El nuevo marco internacional de la fiscalidad de las multinacionales

43 p.Este trabajo tiene como objetivo ofrecer una visión introductoria acerca del alcance y las implicaciones de la reforma del marco internacional de la fiscalidad de las multinacionales acordada en la reunión del G7 de junio de 2021 y posteriormente asumida por 132 países, así como por el G20. Inicialmente se exponen los fundamentos del sistema que ha estado vigente desde hace un siglo, así como las deficiencias puestas de manifiesto a lo largo del tiempo, acentuadas en un contexto de globalización y digitalización. Posteriormente, tras aludir a los antecedentes sobre la materia, se efectúa un repaso del desarrollo del proyecto impulsado por la OCDE para hacer frente al fenómeno BEPS, en el que se basa el referido acuerdo del G7. Los principales aspectos de éste, sustentando en los denominados Pilares Uno y Dos, son objeto de exposición y análisis. Su implementación representa un hito de gran trascendencia que dará lugar a una importante transformación en el ámbito de la fiscalidad de las multinacionales.This paper aims to provide an introductory view on the scope and implications of the reform of the international framework for multinational taxation agreed at the G7 meeting in June 2021 and subsequently assumed by 132 countries, as well as by the G20. Initially, the foundations of the system in place for a century are exposed, as well as the deficiencies revealed over time, accentuated in a context of globalization and digitization. Subsequently, after a brief background on the matter, a review is made of the development of the project promoted by the OECD to deal with the BEPS phenomenon, on which the aforementioned G7 agreement is based. The main aspects of this, based on the so-called Pillars One and Two, are the object of exposition and analysis. Its implementation represents a major milestone of great significance that will lead to an important transformation in the field of multinational taxation

Vaccination sequence effects on immunological response and tissue bacterial burden in paratuberculosis infection in a rabbit model

[EN] Paratuberculosis (PTB), a chronic granulomatous enteritis produced by Mycobacterium avium subspecies paratuberculosis (MAP), is considered as one of the diseases with the highest economic impact in the ruminant industry. Vaccination against MAP is recommended during the first months after birth on the basis that protection would be conferred before the first contact with mycobacteria. However, little is known about the therapeutic effect of MAP vaccination in controlled experimental conditions. The current study was designed to evaluate the efficacy of vaccination before and after challenge with MAP in a rabbit infection model. The rabbits were divided into four groups: non-infected control (NIC, n = 4), infected control challenged with MAP (IC, n = 5), vaccinated and challenged 1 month after with MAP (VSI, n = 5) and challenged with MAP and vaccinated 2 months later (IVS, n = 5). The results from this study show a quick increase in IFN-γ release upon stimulation with bovine, avian and johnin PPD in animals vaccinated before MAP challenge. All vaccinated animals show an increased humoral response as seen by western blot and ELISA. The final bacteriology index (considering tissue culture and qPCR) shows that the IC group was the most affected. Vaccination after infection (IVS) produced the lowest bacteriology index showing significant differences with the IC group (p = 0.034). In conclusion, vaccination against MAP shows positive effects in a rabbit model. However, vaccination after infection shows a slightly stronger protective effect compared to vaccination before infection, suggesting a therapeutic effect. This feature could be applied to previously infected adult animals under field conditionsSIThe authors thank Felix Blanco from the animal facilities (NEIKER-Tecnalia). This study was supported with funds from the Ministerio de Economía y Competitividad from the Spanish Government (AGL 2012-39818-C02-02). RA acknowledges support from the Departamento de Educación y Universidades of the Basque Government (BFI-2012-237

Effect of various dietary regimens on oral challenge with Mycobacterium avium subsp. paratuberculosis in a rabbit model

Rabbits are susceptible to infection by Mycobacterium avium subspecies paratuberculosis (MAP) in both wildlife and experimental conditions. Under the hypotheses that nutrient balance might influence the establishment of infection, we designed an experiment where MAP intestinal colonization was assessed under three dietary regimens: high fiber, high protein, and regular diet in New Zealand white rabbits submitted to oral challenge with MAP.Lowest weight gain (F=5.17, p=0.024), higher tissue culture positivity rates (X2=7.43, p=0.024) and especially extended MAP-compatible lesions (F=5.78, p=0.017) were detected in the regular diet.Taken altogether, results indicate that paratuberculosis infection was achieved affecting mostly regular diet animals and showing that dietary changes may modulate the course of the infection

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival : an updated analysis of KEYNOTE-010 trial

Background: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. Patients and methods: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) 50% and 1%; pembrolizumab doses were pooled in this analysis. Results: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS 50%. For TPS 50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS 1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS 50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS 1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. Conclusion: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples

Prevalence of potentially thermophilic microorganisms in biofilms from greenhouse-enclosed drip irrigation systems

Drip irrigation systems using reclaimed water often present clogging events of biological origin. Microbial communities in biofilms from microirrigation systems of an experimental greenhouse in Almería, SE Spain, which used two different qualities of water (treated wastewater and reclaimed water), were analyzed by denaturing gradient gel electrophoresis and subsequent sequencing of amplified 16S rRNA gene bands. The most remarkable feature of all biofilms was that regardless of water origin, sequences belonging to Firmicutes were prevalent (53.5 % of total mean band intensity) and that almost all sequences recovered had some similarity (between 80.2 and 97 %) to thermophilic microorganisms. Mainly, sequences were closely related to potentially spore-forming organisms, suggesting that microbial communities able to grow at high temperatures were selected from the microbiota present in the incoming water. These pioneer results may contribute to improve management strategies to minimize the problems associated to biofouling in irrigation systems

Alternative Vaccination Routes against Paratuberculosis Modulate Local Immune Response and Interference with Tuberculosis Diagnosis in Laboratory Animal Models

[EN] Paratuberculosis (PTB) is an enteric granulomatous disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly aects ruminants. Current vaccines have shown to be cost-eective control reagents, although they are restricted due to cross-interference with bovine tuberculosis (bTB). Therefore, novel vaccination strategies are needed and this study is focused on evaluating alternative vaccination routes and their eect on the local immune response. The MAP oral challenge rabbit model was used to evaluate and compare an experimental inactivated MAP vaccine through oral (VOR) and intradermal (VID) routes. The VID group presented the highest proportion of animals with no visible lesions and the lowest proportion of animals with MAP positive tissues. Immunohistochemistry analysis revealed that the VID group presented a dominantly M1 polarized response indicating an ability to control MAP infection. In general, all vaccinated groups showed lower calprotectin levels compared to the non-vaccinated challenged group suggesting less active granulomatous lesions. The VID group showed some degree of skin test reactivity, whereas the same vaccine through oral administration was completely negative. These data show that PTB vaccination has an eect on macrophage polarization and that the route influences infection outcome and can also have an impact on bTB diagnosis. Future evaluation of new immunological products against mycobacterial diseases should consider assaying dierent vaccination routesSIThe research was funded by the Department of Economy and Infrastructures (DEI) of the Basque Government and partially by grant RTA 2017-00089-00-00 of the National Institute for Agronomic Research (INIA). R.A. held a pre-doctoral fellowship (BFI-2012-237) from the Department of Education, Universities and Research of the Basque Government and IL is recipient of a pre-doctoral fellowship from the DEI of the Basque Governmen

Autoevaluación mediante la reflexión en la práctica educativa y el pensamiento crítico

El propósito de este estudio consiste en potenciar el proceso de autoevaluación del alumnado mediante la aplicación de la reflexión en la práctica educativa y el pensamiento crítico. Asimismo, con este fin, se diseñó e implementó un documento específico para la autoevaluación. El documento elaborado constaba de tres grandes bloques con subapartados específicos para cada uno de ellos. El primer bloque destinado a la reflexión sobre el proceso de enseñanza- aprendizaje, el segundo relacionado con las fortalezas y debilidades y un tercero vinculado con el pensamiento crítico del proceso de autoevaluación. Los participantes del estudio fueron los alumnos de tercero y cuarto cuso del grado de enfermería y los alumnos del máster de investigación en Ciencias de la enfermería. Los principales resultados obtenidos son: la principal dificultad en el aprendizaje la relacionan con los contenidos teóricos de la asignatura en determinados temas, así mismo generalmente suele coincidir los conocimientos más significativos con aquellos que más grado de dificultad le atribuyen. El 95% de los alumnos puntúan su rendimiento académico con la nota más elevada paradójicamente coinciden en afirmar que no le han dedicado suficiente tiempo debido al exceso de actividades por parte de los profesores

Effects of Leucine Administration in Sarcopenia:A Randomized and Placebo-controlled Clinical Trial

Treating sarcopenia in older individuals remains a challenge, and nutritional interventions present promising approaches in individuals that perform limited physical exercise. We assessed the efficacy of leucine administration to evaluate whether the regular intake of this essential amino acid can improve muscle mass, muscle strength and functional performance and respiratory muscle function in institutionalized older individuals. The study was a placebo-controlled, randomized, double-blind design in fifty participants aged 65 and over (ClinicalTrials.gov identifier NCT03831399). The participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day). The primary outcome was to study the effect on sarcopenia and respiratory muscle function. The secondary outcomes were changes in the geriatric evaluation scales, such as cognitive function, functional impairment and nutritional assessments. We also evaluated whether leucine administration alters blood analytical parameters and inflammatory markers. Administration of leucine was well-tolerated and significantly improves some criteria of sarcopenia in elderly individuals such as functional performance measured by walking time (p = 0.011), and improved lean mass index. For respiratory muscle function, the leucine-treated group improved significantly (p = 0.026) in maximum static expiratory force compared to the placebo. No significant effects on functional impairment, cognitive function or nutritional assessment, inflammatory cytokines IL-6, TNF-alpha were observed after leucine administration compared to the placebo. The use of l-leucine supplementation can have some beneficial effects on sarcopenia and could be considered for the treatment of sarcopenia in older individuals

Tuberculosis detection in paratuberculosis vaccinated calves:New alternatives against interference

Paratuberculosis vaccination in cattle has been restricted due to its possible interference with the official diagnostic methods used in tuberculosis eradication programs. To overcome this drawback, new possibilities to detect Mycobacterium bovis infected cattle in paratuberculosis vaccinated animals were studied under experimental conditions. Three groups of 5 calves each were included in the experiment: one paratuberculosis vaccinated group, one paratuberculosis vaccinated and M. bovis infected group and one M. bovis infected group. The performance of the IFN-gamma release assay (IGRA) and the skin test using conventional avian and bovine tuberculins (A- and B-PPD) but also other more specific antigens (ESAT-6/CFP10 and Rv3615c) was studied under official and new diagnostic criteria. Regarding the IGRA of vaccinated groups, when A- and B-PPD were used the sensitivity reached 100% at the first post-challenge sampling, dropping down to 40-80% in subsequent samplings. The sensitivity for the specific antigens was 80-100% and the specificity was also improved. After adapting the diagnostic criteria for the conventional antigens in the skin test, the ability to differentiate between M. bovis infected and non-infected animals included in paratuberculosis vaccinated groups was enhanced. Taking for positive a relative skin thickness increase of at least 100%, the single intradermal test specificity and sensitivity yielded 100%. The comparative intradermal test was equally accurate considering a B-PPD relative skin increase of at least 100% and greater than or equal to that produced by A-PPD. Using the specific antigens as a proteic cocktail, the specificity and sensitivity reached 100% considering the new relative and absolute cut-offs in all experimental groups (Δ≥30% and Δmm ≥ 2, respectively). Results suggest that the interference caused by paratuberculosis vaccination in cattle could be completely overcome by applying new approaches to the official tuberculosis diagnostic tests