Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years - Relationships to hormone replacement therapy

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34: 1.26, 1.35), or fibrin D-dimer (3.84; 1.99, 7.32). HRT use increased the risk of VTE in women without any of these thrombotic static; (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95%, CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However. HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed

Agriculture, meteorology and water quality in Ireland: a regional evaluation of pressures and pathways of nutrient loss to water

peer-reviewedThe main environmental impact of Irish agriculture on surface and ground water quality is the potential transfer of nutrients to water. Soil water dynamics mediate the transport of nutrients to water, and these dynamics in turn depend on agro-meteorological conditions, which show large variations between regions, seasons and years. In this paper we quantify and map the spatio-temporal variability of agro-meteorological factors that control nutrient pressures and pathways of nutrient loss. Subsequently, we evaluate their impact on the water quality of Irish rivers. For nitrogen, pressure and pathways factors coincide in eastern and southern areas, which is reflected in higher nitrate levels of the rivers in these regions. For phosphorus, pathway factors are most pronounced in north-western parts of the country. In south-eastern parts, high pressure factors result in reduced biological water quality. These regional differences require that farm practices be customised to reflect the local risk of nutrient loss to water. Where pathways for phosphorus loss are present almost year-round—as is the case in most of the north-western part of the country—build-up of pressures should be prevented, or ameliorated where already high. In south-eastern areas, spatio-temporal coincidence of nutrient pressures and pathways should be prevented, which poses challenges to grassland management

Metabolomics Identifies multiple candidate biomarkers to diagnose and stage human African trypanosomiasis

Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of “sleeping sickness”. Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control

Improved Constraints on the Acceleration History of the Universe and the Properties of the Dark Energy

We extend and apply a model-independent analysis method developed earlier by Daly & Djorgovski to new samples of supernova standard candles, radio galaxy and cluster standard rulers, and use it to constrain physical properties of the dark energy as functions of redshift. Similar results are obtained for the radio galaxy and supernova data sets. The first and second derivatives of the distance are compared directly with predictions in a standard model based on General Relativity. The good agreement indicates that General Relativity provides an accurate description of the data on look-back time scales of about ten billion years. The first and second derivatives are combined to obtain the acceleration parameter, assuming only the validity of the Robertson-Walker metric, independent of a theory of gravity and of the physical nature of the dark energy. The acceleration of the universe at the current epoch is indicated by the analysis. The effect of non-zero space curvature on q(z) is explored. We solve for the pressure, energy density, equation of state, and potential and kinetic energy of the dark energy as functions of redshift assuming that General Relativity is the correct theory of gravity, and the results indicate that a cosmological constant in a spatially flat universe provides a good description of each of these quantities over the redshift range from zero to about one. We define a new function, the dark energy indicator, in terms of the first and second derivatives of the coordinate distance and show how this can be used to measure deviations of w from -1 and to obtain a new and independent measure of Omega.Comment: 46 pages, submitted for publicatio