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In environmental epidemiology, there is wide interest in creating and using comprehensive indices that can summarize information from different environmental exposures while retaining strong predictive power on a target health outcome. In this context, the present article proposes a model called the constrained groupwise additive index model (CGAIM) to create easy-to-interpret indices predictive of a response variable, from a potentially large list of variables. The CGAIM considers groups of predictors that naturally belong together to yield meaningful indices. It also allows the addition of linear constraints on both the index weights and the form of their relationship with the response variable to represent prior assumptions or operational requirements. We propose an efficient algorithm to estimate the CGAIM, along with index selection and inference procedures. A simulation study shows that the proposed algorithm has good estimation performances, with low bias and variance and is applicable in complex situations with many correlated predictors. It also demonstrates important sensitivity and specificity in index selection, but non-negligible coverage error on constructed confidence intervals. The CGAIM is then illustrated in the construction of heat indices in a health warning system context. We believe the CGAIM could become useful in a wide variety of situations, such as warning systems establishment, and multipollutant or exposome studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epidemiological evidence on the health risks of sulfur dioxide (SO2) is more limited compared with other pollutants, and doubts remain on several aspects, such as the form of the exposure–response relationship, the potential role of copollutants, as well as the actual risk at low concentrations and possible temporal variation in risks. OBJECTIVES: Our aim was to assess the short-term association between exposure to SO2 and daily mortality in a large multilocation data set, using advanced study designs and statistical techniques. METHODS: The analysis included 43,729,018 deaths that occurred in 399 cities within 23 countries between 1980 and 2018. A two-stage design was applied to assess the association between the daily concentration of SO2 and mortality counts, including first-stage time-series regressions and second-stage multilevel random-effect meta-analyses. Secondary analyses assessed the exposure–response shape and the lag structure using spline terms and distributed lag models, respectively, and temporal variations in risk using a longitudinal meta-regression. Bi-pollutant models were applied to examine confounding effects of particulate matter with an aerodynamic diameter of less than or equal to 10 micrometers = 10µm (PM10) and 2.5µm (PM2.5), ozone, nitrogen dioxide, and carbon monoxide. Associations were reported as relative risks (RRs) and fractions of excess deaths. RESULTS: The average daily concentration of SO2 across the 399 cities was 11.7 μg/m³, with 4.7% of days above the World Health Organization (WHO) guideline limit (40 μg/m³, 24-h average), although the exceedances occurred predominantly in specific locations. Exposure levels decreased considerably during the study period, from an average concentration of 19.0 μg/m³ in 1980-1989 to 6.3 μg/m³ in 2010-2018. For all locations combined, a 10-μg/m³ increase in daily SO2 was associated with an RR of mortality of 1.0045 [95% confidence interval (CI): 1.0019, 1.0070], with the risk being stable over time but with substantial between-country heterogeneity. Short-term exposure to SO2 was associated with an excess mortality fraction of 0.50% [95% empirical CI (eCI): 0.42%, 0.57%] in the 399 cities, although decreasing from 0.74% (0.61%, 0.85%) in 1980-1989 to 0.37% (0.27%, 0.47%) in 2010-2018. There was some evidence of nonlinearity, with a steep exposure-response relationship at low concentrations and the risk attenuating at higher levels. The relevant lag window was 0-3 d. Significant positive associations remained after controlling for other pollutants. DISCUSSION: The analysis revealed independent mortality risks associated with short-term exposure to SO2, with no evidence of a threshold. Levels below the current WHO guidelines for 24-h averages were still associated with substantial excess mortality, indicating the potential benefits of stricter air quality standards. [ABSTRACT FROM AUTHOR]

Measuring the progress towards the Sustainable Development Goals (SDGs) requires the collection of relevant and reliable data. To do so, Citizen Science can provide an essential source of non-traditional data for tracking progress towards the SDGs, as well as generate social innovations that enable such progress. At its core, citizen science relies on participatory processes involving the collaboration of stakeholders with diverse standpoints, skills, and backgrounds. The ability to measure these participatory processes is therefore key for the monitoring and evaluation of citizen science projects and to support the decisions of their coordinators. Here, we show that the monitoring of social interaction networks provides unique insights on the participatory processes and outcomes of citizen science projects. We studied fourteen early-stage citizen science projects that participated in an innovation cycle focused on SDG 13, Climate Action, as part of the Crowd4SDG project. We implemented a monitoring strategy to measure the collaborative profiles of citizen science teams. This allowed us to generate dynamic interaction networks across complementary dimensions, making visible both formal and informal interactions associated with the division of labor, collaborations, advice seeking, and communication processes of the projects during their development. Leveraging jury evaluation data, we showed that while team composition and communication are associated with project quality, measures of collaboration and activity are associated with engagement quality. Overall, monitoring social interaction dynamics helps build a more comprehensive picture of participatory processes, which is of importance for guiding citizen science projects and for designing initiatives leveraging citizen science to address the SDGs. [ABSTRACT FROM AUTHOR]

Given the link between climatic factors on one hand, such as climate change and low frequency climate oscillation indices, and the occurrence and magnitude of heat waves on the other hand, and given the impact of heat waves on mortality, these climatic factors could provide some predictive skill for mortality. We propose a new model, the Mortality-Duration-Frequency (MDF) relationship, to relate the intensity of an extreme summer mortality event to its duration and frequency. The MDF model takes into account the non-stationarities observed in the mortality data through covariates by integrating information concerning climate change through the time trend and climate variability through climate oscillation indices. The proposed approach was applied to all-cause mortality data from 1983 to 2018 in the metropolitan regions of Quebec and Montreal in eastern Canada. In all cases, models introducing covariates lead to a substantial improvement in the goodness-of-fit in comparison to stationary models without covariates. Climate change signal is more important than climate variability signal in explaining maximum summer mortality. However, climate indices successfully explain a part of the interannual variability in the maximum summer mortality. Overall, the best models are obtained with the time trend and the North Atlantic Oscillation (NAO) used as covariates. No country has yet integrated teleconnection information in their heat-health watch and warning systems or adaptation plans. MDF modeling has the potential to be useful to public health managers for the planning and management of health services. It allows predicting future MDF curves for adaptive management using the values of the covariates. [ABSTRACT FROM AUTHOR]

Background: The rise of major complex public health problems, such as vaccination hesitancy and access to vaccination, requires innovative, open, and transdisciplinary approaches. Yet, institutional silos and lack of participation on the part of nonacademic citizens in the design of solutions hamper efforts to meet these challenges. Against this background, new solutions have been explored, with participatory research, citizen science, hackathons, and challenge-based approaches being applied in the context of public health. Objective: Our aim was to develop a program for creating citizen science and open innovation projects that address the contemporary challenges of vaccination in France and around the globe. Methods: We designed and implemented Co-Immune, a program created to tackle the question of vaccination hesitancy and access to vaccination through an online and offline challenge-based open innovation approach. The program was run on the open science platform Just One Giant Lab. Results: Over a 6-month period, the Co-Immune program gathered 234 participants of diverse backgrounds and 13 partners from the public and private sectors. The program comprised 10 events to facilitate the creation of 20 new projects, as well as the continuation of two existing projects, to address the issues of vaccination hesitancy and access, ranging from app development and data mining to analysis and game design. In an open framework, the projects made their data, code, and solutions publicly available. Conclusions: Co-Immune highlights how open innovation approaches and online platforms can help to gather and coordinate noninstitutional communities in a rapid, distributed, and global way toward solving public health issues. Such initiatives can lead to the production and transfer of knowledge, creating novel solutions in the public health sector. The example of Co-Immune contributes to paving the way for organizations and individuals to collaboratively tackle future global challenges. [ABSTRACT FROM AUTHOR]

Previous studies have reported a decrease in air pollution levels following the enforcement of lockdown measures during the first wave of the COVID-19 pandemic. However, these investigations were mostly based on simple pre-post comparisons using past years as a reference and did not assess the role of different policy interventions. This study contributes to knowledge by quantifying the association between specific lockdown measures and the decrease in NO2, O3, PM2.5, and PM10 levels across 47 European cities. It also estimated the number of avoided deaths during the period. This paper used new modelled data from the Copernicus Atmosphere Monitoring Service (CAMS) to define business-as-usual and lockdown scenarios of daily air pollution trends. This study applies a spatio-temporal Bayesian non-linear mixed effect model to quantify the changes in pollutant concentrations associated with the stringency indices of individual policy measures. The results indicated non-linear associations with a stronger decrease in NO2 compared to PM2.5 and PM10 concentrations at very strict policy levels. Differences across interventions were also identified, specifically the strong effects of actions linked to school/workplace closure, limitations on gatherings, and stay-at-home requirements. Finally, the observed decrease in pollution potentially resulted in hundreds of avoided deaths across Europe. [ABSTRACT FROM AUTHOR]

Hydrological systems are naturally complex and nonlinear. A large number of variables, many of which not yet well considered in regional frequency analysis (RFA), have a significant impact on hydrological dynamics and consequently on flood quantile estimates. Despite the increasing number of statistical tools used to estimate flood quantiles at ungauged sites, little attention has been dedicated to the development of new regional estimation (RE) models accounting for both nonlinear links and interactions between hydrological and physio-meteorological variables. The aim of this paper is to simultaneously take into account nonlinearity and interactions between variables by introducing the multivariate adaptive regression splines (MARS) approach in RFA. The predictive performances of MARS are compared with those obtained by one of the most robust RE models: the generalized additive model (GAM). Both approaches are applied to two datasets covering 151 hydrometric stations in the province of Quebec (Canada): a standard dataset (STA) containing commonly used variables and an extended dataset (EXTD) combining STA with additional variables dealing with drainage network characteristics. Results indicate that RE models using MARS with the EXTD outperform slightly RE models using GAM. Thus, MARS seems to allow for a better representation of the hydrological process and an increased predictive power in RFA. [ABSTRACT FROM AUTHOR]

Corporate board gender diversity has been canvassed for two reasons—business benefits and gender equality. The most convincing reason for board gender diversity seems to be that diverse boards are more effective monitors of management. In other words, the corporate governance case is the most convincing aspect of the business case. Drawing from the analogy of independent directors who are meant to improve corporate governance, this article focuses on the effectiveness of board gender diversity as a corporate governance measure in India. The article also examines, to a limited extent, the equality case for board gender diversity, its articulation, and its effectiveness in the Indian context. Finally, the article makes recommendations to ensure that the gender diversity measures are effective both in terms of corporate governance and equality in India. Thus, the article addresses a gap in legal scholarship on the effectiveness of the board gender diversity measures in India. [ABSTRACT FROM AUTHOR]

Using numerous research findings about the practices of schoolteachers who teach math and the training they received, this paper aims to identify the principles that can serve as a basis for developing and analyzing training methods for helping schoolteachers learn to teach math. In the first section, with reference to the contexts in which the information was gathered, we present research findings on teaching practices, their origins, and the training the teachers received (content and strategies). This provides the context of what we were able to draw from to conceptualize initial training and continuing education methods. In the second section, we state five major principles for developing what we believe to be a holistic training method that takes into account the complexity and coherence of practices. In the third section, after presenting four intervention techniques at the trainer's disposal, we describe how the aforementioned principles were applied in the training of different groups: future schoolteachers in training, new teachers, and experienced teachers who work in priority education areas. [ABSTRACT FROM AUTHOR]

In environmental epidemiology studies, health response data ( e.g. hospitalization or mortality) are often noisy because of hospital organization and other social factors. The noise in the data can hide the true signal related to the exposure. The signal can be unveiled by performing a temporal aggregation on health data and then using it as the response in regression analysis. From aggregated series, a general methodology is introduced to account for the particularities of an aggregated response in a regression setting. This methodology can be used with usually applied regression models in weather-related health studies, such as generalized additive models (GAM) and distributed lag nonlinear models (DLNM). In particular, the residuals are modelled using an autoregressive-moving average (ARMA) model to account for the temporal dependence. The proposed methodology is illustrated by modelling the influence of temperature on cardiovascular mortality in Canada. A comparison with classical DLNMs is provided and several aggregation methods are compared. Results show that there is an increase in the fit quality when the response is aggregated, and that the estimated relationship focuses more on the outcome over several days than the classical DLNM. More precisely, among various investigated aggregation schemes, it was found that an aggregation with an asymmetric Epanechnikov kernel is more suited for studying the temperature-mortality relationship. [ABSTRACT FROM AUTHOR]

In a number of environmental studies, relationships between nat4ural processes are often assessed through regression analyses, using time series data. Such data are often multi-scale and non-stationary, leading to a poor accuracy of the resulting regression models and therefore to results with moderate reliability. To deal with this issue, the present paper introduces the EMD-regression methodology consisting in applying the empirical mode decomposition (EMD) algorithm on data series and then using the resulting components in regression models. The proposed methodology presents a number of advantages. First, it accounts of the issues of non-stationarity associated to the data series. Second, this approach acts as a scan for the relationship between a response variable and the predictors at different time scales, providing new insights about this relationship. To illustrate the proposed methodology it is applied to study the relationship between weather and cardiovascular mortality in Montreal, Canada. The results shed new knowledge concerning the studied relationship. For instance, they show that the humidity can cause excess mortality at the monthly time scale, which is a scale not visible in classical models. A comparison is also conducted with state of the art methods which are the generalized additive models and distributed lag models, both widely used in weather-related health studies. The comparison shows that EMD-regression achieves better prediction performances and provides more details than classical models concerning the relationship. [ABSTRACT FROM AUTHOR]

Regional frequency analysis is an important tool to properly estimate hydrological characteristics at ungauged or partially gauged sites in order to prevent hydrological disasters. The delineation of homogeneous groups of sites is an important first step in order to transfer information and obtain accurate quantile estimates at the target site. The Hosking-Wallis homogeneity test is usually used to test the homogeneity of the selected sites. Despite its usefulness and good power, it presents some drawbacks including the subjective choice of a parametric distribution for the data and a poorly justified rejection threshold. The present paper addresses these drawbacks by integrating nonparametric procedures in the L-moment homogeneity test. To assess the rejection threshold, three resampling methods (permutation, bootstrap and Pólya resampling) are considered. Results indicate that permutation and bootstrap methods perform better than the parametric Hosking-Wallis test in terms of power as well as in time and procedure simplicity. A real-world case study shows that the nonparametric tests agree with the HW test concerning the homogeneity of the volume and the bivariate case while they disagree for the peak case, but that the assumptions of the HW test are not well respected. [ABSTRACT FROM AUTHOR]

Summary Streamflow, as a natural phenomenon, is continuous in time and so are the meteorological variables which influence its variability. In practice, it can be of interest to forecast the whole flow curve instead of points (daily or hourly). To this end, this paper introduces the functional linear models and adapts it to hydrological forecasting. More precisely, functional linear models are regression models based on curves instead of single values. They allow to consider the whole process instead of a limited number of time points or features. We apply these models to analyse the flow volume and the whole streamflow curve during a given period by using precipitations curves. The functional model is shown to lead to encouraging results. The potential of functional linear models to detect special features that would have been hard to see otherwise is pointed out. The functional model is also compared to the artificial neural network approach and the advantages and disadvantages of both models are discussed. Finally, future research directions involving the functional model in hydrology are presented. [ABSTRACT FROM AUTHOR]

The present study aimed at detecting the exogenously applied probiotic Lactobacillus farciminis in rats, after exposure to IBS-like chronic stress, based on 4-day Water Avoidance Stress (WAS). The presence of L. farciminis in both ileal and colonic mucosal tissues was demonstrated by FISH and qPCR, with ileum as the preferential niche, as for the SFB population. A different spatial distribution of the probiotic was observed: in the ileum, bacteria were organized in micro-colonies more or less close to the epithelium whereas, in the colon, they were mainly visualized far away from the epithelium. When rats were submitted to WAS, the L. farciminis population substantially decreased in both intestinal regions, due to a stress-induced increase in colonic motility and defecation, rather than a modification of bacterial binding to the intestinal mucin Muc2. [ABSTRACT FROM AUTHOR]

The importance of accessible, affordable, flexible and high-quality childcare facilities is acknowledged by the European Union (EU) as an essential element to achieving gender equality and full employment for parents. However, legal and policy development in this area has been slow and lacking cohesion. Following the 2008 financial crisis, EU intervention on childcare issues appears to have been dictated by economic priorities and by the rights of the child. The early underpinning of childcare policy with the principle of gender equality is fading fast. This article argues that to date childcare remains dominated by rhetoric: the targets set are far from being achieved, disparities between Member States continue to occur, and women in Europe continue to bear the cost of reproduction disproportionately. In this context, childcare remains gendered, unvalued, unaccounted for and often unpaid. [ABSTRACT FROM AUTHOR]

New Zealand has a low proportion of female board members on large listed private companies and currently has no plans to introduce measures to tackle this problem. By contrast, several European countries including Norway and France have recently introduced legislative corporate quotas aimed at increasing the number of women on the boards of large companies. Similarly, the European Union is introducing a 40 per cent procedural quota, which requires member states to appoint female applicants to supervisory boards providing that they are at least equally qualified as competing male applicants. The rise of such measures has not been restricted to Europe; India and Malaysia have also turned to legislative action. Other countries such as the United Kingdom and Australia have adopted a self-regulatory approach to the issue with mixed results. This article explores why New Zealand has favoured either no action or very 'soft' measures aimed at increasing the number of female board members. It is found that historically there has been significant resistance to the introduction of mandatory measures due to the lack of 'quota culture' in New Zealand policy making. Does New Zealand need to force change to its regulatory framework to effect change in this area? And if so, how?. [ABSTRACT FROM AUTHOR]

Despite well-known intestinal epithelial barrier impairment and visceral hypersensitivity in irritable bowel syndrome (IBS) patients and IBS-like models, structural and physical changes in the mucus layer remain poorly understood. Using a water avoidance stress (WAS) model, we aimed at evaluating whether 1) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans, and related mucus physical properties, and 2) whether Lactobacillus farciminis treatment prevented these alterations. Wistar rats received orally L. farciminis or vehicle for 14 days; at day 10, they were submitted to either sham or 4-day WAS. Intestinal paracellular permeability and visceral sensitivity were measured in vivo. The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ. The mucin O-glycosylation profile was obtained by mass spectrometry. Surface imaging of intestinal mucus was performed at nanoscale by atomic force microscopy. WAS induced gut hyperpermeability and visceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expression. In contrast, O-glycosylation of mucins was strongly affected, with the appearance of elongated polylactosaminic chain containing O-glycan structures, associated with flattening and loss of the mucus layer cohesive properties. L. farciminis bound to intestinal Muc2 and prevented WAS-induced functional alterations and changes in mucin O-glycosylation and mucus physical properties. WAS-induced functional changes were associated with mucus alterations resulting from a shift in O-glycosylation rather than from changes in mucin expression. L. farciminis treatment prevented these alterations, conferring epithelial and mucus barrier strengthening. [ABSTRACT FROM AUTHOR]

Cell growth pathways are mediated through protein–glycan interactions including O-glycosylation. Investigation of these growth pathways can be carried out using appropriate inhibitors to identify stage-specific events. We have adopted this approach to study a group of benzyl-O-N-acetyl-D-galactosamine analogues in human colorectal cancer cell lines. Exposure to O-glycan inhibitors resulted in the induction of apoptosis, a block in proliferation, accumulation of intracellular aryl-glycans and changes in related genes as detected by gene array. Colorectal cancer cell lines susceptible to the inhibitors showed growth arrest with all compounds. However, a differential action of each inhibitor was detected in the pattern of genes affected and in the structure of aryl-glycans formed. [ABSTRACT FROM AUTHOR]

This paper seeks to critically assess the way the EU guarantees the protection of individuals who are discriminated on multiple grounds. As EU law does not recognise that multiple identities can intersect, it is argued that the current anti-discrimination legal framework is not adequate to deal with claims of multiple and intersectional discrimination. Recent legislative developments have, however, raised the issue of multiple discrimination and intersectional disadvantage but they remain guarded and often take a simplistic, rather than an intersectional approach. The EU anti-discrimination legal framework appears to be at a cross-road and choices made by the legislator to promote the concept of multiple discrimination over that of intersectional disadvantage will have profound consequences for the EU anti-discrimination legal framework as a whole and its future developments. [ABSTRACT FROM AUTHOR]

Abstract: The ability of inhibitors of transcription and translation to prevent glucocorticoid-induced apoptosis has been interpreted to indicate that the cell death machinery requires de novo protein synthesis. The transcriptional inhibitors actinomycin D (Act D) and DRB as well as the translational inhibitors CHX and puromycin inhibited early loss of mitochondrial membrane integrity in a dose-dependent manner. This effect was not observed with the transcriptional inhibitor α-amanitin suggesting they may have additional effects. Their role in the glucocorticoid receptor (GR) intracellular trafficking was therefore investigated. Here, we show that Act D and CHX reduced glucocorticoid binding, GR turnover and impaired GR nuclear translocation. We performed the same experiments in different thymocyte subpopulations of Balb/c mice. At the highest dose tested, actinomycin D and cycloheximide abolished glucocorticoid-induced cell death of CD4+CD8+ and CD4+CD8−. In all subsets, Act D, DRB, as well as CHX and puromycin prevented receptor nuclear translocation, indicating a general alteration of GR trafficking. Overall, our data support a direct effect of macromolecular inhibitors on GR activation and trafficking. Finally, direct alterations of the functional properties of the glucocorticoid receptor might be responsible for cell death prevention by actinomycin D, DRB, cycloheximide and puromycin. [Copyright &y& Elsevier]

This article assesses critically the recent law and policy initiatives in European Union gender equality. As a fundamental right, the principle of gender equality is to apply in all areas of EU law. Its scope has been extended to the access to and supply of goods and services and, according to the European Court of Justice, to the Third Pillar. Despite efforts to render the principle visible and accessible, a number of provisions remain unclear and contradictory. The contribution of external actors in this field is set to help safeguarding and enhancing the Community gender equality acquis. [ABSTRACT FROM AUTHOR]

Techniques for analyzing tandem mass spectrometry (MS/MS) data are moving from empirically determined heuristics to standard statistical methods. OLAV, an advanced database search engine, applies statistical models to capture essential structural properties of correct peptide identifications. Moreover, as exemplified by OLAV, it is important to have extended functionalities in MS/MS search engines both to exploit database annotations and to carry out advanced search strategies. [Copyright &y& Elsevier]

Directive 2002/73 enacted by the Council and Parliament of the European Union introduces substantial and procedural amendments to the European Community's `old' Equal Treatment Directive 76/207, providing, in particular, clarification of the definitions of concepts such as direct and indirect discrimination and (sexual) harassment. Yet, while the European Commission has praised the progressive nature of the new European legislation, a critical assessment of its provisions reveals some serious shortcomings and a host of missed opportunities. Although the new Directive generally reflects the spirit of the case law of the E.C.J., it does so without any originality or pro-activism meaning that the European legislature has once again left the initiative of pursuing sex equality in the E.U. to the Court. [ABSTRACT FROM AUTHOR]

X-ray micro-computed tomography was applied to determine the influence of stabilizers on the microstructure of fresh sorbets (i.e. at the outlet of a batch freezer), and more particularly on the air phase and the ice phase. Sucrose sorbets were tested with addition of one stabilizer: locust bean gum (LBG), hydroxypropylmethylcellulose (HPMC) or carboxymethylcellulose (CMC). It was shown that HPMC increased the quantity and decreased the size of air bubbles; it also decreased the ice crystals size unlike other stabilizers which had no effect on the size of ice crystals. Results were successfully compared with data from Cryo-Scanning Electron Microscopy (cryo-SEM) and completed with Focused Beam Reflectance Measurement (FBRM) analyses applied for dynamic studies during freezing process. The effect of HPMC on the ice phase would be linked to its surfactant properties; air bubbles could prevent crystal growth during the freezing process. • The microstructure of stabilized sorbets was studied directly after their freezing. • HPMC increased the quantity and decreased the size of air bubbles and ice crystals. • LBG and CMC did not affect the quantity of air or the size of ice crystals. • Air bubbles incorporated using HPMC would prevent ice crystals from growing. • HPMC, LBG and CMC would prevent ice crystals from agglomerating during freezing. [ABSTRACT FROM AUTHOR]

X-ray micro-computed tomography and image processing techniques were used to analyze fresh frozen sorbets at the outlet of a batch freezer. Sorbets made from water and sucrose were visualized and their microstructure was quantified with a resolution of 9 μm. Sodium iodide was confirmed to enhance the contrast between the unfrozen water and ice in sorbets. A thermostated box was employed to keep the samples at frozen state and constant temperature (close to −6 °C) during imaging. A reproducible quantification of size distributions and volume fractions of ice crystals and air bubbles were obtained. Data concerning ice crystals were in agreement with cryo-SEM imaging. Ice crystals represented approximately 50%wt of the product and their mean size was about 60 μm whereas air bubbles represented about 6% of the volume. Finally, X-ray microtomography equipped with a thermostated box was found to be a particularly relevant technique for the analysis of the microstructure of frozen desserts. • X-ray micro-computed tomography was used to analyze sorbets directly after freezing. • A thermostated box was used to keep the sample at frozen state during imaging. • Qualitative and quantitative analysis of sorbets 3D microstructure was obtained. • Mass fraction of ice was determined from 3D reconstruction. • Quantitative results about ice crystals were confirmed using cryo-SEM analyses. [ABSTRACT FROM AUTHOR]

The article introduces the contents published within the issue, including one by Heli Askola which explores the situation of women with regard to violence, trafficking and migration in the European Union and another by Susan Millins on gender equality and citizenship.

During the freezing of sorbets, the concentration of sucrose and stabilizing macromolecules increases in the unfrozen phase. Rheological properties of this unfrozen phase were studied, depending on nature and concentration of hydrocolloids in sucrose solutions at temperatures below zero. Three stabilizers were tested individually in sucrose-rich solutions: locust bean gum (LBG), hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC). The parameters of the Ostwald-de Waele model were determined and apparent viscosities of solutions were calculated at shear rates encountered during the process. Intrinsic viscosities and critical concentrations of entanglement were determined to evaluate the expansion of polymers in solutions and the transition of concentration regimes according to process conditions. Viscoelastic properties were also tested to study the possible cryogelation. For HPMC and LBG, the shear thinning behavior increased quite linearly with the concentration in stabilizer whereas CMC was highly shear thinning. Increasing sugar did not reveal large effect on these properties. The increase in apparent viscosity of the unfrozen matrix in process conditions was dependent on stabilizers; solutions containing LBG were less viscous than the others. Intrinsic viscosities revealed that HPMC and LBG became progressively less expanded as the concentration of sucrose increased whereas CMC tended to aggregate. Measurements of viscoelastic properties evidenced a dominant viscous behavior for HPMC and LBG systems whereas CMC systems showed dominant elastic behavior at frequencies higher than 0.1 Hz. The next challenge will be to better understand the potential link between the particular rheological behavior of hydrocolloids in process conditions and their possible influence on crystallization mechanisms. Image 1 • Stabilizers influence rheological properties of the unfrozen phase of a sorbet. • During freezing, the unfrozen phase becomes increasingly viscous and shear-thinning. • During the process and according to the stabilizer, polymers are more or less expanded. • At low temperature, sucrose solutions with stabilizers are macromolecular solutions. • HPMC and LBG show dominant viscous behavior and CMC has dominant elastic behavior. [ABSTRACT FROM AUTHOR]

Epidemiological analyses of health risks associated with non-optimal temperature are traditionally based on ground observations from weather stations that offer limited spatial and temporal coverage. Climate reanalysis represents an alternative option that provide complete spatio-temporal exposure coverage, and yet are to be systematically explored for their suitability in assessing temperature-related health risks at a global scale. Here we provide the first comprehensive analysis over multiple regions to assess the suitability of the most recent generation of reanalysis datasets for health impact assessments and evaluate their comparative performance against traditional station-based data. Our findings show that reanalysis temperature from the last ERA5 products generally compare well to station observations, with similar non-optimal temperature-related risk estimates. However, the analysis offers some indication of lower performance in tropical regions, with a likely underestimation of heat-related excess mortality. Reanalysis data represent a valid alternative source of exposure variables in epidemiological analyses of temperature-related risk. [ABSTRACT FROM AUTHOR]

Regional Frequency Analysis (RFA) relies on a wide range of physiographical and meteorological variables to estimate hydrological quantiles at ungauged sites. However, additional catchment characteristics related to its drainage network are not yet fully understood and integrated in RFA procedures. The aim of the present paper is to propose the integration of several physiographical variables characterizing the drainage network systems in RFA, and to evaluate their added value in predicting quantiles at ungauged sites. The proposed extended dataset (EXTD) includes several variables characterising drainage network characteristics. To evaluate the new variables, a number of commonly used RFA approaches are applied to the extended data representing 151 stations in Quebec (Canada) and compared to a standard dataset (STA) that excludes the new variables. The considered RFA approaches include the combination of two neighborhood methods namely the canonical correlation analysis (CCA) and the region of influence (ROI) with two regional estimation (RE) models which are the log-linear regression model (LLRM) and the generalized additive model (GAM). The RE models are also applied without the hydrological neighborhood. Results show that regional models using the extended dataset lead to significantly better flood quantile predictions, especially for large basins. Indeed, the variable selection performed with EXTD consistently includes some of the new variables, in particular the drainage density, the stream length ratio, and the ruggedness number. Two other new variables are also identified and included in the DHR step: the circularity ratio and the texture ratio. This leads to better predictions with relative errors about 29% for EXTD, versus around 42% for STA in the case of the best combination of RFA approaches. Thus, the proposed new variables allow for a better representation of the physical dynamics within the watersheds. [ABSTRACT FROM AUTHOR]

Background: Many countries have developed heat-health watch and warning systems (HHWWS) or early-warning systems to mitigate the health consequences of extreme heat events. HHWWS usually focuses on the four hottest months of the year and imposes the same threshold over these months. However, according to climate projections, the warm season is expected to extend and/or shift. Some studies demonstrated that health impacts of heat waves are more severe when the human body is not acclimatized to the heat. In order to adapt those systems to potential heat waves occurring outside the hottest months of the season, this study proposes specific health-based monthly heat indicators and thresholds over an extended season from April to October in the northern hemisphere.Methods: The proposed approach, an adoption and extension of the HHWWS methodology currently implemented in Quebec (Canada). The latter is developed and applied to the Greater Montreal area (current population 4.3 million) based on historical health and meteorological data over the years. This approach consists of determining excess mortality episodes and then choosing monthly indicators and thresholds that may involve excess mortality.Results: We obtain thresholds for the maximum and minimum temperature couple (in °C) that range from (respectively, 23 and 12) in April, to (32 and 21) in July and back to (25 and 13) in October. The resulting HHWWS is flexible, with health-related thresholds taking into account the seasonality and the monthly variability of temperatures over an extended summer season.Conclusions: This adaptive and more realistic system has the potential to prevent, by data-driven health alerts, heat-related mortality outside the typical July-August months of heat waves. The proposed methodology is general and can be applied to other regions and situations based on their characteristics. [ABSTRACT FROM AUTHOR]

A major challenge of climate change adaptation is to assess the effect of changing weather on human health. In spite of an increasing literature on the weather-related health subject, many aspect of the relationship are not known, limiting the predictive power of epidemiologic models. The present paper proposes new models to improve the performances of the currently used ones. The proposed models are based on functional data analysis (FDA), a statistical framework dealing with continuous curves instead of scalar time series. The models are applied to the temperature-related cardiovascular mortality issue in Montreal. By making use of the whole information available, the proposed models improve the prediction of cardiovascular mortality according to temperature. In addition, results shed new lights on the relationship by quantifying physiological adaptation effects. These results, not found with classical model, illustrate the potential of FDA approaches. [ABSTRACT FROM AUTHOR]

Summary: pViz.js is a visualization library for displaying protein sequence features in a Web browser. By simply providing a sequence and the locations of its features, this lightweight, yet versatile, JavaScript library renders an interactive view of the protein features. Interactive exploration of protein sequence features over the Web is a common need in Bioinformatics. Although many Web sites have developed viewers to display these features, their implementations are usually focused on data from a specific source or use case. Some of these viewers can be adapted to fit other use cases but are not designed to be reusable. pViz makes it easy to display features as boxes aligned to a protein sequence with zooming functionality but also includes predefined renderings for secondary structure and post-translational modifications. The library is designed to further customize this view. We demonstrate such applications of pViz using two examples: a proteomic data visualization tool with an embedded viewer for displaying features on protein structure, and a tool to visualize the results of the variant_effect_predictor tool from Ensembl.Availability and implementation: pViz.js is a JavaScript library, available on github at https://github.com/Genentech/pviz. This site includes examples and functional applications, installation instructions and usage documentation. A Readme file, which explains how to use pViz with examples, is available as Supplementary Material A.Contact: masselot.alexandre@gene.comSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG's capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways. [ABSTRACT FROM AUTHOR]

In the mid-1990s, a team of math education researchers at the Université du Québec à Montréal (UQAM) developed a role-playing approach for use in the initial training of primary teachers. Since its introduction, this approach has been the topic of several articles, thus allowing its potential to be analyzed from various angles. We "exported" this role-playing technique to the initial math training of school teachers in France, believing that the approach could benefit the practices of these future teachers. The approach provides an opportunity for the trainers first to observe the emerging practices being used by the trainees and then to intervene in the trainees' zone of proximal development with regard to these practices. For our study, we created a role-play-based training scenario in which future teachers must help a student having difficulties with a task related to decimal numbers. In this article, we document the knowledge and practices demonstrated by the future teachers under these circumstances as well as the possibilities for trainers to use these results to help advance the trainees' development. [ABSTRACT FROM AUTHOR]

The article focuses on the mechanism-driven entry to heterocyclic tetraphenylenes. The authors aimed at intercepting palladacycles and offers and unusual synthetic entry to novel polyarene variants. They initially focused on the 4-nitrophenyl derivative given that this substrate has shown the highest propensity to undergo carbon to hydrogen insertion.

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG's capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways. [ABSTRACT FROM AUTHOR]

This article applies Walby's Gender Regime Theory to examine the EU's role as a gender actor in the context of crisis. We build on Walby's analysis of the EU as a public gender regime to understand continuity and change as the European Commission sought to lead the EU and its Member States through one of the most existential crises faced by the organisation: the Covid-19 pandemic. Gender Regime Theory provides a useful way to think about the impact of multiple and overlapping crises on the European gender acquis and the way it contributes to the development of a European gender regime. In order to understand the way the EU gender regime has evolved, and is continuing to evolve, we bring together two distinct bodies of literature, GRT and Feminist EU Studies in order to understand the interaction between national and EU gender regimes and the ways in which these are intertwined in the EU's Covid recovery plan. [ABSTRACT FROM AUTHOR]

High ambient temperatures are associated with many health effects, including premature mortality. The combination of global warming due to climate change and the expansion of the global built environment mean that the intensification of urban heat islands (UHIs) is expected, accompanied by adverse effects on population health. Urban green infrastructure can reduce local temperatures. We aimed to estimate the mortality burden that could be attributed to UHIs and the mortality burden that would be prevented by increasing urban tree coverage in 93 European cities. We did a quantitative health impact assessment for summer (June 1–Aug 31), 2015, of the effect of UHIs on all-cause mortality for adults aged 20 years or older in 93 European cities. We also estimated the temperature reductions that would result from increasing tree coverage to 30% for each city and estimated the number of deaths that could be potentially prevented as a result. We did all analyses at a high-resolution grid-cell level (250 × 250 m). We propagated uncertainties in input analyses by using Monte Carlo simulations to obtain point estimates and 95% CIs. We also did sensitivity analyses to test the robustness of our estimates. The population-weighted mean city temperature increase due to UHI effects was 1·5°C (SD 0·5; range 0·5–3·0). Overall, 6700 (95% CI 5254–8162) premature deaths could be attributable to the effects of UHIs (corresponding to around 4·33% [95% CI 3·37–5·28] of all summer deaths). We estimated that increasing tree coverage to 30% would cool cities by a mean of 0·4°C (SD 0·2; range 0·0–1·3). We also estimated that 2644 (95% CI 2444–2824) premature deaths could be prevented by increasing city tree coverage to 30%, corresponding to 1·84% (1·69–1·97) of all summer deaths. Our results showed the deleterious effects of UHIs on mortality and highlighted the health benefits of increasing tree coverage to cool urban environments, which would also result in more sustainable and climate-resilient cities. GoGreenRoutes, Spanish Ministry of Science and Innovation, Institute for Global Health, UK Medical Research Council, European Union's Horizon 2020 Project Exhaustion. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine workers’ psychological distress during the COVID19 pandemic as a function of their individual coping, dyadic coping, and work-family conflict. We also tested the moderating role of gender and culture in these associations. To achieve this aim, we run HLM analyses on data from 1521 workers cohabiting with a partner, coming from six countries (Italy, Spain, Malta, Cyprus, Greece, and Russia) characterized by various degrees of country-level individualism/collectivism. Across all six countries, findings highlighted that work-family conflict as well as the individual coping strategy social support seeking were associated with higher psychological distress for workers, while the individual coping strategy positive attitude and common dyadic coping were found to be protective against workers’ psychological distress. This latter association, moreover, was stronger in more individualistic countries. [ABSTRACT FROM AUTHOR]

Androgen-metabolizing enzymes convert cholesterol, a relatively inert molecule, into some of the most potent chemical messengers in vertebrates. This conversion involves thermodynamically challenging reactions catalyzed by P450 enzymes and redox reactions catalyzed by Aldo-Keto Reductases (AKRs). This review covers the structures of these enzymes with a focus on active site interactions and proposed mechanisms. Due to their role in a number of diseases, particularly in cancer, androgen-metabolizing enzymes have been targets of drug design. Hence we will also highlight how existing knowledge of structure is being used to this end. [ABSTRACT FROM AUTHOR]

As the world becomes increasingly urbanised, there is recognition that public and planetary health relies upon a ubiquitous transition to sustainable cities. Disentanglement of the complex pathways of urban design, environmental exposures, and health, and the magnitude of these associations, remains a challenge. A state-of-the-art account of large-scale urban health studies is required to shape future research priorities and equity- and evidence-informed policies. The purpose of this review was to synthesise evidence from large-scale urban studies focused on the interaction between urban form, transport, environmental exposures, and health. This review sought to determine common methodologies applied, limitations, and future opportunities for improved research practice. Based on a literature search, 2958 articles were reviewed that covered three themes of: urban form; urban environmental health; and urban indicators. Studies were prioritised for inclusion that analysed at least 90 cities to ensure broad geographic representation and generalisability. Of the initially identified studies, following expert consultation and exclusion criteria, 66 were included. The complexity of the urban ecosystem on health was evidenced from the context dependent effects of urban form variables on environmental exposures and health. Compact city designs were generally advantageous for reducing harmful environmental exposure and promoting health, with some exceptions. Methodological heterogeneity was indicative of key urban research challenges; notable limitations included exposure and health data at varied spatial scales and resolutions, limited availability of local-level sociodemographic data, and the lack of consensus on robust methodologies that encompass best research practice. Future urban environmental health research for evidence-informed urban planning and policies requires a multi-faceted approach. Advances in geospatial and AI-driven techniques and urban indicators offer promising developments; however, there remains a wider call for increased data availability at local-levels, transparent and robust methodologies of large-scale urban studies, and greater exploration of urban health vulnerabilities and inequities. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-09049-4, published online 25 March 2022 The original version of this Article contained an error in Affiliation 25, which was incorrectly given as 'Faculty of Medicine ArqFuturo INSPER, University of São Paulo, São Paulo, Brazil'. Faculty of Medicine, University of São Paulo, São Paulo, Brazil The original Article has been corrected. [Extracted from the article]

The bovine gastrointestinal ( GI) tract is the main reservoir for enterohaemorrhagic Escherichia coli ( EHEC) responsible for food-borne infections. Characterization of nutrients preferentially used by EHEC in the bovine intestine would help to develop ecological strategies to reduce EHEC carriage. However, the carbon sources that support the growth of EHEC in the bovine intestine are poorly documented. In this study, a very low concentration of glucose, the most abundant monomer included in the cattle dietary polysaccharides, was detected in bovine small intestine contents ( BSIC) collected from healthy cows at the slaughterhouse. Six carbohydrates reported to be included in the mucus layer covering the enterocytes [galactose, N-acetyl-glucosamine ( GlcNAc), N-acetyl- galactosamine ( GalNAc), fucose, mannose and N-acetyl neuraminic acid ( Neu5Ac)] have been quantified for the first time in BSIC and accounted for a total concentration of 4.2 mM carbohydrates. The genes required for enzymatic degradation of the six mucus-derived carbohydrates are highly expressed during the exponential growth of the EHEC strain O157: H7 EDL933 in BSIC and are more strongly induced in EHEC than in bovine commensal E. coli. In addition, EDL933 consumed the free monosaccharides present in the BSIC more rapidly than the resident microbiota and commensal E. coli, indicating a competitive ability of EHEC to catabolize mucus-derived carbohydrates in the bovine gut. Mutations of EDL933 genes required for the catabolism of each of these sugars have been constructed, and growth competitions of the mutants with the wild-type strain clearly demonstrated that mannose, GlcNAc, Neu5Ac and galactose catabolism confers a high competitive growth advantage to EHEC in BSIC and probably represents an ecological niche for EHEC strains in the bovine small intestine. The utilization of these mucus-derived monosaccharides by EDL933 is apparently required for rapid growth of EHEC in BSIC, and for maintaining a competitive growth rate as compared with that of commensal E. coli. The results suggest a strategy for O157: H7 E. coli survival in the bovine intestine, whereby EHEC rapidly consumes mucus-derived carbohydrates that are poorly consumed by bacteria belonging to the resident intestinal microbiota, including commensal E. coli. [ABSTRACT FROM AUTHOR]

Osmoregulated periplasmic glucans (OPGs) are oligosaccharides found in the periplasm of many Gram-negative bacteria. Glucose is the sole constitutive sugar and this backbone may be substituted by various kinds of molecules depending on the species. In E. coli, OPG are substituted by phosphoglycerol and phosphoethanolamine derived from membrane phospholipids and by succinyl residues. In this study, we describe the isolation of the opgE gene encoding the phosphoethanolamine transferase by a screen previously used for the isolation of the opgB gene encoding the phosphoglycerol transferase. Both genes show structural and functional similarities without sequence similarity. [ABSTRACT FROM AUTHOR]

We discuss the cellular automata approach and its extensions, the lattice Boltzmann and multiparticle methods. The potential of these techniques is demonstrated in the case of modeling complex systems. In particular, we consider applications taken from various fields of physics, such as reaction-diffusion systems, pattern formation phenomena, fluid flows, fracture processes and road traffic models. [ABSTRACT FROM AUTHOR]

Arenicola marina possesses cuticular and interstitial collagens, which are mostly synthesised by its epidermis. A cDNA library was constructed from the body wall. This annelid cDNA library was screened with a sea-urchin-collagen cDNA probe, and several overlapping clones were isolated. Nucleotide sequencing of these clones revealed an open reading frame of 2052 nucleotides. The translation product exhibits a triple helical domain of 138 Gly-Xaa-Yaa repeats followed by a 269-residue-long C-terminal non-collagenous domain (C-propeptide). The triple helical domain exhibits an imperfection that has been previously described in a peptide produced by cyanogen bromide digestion (CNBr peptide) of A. marina interstitial collagen. This imperfection occurs at the same place in the interstitial collagen of the vestimentiferan Riftia pachyptila. This identifies the clone as coding for the C-terminal part of a fibrillar collagen chain. It was called FAm1α, for fibrillar collagen 1α chain of A. marina. The non-collagenous domain possesses a structure similar to carboxy-terminal propeptides of fibrillar pro-α chains. Only six conserved cysteine residues are observed in A. marina compared with seven or eight in all other known C-propeptides. This provides information on the importance of disulfide bonds in C-propeptide interactions and in the collagen-assembly process. Phylogenetic studies indicate that the fibrillar collagen 1α chain of A. marina is homologous to the R. pachyptila interstitial collagen and that the FAm1α gene evolved independently from the other α-chain genes. Complementary analyses indicate that the vertebrate fibrillar collagen family is composed of two monophyletic subgroups with a specific position of the collagen type-V chains. [ABSTRACT FROM AUTHOR]

A number of studies have shown that cold has an important impact on human health. However, almost no studies focused on cold warning systems to prevent those health effects. For Nordic regions, like the province of Quebec in Canada, winter is long and usually very cold with an observed increase in mortality and hospitalizations throughout the season. However, there is no existing system specifically designed to follow in real-time this mortality increase throughout the season and to alert public health authorities prior to cold waves. The aim is to establish a watch and warning system specifically for health impacts of cold, applied to different climatic regions of the province of Quebec. A methodology previously used to establish the health-heat warning system in Quebec is adapted to cold. The approach identifies cold weather indicators and establishes thresholds related to extreme over-mortality or over-hospitalization events in the province of Quebec, Canada. The final health-related thresholds proposed are between (−15 °C, −23 °C) and (−20 °C, −29 °C) according to the climatic region for excesses of mortality, and between (−13 °C, −23 °C) and (−17 °C, −30 °C) for excesses of hospitalization. These results suggest that the system model has a high sensitivity and an acceptable number of false alarms. This could lead to the establishment of a cold-health watch and warning system with valid indicators and thresholds for each climatic region of Quebec. It can be seen as a complementary system to the existing one for heat warnings, in order to help the public health authorities to be well prepared during an extreme cold event. Unlabelled Image • This is the first developed health alert system dedicated to cold. • A number of new aspects are employed in the methodology. • The developed method is general and can be applied elsewhere. [ABSTRACT FROM AUTHOR]

• CFTR-deficient pigs present increased lung mucin sialylation at birth in the absence of inflammation. • Increased mucin sialylation is linked to increased pseudomonas aeruginosa adhesion to mucins. • CF pigs also present a mucociliary clearance defect, in the absence of inflammation, which may contribute bacterial colonization and development of early lung disease. These defects seems to be linked to the absence of CFTR functionality since they are independent of an inflammatory environment in the lungs. Bacterial colonization in cystic fibrosis (CF) lungs has been directly associated to the loss of CFTR function, and/or secondarily linked to repetitive cycles of chronic inflammation/infection. We hypothesized that altered molecular properties of mucins could contribute to this process. Newborn CFTR+/+ and CFTR−/− were sacrificed before and 6 h after inoculation with luminescent Pseudomonas aeruginosa into the tracheal carina. Tracheal mucosa and the bronchoalveolar lavage (BAL) fluid were collected to determine the level of mucin O-glycosylation, bacteria binding to mucins and the airways transcriptome. Disturbances in mucociliary transport were determined by ex-vivo imaging of luminescent Pseudomonas aeruginosa. We provide evidence of an increased sialylation of CF airway mucins and impaired mucociliary transport that occur before the onset of inflammation. Hypersialylation of mucins was reproduced on tracheal explants from non CF animals treated with GlyH101, an inhibitor of CFTR channel activity, indicating a causal relationship between the absence of CFTR expression and the sialylation of mucins. This increased sialylation was correlated to an increased adherence of P. aeruginosa to mucins. In vivo infection of newborn CF piglets by live luminescent P. aeruginosa demonstrated an impairment of mucociliary transport of this bacterium, with no evidence of pre-existing inflammation. Our results document for the first time in a well-defined CF animal model modifications that affect the O-glycan chains of mucins. These alterations precede infection and inflammation of airway tissues, and provide a favorable context for microbial development in CF lung that hallmarks this disease. [ABSTRACT FROM AUTHOR]