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BackgroundTo explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aβ) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD).MethodsTwo hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI),18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables.ResultsAdjusted multiple linear regression models showed that FreeSurfer (B − .245; 95% CI − .1.676, − .393,p = .016) and β burden (SUVR) (B − .180; 95% CI − 2.140, − .292;p = .070) were associated with face–name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face–name associative performance indicated that those individuals with either higher WMH load or higher Aβ burden showed the worst performance on the face–name associative memory CCs domain score.ConclusionsOur results suggest that increased WMH load and increased Aβ are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

Background Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. Objectives We aimed to analyze the characteristics of patients with a confirmed thrombotic event including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. Methods Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. Results Among 1,127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). 43 patients (62%) suffered venous thromboembolism, 18 (26%) arterial events and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic event where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR=18, 95% CI: 2.4-142, p, Highlights • COVID-19-associated coagulopathy and thrombogenesis are under scrutiny • Retrospective study of 80 thrombotic events in 69 patients from a 1,100-patient cohort • COVID-19 lead to a myriad of arteriovenous thrombotic events despite thromboprophylaxis • Hemostatic and inflammatory abnormalities are associated with mortality • Arterial thromboembolic events confer a high risk of death

BACKGROUND: Fundacio ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution. OBJECTIVE: To share our experience in adapting our model of care to the new situation to ensure continuity of care. METHODS: We detail the sequence of events and the actions taken within Fundacio ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed. RESULTS: The total number of individuals being actively followed by Fundacio ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began. DISCUSSION: We have shown that Fundacio ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care.

Background: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake. Aims: We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. Methods: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/-) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2. Results: Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02-1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months. Conclusions: Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 796706, and the Instituto de Salud Carlos III (ISCIII) grant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National R+D+I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa") awarded to M.M. Funds were also obtained from donations from “La nit de l’Alzheimer”, a charity dinner initiative that takes place yearly as part of the “Festival Castell de Peralada” (2016-2018). The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of C.H. Funds from Fundació ACE Institut Català de Neurociències Aplicades, Grifols, Life Molecular Imaging, Araclon Biotech, Alkahest, Laboratorio de análisis Echevarne and IrsiCaixa are supporting the FACEHBI study. These sponsors were not involved in the study design, data collection, analysis or interpretation. The sponsors have reviewed the manuscript and have given their approval.

Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER) Altres ajuts: Generalitat de Catalunya. Programa CERCA Altres ajuts: Instituto de Salud Carlos III (CIBERSAM i CIBERNED) Altres ajuts: Fundació "La Caixa" Altres ajuts: Grífols SA (GR@ACE project) Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Societies at large are increasingly accepting the need for a transition to a lower-carbon energy system. How this transition is conducted and its final results, however, are matters of concern. In fact, there is already some available evidence based on qualitative and case-study research showing that, in some cases, costly and uncertain technologies are being promoted instead of cheaper small-scale alternatives. This research intends to shed some quantitative light on this issue by looking at the stock market performance of electric utilities in the major European economies and their behavior in the face of increasing renewable energy deployments. The main result is that their performance has not worsened due to those deployments, except for the photovoltaic energy, which shows a consistent and negative impact across all countries, with Spain's remarkable exception. This is due to this energy source's characteristics, particularly its scalability, unabated cost declines, and technical simplicity, paving the way for decentralized and distributed energy markets instead of the current unique and centralized distribution system. The paper also discusses the shortcomings of the creative-destruction paradigm when applied in this context, showing that even an active 'exnovation' policy might not be enough to ensure this outcome. An active political stance supporting the appropriate kind of regulation to enable the right environment for these efficient developments to be realized is therefore required.

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3–2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection. The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism. We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak. We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization. The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE. PE incidence was 6.4% (29/452 patients). Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29). D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03). In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18–12.16), p = 0.03). We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88–43.60). Predictive value of AUC for ROC is 75.5%. We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis. An increase in D-dimer levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl.

