Continuous-time branching processes (CTBPs) are powerful tools in random graph theory, but are not appropriate to describe real-world networks since they produce trees rather than (multi)graphs. In ...this paper we analyze collapsed branching processes (CBPs), obtained by a collapsing procedure on CTBPs, in order to define multigraphs where vertices have fixed out-degree m≥2. A key example consists of preferential attachment models (PAMs), as well as generalized PAMs where vertices are chosen according to their degree and age. We identify the degree distribution of CBPs, showing that it is closely related to the limiting distribution of the CTBP before collapsing. In particular, this is the first time that CTBPs are used to investigate the degree distribution of PAMs beyond the tree setting.
We have previously reported that genetic immunization with Tc13Tul antigen of Trypanosoma cruzi, the aetiological agent of Chagas' disease, triggers harmful effects and non-protective immune ...responses. In order to confirm the role of Tc13 antigens during T. cruzi infection, herein we studied the humoral and cellular immune responses to the Tc13Tul molecule and its EPKSA C-terminal portion in BALB/c T. cruzi-infected mice or mice immunized with recombinant Tc13Tul. Analysis of the antibody response showed that B-cell epitopes that stimulate a sustained IgM production along the infection and high levels of IgG in the acute phase are mainly located at the Tc13 N- and C-terminal domains, respectively. DTH assays showed that T-cell epitopes are mainly at the Tc13 N-terminal segment and that they do not elicit an efficient memory response. Recombinant Tc13Tul did not induce IFN-gamma secretion in either infected or immunized mice. However, a putative CD8+Tc13Tul-derived peptide was found to elicit IFN-gamma production in chronically infected animals. Immunization with recombinant Tc13Tul did not induce pathology in tissues and neither did it protect against the infection. Our results show that in the outcome of T. cruzi infection the Tc13 family protein mainly triggers non-protective immune responses.
Abstract
Background
Lipid lowering treatment (LLT) and LDL–C target across CV risk categories might prompt consideration on further lower LDL–C levels advocated by last EAS/ESC guidelines.
Aim
The ...aim of the study was to provide current prevalence, clinical characteristics, LLT across different CV risk classes at the time of publication of current ESC/EAS Guidelines. Short–term prognosis was also addressed.
Methods and Results
This community–based study enrolled 6851 patients (mean age 71 years) with an LDL–C measurement and cardiological evaluation from 01–Jan–2018 until 31–Dec–2018. Of those, 4578 (67%) patients were at very high risk, 1494 (22%) at high risk, 420 (6%) at moderate risk, and 359 (5%) at low risk according to EAS/ESC 2019 guidelines. Dyslipidemia was present in three quarter of patients, and 3888 (57%) received LLT. High Efficacy (potency to reduce LDL–C ≥ 50%) LLT was prescribed in 21% of patients (23% and 10% in very high and high risk categories). There was a statistically significant difference between CV categories with respect to demographic, CV risk factors, and comorbidities. Patients at very high risk were more frequently elderly with a high proportion of patients affected by atherosclerotic CVD (ASCVD) and non–cardiac comorbidities. 394 (9%) patients at very high risk and 102 (7%) patients at high risk presented LDL–C at target. Among very high risk patients, 439 (10%) were treated with ezetimibe. At 24 months of follow–up, death occurred in 676 (8%) patients. In survival curves, adjusted for age and comorbidities, an increased risk of death and CV hospitalization was confirmed in the high risk and very high risk categories. Similar trend was confirmed considering composite endpoint of myocardial infarction and stroke.
Conclusion
In a contemporary population the strategy to achieve the ambitious LDL–C target of current Guidelines continue to be largely suboptimal and LLT is widely underused. This underlines the huge unmet need when assessed more aggressive LDL–C target advocated in current EAS/ESC guidelines.
Abstract
Aims
The aim of the study was to provide real–world data on low–density lipoprotein cholesterol (LDL–C) goal achievement at the time of current 2019 ESC/EAS Guidelines, treatment patterns ...and patient adherence to lowering lipid treatment (LLT).
Methods and Results
This community–based study identified patients with at least one LDL–C measurement and cardiological evaluation from 01–Jan–2016 to 31–Dec–2018. Patients risk stratification and LDL–C target achievement were assessed according to 2019 EAS/ESC guidelines. To identify the proportion of patients at LDL–C target, only patients with an available LDL–C evaluation after 1 year from baseline were considered (7317 patients, 51% of initial cohort 14317 pts). Of those, 492 pts (7%) presented LDL–C at target. Among them, 187 were at very high risk (4% of very high risk subgroup) and 47 at high risk (3% of high risk subgroup). Statin intolerance was reported in 7,5% of patients (1073 out of 14317). The adherence evaluation was performed in patients having 1–year of follow–up and at least one statin purchase. It was estimated through the Proportion of Days Covered (PDC), defining as adherent patients with a PDC value ≥ 75%. 8332 (58% of initial cohort 14317 pts) met the selection criteria for PDC calculation. Of those, 3346 (40%) patients resulted as adherent (46% and 22% in very high e high CV risk categories). In a multivariable Cox regression model, adjusted for age, sex, risk factors and comorbidities, patients adherence emerged as a protective factor (HR 0.62; 95% CI 0.43–0.89; p = 0,010).
Conclusion
In a real–world setting, the achievement of LDL–C target and patient adherence was suboptimal across different CV risk categories. In a full adjusted survival model, patient adherence was independently associated with a prognosis improvement.
Drugs currently used for treatment of Trypanosoma cruzi infection, the ethiological agent of Chagas’ disease, have shown side effects and variable efficiency. With the aim to describe parasite ...enzymes involved in the mechanisms of action of trypanocidal drugs and since it has been reported that reductases are crucial in their metabolism, we attempted to identify novel NADPH-dependent oxido-reductases from T. cruzi. The percolation of a soluble fraction of epimastigote lysates through a Cibacron Blue-Sepharose column followed by elution by NADPH yielded a predominant protein with an apparent molecular weight of 32kDa. This protein was identified by MALDI-TOF as an aldo-keto reductase (AKR) and hence denominated TcAKR. TcAKR was mainly localized in the cytosol and was also present in trypomastigote and amastigote lysates. The recombinant TcAKR (recTcAKR) showed NADPH-dependent reductase activity with the AKR substrates 4-nitrobenzaldehyde and 2-dihydroxyacetone. The saturation curves for both substrates were consistent with the Michaelis–Menten model. We also tested whether recTcAKR may reduce naphthoquinones (NQ), since many of these compounds have displayed important trypanocidal activity. recTcAKR reduced o-NQ (1,2-naphthoquinone, 9,10-phenanthrenquinone and β-lapachone) with concomitant generation of free radicals but did not exhibit affinity for p-NQ (5-hydroxy-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone, α-lapachone and menadione). The substrate saturation curve with o-NQ fitted to a sigmoidal curve, suggesting that recTcAKR presents a cooperative behavior. In addition, three peaks assigned to monomers, dimers and tetramers were obtained when recTcAKR was submitted to a Superose 12 gel chromatography column. TcAKR is the first member of the AKR family described in T. cruzi. Our results indicate that this enzyme may participate in the mechanisms of action of trypanocidal drugs.
Aim of this work is to investigate the impact of soft breakdown on the main transistor parameters and the recovery of transistor leakage and performance after an annealing treatment. The correlation ...between soft (SBD) and hard breakdown (HBD) failures is also analysed considering the different impact of a thermal treatment. This treatment does not significantly improve the localised leakage current. On the other hand, the oxide recovery, measured by transistor parameters affected mainly by interface properties, is sufficient to cure the oxide reliability. In order to induce a new SBD event, the percolation path needs to inject the same amount of charge through the oxide, generating the same critical “bulk” and interface defect density of the virgin oxide.
Oxide reliability is a key issue and the main topic of several recent works. We study the impact of gate oxide stress on transistor performances following a methodology similar to oxide lifetime ...characterisation in capacitors. A universal trend for degradation of the threshold voltage and drain saturation current with injected charge is observed and the impact of boron on trapping enhancement has been separated by comparing n-MOS and p-MOS.
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