iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy

Background: HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro. Methods/design: This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes. Discussion: This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection

Making sense of big data in health research: Towards an EU action plan.

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans

The SeeRRI booklet: Bringing responsibility and RRI into regional planning - from theory to practice

Regional planning is a complex endeavour that requires a collective approach. For two and a half years, the SeeRRI project has been working with pilot territories in Norway, Austria, and Spain to develop and refine a method for integrating RRI principles into regional planning and smart specialisation policy. This booklet presents the method, explains its background, and discusses its implications. The booklet also offers intriguing third party perspectives from a range of distinguished guest authors

Influencia de las Nuevas Tecnologías en el aprendizaje de los ACNEES

Se desarrolla un proyecto de innovación educativa sobre la influencia de las Nuevas Tecnologías en el aprendizaje del Alumnado con Necesidades Educativas Especiales (ACNEES). Se trata de un proyecto que despierta en el alumnado el interés por el aprendizaje y la asimilación de contenidos, ofreciendo a los ACNEES nuevas experiencias educativas vinculadas a la realidad y con sentido práctico. Se pretende mejorar la autoestima del alumnado y la confianza en sus pasibilidades educativas. Se utilizan las TIC como medio para la ampliación, refuerzo o recuperación de contenidos en áreas instrumentales básicas y para propiciar la asimilación de las diferentes funciones del lenguaje en distintos contextos, favoreciendo la comunicación lingüística y descubriendo la diversidad de recursos de la lengua. El proyecto pretende compensar o reeducar las deficiencias lingüísticas debidas al medio sociocultural y a las particularidades etnolingüísticas para paliar los desequilibrios sociolingüísticos del alumnado, enriqueciendo el léxico, fomentando la buena organización sintáctica y corrigiendo sus errores. Para conseguir los objetivos propuestos se utilizan estrategias que posibilitan al alumnado trabajar a ritmos diferentes, favoreciendo la participación de todos, propiciando la comunicación y el uso del lenguaje a través de la creatividad. Los materiales elaborados se realizan con los ACNEES de Secundaria de forma individualizada o en grupos reducidos con el fin de reducir el fracaso escolar.Castilla y LeónConsejería de Educación. Dirección General de Universidades e Investigación; Monasterio de Nuestra Señora de Prado, Autovía Puente Colgante s. n.; 47071 Valladolid; +34983411881; +34983411939ES

DLST mutations in pheochromocytoma and paraganglioma cause proteome hyposuccinylation and metabolic remodeling

This work was supported by the Instituto de Salud Carlos III (ISCIII) through the "Acción Estratégica en Salud" (AES) (projects PI18/00454 and PI22/01490 to A.C. and PI20/01169 to M.R.), cofounded by the European Regional Development Fund (ERDF). Sara Mellid was supported by the Spanish Ministry of Science, Innovation and Universities "Formación del Profesorado Universitario- FPU" fellowship with ID number FPU19/04940. Luis J. Leandro-García is supported by 'la Caixa' Foundation (ID 100010434) under agreement LCF/BQ/PI20/11760011

Erratum to: Making sense of big data in health research: towards an EU action plan

The published article [1] has two points of confusion in the section entitled “Technical challenges related to the management of electronic health records”. Firstly, the International Rare Diseases Research Consortium (IRDiRC) has developed policies and guidelines on approaches to data sharing meant to enable and improve the development of diagnoses and therapies for rare diseases. However, at present, IRDiRC has not developed best practices for the management of electronic health records (EHRs). Secondly, RARE-Bestpractices is a European Commission 7th Framework Programme (FP7) funded initiative, independent of IRDiRC. RARE-Bestpractices contributes to IRDiRC goals and objectives; however the initiative itself is not sponsored nor connected to IRDiRC