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In this article, the performance of multilevel inverter-fed position sensorless permanent magnet synchronous motor (PMSM) drive is analyzed using modified model predictive torque control (MPTC) met...

International audience; Chronic kidney disease (CKD) is the leading complication in type 2 diabetes (T2D) and current therapies that limit CKD progression and the development of cardiovascular disease (CVD) include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and sodium–glucose co-transporter 2 (SGLT2) inhibitors. Despite the introduction of these therapeutics, an important residual risk of CKD progression and cardiovascular death remains in patients with T2D. Mineralocorticoid receptor antagonists (MRAs) are a promising therapeutic option in diabetic kidney disease (DKD) owing to the reported effects of mineralocorticoid receptor activation in inflammatory cells, podocytes, fibroblasts, mesangial cells and vascular cells. In preclinical studies, MRAs consistently reduce albuminuria, CKD progression, and activation of fibrotic and inflammatory pathways. DKD clinical studies have similarly demonstrated that steroidal MRAs lead to albuminuria reduction compared with placebo, although hyperkalaemia is a major secondary effect. Non-steroidal MRAs carry a lower risk of hyperkalaemia than steroidal MRAs, and the large FIDELIO-DKD clinical trial showed that the non-steroidal MRA finerenone also slowed CKD progression and reduced the risk of adverse cardiovascular outcomes compared with placebo in patients with T2D. Encouragingly, other non-steroidal MRAs have anti-albuminuric properties in DKD. Whether or not combining MRAs with other renoprotective drugs such as SGLT2 inhibitors might provide additive protective effects warrants further investigation.

Introduction Aldosterone synthase (AS) is a key enzyme involved in the final three rate-limiting steps of the biosynthesis pathway of aldosterone, and its inhibition has been considered as an effective strategy to treat hypertension, heart failure and related cardio-metabolic diseases. Area covered This review provides an update on the discovery and development of aldosterone synthase inhibitors by means of patents published between January 2014 and March 2021. The molecules are classified by pharmaceutical company with progress that has been made in clinical trials being highlighted. Expert opinion Mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASI) represent two of the main approaches for the blockade of aldosterone. Clinical success, as well as foreseen side effects of steroidal MRAs, prompted the discovery and development of ASI. Since the observation of decreased cortisol levels in clinical trials for LCI699, subsequent efforts have been largely focused on improving its selectivity over hCYP11B1. Candidates with improved potency and selectivity are under investigation across a wide range of indications. Whether ASI will provide an additional therapeutic advantage over current safe and selective non-steroidal MRAs is highly anticipated.

Treatment of chronic heart failure (CHF) is very controversial. The issue of optimal doses of beta-blockers, ACE inhibitors, aldosterone receptor antagonists, statins in patients with CHF has not been conclusively addressed. Achieving the maximum tolerated doses of drugs, though related to reduced mortality, but is accompanied by an increase in adverse drug reactions. The aim. To present and discuss our own clinical and scientific data concerning the role of beta-blockers and inhibitors of the renin-angiotensin aldosterone system, diuretics, statins in the treatment of CHF patients and optimization of dosage schemes. Material and methods. The study included 88 patients with CHF of ischemic origin, with sinus rhythm, stage II AB, NYHA FC II–IV, 58 – with reduced LV EF (HFrEF) and 30 – with preserved LV EF (HFpEF). The mean age of patients was 69.18 ± 9.97 years, men 52 % (n = 46). The median follow-up of the CHF patients was 396 days, the maximum number of follow-up days was 1302. During the observation period, 14 endpoints were registered, which accounted for 15.91 % of events: 7 deaths (8.0 %), 2 strokes (2.3 %), 2 cases of acute coronary syndrome (2.3 %), 3 progressive heart failure cases (3.4 %). Kaplan–Mayer curves were drawn to assess survival rate, and the significance of difference between groups was calculated by the criteria of Gehan–Wilcoxon, Cox–Mantel and log-rank test. Risk factors were determined, and prognostic uni- and multi-variant Cox proportional hazards regression models were used. The cut-off values of quantitative risk factors were obtained by ROC analysis. Results. The increase in the relative risk of adverse cardiovascular events in the CHF patients regardless of LV EF was associated with a daily carvedilol dose of more than 25 mg (HR = 1.05; 95 % CI 1.009–1.093; P = 0.0171); eplerenone – more than 12.5 mg (HR = 1.073; 95 % CI 1.005–1.144; P = 0.034), torasemide – more than 5 mg (HR = 1.13; 95 % CI 1.021–1.255; P = 0.019); rosuvastatin – more than 10 mg (HR = 1.107; 95 % CI 1.007–1.203; P = 0.035), and the trend in using atorvastatin at a dose of less than 10 mg (HR = 1.05; 95 % CI 0.951–1.165; P = 0.327). The use of ramipril in a daily dose of less than 2.5 mg was accompanied by a trend towards the 22 % reduced relative risk of adverse cardiovascular events (HR = 0.78; 95 % CI 0.384–1.580; P = 0.491). Conclusions. Positive treatment outcomes in the CHF patients, regardless of the phenotype, were associated with low daily doses of ramipril (10.0 mg).

Noonan syndrome (NS) is a Mendelian phenotype, member of a group of disorders sharing neurocardiofaciocutaneous involvement, known as RASopathies, caused by germline variants in genes coding for components of the RAS/MAPK signaling pathway. Recently, a novel gene of the RAS family (MRAS) was reported to be associated with NS in five children, all of them presenting, among the cardinal features of NS, the same cardiac finding, hypertrophic cardiomyopathy (HCM). We report on a 2-month-old infant boy also presenting this cardiac anomaly that evolved to a fatal outcome after a surgical myectomy. In addition, a thick walled left ventricle apical aneurysm, rarely described in NS, was also disclosed. Next-generation sequencing revealed a missense, previously reported variant in MRAS (p.Thr68Ile). This report reinforces the high frequency of HCM among individuals harboring MRAS variants, contrasting to the 20% overall prevalence of this cardiac anomaly in NS. Thus, these preliminary data suggest that variants in MRAS per se are high risk factors for the development of an early, severe HCM, mostly of them with left ventricle outflow tract obstruction, with poor prognosis. Because of the severity of the cardiac involvement, other clinical findings could not be addressed in detail. Therefore, long-term follow-up of these individuals and further descriptions are required to fully understand the complete phenotypic spectrum of NS associated with MRAS germline variants, including if these individuals present an increased risk for cancer.

In this paper, unipolar excitation-based speed sensorless vector-controlled switched reluctance motor (SRM) drive is addressed. The use of position/speed sensors has few apprehensions in terms of price, dependability, compactness, especially from electric vehicle (EV) application view point. Therefore, for speed/torque control of SRM, it is mandatory to have some estimation technique which estimates the speed/position satisfactorily and with ease. In this paper, F-MRAS (flux-based model reference adaptive system) speed estimator is employed for estimating the speed/position. The reason for selection of this speed estimator is because of its simplicity, no large lookup table requirement and no external circuitry requirement for pulses injection. This estimator depends on stator resistance of the machine. Therefore, to make the speed estimator robust to stator resistance variations, on-line estimation of the resistance and its compensation is required. From this view point, a novel stator resistance estimator is proposed which estimates the resistance on-line. Further, this paper discusses in detail about the stability analysis of proposed resistance estimator and F-MRAS-based speed estimator. The speed estimator in combination with the proposed resistance estimator performs well in both motoring and regeneration modes. An exhaustive simulation of the drive has been carried out in MATLAB/SIMULINK. Also, the results are confirmed experimentally on a dSPACE-1104 platform.

This review covers the last 80 years of remarkable progress in the development of mineralocorticoid receptor (MR) antagonists (MRAs) from synthesis of the first mineralocorticoid to trials of nonsteroidal MRAs. The MR is a nuclear receptor expressed in many tissues/cell types including the kidney, heart, immune cells, and fibroblasts. The MR directly affects target gene expression—primarily fluid, electrolyte and haemodynamic homeostasis, and also, but less appreciated, tissue remodelling. Pathophysiological overactivation of the MR leads to inflammation and fibrosis in cardiorenal disease. We discuss the mechanisms of action of nonsteroidal MRAs and how they differ from steroidal MRAs. Nonsteroidal MRAs have demonstrated important differences in their distribution, binding mode to the MR and subsequent gene expression. For example, the novel nonsteroidal MRA finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys. Compared with eplerenone, equinatriuretic doses of finerenone show more potent anti-inflammatory and anti-fibrotic effects on the kidney in rodent models. Overall, nonsteroidal MRAs appear to demonstrate a better benefit–risk ratio than steroidal MRAs, where risk is measured as the propensity for hyperkalaemia. Among patients with Type 2 diabetes, several Phase II studies of finerenone show promising results, supporting benefits on the heart and kidneys. Furthermore, finerenone significantly reduced the combined primary endpoint (chronic kidney disease progression, kidney failure, or kidney death) vs. placebo when added to the standard of care in a large Phase III trial.

Objective: laparoscopic donor nephrectomy (LDN) has been shown to be a safe approach with better morbidity results. Impact of multiple renal arteries (MRAs) and anatomical variations has been reviewed by many authors. In our study, the relationship between the donors with MRAs and risk of perioperative vascular complications related to donor nephrectomy was investigated. Material and methods: patients who underwent hand-assisted LDNs between January 2007 and February 2018 were reviewed retrospectively. Patient age, sex, body mass index (BMI), waist circumference, side of donor nephrectomies, donors with MRAs, intraoperative vascular complications, conversion rates, hospitalization durations, and operative times were extracted. Risk factors for perioperative vascular complications were defined. Results: there were MRAs in 288 kidney donors (21.3%). The number of patients who underwent a right donor nephrectomy was 113 (8.4%). BMI, waist circumference, and postoperative hospital stay were not significantly different between donors with one artery and those with MRAs (p>0.05). The renovascular complication rate and overall conversion rate to open surgery were significantly higher in donors with MRAs (p, NA

International audience; Rotational speed sensor is one of the most important components used in wind energy conversion system control strategies. The latter is very expensive and may be faulty due to the harsh environment working, causing by that a low efficiency operation of the system. The use of a speed estimator or an observer may be a good alternative solution for the use either in sensorless control or detecting the sensor failure or degradation (FDI and FTC), provided that the observer is robust and ensures high rotational speed estimation accuracy. This paper presents a comprehensive study to solve the optimization problem of a model reference adaptive speed (MRAS) observer in a typical wind energy generation system based on permanent magnet synchronous generator using five adaptation mechanisms: The first one is the classical MRAS observer; it is based on proportional-integral (PI) controller. The second one uses a fuzzy logic controller (FLC) with two inputs. The third one uses the single-input fuzzy logic controller which represents the simplification of the conventional FLC. The fourth one uses the sliding mode controller, and the last one uses the super-twisting algorithm. A detailed comparison between the five adaptation mechanisms is carried out. The obtained results show a good estimation stability as well as a fast speed estimation at dynamic regime for the improved adaptation mechanisms compared with the conventional PI controller.

Purpose of review Congestive heart failure (CHF) and chronic kidney disease (CKD) often coexist. However, and despite their established benefits, the use of mineralcorticoid receptor antagonists (MRAs) in patients with both comorbidities is inconsistent. This review will focus on the role of aldosterone in CHF, as well as timing, selection, and management of MRAs in CHF patients with CKD. Recent findings Aldosterone in CHF patients contributes to worsening sodium retention, hypokalemia, metabolic alkalosis, cardiac fibrosis, and CKD progression. MRAs are beneficial in CHF patients with CKD despite the adverse events of hyperkalemia and acute kidney injury. MRAs were previously studied in patients with CKD stage III but were recently found to be safe in end-stage kidney disease (ESKD) patients. New nonsteroidal MRAs are more selective for the mineralocorticoid receptor and have a better side effect profile. The use of potassium lowering agents, such as patriomer, helps maintain normokalemia in patients with CKD who are treated with MRAs. Summary It is recommended to use MRAs in CHF patients with normal potassium levels and a glomerular filtration rate of more than 30 ml/min. Their use is also safe in ESKD patients. In nondialysis advanced CKD patients, they may need to be combined to medications such as patiromer. New nonsteroidal MRAs are currently being studied.

International audience; Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics Abstract Introduction: Mineralocorticoid receptor (MR) antagonists (MRAs) provide cardiorenal protection. However steroidal MRAs might induce hyperkalemia and sex hormone-related adverse effects. Several novel non-steroidal MRAs are being developed that are highly selective for the MR and may have an improved safety profile. Areas covered: This narrative review summarizes data from head-to-head comparisons of emerging non-steroidal MRAs with older steroidal MRAs, including pharmacological characteristics, pharmacokinetic properties, clinical outcomes, and safety, and highlights similarities and differences between emerging agents and established steroidal MRAs. Expert opinion: Head-to-head comparisons in phase 2 trials suggest that the new non-steroidal MRAs exhibit at least equivalent efficacy to steroidal MRAs but may have a better safety profile in patients with heart failure and/or kidney disease. When also taking into account data from recent phase 3 placebo-controlled trials, these novel non-steroidal MRAs have the potential to provide a cardiorenal benefit above that of current optimized standard-of-care treatment in a high-risk population with reduced renal function, with a low risk of hyperkalemia. To optimize therapy, further research is needed to clarify the molecular differences in the mode of action of non-steroidal MRAs versus steroidal MRA, and biomarkers that are predictive of MRA response need to be identified and validated.

Mineralocorticoid receptor antagonists (MRAs) are key agents in guideline-oriented drug therapy for cardiovascular diseases such as chronic heart failure with reduced ejection fraction and resistant hypertension. Currently available steroidal MRAs are efficacious in reducing morbidity and mortality; however, they can be associated with intolerable side effects including hyperkalaemia in everyday clinical practice. Recently, a new class of non-steroidal MRAs (including esaxerenone, AZD9977, apararenone, KBP-5074 and finerenone) have been developed with an improved benefit-risk profile and a novel indication for finerenone for diabetic kidney disease. To better understand the non-steroidal MRAs, this review provides information on the molecular pharmacology as well as relevant current preclinical and clinical data on cardiorenal outcomes. A comparative review of all compounds in the class is discussed with regard to clinical efficacy and safety as well as a perspective outlining their future use in clinical practice. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

This paper presents the structure of a Permanent Magnet Synchronous Motor (PMSM) multi-motor sensorless automation control system based on the Field Oriented Control (FOC) type method. It presents the description of the component blocks of each Master/Slave subsystem, the optimal tuning of the Master and Slave controllers by using a Particle Swarm Optimization (PSO) algorithm and estimations of the PMSM rotor position and velocity by using a Model Reference Adaptive System (MRAS) observer. In Simulink development software are achieved the numerical simulations to prove the performance of optimized controllers in case of uneven distribution of the load torque between Master and Slave. It also presents the implementation of a Supervisory Control and Data Acquisition (SCADA) system which is characterized both by the implementation of PMSM Master/Slave control algorithms in dedicated controllers and the communication between Simulink and LabVIEW development software based on the Open Platform Communications (OPC) technology.

Mineralocorticoid receptor antagonists (MRAs) are highly effective therapies for cardiovascular and renal disease. However, the widespread clinical use of currently available MRAs in cardiorenal medicine is hampered by an increased risk of hyperkalaemia. The mineralocorticoid receptor (MR) is a nuclear receptor responsible for fluid and electrolyte homeostasis in epithelial tissues, whereas pathophysiological MR activation in nonepithelial tissues leads to undesirable pro-inflammatory and profibrotic effects. Therefore, new strategies that selectively target the deleterious effects of the MR but spare its physiological function are needed. In this review, we discuss recent pharmacological developments starting from novel non-steroidal MRAs, such as finerenone or esaxerenone, that are now entering clinical use, to concepts arising from the current knowledge of the MR signalling pathway, aiming at receptor-coregulator interaction, epigenetics or downstream effectors of the MR. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

A new model reference adaptive system based estimation technique for vector control of real and reactive power of a brushless doubly fed reluctance generator without a shaft position sensor is proposed. The rotor speed is being precisely observed in a closed‐loop manner by eliminating the error between the measured and estimated inverter‐fed (secondary) winding current angles in a stationary frame. Contrary to the existing model reference adaptive system observer designs reported in the brushless doubly fed reluctance generator literature, the reference model is entirely parameter‐free and only utilises direct measurements of the secondary currents. Furthermore, the current estimates coming from the adaptive model are obtained using the measured voltages and currents of the grid‐connected (primary) winding, which has provided prospects for much higher accuracy and superior overall performance. The realistic simulations, preliminary experimental results, and the accompanying parameter sensitivity studies have shown the great controller potential for typical operating conditions of variable speed wind turbines with maximum power point tracking.

