Numerical modeling of air-vented parallel plate ionization chambers for ultra-high dose rate applications

Purpose: air-vented ionization chambers have been the secondary standard for radiation dosimetry since the origins of radiation metrology. However, the feasibility of their use in ultra-high dose rate pulsed beams has been a matter of discussion, as large losses are caused by ion recombinations and no suitable theoretical model is available for their correction. The theories developed by Boag and his contemporaries since the 1950s, which have provided the standard ion recombination correction factor in clinical dosimetry, do not provide an accurate description when used under the limit conditions of ultra-high dose rates (UHDRs). Moreover, the high-ion recombination effects of ionization chambers under extreme dose-rate applications are an obstacle to the development of adequate dosimetry standardsThis work has received funding from the EMPIR programme project 18HLT04 UHDpulse co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programmeS

Small static radiosurgery field dosimetry with small volume ionization chambers

Purpose: To evaluate the response of the four smallest active volume thimble type ionization chambers commercially available (IBA-dosimetry RAZOR Nano Chamber, Standard Imaging Exradin A16, IBA-dosimetry CC01 and PTW T31022) when measuring SRS cone collimated Flattening Filter Free (FFF) fields. Methods: We employed Monte Carlo simulation for calculating correction factors as defined in IAEA TRS-483. Monte Carlo simulation beam model and ion chamber geometry definitions were supported by an extensive set of measurements. Type A and B uncertainty components were evaluated.Results: Commissioning of Monte Carlo 6 MV and 10 MV FFF beam models yielded relative differences between measured and simulated dose distributions lower than 1.5%. Monte Carlo simulated output factors for 5 mm SRS field agree with experimental values within 1% local relative difference for all chambers. Smallest active volume ion chamber (IBA-dosimetry RAZOR Nano Chamber) exhibits smallest correction, being compatible with unity. Correction factor combined uncertainties range between 0.7% and 0.9%. Smallest uncertainties were recorded for smallest and largest active volume ion chambers, although the latter exhibited largest correction factor. Highest contribution to combined uncertainty was type B component associated with beam model initial electron spatial Full Width Half Maximum (FWHM) uncertainty. Conclusions: Among the investigated chambers, the IBA RAZOR Nano Chamber was found to be an excellent choice for narrow beam output factor measurement since it requires minimum correction (in line with IAEA TRS-483 recommendations). This is caused by its tiny size and tissue equivalence materials which produce minimum volume averaging and fluence perturbationS

Development of an ultra-thin parallel plate ionization chamber for dosimetry in FLASH radiotherapy

Conventional air ionization chambers (ICs) exhibit ion recombination correction factors that deviate substantially from unity when irradiated with dose per pulse magnitudes higher than those used in conventional radiotherapy. This fact makes these devices unsuitable for the dosimetric characterization of beams in ultra-high dose per pulse as used for FLASH radiotherapyParticipating States; Horizon 2020; European Metrology Programme for Innovation and Research, Grant/Award Number: 18HLT04UHD PulseS

eIMRT: a web platform for the verification and optimization of radiation treatment plans

The eIMRT platform is a remote distributed computing tool that provides users with Internet access to three different services: Monte Carlo optimization of treatment plans, CRT & IMRT treatment optimization, and a database of relevant radiation treatments/clinical cases. These services are accessible through a user-friendly and platform independent web page. Its flexible and scalable design focuses on providing the final users with services rather than a collection of software pieces. All input and output data (CT, contours, treatment plans and dose distributions) are handled using the DICOM format. The design, implementation, and support of the verification and optimization algorithms are hidden to the user. This allows a unified, robust handling of the software and hardware that enables these computation-intensive services. The eIMRT platform is currently hosted by the Galician Supercomputing Center (CESGA) and may be accessible upon request (there is a demo version at http://eimrt.cesga.es:8080/ eIMRT2/demo; request access in http://eimrt.cesga.es/signup.html). This paper describes all aspects of the eIMRT algorithms in depth, its user interface, and its services. Due to the flexible design of the platform, it has numerous applications including the intercenter comparison of treatment planning, the quality assurance of radiation treatments, the design and implementation of new approaches to certain types of treatments, and the sharing of information on radiation treatment techniques. In addition, the web platform and software tools developed for treatment verification and optimization have a modular design that allows the user to extend them with new algorithms. This software is not a commercial product. It is the result of the collaborative effort of different public research institutions and is planned to be distributed as an open source project. In this way, it will be available to any user; new releases will be generated with the new implemented codes or upgradesThis work was financed by Xunta de Galicia of Spain through grant PGIDT05SIN00101CT and by the European Community through the BeInGrid projectS

Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols

Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox-based approaches to cancer therapyThis research was partially supported by 1) “la Caixa” Foundation, Ref. LCF/PR/PR12/11070003 to F.D. and M.A.L.Q.; 2) Ministerio de Ciencia, Innovación y Universidades (MAT2017-89678-R, AEI/FEDER, UE) to F.D. and A.V.; 3) the Consellería de Educación (Xunta de Galicia), Grants No. Grupos Ref. Comp. ED431C 2017/22, ED431C 2019/13 and AEMAT-ED431E2018/08 to M.A.L.Q.; and ED431C 2019/13 to A.V. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme (Bac-To-Fuel) under Grant Agreement No. 825999 (M.A.L.Q.). J.C.H. acknowledge financial support from European Union's Horizon 2020 research and innovation programme under grant agreement no. 823717-ESTEEM3, and the MICIIN (projects PID2019-107578GA-100 and PID-110018GA-100). J.M.D, L.J.G., and F.G.R. thank to the ANPCyT (PICT 2015-2285 and 2017-3944), UNLP (Project 11/X790) and the partial support by the Laboratório Nacional de Luz Síncrotron (LNLS, Brazil) under proposal SXS-20180280. G.B. acknowledges the CINECA Award N. IsC51, year 2017, under the ISCRA initiative, for the availability of high-performance computing resources and support. D.B. expresses gratitude for a postdoctoral grant from Xunta de Galicia, Spain (POS-A/2013/018). B.D. expresses gratitude for a predoctoral grant from MICINN, Spain (BES-2016-076765). F.D. and A.V. also acknowledged Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022 ref ED431G 2019/02) and the European Union (European Regional Development Fund – ERDF). Work in M.P.M.'s lab was supported by the Medical Research Council UK (MC_U105663142). T.G.C. gratefully acknowledges the technical assistance of María José Otero-Fraga (FIDIS)S

INFOTIC. Infografías académicas y herramientas de visualización de datos científicos con herramientas TIC: formación docente, diseño de recursos multimedia y experiencias didácticas para la enseñanza semipresencial

El proyecto ha gravitado en torno al uso didáctico de las infografías científicas como una herramienta destinada a la enseñanza semipresencial y telemática, aportando nuevos recursos para estudiantes y docentes y permitiendo implementar dinámicas adaptadas a las nuevas tecnologías. En este sentido, una infografía se puede definir como un conjunto de ideas complejas representadas mediante palabras, imágenes, gráficos, etc., que les confieren un aspecto visualmente atractivo. Las infografías conforman un hilo comunicativo de transmisión de estas ideas gracias al uso de textos informativos, que refuerzan su carácter pedagógico, e imágenes ilustrativas para potenciar la claridad y el dinamismo del mensaje. La visualidad de los datos integrados en las infografías es la característica más destacable de estos recursos, haciéndolas interesantes para su aplicación en la enseñanza y divulgación académica. En el marco de este proyecto, poseen una finalidad eminentemente didáctica, ayudando a que temas complejos puedan ser entendidos por un público no especializado

I Congreso - Convergencias y divergencias. Hacia educaciones y desarrollo otros.

La presente colección, en su primera publicación, recoge la experiencia del I Congreso Internacional de Educación para el Desarrollo en Perspectiva Latinoamericana- EpDl “Convergencias y divergencias. Hacia educaciones y desarrollos otros.” organizado por el Centro de Educación para el Desarrollo-CED de UNIMINUTO, específicamente en relación con las ponencias, libros e iniciativas fotográficas presentadas en las seis líneas temáticas de este evento académico, a saber: (a) experiencias y prácticas pedagógicas; (b) acciones colectivas, movimientos y redes sociales; (c) perspectivas críticas al desarrollo; (d) producción de conocimiento; (e) diferencias, identidades y ciudadanía; (f) cuerpos, emociones y espiritualidades; a partir de éstas propuestas y en el marco de estas líneas, se reflexionó sobre las dinámicas y problemáticas derivadas del desarrollo hegemónico, así como sobre la posibilidad de diálogo entre saberes y conocimientos construidos de forma contextualizada, que permitan agenciar apuestas y proyectos alternativos disidentes en la búsqueda de “desarrollos y educaciones otras” desde América Latina

CropPol: a dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639