Evolution of virulence: triggering host inflammation allows invading pathogens to exclude competitors.

Virulence is generally considered to benefit parasites by enhancing resource-transfer from host to pathogen. Here, we offer an alternative framework where virulent immune-provoking behaviours and enhanced immune resistance are joint tactics of invading pathogens to eliminate resident competitors (transferring resources from resident to invading pathogen). The pathogen wins by creating a novel immunological challenge to which it is already adapted. We analyse a general ecological model of 'proactive invasion' where invaders not adapted to a local environment can succeed by changing it to one where they are better adapted than residents. However, the two-trait nature of the 'proactive' strategy (provocation of, and adaptation to environmental change) presents an evolutionary conundrum, as neither trait alone is favoured in a homogenous host population. We show that this conundrum can be resolved by allowing for host heterogeneity. We relate our model to emerging empirical findings on immunological mediation of parasite competition

The Evolutionary Dynamics of a Rapidly Mutating Virus within and between Hosts: The Case of Hepatitis C Virus

Many pathogens associated with chronic infections evolve so rapidly that strains found late in an infection have little in common with the initial strain. This raises questions at different levels of analysis because rapid within-host evolution affects the course of an infection, but it can also affect the possibility for natural selection to act at the between-host level. We present a nested approach that incorporates within-host evolutionary dynamics of a rapidly mutating virus (hepatitis C virus) targeted by a cellular cross-reactive immune response, into an epidemiological perspective. The viral trait we follow is the replication rate of the strain initiating the infection. We find that, even for rapidly evolving viruses, the replication rate of the initial strain has a strong effect on the fitness of an infection. Moreover, infections caused by slowly replicating viruses have the highest infection fitness (i.e., lead to more secondary infections), but strains with higher replication rates tend to dominate within a host in the long-term. We also study the effect of cross-reactive immunity and viral mutation rate on infection life history traits. For instance, because of the stochastic nature of our approach, we can identify factors affecting the outcome of the infection (acute or chronic infections). Finally, we show that anti-viral treatments modify the value of the optimal initial replication rate and that the timing of the treatment administration can have public health consequences due to within-host evolution. Our results support the idea that natural selection can act on the replication rate of rapidly evolving viruses at the between-host level. It also provides a mechanistic description of within-host constraints, such as cross-reactive immunity, and shows how these constraints affect the infection fitness. This model raises questions that can be tested experimentally and underlines the necessity to consider the evolution of quantitative traits to understand the outcome and the fitness of an infection

'Well London' and the benefits of participation: results of a qualitative study nested in a cluster randomised trial

Background: Well London is a multicomponent community engagement and coproduction programme designed to improve the health of Londoners living in socioeconomically deprived neighbourhoods. To evaluate outcomes of the Well London interventions, a cluster randomised trial (CRT) was conducted that included a longitudinal qualitative component, which is reported here. The aim is to explore in depth the nature of the benefits to residents and the processes by which these were achieved. Methods: The 1-year longitudinal qualitative study was nested within the CRT. Purposive sampling was used to select three intervention neighbourhoods in London and 61 individuals within these neighbourhoods. The interventions comprised activities focused on: healthy eating, physical exercise and mental health and well-being. Interviews were conducted at the inception and following completion of the Well London interventions to establish both if and how they had participated. Transcripts of the interviews were coded and analysed using Nvivo. Results: Positive benefits relating to the formal outcomes of the CRT were reported, but only among those who participated in project activities. The extent of benefits experienced was influenced by factors relating to the physical and social characteristics of each neighbourhood. The highest levels of change occurred in the presence of: (1) social cohesion, not only pre-existing but also as facilitated by Well London activities; (2) personal and collective agency; (3) involvement and support of external organisations. Where the physical and social environment remained unchanged, there was less participation and fewer benefits. Conclusions: These findings show interaction between participation, well-being and agency, social interactions and cohesion and that this modulated any benefits described. Pathways to change were thus complex and variable, but personal well-being and local social cohesion emerged as important mediators of change

