Moving forward to achieve the ambitions of the European Water Framework Directive: Lessons learned from the Netherlands

The restoration and preservation of freshwater ecosystems is one of the prerequisites for a sustainable and fair future for all and therefore part of the United Nations Sustainable Development Goals (SDG 6). However, countries worldwide are facing a challenge to achieve this ambition by 2030. This paper focuses on the legal and governance challenges faced in the European context with regard to achieving water quality ambitions, using experiences from the Netherlands as a case study. Although many EU Member States (MS) are facing a challenge to meet the ambitions set by the Water Framework Directive (WFD) in 2027, literature on effectiveness of governance approaches in terms of actual water quality improvement, seems to be scarce. Based on interviews, a survey, expert panel discussions and literature we show that in the Netherlands, an important problem is that stakeholders, also within organisations, have different views on ambitions, achievements and necessary follow-up actions. This is problematic because for realising the water quality ambitions, cross-sectoral cooperation (e.g. from agriculture and spatial development) as well as strengthened interlinkages between these related policy fields is crucial. Moreover, there is a tendency to stick to the status quo. In order to increase effectiveness, a better understanding of the underlying mechanisms for this lock-in will be necessary. This will enable the development of practical tools and instruments to support cross-sectoral and multi-level collaboration. The sectoral implementation of the WFD in the Netherlands was chosen by many other MS, resulting in similar cross-sectoral challenges as we found in the Netherlands. Insight into how other MS deal with lock-in situations is needed to develop pathways to achieving WFD ambitions

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins

The cell envelope of mycobacteria, a group of Gram positive bacteria, is composed of a plasma membrane and a Gram-negative-like outer membrane containing mycolic acids. In addition, the surface of the mycobacteria is coated with an ill-characterized layer of extractable, non-covalently linked glycans, lipids and proteins, collectively known as the capsule, whose occurrence is a matter of debate. By using plunge freezing cryo-electron microscopy technique, we were able to show that pathogenic mycobacteria produce a thick capsule, only present when the cells were grown under unperturbed conditions and easily removed by mild detergents. This detergent-labile capsule layer contains arabinomannan, α-glucan and oligomannosyl-capped glycolipids. Further immunogenic and proteomic analyses revealed that Mycobacterium marinum capsule contains high amounts of proteins that are secreted via the ESX-1 pathway. Finally, cell infection experiments demonstrated the importance of the capsule for binding to cells and dampening of pro-inflammatory cytokine response. Together, these results show a direct visualization of the mycobacterial capsular layer as a labile structure that contains ESX-1-secreted proteins

Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts

Learning from failure at the science–policy interface for climate action in agriculture

Science–policy engagement efforts to accelerate climate action in agricultural systems are key to enable the sector to contribute to climate and food security goals. However, lessons to improve science–policy engagement efforts in this context mostly come from successful efforts and are limited in terms of empirical scope. Moreover, lessons have not been generated systematically from failed science–policy engagement efforts. Such analysis using lessons from failure management can improve or even transform the efficacy of efforts. To address this knowledge gap, we examined challenges and failures faced in science–policy engagement efforts of the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS). We developed an explanatory framework inspired by Cash et al.’s criteria for successful knowledge systems for sustainable development: credibility, salience, and legitimacy, complemented with insights from the wider literature. Using this framework in a survey, we identified factors which explain failure. To effectively manage these factors, we propose a novel approach for researchers working at the science–policy interface to fail intelligently, which involves planning for failure, minimizing risks, effective design, making failures visible, and learning from failures. This approach needs to be complemented by actions at the knowledge system level to create an enabling environment for science–policy interfaces

Moving forward to achieve the ambitions of the European Water Framework Directive: Lessons learned from the Netherlands

The restoration and preservation of freshwater ecosystems is one of the prerequisites for a sustainable and fair future for all and therefore part of the United Nations Sustainable Development Goals (SDG 6). However, countries worldwide are facing a challenge to achieve this ambition by 2030. This paper focuses on the legal and governance challenges faced in the European context with regard to achieving water quality ambitions, using experiences from the Netherlands as a case study. Although many EU Member States (MS) are facing a challenge to meet the ambitions set by the Water Framework Directive (WFD) in 2027, literature on effectiveness of governance approaches in terms of actual water quality improvement, seems to be scarce. Based on interviews, a survey, expert panel discussions and literature we show that in the Netherlands, an important problem is that stakeholders, also within organisations, have different views on ambitions, achievements and necessary follow-up actions. This is problematic because for realising the water quality ambitions, cross-sectoral cooperation (e.g. from agriculture and spatial development) as well as strengthened interlinkages between these related policy fields is crucial. Moreover, there is a tendency to stick to the status quo. In order to increase effectiveness, a better understanding of the underlying mechanisms for this lock-in will be necessary. This will enable the development of practical tools and instruments to support cross-sectoral and multi-level collaboration. The sectoral implementation of the WFD in the Netherlands was chosen by many other MS, resulting in similar cross-sectoral challenges as we found in the Netherlands. Insight into how other MS deal with lock-in situations is needed to develop pathways to achieving WFD ambitions

Modulation of Lactobacillus plantarum Gastrointestinal Robustness by Fermentation Conditions Enables Identification of Bacterial Robustness Markers.

Contains fulltext : 108700.pdf (publisher's version ) (Open Access)BACKGROUND: Lactic acid bacteria (LAB) are applied worldwide in the production of a variety of fermented food products. Additionally, specific Lactobacillus species are nowadays recognized for their health-promoting effects on the consumer. To optimally exert such beneficial effects, it is considered of great importance that these probiotic bacteria reach their target sites in the gut alive. METHODOLOGY/PRINCIPAL FINDINGS: In the accompanying manuscript by Bron et al. the probiotic model organism Lactobacillus plantarum WCFS1 was cultured under different fermentation conditions, which was complemented by the determination of the corresponding molecular responses by full-genome transcriptome analyses. Here, the gastrointestinal (GI) survival of the cultures produced was assessed in an in vitro assay. Variations in fermentation conditions led to dramatic differences in GI-tract survival (up to 7-log) and high robustness could be associated with low salt and low pH during the fermentations. Moreover, random forest correlation analyses allowed the identification of specific transcripts associated with robustness. Subsequently, the corresponding genes were targeted by genetic engineering, aiming to enhance robustness, which could be achieved for 3 of the genes that negatively correlated with robustness and where deletion derivatives displayed enhanced survival compared to the parental strain. Specifically, a role in GI-tract survival could be confirmed for the lp_1669-encoded AraC-family transcription regulator, involved in capsular polysaccharide remodeling, the penicillin-binding protein Pbp2A involved in peptidoglycan biosynthesis, and the Na(+)/H(+) antiporter NapA3. Moreover, additional physiological analysis established a role for Pbp2A and NapA3 in bile salt and salt tolerance, respectively. CONCLUSION: Transcriptome trait matching enabled the identification of biomarkers for bacterial (gut-)robustness, which is important for our molecular understanding of GI-tract survival and could facilitate the design of culture conditions aimed to enhance probiotic culture robustness