Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment ...options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver–kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.
Vector space decomposition (VSD) model is widely used for dual three-phase permanent magnet synchronous machine (dual-PMSM) control, in which two direct-quadrature (DQ) frames, DQ1 and DQ2, are ...introduced to facilitate the controller design. Existing studies show that harmonic current injection in DQ2 frame can increase the output torque for a given peak phase current, which is referred as maximum torque per peak current (MTPPC) control. However, the injected harmonic current will induce a small dc torque and the harmonic torque. This paper first proposes a comprehensive torque model considering the harmonics in PM flux linkages, inductances and stator currents to investigate the induced torque components, which are neglected in existing approaches. These torque components are then considered in the harmonic current design to improve the MTPPC control performance. The harmonic current design results in a multiobjective optimization problem, and genetic algorithm (GA) is employed to optimize the harmonic current to maximize the output torque with minimal torque harmonic. Compared with existing approaches, the proposed approach is applicable to both surface-mounted and interior dual-PMSMs. Experimental investigations on a laboratory interior dual-PMSM show that the output torque of the test motor can be increased by more than ten percent with a negligible increase in torque ripple.
With the introduction of the complement C5-inhibitor eculizumab, a new era was entered for patients with atypical hemolytic uremic syndrome (aHUS). Eculizumab therapy very effectively reversed ...thrombotic microangiopathy and reduced mortality and morbidity. Initial guidelines suggested lifelong treatment and recommended prophylactic use of eculizumab in aHUS patients receiving a kidney transplant. However, there is little evidence to support lifelong therapy or prophylactic treatment in kidney transplant recipients. Worldwide, there is an ongoing debate regarding the optimal dose and duration of treatment, particularly in view of the high costs and potential side effects of eculizumab. An increasing but still limited number of case reports and small cohort studies suggest that a restrictive treatment regimen is feasible. We review the current literature and focus on the safety and efficacy of restrictive use of eculizumab. Our current treatment protocol is based on restrictive use of eculizumab. Prospective monitoring will provide more definite proof of the feasibility of such restrictive treatment.
Torque ripple modeling and minimization for interior permanent magnet synchronous machines (IPMSMs) requires accurate information of the inductances, which vary nonlinearly due to magnetic ...saturation. However, existing approaches fail to consider the magnetic saturation and, thus, their performance are limited under different load conditions. Therefore, this paper improves the torque ripple model by considering magnetic saturation, and employs this model for the optimal current design to improve the performance of torque ripple minimization for IPMSMs under different load conditions. At first, numerical studies are performed to analyze and understand how magnetic saturation affects the torque ripples in IPMSMs. Then, a novel torque ripple model for IPMSMs is developed, in which the inductance term is replaced by exploring the machine electrical model. This improved torque ripple model is computationally efficient and it can provide fast and accurate torque ripple prediction. Based on this model, a genetic algorithm (GA)-based optimal stator current design approach is proposed to minimize the torque ripple in IPMSMs. The proposed GA-based approach can adaptively optimize the stator current under different load conditions, which can guarantee the robust performance of torque ripple minimization under different saturation levels. The proposed approach is validated through an experimental test on a laboratory IPMSM drive system.
This paper proposes a novel method of efficiency improvement in a vector controlled permanent magnet synchronous motors (PMSM) through system level maximum efficiency point determination using ...current angle as a control variable. Loss models for the inverter and the motor fundamental and harmonic losses, which are capable of being solved online using available terminal measurements in the system are initially developed. The loss models and dc-link power measurement are then used to seek the maximum efficiency angle for different operating conditions using a gradient descent optimization algorithm. The developed method is robust against changes in inductances due to saturation and cross saturation with loading conditions as well as temperature effects. The effectiveness of the developed method in improving the system efficiency is verified and compared with conventional maximum torque per ampere method. The proposed strategy has been validated on a laboratory interior PMSM, and the efficiency has been calculated for different speed and torque conditions. The experimental validations confirm the effectiveness of the proposed solution in improving the motor drive system energy efficiency.
In permanent magnet synchronous machine, high-frequency (HF) signal injection has been extensively investigated for permanent magnet temperature (PMT) estimation, in which PMT is estimated from the ...temperature-dependent HF resistance. Existing studies require prior knowledge on the HF resistance and neglect the fact that PMT is temporally correlated. This paper proposes a state-space model for PMT estimation, in which PMT is modeled with a piecewise linear equation to explore the temporal correlation. The state-space model is nonlinear due to unknown model parameters, which is required to be known in existing studies. This paper proposes to use expectation maximization particle filter (EM-PF) for simultaneous PMT and model parameter estimation. After EM-PF estimation, the state-space model becomes linear, so Kalman filter is employed for online PMT estimation. The proposed EM-PF along with a Kalman-filter-based approach can explore the temporal correlation among PMTs to improve the estimation performance, which can be hardly achieved in existing studies regarding PMT as a time-independent parameter. It should be noted that EM-PF is for initial PMT and model parameter estimation, while Kalman filter is for online PMT estimation ensuring computation efficiency and real-time capability. Our approach is validated with both numerical and experimental investigations.
The accurate control of interior permanent magnet synchronous machine (IPMSM) and drive in electric vehicle applications is vital for achieving superior performance over a wide range of speeds and ...loads. Many control methods such as loss minimization and maximum efficiency (ME) have been developed to improve the efficiency of the motor-drive, by mainly considering the controllable fundamental losses. This article includes the effect of stator harmonic iron losses caused primarily by inverter sideband time harmonics that contribute to a significant amount of controllable electrical losses in IPMSMs. The sideband harmonic iron losses have been analytically modeled using a novel dq -axis model incorporating harmonic iron loss resistance. Subsequently, the harmonic iron losses have been included in an offline procedure used to determine optimal current advance angle for increased motor efficiency. The improved IPMSM losses and subsequently, the analytical efficiency models have been derived by considering varying motor parameters due to saturation and cross-saturation effects. The accuracy of the developed model and the improved ME control using the optimal current angle have been validated using numerical simulations and experimental investigations on a laboratory IPMSM.
The haemolytic uraemic syndrome (HUS) is part of a spectrum of thrombotic microangiopathies. The most common etiologies of HUS are the ones seen in childhood caused by an infection of Shiga ...toxin-producing Escherichia coli, HUS caused by an infection with Streptococcus pneumoniae and HUS due to abnormalities in the alternative pathway of the complement system. In the past decade, enormous progress has been made in understanding the pathogenesis in the latter group of patients. The analysis of genes that encode for complement regulatory proteins and the development of assays for measuring the activity of ADAMTS13 and the detection of antibodies against factor H contributed significantly to the diagnostic tools in patients with HUS. These assays have made it possible to clearly differentiate between thrombotic thrombocytopenic purpura and various forms of HUS. With the introduction of eculizumab, a monoclonal anti-C5 inhibitor, in the clinical arena as effective treatment of most complement-mediated forms of HUS, a new era of treatment in HUS has begun. We review the recent advances in HUS, with the focus on treatment. We discuss unsolved questions, which should be addressed in future studies.
Thrombotic microangiopathy (TMA) in association with RNA exosome encoding mutations has only recently been recognized. Here, we present an infant (female) with an EXOSC5 mutation (c.230_232del ...p.Glu77del) associated with the clinical phenotype known as CABAC syndrome (cerebellar ataxia, brain abnormalities, and cardiac conduction defects), including pontocerebellar hypoplasia, who developed renal TMA. At the age of four months, she presented with signs of septic illness, after which she developed TMA. A stool culture showed rotavirus as a potential trigger. The patient received eculizumab once, alongside supportive treatment, while awaiting diagnostic analysis of TMA, including genetic complement analysis, all of which were negative. Eculizumab was withdrawn and the patient’s TMA recovered quickly. A review of the literature identified an additional four patients (age < 1 year) who developed TMA after a viral trigger in the presence of mutations in EXOSC3. The recurrence of TMA in one of these patients with an EXOSC3 mutation while on eculizumab treatment underscores the apparent lack of responsiveness to C5 inhibition. In conclusion, mutations in genes influencing the RNA exosome, like EXOSC3 and EXOSC5, characterized by neurodevelopment and neurodegenerative disorders could potentially lead to TMA in the absence of complement dysregulation. Hence, these patients were likely non-responsive to eculizumab.
Permanent magnet (PM) temperature is critical to ensure high-performance and reliable control of permanent magnet synchronous machines (PMSMs) for electric vehicle (EV) applications. High-frequency ...(HF) voltage injection based approach has been shown to be capable of PM temperature estimation under all-speed range with simple implementation. This paper improves existing HF voltage injection based PM temperature estimation approach by considering the cross-coupling effect. The key to PM temperature estimation is the temperature-dependent HF resistance estimated from the injected HF voltage and the current response. It is found that the cross-coupling effect has a great influence on the HF resistance estimation. This paper firstly improves the HF voltage injection model by considering the cross-coupling effect. Then, a comparative numerical investigation is conducted to analyze the estimation errors induced by the cross-coupling effect. A novel HF resistance estimation approach is derived from the proposed improved model and the PM temperature is calculated from the HF resistance with a linear thermal model. The influence of inverter nonlinearity is also analyzed. Experimental investigations demonstrate that the proposed approach is able to improve the performance of PM temperature estimation.
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