Artículo 47 CDFUE y jurisdicción civil: el asunto de cláusulas de arbitraje y los contratos celebrados con los consumidores (Países Bajos v. España)

[eng] The law of the European Union confers subjective rights on citizens, such as those they derive – in their role of consumers – from the Unfair Contract Terms Directive (93/13/EEC). Civil courts play a key role in the enforcement and protection of those rights. Article 47 of the EU Charter of Fundamental Rights (EUCFR) safeguards the right to an effective remedy before a court of law for infringements of substantive EU rights. It may entail a change in perspective towards the autonomy of the Member States as regards remedies, procedures and, in particular, judicial protection under the Directive. It provides civil courts with an instrument for the assessment, (consistent) interpretation and (dis)application of both contractual clauses and procedural rules governing disputes between consumers and their professional counterparties. The ‘proceduralized constitutionalization’ of consumer protection can be illustrated by the example of arbitration clauses, which are regulated differently in the EU Member States. In the Netherlands, (online) arbitration in consumer cases has given rise to a debate about the lack of judicial control over commercial ‘adjudication’. This will be discussed in light of the case law of the EU Court of Justice concerning unfair terms control and access to court – e.g. Asturcom (C-40/08) and, more recently, Menini (C-75/16) – as well as the groundbreaking decision in Achmea (C-284/16). The aim is to examine the function of Article 47 EUCFR at EU level and at the national level with respect to consumer arbitration and with a focus on the Netherlands and Spain. The Spanish experience can inform Dutch civil courts on how to deal with this issue.[spa] El Derecho de la Unión Europea confiere derechos subjetivos a los ciudadanos, como los que derivan – en su cualidad de consumidores – de la Directiva sobre las cláusulas abusivas (93/13/CEE). Los tribunales del orden civil ejercen un papel clave en la aplicación y protección de estos derechos. El artículo 47 de la Carta de los Derechos Fundamentales de la UE (CDFUE) protege el derecho a la tutela judicial efectiva frente a infracciones del Derecho material de la UE. Este precepto puede suponer un cambio de perspectiva en la que se refiere a la autonomía de los Estados miembros en relación con los remedios, los procedimientos y, en particular, la tutela judicial de los que gozan las consumidores con arreglo a la Directiva. La norma proporciona a los tribunales civiles un instrumento para la evaluación, la interpretación (coherente) y la (des)aplicación tanto de las cláusulas contractuales como de las normas procesales que rigen los litigios entre los consumidores y los profesionales. La "constitucionalización procesalizada" de la protección del consumidor puede ilustrarse mediante el ejemplo de las cláusulas de arbitraje, que están reguladas de manera diferente en los Estados miembros de la UE. En los Países Bajos, la resolución privada de conflictos mediante el arbitraje (en línea) en casos de consumo ha dado lugar a un debate sobre la posible mercantilización del sistema, atendida la falta de control judicial de las decisiones del árbitro. Ello se analizará a la luz de la jurisprudencia del Tribunal de Justicia de la UE sobre el control de las cláusulas abusivas y el acceso a los tribunales – por ejemplo, Asturcom (C-40/08) y, más recientemente, Menini (C-75/16) – así como la decisión innovadora en Achmea (C-284/16). El objetivo es examinar la función del artículo 47 CDFUE en la UE y a nivel nacional con respecto al arbitraje de consumo, con particular atención a los Países Bajos y España. La experiencia española puede ilustrar a los tribunales civiles holandeses sobre la manera de tratar este problema

Strain Measurements During Structural Conservation Treatment and the Long-term Monitoring of a 17th-century Dutch Panel Painting

No abstract available

Strain Measurements During Structural Conservation Treatment and the Long-term Monitoring of a 17th-century Dutch Panel Painting

No abstract available

RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response

Chromosomal region 1p22 is deleted in 6520% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients

Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging

Health professions and risk of sporadic Creutzfeldt- Jakob disease, 1965 to 2010

In 2009, a pathologist with sporadic Creutzfeldt- Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD. Five countries reported 15 physicians and 68 other health professionals among 2,968 controls or non-cases, suggesting no relative excess of sCJD among healthcare professionals. A literature review revealed: (i) 12 case or small case-series reports of 66 health professionals with sCJD, and (ii) five analytical studies on health-related occupation and sCJD, where statistically significant findings were solely observed for persons working at physicians' offices (odds ratio: 4.6 (95 CI: 1.2-17.6)). We conclude that a wide spectrum of medical specialities and health professions are represented in sCJD cases and that the data analysed do not support any overall increased occupational risk for health professionals. Nevertheless, there may be a specific risk in some professions associated with direct contact with high human-infectivity tissue

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

11 páginas, 4 figuras, 2 tablas. Datasets en su material suplementario. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2302720120/-/DCSupplemental.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.This work was supported by the Michael J. Fox Foundation grant MJFF-020161 (E.M., Z.G.-O.), NIH and National Institute of Aging grants AG060747 (M.D.G.), AG066206 (Z.H.), AG066515 (Z.H., M.D.G.), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, Y.L.G.), the Alzheimer’s Association (AARF-20-683984, M.E.B.), and the Iqbal Farrukh and Asad Jamal Fund, a grant from the EU Joint Programme—Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB; JPND), the Japan Agency for Medical Research and Development JP21dk0207045 (T.I.), JP21dk020704 (K.O., S.N.), JP21km040550 (K.O.), the Einstein Center for Neurosciences in Berlin (S.M.Y.), the Swedish Research Council (#2018-02532, H.Z.), the European Research Council (#681712, H.Z.), and the Swedish State Support for Clinical Research (#ALFGBG-720931, H.Z.). Inserm UMR1167 is also funded by the Inserm, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine, and the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Additional funders of individual investigators and institutions who contributed to data collection and genotyping are provided in SI Appendix.Peer reviewe

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight