Influencing politics with signatures? : models and experiences of local citizens’ initiative

Podeu consultar la versió en català: http://hdl.handle.net/11703/111655Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/11165

Signar per influir en política? : models i experiències d’iniciativa ciutadana local

Podeu consultar la versió en castellà a: http://hdl.handle.net/11703/111654Podeu consultar la versió en anglès a: http://hdl.handle.net/11703/11165

¿Firmar para influir en política? : modelos y experiencias de iniciativa ciudadana local

Podeu consultar la versió en català: http://hdl.handle.net/11703/111655Podeu consultar la versió en anglès a: http://hdl.handle.net/11703/11165

Long runs of homozygosity are associated with Alzheimer's disease

Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017).Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ β (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10 −5 ; β (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10 −16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10 −4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability

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

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

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

Local political participation: what citizens want, what governments do, and what academics assume. Southern european evidence for an international debate

La implementació d’innovacions democràtiques incorporant a la ciutadania en el procés de presa de decisions s’ha estès globalment durant les darreres dècades. Els mecanismes de participació local han esdevingut molt coneguts a partir d’algunes experiències d'èxit com els Pressupostos Participatius de Porto Alegre. Acadèmicament, les i els investigadors han estudiat àmpliament aquestes innovacions, principalment mitjançant estudis de cas d’experiències d'èxit. Els mecanismes de participació en l'àmbit local són l’objecte d’estudi d’aquesta tesi, abordats des d’una perspectiva triple. Descriurem i analitzarem què vol la ciutadania en termes de democràcia participativa, què fan els governs locals (és a dir, quin tipus de mecanismes participatius s’estan desenvolupant), i què s’assumeix des de l’acadèmia sobre aquestes innovacions democràtiques. L’objectiu global d’aquesta recerca és contribuir a la comprensió de la realitat participativa més enllà del debat teòric i l’anàlisi dels estudis de cas, centrant l’atenció al Sud d’Europa. Les preferències ciutadanes sobre els processos de presa de decisions s'emmarquen al context espanyol. Mitjançant l’estudi de dades d’enquesta, analitzarem les preferències ciutadanes pel que fa a qui pren les decisions, si la ciutadania o els polítics. Aquestes preferències es relacionaran alhora amb diverses actituds: l’experiència participativa prèvia, la intensitat de les actituds envers diferents temes, la percepció que les idees pròpies formen part d’un consens general i l’aversió al conflicte. Respecte als mecanismes participatius, indagarem en com són aquestes innovacions des d’una perspectiva de N gran a partir d’un mapatge participatiu de cinc regions del Sud d’Europa. L’anàlisi se centrarà en diferents qualitats referents a la participació ciutadana, la deliberació i l’apoderament. Finalment, després de demarcar aquestes preferències i mecanismes participatius, entaularem un debat entre l’evidència empírica i alguns debats i assumpcions acadèmiques. Adreçarem el debat metodològic sobre quin tipus de mecanismes participatius es recull mitjançant diferents estratègies de N gran. Així mateix, en diàleg amb alguns debats de l’acadèmia anglosaxona, abordarem el debat sobre la definició de l’objecte d’estudi (la tensió entre la democràcia participativa i deliberativa), les característiques dels actors que promouen les innovacions, el rol dels professionals de la participació o la reproducció de les desigualtats preexistents entre els i les participants. Comprovarem si la regió del Sud d’Europa presenta algunes especificitats participatives en comparació amb les regions que han estat més estudiades des de l’acadèmia. Per últim farem referència a algunes implicacions, per exemple en relació al context polític espanyol actual. El moviment 15M va obrir un ampli debat envers el procés de presa de decisions, defensant una “democràcia real”. Noves candidatures d'èxit com Podemos i Ganemos/Guanyem han incorporat la democràcia participativa als seus discursos, propostes i pràctiques. Abordarem la qüestió de quina relació pot haver-hi entre aquest context sociopolític i les preferències ciutadanes i mecanismes participatius analitzats en aquesta tesi.The implementation of democratic innovations for involving citizens in the decision-making process has spread globally over the last decades. Local participatory mechanisms have become well-known due to some successful experiences such as the Participatory Budgeting in Porto Alegre. Academically, researchers have broadly studied these innovations, mainly through case studies of successful experiences. Participatory mechanisms at the local level are the object of study in this dissertation, addressed from a threefold perspective. We will describe and analyse what citizens want in terms of participatory democracy, what local governments do (i.e. what kind of participatory mechanisms is being developed), and what academics assume about these democratic innovations. The main goal of this research is to help to understand the participatory reality beyond the theoretical debate and case study analysis, focusing on Southern Europe. The citizens’ preferences toward decision-making processes focus on the Spanish context. Through survey data analysis, we will analyse citizens’ preferences in terms of who makes the decisions, either citizens or politicians. These preferences will also be related to different attitudes: previous participatory experiences, the intensity of the attitudes toward different issues, the perception that one’s own ideas are part of a general consensus, and conflict aversion. In terms of participatory mechanisms, we will discuss what these innovations are like from a large-N perspective using a participatory mapping of five Southern European regions. The analysis will focus on different qualities paying attention to citizens’ participation, deliberation, and empowerment. Finally, after demarcating these participatory preferences and mechanisms, we will establish a debate between the empirical data and some academic debates and assumptions. The methodological debate about what kind of participatory mechanisms is collected through different large-N strategies will be addressed. Also, in a dialogue with some debates in the English-speaking academy, we will address the debate about the definition of the object of study (the tension between participatory and deliberative democracy), the characteristics of the actors promoting these innovations, the role of participatory professionals or the reproduction of the already existing inequalities among participants. We will check if the Southern European region presents some participatory specifities in comparison with the regions that have been more studied by the academy. Lastly, some implications will be pointed at, for example in relation to the current Spanish political context. The indignados movement opened a broad debate about the decision-making process, defending a “real democracy”. New successful candidacies like Podemos and Ganemos/Guanyem have incorporated participatory democracy into their discourses, proposals and practices. We will address the question of what the relation between this new socio-political context and the citizens’ preferences and participatory mechanisms analysed in this dissertation could be