Real-world evaluation of the tolerability to onabotulinum toxin A: The RETO study

Producción CientíficaOnabotulinumtoxin A (onabotA) has shown efficacy in chronic migraine (CM), with good tolerability and a low rate of adverse effects, most of them not severe. The aim of this study is to evaluate tolerability and adverse effects of onabotA in clinical practice and to analyze if there is a relationship between tolerability to treatment administration, adverse effects’ (AEs) occurrence and clinical response. We included patients with CM that received treatment with onabotA for the first time. Tolerability to treatment was evaluated by a 0–10 numeric rating scale (0: worst possible, 10: optimal tolerability). We assessed the presence of AEs by using a standardized questionnaire. Treatment response was based on the 50 and 75% responder rate between weeks 20 and 24, compared with the baseline, according to headache diaries. We analyzed whether the tolerability was associated with a higher frequency of AEs or a higher probability of clinical response. We included 105 patients, 87.7% female, with an age of 43.9 ± 10.7 years. Mean tolerability was 7.8/10 and 7.2/10 in the first and second onabotA administration, respectively. AEs were reported by (first-second) 71.4–68.6% patients. The percentage of patients with a 50% response was 56.3%. There was no association between tolerability and AEs’ occurrence or clinical response

Four-channel self-compensating single-slope ADC for space environments

A multichannel high-resolution single-slope analogue-to-digital converter (SS ADC) is presented that automatically compensates for process, voltage and temperature variations, as well as for radiation effects, in order to be used in extreme environmental conditions. The design combines an efficient implementation by using a feedback loop that ensures an inherently monotonic and very accurate ramp generation, with high levels of configurability in terms of resolution and conversion rate, as well as input voltage range. The SS ADC was designed in a standard 0.35 μm CMOS technology. Experimental measurements of the performance and stability against radiation and temperature are presented to verify the proposed approach

A Front-End ASIC for a 3-D Magnetometer for Space Applications by Using Anisotropic Magnetoresistors

This paper presents an application-specific integrated circuit (ASIC) aimed for an alternative design of a digital 3-D magnetometer for space applications, with a significant reduction in mass and volume while maintaining a high sensitivity. The proposed system uses magnetic field sensors based on anisotropic magnetoresistances and a rad-hard mixed-signal ASIC designed in a standard 0.35 μm CMOS technology. The ASIC performs sensor-signal conditioning and analogue-to-digital conversion, and handles calibration tasks, system configuration, and communication with the outside. The proposed system provides high sensitivity to low magnetic fields, down to 3 nT, while offering a small and reliable solution under extreme environmental conditions in terms of radiation and temperature.Ministerio de Ciencia e Innovación AYA2011-29967-C05-05, AYA2009-14212-C05-04, AYA2008-06420-C04-0

OWLs: A mixed-signal ASIC for optical wire-less links in space instruments

This paper describes the design of a mixed-signal ASIC for space application and the techniques employed for radiation hardening and temperature effects compensation. The work is part of a planned long-term effort and collaboration between "Instituto de Microelectrónica de Sevilla (IMSE)", "Universidad de Sevilla (US)", and "Instituto Nacional de Técnica Aeroespacial (INTA)" aimed to consolidate a group of experienced mixed-signal space-ASIC designers. The initiative is partially funded by the Spanish National Research Program. The ASIC performs the function of an optical digital transceiver for diffuse-light intra-satellite optical communications. It has been designed in a 0.35μm CMOS technology from austriamicrosystems (ams). The chip has been manufactured and verified from a functional perspective. Radiation characterization is planned for the third quarter of 2012. Power- and temperature-stress tests, as well as life-tests are also planned for this next quarter, and will be carried out by Alter Technology TÜV Nord S.A.U. Given the previous characterization of the technology [1] and the hardening techniques employed in the design and layout, radiation is not expected to be a problem. The specified environmental limits are a pedestal hard limit of 50KRads with the goal of maximizing TID tolerance, SEU and SET LET-thresholds above 70MeV/(mg/cm2), and latchup free behavior up to the same LET limit. Concerning temperature, the specified operation range is from -90 to +125ºC, while the non-operating temperature range is from -135 to +150ºC.Ministerio de Ciencia e Innovación (MICINN) MEIGA AYA2009-14212-C05-04, AYA2008-06420-C04-0

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial

[Background] Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke.[Methods] The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.[Findings] Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.[Interpretation] Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.The Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation is the study sponsor. We acknowledge all the participants of the trial and the investigators. We thank the funding bodies Instituto de Salud Carlos III through the projects PI18/01414, PI15/01197, RD16/0019/0015 (INVICTUS+), and RD21/0006/0015 (co-funded by the European Regional Development Fund “A way to make Europe” and by the European Social Fund [FSE] “The FSE invests in your future”), Mutua Madrileña grant, and the Regional Ministry of Health of Andalusia, who financed the costs incurred by participating hospitals and the Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation. MM-R has a Rio Hortega grant (CM21/00096). We acknowledge the Methodological and Statistical Support Unit from the Andalusian Public Foundation for Health Research Management in Seville (FISEVI) for their support in the statistical analysis.Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Chronological context, species occurrence, and environmental remarks on the Gelasian site Pedrera del Corral d'en Bruach (Barcelona, Spain) based on the small-mammal associations

Altres ajuts: J.G. is the recipent of a postdoctoral contract [ESPDOC20/83] from the University of the Basque Country (UPV/EHU) and her work was also supported by the Eusko Jaurlaritza [IT1485-22]. B.M.-S. was funded by the Consellería de Cultura, Educación e Universidade, Xunta de Galicia, Spain (ED481D-2022-013).Here we present the results of a study of the small mammal assemblage recovered from a now disappeared karstic fissure located in a quarry called 'Pedrera del Corral d'en Bruach'. The site was located at 330 m a.s.l. in the Garraf Massif, ca. 20 km south of Barcelona. An archaeological rescue excavation was conducted in 2006 by the Grup de Recerca del Quaternari, focusing on sieving the sediments that had accumulated at the foot of the quarry face. Fortunately, some faunal remains and sediment were recovered, which were later processed and sorted. Two hundred and seventy small mammal remains were identified at genus or species level, bringing to light 15 taxa. The assemblage is typical of the Mammal Neogene 17 (MN17) biozone, placing this site in the Gelasian stage of the Early Pleistocene. It is noteworthy that the first record of the glirid Glirulus pusillus in Iberia is documented. Based on the small mammals identified, the surrounding environment of the Garraf Massif is judged to have been characterised by open forest landscape and more humid environmental conditions than nowadays. Finally, the site provides a remarkable contribution to what is known of the Iberian small mammals of this time period

Reseñas de Libros

<div>Andrés Cabello, Sergio; Capellán de Miguel, Gonzalo; Fandiño Pérez, Roberto y Orduña Prada, Mónica, La transición a la democracia en La Rioja. Logroño, Gobierno de La Rioja, 2001, 291 pp.</div><div><br /></div><div>Páginas 199-200</div><div><br /></div><div>José Miguel Delgado Idarreta</div><div><br /></div><div><br /></div><div>Beneyto, José María; Martín de la Guardia, Ricardo y Pérez Sánchez, Guillermo (dirs.), Europa y Estados Unidos. Una historia de la relación atlántica en los últimos cien años. Madrid, Biblioteca Nueva, 2005, 356 pp.</div><div><br /></div><div>Páginas 201-203</div><div><br /></div><div>David Molina Rabadán</div><div><br /></div><div><br /></div><div>Bosworth, Richard J. B., Mussolini’s Italy. Life under the Fascist Dictatorship 1915-1945. New York, Penguin, 2006, 692 pp.</div><div><br /></div><div>Páginas 203-205</div><div><br /></div><div>Jan Nelis</div><div><br /></div><div><br /></div><div>Dávila A., Mireya; Fuentes S., Claudio (eds.), Promesas de cambio. Izquierda y derecha en el Chile contemporáneo. Santiago de Chile, Editorial Universitaria, FLACSO, 2003, 189 pp.</div><div><br /></div><div>Páginas 205-208</div><div><br /></div><div>David Oviedo Silva</div><div><br /></div><div><br /></div><div>Delgado Idarreta, José Miguel; Andrés Cabello, Sergio, Actas del V Simposio de Historia Actual: La Rioja, España, Europa. Logroño, Instituto de Estudios Riojanos, 2006, 449 pp.</div><div><br /></div><div>Páginas 208-212</div><div><br /></div><div>Alfonso Pinilla García</div><div><br /></div><div><br /></div><div>Evans, Richard J., La llegada del Tercer Reich. Barcelona, Península, 2005, 672 pp.</div><div><br /></div><div>Páginas 212-214</div><div><br /></div><div>Alejandro Piñero González</div><div><br /></div><div><br /></div><div>Friedman, Thomas L., La Tierra es plana. Breve historia del mundo globalizado del siglo XXI. Madrid, Martínez Roca, 2006, 496 pp.</div><div><br /></div><div>Páginas 214-216</div><div><br /></div><div>David Molina Rabadán</div><div><br /></div><div><br /></div><div>Gil Calvo, Enrique, El miedo es el mensaje. Riesgo, incertidumbre y medios de comunicación. Madrid, Alianza Editorial, 2004, 320 pp.</div><div><br /></div><div>Páginas 216-218</div><div><br /></div><div>Lucía Benítez Eyzaguirre</div><div><br /></div><div><br /></div><div>Goicovic Donoso, Igor, Entre el dolor y la ira. La venganza de Antonio Ramón Ramón. Chile, 1914. Osorno, Editorial Universidad de los Lagos, 2005, 188 pp.</div><div><br /></div><div>Páginas 218-221</div><div><br /></div><div>Alejandra Brito Peña</div><div><br /></div><div><br /></div><div>Griffin, Roger (ed.), Fascism, Totalitarianism and Political Religion. New York, Routledge, 2005, 225 pp.</div><div><br /></div><div>Páginas 221-222</div><div><br /></div><div>Jan Nelis</div><div><br /></div><div><br /></div><div>McNeill, John R., Algo nuevo bajo el Sol. Historia medioambiental del mundo en el siglo XX. Alianza Editorial, Madrid, 2003, 504 pp.</div><div><br /></div><div>Páginas 222-224</div><div><br /></div><div>Alejandro Román Antequera</div><div><br /></div><div><br /></div><div>Pacheco Silva, Arnoldo, Economía y sociedad de Concepción, siglo XIX: Sectores populares urbanos, 1800 – 1885. Concepción, Universidad de Concepción, 2003, 319 pp.</div><div><br /></div><div>Páginas 224-226</div><div><br /></div><div>Mario Valdés Urrutia</div><div><br /></div><div><br /></div><div>Paxton, Robert O., Anatomía del fascismo. Barcelona, Península, 2005, 366 pp.</div><div><br /></div><div>Páginas 226-228</div><div><br /></div><div>Miguel Ángel del Arco Blanco</div><div><br /></div><div><br /></div><div>Rashke, Richard, Escapar de Sobibor. Barcelona, Planeta, 2004, 592 pp.</div><div><br /></div><div>Páginas 228-230</div><div><br /></div><div>Daniel Francisco Álvarez Espinosa</div><div><br /></div><div><br /></div><div>Said, Edward W., Cultura e Imperialismo. Barcelona, Editorial Anagrama, 2004, 542 pp.</div><div><br /></div><div>Páginas 230-232</div><div><br /></div><div>Joaquín Piñeiro Blanca</div><div><br /></div><div><br /></div><div>Skoutelsky, Rémi, Novedad en el frente. Las Brigadas Internacionales en la Guerra Civil. Madrid, Temas de Hoy, 2006, 503 pp.</div><div><br /></div><div>Páginas 232-234</div><div><br /></div><div>Alejandro Piñero González</div><div><br /></div><div><br /></div><div>“Pratiques de l'histoire immédiate”. Cahiers d'histoire immédiate, 29 (2006), 501 pp. Número especial: Colección de artículos aparecidos en los Cahiers d'histoire immédiate entre 1991 y 2005, presentada por Jean-François Soulet.</div><div><br /></div><div>Páginas 234-236</div><div><br /></div><div>Iván López Cabello</div><div><br /></div><div><br /></div><div>Wacquant, Loïc (Dir.) Repensar los Estados Unidos. Para una sociología del hiperpoder. Barcelona, Anthropos Editorial, 2005, 239 pp.</div><div><br /></div><div>Páginas 236-238</div><div><br /></div><div>Marcela Iglesias Onofrio</div><div><br /></div

Avances de investigación en educación matemática

Resumen basado en el de la publicaciónResumen en inglésSe presenta y justifica el diseño de POEMat.ES, una pauta de observación de acciones del profesorado de matemáticas en clase. POEMat.ES ha sido desarrollado con el fin de sistematizar la observación de la práctica de enseñanza para enteder e interpretar el proceso de enseñanza de matemáticas en educación secundaria en el contexto español. El diseño de POEMat.ES se ha basado en modelos específicos del conocimiento del profesor de matemáticas. Su construcción se aborda desde dos aproximaciones complementarias: se proponen categorías de observación de acciones del profesor desde una revisión sistemática de la literatura, y se redefinen y validan a través de los visionados de vídeosES