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Objectives To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. Methods The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. Results Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren’s syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. Conclusions Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Atrial fibrillation; Oral anticoagulants; Adherence; Persistence; Electronic health records Fibrilación auricular; Tratamiento anticoagulante oral; Adherencia; Persistencia; Registros electrónicos de salud Fibril·lació auricular; Tractament anticoagulant oral; Adherència; Persistència; Registres electrònics de salut Objective: We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC. Setting: Primary Health Care (PHC) in the Catalan Health Institute (ICS), Catalunya, Spain. Participants: All NVAF adult patients initiating OAC for stroke prevention in August 2013---December 2015. Methods: Population-based cohort study. Persistence was measured in patients initiating OAC in August 2013---December 2014. Data source: SIDIAP, which captures electronic health records from PHC in the (ICS), covering approximately 5.8 million people. Results: 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 (62.7%) initiated acenocoumarol. Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9105 (17.6%) of the patients. Persistence and adherence were estimated up to the end of follow-up. For 22,075 patients, persistence was higher among the non-naive patients [n = 258 (61.7%)] than among the naive [n = 11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and it was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n = 360 (80.1%)] of good adherence at implementation (MPR > 80%) while patients starting dabigatran were less adherent [n = 203 (47.8%)]. Conclusions: Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest. Objetivo: Describir datos sociodemográficos, comorbilidades, comedicaciones y riesgo de eventos tromboembólicos y hemorrágicos de los pacientes con fibrilación auricular no valvular (FANV) que inician tratamiento anticoagulante por vía oral (TAO) para prevención del ictus. Estimar adherencia y persistencia al TAO. Emplazamiento: Atención primaria (AP) del Instituto Catalán de Salud (ICS), Cataluña, España. Participantes: Adultos con FANV que inician TAO para prevención de ictus entre agosto del 2013 y diciembre del 2015. Métodos: Estudio de cohortes de base poblacional. Adherencia y persistencia se midieron en pacientes que iniciaban TAO entre agosto del 2013 y diciembre del 2014. Fuente de datos: SIDIAP, base de datos procedentes de registros electrónicos de AP del ICS, que cubre aproximadamente una población de 5,8 millones de personas. Resultados: Cincuenta y un mil seiscientos noventa pacientes con FANV iniciaron TAO, 47.197 (91,3%) eran naïve al TAO y 32.404 (62,7%) iniciaron acenocumarol. Su edad media era 72,8 años (DE 12,3) y el 49,4% eran mujeres; 90105 (17,6%) recibían tratamiento antiagregante plaquetario. Persistencia y adherencia se estimaron hasta el final del seguimiento. La persistencia a anticoagulantes orales directos (ACOD) fue mayor en no naïve que en naïve (61,7% vs. 53,1%). La adherencia a ACOD fue similar en los 2 grupos. Entre los naïve, los pacientes que iniciaban rivaroxabán (80,1%) mostraron mayor adherencia en la implementación (MPR > 80%), mientras que los que iniciaban dabigatrán fueron menos adherentes (47,8%). Conclusiones: Acenocumarol fue el anticoagulante más prescrito. Los pacientes no naïve mostraron mejor persistencia al tratamiento que los naïve. Rivaroxabán mostró mayores tasas de adherencia que apixabán y dabigatrán, las menores.

Objective: To evaluate the association between prematurity (by the gestational week [gw]) and ADHD during childhood. Method: Observational, matched cohort study using data from children born in a tertiary-level hospital (Hospital Universitari Vall d'Hebron, Catalonia, Spain) during 1995-2007 and data from the Information System for the Development of Research in Primary Health Care (SIDIAP database, Catalonia, Spain). Results: Prevalence of ADHD increases as gestational age decreases, 12.7% for those born =28 gw, compared to 3.2% for those born after the 37 gw. The risk of developing ADHD in the non-premature children tends to increase as the gw decreases (35-36 gw, hazard ratio [HR] = 1.70, 95% confidence interval [CI] [1.19, 2.44]; 33-34 gw, HR = 3.38, 95% CI [2.08, 5.50]; 29-32 gw, HR = 2.37, 95% CI [1.54, 3.63]; and =28 gw, HR = 5.57, 95% CI [2.49, 12.46]) Conclusion: Being born preterm is associated with a risk of developing ADHD, also in late preterm children (35-36 gw). Attention when taking care of these infants regarding their mental health must be made.

© 2019 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Objectives The objective of the study was to identify factors affecting the use of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, specifically authors’ attitudes toward and experiences with it. Study Design and Setting An online survey was distributed to authors of observational studies recruited via social media, personal network snowballing, and mass mailings using targeted search strategies. Data on demographics, awareness, motivators, and usage were collected in conjunction with a modified Unified Theory of Acceptance and Use of Technology (UTAUT) scale on which confirmatory factor analysis (CFA) was performed. Results One thousand fifteen participants completed the survey. Of these, 185 (18.2%) indicated they had never heard of STROBE nor used it previously, 195 (19.2%) had heard of it but never used it, and 635 (62.6%) had used it. Journals promoting STROBE were both key motivators and awareness mechanisms; peers and educational workshops were also important influencing factors to a lesser degree. The internal consistency of the modified UTAUT scale was strong (Cronbach's alpha = 0.94). CFA supported a four-factor model with 23 questions. Conclusion The endorsement of STROBE by journals is key to authors’ awareness and use of the guideline. We tested and validated our scale which can guide future research on reporting guidelines. The authors would like to acknowledge the Methods in Research on Research (MiRoR) network for their support and guidance. The authors would also like to thank Dr. Michail Kovanis for assistance gathering author emails and Ms. Alice Biggane for her assistance with the recruitment strategy.

La millora i el manteniment continu de la qualitat de l’atenció als malalts amb ictus agut requereix una avaluació periòdica de la pràctica clínica. Els Audits de l’Ictus són l’instrument avaluatiu del PDMVC. La millora dels seus resultats pretén garantir la millora dels resultats dels pacients. S’han auditat 4.008 casos ingressats per ictus agut entre 2018 i 2019. El període d’estudi s’ha ampliat a 6 mesos, en períodes de 1 mes i mig al llarg de 12 mesos, similars per a tots els centres. L’obtenció prospectiva de dades s’ha realitzat majoritàriament per infermeres de cada hospital. La mediana del temps entre l’inici dels símptomes i l’arribada a urgències va ser de 2,1 hores. El 72% dels casos van arribar a l’hospital dins les primeres quatre hores i mitja. Respecte al 4t Audit: * Augmenten els ingressos en Unitat d’ictus agut (44,2% a 61,3%), les activacions del Codi Ictus (42,9 a 61,4; realitzades pel SEM de 43,4 a 67,8%) i els tractaments de reperfusió (16% a 30% dels ictus isquèmics) * Augmenta el nombre de pacients en els que es diagnostica durant l’ingrés una fibril·lació auricular no coneguda prèviament (7% a 18,8%). * Hi ha un lleuger augment de les pneumònies(6% a 8%)ibaixa la mor talitat intrahospitalària (12% a 9%). * Sis indicadors de qualitat milloren significativament, tres 3 indicadors es mantenen i 3 indicadors empitjoren. Destaca una important millora en alguns indicadors de qualitat rellevants com són la realització del test de disfàgia, l’avaluació del perfil lipídic, l’educació sanitària als pacients i familiars, el registre de l’etiologia de l’ictus i la utilització d’escales neurològiques. Es necessiten accions de milloradels indicadors següents: pauta d’antitrombòtics abans de 48 hores, mobilització precoç i avaluació de l’estat d’ànim. L’estat d’ànim s’avalua en un baix percentatge i es fa servir una gran variabilitat d’eines de mesura.

Son casi innumerables las reflexiones que se han hecho en el campo de la metodología de las ciencias sociales, sobre la dicotomía, real o inexistente, entre las perspectivas de análisis cuantitativo y cualitativo, mientras que han sido menos abundantes los trabajos teóricos, aunque van siendo más frecuentes los empíricos, que han tratado de compatibilizar y/o complementar ambas perspectivas. En muchos casos los trabajos cualitativos cubren solamente los primeros pasos de la investigación social, como fases previas o exploratorias de la misma, para prolongarla después con una metodología más cuantitativa y extensiva como la inherente a las encuestas, al análisis de datos, multivariados, causales u otros. Este artículo presenta un ejemplo concreto del planteamiento inverso. Se parte de una gran encuesta con el objetivo de estructurar la realidad objeto de estudio, para posteriormente aplicar técnicas cualitativas, concretamente grupos de discusión. Most times, the qualitative works have been the beginnings of research, or even more, they have shaped the exploratory stages before the dimensionalisation and categorisation for the use of extensive techniques as surveys. This article is an example of an inverse planning which starts from a large survey in order to structure the reality which is the target of the research and afterwards to apply qualitative techniques, concretely discussion groups. As a result, it is concerned with increasing the validity and representativeness of the discourses by individuals and groups which have been gained from the features obtained in the structural stage.

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948–2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.

Treballs Finals del Grau d'Economia i Estadística. Doble titulació interuniversitària, Universitat de Barcelona i Universitat Politècnica de Catalunya. Curs: 2019-2020. Tutors: Montserrat Guillén; Mònica Serrano, [cat] Són evidents les transformacions i la rellevància del consum en el segle XXI, on el nivell de benestar, qualitat de vida i classe social estan fortament lligades a la capacitat d’adquisició. A més, la globalització, el consum de masses i la identitat personal enforteix la importància de conèixer i estudiar els nous patrons de consum, tant a nivell econòmic com sociodemogràfic. De la mateixa manera, també resulta essencial analitzar la diversitat en la configuració de les llars per entendre millor els patrons de consum per un millor disseny de les polítiques econòmiques i socials. Per aquesta raó, sorgeix la necessitat d’interpretar les estadístiques oficials des de una altra perspectiva. L’objectiu d’aquest projecte és conèixer quins factors determinen els patrons de consum en funció de la configuració de les llars d’Espanya per l’any 2018., [eng] There is evidence that consumption in the 21st century has transformed and has gained new relevance when relating the level of wellbeing, quality of life and social class to acquisition power. In addition, globalization, mass consumption and personal identity reinforces the importance of studying and analyzing new patterns of consumption, both economically and socio - demographically. Similarly, it is also essential to analyze the diversity of household composition to better understand the consumer spending to design and apply better economic policies. For this reason, there is a need to interpret official statistics from another perspective. The aim of this project is to study which factors determine the consumption patterns by the different types of household composition in Spain.

Objective: Patient recruitment in clinical trials is challenging with failure to recruit to time and target sample size common. This may be caused by unanticipated problems or by overestimation of the recruitment rate. This study is a systematic review of statistical models to predict recruitment at the design stage of clinical trials. Study Design and Setting: The Online Resource for Recruitment research in Clinical triAls database was searched to identify articles published between 2008 and 2016. Articles published before 2008 were identified from a relevant systematic review. Google search was used to find potential methods in gray literature. Results: Thirteen eligible articles were identified of which, 11 focused on stochastic approaches, one on deterministic models, and one included both stochastic and deterministic methods. Models varied considerably in the factors included and in their complexity. Key aspects included their ability to condition on time; whether they used average or center-specific recruitment rates; and assumptions around center initiation rates. Lack of flexibility of some models restricts their implementation. Conclusion: Deterministic models require specification of few parameters but are likely unrealistic although easy to implement. Increasingly, stochastic models require greater parameter specification, which, along with greater complexity may be a barrier to their implementation.

International audience; Objective: Identify the current practice for recruitment prediction and monitoring within clinical trials.Study Design and Setting: Chief investigators (CIs) were surveyed to identify data sources and adjustments made to support recruitment prediction. Statisticians were surveyed to determine methods and adjustments used when predicting and monitoring recruitment. Participants were identified from the National Institute for Health Research recently funded studies, the UK Clinical Research Collaboration registered Clinical Trial Units network or by the European Clinical Research Infrastructure Network.Results: A total of 51 CIs (UK = 32, ECRIN = 19) and 104 statisticians (UK = 51, ECRIN = 53) were contacted. Response rates varied (CIs UK = 53% ECRIN = 32%; statisticians UK = 98% ECRIN = 36%).Multiple data sources are used to support recruitment rates, most commonly audit data from multiple sites. Variation in individual site recruitment rates are frequently incorporated, but staggered site openings were featured more commonly among UK respondents. Simple prediction methods are preferred to rarely used statistical models. Lack of familiarity with statistical methods are barriers to their use with evidence needed to justify the time required to support their implementation.Conclusion: Simplistic methods will continue as the mainstay of prediction; however, generation of evidence supporting the benefits of complex statistical models should promote their implementations. Multiple data sources to support recruitment prediction are being used, and further work on the quality of these data is needed. Pressure to be optimistic about recruitment rates for the trial to be attractive to funders was felt by a sizable minority. (C) 2020 The Authors. Published by Elsevier Inc.

This is the peer reviewed version of the following article: Forns, J. [et al.]. Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: a study in three European data sources. "Pharmacoepidemiology and drug safety", 6 Juny 2019, vol. 28, núm. 7, p. 965-975, which has been published in final form at 10.1002/pds.4803. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." Purpose Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). Methods Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. Results Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code “unspecified jaundice” had high PPVs in Denmark. Conclusions PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.

This is the peer reviewed version of the following article: Bofill, M.; Gómez Melis, G. A new approach for sizing trials with composite binary endpoints using anticipated marginal values and accounting for the correlation between components. "Statistics in medicine", 20 Maig 2019, vol. 38, núm. 11, p. 1935-1956, which has been published in final form at https://doi.org/10.1002/sim.8092. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for the primary endpoint. As shown in this work, when using a composite binary endpoint to size a trial, one needs to specify the event rates and the effect sizes of the composite components as well as the correlation between them. In practice, the marginal parameters of the components can be obtained from previous studies or pilot trials; however, the correlation is often not previously reported and thus usually unknown. We first show that the sample size for composite binary endpoints is strongly dependent on the correlation and, second, that slight deviations in the prior information on the marginal parameters may result in underpowered trials for achieving the study objectives at a pre-specified significance level. We propose a general strategy for calculating the required sample size when the correlation is not specified and accounting for uncertainty in the marginal parameter values. We present the web platform CompARE to characterize composite endpoints and to calculate the sample size just as we propose in this paper. We evaluate the performance of the proposal with a simulation study and illustrate it by means of a real case study using CompARE.

Summary Background & aims Individuals with Down syndrome (DS) have higher rates of obesity. In the general population green tea extracts, and in particular epigallocatechin gallate (EGCG), have been studied for their antiobesogenic effects. The aim of this study is to elucidate the effect of EGCG on body weight in young DS adults and whether it could be related to changes in lipid profile. Methods In the context of a double-blind phase II clinical trial comparing the effect of EGCG to that of placebo, the body composition of 77 young adults with DS was analyzed through bioelectrical impedance analysis. Lipids were analyzed using standard laboratory procedures. The factors tested in the ANCOVA model for the differences from baseline were treatment, sex as well as their interaction as independent variables. Baseline values were included in the models as covariates. Results Individuals receiving placebo showed an increase in body weight and body mass index (BMI) that was not detected in those with EGCG treatment. EGCG effect on body composition was mainly observed in males, with significant differences between the EGCG and the placebo group after 12 months for weight (estimated adjusted mean difference (AMD) = −2.34, 95% CI = [−4.21, −0.48]; p = 0.015) and body fat (estimated AMD = −1.23, 95% CI = [−2.43,−0.04], p = 0.043). The changes detected in body composition were associated with changes in lipid profile. Conclusions Our results suggest that EGCG could have a modest beneficial effect on weight management in DS. Furthermore, EGCG has also a sex-dependent effect on lipid profile that is related to changes in body mass and composition.

The hazard ratio is routinely used as a summary measure to assess the treatment effect in clinical trials with time-to-event endpoints. It is frequently assumed as constant over time although this assumption often does not hold. When the hazard ratio deviates considerably from being constant, the average of its plausible values is not a valid measure of the treatment effect, can be clinically misleading and common sample size formulas are not appropriate. In this paper, we study the hazard ratio along time of a two-component composite endpoint under the assumption that the hazard ratio for each component is constant. This work considers two measures for quantifying the non-proportionality of the hazard ratio: the difference $D$ between the maximum and minimum values of hazard ratio over time and the relative measure $R$ representing the ratio between the sample sizes for the minimum detectable and the average effects. We illustrate $D$ and $R$ by means of the ZODIAC trial where the primary endpoint was progression-free survival. We have run a simulation study deriving scenarios for different values of the hazard ratios, different event rates and different degrees of association between the components. We illustrate situations that yield non-constant hazard ratios for the composite endpoints and consider the likely impact on sample size. Results show that the distance between the two component hazard ratios plays an important role, especially when they are close to 1. Furthermore, even when the treatment effects for each component are similar, if the two-component hazards are markedly different, hazard ratio of the composite is often non-constant., Comment: 17 pages, 3 figures, 2 tables

Introduction: Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. Objectives: To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAR. Design: Multicentre, parallel, double-blind, controlled, randomized clinical trial. Setting: 31 primary care centers in Spain. Participants: Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000 mg three times per day for 10 days. Main measurements: The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63. Results: A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3-58.1%; p =.009 for superiority). The number of adverse events was similar in both groups. Conclusions: There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAR The main limitation of this trial was the low statistical power due to the low number of patients included., The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded in the 2011 call under the Health Strategy Action 2013-2016, within the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2008-2011, with reference PI11/02471, co-funded with European Union ERDF funds. It was also supported by the Spanish Clinical Research Network (SCReN), PT13/0002/0030. The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: From 2005 to 2010, we conducted 2 randomized studies on a journal (Medicina Clínica), where we took manuscripts received for publication and randomly assigned them to either the standard editorial process or to additional processes. Both studies were based on the use of methodological reviewers and reporting guidelines (RG). Those interventions slightly improved the items reported on the Manuscript Quality Assessment Instrument (MQAI), which assesses the quality of the research report. However, masked evaluators were able to guess the allocated group in 62% (56/90) of the papers, thus presenting a risk of detection bias. In this post-hoc study, we analyse whether those interventions that were originally designed for improving the completeness of manuscript reporting may have had an effect on the number of citations, which is the measured outcome that we used. Methods: Masked to the intervention group, one of us used the Web of Science (WoS) to quantify the number of citations that the participating manuscripts received up December 2016. We calculated the mean citation ratio between intervention arms and then quantified the uncertainty of it by means of the Jackknife method, which avoids assumptions about the distribution shape. Results: Our study included 191 articles (99 and 92, respectively) from the two previous studies, which all together received 1336 citations. In both studies, the groups subjected to additional processes showed higher averages, standard deviations and annual rates. The intervention effect was similar in both studies, with a combined estimate of a 43% (95% CI: 3 to 98%) increase in the number of citations. Conclusions: We interpret that those effects are driven mainly by introducing into the editorial process a senior methodologist to find missing RG items. Those results are promising, but not definitive due to the exploratory nature of the study and some important caveats such as: the limitations of using the number of citations as a measure of scientific impact; and the fact that our study is based on a single journal. We invite journals to perform their own studies to ascertain whether or not scientific repercussion is increased by adhering to reporting guidelines and further involving statisticians in the editorial process. DGA, JAG and EC belong to MiRoR (Methods in Research on Research), which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 676207. EC and JC are partially supported by the grants MTM2015–64465-C2–1-R (MINECO/FEDER, UE) from the Secretaría de Estado de Investigación, Desarrollo e Innovación del Ministerio de Economía y Competitividad (Spain) and through grant 2017 SGR 622 from the Departament d’Economia i Coneixement de la Generalitat de Catalunya (Spain). The funding bodies had no role in the study design, data collection and analysis, results interpretation, or in writing the manuscript.

Prevention and nutrition are key for healthy lifestyles and are crucial in the new paradigm of patient-centered medicine, as healthy diet protects against chronic diseases and helps to delay diseases in general population. Making healhty diets is becoming essential and there are no well-formalized support mechanisms for suporting nutritionists when designing diets of specific patients. The project Diet4You proposes an intelligent decision support system oriented to the adaptive and dynamic preparation of personalized diets for specific individuals from general population, with or without comorbidities. Diet4You is a hybrid system interacting several AI and data science components in a complex way to compose diets by taking into account all the information available on the person, including their characteristics, health conditions, personal and cultural habits and eventual drugs intake and their genomic information. Authors are not aware of other menus recommenders with such a holistic view. The system is highly configurable. It relies on an information system that can formalize all contextual knowledge to improve optimization, and the menus are composed over a food database containing prepared dishes with known nutritional decomposition. This work has been partially supported by project Diet4You (TIN2014-60557-R), and the Consolidated Research Group Grant from AGAUR (Generalitat de Catalunya, cataalan government) IDEAI-UPC (AGAUR SGR2017-574).

El objetivo de este estudio fue describir la localización anatómica, el tipo y la gravedad de las lesiones ocurridas en las competiciones oficiales de las ligas de verano masculinas (2005-2015) de Lucha Leonesa. Al objeto de realizar un análisis más profundo, se tuvo en cuenta, el perfil del luchador. Se produjeron un total de 401 lesiones, siendo los luchadores de mayor nivel los que menos número de lesiones sufrieron. Las contusiones fueron las lesiones más frecuentes (41,4%) pero entre las graves fueron los esguinces (42,3%). Los miembros inferiores fueron la localización más frecuente en el total de lesiones (38,2%) y entre las graves (45,4%). La rodilla, el tórax y el hombro acumulaban casi la mitad de las lesiones y el 68% de las lesiones graves. Los resultados obtenidos sugieren que las características de las lesiones que se pueden observar en la lucha leonesa son similares a las de otros deportes de combate, This study aimed at describing the anatomical location, type and severity of the sport injuries observed during the Leonese Wrestling “masculine summer leagues” official tournaments (2005-2015). The wrestler’s profile was taken into account as a way to achieve a deep analysis. A total of 401 injuries were registered. The best wrestlers were the ones that suffered the least number of injuries. Contusions were the type of injuries more frequently registered (41.4%), while sprains were the most common cause of severe injury (42.3%). The most frequent anatomical location affected and the one in which a great number of severe injuries occurred were the lower limbs (38.2% and 45.4%). The knee, thorax, and shoulder accounted for almost half of the total injuries and represented 68% of the severe injuries. The obtained results suggest that Leonese Wrestling show a similar injury pattern to the one observed in other combat sports, Este trabajo contó con financiación parcial de la Diputación de León, la Federación Territorial de Castilla y León de Lucha y CIBERESP (MTM2015-64465-C2-1-R; MINECO / FEDER)

© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The objective of this study is to analyze the effect of different imaging modalities in treatment decision making in proximal humeral fractures. After evaluation of 116 consecutive proximal humeral fractures, observers were asked to give treatment recommendation (conservative vs. surgery). If surgery was proposed, they were told to select surgery of choice. When 3D imaging was added, complexity of fractures significantly increased (p¿

OBJECTIVE: To evaluate the effect of effervescent paracetamol on office and ambulatory blood pressure (BP) compared with noneffervescent paracetamol in hypertensive patients. DESIGN: This was a multicenter open crossover randomized clinical trial. SETTING: Primary care centers in Catalonia and the Basque Country. PARTICIPANTS: Inclusion criteria were office BP 150/95¿mmHg or less and daytime ambulatory BP 140/90¿mmHg or less, stable pharmacologic or nonpharmacologic antihypertensive treatment, and concomitant chronic osteoarticular pain. INTERVENTIONS: Baseline randomized assignment to 3-week periods of effervescent paracetamol (1¿g three times a day) first and noneffervescent paracetamol later, or inversely, during a 7-week study period. At the start and end of each treatment period, 24-h ambulatory BP monitoring was performed. MAIN OUTCOME MEASURES: Differences in 24-h SBP between baseline and end of both treatment periods. The main analyses were performed according to the intention-to-treat principle. RESULTS: In intention-to-treat analysis, 46 patients were analyzed, 21 were treated with paracetamol effervescent and noneffervescent later, and 25 followed the opposite sequence. The difference in 24-h SBP between the two treatments was 3.99¿mmHg (95% confidence interval 1.35-6.63; P¿=¿0.004), higher in the effervescent paracetamol treatment period. Similarly, the per-protocol analysis showed a difference in 24-h SBP between the two groups of 5.04¿mmHg (95% confidence interval 1.80-8.28; P¿=¿0.004), higher in the effervescent paracetamol treatment period. Self-reported pain levels did not differ between groups and did not vary by treatment period. No serious adverse events were reported in either study arm. CONCLUSION: Effervescent paracetamol tablets are responsible for a significant daytime and overall increase in ambulatory 24-h SBP. TRIAL REGISTRATION: NCT: 02514538 EudraCT: 2010-023485-53.

Treballs Finals de Grau en Estadística UB-UPC, Facultat d'Economia i Empresa (UB) i Facultat de Matemàtiques i Estadística (UPC), Curs: 2017-2018, Tutor: Montserrat Guillen Estany, (cat) El futur de les pensions és un debat actual en l'àmbit econòmic, social i polític. No només a Espanya, sinó també a la resta d'Europa, els països participen en la reforma dels processos per assegurar la sostenibilitat dels seus sistemes de pensions. El sistema de pensions a Espanya és públic, obligatori, contributiu i de distribució. Pateix un desequilibri a causa de la reducció dels contribuents per cada beneficiari i pel procés d'envelliment generacional. La Muestra Contínua de Vidas Laborables (MCVL) proporciona informació administrativa de més d'un milió de treballadors i pensionistes a Espanya, per tant, hi ha informació vàlida de tota la seva vida activa. El propòsit d'aquest treball és analitzar la diferència entre l’últim salari i la primera pensió de jubilació i mirant entre d’altres la diferència que hi ha entre homes i dones. Per dur a terme l'anàlisi, s'utilitzarà el programari estadístic "R" i els paquets relacionats amb la gestió de grans bases de dades., (eng) The future of pensions is a current debate in the economic, social and political spheres. Not only in Spain but also in the rest on Europe, the countries are involved in the processes reform in order to ensure the sustainability of their pension systems. The pension system in Spain is, public, compulsory, contributory and of distribution. It suffers from an imbalance due to the reduction of contributors to each beneficiary and to the process of generational aging. The MCVL provides administrative information from more than one million workers and pensioners in Spain, therefore, there is enough information of all their active lives. The purpose of this paper is to analyze the difference between the last salary and the first retirement pension and looking among others for the difference between men and women. To carry out the analysis, the statistical software "R" and the packages related to the management of big databases will be used.

School is an essential context that contributes to children's communicative competence. Decision Support Systems (DSS) are tools that can help teachers to assess their own practice and to make decisions to improve it (Gregg, 2009). Our aim is the construction, implementation and validation of a digital Decision Support System (EVALOE-DSS), conceived as a teacher empowerment tool for self-assessment and decision making about their teaching practice concerning students' oral skills. Participants are 4 teachers and their groups of students of 4 diverse schools. The research procedure includes: 1) design and development of a DSS for different type of schools; 2) researcher assessment of one classroom observation using EVALOE-DSS; 3) weekly teacher self-assessment of classroom observation and decision making using EVALOE-DSS; 4) analysis of self-assessments, decision making and changes in teaching practices; 5) teacher-researcher assessment of the helpfulness of DSS and introduction of changes. EVALOE-DSS is a multimedia tool consisting of 30 items that assess 5 dimensions: teaching management, instructional design, communicative functions and teacher strategies, students' communicative functions, and students' management. It includes, also, a brief description of each item and a variety of resources to help teachers to make decisions and introduce the actions in their teaching practice.

Surveys applying quota sampling in their final step are widely used in opinion and market research all over the world. This is also the case in Spain, where the surveys carried out by CIS (a public institution for sociological research supported by the government) have become a point of reference. The rules used by CIS to select individuals within quotas, however, could be improved as they lead to biases in age distributions. Analysing more than 545,000 responses collected in the 220 monthly barometers conducted between 1997 and 2016 by CIS, we compare the empirical distributions of the barometers with the expected distributions from the sample design and/or target populations. Among other results, we find, as a consequence of the rules used, significant overrepresentations in the observed proportions of respondents with ages equal to the minimum and maximum of each quota (age and gender group). Furthermore, in line with previous literature, we also note a significant overrepresentation of ages ending in zero. After offering simple solutions to avoid all these biases, we discuss some of their consequences for modelling and inference and about limitations and potentialities of CIS data.

It is currently well-known that diet plays an important role in the promotion of healthy lifestyle and the prevention of chronic diseases. The Diet4You project is conceived to support the creation of an intelligent decision support system that provides personalized menus fitting a nutritional plan and taking into account the characteristics, needs and preferences of the person. The system involves a background food database, recording a collection of foods and prepared dishes with their standard portions as well as their nutritional decomposition in different food families. This DB is used to search the best combination of dishes approaching the total intake of different nutrients specified in the prescribed nutritional plan. The available background databases, specify the quantities of standard portions of several foods based on different measurement units which are not standardized, and it happens that the weight specified by one cup of melon is different from that of one cup of berries, among others. This arises the need of applying variable conversion factors to the dish description, before assessing whereas the total quantities of a certain menu fit well to the prescription. In this paper, a knowledge based approach is presented to the automatically management. An annotated reference food ontology is built on the basis of additional documentation. However the granularity of the information provided is heterogeneous and non exhaustive. The ontology-based missing values imputation is presented to overcome this limitations.

Background Osteoporotic fractures still remain very infrequent and physicians rarely evaluate bone health. We wanted to assess the magnitude of this problem in the near future by determining the risk and likelihood of progression to osteoporosis. Methods We estimated the risk of progression to osteopenia/osteoporosis among HIV-infected patients with at least 2 DXA scans (3726 scans from 875 patients). Time-non-homogeneous bidirectional multistate models based on three states (normal bone mineral density, osteopenia and osteoporosis) were used to model the progression of bone mineral density as a function of age and to study the association between the risk of bone loss and antiretroviral use. Results The HRs associated with age (>45 versus ≤45 years) were: (i) from normal bone mineral density to osteopenia, 0.71 (95% CI 0.45-1.11) for men and 1.06 (95% CI 0.55-2.05) for women; and (ii) from osteopenia to osteoporosis, 0.83 (95% CI 0.51-1.35) for men and 0.99 (95% CI 0.38-2.56) for women. The transition probabilities from osteopenia to osteoporosis over 10 years among men aged 30 and 50 years were 14.9% (95% CI 10.5%-20.4%) and 19% (95% CI 14.3%-24.3%), respectively; and for women, 6.9% (95% CI 3.1%-14.4%) and 30.1% (95% CI 19.8%-41.8%), respectively. An increased osteoporosis risk was observed for PIs and PIs + tenofovir disoproxil fumarate; darunavir was associated with a higher risk of osteoporosis among men (HR 3.9; 95% CI 2-7.5) and women (HR 4.5; 95% CI 1.4-14.7); and atazanavir was associated with a higher risk of osteoporosis among women (HR 4.2; 95% CI 1.3-14). Conclusions Our results highlight the importance of monitoring bone mineral density given the high probability of progression to osteopenia/osteoporosis, especially in women. In the future, changes in antiretrovirals other than tenofovir, such as PIs, should be recommended to reduce the risk of fracture.

Prevention and nutrition are key issues to guarantee a healthy lifestyle and are in the kernel of the new paradigm of patient-centered medicine. A healthy diet protects against risk factors of a large number of chronic diseases and contribute to delay the disease appearance in the general population. More and more, making right diets is becoming essential from the health point of view. However, nutritionists design diets on the specific needs of each patient, using their accumulated experience and there are no well-formalized support mechanisms for such activity. The project Diet4You proposes the creation of an intelligent decision support system oriented to the adaptive and dynamic preparation of personalized diets for the specific individuals of general population, having or not, one or more diseases, by taking into account all the information available on the person. The diets will be built by considering the characteristics of the person, their health conditions, their habits and eventual drugs intake and their genetic information, which until now were not taken into account. The Diet4You tool is a hybrid system interacting several components in a complex way. One of those components is a subsystem able to compose complete menus, for a certain period of time, based on the nutritional prescriptions given by the nutritionists, in terms of balance of different families of nutrients. This component is based on a a Case-Based Reasoning (CBR) engine that adaptively creates menus with breakfast, lunch and dinner on the bases of real food databases containing dishes with their nutritional composition. In this work, this component of the whole system is presented, described and tested.

Summary Background The REVASCAT trial and other studies have shown that the neurovascular thrombectomy improves outcomes at 90 days post stroke. However, whether the observed benefit is sustained in the long term remains unknown. We report the results of the prespecified 12-month analysis of the REVASCAT trial. Methods Patients with acute ischaemic stroke who could be treated within 8 h of symptom onset were randomly assigned to medical therapy (including intravenous alteplase when eligible) and neurovascular thrombectomy with Solitaire FR or medical therapy alone. The main secondary outcome measure at 1 year follow-up was disability, measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) with categories 5 (severe disability) and 6 (death) collapsed into one category (severe disability or death), analysed as the distribution of the mRS. Additional prespecified secondary outcome measures included health-related quality of life measured with the EuroQol five dimensions questionnaire (EQ-5D) utility index (ranging from −0·3 to 1, higher values indicate better quality of life), the rate of functional independence (mRS 0–2), and cognitive function measured with the Trail Making Test (reported elsewhere). Treatment allocation was open label but endpoints at 12 months were assessed by masked investigators. The trial was registered at ClinicalTrials.gov, number NCT01692379. Findings From Nov 24, 2012, to Dec 12, 2014, 206 patients were randomly assigned to medical therapy plus endovascular treatment (n=103) or medical treatment alone (n=103), at four centres in Catalonia, Spain. At 12 months post randomisation, based on 205 of 206 outcomes available at 12 months, thrombectomy reduced disability over the range of the mRS (common adjusted odds ratio [aOR] 1·80, 95% CI 1·09–2·99), and improved functional independence (mRS=0–2; 45 [44%] of 103 patients vs 31 [30%] of 103 patients; aOR 1·86, 95% CI 1·01–3·44). Health-related quality of life was superior in the thrombectomy group (mean EQ-5D utility index score, 0·46 [SD 0·38] in the thrombectomy group vs 0·33 [0·33] in the control group, difference 0·12 [95% CI 0·03–0·22]; p=0·01). 1-year mortality was 23% (24 of 103 patients) in the thrombectomy group versus 24% (25 of 103 patients) in the control group. Interpretation At 12 months follow-up, neurovascular thrombectomy reduced post-stroke disability and improved health-related quality of life, indicating sustained benefit. These findings have important clinical and public health implications for evaluating the cost-effectiveness of the intervention in the long term. Funding Fundacio Ictus Malaltia Vascular through an unrestricted grant from Medtronic.

This is the peer reviewed version of the following article: Chacon, A., Mateu Jimenez, M., Langohr, K., Fermoselle, C., García Arumí, E., Andreu, A., Yelamos, J., Barreiro, E. Role of PARP activity in lung cancer-induced cachexia: effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype. "Journal of cellular physiology", Desembre 2017, vol. 232, núm. 12, p. 3744-3761, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/jcp.25851/pdf. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1-/-) and Parp-2-/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1-/-, and Parp-2-/-), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-¿B signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1-/- and Parp-2-/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-¿B signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention.

Report de Recerca aprovat per la Comissió de doctorat i de recerca del Departament d'EIO Conclusions from randomized clinical trials (RCT) rely primarily on the primary endpoint (PE) chosen at the design stage of the study. There should generally be only one PE which should be able to provide the most clinically relevant and scientific evidence regarding the potential eficacy of the new treatment. Therefore, it is of utmost importance to select it appropriately. Composite endpoints, consisting of the union of several endpoints, are often used as PE in RCT. Gomez and Lagakos (2013) develop a statistical methodology to evaluate the convenience of using a CE as opposed to one of its components. Their strategy is based on the asymptotic relative eficiency (ARE), relating the efi is based on the asymptotic relative eficiency (ARE), relating the eciency of using the logrank test based on the CE versus the eficiency based on one of its components. This paper introduces the freeware online platform CompARE that facilitates the study of the performance of different candidate endpoints which could be used as PE at the design stage of a trial. CompARE, through an intuitive interface, implements the novel ARE method.

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although only an ideal, a constant effect of treatment would facilitate individual management. A direct consequence of a constant effect is that the variance of the outcome measure would be the same in the treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively required. Methods: We reviewed parallel clinical trials with numerical primary endpoints published in 2004, 2007, 2010 and 2013. We collected the baseline and final standard deviations of the main outcome measure. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of five studies (n = 40, 19.2%) had statistically different variances between groups, implying a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: The mean variance ratio is significantly lower than 1 and the lower variance was found more often in the intervention group than in the control group, suggesting it is more usual for treated patients to be stable. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit from treatment. This would require further study as to whether the treatment effect outweighs the side effects as well as the economic costs. We have shown that there are ways to analyze the apparently unobservable constant effect.

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites. Electronic supplementary material The online version of this article (doi:10.1186/s40814-016-0105-8) contains supplementary material, which is available to authorized users.

Down syndrome (DS) is an aneuploidy syndrome that is caused by trisomy for human chromosome 21 resulting in a characteristic cognitive and behavioral phenotype, which includes executive functioning and adaptive behavior difficulties possibly due to prefrontal cortex (PFC) deficits. DS also present a high risk for early onset of Alzheimer Disease-like dementia. The dopamine (DA) system plays a neuromodulatory role in the activity of the PFC. Several studies have implicated trait differences in DA signaling on executive functioning based on genetic polymorphisms in the genes encoding for the catechol-O-methyltransferase (COMTVal158Met) and the dopamine transporter (VNTR-DAT1). Since it is known that the phenotypic consequences of genetic variants are modulated by the genetic background in which they occur, we here explore whether these polymorphisms variants interact with the trisomic genetic background to influence gene expression, and how this in turn mediates DS phenotype variability regarding PFC cognition. We genotyped 69 young adults of both genders with DS, and found that VNTR-DAT1 was in Hardy-Weinberg equilibrium but COMTVal158Met had a reduced frequency of Met allele homozygotes. In our population, genotypes conferring higher DA availability, such as Met allele carriers and VNTR-DAT1 10-repeat allele homozygotes, resulted in improved performance in executive function tasks that require mental flexibility. Met allele carriers showed worse adaptive social skills and self-direction, and increased scores in the social subscale of the Dementia Questionnaire for People with Intellectual Disabilities than Val allele homozygotes. The VNTR-DAT1 was not involved in adaptive behavior or early dementia symptoms. Our results suggest that genetic variants of COMTVal158Met and VNTR-DAT1 may contribute to PFC-dependent cognition, while only COMTVal158Met is involved in behavioral phenotypes of DS, similar to euploid population. This work was supported by grants, donations and agreements from Fondation Jérôme Lejeune (Paris, France), Instituto de Salud Carlos III FEDER, (PI11/00744), MINECO (SAF2010-19434 and SAF2013-49129-C2-1-R), EU (Era Net Neuron PCIN-2013-060), DIUE de la Generalitat de Catalunya (SGR 2009/1450, 2014SGR 680, 2014 SGR 464, SGR 2009/718, and SGR 2014/1125). LdH is recipient of a pre-doctoral fellowship from ISCIII [FI12/00319]. CRG is Center of Excellence Severo Ochoa SEV-2012-0208.

To estimate treatment effects, trials are initiated by randomising patients to the interventions under study and finish by comparing patient evolution. In order to improve the trial report, the CONSORT statement provides authors and peer reviewers with a guide of the essential items that would allow research replication. Additionally, WebCONSORT aims to facilitate author reporting by providing the items from the different CONSORT extensions that are relevant to the trial being reported. WebCONSORT has been estimated to improve the proportion of reported items by 0.04 (95% CI, -0.02 to 0.10), interpreted as "no important difference", in accordance with the scheduled desired scenario of a 0.15 effect size improvement. However, in a non-scheduled analysis, it was found that, despite clear instructions, around a third of manuscripts selected for trials by the editorial staff were not actually randomised trials. We argue that surprises benefit science, and that further research should be conducted in order to improve the performance of editorial staff.Please see related research: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0736-x.

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the “Sniffin´Sticks” test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects. The work was supported by the following: Instituto Salud Carlos III, http://www.isciii.es, FIS PI11/210, FIS14/290; Centro de Investigación Biomédica en Red. Fisiopatología de la Obesidad y Nutrición (CIBEROB), http://www.ciberobn.es; and Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR), www.gencat.cat/agaur/, 2014 SGR 1672. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. SI

IDESCAT Aquest treball s'emmarca dins de l'estadística oficial catalana i té com a objectiu final quantificar els errors de mostreig dels principals col lectius poblacionals de l'Enquesta de població activa, que és una enquesta complexa amb un disseny mostral bietàpic, estratificat i amb resultats calibrats per diferents variables. Per fer-ho, hem estudiat els diferents mètodes de remostreig i la linealització de Taylor, i els hem comparat mitjançant les funcions del paquet Survey per a R.

We consider estimation techniques from dual frame surveys in the case of estimation of proportions when the variable of interest has multinomial outcomes. We propose to describe the joint distribution of the class indicators by a multinomial logistic model. Logistic generalized regression estimators and model calibration estimators are introduced for class frequencies in a population. Theoretical asymptotic properties of the proposed estimators are shown and discussed. Monte Carlo experiments are also carried out to compare the efficiency of the proposed procedures for finite size samples and in the presence of different sets of auxiliary variables. The simulation studies indicate that the multinomial logistic formulation yields better results than the classical estimators that implicitly assume individual linear models for the variables. The proposed methods are also applied in an attitude survey.

Centre d’Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i SIDA de Catalunya En aquest treball s ha prensentat una metodologia de mostreig innovadora que no està descrita a la teoria clàssica de mostrejos i que cada vegada s'utilitza en més àmbits, ja que ha demostrat ser un mostreig adequat per reclutar individus de poblacions ocultes. En l anàlisi de dades obtingudes a partir d un mostreig Time-Location Sampling s ha de tenir en compte la probabilitat de selecció dels individus en el lloc de reclutament, la qual cosa comporta que s ha de realitzar una anàlisi de dades ponderades. En aquesta memòria s han revisat els fonaments estadístics de la metodologia Time-Location Sampling, s ha revisat les propostes d estimador de probabilitat de selecció existents a la literatura i també s ha presentat una proposta personal d estimador de probabilitat de selecció. El rendiment d aquesta nova proposta s ha avaluat analitzant les dades d un estudi europeu (SIALON II) que té com objectiu estimar la prevalença del VIH en la població d homes que tenen sexe amb homes, i s ha completat mitjançant un estudi de simulació.

This paper deals with small area estimation of poverty indicators. Small area estimators of these quantities are derived from partitioned time-dependent area-level linear mixed models. The introduced models are useful for modelling the different behaviour of the target variable by sex or any other dichotomic characteristic. The mean squared errors are estimated by explicit formulas. An application to data from the Spanish Living Conditions Survey is given.

En el context de les enquestes sobre les assignatures i l'activitat docent,i davant de la problemàtica de la baixa participació en les enquestes, vam veure la necessitat de crear un model per tal de definir estadísticament la capacitat mínima de resposta per poder considerar els resultats de les enquestes com a representatives de l'actuació docent i les assignatures. L'objectiu d'aquest treball és donar un criteri per garantir que les hipòtesis testades pugin ser resoltes amb suficients garanties de sensibilitat i especificitat. Es decideix plantejar un test d'hipòtesis sobre població de mida finita i amb mostra de grandària variable. La metodologia desenvolupada ha de permetre caracteritzar la prova diagnòstica en base a la seva capacitat de decisió correcte del test.

La Encuesta de Salud de Cataluña, ESCA 2010-2014, tiene un diseño muestral polietápico con ponderaciones, estratos y selección de conglomerados. Requiere la utilización de ponderaciones para conseguir un tamaño muestral mínimo a nivel pequeño de desagregación territorial. Este trabajo consiste en analizar los efectos del diseño en la estimación de las proporciones para los seis primeros semestres de esta operación estadística, mediante el uso de los softwares estadísticos SAS, R y Stata. Para ello, hay que comparar los resultados obtenidos según cual sea el nivel de complejidad del diseño que se considere para el cálculo de los efectos del diseño. Se concluye que ningún efecto del diseño estimado es excesivamente elevado.

The final publication is available at Springer via http://dx.doi.org/10.1007/s10439-014-0995-7 The objective of this work is to develop a remodeling model for biological matter coupling two different processes in a 3D framework: reorientation of the preferential direction of a given fibered structure and reorientation of the fibrils or filaments that make up such a structure. This work uses the microsphere-based approach to take into account the micro mechanics involved in biological fibered structures regarding both their passive behavior and the reorientation of their micro constituents. Moreover, the macro behavior of the material as a whole is obtained by means of homogenizing the underlying micro response. We associate the orientation space of the integration directions to the physical space of micro-fibrils. To approximate the directional distribution of the fibrils within each fiber bundle, a Bingham probability orientation density function is introduced into the Helmholtz energy function. With all these assumptions, the problem is studied from an energetic point of view, describing the dissipation inherent to remodeling processes, and the evolution equations for both reorientations (change in preferential direction of the network and change in shape of the fibril distribution) re obtained. The model is included in a finite element code which allows computing different geometries and boundary value problems. This results in a complete methodology for characterizing the reorientation evolution of different fibered biological structures, such as cells. Our results show remodeling of fibered structures in two different scales, presenting a qualitatively good agreement with experimental findings in cell mechanics. Hierarchical structures align in the direction of the maximum principal direction of the considered stimulus and narrow in the perpendicular direction. The dissipation rates follows predictable trends although there are no experimental findings to date for comparison. The incorporation of metabolic processes and an insight into cell-oriented mechano-sensing processes can help to overcome the limitations involved.

In situations where the sampling units in a study can be more easily ranked based on the measurement of an auxiliary variable, ranked set sampling provide unbiased estimators for the mean of a population that they are more efficient than unbiased estimator based on simple random sample. In this paper, we consider the Morgenstern type bivariate generalized exponential distribution (MTBGED) and obtain several unbiased estimators for a parameter mean of the marginal distribution of MTBGED based on different ranked set sampling schemes. The efficiency of all considered estimators are evaluate and has also been demonstrated with numerical illustrations., Accepted for publication SORT - Statistics and Operations Research Transactions; 2014

En el contexto de los estudios longitudinales observacionales, hemos obtenido los valores óptimos para el número de participantes y el número de medidas repetidas que maximizan la potencia para detectar el hipotético efecto, sin rebasar un presupuesto económico determinado, o que minimizan el coste total del estudio, alcanzando una potencia determinada. Hemos considerado una variable respuesta continua, cuya estructura de covarianza se supone exponencialmente amortiguada, y una exposición binaria variable en el tiempo, tanto para un efecto agudo y transitorio de la exposición, a través de una diferencia constante en la media entre expuestos y no expuestos, como para un efecto acumulativo, a través de una diferencia linealmente divergente. Hemos derivado expresiones cerradas para la solución del problema en el caso particular en que se supone que la estructura de covarianza de la respuesta es de simetría compuesta. Los resultados mostraron la importancia de la correlación intraclase de la exposición sobre la determinación de la combinación óptima del número de participantes y el número de medidas repetidas y, por tanto, sobre la potencia o el coste optimizados. Así, la incorrecta asunción de una exposición constante conduce a resultados sesgados en el cálculo del tamaño de la muestra y de la potencia o el coste del estudio. También analizamos la sensibilidad de los resultados a la presencia de datos faltantes debido al abandono de participantes durante el seguimiento, al cambio de la estructura de covarianza de la respuesta y a una prevalencia de la exposición variable en el tiempo. Como ejemplo, ilustramos algunos de estos resultados aplicando nuestros métodos en un estudio real. Además, proporcionamos el paquete de R optimalAllocation para realizar todos los cálculos necesarios para obtener la combinación óptima del número de participantes y el número de medidas repetidas In the context of observational longitudinal studies, the aim of this work is to obtain optimal values of the number of participants and the number of repeated measurements that maximize the power to detect the hypothesized effect, given the total financial cost of the study

Aquest treball es centra en el control de qualitat de la informació recollida en les enquestes de mobilitat centrant-se en una de les enquestes més importants que es realitzen a Catalunya i a Espanya, l'Enquesta de Mobilitat en Dia Feiner (EMEF) que té 10 anys d'història.. L¿objectiu del projecte es jo plantejar un procés de depuració de dades de una enquesta per tal de garantir la qualitat final de las que seran analitzades.El projecte es desenvoluparà en un centre universitari d'investigació social (www.iermb.cat) en el qual es treballa l¿EMEF (Enquesta de Mobilitat en dia Feiner). L'enquesta és propietat de l'Autoritat del Transport Metropolità (ATM-GenCat), Ajuntament de BCN i Entitat Metropolitana del Transport (CAMB). Es disposarà de permís per fer-la servir

The main objective of this paper is to detect the existence of financial contagion between the North American and European markets during the recent crises. To accomplish this, the relationships between the US and the Euro zone stock markets are considered, taking the daily equity prices of the Standard and Poor’s 500 as representative of the United States market and for the European market, the five most representative indexes. Time Series Factor Analysis (TSFA) procedure has allowed concentrating the information of the European indexes into a unique factor, which captures the underlying structure of the European return series. The relationship between the European factor and the US stock return series has been analyzed by means of the dynamic conditional correlation model (DCC). Once the DCC is estimated, the contagion between both markets is analyzed. Finally, in order to explain the sudden changes in dynamic US-EU correlation, a Markov switching model is fitted, using as input variables the macroeconomic ones associated with the monetary policies of the US as well as those related to uncertainty in the markets. The results show that there was contagion between the United States and European markets in the Subprime and Global Financial crises. The two-regime Markov switching model has helped to explain the variability of the pair-wise correlation. The first regime contains mostly the financially stable periods, and the dynamic correlations in this regime are explained by macroeconomic variables and other related with monetary policies in Europe and US. The second regime is explained mainly by the Federal Funds rate and the evolution of the Euro/US Exchange rate.

In this paper we have adopted the Khoshnevisan et al. (2007) family of estimators to extreme ranked set sampling (ERSS) using information on single and two auxiliary variables. Expressions for mean square error (MSE) of proposed estimators are derived to first order of approximation. Monte Carlo simulations and real data sets have been used to illustrate the method. The results indicate that the estimators under ERSS are more efficient as compared to estimators based on simple random sampling (SRS), when the underlying populations are symmetric.

In the last few years, European countries have shown a deep interest in applying small area techniques to produce reliable estimates at county level. However, the specificity of every European country and the heterogeneity of the available auxiliary information, make the use of a common methodology a very difficult task. In this study, the performance of several design-based, model-assisted, and model-based estimators using different auxiliary information for estimating unemployment at small area level is analyzed. The results are illustrated with data from Navarre, an autonomous region located at the north of Spain and divided into seven small areas. After discussing pros and cons of the different alternatives, a composite estimator is chosen, because of its good trade-off between bias and variance. Several methods for estimating the prediction error of the proposed estimator are also provided. This research has been supported by the Spanish Ministry of Science and Education (project MTM2005-00511) and the Spanish Ministry of Science and Innovation (MTM2008-03085).

In the present study, we propose a general class of estimators for population mean of the study variable in the presence of non-response using auxiliary information under double sampling. The expression of mean squared error (MSE) of the proposed class of estimators is derived under double (two-stage) sampling. Some estimators are also derived from the proposed class by allocating the suitable values of constants used. Comparisons of the proposed strategy with the usual unbiased estimator and other estimators are carried out. The results obtained are illustrated numerically using an empirical sample considered in the literature.

Este proyecto final de carrera, consiste en analizar la parte estadística de una tesis doctoral. Dicha tesis la ha realizado un alumno y trata sobre el turismo de una población brasileña llamada Tiradentes caracterizada por sus riquezas culturales, y se han elaborado unas encuestas para verificar el estado que tiene el turismo en la actualidad y analizar posibles mejoras para un futuro. El estadístico se encarga de recoger los resultados de la encuesta y analizarlos con todas las técnicas que se puedan utilizar. Finalmente, cuando estén las conclusiones extraídos se reunirán el cliente y el estadístico y valorarán los resultados obtenidos.