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.

Application of Asymmetric Marcus-Hush Theory to Voltammetry in Room-Temperature Ionic Liquids

Asymmetric MarcusHush (AMH) theory is applied for the first time in ionic solvents to model the voltammetric reduction of oxygen in 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)-imide and of 2-nitrotoluene (2-NT), nitrocyclopentane (NCP), and 1-nitro-butane (BuN) in trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate on a gold microdisc electrode. An asymmetry parameter, gamma, was estimated for all systems as -0.4 for the reduction of oxygen and -0.05, 0.25, and 0 +/- 0.05 for the reductions of 2-NT, NCP, and BuN, respectively, which suggests equal force constants of reactants and products in the case of 2-NT and BuN and unequal force constants for oxygen and NCP where the force constants of the oxidized species are greater than the reduced species in the case of oxygen and less than the reduced species in the case of NCP. Previously measured values for a, the Butler-Volmer transfer coefficient, reflect this in each case. Where appreciable asymmetry occurs, AMH theory was seen to parametrize the experimental data better than either Butler-Volmer or symmetric Marcus-Hush theory, allowing additionally the extraction of reorganization energy. This is the first study to provide key physical insights into electrochemical systems in room-temperature ionic liquids using AMH theory, allowing elucidation of the reorganization energies and the relative force constants of the reactants and products in each reaction.

Texto, tradução e notas de Marcus Fabius Quintilianus, livro III

Tese de mestrado, Estudos Clássicos, Universidade de Lisboa, Faculdade de Letras, 2013

Diogenis Laertii de vitis, dogmatibus et apophthegmatibus clarorum philosophorum, libri. Graece et Latine : cum subjunctis integris annotationibus Is. Casauboni, Th. Aldobrandidni & Mer. Casauboni. Latinam Ambrosii versionem complevit & emendavit, Marcus Meibomius. Seorsum excusas Aeg. Menagii in Diogenem observationes auctiores habet volumen II. Ut & ejusdem syntagma de mulieribus philosophis; et Joachimi Kühnii adDiogenem notas, additae denique sunt priorum editionum praefationes, &indices locupletissimi

UANL

The sediment trapping efficiency of the macro-tidal Daly Estuary, tropical Australia

Field studies were carried out on the water and sediment dynamics in the tropical, macro-tidal, Daly Estuary. The estuary is shallow, very-turbid, about 100 km long, and the entrance is funnel-shape. In the wet, high flow season, normal tidal ranges can be suppressed in the estuary, depending on inflow rates, and freshwater becomes dominant up to the mouth. At that time a fraction of the fine sediment load is exported offshore as a bottom-tagging nepheloid layer after the sediment falls out of suspension of the thin, near-surface, river plume. The remaining fraction and the riverine coarse sediment form a large sediment bar 10 km long, up to 6 m in height and extending across the whole width of the channel near the mouth. This bar, as well as shoals in the estuary, partially pond the mid- to upper-estuary. This bar builds up from the deposition of riverine sediment during a wet season with high runoff and can raise mean water level by up to 2 m in the upper estuary in the low flow season. This ponding effect takes about three successive dry years to disappear by the sediment forming the bar being redistributed all over the estuary by tidal pumping of fine and coarse sediment in the dry season, which is the low flow season. The swift reversal of the tidal currents from ebb to flood results in macro-turbulence that lasts about 20 min. Bed load transport is preferentially landward and occurs only for water currents greater than 0.6 m s(-1). This high value of the threshold velocity suggests that the sand may be cemented by the mud. The Daly Estuary thus is a leaky sediment trap with an efficiency varying both seasonally and inter-annually. (c) 2006 Elsevier Ltd. All rights reserved.

Gallic war songs (II): Marcus Cicero, Quintus Cicero, and Caesar’s invasion of Britain

This article assembles and examines the evidence for the poetic outputs of Marcus and Quintus Cicero related to Caesar’s invasion of Britain. Following the establishment of a relative chronology of the evidence for their work, it is argued that Quintus Cicero most likely produced a fabula praetexta (not an epic poem, as commonly assumed). His brother, in turn, wrote an epic, based on Quintus’ eye-witness reports. Careful analysis of the ancient discourse about this piece reveals insights in Cicero’s poetic workshop and the creation of ‘archival truth’ through narrativising historical events in epic poetry. Finally, a case is made for greater attention to financial affairs between Caesar and the Ciceros that happen to coincide with the drafting process of their respective literary works.

Measuring health in a vacuum: examining the disability weight of the DALY

The Disability Adjusted Life Year (DALY) is a widely used summary measure of population health combining years of life lost due to mortality and years of healthy life lost due to disability. A feature of the DALY is that, in the assessment of morbidity, each health condition is associated with a disability weight. The disability weight lies on a scale between 0 (indicating the health condition is equivalent to full health) and 1 (indicating the health condition is equivalent to death). The disability weight associated with each health condition is currently fixed across all social, cultural and environmental contexts. Thus blindness in the United Kingdom has the same disability weight as blindness in Niger in spite of structural interventions in the UK that make the disability less severe than in Niger. Although the fixed disability weight is defended on grounds that it supports a strongly egalitarian flavour in the DALY, we argue that the lack of consideration of realistic contexts results in a measure that will underestimate the burden associated with morbidity in disadvantaged populations and overestimate the burden in advantaged populations. There is, consequently, a loss of information on possible non-clinical points of intervention. Disaggregated estimates of the burden of disease such as those in the World Health Report 2000 should be interpreted with caution.