• Urban road traffic noise and noise annoyance-a study on perceived noise control and its value among the elderly.

      Riedel, Natalie; Köckler, Heike; Scheiner, Joachim; van Kamp, Irene; Erbel, Raimund; Loerbroks, Adrian; Claßen, Thomas; Bolte, Gabriele (2018-07-26)
      Noise annoyance may reflect a pro-participatory attitude towards public information and consultation according to the European Environmental Noise Directive. However, noise annoyance is also indicative of a stress response to perceived uncontrollable noise exposure. Using cross-sectional data on a sample of elderly citizens (n = 1772), we investigated whether the value residents ascribed to being able to control noise exposure at home moderated the potential indirect effect of road traffic noise on annoyance through perceived noise control. Our results confirmed the presence of such a moderated mediation, which may justify studying the impact of residents' valuing perceived noise control on participation readiness.
    • The urgency for optimization and harmonization of thyroid hormone analyses and their interpretation in developmental and reproductive toxicology studies.

      Beekhuijzen, Manon; Schneider, Steffen; Barraclough, Narinder; Hallmark, Nina; Hoberman, Alan; Lordi, Sheri; Moxon, Mary; Perks, Deborah; Piersma, Aldert H; Makris, Susan L (2018-05-02)
      In recent years several OECD test guidelines have been updated and some will be updated shortly with the requirement to measure thyroid hormone levels in the blood of mammalian laboratory species. There is, however, an imperative need for clarification and guidance regarding the collection, assessment, and interpretation of thyroid hormone data for regulatory toxicology and risk assessment. Clarification and guidance is needed for 1) timing and methods of blood collection, 2) standardization and validation of the analytical methods, 3) triggers for additional measurements, 4) the need for T4 measurements in postnatal day (PND) 4 pups, and 5) the interpretation of changes in thyroid hormone levels regarding adversity. Discussions on these topics have already been initiated, and involve expert scientists from a number of international multisector organizations. This paper provides an overview of existing issues, current activities and recommendations for moving forward.
    • Urine as Sample Type for Molecular Diagnosis of Natural Yellow Fever Virus Infections.

      Reusken, Chantal B E M; Knoester, Marjolein; GeurtsvanKessel, Corine; Koopmans, Marion; Knapen, Daan G; Bierman, Wouter F W; Pas, Suzan (2017-11)
    • Ursodeoxycholic acid improves feto-placental and offspring metabolic outcomes in hypercholanemic pregnancy.

      Borges Manna, Luiza; Papacleovoulou, Georgia; Flaviani, Flavia; Pataia, Vanessa; Qadri, Asaad; Abu-Hayyeh, Shadi; McIlvride, Saraid; Jansen, Eugene; Dixon, Peter; Chambers, Jennifer; et al. (2020-06-25)
    • Usability of the international HAVNet hepatitis A virus database for geographical annotation, backtracing and outbreak detection.

      Kroneman, Annelies; de Sousa, Rita; Verhoef, Linda; Koopmans, Marion P G; Vennema, Harry; On Behalf Of The HAVNet Network (2018-09)
      BackgroundHAVNet is an international laboratory network sharing sequences and corresponding metadata on hepatitis A virus in an online database. Aim: We give an overview of the epidemiological and genetic data and assess the usability of the present dataset for geographical annotation, backtracing and outbreak detection. Methods: A descriptive analysis was performed on the timeliness, completeness, epidemiological data and geographic coverage of the dataset. Length and genomic region of the sequences were reviewed as well as the numerical and geographical distribution of the genotypes. The geographical signal in the sequences was assessed based on a short common nt stretch using a 100% identity analysis. Results: The 9,211 reports were heterogeneous for completeness and timeliness, and for length and genomic region of the sequences. Some parts of the world were not represented by the sequences. Geographical differences in prevalence of HAV genotypes described previously could be confirmed with this dataset and for a third (1,075/3,124) of the included sequences, 100% identity of the short common sequence coincided with an identical country of origin. Conclusion: Analysis of a subset of short, shared sequences indicates that a geographical annotation on the level of individual countries is possible with the HAVNet data. If the current incompleteness and heterogeneity of the data can be improved on, HAVNet could become very useful as a worldwide reference set for geographical annotation and for backtracing and outbreak detection.
    • Use of a Whole Genome Sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study.

      Tagliani, Elisa; Anthony, Richard; Kohl, Thomas A; de Neeling, Albert; Nikolayevskyy, Vlad; Ködmön, Csaba; Maurer, Florian P; Niemann, Stefan; van Soolingen, Dick; van der Werf, Marieke J; et al. (2020-07-30)
      Whole genome sequencing (WGS) can be used for molecular typing and characterisation of Mycobacterium tuberculosis complex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learned to be considered for the future development of a WGS-based surveillance system.WGS and epidemiological data of patients with rifampicin (RR) and multi-drug resistant (MDR)-tuberculosis (TB) were collected from EU/EEA countries between January 2017 and December 2019. WGS-based genetic relatedness analysis was performed using a standardised approach including both core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP)-based calculation of distances on all WGS data that fulfilled minimum quality criteria to ensure data comparability.From 25 countries, 2218 RR/MDR-MTBC isolates were collected. Fifty-six cross-border clusters with increased likelihood of recent transmission (≤5 SNPs distance) comprising a total of 316 RR/MDR-MTBC isolates were identified. The cross-border clusters included between two and thirty resistant isolates from two to six countries unravelling different RR/MDR-TB transmission patterns in Western and Eastern EU.This pilot study shows that a WGS-based surveillance system is not only feasible but can efficiently elucidate the dynamics of in-country and cross-border RR/MDR-TB transmission across EU/EEA countries. Lessons learned from this study highlight how the establishment of an EU/EEA centralised WGS-based surveillance system for TB will require strengthening of national integrated systems performing prospective WGS surveillance and the development of clear procedures to facilitate international collaboration for the investigation of cross-border clusters.
    • Use of Ambulance Dispatch Calls for Surveillance of Severe Acute Respiratory Infections.

      Monge, Susana; Duijster, Janneke; Kommer, Geert Jan; van de Kassteele, Jan; Donker, Gé A; Krafft, Thomas; Engelen, Paul; Valk, Jens P; de Waard, Jan; de Nooij, Jan; et al. (2020-01-01)
    • The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review.

      van Duijkeren, Engeline; Schwarz, Christine; Bouchard, Damien; Catry, Boudewijn; Pomba, Constança; Baptiste, Keith Edward; Moreno, Miguel A; Rantala, Merja; Ružauskas, Modestas; Sanders, Pascal; et al. (2019-04-19)
      Aminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.
    • The use of generic failure frequencies in QRA: the quality and use of failure frequencies and how to bring them up-to-date.

      Beerens, H I; Post, J G; Uijt de Haag, P A M (2006-03-31)
      Quantitative Risk Assessment (QRA) is a method which is often used in the chemical industry and, in some countries, also in land-use planning. In QRA calculations the frequency of an accident scenario is most often assessed by a generic failure frequency approach. The credibility and validity of the failure frequencies used in the Netherlands for land-use planning is evaluated by means of an historical review. Furthermore, the possibility is presented how these generic data can be revised and updated.
    • The use of genomic DNA sequences as type material for valid publication of bacterial species names will have severe implications for clinical microbiology and related disciplines.

      Bisgaard, Magne; Christensen, Henrik; Clermont, Dominique; Dijkshoorn, Lenie; Janda, J Michael; Moore, Edward R B; Nemec, Alexandr; Nørskov-Lauritsen, Niels; Overmann, Jörg; Reubsaet, Frans A G (2019-03-22)
    • Use of in vitro 3D tissue models in genotoxicity testing: Strategic fit, validation status and way forward. Report of the working group from the 7 International Workshop on Genotoxicity Testing (IWGT).

      Pfuhler, Stefan; van Benthem, Jan; Curren, Rodger; Doak, Shareen H; Dusinska, Maria; Hayashi, Makoto; Heflich, Robert H; Kidd, Darren; Kirkland, David; Luan, Yang; et al.
      Use of three-dimensional (3D) tissue equivalents in toxicology has been increasing over the last decade as novel preclinical test systems and as alternatives to animal testing. In the area of genetic toxicology, progress has been made with establishing robust protocols for skin, airway (lung) and liver tissue equivalents. In light of these advancements, a "Use of 3D Tissues in Genotoxicity Testing" working group (WG) met at the 7th IWGT meeting in Tokyo in November 2017 to discuss progress with these models and how they may fit into a genotoxicity testing strategy. The workshop demonstrated that skin models have reached an advanced state of validation following over 10 years of development, while liver and airway model-based genotoxicity assays show promise but are at an early stage of development. Further effort in liver and airway model-based assays is needed to address the lack of coverage of the three main endpoints of genotoxicity (mutagenicity, clastogenicity and aneugenicity), and information on metabolic competence. The IWGT WG believes that the 3D skin comet and micronucleus assays are now sufficiently validated to undergo an independent peer review of the validation study, followed by development of individual OECD Test Guidelines.
    • Use of literature mining for early identification of emerging contaminants in freshwater resources.

      Hartmann, J; Wuijts, S; van der Hoek, JP; de Roda Husman, AM (2019-10-28)
    • Use of medicine pricing and reimbursement policies for universal health coverage in Indonesia.

      Wasir, Riswandy; Irawati, Sylvi; Makady, Amr; Postma, Maarten; Goettsch, Wim; Buskens, Erik; Feenstra, Talitha (2019-01-01)
      This study aimed to define the problems of the current use of the e-Catalogue and the national formulary (NF)-two elements of medicine pricing and reimbursement policies in Indonesia for achieving universal health coverage (UHC)-by examining the knowledge and attitudes of stakeholders. Specifically, to investigate (1) the perceived challenges involved in the further implementation of the e-Catalogue and the NF, (2) reasons of prescribing medicines not listed in the NF, and (3) possible improvements in the acceptance and use of the e-Catalogue and the NF. Semi-structured interviews were conducted with stakeholders (policymakers, healthcare providers, a pharmaceutical industry representative, and experienced patients) to collect the qualitative data. The data was analysed using directed content analysis, following the guidelines of the COnsolidated criteria for REporting Qualitative studies (COREQ) in reporting the findings. Interestingly, 20 of 45 participants decided to withdraw from the interview due to their lack of knowledge of the e-Catalogue and the NF. All 25 stakeholders who fully participated in this research were in favor of the e-Catalogue and the NF. However, interviewees identified a range of challenges. A major challenge was the lack of harmonization between the lists of medicines in the e-Catalogue and the NF. Several system and personal reasons for prescribing medicines not listed in the NF were identified. Important reasons were a lack of incentives for physicians as well as a lack of transparent and evidence-based methods of selection for the medicines to be listed in the NF. The e-Catalogue and the NF have not been fully utilized for achieving UHC in Indonesia. Some possible improvements suggested were harmonization of medicines listed in the e-Catalogue and the NF, restructuring incentive programs for prescribing NF medicines, and increasing the transparency and evidence-based approach for selection of medicines listed in the e-Catalogue and the NF.
    • Use of oseltamivir in Dutch nursing homes during the 2004-2005 influenza season.

      Sande, Marianne A B van der; Ruijs, Wilhelmina L M; Meijer, Adam; Cools, Herman J M; Plas, Simone M van der (2006-11-10)
      To assess the implementation of guidelines for using neuraminidase inhibitors in the control of influenza outbreaks in Dutch nursing homes, data were collected on prophylactic and therapeutic use of anti-viral medication, indications for use and criteria for prescribing, based on experiences during the influenza season 2004-2005 in a retrospective cross-sectional survey among Dutch nursing homes after the 2004-2005 season. Ninety/194 (49%) participating nursing homes reported an outbreak of influenza-like illness; in 57/194 (29%) influenza was laboratory confirmed. In 37/57 homes (65%) oseltamivir had been used as prophylaxis. Prophylactic use was extended to all residents and staff in 6/37 (16%) of homes, but limited in the others. In 9/37 (24%) no staff were issued prophylaxis. Among clinicians with laboratory confirmed influenza, 41/46 (89%) had used oseltamivir therapeutically. Main reasons for not prescribing oseltamivir for prophylaxis and/or therapy were lack of scientific evidence, high costs, and absent or delayed laboratory confirmation. Logistical bottlenecks in diagnosis, cost-effectiveness concerns, and lack of an evidence-base hamper full integration in policy and should be addressed.
    • Use of quantum-chemical descriptors to analyse reaction rate constants between organic chemicals and superoxide/hydroperoxyl (O2•-/HO2•).

      Nolte, Tom M; Peijnenburg, Willie J G M (2018-11-13)
      The reaction between superoxide (O2•-) and organic chemicals is of interest in many scientific disciplines including biology and synthetic chemistry, as well as for the evaluation of chemical fate in the environment. Due to limited data and lack of congeneric modelling, the involvement of superoxide in many complex processes cannot be adequately evaluated. In this study, we developed new quantitative structure-property relationship (QSPR) models for the prediction of the aqueous-phase rate constant for the reaction between superoxide and a wide variety of organic chemicals reacting via one-electron oxidation, reduction and hydrogen-transfer. It is shown that the relative importance of these pathways is related to frontier molecular orbital (FMO) interaction and to pH. The class-specific QSPRs developed have good statistics (0.84 ≤ R2 ≤ 0.92). For non-congeneric chemicals it is demonstrated that the reactivity toward superoxide can be described by applying explicit descriptions for competition kinetics and speciation. Therefore, the relationships developed in this study are useful as a starting point to evaluate more complex molecules having, for example, multiple reactive functional groups, labile H bonds, or delocalised cationic charges. However, additional kinetic data and more rigorous computation are needed to evaluate such molecules.
    • Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

      Paige, Ellie; Barrett, Jessica; Pennells, Lisa; Sweeting, Michael; Willeit, Peter; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Nordestgaard, Børge G; Psaty, Bruce M; Goldbourt, Uri; et al. (2017-10-15)
      The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.
    • Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection.

      van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M (2019-01-05)
      Mucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C. Measurements of salivary antibodies as replacement for blood testing has important (cost-effective) advantages, particular in studies that assess the impact of large-scale vaccination or in populations in which blood sampling is difficult. This study aimed to estimate a threshold for meningococcal IgG salivary antibody levels to discriminate between unprotected and protected vaccinated individuals. MenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG levels in serum and saliva from participants in a meningococcal vaccination study were measured using the fluorescent-bead-based multiplex immunoassay. Functional antibody titers in serum against the four serogroups were measured with serum bactericidal assay using rabbit complement (rSBA). A threshold for salivary IgG was determined by analysis of ROC curves using a serum rSBA titer ≥128 as correlate of protection. The area under the curve (AUC) was calculated to quantify the accuracy of the salivary test and was considered adequate when ≥0.80. The optimal cut-off was considered adequate when salivary IgG cut-off levels provided specificity of ≥90%. True positive rate (sensitivity), positive predictive value, and negative predictive value were calculated to explore the possible use of salivary antibody levels as a surrogate of protection. The best ROC curve (AUC of 0.95) was obtained for MenC, with an estimated minimum threshold of MenC-PS specific salivary IgG ≥3.54 ng/mL as surrogate of protection. An adequate AUC (> 0.80) was also observed for MenW and MenY with an estimated minimal threshold of 2.00 and 1.82 ng/mL, respectively. When applying these thresholds, all (100%) samples collected 1 month and 1 year after the (booster) meningococcal vaccination, that were defined as protective in the saliva test for MenC, MenW and MenY, corresponded with concomitant serum rSBA titer ≥128 for the respective meningococcal serogroups. The saliva test offers an alternative screening tool to monitor protective vaccine responses up to one year after meningococcal vaccination against MenC, MenW and MenY. Future (large) longitudinal vaccination studies evaluating also clinical protection against IMD or carriage acquisition are required to validate the currently proposed threshold in saliva.
    • The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

      Hoogenboom, Ron; Bovee, Toine; Traag, Win A; Hoogerbrugge, Ronald; Baumann, Bert; Portier, Liza; Weg, Guido van de; Vries, Jaap de (2006-10-01)
      The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed.
    • Use of the kinetically-derived maximum dose concept in selection of top doses for toxicity studies hampers proper hazard assessment and risk management.

      Heringa, Minne B; Cnubben, Nicole H P; Slob, Wout; Pronk, Marja E J; Muller, Andre; Woutersen, Marjolijn; Hakkert, Betty C (2020-07-01)