| 1. |
- Brinkman, Paul, et al.
(author)
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Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:5, s. 1811-1820.e7
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Journal article (peer-reviewed)abstract
- Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.
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| 3. |
- Dorlo, Thomas P C, et al.
(author)
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Characterization and identification of suspected counterfeit miltefosine capsules.
- 2012
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In: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 137:5, s. 1265-74
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Journal article (peer-reviewed)abstract
- Recently, it was revealed that generic miltefosine capsules for the treatment of visceral leishmaniasis, a fatal parasitic disease, were possibly counterfeit products. Here we report on the methods to characterize and identify miltefosine in pharmaceutical products and the procedures that were used to assess the quality of these suspected counterfeit products. Characterization and identification of miltefosine were done with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), Fourier transform infrared (FT-IR) spectroscopy and near-infrared (NIR) spectroscopy. Moreover, a simple, rapid and inexpensive colorimetric test was developed and evaluated for the detection of miltefosine in pharmaceutical products that can be used in the field. The complementary analytical techniques presented here were able to determine qualitatively or (semi-)quantitatively the presence or absence of miltefosine in pharmaceutical preparations and could identify suspected counterfeit miltefosine capsules. This finding of a suspected counterfeit drug intended to treat a neglected disease in a resource-poor country emphasizes the urgent need to develop more simple inexpensive assays to evaluate drug quality for use in the field.
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| 4. |
- Dorlo, Thomas P C, et al.
(author)
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Development and validation of a quantitative assay for the measurement of miltefosine in human plasma by liquid chromatography-tandem mass spectrometry.
- 2008
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In: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 865:1-2, s. 55-62
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Journal article (peer-reviewed)abstract
- A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of miltefosine is presented. A 250 microL human EDTA plasma aliquot was spiked with miltefosine and extracted by a solid-phase extraction method. Separation was performed on a Gemini C18 column (150 mm x 2.0 mm I.D., 5 microm) using an alkaline eluent. Detection was performed by positive ion electrospray ionization followed by triple-quadrupole mass spectrometry. The assay has been validated for miltefosine from 4 to 2000 ng/mL using 250 microL human EDTA plasma samples. Results from the validation demonstrate that miltefosine can be accurately and precisely quantified in human plasma. At the lowest level, the intra-assay precision was lower than 10.7%, the inter-assay precision was 10.6% and accuracies were between 95.1 and 109%. This assay is successfully used in a clinical pharmacokinetic study with miltefosine.
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| 5. |
- Jacobs, Rianne, et al.
(author)
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Identifying the source of food-borne disease outbreaks : An application of Bayesian variable selection
- 2019
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In: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 28:4, s. 1126-1140
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Journal article (peer-reviewed)abstract
- Early identification of contaminated food products is crucial in reducing health burdens of food-borne disease outbreaks. Analytic case-control studies are primarily used in this identification stage by comparing exposures in cases and controls using logistic regression. Standard epidemiological analysis practice is not formally defined and the combination of currently applied methods is subject to issues such as response misclassification, missing values, multiple testing problems and small sample estimation problems resulting in biased and possibly misleading results. In this paper, we develop a formal Bayesian variable selection method to account for misclassified responses and missing covariates, which are common complications in food-borne outbreak investigations. We illustrate the implementation and performance of our method on a Salmonella Thompson outbreak in the Netherlands in 2012. Our method is shown to perform better than the standard logistic regression approach with respect to earlier identification of contaminated food products. It also allows relatively easy implementation of otherwise complex methodological issues.
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| 6. |
- Rosenbaum, Ralph K., et al.
(author)
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The Glasgow consensus on the delineation between pesticide emission inventory and impact assessment for LCA
- 2015
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In: The International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 20:6, s. 765-776
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Journal article (peer-reviewed)abstract
- Purpose: Pesticides are applied to agricultural fields to optimise crop yield and their global use is substantial. Their consideration in life cycle assessment (LCA) is affected by important inconsistencies between the emission inventory and impact assessment phases of LCA. A clear definition of the delineation between the product system model (life cycle inventory—LCI, technosphere) and the natural environment (life cycle impact assessment—LCIA, ecosphere) is missing and could be established via consensus building.Methods: A workshop held in 2013 in Glasgow, UK, had the goal of establishing consensus and creating clear guidelines in the following topics: (1) boundary between emission inventory and impact characterisation model, (2) spatial dimensions and the time periods assumed for the application of substances to open agricultural fields or in greenhouses and (3) emissions to the natural environment and their potential impacts. More than 30 specialists in agrifood LCI, LCIA, risk assessment and ecotoxicology, representing industry, government and academia from 15 countries and four continents, met to discuss and reach consensus. The resulting guidelines target LCA practitioners, data (base) and characterisation method developers, and decision makers.Results and discussion: The focus was on defining a clear interface between LCI and LCIA, capable of supporting any goal and scope requirements while avoiding double counting or exclusion of important emission flows/impacts. Consensus was reached accordingly on distinct sets of recommendations for LCI and LCIA, respectively, recommending, for example, that buffer zones should be considered as part of the crop production system and the change in yield be considered. While the spatial dimensions of the field were not fixed, the temporal boundary between dynamic LCI fate modelling and steady-state LCIA fate modelling needs to be defined.Conclusions and recommendations: For pesticide application, the inventory should report pesticide identification, crop, mass applied per active ingredient, application method or formulation type, presence of buffer zones, location/country, application time before harvest and crop growth stage during application, adherence with Good Agricultural Practice, and whether the field is considered part of the technosphere or the ecosphere. Additionally, emission fractions to environmental media on-field and off-field should be reported. For LCIA, the directly concerned impact categories and a list of relevant fate and exposure processes were identified. Next steps were identified: (1) establishing default emission fractions to environmental media for integration into LCI databases and (2) interaction among impact model developers to extend current methods with new elements/processes mentioned in the recommendations.
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| 7. |
- Westrell, Therese, et al.
(author)
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Short- and long-term variations of norovirus concentrations in the Meuse river during a 2-year study period
- 2006
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In: Water Research. - : Elsevier BV. - 0043-1354. ; 40:14, s. 2613-2620
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Journal article (peer-reviewed)abstract
- Faecally impacted surface waters used for drinking water production may encompass risk for norovirus infections. To be able to assess a possible health risk, noroviruses should be quantified and fluctuations identified. In 2001, norovirus concentrations in the river Meuse displayed a seasonal distribution with high peaks during wintertime as determined by RT-PCR on serially diluted RNA. An intensified day-by-day sampling scheme in the winter of 2002/2003 revealed that the winter peak consisted of several peaks of varying duration and magnitude, possibly due to contamination events in the catchment. The highest estimated concentration was 1700 PCR-detectable units per litre (95% CI 250–8000), which if coinciding with failing treatment could lead to significant numbers in drinking water. Adaptive dynamic filtering was shown to adequately predict subsequent sample concentrations. If valid, such analyses could prove to be useful as early warning systems in risk management of water sources.
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