Meningococcal disease in children in Merseyside, England:a 31 year descriptive study

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD

Hypoxia-induced responses by endothelial colony-forming cells are modulated by placental growth factor

BACKGROUND: Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. METHODS: In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O(2) exposure at acute and chronic time points. RESULTS: In response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O(2). Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect. CONCLUSIONS: This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0430-0) contains supplementary material, which is available to authorized users

Oriented Matroids -- Combinatorial Structures Underlying Loop Quantum Gravity

We analyze combinatorial structures which play a central role in determining spectral properties of the volume operator in loop quantum gravity (LQG). These structures encode geometrical information of the embedding of arbitrary valence vertices of a graph in 3-dimensional Riemannian space, and can be represented by sign strings containing relative orientations of embedded edges. We demonstrate that these signature factors are a special representation of the general mathematical concept of an oriented matroid. Moreover, we show that oriented matroids can also be used to describe the topology (connectedness) of directed graphs. Hence the mathematical methods developed for oriented matroids can be applied to the difficult combinatorics of embedded graphs underlying the construction of LQG. As a first application we revisit the analysis of [4-5], and find that enumeration of all possible sign configurations used there is equivalent to enumerating all realizable oriented matroids of rank 3, and thus can be greatly simplified. We find that for 7-valent vertices having no coplanar triples of edge tangents, the smallest non-zero eigenvalue of the volume spectrum does not grow as one increases the maximum spin \jmax at the vertex, for any orientation of the edge tangents. This indicates that, in contrast to the area operator, considering large \jmax does not necessarily imply large volume eigenvalues. In addition we give an outlook to possible starting points for rewriting the combinatorics of LQG in terms of oriented matroids.Comment: 43 pages, 26 figures, LaTeX. Version published in CQG. Typos corrected, presentation slightly extende

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

Construction of reference chromosome-scale pseudomolecules for potato: integrating the potato genome with genetic and physical maps

The genome of potato, a major global food crop, was recently sequenced. The work presented here details the integration of the potato reference genome (DM) with a new STS marker based linkage map and other physical and genetic maps of potato and the closely related species tomato. Primary anchoring of the DM genome assembly was accomplished using a diploid segregating population, which was genotyped with several types of molecular genetic markers to construct a new ~936 cM linkage map comprising 2,469 marker loci. In silico anchoring approaches employed genetic and physical maps from the diploid potato genotype RH and tomato. This combined approach has allowed 951 superscaffolds to be ordered into pseudomolecules corresponding to the 12 potato chromosomes. These pseudomolecules represent 674 Mb (~93%) of the 723 Mb genome assembly and 37,482 (~96%) of the 39,031 predicted genes. The superscaffold order and orientation within the pseudomolecules is closely collinear with independently constructed high density linkage maps. Comparisons between marker distribution and physical location reveal regions of greater and lesser recombination, as well as regions exhibiting significant segregation distortion. The work presented here has led to a greatly improved ordering of the potato reference genome superscaffolds into chromosomal 'pseudomolecules'.Fil: Carboni, Martín Federico. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires. Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: D'ambrosio, Juan Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional San Cristobal de Huamanga. Laboratorio de Genética y Biotecnología Vegetal; PerúFil: Sharma, Sanjeev Kumar. The James Hutton Institute; Reino UnidoFil: Bolser, Daniel. University of Dundee; Reino UnidoFil: de Boer, Jan. Wageningen University & Researc; Países BajosFil: Sønderkær, Mads . Aalborg University; DinamarcaFil: Amoros, Walter. International Potato Center; PerúFil: de la Cruz, Germán. Universidad Nacional San Cristobal de Huamanga; PerúFil: Di Genova, Alex. Universidad de Chile; ChileFil: Douches, David S.. Michigan State University; Estados UnidosFil: Eguiluz, Maria. Universidad Peruana Cayetano Heredia; PerúFil: Guo, Xiao. Shandong Academy of Agricultural Sciences; ChinaFil: Guzman, Frank. Universidad Peruana Cayetano Heredia; PerúFil: Hackett, Christine A.. Biomathematics and Statistics Scotland; Reino UnidoFil: Hamilton, John P.. Crops Environment and Land Use Programme; IrlandaFil: Li, Guangcun. Shandong Academy of Agricultural Sciences; ChinaFil: Li, Ying. The New Zealand Institute for Plant & Food Research; Nueva ZelandaFil: Lozano, Roberto. Universidad Peruana Cayetano Heredia; PerúFil: Maass, Alejandro. Universidad de Chile; ChileFil: Marshall, David. The James Hutton Institute; Reino UnidoFil: Martinez, Diana. Universidad Peruana Cayetano Heredia; PerúFil: McLean, Karen. The James Hutton Institute; Reino UnidoFil: Mejía, Nilo. Instituto de Investigaciones Agropecuarias. Centro Regional de Investigación La Platina; ChileFil: Milne, Linda. The James Hutton Institute; Reino UnidoFil: Munive, Susan. International Potato Center; PerúFil: Nagy, Istvan. Crops Environment and Land Use Programme; IrlandaFil: Ponce, Olga. Universidad Peruana Cayetano Heredia; PerúFil: Ramirez, Manuel. Universidad Peruana Cayetano Heredia; PerúFil: Simon, Reinhard. International Potato Center; PerúFil: Thomson, Susan J.. Chinese Academy of Agricultural Sciences; Chin

The genome-defence gene Tex19.1 suppresses LINE-1 retrotransposons in the placenta and prevents intra-uterine growth retardation in mice

DNA methylation plays an important role in suppressing retrotransposon activity in mammalian genomes, yet there are stages of mammalian development where global hypomethylation puts the genome at risk of retrotransposition-mediated genetic instability. Hypomethylated primordial germ cells appear to limit this risk by expressing a cohort of retrotransposon-suppressing genome-defence genes whose silencing depends on promoter DNA methylation. Here, we investigate whether similar mechanisms operate in hypomethylated trophectoderm-derived components of the mammalian placenta to couple expression of genome-defence genes to the potential for retrotransposon activity. We show that the hypomethylated state of the mouse placenta results in activation of only one of the hypomethylation-sensitive germline genome-defence genes: Tex19.1. Tex19.1 appears to play an important role in placenta function as Tex19.1(−/−) mouse embryos exhibit intra-uterine growth retardation and have small placentas due to a reduction in the number of spongiotrophoblast, glycogen trophoblast and sinusoidal trophoblast giant cells. Furthermore, we show that retrotransposon mRNAs are derepressed in Tex19.1(−/−) placentas and that protein encoded by the LINE-1 retrotransposon is upregulated in hypomethylated trophectoderm-derived cells that normally express Tex19.1. This study suggests that post-transcriptional genome-defence mechanisms are operating in the placenta to protect the hypomethylated cells in this tissue from retrotransposons and suggests that imbalances between retrotransposon activity and genome-defence mechanisms could contribute to placenta dysfunction and disease

Tropical secondary forest regeneration conserves high levels of avian phylogenetic diversity

Secondary forests are promoted as having pivotal roles in reversing the tropical extinction crisis. While secondary forests recover carbon and species over time, a key question is whether phylogenetic diversity—the total evolutionary history across all species within a community—also recovers. Conserving phylogenetic diversity protects unique phenotypic and ecological traits, and benefits ecosystem functioning and stability. We examined the extent to which avian phylogenetic diversity recovers in secondary forests in the Colombian Chocó-Andes. sesPD, a measure of phylogenetic richness corrected for species richness, recovered to old-growth forest levels after ~ 30 years, while sesMPD, a measure of the phylogenetic distance between individuals in a community, recovered to old-growth levels even within young secondary forest. Mean evolutionary distinctiveness also recovered rapidly in secondary forest communities. Our results suggest that secondary forests can play a vital role in conserving distinct evolutionary lineages and high levels of evolutionary history. Focusing conservation and carbon-based payments for ecosystem services on secondary forest recovery and their subsequent protection thus represent a good use of scarce conservation resources