Modelling Stochastic and Deterministic Behaviours in Virus Infection Dynamics

Many human infections with viruses such as human immunodeficiency virus type 1 (HIV--1) are characterized by low numbers of founder viruses for which the random effects and discrete nature of populations have a strong effect on the dynamics, e.g., extinction versus spread. It remains to be established whether HIV transmission is a stochastic process on the whole. In this study, we consider the simplest (so-called, 'consensus') virus dynamics model and develop a computational methodology for building an equivalent stochastic model based on Markov Chain accounting for random interactions between the components. The model is used to study the evolution of the probability densities for the virus and target cell populations. It predicts the probability of infection spread as a function of the number of the transmitted viruses. A hybrid algorithm is suggested to compute efficiently the dynamics in state space domain characterized by a mix of small and large species densities

Limited role of spatial selfstructuring in emergent trade-offs during pathogen evolution

Pathogen transmission and virulence are main evolutionary variables broadly assumed to be linked through trade-offs. In well-mixed populations, these trade-offs are often ascribed to physiological restrictions, while populations with spatial self-structuring might evolve emergent trade-offs. Here, we reexamine a spatially-explicit, SIR model of the latter kind proposed by Ballegooijen and Boerlijst with the aim of characterising the mechanisms causing the emergence of the trade-off and its structural robustness. Using invadability criteria, we establish the conditions under which an evolutionary feedback between transmission and virulence mediated by pattern formation can poise the system to a critical boundary separating a disordered state (without emergent trade-off) from a self-structured phase (where the trade-off emerges), and analytically calculate the functional shape of the boundary in a certain approximation. Beyond evolutionary parameters, the success of an invasion depends on the size and spatial structure of the invading and invaded populations. Spatial self-structuring is often destroyed when hosts are mobile, changing the evolutionary dynamics to those of a well-mixed population. In a metapopulation scenario, the systematic extinction of the pathogen in the disordered phase may counteract the disruptive effect of host mobility, favour pattern formation and therefore recover the emergent trade-off.This work has been supported by the Spanish Ministerio de Economía, Industria y Competitividad and FEDER funds of the EU through grants ViralESS (FIS2014-57686-P and FIS2017-84256-P). The internship of VB was financed by the Severo Ochoa Centers of Excellence Program (SEV-2013-0347)

InP based lasers and optical amplifiers with wire-/dot-like active regions

Long wavelength lasers and semiconductor optical amplifiers based on InAs quantum wire-/dot-like active regions were developed on InP substrates dedicated to cover the extended telecommunication wavelength range between 1.4 and 1.65 mu m. In a brief overview different technological approaches will be discussed, while in the main part the current status and recent results of quantum-dash lasers are reported. This includes topics like dash formation and material growth, device performance of lasers and optical amplifiers, static and dynamic properties and fundamental material and device modelin

Measures of exposure to the Well London Phase-1 intervention and their association with health well-being and social outcomes

In this paper, we describe the measures of intervention exposure used in the cluster randomised trial of the Well London programme, a public health intervention using community engagement and community-based projects to increase physical activity, healthy eating and mental health and well-being in 20 of the most deprived neighbourhoods in London.10 No earmarked resources to support the development of these measures and associated data collection were provided to either the research team or to those delivering the interventions on the ground. Instead, these were derived from contractually specified performance management information reported quarterly by partners and by inclusion of questions seeking information about participation in the follow-up questionnaires used to measure the main trial outcomes. The exposure measures are consequently considerably less sophisticated than those used in the US studies, where earmarked funding was available

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Network theory may explain the vulnerability of medieval human settlements to the Black Death pandemic

Epidemics can spread across large regions becoming pandemics by flowing along transportation and social networks. Two network attributes, transitivity (when a node is connected to two other nodes that are also directly connected between them) and centrality (the number and intensity of connections with the other nodes in the network), are widely associated with the dynamics of transmission of pathogens. Here we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. We found that, after controlling for the city spatial location and the disease arrival time, cities with higher values of both centrality and transitivity were more severely affected by the plague. A simulation study indicates that this association was due to central cities with high transitivity undergo more exogenous re-infections. Our study provides an easy method to identify hotspots in epidemic networks. Focusing our effort in those vulnerable nodes may save time and resources by improving our ability of controlling deadly epidemics

The evolution of sex-specific virulence in infectious diseases

Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females