Methods to assess global renewable energy investment plans are presented and applied to photovoltaic and wind energy roadmaps recently published by international organizations. Price learning rate effects, uncertainty and derived risk, social discounting, investment depreciation, cost of capital and other factors are dealt with in detail. Some significant empirical results are: a) the roadmaps are market competitive globally, and also economically efficient from an environmental point of view; b) the volume of funds required is significant, but the investments can be financed with moderate carbon taxes; c) more expansive roadmaps yield enhanced results regarding both competitiveness and environmental efficiency; d) risks derived from the uncertainty in estimated Learning Rates may be significant and measures to control them are presented.

The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.

Background: The PROFRUVE study is a controlled intervention based on the Theory of Planned Behavior (TPB), which follows those behavioral theories that have proved to be the most effective at changing infant fruit and vegetable (F\/) intake pattern. The main purpose of the study is to evaluate the effectiveness of an intervention program in increasing FV consumption in schoolchildren aged 8 to 10 and based on TPB. Methods: Eligible classrooms within schools from Vitoria-Gasteiz (Basque Country, Spain) will be randomly assigned to the intervention (classrooms n = 4; children n = 86) or control (classrooms n = 4; children n = 86) group. The intervention group will receive 14 sessions of 60 min during an academic year (October to June). These sessions, designed by a multidisciplinary team, are based on TPB and are directed at modifying determinants of behavior (attitudes, subjective norms, perceived behavioral control and intention of consumption), and intake of FV itself. Both the process and the evolution of consumption and determinants of behavior will be evaluated (before, during, shortly after and a year after) using validated surveys, 7 day food records, 24 h reminders and questionnaires. Discussion: This study will provide a valid and useful tool to achieve changes in the consumption of FV at school level. A negative result will be helpful in redefining new strategies in the framework of changing habits in the consumption of FV. This study is supported by the Government of the Basque Country (IT572/13), CIBERobn (Centro de Investigacion Biomedica en Red, ISCIII), City Council of Vitoria-Gasteiz and University of the Basque Country (Programa de Fomento del Consumo de Fruta y Verdura en la Poblacion Infantil de Vitoria-Gasteiz FASE II US14/15). In order to be founded by the University of the Basque Country, the project "Programa de Fomento del Consumo de Fruta y Verdura en la Poblacion Infantil de Vitoria-Gasteiz FASE II US14/15" was evaluated and peer reviewed by ANEP (National Agency for Evaluation and Forecastig). Arrizabalaga-Lopez M is a PhD fellowship holder from the University of the Basque Country UPV/EHU. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.

En aras al principio de adhesión voluntaria y abierta, las cooperativas presentan singularidades en torno a la figura del capital social, que las diferencia de otras entidades mercantiles. Dichas peculiaridades comportan un tratamiento contable especial del capital cooperativo. Las normas internacionales de contabilidad prevén la calificación contable del capital cooperativo como pasivo financiero o como fondo propio, según la regulación legal y/o estatutaria del derecho de baja del socio. Este planteamiento se ha traspuesto al derecho contable de la Unión Europea y de España, afectando a un buen número de cooperativas europeas, incidiendo en su imagen financiera. En este trabajo tratamos las peculiaridades contables que emanan de la posibilidad de la baja del socio en el marco de la normativa contable internacional, nacional y los últimos posicionamientos de organismos reguladores.Recibido: 12 junio 2017Aceptado: 14 octubre 2017Publicación en línea: 22 diciembre 2017

Resumen En esta actualizacion se presentan los principales sindromes geriatricos, concretamente el deterioro cognitivo, las caidas, la inmovilidad, la incontinencia y la fragilidad. Estos sindromes comparten una serie de caracteristicas como son su elevada frecuencia en la poblacion de edad avanzada, la perdida de autonomia personal y de la calidad de vida que provocan y la posibilidad de actuar clinicamente sobre ellos, especialmente en sus formas precoces. Se define brevemente el concepto de cada uno y los criterios e instrumentos para su diagnostico. En unos casos, los tratamientos son principalmente farmacologicos y, en otros, el manejo se basa en la prevencion o en otro tipo de terapias como los tratamientos cognitivos o funcionales.

