Greedy Connectivity of Geographically Embedded Graphs

We introduce a measure of {\em greedy connectivity} for geographical networks (graphs embedded in space) and where the search for connecting paths relies only on local information, such as a node's location and that of its neighbors. Constraints of this type are common in everyday life applications. Greedy connectivity accounts also for imperfect transmission across established links and is larger the higher the proportion of nodes that can be reached from other nodes with a high probability. Greedy connectivity can be used as a criterion for optimal network design

Asymptotic behavior of the Kleinberg model

We study Kleinberg navigation (the search of a target in a d-dimensional lattice, where each site is connected to one other random site at distance r, with probability proportional to r^{-a}) by means of an exact master equation for the process. We show that the asymptotic scaling behavior for the delivery time T to a target at distance L scales as (ln L)^2 when a=d, and otherwise as L^x, with x=(d-a)/(d+1-a) for ad+1. These values of x exceed the rigorous lower-bounds established by Kleinberg. We also address the situation where there is a finite probability for the message to get lost along its way and find short delivery times (conditioned upon arrival) for a wide range of a's

Animated PowerPoint Presentations For Teaching Operations And Supply Chain Management: Perceived Value And Electronic Exchange Of Files

This paper presents the innovation of sharing animated PowerPoint presentations used in teaching operations and supply chain management techniques and concepts through an international electronic exchange. The plan for the exchange is presented and discussed. The potential benefits to faculty and students of using PowerPoint animations in operations and supply chain management classes are discussed. Evidence of these benefits is also provided. Readers are provided with information about how to join the exchange

Applications of graphics to support a testbed for autonomous space vehicle operations

Researchers describe their experience using graphics tools and utilities while building an application, AUTOPS, that uses a graphical Machintosh (TM)-like interface for the input and display of data, and animation graphics to enhance the presentation of results of autonomous space vehicle operations simulations. AUTOPS is a test bed for evaluating decisions for intelligent control systems for autonomous vehicles. Decisions made by an intelligent control system, e.g., a revised mission plan, might be displayed to the user in textual format or he can witness the effects of those decisions via out of window graphics animations. Although a textual description conveys essentials, a graphics animation conveys the replanning results in a more convincing way. Similarily, iconic and menu-driven screen interfaces provide the user with more meaningful options and displays. Presented here are experiences with the SunView and TAE Plus graphics tools used for interface design, and the Johnson Space Center Interactive Graphics Laboratory animation graphics tools used for generating out out of the window graphics

Resilience of the Internet to random breakdowns

A common property of many large networks, including the Internet, is that the connectivity of the various nodes follows a scale-free power-law distribution, P(k)=ck^-a. We study the stability of such networks with respect to crashes, such as random removal of sites. Our approach, based on percolation theory, leads to a general condition for the critical fraction of nodes, p_c, that need to be removed before the network disintegrates. We show that for a<=3 the transition never takes place, unless the network is finite. In the special case of the Internet (a=2.5), we find that it is impressively robust, where p_c is approximately 0.99.Comment: latex, 3 pages, 1 figure (eps), explanations added, Phys. Rev. Lett., in pres

Assessing urinary flow rate, creatinine, osmolality and other hydration adjustment methods for urinary biomonitoring using NHANES arsenic, iodine, lead and cadmium data

Background There are numerous methods for adjusting measured concentrations of urinary biomarkers for hydration variation. Few studies use objective criteria to quantify the relative performance of these methods. Our aim was to compare the performance of existing methods for adjusting urinary biomarkers for hydration variation. Methods Creatinine, osmolality, excretion rate (ER), bodyweight adjusted ER (ERBW) and empirical analyte-specific urinary flow rate (UFR) adjustment methods on spot urinary concentrations of lead (Pb), cadmium (Cd), non-arsenobetaine arsenic (AsIMM) and iodine (I) from the US National Health and Nutrition Examination Survey (NHANES) (2009–2010 and 2011–2012) were evaluated. The data were divided into a training dataset (n = 1,723) from which empirical adjustment coefficients were derived and a testing dataset (n = 428) on which quantification of the performance of the adjustment methods was done by calculating, primarily, the correlation of the adjusted parameter with UFR, with lower correlations indicating better performance and, secondarily, the correlation of the adjusted parameters with blood analyte concentrations (Pb and Cd), with higher correlations indicating better performance. Results Overall performance across analytes was better for Osmolality and UFR based methods. Excretion rate and ERBW consistently performed worse, often no better than unadjusted concentrations. Conclusions Osmolality adjustment of urinary biomonitoring data provides for more robust adjustment than either creatinine based or ER or ERBW methods, the latter two of which tend to overcompensate for UFR. Modified UFR methods perform significantly better than all but osmolality in removing hydration variation, but depend on the accuracy of UFR calculations. Hydration adjustment performance is analyte-specific and further research is needed to establish a robust and consistent framework

Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program)

Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a)

Statistics of Cycles: How Loopy is your Network?

