Trigger Point Injections for Headache Disorders: Expert Consensus Methodology and Narrative Review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109332/1/head12442.pd

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Identification of Salmonella enterica Serovar Dublin-Specific Sequences by Subtractive Hybridization and Analysis of Their Role in Intestinal Colonization and Systemic Translocation in Cattle

Salmonella enterica serovar Dublin is a host-restricted serovar associated with typhoidal disease in cattle. In contrast, the fowl-associated serovar S. enterica serovar Gallinarum is avirulent in calves, yet it invades ileal mucosa and induces enteritis at levels comparable to those induced by S. enterica serovar Dublin. Suppression subtractive hybridization was employed to identify S. enterica serovar Dublin strain SD3246 genes absent from S. enterica serovar Gallinarum strain SG9. Forty-one S. enterica serovar Dublin fragments were cloned and sequenced. Among these, 24 mobile-element-associated genes were identified, and 12 clones exhibited similarity with sequences of known or predicted function in other serovars. Three S. enterica serovar Dublin-specific regions were homologous to regions from the genome of Enterobacter sp. strain 638. Sequencing of fragments adjacent to these three sequences revealed the presence of a 21-kb genomic island, designated S. enterica serovar Dublin island 1 (SDI-1). PCR analysis and Southern blotting showed that SDI-1 is highly conserved within S. enterica serovar Dublin isolates but rarely found in other serovars. To probe the role of genes identified by subtractive hybridization in vivo, 24 signature-tagged S. enterica serovar Dublin SD3246 mutants lacking loci not present in Salmonella serovar Gallinarum SG9 were created and screened by oral challenge of cattle. Though attenuation of tagged SG9 and SD3246 Salmonella pathogenicity island-1 (SPI-1) and SPI-2 mutant strains was detected, no obvious defects of these 24 mutants were detected. Subsequently, a DeltaSDI-1 mutant was found to exhibit weak but significant attenuation compared with the parent strain in coinfection of calves. SDI-1 mutation did not impair invasion, intramacrophage survival, or virulence in mice, implying that SDI-1 does not influence fitness per se and may act in a host-specific manner

The role of caretakers in disease dynamics

One of the key challenges in modeling the dynamics of contagion phenomena is to understand how the structure of social interactions shapes the time course of a disease. Complex network theory has provided significant advances in this context. However, awareness of an epidemic in a population typically yields behavioral changes that correspond to changes in the network structure on which the disease evolves. This feedback mechanism has not been investigated in depth. For example, one would intuitively expect susceptible individuals to avoid other infecteds. However, doctors treating patients or parents tending sick children may also increase the amount of contact made with an infecteds, in an effort to speed up recovery but also exposing themselves to higher risks of infection. We study the role of these caretaker links in an adaptive network models where individuals react to a disease by increasing or decreasing the amount of contact they make with infected individuals. We find that pure avoidance, with only few caretaker links, is the best strategy for curtailing an SIS disease in networks that possess a large topological variability. In more homogeneous networks, disease prevalence is decreased for low concentrations of caretakers whereas a high prevalence emerges if caretaker concentration passes a well defined critical value.Comment: 8 pages, 9 figure

Modelling the Influence of Foot-and-Mouth Disease Vaccine Antigen Stability and Dose on the Bovine Immune Response

Foot and mouth disease virus causes a livestock disease of significant global socio-economic importance. Advances in its control and eradication depend critically on improvements in vaccine efficacy, which can be best achieved by better understanding the complex within-host immunodynamic response to inoculation. We present a detailed and empirically parametrised dynamical mathematical model of the hypothesised immune response in cattle, and explore its behaviour with reference to a variety of experimental observations relating to foot and mouth immunology. The model system is able to qualitatively account for the observed responses during in-vivo experiments, and we use it to gain insight into the incompletely understood effect of single and repeat inoculations of differing dosage using vaccine formulations of different structural stability

Beers and blurred boundaries: The spatial and gendered organisation of pre-match venues for English football fans

Academic research into sports fans has grown in recent years with studies examining a variety of aspects associated with fandom. However, recent changes in the professionalisation and commercialisation of sport have resulted in the creation of new spaces for fan experiences. In this article, we examine one of these created spaces, the fan zone. Through a case study on matchgoing fans from Everton Football Club we explore how this new space sits alongside traditional pre-match gathering places such as the ?pub? and examine the gendered organisation of these spaces. Drawing on Bale?s concept of boundaries within sports fan communities we show that traditional venues for pre-match activities enhance, maintain and legitimise masculine boundaries within sports fandom. We argue that fan zones provide an alternative match day atmosphere and experience that is centred on a family-friendly or at least family-inclusive culture

Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals