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We consider the spread of an infectious disease on a heterogeneous metapopulation defined by any (correlated or uncorrelated) network. The infection evolves under transmission, recovery and migration mechanisms. We study some spectral properties of a connectivity matrix arising from the continuous-time equations of the model. In particular we show that the classical sufficient condition of instability for the disease-free equilibrium, well known for the particular case of uncorrelated networks, works also for the general case. We give also an alternative condition that yields a more accurate estimation of the epidemic threshold for correlated (either assortative or dissortative) networks Supported by Ministry of Economy and Competitiveness of the Spanish Government grant numbers MTM2011-27739-C04-03 (first author) and DPI2011-25822 (second author). Also by Generalitat de Catalunya projects 2009-SGR-345 (first author) and 2009-SGR-1228 (second author).

© 2022 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/ Uncertainty Quantification (UQ) is a booming discipline for complex computational models based on the analysis of robustness, reliability and credibility. UQ analysis for nonlinear crash models with high dimensional outputs presents important challenges. In crashworthiness, nonlinear structural behaviours with multiple hidden modes require expensive models (18 h for a single run). Surrogate models (metamodels) allow substituting the full order model, introducing a response surface for a reduced training set of numerical experiments. Moreover, uncertain input and large number of degrees of freedom result in high dimensional problems, which derives to a bottle neck that blocks the computational efficiency of the metamodels. Kernel Principal Component Analysis (kPCA) is a multidimensionality reduction technique for non-linear problems, with the advantage of capturing the most relevant information from the response and improving the efficiency of the metamodel. Aiming to compute the minimum number of samples with the full order model. The proposed methodology is tested with a practical industrial problem that arises from the automotive industry. This work is partially funded by Generalitat de Catalunya (Grant Number 1278 SGR 2017-2019 and Pla de Doctorats Industrials 2017 DI 058) and Ministerio de Economía y Empresa and Ministerio de Ciencia, Innovación y Universidades (Grant Number DPI2017-85139-C2-2-R).

Markov chain Monte Carlo (MCMC) methods have become standard in Bayesian inference and multi-observable inversions in almost every discipline of the Earth sciences. In the case of geodynamic and/or coupled geophysical-geodynamic inverse problems, however, the computational cost associated with the solution of large-scale 3-D Stokes forward problems has rendered probabilistic formulations impractical. Here we present a novel and extremely efficient method to produce ultrafast solutions of the 3-D Stokes problem for MCMC simulations. Our approach combines the individual benefits of Reduced Basis techniques, goal-oriented error formulations, and MCMC algorithms to produce an accurate and computationally efficient surrogate for the forward problem. Importantly, the surrogate adapts itself during the MCMC simulation according to the history of the chain and the goals of the inversion. This maximizes the efficiency of the forward problem and removes the need for preinversion off-line computations to build a surrogate. We demonstrate the benefits and limitations of the method with several numerical examples and show that in all cases the computational cost is of the order of

This study aimed to assess the effect of the scoring moment on the conditional probability of winning or losing a professional soccer match, as well as identified the most influential variables contributing to victory in Major League Soccer (MLS), the men’s professional league in the United States. Data from 680 matches played in the 2015 and 2016 regular seasons were analysed, by dividing the matches into fifteen-minute periods. Additionally, the influence of playing home or away on the match outcome and the type of technical-tactical actions that lead to a goal was also analysed. The temporal analysis revealed that scoring first increased the probability of winning the match significantly and showed dependency on the time in which the goal was scored. The two principal components of the principal component analysis (PCA) were counterattacks (PC1) and crosses (PC2). These were the most critical variables during open play to determine how MLS teams scored goals. Nevertheless, scoring first, playing as a home team always gave a better chance to win the game than scoring first and playing away (0.72 vs. 0.32 probability). As the match approached the end, winning or losing was even more determinant and less reversible (0.85 vs. 0.72 for the home and away team respectively when they were ahead on the score in the minute 75 or later). These findings can contribute to a better understanding of the performance indicators in professional soccer, helping coaches to determine the right strategies and improving the tactical patterns to succeed in competition

Efficient coordination of unmanned aerial vehicles (UAVs) requires the solving of challenging operational problems. One of them is the integrated team task assignment and orienteering problem (TAOP). The TAOP can be seen as an extension of the well-known team orienteering problem (TOP). In the classical TOP, a homogeneous fleet of UAVs has to select and visit a subset of customers in order to maximize, subject to a maximum travel time per route, the total reward obtained from these visits. In the TAOP, a number of different tasks (customer services) have to be assigned to a fleet of heterogeneous UAVs, while the best routing plan must also be determined to cover these services. Since factors such as weather conditions might influence travel times, these are modeled as random variables. Reliability issues are also considered, since random times might prevent a route from being successfully completed before a UAV runs out of battery. Peer Reviewed Objectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats Sostenibles

A family A of k-subsets of { 1 , 2 , … , N } is a Sidon system if the sumsets A + A ′ , A , A ′ ∈ A are pairwise distinct. We show that the largest cardinality F k ( N ) of a Sidon system of k-subsets of [ N ] satisfies F k ( N ) ≤ ( N − 1 k − 1 ) + N − k and the asymptotic lower bound F k ( N ) = Ω k ( N k − 1 ) . More precise bounds on F k ( N ) are obtained for k ≤ 3 . We also obtain the threshold probability for a random system to be Sidon for k = 2 and 3.

This paper characterizes the robust second-moment stability of stochastic linear systems subject to varying delays. The delays assume a particular form suitable to represent packet loss in networked control systems, under the zero-order hold feedback. The proposed robust stability condition requires checking the spectral radius of an appropriate matrix that that depends on uncertain parameters belonging to a polytope. Due to this polytope’s dependence, checking the spectral radius is difficult from the numerical viewpoint. As an attempt to solve the problem, we convert the polytope-based condition into a randomized approach. Namely, we present probability bounds that help us certificate the robust second-moment stability under high probability. A real-time electronic application illustrates the potential benefits of our approach.

Rework adversely impacts the performance of building projects. In this study, data were analyzed from 788 construction incidents in 40 Spanish building projects to determine the effects of project and managerial characteristics on rework costs. Finally, regression analysis was used to understand the relationships among contributing factors and to develop a model for rework prediction. Interestingly, the rework prediction model showed that only the original contract value (OCV) and the project location in relation to the company’s headquarters contributed to the regression model. Project type, type of organization, type of contract, and original contract duration (OCD), which represents the magnitude and complexity of a project, were represented by the OCV. This model for rework prediction based on original project conditions enables strategies to be put in place prior to the start of construction, to minimize uncertainties, to reduce impacts on project cost and schedule, and, thus, to improve productivity.

Prehospital clinical scales to identify patients with acute stroke with a large vessel occlusion and direct them to an endovascular-capable stroke center are needed. We evaluated whether simplification of the Rapid Arterial oCclusion Evaluation (RACE) scale, a 5-item scale previously validated in the field, could maintain its high performance to identify patients with large vessel occlusion. Methods: Using the original prospective validation cohort of the RACE scale, 7 simpler versions of the RACE scale were designed and retrospectively recalculated for each patient. National Institutes of Health Stroke Scale score and proximal large vessel occlusion were evaluated in hospital. Receiver operating characteristic analysis was performed to test performance of the simplified versions to identify large vessel occlusion in patients with suspected stroke. For each version, the threshold with sensitivity closest to the original scale (85%) was used, and the variation in specificity and correct classification were assessed. Results: The study included 341 patients with suspected stroke; 20% had large vessel occlusion. The 7 simpler versions of the RACE scale had slightly lower area under the curve for detecting large vessel occlusion because of lower specificity at the chosen sensitivity level. Correct classification rate decreased 9% if facial palsy was simplified or if eye or gaze deviation was removed, and decreased 4.5% if the aphasia or agnosia cortical sign was removed. Conclusions: We recommend the original RACE scale for prehospital assessment of patients with suspected stroke for its ease of use and its high performance to predict the presence of a large vessel occlusion. The use of simplified versions would reduce its predictive value.

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

This article aims to show the results from the Perception Evaluation Kit workshop: A Case Study with Materials. The study attempts to understand people’s sensorial perception of materials as a stimulus and what constitutes the most appropriate communication format for learning about their characteristics without losing information. Eleven people participated in this activity and, using evaluation tools in a test format, evaluated all the sensory properties of the following materials: Alusion, Cladonia stellaris, and Silkworms. These materials were presented in various interaction formats, called channels: text plus image–C1, video–C2, and physical sample plus audio–C3. Each participant evaluated one material per channel, without repeating samples or interaction formats. The activity was then discussed and, a month later, a question was asked to see what material they remembered best and how they described it. The data obtained were analysed with a two-way ANOVA statistical test to detect and compare the most notable differences. The most relevant results indicate a significant difference depending on the channel used to transmit the information of the materials and their sensory attributes, making it possible to evaluate the choice of the channel or the combination of channels to encourage more effective learning regarding materials

The Poisson distribution is a distribution commonly used in statistics. It also plays a central role in the analysis of the transient behaviour of continuous-time Markov chains. Several methods have been devised for evaluating using floating-point arithmetic the probability mass function (PMF) of the Poisson distribution. Restricting our attention to published methods intended for the computation of a single probability or a few of them, we show that neither of them is completely satisfactory in terms of accuracy. With that motivation, we develop a new method for the evaluation of the PDF of the Poisson distribution. The method is intended for the computation of a single probability or a few of them. Numerical experimentation illustrates that the method can be more accurate and slightly faster than the previous methods. Besides, the method comes with guaranteed approximation relative error.

OD matrices that describe mobility patterns provide major input to most transport analysis models. Since OD matrices are not yet directly observable, they are usually estimated indirectly. Data from new sources such as mobile phone records and GPS traces from mobile apps are emerging alternatives that allow for cheaper and timely estimates. However, they are still hindered by weaknesses that must be studied for use as input to transportation models. This paper presents a case study using mobility data from mobile phone records, with the goal of establishing a methodology for validating the obtained OD matrices and generating the appropriate input for traffic assignment models. Spatial and temporal consistency of OD data elaborated from mobile records has been proved to be useful for transportation modelling needs.

Objective:To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial.Methods:REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded.Results:From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51–6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60–8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life.Conclusions:Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery.ClinicalTrials.gov identifier:NCT01692379.Classification of evidence:This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months.

Canard-induced phenomena have been extensively studied in the last three decades, both from the mathematical and from the application viewpoints. Canards in slow-fast systems with (at least) two slow variables, especially near folded-node singularities, give an essential generating mechanism for Mixed-Mode oscillations (MMOs) in the framework of smooth multiple timescale systems. There is a wealth of literature on such slow-fast dynamical systems and many models displaying canard-induced MMOs, in particular in neuroscience. In parallel, since the late 1990s several papers have shown that the canard phenomenon can be faithfully reproduced with piecewise-linear (PWL) systems in two dimensions although very few results are available in the three-dimensional case. The present paper aims to bridge this gap by analysing canonical PWL systems that display folded singularities, primary and secondary canards, with a similar control of the maximal winding number as in the smooth case. We also show that the singular phase portraits are compatible in both frameworks. Finally, we show on an example how to construct a (linear) global return and obtain robust PWL MMOs., to appear in SIAM Review (2016)

The Flexible Periodic Vehicle Routing Problem is the problem of visiting a given set of customers considering a certain periodicity to attend their demands. It is a generalization of the Periodic Vehicle Routing Problem where the fixed schedule constraint is relaxed and the quantity to deliver to each customer at each visit is a decision variable. This flexibility leads to remarkable savings in total costs and this explains the interest in studying the problem and developing effective solution approaches. In this work, an iterative two-phase matheuristic is developed to solve medium and large instances of the problem. Computational tests are made on benchmark instances and on newly generated instances. The results of the matheuristic are compared to the best-known solutions, on small-size instances, and to lower bounds on larger instances. Computational results show that good quality solutions are obtained in a reasonable amount of time.

During cardiac diseases many types of anatomical and functional remodeling of cardiac tissue can occur. In this work, we focus on two conditions: hypoxia and fibrosis, which are part of complex pathological modifications that take place in many cardiac diseases (hypertrophic cardiomyopathy, hypertensive heart disease, and recurrent myocardial infarction) and respiratory diseases (obstructive pulmonary disease, obstructive sleep apnea, and cystic fibrosis). Using computational models of cardiac electrophysiology, we evaluate if the interplay between hypoxia and fibrosis is sufficient to trigger cardiac arrhythmia. We study the mechanisms behind the generation of ectopic beats, an arrhythmic trigger also known as premature ventricular contractions (PVCs), in regions with high hypoxia and fibrosis. First, we modify an electrophysiological model of myocytes of the human left ventricle to include the effects of hypoxia. Second, diffuse fibrosis is modeled by randomly replacing cardiac myocytes by non-excitable and non-conducting cells. The Monte Carlo method is used to evaluate the probability of a region to generate ectopic beats with respect to different levels of hypoxia and fibrosis. In addition, we evaluate the minimum size of three-dimensional slabs needed to sustain reentries for different stimulation protocols. The observed mechanism behind the initiation of ectopic beats is unidirectional block, giving rise to sustained micro-reentries inside the region with diffuse fibrosis and hypoxia. In summary, our results suggest that hypoxia and fibrosis are sufficient for the creation of a focal region in the heart that generates PVCs. We acknowledge support from CAPES by the grant 88881.065002/2014-01 of the Brazilian program Science without borders, and from MINECO of Spain under the Ramon y Cajal program with the grant number RYC-2012-11265

Document tècnic sobre l´ús de mesures de similitud estructural per l'avaluació del goodness of fit en procediments d'estimació de matrius OD dinàmiques. Tesi 2017 DI 41.

The discrete case of Bayes’ formula is considered the paradigm of information acquisition. Prior and posterior probability functions, as well as likelihood functions, called evidence functions, are compositions following the Aitchison geometry of the simplex, and have thus vector character. Bayes’ formula becomes a vector addition. The Aitchison norm of an evidence function is introduced as a scalar measurement of information. A fictitious fire scenario serves as illustration. Two different inspections of affected houses are considered. Two questions are addressed: (a) which is the information provided by the outcomes of inspections, and (b) which is the most informative inspection.

Altres ajuts: we are indebted to CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER) for funding AV. Also, to Marató de TV3 foundation (TV32013-3930). Marató TV3 (2013-2030) granted to RM, for funding research on targeted, protein-based drug delivery. MTPF received a fellowship from Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil (2015/20193-3).NS by a predoctoral fellowship from the Government of Navarra and UU received a Sara Borrell postdoctoral fellowship from ISCIII. AV received an Icrea Academia Award. Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.

In the context of aircraft turnaround processes, this paper illustrates how simulation can be used not only to analyze critical activities and paths, but also to generate the associated survival functions –thus providing the probabilities that the turnaround can be completed before a series of target times. After motivating the relevance of the topic for both airlines and airports, the paper reviews some related work and proposes the use of Monte Carlo simulation to obtain the critical paths of the turnaround process and generate the associated survival function. This analysis is performed assuming stochastic completion times for each activity in the process –which contrast with current practices in which deterministic times are usually assumed. A series of numerical experiments contribute to illustrate these ideas. These experiments are based on a realistic environment considering the Boeing 737-800 aircraft, although the analysis can be easily extended to any other configuration. Different levels of passengers’ occupancy are analyzed, as well as two alternative designs for the turnaround stage.

We are interested in characterising pairs $S,T$ of $F$-linear subspaces in a field extension $L/F$ such that the linear span $ST$ of the set of products of elements of $S$ and of elements of $T$ has small dimension. Our central result is a linear analogue of Vosper's Theorem, which gives the structure of vector spaces $S, T$ in a prime extension $L$ of a finite field $F$ for which $\dim_FST =\dim_F S+\dim_F T-1,$ when $\dim_F S, \dim_F T\ge 2$ and $\dim_F ST\le [L:F]-2$., 33 pages

PURPOSE: The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). MATERIALS AND METHODS: In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. RESULTS: Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. CONCLUSIONS: Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).

Aims Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of alcohol that can be detected in conventional and non-conventional biological matrices for longer periods than alcohol. The aim was to describe the time courses of both biomarkers after ingestion of acute low–moderate doses of ethanol. Methods The study design was double-blind, randomized, crossover and controlled with placebo. Participants were distributed in three different cohorts: (a) Cohort-1: two doses of 18 and 30 g of ethanol and placebo were administered to 12 subjects; (b) Cohort-2: two doses of 6 and 12 g of ethanol and placebo were administered to six subjects and (c) Cohort-3: two doses of 24 and 42 g of ethanol and placebo were administered to six subjects. Each participant received two doses of ethanol and placebo. Plasma concentrations (0–6 h) of ethanol and specific FAEEs (palmitic, stearic, linoleic and oleic acid ethyl esters) and urinary concentrations of EtG (0–24 h) were measured. Results A dose-dependent increase in blood ethanol concentrations was observed. EtG excretion and FAEEs plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. Area under the curve (AUC0-6h) of ethanol concentrations showed a linear trend with non-oxidative metabolites’ concentrations. Conclusion The formation rate of ethanol non-oxidative biomarkers does not follow a linear trend, explained mainly by a disproportionate increase in AUC0-6h of ethanol concentrations in relation to dose. This observation should be taken into account when interpreting results in biological matrices in clinical and forensic settings. Short summary A double-blind, randomized, crossover and controlled study was conducted administering ethanol (6–42 g). Ethyl glucuronide (EtG) excretion and fatty acid ethyl esters (FAEEs) plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. This observation should be taken into account when interpreting biomarker concentrations in clinical settings.

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.

Introduction Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms. Methods We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale ≤ 2) as primary end point, and final infarct volume as secondary outcome. Results We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes. Conclusions Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed.

The net harmonic currents generated by a cluster of desktop personal computers are studied statistically. Personal computers (PCs) are single-phase non-linear loads with low individual consumption but significant collective distortion effects, as many of them can be connected to the same bus (personal computer cluster). This article reports experimental measurements of harmonic currents injected by single-phase rectifiers and seven personal computer types during four operating modes. The probability density functions (pdfs) of the harmonic currents (magnitude and phase angle) are investigated from the measurements. An analytical procedure to obtain these probability density functions for any typical personal computer working session is described and experimentally validated. The obtained probability density functions are found to be applicable to large-scale harmonic penetration statistical studies. Furthermore, attenuation and diversity effects are analyzed from the previous probability density functions, and the harmonic current cancellation effect on personal computer clusters is investigated with Monte Carlo simulations.

We use multinomial values to study the effects of the partnership formation in cooperative games, comparing the joint effect on the involved players with the alternative alliance formation. The simple game case is especially considered and the application to the Catalonia Parliament (Legislature 2003-2007) is also studied.

A numerically stable method is developed which computes seemingly tight bounds at a small computational cost relative to the model size, when that model size is large, for the unreliability and bounds for the unreliability using, respectively, exact and bounding failure/repair continuous-time Markov chain models of fault-tolerant systems with exponential failure and repair time distributions, in which repair is deferred until some condition on the collection of failed components is satisfied, and, then, proceeds until reaching the state without failed components, with failure rates much smaller than repair rates and not too different output rates from states with deferred repair.

Given any two vertices u, v of a random geometric graph G(n, r), denote by dE(u, v) their Euclidean distance and by dE(u, v) their graph distance. The problem of finding upper bounds on dG(u, v) conditional on dE(u, v) that hold asymptotically almost surely has received quite a bit of attention in the literature. In this paper we improve the known upper bounds for values of r=ω(√logn) (that is, for r above the connectivity threshold). Our result also improves the best known estimates on the diameter of random geometric graphs. We also provide a lower bound on dE(u, v) conditional on dE(u, v).

