Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease

Whole-genome sequencing offers new insights into the evolution of bacterial pathogens and the etiology of bacterial disease. Staph- ylococcus aureus is a major cause of bacteria-associated mortality and invasive disease and is carried asymptomatically by 27% of adults. Eighty percent of bacteremias match the carried strain. How- ever, the role of evolutionary change in the pathogen during the progression from carriage to disease is incompletely understood. Here we use high-throughput genome sequencing to discover the genetic changes that accompany the transition from nasal carriage to fatal bloodstream infection in an individual colonized with meth- icillin-sensitive S. aureus. We found a single, cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms and four insertion/deletion variants. Mutations accumulated at a steady rate over a 13-mo period, except for a cluster of mutations preceding the transition to disease. Although bloodstream bacteria differed by just eight mutations from the original nasally carried bacteria, half of those mutations caused truncation of proteins, including a prema- ture stop codon in an AraC-family transcriptional regulator that has been implicated in pathogenicity. Comparison with evolution in two asymptomatic carriers supported the conclusion that clusters of pro- tein-truncating mutations are highly unusual. Our results demon- strate that bacterial diversity in vivo is limited but nonetheless detectable by whole-genome sequencing, enabling the study of evolutionary dynamics within the host. Regulatory or structural changes that occur during carriage may be functionally important for pathogenesis; therefore identifying those changes is a crucial step in understanding the biological causes of invasive bacterial disease.

Forecasting extinction risk of ectotherms under climate warming: an evolutionary perspective

1. It has been postulated that climate warming may pose the greatest threat species in the tropics, where ectotherms have evolved more thermal specialist physiologies. Although species could rapidly respond to environmental change through adaptation, little is known about the potential for thermal adaptation, especially in tropical species. 2. In the light of the limited empirical evidence available and predictions from mutation-selection theory, we might expect tropical ectotherms to have limited genetic variance to enable adaptation. However, as a consequence of thermodynamic constraints, we might expect this disadvantage to be at least partially offset by a fitness advantage, that is, the ‘hotter-is-better’ hypothesis. 3. Using an established quantitative genetics model and metabolic scaling relationships, we integrate the consequences of the opposing forces of thermal specialization and thermodynamic constraints on adaptive potential by evaluating extinction risk under climate warming. We conclude that the potential advantage of a higher maximal development rate can in theory more than offset the potential disadvantage of lower genetic variance associated with a thermal specialist strategy. 4. Quantitative estimates of extinction risk are fundamentally very sensitive to estimates of generation time and genetic variance. However, our qualitative conclusion that the relative risk of extinction is likely to be lower for tropical species than for temperate species is robust to assumptions regarding the effects of effective population size, mutation rate and birth rate per capita. 5. With a view to improving ecological forecasts, we use this modelling framework to review the sensitivity of our predictions to the model’s underpinning theoretical assumptions and the empirical basis of macroecological patterns that suggest thermal specialization and fitness increase towards the tropics. We conclude by suggesting priority areas for further empirical research.

Formal theory building for the avalanche game: explaining counter-intuitive behaviour of a complex system using geometrical and human behavioural/physiological effects

In 'Avalanche', an object is lowered, players staying in contact throughout. Normally the task is easily accomplished. However, with larger groups counter-intuitive behaviours appear. The paper proposes a formal theory for the underlying causal mechanisms. The aim is to not only provide an explicit, testable hypothesis for the source of the observed modes of behaviour-but also to exemplify the contribution that formal theory building can make to understanding complex social phenomena. Mapping reveals the importance of geometry to the Avalanche game; each player has a pair of balancing loops, one involved in lowering the object, the other ensuring contact. For more players, sets of balancing loops interact and these can allow dominance by reinforcing loops, causing the system to chase upwards towards an ever-increasing goal. However, a series of other effects concerning human physiology and behaviour (HPB) is posited as playing a role. The hypothesis is therefore rigorously tested using simulation. For simplicity a 'One Degree of Freedom' case is examined, allowing all of the effects to be included whilst rendering the analysis more transparent. Formulation and experimentation with the model gives insight into the behaviours. Multi-dimensional rate/level analysis indicates that there is only a narrow region in which the system is able to move downwards. Model runs reproduce the single 'desired' mode of behaviour and all three of the observed 'problematic' ones. Sensitivity analysis gives further insight into the system's modes and their causes. Behaviour is seen to arise only when the geometric effects apply (number of players greater than degrees of freedom of object) in combination with a range of HPB effects. An analogy exists between the co-operative behaviour required here and various examples: conflicting strategic objectives in organizations; Prisoners' Dilemma and integrated bargaining situations. Additionally, the game may be relatable in more direct algebraic terms to situations involving companies in which the resulting behaviours are mediated by market regulations. Finally, comment is offered on the inadequacy of some forms of theory building and the case is made for formal theory building involving the use of models, analysis and plausible explanations to create deep understanding of social phenomena.

Femtosecond pulse shaping using differential evolutionary algorithm and wavelet operators

Evolutionary meta-algorithms for pulse shaping of broadband femtosecond duration laser pulses are proposed. The genetic algorithm searching the evolutionary landscape for desired pulse shapes consists of a population of waveforms (genes), each made from two concatenated vectors, specifying phases and magnitudes, respectively, over a range of frequencies. Frequency domain operators such as mutation, two-point crossover average crossover, polynomial phase mutation, creep and three-point smoothing as well as a time-domain crossover are combined to produce fitter offsprings at each iteration step. The algorithm applies roulette wheel selection; elitists and linear fitness scaling to the gene population. A differential evolution (DE) operator that provides a source of directed mutation and new wavelet operators are proposed. Using properly tuned parameters for DE, the meta-algorithm is used to solve a waveform matching problem. Tuning allows either a greedy directed search near the best known solution or a robust search across the entire parameter space.

The evolutionary basis for differences between the immune systems of man, mouse, pig and ruminants

Studying the pathogenesis of an infectious disease like colibacillosis requires an understanding of the responses of target hosts to the organism both as a pathogen and as a commensal. The mucosal immune system constitutes the primary line of defence against luminal micro-organisms. The immunoglobulin-superfamily-based adaptive immune system evolved in the earliest jawed vertebrates, and the adaptive and innate immune system of humans, mice, pigs and ruminants co-evolved in common ancestors for approximately 300 million years. The divergence occurred only 100 mya and, as a consequence, most of the fundamental immunological mechanisms are very similar. However, since pressure on the immune system comes from rapidly evolving pathogens, immune systems must also evolve rapidly to maintain the ability of the host to survive and reproduce. As a consequence, there are a number of areas of detail where mammalian immune systems have diverged markedly from each other, such that results obtained in one species are not always immediately transferable to another. Thus, animal models of specific diseases need to be selected carefully, and the results interpreted with caution. Selection is made simpler where specific host species like cattle and pigs can be both target species and reservoirs for human disease, as in infections with Escherichia coli.

An evolutionary innovation perspective on the selection of low and zero carbon technologies in new housing

The Code for Sustainable Homes (the Code) will require new homes in the United Kingdom to be ‘zero carbon’ from 2016. Drawing upon an evolutionary innovation perspective, this paper contributes to a gap in the literature by investigating which low and zero carbon technologies are actually being used by house builders, rather than the prevailing emphasis on the potentiality of these technologies. Using the results from a questionnaire three empirical contributions are made. First, house builders are selecting a narrow range of technologies. Second, these choices are made to minimise the disruption to their standard design and production templates (SDPTs). Finally, the coalescence around a small group of technologies is expected to intensify with solar-based technologies predicted to become more important. This paper challenges the dominant technical rationality in the literature that technical efficiency and cost benefits are the primary drivers for technology selection. These drivers play an important role but one which is mediated by the logic of maintaining the SDPTs of the house builders. This emphasises the need for construction diffusion of innovation theory to be problematized and developed within the context of business and market regimes constrained and reproduced by resilient technological trajectories.

Good machine performance in Turing’s imitation game

In this paper we consider transcripts which originated from a practical series of Turing’s Imitation Game which was held on 23rd June 2012 at Bletchley Park, England. In some cases the tests involved a 3-participant simultaneous comparison of two hidden entities whereas others were the result of a direct 2-participant interaction. Each of the transcripts considered here resulted in a human interrogator being fooled, by a machine, into concluding that they had been conversing with a human. Particular features of the conversation are highlighted, successful ploys on the part of each machine discussed and likely reasons for the interrogator being fooled are considered. Subsequent feedback from the interrogators involved is also included

Game-theoretic aspects of international mergers: Theory and case studies

This paper studies the exclusion of potential competition as a motivating factor for international mergers. We propose a simple game-theoretic framework in order to discuss the conditions under which mergers that prevent reciprocal domestic competition will occur. Our analysis highlights the shortcomings of antitrust policies based on pre-merger/post-merger concentration comparisons. A review of several recent European cases suggests that actual merger policy often fails to consider potential competition.

Evolutionary and revolutionary effects of transcomputation

Mathematics in Defence 2011 Abstract. We review transreal arithmetic and present transcomplex arithmetic. These arithmetics have no exceptions. This leads to incremental improvements in computer hardware and software. For example, the range of real numbers, encoded by floating-point bits, is doubled when all of the Not-a-Number(NaN) states, in IEEE 754 arithmetic, are replaced with real numbers. The task of programming such systems is simplified and made safer by discarding the unordered relational operator,leaving only the operators less-than, equal-to, and greater than. The advantages of using a transarithmetic in a computation, or transcomputation as we prefer to call it, may be had by making small changes to compilers and processor designs. However, radical change is possible by exploiting the reliability of transcomputations to make pipelined dataflow machines with a large number of cores. Our initial designs are for a machine with order one million cores. Such a machine can complete the execution of multiple in-line programs each clock tick

An experiment on subjective game valuations

We report experimental results on a prisoners' dilemma implemented in a way which allows us to elicit incentive−compatible valuations of the game. We test the hypothesis that players' valuations coincide with their Nash equilibrium earnings. Our results offer significantly less support for this hypothesis than for the prediction of Dominant Strategy (DS) play.

The Kasparov-World Game

Kasparov-World, initiated by Microsoft and also sponsored by First USA, was a novel correspondence game played on the World Wide Web at one ply per day. This was the first time that any group had attempted to form on the Web and then solve shared problems against fixed, short-term deadlines. The first author first became involved in his role as a Web consultant, observing the dynamics and effectiveness of the group. These are fully described, together with observations on the technological contribution and the second author's post-hoc computation of some relevant Endgame Tables.

Motherhood, evolutionary psychology and mirror neurons or: ‘Grammar is politics by other means’

Through a close analysis of socio-biologist Sarah Blaffer Hrdy’s work on motherhood and ‘mirror neurons’ it is argued that Hrdy’s claims exemplify how research that ostensibly bases itself on neuroscience, including in literary studies ‘literary Darwinism’, relies after all not on scientific, but on political assumptions, namely on underlying, unquestioned claims about the autonomous, transparent, liberal agent of consumer capitalism. These underpinning assumptions, it is further argued, involve the suppression or overlooking of an alternative, prior tradition of feminist theory, including feminist science criticism.

The ebbing hegemon? An evolutionary perspective on the emergence of holistic governance and the efficient role of Institutional Investors in Environmental, Social and Governance issues (ESG)

This paper seeks to chronicle the roots of corporate governance form its narrow shareholder perspective to the current bourgeoning stakeholder approach while giving cognizance to institutional investors and their effective role in ESG in light of the King Report III of South Africa. It is aimed at a critical review of the extant literature from the shareholder Cadbury epoch to the present day King Report novelty. We aim to: (i) offer an analytical state of corporate governance in the Anglo-Saxon world, Middle East and North Africa (MENA), Far East Asia and Africa; and (ii) illuminate the lead role the king Report of South Africa is playing as the bellwether of the stakeholder approach to corporate governance as well as guiding the role of institutional investors in ESG.

Impact of game bird release on the Adonis blue butterfly Polyommatus bellargus (Lepidoptera Lycaenidae) on chalk grassland

Polyommatus bellargus is a priority species of butterfly in the UK as a result of its scarcity and the rate of population decline over the last few years. In the UK, the species is associated with chalk grassland on hot, south-facing slopes suitable for the growth of the food plant Hippocrepis comosa. Shooting game birds is a popular pastime in the UK. Over 40 million game birds, principally Phasianus colchicus and Alectoris rufa, are bred and released into the countryside each year for shooting interests. There is a concern that the release of such a large number of non-native birds has an adverse effect on native wildlife. A study was carried out over a period of 3 years out to examine whether there was any evidence that A. rufa released into chalk grassland habitat negatively affects populations of P. bellargus. A comparison was made between sites where large numbers of A. rufa were released versus sites where no, or few, birds were released. The study involved the construction of exclosures in these sites to allow an examination of the number of butterflies emerging from H. comosa when the birds were excluded versus when the birds had free range across the area. Where birds were present the on-site vegetation was shorter than where they were absent indicating that the birds were definitely influencing habitat structure. However, the evidence that A. rufa was negatively influencing the number of adult butterflies emerging was not strong, although there was a largely non-significant tendency for higher butterfly emergence when the birds were excluded or absent.