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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

The production of biofuels has had a great impact on climate change and the reduction of the use of fossil fuels. There are different technologies used for the separation and production of biofuels, which allow having compounds such as ethanol, methane, oxygen, and hydrogen, one of these promising technologies is the Pressure Swing Adsorption process (PSA). The objectives of this article focus on the production and purification of compounds that achieve purities of 99.5% bioethanol, 94.85% biohydrogen, 95.00% medical oxygen, and 99.99% biomethane through the PSA process; also, a significant review is contemplated to identify the different natural and synthetic adsorbents that have greater adsorption capacity, the different configurations in which a PSA operates are studied and identified, and the different mathematical models that describe the dynamic behavior of all the variables are established that interact in this PSA process, parametric studies are carried out in order to identify the variables that have the greatest effect on the purity obtained. The results obtained in this review allow facilitating the calculation of parameters, the optimization of the process, the automatic control to manipulate certain variables and to achieve the rejection of disturbances to have a recovery and production of biofuels with a high degree of purity.

The climate emergency raises the most formidable challenge to economic and social rights (ESRs). The task of urgently advancing climate action through ESRs is what this chapter calls “climatizing” ESRs. There are two complementary routes to climatizing ESRs. The first route involves applying the existing ESR conceptual and legal tools to the climate emergency. This entails both addressing the impacts of global warming on ESRs and ensuring that climate action follows ESR norms. Although much has yet to be done, this chapter shows that human rights actors have made important initial inroads. The second route entails updating ESRs to the Anthropocene’s realities and challenges. This goal requires protecting the planetary boundaries that make life on Earth possible, and thus entails a concern with the limits to human economic activity as well as with the rights of future generations and nonhumans. This chapter theorizes and documents emerging developments in human rights thought and practice that contribute to this goal, including rights-based climate litigation and the recognition of rights of nature.

Elites y política colonia en los márgenes del imperio. Puerto Rico, 1765-1815, es una obra bien lograda que cubre un amplio espectro de la historia de Puerto Rico, José Manuel Espinosa presenta una interpretación de cómo los grupos dirigentes de dicha isla se adaptan a los procesos de cambio generados por la política del gobierno isleño y peninsular durante las reformas borbónicas, los movimientos de independencia hispanoamericanos y la reorganización administrativa derivada de las Cortes de Cádiz.

El presente documento presenta un breve análisis del nuevo procedimiento sucesorio del Código de Procedimientos Civiles en vigor en el estado de Chihuahua, y comentarios respecto de lo que consideramos algunas omisiones legisla!ivas importantes así como lo rela!ivo al régimen fiscal de las sucesiones; conclusiones y bibliografía o fuentes de información.

The WHO has approved the use of several vaccines during the COVID-19 pandemic; experience over the last 2 years has indicated that dose demand can only be covered using more than one design. Therefore, having scientific evidence of the performance of the different vaccines applied in a country is highly relevant. In Mexico, 5 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were used, allowing a cohort study to analyze the generation of anti-S1/S2 IgG antibodies and anti-RBD antibodies with neutralizing activity at 0, 21, 90, and 180 days after vaccination. Five groups of participants were formed on the basis of the type of vaccine received and were divided on the basis of whether they previously had or did not have COVID-19. After completing the vaccination schedule, the seroprevalence was 95.5, 97.5, 81.0, 95.2, and 90.0% (BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac, respectively). Among the participants without COVID-19 prior to vaccination, the largest amount of antibodies in the 90-day period was observed in the BNT162b2 group, and the amount of antibodies in the Sputnik V group decreased the least over time. Even though the percentages of seroconversion obtained in this study were lower than those currently reported in other parts of the world, the tested vaccines are able, in most cases, to induce a good production of IgG antibodies anti-S1/S2 and neutralizing capacity. The fact that there are people who have not produced antibodies during the study leaves open some questions that must be investigated to avoid the appearance of serious cases of COVID-19.

Background Santa Ana is home to an Afro-descendant rural population of the island of Barú in Cartagena, Colombia. While a popular area for tourism, Santa Ana’s population is affected by multidimensional poverty, precarious work conditions, homelessness, broken streets and sewer systems, limited quality education, and a lack of recreation and sport spaces. While Santa Ana’s Community Action Board aims to unify efforts and resources to solve these problems, the state’s capacity to meet the requirements of the Board is limited. Methods We evaluated the relationship between healthy lifestyles and characteristics of Santa Ana’s school using the Our Voice Citizen Science Research Method. This systemic approach combines information and communication technologies with group facilitation to empower adolescents to: 1) collect and discuss data about factors in their local environments that facilitate or hinder well-being within their school community; 2) identify relevant local stakeholders who could help to address the issues identified; and 3) advocate collectively for local improvements to support increased well-being at a community level. Results Eleven citizen scientists ages 13 to 17 years from the science club of Institución Educativa Santa Ana were recruited and together conducted 11 walks within the school to collect data about the facilitators and barriers to student well-being. They identified barriers to well-being related to school infrastructure, furniture, bathrooms, and sense of belonging. They then advocated with school stakeholders and reached agreements on concrete actions to address identified barriers, including fostering a culture among students of caring for school property and presenting their findings to the community action board. This methodology allowed the community to realize how students can become agents of change and take collective action when motivated by solution-oriented methodologies such as Our Voice. Project ripple effects, including greater empowerment and participation in collective actions by students, also were observed. Conclusions This study underscores the importance of the school’s built environment in the well-being of students in rural areas. The Our Voice method provided the opportunity to inform school-based interventions, and promoted ripple effects that expanded productive dialogue to the community level and generated systemic actions involving actors outside of the school community.

