Entrenamiento de las señales corticales a través de un sistema BMI-EEG, evolución e intervención. A propósito de un caso = Training cortical signals by means of a BMI-EEG system, its evolution and intervention. A case report

INTRODUCTION: In the last years, new technologies such as the brain-machine interfaces (BMI) have been incorporated in the rehabilitation process of subjects with stroke. These systems are able to detect motion intention, analyzing the cortical signals using different techniques such as the electroencephalography (EEG). This information could guide different interfaces such as robotic devices, electrical stimulation or virtual reality. CASE REPORT: A 40 years-old man with stroke with two months from the injury participated in this study. We used a BMI based on EEG. The subject's motion intention was analyzed calculating the event-related desynchronization. The upper limb motor function was evaluated with the Fugl-Meyer Assessment and the participant's satisfaction was evaluated using the QUEST 2.0. The intervention using a physical therapist as an interface was carried out without difficulty. CONCLUSIONS: The BMI systems detect cortical changes in a subacute stroke subject. These changes are coherent with the evolution observed using the Fugl-Meyer Assessment

Majorana Neutrino Masses from Anomalous U(1) Symmetries

We explore the possibility of interpreting the solar and atmospheric neutrino data within the context of the Minimal Supersymmetric Standard Model augmented by a single U(1) anomalous family symmetry spontaneously broken by non-zero vacuum expectation values of a pair of singlet fields. The symmetry retains a dimension-five operator which provides Majorana masses for left-handed neutrino states. Assuming symmetric lepton mass matrices, the model predicts inverse hierarchical neutrino mass spectrum, theta_{13}=0 and large mixing while at the same time it provides acceptable mass matrices for the charged fermions.Comment: 14 pages, no figure

The Low Redshift survey at Calar Alto (LoRCA)

The Baryon Acoustic Oscillation (BAO) feature in the power spectrum of galaxies provides a standard ruler to measure the accelerated expansion of the Universe. To extract all available information about dark energy, it is necessary to measure a standard ruler in the local, z<0.2, universe where dark energy dominates most the energy density of the Universe. Though the volume available in the local universe is limited, it is just big enough to measure accurately the long 100 Mpc/h wave-mode of the BAO. Using cosmological N-body simulations and approximate methods based on Lagrangian perturbation theory, we construct a suite of a thousand light-cones to evaluate the precision at which one can measure the BAO standard ruler in the local universe. We find that using the most massive galaxies on the full sky (34,000 sq. deg.), i.e. a K(2MASS)<14 magnitude-limited sample, one can measure the BAO scale up to a precision of 4\% and 1.2\% using reconstruction). We also find that such a survey would help to detect the dynamics of dark energy.Therefore, we propose a 3-year long observational project, named the Low Redshift survey at Calar Alto (LoRCA), to observe spectroscopically about 200,000 galaxies in the northern sky to contribute to the construction of aforementioned galaxy sample. The suite of light-cones is made available to the public.Comment: 15 pages. Accepted in MNRAS. Please visit our website: http://lorca-survey.ft.uam.es

Single breath-hold saturation recovery 3D cardiac T1 mapping via compressed SENSE at 3T.

To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy.TFdS has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N722427. CGA is a P-FIS fellow (Instituto deSalud Carlos III). This study was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Metoprolol blunts the time-dependent progression of infarct size.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.This study received funding from the Ministry of Science and Innovation (“RETOS 2019” Grant no. PID2019-107332RB-I00), from the Instituto de Salud Carlos III (ISCIII; PI16/02110) and the European Regional Development Fund (ERDF) “A way of making Europe” (# AC16/00021), and from the Spanish Society of Cardiology through a 2017 Translational Research grant. BI has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-Consolidator Grant agreement no. 819775). M.L received support from a 2015 Severo Ochoa CNIC intramural grant. X.R. received support from the SEC-CNIC CARDIOJOVEN fellowship program. R.F-J is a recipient of funding from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI19/01704) and has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atracción de Talento (2017-T1/BMD-5185) of Comunidad de Madrid. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Neutrino Unification

Present neutrino data are consistent with neutrino masses arising from a common seed at some ``neutrino unification'' scale $M_X$. Such a simple theoretical ansatz naturally leads to quasi-degenerate neutrinos that could lie in the electron-volt range with neutrino mass splittings induced by renormalization effects associated with supersymmetric thresholds. In such a scheme the leptonic analogue of the Cabibbo angle $\theta_{\odot}$ describing solar neutrino oscillations is nearly maximal. Its exact value is correlated with the smallness of $\theta_{reactor}$. These features agree both with latest data on the solar neutrino spectra and with the reactor neutrino data. The two leading mass-eigenstate neutrinos present in \ne form a pseudo-Dirac neutrino, avoiding conflict with neutrinoless double beta decay.Comment: RevTex format, 2 figures, 4 pages, a few new references, no other important change, figures unchanged, version to be published in PR

Generation and characterization of a novel knockin minipig model of Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder for which no cure exists. The disease is characterized by premature aging and inevitable death in adolescence due to cardiovascular complications. Most HGPS patients carry a heterozygous de novo LMNA c.1824C > T mutation, which provokes the expression of a dominant-negative mutant protein called progerin. Therapies proven effective in HGPS-like mouse models have yielded only modest benefit in HGPS clinical trials. To overcome the gap between HGPS mouse models and patients, we have generated by CRISPR-Cas9 gene editing the first large animal model for HGPS, a knockin heterozygous LMNA c.1824C > T Yucatan minipig. Like HGPS patients, HGPS minipigs endogenously co-express progerin and normal lamin A/C, and exhibit severe growth retardation, lipodystrophy, skin and bone alterations, cardiovascular disease, and die around puberty. Remarkably, the HGPS minipigs recapitulate critical cardiovascular alterations seen in patients, such as left ventricular diastolic dysfunction, altered cardiac electrical activity, and loss of vascular smooth muscle cells. Our analysis also revealed reduced myocardial perfusion due to microvascular damage and myocardial interstitial fibrosis, previously undescribed readouts potentially useful for monitoring disease progression in patients. The HGPS minipigs provide an appropriate preclinical model in which to test human-size interventional devices and optimize candidate therapies before advancing to clinical trials, thus accelerating the development of effective applications for HGPS patients.This project was mainly supported by an Established Investigator Award from the Progeria Research Foundation (2014-52), and from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU), and the European Regional Development Fund (FEDER, “A way to build Europe”) (SAF2016-79490-R, CB16/11/00405). Ana Barettino has a predoctoral contract from MCIU (BES-2017-079705). Work at Universidad de Murcia is supported by Fundación Seneca-Agencia de Ciencia y Tecnología de la Región de Murcia (20040/GERM/16). The CNIC is supported by the MCIU and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Lung ultrasound as a translational approach for non-invasive assessment of heart failure with reduced or preserved ejection fraction in mice

Aims: Heart failure (HF) has become an epidemic and constitutes a major medical, social, and economic problem worldwide. Despite advances in medical treatment, HF prognosis remains poor. The development of efficient therapies is hampered by the lack of appropriate animal models in which HF can be reliably determined, particularly in mice. The development of HF in mice is often assumed based on the presence of cardiac dysfunction, but HF itself is seldom proved. Lung ultrasound (LUS) has become a helpful tool for lung congestion assessment in patients at all stages of HF. We aimed to apply this non-invasive imaging tool to evaluate HF in mouse models of both systolic and diastolic dysfunction. Methods and results: We used LUS to study HF in a mouse model of systolic dysfunction, dilated cardiomyopathy, and in a mouse model of diastolic dysfunction, diabetic cardiomyopathy. LUS proved to be a reliable and reproducible tool to detect pulmonary congestion in mice. The combination of LUS and echocardiography allowed discriminating those mice that develop HF from those that do not, even in the presence of evident cardiac dysfunction. The study showed that LUS can be used to identify the onset of HF decompensation and to evaluate the efficacy of therapies for this syndrome. Conclusions: This novel approach in mouse models of cardiac disease enables for the first time to adequately diagnose HF non-invasively in mice with preserved or reduced ejection fraction, and will pave the way to a better understanding of HF and to the development of new therapeutic approaches.This study was supported by grants from the Spanish Ministerio de Economia y Competitividad (SAF2015-65722-R), Comunidad Autonoma de Madrid (2010-BMD2321, FIBROTEAM Consortium), European Union's FP7 (CardioNeT-ITN-289600, CardioNext-ITN-608027) and the Spanish Instituto de Salud Carlos III (CPII14/00027 to E.L-P, RD12/0042/0054 to B.I. and RD12/0042/066 to P.G.-P. and E.L-P). This work was also supported by the Plan Estatal de I+D+I 2013-2016 - European Regional Development Fund (FEDER) "A way of making Europe", Spain. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Neutrino Masses and Mixings from Supersymmetry with Bilinear R--Parity Violation: A Theory for Solar and Atmospheric Neutrino Oscillations

The simplest unified extension of the MSSM with bi-linear R--Parity violation naturally predicts a hierarchical neutrino mass spectrum, in which one neutrino acquires mass by mixing with neutralinos, while the other two get mass radiatively. We have performed a full one-loop calculation of the neutralino-neutrino mass matrix in the bi-linear \rp MSSM, taking special care to achieve a manifestly gauge invariant calculation. Moreover we have performed the renormalization of the heaviest neutrino, needed in order to get meaningful results. The atmospheric mass scale and maximal mixing angle arise from tree-level physics, while solar neutrino scale and oscillations follow from calculable one-loop corrections. If universal supergravity assumptions are made on the soft-supersymmetry breaking terms then the atmospheric scale is calculable as a function of a single \rp violating parameter by the renormalization group evolution due to the non-zero bottom quark Yukawa coupling. The solar neutrino problem must be accounted for by the small mixing angle (SMA) MSW solution. If these assumptions are relaxed then one can implement large mixing angle solutions, either MSW or just-so. The theory predicts the lightest supersymmetic particle (LSP) decay to be observable at high-energy colliders, despite the smallness of neutrino masses indicated by experiment. This provides an independent way to test this solution of the atmospheric and solar neutrino anomalies.Comment: 46 pages, references added + several misprints correcte