This paper proposes an active power based model reference adaptive system for sensorless speed estimation of primary field oriented brushless doubly-fed reluctance generator (BDFRG). In this regard, the active power associated with secondary winding of BDFRG is used for the process of speed estimation. BDFRG is more reliable and requires less maintenance. Its structural advantages demonstrate higher working efficiency and lower losses as compared to equivalent doubly-fed induction machines. Moreover, active power of BDFRG can be controlled by suitable speed regulation, which in turn can be achieved by a low rating bidirectional converter connected to the stator secondary (i.e., control) winding. These inherent features make BDFRG as a prospective candidate in the applications like wind and tidal power generation. The efficacy of the proposed control technique is established by a 1.6 kW BDFRG in Matlab /Simulink. A dSPACE-1103 based laboratory prototype is used for the hardware validation.

The goal of continuing medical education (CME) is professional growth and improved patient care. We sought to determine if a curriculum of online continuing medical education (CME) activities could improve the clinical knowledge and confidence of diabetologists and endocrinologists (D/Es) related to use of mineralocorticoid receptor antagonists (MRAs) in the management of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). The online CME curriculum consisted of 5 online activities. Of these, 4 used repeated pairs pre-/post-assessment study design was used and McNemar’s test (P Overall, knowledge improved by 9% among D/Es (N=1,111, P Of the D/Es who were included, 34% had a measurable increase in confidence, and among those the average level of confidence increased 50%. While this curriculum demonstrated success in educating on this topic, some gaps still remain after education. On average, 22% of the questions assessing knowledge on the MOA of MRAs in managing CKD in T2D and 29% of the questions assessing knowledge related to the role of MRAs in the management of CKD in T2D were still incorrectly answered after education, demonstrating a need for more education in these areas. Disclosure A. Larkin: None. K. L. Hanley: None. A. Le: None. Funding Bayer AG

This paper presents an efficient sensorless permanent magnet synchronous motor (PMSM) drive based on model reference adaptive system (MRAS) speed and position estimation for solar photovoltaic (PV)- battery power driven electric vehicle (EV). The aim of this work is to include a technique that encourages renewable energy applications. This work involves regenerative braking to increase the range of EV. The kinetic energy of the vehicle is recovered during braking conditions and utilized to charge the battery as well as to avoid deep discharge of the battery during the uphill driving condition. In order to reduce cost, weight, and increase robustness of the drive, MRAS based sensorless control is used for speed and position estimation. In this method, a current adaptable model is analyzed in which, PMSM itself acts as a reference model. A solar PV array integrated with a battery provides a seamless and continuing operation independent of environmental conditions. A Cuk DC-DC converter is utilized for maximum power point tracking (MPPT), which ensures continuous input and output currents. This system is efficient, cost-effective, and suits for practical implementation. A study of the PMSM control and the effectiveness of the drive system simulated using MATLAB simulink is presented in this paper.

Introduction: Our aim was to evaluate the safety and efficacy of low-dose mineralocorticoid receptor antagonists (MRAs) in dialysis patients. Methods: We systematically searched PubMed, EMBASE, and Cochrane libraries for clinical trials on the use of MRAs in dialysis patients. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. Results: We identified nine randomized controlled trials including 1128 chronic dialysis patients. In terms of safety, when hyperkalemia was defined as serum potassium level ≥5.5 mmol/L, low-dose MRAs were significantly associated with hyperkalemia (relative risk [RR] 1.76, 95% confidence intervals [CI] 1.07–2.89, P = .02); however, when hyperkalemia was defined as serum potassium level ≥6.0 mmol/L or serum potassium level ≥6.5 mmol/L, no significant association was observed between low-dose MRAs and hyperkalemia (RR 1.40, 95% CI 0.83–2.37, P = .20; RR 1.98, 95% CI 0.91–4.30, P = .09, respectively). Use of low-dose MRAs can reduce cardiovascular mortality by 54% compared with the control group (0.46, 95% CI 0.28–0.76, P = .003). Similarly, the RR of all-cause mortality for the low-dose MRAs group was 0.48 (95% CI 0.33–0.72, P = .0003). Conclusion: Low-dose MRAs may benefit dialysis patients without significantly increasing moderate to severe hyperkalemia.

Time-of-Flight Magnetic Resonance Angiographs (TOF-MRAs) enable visualization and analysis of cerebral arteries. This analysis may indicate normal variation of the configuration of the cerebrovascular system or vessel abnormalities, such as aneurysms. A model would be useful to represent normal cerebrovascular structure and variabilities in a healthy population and to differentiate from abnormalities. Current anomaly detection using autoencoding convolutional neural networks usually use a voxelwise mean-error for optimization. We propose optimizing a variational-autoencoder (VAE) with structural similarity loss (SSIM) for TOF-MRA reconstruction. A patch-trained 2D fully-convolutional VAE was optimized for TOF-MRA reconstruction by comparing vessel segmentations of original and reconstructed MRAs. The method was trained and tested on two datasets: the IXI dataset, and a subset from the ADAM challenge. Both trained networks were tested on a dataset including subjects with aneurysms. We compared VAE optimization with L2-loss and SSIM-loss. Performance was evaluated between original and reconstructed MRAs using mean square error, mean-SSIM, peak-signal-to-noise-ratio and dice similarity index (DSI) of segmented vessels. The L2-optimized VAE outperforms SSIM, with improved reconstruction metrics and DSIs for both datasets. Optimization using SSIM performed best for visual image quality, but with discrepancy in quantitative reconstruction and vascular segmentation. The larger, more diverse IXI dataset had overall better performance. Reconstruction metrics, including SSIM, were lower for MRAs including aneurysms. A SSIM-optimized VAE improved the visual perceptive image quality of TOF-MRA reconstructions. A L2-optimized VAE performed best for TOF-MRA reconstruction, where the vascular segmentation is important. SSIM is a potential metric for anomaly detection of MRAs., Comment: SPIE Medical Imaging 2021

A new model reference adaptive system (MRAS) based estimation technique for vector control of a brushlesss doubly fed reluctance generator (BDFRG) without a shaft position sensor is proposed. The rotor speed is being precisely observed in a closed-loop fashion through an iterative error eradication process between the measured and estimated secondary current angles in a stationary frame. Contrary to the existing MRAS designs reported in the BDFRG literature, the reference model only utilises direct measurements of the secondary currents with-out any machine parameters. Furthermore, the current estimates coming from the adaptive model are obtained using the measured grid voltages and currents, which has provided prospects for much higher accuracy and superior overall performance. The realistic simulations and the accompanying parameter sensitivity studies have shown the great controller potential for typical operating conditions of wind turbines as the main target application.

We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects. MRAs are well known for their utility in treating heart failure, refractory hypertension, and diverse nephropathies, namely, diabetic nephropathy. As their name denotes, MRAs inhibit the action of aldosterone at the mineralocorticoid receptor, preventing receptor activation. This prevents remodeling, decreases inflammation, and improves proteinuria. There are not significant differences in outcomes between selective and non-selective MRAs. A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels. This medication is not yet approved as it is still in phase 3 clinical trials (FIGARO-DKD and FIDELIO-DKD trials). MRAs are beneficial in several disease states. Newer medications, such as finerenone, should be considered in patients with heart failure and diabetic nephropathy who may benefit from a reduction in albuminuria and BNP/NT-ProBNP. Data surrounding finerenone are limited to date. However, results from ongoing clinical trials, as well as new trials to evaluate use in other pathologies, could validate the implementation of this medication in daily practice.

A new model reference adaptive system based estimation technique for vector control of a brushlesss doubly fed reluctance generator without a shaft position sensor is proposed. The rotor speed is being precisely observed in a closed-loop fashion through an iterative error elimination process between the measured and estimated secondary current angles in a stationary frame. Contrary to the existing adaptive observer designs reported in the open literature for this emerging generator technology, the reference model only uses the secondary current measurements and does not need any machine parameters for calculations. Furthermore, the stationary frame current components estimates are obtained using the measured grid voltages and currents, which has provided prospects for much higher accuracy and superior overall performance. The realistic simulations and the accompanying parameter sensitivity studies have shown the great controller potential for typical operating conditions of wind turbines as the main target application.

International audience

Background and Aims Hyperkalemia (HK) is a potentially life-threatening condition, in patients with chronic kidney disease (CKD) and congestive heart failure (CHF). The majority of patients affected with CKD or CHF, must be treated with inhibitors of renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRAs). However, the treatments previously mentioned, increase the risk of HK episodes, which is the main cause of RAASi and MRAs downtitration or discontinuation, representing an undesirable clinical scenario, given that the patients are at high risk of be deprived of their nephroprotective effect and cardio-renal benefits The aim of the study is: to analyze if, in patients with HK, CKD and CHF treated with RAASi and/or MRA, serum potassium (sK) reduction by Sodium zirconium cyclosilicate (SZC) treatment is non-inferior to RAASi and/or MRAs discontinuation or downtitration. Method Results The study will demonstrate results on serum electrolytes, renal function, albuminuria, KDQoL questionnaire and changes in relative overhydration (multifrequency bioimpedance -BCM Fresenius-) Conclusion The KEEP ON study will define the ability of SZC to facilitate the use of RAAS-I and / or MRA in patients with HK and cardiorenal syndrome allowing the maintenance of the medications recommended by international guidelines for the treatment of CHF at different degrees of CKD while maintaining the potential cardio-renal and nephroprotective benefit.

A novel rotor speed and position observer for sensor-less vector control of a brushlesss doubly fed reluctance generator (BDFRG) is put forward in this paper. Implementing such an estimation technique would eliminate the need for a shaft encoder, improving so the reliability and reducing the maintenance costs in wind power applications, off-shore in particular. The proposed model reference adaptive system (MRAS) observer retrieves the rotor speed information by driving the errors between the measured secondary currents and their speed dependent estimates to zero. Unlike the documented MRAS schemes for the BDFRG, the estimated currents are accurately derived from the grid voltage and current measurements, which has ensured a more robust performance and higher observer precision. The realistic simulation studies have showcased the prospective controller stability and insensitivity to the machine parameter mismatches across the whole speed range under variable loading conditions of the BDFRG typical for horizontal-axis wind turbines.

This paper proposes a new model reference adaptive system (MRAS) for sensorless control of a grid-connected brushless doubly-fed reluctance generator (BDFRG). The main BDFRG advantage over a conventional doubly-fed induction generator (DFIG) is the lack of slip-rings and brushes, hence the higher reliability, maintenance-free operation and lower cost. The desired active and reactive power variations are accomplished using a vector control scheme, which requires the rotor position and speed information in wind power applications with maximum wind energy extraction. Electro-mechanical shaft sensors, commonly used for this purpose, are prone to failures in harsh environments, like those encountered in off-shore wind turbines, and particularly with regular brush replacement intervals of DFIGs, making the BDFRG an attractive brushless alternative. The proposed controller design has been shown robust and capable of producing quality rotor angular position and velocity estimates by implementing an inverter-fed winding (secondary) current based MRAS. The realistic simulation results presented have proven the high accuracy and effectiveness of the estimation technique for different test scenarios of the BDFRG.

This paper addresses frequency regulation and the economic dispatch problem of an Autonomous Renewable Grid (ARG) primarily composed of Multi Renewable Energy Agents (MRAs), interfaced through DC/AC inverters. A large number of MRAs that have an inherent fluctuating nature and frequent disturbances in inter-connected systems require fast and robust control to stabilize the frequency and to maintain cost-effective operation of an ARG. To address the above control challenges, Distributed Averaging Integrator (DAI) based control schemes were proposed in various research works. The main flaws of such schemes were slow convergence, sluggish response, poor transient performance and a difficult selection of an appropriate damping-factor. The proposed approach introduces a Distributed Sliding Mode Control (DSMC) based solution for fast convergence and improved transient response. The DSMC control is based on a distributed sliding surface, designed using a combination of local information and information from neighbouring MRAs. The control is implemented locally at each MRA and achieves the asymptotic global consensus. Finally, the convergence of the proposed control scheme is proved mathematically, and performance is validated using the MRA system which has been implemented using MATLAB/Simulink. The results of the proposed control technique are compared with conventional DAI control, which shows that the proposed scheme outperforms the conventional scheme in terms of fast convergence, considering renewable resources as distributed generation.

Recently, nonsteroidal mineralocorticoid receptor (MR) antagonists (MRAs), which have been proposed to be called MR blockers (MRBs), have become available for clinical use, but their clinical role is unknown. We reviewed the clinical roles of MRAs and MRBs based on previous knowledge and as demonstrated in representative clinical trials. Steroidal MRAs, such as spironolactone and eplerenone, inhibit the action of aldosterone and cortisol in MRs expressed in several organs and cell types, and accumulating clinical studies have revealed that they exert hypotensive and cardiorenal protective effects. Recently, MRBs, including finerenone and esaxerenone, have been developed and are expected to lower the risk of hyperkalemia, which is common when steroidal MRAs are used. Although the differences between MRAs and MRBs in clinical practice have not yet been established, further studies in this field are expected to broaden our understanding. MRBs exert antihypertensive and cardiorenal protective effects, and their potency is thought to be far superior to that of MRAs, because MRBs have both strong MR inhibitory action and high selectivity. Thus, MRBs could be a promising agent for the treatment of hypertension and cardiorenal, cerebral, and metabolic disorders.

This pilot study tests the feasibility of rapid carotid MR angiography using the liver acquisition with volume acceleration-flex technique (LAVA MRA). Seven healthy volunteers and 21 consecutive patients suspected of carotid stenosis underwent LAVA and conventional time-of-flight (cTOF) MRAs. Artery-to-fat and artery-to-muscle signal intensity ratios were manually measured. LAVA MRA exhibited a significantly larger artery-to-fat signal intensity ratio compared with cTOF MRA in all slices (P < 0.001) and exhibited a larger (P < 0.001) or equivalent (P = 1.0) artery-to-muscle signal intensity ratio in the extracranial carotid arteries. The image quality of the cervical carotid bifurcation and the signal change on each MRA were visually assessed and compared among the MRAs. There was no significant difference between the two MRAs in visual assessment. LAVA MRA can provide visualization similar to cTOF MRA in the evaluation of the cervical carotid bifurcation while reducing scan time by one-fifth. Electronic supplementary material The online version of this article (10.1007/s00234-020-02452-6) contains supplementary material, which is available to authorized users.

Mineralocorticoid receptor antagonists (MRAs) are known to have a proven mortality benefit in heart failure with reduced ejection fraction (HFrEF) without kidney disease. As patients with end-stage renal disease (ESRD) requiring either peritoneal dialysis or hemodialysis were excluded in clinical trials of HFrEF, the data are scant on the appropriate use of MRAs in this population. The unknown efficacy, along with concerns of adverse effects such as hyperkalemia, has limited the willingness of clinicians to consider using MRAs in these patients. However, it is unclear whether the risk of hyperkalemia is present if a patient is oliguric or anuric. Current guidelines recommend against the use of MRAs in patients with chronic kidney disease, but do not address the use of MRAs in patients requiring dialysis. This article will review the epidemiology of heart failure in ESRD, the pathophysiological derangements of the renin-angiotensin-aldosterone system in patients with kidney disease, and the results from case series and trials of the use of MRAs in ESRD with HFrEF. Although limited to several small trials using MRAs in peritoneal and hemodialysis patients with or without HFrEF, the current literature appears to show the potential for clinical benefits with little risk.

In this paper, the pure electric brake of the train and the vector control of the asynchronous motor without speed sensor are studied, respectively. The pure electric brake of the train is controlled by a combination of regenerative brake and reverse brake. The estimation method of the feedback speed is based on the Model Reference Adaptive System (MRAS), and both the traditional MRAS and the improved MRAS are analyzed. In this paper, pure electric brake and MRAS estimation are combined to get a better system. Finally, by using the improved MRAS speed estimation method, a simulation of the pure electric brake with speed sensorless control is established with MATLAB simulation software to verify the study.

The classification describes common methods for estimating motor speed. Methods completely dependent on the physical parameters of the motor and the electromagnetic equation are easy to implement, but have poor robustness and anti-noise ability. Methods partially dependent on the physical parameters of the motor and the electromagnetic equation are introduced. Simulated and compared Model Reference Adaptive System (MRAS) and Sliding Mode Observer (SMO). Methods independent of the physical motor parameters and electromagnetic equations are introduced. Introduced common artificial intelligence algorithms. The applicability of various algorithms is summarized.

