The role of cartoons on European generalist televisions between 2010 and 2020

Cartoons have been and still are a fundamental genre in children’s television programming and are a key product for the media industry due to their easy interpretation by children and their presence in distribution channels. This paper presents an analysis of the supply of children’s and cartoons broadcast over the last decade on 25 European general-interest television channels, both public and private, of Germany, Spain, France, Italy and the United Kingdom. The research findings focus on the genre programming strategies applied in terms of channels, broadcasting time slots and types of production in a multiplatform context driven by the consumption of digital content through streaming and SVOD services. The results show the continued leadership of cartoons in an environment of scarcity of children’s supply on European generalist television channels, reaffirming itself as a morning and weekend product highly shaped by commercial logics. However, distinctive programmatic policies are prominent in the role of public broadcasters in the supply of domestic products, both due to the broadcasting quotas of local cartoons and the consistency of their strategy over the period 2010-2020.Los dibujos animados han sido y son un género fundamental en las programaciones infantiles y un producto clave de la industria audiovisual por su fácil interpretación por parte del público infantil y su presencia en los circuitos de distribución. Este artículo presenta un análisis de la oferta infantil y de dibujos animados emitidos durante la última década en 25 televisiones generalistas europeas, públicas y privadas, de Alemania, España, Francia, Italia y Reino Unido. Los hallazgos de la investigación se centran en las estrategias de la oferta de este género respecto a la programación de las cadenas, las franjas de emisión y el tipo de producción que los operadores están programando en un entorno multiplataforma y de consumo de contenidos digitales por streaming y servicios SVOD. Los resultados obtenidos demuestran el continuado liderazgo de los dibujos animados en un entorno de escasez de oferta infantil en las televisiones generalistas europeas, reafirmándose como un producto matinal y de fin de semanas altamente moldeado por unas lógicas comerciales. Sin embargo, también se observan unas políticas programáticas distintivas en el papel de los programadores públicos respecto a la oferta de productos domésticos, tanto por las cuotas de emisión de dibujos animados locales como por la constancia en su estrategia durante el periodo 2010-2020

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

The role of cartoons on European generalist televisions between 2010 and 2020

Cartoons have been and still are a fundamental genre in children’s television programming and are a key product for the media industry due to their easy interpretation by children and their presence in distribution channels. This paper presents an analysis of the supply of children’s and cartoons broadcast over the last decade on 25 European general-interest television channels, both public and private, of Germany, Spain, France, Italy and the United Kingdom. The research findings focus on the genre programming strategies applied in terms of channels, broadcasting time slots and types of production in a multiplatform context driven by the consumption of digital content through streaming and SVOD services. The results show the continued leadership of cartoons in an environment of scarcity of children’s supply on European generalist television channels, reaffirming itself as a morning and weekend product highly shaped by commercial logics. However, distinctive programmatic policies are prominent in the role of public broadcasters in the supply of domestic products, both due to the broadcasting quotas of local cartoons and the consistency of their strategy over the period 2010-2020.Los dibujos animados han sido y son un género fundamental en las programaciones infantiles y un producto clave de la industria audiovisual por su fácil interpretación por parte del público infantil y su presencia en los circuitos de distribución. Este artículo presenta un análisis de la oferta infantil y de dibujos animados emitidos durante la última década en 25 televisiones generalistas europeas, públicas y privadas, de Alemania, España, Francia, Italia y Reino Unido. Los hallazgos de la investigación se centran en las estrategias de la oferta de este género respecto a la programación de las cadenas, las franjas de emisión y el tipo de producción que los operadores están programando en un entorno multiplataforma y de consumo de contenidos digitales por streaming y servicios SVOD. Los resultados obtenidos demuestran el continuado liderazgo de los dibujos animados en un entorno de escasez de oferta infantil en las televisiones generalistas europeas, reafirmándose como un producto matinal y de fin de semanas altamente moldeado por unas lógicas comerciales. Sin embargo, también se observan unas políticas programáticas distintivas en el papel de los programadores públicos respecto a la oferta de productos domésticos, tanto por las cuotas de emisión de dibujos animados locales como por la constancia en su estrategia durante el periodo 2010-2020

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

Nat Commun

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele