Transmission and lineage displacement drive rapid population genomic flux in cystic fibrosis airway infections of a Pseudomonas aeruginosa epidemic strain

Pseudomonas aeruginosa chronic infections of cystic fibrosis (CF) airways are a paradigm for within-host evolution with abundant evidence for rapid evolutionary adaptation and diversification. Recently emerged transmissible strains have spread globally, with the Liverpool Epidemic Strain (LES) the most common strain infecting the UK CF population. Previously we have shown that highly divergent lineages of LES can be found within a single infection, consistent with super-infection among a cross-sectional cohort of patients. However, despite its clinical importance, little is known about the impact of transmission on the genetic structure of these infections over time. To characterize this, we longitudinally sampled a meta-population of 15 genetic lineages within the LES over 13 months among seven chronically infected CF patients by genome sequencing. Comparative genome analyses of P. aeruginosa populations revealed that the presence of coexisting lineages contributed more to genetic diversity within an infection than diversification in situ. We observed rapid and substantial shifts in the relative abundance of lineages and replacement of dominant lineages, likely to represent super-infection by repeated transmissions. Lineage dynamics within patients led to rapid changes in the frequencies of mutations across suites of linked loci carried by each lineage. Many loci were associated with important infection phenotypes such as antibiotic resistance, mucoidy and quorum sensing, and were repeatedly mutated in different lineages. These findings suggest that transmission leads to rapid shifts in the genetic structure of CF infections, including in clinically important phenotypes such as antimicrobial resistance, and is likely to impede accurate diagnosis and treatment

Behavioural and physiological correlates of impulsivity in the domestic dog (Canis familiaris)

Impulsivity is a trait related to inhibitory control which is expressed in a range of behaviours. Impulsive individuals show a decreased ability to tolerate delay of reinforcement, and more impulsive behaviour has been linked to decreased levels of serotonin and dopamine in a number of species. In domestic dogs, impulsivity is implicated in problem behaviours that result from a lack of self control, but currently there are no published studies that assess behavioural and physiological measures of impulsivity in relation to this trait. Impulsivity scores were calculated for 41 dogs using an owner-report assessment, the Dog Impulsivity Assessment Scale (DIAS). Twenty-three of these subjects completed an operant choice task based on a delayed reward paradigm, to assess their tolerance to delay of reinforcement. High Pressure Liquid Chromatography (HPLC) with Fluorometric Detection was used to detect levels of the metabolites of serotonin (5-HIAA) and dopamine (HVA) in the urine of 17 of the subjects. Higher impulsivity scores were found to be significantly correlated with more impulsive behaviour (reduced tolerance to delay of reinforcement) in the behaviour tests and lower levels of urinary 5-HIAA and 5-HIAA/HVA ratio. The results demonstrate convergent validity between impulsivity (as assessed by the DIAS) and behavioural and physiological parameters

Some general properties of the renormalized stress-energy tensor for static quantum states on (n+1)-dimensional spherically symmetric black holes

We study the renormalized stress-energy tensor (RSET) for static quantum states on (n+1)-dimensional, static, spherically symmetric black holes. By solving the conservation equations, we are able to write the stress-energy tensor in terms of a single unknown function of the radial co-ordinate, plus two arbitrary constants. Conditions for the stress-energy tensor to be regular at event horizons (including the extremal and ``ultra-extremal'' cases) are then derived using generalized Kruskal-like co-ordinates. These results should be useful for future calculations of the RSET for static quantum states on spherically symmetric black hole geometries in any number of space-time dimensions.Comment: 9 pages, no figures, RevTeX4, references added, accepted for publication in General Relativity and Gravitatio