Aldosterone status associates with insulin resistance in patients with heart failure-data from the ALOFT study

<b>Background</b>: Aldosterone plays a key role in the pathophysiology of heart failure. In around 50% of such patients, aldosterone 'escapes' from inhibition by drugs that interrupt the renin-angiotensin axis; such patients have a worse clinical outcome. Insulin resistance is a risk factor in heart failure and cardiovascular disease. The relationship between aldosterone status and insulin sensitivity was investigated in a cohort of heart failure patients. <b>Methods</b>: 302 patients with New York Heart Association (NYHA) class II-IV heart failure on conventional therapy were randomized in ALiskiren Observation of heart Failure Treatment study (ALOFT), designed to test the safety of a directly acting renin inhibitor. Plasma aldosterone and 24-hour urinary aldosterone excretion as well as fasting insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Subjects with aldosterone escape and high urinary aldosterone were identified according to previously accepted definitions. <b>Results</b>: Twenty per-cent of subjects demonstrated aldosterone escape and 34% had high urinary aldosterone levels. At baseline, there was a positive correlation between fasting insulin and plasma(r=0.22 p<0.01) and urinary aldosterone(r=0.19 p<0.03). Aldosterone escape and high urinary aldosterone subjects both demonstrated higher levels of fasting insulin (p<0.008, p<0.03), HOMA-IR (p<0.06, p<0.03) and insulin-glucose ratios (p<0.006, p<0.06) when compared to low aldosterone counterparts. All associations remained significant when adjusted for potential confounders. <b>Conclusions</b>: This study demonstrates a novel direct relationship between aldosterone status and insulin resistance in heart failure. This observation merits further study and may identify an additional mechanism that contributes to the adverse clinical outcome associated with aldosterone escape

BRST Detour Quantization

We present the BRST cohomologies of a class of constraint (super) Lie algebras as detour complexes. By giving physical interpretations to the components of detour complexes as gauge invariances, Bianchi identities and equations of motion we obtain a large class of new gauge theories. The pivotal new machinery is a treatment of the ghost Hilbert space designed to manifest the detour structure. Along with general results, we give details for three of these theories which correspond to gauge invariant spinning particle models of totally symmetric, antisymmetric and K\"ahler antisymmetric forms. In particular, we give details of our recent announcement of a (p,q)-form K\"ahler electromagnetism. We also discuss how our results generalize to other special geometries.Comment: 43 pages, LaTeX, added reference

Gravity, Two Times, Tractors, Weyl Invariance and Six Dimensional Quantum Mechanics

Fefferman and Graham showed some time ago that four dimensional conformal geometries could be analyzed in terms of six dimensional, ambient, Riemannian geometries admitting a closed homothety. Recently it was shown how conformal geometry provides a description of physics manifestly invariant under local choices of unit systems. Strikingly, Einstein's equations are then equivalent to the existence of a parallel scale tractor (a six component vector subject to a certain first order covariant constancy condition at every point in four dimensional spacetime). These results suggest a six dimensional description of four dimensional physics, a viewpoint promulgated by the two times physics program of Bars. The Fefferman--Graham construction relies on a triplet of operators corresponding, respectively to a curved six dimensional light cone, the dilation generator and the Laplacian. These form an sp(2) algebra which Bars employs as a first class algebra of constraints in a six-dimensional gauge theory. In this article four dimensional gravity is recast in terms of six dimensional quantum mechanics by melding the two times and tractor approaches. This "parent" formulation of gravity is built from an infinite set of six dimensional fields. Successively integrating out these fields yields various novel descriptions of gravity including a new four dimensional one built from a scalar doublet, a tractor vector multiplet and a conformal class of metrics.Comment: 27 pages, LaTe

Pentraxin 3 in cardiovascular disease

The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality

Local attitudes toward Apennine brown bears: Insights for conservation issues

Human-carnivore coexistence is a multi-faceted issue that requires an understanding of the diverse attitudes and perspectives of the communities living with large carnivores. To inform initiatives that encourage behaviors in line with conservation goals, we focused on assessing the two components of attitudes (i.e., feelings and beliefs), as well as norms of local communities coexisting with Apennine brown bears (Ursus arctos marsicanus) for a long time. This bear population is under serious extinction risks due to its persistently small population size, which is currently confined to the long-established protected area of Abruzzo, Lazio and Molise National Park (PNALM) and its surrounding region in central Italy. We interviewed 1,611 residents in the PNALM to determine attitudes and values toward bears. We found that support for the bear's legal protection was widespread throughout the area, though beliefs about the benefits of conserving bears varied across geographic administrative districts. Our results showed that residents across our study areas liked bears. At the same time, areas that received more benefits from tourism were more strongly associated with positive feelings toward bears. Such findings provide useful information to improve communication efforts of conservation authorities with local communities

General method for prediction of thermal conductivity for well-characterized hydrocarbon mixtures and fuels up to extreme conditions using entropy scaling

A general and efficient technique is developed to predict the thermal conductivity of well-characterized hydrocarbon mixtures, rocket propellant (RP) fuels, and jet fuels up to high temperatures and high pressures (HTHP). The technique is based upon entropy scaling using the group contribution method coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state. The mixture number averaged molecular weight and hydrogen to carbon ratio are used to define a single pseudo-component to represent the compounds in a well-characterized hydrocarbon mixture or fuel. With these two input parameters, thermal conductivity predictions are less accurate when the mixture contains significant amounts of iso-alkanes, but the predictions improve when a single thermal conductivity data point at a reference condition is used to fit one model parameter. For eleven binary mixtures and three ternary mixtures at conditions from 288 to 360 K and up to 4,500 bar, thermal conductivities are predicted with mean absolute percent deviations (MAPDs) of 16.0 and 3.0% using the two-parameter and three-parameter models, respectively. Thermal conductivities are predicted for three RP fuels and three jet fuels at conditions from 293 to 598 K and up to 700 bar with MAPDs of 14.3 and 2.0% using the two-parameter and three-parameter models, respectively

Changes in impervious surface area, flood frequency, and water chemistry within the Delaware River basin during the past 50 years: initial results

Proceedings of the Seventh International Conference on Hydroscience and Engineering, Philadelphia, PA, September 2006. http://hdl.handle.net/1860/732Housing development and total road mileage expansion, which result from the growing population and economic activity in the region, increased the total impervious surface area (ISA) within the Delaware River Basin (DRB) from either 3.19% or 3.69% of the total basin area in 1950 to either 5.41% or 6.44% of the total basin area in 2000, depending on which of two plausible scenarios are used for interpreting the available housing and road mileage data. Assuming an average area of 0.3 acre and 35% ISA for a single-unit detached house and 0.1 acre and 60% ISA for all other housing units, the projected ISA for the DRB is 5.66% in 2006. This result is comparable with the existing GIS data from the LandSat Thematic Mapper Imager for part of the DRB. Associated with the increasing ISA in the DRB, there also is an increase in flood events for recent years. Increased peak flows in July and August, which are the two months with the highest precipitation, also are noticeable. Concentrations of sodium and chloride in the Delaware River water increased between 2-4.6 times over the last 50 years at both upstream and downstream locations. Increased application of sodium chloride, in the form of deicing salt that is tied to the expansion of total road mileage in the basin, may be one of the main reasons for the increase of these ions in the waters of the Delaware River

The value of some Corsican sub-populations for genetic association studies

<p>Abstract</p> <p>Background</p> <p>Genetic isolates with a history of a small founder population, long-lasting isolation and population bottlenecks represent exceptional resources in the identification of disease genes. In these populations the disease allele reveals Linkage Disequilibrium (LD) with markers over significant genetic intervals, therefore facilitating disease locus identification. In a previous study we examined the LD extension on the Xq13 region in three Corsican sub-populations from the inner mountainous region of the island. On the basis of those previous results we have proposed a multistep procedure to carry out studies aimed at the identification of genes involved in complex diseases in Corsica. A prerequisite to carry out the proposed multi-step procedure was the presence of different degrees of LD on the island and a common genetic derivation of the different Corsican sub-populations. In order to evaluate the existence of these conditions in the present paper we extended the analysis to the Corsican coastal populations.</p> <p>Methods</p> <p>Samples were analyzed using seven dinucleotide microsatellite markers on chromosome Xq13-21: DXS983, DXS986, DXS8092, DXS8082, DXS1225, DXS8037 and DXS995 spanning approximately 4.0 cM (13.3 Mb). We have also investigated the distribution of the DXS1225-DXS8082 haplotype which has been recently proposed as a good marker of population genetic history due to its low recombination rate.</p> <p>Results</p> <p>the results obtained indicate a decrease of LD on the island from the central mountainous toward the coastal sub-populations. In addition the analysis of the DXS1225-DXS8082 haplotype revealed: 1) the presence of a particular haplotype with high frequency; 2) the derivation from a common genetic pool of the sub-populations examined in the present study.</p> <p>Conclusion</p> <p>These results indicate the Corsican sub-populations useful for the fine mapping of genes contributing to complex diseases.</p

Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe