Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone

BACKGROUND New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype. AIM To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England. METHODS Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains. FINDINGS By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 × 10(-6), Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006. CONCLUSIONS Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms

Dilatonic Interpretation of the Quintessence?

We discuss the possibility that "quintessential effects", recently displayed by large scale observations, may be consistently described in the context of the low-energy string effective action, and we suggest a possible approach to the problem of the cosmic coincidence based on the link between the strength of the dilaton couplings and the cosmological state of our Universe.Comment: 6 pages, Revtex, four figures included using epsfig. To appear in Phys. Rev.

Quintessence arising from exponential potentials

We demonstrate how exponential potentials that could arise in the early Universe as a result of Kaluza-Klein type compactifications of string theory, can lead to cosmological solutions which correspond to the currently observed accelerating Universe. The idea is simple, relying solely on the known scaling properties associated with exponential potentials. In particular we show that the existence of stable attractor solutions implies that the results hold for a wide range of coupling constants and initial conditions.Comment: 4 pages, 3 figures, published versio

Analytically Solvable Asymptotic Model of Atrial Excitability

We report a three-variable simplified model of excitation fronts in human atrial tissue. The model is derived by novel asymptotic techniques \new{from the biophysically realistic model of Courtemanche et al (1998) in extension of our previous similar models. An iterative analytical solution of the model is presented which is in excellent quantitative agreement with the realistic model. It opens new possibilities for analytical studies as well as for efficient numerical simulation of this and other cardiac models of similar structure

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Improving particulate carbon loss estimates in eroding peatlands through the use of terrestrial laser scanning

Blanket bogs act as the largest terrestrial store of carbon within the UK. Unfortunately many are degraded with exacerbated erosion being common. Although considerable efforts have been made to quantify carbon fluxes across blanket bogs, less attention has focussed on quantifying losses associated with erosion. Traditional approaches to measuring erosion have relied on erosion pins and sediment traps. However, both methods suffer from several problems and are unable to provide data over large areas. Terrestrial laser scanning has been used widely in geomorphology to create detailed 3D topographic maps in a range of environments. A pilot study was carried out over winter 2010-2011 to test the applicability of terrestrial laser scanning to measure erosion across a blanket bog within the North Pennines, UK. The technique was found to be superior to traditional methods providing high resolution spatial data on surface elevation change. A net increase in the peat surface height of 2.5. mm was calculated from the terrestrial laser scans between October 2010 and March 2011. This compares with a net surface lowering of 38. mm measured using pins. These results suggest that previous erosion data from peatland sites based on pin measurements ought to be treated with caution. However, several improvements are required to the laser scanning technique before it is fully implemented in peatland environments including the development of a filter to remove vegetation from the scan results, and taking account of 'mire-breathing' which can cause surface level rise and fall in peatlands. It is clear that once these factors are dealt with, regular repeated ground based laser scanning will vastly improve our understanding of the role of processes that affect the surface elevation of peatlands including the relative roles of storm events and long-term seasonal cycles, and 'roughening' of the peat surface as a result of needle-ice formation, desiccation and wind-scouring