Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats

We studied the mechanisms underlying long-term functional recovery of hemiparkinsonian rats grafted intrastriatally with carotid body (CB) cell aggregates. Amelioration of their motor syndrome is a result of the trophic actions of these grafts on the remaining ipsilateral substantia nigra neurons rather than of the release of dopamine from the CB grafts. The grafts maintain a stable morphological appearance and differentiated cell phenotype for the duration of the life of the host. Adult CB expresses high levels of glial cell line-derived neurotrophic factor (GDNF) and the multicomponent GDNF receptor complex. These properties may contribute to the trophic actions of the CB transplants on nigrostriatal neurons and to their extraordinary longevity. We show that CB glomus cells, although highly dopaminergic, are protected from dopamine-mediated oxidative damage because of the absence of the high-affinity dopamine transporter. Thus, intrastriatal CB grafts are uniquely suited for long-term delivery of trophic factors capable of promoting restoration of the nigrostriatal pathway

A New Approach to the Modeling of Anisotropic Media with the Transmission Line Matrix Method

A reformulation of the Transmission Line Matrix (TLM) method is presented to model non-dispersive anisotropic media. Two TLM-based solutions to solve this problem can already be found in the literature, each one with an interesting feature. One can be considered a more conceptual approach, close to the TLM fundamentals, which identifies each TLM in Maxwell's equations with a specific line. But this simplicity is achieved at the expense of an increase in the memory storage requirements of a general situation. The second existing solution is a more powerful and general formulation that avoids this increase in memory storage. However, it is based on signal processing techniques and considerably deviates from the original TLM method, which may complicate its dissemination in the scientific community. The reformulation presented in this work exploits the benefits of both methods. On the one hand, it maintains the direct and conceptual approach of the original TLM, which may help to better understand it, allowing for its future use and improvement by other authors. On the other hand, the proposal includes an optimized treatment of the signals stored at the stub lines in order to limit the requirement of memory storage to only one accumulative term per field component, as in the original TLM versions used for isotropic media. The good behavior of the proposed algorithm when applied to anisotropic media is shown by its application to different situations involving diagonal and off-diagonal tensor properties

Design & Optimization of Large Cylindrical Radomes with Subcell and Non-Orthogonal FDTD Meshes Combined with Genetic Algorithms

The word radome is a contraction of radar and dome. The function of radomes is to protect antennas from atmospheric agents. Radomes are closed structures that protect the antennas from environmental factors such as wind, rain, ice, sand, and ultraviolet rays, among others. The radomes are passive structures that introduce return losses, and whose proper design would relax the requirement of complex front-end elements such as amplifiers. The radome consists mostly in a thin dielectric curved shape cover and sometimes needs to be tuned using metal inserts to cancel the capacitive performance of the dielectric. Radomes are in the near field region of the antennas and a full wave analysis of the antenna with the radome is the best approach to analyze its performance. A major numerical problem is the full wave modeling of a large radome-antenna-array system, as optimization of the radome parameters minimize return losses. In the present work, the finite difference time domain (FDTD) combined with a genetic algorithm is used to find the optimal radome for a large radome-antenna-array system. FDTD uses general curvilinear coordinates and sub-cell features as a thin dielectric slab approach and a thin wire approach. Both approximations are generally required if a problem of practical electrical size is to be solved using a manageable number of cells and time steps in FDTD inside a repetitive optimization loop. These approaches are used in the full wave analysis of a large array of crossed dipoles covered with a thin and cylindrical dielectric radome. The radome dielectric has a thickness of ~λ/10 at its central operating frequency. To reduce return loss a thin helical wire is introduced in the radome, whose diameter is ~0.0017λ and the spacing between each turn is ~0.3λ. The genetic algorithm was implemented to find the best parameters to minimize return losses. The inclusion of a helical wire reduces return losses by ~10 dB, however some minor changes of radiation pattern could distort the performance of the whole radome-array-antenna system. A further analysis shows that desired specifications of the system are preserved

A 3D TLM code for the study of the ELF electromagnetic wave propagation in the Earth's atmosphere

The interest in the study of electromagnetic propagation through planetary atmospheres is briefly discussed. Special attention is devoted to extremely-low-frequency fields in the Earth's atmosphere for its global nature and possible applications to climate monitoring studies among others. In the Earth's case, the system can be considered as a spherical electromagnetic shell resonator in which two concentric and large conducting spheres with a radius around 6300 km are separated by a very small distance of around 100 km, the atmosphere height. A numerical solution using the Transmission Line Method is proposed. The classical spherical-coordinate description is easy to use, however, the important difference in the dimensions along the three coordinate directions causes high numerical dispersion in the results. A Cartesian scheme with equal node size for all directions is used to reduce this undesired dispersion. A pre-processing stage is the key point introduced to lessen the resulting high demand of memory and time calculation and make the solution feasible. A parallelized Fortran code together with pre- and post-processing Python programs to ease the user interface are provided with this work. Details on the Fortran code and the Python modules are included both in the paper and the source codes to allow the use and modifications by other researchers interested in electromagnetic propagation through planetary atmospheres. The program allows calculation of the time evolution of the electromagnetic field at any point in the atmosphere. It includes the possibility of considering multiple time-dependent sources and different homogeneous and inhomogeneous conductivity profiles to model different situations. Profiles to study day-night asymmetries or locally perturbed profiles which have been attributed to earthquakes in the literature are implemented, for instance.MCIN/AEI 10.13039/501100011033 (grant PID 2020-112805 GA-I00)Grant PID 2020-112805 GA-I00 funded by MCIN/AEI/10.13039/ 50110001103

Schumann resonance data processing programs and four-year measurements from Sierra Nevada ELF station

In this work, we present to the scientific community the measurements taken during four years, from March 2013 to February 2017 inclusive, by the Extremely Low Frequency Sierra Nevada station, Spain, together with the data processing programs developed in Python (version 3.8) to extract the Schumann resonance (SR) parameters (i.e., amplitudes, resonant frequencies, resonance widths) in 10 min time periods from these records. The measure- ments correspond to the voltage induced by the atmospheric electromagnetic field at the north-south and east- west oriented magnetometers of the station. The process comprises four stages. The spectrum, calibrated in the frequency band ranging from 6 Hz to 25 Hz, is obtained at the first stage using the Welch method with Hann windows. The second step eliminates the anthropogenic noise generated by different undesired sources. Next, a non-linear fit of the measured spectrum combining Lorentzian functions together with a linear term is carried out in order to identify the presence of SRs and quantitatively characterize them. This third step is carried out using the Python package Lmfit, which implements the Levenberg-Marquad algorithm. Finally, a compact and easy-to- read output is generated at the fourth stage, using the power of the Numpy arrays and the npz format. In addition, four Jupyter notebooks with the description of the code and the possibility of their use in interactive mode are presented as supplementary material with this paper

Observations of the step-like accelerating processes of cold ions in the reconnection layer at the dayside magnetopause

Cold ions of plasmaspheric origin have been observed to abundantly appear in the magnetospheric side of the Earth’s magnetopause. These cold ions could affect the magnetic reconnection processes at the magnetopause by changing the Alfvén velocity and the reconnection rate, while they could also be heated in the reconnection layer during the ongoing reconnections. We report in situ observations from a partially crossing of a reconnection layer near the subsolar magnetopause. During this crossing, step-like accelerating processes of the cold ions were clearly observed, suggesting that the inflow cold ions may be separately accelerated by the rotation discontinuity and slow shock inside the reconnection layer

Ion-scale kinetic Alfvén turbulence: MMS measurements of the Alfvén ratio in the magnetosheath

Turbulence in the Earth's magnetosheath at ion kinetic scales is investigated with the magnetospheric multiscale spacecraft. Several possibilities in the wave paradigm have been invoked to explain plasma turbulence at ion kinetic scales such as kinetic Alfvén, slow, or magnetosonic waves. To differentiate between these different plasma waves is a challenging task, especially since some waves, in particular, kinetic slow waves and kinetic Alfvén waves, share some properties making the possibility to distinguishing between them very difficult. Using the excellent time resolution data set provided from both the fluxgate magnetometer and the Fast Plasma Instrument, the ratio of trace velocity fluctuations to the magnetic fluctuations (in Alfvén units), which is termed the Alfvén ratio, can be calculated down to ion kinetic scales. Comparison of the measured Alfvén ratio is performed with respect to the expectation from two‐fluid magnetohydrodynamic theory for the kinetic slow wave and kinetic Alfvén wave. Moreover, the plasma data also allow normalized fluctuation amplitudes of density and magnetic field to be compared differentiating between magnetosonic‐like and kinetic Alfvén‐like turbulence. Using these two different ratios, we can rule out that the fluctuations at ion scales are dominated by magnetosonic‐like fluctuations or kinetic slow‐like fluctuations and show that they are consistent with kinetic Alfvén‐like fluctuations. This suggests that in the wave paradigm, heating in the direction of the parallel magnetic field is predominantly by the Landau damping of the kinetic Alfvén wave

Real-Life Effectiveness and Tolerability of Brivaracetam in Focal to Bilateral and Primary Generalized Tonic-Clonic Seizures

Effectiveness; Brivaracetam; Tonic-clonic seizuresEfectividad; Brivaracetam; Convulsiones tónico-clónicasEfectivitat; Brivaracetam; Convulsions tònic-clòniquesPurpose. Brivaracetam (BRV), an antiseizure medication indicated for focal-onset seizures, has shown efficacy in the treatment of focal to bilateral tonic-clonic seizures (FBTCS). We aimed to determine the effectiveness and safety of BRV in patients with FBTCS and generalized tonic-clonic seizures (GTCS). Methods. We performed a multicenter, retrospective, longitudinal study in adult patients with epilepsy who experienced at least one FBTCS or GTCS before starting BRV (baseline visit). Data were collected from consecutive outpatient visits over a 4-year period. All patients had been followed for at least 3 months before the baseline visit and completed a minimum follow-up of 3 months after starting BRV. Response (≥50% reduction in FBTCS/GTCS frequency) and retention rates, as well as seizure freedom and presence of adverse events at 3, 6, and 12 months, were recorded as outcome measures. Results. 114 patients were included (mean age years, 52% male, 36.6% genetic generalized epilepsy); 94 had a 12-month follow-up period. At 12 months’ follow-up, the response rate was 83%, and 73.4% of patients were FBTCS/GTCS-free. Retention was 79% at 12 months. Adverse events occurred in 29.8% of patients, the most common being drowsiness (14.9%). No significant differences were found in response rates between FBTCS and GTCS. Drug resistance was independently associated with lower response and seizure freedom rates at follow-up. The absence of a titration period predicted seizure freedom and response at 3 months. Conclusions. BRV is an effective and well-tolerated treatment in patients with focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures.E. Fonseca declares research funding and honoraria from UCB Pharma, Esteve Laboratorios, Eisai Inc., Bial Pharmaceutical, GW Pharmaceuticals, Angelini Pharma, and Sanofi Genzyme. A. Gifreu declares research funding from UCB Pharma and Bial Pharmaceutical. Manuel Quintana has received honoraria from UCB Pharma, Eisai Inc., Sanofi, GW Pharmaceuticals, Neuraxpharm Spain, and Pierre Fabre Ibérica. S. Lallana has received travel support and research funding from UCB Pharma and Bial Pharmaceutical. S. López-Maza declares travel support and research funding from Eisai Inc., UCB Pharma, and Neuraxpharm Spain. L. Abraira has received research funding and speaker fees from UCB Pharma, Bial Pharmaceutical, Eisai Inc., Sanofi Genzyme, and Esteve Laboratorios. D. Campos-Fernández has received research funding from UCB Pharma. E. Santamarina has received research funding and speaker fees from UCB Pharma, Bial Pharmaceutical, Eisai Inc., Arvelle, and Esteve Laboratorios. J. Rodríguez Uranga declares honoraria from Arvelle, Angelini Pharma, Bial Pharmaceutical, Eisai Inc., Esteve Laboratorios, UCB Pharma, and Pfizer Inc. M. Toledo declares research funding and speaker fees from UCB Pharma, GW Pharmaceuticals, Bial Pharmaceutical, Eisai Inc., Sanofi, Arvelle, and Esteve Laboratorios. J Abril Jaramillo and L. Redondo Vergé have no conflict of interest to declare

The impact of silent vascular brain burden in cognitive impairment in Parkinson's disease

White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies