Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Exploring the effects of replicating shape, weight and recoil effects on VR shooting controllers

Commercial Virtual Reality (VR) controllers with realistic force feedback are becoming available, to increase the realism and immersion of first-person shooting (FPS) games in VR. These controllers attempt to mimic not only the shape and weight of real guns but also their recoil effects (linear force feedback parallel to the barrel, when the gun is shot). As these controllers become more popular and affordable, this paper investigates the actual effects that these properties (shape, weight, and especially directional force feedback) have on performance for general VR users (e.g. users with no marksmanship experience), drawing conclusions for both consumers and device manufacturers. We created a prototype replicating the properties exploited by commercial VR controllers (i.e. shape, weight and adjustable force feedback) and used it to assess the effect of these parameters in user performance, across a series of user studies. We first analysed the benefits on user performance of adding weight and shape vs a conventional controller (e.g. Vive controller). We then explore the implications of adding linear force feedback (LFF), as well as replicating the shape and weight. Our studies show negligible effects on the immediate shooting performance with some improvements in subjective appreciation, which are already present with low levels of LFF. While higher levels of LFF do not increase subjective appreciations any further, they lead users to reach their maximum distance skillset more quickly. This indicates that while adding low levels of LFF can be enough to influence user’s immersion/engagement for gaming contexts, controllers with higher levels of LFF might be better suited for training environments and/or when dealing with particularly demanding aiming tasks

Dendritic Cells Transduced to Express Interleukin 4 Reduce Diabetes Onset in Both Normoglycemic and Prediabetic Nonobese Diabetic Mice

Background: We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown. Methodology/Principal Findings: DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 106 DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals. Conclusions: Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D. © 2010 Ruffner, Robbins

In Situ-Targeting of Dendritic Cells with Donor-Derived Apoptotic Cells Restrains Indirect Allorecognition and Ameliorates Allograft Vasculopathy

Chronic allograft vasculopathy (CAV) is an atheromatous-like lesion that affects vessels of transplanted organs. It is a component of chronic rejection that conventional immuno-suppression fails to prevent, and is a major cause of graft loss. Indirect allo-recognition through T cells and allo-Abs are critical during CAV pathogenesis. We tested whether the indirect allo-response and its impact on CAV is down-regulated by in situ-delivery of donor Ags to recipient's dendritic cells (DCs) in lymphoid organs in a pro-tolerogenic fashion, through administration of donor splenocytes undergoing early apoptosis. Following systemic injection, donor apoptotic cells were internalized by splenic CD11chi CD8α+ and CD8− DCs, but not by CD11cint plasmacytoid DCs. Those DCs that phagocytosed apoptotic cells in vivo remained quiescent, resisted ex vivo-maturation, and presented allo-Ag for up to 3 days. Administration of donor apoptotic splenocytes, unlike cells alive, (i) promoted deletion, FoxP3 expression and IL-10 secretion, and decreased IFN-γ-release in indirect pathway CD4 T cells; and (ii) reduced cross-priming of anti-donor CD8 T cells in vivo. Targeting recipient's DCs with donor apoptotic cells reduced significantly CAV in a fully-mismatched aortic allograft model. The effect was donor specific, dependent on the physical characteristics of the apoptotic cells, and was associated to down-regulation of the indirect type-1 T cell allo-response and secretion of allo-Abs, when compared to recipients treated with donor cells alive or necrotic. Down-regulation of indirect allo-recognition through in situ-delivery of donor-Ag to recipient's quiescent DCs constitutes a promising strategy to prevent/ameliorate indirect allorecognition and CAV

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Thermal Properties of Carbon Nanotube–Copper Composites for Thermal Management Applications

Carbon nanotube–copper (CNT/Cu) composites have been successfully synthesized by means of a novel particles-compositing process followed by spark plasma sintering (SPS) technique. The thermal conductivity of the composites was measured by a laser flash technique and theoretical analyzed using an effective medium approach. The experimental results showed that the thermal conductivity unusually decreased after the incorporation of CNTs. Theoretical analyses revealed that the interfacial thermal resistance between the CNTs and the Cu matrix plays a crucial role in determining the thermal conductivity of bulk composites, and only small interfacial thermal resistance can induce a significant degradation in thermal conductivity for CNT/Cu composites. The influence of sintering condition on the thermal conductivity depended on the combined effects of multiple factors, i.e. porosity, CNTs distribution and CNT kinks or twists. The composites sintered at 600°C for 5 min under 50 MPa showed the maximum thermal conductivity. CNT/Cu composites are considered to be a promising material for thermal management applications

Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians

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