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We present a computational study of network ensembles with two types of coexisting vehicle classes: an altruistically routing vehicle (ARV) class – potentially automated vehicles that are routed to reduce total system travel time – and a selfishly routing vehicle (SRV) class, corresponding to human-driven vehicles. We investigate the performance of these networks when some links are reserved for exclusive use by the ARVs. The goal of these interventions is to avoid or mitigate the detrimental effects of the SRVs on the costs of the ARVs. We formulate the problem as a bi-level network design problem, where the upper level deals with optimising the choice of ARV-exclusive links minimising the statistical dispersion of used-route costs, while the lower level finds the corresponding traffic equilibrium under static traffic assignment conditions. We tackle the ARV-exclusive link selection with a genetic algorithm, where the fitness of solutions is based on the dispersion of the costs of routes used by ARVs. The mixed equilibrium is found by solving a multi-class static traffic assignment problem, with constraints on the SRV flows on the ARV-exclusive links. SRVs attempt to minimise their personal travel time, whilst ARVs attempt to drive the flows to system optimal. Our approach is effective in reducing the per-vehicle travel cost of the ARVs to below that of the SRVs, making altruistic routing a more attractive option on average. Our results are consistent across networks with different structures and demand levels.

Antibiotics are among the emerging contaminants of greatest concern to the scientific community. However, the occurrence and behaviour of their metabolites in soils have been scarcely studied. To address this research gap, this study investigates the occurrence, sorption, dissipation kinetics, and environmental risk of highly important antibiotics (sulfamethazine, sulfadiazine, sulfamethoxazole, trimethoprim) and their main metabolites in Mediterranean agricultural soils. Batch experiments were conducted under natural conditions for 120 days. Five different dissipation kinetics models were applied to elucidate antibiotics degradation. The sorption isotherms were evaluated by three different models. Most of the antibiotics and metabolites tested showed a good fit with the Linear Isotherm model (R 2 >0.96) and biphasic dissipation kinetic models (R 2 >0.90). The dissipation and the endpoints values (DT 50 and DT 90 ) depended on the soil type properties. A Lixisol soil demonstrated reduced degradation of the investigated compounds. Trimethoprim showed the highest persistence, followed by sulfamethazine, sulfamethoxazole, and sulfadiazine. Parent compounds exhibited lower degradation rates than their metabolites. Remaining antibiotic concentrations were found to be below the predicted no-effect concentration in soil, suggesting that they may not pose a risk to terrestrial biota. This study provides valuable insights into the behaviour of these antibiotics and their metabolites in soil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Wastewater treatment plants (WWTPs) are recognized as significant contributors of paracetamol (APAP) into the environment due to their limited ability to degrade it. This study used a bioaugmentation strategy with Pseudomonas extremaustralis CSW01 and Stutzerimonas stutzeri CSW02 to achieve APAP biodegradation in solution in wide ranges of temperature (10-40 °C) and pH (5-9), reaching DT 50 values < 1.5 h to degrade 500 mg L -1 APAP. Bacterial strains also mineralized APAP in solution (<30 %), but when forming consortia with Mycolicibacterium aubagnense HPB1.1, mineralization significantly increased (up to 74 % and 58 % for CSW01 +HPB1.1 and CSW02 +HPB1.1, respectively), decreasing DT 50 values to only 1 and 9 days. Despite the complete degradation of APAP and its high mineralization, residual toxicity throughout the process was observed. Three APAP metabolites were identified (4-aminophenol, hydroquinone and trans-2-hexenoic acid) that quickly disappeared, but residual toxicity remained, indicating the presence of other non-detected intermediates. CSW01 and CSW02 degraded also 100 % APAP (50 mg kg -1 ) adsorbed on sewage sludge, with DT 50 values of only 0.7 and 0.3 days, respectively, but < 15 % APAP was mineralized. A genome-based analysis of CSW01 and CSW02 revealed that amidases, deaminases, hydroxylases, and dioxygenases enzymes were involved in APAP biodegradation, and a possible metabolic pathway was proposed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigates the chronic impact of two of the most widely consumed antineoplastic drugs, Ifosfamide (IF) and Cisplatin (CDDP), on the bivalve species Mytilus galloprovincialis under current (17 °C) and predicted warming conditions (21 °C). Accompanying the expected increase in worldwide cancer incidence, antineoplastics detection in the aquatic environment is also expected to rise. Mussels were exposed to varying concentrations of IF (10, 100, 500 ng/L) and CDDP (10, 100, 1000 ng/L) for 28 days. Biochemical analyses focused on metabolic, antioxidant and biotransformation capacities, cellular damage, and neurotoxicity. Results showed temperature-dependent variations in biochemical responses. Metabolic capacity remained stable in mussels exposed to IF, while CDDP exposure increased it at 1000 ng/L for both temperatures. Antioxidant enzyme activities were unaffected by IF, but CDDP activated them, particularly at 21 °C. Biotransformation capacity was unchanged by IF but enhanced by CDDP. Nevertheless, cellular damage occurred at CDDP concentrations above 100 ng/L, regardless of temperature. Integrated biomarker responses highlighted CDDP's greater impact, emphasizing the critical role of temperature in shaping organismal responses and underscoring the complexity of environmental stressor interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Waterbirds are vectors for the dissemination of antimicrobial resistance across environments, with some species increasingly reliant on highly anthropized habitats for feeding. However, data on the impact of their feeding habits on the carriage of antibiotic resistance genes (ARGs) are still scarce. To fill this gap, we examined the microbiota (16S rRNA amplicon gene sequencing) and the prevalence of ARG (high-throughput qPCR of 47 genes) in faeces from white storks (Ciconia ciconia) and lesser black-backed gulls (Larus fuscus) feeding in highly (landfill) and less (paddy fields) polluted habitats. Faecal bacterial richness and diversity were higher in gulls feeding upon landfills and showed a greater abundance of potential pathogens, such as Staphylococcus. In contrast, faecal bacterial communities from storks were similar regardless of habitat preferences, maybe due to a less intense habitat use compared to gulls. In addition, birds feeding in the landfill carried a higher burden of ARGs compared to the surrounding soil and surface waters. Network analysis revealed strong correlations between ARGs and potential pathogens, particularly between tetM (resistance to tetracyclines), bla CMY (beta-lactam resistance), sul1 (sulfonamide resistance) and members of the genera Streptococcus, Peptostreptococcus, and Peptoclostridium. Our work demonstrates how transitioning from paddy fields to landfills fosters the carriage of ARGs and potential pathogens in the bird gut, shedding light on the ecological role of these avian vectors in antimicrobial resistance dissemination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of zinc oxide nanoparticles (ZnO NPs) in cosmetic and pharmaceutical industry has been increased in recent years due to their good properties as solar radiation filters and antibacterial agent. According to the literature, the potential toxicity of these NPs could be size-dependent and the amount of solubilized metal. This work investigates new reliable and straightforward methodologies that enables the determination of ZnO NPs, discriminating them from ionic zinc in cosmetic samples. Two different techniques of analysis have been applied in this study: high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS-GFAAS), and "single particle" inductively coupled plasma mass spectrometry (sp-ICP-MS). Triton X-100 has been used as a surfactant for the formation of homogeneous and stable slurries which allowed the determination of the concentration and sizes of ZnO NPs and Zn 2+ in baby creams, eyeshadows, and lotions. A central composite design (CCD) was performed for the two techniques to optimize the concentration of Triton X-100 and sonication time. For validation purpose, the results of Zn 2+ and ZnO NPs contents achieved by HR-CS-GFAAS were compared with the total Zn content obtained by acid digestion of the samples. A size comparison of the ZnO NPs was also carried out with the data obtained through the two methodologies and validated with transmission electron microscopy (TEM). In the case of TEM analysis, two different media were tried to study possible agglomerates and interactions between the particles and the matrix., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

