Desarrollo de una metodología para el diseño de microrredes de hasta 10 kW en el sector doméstico considerando parámetros técnicos y económicos

[ES] El presente trabajo persigue el objetivo de crear una metodología que sirva para establecer unos cálculos básicos del diseño de una microrred: selección de las tecnologías necesarias, potencias requeridas, tarifa adecuada, etc. El trabajo se dividirá en dos partes diferenciadas: el estudio de un caso concreto (un suministro doméstico) y la extrapolación de los resultados obtenidos para aplicarlos en instalaciones del mismo sector. La motivación de realizar este proyecto surge a raíz de la constante y creciente demanda de electricidad y el cambio en la producción: de centralizada a distribuida. Por ello, se desea crear unos patrones de trabajo que ayuden a la instalación de microrredes de forma que se reduzcan costes y tengan un correcto funcionamiento técnico. Se comienza estudiando casos que puedan acogerse a PVPC esperando, en un futuro, una continuación para poder aplicarlo en empresas con grandes consumos.Molina Martínez, N. (2019). Desarrollo de una metodología para el diseño de microrredes de hasta 10 kW en el sector doméstico considerando parámetros técnicos y económicos. http://hdl.handle.net/10251/124841TFG

La Ley de Presupuestos de la Comunidad Autónoma de Aragón: naturaleza jurídica, contenido y efectos.

En este Trabajo de Fin de Grado se hace referencia a la Ley de Presupuestos de la Comunidad Autónoma de Aragón para el ejercicio 2016. En éste se abordan cuestiones tales como la controversia de su naturaleza jurídica (si se considera ésta ley formal o ley material), su contenido; realizando un análisis de carácter económico del Presupuesto y llevando a cabo una comparación respecto de su homóloga en el año 2015 y de carácter jurídico analizando detalladamente qué puede incluirse en esta ley; abordando finalmente los efectos que la misma produce en el conjunto de la sociedad aragonesa. Así mismo, se ha hecho especial mención a la prórroga que se ha producido de la Ley de Presupuestos en este ejercicio

White Matter Microstructure Reflects Individual Differences in Music Reward Sensitivity

People show considerable variability in the degree of pleasure they experience from music. These individual differences in music reward sensitivity are driven by variability in functional connectivity between the nucleus accumbens (NAcc), a key structure of the reward system, and the right superior temporal gyrus (STG). However, it is unknown whether a neuroanatomical basis exists for this variability. We used diffusion tensor imaging and probabilistic tractography to study the relationship between music reward sensitivity and white matter microstructure connecting these two regions via the orbitofrontal cortex (OFC) in 38 healthy human participants (24 females and 14 males). We found that right axial diffusivity (AD) in the STG-OFC connectivity inversely correlated with music reward sensitivity. Additionally, right mean diffusivity and left AD in the NAcc-OFC tract also showed an inverse correlation. Further, AD in this tract also correlated with previously acquired BOLD activity during music listening, but notfor a control monetary reward task in the NAcc. Finally, we used mediation analysis to show that AD in the NAcc-OFC tract explains the influence of NAcc activation during a music task on music reward sensitivity. Overall, our results provide further support for the idea that the exchange of information among perceptual, integrative, and reward systems is important for musical pleasure, and that individual differences in the structure of the relevant anatomical connectivity influences the degree to which people are able to derive such pleasure

Differential effects of ageing on the neural processing of speech and singing production

BackgroundUnderstanding healthy brain ageing has become vital as populations are ageing rapidly and age-related brain diseases are becoming more common. In normal brain ageing, speech processing undergoes functional reorganisation involving reductions of hemispheric asymmetry and overactivation in the prefrontal regions. However, little is known about how these changes generalise to other vocal production, such as singing, and how they are affected by associated cognitive demands.MethodsThe present cross-sectional fMRI study systematically maps the neural correlates of vocal production across adulthood (N=100, age 21–88 years) using a balanced 2x3 design where tasks varied in modality (speech: proverbs / singing: song phrases) and cognitive demand (repetition / completion from memory / improvisation).ResultsIn speech production, ageing was associated with decreased left pre- and postcentral activation across tasks and increased bilateral angular and right inferior temporal and fusiform activation in the improvisation task. In singing production, ageing was associated with increased activation in medial and bilateral prefrontal and parietal regions in the completion task, whereas other tasks showed no ageing effects. Direct comparisons between the modalities showed larger age-related activation changes in speech than singing across tasks, including a larger left-to-right shift in lateral prefrontal regions in the improvisation task.ConclusionThe present results suggest that the brains’ singing network undergoes differential functional reorganisation in normal ageing compared to the speech network, particularly during a task with high executive demand. These findings are relevant for understanding the effects of ageing on vocal production as well as how singing can support communication in healthy ageing and neurological rehabilitation

Neural correlates of specific musical anhedonia

Although music is ubiquitous in human societies, there are some people for whom music holds no reward value despite normal perceptual ability and preserved reward-related responses in other domains. The study of these individuals with specific musical anhedonia may be crucial to understand better the neural correlates underlying musical reward. Previous neuroimaging studies have shown that musically induced pleasure may arise from the interaction between auditory cortical networks and mesolimbic reward networks. If such interaction is critical for music-induced pleasure to emerge, then those individuals who do not experience it should show alterations in the cortical-mesolimbic response. In the current study, we addressed this question using fMRI in three groups of 15 participants, each with different sensitivity to music reward. We demonstrate that the music anhedonic participants showed selective reduction of activity for music in the nucleus accumbens (NAcc), but normal activation levels for a monetary gambling task. Furthermore, this group also exhibited decreased functional connectivity between the right auditory cortex and ventral striatum (including the NAcc). In contrast, individuals with greater than average response to music showed enhanced connectivity between these structures. Thus, our results suggest that specific musical anhedonia may be associated with a reduction in the interplay between the auditory cortex and the subcortical reward network, indicating a pivotal role of this interaction for the enjoyment of music

Neurological Music Therapy Rebuilds Structural Connectome after Traumatic Brain Injury: Secondary Analysis from a Randomized Controlled Trial

Background: Traumatic brain injury (TBI) is a common and devastating neurological condition, associated often with poor functional outcome and deficits in executive function. Due to the neuropathology of TBI, neuroimaging plays a crucial role in its assessment, and while diffusion MRI has been proposed as a sensitive biomarker, longitudinal studies evaluating treatment-related diffusion MRI changes are scarce. Recent evidence suggests that neurological music therapy can improve executive functions in patients with TBI and that these effects are underpinned by neuroplasticity changes in the brain. However, studies evaluating music therapy induced structural connectome changes in patients with TBI are lacking. Design: Single-blind crossover (AB/BA) randomized controlled trial (NCT01956136). Objective: Here, we report secondary outcomes of the trial and set out to assess the effect of neurological music therapy on structural white matter connectome changes and their association with improved execute function in patients with TBI. Methods: Using an AB/BA design, 25 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 16) or second (BA, n = 9) half of a 6-month follow-up period. Neuropsychological testing and diffusion MRI scans were performed at baseline and at the 3-month and 6-month stage. Findings: Compared to the control group, the music therapy group increased quantitative anisotropy (QA) in the right dorsal pathways (arcuate fasciculus, superior longitudinal fasciculus) and in the corpus callosum and the right frontal aslant tract, thalamic radiation and corticostriatal tracts. The mean increased QA in this network of results correlated with improved executive function. Conclusions: This study shows that music therapy can induce structural white matter neuroplasticity in the post-TBI brain that underpins improved executive function

Neurological Music Therapy Rebuilds Structural Connectome after Traumatic Brain Injury: Secondary Analysis from a Randomized Controlled Trial

Background: Traumatic brain injury (TBI) is a common and devastating neurological condition, associated often with poor functional outcome and deficits in executive function. Due to the neuropathology of TBI, neuroimaging plays a crucial role in its assessment, and while diffusion MRI has been proposed as a sensitive biomarker, longitudinal studies evaluating treatment-related diffusion MRI changes are scarce. Recent evidence suggests that neurological music therapy can improve executive functions in patients with TBI and that these effects are underpinned by neuroplasticity changes in the brain. However, studies evaluating music therapy induced structural connectome changes in patients with TBI are lacking. Design: Single-blind crossover (AB/BA) randomized controlled trial (NCT01956136). Objective: Here, we report secondary outcomes of the trial and set out to assess the effect of neurological music therapy on structural white matter connectome changes and their association with improved execute function in patients with TBI. Methods: Using an AB/BA design, 25 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 16) or second (BA, n = 9) half of a 6-month follow-up period. Neuropsychological testing and diffusion MRI scans were performed at baseline and at the 3-month and 6-month stage. Findings: Compared to the control group, the music therapy group increased quantitative anisotropy (QA) in the right dorsal pathways (arcuate fasciculus, superior longitudinal fasciculus) and in the corpus callosum and the right frontal aslant tract, thalamic radiation and corticostriatal tracts. The mean increased QA in this network of results correlated with improved executive function. Conclusions: This study shows that music therapy can induce structural white matter neuroplasticity in the post-TBI brain that underpins improved executive function

Severity of radiation pneumonitis, from clinical, dosimetric and biological features: a pilot study

Background and objective: Radiation pneumonitis (RP) could be a lethal complication of lung cancer treatment. No reliable predictors of RP severity have been recognized. This prospective pilot study was performed to identify early predictors of high grade lung toxicity and to evaluate clinical, biological or dosimetric features associated with different grades of toxicity. Method: Sixteen patients with non‐small cell lung cancer with indication of concurrent chemoradiotherapy using 60 Gy/2 Gy/fraction starting at cycle one of platinum based chemotherapy were included. Bronchoalveolar lavage (BAL), pulmonary function testing (PFT), and 18F‐2‐fluoro‐2‐deoxy‐D‐glucose positron‐emission tomography was per‐ formed before radiotherapy (RT), after three weeks of treatment, and two months post‐RT. For analysis, patients were grouped by grade (low [G1‐G2] vs. high [G3‐G5]). The two groups were compared to identify predictors of RP. Protein expression BAL and lung tissue metabolism was evaluated in two patients (RP‐G1 vs. RP‐G3). Categorical variables such as comorbidities, stages and locations were summarized as percentages. Radiation doses, pulmonary function values and time to RP were summarized by medians with ranges or as means with standard deviation. Longitudinal analysis PFT was performed by a T‐test. Results: All 16 patients developed RP, as follows: G1 (5 pts; 31.3%); G2 (5 pts; 31.3%); G3 (5 pts; 31.3%); and G5 (1 pts; 6.1%). Patients with high grade RP presented significant decrease (p = 0.02) in diffusing lung capacity for carbon monoxide (DLCO) after three weeks of RT. No correlation between dosimetric values and RP grades was observed. BAL analysis of the selected patients showed that CXCL‐1, CD154, IL‐1ra, IL‐23, MIF, PAI‐1 and IFN‐γ were overexpressed in the lungs of the RP‐G3 patient, even before treatment. The pre‐RT SUVmax value in the RP‐G3 patient was non‐ significantly higher than in the patient with RP‐G1. Conclusions: RT induces some degree of RP. Our data suggest that decrease in DLCO% is the most sensitive param‐ eter for the early detection of RP. Moreover, we detect biological differences between the two grades of pneumonitis, highlighting the potential value of some cytokines as a prognostic marker for developing high grade lung toxicity. Further multicenter studies with larger sample size are essential to validate these findings

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma

Autologous T cells expressing the Chimeric Antigen Receptor (CAR) have been approved as advanced therapy medicinal products (ATMPs) against several hematological malignancies. However, the generation of patient-specific CART products delays treatment and precludes standardization. Allogeneic off-theshelf CAR-T cells are an alternative to simplify this complex and timeconsuming process. Here we investigated safety and efficacy of knocking out the TCR molecule in ARI-0001 CAR-T cells, a second generation aCD19 CAR approved by the Spanish Agency of Medicines and Medical Devices (AEMPS) under the Hospital Exemption for treatment of patients older than 25 years with Relapsed/Refractory acute B cell lymphoblastic leukemia (B-ALL). We first analyzed the efficacy and safety issues that arise during disruption of the TCR gene using CRISPR/Cas9. We have shown that edition of TRAC locus in T cells using CRISPR as ribonuleorproteins allows a highly efficient TCR disruption (over 80%) without significant alterations on T cells phenotype and with an increased percentage of energetic mitochondria. However, we also found that efficient TCRKO can lead to on-target large and medium size deletions, indicating a potential safety risk of this procedure that needs monitoring. Importantly, TCR edition of ARI-0001 efficiently prevented allogeneic responses and did not detectably alter their phenotype, while maintaining a similar anti-tumor activity ex vivo and in vivo compared to unedited ARI-0001 CAR-T cells. In summary, we showed here that, although there are still some risks of genotoxicity due to genome editing, disruption of the TCR is a feasible strategy for the generation of functional allogeneic ARI-0001 CAR-T cells. We propose to further validate this protocol for the treatment of patients that do not fit the requirements for standard autologous CAR-T cells administration.Spanish ISCIII Health Research FundEuropean Commission PI15/02015 PI18/00337 PI21/00298Red TerAv RD21/ 0017/0004 PI18/ 00330 PI17/00672CECEyU and CSyF of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) for Andalusia 2016000073391-TRA 2016000073332-TRA PI-57069 PAIDIBio326 CARTPI-0001- 201 PECART-0031-2020 PI0014-2016 PEER-0286-2019Spanish Government 00123009/SNEO-20191072 PLEC2021-008094regional Ministry of Health 0006/2018 C2-0002-2019Spanish Government FPU16/05467 FPU17/02268 FPU17/04327Junta de Andalucia PECART-00312020Consejeria de Salud y Familias PECART-0027-2020 MCI DIN2018-010180 DIN2020-01155

The Menstrual Cycle Modulates Whole-Brain Turbulent Dynamics

Brain dynamics have recently been shown to be modulated by rhythmic changes in female sex hormone concentrations across an entire menstrual cycle. However, many questions remain regarding the specific differences in information processing across spacetime between the two main follicular and luteal phases in the menstrual cycle. Using a novel turbulent dynamic framework, we studied whole-brain information processing across spacetime scales (i.e., across long and short distances in the brain) in two open-source, dense-sampled resting-state datasets. A healthy naturally cycling woman in her early twenties was scanned over 30 consecutive days during a naturally occurring menstrual cycle and under a hormonal contraceptive regime. Our results indicated that the luteal phase is characterized by significantly higher information transmission across spatial scales than the follicular phase. Furthermore, we found significant differences in turbulence levels between the two phases in brain regions belonging to the default mode, salience/ventral attention, somatomotor, control, and dorsal attention networks. Finally, we found that changes in estradiol and progesterone concentrations modulate whole-brain turbulent dynamics in long distances. In contrast, we reported no significant differences in information processing measures between the active and placebo phases in the hormonal contraceptive study. Overall, the results demonstrate that the turbulence framework is able to capture differences in whole-brain turbulent dynamics related to ovarian hormones and menstrual cycle stages