The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour (...) cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity. (shrink)

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease. A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex, a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD, as well as PD participants (...) with either normal cognition, mild cognitive impairment, or dementia. Ratios to Creatine resonance were obtained for glutamate, glutamine and glutamate combined, N-acetylaspartate, myoinositol, and total choline, and correlated with cognitive scores across multiple domains administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups. (shrink)

We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of information and in most cases, individual consent. Patients expect information about this research to come through their physician, whom they rely on to identify and filter associated risks. (...) In general, patients support this research, but worry that participation in research involving randomization may undermine individualized care that acknowledges their unique medical histories. These findings suggest the need for public education on variation in practice among physicians and the need for a collaborative approach to the governance of research on medical practices that addresses core values of trust, transparency, and partnership. (shrink)

In recent years, the biopharmaceutical industry has seen an increase in the development of so-called orphan drugs for the treatment of rare and neglected diseases. This increase has been spurred on by legislation in the United States, Europe, and elsewhere designed to promote orphan drug development. In this article, we examine the drivers of corporate social responsibility (CSR) activities in orphan drug markets and the extent to which biopharmaceutical firms engage in these activities with a strategic orientation. The unique context (...) of orphan drugs constitutes a research opportunity to test the applicability of existing theoretical perspectives on CSR and strategic CSR. Using Schwartz and Carroll’s (Bus Ethics Q, 13(4):503–530, 2003) three-domain approach to CSR and the literature on strategic CSR as a theoretical background, we employ a combination of semi-structured interviews and a quantitative website content analysis to study practices of biopharmaceutical firms in the United States and European Union. Our findings show that both US- and EU-based companies engaged in orphan drugs development perceive their involvement as a responsible business activity beyond the economic dimension of CSR. However, for the majority of these companies their CSR activities do not qualify as strategic according to the criteria established in the literature. We also find significant differences between larger and smaller firms in their use of CSR. Based on these findings, we make several suggestions regarding orphan drug legislation and other measures that might help firms exploit strategic CSR benefits. (shrink)

BackgroundRandomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in (...) a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data.MethodsThe development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial “long list” of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the “long list” and generate a “short list” of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline.DiscussionDevelopment of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data. (shrink)

Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries, participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity (...) for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people's lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress. (shrink)

Stoffregen & Bardy's proposal that perceptual systems can use information defined across two or more sensory domains is valuable and urgent in its own right. However, their claim of exclusive validity for global-array information is superfluous and perpetuated for incorrect reasons. The seeming ambiguities of individual arrays emanate from failures to consider relevant ecological constraints and higher-order variables.

We argue four points. First, perception always relies on environmental constraints, not only in special cases. Second, constraints are taken advantage of by detecting information granted by the constraints rather than by internalizing them. Third, apparent motion phenomena reveal reliance on constraints that are irrelevant in everyday perception. Fourth, constraints are selected through individual learning as well as evolution. The “perceptual-concept-of-velocity” phenomenon is featured as a relevant case. [Hecht; Kubovy & Epstein; Shepard].

Recent research has shown that cultural, linguistic, and sociodemographic peculiarities influence the measurement of trait emotional intelligence. Assessing trait EI in different populations fosters cross-cultural research and expands the construct’s nomological network. In mental health, the trait EI of clinical populations has been scarcely researched. Accordingly, the present study examined the relationship between trait EI and key sociodemographic variables on Trait Emotional Intelligence Questionnaire datasets with mental healthcare patients from three different Spanish-speaking countries. Collectively, these datasets comprised 528 participants, 23% (...) from Chile, 28% from Peru, and 49% from Spain. The sociodemographic variables we used for trait EI comparisons were gender, age, educational level, civil status, and occupational status. Analyses involved Multigroup Exploratory Structural Equation Modelling and analysis of covariance. Our results revealed significant between-country differences in trait EI across the studied sociodemographic variables and interactions between these variables. Measurement invariance across the datasets was attained up to the scalar level regarding gender and education, although analyses on age, civil status, and occupation displayed non-invariance. The resultant psychometric evidence supports the suitability of the TEIQue-SF for the accurate cross-cultural assessment of trait EI in mental health settings. It also highlights the importance of incorporating trait EI into extant psychotherapeutic frameworks to enhance non-pharmacological treatment efficacy. (shrink)

Strong evidence shows that exposure and engagement with the natural world not only improve human wellbeing but can also help promote environmentally friendly behaviors. Human-nature relationships are at the heart of global agendas promoted by international organizations including the World Health Organization’s “One Health” and the United Nations “Ocean Decade.” These agendas demand collaborative multisector interdisciplinary efforts at local, national, and global levels. However, while global agendas highlight global goals for a sustainable world, developing science that directly addresses these agendas (...) from design through to delivery and outputs does not come without its challenges. In this article, we present the outcomes of international meetings between researchers, stakeholders, and policymakers from the United Kingdom and Brazil. We propose a model for interdisciplinary work under such global agendas, particularly the interface between One Health and the UN Ocean Decade and identify three priority research areas closely linked to each other: human-nature connection, conservation-human behavior, and implementation strategies. We also discuss a number of recommendations for moving forward. (shrink)

Despite the pervasive use of ethics training by companies, research in management accounting has not considered the effectiveness of such training in curtailing managers’ misreporting. This study examines the effect of ethics training on misreporting as a reminder to raise the awareness of employees’ ethical commitment. Furthermore, this study investigates the extent to which reciprocity in the workplace affects managers’ misreporting. The results from an experiment involving 124 managers show that in the absence of an ethical commitment reminder, managers are (...) more likely to engage in misreporting than when an ethical commitment reminder is present. The results suggest that ethical commitment reminder interacts with reciprocity in the workplace, affecting managers’ misreporting. Specifically, the results reveal that managers are more likely to engage in misreporting under the reciprocity in the workplace condition when the ethical commitment reminder is absent. The theoretical and practical implications of these findings are discussed. (shrink)

We give recursion-theoretic characterizations of the counting class \(\textsf {\#P} \), the class of those functions which count the number of accepting computations of non-deterministic Turing machines working in polynomial time. Moreover, we characterize in a recursion-theoretic manner all the levels \(\{\textsf {\#P} _k\}_{k\in {\mathbb {N}}}\) of the counting hierarchy of functions \(\textsf {FCH} \), which result from allowing queries to functions of the previous level, and \(\textsf {FCH} \) itself as a whole. This is done in the style of (...) Bellantoni and Cook’s safe recursion, and it places \(\textsf {\#P} \) in the context of implicit computational complexity. Namely, it relates \(\textsf {\#P} \) with the implicit characterizations of \(\textsf {FPTIME} \) (Bellantoni and Cook, Comput Complex 2:97–110, 1992) and \(\textsf {FPSPACE} \) (Oitavem, Math Log Q 54(3):317–323, 2008), by exploiting the features of the tree-recursion scheme of \(\textsf {FPSPACE} \). (shrink)

The current times call for reforms in educational processes. The Covid-19 pandemic had an unforeseen impact on the educational system in all countries. This need for change requires new pedagogies and new methods for teaching and learning. Understanding the need for change is essential for the formulation of adaptive proposals, as well as for the generation of training activities to complement the teaching curriculum. New educational practices lead to a vision of educational quality, with new approaches that allow the continuous (...) integration of knowledge and permanent interaction with the student. This paper presents an analysis of the new teaching methodologies in times of confinement due to the pandemic caused by Covid-19. Keywords: Teaching methodologies, educational system, learning process. References [1]É. Tremblay-Wragg, C. Raby, L. Ménard y I. Plante, «El uso de estrategias didácticas diversificadas por cuatro profesores universitarios: ¿qué contribución a la motivación de aprendizaje de sus alumnos?,» Docencia en educación superior, vol. 26, nº 21, 2021. [2]L. Czerniewicz, R. Mogliacci, S. Walji, A. Cliff, B. Swinnerton y N. Morris, «Enseñanza y aprendizaje académico en el nexo: desagregación, mercantilización y digitalización en la educación superior,» Teaching in Higher Education, vol. 26, nº 2021, p. 16, 2021. [3]S. Dogan y A. Adam, «Aumentar el efecto del desarrollo profesional en la instrucción efectiva a través de comunidades profesionales,» Docentes y docencia: teoría y práctica, vol. 26, nº 3-4, pp. 326-349, 2020. [4]I. M. Torres Salas, «La enseñanza tradicional de las ciencias versus las nuevas tendencias educativas,» Educare, vol. 14, nº 1, pp. 131-142, 2010. [5]B. Fabio, J. Antonio Palomino y J. González Henríquez, «Evaluación y contraste de los métodos de enseñanza tradicional y lúdico,» Revista de Educación física y deportes, vol. 13, nº 94, pp. 29-36, 2008. [6]Y. Benítez y C. Mora, «Enseñanza tradicional vs aprendizaje activo,» Revista Cubana de Física, vol. 27, nº 2A, pp. 175-179, 2010. [7]P. Morales Bueno y V. Landa Fitzgerald, «Aprendizaje basado en problemas,» Theoria, vol. 13, nº 1, pp. 145-157, 2004. [8]R. Gil-Galván, I. Martín-Espinosa y F. Gil-Galván, «University student perceptions of competences acquired through problem-based learning,» Educación XXI, vol. 24, nº 1, pp. 271-295, 2020. [9]E. Ortiz Cermeño, «El aprendizaje basado en problemas,» Perfiles Educativos, vol. 41, nº 164, pp. 208-213, 2019. [10]E. Araos-Baeriswyl, C. Moll-Manzur, Á. Paredes y J. Landeros, «Aprendizaje invertido: un enfoque pedagógico en tiempos de pandemia,» Rev. Atención Primaria, vol. 53, nº 1, p. 117, 2021. [11]V. León-Carrascosa, M. Belando-Montoro y S. Sánchez-Serrano, «Design and validation of a questionnaire to evaluate the service-learning methodology,» Rev.Estudios sobre educación, vol. 39, nº 1, pp. 247-266, 2020. [12]J. Collado-Ruano, M. Ojeda, M. Malo y D. Amino, «Educación, arte e interculturalidad: El cine documental como lenguaje comunicativo y tecnología innovadora para el aprendizaje de la metodología I + D + I,» Rev. Texto livre, vol. 13, nº 3, pp. 376-393, 2020. [13]P. M. Bueno y V. Landa Fitzgerald, «Aprendizaje basado en problemas,» Theoria, vol. 13, nº 1, pp. 145-157, 2004. [14]J. A. Martí, M. Heydrich, M. Rojas y A. Hernández, «Aprendizaje basado en proyectos: Una experiencia de innovación docente,» Universidad EAFIT, vol. 46, nº 158, pp. 11-21, 2010. [15]L. Rojas y N. M. Jaimes, «Canvas LMS y el trabajo colaborativo como metodología de aprendizaje en entornos virtuales,» de Congreso Ibérico de Sistemas y Tecnologías de la Información, CISTI, Bogotá, Colombia, 2020. [16]B. Bordel y P. Mareca, «Results and Trends in educational MOOCs in the engineering area with MIRIADAX platform. A case study,» de 15th Iberian Conference on Information Systems and Technologies, CISTI 2020; Seville; Sevilla, España, 2020. [17]K. Vermeir y G. Kelchtermans, «Innovative practice as interpretative negotiation.A case-study on the kamishibai in Kindergarten.,» Teachers and Teaching: Theory and Practice, vol. 26, nº 3-4, pp. 248-263, 2020. [18]B. Tucker, «The Flipped Classroom: Online instruction at home frees class time for learning,» Education Next, vol. 1, nº 1, pp. 82-84, 2012. [19]M. V. Ledo, N. R. Michelena, N. N. Cao, I. d. R. M. Suárez y M. N. Vialart Vidal, « Aula invertida, nueva estrategia didáctica,» Educación Médica Superior, vol. 30, nº 3, pp. 678-688, 2016. [20]Metodologías activas por medio de las TIC, [Online]. Available: https://www.campuseducacion.com/blog/recursos/articulos-campuseducacion metodologias-activas-por-medio-de-las-tic/?cn-reloaded=1. [Last access: February 14, 2021]. (shrink)

Cet hommage à Christiane Klapisch-Zuber est mené à plusieurs voix. Mais les éditeurs ont le mérite d’avoir conféré une ligne originale à ce recueil d’essais en convainquant C. K.-Z. d’y publier un texte présenté au congrès annuel de la Renaissance Society of America qui s’était tenu à Florence en mars 2000, texte déjà publié en italien dans la revue Genesis. Rivista della Società italiana delle Storiche en 2002. Le présent volume s’ouvre donc, d’une façon plutôt inhabituelle, par les mots mê...

In Gandhi's Printing Press, Isabel Hofmeyr introduces readers to the nuances of the newspaper in a far-flung colony in the age when mail and news traveled by ship and when readers were encouraged by Gandhi to read slowly and deeply. This article explores the ways in which Thoreau's concept of slow reading influenced Gandhi and Hofmeyr herself. She discusses the community that surrounded Gandhi and the role it played in supporting the newspaper. Yet, I argue, the role of women (...) of all races as well as Coloured and black South African men in leading, modeling, and shaping the movement of resistance to pass laws and other racist legislation might have been integrated more into the main narrative. Gandhi's newspaper, Indian Opinion, reported on the pass law protests of the African women of Bloemfontein, and Abdurahman's APO newspaper (popular in the Coloured community) reported on Gandhi's protests. Indian Opinion included speeches given by John Dube, and it often praised Dube and the work at Ohlange and reprinted stories from the black press. I offer these remarks to supplement Hofmeyr's fascinating account by providing additional information in portraying the newspaper in its historical and social context. (shrink)

Shavelson et al. (2023) identify an important problem in their Target article: a significant number of terminally ill patients with impaired motor function are wrongfully excluded from receiving ai...

This exploratory study is part of a post-doctoral project investigating how Brazilian and Portuguese textbooks present slavery and the slavery trade, as well as how Portuguese students interpret these issues, particularly when they use the sources in their textbooks. A group of 8th-grade students (aged 13–14) from a school in northern Portugal was asked to reflect on the meaning of slavery and its potential consequences for Brazil and Portugal, drawing on evidence related to the slave trade and labour during the (...) 16th century, as presented in their textbooks. The students’ responses were analysed inductively, and the findings are discussed in terms of (a) the specific analytical process employed and (b) the insights gained regarding the relationship between textbook representations and students’ perceptions, framed within the context of situated learning. This framework suggests that prior knowledge, personal experience, and the specific task at hand may influence students' ideas and outcomes. (shrink)

En este artículo consideramos la pobreza extrema como un caso de violación de los derechos humanos en tanto que la situación de las personas que la padecen vulnera el mínimo de dignidad o justicia que permitiría reconocerlos como seres valiosos. La respuesta internacional en esos casos no puede entenderse como una cuestión de beneficencia sino que debe ir orientada prioritariamente con medidas de justicia que busquen el reconocimiento de la dignidad y las libertades de esas personas. En este sentido consideramos (...) la posibilidad de defender una propuesta de justicia global distributiva como la de Thomas Pogge y, por otra parte, reconocemos el valor de los derechos humanos como imperativos éticos globales para la fundamentación y la defensa de una justicia global desde el enfoque de la capacidad de Amartya Sen.In this article we consider extreme poverty as a case of violation of human rights as the situation of people who suffer it do not have the minimum of dignity or justice that would recognize them as valuable beings. The international response in such cases cannot be understood as a matter of charity but should be oriented primarily with justice measures seeking the recognition of the dignity and freedoms of those people. In this regard we consider the possibility of presenting a proposal for distributive global justice as Thomas Pogge does and, on the other hand, we recognize the value of human rights as global ethical imperatives for foundation and defense of a proposal of global justice from the perspective of the capability approach by Amartya Sen. (shrink)

Los libros de doctrina o tratados pocas veces se hacen cargo de todas las consideraciones teóricas que están involucradas en exponer una materia. Estas consideraciones, por consiguiente, tienden a volverse una rutina que se repite sin muchas consecuencias. El propósito de este trabajo es presentar tres modelos con los que dentro de nuestra tradición, la latinoamericana, se han pensado las reglas sobre matrimonio, divorcio y paternidad. El fin último es enriquecer el debate contemporáneo sobre la reforma de estas reglas al (...) proporcionar herramientas, argumentos y perspectivas sobre los límites y oportunidades de cada modelo. (shrink)

The business world is facing a very complicated situation due to the COVID-19 pandemic. Small- and medium-sized companies —both in Spain and at the global level—are seeing their survival jeopardized by a fall in revenues. This scenario is aggravated in the case of micro-SMEs headed by female entrepreneurs. Accordingly, micro-SMEs, particularly those led by female entrepreneurs, need to reinvent themselves to overcome the current adversities that could lead to the destruction of their businesses and hence their jobs. One of the (...) ways to do this is to take advantage of digital transformation. Therefore, the aim of this paper is to analyze which variables influence the financial results of female-led Spanish micro-SMEs when they carry out social marketing actions. For that purpose, an online survey was designed and analyzed using the “PROCESS” macro. Results show that social media marketing actions have significant effects on financial performance. (shrink)

Rising economic inequality has aggravated long-standing labor market disparities, with one exception: government employment. This article considers the puzzle of black-white wage parity in the American public sector. African Americans are more likely to work in the public than in the private sector, and their wages are higher there. The article builds on prior work emphasizing institutional factors conditioning this outcome to argue that employee mobilization can motor it. As public sector unions gained political influence postwar, their large constituencies of (...) black, blue-collar workers, drawing on both militant and nonviolent tactics of the urbanizing civil rights movement, advocated for improved working conditions. Archival sources confirm this pattern at the federal level. The employment and activism of African Americans in low-skilled federal jobs pivoted union attention to blue-collar issues and directly contributed to the enactment of a transparent, universal wage schedule for the blue-collar federal workforce. The result was greater pay parity for African Americans, as well as for other disadvantaged groups. (shrink)

All the osteological data analyzed in this article belongs to two muslim necropolis of Toledo. This study has enabled us to make inferences about the physical characteristics of the Andalusian population who lived in the city in the 8th-11th centuries. We have to keep in mind that Toledo has been a city open to the mixing of cultures and therefore, has received a great weight of external influences during Antiquity and the Middle Ages. For this reason, archaeologists must examine in (...) great detail characteristics such as the extension of the cemetery areas, the proportions of the graves and the placement of the bodies. However, the simplicity of the Muslim ritual, makes the skeletal remains one of the main subject of study. However, the special relevance that these maqābir have had for centuries, contrasts with the absence of scientific publications in relation to its anthropological study. In this sense, this work offers consistent and unpublished documentation of a society, whose strong indigenous component, has maintained its own impact during the process of Islamization. (shrink)

La geometría y el dibujo son herramientas esenciales para la expresión gráfica, quizás el lenguaje fundamental en los ámbitos de la arquitectura y la ingeniería. Aunque su importancia es innegable, muchos de los alumnos que abordan el estudio de la geometría la perciben como una materia abstracta y compleja, sin relación con la realidad, por lo que no les motiva suficientemente. Este trabajo presenta tres experiencias docentes dirigidas a solucionar este problema en las que se plantea un reto: la construcción (...) de una bóveda o una cúpula. De este modo, los alumnos tuvieron que investigar y entender diversos conceptos geométricos. (shrink)

La distinción entre transmedia y cross-media con frecuencia resulta confusa en los estudios sobre la comunicación. Esta investigación tiene como objetivo revisar el uso de ambos conceptos en la literatura científica publicada en Web of Science y SciELO Citation Index. La investigación parte de una muestra de 895 artículos a los que se les aplica un análisis bibliométrico y un análisis de redes para descubrir las relaciones entre textos. Los resultados del estudio son útiles para conocer la configuración del campo (...) de conocimiento desde una perspectiva que integra las diversas disciplinas implicadas y abren el espectro para entender la comunicación transmedia y cross-media como objetos de estudio afines que deben ser estudiados de forma interdisciplinar. (shrink)