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Early identification of Parkinson’s disease (PD) patients at risk for becoming functionally dependent is important for patient counseling. Several models describing the relationship between predictors and outcome have been reported, however, most of these require computer software for practical use. Here we report the development of a risk nomogram allowing an approximate graphical computation of the risk of becoming functionally dependent in early PD. We analyzed data form the Parkinson’s Progression Markers Initiative cohort of newly diagnosed PD patients from baseline through the first 5 years of follow-up. Functional dependence was defined as a score < 80 on the Schwab & England Activities of Daily Living scale. A binary logistic model was developed to estimate the risk of functional dependence and based on the results, a nomogram for the prediction of functional dependence was drawn in order to provide an easy-to-use tool in clinical and academic settings as a part of personalized medicine approach to PD treatment. At baseline, three patients and over the five-year follow-up, 85 (22%) out of 395 patients were functionally dependent as scored by the Schwab & England Activities of Daily Living rating scale. The binary logistic model showed that clinical parameters such as MDS-UPDRS I (rater part), MDS-UPDRS II, and MDS-UPDRS axial motor score were significant predictors for functional dependence within 5 years. We here provide an easy-to-use tool to estimate the risk of functional dependence in PD patients based on the MDS-UPDRS part I, II and axial motor score.

Sarcopenia is characterized by a progressive loss of muscle mass, strength, and function resulting in adverse health outcomes. Current assessment strategies are bothersome and means to simplify the diagnosis are an unmet medical need in Parkinson’s disease (PD). To evaluate temporal muscle thickness (TMT) obtained on routine cranial MRI as a surrogate marker of sarcopenia in PD patients. We correlated TMT from axial non-contrast-enhanced T1-weighted sequences of MRI close (±12 months) to an outpatient visit including sarcopenia (EWGSOP1, EWGSOP2, SARC-F), frailty (Fried’s criteria, clinical frailty scale), and disease characteristics of Parkinson’s patients (Hoehn and Yahr-scale, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, quality of life with the Parkinson’s Disease Questionnaire-8) assessments. Cranial MRI was available in 32 patients with a mean age of 73.56±5.14 years, mean disease duration of 11.46±5.66 years, and median Hoehn and Yahr stage of 2.5. The mean TMT was 7.49±2.76 (7.15) mm. Mean TMT was significantly associated with sarcopenia (EWGSOP2, p = 0.018; EWGSOP1, p = 0.023) and frailty status (physical phenotype; p = 0.045). Moreover, there were significant moderate to strong correlations between TMT measurement and appendicular skeletal muscle mass index (r: 0.437, p = 0.012), as well as handgrip strength (r: 0.561, p < 0.001). Reduced TMT seems to be a promising surrogate marker for sarcopenia (EWGSOP2) and muscle strength in this pilot study in PD patients.

The galvanic isolation of solid-state transformers (SSTs) is typically realized with a medium-frequency (MF) magnetic-core transformer (MCT). Previous demonstrations indicate that achieving highly power-dense and lightweight MCTs imposes several challenges on the design because of stringent requirements related to insulation and cooling. This work investigates the achievable efficiency of an optimized 166 kW/7 kV air-core transformer (ACT), which is a core part of a dc transformer (DCX), i.e., an unregulated dc–dc SST with a voltage scaling defined by the transformer turns ratio. The ACT features relatively low complexity of the construction, comparably high coupling values, and high efficiency. Modeling, optimization, and construction of the realized ACT are explained and guidelines regarding insulation, cooling, and shielding of the magnetic stray flux are discussed in detail. Furthermore, the prototype is experimentally validated to demonstrate its full functionality. In the investigated DCX, which is based on a series resonant converter (SRC) topology, the realized ACT is found to achieve a full-load efficiency of 99.5% and an unprecedented gravimetric power density of 16.5 kW/kg. With the use of 10 kV SiC MOSFETs, the complete DCX is estimated to reach an efficiency of 99% at 166 kW output power.

Multiple system atrophy is a rapidly progressive and fatal neurodegenerative disorder. While numerous preclinical studies suggested efficacy of potentially disease modifying agents, none of those were proven to be effective in large-scale clinical trials. Three major strategies are currently pursued in preclinical and clinical studies attempting to slow down disease progression. These target α-synuclein, neuroinflammation, and restoration of neurotrophic support. This review provides a comprehensive overview on ongoing preclinical and clinical developments of disease modifying therapies. Furthermore, we will focus on potential shortcomings of previous studies that can be avoided to improve data quality in future studies of this rare disease.

Essential tremor (ET) and the tremor of Parkinson’s disease (PD) are the most common tremors encountered in clinical practice. Especially in early disease stages, discrimination between the tremors of ET and PD can be challenging. The aim of this study was to evaluate the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra echogenicity for differential diagnosis of PD versus ET. A systematic PubMed search identified 512 studies. Sensitivity and specificity of substantia nigra hyperechogenicity was estimated. Data synthesis was carried applying a random effects bivariate binomial model. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eighteen studies were suitable for analysis including 1,264 PD and 824 ET patients. The meta analysis showed a pooled sensitivity and specificity for TCS in the differential diagnosis of PD versus ET of 84.6% (95% CI, 79.4–88.6%) and 83.9% (95% CI, 78.4–88.2%), respectively. Furthermore, we found nearly similar results in sensitivity and specificity comparing TCS and DaTSCAN in a subgroup-analysis of three studies using both diagnostic tools including 107 patients with PD and 62 patients with ET. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection. Substantia nigra hyperechogenicity yield high diagnostic accuracy for the discrimination of PD from ET. TCS is a low cost, widely available, non-invasive marker without radiation Therefore, a diagnostic algorithm based on presence or absence of substantia nigra hyperechogenicity is highly warranted.

Solid-state transformers (SSTs) are employing compact high-power medium-voltage (MV) medium-frequency transformers (MFTs) and enable the power transfer between galvanically isolated DC systems. Considering a typical SST isolation stage, i.e., a 166 kW unregulated series-resonant DC–DC converter acting as a DC transformer (DCX) with equal input and output MV DC voltages of 7 kV (1:1-DCX), we derive component- and system-level performance limits of air-cooled realizations with either an air-core transformer (ACT) or with a magnetic-core transformer (MCT). We describe the design of two fully rated MFT prototypes in detail and provide a comprehensive experimental characterization to validate the derived performance limits, including the dielectric losses and the analysis of stray magnetic fields. The realized ACT and MCT prototypes achieve measured efficiencies of 99.5% and 99.7% at gravimetric power densities of 16.5 and 6.7 kW/kg, respectively. Considering 10 kV SiC MOSFETs, calculated system-level efficiencies of the ACT-based and MCT-based 1:1-DCX result in 99.0% and 99.2% at the nominal operating point, with similar part-load efficiency characteristics. This article concludes with an application-oriented qualitative evaluation of the two concepts.

Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa. To survey the accessible MD clinical training in these regions. We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs. The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology. Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries.

Newly available medium-voltage (MV) silicon carbide (SiC) transistors are setting new limits for the design space of MV converters. Unprecedented blocking voltages, higher switching frequencies, higher commutation speeds, lower losses, and high temperature operation can be reached, which, however, create new challenges for the electrical insulation. In particular, the dielectric losses can become significant for MV converters operated at higher switching frequencies. Moreover, the evaluation of the dielectric losses is a key element for assessing the insulation stress and for insulation diagnostics. Therefore, this paper analyzes the modeling and the computation of dielectric losses with pulsewidth modulated (PWM) voltages. After a review of the dielectric loss mechanisms occurring in polymeric insulation materials, scalable analytical expressions are proposed for the losses produced by PWM voltages. Afterward, the dielectric losses of a medium-frequency (MF) transformer, employed in a 25 kW MV dc–dc converter (7 kV–400 V) operated at 48 kHz, are analyzed and measured in detail. With epoxy resin, the insulation losses represent a significant share, i.e., up to 17%, of the total transformer losses. As shown, the transformer performance can be significantly improved with silicone elastomer insulation. Finally, design guidelines are provided for the selection of insulation materials.

Multiple system atrophy (MSA) is a devastating and fatal neurodegenerative disorder. The clinical presentation of this disease is highly variable, with parkinsonism, cerebellar ataxia and autonomic failure being the most common — and often debilitating — symptoms. These symptoms progress rapidly, and patients die from MSA-related complications after 9 years of symptom duration on average. Unfortunately, the course of the disease cannot be improved by drug or surgical treatment. In addition, symptomatic treatment options are currently limited, and therapeutic benefits are often only transient. Thus, further interventional studies of candidate disease-modifying and symptomatic therapies are essential to improve patient care. In the past 15 years, the understanding of MSA-specific requirements in trial methodology has improved, resulting in a substantial increase in high-quality interventional studies. In this Review, we discuss MSA risk factors, clinical presentation and neuropathology, and we provide a hypothesis on key pathophysiological events, a summary of recent randomized controlled trials, and an overview of ongoing international collaborations.

Solid-state transformers (SSTs) are a promising technology as they provide new functionalities and services enabling future smart grids. An SST establishes the interface between an MV ac grid and an LV (ac or dc) grid or load. The SST must provide high reliability even in the event of certain grid faults, where the SST is subject to exceptional electrical stresses. In addition, the MV and LV grids are exposed to failures of the SSTs. Spurred by such challenging requirements, this paper defines the different relevant stresses, identifies the corresponding protection needs, and proposes adequate protection circuitries and devices. The protection mechanisms that are currently used for low-frequency transformers are analyzed and an adapted version is proposed for SSTs. MV short circuits and overvoltages are identified as the most critical situations and are analyzed in detail. From the presented in-depth investigation, guidelines are extracted for designing robust SSTs and are applied to a 1 MVA, 10 kV SST.

This paper details the design, implementation, and experimental verification of a minimum weight input series output parallel structured dual active bridge (DAB) converter for an airborne wind turbine system. The main power components of the DAB converter, particularly the bridge circuits, the actively cooled high-frequency transformer and inductor, and the cooling system, which largely contribute to the total system weight, are designed and realized based on multiobjective considerations, i.e., with respect to weight and efficiency. Furthermore, the design includes all necessary considerations to realize a fully functional prototype, i.e., it also considers the auxiliary supply, the control for a stable operation of the system, which also comprises an input filter, over the specified operating range, and the start-up and shut down procedures. These considerations show the complex interactions of the various system parts and reveal that a comprehensive conceptualization is necessary to arrive at a reliable minimum weight design. Experimental results validate the proposed design procedure for a realized lightweight DAB hardware prototype with a rated power of $ \mathrm {6.25~\,kW}$ . The prototype weighs $ \mathrm {1.46~\,kg}$ , i.e., features a power-to-weight ratio of $ \mathrm {4.28~\,kW{/}\,kg}$ ( $ \mathrm {1.94~\,kW{/}\,lb}$ ), and achieves a maximum full-load efficiency of 97.5%.

Atypical parkinsonian disorders (APDs) comprise a heterogenous group of disorders including multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Based on literature published in 2010, we here review recent advances in the APD field.