Skeletally Dugundji spaces

We introduce and investigate the class of skeletally Dugundji spaces as a skeletal analogue of Dugundji space. The main result states that the following conditions are equivalent for a given space $X$: (i) $X$ is skeletally Dugundji; (ii) Every compactification of $X$ is co-absolute to a Dugundji space; (iii) Every $C^*$-embedding of the absolute $p(X)$ in another space is strongly $\pi$-regular; (iv) $X$ has a multiplicative lattice in the sense of Shchepin \cite{s76} consisting of skeletal maps

Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa

Multihost multiparasite systems are evolutionarily and ecologically dynamic, which presents substantial trans‐disciplinary challenges for elucidating their epidemiology and designing appropriate control. Evidence for hybridizations and introgressions between parasite species is gathering, in part in line with improvements in molecular diagnostics and genome sequencing. One major system where this is becoming apparent is within the Genus Schistosoma, where schistosomiasis represents a disease of considerable medical and veterinary importance, the greatest burden of which occurs in sub‐Saharan Africa. Interspecific hybridizations and introgressions bring an increased level of complexity over and above that already inherent within multihost, multiparasite systems, also representing an additional source of genetic variation that can drive evolution. This has the potential for profound implications for the control of parasitic diseases, including, but not exclusive to, widening host range, increased transmission potential and altered responses to drug therapy. Here, we present the challenging case example of haematobium group Schistosoma spp. hybrids in West Africa, a system involving multiple interacting parasites and multiple definitive hosts, in a region where zoonotic reservoirs of schistosomiasis were not previously considered to be of importance. We consider how existing mathematical model frameworks for schistosome transmission could be expanded and adapted to zoonotic hybrid systems, exploring how such model frameworks can utilize molecular and epidemiological data, as well as the complexities and challenges this presents. We also highlight the opportunities and value such mathematical models could bring to this and a range of similar multihost, multi and cross‐hybridizing parasites systems in our changing world

Probabilistic reconstruction of measles transmission clusters from routinely collected surveillance data.

Pockets of susceptibility resulting from spatial or social heterogeneity in vaccine coverage can drive measles outbreaks, as cases imported into such pockets are likely to cause further transmission and lead to large transmission clusters. Characterizing the dynamics of transmission is essential for identifying which individuals and regions might be most at risk. As data from detailed contact-tracing investigations are not available in many settings, we developed an R package called o2geosocial to reconstruct the transmission clusters and the importation status of the cases from their age, location, genotype and onset date. We compared our inferred cluster size distributions to 737 transmission clusters identified through detailed contact-tracing in the USA between 2001 and 2016. We were able to reconstruct the importation status of the cases and found good agreement between the inferred and reference clusters. The results were improved when the contact-tracing investigations were used to set the importation status before running the model. Spatial heterogeneity in vaccine coverage is difficult to measure directly. Our approach was able to highlight areas with potential for local transmission using a minimal number of variables and could be applied to assess the intensity of ongoing transmission in a region

Potential for large outbreaks of Ebola virus disease.

Outbreaks of Ebola virus can cause substantial morbidity and mortality in affected regions. The largest outbreak of Ebola to date is currently underway in West Africa, with 3944 cases reported as of 5th September 2014. To develop a better understanding of Ebola transmission dynamics, we revisited data from the first known Ebola outbreak, which occurred in 1976 in Zaire (now Democratic Republic of Congo). By fitting a mathematical model to time series stratified by disease onset, outcome and source of infection, we were able to estimate several epidemiological quantities that have previously proved challenging to measure, including the contribution of hospital and community infection to transmission. We found evidence that transmission decreased considerably before the closure of the hospital, suggesting that the decline of the outbreak was most likely the result of changes in host behaviour. Our analysis suggests that the person-to-person reproduction number was 1.34 (95% CI: 0.92-2.11) in the early part of the outbreak. Using stochastic simulations we demonstrate that the same epidemiological conditions that were present in 1976 could have generated a large outbreak purely by chance. At the same time, the relatively high person-to-person basic reproduction number suggests that Ebola would have been difficult to control through hospital-based infection control measures alone

Comparative Evaluation of the Hemodynamic Effects of Oral Cimetidine, Ranitidine, and Famotidine as Determined by Echocardiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90052/1/j.1875-9114.1995.tb04349.x.pd

Towards a unified generic framework to define and observe contacts between livestock and wildlife: a systematic review

Wild animals are the source of many pathogens of livestock and humans. Concerns about the potential transmission of economically important and zoonotic diseases from wildlife have led to increased surveillance at the livestock-wildlife interface. Knowledge of the types, frequency and duration of contacts between livestock and wildlife is necessary to identify risk factors for disease transmission and to design possible mitigation strategies. Observing the behaviour of many wildlife species is challenging due to their cryptic nature and avoidance of humans, meaning there are relatively few studies in this area. Further, a consensus on the definition of what constitutes a ‘contact’ between wildlife and livestock is lacking. A systematic review was conducted to investigate which livestock-wildlife contacts have been studied and why, as well as the methods used to observe each species. Over 30,000 publications were screened, of which 122 fulfilled specific criteria for inclusion in the analysis. The majority of studies examined cattle contacts with badgers or with deer; studies involving wild pig contacts with cattle or with domestic pigs were the next most frequent. There was a range of observational methods including motion-activated cameras and global positioning system collars. As a result of the wide variation and lack of consensus in the definitions of direct and indirect contacts, we developed a unified framework to define livestock-wildlife contacts that is sufficiently flexible to be applied to most wildlife and livestock species for non-vector-borne diseases. We hope this framework will help standardise the collection and reporting of contact data; a valuable step towards being able to compare the efficacy of wildlife-livestock observation methods. In doing so, it may aid the development of better disease transmission models and improve the design and effectiveness of interventions to reduce or prevent disease transmission

Canalization of the evolutionary trajectory of the human influenza virus

Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. Antigenic evolution occurs in the context of a two-dimensional 'antigenic map', while genetic evolution shows a characteristic ladder-like genealogical tree. Here, we use a large-scale individual-based model to show that evolution in a Euclidean antigenic space provides a remarkable correspondence between model behavior and the epidemiological, antigenic, genealogical and geographic patterns observed in influenza virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis. Thus, selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable and hence, in theory, predictable.Comment: 29 pages, 5 figures, 10 supporting figure

Effective suppression of Dengue virus using a novel group-I intron that induces apoptotic cell death upon infection through conditional expression of the Bax C-terminal domain

Introduction: Approximately 100 million confirmed infections and 20,000 deaths are caused by Dengue virus (DENV) outbreaks annually. Global warming and rapid dispersal have resulted in DENV epidemics in formally non-endemic regions. Currently no consistently effective preventive measures for DENV exist, prompting development of transgenic and paratransgenic vector control approaches. Production of transgenic mosquitoes refractory for virus infection and/or transmission is contingent upon defining antiviral genes that have low probability for allowing escape mutations, and are equally effective against multiple serotypes. Previously we demonstrated the effectiveness of an anti-viral group I intron targeting U143 of the DENV genome in mediating trans-splicing and expression of a marker gene with the capsid coding domain. In this report we examine the effectiveness of coupling expression of ΔN Bax to trans-splicing U143 intron activity as a means of suppressing DENV infection of mosquito cells. Results: Targeting the conserved DENV circularization sequence (CS) by U143 intron trans-splicing activity appends a 3’ exon RNA encoding ΔN Bax to the capsid coding region of the genomic RNA, resulting in a chimeric protein that induces premature cell death upon infection. TCID50-IFA analyses demonstrate an enhancement of DENV suppression for all DENV serotypes tested over the identical group I intron coupled with the non-apoptotic inducing firefly luciferase as the 3’ exon. These cumulative results confirm the increased effectiveness of this αDENV-U143-ΔN Bax group I intron as a sequence specific antiviral that should be useful for suppression of DENV in transgenic mosquitoes. Annexin V staining, caspase 3 assays, and DNA ladder observations confirm DCA-ΔN Bax fusion protein expression induces apoptotic cell death. Conclusion: This report confirms the relative effectiveness of an anti-DENV group I intron coupled to an apoptosis-inducing ΔN Bax 3’ exon that trans-splices conserved sequences of the 5’ CS region of all DENV serotypes and induces apoptotic cell death upon infection. Our results confirm coupling the targeted ribozyme capabilities of the group I intron with the generation of an apoptosis-inducing transcript increases the effectiveness of infection suppression, improving the prospects of this unique approach as a means of inducing transgenic refractoriness in mosquitoes for all serotypes of this important disease