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The aim was to develop a predictive model of infection by multidrug-resistant microorganisms (MDRO). A national, retrospective cohort study was carried out including all patients attended for an infectious disease in 54 Spanish Emergency Departments (ED), in whom a microbiological isolation was available from a culture obtained during their attention in the ED. A MDRO infection prediction model was created in a derivation cohort using backward logistic regression. Those variables significant at p < 0.05 assigned an integer score proportional to the regression coefficient. The model was then internally validated by k-fold cross-validation and in the validation cohort. A total of 5460 patients were included; 1345 (24.6%) were considered to have a MDRO infection. Twelve independent risk factors were identified in the derivation cohort and were combined into an overall score, the ATM (assessment of threat for MDRO) score. The model achieved an area under the curve-receiver operating curve of 0.76 (CI 95% 0.74-0.78) in the derivation cohort and 0.72 (CI 95% 0.70-0.75) in the validation cohort (p = 0.0584). Patients were then split into 6 risk categories and had the following rates of risk: 7% (0-2 points), 16% (3-5 points), 24% (6-9 points), 33% (10-14 points), 47% (15-21 points), and 71% (> 21 points). Findings were similar in the validation cohort. Several patient-specific factors were independently associated with MDRO infection risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were related to an increased risk for MDRO infection. This clinical prediction rule could be used by providers to identify patients at high risk and help to guide antibiotic strategy decisions, while accounting for clinical judgment.

Objective. The aim of this study was to determine the utility of a post hoc lactate added to SIRS and qSOFA score to predict 30-day mortality in older non-severely dependent patients attended for infection in the Emergency Department (ED). Methods. We performed an analytical, observational, prospective cohort study including patients of 75 years of age or older, without severe functional dependence, attended for an infectious disease in 69 Spanish ED for 2-day three seasonal periods. Demographic, clinical and analytical data were collected. The primary outcome was 30-day mortality after the index event. Results. We included 739 patients with a mean age of 84.9 (SD 6.0) years; 375 (50.7%) were women. Ninety-one (12.3%) died within 30 days. The AUC was 0.637 (IC 95% 0.587-0.688; p= 2 and 0.698 (IC 95% 0.635- 0.761; p= 2. Comparing receiver operating characteristic (ROC) there was a better accuracy of qSOFA vs SIRS (p=0.041). Both scales improve the prognosis accuracy with lactate inclusion. The AUC was 0.705 (IC95% 0.652-0.758; p

We find the form of the potential depending on the coordinates and the time such that a solution, $S$, of the Hamilton--Jacobi equation yields an exact solution, $\exp ({\rm i} S/\hbar)$, of the corresponding Schr��dinger equation.

With the aim of ensuring the quality and homogenising the colour of commercial batches of pomegranate arils, a new prototype for the automatic inspection of pomegranate arils and their separation into categories by means of air ejectors has been developed. Arils are singulated and transported on conveyor belts. Images of the arils are acquired using two cameras to allow estimation of the quality and are then expelled through different outlets according to the category. New control software were developed that synchronise the advance of the conveyor belts, the acquisition of images and the separation by air ejectors, which also includes mechanisms for the synchronisation and communication between the vision and control computers. A new computer vision system has been developed for the inspection of arils that distinguish between arils and raw material by estimating the colour of the objects and then classify the arils by size and colour. The prototype was tested over a six-month period in a Spanish pomegranate producer, with the inspection of about 5 Mg of product. The new prototype achieves the objective of inspecting and sorting pomegranate arils according to their quality, reaching the performance specifications. Con el objetivo de asegurar la calidad y homogeneizar el color de los lotes, el Centro de Agroingeniería del IVIA ha diseñado y construido un nuevo prototipo para la inspección automática de arilos de granada mediante visión por computador y su separación en categorías mediante eyecciones de aire comprimido. Los arilos se individualizan y se transportan en cintas, se adquieren imágenes que sirven para determinar su calidad y, finalmente, se expulsan por la salida correspondiente a su categoría. Se ha desarrollado el software de control que sincroniza el avance de las líneas, la adquisición de las imágenes y la expulsión de los arilos por las salidas correspondientes, ideando mecanismos de sincronización y paso de información entre los computadores de visión y control. Se ha implementado un sistema basado en la visión por computador para la inspección automática de los arilos, que distingue entre membranas o pieles y arilos por medio del tamaño y del color. El prototipo se ha probado en una industria española productora de granadas durante 6 meses, inspeccionando más de 5 toneladas de arilos. El nuevo prototipo diseñado cumple con los objetivos de inspeccionar y separar los arilos en diferentes calidades, alcanzando las especificaciones iniciales.

