Biomedical subjects
Publications and source records attributed to S J Cox.
We use the Surface Evolver to determine the shear modulus G of a dry 2D foam of 2500 bubbles, using both extensional and simple shear. We examine G for a range of monodisperse, bidisperse and polydisperse foams, and relate it to various measures of the structural disorder of each foam. In all cases, the shear modulus of a foam decreases with increasing disorder.
Previous work, in sheep vaccinated with emergency foot-and-mouth disease (FMD) vaccine, indicated the benefit of increasing the antigen payload in inhibiting local virus replication and consequently persistence following an indirect aerosol challenge with a virus homologous to the vaccine strain. The work presented here investigates this possibility further using cattle and a more severe semi-heterologous direct contact challenge. The quantitative dynamics of virus replication and excretion in both vaccinated and non-vaccinated cattle following challenge are examined. Two experiments were carried out each involving 20 vaccinated and 5 non-vaccinated cattle. An O(1) Manisa vaccine (18 PD(50)) was used for the first, previously reported experiment [Cox SJ, Voyce C, Parida S, Reid SM, Hamblin PA, Paton DJ, et al. Protection against direct contact challenge following emergency FMD vaccination of cattle and the effect on virus excretion from the oropharynx. Vaccine 2005;23:1106-13]. The same vaccine was used for the second experiment described in this paper except the antigen payload was increased 10-fold per bovine dose, resulting in significantly higher FMD virus neutralising antibody titres prior to challenge. Twenty-one days post-vaccination the cattle received a 5-day direct contact challenge with FMD virus from five further non-vaccinated cattle infected 24h earlier with O UKG 34/2001. All vaccinated cattle regardless of antigen payload were protected against clinical disease. Sub-clinical oropharyngeal infection was detected in animals from both experiments but the level of virus replication shortly after direct contact challenge was significantly reduced in vaccinated animals. Cattle immunised with the 10-fold antigen payload cleared the virus more readily and consequently at 28 days post-challenge fewer animals were persistently infected compared to the single strength vaccine. Following a severe challenge, the results from both experiments show that use of emergency vaccine can prevent or decrease local virus replication and thereby dramatically reduce the amount of virus released into the environment, particularly during the early post-exposure period. Additionally, increasing the antigen payload of the vaccine may reduce sub-clinical infection, leading to fewer persistently infected virus carrier animals.
When liquid is added to a foam at sufficiently large flow rates, convective bubble motion will occur. Experiments are described in which the foam is confined in a tube which is tilted from the vertical. The theory of foam drainage is applied to this problem to show that the critical angle of tilt theta(c) at which convection occurs is related to the liquid flow-rate Q by theta(c) proportional to Q(-3/4).
Detection of antibodies to the non-structural proteins (NSP) of foot-and-mouth disease virus (FMDV) was compared with conventional serological and virological methods and with RT-PCR for the identification of FMDV carrier animals obtained after experimental contact challenge of vaccinated cattle. Transmission from carriers to sentinels was also monitored. Twenty FMDV vaccinated and five unvaccinated cattle were challenged by direct contact with five donor cattle excreting FMDV and monitored until 28 days post challenge-exposure . Twelve vaccinated and three unvaccinated animals were retained up to 24 weeks post exposure to FMDV in order to monitor viral persistence, transmission and antibody responses. In nine vaccinated animals, infection persisted beyond 28 days post exposure, virus being detected more frequently and for longer in oesophagopharyngeal samples from these animals when examined by RT-PCR rather than by virus isolation. Although recovery of FMDV RNA became increasingly sporadic over time, the number of RNA copies detected in positive samples declined only slowly. Two naïve sentinel cattle housed with the persistently infected animals between 93 and 168 days after the latter had been challenge-exposed to FMDV did not become infected. There were differences in the ability of commercially available serological tests to detect antibodies to FMDV non-structural proteins (NSP) in vaccinated and subsequently challenged cattle. Although no single test could identify all of the vaccinated cattle that became persistently infected, the most poorly recognised animals were those with the least evidence of virus replication based on other tests. The potential of the detection of antibodies to the 2B NSP of FMDV for diagnosing persistent FMDV infection was demonstrated.
Studies were performed to determine whether a rapid method to detect cell mediated immune responses to foot-and-mouth disease virus (FMDV) could be used either as a diagnostic test or provide a correlate of protection in animals post-vaccination. Using protocols based on the BOVIGAM assay for tuberculosis, whole blood samples from FMDV vaccinated or control animals, before and after challenge infection, were stimulated overnight with inactivated FMDV antigen. The quantity of interferon gamma (IFN-gamma) produced in the supernatants was measured using an ELISA. Specific induction of IFN-gamma was detected in samples from vaccinated, infected and vaccinated-then-infected cattle. Further development of this assay may provide a useful tool for the diagnosis of FMDV immune animals, including the identification of vaccinated animals that have been subsequently infected with FMDV. In these studies, combining the results of the IFN-gamma assay with virus neutralising antibody titre, in groups of vaccinated animals, provided a correlation with the capacity to control virus replication after subsequent challenge.
The ability of emergency foot-and-mouth disease (FMD) vaccine to protect cattle from a heterologous direct-contact challenge and the effect on virus excretion from the oropharynx were examined. An oil adjuvant O1 Manisa FMD vaccine protected 20 cattle from clinical disease following 5 days of direct-contact exposure to five infected cattle at 21 days post vaccination. The donor cattle had been infected by tongue inoculation with a different FMD virus of the same serotype (O UKG 2001). Protection from clinical disease did not prevent localised sub-clinical infection at the oropharynx in most animals, although quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the level of virus replication shortly after direct-contact challenge was greatly reduced in vaccinated animals. Nevertheless, 45% of the vaccinated cattle became persistently infected with 10(3)-10(6) RNA copies per millilitre of oropharyngeal fluid at 28 days post challenge. However, since live virus could not be readily isolated, the risk of these animals transmitting disease was probably very low. The findings show that even after an extremely severe challenge, use of an emergency vaccine will prevent or reduce local virus replication and thereby dramatically reduce the amount of virus released into the environment in the all-important early post-exposure period. These data should help to model the dynamics of virus transmission in future outbreaks of disease where vaccination is considered.
The specificity and sensitivity of an ELISA for detecting IgG to the 3ABC non-structural protein of foot-and-mouth disease (FMD) virus was evaluated in FMD naive, aerosol-infected, aerosol plus direct contact infected and field-exposed sheep. All 12 sheep that were experimentally infected without prior vaccination seroconverted in the test, although fewer field sera from FMD-exposed sheep were scored seropositive compared to test results for structural protein antibodies. The 3ABC test specificity was 98 or 100% according to whether sera reacting in the doubtful range were scored as positive or negative. The test was then used to investigate the antibody response of sheep vaccinated against FMD and exposed to the virus by an aerosol challenge 4-14 days later. The response of individual animals varied. Whether immunised with high or low doses of vaccine, the development of 3ABC antibody was most likely in sheep from which live virus was recovered at or beyond 9 days post-challenge. Non-structural responses were also more frequent in animals from which multiple incidences of live FMD virus isolation (perhaps more indicative of true virus replication) were demonstrated.
The two-dimensional viscous froth model is a simple tractable model for foam rheology and coarsening. It includes, but is not confined to, the quasistatic regime. Here we present a detailed analysis and implementation of the model, illustrated with various examples. With certain simplifying assumptions, it provides significant insight into strain-rate-dependent effects in foam rheology and elsewhere, particularly in relation to recent experiments.
We consider three-dimensional clusters of equal-volume bubbles packed around a central bubble and calculate their energy and optimal shape. We obtain the surface area and bubble pressures to improve on existing growth laws for three-dimensional bubble clusters. We discuss the possible number of bubbles that can be packed around a central one: the "kissing problem," here adapted to deformable objects.
The ability of a single administration of a high, medium and low potency foot-and-mouth disease (FMD) vaccine to decrease or inhibit local virus replication and excretion in the oropharynx of sheep following aerosol challenge with homologous live virus 14 days later was examined. Unvaccinated sheep showed signs of clinical FMD, whereas all of the vaccinated sheep, regardless of antigen payload, were protected against clinical disease and development of viraemia. Virological and serological results confirmed that there had been no local virus replication in the oropharynx of sheep from the high potency vaccine group in contrast to moderate or substantial virus replication in the oropharynx of the low potency vaccinated or unvaccinated sheep respectively. The vaccines showed no evidence of promoting a local mucosal antibody response at the time of virus challenge, but were capable of stimulating a systemic gamma interferon response, the level of which was related to the antigen payload. This suggests that the systemic gamma interferon response could be a useful indicator of the ability of a FMD vaccine to elicit a sterile immunity and indicates that further work is warranted to investigate the role of systemic gamma interferon in this immunity. This is the first experiment to clearly show that high potency, high payload, FMD vaccines are capable of inhibiting local virus replication and consequently persistence and the carrier state in this target species.
The frozen niche variation hypothesis proposes that asexual clones exploit a fraction of a total resource niche available to the sexual population from which they arise. Differences in niche breadth may allow a period of coexistence between a sexual population and the faster reproducing asexual clones. Here, we model the longer term threat to the persistence of the sexual population from an accumulation of clonal diversity, balanced by the cost to the asexual population resulting from a faster rate of accumulation of deleterious mutations. We use Monte-Carlo simulations to quantify the interaction of niche breadth with accumulating deleterious mutations. These two mechanisms may act synergistically to prevent the extinction of the sexual population, given: (1) sufficient genetic variation, and consequently niche breadth, in the sexual population; (2) a relatively slow rate of accumulation of genetic diversity in the clonal population; (3) synergistic epistasis in the accumulation of deleterious mutations.
The ability of high potency emergency foot-and-mouth disease (FMD) vaccines to promote sustainable immune responses in sheep and pigs following a single application was examined. All vaccine formulations induced a rapid seroconversion in both species, as expected, which was maintained at near peak titres for up to 6 months in sheep and 7 months in pigs. The Montanide ISA 206 formulation gave the best results in sheep. Vaccinated pigs challenged with homologous FMDV were protected from disease at 7 months post vaccination. Systemic levels of cytokines IL-6, IL-8, and in some pigs IL-12, increased following vaccination and were often maintained at an increased level for the duration of the trials. These initial results suggest that high potency vaccines may promote longer lasting immunity than the conventional lower potency vaccines in ruminants and a comparable response in pigs. Results indicate that in an outbreak situation, should emergency vaccination be done with these high potency vaccines, protection should be conferred for a long enough period for the outbreak to be brought under control without the need to revaccinate. Given the increased interval for re-vaccination the use of high potency vaccines for routine prophylactic campaigns could provide a more cost-effective and efficient means of maintaining herd immunity and is an area thus worthy of further examination.
Experiments on a small cluster of bubbles in a nominally two-dimensional foam show an instability in which a topological change forces one of the bubbles to be ejected to the outside of the cluster at a point where this is not predicted by a two-dimensional model of a foam. This is interpreted in terms of the energy of the initial and ejected states and of the finite liquid content of the experimental system. A description of the distribution of liquid in various experimental set-ups suggests that the exact response may depend critically upon the type of system used. This is demonstrated experimentally with reference to small clusters of bubbles undergoing a single topological change.
The ability of an emergency oil adjuvanted foot-and-mouth disease (FMD) vaccine to elicit early protective immunity in pigs against direct contact homologous challenge was examined. All vaccinates showed reduced viraemia and shedding of FMDV, and certain animals were protected, showing no clinical signs. IL-6, IL-8 and IL-12 were consistently detected in challenged animals that had been vaccinated. Other cytokines--IL-1, IL-2, TNF, TGF and interferons--were not detected. This demonstrates that the vaccine did not induce a systemic inflammatory response, nor a systemic elevation of T lymphocyte activity. Although the IL-6 and IL-8 did not relate to protection, IL-12 production was highest in the protected vaccinated pigs. Thus, the induction of monocytic cell activity, demonstrable by the production of IL-6, IL-8 and IL-12, appears to play a critical role in FMDV emergency vaccine induction of the innate immune defences which relate to early protection against FMD. The possible modes of defence in which such cytokine activity would be involved are discussed.
The excitable nature of a biological cell is manifested in the many voltage gated ion channels that perforate its membrane. The forms of the associated ionic currents, and in particular the functions that govern their kinetics, permit one to distinguish, electrophysiologically, between various cell types. We show, in the context of FitzHugh-Nagumo and Morris-Lecar models and without recourse to voltage or space clamping, that such currents and kinetics may be stably inferred from a cell's voltage response to a specified input current.
Adaptive mesh refinement techniques can be applied to increase the efficiency of electrical impedance tomography reconstruction algorithms by reducing computational and storage cost as well as providing problem-dependent solution structures. A self-adaptive refinement algorithm based on an a posteriori error estimate has been developed and its results are shown in comparison with uniform mesh refinement for a simple head model.
Why sex prevails in nature remains one of the great puzzles of evolution. Sexual reproduction has an immediate cost relative to asexual reproduction, as males only express their contribution to population growth through females. With no males to sustain, an asexual mutant can double its relative representation in the population in successive generations. This is the widely accepted 'twofold cost of males'. Many studies have attempted to explain how sex can recoup this cost from fitness benefits associated with the recombination of parental genotypes, but these require complex biological environments that cycle over evolutionary timescales. In contrast, we have considered the ecological dynamics that govern asexual invasion. Here we show the existence of a threshold growth rate for the sexual population, above which the invasion is halted by intraspecific competition. The asexual population then exerts a weaker inhibitory effect on the carrying capacity of the sexual population than on its own carrying capacity. The stable outcome of this is coexistence on a depleted resource base. Under these ecological circumstances, longer-term benefits of sex may eventually drive out the asexual competitor.
We show that the first five moments of the soma potential and soma current uniquely and stably determine the soma conductance and capacitance and the dendritic electrotonic length, conductance, and capacitance in the so-called somatic shunt model of the passive behavior of a neuron. We test our resulting input admittance algorithm on synthetic data and demonstrate the regularizing effect of knowledge of the ratio of soma to dendrite surface areas.