Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

The Impact of EU Membership on the Economic Governance of Spain

[spa] España no fue admitida en la Comunidad Económica Europea durante el régimen de Franco por razones políticas. Integrarse a la Comunidad Europea en enero de 1986 fue el último peldaño hacia la consolidación definitiva de la democracia en España y de la apertura de su economía.. Los resultados de los veinticinco años como miembro de la UE se han traducido en un impulso sin precedentes de modernización y progreso. España adoptó el “Acervo Comunitario” y recibió considerables beneficios de su integración a la Comunidad, eliminando barreras, siguiendo las políticas comunes, recibiendo fondos europeos y adoptando la moneda europea común. A partir de un nivel del 60% del promedio europeo de renta per capita en 1986, el nivel actual –incluso con la crisis que estalló en 2008- se sitúa en torno al 105 por ciento. Los últimos tres años han sido diferentes y difíciles como consecuencia de la severa crisis económica y financiera.En este contexto este trabajo analiza como los sucesivos gobiernos de España han organizado la gobernanza económica para adaptarla a los cambios cuantitativos y cualitativos que se han ido produciendo en la integración europea.

The Impact of EU Membership on the Economic Governance of Spain

[spa] España no fue admitida en la Comunidad Económica Europea durante el régimen de Franco por razones políticas. Integrarse a la Comunidad Europea en enero de 1986 fue el último peldaño hacia la consolidación definitiva de la democracia en España y de la apertura de su economía.. Los resultados de los veinticinco años como miembro de la UE se han traducido en un impulso sin precedentes de modernización y progreso. España adoptó el “Acervo Comunitario” y recibió considerables beneficios de su integración a la Comunidad, eliminando barreras, siguiendo las políticas comunes, recibiendo fondos europeos y adoptando la moneda europea común. A partir de un nivel del 60% del promedio europeo de renta per capita en 1986, el nivel actual –incluso con la crisis que estalló en 2008- se sitúa en torno al 105 por ciento. Los últimos tres años han sido diferentes y difíciles como consecuencia de la severa crisis económica y financiera.En este contexto este trabajo analiza como los sucesivos gobiernos de España han organizado la gobernanza económica para adaptarla a los cambios cuantitativos y cualitativos que se han ido produciendo en la integración europea.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

Passport to a profession in the degree of pharmacy: how to integrate university students into the real world of work: "Passport to a profession in Pharmacy"

The incorporation of the Spanish university system into the European Higher Education Areahas brought about a series of adaptations. Among the recommendations is the inclusion ofan external training period in a company, which has resulted in significant changes in thedegree syllabus in order to balance the theoretical and practical education required by thestudents. This new framework has been legally confirmed by the Spanish Government and, inthe case of the University of Barcelona, by the publication of internal guidelines. Takingadvantage of this new opportunity to adapt the Pharmacy degree to real-world problems inindustry, the Dean’s team of the Faculty of Pharmacy, with the support of the Facultyadministrative staff and the Students Advisory Service, have assumed the challenge ofincluding a new subject in the syllabus entitled Training in Companies.In parallel, a new activity has been set up to ensure that the students choose the mostsuitable company department/job for them and to help them pass the company interview.Under the name of Passport to a Profession, a series of ten explanatory talks has beenscheduled every academic year. These talks deal with a broad range of topics aimed atproviding the students with the basic tools they will need to make the most of a companytraining period and to make headway in the professional world when they finish theirdegree. In addition, three Faculty of Pharmacy-Pharmaceutical company workshops and tworound-table conferences have been held in the last two years in order to bring the universityand industry together. Notably, the project to provide students with company training isexpanding on an international level, with two to three undergraduate students contractedevery year by a United Kingdom-based multinational pharmaceutical company.The statistical data of the whole process has been analysed for a more in-depthunderstanding of the activity and to improve the programme.