In spite of the great popularity which mobile devices have in our days, the Internet access through these devices is extremely limited. This must to that Web sites have not been developed taking into account the characteristics and limitations of mobile devices. Thus for example, screen restrictions, low capacity of memory and storage, high costs of Internet connection and the deficient bandwidth; among others, they have restrained the visualization of Web sites through mobile devices. This work is tried to increase the visualization of Web sites on mobile devices improving the user?s navigation experience, on the one hand, handling different formats from the resources and by another one, handling to a communications scheme more efficient for exchanging information, which with takes to diminish costs of accessing to the Web by airtime connection or by volume of information, given that the size of resources is diminished and the access time is made agile.

In this paper we address the problem of designing allocation schemas of large database-objects in a Web environment that may be exposed to significant changes in usage and access patterns and scaling of data. In these circumstances, if the design is not adjusted to the new changes, the system can undergo a severe degradation in data access costs and response time. In order to solve this problem, we propose a formal model to generate a new database-object allocation. The model uses current state information of the system and usage statistical data collected during a given period, and adapts the system to the new usage patterns so as to minimize communication costs. Implicitly the mathematical model handles database-object migration and scaling of the number of sites. Model tests have been conducted with satisfactory and promising results. The principles used in the model can be applied to other models for the optimization of Web resources.

Due to their excellent physicochemical properties, carbon-based nanomaterials (CBNs) have attracted considerable attention for multiple applications, including electronics, optoelectronics, photonics and biomedicine. An active area of research is related to their potential exploitation at the skin level, mainly as wearable and stretchable electronic devices for health-care monitoring, cosmetics, sunscreens, but also in the field of regenerative medicine for wound healing. These applications and the potential occupational exposure to CBNs during their manufacturing can lead to a significant skin contact as one of the major but underestimated exposure routes for humans, raising concern for possible adverse effects. This issue motivated an up-to-date revision of the available toxicological data on the effects of CBNs (fullerenes, carbon-nanotubes, graphene-based materials, carbon nano-onions and carbon nano-horns) after cutaneous exposure. The review is focused on the main adverse outcomes at the skin level (irritation, corrosion, sensitization, phototoxicity and relevant mechanisms) as available evidences useful to address human health risk issues related to CBNs. Currently, toxicity data on CBNs are very scarce, representing only 3.8% of total publications on CBN-based skin applications. Among all CBNs, the main data are available for fullerenes and carbon-nanotubes, with very scanty or no information for the others. Although some of them (e.g., fullerenes or some kinds of carbon-nanotubes) appear skin biocompatible, available toxicological data are not sufficient to fully characterize the hazard posed at the cutaneous level. Therefore, toxicological studies on CBN skin applications need to be implemented, enabling their wide and safe use.

To date, the putative shellfish toxin azaspiracid 59 (AZA-59) produced by Azadinium poporum (Dinophyceae) has been the only AZA found in isolates from the Pacific Northwest coast of the USA (Northeast Pacific Ocean). Anecdotal reports of sporadic diarrhetic shellfish poisoning-like illness, with the absence of DSP toxin or Vibrio contamination, led to efforts to look for other potential toxins, such as AZAs, in water and shellfish from the region. A. poporum was found in Puget Sound and the outer coast of Washington State, USA, and a novel AZA (putative AZA-59) was detected in low quantities in SPATT resins and shellfish. Here, an A. poporum strain from Puget Sound was mass-cultured and AZA-59 was subsequently purified and structurally characterized. In vitro cytotoxicity of AZA-59 towards Jurkat T lymphocytes and acute intraperitoneal toxicity in mice in comparison to AZA-1 allowed the derivation of a provisional toxicity equivalency factor of 0.8 for AZA-59. Quantification of AZA-59 using ELISA and LC-MS/MS yielded reasonable quantitative results when AZA-1 was used as an external reference standard. This study assesses the toxic potency of AZA-59 and will inform guidelines for its potential monitoring in case of increasing toxin levels in edible shellfish.

Palytoxin (PLTX) and its analogues are marine polyethers identified in Palythoa and Zoanthus corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Humans can be exposed to these toxins by different routes with a series of adverse effects but the most severe risk is associated with poisonings by the consumption of edible marine organisms accumulating these toxins, as occurs in (sub)-tropical areas. In temperate areas, adverse effects ascribed to PLTXs have been recorded after inhalation of marine aerosols and/or cutaneous contact with seawater during Ostreopsis blooms, as well as during cleaning procedures of Palythoa-containing home aquaria. Besides instrumental analytical methods, in the last years a series of alternative or complementary methods based on biological/biochemical tools have been developed for the rapid and specific PLTX detection required for risk assessment. These methods are usually sensitive, cost- and time-effective, and do not require highly specialized operators. Among them, structural immunoassays and functional cell-based assays are reviewed. The availability of specific anti-PLTX antibodies allowed the development of different sensitive structural assays, suitable for its detection also in complex matrices, such as mussels. In addition, knowing the mechanism of PLTX action, a series of functional identification methods has been developed. Despite some of them being limited by matrix effects and specificity issues, biological methods for PLTX detection represent a feasible tool, suitable for rapid screening.

Besides inhalation, skin contact may be considered one of the most relevant exposure routes to graphene-based materials (GBMs). However, very few data on the cutaneous toxicity of these materials are available, so far. This study is focused on skin irritation potential of a panel of GBMs: few-layer graphene (FLG), exfoliated by ball milling of graphite, FLG exfoliated by ultrasonication using sodium dodecyl sulfate (FLG-SDS) or sodium dodecylbenzenesulfonate (FLG-SDBS), CVD-graphene, obtained by chemical vapor deposition, graphene oxide (GO) and reduced GO (rGO). Skin irritation was assessed using the SkinEthic™ Reconstructed human Epidermis (RhE), following the Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 439. Even though not validated for nanomaterials, the OCED TG 439 turned out to be applicable also for GBM testing, since no interference with the methylthiazolyldiphenyl-tetrazolium bromide (MTT) reduction, used as a final readout, was found. Furthermore, direct epidermal exposure to powdered GBMs mimics the actual human exposure, avoiding interference by the cell culture medium (protein corona formation). Only GBMs prepared with irritant surfactants (FLG-SDS and FLG-SDBS), but not the others, reduced RhE viability at levels lower than those predicting skin irritation (≤50%), suggesting irritant properties. This result was further confirmed by measuring cytokine (IL-1α, IL-6 and IL-8) release by GBM-treated RhE and by histological analysis as additional readouts to implement the guideline. On the whole, these results demonstrate that GBMs prepared with non-irritant exfoliation agents do not induce skin irritation after a single acute exposure.

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8&ndash, 450 &micro, g kg&minus, 1). At the dose of 220 &micro, 1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 &micro, 1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 g kg&minus, 1 (95% confidence limits: 155&ndash, 281 &micro, 1) and to estimate a provisional NOEL of 120 &micro, 1.

In September 2015, a massive occurrence of the Ostreopsis species was recorded in central Adriatic Ka&scaron, tela Bay. In order to taxonomically identify the Ostreopsis species responsible for this event and determine their toxin profile, cells collected in seawater and from benthic macroalgae were analyzed. Conservative taxonomic methods (light microscopy and SEM) and molecular methods (PCR-based assay) allowed the identification of the species Ostreopsis cf. ovata associated with Coolia monotis. The abundance of O. cf. ovata reached 2.9 &times, 104 cells L&minus, 1 in seawater, while on macroalgae, it was estimated to be up to 2.67 &times, 106 cells g&minus, 1 of macroalgae fresh weight and 14.4 &times, 1 of macroalgae dry weight. An indirect sandwich immunoenzymatic assay (ELISA) and liquid chromatography&ndash, high-resolution mass spectrometry (LC-HRMS) were used to determine the toxin profile. The ELISA assay revealed the presence of 5.6 pg palytoxin (PLTX) equivalents per O. cf. ovata cell. LC-HRMS was used for further characterization of the toxin profile, which showed that there were 6.3 pg of the sum of ovatoxins (OVTXs) and isobaric PLTX per O. cf. ovata cell, with a prevalence of OVTXs (6.2 pg cell&minus, 1), while the isobaric PLTX concentration was very low (0.1 pg cell&minus, 1). Among OVTXs, the highest concentration was recorded for OVTX-a (3.6 pg cell&minus, 1), followed by OVTX-b (1.3 pg cell&minus, 1), OVTX-d (1.1 pg cell&minus, 1), and OVTX-c (0.2 pg cell&minus, 1).

N6-isopentenyladenosine (iPA) is a modified adenosine with an isopentenyl moiety derived from the mevalonate pathway which displays pleiotropic biological effects, including anti-tumor and anti-angiogenic activity. Previous evidence revealed a biphasic effect of iPA on phytohemagglutinin-stimulated lymphocytes, being pro-proliferative at low doses and anti-proliferative at high doses. Analogously, we have recently shown that low iPA concentrations (

BACKGROUND AND PURPOSE: There is growing evidence that the cannabinoid CB(1) receptor antagonist, rimonabant (SR141716) exerts potential anti-proliferative and anti-inflammatory actions. Here, we have assessed the effects of rimonabant in vitro in murine immortalized keratinocytes and in vivo by assaying the topical anti-inflammatory activity. EXPERIMENTAL APPROACH: Cell viability and death in a keratinocyte cell line (C5N cells) were measured by Trypan blue exclusion assay and cytotoxicity by sulphorhodamine B test. Cell cycle progression was assessed by flow cytometry and the expression of apoptotic and anti-apoptotic markers, cyclins, pathways of signal transduction and CB1 receptor levels were evaluated by Western blot. The topical anti-inflammatory properties of rimonabant were analysed by inhibition of croton oil-induced ear dermatitis in mice. KEY RESULTS: Rimonabant reduced cell viability and induced apoptosis as shown by the enhanced number of cells in the subG0 phase of the cell cycle, the expression of Bax and reduced levels of Bcl-2 and X-inhibitor of apoptosis protein. In addition, reduced levels of phosphorylated serine/threonine protein kinase Akt and nuclear factor-kappa B were detected associated with regulation of total nuclear factor-kappa B and inhibitor of kappa B-±, phosphorylated inhibitor of kappa B-±, cyclins D1, E and A. In croton oil-induced ear dermatitis, rimonabant significantly reduced oedema and leukocyte infiltrate. CONCLUSIONS AND IMPLICATIONS: Rimonabant reduced cell viability, inducing cell death in keratinocytes and decreased croton oil-induced ear dermatitis. Our findings suggest a potential application of rimonabant as a topical anti-inflammatory drug. We did not assess the involvement of CB(1) receptors in these effects of rimonabant.