Deep electrical resistivity structure of northwestern Costa Rica

First long-period magnetotelluric investigations were conducted in early 2008 in northwestern Costa Rica, along a profile that extends from the coast of the Pacific Ocean, traverses the volcanic arc and ends currently at the Nicaraguan border. The aim of this study is to gain insight into the electrical resistivity structure and thus fluid distribution at the continental margin where the Cocos plate subducts beneath the Caribbean plate. Preliminary two-dimensional models map the only moderately resistive mafic/ultramafic complexes of the Nicoya Peninsula (resistivity of a few hundred Ωm), the conductive forearc and the backarc basins (several Ωm). Beneath the backarc basin the data image a poor conductor in the basement with a clear termination in the south, which may tentatively be interpreted as the Santa Elena Suture. The volcanic arc shows no pronounced anomaly at depth, but a moderate conductor underlies the backarc with a possible connection to the upper mantle. A conductor at deep-crustal levels in the forearc may reflect fluid release from the downgoing slab

Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6×10−5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP × sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63×10−8), as well as the sex-interaction with rs16847548 (P = 8.68×10−6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval

Fluxes and origin of halogenated organic trace gases from Momotombo volcano (Nicaragua)

In order to assess the contribution of quiescent degassing volcanoes to the global halo(hydro)carbon inventory, we have quantified volcanic fluxes of methyl halides (CH3Cl, CH3Br, and CH3I), ethyl halides (C2H5Cl, C2H5Br, and C2H5I), and higher chlorinated methanes (CH2Cl2, CHCl3, and CCl4). About every eight months over a 2-year period (July 2001 to July 2003), gas samples were collected and analyzed from high-temperature fumaroles (472°C–776°C) at the Nicaraguan subduction zone volcano Momotombo. Using a simultaneous record of trace and main compounds in fumarolic gases as well as SO2 fluxes of the plume, we were able to calculate halo(hydro)carbon fluxes for Momotombo and extrapolate our results to estimate halo(hydro)carbon fluxes for the whole Quaternary Nicaraguan volcanic arc and, in addition, for all volcanoes globally. The most abundant halohydrocarbon was CH3Cl with concentrations up to 19 ppmv. Further major halo(hydro)carbons were CH3Br, CH3I, CH2Cl2, CHCl3, CCl4, C2H5Cl, C2H5Br, C2H5I, and C2H3Cl with an average concentration of 0.20 to 720 ppbv. Estimated mean halo(hydro)carbon fluxes from Momotombo were in the range of 630–5000 g/yr for methyl halides, 49–260 g/yr for ethyl halides, and 2.4–24 g/yr for higher chlorinated methanes. When the results for Momotombo are scaled up to SO2 fluxes of the Nicaraguan volcanic transect, fluxes of 1.7 × 105 g/yr CH3Cl and 82 g/yr CCl4 are attained for Nicaragua. Scaled up to the estimated global SO2 flux, this translates to hypothetical global fluxes of 5.6 × 106 g/yr CH3Cl and 2.7 × 103 g/yr CCl4. These volcanic fluxes are negligible compared to global anthropogenic and natural emissions of about 3 × 1012 g/yr CH3Cl and 2 × 1010 g/yr CCl4

QT dispersion in patients with systemic lupus erythematosus: the impact of disease activity

<p>Abstract</p> <p>Background</p> <p>Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.</p> <p>Methods and Results</p> <p>One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).</p> <p>QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; <it>P </it>< 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, <it>P </it>= 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, <it>P </it>= 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (<it>P </it>< 0.004).</p> <p>Conclusions</p> <p>QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.</p> <p>Trial registration</p> <p>Clinicaltrial.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031797">NCT01031797</a></p

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

&lt;p&gt;Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.&lt;/p&gt; &lt;p&gt;The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.&lt;/p&gt; &lt;p&gt;Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.&lt;/p&gt; &lt;p&gt;Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.&lt;/p&gt; &lt;p&gt;Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.&lt;/p&gt; &lt;p&gt;Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.&lt;/p&gt

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis

BACKGROUND\nOBJECTIVES\nPATIENTS AND METHODS\nRESULTS\nCONCLUSIONS\nLinezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.\nBecause rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.\nPharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.\nWe demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.\nA substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.Pharmacolog

The production and reproduction of inequality in the UK in times of austerity

Inequality appears to be back on the intellectual and political agenda. This paper provides a commentary on this renewed interest, drawing on an empirical discussion of inequality in the UK. The paper argues that inequality should be seen as produced in the inherently unequal social relations of production, drawing attention to the role of social struggle in shaping dynamics of inequality. However, inequality is not just produced in dynamic class struggle in the formal economy, but also through the social reproduction of labour power on a day-to-day and inter-generational basis. As such, inequalities of household resources at any point in time may be reproductive of greater future inequality. It is argued that inequality has risen in the UK over recent decades because of changes in the social relations of production in the formal economy and social reproduction in the domestic sector, both of which have witnessed significant state interventions that have increased structural inequalities. It is argued that, absent of significant change, the underpinning structural dynamics in the UK will lead to further increases in inequality over the short and longer-term. Given this, we might expect to see an already emergent ‘New Politics of Inequality’ intensifying in the coming decades.n/