Neste trabalho estudou-se a solubilização e difusão do cloreto de magnésio em água. Para isso, foram realizados ensaios de condutividade elétrica com diferentes posicionamentos do sensor e da pastilha de MgCl2. Independente da configuração geométrica da pastilha e dos sensores, todos os ensaios seguiram a mesma metodologia: uma pastilha, previamente prensada, de MgCl2 foi posicionada em uma determinada localização do recipiente contendo água deionizada e, a partir daí, mediu-se a condutividade do eletrólito ao longo do tempo. Para minimizar a interferência de outros fenômenos, como a convecção, os ensaios foram realizados de forma estática. Entretanto, observou-se que, mesmo sem agitação do recipiente, a convecção ainda ocorreu na maioria dos ensaios devido à liberação de gases aprisionados nos poros da pastilha prensada ou por desprendimento de partículas devido à gravidade.

Introducción: La disciplina científica de la bioinformática tiene el potencial de generar aplicaciones innovadoras para las sociedades humanas. Costa Rica, pequeña en tamaño y población en comparación con otros países de América Latina, ha ido adoptando la disciplina de manera progresiva. El reconocer los avances permite determinar hacia dónde puede dirigirse el país en este campo, así como su contribución a la región latinoamericana. Objetivo: En este manuscrito se reporta evidencia de la evolución de la bioinformática en Costa Rica, para identificar debilidades y fortalezas que permitan definir acciones a futuro. Métodos: Se realizaron búsquedas en bases de datos de publicaciones científicas y repositorios de secuencias, así como información de actividades de capacitación, redes, infraestructura, páginas web y fuentes de financiamiento. Resultados: Se observan avances importantes desde el 2010, incluyendo un aumento en oportunidades de entrenamiento y número de publicaciones, aportes significativos a las bases de datos de secuencias y conexiones por medio de redes. Sin embargo, ciertas áreas, como la masa crítica y la financiación requieren más desarrollo. La comunidad científica y sus patrocinadores deben promover la investigación basada en bioinformática, invertir en la formación de estudiantes de posgrado, aumentar la formación de profesionales, crear oportunidades laborales para carreras en bioinformática y promover colaboraciones internacionales a través de redes. Conclusiones: Se sugiere que para experimentar los beneficios de las aplicaciones de la bioinformática se deben fortalecer tres aspectos clave: la comunidad científica, la infraestructura de investigación y las oportunidades de financiamiento. El impacto de tal inversión sería el desarrollo de proyectos ambiciosos pero factibles y colaboraciones extendidas dentro de la región latinoamericana. Esto permitiría realizar contribuciones significativas para abordar los desafíos globales y la aplicación de nuevos enfoques de investigación, innovación y transferencia de conocimiento para el desarrollo de la economía, dentro de un marco de ética de la investigación. Introduction: The scientific discipline of bioinformatics has the potential to generate innovative applications for human societies. Costa Rica, small in size and population compared to other Latin American countries, has been progressively adopting the discipline. Recognizing progress makes it possible to determine where the country can go in this field, as well as its contribution to the Latin American region. Objective: This manuscript reports evidence of the evolution of bioinformatics in Costa Rica, to identify weaknesses and strengths allowing future actions plans. Methods: We searched databases of scientific publications and sequence repositories, as well as information on training activities, networks, infrastructure, web pages and funding sources. Results: Important advances have been observed since 2010, such as increases in training opportunities and the number of publications, significant contributions to the sequence databases and connections through networks. However, areas such as critical mass and financing require further development. The scientific community and its sponsors should promote bioinformatics-based research, invest in graduate student training, increase professional training, create career opportunities in bioinformatics, and promote international collaborations through networks. Conclusions: It is suggested that in order to experience the benefits of bioinformatics applications, three key aspects must be strengthened: the scientific community, the research infrastructure, and funding opportunities. The impact of such investment would be the development of ambitious but feasible projects and extended collaborations within the Latin American region and abroad. This would allow significant contributions to address global challenges and the implementation of new approaches to research, innovation and knowledge transfer for the development of the economy, within an ethics of research framework. Universidad de Costa Rica/[801-B6-767]/UCR/Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM) UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET) UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biología

The grain size refinement of metallic materials to the nanometer scale produces interesting properties compared to the coarse-grained counterparts. Their mechanical behavior, however, cannot be explained by the classical deformation mechanisms. Using molecular dynamics simulations, the present work examines the influence of grain size on the deformation mechanisms and mechanical properties of nanocrystalline nickel. Samples with grain sizes from 3.2 to 24.1 nm were created using the Voronoi tessellation method and simulated in tensile and relaxation tests. The yield and ultimate tensile stresses follow an inverse Hall-Petch relationship for grain sizes below ca. 20 nm. For samples within the conventional Hall-Petch regime, no perfect dislocations were observed. Nonetheless, a few extended dislocations were nucleated from triple junctions, suggesting that the suppression of conventional slip mechanism is not uniquely responsible for the inverse Hall-Petch behavior. For samples respecting the inverse Hall-Petch regime, the high number of triple junctions and grain boundaries allowed grain rotation, grain boundary sliding, and diffusion-like behavior that act as competitive deformation mechanisms. For all samples, the atomic configuration analysis showed that Shockley partial dislocations are nucleated at grain boundaries, crossing the grain before being absorbed in opposite grain boundaries, leaving behind stacking faults. Interestingly, the stress relaxation tests showed that the strain rate sensitivity decreases with grain size for a specific grain size range, whereas for grains below approximately 10 nm, the strain rate sensitivity increases as observed experimentally. Repeated stress relaxation tests were also performed to obtain the effective activation volume parameter. However, the expected linear trend in pertinent plots required to obtain this parameter was not found.

PurposeThe paper aims to present what is known from the school principals who participated in the International Successful School Principalship Project (ISSPP) in Mexico. The paper reviews 14 publications (5 articles, 5 conference papers and 4 books) on successful school principals in Mexico that were published between 2009 and 2021 as part of the ISSPP. The papers were analysed using a conceptual framework consisting of perceived qualities of the principal, school organisation, suitability of teachers and principals, educational materials and methods and educational infrastructure.Design/methodology/approachA scoping study review methodology was used to explore publications and conference proceedings on ISSPP research on Mexican principals and schools in order to answer the question: What do we know about successful school principals in the Mexican context? Conference papers, journal articles, book chapters and books formed the knowledge base for the review.FindingsAs a result of the analysis across the five analysis categories it was found that the principals emphasised improving the educational quality of their schools and understood this as the basic criterion to judge their leadership success. Principals were central to school success and a nested model was produced to show how the successful school is built from the core of the principal, as a socio-emotional skills role model, to a culture of continuous improvement. The model included principal socio-emotional skills, school organisation, continuous improvement of teaching and principal practices and having appropriate educational materials, methods and infrastructure.Originality/valueThe ISSPP has produced a large amount of research. The paper is the first review of the substantial contribution from ISSPP research in Mexico. The model produced from the review adds to the several models produced in the ISSPP.

A green method for synthesizing gold nanoparticles is proposed using hydroethanolic extract of Vitex mollis fruit (Vm extract) as a reducer and stabilizer. The formation of gold nanoparticles synthesized with Vm extract (AuVmNPs) was monitored by measuring the ultraviolet–visible spectra. The morphology and crystalline phase were determined using scanning electron microscopy, X-ray diffraction, and high-resolution transmission electron microscopy. Synthesized nanoparticles were generally spherical, and the size distribution obtained by transmission electron microscopy shows two populations with mean sizes of 12.5 and 22.5 nm. Cell viability assay using MTT and cellular apoptosis studies using annexin V on human umbilical vein endothelial cells (HUVECs) and the human mammary epithelial cell line (MCF10A) indicate that AuVmNPs have low toxicity. Cell migration tests indicate that AuVmNPs significantly inhibit HUVEC cell migration in a dose-dependent manner. The evaluation of the localization of AuVmNPs in HUVECs using confocal laser scanning microscopy indicates that nanoparticles penetrate cells and are found in the cytosol without preferential distribution and without entering the nucleus. The inhibitory effect on cellular migration and low toxicity suggest AuVmNPs as appropriate candidates in future studies of antiangiogenic activity.

Sarcomas of the uterus are a group of tumors that make up 1% of neoplasms of the female genital tract.1 The global incidence is 0.5 to 3.3 cases per 100,000 women per year 1 the rarity of this tumor, and its histological diversity, contributes to the lack of consensus on diagnostic behavior and timely treatment.1 The incidence increases in ages over 40years, tied to other risk factors.1 The preoperative diagnosis is a challenge, since the clinical presentation is variable, it frequently presents with transvaginal bleeding and a rapid increase in the size of the uterus,2 accompanied by symptoms of pelvic pressure, anemic syndrome stands out in these women in different degrees.2 however there are high frequency pathologies that share clinical characteristics that direct the diagnosis and is easily confused with benign leiomyoma and adenomyosis3 The objective of this presentation of the case is to take into account as a differential diagnosis in abnormal uterine bleeding and constitutional syndrome,2 due to the rarity of this tumor, only some articles of review and report of cases have been published.3