Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing

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Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with I-125 brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making. Study identifier at ClinicalTrials.gov: NCT01492751

CSVS, a crowdsourcing database of the Spanish population genetic variability

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variabilityworldwide. CSVS is also part of the GA4GH Beacon network.Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721European Union (EU)European Union (EU) 676559University Chair UAM-IIS-FJD of Genomic MedicineRamon Areces Foundatio

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

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

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

Tres brotes de brucelosis investigados en un año de vigilancia de salud laboral en Ciudad Real Three outbreaks of brucellosis in a one-year period investigated by the occupational health service in Ciudad Real (Spain)

Presentamos 3 brotes investigados por nuestro servicio de salud laboral en el periodo de 1 año. Dos de ellos, con 2 casos cada uno, en sendas queserías industriales, y el tercero en un laboratorio pecuario perteneciente a la administración autonómica, también con 2 casos. En las 2 queserías se encontraron numerosas oportunidades para que los trabajadores pudieran haberse infectado; se consideró como de mayor riesgo la zona de descarga de leche, y la no utilización de equipos de protección individual por los trabajadores, las deficiencias en los laboratorios y la falta de separación efectiva de las dependencias fueron también potencials factores de riesgo. Respecto al laboratorio pecuario, se hallaron al menos 13 deficiencias importantes que permitían la fácil transmisión del agente infeccioso. En España, el riesgo de adquirir una infección por Brucella en laboratorios o industrias queseras es importante, y las condiciones y medidas para evitarlo que actualmente existen no son efectivas.We describe 3 outbreaks of brucellosis investigated by our Occupational Health Service in a 1-year period. Two of these outbreaks, with 2 cases each, occurred in 2 cheese factories and the third outbreak, also with 2 cases, occurred in a cattle laboratory belonging to the local government. In both cheese factories, numerous opportunities for the workers to become infected were found. The greatest risk was considered to be the area for unloading milk, while failure to use personal protection equipment by workers, deficiencies in the laboratories, and the lack of effective separation between areas were also potential risk factors. In the cattle laboratory, we found at least 13 major risk factors that could allow brucellosis transmission. In Spain, there is a substantial risk of Brucella infection in laboratories or dairy factories and current preventive measures are ineffective

Speech pause distribution as an early marker for Alzheimer’s disease

Background: Pause duration analysis is a common feature in the study of discourse in Alzheimer’s disease (AD) since this patient group has shown a consistent trend for longer pauses in comparison to healthy controls. This speech feature may also be helpful for early detection; however, studies involving patients at the pre-clinical, high-risk phase of amnestic mild cognitive impairment (aMCI) have yielded varying results. Objective: To characterize the probability density distribution of speech pause durations in 26 patients with AD, 57 amnestic multi-domain amnestic MCI patients (29 with memory encoding deficits, a-mdMCI-E, and 28 with retrieval impairment only, a-mdMCI-R) and 29 healthy controls (HC) in order assess whether there are significant differences between them. To explore the potential differences in pause production between patients with a-mdMCI-E and a-mdMCI-R, as the former are considered to be at higher risk of progressing to dementia. Methods: The 112 picture-based oral narratives obtained were manually transcribed and annotated for the automatic extraction and analysis of pause durations. Different probability distributions were tested for the fitting of pause durations while truncating shorter ranges. Recent findings in the field of Statistics were considered in order to avoid the inherent methodological uncertainty that this type of analysis entails by addressing the question of temporal thresholding and its potential repercussions on inter-annotator reliability in manual transcriptions. Results: A lognormal distribution (LND) explained the distribution of pause duration for all groups. Its fitted parameters (, ) followed a gradation from the group with shorter durations and a higher tendency to produce short pauses (HC) to the group with longer pause durations and a considerably higher tendency to produce long pauses with greater variance (AD). Importantly, a-mdMCI-E produced significantly longer pauses and with greater variability than their a-mdMCI-R counterparts (alpha=0.05). Conclusion: We report significant differences at the group level in pause distribution across all groups of study that could be used in future diagnostic tools and discuss the clinical implications of these findings, particularly regarding the characterization of a-mdMCI.This work is supported through a PhD grant awarded to P.P-D. by the banking Foundation ‘‘La Caixa’’ (ID 100010434, code: LCF/BQ/ES15/10360020). F.D-V. was supported by a grant awarded to project no. PID2019-107042GB-I00 (Ministerio de Ciencia e Innovación). A.H-F. and I.G.T. were supported by the grant no. TIN2017- 89244-R (MACDA) (Ministerio de Economia, Industria y Competitivi- dad, Gobierno de España) and the project PRO2020-S03 (RCO03080 Lingüística Quantitativa) of l’Institut d’Estudis Catalans.Peer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Speech pause distribution as an early marker for Alzheimer’s disease

Background: Pause duration analysis is a common feature in the study of discourse in Alzheimer’s disease (AD) and may also be helpful for its early detection. However, studies involving patients at the preclinical stage of mild cognitive impairment (MCI) have yielded varying results. Objectives: To characterize the probability density distribution of speech pause duration in AD, two multi-domain amnestic MCI patients (with memory encoding deficits, a-mdMCI-E, and only with retrieval impairment, a-mdMCI-R) and healthy control groups (HC) and to check if there are significant differences between them. To discuss the potential of those findings in clinical practice. Method: 112 picture-based oral narratives were manually transcribed and annotated for the automatic extraction of pause durations and their subsequent logconversion. We consider different probability distributions to fit speech pause duration truncating shorter ranges taking into account latest statistical findings to avoid inherent methodological uncertainties present in them. Results: Lognormal distribution (LND) explains the distribution of pause duration in speech for all groups, and its fitted parameters (m,s) followed a gradation from the group with shorter durations and a higher tendency to produce short pauses (HC) to the group with longer pause durations and a considerably higher tendency to produce long pauses with more variance (AD). Importantly, a-mdMCI-E produced significantly longer pauses with greater variability than their a-mdMCI-R counterparts (a = 0:05) across all groups of study. Conclusion: We characterize and report significant differences at group level in the speech pause distribution across all groups of study that could be used to design tools and experiments for early prediction of AD progression.This work is supported through a PhD grant awarded to P.P-D. by the banking Foundation ”La Caixa” (ID 100010434, code: LCF/BQ/ES15/10360020). F.D-V. was supported by a grant awarded to project no. PID2019-107042GB-I00 (Ministerio de Ciencia e Innovacion). A.H-F. and I.G.T. were supported by the grant no. TIN2017-89244-R (MACDA) (Ministerio de Economia, Industria y Competitividad, Gobierno de Espana) and the project PRO2020-S03 (RCO03080 Lingüística Quantitativa) of l’Institut d’Estudis CatalansPreprin

Produire et réguler l’habitat dans la péninsule Ibérique

Ce numéro étudie les dynamiques politiques, sociales et financières contemporaines de la production de logements en Espagne et dans une moindre mesure au Portugal. L’actualité scientifique de cette thématique se justifie par l’impact de la crise de 2008 et ses effets en chaîne qui ont fortement déstabilisé le modèle de production et les conditions d’accès au logement, dans le contexte d ’ une série de chocs interdépendants : éclatement de la bulle immobilière, multiplication des expropriations, explosion du chômage, en particulier chez les jeunes adultes, et montée de la contestation politique qui a ébranlé le traditionnel bipartisme avec la percée aux élections municipales espagnoles de 2015 des coalitions nées dans le sillage des mouvements des Indignés. Ce numéro aborde donc la question du logement à la double lumière des recompositions du marché immobilier et des reconfigurations locales de l’action publique. Cette question s’ancre aussi dans une mise en perspective d ’ approches et de cultures scientifiques différentes du cas français. En France, la question du logement social est traditionnellement associée à celle de la mixité sociale, de la ségrégation, mais aussi des politiques de renouvellement urbain. En Espagne, la question gravite autour de l’éclatement de la bulle spéculative et sur ses effets en termes de recomposition des politiques de logements ; cela s’accompagne de nombreux travaux sur les manifestations anti-éviction et les mouvements de squatteurs, ainsi que de recherches sur les mobilisations collectives et les nouvelles formes de participation locale qui les ont précédés ou accompagnés. L’ambition de ce numéro est donc de proposer de nouveaux angles de réflexion sur ces différentes questions en interrogeant l’articulation entre les dimensions financières (recapitalisation par des opérateurs privés et internationaux, apparition de nouveaux acteurs sur le marché), politiques (places du logement dans les nouvelles politiques publiques) et sociales (accession à la propriété, dynamiques de circulation au sein du parc de logement). Deux articles complètent ce numéro thématique, l’un traitant de la situation des retraités français installés dans l’Algarve (Portugal), l’autre s’interrogeant sur les recherches portant sur le versant français des Pyrénées depuis 1999

Buenas prácticas en docencia y política universitaria

Recoge diez experiencias docentes realizadas en el ámbito de la educación superior con el objetivo de reflejar procedimientos innovadores sobre enseñanza y aprendizaje en dicho ámbito. Son investigaciones y proyectos pilotos realizados en distintas universidades españolas, y en distintas carreras como ingenierías, magisterio, enfermería, administración y dirección de empresas, derecho o psicopedagogía.Castilla La ManchaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]