Summary Background Early cognitive intervention is the only routine therapeutic approach used for amelioration of intellectual deficits in individuals with Down's syndrome, but its effects are limited. We hypothesised that administration of a green tea extract containing epigallocatechin-3-gallate (EGCG) would improve the effects of non-pharmacological cognitive rehabilitation in young adults with Down's syndrome. Methods We enrolled adults (aged 16–34 years) with Down's syndrome from outpatient settings in Catalonia, Spain, with any of the Down's syndrome genetic variations (trisomy 21, partial trisomy, mosaic, or translocation) in a double-blind, placebo-controlled, phase 2, single centre trial (TESDAD). Participants were randomly assigned at the IMIM-Hospital del Mar Medical Research Institute to receive EGCG (9 mg/kg per day) or placebo and cognitive training for 12 months. We followed up participants for 6 months after treatment discontinuation. We randomly assigned participants using random-number tables and balanced allocation by sex and intellectual quotient. Participants, families, and researchers assessing the participants were masked to treatment allocation. The primary endpoint was cognitive improvement assessed by neuropsychologists with a battery of cognitive tests for episodic memory, executive function, and functional measurements. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01699711. Findings The study was done between June 5, 2012, and June 6, 2014. 84 of 87 participants with Down's syndrome were included in the intention-to-treat analysis at 12 months (43 in the EGCG and cognitive training group and 41 in the placebo and cognitive training group). Differences between the groups were not significant on 13 of 15 tests in the TESDAD battery and eight of nine adaptive skills in the Adaptive Behavior Assessment System II (ABAS-II). At 12 months, participants treated with EGCG and cognitive training had significantly higher scores in visual recognition memory (Pattern Recognition Memory test immediate recall, adjusted mean difference: 6·23 percentage points [95% CI 0·31 to 12·14], p=0·039; d 0·4 [0·05 to 0·84]), inhibitory control (Cats and Dogs total score, adjusted mean difference: 0·48 [0·02 to 0·93], p=0·041; d 0·28 [0·19 to 0·74]; Cats and Dogs total response time, adjusted mean difference: −4·58 s [–8·54 to −0·62], p=0·024; d −0·27 [–0·72 to −0·20]), and adaptive behaviour (ABAS-II functional academics score, adjusted mean difference: 5·49 [2·13 to 8·86], p=0·002; d 0·39 [–0·06 to 0·84]). No differences were noted in adverse effects between the two treatment groups. Interpretation EGCG and cognitive training for 12 months was significantly more effective than placebo and cognitive training at improving visual recognition memory, inhibitory control, and adaptive behaviour. Phase 3 trials with a larger population of individuals with Down's syndrome will be needed to assess and confirm the long-term efficacy of EGCG and cognitive training. Funding Jerome Lejeune Foundation, Instituto de Salud Carlos III FEDER, MINECO, Generalitat de Catalunya.

Cano Garrido, Olivia et al., Inclusion bodies (IBs) are protein-based nanoparticles formed in Escherichia coli through stereospecific aggregation processes during the overexpression of recombinant proteins. In the last years, it has been shown that IBs can be used as nanostructured biomaterials to stimulate mammalian cell attachment, proliferation, and differentiation. In addition, these nanoparticles have also been explored as natural delivery systems for protein replacement therapies. Although the production of these protein-based nanomaterials in E. coli is economically viable, important safety concerns related to the presence of endotoxins in the products derived from this microorganism need to be addressed. Lactic acid bacteria (LAB) are a group of food-grade microorganisms that have been classified as safe by biologically regulatory agencies. In this context, we have demonstrated herein, for the first time, the production of fully functional, IB-like protein nanoparticles in LAB. These nanoparticles have been fully characterized using a wide range of techniques, including field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, zymography, cytometry, confocal microscopy, and wettability and cell coverage measurements. Our results allow us to conclude that these materials share the main physico-chemical characteristics with IBs from E. coli and moreover are devoid of any harmful endotoxin contaminant. These findings reveal a new platform for the production of protein-based safe products with high pharmaceutical interest., This work was supported by grants from INIA, MINECO, Spain to AA and EGF (RTA2012-00028-C02-02), from DGI to JV (BeWell CTQ2013-40480-R), from MINECO to EGF and IR (MAT2013-50036-EXP) and to ICMAB (Severo Ochoa Programme for Centres of Excellence in R&D – SEV – 2015-0496), from Agència de Gestió d’Ajuts Universitaris i de Recerca to AV and JV (2014SGR-132 and 2014-SGR-17, respectively) and from EU to JV, AV and IR (H2020-INFRAIA-2014-2015; NFFA-654360). Besides, the authors acknowledge the financial support granted to AV and JV from the Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina financed by the Instituto de Salud Carlos III with assistance from the European Regional Development. OCG and WIT received a PhD fellowship from MECD (FPU) and CSIC (JAE-pre), respectively, and EGF a post-doctoral fellowship from INIA (DOC-INIA). AV has been distinguished with an ICREA ACADEMIA Award. The authors also acknowledge Micalis Institute, INRA, France that kindly provide us the strain clpP− htrA−-NZ9000 (patent n° EP1141337B1/US6994997B1). We are also indebted to “Servei de Microscopia” (UAB) and ICTS “NANBIOSIS”, more specifically to the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/IBB, at the UAB SepBioES scientific-technical service (http://www.nanbiosis.es/unit/u1-protein-production-platform-ppp/). No other potential conflicts of interest were identified.

Altres ajuts: CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER). A Villaverde received an ICREA ACADEMIA award. OC Garrido received a PhD fellowship from MECD and EGF a postdoctoral fellowship from INIA (DOC-INIA, INIA, MINECO). Unzueta received a Sara Borrell postdoctoral fellowship from ISCIII. Aim: Lactococcus lactis is a Gram-positive (endotoxin-free) food-grade bacteria exploited as alternative to Escherichia coli for recombinant protein production. We have explored here for the first time the ability of this platform as producer of complex, self-assembling protein materials. Materials & methods: Biophysical properties, cell penetrability and in vivo biodistribution upon systemic administration of tumor-targeted protein nanoparticles produced in L. lactis have been compared with the equivalent material produced in E. coli. Results: Protein nanoparticles have been efficiently produced in L. lactis, showing the desired size, internalization properties and biodistribution. Conclusion: In vitro and in vivo data confirm the potential and robustness of the production platform, pointing out L. lactis as a fascinating cell factory for the biofabrication of protein materials intended for therapeutic applications.

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.

Mechanical characteristics of vascular tissue may play a role in different arterial pathologies, which, amongst others, requires robust constitutive descriptions to capture the vessel wall's anisotropic and non-linear properties.Specifically, the complex 3D network of collagen and its interaction with other structural elements has a dominating effect of arterial properties at higher stress levels.The aim of this study is to collect quantitative collagen organization as well as mechanical properties to facilitate structural constitutive models for the porcine carotid artery.This helps the understanding of the mechanics of swine carotid arteries, being a standard in clinical hypothesis testing, in endovascular preclinical trials for example.Porcine common carotid arteries (n=10) were harvested and used to (i) characterize the collagen fiber organization with polarized light microscopy, and (ii) the biaxial mechanical properties by inflation testing.The collagen organization was quantified by the Bingham orientation density function (ODF), which in turn was integrated in a structural constitutive model of the vessel wall.A one-layered and thick-walled model was used to estimate mechanical constitutive parameters by least-square fitting the recorded in vitro inflation test results.Finally, uniaxial data published elsewhere were used to validate the mean collagen organization described by the Bingham ODF.Thick collagen fibers, i.e.the most mechanically relevant structure, in the common carotid artery are dispersed around the circumferential direction.In addition, almost all samples showed two distinct families of collagen fibers at different elevation, but not azimuthal, angles.Collagen fiber organization could be accurately represented by the Bingham ODF (κ1,2,3=[13.5,0.0,25.2] and κ1,2,3=[14.7,0.0,26.6]; average error of about 5%), and their integration into a structural constitutive model captured the inflation characteristics of individual carotid artery samples.Specifically, only four mechanical parameters were required to reasonably (average error from 14% to 38%) cover the experimental data over a wide range of axial and circumferential stretches.However, it was critical to account for fibrilar links between thick collagen fibers.Finally, the mean Bingham ODF provide also good approximation to uniaxial experimental data.The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, the collagen fiber orientations measured from polarized light microscopy, alone, seem to be insufficient structural information. Alternatively, a larger dispersion of collagen fiber orientations, that is likely to arise from analyzing larger wall sections, could have had a similar effect, i.e. could have avoided coupling amongst thick collagen fibers.The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial and uniaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, an effective orientation density that accounts for cross-links between the main collagen fibers has been porposed. The model provides a good approximation to the experimental data.

Optimizing the ratio between the maximum length of the shares and the length of the secret value in secret sharing schemes for general access structures is an extremely difficult and long-standing open problem. In this paper, we study it for bipartite access structures, in which the set of participants is divided in two parts, and all participants in each part play an equivalent role. We focus on the search of lower bounds by using a special class of polymatroids that is introduced here, the tripartite ones. We present a method based on linear programming to compute, for every given bipartite access structure, the best lower bound that can be obtained by this combinatorial method. In addition, we obtain some general lower bounds that improve the previously known ones, and we construct optimal secret sharing schemes for a family of bipartite access structures.

This paper presents the SR-GCWS-CS probabilistic algorithm that combines Monte Carlo simulation with splitting techniques and the Clarke and Wright savings heuristic to find competitive quasi-optimal solutions to the Capacitated Vehicle Routing Problem (CVRP) in reasonable response times. The algorithm, which does not require complex fine-tuning processes, can be used as an alternative to other metaheuristics—such as Simulated Annealing, Tabu Search, Genetic Algorithms, Ant Colony Optimization or GRASP, which might be more difficult to implement and which might require non-trivial fine-tuning processes—when solving CVRP instances. As discussed in the paper, the probabilistic approach presented here aims to provide a relatively simple and yet flexible algorithm which benefits from: (a) the use of the geometric distribution to guide the random search process, and (b) efficient cache and splitting techniques that contribute to significantly reduce computational times. The algorithm is validated through a set of CVRP standard benchmarks and competitive results are obtained in all tested cases. Future work regarding the use of parallel programming to efficiently solve large-scale CVRP instances is discussed. Finally, it is important to notice that some of the principles of the approach presented here might serve as a base to develop similar algorithms for other routing and scheduling combinatorial problems.

Background and Purpose— The standard outcome measure in stroke research is modified Rankin scale (mRS) evaluated by local blinded investigators. We aimed to assess feasibility and reliability of 2 central adjudication methods of mRS in the setting of a randomized endovascular stroke trial. Methods— This is a secondary analysis derived from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) trial cohort. Primary outcome was distribution of mRS at 90 days. Local evaluation was done by certified investigators masked to treatment assignment using structured face-to-face interviews. In addition, central assessment was performed by 2 independent raters via structured phone interview (n=120) and via video recordings of the face-to-face interviews with local investigators (n=106). Interrater agreement was evaluated using kappa and discordance statistics. Sensitivity analyses for the primary end point using different adjudication approaches were performed. Correlation between mRS obtained with each modality and 24-hour follow-up infarct volumes was studied. Results— Using local evaluation as the reference, higher agreement rates were noted with central video than with central phone evaluations ( k w 0.92 [0.88–0.96] versus 0.77 [0.72–0.83]). Discrepancies in mRS scoring between local and central raters (phone- and video-based) were similar in both treatment allocation arms. Sensitivity analyses showed benefit of endovascular treatment irrespective of adjudication method, but higher odds ratios were observed with local evaluations. Final infarct volume was similarly correlated with mRS across all 3 evaluation modalities. Conclusions— Central adjudication of mRS is feasible, reducing interrater variability and avoiding potential problems related to lack of blinding. Our findings may have implications in the planning of future randomized acute stroke trials, especially in those including nonpharmacological interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01692379.

The note presents an output feedback control strategy for Markov jump linear systems with no mode observation. Based on minimizing a finite-time quadratic cost, we derive an algorithm that generates output feedback gains that satisfy a necessary optimality condition. These gains can be computed off-line relying only on the initial condition of the system. This result expands a previous one from the literature that considered state-feedback only. To illustrate the usefulness of the approach, real-time laboratory experiments were performed to control an automotive electronic throttle valve subject to Markov-driven voltage fluctuations.

Endothelial cells are key units in the regulatory biological process of blood vessels. They represent an interface to transmit variations on the fluid dynamic changes. They are able to adapt its cytoskeleton, by means of microtubules reorientation and F-actin reorganization, due to new mechanical environments. Moreover, they are responsible for initiating a huge cascade of biological processes, such as the release of endothelins (ET-1), in charge of the constriction of the vessel and growth factors such as TGF β and PDGF. Although a huge efforts have been made in the experimental characterization and description of these two issues the computational modeling has not gained such an attention. In this work we study the 3D remodeling of endothelial cells based on the main features of blood flow. In particular we study how different oscillatory shear index and the time average wall shear stresses modify the endothelial cell shape. We found our model fitted the experimental works presented before in in vitro studies. We also include our model within a computational fluid dynamics simulation of a carotid artery to evaluate endothelial cell shape index which is a key predictor of atheroma plaque formation. Moreover, our approach can be coupled with models of collagen and smooth muscle cell growth, where remodeling and the associated release of chemical substance are involved. Financial support for this research was provided by the Spanish Ministry of Science and Technology through research project DPI2013-44391-P, the Instituto de Salud Carlos III (ISCIII) through the CIBER initiative. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.

This is the peer reviewed version of the following article: Saez, P., Peña, E., Tarbell, J., Martínez, M. Computational model of collagen turnover in carotid arteries during hypertension. "International journal for numerical methods in biomedical engineering - Online", Febrer 2015, vol. 31, núm. 2, p. 1-25, which has been published in final form at https://doi.org/10.1002/cnm.2705. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. t is well known that biological tissues adapt their properties because of different mechanical and chemical stimuli. The goal of this work is to study the collagen turnover in the arterial tissue of hypertensive patients through a coupled computational mechano-chemical model. Although it has been widely studied experimen- tally, computational models dealing with the mechano-chemical approach are not. The present approach can be extended easily to study other aspects of bone remodeling or collagen degradation in heart diseases. The model can be divided into three different stages. First, we study the smooth muscle cell synthesis of differ- ent biological substances due to over-stretching during hypertension. Next, we study the mass-transport of these substances along the arterial wall. The last step is to compute the turnover of collagen based on the amount of these substances in the arterial wall which interact with each other to modify the turnover rate of collagen. We simulate this process in a finite element model of a real human carotid artery. The final results show the well-known stiffening of the arterial wall due to the increase in the collagen content.

This paper deals with the question of completing a monotone increasing family of subsets Gamma of a finite set Omega to obtain the linearly dependent subsets of a family of vectors of a vector space. Specifically, we prove that such vectorial completions of the family of subsets Gamma exist and, in addition, we show that the minimal vectorial completions of the family Gamma provide a decomposition of the clutter Lambda of the inclusion-minimal elements of Gamma. The computation of such vectorial decomposition of clutters is also discussed in some cases. (C) 2015 Elsevier Inc. All rights reserved.

