Paradigm (France)

Abstract Nanomedicines are among the most promising novel delivery systems and are highly promising as therapeutic agents in oncology. However, their use is still limited by nanoparticle hepatic clearance which is responsible for low delivery to the target site. Moreover, the unintended liver distribution could cause harmful side effects. Curadigm’s innovative Nanoprimer technology aims to shift the balance of therapeutics bioavailability and toxicity. The platform is designed to decrease nanomedicines' liver trapping and increase their systemic bioavailability for optimal accumulation in target tissues. This technology can redefine the benefit/risk ratio of therapeutics, improving their clinical outcomes and treatment value. The Nanoprimer is an engineered, biocompatible liposome that transiently and specifically occupies the cells of the mononuclear phagocytic system responsible for sub-optimal therapeutics bioavailability. The Nanoprimer is administered just before the therapeutic, temporarily reducing drug clearance and elimination. Proofs-of-concept were realized by combining the Nanoprimer with different therapeutic agents such as irinotecan-loaded liposomes and nucleic acid-loaded lipid nanoparticles (LNP). One example is a study conducted in collaboration with the Langer Lab at MIT that shows that the Nanoprimer increases mRNA- and siRNA-based therapeutics efficiency by 32% and 49% respectively. Efficacy studies in a triple-negative breast cancer mouse model reveal that the Nanoprimer increases by 2-fold the anti-tumor efficacy of siRNA LNP therapy. Data demonstrate the safety of the Nanoprimer, along with its ability to maximize the inhibition of primary tumor growth and pulmonary metastasis by systemic siRNA LNP treatment. In a collaborative study with the NCL*, the Nanoprimer was shown to stimulate the immune response in a systemic vaccine model using ovalbumin-coated gold nanoparticles (GNP-OVA). Administration of the Nanoprimer before immunization of mice by intravenous injection of GNP-OVA, results in a dramatic increase in anti-OVA antibody levels with IgGs detected as early as 7 days. Furthermore, IgG and IgM antibodies remain elevated at day 28 showing a robust and sustainable immune response. Nanoprimer ability to enhance immune response shows its great potential in immunotherapy, especially for cancer vaccines. Altogether, these data demonstrate that the ubiquitous nature of the Nanoprimer mode of action allows its application to a broad spectrum of therapeutics, from nucleic acid-loaded LNP to immunotherapy. Efficacy studies conducted in mouse models highlight the potential for the Nanoprimer to empower nanotechnology for oncology treatments. *We acknowledge NCL, Frederick National Laboratory for Cancer Research sponsored by the NCI for the help with conducting these experiments. Citation Format: Julie Devallière, Laurence Poul, Maxime Bergère, Francis Mpambani, Audrey Darmon, Océane Jibault, Matthieu Germain. The Nanoprimer: A significant opportunity to boost the efficacy of cancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3902.

El capítulo aborda la complejidad de definir legalmente el tráfico ilícito de sustancias sujetas a fiscalización, destacando su relación con el concepto de droga. El tráfico de drogas comprende diversas acciones con impacto en la salud pública, presentando desafíos para establecer una definición única. Se trata de procesos orientados a obtener beneficios económicos mediante la venta de sustancias clasificadas como drogas, sin la debida autorización legal. Destaca la presencia del tráfico de sustancias sujetas a fiscalización con notables repercusiones a nivel local, nacional e internacional. El capítulo explora detalladamente los impactos en la salud pública, seguridad, sistema judicial, economía y sociedad. Se resalta la contribución del tráfico de drogas a la propagación de adicciones y problemas de salud mental, abordando riesgos para la salud, transmisión de enfermedades y consecuencias sociales como desestabilización y carga para el sistema judicial. En términos económicos, se señala el impacto negativo del tráfico de drogas al desalentar inversión y desarrollo, generando costos sanitarios y afectando la productividad laboral. Socialmente, se destaca la desestructuración familiar, estigmatización y discriminación hacia personas con problemas de drogadicción. El capítulo también aborda la prevención y tratamiento, resaltando inversiones de gobiernos y organizaciones en programas para abordar problemas derivados del abuso de drogas. Se destaca la importancia de la rehabilitación y reinserción social como componentes clave en la gestión de estos problemas. Concluye enfatizando que el impacto de las drogas varía según diversos factores, subrayando la necesidad de estrategias de prevención, educación y tratamiento para mitigar los efectos negativos en la sociedad. La obra aborda la complejidad y las múltiples dimensiones del tráfico ilícito de sustancias, proporcionando una visión integral de sus impactos y la importancia de enfoques holísticos en su abordaje.

La legislación española en materia de delitos contra la libertad sexual ha trascurrido por distintas etapas con características bien definidas, así se pasó de la protección de la honestidad, a la protección de la libertad sexual y, recientemente, el acaecimiento del caso de «La Manada» y la coyuntura política actual posibilitaron la irrupción de la perspectiva de género en esta materia. En este trabajo se exponen los pilares sobre los que se asienta la teoría del género y se cuestionan las bondades de esta nueva forma de entender la protección de la sexualidad en el Código penal español.

Le présent travail propose de mettre en lumière certains dispositifs d’imposition de la différence coloniale pour appréhender sous un nouveau jour les interactions interethniques autour de la frontière interne sud argentine au XIXe siècle. Après avoir analysé l’existence d’une diglossie au sein de la société de frontière, nous nous proposons de démontrer que le paradigme diglossique se manifeste aussi dans les pratiques culturelles et épistémiques. L’analyse de la hiérarchisation et de la fonctionnalisation des normes culturelles et épistémiques chez les peuples natifs de la Pampa à travers une série d’exemples illustre alors comment la différence coloniale fut imposée pendant les échanges sur la frontière entre la société argentine et les sociétés indigènes avant la Conquête du Désert. Finalement, l’article tente de démontrer que si le paradigme diglossique eut des conséquences néfastes pour les peuples natifs lors du XIXe siècle, il semble aussi représenter, de nos jours, la voie vers une remédiation de la différence coloniale (ou impériale), à travers la revendication de la subjectivité de frontière, au-delà de sa conception territoriale, comme identité.

Abstract The Future of Systems Engineering (FuSE) is an INCOSE‐led multiorganizational collaborative initiative pursuing INCOSE's Vision 2025 and beyond. To accomplish this the FuSE initiative encompasses a number of topic areas with active projects to shape the future of systems engineering. This paper addresses the FuSE Security topic area and provides a roadmap of eleven foundational concepts for building the security vision. The purpose of this paper is to instigate and inspire thinking and involvement in the development and practice of the foundational concepts.

A questão agrária é multidimensional, multiescalar e envolve tanto momentos de conflito, bem como de conflitualidade. A questão agrária também está inserida no debate paradigmático – Paradigma da Questão Agrária e Paradigma do Capitalismo Agrário – em que ambos propõem modelos de desenvolvimento para o espaço agrário. Desde a década de 1990, o espaço agrário latino-americano é alvo da expansão de políticas neoliberais que incentivam o agronegócio pautado na produção de commodities para a exportação. Ao mesmo tempo, o campesinato e demais povos tradicionais da América Latina se organizam em movimentos socioterritoriais e promovem práticas de desenvolvimento contra-hegemônicas, ordenadas pela reforma agrária popular, agroecologia, soberania alimentar, educação do campo, entre outros. Estes modelos de desenvolvimento estão em conflito e em permanente conflitualidade, conformando o espaço agrária latino-americano. Como citar este artigo:PEREIRA, Lorena Izá; COCA, Estevan Leopoldo de Freitas; ORIGUÉLA, Camila Ferracini. Conflitualidade e questão agrária: os modelos de desenvolvimento para o espaço agrário latino-americano. Revista NERA, v. 23, n. 53, p. 09-21, mai.-ago., 2020.

The article aims at identifying promising directions for managing the competitive, innovative and investment behavior of agricultural enterprises, immanent to the general trends in the global economy performance, based on the studies in the evolution of the sustainable development paradigm. The analysis is based on the hypothesis that mitigating the impact of global challenges in the agricultural sector, associated with industrialization processes, as well as ensuring the growth of production efficiency and competitive potential, requires the sustainable development paradigm to be implemented in the activities of agricultural enterprises, thus ensuring the harmonious development of the following interrelated components: the economic, social and environmental ones. Having assessed the degree of their balance, we have discovered insufficient development of the social component, which hinders the development of human capital. It has been proved that building up the social assets of agricultural enterprises and strengthening the competitive potential are closely related to changes in the social subsystem of management. Within its framework, the phenomenon of organizational culture is recognized as a significant factor of indirect impact. The courses of the transformation in the interaction processes between society and business within the framework of the sustainable development paradigm are revealed. The authors come to conclusion that it is necessary to update a company’s mission in accordance with the principles of social responsibility, which implies the involvement of social and environmental aspects in business activities on the basis of interaction among various stakeholders (influence groups). Compliance with the principles of social responsibility positively affects the competitiveness of agribusiness entities in the following areas: improving the image and reputation of brands; increasing sales and consumer loyalty to the company’s products; reducing staff turnover rates; establishing partnership relations with the authorities; facilitating access to the media; increasing investors’ interest.