This research intends to contribute to the analysis of planned and forecast future paths of renewable energy capacity deployments - mainly wind and solar photovoltaic. The paths forecast by the International Energy Agency as published in its roadmaps are considered. The learning rate of both energies, or 'learning by doing', that implies cost decreases as a result of capacity deployment is explicitly considered, as well as its variability. New values for both wind and photovoltaic learning rates are estimated and presented, that allow a significant simulation analysis. The implied uncertainty by that variability induces risks for the financial planning of investments, and a framework to assess and manage that risk is presented and implemented in the simulations conducted. It is shown that this parameter-variability is significant and yields less favorable results as compared to standard static-fixed parameter simulations. Alternative investment paths are considered, the results showing that a faster path does not necessarily result in a significant increase in the accumulated final investment. Thus, accelerated deployment paths are advised to fight climate change.

Background Computerized neuropsychological tests for early detection of Alzheimer’s disease (AD) have attracted increasing interest. Memory for faces and proper names is a complex task because its association is arbitrary. It implicates associative occipito-temporal cerebral regions, which are disrupted in AD. The short form of the Face-Name Associative Memory Exam (FNAME-12), developed to detect preclinical and prodromal AD, asks individuals to learn the names and occupations associated with 12 faces. The current work advances this field by using voice recognition and touchscreen response format. The purpose of this study is to create the first self-administered episodic memory test, FACEmemory®, by adapting the FNAME-12 for tablet use with voice recognition, touchscreen answers, and automatic scoring. The test was minimally supervised by a psychologist to avoid technological problems during execution and scored manually to assess the reliability of the automatic scoring. The aims of the present study were (1) to determine whether FACEmemory® is a sensitive tool for the detection of cognitive impairment, (2) to examine whether performances on FACEmemory® are correlated with those on the S-FNAME (paper-and-pencil version with 16 images), and (3) to determine whether performances on FACEmemory® are related to AD biomarkers in the cerebrospinal fluid (CSF) (Aβ42, p-tau, and Aβ42/p-tau ratio). Methods FACEmemory® was completed by 154 cognitively healthy (CH) individuals and 122 subjects with mild cognitive impairment, of whom 61 were non-amnestic (naMCI) and 61 amnestic (aMCI). A subsample of 65 individuals completed the S-FNAME, and 65 subjects received lumbar punctures. Results Performance on FACEmemory® was progressively worse from CH to the naMCI and aMCI groups. A cutoff of 31.5 in total FACEmemory® obtained 80.5% and 80.3% sensitivity and specificity values, respectively, for discriminating between CH and aMCI. Automatically corrected FACEmemory® scores were highly correlated with the manually corrected ones. FACEmemory® scores and AD CSF biomarker levels were significantly correlated as well, mainly in the aMCI group. Conclusions FACEmemory® may be a promising memory prescreening tool for detecting subtle memory deficits related to AD. Our findings suggest FACEmemory® performance provides a useful gradation of impairment from normal aging to aMCI, and it is related to CSF AD biomarkers.

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between Aβ deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral Aβ deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.

Building on previous studies that report thinning of the macula in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients, the use of optical coherence tomography (OCT) has been proposed as a potential biomarker for AD. However, other studies contradict these results. A total of 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients) from a memory clinic were consecutively included in this study and underwent a spectral domain OCT scan (Maestro, Topcon) to assess total macular volume and thickness. Macular width measurements were also taken in several subregions (central, inner, and outer rings) and in layers such as the retinal nerve fiber (RNFL) and ganglion cell (CGL). The study employed a design of high ecological validity, with adjustment by age, education, sex, and OCT image quality. AD, MCI, and control groups did not significantly vary with regard to volume and retinal thickness in different layers. When these groups were compared, multivariate-adjusted analysis disclosed no significant differences in total (p = 0.564), CGL (p = 0.267), RNFL (p = 0.574), and macular thickness and volume (p = 0.380). The only macular regions showing significant differences were the superior (p = 0.040) and nasal (p = 0.040) sectors of the inner macular ring. However, adjustment for multiple comparisons nullified this significance. These results are not supporting existing claims for the usefulness of macular thickness as a biomarker of cognitive impairment in a memory unit. OCT biomarkers for AD should be subject to further longitudinal testing. The authors thank the study participants and their families for their collaboration, and Topcon for its reliability as technological partnership. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 796706 awarded to MM; from Fundació ACE Institut Català de Neurociències Aplicades in Barcelona, Spain and from a donation of “La nit de l’Alzheimer”, a charity dinner initiative that took place on August 8th 2016 as part of the “Festival Castell de Peralada”. The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of CH. The present work was performed as part of Domingo Sánchez Ruiz’ doctoral program with title “Clinical Utility of OCT in diagnosing and monitoring of cognitive impairment” in the Department of Surgery and Morphological Sciences at Universitat Autonoma Barcelona (Barcelona, Spain).

At a European level, sustainable development (SD) is of the objectives of the European Union (EU) and has been included in EU policies and regulations. After ascertaining the untenable traditional production model, the concept of sustainability, and more precisely, ‘sustainable development’, became a central issue and led to a global concern where the progress towards it seemed highly imperative. There is an increasing interest in sustainability in Spain: many institutional statements have emphasized the need to implement SD at Higher Education Institutions (HEIs). Sustainability assessment and reporting results can help HEIs to focus on coverage and performance weaknesses, thereby highlighting where actions should be taken, as well as better sustainability plans. Regarding the GreenMetric ranking, which is open to global participation, an increase in the participation of Spanish universities has been observed. It indicates the interest of these HEIs to assess their policies and actions in relation to their efforts on sustainability and green campuses.

This research implements a methodology to the joint assessment of the photovoltaic and onshore wind investment roadmaps put forward by the main institutions in the field, International Renewable Energy Association (Irena) and the International Energy Agency, to achieve a low carbon emissions economy with near zero net greenhouse gases emissions. The two energies taken together account for over 80% of the renewable energy deployments envisaged by both roadmaps. The assessment is conducted according to economic criteria (the levelized cost of energy, capital requirements and financial risks), and environmental (carbon avoided, its value, and its cost). Given the recent Intergovernmental Panel on Climate Change (IPCC) report on the urgency to tackle climate change, accelerated deployments of the roadmaps are assessed as well. Overall, it is found that the roadmaps are financially sound, even under an accelerated scenario. Possible limits to the deployment of renewable energies roadmaps derived from the availability of raw materials and other constraints are also discussed, showing likely constraints for lithium batteries but not for photovoltaic and wind energies.

Purpose The main objective of the PROFRUVE study was to evaluate the effectiveness of a TPB-based intervention program at increasing fruit and vegetable (FV) consumption in schoolchildren aged 7–10. Methods Eight eligible classrooms were randomly assigned to the intervention (classrooms n = 4; children n = 90) or control group (classrooms n = 4; children n = 95). The intervention group received 14 sessions of 1 h during an academic year (from October to June) but the control group did not. Sessions were based on the Theory of Planned Behavior (TPB) and focused on modifying FV intake. FV consumption was evaluated before, shortly after and 1 year after intervention ended using validated 7-day food records. Results FV intake increased significantly in the intervention group (+ 0.45 servings/day; 95% CI 0.17–0.74; p = 0.001) but not in the control group (+ 0.01 servings/day; 95% CI −0.20–0.22; p = 0.409) shortly after the intervention. Long-term measurement showed that 1 year after intervention finished, the intervention group maintained the effect (+ 0.52 servings/day from baseline; 95% CI 0.22–0.78; p = 0.003). Linear mixed model also showed that nested groups by classrooms differ from intervention and control groups regarding FV intake change (p = 0.002). Multiple linear regression showed that receiving the intervention (B = 0.345, p = 0.045) and FV baseline intake (B = − 0.383, p = 0.000) were associated with FV intake change after adjusting the model by age, gender and family social economic status (SES) (R2 = 0.196). Conclusions The intervention program based on TPB seemed to be moderately effective in increasing FV intake and successful in maintaining the effect of the reached increase. Moreover, baseline FV intake determined the effect size of the intervention. Trial Registration This study was registered at ClinicalTrials.gov. Identifier: NCT03400891. Data registered 17/01/2018. This study was supported by the Government of the Basque Country (IT572/13), CIBERobn (Centro de Investigación Biomédica en Red, ISCIII), University of the Basque Country and City Council of Vitoria-Gasteiz (Programa de Fomento del Consumo de Fruta y Verdura en la Población Infantil de Vitoria-Gasteiz FASE II US14/15). Arrizabalaga-Lopez M is a PhD fellowship holder from the University of the Basque Country UPV/EHU.

BACKGROUND Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer's disease dementia, but little is known about its influence in subjective cognitive decline (SCD). OBJECTIVE To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. METHODS We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the neuropsychological variables. RESULTS The OHI sample were mostly women (75.9% versus 64.5%, p

Current research links the shadow economy (SE) and the unemployment rate either indirectly or by means of a preliminary estimate. This article establishes and empirically implements a methodology for estimating the size of the SE as a direct function of the tax and unemployment rates. This link is found to be extremely relevant in countries with high unemployment rates (such as Greece and Spain) and less relevant in countries with moderate unemployment rates (such as Germany and Italy). Unemployment’s contribution to the SE is shown to be significant, especially in the years following the economic downturn of 2008. The calculation of the variance and distribution of these estimates is another significant contribution. The common criticism that SE estimates are unreliable is addressed by calculating the variance and the distribution of the estimates, and the large size of the SE in Greece and Spain is once again confirmed.

This paper surveys the results of estimating learning rate (LR) equations for the photovoltaic (PV) industry at the world level, and reports new results, placing emphasis on estimation issues, and other shortcomings surveyed recently. The results are reported in detail, one relevant finding being that the learning rate parameter might reach values substantially higher than those usually reported (18–20%). This result, however, does not necessarily translate to other energies. The relevance of selecting the estimation sample, dynamic specification, and omitted variables in simple standard specifications for the estimated learning rate is highlighted. A solution for the LR in dynamic non stationary models is presented. The modeling of silicon prices is also discussed, and the concept of the total learning rate (TLR) is introduced. Probability confidence intervals for the main estimated learning rate parameters are analyzed, and the time decomposition of PV module prices is discussed, highlighting the role of fossil energy prices. It is found that the total LR might reach values above 27% with a 95% probability.

The main interlinked challenges to achieve a low-carbon emission economy are analyzed. It is argued first that there are no obstacles to a free market working effectively with a high penetration of distributed Renewable Energies (RE), since intermittency has been overstated, and affordable storage solutions are available because of strong learning rates. Demand-side management policies are promising too, neither are there foreseeable boundaries to the availability of economically extractable photovoltaic and wind energies. A full 100% RE system may be more challenging though, partly because bioenergy, a key dispatchable source in most available RE roadmaps, clashes with growing food needs and reforestation to counter greenhouse gases emissions. Similarly, the green growth proposal is constrained by materials availability, mainly cobalt and phosphorus, which will also constrain the deployment of electric vehicles. Alternatively, the United Nations Human Development Index may be a more suitable target for a sustainable RE system. Although history is not reassuring, the main global economic hurdle is possibly existing fossil fuel-related investments, likely to become stranded. An assessment of their value yields a substantially lower figure than is sometimes claimed, though. Finally, a limited role for nuclear energy is assessed positively, provided it is publicly owned.

Citizen science (CS) aims primarily to create a new scientific culture able to improve upon the triple interaction between science, society, and policy in the dual pursuit of more democratic research and decision-making informed by sound evidence. It is both an aim and an enabler of open science (OS), to which it contributes by involving citizens in research and encouraging participation in the generation of new knowledge. This study analyses scientific output on CS using bibliometric techniques and Web of Science (WoS) data. Co-occurrence maps are formulated to define subject clusters as background for an analysis of the impact of each on social media. Four clusters are identified: HEALTH, BIO, GEO and PUBLIC. The profiles for the four clusters are observed to be fairly similar, although BIO and HEALTH are mentioned more frequently in blogposts and tweets and BIO and PUBLIC in Facebook and newsfeeds. The findings also show that output in the area has grown since 2010, with a larger proportion of papers (66%) mentioned in social media than reported in other studies. The percentage of open access documents (30.7%) is likewise higher than the overall mean for all areas. This project received funding from the European Unions’ Horizon 2020 Research and Innovation Programme under grant 741657, with the name SciShops.eu. The content of this article does not reflect the official opinion of the European Union. Responsibility for the information and views expressed in the article lies entirely with the authors.

The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer's Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer's disease's (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.

Background Peripheral biomarkers that identify individuals at risk of developing Alzheimer’s disease (AD) or predicting high amyloid beta (Aβ) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aβ species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. Methods The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aβ40 and Aβ42 peptides. The association between Aβ40 and Aβ42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aβ levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aβ plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. Results FBB-PET global SUVR correlated weakly but significantly with Aβ42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aβ measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aβ FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aβ measurements (p value for interaction = 0.105). Conclusion Brain and plasma Aβ levels are partially correlated in individuals diagnosed with SCD. Aβ plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted. Electronic supplementary material The online version of this article (10.1186/s13195-018-0444-1) contains supplementary material, which is available to authorized users.

The role of genetic risk markers for Alzheimer's disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundació ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-ε4 was significantly associated with the memory function NEs 'delayed recall (DR)' (β = -0.76, p = 4.1 × 10-10), 'learning' (β = -1.35, p = 2.91 × 10-6), and 'recognition memory' (β = -0.58, p = 9.67 × 10-5); and with 'DR' in the aMCI group (β = -0.36, p = 2.96 × 10-5). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-ε4 was also significantly associated with the NE 'learning' in individuals classified as having Pss-aMCI (β = -1.37, p = 5.82 × 10-5). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the 'backward digits' working memory NE (β = 0.52, p = 7.57 × 10-5) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE 'repetition' (β = -0.19, p = 5.34 × 10-6). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.

Summary Background To develop a prediction rule to describe the risk of death as a result of enterococcal bloodstream infection. Methods A prediction rule was developed by analysing data collected from 122 patients diagnosed with enterococcal BSI admitted to the Clinica Universidad de Navarra (Pamplona, Spain); and validated by confirming its accuracy with the data of an external population (Hospital del Mar, Barcelona). Results According to this model, independent significant predictors for the risk of death were being diabetic, have received appropriate treatment, severe prognosis of the underlying diseases, have renal failure, received solid organ transplant, malignancy, source of the bloodstream infection and be immunosuppressed. The prediction rule showed a very good calibration (Hosmer–Lemeshow statistic, P = 0.93) and discrimination for both training and testing sets (area under ROC curve = 0.84 and 0.83 respectively). Conclusions The predictive rule was able to predict risk of death as a result of enterococcal bloodstream infection as well as to identify patients, who being below the threshold value, will have a low risk of death with a negative predictive value of 96%.

Introduction Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods We evaluated apolipoprotein E ( APOE ) e4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE e4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion The FACEHBI sample presents APOE e4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

BackgroundVerb fluency (VF) is the less commonly used fluency test, despite several studies suggesting its potential as a neuropsychological assessment tool. Objective: To investigate the presence of VF deficits in mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia; to assess the usefulness of VF in the detection of cognitively healthy (CH) people who will convert to MCI, and from MCI to dementia; and to establish the VF cut-offs useful in the cognitive assessment of Spanish population.Methods568 CH, 885 MCI, and 367 mild AD dementia individuals were administered the VF test and a complete neuropsychological battery. Longitudinal analyses were performed in 231 CH and 667 MCI subjects to search for VF predictors of diagnosis conversion.ResultsA worsening on VF performance from CH, MCI to AD dementia groups was found. Lower performances on VF were significantly related to conversion from CH to MCI/MCI to dementia. When the effect of time to conversion was analyzed, a significant effect of VF was found on the faster conversion from CH to MCI, but not from MCI to dementia. Moreover, VF cut-off scores and sensitivity/specificity values were calculated for 6 conditions (3 age ranges by 2 educational levels). ConclusionThe VF test may be a useful tool for the differential diagnosis of cognitive failure in the elderly. Since VF deficits seem to take place in early stages of the disease, it is a suitable neuropsychological tool for the detection not only of CH people who will convert to MCI, but also from MCI to dementia.