En este trabajo se presenta una forma de resolver problemas de Poisson en redes subdivididas. A partir de una red dada y de la solución de un problema de Poisson concreto en ésta, se establecen las condiciones necesarias y suficientes para poder relacionar la solución de un problema de Poisson en la red subdividida con la solución en la red base. Aplicamos los resultados obtenidos al cálculo de las resistencias efectivas en la red subdividida, y encontramos una expresión para estas en términos de las resistencias efectivas de la red base

El Trabajo de Final de Grado “Evaluación de un escenario de Pérdida de Potencia Exterior en el Análisis Probabilista de Seguridad (APS) de una central nuclear PWR teniendo en cuenta las medidas post Fukushima” tiene como objeto estudiar las consecuencias de la indisponibilidad por mantenimiento preventivo de los Generadores Diésel en un escenario de Pérdida de Potencia Exterior (PPE) durante la Operación de Recarga en una central tipo PWR (Pressurized Water Reactor). Para ello se utiliza el Análisis Probabilista de Seguridad (APS) el cual es una herramienta que permite cuantificar el riesgo en forma de frecuencia de consecuencia negativa. En primer lugar se realiza la familiarización con las instalaciones. Esta parte del proyecto incluye la descripción de la Piscina de Combustible Gastado (PCG), la definición de las Funciones Clave de Seguridad, la identificación de los Sistemas Frontales, la descripción del Sistema Eléctrico de Potencia y la descripción de los Generadores Diésel. En la familiarización se ha identificado que el mantenimiento preventivo de los generadores diésel se efectúa en la Operación de Recarga. La Piscina de Combustible Gastado es la instalación con más riesgo de consecuencia negativa en Operación de Recarga debido a que es la única que contiene combustible nuclear gastado. El escenario que comporta más riesgo respecto a la PCG en Operación en Recarga es el escenario de Pérdida de Potencia Exterior. La siguiente tarea desarrollada ha sido determinar qué cambios, revisiones e incorporaciones necesita el modelo APS para introducir correctamente la indisponibilidad por mantenimiento preventivo de los generadores diésel. Se ha adaptado el modelo en base a los Esquemas de Niveles Primarios y Actividades Relacionadas con la Recarga que se dispone[1]–[6]. Finalmente se ha llevado a cabo el proceso de Cuantificación del APS nivel I mediante el software RiskSpectrum®. La Frecuencia de Daño al Combustible en el escenario de Pérdida de Potencia Exterior en la Piscina de Combustible Gastado estimada es de 4,35·10-9 año-1. Como conclusión final se extrae que, aunque mediante la incorporación de la indisponibilidad por mantenimiento preventivo de los generadores diésel en modelo ha aumentado la Frecuencia de Daño al Combustible de 4,6·10-11 año-1 a 4,35·10-9 año-1, ésta sigue lejos de la Frecuencia de Daño al Núcleo en Operación Normal de 1,26·10-5 año-1. Por lo tanto, el riesgo de consecuencias negativas en la CENTRAL-NUCLEAR es mayor en Operación Normal que en Operación de Recarga.

The inference of an underlying network topology from local observations of a complex system composed of interacting units is usually attempted by using statistical similarity measures, such as Cross-Correlation (CC) and Mutual Information (MI). The possible existence of a direct link between different units is, however, hindered within the time-series measurements. Here we show that, for the class of systems studied, when an abrupt change in the ordered set of CC or MI values exists, it is possible to infer, without errors, the underlying network topology from the time-series measurements, even in the presence of observational noise, non-identical units, and coupling heterogeneity. We find that a necessary condition for the discontinuity to occur is that the dynamics of the coupled units is partially coherent, i.e., neither complete disorder nor globally synchronous patterns are present. We critically compare the inference methods based on CC and MI, in terms of how effective, robust, and reliable they are, and conclude that, in general, MI outperforms CC in robustness and reliability. Our findings could be relevant for the construction and interpretation of functional networks, such as those constructed from brain or climate data., 8 pages, 18 figures, 6 figure captions

Groundwater wells are one of the most important water resources in the world. Control and management of these resources are of high importance due to the implicit need of water as the main resource for life. This research focuses on a hydrogeological analysis with clustering, which is one of the most popular data mini ng methods, including In the classical data mining scheme, last step corresponds to the effective production of knowledge. In this paper, special focus on that part is done, by means of post - processing tools. The main goal is to discover prototypical profi les from the a c q uifer Pedro Gonzá lez in Marga rita Island (Venezuela), in order to understand the prototypical water conditions regarding quality and supply level. The database contain s 36 groundwater wells and their hydrogeological variables, i.e., electri c al conductivity, static level, pH and geographical coordinates that were collected in five annual measurement campaigns. Clustering methods were used to discover profiles and a typology of three types of wells was extracted. Post - processing tools were use d to get a conceptualization of the resulting classes and comprehensible profiles were finally described. The Class Panel Graph (CPG) and the Traffic Light Panel (TLP) were used to post - process the classes and understand the resulting profiles through symb olic visualization. The TLP was presented to the expert to support a multidisciplinary discussion and to create the mechanisms for a detailed understanding of the evolution of the aquifer. Results reported that the aquifer is in a critical situation in bot h water quality and supply levels. From this research, public administration performed some technical actions to improve the performance of the aquifer and its preservation. At present, predictive models local to profile s are developed