has occurred. It is suggested that these two regimes of water behaviour inside initially wax-filled pores might explain previously reported aspects of the behaviour of Fischer-Tropsch catalyst performance as a function of pore size and amount of co-fed water

Recent TB transmission, clustering and predictors of large clusters in London, 2010-2012: results from first 3 years of universal MIRU-VNTR strain typing

BACKGROUND: The incidence of TB has doubled in the last 20 years in London. A better understanding of risk groups for recent transmission is required to effectively target interventions. We investigated the molecular epidemiological characteristics of TB cases to estimate the proportion of cases due to recent transmission, and identify predictors for belonging to a cluster. METHODS: The study population included all culture-positive TB cases in London residents, notified between January 2010 and December 2012, strain typed using 24-loci multiple interspersed repetitive units-variable number tandem repeats. Multivariable logistic regression analysis was performed to assess the risk factors for clustering using sociodemographic and clinical characteristics of cases and for cluster size based on the characteristics of the first two cases. RESULTS: There were 10 147 cases of which 5728 (57%) were culture confirmed and 4790 isolates (84%) were typed. 2194 (46%) were clustered in 570 clusters, and the estimated proportion attributable to recent transmission was 34%. Clustered cases were more likely to be UK born, have pulmonary TB, a previous diagnosis, a history of substance abuse or alcohol abuse and imprisonment, be of white, Indian, black-African or Caribbean ethnicity. The time between notification of the first two cases was more likely to be <90 days in large clusters. CONCLUSIONS: Up to a third of TB cases in London may be due to recent transmission. Resources should be directed to the timely investigation of clusters involving cases with risk factors, particularly those with a short period between the first two cases, to interrupt onward transmission of TB

The developmental dynamics of terrorist organizations

We identify robust statistical patterns in the frequency and severity of violent attacks by terrorist organizations as they grow and age. Using group-level static and dynamic analyses of terrorist events worldwide from 1968-2008 and a simulation model of organizational dynamics, we show that the production of violent events tends to accelerate with increasing size and experience. This coupling of frequency, experience and size arises from a fundamental positive feedback loop in which attacks lead to growth which leads to increased production of new attacks. In contrast, event severity is independent of both size and experience. Thus larger, more experienced organizations are more deadly because they attack more frequently, not because their attacks are more deadly, and large events are equally likely to come from large and small organizations. These results hold across political ideologies and time, suggesting that the frequency and severity of terrorism may be constrained by fundamental processes.Comment: 28 pages, 8 figures, 4 tables, supplementary materia

Unicellular cyanobacteria are important components of phytoplankton communities in Australia's northern oceanic ecoregions

© 2019 Moore, Huang, Ostrowski, Mazard, Kumar, Gamage, Brown, Messer, Seymour and Paulsen. The tropical marine environments of northern Australia encompasses a diverse range of geomorphological and oceanographic conditions and high levels of productivity and nitrogen fixation. However, efforts to characterize phytoplankton assemblages in these waters have been restricted to studies using microscopic and pigment analyses, leading to the current consensus that this region is dominated by large diatoms, dinoflagellates, and the marine cyanobacterium Trichodesmium. During an oceanographic transect from the Arafura Sea through the Torres Strait to the Coral Sea, we characterized prokaryotic and eukaryotic phytoplankton communities in surface waters using a combination of flow cytometry and Illumina based 16S and 18S ribosomal RNA amplicon sequencing. Similar to observations in other marine regions around Australian, phytoplankton assemblages throughout this entire region were rich in unicellular picocyanobacterial primary producers while picoeukaryotic phytoplankton formed a consistent, though smaller proportion of the photosynthetic biomass. Major taxonomic groups displayed distinct biogeographic patterns linked to oceanographic and nutrient conditions. Unicellular picocyanobacteria dominated in both flow cytometric abundance and carbon biomass, with members of the Synechococcus genus dominating in the shallower Arafura Sea and Torres Strait where chlorophyll a was relatively higher (averaging 0.4 ± 0.2 mg m-3), and Prochlorococcus dominating in the oligotrophic Coral Sea where chlorophyll a averaged 0.13 ± 0.07 mg m-3. Consistent with previous microscopic and pigment-based observations, we found from sequence analysis that a variety of diatoms (Bacillariophyceae) exhibited high relative abundance in the Arafura Sea and Torres Strait, while dinoflagellates (Dinophyceae) and prymnesiophytes (Prymnesiophyceae) were more abundant in the Coral Sea. Ordination analysis identified temperature, nutrient concentrations and water depth as key drivers of the region's assemblage composition. This is the first molecular and flow cytometric survey of the abundance and diversity of both prokaryotic and picoeukaryotic phytoplankton in this region, and points to the need to include the picocyanobacterial populations as an essential oceanic variable for sustained monitoring in order to better understand the health of these important coastal waters as global oceans change

Single-valued harmonic polylogarithms and the multi-Regge limit

We argue that the natural functions for describing the multi-Regge limit of six-gluon scattering in planar N=4 super Yang-Mills theory are the single-valued harmonic polylogarithmic functions introduced by Brown. These functions depend on a single complex variable and its conjugate, (w,w*). Using these functions, and formulas due to Fadin, Lipatov and Prygarin, we determine the six-gluon MHV remainder function in the leading-logarithmic approximation (LLA) in this limit through ten loops, and the next-to-LLA (NLLA) terms through nine loops. In separate work, we have determined the symbol of the four-loop remainder function for general kinematics, up to 113 constants. Taking its multi-Regge limit and matching to our four-loop LLA and NLLA results, we fix all but one of the constants that survive in this limit. The multi-Regge limit factorizes in the variables (\nu,n) which are related to (w,w*) by a Fourier-Mellin transform. We can transform the single-valued harmonic polylogarithms to functions of (\nu,n) that incorporate harmonic sums, systematically through transcendental weight six. Combining this information with the four-loop results, we determine the eigenvalues of the BFKL kernel in the adjoint representation to NNLLA accuracy, and the MHV product of impact factors to NNNLLA accuracy, up to constants representing beyond-the-symbol terms and the one symbol-level constant. Remarkably, only derivatives of the polygamma function enter these results. Finally, the LLA approximation to the six-gluon NMHV amplitude is evaluated through ten loops.Comment: 71 pages, 2 figures, plus 10 ancillary files containing analytic expressions in Mathematica format. V2: Typos corrected and references added. V3: Typos corrected; assumption about single-Reggeon exchange made explici

Quantizing higher-spin gravity in free-field variables

We study the formulation of massless higher-spin gravity on AdS$_3$ in a gauge in which the fundamental variables satisfy free field Poisson brackets. This gauge choice leaves a small portion of the gauge freedom unfixed, which should be further quotiented out. We show that doing so leads to a bulk version of the Coulomb gas formalism for $W_N$ CFT's: the generators of the residual gauge symmetries are the classical limits of screening charges, while the gauge-invariant observables are classical $W_N$ charges. Quantization in these variables can be carried out using standard techniques and makes manifest a remnant of the triality symmetry of $W_\infty[\lambda]$. This symmetry can be used to argue that the theory should be supplemented with additional matter content which is precisely that of the Prokushkin-Vasiliev theory. As a further application, we use our formulation to quantize a class of conical surplus solutions and confirm the conjecture that these are dual to specific degenerate $W_N$ primaries, to all orders in the large central charge expansion.Comment: 31 pages + appendices. V2: typos corrected, reference adde