Brushless doubly-fed reluctance generator (BDFRG) is drawing a growing attention of research over the traditional doubly-fed induction generator in variable speed application like wind power generation nowadays, due to its brushless structure. In this work, the applicability of different model reference adaptive system (MRAS) based sensorless speed estimation techniques for BDFRG in wind power application is explored. The MRAS estimators developed, in this context, are based on active power, reactive power and fictitious quantity. All these schemes are implemented under primary field orientation using machine secondary winding quantities as the functional variables. Matlab/Simulink study and hardware test results under variable wind speed (between cut-in and rated speed) are presented for the aforementioned speed estimation techniques. Furthermore, to ensure the robustness of the drive system, stability study using Popov's criteria for hyperstability and sensitivity analyses is presented.

Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Experimental studies have shown that aldosterone plays a role in the genesis of myocardial hypertrophy and fibrosis, thereby enhancing LV diastolic dysfunction, and that aldosterone antagonists (mineralocorticoid receptor antagonists [MRAs]) prevents myocardial hypertrophy and fibrosis. Although the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients. The search of electronic databases identified 6 studies including 755 HFpEF patients. In the pooled analysis, MRAs increased early diastolic mitral annular velocity (weighted mean difference [95% CI] = 0.455 [0.232–0.679] cm/s; Pfix

This paper addresses an optimal model reference adaptive system (MRAS) to design power system stabilizer (PSS) in multi-machine electric power systems. Weighting factors of the proposed MRAS are adjusted by particle swarm optimization (PSO) as well as its input signal is limited by a normalization technique to assure network stability. The proposed modified-optimal MRAS-PSS is evaluated against conventional PSS to demonstrate its advantages. In order to investigate the performance of the proposed MRAS-PSS under parametric uncertainties, three operating conditions are defined and simulated. Several nonlinear and time-domain simulations are carried out to validate the viability and effectiveness of the proposed MRAS-PSS under network uncertainties.

Although mineralocorticoid antagonists (MRAs) have been proposed as effective fourth-line blood pressure (BP) lowering agents in resistant hypertension, this effect in heart failure is undetermined. In this synthesis of heart failure randomized controlled trials (RCTs), we evaluated the extent of BP lowering following MRA treatment against placebo. We searched Medline and the Cochrane Collaboration Library databases from 1991 to September 2016 for RCTs, in which MRAs were compared with placebo. The quality of RCTs was assessed with Cochrane risk of bias tool. Outcomes were the extent of systolic and diastolic BP lowering. We included seven studies (13,354 patients, 65.8% males, mean age of 66.3 years, mean follow-up period of 9.4 months, mean baseline BP of 123.5/75.0 mmHg) of MRAs compared with placebo. MRAs were not significantly associated with systolic - 1.8 (95% CI: - 8.0, 4.4) mmHg or diastolic - 0.3 (95% CI: - 3.4, 2.7) mmHg, BP reduction. Although systolic BP was not lowered by spironolactone, diastolic BP was lowered by - 3.0 (95% CI: - 3.4, - 2.6) mmHg. Eplerenone treatment did not significantly lowered systolic [- 0.04 (95% CI: - 4.4, 4.3) mmHg], but it was associated with minimal diastolic BP increase [1.0 (95% CI: 0.5, 1.53) mmHg]. MRAs were not associated with systolic and diastolic BP reduction in heart failure patients. This finding suggests that MRAs should be used according to their indications in heart failure independently of initial BP levels.

In this paper, a new sensorless deadbeat control method is proposed. In the deadbeat method, the desired voltage is calculated via the model of the induction motor and inverter (prediction model). This voltage impels the motor to track the references of the torque and flux in the next control interval. Robustness is an important issue about the deadbeat method. Two new techniques are used to reach a robust speed-independent sensorless deadbeat method. A speed-independent model is sued for prediction. Therefore, the estimated speed will not be used in the prediction model. It will reduce the drift error problem. Also, a new adaptive predictive method is proposed for simultaneous estimation of the stator resistance and speed. Only direct-axis equation is used in the adaptive method. This will reduce the calculation burden. The new adaptive function is achieved via the Lyapunov technique. The stability of the multiple-input multiple-output system for simultaneous adaptation is analyzed for the gain design problem. Simulation and experimental results in wide range of speed are depicted in order to verify the proposed method.

The role and adverse effects of mineralocorticoid receptor overactivation in the pathophysiology of heart failure (HF) is wellrecognised. MR antagonists (MRAs) have been tested in HF and shown to be effective in improving outcomes. Steroid-type MRAs spironolactone and eplerenone, have been proven to reduce mortality in HFrEF. In patients with HFpEF, the TOPCAT trial found no significant benefits of spironolactone on cardiovascular outcomes. In order to overcome the limitations of existing steroidal MRAs, novel MRAs have been recently developed, finerenone and PF-03882845. These newer agents aim to optimise the benefits of MRAs and reduce their side-effects, especially hyperkalaemia.

The reduced number of sensors in sparse arrays create high peak sidelobe levels (PSLs). This letter compares the PSLs of minimum redundancy arrays (MRAs), minimum hole arrays (MHAs), and co-prime sensor arrays (CSAs) (conventionally beamformed and product processed) with fully populated uniform linear arrays (ULAs) as a function of aperture using both numerical simulations and experimental data. This letter finds that PSLs of MRAs, MHAs, and conventionally processed CSAs are much higher than the ULA PSL and are largely insensitive to aperture extension. In contrast, CSA product processing decreases the PSL with increasing aperture, eventually matching the ULA PSL.

Mineralocorticoid-receptor antagonists (MRAs) have proven to be effective in some types of hypertension, especially in resistant hypertension (RHTN). In this phenotype of hypertension, the renin-angiotensin-aldosterone pathway plays an important role, with MRAs being especially effective in reducing blood pressure. In this review, we show the relevance of aldosterone in RHTN, as well as some clinical characteristics of this condition and the main concepts involving its pathophysiology and cardiovascular damage. We analyzed the mechanisms of action and clinical effects of two current MRAs - spironolactone and eplerenone - both of which are useful in RHTN, with special attention to the former. RHTN represents a significant minority (10%-15%) of hypertension cases. However, primary-care physicians, cardiologists, nephrologists, neurologists, and geriatricians face this health problem on a daily basis. MRAs are likely one of the best pharmacological options in RHTN patients; however, they are still underused.

As a result of dead-time, device on-state voltage drop, dc bus voltage measurement error, etc., volt-second errors degrade precise control of torque and flux linkage, particularly at low speeds. This is true for deadbeat-direct torque and flux control (DB-DTFC), which directly manipulates the volt-second vector sourced by inverters as well as for indirect field oriented control (IFOC) drives. This paper introduces a real-time sensing scheme to measure the motor terminal volt-second vectors for each switching period with negligible phase lag. Based on the volt-second sensing, a model reference adaptive system (MRAS)-based approach is developed to decouple the volt-second errors from inverter nonlinearity and dc bus voltage fluctuation and measurement error. By delivering an accurate volt-second vector for each switching period, torque and flux control accuracy, self-sensing performance and parameter estimation accuracy are significantly enhanced.

This paper describes an induction motor speed estimation using the observer with back electromotive force-based model reference adaptive system and Kalman filter. In the first part of the paper, there is a mathematical description of the rotor speed observer. The second part of the paper includes Kalman filter that is used for the filtration of measured stator currents and obtaining their time derivatives. The third part contains a description of the laboratory workplace with the induction motor drive and active load unit that was used for an experimental verification of the rotor speed observer. The last section of the paper shows experimental results that were obtained for different changes in the induction motor speed. The experimental results confirmed expected dynamic properties of the induction motor drive with sensorless control.

The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinicalin vivomodels, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct. The salient example is eplerenone, first described in 1987, coincidentally with the cloning of MR cDNA. Its launch on the market in 2003 paralleled intensive drug discovery programs for a new generation of non-steroidal MRAs. Now, 30 years after the cDNA cloning of MR and 60 years of clinical use of steroidal MRAs, novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease (CKD), hypertension and liver disease. Finerenone has already been studied in over 2000 patients with heart failure plus chronic kidney disease and/or diabetes, and in patients with diabetic kidney disease, in five phase II clinical trials. Here, we reflect on the history of the various generations of MRAs and review characteristics of the most important steroidal and non-steroidal MRAs.

This study presents a new model reference adaptive system (MRAS)-based speed estimation strategy for a grid-connected doubly fed induction machine (DFIM) drive. The reference and the adaptive models of the proposed MRAS utilise instantaneous and steady-state values, respectively, of a fictitious quantity obtained as the difference between two fictitious ratios of rotor voltage to current along the d and q axes. The dimension of this fictitious quantity is ohm (Ω) and has no physical significance. The proposed formulation is free from flux estimation and independent of stator and rotor resistance variations. This new formulation shows stable performance in the regenerating mode of operation of DFIM. All the relevant studies, in this context, are done in MATLAB/Simulink. The simulation study is further validated with a dSPACE-1104-based DFIM laboratory prototype.

We propose a new way to enlarge gain bandwidth of a miniaturized reflectarray antenna (MRA), a new type of reflectarray antenna (RA) with significantly reduced volume. To extend the gain bandwidth, we have used meander-line based sub-wavelength elements as reflectarray cells, which can fully cover a required reflection phase range ideally, 360°. As a result, we have accomplished a three times wider gain bandwidth than that of our previous MRAs. In addition, the proposed MRA can also provide high gain with good aperture efficiency even though a main beam directs toward a tilted direction. Furthermore, remarkably reduced electrical volume, which is 700 times smaller than the smallest conventional RAs, is still maintained. Measured aperture efficiency of the proposed MRA is 41.1% which is comparable with conventional RAs. And the measurement results show that the main lobe direction is very stable around the target direction within the given −1 dB gain bandwidth without any degradation in other performances. As a result, the proposed MRAs with wide gain bandwidth stands out as a good alternative of the conventional RAs.

This paper presents methods to enhance the quality of spatial information that can be extracted when using the motor drive as a diagnostic sensor. When using the state-of-the-art motor drive-based techniques for extracting spatial information related to the state of wear in a gear train driven by an ac machine, position sensor-induced periodic position measurement errors and machine-induced spatial harmonic torque ripple can degrade the quality and the detail of the information that can be extracted. In this work, this degradation of information is displayed experimentally, and it is demonstrated that the quality of the spatial information extracted can be significantly improved through implementation of existing model reference adaptive system (MRAS)-based nonideal sensor property decoupling techniques and newly developed MRAS-based spatial harmonic torque ripple decoupling techniques. Furthermore, it is identified and demonstrated in this work that by removing the gear mesh harmonic component from the gear wear information extracted using the state-of-the-art techniques, and then calculating the spatial rate of change of this new information, a new signal is generated that strongly correlates to local gear tooth defects in a gear train driven by an ac machine.

The model of speed sensor-less vector control system of induction motors has been built on the AMEsim and Matlab/Simulink platform, AMEsim and Simulink can be connected by creating an S-function interface. The results of Co-simulation indicate that the algorithms of model reference adaptive system (MRAS) based on counter electromotive force (EMF) can estimate the speed with some accuracy in static and dynamic conditions and make the electro-hydraulic power steering (EHPS) system offer the assist force as quickly as the sensor-based system. So the proposed model and control algorithms are correct and have reached the expectation.