Background: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. Objectives: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). Design: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. Setting: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. Participants: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. Measurements: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. Results: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. Conclusions: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

We investigated the antinociceptive properties of dexketoprofen trometamol [S(+)-ketoprofen tromethamine salt; SKP], a new analgesic, antiinflammatory drug, using the pain-induced functional impairment model in the rat (PIFIR), an animal model of arthritic pain. SKP was compared with racemic ketoprofen tromethamine salt (rac-KP), R(-)-ketoprofen tromethamine salt (RKP), ketorolac (KET), and morphine (MOR). We also assessed the effects of flurbiprofen (rac-FB) and its enantiomers (SFB and RFB) in the same model. Groups of six rats received either vehicle or analgesic drug and antinociception was evaluated by evaluating the dose-response curves over time. SKP was an effective antinociceptive drug in this model and was almost equally potent by either oral or intracerebroventricular administration. The oral potency of SKP was similar to that of oral KET and greater than that of oral MOR. No significant differences were observed between racemic ketoprofen and its enantiomers when administered orally. In the rat, significant bioinversion of RKP to SKP occurs when RKP is given orally. After oral administration of RKP, SKP was detectable in 30 min and surpassed the concentration of RKP after 3 h. Nevertheless, when the compounds were given intracerebroventricularly, some stereoselectivity in favor of SKP was observed. Stereoselectivity was observed with flurbiprofen, an analogue of ketoprofen that does not undergo significant metabolic inversion. Whereas SFB was an effective antinociceptive, RFB had no antinociceptive effect at the doses tested when given either orally or intracerebroventricularly.

Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit prostaglandin synthesis in the gastrointestinal mucosa, which can lead not only to stomach ulcers but also ulcers in the small and large intestines. Ulcers of the small intestine are less common than those of the stomach, but intestinal lesions are more life threatening. Although the R(-)-enantiomers of the arylpropionic acid (APA) class of NSAIDs are assumed to lack the toxic effects of cyclooxygenase inhibition, they may contribute to the ulcerogenicity of racemates. We have examined the intestinal ulcerogenic effects of single oral doses of S(+)-ketoprofen compared with racemic ketoprofen in the small intestine and cecum of rats. The toxicity in the small intestine was measured as the weight ratio between portions of intestine showing lesions and the total weight of the tissue. Toxicity in the cecum was evaluated by measuring the size of the ulcers. S(+)-ketoprofen had no significant ulcerogenic effect at 10 or 20 mg/kg. However, racemic ketoprofen was clearly ulcerogenic in the small intestine and cecum at the 40 mg dose. R(-)-ketoprofen at 20 mg/kg does not show any effect in the cecum and only limited ulcerogenesis in the small intestine: The latter effect may be the result of racemic inversion. Therefore, the ulcerogenic action of racemic ketoprofen can be interpreted as a synergism between S(+)- and R(-)-ketoprofen. The mechanism of this synergism is not well understood but may be a general feature of APA NSAIDs.

