1,910 research outputs found

    From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

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    Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, ReR_e, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase ReR_e and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of ReR_e when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

    Analogue peptides for the immunotherapy of human acute myeloid leukemia

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    Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

    Dynamics of multi-stage infections on networks

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    This paper investigates the dynamics of infectious diseases with a nonexponentially distributed infectious period. This is achieved by considering a multistage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider

    Quantitative plane-resolved crystal growth and dissolution kinetics by coupling in situ optical microscopy and diffusion models : the case of salicylic acid in aqueous solution

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    The growth and dissolution kinetics of salicylic acid crystals are investigated in situ by focusing on individual microscale crystals. From a combination of optical microscopy and finite element method (FEM) modeling, it was possible to obtain a detailed quantitative picture of dissolution and growth dynamics for individual crystal faces. The approach uses real-time in situ growth and dissolution data (crystal size and shape as a function of time) to parametrize a FEM model incorporating surface kinetics and bulk to surface diffusion, from which concentration distributions and fluxes are obtained directly. It was found that the (001) face showed strong mass transport (diffusion) controlled behavior with an average surface concentration close to the solubility value during growth and dissolution over a wide range of bulk saturation levels. The (1̅10) and (110) faces exhibited mixed mass transport/surface controlled behavior, but with a strong diffusive component. As crystals became relatively large, they tended to exhibit peculiar hollow structures in the end (001) face, observed by interferometry and optical microscopy. Such features have been reported in a number of crystals, but there has not been a satisfactory explanation for their origin. The mass transport simulations indicate that there is a large difference in flux across the crystal surface, with high values at the edge of the (001) face compared to the center, and this flux has to be redistributed across the (001) surface. As the crystal grows, the redistribution process evidently can not be maintained so that the edges grow at the expense of the center, ultimately creating high index internal structures. At later times, we postulate that these high energy faces, starved of material from solution, dissolve and the extra flux of salicylic acid causes the voids to close
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