22,184 research outputs found
Testing Modeling Assumptions in the West Africa Ebola Outbreak
The Ebola virus in West Africa has infected almost 30,000 and killed over
11,000 people. Recent models of Ebola Virus Disease (EVD) have often made
assumptions about how the disease spreads, such as uniform transmissibility and
homogeneous mixing within a population. In this paper, we test whether these
assumptions are necessarily correct, and offer simple solutions that may
improve disease model accuracy. First, we use data and models of West African
migration to show that EVD does not homogeneously mix, but spreads in a
predictable manner. Next, we estimate the initial growth rate of EVD within
country administrative divisions and find that it significantly decreases with
population density. Finally, we test whether EVD strains have uniform
transmissibility through a novel statistical test, and find that certain
strains appear more often than expected by chance.Comment: 16 pages, 14 figure
Modelling Cell Cycle using Different Levels of Representation
Understanding the behaviour of biological systems requires a complex setting
of in vitro and in vivo experiments, which attracts high costs in terms of time
and resources. The use of mathematical models allows researchers to perform
computerised simulations of biological systems, which are called in silico
experiments, to attain important insights and predictions about the system
behaviour with a considerably lower cost. Computer visualisation is an
important part of this approach, since it provides a realistic representation
of the system behaviour. We define a formal methodology to model biological
systems using different levels of representation: a purely formal
representation, which we call molecular level, models the biochemical dynamics
of the system; visualisation-oriented representations, which we call visual
levels, provide views of the biological system at a higher level of
organisation and are equipped with the necessary spatial information to
generate the appropriate visualisation. We choose Spatial CLS, a formal
language belonging to the class of Calculi of Looping Sequences, as the
formalism for modelling all representation levels. We illustrate our approach
using the budding yeast cell cycle as a case study
Some Remarks about the Complexity of Epidemics Management
Recent outbreaks of Ebola, H1N1 and other infectious diseases have shown that
the assumptions underlying the established theory of epidemics management are
too idealistic. For an improvement of procedures and organizations involved in
fighting epidemics, extended models of epidemics management are required. The
necessary extensions consist in a representation of the management loop and the
potential frictions influencing the loop. The effects of the non-deterministic
frictions can be taken into account by including the measures of robustness and
risk in the assessment of management options. Thus, besides of the increased
structural complexity resulting from the model extensions, the computational
complexity of the task of epidemics management - interpreted as an optimization
problem - is increased as well. This is a serious obstacle for analyzing the
model and may require an additional pre-processing enabling a simplification of
the analysis process. The paper closes with an outlook discussing some
forthcoming problems
Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection
HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free
infection following fluid-phase diffusion of virions and by highly-efficient
direct cell-to-cell transmission at immune cell contacts. The contribution of
this hybrid spreading mechanism, which is also a characteristic of some
important computer worm outbreaks, to HIV-1 progression in vivo remains
unknown. Here we present a new mathematical model that explicitly incorporates
the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the
consequences for HIV-1 pathogenenesis. The model captures the major phases of
the HIV-1 infection course of a cohort of treatment naive patients and also
accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at
Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading
is critical to seed and establish infection, and that cell-to-cell spread and
increased CD4+ T cell activation are important for HIV-1 progression. Notably,
the model predicts that cell-to-cell spread becomes increasingly effective as
infection progresses and thus may present a considerable treatment barrier.
Deriving predictions of various treatments' influence on HIV-1 progression
highlights the importance of earlier intervention and suggests that treatments
effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS.
This study suggests that hybrid spreading is a fundamental feature of HIV
infection, and provides the mathematical framework incorporating this feature
with which to evaluate future therapeutic strategies
Assembling evidence for identifying reservoirs of infection
Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems
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