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Characterizations of autism include multiple references to rigid or inflexible features, but the notion of rigidity itself has received little systematic discussion. In this paper we shed some light on the notion of rigidity in autism by identifying different facets of this phenomenon as discussed in the literature, such as fixed interests, insistence on sameness, inflexible adherence to routines, black-and-white mentality, intolerance of uncertainty, ritualized patterns of verbal and non-verbal behavior, literalism, and discomfort with change. Rigidity is typically approached in a disjointed fashion (i.e., facet by facet), although there are recent attempts at providing unifying explanations. Some of these attempts assume that the rigidity facets mainly relate to executive functioning: although such an approach is intuitively persuasive, we argue that there are equally plausible alternative explanations. We conclude by calling for more research on the different facets of rigidity and on how they cluster together in the autistic population, while suggesting some ways in which intervention could benefit from a finer-grained view of rigidity. All authors were supported by a BBVA Foundation Grant for Scientific Research Projects 2021 (RILITEA). The Foundation takes no responsibility for the opinions, statements and contents of this project, which are entirely the responsibility of its authors. AV and VP’s research was supported by the Agencia Estatal de Investigación and Ministry of Science and Innovation (grant number PID2021-122233OB-I00) and the Basque Government (grant number IT1537-22). VP’s research was supported by the Agencia Estatal de Investigación and Ministry of Science and Innovation (grant numbers PID2021-128950OB-I00 and IJC2020-043408-I. MJ’s research was supported by the Agencia Estatal de Investigación and Ministry of Science and Innovation (grant number PID2020-115052GA-I00) and a 2019 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (the Foundation takes no responsibility for the opinions, statements and contents of this project, which are entirely the responsibility of its authors).

To examine the equivalency of ECAS versions A, B, and C in an Irish cohort, and to examine potential practice effects, 236 healthy controls were recruited through the Irish ALS control database. One hundred and seventy-six (176) controls completed ECAS version A, B, or C. Separately, 60 controls completed all three versions (A–B–C), consecutively, four months apart. TOST analysis found that ECAS A was equivalent to ECAS B and C. ECAS B and C were not statistically equivalent, however the difference between them was minimal. Participants showed improvement in ECAS performance over time, indicative of practice effects. Significant improvement was observed from time 1 to 2, but not from time 2 to 3. We propose Irish specific reliable change index (RCI) scores that take into consideration practice effects and measurement error. These thresholds will help quantify clinically meaningful cognitive decline in ALS patients, leading to improved quality of care.

This study aims to explore the lived experience of informal caregivers of a person diagnosed with dementia during the acute phase of the Covid-19 pandemic using Interpretative Phenomenological Analysis.

Additional file 1: mRNA levels following overexpression and siRNA transfection.

We study whether incumbents facing uncontested elections channel public spending towards co-partisan officials more than is the case of incumbents that are worried about their chances of re-election. To do so, we draw on data detailing capital transfers allocated by Spanish regions to local governments during the period 1995-2007. Using a regression discontinuity design, we document strong and robust effects. We find that, on average, a mayor belonging to the same party as that of the regional president obtains nearly twice the amount in grants as is received by a mayor belonging to an opposition party. This effect is much greater for regional incumbents that won the previous election by a large margin, but it disappears in the case of highly competitive elections. The effects estimated by difference-in-differences are not so great but they point in the same direction. Overall, the results are consistent with predictions that regional incumbents focus on obtaining the most votes possible when elections are strongly contested, while they seek to increase the number of aligned mayors when their position at the ballot box is not vulnerable.

Ante nosotros se nos presenta una obra que elabora un profundo estudio acerca de una práctica nociva llevada a cabo en numerosos países del mundo y que supone una grave violación de derechos humanos. En este contexto, la aportación de la autora resulta especialmente grata, asimismo, el desarrollo de la obra nos aporta un conocimiento completo del marco legislativo y jurisprudencial que prohíbe esta práctica e, igualmente, nos incita a reflexionar sobre las lagunas normativas y sobre la necesidad de crear nuevas y mejores medidas que protejan, verdaderamente, los derechos de aquellas personas que ven el desarrollo de sus vidas determinadas por el matrimonio infantil. La obra se compone de cinco capítulos. En primer lugar, la autora comienza con una introducción donde ofrece un análisis del concepto de matrimonio infantil, precoz y forzado y, para ello, acude a diversos informes y resoluciones de organizaciones internacionales. Tras el desglose de cada uno de estos conceptos, llega a la conclusión de que todos ellos se encuentran relacionados entre sí y que, por consiguiente, siempre que sea un matrimonio infantil, es también un matrimonio forzado, ya que, un menor de dieciocho años carece de capacidad suficiente para dar consentimiento de contraer matrimonio.

Objective To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).Methods A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing.Results Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores.Conclusion ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems.

BACKGROUND: Cognitive impairment affects approximately 50% of people with amyotrophic lateral sclerosis (ALS). Research has indicated that impairment may worsen with disease progression. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was designed to measure neuropsychological functioning in ALS, with its alternate forms (ECAS-A, B, and C) allowing for serial assessment over time.OBJECTIVE: The aim of the present study was to establish reliable change scores for the alternate forms of the ECAS, and to explore practice effects and test-retest reliability of the ECAS's alternate forms.METHOD: Eighty healthy participants were recruited, with 57 completing two and 51 completing three assessments. Participants were administered alternate versions of the ECAS serially (A-B-C) at four-month intervals. Intra-class correlation analysis was employed to explore test-retest reliability, while analysis of variance was used to examine the presence of practice effects. Reliable change indices (RCI) and regression-based methods were utilized to establish change scores for the ECAS alternate forms.RESULTS: Test-retest reliability was excellent for ALS Specific, ALS Non-Specific, and ECAS Total scores of the combined ECAS A, B, and C (all > .90). No significant practice effects were observed over the three testing sessions. RCI and regression-based methods produced similar change scores.CONCLUSION: The alternate forms of the ECAS possess excellent test-retest reliability in a healthy control sample, with no significant practice effects. The use of conservative RCI scores is recommended. Therefore, a change of ≥8, ≥4, and ≥9 for ALS Specific, ALS Non-Specific, and ECAS Total score is required for reliable change.

Ante nosotros se nos presenta una obra que elabora un profundo estudio acerca de una práctica nociva llevada a cabo en numerosos países del mundo y que supone una grave violación de derechos humanos. En este contexto, la aportación de la autora resulta especialmente grata, asimismo, el desarrollo de la obra nos aporta un conocimiento completo del marco legislativo y jurisprudencial que prohíbe esta práctica e, igualmente, nos incita a reflexionar sobre las lagunas normativas y sobre la necesidad de crear nuevas y mejores medidas que protejan, verdaderamente, los derechos de aquellas personas que ven el desarrollo de sus vidas determinadas por el matrimonio infantil. La obra se compone de cinco capítulos. En primer lugar, la autora comienza con una introducción donde ofrece un análisis del concepto de matrimonio infantil, precoz y forzado y, para ello, acude a diversos informes y resoluciones de organizaciones internacionales. Tras el desglose de cada uno de estos conceptos, llega a la conclusión de que todos ellos se encuentran relacionados entre sí y que, por consiguiente, siempre que sea un matrimonio infantil, es también un matrimonio forzado, ya que, un menor de dieciocho años carece de capacidad suficiente para dar consentimiento de contraer matrimonio.

Objective: To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).Methods: A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing. Results: Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores. Conclusions: ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems.

We study whether incumbents facing uncontested elections channel public spending towards co‐partisan officials more than is the case of incumbents that are worried about their chances of re‐election. To do so, we draw on data detailing capital transfers allocated by Spanish regions to local governments during the period 1995‐2007. Using a regression discontinuity design, we document strong and robust effects. We find that, on average, a mayor belonging to the same party as that of the regional president obtains nearly twice the amount in grants as is received by a mayor belonging to an opposition party. This effect is much greater for regional incumbents that won the previous election by a large margin, but it disappears in the case of highly competitive elections. The effects estimated by difference‐in‐differences are not so great but they point in the same direction. Overall, the results are consistent with predictions that regional incumbents focus on obtaining the most votes possible when elections are strongly contested, while they seek to increase the number of aligned mayors when their position at the ballot box is not vulnerable.

Niemann-Pick disease type C (NPC) is a rare neurovisceral disease caused mainly by mutations in the NPC1 gene. This autosomal recessive lysosomal disorder is characterised by the defective lysosomal secretion of cholesterol and sphingolipids. No effective therapy exists for the disease. We previously described a deep intronic point mutation (c.1554-1009 G > A) in NPC1 that generated a pseudoexon, which could be corrected at the cellular level using antisense oligonucleotides. Here, we describe the generation of two mouse models bearing this mutation, one in homozygosity and the other in compound heterozygosity with the c.1920delG mutation. Both the homozygotes for the c.1554-1009 G > A mutation and the compound heterozygotes recapitulated the hallmarks of NPC. Lipid analysis revealed accumulation of cholesterol in the liver and sphingolipids in the brain, with both types of transgenic mice displaying tremor and ataxia at 7-8 weeks of age. Behavioural tests showed motor impairment, hyperactivity, reduced anxiety-like behaviour and impaired learning and memory performances, features consistent with those reported previously in NPC animal models and human patients. These mutant mice, the first NPC models bearing a pseudoexon-generating mutation, could be suitable for assessing the efficacy of specific splicing-targeted therapeutic strategies against NPC. © The Author(s) 2017., The authors declare no competing financial interests. This study was partly funded by grants from the Spanish Ministry of Science and Innovation (SAF2011-25431, SAF2013-49129-C2-1-R and SAF2014-56562-R) and from the Catalan Government (2014SGR/932 and SGR2014/1125), as well as the Addi and Cassi Fund. We are particularly grateful for the support from the Addi and Cassi Fund, who also provided the heterozygous mice. The Centre for Genomic Regulation has received support as a Severo Ochoa Centre of Excellence SEV- 2012–0208. We thank Alexandre Garcia for technical assistance. The authors are also grateful for the support from the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), which is an initiative of the ISCIII. MGG was supported by a grant from the University of Barcelona (APIF).

We study whether incumbents facing uncontested elections channel public spending towards co‐partisan officials more than is the case of incumbents that are worried about their chances of re‐election. To do so, we draw on data detailing capital transfers allocated by Spanish regions to local governments during the period 1995‐2007. Using a regression discontinuity design, we document strong and robust effects. We find that, on average, a mayor belonging to the same party as that of the regional president obtains nearly twice the amount in grants as is received by a mayor belonging to an opposition party. This effect is much greater for regional incumbents that won the previous election by a large margin, but it disappears in the case of highly competitive elections. The effects estimated by difference‐in‐differences are not so great but they point in the same direction. Overall, the results are consistent with predictions that regional incumbents focus on obtaining the most votes possible when elections are strongly contested, while they seek to increase the number of aligned mayors when their position at the ballot box is not vulnerable.

This paper studies the relationship between party discipline and discretionary spending with theory and data. We propose a theoretical model in which a politician faces a conflict between her constituents' interests and the party line. Party loyalty is electorally costly for the politician and is therefore rewarded by the party leader with greater amounts of discretionary spending allocated to the politician's constituency. The more intense the conflict between the voters' and the party's interests, the more grants the district receives. Using panel data on party discipline in the U.S. House of Representatives and federal grants to congressional districts between 1984 and 2010, we provide evidence that districts represented by loyal legislators receive greater amounts of discretionary spending. This effect holds only for legislators in the majority party, who may enjoy a legislative advantage. Districts represented by loyal legislators who face a greater conflict of interest between following the party and serving their constituents (e.g., Republican legislators representing liberal-leaning districts) are rewarded to a larger extent.

A inicios del siglo XXI, se puede observar como se ha creado una codependencia entre el cine independiente americano y la industria de Hollywood, por lo que el objetivo de esta tesis ha sido investigar si siguen persistiendo algunos elementos esenciales de la narrativa clásica que han permitido a ciertas películas independientes ser fácilmente absorbidas y distribuidas por Hollywood. A través de una perspectiva neurocientífica particularmente centrada en la psicología cognitiva y partiendo de una base intrínsecamente vinculada a la narratología, hemos buscado aquellos elementos claves en el procesamiento emocional y cognitivo del cerebro, para comprender cuáles son esos componentes fundamentales de la narrativa clásica que han pervivido escondidos bajo las complejas mecánicas narrativas de películas de algunos de los autores independientes americanos contemporáneos (Tarantino, Jonze, Lynch, Linklater, González Iñárritu, Nolan...)., A inicis del segle XXI, es pot observar que s'ha creat una codependència entre el cinema independent americà i la indústria de Hollywood, de tal manera que l'objectiu d'aquesta tesi ha estat investigar si segueixen persistint alguns elements essencials de la narrativa clàssica que han permès a certes pel•lícules independents ser fàcilment absorbides i distribuïdes per Hollywood. A través d'una perspectiva neurocientífica particularment centrada en la psicologia cognitiva i partint d'una base intrínsecament vinculada a la narratologia, hem buscat aquells elements claus en el processament emocional i cognitiu del cervell, per comprendre quins són aquests components fonamentals de la narrativa clàssica que han perviscut amagats sota les complexes mecàniques narratives de pel•lícules d'alguns dels autors independents americans contemporanis (Tarantino, Jonze, Lynch, Linklater, González Iñárritu, Nolan...)., At the beginning of the 21st century we can see how a co-dependency between independent American cinema and the Hollywood film industry has been created. Thus, the aim of this thesis is to investigate if some essential elements of classical narrative persist which have allowed certain independent films to be easily absorbed and distributed by Hollywood. From a neuroscientific perspective, particularly focused on cognitive psychology, and from a starting point intrinsically tied to narratology, key elements in the emotional and cognitive processing of the brain have been researched in order to understand what are the essentials of classical narrative which have survived hidden under the complex narrative mechanics of some contemporary American independent authors' films (Tarantino, Jonze, Lynch, Linklater, González Iñárritu, Nolan...).

Lysosomal storage disorders (LSDs) are a group of more than 50 different genetic disorders due to the lack of degradation of substrates within lysosomes. Most of them are caused by mutations in genes coding for lysosomal hydrolases. LSDs are mainly inherited in an autosomal recessive manner. Although in the last 25 years there has been much effort and progress to develop therapies aiming the correction of metabolic defects for these diseases, yet there is no effective therapy for many of them, and patients are exclusively treated with supportive care. For several non-neurological LSDs, enzyme replacement therapy may be an option. However, this approach is not efficient, at the moment, for neurological patients. Thus, new therapeutic approaches need to be developed. One of these approaches is the use of drugs that are able to produce a read-through of premature stop codons. One advantage of this strategy is that, if successful, it can be applied to any disease, provided that the molecular cause is a nonsense mutation. The most extensively studied approach involves read-through by drugs affecting the ribosome-decoding site. Niemann-Pick A/B (NPA/B) and Niemann-Pick C (NPC) are two rare inherited monogenic diseases. Although initially were defined as types of the same disease, subsequently they have been considered independent diseases due to the fact that they have different biochemical and molecular features. NPA/B disease is caused by mutations in the SMPD1 gene, localized in chromosome 11, which codes for the enzyme acid sphingomyelinase, a soluble lysosome hydrolase. NPC disease is caused by mutations in the NPC1 gene, localized in chromosome 18, which codes for a lysosomal membrane protein, involved in cholesterol transport. NPC disease also may be caused by mutations in the NPC2 gene, localized in chromosome 14, which codes for a lysosomal soluble protein, involved in cholesterol transport too. The abnormal action of these proteins in patients promotes the accumulation of lipids, which differ in each disease, inside the lysosomes, causing their dysfunction. This thesis makes contributions to the field of LSDs study. Various aspects have been addressed: therapeutic approaches have been tested as a first step in the achievement of a successful therapy for those LSDs bearing nonsense mutations. Important steps in the generation of a new cellular model for NPA/B have been achieved. This model would be helpful to understand the molecular processes that contribute to the development of this pathology and would be a valuable tool for the search of successful treatments. Finally, two new mouse models for NPC have been generated and characterized while one dies few days after birth, the other mimics the main characteristics of the disease and will be useful to probe specific treatments., Las enfermedades de acúmulo lisosómico (LSDs) son un grupo de más de 50 trastornos genéticos diferentes, debido a la falta de degradación de sustratos dentro de los lisosomas. La mayoría de ellas están causadas por mutaciones en los genes que codifican para las hidrolasas lisosomales. Las LSDs se heredan principalmente de forma autosómica recesiva. Aunque en los últimos 25 años ha habido un gran esfuerzo y progreso para desarrollar terapias dirigidas a la corrección de los defectos metabólicos de estas enfermedades, sin embargo, no hay un tratamiento eficaz para muchas de ellas, y los pacientes son tratados exclusivamente con terapias de soporte. Para muchas LSDs sin afectación neurológica, la terapia de reemplazo enzimático puede ser una opción. Sin embargo, este enfoque no es eficiente por el momento para los pacientes con afectación neurológica. Por lo tanto, nuevos aproximaciones terapéuticas han de ser desarrolladas. Una de estas aproximaciones es el uso de fármacos que son capaces de proseguir la lectura a través de los codones de parada prematuros. La ventaja de esta estrategia es que, si tiene éxito, se puede aplicar a cualquier enfermedad cuya causa molecular sea una mutación sin sentido. Niemann-Pick A/B (NPA/B) y Niemann-Pick C (NPC) son dos enfermedades raras, monogénicas y hereditarias. Aunque inicialmente se definieron como tipos de la misma enfermedad, posteriormente se han considerado enfermedades independientes debido al hecho de que tienen diferentes características bioquímicas y moleculares. La enfermedad de NPA/B está causada por mutaciones en el gen SMPD1, localizado en el cromosoma 11, que codifica para la enzima esfingomielinasa ácida, una hidrolasa soluble lisosomal. La enfermedad de NPC está causada por mutaciones en el gen NPC1, localizado en el cromosoma 18, que codifica para una proteína de membrana lisosomal, dicha proteína participa en el transporte del colesterol. La enfermedad de NPC también puede estar causada por mutaciones en el gen NPC2, localizado en el cromosoma 14, que codifica para una proteína soluble lisosomal, que también participa en el transporte del colesterol. La acción anormal de estas proteínas en los pacientes promueve la acumulación de lípidos, diferentes en cada enfermedad, el interior de los lisosomas, provocando su disfunción. Esta tesis realiza contribuciones en el campo de estudio de las LSDs. Se han abordado diversos aspectos. Varias aproximaciones terapéuticas han sido probadas como un primer paso en el logro de una terapia satisfactoria para aquellas LSDs causadas por mutaciones sin sentido. Se han alcanzado importantes avances en la generación de un nuevo modelo celular para NPA/B. Este modelo podría ser útil para entender los procesos moleculares que contribuyen al desarrollo de dicha patología y podría ser una valiosa herramienta para la búsqueda de tratamientos. Por último, se han generado dos nuevos modelos de ratón de NPC y se han caracterizado. Uno de ellos muere pocos días después de su nacimiento, el otro imita las principales características de la enfermedad y podría ser útil para la investigación de tratamientos específicos.

Treball Final del Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes. Codi: SAP139. Curs: 2013-2014 Aquest Treball Final de Màster conté la investigació realitzada durant la meva estada a l’IES Bovalar de Castelló de la Plana, en el qual s’ha implementat la unitat didàctica “Els ésservs vius més senzills” als alumnes de primer curs d’Educació Secundària Obligatòria (ESO) mitjançant un procés d’ensenyament-aprenentatge significatiu basat en la participació activa.

La teoria del contracte social o contractualisme és una teoria política que explica l'origen i el propòsit de l'estat i del drets civils que hi van lligats. La idea bàsica del contractualisme clàssic és que l'estat es forma a través d'un acord –real o fictici– entre els membres d'un determinat grup que es troben en l'estat de naturalesa, mitjançant el qual s'estableixen una sèrie de drets i deures entre l'estat i la societat civil o els ciutadans. En aquest article presentarem la teoria contractualista de John Locke i la crítica feminista que la teòrica política Carole Pateman fa als fonaments d'aquesta teoria. Pateman identifica tres contradiccions en la teoria de Locke que mostren l'absència d'una explicació per a la situació de les dones en la teoria i proposa explicar aquesta situació mitjançant la teoria del contracte sexual. Veurem les implicacions d'aquesta crítica per a la teoria de Locke i per a la nostra actualitat política i social, i examinaren possibles objeccions que se li poden fer., The social contract theory or contractualism is a political theory that explains the origin and purpose of the state and the civil rights tied to it. The basic idea of classical contractualism is that the state is formed through an agreement –real or fictional– among the members of a certain group in the state of nature, where a set of rights and duties are established between the state and the civil society or the citizens. In this article I will present John Locke’s contractualist theory and the feminist critique that the political theorist Carole Pateman raises against the foundations of this theory. Pateman identifies three contradictions in Locke’s theory that show the absence of an explanation of the situation of women in the theory and she proposes to explain this situation through the theory of the sexual contract, a previous contract to the social contract on which the social contract is based. I will then draw the implications of this critique for the theory and for our present time and some possible objections will be discussed.

This paper examines whether the distribution of public employment affects the electoral support for the incumbent government that allocates jobs. To do this we focus on the Spanish Plan for Rural Employment (PER), a program of temporary public employment introduced by the central government in two lagging regions. We evaluate voters’ responsiveness to this policy using municipal-level electoral data and employing an estimator that combines propensity score matching with a difference-indifferences strategy (Heckman et al., Econometrica 65 (1998) 2). We show that the average treatment effect on the treated is a 2 percentage-point increase of the vote share for the ruling party at general elections and we also find evidence of an increase in electoral participation.

[eng] Nevertheless, this peculiarity of the Spanish political system did not eliminate the incentives for governments to use pork-barrel policies. On the one hand, despite electoral results being centrally planned, Madrid’s limited capacity to intervene in society implied that elections outcomes had to be negotiated with the local elites, who demanded compensations (such as public funds) for their districts’ electoral support. On the other hand, the two-party system may be seen as a duopoly regime, in which opposition districts were actually those which did not respect the alternation system, and voted for either the dynastic party that was going to lose the election or for a third political force. Restoration Spain provides therefore an interesting case of a political system in which a dominating duopoly used pork-barrel strategies to persuade the electorate to change the sign of their votes in every electoral call. In this setting, two kinds of political economy models may be relevant to analyze pork-barrel in Restoration Spain. One can see the Spanish Restoration as a semi-democratic regime ruled by a duopoly that furthered its political goals by using the geographical allocation of public resources. More specifically, governments showered resources on those districts that were loyal to the alternation system, and starved the rebellious ones. This would be similar to a typical semi-democratic system, although one in which the hegemonic political force was not a single party but a duopoly. On the other hand, given the importance of local elites, non-partisan motivations may also offer a partial description of the political process. In non-partisan models, the distribution of public funds reflects the influence and ability of individual MPs, who compete for administrative resources to reinforce their links with their electorates. Indeed, bringing home the pork increases MPs’ reputation with local elites (Levitt and Snyder, 1995; Levitt and Poterba, 1999; Milligan and Smart, 2005).

L'objectiu principal d'aquest article és presentar el concepte d'intencionalitat en la fenomenologia de Husserl, en tant que descriu una de les principals característiques de l'experiència conscient: el seu estar dirigida a alguna cosa o el seu ser sobre alguna cosa. Husserl hereta una discussió sobre representacions sense objecte de l'escola de Brentano i en fa una primera aproximació a l'obra inacabada Objectes Intencionals (1894). És a les Investigacions Lògiques (1900/1901) on Husserl desenvolupa una primera teoria de la intencionalitat, a partir de la tematització de les vivències intencionals, o actes, que tenen uns continguts intencionals i uns objectes intencionals, els quals queden fora del corrent de consciència i de la descripció fenomenològica. Aquesta teoria és modificada a partir de la introducció del mètode de la reducció transcendental que permet a Husserl la formulació d'una segona teoria de la intencionalitat a Idees I (1913). Segons aquesta teoria, l'objecte intencional passa a formar part del corrent de vivències i, així, pot ser descrit fenomenològicament. Es tematitza sota la noció de «noema», que és el correlat objectiu de la «noesi». El tipus d'intencionalitat desenvolupada en aquestes obres és la intencionalitat objectivant, que Husserl complementa amb la tematització de la intencionalitat impressional, pròpia de la consciència del món «predonat» i de la relació «prereflexiva» del subjecte amb si mateix. Aquest tipus d'intencionalitat es tematitza sobretot a partir de les anàlisis sobre el subjecte carnal i la consciència del temps, en l'etapa husserliana de la fenomenologia genètica. Finalitzem l'article amb una breu indicació de la recepció del concepte per part de l'escola fenomenològica posterior i de la filosofia analítica., The concept of intentionality is a central concept in the phenomenological school, as it describes one of the main features of conscious experience: its being directed at something or its being about something. Husserl inherits a discussion over representations without object from Brentano’s school and he first approaches the topic in the unfinished work Intentional Objects (1894). It is in the Logical Investigations (1900/1901) where Husserl develops a first theory of intentionality, thematizing intentional experiences, or acts, that have intentional contents and intentional objects, which are left outside the stream of consciousness and the phenomenological description. This theory is modified with the introduction of the method of the transcendental reduction, that allowsHusserl to formulate the second theory of intentionality in Ideas I (1913). According to this theory, the intentional object becomes part of the stream of consciousness and thus can be phenomenologically described. It is thematized under the notion of «noema», that is the objective correlate of the «noesis». The kind of intentionality developed in these works is objectifying intentionality, which Husserl complements with the thematization of impressional intentionality, peculiar to the consciousness of the «pregiven» world and to the «prereflexive» relation of the subject with itself. This kind of intentionality is thematized with the analysis of the embodied subject and time consciousness, in the husserlian stage of genetic phenomenology. We finish the article with a brief indication of the reception of the concept in the phenomenological school after Husserl and in the analytic philosophy.

The aim of this dissertation is to provide a non-reductive account of cognitive phenomenology and the experience of thinking. The nature of conscious thought is an issue that has occupied philosophers since ancient times, and still many questions in this domain remain unanswered. One of them is the relation between thought and experience or phenomenal consciousness, in the particular way explored in this thesis: when we undergo a certain cognitive mental episode, should we recognize an experience like our other sensory, perceptual, or emotional experiences or should we rather recognize a very different sort of experience? Experiences are usually characterized by a phenomenal character or what-it-is-likeness for the subject to undergo them, which is usually taken as the mark of phenomenal consciousness and which, for mainstream contemporary philosophy of mind, has been limited to sensory and perceptual experiences, or even to emotional experiences. My general thesis is that conscious thought should be included in the domain of phenomenal consciousness and that there is an experience of thinking or conscious thought with a specific phenomenal character, namely, a phenomenal character that cannot be reduced to other non-cognitive kinds of phenomenologies. The thesis has three main parts, which are divided in several chapters. In the first part, Introduction, I present the basic elements to be able to start the investigation. I firstly clarify the relevant issues involved in the debate (Chapter 1), I justify the terminology chosen and I present the main views and a brief history of the problem. I then propose a way to approach the experience of thinking from a methodological point of view (Chapter 2), through a study of some methodological problems in philosophy and psychology, mainly related to introspection and introspective evidence. In the second part of the thesis, Main Arguments in Cognitive Phenomenology, I defend my non-reductive view with several arguments. I present the obvious argument (Chapter 3) for the conclusion that conscious thoughts have phenomenal properties and I resist some putative cases against the argument. I then present my version of the phenomenal argument (Chapter 4), which shows that there is a phenomenal change between two cognitive experiences contrasted and that this change cannot be explained by appealing to the sensory/emotional elements that by hypothesis remain constant. My presentation of this argument is complemented by a defense against some restrictivist views (Chapter 5). I then present the epistemic argument, which claims that we have introspective immediate knowledge of the kind of mental episode we are in (and of different cognitive atittudes), and that this would not be possible unless cognitive episodes have a specific cognitive phenomenology (Chapter 6). I finally consider another argument, the ontological argument, that might support the reductionist view , but I argue that it does not succeed (Chapter 7). In the third part of the thesis, The Specification of Cognitive Phenomenology, and as a further step in the discussion, I propose a specification of cognitive phenomenology in relation to intentionality and its two main components in conscious thought, cognitive content (Chapter 8) and cognitive attitude (Chapter 9). This proposal provides us with a way of determining similarities and differences in cognitive phenomenology that result in different experiential kinds and different types of conscious thought in virtue of their phenomenology. Moreover, it offers an answer to the question of the relation of determination between both components and their phenomenal character. This dissertation questions well some well-established assumptions in philosophy of mind and consciousness studies: (i) it implies a comprehension of phenomenal consciousness as including cognition, (ii) it rejects the assymetry between sensory/perceptual experience and cognitive one (regarding temporal structure and specification attempts) and (iii) it questions separatist positions between intentionality and phenomenal consciousness. It also opens new research in relation to other philosophical topics and empirical studies and it contributes to the examination of two research fields (consciousness and cognition) that have normally been investigated separately., L’objectiu d’aquesta tesi és presentar una teoria no reductivista de la fenomenologia cognitiva i de l’experiència del pensament. La naturalesa del pensament conscient és una qüestió que ha preocupat als filòsofs des de l’antiguitat i un àmbit on encara trobem moltes qüestions que no tenen resposta. Una d’elles és la relació entre el pensament i l’experiència o la consciencia fenomènica, en el sentit particular que exploro en aquesta tesi: quan tenim una experiència d’un cert episodi mental cognitiu, es tracta d’una experiència com les altres experiències sensorials, perceptives o emocionals, o bé es tracta d’un tipus molt diferent d’experiència? Les experiències normalment es caracteritzen per tenir un caràcter fenomènic o un “com a què és” (what it is like) pel subjecte tenir aquestes experiències, que es prèn com la marca de la consciència fenomènica i que, en filosofia contemporània de la ment, generalment es restringeix a les experiències sensorials, perceptives o, fins i tot, emocionals. La tesi general que defenso és que el pensament conscient ha de ser inclòs en l’extensió de la consciència fenomènica i que existeix una experiència de pensament conscient amb un caràcter fenomènic específic, és a dir, un caràcter fenomènic que no es pot reduir a altres tipus de fenomenologies. Aquesta conclusió general qüestiona alguns supòsits ben establerts en filosofia de la ment i estudis sobre consciència, i així obre la porta a noves investigacions en aquesta direcció. Per tal de defensar aquesta teoria no reductivista, primerament clarifico les qüestions rellevants en el debat i examino com hem d’aproximar-nos a l’experiència del pensament (Capítols 1 i 2). En segon lloc, presento una sèrie d’arguments a favor de la meva tesi (Capítols 3, 4 i 6) i argumento en contra d’estratègies restrictivistes (Capítols 5 i 7). Finalment, com a un pas més en la discussió, proposo una especificació de la fenomenologia cognitiva en relació a la intencionalitat i els seus dos components principals en el pensament conscient, el contingut cognitiu (Capítol 8) i l’actitud cognitiva (Capítol 9), oferint respostes a la qüestió de la relació de determinació entre ambdós components i el seu caràcter fenomènic.

This paper analyzes the effects of parliamentary representation on road infrastructure expenditure during the Spanish Restoration. Using a panel dataset of Spanish provinces in 1880-1914 we find that the allocation of administrative resources among provinces depended both on the delegation characteristics (such as the share of MPs with party leadership positions, and their degree of electoral independence), and the regime"s global search for stability. These results point to the importance of electoral dynamics within semi-democratic political systems, and offer an example of the influence of government tactics on infrastructure allocation.

