Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

Introduction The precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis. Methods Fieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates. Results Podoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence. Conclusions More quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients

Traffic Network Optimum Principle - Minimum Probability of Congestion Occurrence

We introduce an optimum principle for a vehicular traffic network with road bottlenecks. This network breakdown minimization (BM) principle states that the network optimum is reached, when link flow rates are assigned in the network in such a way that the probability for spontaneous occurrence of traffic breakdown at one of the network bottlenecks during a given observation time reaches the minimum possible value. Based on numerical simulations with a stochastic three-phase traffic flow model, we show that in comparison to the well-known Wardrop's principles the application of the BM principle permits considerably greater network inflow rates at which no traffic breakdown occurs and, therefore, free flow remains in the whole network.Comment: 22 pages, 6 figure

Characterising sand and gravel deposits using electrical resistivity tomography (ERT) : case histories from England and Wales

Electrical Resistivity Tomography (ERT) is a rapidly developing geophysical imaging technique that is now widely used to visualise subsurface geological structure, groundwater and lithological variations. It is being increasingly used in environmental and engineering site investigations, but despite its suitability and potential benefits, ERT has yet to be routinely applied by the minerals industry to sand and gravel deposit assessment and quarry planning. The principal advantages of ERT for this application are that it is a cost-effective non-invasive method, which can provide 2D or 3D spatial models of the subsurface throughout the full region of interest. This complements intrusive sampling methods, which typically provide information only at discrete locations. Provided that suitable resistivity contrasts are present, ERT has the potential to reveal mineral and overburden thickness and quality variations within the body of the deposit. Here we present a number of case studies from the UK illustrating the use of 2D and 3D ERT for sand and gravel deposit investigation in a variety of geological settings. We use these case studies to evaluate the performance of ERT, and to illustrate good practice in the application of ERT to deposit investigation. We propose an integrated approach to site investigation and quarry planning incorporating both conventional intrusive methods and ERT

The problem of shot selection in basketball

In basketball, every time the offense produces a shot opportunity the player with the ball must decide whether the shot is worth taking. In this paper, I explore the question of when a team should shoot and when they should pass up the shot by considering a simple theoretical model of the shot selection process, in which the quality of shot opportunities generated by the offense is assumed to fall randomly within a uniform distribution. I derive an answer to the question "how likely must the shot be to go in before the player should take it?", and show that this "lower cutoff" for shot quality $f$ depends crucially on the number $n$ of shot opportunities remaining (say, before the shot clock expires), with larger $n$ demanding that only higher-quality shots should be taken. The function $f(n)$ is also derived in the presence of a finite turnover rate and used to predict the shooting rate of an optimal-shooting team as a function of time. This prediction is compared to observed shooting rates from the National Basketball Association (NBA), and the comparison suggests that NBA players tend to wait too long before shooting and undervalue the probability of committing a turnover.Comment: 7 pages, 2 figures; comparison to NBA data adde

Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis

Congested traffic equilibria and degenerate anisotropic PDEs

Congested traffic problems on very dense networks lead, at the limit, to minimization problems posed on measures on curves as shown in Baillon and Carlier (Netw. Heterogenous Media 7: 219--241, 2012). Here, we go one step further by showing that these problems can be reformulated in terms of the minimization of an integral functional over a set of vector fields with prescribed divergence. We prove a Sobolev regularity result for their minimizers despite the fact that the Euler-Lagrange equation of the dual is highly degenerate and anisotropic. This somehow extends the analysis of Brasco et al. (J. Math. Pures Appl. 93: 652--671, 2010) to the anisotropic case

Bcl-2 Inhibits the Innate Immune Response during Early Pathogenesis of Murine Congenital Muscular Dystrophy

Laminin α2 (LAMA2)-deficient congenital muscular dystrophy is a severe, early-onset disease caused by abnormal levels of laminin 211 in the basal lamina leading to muscle weakness, transient inflammation, muscle degeneration and impaired mobility. In a Lama2-deficient mouse model for this disease, animal survival is improved by muscle-specific expression of the apoptosis inhibitor Bcl-2, conferred by a MyoD-hBcl-2 transgene. Here we investigated early disease stages in this model to determine initial pathological events and effects of Bcl-2 on their progression. Using quantitative immunohistological and mRNA analyses we show that inflammation occurs very early in Lama2-deficient muscle, some aspects of which are reduced or delayed by the MyoD-hBcl-2 transgene. mRNAs for innate immune response regulators, including multiple Toll-like receptors (TLRs) and the inflammasome component NLRP3, are elevated in diseased muscle compared with age-matched controls expressing Lama2. MyoD-hBcl-2 inhibits induction of TLR4, TLR6, TLR7, TLR8 and TLR9 in Lama2-deficient muscle compared with non-transgenic controls, and leads to reduced infiltration of eosinophils, which are key death effector cells. This congenital disease model provides a new paradigm for investigating cell death mechanisms during early stages of pathogenesis, demonstrating that interactions exist between Bcl-2, a multifunctional regulator of cell survival, and the innate immune response

The Value of Information in Selfish Routing

Path selection by selfish agents has traditionally been studied by comparing social optima and equilibria in the Wardrop model, i.e., by investigating the Price of Anarchy in selfish routing. In this work, we refine and extend the traditional selfish-routing model in order to answer questions that arise in emerging path-aware Internet architectures. The model enables us to characterize the impact of different degrees of congestion information that users possess. Furthermore, it allows us to analytically quantify the impact of selfish routing, not only on users, but also on network operators. Based on our model, we show that the cost of selfish routing depends on the network topology, the perspective (users versus network operators), and the information that users have. Surprisingly, we show analytically and empirically that less information tends to lower the Price of Anarchy, almost to the optimum. Our results hence suggest that selfish routing has modest social cost even without the dissemination of path-load information.Comment: 27th International Colloquium on Structural Information and Communication Complexity (SIROCCO 2020

Heparin and Heparan Sulfate: Analyzing Structure and Microheterogeneity [chapter]

available in PMC 2013 August 28The structural microheterogeneity of heparin and heparan sulfate is one of the major reasons for the multifunctionality exhibited by this class of molecules. In a physiological context, these molecules primarily exert their effects extracellularly by mediating key processes of cellular cross-talk and signaling leading to the modulation of a number of different biological activities including development, cell proliferation, and inflammation. This structural diversity is biosynthetically imprinted in a nontemplate-driven manner and may also be dynamically remodeled as cellular function changes. Understanding the structural information encoded in these molecules forms the basis for attempting to understand the complex biology they mediate. This chapter provides an overview of the origin of the structural microheterogeneity observed in heparin and heparan sulfate, and the orthogonal analytical methodologies that are required to help decipher this information