Mapping the Spread of Malaria Drug Resistance

Tim Anderson discusses a new study of molecular variation in alleles at the dihydropteroate synthase locus, which underlies resistance to sulfadoxine, in over 5,000 parasites from 50 locations

Alpha, Betti and the Megaparsec Universe: on the Topology of the Cosmic Web

We study the topology of the Megaparsec Cosmic Web in terms of the scale-dependent Betti numbers, which formalize the topological information content of the cosmic mass distribution. While the Betti numbers do not fully quantify topology, they extend the information beyond conventional cosmological studies of topology in terms of genus and Euler characteristic. The richer information content of Betti numbers goes along the availability of fast algorithms to compute them. For continuous density fields, we determine the scale-dependence of Betti numbers by invoking the cosmologically familiar filtration of sublevel or superlevel sets defined by density thresholds. For the discrete galaxy distribution, however, the analysis is based on the alpha shapes of the particles. These simplicial complexes constitute an ordered sequence of nested subsets of the Delaunay tessellation, a filtration defined by the scale parameter, $\alpha$. As they are homotopy equivalent to the sublevel sets of the distance field, they are an excellent tool for assessing the topological structure of a discrete point distribution. In order to develop an intuitive understanding for the behavior of Betti numbers as a function of $\alpha$, and their relation to the morphological patterns in the Cosmic Web, we first study them within the context of simple heuristic Voronoi clustering models. Subsequently, we address the topology of structures emerging in the standard LCDM scenario and in cosmological scenarios with alternative dark energy content. The evolution and scale-dependence of the Betti numbers is shown to reflect the hierarchical evolution of the Cosmic Web and yields a promising measure of cosmological parameters. We also discuss the expected Betti numbers as a function of the density threshold for superlevel sets of a Gaussian random field.Comment: 42 pages, 14 figure

Resonances in a spring-pendulum: algorithms for equivariant singularity theory

A spring-pendulum in resonance is a time-independent Hamiltonian model system for formal reduction to one degree of freedom, where some symmetry (reversibility) is maintained. The reduction is handled by equivariant singularity theory with a distinguished parameter, yielding an integrable approximation of the Poincaré map. This makes a concise description of certain bifurcations possible. The computation of reparametrizations from normal form to the actual system is performed by Gröbner basis techniques.

Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease typeIIIaare phenotype-specific:An investigator-initiated, randomized, crossover study

Glycogen storage disease type IIIa (GSDIIIa) is an inborn error of carbohydrate metabolism caused by a debranching enzyme deficiency. A subgroup of GSDIIIa patients develops severe myopathy. The purpose of this study was to investigate whether acute nutritional ketosis (ANK) in response to ketone-ester (KE) ingestion is effective to deliver oxidative substrate to exercising muscle in GSDIIIa patients. This was an investigator-initiated, researcher-blinded, randomized, crossover study in six adult GSDIIIa patients. Prior to exercise subjects ingested a carbohydrate drink (~66 g, CHO) or a ketone-ester (395 mg/kg, KE) + carbohydrate drink (30 g, KE + CHO). Subjects performed 15-minute cycling exercise on an upright ergometer followed by 10-minute supine cycling in a magnetic resonance (MR) scanner at two submaximal workloads (30% and 60% of individual maximum, respectively). Blood metabolites, indirect calorimetry data, and in vivo 31P-MR spectra from quadriceps muscle were collected during exercise. KE + CHO induced ANK in all six subjects with median peak βHB concentration of 2.6 mmol/L (range: 1.6-3.1). Subjects remained normoglycemic in both study arms, but delta glucose concentration was 2-fold lower in the KE + CHO arm. The respiratory exchange ratio did not increase in the KE + CHO arm when workload was doubled in subjects with overt myopathy. In vivo 31P MR spectra showed a favorable change in quadriceps energetic state during exercise in the KE + CHO arm compared to CHO in subjects with overt myopathy. Effects of ANK during exercise are phenotype-specific in adult GSDIIIa patients. ANK presents a promising therapy in GSDIIIa patients with a severe myopathic phenotype. Trial registration number: ClinicalTrials.gov identifier: NCT03011203

Building a circular supply chain:Achieving resilient operations with the circular economy

This paper highlights the fundamental contribution that supply chain professionals can make to the transition to a circular economy. It aims to provide a general understanding of how the circular economy and supply chain management fields are related to one another. By exploring the concept of a circular supply chain, the paper illustrates the role of supply chain professionals in operationalising circular economy initiatives within their organisations, as well as the opportunities and challenges they may encounter along the way. The paper also provides initialrecommendations for and examples of companies overcoming some of these challenges, based on the experiences of supply chain professionals involved in the research

Identification of plastic constitutive parameters at large deformations from three dimensional displacement fields

The aim of this paper is to provide a general procedure to extract the constitutive parameters of a plasticity model starting from displacement measurements and using the Virtual Fields Method. This is a classical inverse problem which has been already investigated in the literature, however several new features are developed here. First of all the procedure applies to a general three-dimensional displacement field which leads to large plastic deformations, no assumptions are made such as plane stress or plane strain although only pressure-independent plasticity is considered. Moreover the equilibrium equation is written in terms of the deviatoric stress tensor that can be directly computed from the strain field without iterations. Thanks to this, the identification routine is much faster compared to other inverse methods such as finite element updating. The proposed method can be a valid tool to study complex phenomena which involve severe plastic deformation and where the state of stress is completely triaxial, e.g. strain localization or necking occurrence. The procedure has been validated using a three dimensional displacement field obtained from a simulated experiment. The main potentialities as well as a first sensitivity study on the influence of measurement errors are illustrated

Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Background: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.Methods: Associations between 16 biomarkers predictive for 180 day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48 hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.Results: No significant correlations were found at hospital admission. However, after 48 hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n = 21); miR-16-5p was correlated to C-reactive protein (R = -0.66, p-value = 0.0027), miR-106a-5p to creatinine (R = -0.68, p-value = 0.002), miR-223-3p to growth differentiation factor 15 (R = -0.69, p-value = 0.0015), miR-652-3p to soluble ST-2 (R = -0.77, p-value &lt;0.001), miR-199a-3p to procalcitonin (R = -0.72, p-value &lt;0.001) and galectin-3 (R = -0.73, p-value &lt;0.001) and miR-18a-5p to procalcitonin (R = -0.68, p-value = 0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.Conclusions: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48 hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.</p