El presente trabajo se centra en el estudio de algunos aspectos de la agresividad del perro y del gato. El estudio de la agresividad canina y felina es importante por varios motivos. En primer lugar, los problemas de agresividad del perro y del gato son muy frecuentes y, al menos en los centros de referencia, son el principal problema de comportamiento. La agresividad del perro y del gato también es importante, porque constituye una de las principales causas de eutanasia y abandono de perros y gatos sanos. A las razones citadas anteriormente debemos añadir que la mayoría de los problemas de agresividad afectan negativamente al bienestar del animal ya que estimulan los centros nerviosos responsables del castigo, es decir, generan un estado afectivo negativo y, además, van acompañadas de una respuesta de estrés. El primer objetivo del trabajo era estudiar la epidemiología de los problemas de comportamiento del gato, incluyendo su prevalencia y los factores de riesgo relativos a la raza, sexo, estado reproductor, procedencia, acceso al exterior y número de gatos que conviven en un mismo domicilio. En este sentido se obtuvo que los problemas de agresividad y los problemas de eliminación inadecuada suponen la mayoría de las consultas de etología clínica felina recibidas en el Servicio de Etología de la Fundació Hospital Clínic Veterinari. Los problemas de agresividad entre gatos son más frecuentes que los problemas de agresividad hacia las personas. En relación a los problemas de agresividad hacia las personas, los miembros de la familia son el blanco más frecuente. Dentro de la categoría de problemas de eliminación inadecuada, los más frecuentes son los de micción inadecuada, seguidos por los problemas que afectan tanto a la micción como a la defecación y finalmente por los que afectan a la defecación. Los gatos de raza Persa presentan significativamente más problemas de eliminación inadecuada que las otras razas. En la categoría de problemas de agresividad, los dos diagnósticos más comunes son la agresividad por falta de tolerancia a la manipulación y la agresividad por juego. En la categoría de problemas de eliminación inadecuada, el diagnóstico más común son los problemas de aversión a la bandeja. Estos resultados indican que el desconocimiento de los propietarios acerca del comportamiento normal del gato contribuye en muy buena medida al desarrollo de problemas de comportamiento en esta especie. Según la base de datos del Servicio de Etología, los gatos que proceden de tiendas, que no tienen acceso al exterior y que no conviven con otros gatos, presentan significativamente más problemas de comportamiento. El primero de estos resultados sugiere que una socialización deficiente es un factor importante en el desarrollo de los problemas de comportamiento del gato. Las gatas no castradas presentan más problemas de agresividad que las castradas. No hay diferencias entre machos y hembras en la prevalencia de problemas de comportamiento. Estos resultados indican que los factores hormonales desempeñan un papel diferente en la agresividad del gato y la del perro. El segundo objetivo del trabajo era estudiar el estímulo desencadenante, el blanco alternativo, la postura corporal y los factores de riesgo de la agresividad redirigida del gato. Según nuestra base de datos, el 9% de los casos de comportamiento agresivo del gato analizados son compatibles con un diagnóstico de agresividad redirigida. Los sonidos intensos y las interacciones con otros gatos son los detonantes más comunes. Los propietarios y otros gatos de la vivienda son los blancos alternativos más frecuentes. En la mayoría de episodios de agresividad redirigida el gato adopta una postura defensiva. Los gatos que muestran agresividad redirigida no suelen tener acceso al exterior y presentan frecuentemente fobia a los ruidos. Estos resultados sugieren que el mecanismo responsable de la agresividad redirigida del gato está relacionado con la respuesta de miedo y estrés. El tercer objetivo era estudiar la epidemiología del comportamiento agresivo de los perros de raza Cocker Spaniel Inglés, incluyendo su prevalencia y los factores de riesgo relativos al sexo, estado reproductor, procedencia y color de la capa. Según la base de datos del Servicio de Etología de la Fundació Hospital Clínic Veterinari, el Cocker Spaniel Inglés es la raza que presenta más problemas de agresividad. La agresividad hacia la familia es el problema que se presenta con más frecuencia en esta raza. Los machos presentan significativamente más problemas de agresividad que las hembras y los individuos de capa dorada presentan más problemas de agresividad que los individuos de otras capas. Este último resultado sugiere que el Cocker Spaniel Inglés es un buen modelo para estudiar la relación entre el color de la capa y el temperamento en los animales. El cuarto objetivo era caracterizar el comportamiento agresivo del Cocker Spaniel Inglés para determinar si esta raza presenta una mayor frecuencia de agresividad impulsiva que otras razas de perros. Al comparar una población de perros de raza Cocker Spaniel Inglés con una población de perros de otras razas, ambas con problemas de agresividad, se observa que la impulsividad es una característica más frecuente en la población de Cockers El quinto objetivo era determinar la concentración sérica de serotonina en perros agresivos de raza Cocker Spaniel Inglés como posible mecanismo responsable de la impulsividad en la conducta agresiva de esta raza. La concentración sérica de serotonina es inferior en perros agresivos de raza Cocker Spaniel Inglés que en perros agresivos de otras razas. Los dos resultados anteriores indican que el Cocker Spaniel Inglés podría ser un buen modelo para estudiar los mecanismos fisiológicos responsables de la impulsividad., The present work is focused in the study of canine and feline aggression. The study of canine and feline aggression is important for several reasons. First, these problems are very common, and at least in referral behavior services, they are the main owner’s complaint. The canine and feline aggression is also important because represents one of the main causes of euthanasia and relinquishment of healthy dogs and cats. Moreover, the majority of aggression problems could affect the animal’s well-being since there is evidence that aggressive behavior may involve a stress response. The first objective was to study the epidemiology of feline behaviour problems, including their prevalence and the risk factors related to the breed, sex, neutered status, origin of the cat, the possibility to go outside and the number of cats that live in the same household. According to the results, the aggressive and elimination problems represent the majority of feline cases attended to the Animal Behaviour Services at the Barcelona School of Veterinary Medicine. The intercat aggression problems are more frequent that the aggression towards people. In relation to the aggression towards people, the family members are the most common target. In the category of elimination problems, most of the elimination cases involved urination, followed by urination and defecation, and defecation. Persian cats showed elimination problems out the litter box more frequently than other breeds. The most frequent diagnosis is litterbox aversion. In the category of aggression problems, most cases meet the criteria of play related aggression and petting related aggression. These results point out that the lack of knowledge of the owners about the normal behaviour contributes to the development of some of behavior problems in this specie. According the caseload of Animal Behaviour Services, cats purchased from petshops, without access to the outside, and living alone, show more behavior problems. First result suggests that an inadequate socialization may be an important factor in the development of feline behaviours problems. The intact females show more aggression problems that neutered ones. In relation to the prevalence of behavior problems, there are no differences between males and females. These results suggest that the hormones may play a different role in the canine and feline aggression. The second objective was to identify inciting causes, alternative targets, and risk factors associated with redirected aggression in cats. According our caseload, 9% of the aggressive cases are reported to have displayed behaviour compatible with redirected aggression. The most common inciting stimuli are loud noises followed by interactions with other cats. The most commonly reported alternative target is the owner, followed by another cat living in the same household. In the majority of episodes, the owner describes a defensive posture. Cats with redirected aggression are significantly more likely to have sound phobia and less likely to be outdoor. These results suggest that the physiologic and functional bases of redirected aggression may be related to fear and stress. The third objective was to study the aggressive behavior of English cocker spaniel (ECS) presented for aggression problems to the Animal Behaviour Services at the Barcelona School of Veterinary Medicine, including the prevalence and the risk factors related to the sex, neutering status, source from which the dog was obtained and coat color. According our caseload, English cocker spaniel is the breed that shows more aggression problems. Owner directed aggression is the most commonly reported problem in this breed. Males show more frequently aggression problems than females, and the golden coat cockers show are more common in the group of aggressive ECS than in the group of non-aggressive ECS. This result suggests that this breed coud be a good model to understand the relationship between the coat colour and the behavior of the animals. The fourth objective was to find out if this breed shows more frequently impulsiveness than other breeds. A population of aggressive ECS was compare with a population of aggressive dogs of other breeds. ECSs show impulsiveness more frequently than other breeds. The fifth objective was to analyze possible differences in serum serotonin levels between aggressive ECSs and aggressive dogs of other breeds as a mechanism to understand the impulsiveness. ECSs have lower levels of serum serotonin than aggressive dogs of other breeds. The last two results suggest that the ECS may be a good model to study the physiologic mechanisms underlying impulsiveness.

Las discusiones sobre la intencionalidad en la Filosofía de la mente con-temporánea se plantean en un marco un tanto ajeno al de la Fenomenología, bajo la suposición, de modo bastante generalizado, de que hay una separación entre in-tencionalidad y c

Ante la queja de un exceso de destructividad en el perro, muy común por parte de los propietarios, el veterinario debe poder realizar un diagnóstico diferencial para determinar la causa del problema. En muchos casos el clínico puede ofrecer directamente al cliente unas pautas de tratamiento o, si es preciso, consultar con el especialista. En primer lugar se debe tener en cuenta que no todas las conductas indeseables, por muy molestas que le resulten al propietario, se deben considerar necesariamente patológicas: en muchos casos se trata de la expresión llevada al extremo de comportamientos naturales en una determinada especie. La destructividad en el perro, por ejemplo, puede ser debida a una manifestación excesiva de la conducta exploratoria, que por otro lado se considera normal en un animal joven. Además de la edad, otros factores intrínsecos influyen sobre esta tendencia, como la raza o el sexo. Por otra parte, una destructividad excesiva puede ser la forma en la que se presenta un problema de hiperactividad que, cuando no es patológica o primaria (se denomina hiperquinesis, pero es muy esporádica) puede ser el resultado de errores de manejo por parte del propietario, o bien derivar de un ambiente muy pobre en estímulos. Además, puede que los destrozos aparezcan como resultado de una reacción de estrés cada vez que el perro se queda solo. Cuando se presenta de esta forma, la destructividad es la manifestación de un trastorno de la conducta llamado ansiedad por separación, que presenta entre sus síntomas principales vocalizaciones excesivas, falta de control sobre las eliminaciones y una marcada tendencia a destrozar objetos de la casa, rascar puertas y paredes en ausencia de los propietarios. Finalmente, los destrozos pueden ser secundarios a un problema de fobia a ruidos: el perro intenta hacer frente al miedo que experimenta destrozando objetos en el intento de escaparse, esconderse y así disminuir la ansiedad. En el esquema que ofrecemos a continuación quedan resumidos los factores principales que intervienen en la aparición de un comportamiento destructivo en el perro.

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.

[spa] En este trabajo examinamos si, en la asignación de transferencias, los gobernantes regionales discriminan a favor de los gobiernos locales controlados por el mismo partido político, y si las perspectivas electorales de los gobiernos locales mejoran si están políticamente alineados con el gobierno regional. Con una nueva base de datos que considera 3.000 municipios españoles durante el período 2000-07 y un diseño de discontinuidad en la regresión, documentamos un efecto robusto de importante magnitud: en elecciones ajustadas, los municipios alineados con el gobierno regional reciben, en media, un 83% más de transferencias per cápita y su gobernante obtiene un 10% más de votos en las elecciones locales. También demostramos que el efecto de la alineación política es mayor: (i) si las elecciones regionales y locales se celebran el mismo día, (ii) en regiones donde las elecciones regionales son menos competidas, y (iii) en regiones con más recursos presupuestarios., [eng] We examine whether state-level incumbents discriminate in the allocation of transfers in favour of local governments controlled by co-partisans, and whether the electoral prospects of local incumbents improve when they are aligned with the state incumbent. Using a new database covering around 3,000 Spanish municipalities during the period 2000-07 and a Regression Discontinuity design, we document a very strong and robust effect: in close races, municipalities aligned with the regional government obtain on average 83% more per capita transfers and their incumbents gain 10% more votes at the local elections. We also show that the effect of alignment is stronger: (i) when regional and local elections are held on the same day, (ii) in regions with less competitive regional elections, and (ii) in regions with more budget resources.

Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs could provide a therapeutic option for any disease caused by this type of mutation. Geneticin (G418) and gentamicin were among the first to be described. Novel compounds have been generated, but only a few have shown improved results. PTC124 is the only compound to have reached clinical trials. Here we first investigated the readthrough effects of gentamicin on fibroblasts from one patient with Sanfilippo B, one with Sanfilippo C, and one with Maro- teaux-Lamy. We found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2 - 3 folds and that the amount of this enzyme within the lysosomes was also increased, after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did not respond to gentamicin, the treatments were extended with the use of geneticin and five non-aminogly- coside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough compounds (RTCs). No recovery was observed at the enzyme activity level. However, mRNA recovery was observed in both cases, nearly a two-fold increase for Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C cells with RTC14 and PTC124. Afterwards, some of the products were assessed through in vitro analyses for seven mutations in genes responsible for those diseases and, also, for Niemann-Pick A/B. Using the coupled tran- scription/translation system (TNT), the best results were obtained for SMPD1 mutations with G418, reaching a 35% recovery at 0.25 μ g/ml, for the p.W168X mutation. The use of COS cells transfected with mutant cDNAs gave positive results for most of the mutations with some of the drugs, although to a different extent. The higher enzyme activity recovery, of around two-fold increase, was found for gentamicin on the ARSB p.W146X mutation. Our results are promising and consistent with those of other groups. Further studies of novelcompounds are necessary to find those with more consistent efficacy and fewer toxic effects

This paper examines the extent to which the public allocation of road investment was influenced by political and electoral goals during the Spanish Restoration (1874-1923). More precisely, we seek to identify those provinces that were favoured with higher road construction expenditure and whether tactical strategies adopted by the political parties varied over time to reflect increasing political competition. In so doing, this paper combines concepts from three strands of literature: legislative pork-barrel; clientelism and machine politics; and electoral competition. Our main empirical finding for a panel of Spain’s provinces suggests that constituencies electing a higher proportion of deputies from minority or opposition parties were initially punished through lower levels of road investment but that, by the end of the period, they were instead favoured with more resources than the rest. In addition, we also observe that senior deputies who had been ministers in previous administrations were more capable than other politicians of attracting resources to their constituencies.

We examine whether state-level incumbents discriminate in the allocation of transfers in favour of local governments controlled by co-partisans, and whether the electoral prospects of local incumbents improve when they are aligned with the State incumbent. Using a new database covering around 3,000 Spanish municipalities during the period 2000-07 and a Regression Discontinuity design, we document a very strong and robust effect: in close races, municipalities aligned with the regional government obtain on average 83% more per capita transfers and their incumbents gain 10% more votes at the local elections. We also show that the effect of alignment is stronger: (i) when regional and local elections are held on the same day, (ii) in regions with less competitive regional elections, and (ii) in regions with more budget resources.

Niemann-Pick disease type C (NPC) is a rare neurovisceral disease caused mainly by mutations in the NPC1 gene. This autosomal recessive lysosomal disorder is characterised by the defective lysosomal secretion of cholesterol and sphingolipids. No effective therapy exists for the disease. We previously described a deep intronic point mutation (c.1554-1009 G > A) in NPC1 that generated a pseudoexon, which could be corrected at the cellular level using antisense oligonucleotides. Here, we describe the generation of two mouse models bearing this mutation, one in homozygosity and the other in compound heterozygosity with the c.1920delG mutation. Both the homozygotes for the c.1554-1009 G > A mutation and the compound heterozygotes recapitulated the hallmarks of NPC. Lipid analysis revealed accumulation of cholesterol in the liver and sphingolipids in the brain, with both types of transgenic mice displaying tremor and ataxia at 7-8 weeks of age. Behavioural tests showed motor impairment, hyperactivity, reduced anxiety-like behaviour and impaired learning and memory performances, features consistent with those reported previously in NPC animal models and human patients. These mutant mice, the first NPC models bearing a pseudoexon-generating mutation, could be suitable for assessing the efficacy of specific splicing-targeted therapeutic strategies against NPC. This study was partly funded by grants from the Spanish Ministry of Science and Innovation (SAF2011-25431, SAF2013-49129-C2-1-R and SAF2014-56562-R) and from the Catalan Government (2014SGR/932 and SGR2014/1125), as well as the Addi and Cassi Fund. We are particularly grateful for the support from the Addi and Cassi Fund, who also provided the heterozygous mice. The Centre for Genomic Regulation has received support as a Severo Ochoa Centre of Excellence SEV- 2012-0208. We thank Alexandre Garcia for technical assistance. The authors are also grateful for the support from the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), which is an initiative of the ISCIII. MGG was supported by a grant from the University of Barcelona (APIF).

Els problemes de comportament en els que està implicat l’estrès poden tenir múltiples conseqüències tant pels animals com per al vincle humà-animal. Per quests motius, és necessari disposar d’indicadors adequats per avaluar de forma científica l’impacte de l’estrès a les espècies domèstiques amb les que convivim, així com per valorar la seva evolució durant l’aplicació dels protocols de tractament. En aquest sentit, l’anàlisi dels nivells de cortisol al pèl representa un mètode innovador i avantatjós a nivell metodològic. Tenint en compte aquests antecedents, ens plantegem dos objectius principals en aquesta tesi. Per una banda, avaluar l’efecte de la predictibilitat sobre les respostes defensives comportamentals i fisiològiques conseqüència de l’estrès derivat de l’aplicació d’un estímul aversiu. I, per altra banda, analitzar l’ús potencial de la determinació del cortisol en pèl per valorar l’èxit de les estratègies dirigides a reduir l’estrès dins dels protocols de tractament habituals. En relació amb el primer objectiu, no es va poder demostrar clarament aquesta qüestió, en part degut a una sèrie de limitacions metodològiques. En relació amb el segon objectiu, es va trobar una tendència (P = 0,05) pel que fa a les diferències en els nivells de cortisol entre els grups. Concretament, el nivell de cortisol en pèl tendeix a ser més elevat en el grup de gats que mostraven canvis de comportament relacionats amb l’estrès (4,65±1,79 pg/mg) respecte al grup control (4,13±1,28 pg/mg). Tot i així, no es van trobar diferències significatives entre els grups a l’evolució dels nivells de cortisol en el temps (P = 0,59). Considerant aquests resultats, no sembla que la valoració dels nivells de cortisol en pèl sigui un mètode adequat per analitzar l’èxit de les intervencions utilitzades habitualment. Per altra banda, el color del pèl va tenir una influència significativa (P

Els problemes de comportament en els que està implicat l'estrès poden tenir múltiples conseqüències tant pels animals com per al vincle humà-animal. Per quests motius, és necessari disposar d'indicadors adequats per avaluar de forma científica l'impacte de l'estrès a les espècies domèstiques amb les que convivim, així com per valorar la seva evolució durant l'aplicació dels protocols de tractament. En aquest sentit, l'anàlisi dels nivells de cortisol al pèl representa un mètode innovador i avantatjós a nivell metodològic. Tenint en compte aquests antecedents, ens plantegem dos objectius principals en aquesta tesi. Per una banda, avaluar l'efecte de la predictibilitat sobre les respostes defensives comportamentals i fisiològiques conseqüència de l'estrès derivat de l'aplicació d'un estímul aversiu. I, per altra banda, analitzar l'ús potencial de la determinació del cortisol en pèl per valorar l'èxit de les estratègies dirigides a reduir l'estrès dins dels protocols de tractament habituals. En relació amb el primer objectiu, no es va poder demostrar clarament aquesta qüestió, en part degut a una sèrie de limitacions metodològiques. En relació amb el segon objectiu, es va trobar una tendència (P = 0,05) pel que fa a les diferències en els nivells de cortisol entre els grups. Concretament, el nivell de cortisol en pèl tendeix a ser més elevat en el grup de gats que mostraven canvis de comportament relacionats amb l'estrès (4,65±1,79 pg/mg) respecte al grup control (4,13±1,28 pg/mg). Tot i així, no es van trobar diferències significatives entre els grups a l'evolució dels nivells de cortisol en el temps (P = 0,59). Considerant aquests resultats, no sembla que la valoració dels nivells de cortisol en pèl sigui un mètode adequat per analitzar l'èxit de les intervencions utilitzades habitualment. Per altra banda, el color del pèl va tenir una influència significativa (P

Los perros en colectivos (refugios, perreras, criaderos, instalaciones de investigación) se enfrentan a una serie de condiciones subóptimas que comprometen su bienestar. En esta tesis se analizó el efecto de dos productos ansiolíticos naturales (una feromona apaciguadora sintética y un nutracéutico) sobre indicadores de bienestar, tanto de comportamiento como fisiológicos (concentración de cortisol en el pelo). Se observó que la exposición a la feromona sintética redujo la presencia de conductas repetitivas asociadas a estrés crónico: pacing (P

L’objecte d’estudi d’aquest treball és conèixer si el gènere documental de la fotografia, caracteritzada per ser realista i sense modificacions, és efectiva quan s’aplica a la publicitat social per a persuadir o conscienciar als espectadors sobre una situació social o conflicte determinat. També es vol analitzar quins són els factors que ho permeten, i si són més importants per a conscienciar els factors visuals (és a dir, les imatges) o els informatius