• Method for Extraction and Quantification of Metal-Based Nanoparticles in Biological Media: Number-Based Biodistribution and Bioconcentration.

      Abdolahpur Monikh, Fazel; Chupani, Latifeh; Zusková, Eliška; Peters, Ruud; Vancová, Marie; Vijver, Martina G; Porcal, Petr; Peijnenburg, Willie Jgm (2018-12-11)
      A multistep sample preparation method was developed to separate metal-based engineered nanoparticles (ENPs) from biological samples. The method was developed using spiked zebrafish tissues and standard titanium dioxide (TiO2) and cerium dioxide (CeO2) ENPs. Single-particle inductively coupled plasma mass spectrometry was used to quantify the separated particles in terms of number concentration. This method demonstrated mass recoveries of more than 90% and did not strikingly alter the median particles size. High number recoveries were calculated for CeO2 ENPs (>84%). Particle number recoveries were poor for TiO2 ENPs (<25%), which could be due to the interference of 48Ca with the measured isotope 48Ti. The method was verified using zebrafish exposed to CeO2 ENPs to test its applicability for nanotoxicokinetic investigations. Total mass of Ce and particle number concentration of CeO2 ENPs were measured in different tissues. Notably, the mass-based biodistribution of Ce in the tissues did not follow the number-based biodistribution of CeO2. Moreover, the calculated mass-based bioconcentration factors showed a different pattern in comparison to the number-based bioconcentration factors. Our findings suggest that considering mass as the sole dose-metric may not provide sufficient information to investigate toxicity and toxicokinetics of ENPs.
    • Method selection for sustainability assessments: The case of recovery of resources from waste water.

      Zijp, M C; Waaijers-van der Loop, S L; Heijungs, R; Broeren, M L M; Peeters, R; Van Nieuwenhuijzen, A; Shen, L; Heugens, E H W; Posthuma, L (2017-07-15)
      Sustainability assessments provide scientific support in decision procedures towards sustainable solutions. However, in order to contribute in identifying and choosing sustainable solutions, the sustainability assessment has to fit the decision context. Two complicating factors exist. First, different stakeholders tend to have different views on what a sustainability assessment should encompass. Second, a plethora of sustainability assessment methods exist, due to the multi-dimensional characteristic of the concept. Different methods provide other representations of sustainability. Based on a literature review, we present a protocol to facilitate method selection together with stakeholders. The protocol guides the exploration of i) the decision context, ii) the different views of stakeholders and iii) the selection of pertinent assessment methods. In addition, we present an online tool for method selection. This tool identifies assessment methods that meet the specifications obtained with the protocol, and currently contains characteristics of 30 sustainability assessment methods. The utility of the protocol and the tool are tested in a case study on the recovery of resources from domestic waste water. In several iterations, a combination of methods was selected, followed by execution of the selected sustainability assessment methods. The assessment results can be used in the first phase of the decision procedure that leads to a strategic choice for sustainable resource recovery from waste water in the Netherlands.
    • Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

      Gasull, Magda; Pumarega, José; Kiviranta, Hannu; Rantakokko, Panu; Raaschou-Nielsen, Ole; Bergdahl, Ingvar A; Sandanger, Torkjel Manning; Goñi, Fernando; Cirera, Lluís; Donat-Vargas, Carolina; et al. (2019-02-01)
      The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.
    • Methodology for computing the burden of disease of adverse events following immunization.

      McDonald, Scott A; Nijsten, Danielle; Bollaerts, Kaatje; Bauwens, Jorgen; Praet, Nicolas; van der Sande, Marianne; Bauchau, Vincent; de Smedt, Tom; Sturkenboom, Miriam; Hahné, Susan (2018-03-24)
      Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden.
    • Microbiome composition of airborne particulate matter from livestock farms and their effect on innate immune receptors and cells

      Liu, D; Mariman, R; Gerlofs-Nijland, ME; Boere, JF; Folkerts, G; Cassee, FR; Pinelli, E (2019-07-15)
    • Microscopic examination of Gram-stained smears for anogenital gonorrhoea in men who have sex with men is cost-effective: evidence from a modelling study.

      Zwart, Jolijn M; Mangen, Marie-Josee J; Bartelsman, Menne; van Rooijen, Martijn S; de Vries, Henry J C; Xiridou, Maria (2018-09-08)
      To assess the cost-effectiveness of three testing strategies with or without light microscopic Gram-stained smear (GSS) evaluation for the detection of anogenital gonorrhoea among men who have sex with men (MSM) at the Amsterdam STI clinic using a healthcare payer perspective.
    • Migraine and MTHFR C677T genotype in a population-based sample.

      Scher, Ann I; Terwindt, Gisela M; Verschuren, W M Monique; Kruit, Mark C; Blom, Henk J; Kowa, Hisanori; Frants, Rune R; Maagdenberg, Arn M J M van den; Buchem, Mark A van; Ferrari, Michel D; et al. (2006-02-01)
      OBJECTIVE: Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status. METHODS: We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study. RESULTS: Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine. INTERPRETATION: Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.
    • Mitigation options for chemicals of emerging concern in surface waters; operationalising solutions-focused risk assessment

      van Wezel, Annemarie P.; ter Laak, Thomas L.; Fischer, Astrid; Bäuerlein, Patrick S.; Munthe, John; Posthuma, Leo; KWR Watercycle Institute; KWR Watercycle Institute; Technical University Delft; KWR Watercycle Institute; et al. (2017)
      The water system provides many services to society; industries, municipalities and agriculture all withdraw, use and return water and demand a water quality fit for the intended purposes.
    • Mitochondrial DNA copy number variation, leukocyte telomere length, and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

      Campa, Daniele; Barrdahl, Myrto; Santoro, Aurelia; Severi, Gianluca; Baglietto, Laura; Omichessan, Hanane; Tumino, Rosario; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; et al. (2018-04-17)
      Leukocyte telomere length (LTL) and mitochondrial genome (mtDNA) copy number and deletions have been proposed as risk markers for various cancer types, including breast cancer (BC).
    • Mixtures of chemicals are important drivers of impacts on ecological status in European surface waters.

      Posthuma, L; Brack, W; van Gils, J; Focks, A; Muller, C; de Zwart, D; Birk, S (2019-10-21)
    • A mobile application to collect daily data on pre-exposure prophylaxis adherence and sexual behaviour among men who have sex with men: use over time and comparability with conventional data collection.

      Finkenflügel, Renee N N; Hoornenborg, Elske; Achterbergh, Roel C A; Marra, Elske; Davidovich, Udi; de Vries, Henry J C; Prins, Maria; Schim van der Loeff, Maarten F (2019-03-14)
      We studied the use of a mobile application (app) to measure HIV Pre-Exposure Prophylaxis (PrEP) adherence and sexual behaviour, assessed determinants of app use, and we compared data in app and questionnaires. Men who have sex with men (MSM) participating in the Amsterdam PrEP project (AMPrEP) on daily or event-driven PrEP at the Public Health Service of Amsterdam completed data on sexual risk behaviour and PrEP adherence through three-monthly standard questionnaires and on a daily basis using the project's app. Regression analyses were used to assess factors associated with app use. Among those who reported ≥90% of data in the app, the number of PrEP pills taken and number of unknown casual sex partners were compared between the app and the questionnaires by Wilcoxon signed-rank test. Of all participants (n=374), 94% (352/374) reported data in the app at least once; 72% (261/362) reported data ≥90% of the days in the sixth month and 62% (222/359) in the 12th month following PrEP initiation.Factors associated with reporting data in the app were using daily PrEP and recent initiation of PrEP. The reported numbers of pills taken and unknown sexual partners were comparable between app and questionnaires. The AMPrEP app was used frequently, especially by those using a daily PrEP regimen. Data collected by app regarding adherence and sexual risk behaviour were consistent with questionnaire data among those who used the app consistently. An app is a promising tool to measure PrEP adherence and sexual risk behaviour.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
    • A mobile phone based tool to identify symptoms of common childhood diseases in Ghana: development and evaluation of the integrated clinical algorithm in a cross-sectional study.

      Franke, Konstantin H; Krumkamp, Ralf; Mohammed, Aliyu; Sarpong, Nimako; Owusu-Dabo, Ellis; Brinkel, Johanna; Fobil, Julius N; Marinovic, Axel Bonacic; Asihene, Philip; Boots, Mark; et al. (2018-03-27)
      The aim of this study was the development and evaluation of an algorithm-based diagnosis-tool, applicable on mobile phones, to support guardians in providing appropriate care to sick children.
    • Mobility assessment of a rural population in the Netherlands using GPS measurements.

      Klous, Gijs; Smit, Lidwien A M; Borlée, Floor; Coutinho, Roel A; Kretzschmar, Mirjam E E; Heederik, Dick J J; Huss, Anke (2017-08-09)
      The home address is a common spatial proxy for exposure assessment in epidemiological studies but mobility may introduce exposure misclassification. Mobility can be assessed using self-reports or objectively measured using GPS logging but self-reports may not assess the same information as measured mobility. We aimed to assess mobility patterns of a rural population in the Netherlands using GPS measurements and self-reports and to compare GPS measured to self-reported data, and to evaluate correlates of differences in mobility patterns.
    • A mode-of-action ontology model for safety evaluation of chemicals: Outcome of a series of workshops on repeated dose toxicity.

      Desprez, Bertrand; Birk, Barbara; Blaauboer, Bas; Boobis, Alan; Carmichael, Paul; Cronin, Mark T D; Curie, Richard; Daston, George; Hubesch, Bruno; Jennings, Paul; et al. (2019-04-04)
      Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data.
    • Model predictions of metal speciation in freshwaters compared to measurements by in situ techniques.

      Unsworth, Emily R; Warnken, Kent W; Zhang, Hao; Davison, William; Black, Frank; Buffle, Jacques; Cao, Jun; Cleven, Rob; Galceran, Josep; Gunkel, Peggy; et al. (2006-03-15)
      Measurements of trace metal species in situ in a softwater river, a hardwater lake, and a hardwater stream were compared to the equilibrium distribution of species calculated using two models, WHAM 6, incorporating humic ion binding model VI and visual MINTEQ incorporating NICA-Donnan. Diffusive gradients in thin films (DGT) and voltammetry at a gel integrated microelectrode (GIME) were used to estimate dynamic species that are both labile and mobile. The Donnan membrane technique (DMT) and hollow fiber permeation liquid membrane (HFPLM) were used to measure free ion activities. Predictions of dominant metal species using the two models agreed reasonably well, even when colloidal oxide components were considered. Concentrations derived using GIME were generally lower than those from DGT, consistent with calculations of the lability criteria that take into account the smaller time window available forthe fluxto GIME. Model predictions of free ion activities generally did not agree with measurements, highlighting the need for further work and difficulties in obtaining appropriate input data.
    • Modeled and Perceived Exposure to Radiofrequency Electromagnetic Fields From Mobile-Phone Base Stations and the Development of Symptoms Over Time in a General Population Cohort.

      Martens, Astrid L; Slottje, Pauline; Timmermans, Danielle R M; Kromhout, Hans; Reedijk, Marije; Vermeulen, Roel C H; Smid, Tjabe (2017-07-15)
      We assessed associations between modeled and perceived exposure to radiofrequency electromagnetic fields (RF-EMF) from mobile-phone base stations and the development of nonspecific symptoms and sleep disturbances over time. A population-based Dutch cohort study, the Occupational and Environmental Health Cohort Study (AMIGO) (n = 14,829; ages 31-65 years), was established in 2011/2012 (T0), with follow-up of a subgroup (n = 3,992 invited) in 2013 (T1; n = 2,228) and 2014 (T2; n = 1,740). We modeled far-field RF-EMF exposure from mobile-phone base stations at the home addresses of the participants using a 3-dimensional geospatial model (NISMap). Perceived exposure (0 = not at all; 6 = very much), nonspecific symptoms, and sleep disturbances were assessed by questionnaire. We performed cross-sectional and longitudinal analyses, including fixed-effects regression. We found small correlations between modeled and perceived exposure in AMIGO participants at baseline (n = 14,309; rSpearman = 0.10). For 222 follow-up participants, modeled exposure increased substantially (>0.030 mW/m2) between T0 and T1. This increase in modeled exposure was associated with an increase in perceived exposure during the same time period. In contrast to modeled RF-EMF exposure from mobile-phone base stations, perceived exposure was associated with higher symptom reporting scores in both cross-sectional and longitudinal analyses, as well as with sleep disturbances in cross-sectional analyses.
    • Modeled and perceived RF-EMF, noise and air pollution and symptoms in a population cohort. Is perception key in predicting symptoms?

      Martens, Astrid L; Reedijk, Marije; Smid, Tjabe; Huss, Anke; Timmermans, Danielle; Strak, Maciej; Swart, Wim; Lenters, Virissa; Kromhout, Hans; Verheij, Robert; et al. (2018-05-17)
      Psychosocial research has shown that perceived exposure can influence symptom reporting, regardless of actual exposure. The impact of this phenomenon on the interpretation of results from epidemiological research on environmental determinants of symptoms is unclear.