We study the distribution of cycles of length h in large networks (of size N>>1) and find it to be an excellent ergodic estimator, even in the extreme inhomogeneous case of scale-free networks. The distribution is sharply peaked around a characteristic cycle length, h* ~ N^a. Our results suggest that h* and the exponent a might usefully characterize broad families of networks. In addition to an exact counting of cycles in hierarchical nets, we present a Monte-Carlo sampling algorithm for approximately locating h* and reliably determining a. Our empirical results indicate that for small random scale-free nets of degree exponent g, a=1/(g-1), and a grows as the nets become larger.Comment: Further work presented and conclusions revised, following referee report

A comparative assessment of dilution correction methods for spot urinary analyte concentrations in a UK population exposed to arsenic in drinking water

Spot urinary concentrations of environmental exposure biomarkers require correction for dilution. There is no consensus on the most appropriate method, with creatinine used by default despite lacking theoretical robustness. We comparatively assessed the efficacy of creatinine; specific gravity (SG); osmolality and modifications of all three for dilution correcting urinary arsenic. For 202 participants with urinary arsenic, creatinine, osmolality and SG measurements paired to drinking water As, we compared the performance corrections against two independent criteria: primarily, (A) correlations of corrected urinary As and the dilution measurements used to correct them - weak correlations indicating good performance and (B) correlations of corrected urinary As and drinking water As - strong correlations indicating good performance. More than a third of variation in spot urinary As concentrations was attributable to dilution. Conventional SG and osmolality correction removed significant dilution variation from As concentrations, whereas conventional creatinine over-corrected, and modifications of all three removed measurable dilution variation. Modified creatinine and both methods of SG and osmolality generated stronger correlations of urinary and drinking water As concentrations than conventional creatinine, which gave weaker correlations than uncorrected values. A disparity in optima between performance criteria was observed, with much smaller improvements possible for Criterion B relative to A. Conventional corrections – particularly creatinine - limit the utility spot urine samples, whereas a modified technique outlined here may allow substantial improvement and can be readily retrospectively applied to existing datasets. More studies are needed to optimize urinary dilution correction methods. Covariates of urinary dilution measurements still warrant consideration

Apposition to endometrial epithelial cells activates mouse blastocysts for implantation.

How do interactions between blastocyst-stage embryos and endometrial epithelial cells regulate the early stages of implantation in an in vitro model?Mouse blastocyst apposition with human endometrial epithelial cells initiates trophectoderm differentiation to trophoblast, which goes on to breach the endometrial epithelium.In vitro models using mouse blastocysts and human endometrial cell lines have proven invaluable in the molecular characterisation of embryo attachment to endometrial epithelium at the onset of implantation. Genes involved in embryonic breaching of the endometrial epithelium have not been investigated in such in vitro models.This study used an established in vitro model of implantation to examine cellular and molecular interactions during blastocyst attachment to endometrial epithelial cells.Mouse blastocysts developed from embryonic day (E) 1.5 in vitro were hatched and co-cultured with confluent human endometrial adenocarcinoma-derived Ishikawa cells in serum-free medium. A scale of attachment stability based on blastocyst oscillation upon agitation was devised. Blastocysts were monitored for 48 h to establish the kinetics of implantation, and optical sectioning using fluorescence microscopy revealed attachment and invasion interfaces. Quantitative PCR was used to determine blastocyst gene expression. Data from a total of 680 mouse blastocysts are reported, with 3-6 experimental replicates. T-test and ANOVA analyses established statistical significance at P < 0.05, P < 0.01 and P < 0.001.Hatched E4.5 mouse blastocysts exhibited weak attachment to confluent Ishikawa cells over the first 24 h of co-culture, with intermediate and stable attachment occurring from 28 h (E5.5 + 4 h) in a hormone-independent manner. Attached embryos fixed after 48 h (E6.5) frequently exhibited outgrowths, characterised morphologically and with antibody markers as trophoblast giant cells (TGCs), which had breached the Ishikawa cell layer. Beginning co-culture at E5.5 also resulted in intermediate and stable attachment from E5.5 + 4 h; however, these embryos did not go on to breach the Ishikawa cell layer, even when co-culture was extended to E7.5 (P < 0.01). Blastocysts cultured from E4.5 in permeable transwell inserts above Ishikawa cells before transfer to direct co-culture at E5.5 went on to attach but failed to breach the Ishikawa cell layer by E6.5 (P < 0.01). Gene expression analysis at E5.5 demonstrated that direct co-culture with Ishikawa cells from E4.5 resulted in downregulation of trophectoderm transcription factors Cdx2 (P < 0.05) and Gata3 (P < 0.05) and upregulation of the TGC transcription factor Hand1 (P < 0.05). Co-culture with non-endometrial human fibroblasts did not alter the expression of these genes.None.The in vitro model used here combines human carcinoma-derived endometrial cells with mouse embryos, in which the cellular interactions observed may not fully recapitulate those in vivo. The data gleaned from such models can be regarded as hypothesis-generating, and research is now needed to develop more sophisticated models of human implantation combining multiple primary endometrial cell types with surrogate and real human embryos.This study implicates blastocyst apposition to endometrial epithelial cells as a critical step in trophoblast differentiation required for implantation. Understanding this maternal regulation of the embryonic developmental programme may lead to novel treatments for infertility.This work was supported by funds from the charities Wellbeing of Women (RG1442) and Diabetes UK (15/0005207), and studentship support for SCB from the Anatomical Society. No conflict of interest is declared