The electrical validation of a generalized space error model is reported. This was achieved by comparing inline e-beam "direct" space metrology measurements with an end-of-line, yield-based, space ...error metric. This electrical test (e-test) of the space error is derived from the conductance of metallized test structures with programmed interlayer offsets between line and block layers used for patterning. Local space variation was extracted from voltage contrast arrays, and from inline metrology statistics. A good match was observed between the predicted space error from the weighted sum of the local and non-local terms, and the measured e-test space error. A model is proposed for the experimental validation of the local term (stochastic) of the space error model.
The aim of this review was to summarize evidence on the role of Vitamin D deficiency in heart failure (HF), from pathophysiological mechanisms to clinical effects of Vitamin D supplementation.
...Chronic HF secondary to left ventricular (LV) systolic dysfunction is a growing health problem, still associated with poor clinical outcome. In recent years, experimental and epidemiological evidence focused on the role of Vitamin D in HF. Cross sectional studies demonstrated that prevalence of HF is increased in patients with Vitamin D deficiency or parathyroid hormone (PTH) plasma level increase, whereas longitudinal studies showed enhanced risk of developing new HF in patients with Vitamin D deficiency. In addition, in patients with established HF, low plasma levels of Vitamin D are associated with worsening clinical outcome. Yet, clinical studies did not definitively demonstrate a benefit of Vitamin D supplementation for preventing HF or ameliorating clinical outcome in patients with established HF.
Despite convincing experimental and epidemiological data, treatment with Vitamin D supplementation did not show clear evidence of benefit for preventing HF or influencing its clinical course. Ongoing clinical studies will hopefully shed lights on the effects of Vitamin D supplementation on clinical endpoints along the spectrum of HF.
•Vitamin D deficiency may favour the onset and/or progression of HF and LV remodelling.•Vitamin D deficiency and increase parathyroid hormone are associated with increased prevalence of HF.•Vitamin D deficiency is associated with more adverse prognosis in heart failure patients.•Whether Vitamin D supplementation is associated favourable effect on CV mortality and morbidity remains unclear.
Sleep-disordered breathing (SDB) is common in patients with heart failure (HF), contributes to the progression of cardiac disease, and is associated with adverse prognosis. Previous evidence ...indicates that epicardial adipose tissue (EAT) is independently associated with sleep apnea in obese individuals. We explored the relationship between SDB and EAT in HF patients.
EAT thickness was assessed by echocardiography in 66 patients with systolic HF undergoing nocturnal cardiorespiratory monitoring. A significantly higher EAT thickness was found in patients with SDB than in those without SDB (10.7 ± 2.8 mm vs. 8.3 ± 1.8 mm; p = 0.001). Among SDB patients, higher EAT thickness was found in both those with prevalent obstructive sleep apnea (OSA) and those with prevalent central sleep apnea (CSA). Of interest, EAT thickness was significantly higher in CSA than in OSA patients (11.9 ± 2.9 vs. 10.1 ± 2.5 p = 0.022). Circulating plasma norepinephrine levels were higher in CSA than in OSA patients (2.19 ± 1.25 vs. 1.22 ± 0.92 ng/ml, p = 0.019). According to the apnea-hypopnea index (AHI), patients were then stratified in three groups of SDB severity: Group 1, mild SDB; Group 2, moderate SDB; Group 3, severe SDB. EAT thickness progressively and significantly increased from Group 1 to Group 3 (ANOVA p < 0.001). At univariate analysis, only left ventricular ejection fraction and AHI significantly correlated with EAT (p = 0.019 and p < 0.0001, respectively). At multivariate analysis, AHI was the only independent predictor of EAT (β = 0.552, p < 0.001).
Our results suggest an association between the presence and severity of sleep apneas and cardiac visceral adiposity in HF patients.
•Heart failure (HF) patients with Sleep-disordered breathing (SDB) show an increased epicardial adipose tissue (EAT) thickness. This EAT increase correlates with the severity of sleep apneas.•EAT thickness of HF patients with prevalent central sleep apnea is greater than in presence of obstructive sleep apnea.•The presence and the severity of SDB predict EAT thickness in HF patients.
Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. ...Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients.
One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early 1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05 and late H/M ratio 1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020 were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR.
Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF.
The quantum Hall effect allows the international standard for resistance to be defined in terms of the electron charge and Planck's constant alone. The effect comprises the quantization of the Hall ...resistance in two-dimensional electron systems in rational fractions of R(K) = h/e(2) = 25,812.807557(18) Omega, the resistance quantum. Despite 30 years of research into the quantum Hall effect, the level of precision necessary for metrology--a few parts per billion--has been achieved only in silicon and iii-v heterostructure devices. Graphene should, in principle, be an ideal material for a quantum resistance standard, because it is inherently two-dimensional and its discrete electron energy levels in a magnetic field (the Landau levels) are widely spaced. However, the precisions demonstrated so far have been lower than one part per million. Here, we report a quantum Hall resistance quantization accuracy of three parts per billion in monolayer epitaxial graphene at 300 mK, four orders of magnitude better than previously reported. Moreover, by demonstrating the structural integrity and uniformity of graphene over hundreds of micrometres, as well as reproducible mobility and carrier concentrations across a half-centimetre wafer, these results boost the prospects of using epitaxial graphene in applications beyond quantum metrology.
Abstract
Background
β-blockers are one of the four recommended disease-modifying classes of drugs for the treatment of heart failure with reduced ejection fraction (HFrEF). Although their efficacy ...and prognostic role is unquestionable in the general population of HFrEF patients, the differences in their effect in relation to sex have not been yet investigated in detail. The present study analyzed a large, real-world, Italian population of HFrEF patients aiming to highlight any prognostic difference between males and females in relation to dose and β-selectivity of the ongoing β-blocker treatment.
Methods
Out of the 7900 HFrEF patients included in the MECKI score registry, we retrospectively analyzed those treated with β-blockers. We investigated the prognostic role of β-selectivity, dividing the population in assuming β1/β2-receptor blockers (carvedilol) vs. β1-selective blockers (bisoprolol, nebivolol or metoprolol), according to sex, and the prognostic role of daily carvedilol-equivalent β-blocker dose in relation to sex. The primary outcome of the study was the composite of all cause mortality, urgent heart transplant and LVAD implant analyzed at 5 years, both as raw data and after correction of potential confounders.
Results
6784 HFrEF patients treated with β-blockers were analyzed (1215 females, 5569 males). Patients median follow-up was 4.05 years 1.72-7.47: 4.37 1.6-8.13 for females and 3.99 1.75-7.3 for males (p=ns). According to β-selectivity no prognostic differences were found in the general population, as in female or males (Fig. 1 right panel). Stratification of patients according to β-blockers equivalent dose showed significant difference among groups: mortality decreases with increasing β-blockers dose in both males and females (Fig. 1, left panel), both at baseline and after adjustment for the main confounders (LVEF, age, peakVO2, systolic pressure, hemoglobin, rest heart rate; VE/VCO2 slope, etiology. ICD, MDRD).
Conclusions
In a large, real-life population of chronic HFrEF patients analyzed according to sex, no prognostic differences were found between stratifying for β-selectivity. A better outcome was observed in subjects receiving a high daily dose, independently from sex.Fig 1Table 1
Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could ...represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation.
Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies.
Statin therapy was significantly associated with lower EAT thickness (p < 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p < 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p < 0.0001).
The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.
•Statin therapy is associated with a reduced EAT thickness.•The association between statins and EAT is paralleled by an attenuation of EAT inflammatory profile.•Statins have a direct and selective anti-inflammatory effect on EAT.
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