Multiscale stochastic reaction-diffusion modelling: application to actin dynamics in filopodia

Two multiscale (hybrid) stochastic reaction-diffusion models of actin dynamics in a filopodium are investigated. Both hybrid algorithms combine compartment-based and molecular-based stochastic reaction-diffusion models. The first hybrid model is based on the models previously\ud developed in the literature. The second hybrid model is based on the application of recently developed two-regime method (TRM) to a fully molecular-based model which is also developed in this paper. The results of hybrid models are compared with the results of the molecular-based model. It is shown that both approaches give comparable results, although the TRM model better agrees quantitatively with the molecular-based model

Crystalline Order on a Sphere and the Generalized Thomson Problem

We attack generalized Thomson problems with a continuum formalism which exploits a universal long range interaction between defects depending on the Young modulus of the underlying lattice. Our predictions for the ground state energy agree with simulations of long range power law interactions of the form 1/r^{gamma} (0 < gamma < 2) to four significant digits. The regime of grain boundaries is studied in the context of tilted crystalline order and the generality of our approach is illustrated with new results for square tilings on the sphere.Comment: 4 pages, 5 eps figures Fig. 2 revised, improved Fig. 3, reference typo fixe

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Efficiency of European public higher education institutions: a two-stage multicountry approach

The purpose of this study is to examine efficiency and its determinants in a set of higher education institutions (HEIs) from several European countries by means of non-parametric frontier techniques. Our analysis is based on a sample of 259 public HEIs from 7 European countries across the time period of 2001–2005. We conduct a two-stage DEA analysis (Simar and Wilson in J Economet 136:31–64, 2007), first evaluating DEA scores and then regressing them on potential covariates with the use of a bootstrapped truncated regression. Results indicate a considerable variability of efficiency scores within and between countries. Unit size (economies of scale), number and composition of faculties, sources of funding and gender staff composition are found to be among the crucial determinants of these units’ performance. Specifically, we found evidence that a higher share of funds from external sources and a higher number of women among academic staff improve the efficiency of the institution

Unreliable numbers: error and harm induced by bad design can be reduced by better design

Number entry is a ubiquitous activity and is often performed in safety- and mission-critical procedures, such as healthcare, science, finance, aviation and in many other areas. We show that Monte Carlo methods can quickly and easily compare the reliability of different number entry systems. A surprising finding is that many common, widely used systems are defective, and induce unnecessary human error. We show that Monte Carlo methods enable designers to explore the implications of normal and unexpected operator behaviour, and to design systems to be more resilient to use error. We demonstrate novel designs with improved resilience, implying that the common problems identified and the errors they induce are avoidable

Quantifying Child Mortality Reductions Related to Measles Vaccination

Background: This study characterizes the historical relationship between coverage of measles containing vaccines (MCV) and mortality in children under 5 years, with a view toward ongoing global efforts to reduce child mortality. Methodology/Principal Findings: Using country-level, longitudinal panel data, from 44 countries over the period 1960–2005, we analyzed the relationship between MCV coverage and measles mortality with (1) logistic regressions for no measles deaths in a country-year, and (2) linear regressions for the logarithm of the measles death rate. All regressions allowed a flexible, non-linear relationship between coverage and mortality. Covariates included birth rate, death rates from other causes, percent living in urban areas, population density, per-capita GDP, use of the two-dose MCV, year, and mortality coding system. Regressions used lagged covariates, country fixed effects, and robust standard errors clustered by country. The likelihood of no measles deaths increased nonlinearly with higher MCV coverage (ORs: 13.8 [1.6–122.7] for 80–89% to 40.7 [3.2–517.6] for ≥95%), compared to pre-vaccination risk levels. Measles death rates declined nonlinearly with higher MCV coverage, with benefits accruing more slowly above 90% coverage. Compared to no coverage, predicted average reductions in death rates were −79% at 70% coverage, −93% at 90%, and −95% at 95%. Conclusions/Significance: 40 years of experience with MCV vaccination suggests that extremely high levels of vaccination coverage are needed to produce sharp reductions in measles deaths. Achieving sustainable benefits likely requires a combination of extended vaccine programs and supplementary vaccine efforts

Computational modelling of wound healing insights to develop new treatments

About 1% of the population will suffer a severe wound during their life. Thus, it is really important to develop new techniques in order to properly treat these injuries due to the high socioeconomically impact they suppose. Skin substitutes and pressure based therapies are currently the most promising techniques to heal these injuries. Nevertheless, we are still far from finding a definitive skin substitute for the treatment of all chronic wounds. As a first step in developing new tissue engineering tools and treatment techniques for wound healing, in silico models could help in understanding the mechanisms and factors implicated in wound healing. Here, we review mathematical models of wound healing. These models include different tissue and cell types involved in healing, as well as biochemical and mechanical factors which determine this process. Special attention is paid to the contraction mechanism of cells as an answer to the tissue mechanical state. Other cell processes such as differentiation and proliferation are also included in the models together with extracellular matrix production. The results obtained show the dependency of the success of wound healing on tissue composition and the importance of the different biomechanical and biochemical factors. This could help to individuate the adequate concentration of growth factors to accelerate healing and also the best mechanical properties of the new skin substitute depending on the wound location in the body and its size and shape. Thus, the feedback loop of computational models, experimental works and tissue engineering could help to identify the key features in the design of new treatments to heal severe wounds

Political and social determinants of life expectancy in less developed countries: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine the longitudinal contributions of four political and socioeconomic factors to the increase in life expectancy in less developed countries (LDCs) between 1970 and 2004.</p> <p>Methods</p> <p>We collected 35 years of annual data for 119 LDCs on life expectancy at birth and on four key socioeconomic indicators: economy, measured by log10 gross domestic product per capita at purchasing power parity; educational environment, measured by the literacy rate of the adult population aged 15 years and over; nutritional status, measured by the proportion of undernourished people in the population; and political regime, measured by the regime score from the Polity IV database. Using linear mixed models, we analyzed the longitudinal effects of these multiple factors on life expectancy at birth with a lag of 0-10 years, adjusting for both time and regional correlations.</p> <p>Results</p> <p>The LDCs' increases in life expectancy over time were associated with all four factors. Political regime had the least influence on increased life expectancy to begin with, but became significant starting in the 3rd year and continued to increase, while the impact of the other socioeconomic factors began strong but continually decreased over time. The combined effects of these four socioeconomic and political determinants contributed 54.74% - 98.16% of the life expectancy gains throughout the lag periods of 0-10 years.</p> <p>Conclusions</p> <p>Though the effect of democratic politics on increasing life expectancy was relatively small in the short term when compared to the effects of the other socioeconomic factors, the long-term impact of democracy should not be underestimated.</p