For the first time, a continuous flow solar photo-Fenton demonstration plant has been assessed for wastewater reclamation according to the EU 2020/741 regulation. The treated water qualities achieved under two operating strategies (acidic and neutral pH) in a 100-m 2 raceway pond reactor were explored in terms of liquid depth, iron source, reagent concentrations, and hydraulic residence time over three consecutive days of operation. The results obtained at acidic pH showed removal percentages of contaminants of emerging concern (CECs) > 75% and water quality classes B, C and D according to EU regulation at both assessed operating conditions, with treatment capacities up to 1.92 m 3 m -2 d -1 . At neutral pH with ferric nitrilotriacetate (Fe 3+ -NTA), 50% of CEC removal and only water quality class D were achieved with the most oxidizing condition assessed, giving a treatment capacity of 0.80 m 3 m -2 d -1 . The treatment capacities obtained in this work, which have never been achieved with solar water treatments, demonstrate the potential of this technology for commercial-scale application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Antibiotics are widely used drugs in human and veterinary medicine, which has attracted great attention in relation to the development of bacterial resistance, currently a problem of great concern for governments and states, as it is related to the resurgence of infectious diseases already eradicated. Understanding the bioaccumulation of antibiotics in aquatic organisms is an important key to understanding their risk assessment. The present study was designed to study the bioaccumulation of target antibiotics in relevant organisms inhabiting benthic marine environments. The uptake and elimination of ciprofloxacin (CIP), sulfamethoxazole (SMX) and trimethoprim (TMP) were investigated in sea cucumbers (Holothuria tubulosa), snakelock anemone (Anemonia sulcata) and beadlet anemone (Actinia equina) under controlled laboratory conditions. The results show that antibiotics have a particular trend over time during all periods of absorption and depuration. The tissue distribution of antibiotics in sea cucumber is strongly influenced by the structure of the compounds, while CIP is concentrated in the body wall; TMP is concentrated in the digestive tract. Two different approaches were used to estimate bioconcentration factors (BCFs) in different animal models, based on toxicokinetic data and measured steady-state concentrations. The BCF ranges were 456-2731 L/kg, 6-511 L/kg and 9-100 L/kg for TMP, CIP and SMX, respectively. The estimated BCF values obtained classify TMP as cumulative in A. equina and H. tubulosa, underlining the potential bioconcentration in these marine organisms. A correlation was observed between the BCFs of the target antibiotics and the octanol-water distribution coefficient (D ow ) (r 2 > 0.7). The animal-specific BCF followed the order of beadlet anemone > sea cucumber > snakelock anemone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Coastal ecosystems are currently exposed to pollutants and climate change. Namely, the increasing consumption of antineoplastic drugs and their potential release to aquatic ecosystems are raising concerns. Nevertheless, information regarding the toxicity of these drugs towards non-target species is scarce, especially considering climate change scenarios. Ifosfamide (IF) and cisplatin (CDDP) are among the antineoplastics already detected in aquatic compartments and due to their mode of action (MoA) can negatively affect aquatic organisms. This study evaluates the transcription of 17 selected target genes related to the MoA of IF and CDDP in Mytilus galloprovincialis gills exposed to environmentally relevant and toxicological meaningful concentrations (IF - 10, 100, 500 ng/L; CDDP - 10, 100, 1000 ng/L), under an actual (17 °C) and predicted warming scenario (21 °C). Results showed an upregulation of the cyp4y1 gene when exposed to the highest concentrations of IF, regardless of the temperature. Both drugs upregulated genes related to DNA damage and apoptosis (p53, caspase 8 and gadd45), especially under warmer conditions. Increased temperature also downregulated genes related to stress and immune responses (krs and mydd88). Therefore, the present results showed a gene transcriptional response of mussels to increasing concentrations of antineoplastics and that warmer temperatures modulated those effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The assessment of exposure to the antidepressant venlafaxine and its major metabolite o-desmethylvenlafaxine in Holothuria tubulosa, Anemonia sulcata and Actinia equina is proposed. A 28-day exposure experiment (10 μg/L day) followed by a 52-day depuration period was conducted. The accumulation shows a first-order kinetic process reaching an average concentration of 49,125/54342 ng/g dw in H. tubulosa and 64,810/93007 ng/g dw in A. sulcata. Venlafaxine is considered cumulative (BCF > 2000 L/kg dw) in H. tubulosa, A. sulcata and A. equina respectively; and o-desmethylvenlafaxine in A. sulcata. Organism-specific BCF generally followed the order A. sulcata > A. equina > H. tubulosa. The study revealed differences between tissues in metabolizing abilities in H. tubulosa this effect increases significantly with time in the digestive tract while it was negligible in the body wall. The results provide a description of venlafaxine and o-desmethylvenlafaxine accumulation in common and non-target organisms in the marine environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this work, an analytical method was optimised and validated for the simultaneous extraction and enantioselective determination of chiral β-blockers, antidepressants and two of their metabolites in agricultural soils, compost and digested sludge. Sample treatment was based on ultrasound-assisted extraction and extract clean-up by dispersive solid-phase extraction. Analytical determination was carried out by liquid chromatography-tandem mass spectrometry using a chiral column. Enantiomeric resolutions were in the range from 0.71 to 1.36. Accuracy was in the range from 85 to 127% and precision, expressed as relative standard deviation, was lower than 17% for all the compounds. Method quantification limits were below 1.21-52.9 ng g -1 dry weight (dw) in soil, 0.76-35.8 ng g -1 dw in compost and 13.6-90.3 ng g -1 dw in digested sludge. Application to real samples revealed enantiomeric enrichment in the range especially in compost and digested sludge (enantiomeric fractions up to 1)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A novel sorbent material employing magnetic nanoparticles (MNPs) coupled to graphene oxide (GO) functionalized with 4-aminobenzenesulfonic acid (M@GO-ABS) has been synthesized and applied to develop an inexpensive and automatic method for Cr(III) and Cr(VI) speciation in environmental samples; the developed method combines inductively coupled plasma optical emission spectrometry (ICP-OES) with on-line magnetic solid phase extraction (MSPE). Two magnetic-knotted reactors containing M@GO-ABS were installed in the eight-port injection valve of a flow injection (FI) manifold. Two different eluents were used, one for Cr(VI) (the most toxic chromium species) and one for total Cr concentration. Cr(III) concentration was calculated by the difference between Cr(VI) concentration and total Cr concentration. The optimized method presented detection limits (LOD, peak height) of 0.1 μg L -1 for chromium (VI) and 0.08 μg L -1 for total chromium, and enrichment factors of 15 and 23, respectively. Certified reference materials (TMDA 54.5 fortified lake water and SPS-SW2 surface water) and spiked aqueous samples were used to validate the developed method. The developed method was fruitfully applied to chromium speciation in environmental water samples such as seawater, well water and tap water collected in Málaga (Spain). The obtained values were in good agreement with the certified values, and the recoveries were found in the range of 91-108% for the spiked samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

There is increasing evidence that the presence of certain pharmaceuticals in the environment leads to biota exposure and constitute a potential risk for ecosystems. Bioaccumulation is an essential focus of risk assessment to evaluate at what degree emerging contaminants are a hazard both to the environment and the individuals that inhabit it. The main goals of the present review are 1) to summarize and describe the research and factors that should be taken into account in the evaluation of bioaccumulation of pharmaceuticals in aquatic organisms; and 2) to provide a database and a critical review of the bioaccumulation/bioconcentration factors (BAF or BCF) of these compounds in organisms of different trophic levels. Most studies fall into one of two categories: laboratory-scale absorption and purification tests or field studies and, to a lesser extent, large-scale, semi-natural system tests. Although in the last 5 years there has been considerable progress in this field, especially in species of fish and molluscs, research is still limited on other aquatic species like crustaceans or algae. This revision includes >230 bioconcentration factors (BCF) and >530 bioaccumulation factors (BAF), determined for 113 pharmaceuticals. The most commonly studied is the antidepressant group, followed by diclofenac and carbamazepine. There is currently no reported accumulation data on certain compounds, such as anti-cancer drugs. BCFs are highly influenced by experimental factors (notably the exposure level, time or temperature). Field BAFs are superior to laboratory BCFs, highlighting the importance of field studies for reliable assessments and in true environmental conditions. BAF data appears to be organ, species and compound-specific. The potential impact on food web transfer is also considered. Among different aquatic species, lower trophic levels and benthic organisms exhibit relatively higher uptake of these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Microplastics (MPs) and perfluoroalkyl substances (PFASs) are two types of pollutants coexisting in the environment. Their co-exposure is a source of increasing concern. MPs present in the natural environment suppose an ideal surface for the sorption of hazardous contaminants. This study investigates the adsorption behaviour of six PFASs on polyamide (PA) MPs. Adsorption experiments under various internal (PA and PFASs dosage, PA particle size) and environmental (pH, ionic strength, dissolved organic matter) factors were carried out. Isotherm results (from 0.1 to 25 mg/L of PFASs) showed that the maximum adsorption capacity of the selected PFASs on the PA was as follows: perfluorooctanesulfonic acid (PFOS, 0.873 mg/g) > perfluorooctanoic acid (0.235 mg/g) > perfluoroheptanoic acid (0.231 mg/g) > perfluorohexanoic acid (0.201 mg/g) > perfluoropentanoic acid (0.192 mg/g) > perfluorobutanoic acid (0.188 mg/g) (pH 5.88, 0% salinity and 0% of dissolved organic matter). The PFOS has more tendency to be sorbed onto PA than perfluorocarboxilic acids. The MP characterization by scanning electron microscopy, X ray diffraction and Fourier transform infrared spectroscopy showed changes in the PA surface after adsorption assays. Pore filling, hydrophobic interactions and hydrogen bonds governed sorption process. The sorption capacity of PFASs was crucially affected by the PA size (from 19.6% to 99.9% for 3 mm and 50 μm particle size, respectively). The process was not significantly influenced by salinity while the dissolved organic matter exerted a negative effect (decrease from 100% to 26% for PFOS in presence of 25 mg/L of humic acid). Finally, adsorption rates of PFASs were quantified in real water matrices (influent and effluent wastewater, surface and tap water samples). The results revealed interactions between PA and PFASs and evidenced the role of PA as a vector to transport PFASs in the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nonylphenol (NP) is an anthropogenic pollutant frequently found in sewage sludge due to the insufficient degrading effectiveness of conventional WWTPs and has attracted attention as an endocrine disruptor. The aim of this study was to isolate specific NP-degrading bacteria from sewage sludge to be used in the degradation of this contaminant through bioaugmentation processes in aqueous solution and sewage sludge. Up to eight different bacterial strains were isolated, six of them not previously described as NP degraders. Bacillus safensis CN12 presented the best NP degradation in solution, and glucose used as an external carbon source increased its effect, reaching DT 50 degradation values (time to decline to half the initial concentration of the pollutant) of only 0.9 days and a complete degradation in <7 days. Four NP metabolites were identified throughout the biodegradation process, showing higher toxicity than the parent contaminant. In sewage sludge suspensions, the endogenous microbiota was capable of partially degrading NP, but a part remained adsorbed as bound residue. Bioaugmentation was used for the first time to remove NP from sewage sludge to obtain more environmentally friendly biosolids. However, B. safensis CN12 was not able to degrade NP due to its high adsorption on sludge, but the use of a cyclodextrin (HPBCD) as availability enhancer allowed us to extract NP and degrade it in solution. The addition of glucose as an external carbon source gave the best results since the metabolism of the sludge microbiota was activated, and HPBCD was able to remove NP from sewage sludge to the solution to be degraded by B. safensis CN12. These results indicate that B. safensis CN12 can be used to degrade NP in water and sewage sludge, but the method must be improved using consortia of B. safensis CN12 with other bacterial strains able to degrade the toxic metabolites produced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases., Objectives: To evaluate the association between inflammatory markers and analgesic response to RT in patients with painful bone metastases., Methods: Adult patients from 7 European study sites undergoing RT for painful bone metastases were included in this prospective and longitudinal analysis. The association between RT response and 17 inflammatory markers at baseline, as well as the association between RT response and the changes observed in inflammatory markers between baseline and three and eight weeks after RT, was analyzed with univariate regression analyses. Baseline analyses were adjusted for potential clinical predictors of RT response., Results: None of the inflammatory markers were significantly associated with an upcoming RT response in the analysis of 448 patients with complete baseline data. In patients available for follow-up, the three-week change in TNF (P 0.017), IL-8 (P 0.028), IP-10 (P 0.032), eotaxin (P 0.043), G-CSF (P 0.033) and MCP-1 (P 0.002) were positively associated with RT response, while the three-week change in CRP (P 0.006) was negatively associated., Conclusion: Results from this study show an association between RT response and change in pro-inflammatory mediators and indicate that inflammation may be important to achieve an analgesic RT response in patients with painful bone metastases. None of the investigated inflammatory markers were found to be pre-treatment predictors of RT response., Competing Interests: Disclosures This research received no specific funding/grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Publications assessing health and economic outcomes of risk-sharing arrangements (RSAs) are limited. Better knowledge of these outcomes would shed light on the pertinence of such arrangements, informing design improvements for the future. The aim of the study is to describe the different types of RSAs implemented in Catalonia and their health and economic outcomes., Methods: Retrospective descriptive analysis of RSAs implemented from January 2016 to December 2019 in the Catalan Health Service, CatSalut. Individual RSAs were reviewed and categorized according to standard RSA guidelines. Relevant health and economic outcomes pertaining to the RSAs were analyzed using aggregate data recorded in Catalan central registries., Results: A total of 15 RSAs were implemented over the study period (10 of which are still ongoing). A total of 8 consisted of performance-linked reimbursements (PLRs) and 7 of cost-sharing arrangements (CSAs). The arrangements were implemented in the oncohematology (n = 11), rare disease (n = 3), and neurology (n = 1) areas. A total of 951 patients were included in PLR and 73% achieved the target health outcomes. Total medication costs were €9 295 755 of which 11% were refunded to CatSalut. CSAs involved 2066 patients and resulted in overall refunds of €1 349 564 (2.61%) for CatSalut., Conclusions: Both PLRs and CSAs were used to manage the different uncertainties related to accessing innovative medicines in Catalonia. The data generated provide relevant information to inform decision-making, allowing an adaptation of the initial recommendation for use and access. Additional efforts are required to increase the RSA assessments and their publication., (Copyright © 2021. Published by Elsevier Inc.)

Parabens are widely used in the food, cosmetics and pharmaceutical industry and are widespread in the environment. As endocrine disruptors, parabens have adverse effects on living organisms. However, knowledge of the exposure of domestic animals to parabens is extremely scarce. Therefore, this study assessed the exposure level of dogs to three parabens commonly used in industry (i.e. methylparaben - MeP, ethylparaben - EtP and propylparaben - PrP) using fur sample analysis in liquid chromatography-tandem mass spectrometry. The presence of parabens has been noted in the samples collected from all dogs included in the study (n = 30). Mean concentrations of MeP, EtP and PrP in the fur of dogs were 176 (relative standard deviation - RSD = 127.48%) ng/g dry weight (dw), 48.4 (RSD = 163.64%) ng/g dw and 79.8 ng/g dw (RSD = 151.89%), respectively. The highest concentrations were found for MeP (up to 1023 ng/g dw). Concentrations of MeP and EtP in males were statistically higher than those in females (p < 0.05). Statistically significantly higher concentration levels of PrP in young animals (up to three years old) were also found. This is the first study concerning the use of fur samples to evaluate the exposure of domestic animals to parabens. The results indicate that an analysis of the fur may be a useful tool of paraben biomonitoring in dogs. The presence of parabens in the canine fur also suggests that these substances may play a role in veterinary toxicology. However, many aspects connected with this issue are not clear and require further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is a paucity of evidence regarding the optimal type of tracheal tube to be advanced over a Frova catheter when performing a 'bougie' emergency front-of-neck airway (eFONA) technique in infants during a 'cannot intubate, cannot oxygenate' situation., Methods: A prospective non-inferiority trial in a rabbit cadaver surgical tracheotomy model to assess the performance of the eFONA technique with an uncuffed 3.5 mm ID tracheal tube vs a cuffed 3.0 mm ID tracheal tube. Queried outcomes include success rate, performance time, and severe secondary airway injuries among tracheal tube types., Results: In 60 tracheostomies performed by 30 participants, the overall success rate was 98%. Performance time was independent from tracheal tube choice (uncuffed: 61 s [95% confidence interval (CI), 52-76], cuffed: 64 s [95% CI, 55-79]; P = 0.82). No tracheal tube type was preferred in terms of usability by participants. The cuffed tracheal tube required increased force to be advanced over the Frova catheter and was associated with a risk ratio of 2.5 (95% CI, 0.53-11.9; number needed to harm, 10) for severe secondary airway injuries when compared with the uncuffed tracheal tube., Conclusion: In performing eFONA in the rabbit cadaver model, an ID 3.5 uncuffed is non-inferior to an ID 3.0 cuffed tracheal tube regarding performance time and preference by the operator. Greater force application to advance the cuffed tube over the Frova catheter and more severe airway injuries may argue for the standardised performance of the eFONA technique with a uncuffed tracheal tube in infants., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

A novel magnetic functionalized material based on graphene oxide and magnetic nanoparticles (MGO) was used to develop a magnetic solid phase extraction method (MSPE) to enrich both, inorganic and organic arsenic species in environmental waters and biological samples. An automatic flow injection (FI) system was used to preconcentrate the arsenic species simultaneously, while the ultra-trace separation and determination of arsenobetaine (AsBet), cacodylate, As III and As V species were achieved by high performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The sample was introduced in the FI system where the MSPE was performed, then 1 mL of eluent was collected in a chromatographic vial, which was introduced in the autosampler of HPLC-ICP-MS. Therefore, preconcentration and separation/determination processes were automatic and conducted separately. To the best of our knowledge, this is the first method combining an automatic MSPE with HPLC-ICP-MS for arsenic speciation, using a magnetic nanomaterial based on MGO for automatic MSPE. Under the optimized conditions, the LODs for the arsenic species were 3.8 ng L -1 AsBet, 0.5 ng L -1 cacodylate, 1.1 ng L -1 As III and 0.2 ng L -1 As V with RSDs <5%. The developed method was validated by analyzing Certified Reference Materials for total As concentration (fortified lake water TMDA 64.3 and seawater CASS-6 NRC) and also by recovery analysis of the arsenic species in urine, well-water and seawater samples collected in Málaga. The developed method has shown promise for routine monitoring of arsenic species in environmental waters and biological fluids., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Radiotherapy (RT) reduces pain in about 60% of patients with painful bone metastases, leaving many patients without clinical benefit. This study assesses predictors for RT effectiveness in patients with painful bone metastases., Materials and Methods: We included adult patients receiving RT for painful bone metastases in a multicenter, multinational longitudinal observational study. Pain response within 8 weeks was defined as ≥2-point decrease on a 0-10 pain score scale, without increase in analgesics; or a decrease in analgesics of ≥25% without increase in pain score. Potential predictors were related to patient demographics, RT administration, pain characteristics, tumor characteristics, depression and inflammation (C-reactive protein [CRP]). Multivariate logistic regression analysis with multiple imputation of missing data were applied to identify predictors of RT response., Results: Of 513 eligible patients, 460 patients (90 %) were included in the regression model. 224 patients (44%, 95% confidence interval (CI) 39%-48%) responded to RT. Better Karnofsky performance status (Odds ratio (OR) 1.39, CI 1.15-1.68), breast cancer (OR 2.54, CI 1.12-5.73), prostate cancer (OR 2.83, CI 1.27-6.33) and soft tissue expansion (OR 2.00, CI 1.23-3.25) predicted RT response. Corticosteroids were a negative predictor (OR 0.57, CI 0.37-0.88). Single and multiple fraction RT had similar response. The discriminative ability of the model was moderate; C-statistic 0.69., Conclusion: This study supports previous findings that better performance status and type of cancer diagnosis predicts analgesic RT response, and new data showing that soft tissue expansion predicts RT response and that corticosteroids is a negative predictor for RT response in patients with painful bone metastases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A 'cannot intubate, cannot oxygenate' (CICO) situation is rare in paediatric anaesthesia, but can always occur in children under certain emergency situations. There is a paucity of literature on specific procedures for securing an emergency invasive airway in children younger than 6 yr. A modified emergency front of neck access (eFONA) technique using a rabbit cadaver model was developed to teach invasive airway protection in a CICO situation in children., Methods: After watching an instructional video of our eFONA technique (tracheotomy, intubation with Frova catheter over which a tracheal tube is inserted), 29 anaesthesiologists performed two separate attempts on rabbit cadavers. The primary outcome was the success rate and the performance time overall and in subgroups of trained and untrained participants., Results: The overall success rate across 58 tracheotomies was 95% and the median performance time was 67 s (95% confidence interval [CI], 56-76). Performance time decreased from the first to the second attempt from 72 s (95% CI, 57-81) to 61 s (95% CI, 50-81). Performance time was 59 s (95% CI, 49-79) for untrained participants and 72 s (95% CI, 62-81) for trained participants. Clinical experience and age of the participants was not correlated with performance time, whereas the length of the tracheotomy incision showed a significant correlation (P=0.006)., Conclusion: This eFONA training model for children facilitates rapid skill acquisition under realistic anatomical conditions to perform an emergency invasive airway in children younger than 2 yr., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The application of nanoparticles (NPs) in science and technology is a fast growing field. Therefore, reliable and straightforward analytical methods are required for their fast determination in different types of samples. This work investigates a method that enables the determination of ZnO NPs, discriminating them from ionic zinc in cosmetic samples. The method is based on direct solid sampling high-resolution continuum source electrothermal atomic absorption spectrometry (SS-HR-CS-GFAAS), and has been applied to determination of ZnO NPs, Zn 2+ and total Zn in eye shadow samples. In this work the deconvolution of the atomization peak and the calibration by standard additions have been done in order to discriminate and quantify ionic zinc and ZnO NPs. A Zn wavelength with low sensitivity was selected. The proper optimization of the graphite furnace temperature program, minimizing the mineralization of the sample matrix, enables different atomization profiles between the different chemical species of the analyte. Two multiple response surface designs have been used in order to optimize the adequate furnace program to achieve our aims. All the optimization experiments were performed using a sample of eye shadow. Further, a method for the determination of total Zn by direct solid sampling with calibration by aqueous standards, was also optimized. The optimized method was successfully applied to the determination of ionic Zn and ZnO NPs in different eye shadow samples, and has been validated by recovery assays, obtaining recovery percentages between 80 and 125%. Total Zn concentration in the solid samples was validated by the determination of total Zn by direct solid sampling and by the analysis of the same eye shadow samples digested in microwave oven., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

A bioaccumulation study of 16 emerging contaminants including preservatives, UV-filters, biocides, alkylphenols, anionic surfactants and plasticizers, in Holothuria tubulosa Gmelin, 1791 specimens was developed. Water and sediments from their coastal habitat were also analyzed. Sediment-water distribution coefficients (log Kd) were in the range 0.78 to 2.95. A rapid uptake and bioaccumulation of pollutants was found. Compounds were detected in intestine and gonads of H. tubulosa after only eight days of exposure. Field-based bioconcentration (BCF) and biota-sediment accumulation factors (BSAF) were calculated. Log BCF > 1 were obtained for most of the compounds studied, indicating their tendency to accumulate in tissue of H. Tubulosa. BCF values decrease as follow: Triclocarban > anionic surfactants > benzophenone 3 > non-ionic surfactants > bisphenol A > parabens. These data provide a detailed accounting of the distribution patterns of some emerging contaminants in organisms at the lower trophic level, representing a potential source of contaminants for organisms in higher levels of the food chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, twenty-three endocrine disrupting compounds have been monitored in sludge from different stages of four sludge stabilization treatments (anaerobic digestion, aerobic digestion, composting and anaerobic stabilization ponds). Their occurrence and fate in sludge stabilization plants and their potential environmental risk in treated sludge and in treated sludge-amended soils have been evaluated. Monitored compounds were six perfluoroalkyl compounds (PFC), four anionic surfactants (sodium alkylsulfates), a plasticiser (bisphenol A (BPA)), four preservatives (parabens), six UV-filters (benzophenones) and two biocides (triclosan and triclocarban). Only two of the UV-filters were not detected in any of the 141 analysed samples. Anionic surfactants (mean concentrations up to 1673 ng/g dry matter (dm) for the sum of surfactants) were the compounds at the highest concentration levels followed by biocides (up to 512 ng/g dm) and UV-filters (up to 662 ng/g dm). The concentrations of anionic surfactants, preservatives and UV-filters decreased 78, 25 and 80%, respectively, after anaerobic digestion. The concentration of perfluorinated carboxylic acids only decreased after composting (80% reduction) whereas biocides and BPA were not affected by any of the studied treatments. Environmental risks (risk quotients > 1) were obtained for all compounds, except for triclocarban and sodium octadecylsulfate, in treated sludge. In treated sludge-amended soils, risk quotients were lower than 1 for all compounds except for triclosan., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Preventable risk factors for chronic lymphocytic leukemia (CLL) remain largely unknown. The aim of this study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and CLL, in the MCC-Spain case-control study., Methods: A total of 318 CLL cases and 1293 population-based controls were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on the 2018 recommendations for cancer prevention (on body fatness, physical activity, and diet) was constructed. We used logistic regression analysis adjusting for potential confounders., Results: Individuals in the highest tertile of the WCRF/AICR score had an odds ratio for CLL of 1.25 (95 % CI 0.91; 1.73) compared with individuals with low adherence (p-trend = 0.172). Each point increment in the score was associated with an OR for CLL of 1.06 (95 % CI 0.91; 1.23). Analyses by severity of disease did not show significant heterogeneity of effects., Conclusion: Overall, our results do not support an association between the WCRF/AICR score and CLL, yet we might have been limited by statistical power and study design to detect modest associations. Further research, ideally with a prospective design, long follow-up, and including additional lymphoma subtypes, is warranted to confirm the impact of composite healthy lifestyle behaviors on lymphoma risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Ltd.)

Population is continuously exposed to endocrine disrupting compounds present in everyday products such as parabens, bisphenol A (BPA), and perfluoroalkyl compounds (PFCs). The aims of this study were, first, to evaluate human exposure to three parabens (methylparaben (MeP), ethylparaben (EtP) and propylparaben (PrP)), BPA and six PFCs (perfluorobutanoic acid, perfluoropentanoic acid, perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)) through the analysis of hair samples from children, women and men and, then, to evaluate possible relationships between pollutant concentration in hair and age, gender, smoking and dyeing habits or hair colour. Hair samples were collected from 42 volunteers from Seville (Spain) (10 children, 16 women and 16 men). Six of the monitored pollutants (MeP, EtP, PrP, BPA, PFHpA and PFOS) were detected in at least 76% of the samples analysed. The highest concentrations and frequency of detection (100% of the samples) corresponded to MeP and PrP (up to 14,187 and 9009 ng/g, respectively). BPA was found in 83% of the samples at concentrations in the range from 24 to 1427 ng/g whereas PFCs were detected at concentrations in the range from 0.6 to 15.5 ng/g, being PFHpA and PFOS the ones most frequently detected (86% and 76%, respectively). Concentrations of BPA and parabens in adults were statistically higher than those in children. The results of this study reveal the suitability of hair for biomonitoring endocrine disrupting compounds of high concern (PFCs, parabens and BPA) to which population is internally or/and externally but continuously exposed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Baseline levels of radionuclides in the marine environment of the Balearic Islands in Western Mediterranean have not been reported in literature. Because of their ecological role and acknowledged sensitivity to pollutants, herein, the activity concentrations of 210 Po, 40 K, 210 Pb, 90 Sr, and 234 Th were measured in two types of benthic invertebrate species (mussels and sea urchins) sampled during 2012-2018. The activity concentrations of 210 Po, 40 K, 210 Pb, and 234 Th ranged from 38 ± 1 to 325 ± 11 Bq kg -1 dry weight (d.w.), 220 ± 10 to 996 ± 46 Bq kg -1 d.w., ND (lower than the limit of detection) to 55 ± 8 Bq kg -1 d.w., and ND to 70 ± 15 Bq kg -1 d.w., respectively. In all cases, no artificial 90 Sr activity was detected in the collected samples. The committed effective dose to humans was calculated to be in the range of 48-640 μSv year -1 ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this work, an analytical method has been applied to biomonitor airborne emerging pollutants in urban areas using bitter orange (Citrus aurantium) tree leaves, which is an evergreen species widely extended in the Mediterranean region, as biosampler. Leaves, from trees located in 20 different locations from Seville City (South of Spain) were sampled during one year period. Sampling sites were located in six highly populated areas, in seven lowly populated areas, in six urban parks and in one industrial area. Fifteen of the target compounds were detected in the analysed samples. The highest concentrations corresponded to plasticizers (up to 852ng/g dry matter (dm)) and surfactants (up to 752ng/gdm), especially di(2-ethylhexyl)phthalate and nonylphenol. Spatial distribution allowed assessing the influence of populated areas in the concentration of some of the studied compounds, such as plasticizers and perfluorinated compounds, and the influence of industrial areas, in the concentration of surfactants. No clear influence of the climatic conditions (temperature, solar radiation and rainfall) on the concentrations of studied compounds was observed. This fact could be due to the presence of diffuse sources of these compounds. In the case of the brominated flame retardant, the measured concentrations could be related with two fire episodes in the vicinity, but until now it has not been possible to rigorously demonstrate a causal relationship. This fact could reveal the suitability and valuable use of Citrus aurantium tree leaves for biomonitoring atmospheric pollutants, especially from unexpected emissions in atmospheric pollution episodes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Missed gastric cancer (MGC) is poorly documented in Mediterranean populations., Aims: (1) To assess the rate, predictors and survival of MGC. (2) To compare MGC and non-MGC tumors., Methods: This is a retrospective-cohort study conducted at four centers. MGC was defined as cancer detected within three years after negative esophagogastroduodenoscopy. Gastric adenocarcinomas diagnosed between 2008-2015 were included. Patients with no follow-up were excluded., Results: During the study period 123,395 esophagogastroduodenoscopies were performed, with 1374 gastric cancers being diagnosed (1.1%). A total of 1289 gastric cancers were finally included. The overall rate of MGC was 4.7% (61/1289, 3.7-6%). A negative esophagogastroduodenoscopy in MGC patients was independently associated with PPI therapy (p < 0.001), previous Billroth II anastomosis (p = 0.002), and lack of alarm symptoms (p < 0.001). The most frequent location for MGC was the gastric body(52.4%). MGCs were smaller than non-MGCs (31 vs 41 mm, p = 0.047), more often flat or depressed (p = 0.003) and less likely to be encountered as advanced disease. Overall 2-year survival was similar between MGC (34.1%) and Non-MGC (35.3 %) (p = 0.59)., Conclusion: MGC accounted for nearly five percent of newly-diagnosed gastric adenocarcinomas. Overall survival was poor and not different between MGC and non-MGC., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The presence of natural and artificial radionuclides in the marine environment produces the accumulation of radionuclides in bivalve molluscs consumed by humans, and therefore it could result in a radiological hazard. In this study, the activity concentrations of 210 Po, 40 K, 210 Pb and 234 Th were determined in different types of bivalve molluscs sampled during the period of May 2014-June 2015, along coastal areas from the Andalusian region (South of Spain), through alpha-particle spectrometry and low-level gamma-ray spectrometry. The activity concentrations of 210 Po; 40 K; 210 Pb and 234 Th varied between 40 ± 2 and 515 ± 9 Bq kg -1 dry weight (d.w.); 121 ± 7 and 674 ± 34 Bq kg -1 d.w.; ND (lower than limit of detection) and 73 ± 10 Bq kg -1 d.w.; and ND and 126 ± 27 Bq kg -1 d.w., respectively. The committed effective dose to humans was calculated to range from 41 to 479 μSv year -1 . Both activity concentrations and dose levels were comparable to previous studies from other countries. Finally, a multivariate statistical analysis of natural radioactivity content allowed the discrimination between bivalve molluscs from Atlantic and Mediterranean coasts., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A method for the determination of 23 emerging concern pollutants in digested sludge, compost and soil has been developed. Target pollutants include six perfluorinated compounds (5 perfluorocarboxylic acids and perfluorooctanesulfonic acid), the plasticizer bisphenol A, four anionic surfactants (sodium alkylsulfates), four preservatives (parabens), two antimicrobial agents (triclosan and triclocarban) and six UV-filters (benzophenones). Sample treatment was based on ultrasound-assisted extraction with 3 mL of methanol:acetic acid (95:5, v/v) and clean-up by dispersive solid-phase extraction (d-SPE) with C18. Analytical determination was carried out by liquid chromatography-tandem mass spectrometry. Extraction solvent, sonication time, number of extraction cycles and type and amount of d-SPE sorbent were optimized. Due to the physical-chemical properties of target compounds, and the high number of sample treatment variables involved, a Box-Behnken design was applied to method optimization. The method was validated by means of spiked samples. Method detection limits were in the range from 0.01 to 6.2 ng g -1 dry matter. Accuracy and precision were evaluated at three spike levels in each type of sample matrix. Accuracy, expressed as relative recovery, was in the range from 70% to 120% for most of the compounds and spike levels. Precision, expressed as relative standard deviation, was equal or below 21%. To the best of our knowledge, the proposed method constitute the first analytical method for multiclass determination of emerging pollutants in digested sludge, compost and soils., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, the activity concentrations of 210 Po and 210 Pb were determined in different types of bivalve molluscs sampled during the period of May 2014-June 2015 along the Andalusian littoral. Radioactivity concentrations of 210 Po were determined through alpha-particle spectrometry using 209 Po as an internal tracer. Radioactivity concentrations of 210 Pb were determined through low-level gamma-ray spectrometry. The activity concentrations of 210 Po and 210 Pb varied between 40 ± 2 and 515 ± 9 Bq kg -1  dry weight (d.w.), and ND (lower than limit of detection) and 73 ± 10 Bq kg -1  d.w., respectively. The committed effective dose to humans was calculated to range from 39 to 477 μSv year -1 . Radioactivity and dose levels were compared with previous studies from other countries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We evaluated the efficacy of a new disinfectant product, HLE, to inhibit multiple species of planktonic and biofilm bacterial cultures. The HLE disinfectant comprised of EDTA, lactic acid and hydrogen peroxide, and our data indicated that the disinfectant had effective antimicrobial and anti-biofilm activity even at low concentrations (0.15% to 0.4% HLE, v/v). Furthermore, the HLE disinfectant destabilized biofilm structures eradicated them due to the synergistic effect of EDTA and both antimicrobials (lactic acid and hydrogen peroxide), as revealed by confocal laser scanning microscopy. Additionally, sub-inhibitory concentrations of HLE disinfectant, with EDTA as an efflux pump inhibitor, inhibited the expression of multidrug EfrAB, NorE and MexCD efflux pumps in both planktonic and biofilm cultures. This could provide an alternative way to disinfect surfaces to avoid spreading multi-drug resistant strains in the food chain and the environment by decreasing efflux pump expression and consequently reducing the antibiotic selective pressure caused by systemic antibiotics and disinfectant use., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Arsenic, one of the main environmental pollutants and potent natural poison, is a chemical element that is spread throughout the Earth's crust. It is well known that the toxicity of arsenic is highly dependent on its chemical forms. Generally, the inorganic species are more toxic than its organics forms, and As(III) is 60 times more toxic than As(V). In environmental waters, arsenic exists predominantly in two chemical forms: As(III) and As(V). In view of these facts, fast, sensitive, accurate and simple analytical methods for the speciation of inorganic arsenic in environmental waters are required. In this work, a new magnetic solid phase extraction with a hydride generation system was coupled on line with inductively coupled plasma mass spectrometry (MSPE-HG-ICP-MS). The new system was based on the retention of As(III) and As(V) in two knotted reactors filled with (Fe 3 O 4 ) magnetic nanoparticles functionalized with [1,5-bis (2-pyridyl) 3-sulfophenylmethylene] thiocarbonohydrazide (PSTH-MNPs). As(III) and total inorganic As were sequentially eluted in different reduction conditions. The concentration of As(V) was obtained by subtracting As(III) from total As. The system runs in a fully automated way and the method has proved to have a wide linear range and to be precise, sensitive and fast. The detection limits found were 2.7 and 3.2 ng/L for As(III) and total As, respectively; with relative standard deviations (RSDs) of 2.5% and 2.7% and a sample throughput of 14.4 h -1 . In order to validate the developed method, several certified reference samples of environmental waters including sea water, were analyzed and the determined values were in good agreement with the certified values. The proposed method was successfully applied to the speciation analysis of inorganic arsenic in well-water and sea water., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, the removal of different types of emerging pollutants (four perfluoroalkyl compounds, two preservatives, three surfactants and nine pharmaceutical compounds) from aqueous solution by adsorption onto two novel synthetic clays, a high-charge swelling mica (Na-Mica-4) and an organo-functionalized mica (C 18 -Mica-4), was evaluated. Na-Mica-4 and C 18 -Mica- 4 were prepared and characterized by X-Ray diffraction, Zeta potential, specific surface area, thermogravimetric analysis and transmission electron microscopy, before and after adsorption experiments. The influence of the aqueous sample pH, salt addition and extraction time in the removal were evaluated. The results showed the high adsorption affinity of C 18 -Mica-4 for most of the emerging pollutants analysed after a removal time of 24 h (14 out of 18 pollutants were effectively removed [70-100%]). A high correlation was observed between the log K ow of the selected emerging pollutants and the adsorption onto C 18 -Mica-4. The results also indicate that adsorption occurs in the interlayer space. While the removal rates with Na-Mica-4 were in the range 8-97% after seven days, some of the compounds, perfluorobutanoic acid and most of pharmaceutically active compounds, were not adsorbed onto the high-charge mica. C 18 -Mica- 4 was effectively used for the removal of contaminants from four types of water samples., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Antibiotics represent one of the most widely prescribed therapeutic agents in children. It has been estimated that 30-50% of antibiotic prescriptions for this population are inappropriate. In this scenario, analysis of prescription data provides an invaluable source of information as a basis for implementing strategies for improvement in this field., Objective: To assess the appropriateness of antibiotic prescriptions in a paediatric population at an emergency department., Methods: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years who attended the emergency department during 2013. A random sample of 630 patients was selected (confidence level 99%, accuracy 5%). To assess the suitability of antibiotic prescriptions, the clinical practice was compared with an evidence-based guideline especially designed for this study., Results: Antibiotics were prescribed to 16.5% patients (n=104). Antibiotic treatment was inappropriate in 51.9% patients (n=54). Unnecessary treatment was indicated in 40.7%, with wrong antibiotics chosen in 35.2%, and the posology was incorrect in 24.1% of them. The most frequent diseases with incorrectly prescribed antibiotics were: acute otitis media, episodes of wheezing, fever of unknown origin, acute pharyngo-tonsillitis, and community-acquired pneumonia., Conclusion: Antibiotic prescribing seems to be inappropriate in up to half of the patients. These data reinforce the need to develop a paediatric antimicrobial stewardship program to decrease the unnecessary use of antimicrobial agents., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Titanium cages with 3-D printed trussed open-space architectures may provide an opportunity to deliver targeted mechanical behavior in spine interbody fusion devices. The ability to control mechanical strain, at levels known to stimulate an osteogenic response, to the fusion site could lead to development of optimized therapeutic implants that improve clinical outcomes. In this study, cages of varying design (1.00 mm or 0.75 mm diameter struts) were mechanically characterized and compared for multiple compressive load magnitudes in order to determine what impact certain design variables had on localized strain. Each cage was instrumented with small fiducial sphere markers (88 total) at each strut vertex of the truss structure, which comprised of 260 individual struts. Cages were subjected to a 50 N control, 1000 N, or 2000 N compressive load between contoured loading platens in a simulated vertebral fusion condition, during which the cages were imaged using high-resolution micro-CT. The cage was analyzed as a mechanical truss structure, with each strut defined as the connection of two vertex fiducials. The deformation and strain of each strut was determined from 50 N control to 1000 N or 2000 N load by tracking the change in distance between each fiducial marker. As in a truss system, the number of struts in tension (positive strain) and compression (negative strain) were roughly equal, with increased loads resulting in a widened distribution (SD) compared with that at 50 N tare load indicating increased strain magnitudes. Strain distribution increased from 1000 N (+156 ± 415 με) to 2000 N (+180 ± 605 με) in 1.00 mm cages, which was similar to 0.75 mm cages (+132 ± 622 με) at 1000 N load. Strain amplitudes increased 42%, from 346με at 1000 N to 492με at 2000 N, for 1.00 mm cages. At 1000 N, strain amplitude in 0.75 mm cages (481με) was higher by 39% than that in 1.00 mm cages. These amplitudes corresponded to the mechanobiological range of bone homeostasis+formation, with 63 ± 2% (p < .05 vs other groups), 72 ± 3%, and 73 ± 1% of struts within that range for 1.00 mm at 1000 N, 1.00 mm at 2000 N, and 0.75 mm at 1000 N, respectively. The effective compressive modulus for both cage designs was also dependent on strut diameter, with modulus decreasing from 12.1 ± 2.3 GPa (1.25 mm) to 9.2 ± 7.5 GPa (1.00 mm) and 3.8 ± 0.6 GPa (0.75 mm). This study extended past micro-scale mechanical characterization of trussed cages to compare the effects of design on cage mechanical behavior at moderate (1000 N) and strenuous (2000 N) load levels. The findings suggest that future cage designs may be modulated to target desired mechanical strain regimes at physiological loads., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A green and simple method has been proposed in this work for the simultaneous determination of V, Ni and Fe in fuel ash samples by solid sampling high resolution continuum source graphite furnace atomic absorption spectrometry (SS HR CS GFAAS). The application of fast programs in combination with direct solid sampling allows eliminating pretreatment steps, involving minimal manipulation of sample. Iridium treated platforms were applied throughout the present study, enabling the use of aqueous standards for calibration. Correlation coefficients for the calibration curves were typically better than 0.9931. The concentrations found in the fuel ash samples analysed ranged from 0.66% to 4.2% for V, 0.23-0.7% for Ni and 0.10-0.60% for Fe. Precision (%RSD) were 5.2%, 10.0% and 9.8% for V, Ni and Fe, respectively, obtained as the average of the %RSD of six replicates of each fuel ash sample. The optimum conditions established were applied to the determination of the target analytes in fuel ash samples. In order to test the accuracy and applicability of the proposed method in the analysis of samples, five ash samples from the combustion of fuel in power stations, were analysed. The method accuracy was evaluated by comparing the results obtained using the proposed method with the results obtained by ICP OES previous acid digestion. The results showed good agreement between them. The goal of this work has been to develop a fast and simple methodology that permits the use of aqueous standards for straightforward calibration and the simultaneous determination of V, Ni and Fe in fuel ash samples by direct SS HR CS GFAAS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Chronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLL METHODS: Using the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions., Results: Among the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend<0.016) and for type II diabetes., Conclusion: We confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A multiresidue method has been developed for the determination of emerging pollutants in leafy and root vegetables. Selected compounds were 6 perfluoroalkyl compounds (5 perfluorocarboxylic acids and perfluorooctanesulfonic acid), 3 non-ionic surfactants (nonylphenol and nonylphenolethoxylates), 8 anionic surfactants (4 alkylsulfates and 4 linear alkylbenzene sulfonates), 4 preservatives (parabens), 2 biocides (triclosan and triclocarban), 2 plasticizers (bisphenol A and di-(2-ethylhexyl)phthalate), 6 UV-filters (benzophenones) and 4 hormones. The method is based on ultrasound-assisted extraction, clean-up by dispersive solid-phase extraction (d-SPE) and liquid chromatography-tandem mass spectrometry analysis. Due to the diversity of the physico-chemical properties of the target compounds, and to better evaluate the influence of sample treatment variables in extraction efficiencies, Box-Behnken design was applied to optimize extraction solvent volume, number of extraction cycles and d-SPE sorbent amount. Linearity (R 2 ) higher than 0.992, accuracy (expressed as relative recoveries) in the range from 81 to 126%, precision (expressed as relative standard deviation) lower than 19% and limits of detection between 0.025 and 12.5ngg -1 dry weight were achieved. The method was applied to leafy vegetables (lettuce, spinach and chard) and root vegetables (carrot, turnip and potato) from a local market. The highest concentrations corresponded to the surfactants reaching levels up to 114ngg -1 (dry weight), in one of the lettuce samples analyzed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Circular Mausoleum tomb (Roman Necropolis of Carmona, Spain) dates back from the first century AD and is characterized by a dense microbial (phototrophic) colonization on the walls and ceiling. However, some walls exhibited an important number of violet stains of unknown origin. The microbial communities of these violet stains are mainly composed of cyanobacteria, streptomycetes and fungi. A strain of Streptomyces parvus, isolated from the walls, produces a violet pigment in culture media. High performance liquid chromatography-mass spectrometry of the culture extracts obtained from this Streptomyces revealed the presence of a few granaticins, pigments with a benzoisochromanequinone structure. When metabolically active in the tomb, S. parvus synthesizes the pigments that diffuse into the mortar. During rain and/or wetting periods, the pigments are solubilized by alkaline waters and elute from the starting position to the surrounding mortar, enlarging the pigmented area and thus contributing to this exceptional biodeterioration phenomenon., (Copyright © 2017 Elsevier B.V. All rights reserved.)