Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study

Background: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian random isation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher p=8×10-13) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with noncarriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13 95% CI 1·69-2·69, p=2×10 -10).
Interpretation: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.

Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).

Behavioural skeletons in GCM: autonomic management of grid components

Autonomic management can be used to improve the QoS provided by parallel/distributed applications. We discuss behavioural skeletons introduced in earlier work: rather than relying on programmer ability to design “from scratch” efficient autonomic policies, we encapsulate general autonomic controller features into algorithmic skeletons. Then we leave to the programmer the duty of specifying the parameters needed to specialise the skeletons to the needs of the particular application at hand. This results in the programmer having the ability to fast prototype and tune distributed/parallel applications with non-trivial autonomic management capabilities. We discuss how behavioural skeletons have been implemented in the framework of GCM(the Grid ComponentModel developed within the CoreGRID NoE and currently being implemented within the GridCOMP STREP project). We present results evaluating the overhead introduced by autonomic management activities as well as the overall behaviour of the skeletons. We also present results achieved with a long running application subject to autonomic management and dynamically adapting to changing features of the target architecture.
Overall the results demonstrate both the feasibility of implementing autonomic control via behavioural skeletons and the effectiveness of our sample behavioural skeletons in managing the “functional replication” pattern(s).

Effect of interleukin-6 polymorphisms on human longevity:a systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozygous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I2=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I2=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

Modification of the formation of high-Mach number electrostatic shock-like structures by the ion acoustic instability

The formation of unmagnetized electrostatic shock-like structures with a high Mach number is examined with one- and two-dimensional particle-in-cell (PIC) simulations. The structures are generated through the collision of two identical plasma clouds, which consist of equally hot electrons and ions with a mass ratio of 250. The Mach number of the collision speed with respect to the initial ion acoustic speed of the plasma is set to 4.6. This high Mach number delays the formation of such structures by tens of inverse ion plasma frequencies. A pair of stable shock-like structures is observed after this time in the 1D simulation, which gradually evolve into electrostatic shocks. The ion acoustic instability, which can develop in the 2D simulation but not in the 1D one, competes with the nonlinear process that gives rise to these structures. The oblique ion acoustic waves fragment their electric field. The transition layer, across which the bulk of the ions change their speed, widens and their speed change is reduced. Double layer-shock hybrid structures develop.

Characterisation of deuterium spectra from laser driven multi-species sources by employing differentially filtered image plate detectors in Thomson spectrometers

A novel method for characterising the full spectrum of deuteron ions emitted by laser driven multi-species ion sources is discussed. The procedure is based on using differential filtering over the detector of a Thompson parabola ion spectrometer, which enables discrimination of deuterium ions from heavier ion species with the same charge-to-mass ratio (such as C^{6 +}, O^{8 +}, etc.). Commonly used Fuji Image plates were used as detectors in the spectrometer, whose absolute response to deuterium ions over a wide range of energies was calibrated by using slotted CR-39 nuclear track detectors. A typical deuterium ion spectrum diagnosed in a recent experimental campaign is presented, which was produced from a thin deuterated plastic foil target irradiated by a high power laser.

Observation of the inhomogeneous spatial distribution of MeV ions accelerated by the hydrodynamic ambipolar expansion of clusters

An inhomogeneous spatial distribution of laser accelerated carbon/oxygen ions produced via the hydrodynamic ambipolar expansion of CO₂ clusters has been measured by using CR-39 detectors. An inhomogeneous etch pits spatial distribution has appeared on the etched CR-39 detector installed on the laser propagation direction, while homogeneous ones are appeared on those installed at 45°and 90°from the laser propagation direction. From the range of ions in CR-39 obtained by using the multi-step etching technique, the averaged energies of carbon/oxygen ions for all directions are determined as 0.78 ± 0.09 MeV/n. The number of ions in the laser propagation direction is about 1.5 times larger than those in other directions. The inhomogeneous etch pits spatial distribution in the laser propagation direction could originate from an ion beam collimation and modulation by the effect of electromagnetic structures created in the laser plasma.

Prevotella denticola Lipopolysaccharide from a Cystic Fibrosis Isolate Possesses a Unique Chemical Structure

We report the first complete structural characterization of the lipopolysaccharide (LPS) from a cystic fibrosis (CF) clinical isolate of Prevotella denticola (B003V1S1X). Chemical, spectroscopic, and spectrometric analyses revealed a unique rough-type LPS (LOS) structure. The structure has a highly negatively charged heptasaccharide core region containing hexoses, with the first two sugars, 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and mannose, highly phosphorylated. Furthermore, the lipid A moiety has the typical structure for the genus Prevotella, and was also highly phosphorylated.

Recordações de Vandelli: Literatura e história nas viagens filosóficas de Portugal pelo Brasil

O confronto entre certas criações ficcionais e a dinâmica da colonização nos leva a diversos campos disciplinares. Se a história registrou o intenso intercâmbio de mercadorias e idéias que ocorreu entre Portugal e Brasil, a partir da descoberta do Novo Mundo, a literatura revisitou e recriou esse passado. É o que se constata na obra do escritor brasileiro João Guimarães Rosa, em que articulando a realidade e a imaginação, a natureza e o homem, o regional e o universal, o escritor de perfil naturalista ilumina a linguagem da História e da Ciência pela Arte. Com relação às expedições científicas portuguesas pelo Brasil, a história relata que, na segunda metade do século XVIII, Portugal impulsionou a elaboração de um projeto de confecção de uma História Natural, tendo como espaço de criação cultural a Academia Real das Ciências de Lisboa. Esse empreendimento, no entanto, não teria sido possìvel sem as ―viagens imaginárias‖ do intelectual Domenico Agostino Vandelli, correspondente de Lineu e um dos principais articuladores da política portuguesa dirigida às colônias. Assim, instruídos conforme o livro Viagens filosóficas ou dissertações sobre as importantes regras que o filósofo naturalista nas suas peregrinações deve principalmente observar, alunos da Universidade de Coimbra, onde Vandelli era professor de História Natural e Química, são preparados para explorar as colônias ultramarinas. Em meio à produção literária de Guimarães Rosa, destacamos o conto ―O recado do morro‖, do livro Corpo de baile, lançado em 1956, para um paralelo com a História. Nessa ficção, um narrador conta a estória de uma pitoresca expedição, formada por moradores de um vilarejo, contratados por um viajante alemão, que percorre o interior do estado de Minas Gerais. Região de grutas, minerais, vegetação de cerrado (com diversidade em espécies comestíveis e medicinais), de fazendas de gado, animais em perigo de extinção e homens sábios do sertão, é com o uso dessa enigmática paisagem, que o escritor vai moldar o seu ―recado‖. Através de um estudo comparado entre os ideais naturalistas de Vandelli (evidentes nas correspondências trocadas com Lineu e nas Instruções aos viajantes) e do escritor Guimarães Rosa (expresso de forma ficcional), destacamos a necessidade de se resgatar, nos dias atuais, seus trabalhos, como forma de se propor uma nova relação do homem com o meio ambiente. Nós, de fato, reconhecemos que Deus todo-poderoso escreveu dois livros, a natureza e a revelação [...] (Lineu, 1765) O confronto entre certas criações ficcionais e a dinâmica da colonização nos leva a percorrer interessantes caminhos da História, da Literatura e das Ciências da Natureza. Se a história registrou o intenso intercâmbio de produtos e idéias, que ocorreu entre Portugal e Brasil, via Atlântico, a partir da descoberta do Novo Mundo, alguns escritores do Modernismo brasileiro revisitaram e recriaram esse passado. No que se refere às expedições científicas portuguesas pelo Brasil, o historiador Oswaldo Munteal Filho lembra que, na segunda metade do século XVIII, Portugal impulsionou a elaboração de um projeto de confecção de uma História Natural de suas colônias, tendo como espaço de criação cultural e reflexiva a Academia Real das Ciências de Lisboa. Esse empreendimento, no entanto, não teria sido possìvel sem as ―viagens imaginárias‖ do intelectual ilustrado Domenico Agostino Vandelli, um dos principais articuladores da política portuguesa dirigida às colônias no âmbito da Academia. Segundo seu pensamento, era preciso munir os naturalistas com ferramentas capazes de desvendar um Brasil desconhecido do ponto de vista da ciência e ainda intocado quanto às potencialidades de seus elementos naturais. Portanto, o olhar do naturalista deveria passar, primeiro, pelo utilitário: as virtudes das plantas medicinais, os usos dos gêneros exóticos, o aproveitamento do reino animal e mineral e a fertilidade das extensas terras. Reordenar a Natureza, não mais de forma alegórica, mas através da observação e experiência figurava-lhe como medida necessária e urgente. A par disso e instruídos conforme o livro Viagens filosóficas ou dissertações sobre as importantes regras que o filósofo naturalista, nas suas peregrinações, deve principalmente observar, alunos da Universidade de Coimbra, onde Vandelli era professor de História Natural e Química, são preparados para explorar as colônias ultramarinas (p. 483-518).

Museus sem lugar: ensaios, manifestos e diálogos em rede

Contém artigos de: Helena Barranha - Introdução: manifestos por um museu sem lugar (pp.3-8); Natalie Bookchin e Alexei Shulgin - Introdução à net.art (1994-1999) [1999] (pp.11-18); Andreas Broegger - Net Art, web art, online art, net.art? [2000] (pp.19-24); Josephine Berry - Humano, demasiado Pós-Humano? A Net Art e os seus críticos [2000] (pp.25-33); Jon Ippolito - Dez mitos sobre a Internet Art [2002] (pp.34-44); Manuel Castells - Os museus na era da informação: conectores culturais de tempo e espaço [2001] (pp.47-62); Yehuda Kalay e John Marx - Arquitectura e Internet: projectar lugares no ciberespaço [2005] (pp.63-87); Erkki Huhtamo - Nas (ou para além das) pontas dos dedos: arte contemporânea, práticas expositivas e tactilidade [2008] (pp.88-102); Domenico Quaranta - Perdido na tradução. Ou trazer a Net Art para outro lugar – desculpem, contexto [2008] (pp.103-120); Marisa Olson - Pós-Internet: A Arte depois da Internet [2011] (pp.123-136); Fred Forest - A arte cosa mentale. Do visível ao invisível e da realidade a uma realidade... diferente. [2012] (pp.137-141); Hito Steyerl - Demasiado mundo: a Internet morreu? [2012] (pp.142-158); Excertos das entrevistas realizadas, no âmbito do projecto unplace, a artistas, curadores e investigadores (pp.159-196).