Population genetics of Streptococcus pneumoniae: the response to antibiotic and vaccine pressure

Streptococcus pneumoniae (pneumococcus) is a pathogen and a commensal of the upper respiratory tract, which is a leading cause of child mortality. The development of a successful vaccine against pneumococcal carriage and disease and the ongoing challenge of antimicrobial resistant strains mean that there is an imperative to understand how the pneumococcal population responds to vaccine and antibiotic pressure. Strains of pneumococci with reduced susceptibility to penicillin and other antibiotics have emerged and are a cause of concern, though their clinical impact is unclear. I perform a meta-analysis to examine the impact of antibiotic non-susceptibility on the risk of mortality and show that a meningitis infection with penicillin non-susceptible pneumococci increases the risk of mortality two fold. I then examine why some serotypes of pneumococcus are more likely to carry resistance than others. Using a mathematical model I generate the hypothesis that serotypes with a long duration of carriage are more likely to have a high prevalence of antibiotic resistance than those with a short duration of carriage. Using maximum likelihood estimation, I show that in children less than two years of age, penicillin resistance only occurs in those serotypes whose duration of carriage is nineteen days or more. Having considered the circumstances under which antibiotic resistance carries a selective advantage in a pneumococcal serotype, I then consider the effect that the spread of an advantageous gene has on the genetic diversity in a generalised bacterial population. Most simple models predict that when a novel allele arises in a bacterial population that is fitter than other alleles at that locus, it and its descendents will increase in frequency and sweep to fixation in the population. In the absence of recombination, all genetic diversity at all loci other than those within the sweeping genotype is lost. I consider whether asymmetric recombination can prevent the loss of diversity over the whole genome. I show that asymmetric recombination, when occurring at rates estimated to date from bacterial populations, is not frequent enough to prevent the extinction of alleles from the wild-type population. Finally, I analyse sequence data sampled from carried pneumococci to examine the impact of vaccination on genetic diversity in a pneumococcal population, an example of a selective event in a pneumococcal population

Imagination: A Study of Types With Special Reference to the Imagery of Francis Thompson and Edmund Spenser

Curiosity is doubtless the most valuable asset of the mental make-up of man. In recent years the natural int­erest of human beings in hoe it works has turned within to the investigation of themselves, and how and why they behave like humans. Psychology has become a word to conjure with. Witness the space it and allied subjects occupy on Chautauqua programs, in newspapers, and in magazines. Books attempting to explain our everyday actions and our exceptional ones have become best sellers Complexes, inhibitions, react­ions, stimuli, and a host of other technical terms are familiarly heard in drawing-rooms and even on street cars. Man, curious about himself, has striven to become better acquainted with himself, paradoxically by asking others

Influence of ply configuration and adhesive type on cross-laminated timber in flexure at elevated temperatures

This paper describes experiments on cross-laminated timber (CLT) beams exposed to uniform non-charring temperatures under sustained loading. Two different ply configurations and two different adhesive types were examined under sustained loads of both 30 and 50% of the ultimate ambient temperature flexural capacity. It was found that the adhesive type has a significant influence on the magnitude of the deterioration in structural stiffness during heating. From image correlation analysis this influence was attributed to increased shear strains along the adhesive lines between timber plies for specimens bonded with a polyurethane (PU) adhesive, when compared to those that used a melamine urea formaldehyde (MF) adhesive. It was also found that considerable deflections that were measured during heating were irrecoverable during cooling of the CLT, suggesting that these deformations were driven by creep of the timber – and possibly also the adhesives