Changed concepts and definitions of myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the updated 2008 WHO classification

The purpose of this overview is to discuss the changes in the 2008 WHO classification of myeloid neoplasms, with exclusion of acute myeloid leukaemia. Specific mutations or rearrangements leading to constitutive activation of growth factor receptors or cytoplasmic tyrosine kinases are now recognised as recurrent genetic events characterising the group of myeloproliferative neoplasms (MPN). A newly introduced subgroup consists of patients with persistent eosinophilia and myeloid or lymphoid proliferations harbouring specific genetic changes involving platelet-derived growth factor receptors alpha and beta (PDGFRA and PDGFRB) or fibroblast growth factor receptor 1 (FGFR1). The clinical relevance of recognising myeloid neoplasms with aberrant tyrosine kinase activity is based in novel treatment options with tyrosine kinase inhibitors. The myelodysplastic syndromes (MDS) without increased blasts are further divided into subtypes of refractory cytopaenias with unilineage dysplasia. A new provisional entity is refractory cytopaenia of childhood. Down syndrome- and therapy-related myeloid neoplasms, including MDS, were moved to the section of acute myeloid leukaemia and related precursor neoplasms

Environmental predictors of bovine Eimeria infection in western Kenya

Eimeriosis is caused by a protozoan infection affecting most domestic animal species. Outbreaks in cattle are associated with various environmental factors in temperate climates but limited work has been done in tropical settings. The objective of this work was to determine the prevalence and environmental factors associated with bovine Eimeria spp. infection in a mixed farming area of western Kenya. A total of 983 cattle were sampled from 226 cattle-keeping households. Faecal samples were collected directly from the rectum via digital extraction and analysed for the presence of Eimeria spp. infection using the MacMaster technique. Individual and household level predictors of infection were explored using mixed effects logistic regression. The prevalence of individual animal Eimeria infection was 32.8% (95% CI 29.9–35.9). A positive linear relationship was found between risk of Eimeria infection and increasing temperature (OR = 1.4, 95% CI 1.06–1.86) and distance to areas at risk of flooding (OR = 1.49, 95% CI 1.17–1.91). There was weak evidence of non-linear relationship between Eimeria infection and the proportion of the area around a household that was classified as swamp (OR = 1.12, 95% CI 0.87–1.44; OR (quadratic term) = 0.85, 95% CI 0.73–1.00), and the sand content of the soil (OR = 1.18, 95% CI 0.91–1.53; OR (quadratic term) = 1.1, 95% CI 0.99–1.23). The risk of animal Eimeria spp. infection is influenced by a number of climatic and soil-associated conditions.</p

Optimal Traffic Networks

Inspired by studies on the airports' network and the physical Internet, we propose a general model of weighted networks via an optimization principle. The topology of the optimal network turns out to be a spanning tree that minimizes a combination of topological and metric quantities. It is characterized by a strongly heterogeneous traffic, non-trivial correlations between distance and traffic and a broadly distributed centrality. A clear spatial hierarchical organization, with local hubs distributing traffic in smaller regions, emerges as a result of the optimization. Varying the parameters of the cost function, different classes of trees are recovered, including in particular the minimum spanning tree and the shortest path tree. These results suggest that a variational approach represents an alternative and possibly very meaningful path to the study of the structure of complex weighted networks.Comment: 4 pages, 4 figures, final revised versio

Improving the Price of Anarchy for Selfish Routing via Coordination Mechanisms

We reconsider the well-studied Selfish Routing game with affine latency functions. The Price of Anarchy for this class of games takes maximum value 4/3; this maximum is attained already for a simple network of two parallel links, known as Pigou's network. We improve upon the value 4/3 by means of Coordination Mechanisms. We increase the latency functions of the edges in the network, i.e., if $\ell_e(x)$ is the latency function of an edge $e$, we replace it by $\hat{\ell}_e(x)$ with $\ell_e(x) \le \hat{\ell}_e(x)$ for all $x$. Then an adversary fixes a demand rate as input. The engineered Price of Anarchy of the mechanism is defined as the worst-case ratio of the Nash social cost in the modified network over the optimal social cost in the original network. Formally, if \CM(r) denotes the cost of the worst Nash flow in the modified network for rate $r$ and \Copt(r) denotes the cost of the optimal flow in the original network for the same rate then [\ePoA = \max_{r \ge 0} \frac{\CM(r)}{\Copt(r)}.] We first exhibit a simple coordination mechanism that achieves for any network of parallel links an engineered Price of Anarchy strictly less than 4/3. For the case of two parallel links our basic mechanism gives 5/4 = 1.25. Then, for the case of two parallel links, we describe an optimal mechanism; its engineered Price of Anarchy lies between 1.191 and 1.192.Comment: 17 pages, 2 figures, preliminary version appeared at ESA 201

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

Computation of Equilibrium Distributions of Markov Traffic-Assignment Models

Markov traffic-assignment models explicitly represent the day-to-day evolving interaction between traffic congestion and drivers' information acquisition and choice processes. Such models can, in principle, be used to investigate traffic flows in stochastic equilibrium, yielding estimates of the equilibrium mean and covariance matrix of link or route traffic flows. However, in general these equilibrium moments cannot be written down in closed form. While Monte Carlo simulations of the assignment process may be used to produce “empirical” estimates, this approach can be extremely computationally expensive if reliable results (relatively free of Monte Carlo error) are to be obtained. In this paper an alternative method of computing the equilibrium distribution is proposed, applicable to the class of Markov models with linear exponential learning filters. Based on asymptotic results, this equilibrium distribution may be approximated by a Gaussian process, meaning that the problem reduces to determining the first two multivariate moments in equilibrium. The first of these moments, the mean flow vector, may be estimated by a conventional traffic-assignment model. The second, the flow covariance matrix, is estimated through various linear approximations, yielding an explicit expression. The proposed approximations are seen to operate well in a number of illustrative examples. The robustness of the approximations (in terms of network input data) is discussed, and shown to be connected with the “volatility” of the traffic assignment process

Nash Equilibria in Discrete Routing Games with Convex Latency Functions

In a discrete routing game, each of n selfish users employs a mixed strategy to ship her (unsplittable) traffic over m parallel links. The (expected) latency on a link is determined by an arbitrary non-decreasing, non-constant and convex latency function φ. In a Nash equilibrium, each user alone is minimizing her (Expected) Individual Cost, which is the (expected) latency on the link she chooses. To evaluate Nash equilibria, we formulate Social Cost as the sum of the users ’ (Expected) Individual Costs. The Price of Anarchy is the worst-case ratio of Social Cost for a Nash equilibrium over the least possible Social Cost. A Nash equilibrium is pure if each user deterministically chooses a single link; a Nash equilibrium is fully mixed if each user chooses each link with non-zero probability. We obtain: For the case of identical users, the Social Cost of any Nash equilibrium is no more than the Social Cost of the fully mixed Nash equilibrium, which may exist only uniquely. Moreover, instances admitting a fully mixed Nash equilibrium enjoy an efficient characterization. For the case of identical users, we derive two upper bounds on the Price of Anarchy: For the case of identical links with a monomial latency function φ(x) = x d, the Price of Anarchy is the Bell number of order d + 1. For pure Nash equilibria, a generic upper bound from the Wardrop model can be transfered to discrete routing games. For polynomial latency functions with non-negative coefficients and degree d, this yields an upper bound of d + 1. For th

Spatial monitoring of groundwater drawdown and rebound associated with quarry dewatering using automated time-lapse electrical resistivity tomography and distribution guided clustering

Dewatering systems used for mining and quarrying operations often result in highly artificial and complex groundwater conditions, which can be difficult to characterise and monitor using borehole point sampling approaches. Here automated time-lapse electrical resistivity tomography (ALERT) is considered as a means of monitoring subsurface groundwater dynamics associated with changes in the dewatering regime in an operational sand and gravel quarry. We considered two scenarios: the first was unplanned interruption to dewatering due to a pump failure for a period of several days, which involved comparing ALERT monitoring results before and after groundwater rebound; the second involved a planned interruption to pumping over a period of 6 h, for which near-continuous ALERT monitoring of groundwater rebound and drawdown was undertaken. The results of the second test were analysed using distribution guided clustering (DGC) to provide a more quantitative and objective assessment of changes in the subsurface over time. ALERT successfully identified groundwater level changes during both monitoring scenarios. It provided a more useful indication of the rate of water level rise and maximum water levels than piezometer monitoring results. This was due to the piezometers rapidly responding to pressure changes at depth, whilst ALERT/DGC provided information of slower changes associated with the storage and delayed drainage of water within the sediment. By applying DGC we were able to automatically and quantitatively define changes in the resistivity sections, which correlated well with the direct observations of groundwater at site. For ERT monitoring applications that generate numerous time series, the use of DGC could significantly enhance the efficiency of data interpretation, and provide a means of automating groundwater monitoring through assigning alarm thresholds associated with rapid changes in groundwater conditions

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