The efficacy and tolerability of single doses of dexketoprofen trometamol12.5 mg, 25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind, randomized, placebo-controlled study of 210 patients with moderate to severe pain after removal of one mandibular impacted third molar tooth. Pain intensity and pain relief were monitored for 6 h after administration of medication using visual analogue and verbal rating scales. All four active treatments were significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50 mg produced an analgesic effect within 30 min of administration and their effect persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to those of the higher doses of dexketoprofen trometamol, but it had a slower onset. The 12.5-mg dose of dexketoprofen trometamol was significantly superior to placebo but produced a lower level and shorter duration of analgesia compared to the other active treatments. There were no significant differences between 25 and 50 mg of dexketoprofen trometamol in any measure of analgesic efficacy. No serious adverse events were observed and there were no significant differences in the incidence of adverse events among treatment groups. These results demonstrate that dexketoprofen trometamol 25 mg is at least as effective as the racemic ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid onset of action compared to ketoprofen suggests that dexketoprofen trometamol is more appropriate for treatment of acute pain.

Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo.

The optimization of investment deployment roadmaps for single energy cases under significant learning rate effects is considered. An analytical solution for the minimization of the present value of total discounted cost is first considered. Then it is argued that a more appropriate criterion for roadmap design from the economic point of view would be the minimization of the levelized cost of energy and the analytical solution is also given. Solution methods for the optimization problem based on several kinds of simulations are presented and shown to work adequately. The first empirical result is that the cost minimization criterion leads to delayed investments; minimizing the levelized cost of energy on the contrary, is broadly compatible with accelerated investment deployments. It is also shown that increasing the end target values for capital investment and shortening the end roadmap horizon date, do not imply an increase in the levelized cost of energy, thereby lending support to the urgency required by the latest Intergovernmental Panel on Climate Change report to accelerate the carbon emissions reductions.

The study of journal authorship and editorial board membership from a gender perspective is addressed in this paper following international recommendations about the need to obtain science and technology indicators by gender. Authorship informs us about active scientists who contribute to the production and dissemination of new knowledge through journal articles, while editorial board membership tells us about leading scientists who have obtained scientific recognition within the scientific community. This study analyses by gender the composition of the editorial boards of 131 high-quality Spanish journals in all fields of science, the presence of men and women as authors in a selection of 36 journals, and the evolution of these aspects from 1998 to 2009. Female presence is lower than male presence in authorship, editorial board membership and editorship. The presence of female authors is slightly lower than the presence of women in the Spanish Higher Education sector and doubles female presence in editorial boards, which mirrors female presence in the highest academic rank. The gender gap tends to diminish over the years in most areas, especially in authorship and very slightly in editorial board membership. Large editorial boards and having a female editor-in-chief are positively correlated with women presence in editorial boards. The situation of women in Spanish science is further assessed in an international context analysing a selection of international reference journals. The usefulness of journal-based indicators to monitor the situation of men and women in science and to assess the success of policies oriented to enhance gender equality in science is finally discussed.

Acute intermittent porphyria (AIP) results from haplo-insufficient activity of porphobilinogen deaminase (PBGD) and is characterized clinically by life-threatening, acute neurovisceral attacks. To date, liver transplantation is the only curative option for AIP. The aim of the present preclinical nonhuman primate study was to determine the safety and transduction efficacy of an adeno-associated viral vector encoding PBGD (recombinant AAV serotype 5-codon-optimized human porphobilinogen deaminase, rAAV5-cohPBGD) administered intravenously as part of a safety program to start a clinical study in patients with AIP. Macaques injected with either 1 × 10(13) or 5 × 10(13) vector genomes/kg of clinical-grade rAAV5-cohPBGD were monitored by standardized clinical parameters, and vector shedding was analyzed. Liver transduction efficacy, biodistribution, vector integration, and histopathology at day 30 postvector administration were determined. There was no evidence of acute toxicity, and no adverse effects were observed. The vector achieved efficient and homogenous hepatocellular transduction, reaching transgenic PBGD expression levels equivalent to 50% of the naturally expressed PBGD mRNA. No cellular immune response was detected against the human PBGD or AAV capsid proteins. Integration site analysis in transduced liver cells revealed an almost random integration pattern supporting the good safety profile of rAAV5-cohPBGD. Together, data obtained in nonhuman primates indicate that rAAV5-cohPBGD represents a safe therapy to correct the metabolic defect present in AIP patients.