The impact of adopting a CLIL approach on EFL learners reading skills in Catalonia school

En els últims anys, un gran nombre de docents i escoles han estat introduint programes AICLE a les escoles catalanes. A la majoria d’escoles, però, només s'ensenya anglès com a llengua estrangera, la qual cosa, limita les oportunitats d'estar en contacte amb la llengua estrangera en un context diferent. L’objectiu d'aquest estudi és analitzar si els infants milloren en les seves habilitats lectores i comprovar si existeix un avantatge significatiu respecte els alumnes que només estudien anglès com a llengua estrangera. L’estudi empíric que us presento a continuació, compara els resultats obtinguts en dues proves de comprensió lectora. A les proves hi van participar dos grups d’alumnes de cinquè de d’Educació Primària. Un dels grups seguia un programa AICLE (1 hora a la setmana i , a més aprenia anglès coma llengua estrangera); l’altre grup només estudiava anglès com a llengua estrangera. L'objectiu principal d'aquest projecte d'investigació és esbrinar si els programes AICLE tenen un impacte en les habilitats lectores en llengua anglesa dels alumnes. Així doncs, humilment intentaré contribuir a la literatura existent sobre els beneficis de l’AICLE.

Ancient DNA analysis of 8000 B.C. near eastern farmers supports an early neolithic pioneer maritime colonization of Mainland Europe through Cyprus and the Aegean Islands

The genetic impact associated to the Neolithic spread in Europe has been widely debated over the last 20 years. Within this context, ancient DNA studies have provided a more reliable picture by directly analyzing the protagonist populations at different regions in Europe. However, the lack of available data from the original Near Eastern farmers has limited the achieved conclusions, preventing the formulation of continental models of Neolithic expansion. Here we address this issue by presenting mitochondrial DNA data of the original Near-Eastern Neolithic communities with the aim of providing the adequate background for the interpretation of Neolithic genetic data from European samples. Sixty-three skeletons from the Pre Pottery Neolithic B (PPNB) sites of Tell Halula, Tell Ramad and Dja'de El Mughara dating between 8,700-6,600 cal. B.C. were analyzed, and 15 validated mitochondrial DNA profiles were recovered. In order to estimate the demographic contribution of the first farmers to both Central European and Western Mediterranean Neolithic cultures, haplotype and haplogroup diversities in the PPNB sample were compared using phylogeographic and population genetic analyses to available ancient DNA data from human remains belonging to the Linearbandkeramik-Alföldi Vonaldiszes Kerámia and Cardial/Epicardial cultures. We also searched for possible signatures of the original Neolithic expansion over the modern Near Eastern and South European genetic pools, and tried to infer possible routes of expansion by comparing the obtained results to a database of 60 modern populations from both regions. Comparisons performed among the 3 ancient datasets allowed us to identify K and N-derived mitochondrial DNA haplogroups as potential markers of the Neolithic expansion, whose genetic signature would have reached both the Iberian coasts and the Central European plain. Moreover, the observed genetic affinities between the PPNB samples and the modern populations of Cyprus and Crete seem to suggest that the Neolithic was first introduced into Europe through pioneer seafaring colonization.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.

Pilot study about the effect of rt-PA administration on the excitotoxicity mediated brain damage and its repercussion on the functional prognosis of patients with ischaemic stroke: research protocol

Fibrinolytic therapy with Recombinant Tissue-Plasminogen Activator (rt-PA) is currently the only effective treatment for ischaemic stroke in its acute phase. Even though its use generally improves the prognosis of those patients likely to receive it, rt-PA administration is associated to several risks, such as haemorrhagic transformation ofthe ischaemic lesion and activation of excitotoxic mechanisms that may contribute to an increase in mortality or to a poor outcome in certain occasions, specially when arterial recanalization is not achieved or the rt-PA is lately administrated. Since in the last few years the role of glutamate in the neurotoxicity associated toischaemia has been widely studied and it is known that high plasma glutamate levels are predictors of ischaemic lesion growth and poor neurological outcome, it is necessary to find out which factors can contribute to glutamate release in the brain. The aim of this study is to determine if rt-PA administration is related to an increase in plasma glutamate levels, as well as to define if higher plasma glutamate levels at admission are related to different evolution and prognosis of our patients, both in those in which recanalisation is achieved and not. A series of cases of patients with hemispheric cerebral infarction admitted in our hospital during a year will be studied, and the data obtained from them will be compared to the data obtained from a control group, the samples of wich were takenyears ago, before rt-PA was routinely used

Association between Long-Term Exposure to Traffic-Related Air Pollution and Subclinical Atherosclerosis: The REGICOR Study

Background: Epidemiological evidence of the effects of long-term exposure to air pollu tion on the chronic processes of athero genesis is limited. Objective: We investigated the association of long-term exposure to traffic-related air pollu tion with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle–brachial index (ABI). Methods: We performed a cross-sectional analysis using data collected during the reexamination (2007–2010) of 2,780 participants in the REGICOR (Registre Gironí del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years’ time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates. Results: Exposure contrasts between the 5th and 95th percentiles for NO2 (25 μg/m), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: –1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: –0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ≥ 60 years of age. Conclusions: Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.key words: ankle–brachial index, average daily traffic, cardiovascular disease, exposure assessment, exposure to tailpipe emissions, intima media thickness, land use regression model, Mediterranean diet, nitrogen dioxide

Late Roman amphorae in the eastern Tarraconensis. Some chronological and quantitative approaches

Since the classic study of Simon J. Keay published in 1984, knowledge of late Roman amphorae has progressed markedly, thanks to scholars such as Michel Bonifay and Paul Reynolds, amongst others. The area studied by Keay was Catalonia, the ancient Eastern Tarraconensis. The overview here offered for this same region reveals the central role played by African imports in late Antique times, with a minor presence of the Eastern-Mediterranean and South-Hispanic (both Baetican and Lusitanian) productions. Progress in research in the last 25 years has been centred on a series of new and well-dated contexts: the data they have yielded has clarified more precisely the chronology and the proportions of the different imports. On occasion a quantitative approach may even be applied. At the same time the relationship between town and country with respect to the late Roman amphorae is proving of interest and providing results of significance.

Kinship foster care: a study from the perspective of the of the caregivers, the children and the child welfare workers

In the last twenty years, in most Western countries, kinship foster care has become an integral part of childcare systems,growing progressively with regard to the numbers of children involved and relative weight as a care resource within thesystem; indeed, in some countries it is even more common than other placement options, such as non-kinship foster careand residential care. Research on this phenomenon is still recent and scarce, and there are few programmes targeting thispopulation. In this article we present the results of a descriptive study on kinship foster care in the city of Barcelona,including information and data from the different stakeholders involved. From a quality of life research perspective weanalyze the perceptions, evaluation and expressed satisfaction of caregivers, children and practitioners from the specialistChild and Adolescent Teams (EAIAs) responsible for the study and follow-up of kinship foster care cases. The researchpresented results are in line with those of current research in this field, and lays the basis for the future development ofkinship foster care programmes

Acogimiento en familia extensa: un estudio desde la perspectiva de los acogedores, de los niños y niñas acogidos y de los profesionales que intervienen. = Kinship foster care: a study from the perspective of the caregivers, the children and the child welfare workers

Desde hace aproximadamente dos décadas, en la mayoría de los países occidentales, los acogimientos en familia extensa han entrado a formar parte de los sistemas de protección infantil, siguiendo una evolución creciente en cuanto a número y peso especifico como recurso de acogimiento. Las investigaciones sobre este fenómeno son aún recientes y escasas como también lo son los programas dirigidos a esta población. En el presente artículo presentamos los resultados de un estudio descriptivo sobre los acogimientos en familia extensa en la ciudad de Barcelona, donde se recogen datos de los principales agentes implicados en este fenómeno. Desde la perspectiva de los estudios de la calidad de vida se analizan las percepciones, evaluaciones, y satisfacción expresada, por parte de los acogedores, los niños/as acogidos y los profesionales de los Equipos de Atención a la Infancia y Adolescencia (EAIA) que se encargan del estudio y seguimiento de estos acogimientos. La investigación presenta unos resultados acordes con los estudios que actualmente se realizan en este ámbito y sienta las bases para el despliegue futuro de programas dirigidos a los acogimientos en familia extensa

Otra mirada al tema del cambio de escala: los nuevos espacios de comercio, ocio y turismo = Another look at the theme of the change of scale: new spaces in commerce, leisure and tourism

The technological advances and new organisation of the economy together with a change in ideas in consumer habits andlifestyle that have happened in the last 25 years have placed us in a new state of capitalism. The spatial translation of thisnew state has been immediate and implies among other changes the overcoming of the concept of scale. Commercialspaces and those of leisure and tourism offer us an unbeatable opportunity of exemplifying these changes because they arethe most effected by the new postmodern tendencies