Analyzing the Data-Rich-But-Information-Poor Syndrome in Dutch Water Management in Historical Perspective

Water quality monitoring has developed over the past century from an unplanned, isolated activity into an important discipline in water management. This development also brought about a discontent between information users and information producers about the usefulness and usability of information, in literature often referred to as the data-rich-but-information-poor syndrome. This article aims to gain a better understanding of this issue by studying the developments over some five decades of Dutch national water quality monitoring, by analyzing four studies in which the role and use of information are discussed from different perspectives, and by relating this to what is considered in literature as useful information. The article concludes that a “water information gap” exists which is rooted in different mutual perceptions and expectations between the two groups on what useful information is, that can be overcome by improving the communication. Such communication should be based on willingness to understand and deal with different mindframes and should be based on a methodology that guides and structures the interactions

Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.

Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage (ΦSaeq1) found in six different clonal lineages, almost exclusively in strains cultured from equids. We show that LukPQ is a potent and specific killer of equine neutrophils and identify equine-CXCRA and CXCR2 as its target receptors. Although the S-component (LukP) is highly similar to the S-component of LukED, the species specificity of LukPQ and LukED differs. By forming non-canonical toxin pairs, we identify that the F-component contributes to the observed host tropism of LukPQ, thereby challenging the current paradigm that leukocidin specificity is driven solely by the S-component

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Psychometric properties of the Children's Time Awareness Questionnaire (CTAQ): A study on the validity of a Dutch 20-item questionnaire measuring time awareness in children

This study investigates the validity of Children's Time Awareness Questionnaire (CTAQ), a 20-item task for assessing children's time awareness. The CTAQ was administered to a group of typically developing children ( n  = 107) and children with any developmental problems reported by parents (non-typically developing children, n  = 28), aged 4-8 years old. We found some support for a one-factor structure (EFA), yet the explained variance is relatively low (21%). Our proposed structure of two additional subscales, i.e., "time words" and "time estimation," was not supported by (confirmatory and exploratory) factor analyses. In contrast, exploratory factor analyses (EFA) indicated a six-factor structure, which needs further investigation. We found low, yet non-significant correlations between CTAQ scales and caregiver reports on children's time awareness, planning and impulsivity, and no significant correlations between CTAQ scales and scores on cognitive performance tasks. As expected, we found that older children have higher CTAQ scores than younger children. Non typically developing children had lower scores on CTAQ scales, compared to typically developing children. The CTAQ has sufficient internal consistency. The CTAQ has potential to measure time awareness, future research is indicated to further develop the CTAQ and enhance clinical applicability

Nitric oxide synthase inhibition by dimaprit and dimaprit analogues.

1. The similarity in molecular structure between the histamine H(2)-agonist dimaprit (3-dimethylamino-propyl-isothiourea) and the endogenous nitric oxide synthase (NOS) substrate L-arginine prompted us to study the effect of dimaprit and some dimaprit analogues on NOS activity. Dimaprit and some of its analogues were tested in an in vitro assay which measures the conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline. Dimaprit inhibits rat brain NOS (nNOS) concentration dependently with an IC(50) of 49±14 μM. 2. Removal of one or both of the methyl groups from the non-isothiourea nitrogen of dimaprit improved nNOS inhibitory properties. Aminopropylisothiourea is the most potent compound (IC(50)=4.1±0.9 μM) of the series followed by methylaminopropylisothiourea (IC(50)=7.6± μM). 3. The observed effect of aminopropylisothiourea and methylaminopropyl-isothiourea are probably not due to the compounds themselves but to the corresponding mercaptoalkylguanidines, rearrangement products formed in aqueous solutions. This hypothesis is strengthened by the finding that aminobutylisothiourea is not active since a rearrangement to mercaptobutylguanidine does not occur. 4. Remarkably, nitrosylation of the isothiourea group of dimaprit decreases nNOS inhibitory activity, while nitrosylation of the guanidine analogue of dimaprit increases the inhibition of nNOS activity. 5. The pharmacological profile of dimaprit includes inhibition of nNOS. The nNOS inhibitory activity occurs in the same concentration range as the H(2)-agonist and H(3)-agonist activity of this compound

Astrocyte lipid metabolism is critical for synapse development and function in vivo

The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682

The Information Strategy Model: a framework for developing a monitoring strategy for national policy making and SDG6 reporting

Representatives from 14 countries worldwide worked together on improving their monitoring and ultimately their water management to reach the Sustainable Development Goal (SDG) 6 goals by 2030, thereby testing the Information Strategy Model (ISM). This model is developed to support identifying the need for information for water management. In a workshop setting, participants were instructed and subsequently developed the ISM for their own situation. The results show that the ISM fulfils its task of structuring the development and improvement of a monitoring network, but can be enhanced by adding detailed information for specific elements and needs explanation and assistance to be of use.Water Resource