Analysis of Documental Heritage of CETA in Standardization of the Spanish Manufacturing Automotive Industry

AbstractStandardization has taken an active role in the development of several main industrial sectors and the automotive sector has been one of them. Current work shows the collection, analysis, revision and management process developed on CETA (Center of Automotive Technical Study) standards related to the manufacturing automotive sector, an unknown element of Spanish standardization heritage. Also, a comparative evaluation between CETA standards and current UNE standards has been performed. The results show that CETA standards have had a positive influence in the evolution of the automotive sector as well as an important contribution to the contents of the UNE standards

Optimization of the catalytic layer for alkaline fuel cells based on fumatech membranes and ionomer

Polymer electrolyte fuel cells with alkaline anion exchange membranes (AAEMs) have gained increasing attention because of the faster reaction kinetics associated with the alkaline environment compared to acidic media. While the development of anion exchange polymer membranes is increasing, the catalytic layer structure and composition of electrodes is of paramount importance to maximize fuel cell performance. In this work, we examine the preparation procedures for electrodes by catalyst-coated substrate to be used with a well-known commercial AAEM, Fumasep® FAA-3, and a commercial ionomer of the same nature (Fumion), both from Fumatech GmbH. The anion exchange procedure, the ionomer concentration in the catalytic layer and also the effect of membrane thickness, are investigated as they are very relevant parameters conditioning the cell behavior. The best power density was achieved upon ion exchange of the ionomer by submerging the electrodes in KCl (isopropyl alcohol/water solution) for at least one hour, two exchange steps, followed by treatment in KOH for 30 min. The optimum ionomer (Fumion) concentration was found to be close to 50 wt%, with a relatively narrow interval of functioning ionomer percentages. These results provide a practical guide for electrode preparation in AAEM-based fuel cell research

Sonocrystallisation of ZIF-8 in water with high excess of ligand: Effects of frequency, power and sonication time

A systematic study on the sonocrystallisation of ZIF-8 (zeolitic imidazolate framework-8) in a water-based system was investigated under different mixing speeds, ultrasound frequencies, calorimetric powers and sonication time. Regardless of the synthesis technique, pure crystals of ZIF-8 with high BET (Brunauer, Emmett and Teller) specific surface area (SSA) can be obtained in water after only 5 s. Furthermore, 5 s sonication produced even smaller crystals (~0.08 µm). The type of technique applied for producing the ZIF-8 crystals did not have any significant impact on crystallinity, purity and yield. Crystal morphology and size were affected by the use of ultrasound and mixing, obtaining nanoparticles with a more spherical shape than in silent condition (no ultrasound and mixing). However, no specific trends were observed with varying frequency, calorimetric power and mixing speed. Ultrasound and mixing may have an effect on the nucleation step, causing the fast production of nucleation centres. Furthermore, the BET SSA increased with increasing mixing speed. With ultrasound, the BET SSA is between the values obtained under silent condition and with mixing. A competition between micromixing and shockwaves has been proposed when sonication is used for ZIF-8 production. The former increases the BET SSA, while the latter could be responsible for porosity damage, causing a decrease of the surface area. © 2021 The Author(s

Global methylome scores correlate with histological subtypes of colorectal carcinoma and show different associations with common clinical and molecular features

Background. The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina’s 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI‐H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. Results. SAC has an intermediate methylation pattern between CC and hmMSI‐H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). Conclusion. These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.This work was supported by two grants from Instituto de Salud Carlos III, Ministerio de Sanidad, Spain and FEDER funds (refs: PI12-1232, PI18-0144) and another from the European Union’s Horizon 2020 research and innovation program (ref. 848098

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders

Health care and societal costs of the management of children and adolescents with attention-deficit/hyperactivity disorder in Spain: a descriptive analysis

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. Methods: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. Results: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). Conclusions: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorde

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: Study protocol for the SAFO trial

Introduction Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (=18 years) with isolation of MSSA from at least one blood culture =72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Characterization of protons accelerated from a 3 TW table-top laser system

[EN] We report on benchmark tests of a 3 TW/50 fs, table-top laser system specifically developed for proton acceleration with an intrinsic pump rate up to 100 Hz. In two series of single-shot measurements differing in pulse energy and contrast the successful operation of the diode pumped laser is demonstrated. Protons have been accelerated up to 1.6 MeV in interactions of laser pulses focused on aluminium and mylar foils between 0.8 and 25 mu m thickness. Their spectral distributions and maximum energies are consistent with former experiments under similar conditions. These results show the suitability of our system and provide a reference for studies of laser targets at high repetition rate and possible applications.This project has been funded by Centro para el Desarrollo Tecnologico Industrial (CDTI, Spain) within the INNPRONTA program, grant no. IPT-20111027, by EUROSTARS project E9113, and by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1.Bellido-Millán, PJ.; Lera, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Torres Peiró, S.; Galán, M.; Mur, P.... (2017). Characterization of protons accelerated from a 3 TW table-top laser system. Journal of Instrumentation. 12:1-12. https://doi.org/10.1088/1748-0221/12/05/T05001S11212Daido, H., Nishiuchi, M., & Pirozhkov, A. S. (2012). Review of laser-driven ion sources and their applications. Reports on Progress in Physics, 75(5), 056401. doi:10.1088/0034-4885/75/5/056401Macchi, A., Borghesi, M., & Passoni, M. (2013). Ion acceleration by superintense laser-plasma interaction. Reviews of Modern Physics, 85(2), 751-793. doi:10.1103/revmodphys.85.751Ledingham, K., Bolton, P., Shikazono, N., & Ma, C.-M. (2014). Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress. 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H., Cha, Y.-H., Lee, Y. W., Kim, K. N., & Jeong, Y. U. (2011). Dominant front-side acceleration of energetic proton beams from plastic targets irradiated by an ultraintense laser pulse. Physics of Plasmas, 18(1), 013101. doi:10.1063/1.3496058OKIHARA, S., SENTOKU, Y., SUEDA, K., SHIMIZU, S., SATO, F., MIYANAGA, N., … SAKABE, S. (2002). Energetic Proton Generation in a Thin Plastic Foil Irradiated by Intense Femtosecond Lasers. Journal of Nuclear Science and Technology, 39(1), 1-5. doi:10.1080/18811248.2002.9715150McKenna, P., Ledingham, K. W. D., Spencer, I., McCany, T., Singhal, R. P., Ziener, C., … Clark, E. L. (2002). Characterization of multiterawatt laser-solid interactions for proton acceleration. Review of Scientific Instruments, 73(12), 4176-4184. doi:10.1063/1.1516855Spencer, I., Ledingham, K. W. D., McKenna, P., McCanny, T., Singhal, R. P., Foster, P. S., … Davies, J. R. (2003). Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate tabletop-laser pulses interacting with solid targets. Physical Review E, 67(4). doi:10.1103/physreve.67.046402Kaluza, M., Schreiber, J., Santala, M. I. K., Tsakiris, G. D., Eidmann, K., Meyer-ter-Vehn, J., & Witte, K. J. (2004). Influence of the Laser Prepulse on Proton Acceleration in Thin-Foil Experiments. Physical Review Letters, 93(4). doi:10.1103/physrevlett.93.045003Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.185002Neely, D., Foster, P., Robinson, A., Lindau, F., Lundh, O., Persson, A., … McKenna, P. (2006). Enhanced proton beams from ultrathin targets driven by high contrast laser pulses. Applied Physics Letters, 89(2), 021502. doi:10.1063/1.2220011Steinke, S., Henig, A., Schnürer, M., Sokollik, T., Nickles, P. V., Jung, D., … Habs, D. (2010). Efficient ion acceleration by collective laser-driven electron dynamics with ultra-thin foil targets. Laser and Particle Beams, 28(1), 215-221. doi:10.1017/s0263034610000157Strickland, D., & Mourou, G. (1985). Compression of amplified chirped optical pulses. Optics Communications, 56(3), 219-221. doi:10.1016/0030-4018(85)90120-8Yogo, A., Kondo, K., Mori, M., Kiriyama, H., Ogura, K., Shimomura, T., … Bolton, P. R. (2014). Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers. Optics Express, 22(2), 2060. doi:10.1364/oe.22.002060Trisorio, A., Grabielle, S., Divall, M., Forget, N., & Hauri, C. P. (2012). Self-referenced spectral interferometry for ultrashort infrared pulse characterization. Optics Letters, 37(14), 2892. doi:10.1364/ol.37.002892Seimetz, M., Bellido, P., Soriano, A., Garcia Lopez, J., Jimenez-Ramos, M. C., Fernandez, B., … Benlloch, J. M. (2015). Calibration and Performance Tests of Detectors for Laser-Accelerated Protons. IEEE Transactions on Nuclear Science, 62(6), 3216-3224. doi:10.1109/tns.2015.2480682Nürnberg, F., Schollmeier, M., Brambrink, E., Blažević, A., Carroll, D. C., Flippo, K., … Roth, M. (2009). Radiochromic film imaging spectroscopy of laser-accelerated proton beams. Review of Scientific Instruments, 80(3), 033301. doi:10.1063/1.3086424Oishi, Y., Nayuki, T., Fujii, T., Takizawa, Y., Wang, X., Yamazaki, T., … Andreev, A. A. (2005). Dependence on laser intensity and pulse duration in proton acceleration by irradiation of ultrashort laser pulses on a Cu foil target. Physics of Plasmas, 12(7), 073102. doi:10.1063/1.1943436Nishiuchi, M., Daito, I., Ikegami, M., Daido, H., Mori, M., Orimo, S., … Yoshiyuki, T. (2009). Focusing and spectral enhancement of a repetition-rated, laser-driven, divergent multi-MeV proton beam using permanent quadrupole magnets. Applied Physics Letters, 94(6), 061107. doi:10.1063/1.3078291Antici, P., Fuchs, J., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Pépin, H. (2007). Energetic protons generated by ultrahigh contrast laser pulses interacting with ultrathin targets. Physics of Plasmas, 14(3), 030701. doi:10.1063/1.2480610Green, J. S., Carroll, D. C., Brenner, C., Dromey, B., Foster, P. S., Kar, S., … Zepf, M. (2010). Enhanced proton flux in the MeV range by defocused laser irradiation. New Journal of Physics, 12(8), 085012. doi:10.1088/1367-2630/12/8/085012Zeil, K., Kraft, S. D., Bock, S., Bussmann, M., Cowan, T. E., Kluge, T., … Schramm, U. (2010). The scaling of proton energies in ultrashort pulse laser plasma acceleration. New Journal of Physics, 12(4), 045015. doi:10.1088/1367-2630/12/4/045015Nishiuchi, M., Daido, H., Yogo, A., Orimo, S., Ogura, K., Ma, J., … Azuma, H. (2008). Efficient production of a collimated MeV proton beam from a polyimide target driven by an intense femtosecond laser pulse. Physics of Plasmas, 15(5), 053104. doi:10.1063/1.2928161Macchi, A., Sgattoni, A., Sinigardi, S., Borghesi, M., & Passoni, M. (2013). Advanced strategies for ion acceleration using high-power lasers. Plasma Physics and Controlled Fusion, 55(12), 124020. doi:10.1088/0741-3335/55/12/124020Fuchs, J., Antici, P., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Audebert, P. (2005). Laser-driven proton scaling laws and new paths towards energy increase. Nature Physics, 2(1), 48-54. doi:10.1038/nphys199Schwoerer, H., Pfotenhauer, S., Jäckel, O., Amthor, K.-U., Liesfeld, B., Ziegler, W., … Esirkepov, T. (2006). Laser-plasma acceleration of quasi-monoenergetic protons from microstructured targets. Nature, 439(7075), 445-448. doi:10.1038/nature04492Margarone, D., Klimo, O., Kim, I. J., Prokůpek, J., Limpouch, J., Jeong, T. M., … Korn, G. (2012). Laser-Driven Proton Acceleration Enhancement by Nanostructured Foils. Physical Review Letters, 109(23). doi:10.1103/physrevlett.109.234801Flippo, K. A., d’ Humières, E., Gaillard, S. A., Rassuchine, J., Gautier, D. C., Schollmeier, M., … Hegelich, B. M. (2008). Increased efficiency of short-pulse laser-generated proton beams from novel flat-top cone targets. Physics of Plasmas, 15(5), 056709. doi:10.1063/1.291812