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Context: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. Methods: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å. [ABSTRACT FROM AUTHOR]

Key Points: Question: What are the best-performing organ dysfunction–based criteria to implement the definition of sepsis and septic shock in children with suspected infection? Findings: In this international, multicenter, retrospective cohort study including more than 3.6 million pediatric encounters, a novel score, the Phoenix Sepsis Score, was derived and validated to predict mortality in children with suspected or confirmed infection. The new criteria for pediatric sepsis and septic shock based on the score performed better than existing organ dysfunction scores and the International Pediatric Sepsis Consensus Conference criteria. Meaning: The new data-driven criteria for pediatric sepsis and septic shock based on measures of organ dysfunction had improved performance compared with prior pediatric sepsis criteria. Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria. This cohort study derives and validates novel criteria for diagnosis of pediatric sepsis and septic shock across high-resource and low-resource international settings. [ABSTRACT FROM AUTHOR]

Objectives: When healthcare systems are overwhelmed, accurate assessments of patients' predicted mortality risks are needed to ensure effective allocation of scarce resources. Organ dysfunction scores can serve this essential role, but their evaluation in this context has been limited so far. In this study, we sought to assess the performance of three organ dysfunction scores in both critically ill adults and children at clinically relevant mortality thresholds and timeframes for resource allocation and compare it with two published prioritization schemas.Design: Retrospective observational cohort study.Setting: Three large academic medical centers in the United States.Patients: Critically ill adults and children.Interventions: None.Measurements and Main Results: We calculated the daily Sequential Organ Failure Assessment score in adults and the Pediatric Logistic Organ Dysfunction 2 score and the Pediatric Sequential Organ Failure Assessment score in children. There were 49,290 (11.6% mortality) and 19,983 children (2.5% mortality) included in the analysis. Both the Sequential Organ Failure Assessment and Pediatric Sequential Organ Failure Assessment scores had adequate discrimination across relevant timeframes and adequate distribution across relevant mortality thresholds. Additionally, we found that the only published state prioritization schema that includes pediatric and adult patients had poor alignment of mortality risks, giving adults a systematic advantage over children.Conclusions: In the largest analysis of organ dysfunction scores in a general population of critically ill adults and children to date, we found that both the Sequential Organ Failure Assessment and Pediatric Sequential Organ Failure Assessment scores had adequate performance across relevant mortality thresholds and timeframes for resource allocation. Published prioritization schemas that include both pediatric and adult patients may put children at a disadvantage. Furthermore, the distribution of patient and mortality risk in the published schemas may not adequately stratify patients for some high-stakes allocation decisions. This information may be useful to bioethicists, healthcare leaders, and policy makers who are developing resource allocation policies for critically ill patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). METHODS: Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. RESULTS: Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for inhospital mortality (area under the curve 0.87-0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84-0.92, P < .001 to P = .06). CONCLUSIONS: We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases. [ABSTRACT FROM AUTHOR]

To enhance fish general health, feeds can be supplemented with health-promoting additives, reducing the need to use chemotherapeutics. Incorporation of marine algae biomasses in aquafeeds has been shown to improve fish immune status by enhancing innate immune response. This study evaluated the effects of Phaeodactylum tricornutum incorporation in feed by two different processes, either as freeze-dried biomass or broken cell wall biomass, on fish health status and performance. Triplicate groups of gilthead seabream juveniles (13.3 ± 0.3 g) were either fed a control diet (CTRL) with an extreme (i.e., 0% fishmeal), nutritionally balanced, formulation, or two experimental diets formulated as the CTRL with 1% inclusion of the microalga P. tricornutum at the expense of wheat meal: BC diet contains P. tricornutum broken cells and WC diet microalgae whole cells. After 2 and 12 weeks of feeding, blood was collected for hematological procedures, whereas plasma and mucus were sampled for immune parameters. Head-kidney, liver, and white skeletal muscle were also collected for gene expression measurements. No major differences were observed in hematological nor plasma humoral parameters after 12 weeks irrespective of dietary treatment. Arrays of 29–31 genes were analyzed in the different tissues, revealing an early dietary effect (2 weeks) in a tissue-specific pattern. In the liver, the major effect was found in the GH/IGF axis and in muscle there was a late downregulation of myostatin (mstn) gene, mainly due to WC diet, even though all fish had similar growth performance. Regarding the head-kidney, BC diet led to alpha-2-macroglobulin (a2m) gene upregulation. Also, the same treatment showed increased mucus alternative complement pathway and bactericidal activity at 2 and 12 weeks, respectively. Hence, it seems that BC diet has a potential stimulatory effect that might be relevant as a prophylactic measure before a predictable stressful event. [ABSTRACT FROM AUTHOR]

This study characterised the expression of interferon (IFN)-τ-stimulated genes (ISGs) and Type I IFN receptors in circulating polymorphonuclear cells (PMNs) of beef heifers and compared it with expression in peripheral blood mononuclear cells (PBMCs) up to Day 20 of gestation. Nelore heifers (n = 26) were subjected to fixed-time AI (FTAI) on Day 0. PMNs and PBMCs were isolated on Days 0, 10, 14, 16, 18 and 20 after FTAI. The abundance of target transcripts (ubiquitin-like protein (ISG15), 2′-5′-oligoadenylate synthetase 1 (OAS1), myxovirus resistance 1 (MX1), myxovirus resistance 2 (MX2), IFN receptor I (IFNAR1) and IFN receptor 2 (IFNAR2)) was determined using real-time quantitative polymerase chain reaction and compared between pregnant (n = 8) and non-pregnant (n = 9) females. In both PBMCs and PMNs, ISG15 and OAS1 expression was greater in pregnant than non-pregnant heifers on Days 18 and 20. There were no significant differences in the expression of ISGs between PBMCs and PMNs. A time effect on expression was found for IFNAR1 in PBMCs and IFNAR2 in PMNs, with decreased expression of both genes on Days 18 and 20. When the expression of these genes was compared between cell types only in pregnant heifers, IFNAR2 expression in PMNs had an earlier decrease when compared to its expression in PBMCs, starting from Day 18. In conclusion, PMNs do not respond earlier to the conceptus stimulus, and ISG15 and OAS1 expression in both PMNs and PBMCs can be used as a suitable marker for pregnancy diagnosis on Days 18 and 20. In addition, gestational status did not affect IFNAR1 and IFNAR2 expression, but IFNAR2 showed a distinct response between PMNs and PBMCs of pregnant heifers. Early pregnancy diagnosis in cattle operations allows non-pregnant females to be rapidly detected, allowing new chances of conception in a shorter period. To develop a method to diagnose pregnancy earlier, it is necessary to understand the stimulatory effects of the conceptus on the maternal organism. In this study we found that both circulating peripheral blood mononuclear cells and polymorphonuclear leucocytes respond to the presence of the bovine conceptus by increasing expression of interferon-τ-stimulated genes up to 10 days before pregnancy can be detected when using conventional methods. [ABSTRACT FROM AUTHOR]

Most pathogens start the process of infection at the mucosal surfaces and therefore the mucosal immune response plays an essential role in the course of the infection. Due to the Senegalese sole (Solea senegalensis Kaup) condition of flatfish, the present comparative study aimed to analyse several immune-related enzymes as well as the bactericidal activity in the skin mucus from ocular and blind sides. For this purpose, Senegalese sole juveniles were bath challenged with a sub-lethal dose of Tenacibaculum maritimum for 24 h and sampled at 1, 2 and 3 weeks. The haematological profile and immune-related parameters were also measured in plasma in order to evaluate the systemic immune response after T. maritimum challenge. Results from this study showed that most parameters tested increased in skin mucus of bath challenged fish compared to unchallenged ones. In contrast, the sub-lethal dose tested did not influence the haematological profile including peripheral numbers the different leucocyte types. No variations were observed in plasma lysozyme, peroxidase, protease and haemolytic complement activities between unchallenged and bath challenged fish. This study suggests that the studied innate immune-related molecules are constitutively present in both skin mucus sides but at different levels. Interestingly, the levels of most parameters measured were higher on the ocular side than on the blind side, possibly due to the higher exposure to invasion by waterborne microorganisms on this side. Therefore, the present study brings some insights regarding local immune responses after bacterial challenge in skin mucus from the ocular and blind sides in one of the most valuable flatfish species in southern Europe. Image 1 • Systemic and local immune responses of Senegalese sole bath-challenged with T. maritimum were evaluated. • A comparative study was carried out in skin mucus of Senegalese sole from ocular and blind sides. • Immune parameters increased in skin mucus of challenged fish compared to unchallenged ones. • At systemic level no variations were found between unchallenged and challenged groups. • The most parameters measured were higher on the ocular side than on the blind side. [ABSTRACT FROM AUTHOR]

The application of emerging technologies for the food preservation is a relevant topic for the industry; these technologies are highly efficient to reduce the growth of spoilage microorganisms as well as the production of undesirable microbial metabolites in foods and the processing environment. Spoilage caused by the yeast metabolic activity affects the wine marketability. These novel technologies can be easily implemented during dynamic and customized winemaking processes, in order to control the microbial contaminations and to preserve the wine quality. During the last two decades, the Brettanomyces spp. contamination in the bottled wines and the winery environment has attracted interest due to production of the volatile phenol compounds, the high stress resistance and the peculiar metabolic features. The use of the emerging technologies, such as high hydrostatic pressure, ultrasounds, pulsed electric fields, UV irradiation, microwaves, ozone and electrolyzed water, novel finishing agents, and biotechnological approaches resulted useful to reduce the contamination levels and the production of off-flavours. In addition, the application of the emerging technologies allowed the reduction of sulphur dioxide, considering its allergenic properties and the raise of Brettanomyces spp. resistance to this compound. The effect of these technologies on nutritional and sensory properties of wines is also discussed. This review highlights some useful novel approaches to control Brettanomyces spp. during winemaking, allowing the producers to follow the "hurdle concept" and to minimize wine sensory changes. Image 1 • Evaluation of the antimicrobial effect of emerging technologies on Brettanomyces spp. • Control of volatile phenols production through the emerging technologies application. • Description of the biotechnologies approaches to control Brettanomyces spp. • Application of these emerging technologies for the barrel sanitation. • Brettanomyces spp. risk assessment based on novel analytical tools. [ABSTRACT FROM AUTHOR]

Along the western slope of the Central Andes in the southernmost part of the Pampean flat-slab subduction zone segment (∼33°S), crustal Quaternary west-vergent reverse faults are found, but little is known about them. To better understand and characterize these faults, grouped as the Cariño Botado thrust fault system (CBF), we undertook a multidisciplinary study focused on remote sensing and field geomorphic and geologic mapping, sedimentary relationships, and fault characterization. Optically Stimulated Luminescence (OSL) and U Pb dating samples were obtained from faulted deposits to constrain the timing of fault motion. We combined the mapping, fault relationship descriptions, and age control to understand this system better and quantify tectonic rates here for the first time. The main CBF is best expressed with Late-Cenozoic hanging wall fault rocks over thrusting Quaternary coarse-grained alluvial fan deposits, and the fault zone is found over a large area and with an altered fault zone (∼0.5–2 km wide). The principal reverse fault segment of the CBF is well exposed in creeks, with an average dip of 40°E and an associated vertical throw (up to the east) of the hanging wall from ∼3.2 m up to ∼30 m. Five OSL samples, taken from tilted and untilted alluvial fan deposits adjacent to the CBF's main fault, yielded ages between 2.5 ± 0.2 ka and 9.0 ± 0.7 ka, supporting Holocene activity and ∼4.9 m of fault slip in the last ∼8.7 ka. Ninety-nine detrital zircons from fluvial terrace deposits in the study area were dated using U Pb ICPMS, giving mainly Oligo-Miocene ages. The youngest ages of detrital zircons are Quaternary (n = 3; ∼0.9–4.4 Ma), which indicates that CBF activity could have started as early as ∼0.9 Ma producing an accumulated hanging wall uplift of ∼130 m. The alignment of the fault profiles, creek and river knickpoints, and alluvial and fluvial deposits allows the most recent activity of the main CBF to be traced between 5 km and up to 15 km along the fault trace. Based on fault length, slip characteristics, and earthquake scaling relationships, earthquakes up to Mw 7.5 could be associated with the fault. Because of the clear relationship between the river incision, distribution of fluvial terraces, variation in sinuosity and stream power, and the location of the faults, we suggest that the tectonic uplift controls the hanging wall fluvial incision from ∼0.9 Ma to the present. The Quaternary (at least 0.9 Ma to present) active CBF shares geometric, structural, and rupture timing similarities with the nearby better-characterized San Ramón Fault system. The latter is located ∼50 km to the south along the eastern border of Santiago, the capital city of Chile. Both fault systems share a comparable morpho-structural setting with a consistent average N-S trend. Significant seismic hazard is associated with both the CBF and the San Ramon System, which may be linked structurally and temporally regarding previous surface ruptures and major earthquakes, and therefore remain important research targets. • Tectonic geomorphology of a west-vergent thrust at a flat-slab of the Andes • Studies fault exposures, uplifted terraces, and tilted alluvial fan deposits • Fault activity dated by OSL and U Pb applied to geomorphic markers • Space-time similarities between the San Ramón and Cariño Botado faults • Cariño Botado faults suggests a possible seismic hazard of up to Mw 7.5. [ABSTRACT FROM AUTHOR]

Background Deep learning algorithms have achieved human-equivalent performance in image recognition. However, the majority of clinical data within electronic health records is inherently in a non-image format. Therefore, creating visual representations of clinical data could facilitate using cutting-edge deep learning models for predicting outcomes such as in-hospital mortality, while enabling clinician interpretability. The objective of this study was to develop a framework that first transforms longitudinal patient data into visual timelines and then utilizes deep learning to predict in-hospital mortality. Methods and findings All adult consecutive patient admissions from 2008–2016 at a tertiary care center were included in this retrospective study. Two-dimensional visual representations for each patient were created with clinical variables on one dimension and time on the other. Predictors included vital signs, laboratory results, medications, interventions, nurse examinations, and diagnostic tests collected over the first 48 hours of the hospital stay. These visual timelines were utilized by a convolutional neural network with a recurrent layer model to predict in-hospital mortality. Seventy percent of the cohort was used for model derivation and 30% for independent validation. Of 115,825 hospital admissions, 2,926 (2.5%) suffered in-hospital mortality. Our model predicted in-hospital mortality significantly better than the Modified Early Warning Score (area under the receiver operating characteristic curve [AUC]: 0.91 vs. 0.76, P < 0.001) and the Sequential Organ Failure Assessment score (AUC: 0.91 vs. 0.57, P < 0.001) in the independent validation set. Class-activation heatmaps were utilized to highlight areas of the picture that were most important for making the prediction, thereby providing clinicians with insight into each individual patient’s prediction. Conclusions We converted longitudinal patient data into visual timelines and applied a deep neural network for predicting in-hospital mortality more accurately than current standard clinical models, while allowing for interpretation. Our framework holds promise for predicting several important outcomes in clinical medicine. [ABSTRACT FROM AUTHOR]

Abstract The present study was designed to evaluate possible sugar-based trophic interactions between acetic acid bacteria (AAB) and non- Saccharomyces yeasts (NSY) involved in table grape sour rot, a disease in which berries spoilage is caused by the accumulation of several microbial metabolites. Acetobacter syzygii LMG 21419 (As) and Candida zemplinina CBS 9494 (Cz), a simplified AAB-NSY association responsible for table grape sour rot, grew differently in a minimal medium (YP) supplemented with glucose, ethanol, acetic and gluconic acid under monoculture conditions. In As - Cz co-culture media, after 24 h of incubation, As showed high relative abundance in YP-ethanol, whereas Cz was the dominant strain in YP-glucose medium. Co-culture in YP-glucose showed that glucose was converted into ethanol by Cz that, in turn, promoted the growth of As population. Gluconic acid was the main bacterial metabolite from glucose in monoculture, whereas acetic acid putatively derived from ethanol oxidation was found only in co-culture. However, gluconic acid showed inhibitory effect against As whereas acetic acid mainly inhibited Cz. Negative effects of both metabolites were mitigated in the glucose-supplemented medium. The results suggest a possible metabolic- based temporal succession between AAB and NSY during grape sour rot development. At the begin of sour rot, low glucose concentration promotes NSY producing ethanol, then, the AAB could take advantage from the oxidation of ethanol into acetic acid, becoming the dominant microbial sour rot population during the late stages of the process. Highlights • Co-culture in YP-ethanol and YP-glucose were dominated by As and Cz, respectively. • Acetic acid was detected only in YP-glucose under co-culture conditions. • Gluconic acid affected differently As and Cz growth kinetics. • Co-culture mitigated inhibitory activity of gluconic acid against As. • A metabolic- based temporal succession during grape sour rot is proposed. [ABSTRACT FROM AUTHOR]

The digitalization of the health-care system has resulted in a deluge of clinical big data and has prompted the rapid growth of data science in medicine. Data science, which is the field of study dedicated to the principled extraction of knowledge from complex data, is particularly relevant in the critical care setting. The availability of large amounts of data in the ICU, the need for better evidence-based care, and the complexity of critical illness makes the use of data science techniques and data-driven research particularly appealing to intensivists. Despite the increasing number of studies and publications in the field, thus far there have been few examples of data science projects that have resulted in successful implementations of data-driven systems in the ICU. However, given the expected growth in the field, intensivists should be familiar with the opportunities and challenges of big data and data science. The present article reviews the definitions, types of algorithms, applications, challenges, and future of big data and data science in critical care. [ABSTRACT FROM AUTHOR]

Phenotypic flexibility (reversible phenotypic change) enables organisms to couple internal, ontogenetic responses with external, environmental cues. Phenotypic flexibility also provides organisms with the capacity to buffer stereotypical internal, developmental processes from unpredictable external, ecological events. Echinoids exhibit dramatic phenotypic flexibility in response to variation in exogenous nutrient supplies. The extent to which echinoids display this flexibility has been explored incompletely and research hitherto has been conducted predominantly on larval structures and morphologies. We investigated experimentally the extent to which the primordial juvenile, the developing rudiment, can exhibit the first phase in phenotypic flexibility among individuals. We report for the first time on rudiment regression and complete resorption as a response to starvation during larval development in the sea urchin Strongylocentrotus droebachiensis (O.F. Müller, 1776) and identify a developmental "window of opportunity" within which this can occur. Based on our observations and previous suggestions, we speculate that sea urchin rudiments might provide means of buffering development during unfavorable conditions. [ABSTRACT FROM AUTHOR]

Objective: Modern machine learning-based modeling methods are increasingly applied to clinical problems. One such application is in variable selection methods for predictive modeling. However, there is limited research comparing the performance of classic and modern for variable selection in clinical datasets.Materials and Methods: We analyzed the performance of eight different variable selection methods: four regression-based methods (stepwise backward selection using p-value and AIC, Least Absolute Shrinkage and Selection Operator, and Elastic Net) and four tree-based methods (Variable Selection Using Random Forest, Regularized Random Forests, Boruta, and Gradient Boosted Feature Selection). We used two clinical datasets of different sizes, a multicenter adult clinical deterioration cohort and a single center pediatric acute kidney injury cohort. Method evaluation included measures of parsimony, variable importance, and discrimination.Results: In the large, multicenter dataset, the modern tree-based Variable Selection Using Random Forest and the Gradient Boosted Feature Selection methods achieved the best parsimony. In the smaller, single-center dataset, the classic regression-based stepwise backward selection using p-value and AIC methods achieved the best parsimony. In both datasets, variable selection tended to decrease the accuracy of the random forest models and increase the accuracy of logistic regression models.Conclusions: The performance of classic regression-based and modern tree-based variable selection methods is associated with the size of the clinical dataset used. Classic regression-based variable selection methods seem to achieve better parsimony in clinical prediction problems in smaller datasets while modern tree-based methods perform better in larger datasets. [ABSTRACT FROM AUTHOR]

The release of nanomaterials into the environment is the cause of an emerging concern. Titanium dioxide nanoparticles (nano-TiO 2) among the most produced nanomaterials, has been documented in marine coastal areas posing a threat on marine biota. Sea urchin embryos are recognized as suitable bioindicators in ecological risk assessment and recently for nanomaterials. This study investigated the impact of nano-TiO 2 on fertilization, embryonic and larval development of the tropical sea urchin Lytechinus variegatus in a range of concentrations (0.005–5 μg/mL) which includes environmentally relevant ones. The behavior of nano-TiO 2 in tropical natural seawater was determined by dynamic light scattering (DLS) and toxicity was evaluated through fertilization and embryotoxicity tests, and morphological/morphometric analyses of sea urchin's larvae. Limited toxicity was recorded for nano-TiO 2 in tropical sea urchin embryos and larvae, except for effects at the gastrula stage at 0.005 μg/mL. Large agglomerates of nano-TiO 2 (5 μg/mL) were observed adhering onto sea urchin larvae thus probably preventing nanoparticles uptake at the highest concentrations (>0.005 μg/mL). Environmental levels of nano-TiO 2 are able to cause toxicity on tropical sea urchin L. variegatus embryos with potential consequences on populations and their ecological role in tropical coastal areas. • Nano-TiO 2 showed agglomeration at the microscale in natural seawater • Nano-TiO 2 significantly reduced sea urchin fertilization rate at 0.5 and 5 μg/mL • Nano-TiO 2 induced higher toxicity in gastrulae at environmentally relevant concentration (0.005 μg/mL) • Nano-TiO 2 decreased the length of post-oral arms of larvae at all concentrations • Nano-TiO 2 was toxic to larval development at the highest concentration tested (5 μg/mL). [ABSTRACT FROM AUTHOR]

This work aims at studying the efficacy of low doses of gaseous ozone in postharvest control of the table grape sour rot, a disease generally attributed to a consortium of non- Saccharomyces yeasts (NSY) and acetic acid bacteria (AAB). Sour rot incidence of wounded berries, inoculated with 8 NSYstrains, or 7 AAB, or 56 yeast-bacterium associations, was monitored at 25 °C up to six days. Sour rot incidence in wounded berries inoculated with yeast-bacterium associations resulted higher than in berries inoculated with one single NSY or AAB strain. Among all NSY-AAB associations, the yeast-bacterium association composed of Candida zemplinina CBS 9494 (Cz) and Acetobacter syzygii LMG 21419 (As) showed the highest prevalence of sour rot; thus, after preliminary in vitro assays, this simplified As-Cz microbial consortium was inoculated in wounded berries that were stored at 4 °C for ten days under ozone (2.14 mg m −3 ) or in air. At the end of cold storage, no berries showed sour-rot symptoms although ozonation mainly affected As viable cell count. After additional 12 days at 25 °C, the sour rot index of inoculated As-Cz berries previously cold-stored under ozone or in air accounted for 22.6 ± 3.7% and 66.7 ± 4.5%, respectively. Molecular analyses of dominant AAB and NSY populations of both sound and rotten berries during post-refrigeration period revealed the appearance of new strains mainly belonging to Gluconobacter albidus and Hanseniaspora uvarum species, respectively. Cold ozonation resulted an effective approach to extend the shelf-life of table grapes also after cold storage. [ABSTRACT FROM AUTHOR]

Background Being born large for gestational age ( LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. Objective We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. Methods Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. Results Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non- LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). Conclusions We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma. [ABSTRACT FROM AUTHOR]

We evaluated the performance of check-all-that-apply (CATA) questions and intensity scales to describe Minas Frescal cheese and its reformulation based on consumers' perceptions. Ten commercial samples with different formulations (full-fat, low-fat, or low-lactose) were evaluated by 200 consumers divided equally into 2 groups: 1 evaluated samples and described their ideal cheese using intensity scales and 1 did the same using CATA questions. Both methodologies provided similar information about the sensory characteristics of the Minas Frescal cheeses, the description of the ideal product, and directions for product reformulation. The ideal Minas Frescal cheese was characterized by high moisture, intense white color, homogeneous mass, typical Minas Frescal cheese aroma and flavor, softness, and juiciness. For the intensity scales, the recommendation was to increase the typical aroma and flavor, salty taste, and juiciness, and to decrease the bitter flavor; for the CATA questions, only increasing the typical Minas Frescal cheese flavor was important for all classes of cheeses. Even for a heterogeneous product with no defined manufacturing protocol, both methodologies presented satisfactory results that should be considered for use by cheese producers and the dairy industry. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis and the study of a novel mixed biradical with BDPA and TEMPO radical units that are covalently bound by an ester group (BDPAesterTEMPO) as a polarizing agent for fast dissolution DNP. The biradical exhibits an extremely high DNP NMR enhancement of ＞50 000 times, which constitutes one of the largest signal enhancements observed so far, to the best of our knowledge. [ABSTRACT FROM AUTHOR]

Purpose: Describe a rare and severe clinical presentation of a disease difficult initial diagnosis. Materials and methods: For a woman of 45, who entered the service for multiple episodes of melena and hematemesis, hypovolemic shock that causes, whose diagnosis is found in an emergency exploratory laparotomy is presented. Results: Subtotal pancreatectomy body and tail is made. Without biopsy findings malignant mucinous cystic tumor mucinous cystadenoma type of pancreas, lymph nodes malign tumor. Discussion: Mucinous cystadenoma pancreas constitutes 10% of pancreatic cysts, the vast majority are asymptomatic or present with abdominal pain. The diagnosis is made primarily by imaging techniques, computed tomography or ultrasound diagnosis. Upper gastrointestinal bleeding is a rare clinical presentation, diagnosis low suspect may debut with important hemodynamic compromise. The cause of bleeding is attributed to this tumor communicated by the pancreatic duct into the duodenum. Conclusion: The treatment of choice is surgical resection. The surgical technique used is determined by the location of the tumor and its nature. [ABSTRACT FROM AUTHOR]

The hygienic behavior of Apis mellifera L., the honey bee, is one of the most important defense mechanisms against brood diseases. It is the ability of bees to detect and uncap the combs with diseased or dead brood and remove them. The aim of this study was to determine whether there is a correlation between the infestation of Varroa destructor mite and the hygienic behavior of Africanized Apis mellifera bees in different flowering. Twenty colonies of Africanized Apis mellifera were installed in Langstroth hives. One comb was removed from each colony and approximately 100 uncapped brood aged 10 to 14 days were pierced with an entomological pin. After piercing, the frame of brood was returned to the respective colonies for the worker bees to remove the dead brood. To estimate the hygienic behavior (HB) of each colony, after 24 h, empty cells from which the bees removed the dead brood by the pin were counted. Hygienic colonies were considered those with a removal rate greater than or equal to 80%. The average frequency of HB in the three periods was 82.58%, which categorizes them as hygienic colonies and shows their genetic potential for production of selected queens. Although the data shows that there were no statistical differences between the three periods, the percentage removal of brood in the flowering period was higher than in the dry period, possibly due to the higher food availability during these periods, causing bees to drive their attention more to the internal activities of the colonies such as the cleaning and removal of dead and diseased brood. [ABSTRACT FROM AUTHOR]

In order to overcome the shortage of ^3\mathrm He detectors for subcritical experiments in the IPEN/MB-01 reactor, some experiments were performed employing less sensitive detectors, such as BF3, and a logic input module, which sums the counts from different detectors. Through microscopic and macroscopic neutron noise technique, it was possible to obtain, respectively, Rossi- $\alpha $ distribution and Auto Power Spectral Densities (APSD) for each detector configuration and various subcritical levels, and the prompt neutron decay constant ( $\alpha $ ) was extracted through a least squares procedure. In addition, Cross Power Spectral Densities (CPSD) were acquired for different types of detectors and the correlation among those detectors was confirmed. It was also observed that there was no loss of correlation among the neutron pulses, and therefore, the CPSD curves demonstrated the presence of correlated events. The $\alpha $ parameter was used as an indicator for the comparison of the results and for the quality of the experimental data. The obtained values demonstrate that the sum of counts technique does not present loss of information (correlated neutrons) even for different models and types of detectors, suggesting that the technique may be employed in neutron noise measurements for subcritical reactivity. [ABSTRACT FROM PUBLISHER]

The effective thermal diffusivity ( α) of a porous bed containing rice grains was determined under different experimental conditions. The α values were estimated by the Log method. The effects of rice moisture content (2, 12 and 22 % w.b.) and temperature (15, 35, 55 and 75 °C) on the α values were investigated. Finally, an empirical model was proposed to represent the effective thermal diffusivity as a function of the moisture content ( X) and temperature ( T). The results revealed that the increase in the rice moisture content and temperature caused an increase in α values, which ranged from 0.91 × 10 to 3.23 × 10 m s. In the studied range, the dependence of α with the rice moisture content and temperature can be represented as: α (ms) = (0.63 + 5.63 × 10 X + 1.51 × 10 T + 1.17 × 10 XT) × 10. The proposed empirical model was suitable to predict the α values with mean absolute percentage deviation of 3.8 % and is a tool for future modeling purposes. [ABSTRACT FROM AUTHOR]

The prediction of the path of harmful algal blooms (HABs) along the coast can be achieved using numerical models of ocean circulation in order to reproduce the hydrodynamics of the study area. With this setting, our work aimed at the (1) study of key past events to evaluate the model ability to reproduce the transport pathways of blooms along the Iberian coast, and (2) to assess the relevance of such strictly physical approach. The simulations described here rely on the advection of lagrangian elements after a point release in a hypothetical location for bloom initiation, and the subsequent assessment of the influence of the surface currents transport on the extent of the bloom. Five events were simulated, accounting for blooms of Gymnodinium catenatum , Dinophysis acuminata and Pseudo-nitzschia spp. Model results were compared with field data from the National HAB monitoring program, and were used to evaluate some hypothesis in their interpretation. The effort compiled in this paper, though focused on the transport and dispersion of HAB (after bloom detection), was a critical step toward an integrative forecasting system to determine potential HAB impacted areas, also addressed in this Special Issue. [ABSTRACT FROM AUTHOR]

The development of sustainable shellfish aquaculture is highly dependent on the provision of reliable monitoring and predictive information on the occurrence of harmful algal blooms (HABs). The Portuguese HAB early warning system and shellfish closures presented here is a prototype, developed in the ASIMUTH project. It relies on weekly monitoring data composed of observations of HAB species and toxin concentrations within shellfish, and ocean circulation forecasts generated by an operational oceanographic model. The shellfish harvesting areas comprise coastal areas, estuaries + rías and coastal lagoons. The weekly bulletin characterizes the current shellfish closure situation and next week's forecasts for potentially impacted areas. The period analyzed ranged from 27 July 2013 to 17 March 2014, and describes the first skill assessment of the warning system. The forecast accuracy was evaluated, considering the number of forecasts that were verified to be correct the following week (85%) as well as the number of events not forecasted (false negatives, 12%) and those expected but did not occur (false positives, 3%). Variations were most visible in the first weeks of bulletin implementation and during autumn–winter months. The complementary use of field data, remote sensing and operational models led to more accurate predictions of blooms and range of the event. [ABSTRACT FROM AUTHOR]

The evolution of a mono-disperse gravity current in the lock-exchange configuration is investigated by means of direct numerical simulations for various Reynolds numbers and settling velocities for the deposition. We limit our investigations to gravity currents over a flat bed in which density differences are small enough for the Boussinesq approximation to be valid. The concentration of particles is described in an Eulerian fashion by using a transport equation combined with the incompressible Navier-Stokes equations. The most interesting results can be summarized as follows: (i) the settling velocity is affecting the streamwise vortices at the head of the current with a substantial reduction of their size when the settling velocity is increased; (ii) when the Reynolds number is increased the lobe-and-cleft structures are merging more frequently and earlier in time, suggesting a strong Reynolds number dependence for the spatio-temporal evolution of the head of the current; (iii) the temporal imprint of the lobe-and-cleft structures can be recovered from the deposition map, suggesting that the deposition pattern is defined purely and exclusively by the structures at the front of the current. [ABSTRACT FROM AUTHOR]

Background/purpose When evaluating skin care products for human skin, quantitative test methods need to be simple, precise and reliable. Optical coherence tomography ( OCT), provides high-resolution sectional images of translucent materials to a depth of a few millimeters, a technique usually applied to medical measurements in ophthalmology and dermatology. This study aimed to demonstrate the application of OCT as the main technique for monitoring changes in skin topography during tests of a wrinkle-reduction product in humans. Methods We used a commercial OCT apparatus to perform clinical examinations of skin roughness in treated and non-treated sites in the periorbital region of thirty human voluntaries who were using an anti-aging product commercially available: Natura Chronos® Flavonóides de Passiflora 45+ FPS15, from Natura Cosméticos, Brazil. Measurements were performed days 0, 7, 14 and 28 of treatment. Equipment and software allowed real-time recording of skin roughness parameters and wrinkle depths. Results The OCT measurements have allowed the monitoring of changes in skin roughness, which have shown reduction in treated sites around 10%. The obtained depth distributions also indicate reduction in the occurrence of wrinkles deeper than 170 μm. The verified results are consistent with those typically obtained after successful treatment with modern anti-aging products. Conclusion By using the OCT technique, it was possible to quantify changes in skin roughness and in the distribution of depths of skin wrinkles, with adequate sensitivity. OCT imaging allows the direct visualization of the skin topography with resolution of micrometers, a reliable and interactive tool for clinical use. Therefore, for the first time, we demonstrated the use of OCT technique to verify the efficacy of cosmetic products in real time. [ABSTRACT FROM AUTHOR]

Cohesive sediment dynamics in estuarine systems is a major issue in water quality and engineering problems. Numerical models can help to assess the complex dynamics of cohesive sediments, integrating the information collected in monitoring studies. Following a numerical approach we investigated the main factors that influence the cohesive sediment dynamics in an estuarine system composed of large mudflats (Tagus estuary, Portugal). After a spin up period of the bottom layer and considering the combined effect of waves and currents on the bottom shear stress, the dynamics of cohesive sediment during the fortnightly and daily erosion–sedimentation cycle was properly reproduced by the model. The results of cohesive suspended sediments were validated with data from sixteen monitoring stations located along the estuary and turbidity data measured by two multiparametric probes. The hydrodynamics were previously validated by harmonic analysis and with ADCP data. Although tidal currents are the major cause of cohesive sediment erosion, the results suggest that wind waves also play an important role. The simulated sediment mass involved in the fortnightly tidal cycle was in the same order of magnitude of the annual load from the rivers, as observed in previous studies based on field data. [ABSTRACT FROM AUTHOR]

Chalcopyrite ores are processed mostly by pyrometallurgical techniques due to the refractory nature of the mineral to the current hydrometallurgical techniques. In order to overcome such refractoriness, pretreatment steps such as sulfurization may be applied to produce different copper phases and therefore improve the metal dissolution in the leaching step. The current study investigated the reaction products of the reaction between chalcopyrite and elemental sulfur at different chalcopyrite/sulfur ratios (1/1 and 1/2), reaction time (60 min and 90 min), and temperature (350ºC, 400°C and 450ºC). The sulfurization experiments revealed that covellite, nukundamite, bornite, and pyrite-like compounds were produced according to the experimental conditions applied. Then, the sulfurization products were submitted to chemical leaching tests at temperatures ranging from 32ºC to 70ºC, whereas bioleaching tests were also carried out with Acidithiobacillus ferrooxidans, at 32ºC. In the chemical leaching experiments at 70ºC, only 14% copper was recovered from the original chalcopyrite sample while the maximum copper extraction was 78% from bornite produced at 450ºC (90 min and mass ratio of chalcopyrite/sulfur of 1/2). On the other hand, copper extraction achieved 96% from the same sulfurization product containing synthetic bornite within 20 days of bioleaching. Bioleaching of the original chalcopyrite sample implied in a copper recovery of only 25% in the same period. Summarizing, the current work showed that chalcopyrite sulfurization at 450ºC was able to transform chalcopyrite into a bornite-like phase, which was chemically leached and bioleached by At. ferrooxidans. [ABSTRACT FROM AUTHOR]

• Study of a system of quasilinear PDEs that can be used to model drug release from a polymeric structure enhanced by light. • A numerical scheme to compute the numerical solution of the IBVP based on the system of PDEs is proposed. • The theoretical support (stability and convergence) under weaker assumptions than those usually used is developed. • Numerical results illustrating the theoretical results established are provided. • A comparation between experimental data and simulation results is also presented. In this paper, we analyze a numerical scheme for a nonlinear coupled system of partial differential equations. Our study is motivated by the mathematical modeling of light-triggered drug delivery, a technique that can have a significant impact on cancer treatment. The numerical scheme combines a finite difference method (FDM) in space with an implicit-explicit (IMEX) method in time. For the main variable of interest - free drug concentration - we prove that the scheme is second-order supraconvergent in space in a discrete H 1 -norm and first-order convergent in time in a discrete L 2 -norm. We give numerical results illustrating the theoretical findings and computational simulations based on a laboratory experiment concerned with light-triggered drug delivery. [ABSTRACT FROM AUTHOR]

Terrestrial photogrammetry should be the survey technique of choice when updating large scale urban maps and GIS databases, where 3D data and attribute data are required. Its main drawback is the need for Ground Control Points (GCP) to reference the survey. To make image georeferencing easier and to provide control information, the use of a simple system, made of a photogrammetric camera fastened to a GPS antenna, is proposed. A photogrammetric block, composed by at least three images, is taken around the object with the receiver measuring in kinematic mode. Tie points are automatically extracted by Structure from Motion (SfM) algorithms or measured manually; block orientation is performed by GPS assisted Aerial Triangulation. Advantages as well as limitations of the system are discussed, with particular attention to GPS availability or ill-conditioned block configurations. The issue of system calibration (i.e. measurement of eccentricity between camera and antenna) is also addressed. Several test cases are presented, in which absolute accuracies, verified on check points independently surveyed range from 4 to 7 cm. [ABSTRACT FROM AUTHOR]

. Purpose: To determine whether retinal vessel oxygen saturation in patients with glaucoma is associated with structural optic disc and retinal nerve fibre layer (RNFL) changes and visual field (VF) defects. Methods: Fifty-nine patients with confirmed glaucoma were recruited at University Hospitals Leuven. Retinal oxygen saturation in patients with glaucoma was measured with a noninvasive spectrophotometric retinal oximeter (Oxymap ehf, Reykjavik, Iceland). VF and Heidelberg retinal tomographies (HRTs) were performed on the same day. Statistical analysis was performed using Student's t-test and Pearson's or Spearman correlation coefficient. Results: The mean oxygen saturation in venules was higher in patients with severe VF defects compared to those patients with mild VF defects (69 ± 3% versus 65 ± 6% respectively; p = 0.0003; n = 59). Accordingly, the arteriovenous (AV) difference in oxygen saturation was lower in patients with worse VF compared to those with better VF (29 ± 3% versus 33 ± 6% respectively; p = 0.002). The oxygen saturation in venules correlated with the VF mean defects ( r = −0.42; p = 0.001; n = 59) as well as with the structural HRT parameters rim area and RNFL thickness ( r = −0.39; p = 0.008 and r = −0.26; p = 0.05 respectively; n = 53). The AV difference decreased significantly as the VF defect worsened ( r = 0.38; p = 0.003), as the rim area diminished ( r = 0.29; p = 0.03) and as the RNFL thickness decreased ( r = 0.27; p = 0.05). No correlation was found between the oxygen saturation in retinal arterioles and either of these parameters. Conclusion: Severe glaucomatous damage is associated with increased oxygen saturation in retinal venules and decreased AV difference in oxygen saturation. These data suggest that in eyes with severe glaucomatous damage, reduced retinal oxygen consumption is consistent with tissue loss. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this paper is to study a finite difference method for quasilinear coupled problems of partial differential equations that presents numerically an unexpected second order convergence rate. The error analysis presented allows us to conclude that the finite difference method is supraconvergent. As the method studied in this paper can be seen as a fully discrete piecewise linear finite element method, we conclude the supercloseness of our approximations. [Copyright &y& Elsevier]

Background Interferon-regulatory factors ( IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF-4 was only recently recognized as a further major player in T cell differentiation. Objective As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children. Methods Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI- TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9-11; N = 3099). Replication was performed in our previously established genome-wide association study ( GWAS) data set ( N = 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood ( MAGIC) study and reference children from the ISAAC II study. Results SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma. Conclusions We found genetic associations in IRF-4 to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3′ UTR region of IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis. [ABSTRACT FROM AUTHOR]

Chloride load's association with VFD, hospital LOS, in-hospital mortality, and change in serum chloride from baseline was not significant after adjusting for confounders. B Introduction: b Hyperchloremia is associated with increased morbidity and mortality in critically ill children, but it is unknown if the intravenous (IV) chloride amount administered (chloride load) is associated with hyperchloremia or poor outcomes. B Conclusions: b IV chloride load is independently associated with decreased odds of day 2 and 3 severe AKI, increased odds of hyperchloremia, and higher day 2 serum chloride in critically ill children. [Extracted from the article]

Convection enhanced drug delivery (CED) is a technique used to make therapeutic agents reach, through a catheter, sites of difficult access. The name of this technique comes from the convective flow originated by a pressure gradient induced at the tip of the catheter. This flow enhances passive diffusion and allows a more efficient spread of the agents by the target site. CED is particularly useful in the treatment of diseases that affect the central nervous system, where the blood–brain barrier prevents the diffusion of most therapeutic agents from the cerebral blood vessels to the brain interstitial space. In this work we deal with the numerical analysis of a coupled system of partial differential equations that can be used to simulate CED in an elastic medium like brain tissue. The model variables are the fluid velocity, the pressure, the tissue deformation, and the agents concentration. We prove the stability of the coupled problem and from the numerical point of view we propose a fully discrete piecewise linear finite element method (FEM). The convergence analysis shows that the method has second order convergence for the pressure, displacement, and concentration. Numerical experiments illustrating the theoretical convergence rates and the behavior of the system are also given. [ABSTRACT FROM AUTHOR]

Abstract: Integro-differential equations of Volterra type arise, naturally, in many applications such as for instance heat conduction in materials with memory, diffusion in polymers and diffusion in porous media. The aim of this paper is to study a finite difference discretization of the mentioned integro-differential equations. Second convergence order with respect to the norm is established which means that the discretization proposed is supraconvergent in finite difference methods language. As the finite difference method can be seen as a piecewise linear finite element method combined with special quadrature formulas, our result establishes the supercloseness of the gradient in the finite element language. Numerical results illustrating the discussed theoretical results are included. [Copyright &y& Elsevier]

Abstract: The morphology of estuaries and rivers changes constantly due to the dynamic imbalance between the forcing actions (e.g. river flow, tides, surface waves and wind) and the sedimentary reactions. Understanding and predicting these changes are very important for an scientific-based, sustained management of these systems. Morphodynamic process-based numerical models can be used for this purpose. The development and validation of a new three-dimensional unstructured grid morphodynamic modelling system, MORSELFE, aiming at simulating short-term morphological evolutions of estuaries and sandy rivers (temporal scale of days to month), are presented. MORSELFE couples a three-dimensional hydrodynamic model, with an advection–diffusion transport model for the suspended sediments, an empirical formula for the bed load, and a bed updating module. The model considers the simulation of non-cohesive sediment and does not account for wave effects. A new approach is proposed to compute the erosive fluxes, which adapts them to the vertical grid resolution. The use of unstructured grids and the implementation in parallel mode make MORSELFE particularly adapted to engineering applications. The model was assessed and validated against analytical and experimental test cases, also allowing the inference on the optimum choice of the model parameters and variables. [Copyright &y& Elsevier]

Abstract: Organisms living in coastal ecosystems are frequently subjected to anthropogenic pressures such as metals. Metals, especially those not required for metabolic activity (e.g. mercury, lead and cadmium) can be toxic even at quite low concentrations not only to organisms that accumulate them, but also to their consumers. Throughout the world, Ruditapes decussatus and Ruditapes philippinarum have been successfully commercialised for human consumption and for monitoring environmental conditions such as contamination. These two clam species share similar habitats and requirements, successfully competing both in the natural environment and in aquaculture farms. Because differences in metal accumulation may exist between R. decussatus and R. philippinarum, different risks to public health may overcome as well as distinct ecological implications. The effect of depuration on the metal burden and biochemical status of both clams species may also diverge and since the information available is subjective and scarce, the aims of the present study were to: 1) assess the total metal accumulation and intracellular partitioning, at natural conditions, in the two clam species collected at the same site; 2) evaluate the effect of depuration as a mean of reducing the levels of distinct elements, assessing also the effect of depuration time (2 and 7 days); 3) investigate the efficiency of depuration by biochemical status of the two bivalve species, evaluating changes in lipid peroxidation and activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and of glutathione S-transferase (GST). Metal chelation by metallothioneins (MTs) was also determined. The results obtained showed that concentration of elements in clams was low, presenting very similar concentration levels for all elements. The present work further demonstrated that the total element concentration decreased in the shorter depuration period (2 days) and that R. decussatus and R. philippinarum partitioned elements preferentially in the insoluble fraction. The percentage of elements in the soluble fraction was lower in the longer depuration period, reducing the dietary bioavailability of elements and thus the health risk to consumers of depurated bivalves. In general, LPO, CAT, SOD and GSTs showed a decreased from environmental to depuration conditions, revealing that depuration reduces the oxidative stress that organisms were subjected in the environment. The lower MTs production observed in the longer depuration period, although no significantly different from the remaining periods, may be explained by the distinct metal allocation between both soluble and insoluble fractions. [Copyright &y& Elsevier]

• A mathematical methodology to find the optimal NIR light protocol in transdermal drug delivery; • Strategy based on an optimization problem minimizing the difference between target and simulated drug absorption profile; • The optimization problem relies on a 2D mathematical model for NIR light controlled transdermal drug delivery; • Validation of the transdermal model against laboratory data; • Convergence and stability analysis of a finite difference spatial scheme for a generalization of the transdermal model. Near-infrared light-controlled transdermal drug delivery (NIRTDD) has several advantages over traditional delivery methods, and it is now undergoing extensive research. One prominent aspect of NIRTDD is the possibility of keeping the drug concentration in its optimal therapeutic window using a suitable near-infrared light protocol. The problem is that this ideal protocol is usually unknown. In this paper, we propose a computational tool that aims at solving this issue. The computational tool relies on an optimization problem involving the numerical simulation of a two-dimensional mathematical model for NIRTDD. We also analyze the convergence and stability of a finite difference spatial scheme for a generalized version of this mathematical model. [ABSTRACT FROM AUTHOR]

Abstract: Using Salmonella strains identical to those present in the gastrointestinal tract of different animals we aim to determine and compare the proteome of two serotypes, Salmonella Typhimurium and Enteritidis recovered from faecal samples of wild boars and wild rabbits, respectively. The presence of genes responsible for antibiotic resistance was detected by PCR. Proteomes of the two distinct serotypes were determined using 2-DE in order to identify proteins associated with antibiotic resistance or virulence. Through 2-DE we obtained a total of 229 spots from both strains. All were suitable for MALDI-TOF/TOF and, in correlation with bioinformatic databases, allowed accurate identification and characterization of proteins. S. Enteritidis recovered from wild rabbits was sensitive to all the antibiotics tested in contrast to S. Typhimurium isolated from wild boars which presented a resistance phenotype to ampicillin, streptomycin and chloramphenicol. Nevertheless, despite the different ratio of proteins observed in each proteome according to their biological function, no significant difference was observed in the involvement of these proteins in pathogenicity. Bearing in mind that serotypes are related to infectious processes in humans and animals, it is important to explore the proteome of new strains which might serve as protein biomarkers for biological activity. [Copyright &y& Elsevier]

Aims: To analyse the occurrence of faecal carriage of vancomycin-resistant enterococci (VRE) in Buteo buteo and to study the associated resistance and virulence genes. Methods and Results: The presence of VRE was investigated in 33 faecal samples of B. buteo. Samples were seeded in Slanetz–Bartley agar plates supplemented with vancomycin for VRE recovery. Genes encoding antimicrobial resistance and virulence were studied by polymerase chain reaction. Vancomycin-resistant Enterococcus faecium isolates were characterized by multilocus sequence typing. VRE with an acquired mechanism of resistance ( vanA genotype) were detected in 9% of samples analysed ( Ent. faecium and Enterococcus durans). In addition, 27% of samples contained VRE with an intrinsic mechanism of resistance ( Enterococcus gallinarum, vanC1). All vanA-containing isolates showed resistance to tetracycline and erythromycin and harboured the tet(M) and/or tet(L) genes, in addition to the ermB gene. The vat(E) and/or vat(D), cat(A) and aph(3′)-IIIa genes were identified in quinupristin–dalfopristin-, chloramphenicol-, and kanamycin-resistant vanA-containing strains, respectively. The sequence types ST273 and ST5 were identified in two vanA-positive Ent. faecium isolates, and the presence of hyl, gelE, cylA, cylL and cylM virulence genes and gelatinase activity were identified in Ent. faecium ST5 strain. Conclusions: The intestinal tract of B. buteo could be a reservoir of vanA-positive enterococci. Significance and Impact of the Study: First study focused to define the occurrence of vanA-containing Enterococcus strains in B. buteo. [ABSTRACT FROM AUTHOR]

Expressed sequence tags derived markers have a great potential to be used in functional map construction and QTL tagging. In the present work, sugarcane genomic probes and expressed sequence tags having homology to genes, mostly involved in carbohydrate metabolism were used in RFLP assays to identify putative QTLs as well as their epistatic interactions for fiber content, cane yield, pol and tones of sugar per hectare, at two crop cycles in a progeny derived from a bi-parental cross of sugarcane elite materials. A hundred and twenty marker trait associations were found, of which 26 at both crop cycle and 32 only at first ratoon cane. A sucrose synthase derived marker was associated with a putative QTL having a high negative effect on cane yield and also with a QTL having a positive effect on Pol at both crop cycles. Fifty digenic epistatic marker interactions were identified for the four traits evaluated. Of these, only two were observed at both crop cycles. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39 176–181 Background: Local failure occurs in 13.9–62.6% and it is a well known indicator of poor prognosis in patients with oral squamous cell carcinoma (OSCC), despite aggressive treatments. The purpose of this study was to investigate the value of histopathology and molecular biomarkers in predicting the development of early local recurrence. Methods: This study included a total of 69 patients. There were 23 patients with early recurrent OSCC and 46 patients without local recurrence with the same clinical stage and tumor site, in a pair-matched study design. Their charts were retrospectively analyzed. All surgical specimens of the primary tumors were evaluated according to the system proposed by Anneroth et al. and immunohistochemical for ErbB2 and FAS were performed. Results: A significant correlation of early local recurrence with grade of histological malignancy (more than 15 points) was observed (Fisher’s exact test, P = 0.03). Early local recurrence was also significantly associated with weak FAS expression and strong intracytoplasmic ErbB2 staining (Mantel–Haenszal chi-square, P = 0.0038 and P = 0.0068, respectively). Histological grade of malignancy (more than 15 points) was also correlated with reduced survival (log-rank, P = 0.06). Among the histopathological parameters, keratinization, pattern of invasion and inflammation were important for overall survival (log-rank, P < 0.0001). Regarding the biomarkers, only FAS was significantly associated with overall survival (log-rank, P = 0.0002). Moreover, a positive correlation of FAS and membrane ErbB2 expression with keratinization was noticed. Conclusion: Histopathological characteristics and the expression of FAS and ErbB2 carry prognosis importance in local recurrence and overall survival in OSCC. [ABSTRACT FROM AUTHOR]

Background: Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain-derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation. Aim: We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. Methods: The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross-sectional study population of 3099 children from Dresden and Munich (age 9–11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi-square test andanova using SAS Genetics andspss. Results: We identified nine polymorphisms with minor allele frequency ≥0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross-sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14–1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70–0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00–1.42, P = 0.05). Conclusions: As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma. [ABSTRACT FROM AUTHOR]