964 resultados para 27-31SAE-2801-21


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Background: CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients. Methodology: Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4 +/- 9 years received dexamethasone (mean 0.27 +/- 0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 mu g/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI >= 30 kg/m(2). NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis. Results: Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m(2) +/- 5.3 vs. 26 kg/m(2) +/- 5.3, respectively) and waist circumference (89 cm +/- 12.7 vs. 81 cm +/- 13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ. Conclusion: In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.

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21 cm cosmology opens an observational window to previously unexplored cosmological epochs such as the Epoch of Reionization (EoR), the Cosmic Dawn and the Dark Ages using powerful radio interferometers such as the planned Square Kilometer Array (SKA). Among all the other applications which can potentially improve the understanding of standard cosmology, we study the promising opportunity given by measuring the weak gravitational lensing sourced by 21 cm radiation. We performed this study in two different cosmological epochs, at a typical EoR redshift and successively at a post-EoR redshift. We will show how the lensing signal can be reconstructed using a three dimensional optimal quadratic lensing estimator in Fourier space, using single frequency band or combining multiple frequency band measurements. To this purpose, we implemented a simulation pipeline capable of dealing with issues that can not be treated analytically. Considering the current SKA plans, we studied the performance of the quadratic estimator at typical EoR redshifts, for different survey strategies and comparing two thermal noise models for the SKA-Low array. The simulation we performed takes into account the beam of the telescope and the discreteness of visibility measurements. We found that an SKA-Low interferometer should obtain high-fidelity images of the underlying mass distribution in its phase 1 only if several bands are stacked together, covering a redshift range that goes from z=7 to z=11.5. The SKA-Low phase 2, modeled in order to improve the sensitivity of the instrument by almost an order of magnitude, should be capable of providing images with good quality even when the signal is detected within a single frequency band. Considering also the serious effect that foregrounds could have on this detections, we discussed the limits of these results and also the possibility provided by these models of measuring an accurate lensing power spectrum.

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Magnitudes of peak discharges of 43 non-instrumentally measured Rhine river floods at Basel were reconstructed. The methodology is based on a range of different historic sources, containing flood information (including traditional urban inundation reference points from flood reports of medieval and early modern period chroniclers as well as 19th century journalists, flood marks, paintings and drawings, town maps, longitudinal and cross profiles etc.). These traditional pre-instrumental “flood information systems” still existed in the 19th century, when in 1808 the first instrumental hydrological measurements started. They thus could be calibrated with instrumental measurements in the 19th century overlapping period. The result is a 743 year long quantified Rhine river flood series. Floods of both periods (pre-instrumental as well as instrumental) can thus be directly compared for the very first time. The long-range consequences of rivers Kander and Aare deviations in 1714 and 1878 are reflected in a distinct change of magnitudes of peak discharges in Basel. A clear flood “disaster gap” appears in the 20th century. The lack of any extreme floods for such a long time is completely unique during the 743-year period of analysis. This result will influence the statistical assessment of once-in-a-century events, which might be of great interest for insurance campanies.