Analysis of Surface Charge Effects and Edge Fringing Capacitance in Planar GaAs and GaN Schottky Barrier Diodes

[EN]In this article, by means of a 2-D ensemble Monte Carlo simulator, the Schottky barrier diodes (SBDs) with realistic geometries based on GaAs and GaN are studied as promising devices for increasing the high-frequency performance- and power-handling capability of frequency mixers and multipliers. The nonlinearity of the capacitance–voltage (C–V) characteristic is the most important parameter for optimizing the performance of SBDs as frequencymultipliers. The small size of the diodes used for ultrahigh-frequency applications makes the value of its intrinsic capacitance to deviate from the ideal one due to fringing effects. We have observed that the value of the edge capacitancewell into reverse bias does not depend on the applied voltage. We define an edge-effect parameter beta, which, interestingly, is affected by the presence or absence of surface charges at the semiconductor–dielectric interface, sigma . Two physical models have been considered: a fixed sigma related to a surface potential Vs constant surface-charge model (CCM) and a self-consistent model in which the local value of sigma is dynamically evaluated depending on the surrounding electron density self-consistent surface-charge model (SCCM). Using the CCM, we obtain that beta depends on the depth of the depletion region Ws created by the surface charges, nearly irrespectively of the epilayer doping or semiconductor type. The more realistic SCCM indicates that, at low frequencies, when the surface charges are able to follow the variations of the applied voltage, the value of beta approaches the one obtained without surface charges,while the high-frequency value (the significant one) is smaller.Spanish MINECO and FEDER under Project TEC2017-83910-R and Junta de Castilla y León and FEDER under Project SA254P18

Technological Parameters and Edge Fringing Capacitance in GaN Schottky Barrier Diodes: Monte Carlo Simulations

[EN]Schottky barrier diodes (SBDs) with realistic geometries have been studied by means of a 2-D ensemble Monte Carlo simulator. The non-linearity of the Capacitance-Voltage (C-V) characteristic is the most important parameter for optimizing SBDs as frequency multipliers. In this paper, by changing the values of several technological parameters, we analyze their influence on the edge fringing capacitance in a GaN SBD. We have found that the parameters related with the dielectric used for the passivation and the lateral extension of the epilayer significantly affect the fringing capacitance, thus increasing the value of the total capacitance above the ideal one.Spanish MINECO and FEDER under Project TEC2017-83910-R and Junta de Castilla y León and FEDER under Project SA254P1

Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors.

BACKGROUND: Absence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events. OBJECTIVES: This study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals. METHODS: Participants from the PESA (Progression of Early Subclinical Atherosclerosis) study (n = 4,184) without conventional CVRFs were evaluated (n = 1,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressure <140/90 mm Hg, fasting glucose <126 mg/dl, total cholesterol <240 mg/dl, low-density lipoprotein cholesterol (LDL-C) <160 mg/dl, and high-density lipoprotein cholesterol ≥40 mg/dl. A subgroup with optimal CVRFs (n = 740) was also defined as having blood pressure <120/80 mm Hg, fasting glucose <100 mg/dl, glycosylated hemoglobin <5.7%, and total cholesterol <200 mg/dl. We evaluated ultrasound-detected carotid, iliofemoral, and abdominal aortic plaques; coronary artery calcification; serum biomarkers; and lifestyle. Adjusted odds ratios (with 95% confidence interval) and ordinal logistic regression models were used. RESULTS: Subclinical atherosclerosis (plaque or coronary artery calcification) was present in 49.7% of CVRF-free participants. Together with male sex and age, LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10 mg/dl]: 1.14 to 1.18; p < 0.01 for all). Atherosclerosis presence and extent was also associated in the CVRF-free group with glycosylated hemoglobin levels. CONCLUSIONS: Many CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individuals conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318)

New 3-Dimensional Volumetric Ultrasound Method for Accurate Quantification of Atherosclerotic Plaque Volume.

Carotid and femoral plaque burden is a recognized biomarker of cardiovascular disease risk. A new electronic-sweep 3-dimensional (3D)-matrix transducer method can improve the functionality and image quality of vascular ultrasound atherosclerosis imaging. This study aimed to validate this method for plaque volume measurement in early and intermediate-advanced plaques in the carotid and femoral territories. Plaque volumes were measured ex vivo in pig carotid and femoral artery specimens by 3-dimensional vascular ultrasound (3DVUS) using a 3D-matrix (electronic-sweep) transducer and its associated 3D plaque quantification software, and were compared with gold-standard histology. To test the clinical feasibility and accuracy of the 3D-matrix transducer, an experiment was conducted in intermediate-high risk individuals with carotid and femoral atherosclerosis. The results were compared with those obtained using the previously validated mechanical-sweep 3D transducer and established 2-dimensional (2D)-based plaque quantification software. In the ex vivo study, the authors assessed 19 atherosclerotic plaques (plaque volume, 0.76 µL-56.30 μL), finding strong agreement between measurements with the 3D-matrix transducer and the histological gold-standard (intraclass correlation coefficient [ICC]: 0.992; [95% CI: 0.978-0.997]). In the clinical analysis of 20 patients (mean age 74.6 ± 4.45 years; 40% men), the authors found 64 (36 carotid and 28 femoral) of 80 scanned territories with atherosclerosis (measured atherosclerotic volume, 10 μL-859 μL). There was strong agreement between measurements made from electronic-sweep and mechanical-sweep 3DVUS transducers (ICC: 0.997 [95% CI: 0.995-0.998]). Agreement was also high between plaque volumes estimated by the 2D and 3D plaque quantification software applications (ICC: 0.999 [95% CI: 0.998-0.999]). Analysis time was significantly shorter with the 3D plaque quantification software than with the 2D multislice approach with a mean time reduction of 46%. 3DVUS using new matrix transducer technology, together with improved 3D plaque quantification software, simplifies the accurate volume measurement of early (small) and intermediate-advanced plaques located in carotid and femoral arteries.This study was partially funded by grants from the Ministerio de Economia, Industria y Competividad (MEIC) with cofunding from the European Regional Development Fund (ERDF) (SAF2016-75580-R to Dr Bentzon) and (BES-2016-076633 to Dr Nogales). Research funding was also received from the Instituto de Salud Carlos III Spain (PIE16/ 00021 to Drs Bueno and Fuster). The CNIC is supported by the Min- isterio de Ciencia, Innovacion y Universidades (MICINN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. Drs Sánchez- González, Entrekin, and Collet-Billon are employees of Philips Healthcare. All other authors have reported that they have no re- lationships to disclose related to the contents of this paper.S

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).Severo Ochoa Center of Excellence, Grant/Award Number: CEX2020-001041- S; Pro CNIC Foundation; Ministerio de Ciencia e Innovación; Ministry of Science and Innovation, Grant/ Award Number: PID2019-110369RB- I00; European Commission, Grant/Award Number: ERC-CoG 819775 and H2020-HEALTH 945118; Spanish Ministry of Universities; Ayudas Margarita Salas para la Formación de Jóvenes Doctores—Universidad Autónoma de Madrid, Grant/ Award Number: CA1/RSUE/2021–00577; Formación de Profesorado Universitario, Grant/Award Number: FPU16/03953; Sociedad Española de Alergología e Inmunología Clínica (SEAIC), Grant/ Award Number: BECA20A9; New Frontiers in Research Fund, Grant/ Award Number: NFRFE-2019- 00083; The Nutricia Research Foundation, Grant/Award Number: NRF-2021- 13; Instituto de Salud Carlos III, Grant/Award Number: PI21/00158, PI21/01126, CP20/00043, PI18/01467, PI19/00044, RD16/0006/0015 and RD21/0002/0008; Severo Ochoa Program, Grant/Award Number: AEI/SEV-2017- 0712S

Association of Sleep Duration and Quality With Subclinical Atherosclerosis.

BACKGROUND Sleep duration and quality have been associated with increased cardiovascular risk. However, large studies linking objectively measured sleep and subclinical atherosclerosis assessed in multiple vascular sites are lacking. OBJECTIVES The purpose of this study was to evaluate the association of actigraphy-measured sleep parameters with subclinical atherosclerosis in an asymptomatic middle-aged population, and investigate interactions among sleep, conventional risk factors, psychosocial factors, dietary habits, and inflammation. METHODS Seven-day actigraphic recording was performed in 3,974 participants (age 45.8 4.3 years; 62.6% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study. Four groups were defined: very short sleep duration 8 h. Sleep fragmentation index was defined as the sum of the movement index and fragmentation index. Carotid and femoral 3-dimensional vascular ultrasound and cardiac computed tomography were performed to quantify noncoronary atherosclerosis and coronary calcification. RESULTS When adjusted for conventional risk factors, very short sleep duration was independently associated with a higher atherosclerotic burden with 3-dimensional vascular ultrasound compared to the reference group (odds ratio: 1.27; 95% confidence interval: 1.06 to 1.52; p ¼ 0.008). Participants within the highest quintile of sleep fragmentation presented a higher prevalence of multiple affected noncoronary territories (odds ratio: 1.34; 95% confidence interval: 1.09 to 1.64; p ¼ 0.006). No differences were observed regarding coronary artery calcification score in the different sleep groups. CONCLUSIONS Lower sleeping times and fragmented sleep are independently associated with an increased risk of subclinical multiterritory atherosclerosis. These results highlight the importance of healthy sleep habits for the prevention of cardiovascular disease. (J Am Coll Cardiol 2019;73:134–44) © 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.post-print454 K

Early detection of anthracycline- and trastuzumab-induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters.

Aims To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and results Seventy-two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high-sensitivity cardiac troponin T, NT-proBNP, global longitudinal strain (GLS), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High-sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT-proBNP augmented after each anthracycline cycle (mean pre-cycle levels of 72 ± 68 pg/mL and post-cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post-anthracycline treatment and the decline in GLS was more pronounced ( 17.6% vs. 21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02–1.24), odds ratio = 0.66 (0.44–0.92), P < 0.05] at 1 month post-anthracycline treatment. Neither high-sensitivity troponin T nor NT-proBNP was capable of predicting subsequent cardiotoxicity. Conclusions One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab-induced cardiotoxicity.post-print3194 K

The impact of type 2 immunity and allergic diseases in atherosclerosis.

Allergic diseases are allergen-induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T-cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate-like lymphoid cells, alarmins, IL-4, IL-5, IL-9, IL-13 and IL-17).N