Integrated design of high performance pulsed power converters : application to klystron modulators for the compact linear colider (CLIC)

Ce travail de recherche présente l’étude, conception et validation d’une topologie de convertisseur de puissance pulsé qui compense la chute de tension pour des modulateurs de type klystron de haute performance. Cette topologie est capable de compenser la chute de tension du banc de condensateur principal et, en même temps, de faire fonctionner le modulateur avec une consommation de puissance constante par rapport au réseau électrique. Ces spécifications sont requises par le projet Compact Linear Collider (CLIC) pour les modulateurs klystron de son Drive Beam. Le dimensionnement du système est effectué à partir d’un outil d’optimisation globale développé à partir des modèles analytiques qui décrivent les performances de chaque composant du système. Tous les modèles sont intégrés dans un processus optimal intermédiaire de conception qui utilise des techniques d’optimisation afin de réaliser un dimensionnement optimal du système. Les performances de cette solution optimale intermédiaire sont alors évaluées à l’aide d’un modèle plus fin basé sur des simulations numériques. Une technique d’optimisation utilisant l’approche «space mapping» est alors mise en oeuvre. Si l’écart entre les performances prédites et les performances simulées est important, des facteurs de correction sont appliqués aux modèles analytiques et le processus d’optimisation est relancé. Cette méthode permet d’obtenir une solution optimale validée par le modèle fin en réduisant le nombre de simulations. La topologie finale sélectionnée pour le cahier des charges du modulateur CLIC est validée expérimentalement sur des prototypes à échelle réduite. Les résultats valident la méthodologie de dimensionnement et respectent les spécifications.This research work presents the study, design and validation of a pulsed power converter topology that performs accurate voltage droop compensation for high performance klystron modulators. This topology is capable of compensating the voltage droop of the intermediate capacitor bank and, at the same time, it makes possible a constant power consumption operation of the modulator from the utility grid. These two main specifications are required for the Compact Linear Collider (CLIC) Drive Beam klystron modulators. The dimensioning of the system is performed by developing a global optimization design tool. This tool is first based on developed analytical models describing the performances of each system subcomponent. All these models are integrated into an intermediate design environment that uses nonlinear optimization techniques to calculate an optimal dimensioning of the system. The intermediate optimal solution performances are then evaluated using a more accurate model based on numerical simulation. Therefore, an optimization technique using «space mapping» is implemented. If differences between predicted performances and simulated results are non-negligible, correction factors are applied to the analytical models and the optimization process is launched again. This method makes possible to achieve an optimal solution validated by numerical simulation while reducing the number of numerical simulation steps. The selected final topology for the CLIC klystron modulator is experimentally validated using reduced scale prototypes. Results validate the selected methodology and fulfill the specifications

Valorización agronómica del estiércol deshidratado y granulado de pollo en cultivos hortícolas

Inicialmente, se estudiaron los efectos del proceso de deshidratado y granulado en las propiedades del estiércol fresco obtenido en una explotación de pollos de engorde del noroeste de España. Posteriormente, se aplicaron diferentes dosis del estiércol deshidratado y granulado de pollo (BIOF-1) a cultivos intensivos en invernadero, como la lechuga (cuatro ciclos), y el pimiento (1 ciclo), comparándolo con fertilizantes minerales convencionales y de liberación lenta. Se estudió tanto la producción, como la calidad de dichos cultivos (nitrato en savia en la lechuga, y vitamina C en el pimiento), así como las modificaciones producidas en el suelo tras las cosechas, profundizando en el estudio de la salinidad y la posible acumulación de metales. Se comprobó que, con el BIOF-1, se obtienen cosechas de lechuga y pimiento en cantidades comparables, o superiores, a las conseguidas con fertilizantes de síntesis, además de dejar el suelo en buenas condiciones y obteniendo productos de calidad

Effect of truncating AUC at 12, 24 and 48 hr when evaluating the bioequivalence of drugs with a Long Half-Life

This is the peer reviewed version of the following article: Basic an Clinical Pharmacology and Toxicology 118.1 (2016): 53-7 which has been published in final form at http://dx.doi.org/10.1111/bcpt.12432. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalentThis study was partially funded by the Fundación Teófilo Hernando and Foundation for Biomedical Research at Hospital Universitario de La Princesa F Abad-Santos and D Ochoa have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Janssen-Cilag, Kern, Normon, Servier, Teva, and Zambon

Effect of food on the pharmacokinetics of omeprazole, pantoprazole and rabeprazole

Background: The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole. Setting: The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials. Method: Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81). Main outcome measure: Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Results: Food affected the pharmacokinetics of omeprazole (increased Tmax and decreased AUC and Cmax), pantoprazole (increased Tmax and decreased AUC), and rabeprazole (increased Tmax, Cmax and half-life). Food increased variability in Tmax for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects. Conclusion: As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions. Trial registration: European Union Drug Regulating Authorities Clinical Trials Database: EudraCT: 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).The analysis, interpretation of data and the manuscript writing was partially funded by Fundación Teófilo Hernando, a nonprofit foundation linked to Universidad Autónoma de Madri

Association between genetic polymorphisms and response to anti-TNFs in patients with inflammatory bowel disease

Tumor necrosis factor (TNF) is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathwayThis study was supported by Fundación Teófilo Hernando. Rocío Prieto-Pérez has a grant from Universidad Autónoma de Madrid (research personnel in training (FPI) program 2013)

Una recreación inédita y desconocida del Quijote: El último Quijote (1902) de Jesús de Amber y José Montero

Estudiamos y editamos en este trabajo una recreación teatral desconocida e inédita de Don Quijote: El último Quijote (1902), sainete lírico de Jesús de Amber y José Montero Iglesias, periodistas afincados en Santander en el comienzo del siglo XX. Se trata de una de las primeras parodias de la novela cervantina en la centuria pasada, escrita en momento de especial intensidad a este respecto, tiempo propicio para aquellas y de consolidación del mito quijotesco. La obra que nos ocupa añade, en tanto que recreación, la novedad de situar la acción en un tiempo contemporáneo (aunque nunca concretado de forma explícita), en un espacio inventado pero verosímil, y de acudir a los registros y procedimientos del Género chico para desarrollar la parodia del personaje y libro cervantino

Evaluation of the relationship between pharmacokinetics and the safety of aripiprazole and its cardiovascular effects in healthy volunteers

The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. Methods: The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Blood pressure was measured at the following times: predose and 0.5, 2, 4, 6, and 8 hours postdose. An electrocardiogram was recorded at predose, 4, and 8 hours postdose. Results: Area under the curve (AUC), maximum plasma concentration, half-life, and distribution volume corrected for weight were higher in women. Aripiprazole treatment produced a decrease of BP (9.3 mm Hg on systolic and 6.2 mm Hg on diastolic pressure) and an increase in HR (12.1 beats per minute) and QTc interval (9.1 milliseconds). There were sex differences in BP, HR, and QTc interval. Women and subjects with higher AUC and maximum plasma concentration values were more prone to experience adverse drug reactions and gastrointestinal adverse reactions. The AUC was related with systolic BP and diastolic BP decrease and HR increase but there was no relationship between aripiprazole concentrations and QTc increase. Conclusions: Aripiprazole decreases BP and increases HR and QTc interval. Pharmacokinetics, pharmacodynamics, and safety of aripiprazole are affected by sex. There is a directly proportional relationship between pharmacokinetic parameters and adverse drug reactions and effect on BP and HRThis study was partially funded by Fundación Teófilo Hernando and Foundation for Biomedical Research at Hospital Universitario de La Princes

Characterizing zebra crossing zones using LiDAR data

Light detection and ranging (LiDAR) scanning in urban environments leads to accurate and dense three-dimensional point clouds where the different elements in the scene can be precisely characterized. In this paper, two LiDAR-based algorithms that complement each other are proposed. The first one is a novel profiling method robust to noise and obstacles. It accurately characterizes the curvature, the slope, the height of the sidewalks, obstacles, and defects such as potholes. It was effective for 48 of 49 detected zebra crossings, even in the presence of pedestrians or vehicles in the crossing zone. The second one is a detailed quantitative summary of the state of the zebra crossing. It contains information about the location, the geometry, and the road marking. Coarse grain statistics are more prone to obstacle-related errors and are only fully reliable for 18 zebra crossings free from significant obstacles. However, all the anomalous statistics can be analyzed by looking at the associated profiles. The results can help in the maintenance of urban roads. More specifically, they can be used to improve the quality and safety of pedestrian routesConsellería de Cultura, Educación e Ordenación Universitaria, Grant/Award Numbers: accreditation 2019-2022 ED431G-2019/04, 2022-2024, ED431C2022/16, ED481A-2020/231; European Regional Development Fund (ERDF); CiTIUS-Research Center in Intelligent Technologies of the University of Santiago de Compostela as a Research Center of the Galician University System; Ministry of Economy and Competitiveness, Government of Spain, Grant/Award Number: PID2019-104834GB-I00; National Department of Traffic (DGT) through the project Analysis of Indicators Big-Geodata on Urban Roads for the Dynamic Design of Safe School Roads, Grant/Award Number: SPIP2017-02340S

Automatic Extraction of Road Points from Airborne LiDAR Based on Bidirectional Skewness Balancing

Road extraction from Light Detection and Ranging (LiDAR) has become a hot topic over recent years. Nevertheless, it is still challenging to perform this task in a fully automatic way. Experiments are often carried out over small datasets with a focus on urban areas and it is unclear how these methods perform in less urbanized sites. Furthermore, some methods require the manual input of critical parameters, such as an intensity threshold. Aiming to address these issues, this paper proposes a method for the automatic extraction of road points suitable for different landscapes. Road points are identified using pipeline filtering based on a set of constraints defined on the intensity, curvature, local density, and area. We focus especially on the intensity constraint, as it is the key factor to distinguish between road and ground points. The optimal intensity threshold is established automatically by an improved version of the skewness balancing algorithm. Evaluation was conducted on ten study sites with different degrees of urbanization. Road points were successfully extracted in all of them with an overall completeness of 93%, a correctness of 83%, and a quality of 78%. These results are competitive with the state-of-the-artThis work has received financial support from the Consellería de Cultura, Educación e Ordenación Universitaria (accreditation 2019-2022 ED431G-2019/04 and reference competitive group 2019-2021, ED431C 2018/19) and the European Regional Development Fund (ERDF), which acknowledges the CiTIUS-Research Center in Intelligent Technologies of the University of Santiago de Compostela as a Research Center of the Galician University System. This work was also supported in part by Babcock International Group PLC (Civil UAVs Initiative Fund of Xunta de Galicia) and the Ministry of Education, Culture and Sport, Government of Spain (Grant Number TIN2016-76373-P)S