Simon Ungers, 1980-2006. Espacios de silencio por amor al arte

El presente texto tiene como objetivo principal la investigación sobre la figura del arquitecto y artista alemán, Simon Ungers que desarrolló su actividad profesional entre 1980 y 2006, año de su fallecimiento. El interés por este autor surge, como en muchas otras ocasiones, del azar. Mi relación de amistad con Margarita Blanco, propietaria de la última obra construida de S.U. y amiga de la familia Ungers, me permitió conocer, de primera mano, el trabajo de este fascinante personaje. Simon Ungers se formó y desarrolló su actividad como arquitecto en los Estados Unidos y más concretamente en el estado de Nueva York, lugar donde su padre Oswald Mathias Ungers emigró con su familia para incorporarse como profesor en la AAp de la Universidad de Cornell en 1969. A la vuelta de la familia en 1975 a Colonia, su ciudad de nacimiento, S.U. decide quedarse en Ithaca para iniciar sus estudios como arquitecto. Desde muy temprana edad, destacó por tener unas cualidades excepcionales para el dibujo y poseía, según atestiguan todos los que lo conocieron, un nivel cultural y una lucidez mental que estaba muy por encima de la media, sobre todo de la media de sus compañeros de facultad. Las palabras de su profesor Werner Goehner en referencia a Simon lo deja claro con esta frase; “Cuando sus compañeros llegaban el ya estaba allí”. Su carrera profesional como arquitecto comenzó en 1980, una vez terminada su carrera, cuando forma un estudio con otros dos compañeros de facultad. Los primeros proyectos, en el entorno de la ciudad de Ithaca, reflejan aún los preceptos aprendidos en Cornell, que aunque ya no contaba con su padre como director, si mantenía la influencia de sus enseñanzas. Con el paso del tiempo S.U. irá creando su propio lenguaje y sobre todo, su propia forma de ver la arquitectura. La influencia de su entorno familiar dejó una huella trascendental en él, el interés por el mundo del arte con una importante colección particular, la fabulosa biblioteca de su padre, o la propia figura de O.M. Ungers, arquitecto que se encontraba entre los más importantes en la década de los 70 y 80, le permitió conocer un mundo apasionante que le acompañará a lo largo de su vida. A partir de 1987, Simon Ungers empieza a compaginar su actividad como arquitecto con la de artista. Al principio, como dos actividades sin conexión aparente, pero que con el transcurso del tiempo y como podremos comprobar en el desarrollo de esta Tesis, se volverán solo una al final de su vida. Este será el denominador común que lo diferencia de forma clara del panorama arquitectónico que le tocó vivir, y sobre todo, lo diferencia de cómo vio la arquitectura su padre. En los 26 años de profesión Simon Ungers se fue liberando de ataduras impuestas hasta llegar a la realización de proyectos de un minimalismo rotundo, sin concesiones, con una geometría rigurosa inconfundiblemente tectónica. Si exceptuamos sus pocos proyectos construidos que si tienen una voluntad de permanencia, el resto de su obra es efímera, incluso sus instalaciones en galerías o museos estaban pensadas para ser destruidas al cabo de su periodo de exposición con una vocación clara de ausencia. Sus proyectos monumentales, escultóricos, nacen, sobre todo a partir de 2001, como un ejercicio complejo de llevar esa abstracción sublime experimentada en sus instalaciones, a la arquitectura. Esta dualidad entre lo simple y lo complejo derivará en series de arquitecturas utópicas, acercándose a autores como Ledoux o Boullée. Será su periodo más activo, su fase de creación de esos emocionantes espacios de silencio

Fingolimod phosphate protection against mitochondrial damage in neuronal cells

Background: Major role of oxidative stress in the pathogenesis of neurodegenerative diseases have been suggested, being mitochondria one of the main sources of ROS. Aim: In the present work, we have studied the antioxidant effect of fingolimod phosphate (FP) on neuronal mitochondrial function and morphology using a model of mitochondrial oxidative damage induced by menadione (Vitk3). Methods: SN4741 neuronal cells were grown (70-80% confluence) and used as control (non-treated cells) or treated cells with Vitk3 15 µM alone or in presence of FP 50 nM during 4 hours. Mitochondrial membrane potential (MMP), cytochrome c oxidase (COX) activity, mitochondrial oxygen consumption rate (OCR), mitochondrial distribution (MTG) and morphology (EM) were analysed. Statistical differences were determined using one-way ANOVA. Results: Vitk3 incubation produces a dramatical decrease in MMP compared to control (43.7 %); this can be almost totally reverted by the co-incubation of Vitk3 in presence of FP (p<0.05). A 20.7 % decrease in COX activity has been found after Vitk3 incubation, again this effect was counteracted when Vitk3 and FP are combined, restoring COX activity to control levels (p<0.05). Vitk3 incubation triggers initially an increase in OCR, decreasing dramatically (61%) after 4 hours. In experiments co-incubating Vitk3 in presence of FP, the OCR decrease found was reduced to only 17% (p<0.05). In experiments with MitoTracker™ Green, we found a change in the network pattern distribution after Vitk3 administration that partially disappears when co-incubated in presence of FP. Almost all the mitochondria treated with Vitk3 show ultrastructural alterations at the electron microscopy level while normal mitochondria can be found when Vitk3 and FP are combined. Conclusion: FP protects against the mitochondrial damage induced by Vitk3, as seen by the results obtained in mitochondrial functional markers, distribution and morphology.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. PS13/14: Study of the non-immunological mechanisms of action of Gilenya (Fingolimod) as therapeutic tool in Multiple Sclerosis and/or other neurodegenerative diseases. Novartis Farmacéutica S.A

Pasireotide in the Personalized Treatment of Acromegaly

Tumors endocrins; Hormona del creixement; Adenoma somatòtrofTumores endocrinos; Hormona de crecimiento; Adenoma somatotrofoEndocrine tumors; Growth hormone; Somatotroph adenomaThe delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.This work was partly supported by a grant from Instituto Carlos III, Madrid, Spain, on personalized treatment of acromegaly (PMP:15/00027). Recordati financed medical writing for style and editing but did not influence nor had access to the content of this paper before its submission

Algorithms for Lightweight Key Exchange

This paper is an extended version of our paper published in Álvarez, R.; Santonja, J.; Zamora, A. Algorithms for Lightweight Key Exchange. In Proceedings of the 10th International Conference on Ubiquitous Computing and Ambient Intelligence, UCAmI 2016, San Bartolomé de Tirajana, Spain, 29 November–2 December 2016; Part II 10; Springer International Publishing: Cham, Switzerland, 2016; pp. 536–543.Public-key cryptography is too slow for general purpose encryption, with most applications limiting its use as much as possible. Some secure protocols, especially those that enable forward secrecy, make a much heavier use of public-key cryptography, increasing the demand for lightweight cryptosystems that can be implemented in low powered or mobile devices. This performance requirements are even more significant in critical infrastructure and emergency scenarios where peer-to-peer networks are deployed for increased availability and resiliency. We benchmark several public-key key-exchange algorithms, determining those that are better for the requirements of critical infrastructure and emergency applications and propose a security framework based on these algorithms and study its application to decentralized node or sensor networks.Research partially supported by the Spanish MINECO and FEDER under Project Grant TEC2014-54110-R

The burden of epilepsy and unmet need in people with focal seizures

BACKGROUND: Epilepsy is one of the most common neurological conditions worldwide. As a chronic condition, epilepsy imposes a significant burden on people with epilepsy and society. We aimed to assess the burden and unmet need of individuals with epilepsy and their caregivers, focusing on focal seizures, the main type of seizure in adults and children. METHODS: A targeted evidence review of the burden of epilepsy, focusing on focal seizures, was conducted to identify articles reporting: epidemiology, mortality, morbidity, quality of life (QoL), and costs. RESULTS: Focal seizures affect up to ∼61% of people with epilepsy. They are associated with an increased risk of injury and premature death than the general population. People with epilepsy also have high comorbidity, particularly depression, anxiety, and cognitive impairments. Higher seizure frequency, adverse treatment events, and employment concerns reduce QoL. A reduction in caregivers' QoL is also often reported. Epilepsy requires long-term treatment accounting for high individual costs. Hospitalizations and antiseizure medications (ASMs) are the leading cost drivers of inpatient management and indirect costs with high unemployment rates, particularly in drug-resistant populations. Despite the advent of new treatments, a high unmet need remains unaddressed; approximately 40% of people with epilepsy are drug-resistant, further increasing the risks associated with epilepsy. CONCLUSIONS: Our findings highlight a substantial burden of illness and unmet needs in individuals with focal seizures, especially those with drug-resistant epilepsy. Suboptimal treatment options negatively impact QoL and, consequently, a sizeable economic burden indicating the need for new treatments and prioritizing this condition

Papel del receptor S1P sobre el estrés oxidativo mitocondrial en cultivo neuronal

Introducción: Fingolimod, fármaco inmunomodulador, presenta propiedades neuroprotectoras que podrían promover la recuperación de la función cognitiva en enfermedades neurodegenerativas. El estrés oxidativo parece tener un papel fundamental en la patogénesis de dichas enfermedades, siendo la mitocondria una de las fuentes más importantes de especies reactivas de oxigeno (ROS). Objetivo: Determinar la implicación del receptor S1P en los efectos neuroprotectores mostrados por fingolimod fosfato (FP), forma activa de fingolimod, en un modelo celular de estrés oxidativo mitocondrial inducido por menadiona (Vitk3). Material y métodos: La línea celular SN4741 (70-80 % confluencia), se utilizó como control o se trató con Vitk3 15 µM en presencia o ausencia de FP 50 nM o FP 50 nM + W123 10 µM (antagonista S1P) durante 4 horas para estudiar: niveles de ROS mitocondrial según el marcaje de la producción de anión superóxido (O2−.); activación de caspasa-3; niveles de tioles totales (TTLs); marcadores mitocondriales (potencial de membrana mitocondrial-PMM-, actividad citocromo c oxidasa-COX- y consumo de oxígeno-OCR-). Las diferencias estadísticas se determinaron usando ANOVA de un factor. Resultados: W123 revierte parcialmente el efecto protector de FP sobe muerte celular programada, desencadenada por aumento de ROS (p<0,05) y consumo de reserva de antioxidante (p<0,05). El efecto de FP sobre los marcadores mitocondriales PMM, actividad COX y OCR es abolido con W123 (p<0,05). Conclusión: El receptor S1P está implicado en gran parte de los efectos protectores de FP, indicando un papel fundamental de S1P en el mantenimiento de la homeostasis mitocondrial. Proyecto financiado por Novartis Farmacéutica SA (PS13/14).Campus de Excelencia Internacional Andalucía Tech. Proyecto financiado por Novartis Farmacéutica SA (PS13/14). Programa operativo de empleo juvenil; Junta de Andalucía and Fondo Social Europeo (EU). CTS507 and CTS156 from Consejería de Economía Innovación Ciencia y Empresa, Junta de Andalucía and Plan Propio de la Universidad de Málaga 2016

Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P =.015), SAE-free survival (P =.008), and time to recovery (P =.03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS

Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor–positive metastatic breast cancer: Patient-reported outcomes in the PEARL study

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. Patients and methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQC30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs.-2.1 for capecitabine (95% confidence interval [CI], 1.4-8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. Trial registration number: NCT02028507 (ClinTrials.gov). EudraCT study number: 2013-003170-27. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Smart Solar Micro-exchangers for Sustainable Mobility of University Camps

Publicado el resumen en: https://www.wmcaus.org/files/WMCAUS2020_Book.pdf. Pendiente de publicación de las contribuciones en IOP Conference Series: Materials Science and Engineering.A significant number of universities have several campuses located in urban or rural settings, or with scattered university buildings that require the use of means of transportation. This implies the mobility and potential displacement of a large community of students, professors and researchers. The use of electric bicycles (e-bikes) is an intermediate alternative between the bicycle and electric cars. It can be an important stimulus for the promotion of the decarbonisation of the University Campus, avoiding the traffic congestion and reducing space requirements for parking. This paper presents the smart solar micro-exchanger model managed through a sustainable mobility web platform, applied to the case study of the University of Malaga (Spain). It is a solar charging station for e-bike, whose design is based on the principles of solar architecture (providing great security to e-bike). It managed by a web platform and app that allows the user to make reservations and learn about the savings in CO2 emissions. The system allows performing an aerobic sports activity without sweating problems when you reach the job. The platform also incorporates a database of quiet and safe routes for e-bike users.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec