Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Critical assessment of recent trends related to screening and confirmatory analytical methods for selected food contaminants and allergens
Tsagkaris, A.S. ; Nelis, J.L.D. ; Ross, G.M.S. ; Jafari, S. ; Guercetti, J. ; Kopper, K. ; Zhao, Y. ; Rafferty, K. ; Salvador, J.P. ; Migliorelli, D. ; Salentijn, G. ; Campbell, K. ; Marco, M.P. ; Elliot, C.T. ; Nielen, M.W.F. ; Pulkrabova, J. ; Hajslova, J. - \ 2019
TrAC : Trends in Analytical Chemistry 121 (2019). - ISSN 0165-9936
Confirmatory methods - EU legal framework - Food contaminants - Inventory - Screening methods - Smartphones

Food contaminants monitoring is conducted in an intensive manner yet, there are still food safety scandals related to various chemical compounds. This fact highlights the need to review the requirements posed by the current legal framework on analytical methods performance and evaluate its application in published studies. Herein, we present an inventory including more than 470 publications on screening and confirmatory methods, which were used to control hazardous compounds such as pesticides, antibiotics, mycotoxins, aquatic toxins and allergens. Analytical performance characteristics, trends and state of the art, both merits and shortcomings, are critically discussed and summarized in excel tabulations. This repository highlights the ever-increasing use of screening methods and the necessity to confirm their performance by applying confirmatory methods. In conclusion, more effort is needed on validation and benchmarking, especially of newly developed technology such as smartphone-based methods, to avoid false-negative results and ensure that methods fit for purpose.

Supplementary Material to: Automated Gas and Liquid Chromatography Retention Time Modelling and Prediction Using Open-Access Molecular Database Structures and Quantitative Structure-Chromatography Retention Relationships
Lommen, A. ; Horvatovich, Peter L. ; Vonaparti, Ariadni ; Al-Maadheed, Muhammad ; Nielen, M.W.F. ; Georgakopoulos, Costas - \ 2019
Wageningen University & Research
Ultra-fast retroactive processing of liquid chromatography high-resolution full-scan Orbitrap mass spectrometry data in anti-doping screening of human urine
Lommen, Arjen ; Elaradi, Abdurzag ; Vonaparti, Ariadni ; Blokland, Marco ; Nielen, Michel W. ; Saad, Khadija Ali ; Abushreeda, Wadha Masoud ; Horvatovich, Peter ; Al-Muraikhi, Amal Essa ; Al-Maadheed, Mohammed ; Georgakopoulos, Costas - \ 2019
Rapid Communications in Mass Spectrometry 33 (2019)20. - ISSN 0951-4198 - p. 1578 - 1588.

Rationale: Retroactive analysis of previously tested urine samples has become an important sports anti-doping tool. Retroactive reprocessing of old data files acquired from a generic screening procedure can reveal detection of initially unknown substances, like illegal drugs and newly identified metabolites. Methods: To be able to efficiently search through hundreds to thousands of liquid chromatography high-resolution full-scan Orbitrap mass spectrometry data files of anti-doping samples, a combination of MetAlign and HR_MS_Search software has been developed. MetAlign reduced the data size ca 100-fold making possible local storage of a massive volume of data. Results: The newly developed HR_MS_Search module can search through the reduced data files for new compounds (mass or isotope pattern) defined by mass windows and retention time windows. A search for 33 analytes in 940 reduced data files lasted 10 s. The output of the automatic search was compared to the standard manual routine evaluation. The results of searching were evaluated in terms of false negatives and false positives. The newly banned b2-agonist higenamine and its metabolite coclaurine were successfully searched in reduced data files originating from a testing period for which these substances were not banned, as an example of retroactive analysis. Conclusions: The freeware MetAlign software and its automatic searching module HR_MS_Search facilitated the retroactive reprocessing of reduced full-scan high-resolution liquid chromatography/mass spectrometry screening data files and created a new tool in anti-doping laboratories' network.

Ambient laser ablation electrospray ionization mass spectrometry imaging
Geenen, Freddie A.M.G. van - \ 2019
Wageningen University. Promotor(en): M.W.F. Nielen; H. Zuilhof, co-promotor(en): M.C.R. Franssen. - Wageningen : Wageningen University - ISBN 9789463439220 - 164
Dynamics of faecal shedding of ESBL- or AmpC-producing Escherichia coli on dairy farms
Hordijk, Joost ; Fischer, Egil A.J. ; Werven, Tine van; Sietsma, Steven ; Gompel, Liese Van; Timmerman, Arjen J. ; Spaninks, Mirlin P. ; Heederik, Dick J.J. ; Nielen, Mirjam ; Wagenaar, Jaap A. ; Stegeman, Arjan - \ 2019
Journal of Antimicrobial Chemotherapy 74 (2019)6. - ISSN 0305-7453 - p. 1531 - 1538.

OBJECTIVES: To explore the dynamics of faecal ESBL/AmpC shedding in dairy cattle and farmers, a study was conducted to examine changes in shedding by individual animals, as well as environmental exposure, and to study the association between antimicrobial use (AMU) and ESBL/AmpC shedding. METHODS: The study comprised a cross-sectional survey of 20 farms and a 1 year follow-up of 10 farms. Faecal samples were cultured by both direct inoculation on MacConkey agar + 1 mg/L cefotaxime (MC+) and enrichment in LB-broth + 1 mg/L cefotaxime with subsequent inoculation on MC+. Dust samples were collected using electrostatic dustfall collectors (EDCs). Human faecal samples were collected by the farmers. Presence of ESBL/AmpC genes was screened for by PCR and sequencing. Using mixed effects logistic regression, ORs were determined and population-attributable fractions (PAFs) calculated subsequently. RESULTS: In Phase 1, 8/20 farms were positive for ESBL/AmpC and, with 2 negative farms, were selected for Phase 2. Transient shedding of dominant allele variants was observed in the animals. EDCs and human faecal samples did not reflect what was observed in the animals. AMU was related to shedding of ESBLs in the next sampling moment [OR 14.6 (95% CI 3.0-80.0)] and the PAF of AMU was 0.36 (95% CI 0.08-0.77). Calves fed with colostrum from cows on dry-off therapy was not a risk factor [OR 1.7 (95% CI 0.7-4.9, P = 0.28)]. CONCLUSIONS: The presence of ESBL/AmpC could only be partly explained by AMU. No link was shown between shedding in cattle and humans or the environment. Interventions should focus on prevention of introduction.

Sensor based eating time variables of dairy cows in the transition periodrelated to the time to first service
Hut, P.R. ; Mulder, A. ; Broek, J. van den; Hulsen, Jan ; Hooijer, G.A. ; Stassen, E.N. ; Eerdenburg, F.J.C.M. van; Nielen, M. - \ 2019
Preventive Veterinary Medicine 169 (2019). - ISSN 0167-5877 - 8 p.
In dairy cattle, reproductive diseases and infertility are some of the most important reasons for culling, where postpartum negative energy balance (NEB) reduces reproductive performance. This single cohort observational study reports the association between eating time and the interval between calving and first service in 2036 dairy cows on 17 commercial farms in The Netherlands. Cows were equipped with a commercially available neck sensor (Nedap, Groenlo, The Netherlands), that measured the time cows spent eating, from 28 days (d) before until 28 d after parturition. Primiparous cows spent a mean of +45 minutes (min) eating time per day ante partum and +15 min eating time post partum more than multiparous cows. A Cox proportional hazard model was used to analyze eating time variables in relation to the interval between calving and first service. From 4 weeks before until 4 weeks after calving eating time variables per week were used. Weeks -4, -3 + 3 and +4 were used as weeks with stable eating time patterns and therefore the mean eating time per week and the standard deviation of the mean eating time per week were used. Weeks -2, -1, +1 and +2 were addressed as periods with unstable eating patterns and therefore the slope in eating time per week and the residual variance of the slope per week were modeled. Significant results were the mean eating time in week -4 and +3 where in both weeks higher eating time lead to a higher hazard for first service. Difference between primiparous and multiparous cows were also significant with a higher hazard for first service for primiparous cows. Week 4 post partum presented a significant difference between eating time of primiparous cows and multiparous cows. These results display how eating time variables in the transition period could be related to the interval between calving and first service, and that there is a relation between mean eating time in week -4, +3, +4 and the interval between calving and first insemination.
Online and in situ analysis of organs-on-a-chip
Santbergen, Milou J.C. ; Zande, Meike van der; Bouwmeester, Hans ; Nielen, Michel W.F. - \ 2019
TrAC : Trends in Analytical Chemistry 115 (2019). - ISSN 0165-9936 - p. 138 - 146.
Electrochemical sensor - Mass spectrometry - Online analysis - Optical detector - Organ-on-a-chip

Organ-on-a-chip technology is used to study biological processes that involve multiple cell types and temporal changes like, homeostasis, metabolism and responses to chemical triggers. Main benefits of organ-on-a-chip systems include: improved mimicking of the in vivo situation, easy manipulation of the microenvironment and low reagent consumption. Exploiting the unique dynamic aspects of organ-on-a-chip technology, such as liquid flow, automated online measurement of parameters by sensors or online coupling to analytical equipment becomes feasible. Apart from the challenge to detect drug uptake and chemical changes in real-time with high resolution at the microscale, the biggest challenge, is detection of the analyte of interest in cell culture medium, as this contains high amounts of salts, sugars and proteins required by the living cells. In this review online and in situ analytical techniques integrated with organ-on-a-chip devices are discussed with special emphasis on maintaining the biological relevance, achieving analytical compatibility, system integration and final applicability.

TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry
Geenen, Fred A.M.G. Van; Franssen, Maurice C.R. ; Miikkulainen, Ville ; Ritala, Mikko ; Zuilhof, Han ; Kostiainen, Risto ; Nielen, Michel W.F. - \ 2019
Journal of the American Society for Mass Spectrometry 30 (2019)4. - ISSN 1044-0305 - p. 639 - 646.
In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient ionization mass spectrometry (MS). Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. Here, we introduce a novel (time-resolved) TiO2-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of verapamil, buspirone, testosterone, andarine, and ostarine. Finally, a time-resolved LAESI MS setup was developed and initial results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least 1 h.
Intramammary antimicrobial treatment of subclinical mastitis and cow performance later in lactation
Borne, Bart H.P. van den; Schaik, Gerdien van; Lam, Theo J.G.M. ; Nielen, Mirjam ; Frankena, Klaas - \ 2019
Journal of Dairy Science 102 (2019)5. - ISSN 0022-0302 - p. 4441 - 4451.
antimicrobial - clinical mastitis - dairy cow - milk yield - somatic cell count

The aim of this study was to evaluate long-term therapeutic effects of antimicrobial treatment of recently acquired subclinical mastitis (RASCM) during lactation. Quarter-level clinical mastitis (CM) follow-up, composite somatic cell counts (SCC), and cow-level milk yield later in lactation were evaluated using follow-up data from 2 previously published linked randomized field trials. The first trial randomly assigned antimicrobial treatment with any intramammary product or negative control to culture-positive quarters of cows having a first elevated composite SCC after 2 consecutive low composite SCC measurements. Untreated cows that had a second elevated composite SCC at the next measurement and were staphylococci-positive (i.e., Staphylococcus aureus or non-aureus staphylococci) were randomly assigned to treatment or control. Quarter-level CM cases were reported by the participating herd personnel, and milk yield and composite SCC data were obtained from the regular test-day recording. Frailty survival models were used to evaluate the long-term therapeutic effects of antimicrobial treatment of RASCM on quarter-level CM follow-up. Mixed linear regression models were applied to quantify the effect on milk yield and composite SCC. Data of 638 quarters from 486 cows in 38 herds were available for statistical analyses, of which 229 quarters of 175 cows received antimicrobial treatment for RASCM. Antimicrobial treatment culminated in reduced composite SCC levels later in lactation but did not result in different milk yield levels or CM follow-up compared with control cows. Antimicrobial treatment of cows with RASCM should therefore only be considered in exceptional situations given the current focus on antimicrobial usage reduction in animal husbandry.

Estimating disease prevalence from drug utilization data using the Random Forest algorithm
Slobbe, Laurentius C.J. ; Füssenich, Koen ; Wong, Albert ; Boshuizen, Hendriek C. ; Nielen, Markus M.J. ; Polder, Johan J. ; Feenstra, Talitha L. ; Oers, Hans A.M. Van - \ 2019
European Journal of Public Health 29 (2019)4. - ISSN 1101-1262 - p. 615 - 621.
Background: Aggregated claims data on medication are often used as a proxy for the prevalence of diseases, especially chronic diseases. However, linkage between medication and diagnosis tend to be theory based and not very precise. Modelling disease probability at an individual level using individual level data may yield more accurate results. Methods; Individual probabilities of having a certain chronic disease were estimated using the Random Forest (RF) algorithm. A training set was created from a general practitioners database of 276 723 cases that included diagnosis and claims data on medication. Model performance for 29 chronic diseases was evaluated using Receiver-Operator Curves, by measuring the Area Under the Curve (AUC). Results: The diseases for which model performance was best were Parkinson’s disease (AUC = .89, 95% CI = .77–1.00), diabetes (AUC = .87, 95% CI = .85–.90), osteoporosis (AUC = .87, 95% CI = .81–.92) and heart failure (AUC = .81, 95% CI = .74–.88). Five other diseases had an AUC >.75: asthma, chronic enteritis, COPD, epilepsy and HIV/AIDS. For 16 of 17 diseases tested, the medication categories used in theory-based algorithms were also identified by our method, however the RF models included a broader range of medications as important predictors. Conclusion: Data on medication use can be a useful predictor when estimating the prevalence of several chronic diseases. To improve the estimates, for a broader range of chronic diseases, research should use better training data, include more details concerning dosages and duration of prescriptions, and add related predictors like hospitalizations
Economic and epidemiological impact of different intervention strategies for clinical contagious mastitis
Gussmann, Maya ; Steeneveld, Wilma ; Kirkeby, Carsten ; Hogeveen, Henk ; Nielen, Mirjam ; Farre, Michael ; Halasa, Tariq - \ 2019
Journal of Dairy Science 102 (2019)2. - ISSN 0022-0302 - p. 1483 - 1493.
cow-specific - culling - simulation model - treatment

The overall aim of this study was to compare different intervention strategies for clinical intramammary infections (IMI). We conducted a simulation study to represent a Danish dairy cattle herd with IMI caused mostly by Staphylococcus aureus and 9 different intervention strategies for clinical IMI. A standard intervention of 3 d of treatment consisting of intramammary injections for all clinical cases was used. Two of the strategies reflected the use of more antibiotics and 6 strategies reflected cow-specific treatment or culling decisions. For these strategies, we assessed the cost and effectiveness of culling as an IMI intervention. Our results showed that nearly all strategies could reduce the number of IMI cases [e.g., a median of 37 clinical cases with the extended intramammary treatment over 5 d strategy (Basic5) and 30 clinical cases with the cow culled with recovery probability below 50% (Before50)] compared with the standard intervention (median of 42 clinical cases). This happened alongside either increased antibiotic usage (e.g., from a median of 123 treatment days up to 179 treatment days with strategy Basic5) or an increased number of cows culled in relation to IMI (e.g., from a median of 16 up to 24 cows with strategy Before50). Strategies with more antibiotics or reactive culling had a slightly higher net income (e.g., €190,014 median net income with strategy Basic5 or €196,995 with strategy Before50 compared with €187,666 with the standard strategy). This shows that a cow-specific clinical intervention approach can be cost-effective in reducing IMI incidence.

Functional fluorescence assay of botulinum neurotoxin A in complex matrices using magnetic beads
Klisara, Nevena ; Peters, Jeroen ; Haasnoot, Willem ; Nielen, Michel W.F. ; Palaniappan, Alagappan ; Liedberg, Bo - \ 2019
Sensors and Actuators B: Chemical 281 (2019). - ISSN 0925-4005 - p. 912 - 919.
Botulinum neurotoxin A - Fluorescence detection - Peptide - Superparamagnetic beads

The extremely toxic botulinum neurotoxin poses a threat for health and food safety, requiring rapid and easy-to-use detection platforms. To meet these requirements, we have explored a novel functional assay format for detection of botulinum neurotoxin serotype A light chain (BoNT/A LC) in complex matrices. The proposed assay utilizes a synthetic peptide designed to mimic the SNAP-25 protein (synaptosomal-associated protein 25) as substrate bound to a superparamagnetic bead and a fluorescent dye. Cleavage of the peptide by BoNT/A LC yields a reduction in fluorescence signal revealing the presence of the BoNT/A LC in the sample matrices tested. The superparamagnetic beads enable efficient separation of the cleaved peptides from food matrices, thereby improving the reliability of responses. Herein, we demonstrate a protocol offering an assay time of 6 h and a LOD of 0.5 nM (25 ng/ml). The proposed protocol is validated using carrot juice and diluted milk pending further improvements in sensitivity and overall assay time. Robustness, cost-effectiveness, low sample volume requirements in conjunction with the possibility of multiplexing for other proteolytic enzymes makes the proposed protocol competitive in comparison with conventional BoNT assays reported elsewhere.

A systematic knowledge synthesis on the spatial dimensions of Q fever epidemics
Rooij, Myrna M.T. de; Leuken, Jeroen P.G. van; Swart, Arno ; Kretzschmar, Mirjam E.E. ; Nielen, Mirjam ; Koeijer, Aline A. de; Janse, Ingmar ; Wouters, Inge M. ; Heederik, Dick J.J. - \ 2019
Zoonoses and Public Health 66 (2019)1. - ISSN 1863-1959 - p. 14 - 25.
airborne exposure - Coxiella burnetii - epidemiology - Q fever - risk assessment - spatial analysis

From 2007 through 2010, the Netherlands experienced the largest Q fever epidemic ever reported. This study integrates the outcomes of a multidisciplinary research programme on spatial airborne transmission of Coxiella burnetii and reflects these outcomes in relation to other scientific Q fever studies worldwide. We have identified lessons learned and remaining knowledge gaps. This synthesis was structured according to the four steps of quantitative microbial risk assessment (QMRA): (a) Rapid source identification was improved by newly developed techniques using mathematical disease modelling; (b) source characterization efforts improved knowledge but did not provide accurate C. burnetii emission patterns; (c) ambient air sampling, dispersion and spatial modelling promoted exposure assessment; and (d) risk characterization was enabled by applying refined dose–response analyses. The results may support proper and timely risk assessment and risk management during future outbreaks, provided that accurate and structured data are available and exchanged readily between responsible actors.

Rapid antibody selection using surface plasmon resonance for high-speed and sensitive hazelnut lateral flow prototypes
Ross, Georgina M.S. ; Bremer, Maria G.E.G. ; Wichers, Jan H. ; Amerongen, Aart Van; Nielen, Michel W.F. - \ 2018
Biosensors 8 (2018)4. - ISSN 2079-6374
Antibody selection - Carbon nanoparticles - Food allergen - High-speed lateral flow immunoassay - Smartphone detection - Surface plasmon resonance

Lateral Flow Immunoassays (LFIAs) allow for rapid, low-cost, screening of many biomolecules such as food allergens. Despite being classified as rapid tests, many LFIAs take 10–20 min to complete. For a really high-speed LFIA, it is necessary to assess antibody association kinetics. By using a label-free optical technique such as Surface Plasmon Resonance (SPR), it is possible to screen crude monoclonal antibody (mAb) preparations for their association rates against a target. Herein, we describe an SPR-based method for screening and selecting crude anti-hazelnut antibodies based on their relative association rates, cross reactivity and sandwich pairing capabilities, for subsequent application in a rapid ligand binding assay. Thanks to the SPR selection process, only the fast mAb (F-50-6B12) and the slow (S-50-5H9) mAb needed purification for labelling with carbon nanoparticles to exploit high-speed LFIA prototypes. The kinetics observed in SPR were reflected in LFIA, with the test line appearing within 30 s, almost two times faster when F-50-6B12 was used, compared with S-50-5H9. Additionally, the LFIAs have demonstrated their future applicability to real life samples by detecting hazelnut in the sub-ppm range in a cookie matrix. Finally, these LFIAs not only provide a qualitative result when read visually, but also generate semi-quantitative data when exploiting freely downloadable smartphone apps.

Direct Food Analysis by (transportable) Ambient Ionization Mass Spectrometry
Nielen, Michel - \ 2018
Comparison of gas chromatography/quadrupole time-of-flight and quadrupole Orbitrap mass spectrometry in anti-doping analysis : I. Detection of anabolic-androgenic steroids
Abushareeda, Wadha ; Tienstra, Marc ; Lommen, Arjen ; Blokland, Marco ; Sterk, Saskia ; Kraiem, Suhail ; Horvatovich, Peter ; Nielen, Michel ; Al-Maadheed, Muhammad ; Georgakopoulos, Costas - \ 2018
Rapid Communications in Mass Spectrometry 32 (2018)23. - ISSN 0951-4198 - p. 2055 - 2064.

Rationale: The World Anti-Doping Agency (WADA) encourages drug-testing laboratories to develop screening methods that can detect as many doping substances as possible in urine. The use of full-scan high-resolution acquisition (FS/HR) with gas chromatography/mass spectrometry (GC/MS) for the detection of known and unknown trimethylsilyl (TMS) derivatives of anabolic-androgenic steroids (AAS) provides anti-doping testing bodies with a new analytical tool. Methods: The AAS were extracted from urine samples by generic liquid–liquid extraction, after enzymatic hydrolysis, and TMS derivatization. The extracted urine was analyzed by GC/Q-TOF and GC/Q-Orbitrap to compare the performance of the two instrument types for the detection of 46 AAS in human urine. The quantitation of endogenous anabolic steroids and the ability of the two analytical platforms to comply with the requirements for testing as part of the WADA Athlete Biological Passport (ABP) were also assessed. Results: The data presented show that the analytical performance for both instruments complies with the WADA specifications. The limits of detection (LODs) for both instruments are well below the WADA 50% Minimum Required Performance Levels. The mass errors in the current study for the GC/Q-Orbitrap platform are lower than those obtained for the GC/Q-TOF instrument. Conclusions: The data presented herein proved that both molecular profiling platforms can be used for antidoping screening. The mass accuracies are excellent in both instruments; however, the GC/Q-Orbitrap performs better as it provides higher resolution than the GC/Q-TOF platform.

Reactive Laser Ablation Electrospray Ionization Time-Resolved Mass Spectrometry of Click Reactions
Geenen, Fred A.M.G. van; Franssen, Maurice C.R. ; Zuilhof, Han ; Nielen, Michel W.F. - \ 2018
Analytical Chemistry 90 (2018)17. - ISSN 0003-2700 - p. 10409 - 10416.

Reactions in confined compartments like charged microdroplets are of increasing interest, notably because of their substantially increased reaction rates. When combined with ambient ionization mass spectrometry (MS), reactions in charged microdroplets can be used to improve the detection of analytes or to study the molecular details of the reactions in real time. Here, we introduce a reactive laser ablation electrospray ionization (reactive LAESI) time-resolved mass spectrometry (TRMS) method to perform and study reactions in charged microdroplets. We demonstrate this approach with a class of reactions new to reactive ambient ionization MS: so-called click chemistry reactions. Click reactions are high-yielding reactions with a high atom efficiency, and are currently drawing significant attention from fields ranging from bioconjugation to polymer modification. Although click reactions are typically at least moderately fast (time scale of minutes to a few hours), in a reactive LAESI approach a substantial increase of reaction time is required for these reactions to occur. This increase was achieved using microdroplet chemistry and followed by MS using the insertion of a reaction tube - up to 1 m in length - between the LAESI source and the MS inlet, leading to near complete conversions due to significantly extended microdroplet lifetime. This novel approach allowed for the collection of kinetic data for a model (strain-promoted) click reaction between a substituted tetrazine and a strained alkyne and showed in addition excellent instrument stability, improved sensitivity, and applicability to other click reactions. Finally, the methodology was also demonstrated in a mass spectrometry imaging setting to show its feasibility in future imaging experiments.

Consumer-friendly food allergen detection : moving towards smartphone-based immunoassays
Ross, Georgina M.S. ; Bremer, Monique G.E.G. ; Nielen, Michel W.F. - \ 2018
Analytical and Bioanalytical Chemistry 410 (2018)22. - ISSN 1618-2642 - p. 5353 - 5371.
Citizen science - Consumer - Food allergen - Immunoassay - Multiplex - Smartphone
In this critical review, we provide a comprehensive overview of immunochemical food allergen assays and detectors in the context of their user-friendliness, through their connection to smartphones. Smartphone-based analysis is centered around citizen science, putting analysis into the hands of the consumer. Food allergies represent a significant worldwide health concern and consumers should be able to analyze their foods, whenever and wherever they are, for allergen presence. Owing to the need for a scientific background, traditional laboratory-based detection methods are generally unsuitable for the consumer. Therefore, it is important to develop simple, safe, and rapid assays that can be linked with smartphones as detectors to improve user accessibility. Smartphones make excellent detection systems because of their cameras, embedded flash functions, portability, connectivity, and affordability. Therefore, this review has summarized traditional laboratory-based methods for food allergen detection such as enzyme-linked-immunosorbent assay, flow cytometry, and surface plasmon resonance, and the potential to modernize these methods by interfacing them with a smartphone readout system, based on the aforementioned smartphone characteristics. This is the first review focusing on smartphone-based food-allergen detection methods designed with the intention of being consumer-friendly. [Figure not available: see fulltext.]
Effects of reduced intramammary antimicrobial use during the dry period on udder health in Dutch dairy herds
Vanhoudt, A. ; Hees-Huijps, K. van; Knegsel, A.T.M. van; Sampimon, O.C. ; Vernooij, J.C.M. ; Nielen, M. ; Werven, T. van - \ 2018
Journal of Dairy Science 101 (2018)4. - ISSN 0022-0302 - p. 3248 - 3260.
antimicrobial - dairy cow - dry period - selective dry cow therapy - udder health
Dry cow therapy (DCT) in the Netherlands changedfrom mainly blanket to selective antimicrobial DCT.This transition was supported by a national guideline,with the individual somatic cell count (SCC) at thelast milk recording before dry-off as the main selectioncriterion for antimicrobial DCT. The aim of this retrospectiveobservational study is to evaluate the SCCdynamics during the dry period at the herd and individualdry period level following the national transitionfrom mainly blanket to selective antimicrobial DCT.At the herd level, we used 2 data sets to evaluate theSCC dynamics during the dry period: (1) a nationaldata set containing 3,493 herds with data availablefrom 2011 through 2015 and (2) a veterinary practicedata set containing 280 herds with data available from2013 through 2015. The herd level analysis was carriedout using key performance indicators provided via milkrecording (CRV, Arnhem, the Netherlands): the percentageof cows that developed a new intramammaryinfection (IMI) during the dry period and the percentageof cows cured of an IMI during the dry period.The effect of DCT at individual dry period level wasanalyzed with a mixed-effects logistic regression modelbased on 4,404 dry periods from 2,638 cows in 20 herdswithin the veterinary practice data set. For these 20herds, individual SCC data from milk recordings andindividual cow DCT were available from 2013 through2015. No significant changes were observed to the SCCdynamics during the dry period at the herd level. Thepercentage of cows that developed a new IMI duringthe dry period ranged between 16 and 18%, and thepercentage of cows cured from an IMI during the dryperiod ranged between 74 and 76%. At the individual dry period level, a low SCC at the first milk recordingfollowing a dry period was associated with the use ofintramammary antimicrobial DCT with or without theconcurrent use of an intramammary teat sealer [oddsratio (OR) = 2.16 and OR = 2.07, respectively], the useof DCT with an intramammary teat sealer only (OR =1.35), and a low SCC at the last milk recording beforedry-off (OR = 1.78). This study demonstrates that theselection of cows for DCT without antimicrobials basedon SCC thresholds at the last milk recording is possiblewithout significant changes to udder health andreduced the use of antimicrobials.
Methods and means for determining treatment of subjects with exogenous somatotropin
Smits, N.G.E. ; Blokland, M.H. ; Nielen, M.W.F. - \ 2017
Octrooinummer: US2017354717, verleend: 2017-12-14.
Described are methods for determining whether a subject has been treated with exogenous somatotropin. The disclosure further relates to kits for determining whether a subject has been treated with exogenous somatotropin, and to the use of such kits for determining whether a subject has been treated with exogenous somatotropin.
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