TRANSPORT INFRASTRUCTURES AND REGIONAL GROWTH: EVIDENCE OF THE SPANISH CASE

This paper analyses the impact of transport infrastructures on the economic growth of both regions and sectors, distinguishing among modes of transport. It also attempts to capture the spillover effects or network effects associated with transport infrastructures. Two different methodologies are used: the first adopts an accounting approach on the basis of a regression on total factor productivity (TFP) indices, the second uses econometric estimates of the production function. Our study obtains very similar elasticities with both methodologies for the private sector of the economy, both for the aggregate capital stock of transport infrastructures and for the various types of infrastructure. Important network effects of these infrastructures on the private sector have also been observed. However, the disaggregated results for sectors of production are not conclusive. Este trabajo analiza el impacto de las infraestructuras de transporte sobre elcrecimiento económico, tanto regional como sectorial, distinguiendo el análisis pormodo de transporte. Asimismo, se intentan captar los efectos spillover o efectos redasociados a las infraestructuras de transporte. Para ello, se emplean dos metodologíasdiferentes. La primera utiliza una aproximación contable a partir de una regresión sobrelos índices de productividad total de los factores (TFP). La segunda metodología utilizaestimaciones econométricas de la función de producción. Nuestro trabajo obtiene paraambas metodologías elasticidades muy similares para el sector privado de la economía,tanto para el stock de capital agregado de infraestructuras de transporte como para losdiversos tipos de infraestructuras. También se han constatado importantes efectos red deestas infraestructuras sobre el sector privado. Sin embargo, los resultados desagregadospor sectores productivos no son concluyentes.Infraestructuras de transporte, productividad, regiones, sectores. Transport infrastructures, productivity, regions, sectors.

Actividad tecnológica y crecimiento económico en las regiones españolas

This paper analyses the importance of R&D activities in the explanation of productivitydifferences among the Spanish regions over the period 1986-96. With this aim, we measure the effectof the own technological innovation and the spillovers effects. The analysis is based on the estimationof a production function and also on the effect of R&D on total factor productivity. The results showsthat although R&D has a significant effect at national level in a long-term period, the effect at regionallevel over the period 1987-96 depend on the technological index used. En este trabajo se analiza la importancia de las actividades tecnológicas en la explicación de las diferencias de productividad de las regiones españolas en el periodo 1986-96. Para ello se cuantifica el efecto de la innovación tecnológica propia de la región y las externalidades asociadas al capital tecnológico sobre el desarrollo regional. El análisis se basa en la estimación de funciones de producción, así como una ecuación explicativa de la productividad total de los factores. Si bien se obtiene un efecto positivo y significativo a nivel nacional en un horizonte de largo plazo, la significatividad del efecto de las actividades tecnológicas sobre la productividad de las regiones españolas en el periodo 1987-96 depende del indicador utilizado.I+D, productividad, convergencia R&D, productivity, convergence

Eficiencia productiva sectorial en las regiones españolas: una aproximación frontera

The aim of this paper is to analyse the technical efficiency of the productive sectors of the Spanish regions over the period 1980-91. We estimate a production function using an stochastic frontier approach for the productive sectors under three different distributional assumptions for the inefficiency term. The results obtained show the existence of important inefficiency levels in the production, being the energetic and agriculture sectors those that present the higher inefficiency leve1s.We also estimate the growth rate of the total factor productivity in every productive sector, calculated as the difference between the growth rate of technical change and the growth rate of the inefficiency.Finally, we analyse the convergence process of the inefficiency levels for every productive sectors. El objetivo de este trabajo es analizar la eficiencia técnica de los sectores productivos de las regiones españolas en el periodo 1980-91. Para ello, se estima una función frontera de producción estocástica para los sectores productivos de las regiones españolas bajo tres supuestos distribucionales alternativos para el término de ineficiencia. Los resultados obtenidos muestran la existencia de importantes niveles de ineficiencia en la producción, siendo el sector de la energía y el sector agrícola los que experimentan los mayores niveles de ineficiencia.Asimismo, se estiman las tasas de crecimiento de la productividad total de los factores para cada uno de los sectores productivos obtenidas como la diferencia entre la tasa de crecimiento del progreso técnico y la tasa de crecimiento de la ineficiencia.Finalmente, se analiza la convergencia de los niveles de ineficiencia entre las regiones españolas en cada uno de los sectores analizados.Eficiencia técnica, frontera estocástica, productividad regional Technical efficiency, stochastic frontier, regional productivity

The importance of intangible assets in regional economic growth: a growth accounting approach

Spain is one of the few countries in the world that has information on investment in intangible assets with a regional breakdown, so providing evidence of its importance as a factor in regional growth is the main value added of this paper. Series of capital stock in intangible assets are constructed by regions, which incorporate not only those the national accounts consider as investments and are therefore included in gross value added (GVA), but also the intangible assets not included in GVA, which the recent literature understand to be an important source of economic growth. Using the growth accounting approach, the results show that intangible assets explain 14.3% of Spain’s GVA growth, of which 9.4 pp correspond to the assets included in GVA (software, R&D and intellectual property rights) and 4.9 pp account for the rest (expenditure on design, advertising, market research, firm-provided worker training and improvements to companies’ organizational structure). Notable differences are also seen across the country, with investment in intangibles explaining up to 20% of economic growth in some regions. The importance of the contribution from these intangible assets highlights the need for economic policy measures (including regional policies) that boost investment in intangible assets and improve conditions of access to financing

Synthesis and pharmacology of alkanediguanidinium compounds that block the neuronal nicotinic acetylcholine receptor

Taking as models the polyamine toxin fraction FTX from the funnel-web spider venom, and the guanidinium moiety of guanethidine, a series of azaalkane-1,omega-diguanidinium salts were obtained. Some of them blocked ion fluxes through the neuronal nicotinic receptors for acetylcholine (nAChR). The blockade was exerted at submicromolar concentrations, suggesting a highly selective interaction with the nAChR. In fact, the active compounds on the nAChR ion channel did not recognize the voltage-dependent Na+ or Ca2+ channels of bovine adrenal chromaffin cells. Therefore, these compounds may be useful tools to clarify the functions of nAChR receptors in the central and peripheral nervous systems.Fundación Ramón Arece

Derivados de 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso en el tratamiento de enfermedades neurodegenerativas

Derivados de 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso en el tratamiento de enfermedades neurodegenerativas. Compuestos químicos derivados del sistema heterocíclico 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso como composiciones farmacéuticas para el tratamiento de enfermedades del sistema nervioso central, provocadas por una serie de procesos incluidos en lo que genéricamente se denomina neurodegeneración, en concreto para el tratamiento de Alzheimer, enfermedad de Parkinson o enfermedad de Huntington.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Autónoma de MadridB1 Patente sin examen previ

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

PP2A ligand ITH12246 protects against memory impairment and focal cerebral ischemia in mice

ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8] naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in in vitro models of Alzheimer's disease. These effects were proposed to be due in part to a regulatory action on protein phosphatase 2A inhibition, as it prevented binding of its inhibitor okadaic acid. We decided to investigate the pharmacological properties of ITH12246, evaluating its ability to counteract the memory impairment evoked by scopolamine, a muscarinic antagonist described to promote memory loss, as well as to reduce the infarct volume in mice suffering phototrombosis. Prior to conducting these experiments, we confirmed its in vitro neuroprotective activity against both oxidative stress and Ca2+ overload-derived excitotoxicity, using SH-SY5Y neuroblastoma cells and rat hippocampal slices. Using a predictive model of blood-brain barrier crossing, it seems that the passage of ITH12246 is not hindered. Its potential hepatotoxicity was observed only at very high concentrations, from 0.1 mM. ITH12246, at the concentration of 10 mg/kg i.p., was able to improve the memory index of mice treated with scopolamine, from 0.22 to 0.35, in a similar fashion to the well-known Alzheimer's disease drug galantamine 2.5 mg/kg. On the other hand, ITH12246, at the concentration of 2.5 mg/kg, reduced the phototrombosis-triggered infarct volume by 67%. In the same experimental conditions, 15 mg/kg melatonin, used as control standard, reduced the infarct volume by 30%. All of these findings allow us to consider ITH12246 as a new potential drug for the treatment of neurodegenerative diseases, which would act as a multifactorial neuroprotectant.Peer Reviewe