Single-Pill Combination with Three Antihypertensive Agents to Improve Blood Pressure Control in Hypertension: Focus on Olmesartan-Based Combinations.

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients

High Performance Algorithms for Counting Collisions and Pairwise Interactions

The problem of counting collisions or interactions is common in areas as computer graphics and scientific simulations. Since it is a major bottleneck in applications of these areas, a lot of research has been carried out on such subject, mainly focused on techniques that allow calculations to be performed within pruned sets of objects. This paper focuses on how interaction calculation (such as collisions) within these sets can be done more efficiently than existing approaches. Two algorithms are proposed: a sequential algorithm that has linear complexity at the cost of high memory usage; and a parallel algorithm, mathematically proved to be correct, that manages to use GPU resources more efficiently than existing approaches. The proposed and existing algorithms were implemented, and experiments show a speedup of 21.7 for the sequential algorithm (on small problem size), and 1.12 for the parallel proposal (large problem size). By improving interaction calculation, this work contributes to research areas that promote interconnection in the modern world, such as computer graphics and robotics.Comment: Accepted in ICCS 2019 and published in Springer's LNCS series. Supplementary content at https://mjsaldanha.com/articles/1-hpc-ssp

High-spin structures of 88Kr and 89Rb: Evolution from collective to single-particle behaviors

The high-spin states of the two neutron-rich nuclei, 88Kr and 89R have been studied from the 18O + 208Pb fusion-fission reaction. Their level schemes were built from triple gamma-ray coincidence data and gamma-gamma angular correlations were analyzed in order to assign spin and parity values to most of the observed states. The two levels schemes evolve from collective structures to single-particle excitations as a function of the excitation energy. Comparison with results of shell-model calculations gives the specific proton and neutron configurations which are involved to generate the angular momentum along the yrast lines.Comment: 12 pages, 9 figures, Physical Review C (2013) in pres

Dewetting of Glassy Polymer Films

Dynamics and morphology of hole growth in a film of power hardening viscoplastic solid (yield stress ~ [strain-rate]^n) is investigated. At short-times the growth is exponential and depends on the initial hole size. At long-times, for n > 1/3, the growth is exponential with a different exponent. However, for n < 1/3, the hole growth slows; the hole radius approaches an asymptotic value as time tends to infinity. The rim shape is highly asymmetric, the height of which has a power law dependence on the hole radius (exponent close to unity for 0.25 < n < 0.4). The above results explain recent intriguing experiments of Reiter, Phys. Rev. Lett, 87, 186101 (2001).Comment: 4 pages, 5 figures, RevTe

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents

High-spin structures of 136Cs

Odd-odd 136Cs nuclei have been produced in the 18O + 208Pb and 12C + 238U fusion-fission reactions and their gamma rays studied with the Euroball array. The high-spin level scheme has been built up to ~ 4.7 MeV excitation energy and spin I ~ 16 hbar from the triple gamma-ray coincidence data. The configurations of the three structures observed above ~ 2 MeV excitation energy are first discussed by analogy with the proton excitations identified in the semi-magic 137Cs nucleus, which involve the three high-j orbits lying above the Z=50 gap, pi g_{7/2}, pi d_{5/2} and pi h_{11/2}. This is confirmed by the results of shell-model calculations performed in this work.Comment: 6 pages, 4 figures, 3 table

Protein-RNA and protein-protein interactions mediate association of human EST1A/SMG6 with telomerase

The human EST1A/SMG6 polypeptide physically interacts with the chromosome end replication enzyme telomerase. In an attempt to better understand hEST1A function, we have started to dissect the molecular interactions between hEST1A and telomerase. Here, we demonstrate that the interaction between hEST1A and telomerase is mediated by protein-RNA and protein-protein contacts. We identify a domain within hEST1A that binds the telomerase RNA moiety hTR while full-length hEST1A establishes in addition RNase-resistant and hTR-independent protein-protein contacts with the human telomerase reverse transcriptase polypeptide (TERT). Conversely, within hTERT, we identify a hEST1A interaction domain, which comprises hTR-binding activity and RNA-independent hEST1A-binding activity. Purified, recombinant hEST1A binds the telomerase RNA moiety (hTR) with high affinity (apparent overall K(d) = 25 nM) but low specificity. We propose that hEST1A assembles specifically with telomerase in the context of the hTR-hTERT ribonucleoprotein, through the high affinity of hEST1A for hTR and specific protein-protein contacts with hTERT

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction