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This study determined the gluten content of foods and meals consumed by coeliac disease (CD) patients who adhere to a gluten-free diet, and to estimate the total daily intake of gluten of these patients. CD patients fulfilling defined inclusion criteria were preselected and approached for participation in the study. Duplicate portions (DP) of foods and mixed dishes were collected from the CD patients for evaluating complete daily food intake during two individual days. Also, for these days, written food records were completed by the participants. From each DP, a laboratory sample was prepared and analysed for its gluten concentration and total daily gluten intake was calculated. Each individual’s total daily intakes of energy and macronutrients were calculated using the Dutch food composition database. In total, twenty-seven CD patients participated, seven males and twenty females, aged between 21 and 64 years. In thirty-two (6 %) of 499 food samples collected in total, more than 3 mg/kg gluten was present. In four of these thirty-two samples, the gluten concentration was above the European legal limit of 20 mg/kg and three of the four samples had a gluten-free label. The maximal gluten intake was 3·3 mg gluten/d. The gluten tolerance for sensitive CD patients (>0·75 mg/d) was exceeded on at least six out of fifty-four study days. To also protect these sensitive CD patients, legal thresholds should be re-evaluated and the detection limit of analytical methods for gluten analysis lowered.

Detector data can be used to construct cumulative flow curves, which in turn can be used to estimate the traffic state. However, this approach is subject to the cumulative error problem. Multiple studies propose to mitigate the cumulative error problem using probe trajectory data. These studies often assume “no overtaking” and thus that the cumulative flow is zero over probe trajectories. However, in multi-lane traffic this assumption is often violated. Therefore, we present an approach to estimate the change in cumulative flow along probe trajectories between detectors based on disaggregated detector data. The approach is tested with empirical data and in microsimulation. This shows that the approach is a clear improvement over assuming “no overtaking” in free-flow conditions. However, the benefits are not clear in varying traffic conditions. The approach can be applied in practice to mitigate the cumulative error problem and estimate the traffic state based on the resulting cumulative flow curves. As the performance of the approach depends on the changes in traffic conditions, it is suggested to use the probe speed observations between detectors to assign an uncertainty to the change in cumulative flow estimates. Furthermore, a potential option for future work is to use more elaborate schemes to estimate the probe relative flow between detectors, which may, for instance, combine probe speeds with estimates of the macroscopic states along the probe trajectory. If these macroscopic estimates are based on the cumulative flow curves at the detector locations, this would result in an iterative approach.

The hypothesis of this study is centered around the logic that an enhanced analysis of potential allergens during the food production can lead to increased accuracy and reliability of food labeling. The development of a cost-effective and straightforward optoelectrical microanalytical system for the simultaneous quantification of the six most common food allergens (peanut, hazelnut, almond, milk, wheat, and soybean) is presented. The system uses a regular versatile disc (DVD) functionalized with highly selective antibodies in a microarray format and a DVD drive as the optical detector. The multiplexed assay reliably (RSD < 20 %) determines the level of the allergenic proteins ranging from 0.1 to 143.4 ng mL−1. The analysis of food consumables (biscuits, seafood substitutes, and probiotic foods) revealed a 100 % accuracy in identifying the allergens ingredients declared on the label. The method offers potential for application as a high throughput biosensing tool for screening multiple allergens in commercial foods.

Pregnancy and the postpartum period is a vulnerable phase in life for women and can influence the development or course of a psychiatric disorder. These patients can receive extra guidance during this period by the POP-collaboration (Psychiatry, Obstetrics and Pediatrics) in many hospitals.To describe the characteristics of patients who received psychiatric consultation by the POP-collaboration at the LUMC and the interventions that were conducted.Data of patients who were seen at the psychiatric (outpatient) clinic for POP-guidance between 1 January 2016 and 1 April 2020 were analyzed.292 patients were seen in 310 guidance programs at the psychiatric (outpatient) clinic. Patients referred preconceptionally or during the pregnancy mostly suffered anxiety or unipolar mood disorders. Postpartum it concerned mostly psychotic disorders and bipolar mood disorders. A majority had two or more psychiatric disorders. Interventions were psycho-education, supportive contact, collaboration with their own health-professionals, adjustment of the current treatment, making a prevention plan, a prolonged stay at hospital after childbirth or (rarely) an admission to the psychiatric ward.Patients seen for guidance by the POP-collaboration at the LUMC are a vulnerable patient population with frequently complex psychopathology, and need personalized psychoeducation, supervision and treatment.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Daiichi Sankyo Europe GmbH Background Direct oral anticoagulants (DOACs) have been shown to be non-inferior to vitamin K antagonists (VKA) regarding both efficacy and safety outcomes in patients with atrial fibrillation (AF). However, elderly are underrepresented in the underlying clinical trials. Purpose The aim of this study was to compare risks of major bleeding events and compare healthcare resource utilization (HRU) between AF patients treated with edoxaban or VKA in elderly. Methods A cohort study was conducted using claims databases of Caserta and Palermo Local Heath Units in Italy. AF patients starting use of edoxaban or VKA between August 1st, 2016 and December 31st, 2018 were included. Date of the first dispensing was defined as the index date. The study population was matched based on a propensity score based on factors associated with the outcome. We restricted to patients aged ≥65, ≥1 year database history, and no use of the index drug in the year before index date. Incidence rates of bleeding outcomes and rates of HRU were assessed per 1,000 and 100 person-years follow-up (PY), respectively. Cox regression analyses to adjust for baseline covariates were used for comparisons of incidence rates of bleeding outcomes among all edoxaban and VKA users. Poisson regression analyses were used for comparisons of rates of HRU among all edoxaban and VKA users. Both analyses were adjusted for age. Sex, region and year of index date were considered for the adjusted models as well, using a backward stepwise approach to select eligible variables. Results 1,317 edoxaban users and 2,924 VKA users were included in the matched population. Mean age was 79 in both treatments groups, and 43% of the edoxaban users and 45% of the VKA users was male. Bleeding risks were significantly lower among edoxaban users compared to VKA users aged ≥65 (adjusted HR 0.39 (95% CI 0.19-0.83)) and among patients aged ≥75 (adjusted HR 0.37 (95% CI 0.16-0.86)). Among patients aged ≥65, edoxaban users were significantly less often hospitalised (RR 0.56 (95% CI 0.46-0.68)) and the total number of hospitalised days were also significant lower (RR 0.58 (95% CI 0.42-0.80)) compared to VKA users. Among patients aged ≥75, similar results were observed for the number of hospitalisations. Edoxaban users had significant less out-patient visits compared to VKA users (among patients aged ≥65 the RR was 0.44 (95% CI 0.39-0.50) and among patients ≥75 this was 0.40 (95% CI 0.35-0.47). Use of out-patient medication use was significantly lower among edoxaban users compared to VKA users among patients aged ≥65 (adjusted RR 0.91 (95% CI 0.88-0.95)) as well as among patients aged ≥75 (adjusted RR 0.91 (95% CI 0.87-0.95)). Conclusion Study results show a decreased bleeding risk of edoxaban compared to VKA in both age groups of patients with AF. Hospital based HRU has shown to be lower among edoxaban users compared to VKA users in both age groups. Out-patient HRU was also lower among edoxaban users.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Daiichi Sankyo Europe GmbH Background Based on results of multiple randomised controlled trials, direct oral anticoagulants (DOACs) are frequently used to reduce stroke risk in patients with atrial fibrillation (AF). The hypothesis is that in the real-world setting DOACs are effective in reducing the risk of stroke but ensuring continuous use is essential because of the rapid decline in anticoagulation activity when doses are omitted. Purpose The aim of this study was to assess the relationship between non-adherence, discontinuation of DOAC treatment and incidence of ischaemic stroke. Methods A nested case-control study was conducted in the InGef database, an anonymised healthcare claims database in Germany. AF patients starting DOACs between drug approval date and 31/12/2018 were included. We restricted to patients aged ≥45, ≥1 year database history, ≥1 year follow-up and at least two DOAC dispensings after cohort entry date (CED) (date of first dispensing). Patients with an ischaemic stroke during follow-up were selected as cases and compared with matched controls (matched on age +/- 5 years, sex, year of CED and CHA₂DS₂-VASc-score at CED). Controls were assigned the index date (date of first stroke diagnosis) of the corresponding case. Adherence to treatment was assessed among current users (DOAC use at or within 30 days before index date) and defined as proportion of days covered (PDC) ≥80% during CED and index date. Persistent users were defined as those with continuous DOAC use from CED to index date. We also assessed the effect of current, recent (DOAC use within 30-365 days before index date) and past use (DOAC use more than 1 year before index date). Odds ratios (ORs) with 95% confidence intervals (CIs) for ischaemic stroke were determined in logistic regression models. Results 900 cases and 3,570 controls were included. Among cases and controls, mean ± sd age was 80 ± 8 years and 49% were male. Current users who were non-adherent had a significant 1.21 higher odds (95% CI 1.01-1.45) of ischaemic stroke compared to adherent users. Similar results were observed in twice-daily (BID) users (OR 1.42 (1.15-1.75)). However, among once-daily (QD) users, the odds was not different between the adherent and non-adherent users (OR 0.99 (95% CI 0.58-1.69)). The risk of ischaemic stroke was significantly higher among non-persistent users compared to persistent users (OR 1.91 (95% CI 1.64-2.22)). Similar findings were observed among QD and BID users. The comparison of past and recent users to current users showed that the OR became higher the longer a patient had stopped DOAC use. Conclusion Both non-adherence and non-persistence were found to increase the risk of ischaemic stroke, showing that continuous use is essential for both BID and QD users. In BID users, there seems to be a stronger association between non-adherence and risk of stroke than in QD users. An explanation might be the higher degree of difficulty in adhering to a BID than QD regimen.

The U.S. electrical grid has undergone substantial transformation with increased penetration of wind and solar -- forms of variable renewable energy (VRE). Despite the benefits of VRE for decarbonization, it has garnered some controversy for inducing unwanted effects in regional electricity markets. In this study, the role of VRE penetration is examined on the system electricity price and price volatility based on hourly, real-time, historical data from six Independent System Operators (ISOs) in the U.S. using quantile and skew t-distribution regressions. After correcting for temporal effects, we found an increase in VRE penetration is associated with decrease in system electricity price in all ISOs studied. The increase in VRE penetration is associated with decrease in temporal price volatility in five out of six ISOs studied. The relationships are non-linear. These results are consistent with the modern portfolio theory where diverse volatile assets may lead to more stable and less risky portfolios.

The elimination of recombinant bovine somatotropin (rbST) and its induced antibodies through milk of 2 formulations is studied to propose a control strategy for its use or abuse. Two dairy cows were treated with alanine-rbST (Ala-rbST), which is identical to endogenous bovine somatotropin, and ten dairy cows were treated with methionine-rbST (Met-rbST), which differs by 1 amino acid from endogenous bovine somatotropin. We developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method able to measure rbST at a decision limit (CCα) of 0.8 ng/mL and 2.3 ng/mL for serum and milk, respectively. The results show that the administered Ala-rbST is transferred from blood to milk but that this is not the case for Met-rbST. This suggests a blood-milk barrier-related specificity for these compounds. In addition, rbST-induced antibodies were formed in animals treated with Ala-rbST and those treated with Met-rbST. In both treatments, the rbST-induced antibodies were transferred from blood to milk, showing no blood-milk barrier specificity for these antibodies. These elimination patterns show that, for enforcement purposes, the detection of rbST-induced antibodies in tank milk can serve to screen for rbST administration, and subsequent confirmatory serum analysis by LC-MS/MS is needed to identify whether Ala-rbST or Met-rbST has been used.

Pathogen exposure, including but not limited to herpesviruses, moulds the shape of the immune system, both at a basal state and in response to immune challenge. However, little is known about the impact of high exposure to other viruses on baseline immune signatures and how the immune system copes with repetitive exposures to maintain a balanced functionality. Here we investigated baseline immune signatures, including detailed T cell phenotyping, antigen‐specific CD4(+) and CD8(+) T cell responses and cytokine profile in paediatric (PED) nurses, who have high occupational exposure to viral pathogens including varicella zoster virus (VZV) and respiratory viruses, and in neonatal intensive care unit (NICU) nurses, as a control group with infrequent occupational exposure. Our results show a lower CD4(+) T cell response to two VZV proteins (IE62 and gE) and to tetanus toxoid (TT) in PED nurses who are cytomegalovirus (CMV)‐seronegative, compared to CMV‐seronegative NICU nurses, and that the decline might be more pronounced the more sustained the exposure. This decline might be due to an attrition of VZV‐ and TT‐specific T cells as a result of the continuous pressure on the CD4(+) T cell compartment. Moreover, our data suggest that the distinct T cell phenotypes known to be associated with CMV‐seropositivity might be less prominent in PED nurses compared to NICU nurses, implying a plausible attenuating effect of occupational exposure on CMV‐associated immunosenescence. Overall, this pilot study reveals an impact of occupational exposure to viral pathogens on CD4(+) T cell immunity and supports further investigation in a larger cohort.

The family of macroscopic node models which comply to a set of basic requirements is presented and analysed. Such models are required in macro-, mesoscopic traffic flow models, including dynamic network loading models for dynamic traffic assignment. Based on the behaviour of drivers approaching and passing through intersections, the model family is presented. The headway and the turn delay of vehicles are key variables. Having demand and supply as input creates a natural connection to macroscopic link models. Properties like the invariance principle and the conservation of turning fractions are satisfied. The inherent non-uniqueness is analysed by providing the complete set of feasible solutions. The node models proposed by Tampere et al. (2011), Flotterod and Rohde (2011) and Gibb (2011) are members of the family. Furthermore, two new models are added to the family. Solution methods for all family members are presented, as well as a qualitative and quantitative comparison. Finally, an outlook for the future development of empirically verified models is given.

The use of recombinant bovine somatotropin (rbST) to enhance milk production is approved in several countries, but it is prohibited in the European Union. According to EU legislation, it is necessary to confirm positive screening results prior to enforcement. Although adequate screening assays are available nowadays, development of liquid chromatography tandem mass spectrometry (LC-MS/MS) confirmatory methods to detect low levels of rbST is still a challenge. Here, we present a novel approach using immuno-affinity enrichment on monolithic micro-columns in combination with state-of-the-art ultra-high pressure LC-MS/MS (UHPLC-MS/MS) detection. The developed approach enables detection and confirmation of rbST in serum at a decision limit (CCα) concentration of 0.8 ng mL(-1). Furthermore, the method is easy to handle, robust and reproducible. We successfully applied the confirmatory method to serum samples from rbST treated cows that were found suspect after immunoassay-based screening. The use of rbST could be confirmed over 1 week after treatment, and the developed method demonstrated the sensitivity needed for effective control. Graphical Abstract Graphical summary of the workflow, for serum preparation, enrichment with monolith microcolumns and LC-MS/MS measurement of rbST.

Background Lung cancer is the leading cause of cancer death worldwide. Routine UK lung cancer screening is not yet available, thus understanding barriers to participation in lung screening could help maximize effectiveness if introduced. Methods Population‐based survey of 1007 adults aged 16 and over in Wales using random quota sampling. Computer‐assisted face‐to‐face interviews included demographic variables (age, gender, smoking, social group), four lung cancer belief statements and three lung screening attitudinal items. Determinants of lung screening attitudes were examined using multivariable regression adjusted for age, gender, social group and previous exposure to lung campaign messages. Results Avoidance of lung screening due to fear of what might be found was statistically significantly associated with negative lung cancer beliefs including fatalism (aOR = 8.8, 95% CI = 5.6‐13.9, P ≤ 0.001), low perceived value of symptomatic presentation (aOR = 2.4, 95% CI = 1.5‐3.9, P ≤ 0.001) and low treatment efficacy (aOR = 0.3, CI = 0.2‐0.7, P ≤ 0.01). Low perceived effectiveness of lung screening was significantly associated with fatalism (aOR = 6.4, 95% CI = 3.5‐11.7, P ≤ 0.001), low perceived value of symptom presentation (aOR = 4.9, 95% CI = 2.7‐8.9, P ≤ 0.001) and low treatment efficacy (aOR = 0.1, 95% CI = 0.1‐0.3, P ≤ 0.001). In contrast, respondents who thought lung screening could reduce cancer deaths had positive beliefs about lung cancer (aOR = 0.4, 95% CI = 0.2‐0.7, P ≤ 0.001) and its treatment (aOR = 6.1, 95% CI = 3.0‐12.6, P ≤ 0.001). Conclusion People with negative beliefs about lung cancer may be more likely to avoid lung screening. Alongside the introduction of effective early detection strategies, interventions are needed to modify public perceptions of lung cancer, particularly for fatalism.

In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. Systolic BP response to aliskiren was higher in patients with a BMI > 30.7 kg/m2 compared to patients with a BMI ≤ 30.7 kg/m2 (−21 mmHg versus -4 mmHg). In patients with a hsCRP > 1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (−15 mmHg versus −7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was −13 mmHg when heart rate > 71 beats/min compared to -3 mmHg when heart rate was ≤ 71 beats/min. In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. NCT01138423 . Registered June 4th, 2010.

During the EURAMET TC-F annual meeting, held in Boras in 2015, it was agreed to perform the follow up of the CCM.FF-K4.1.2011 organized for the EURAMET NMIs for volume of liquids at 20 L. The transfer standard was a 20 L pipette supplied by CENAM. The participants of this comparison also involved in the comparison CCM.FF-K4.1.2011 were: CENAM, INRIM, IPQ, RISE and VSL, in total there were twenty-one participants. The comparison was organized in two petals, INIRM perform three measurements, at the beginning, after the first petal and at the end of the circulation. The comparison measurements started in April 2016 and ended in October 2017. It should be noted that most of the participants (thirteen) declared an expanded uncertainty less than 0,005 %. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Static traffic assignment models are still widely applied for strategic transport planning purposes in spite of the fact that such models produce implausible traffic flows that exceed link capacities and predict incorrect congestion locations. There have been numerous attempts to constrain link flows to capacity. Capacity constrained models with residual queues are often referred to as quasi-dynamic traffic assignment models. After reviewing the literature, we come to the conclusion that an important piece of the puzzle has been missing so far, namely the inclusion of a first order node model. In this paper we propose a novel path-based static traffic assignment model for finding a stochastic user equilibrium in general transportation networks. This model includes a first order (steady-state) node model that yields more realistic turn capacities, which are then used to determine consistent capacity constrained traffic flows, residual point (vertical) queues (upstream bottleneck links), and path travel times consistent with queuing theory. The route choice part of the model is specified as a variational inequality problem, while the network loading part is formulated as a fixed point problem. Both problems are solved using existing techniques to find a solution. We illustrate the model using hypothetical examples, and also demonstrate feasibility on large-scale networks.

Recombinant bovine somatotropin (rbST) is licensed for enhancing milk production in dairy cows in some countries, for instance the United States, but is banned in Europe. Serum biomarker profiling can be an adequate approach to discriminate between treated and untreated groups. In this study a multiplex screening tool of a small set of biomarkers for pinpointing recombinant bovine somatotropin (rbST) (ab)use was developed and evaluated: insulin-like growth factor 1 (IGF-1), IGF binding protein 2 (IGFBP2) and rbST-induced antibodies were selected as rbST dependent markers and combined in one parallel assay format. For this, the color-encoded microspheres were used in a suspension array, with a dedicated flow cytometer. Serum samples obtained from an animal experiment with rbST-treated and untreated dairy cows were measured with the developed triplex immunoassay and biomarker responses on rbST treatment were evaluated. This resulted in characteristic treatment-dependent responses for all three individual biomarkers. Combining these results with the statistical prediction model k-nearest neighbours (kNN), resulted in good discrimination of treated and untreated animals: an overall sensitivity (true positive rate) of 89.1% and an overall specificity (true negative rate) of 97.7% were reached. Therefore, this is the first multiplex method which can be applied with high confidence for screening of unknown herds of cattle pinpointing at rbST (ab)use.

This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural hormones. These include both the traditional and generally recognized natural hormones as well as a series of androgenic steroids that can be present in biological samples obtained from a series of species. The fact that natural background concentrations can be present strongly complicates the analyses. The application of mass spectrometry (MS) in combination with gas chromatography (GC) or liquid chromatography (LC) is considered the "gold standard" for analytical methods in residue analysis. The chapter presents an overview of the available bio-based screening methods for the detection of hormones and s-agonists, focusing on estrogens, androgens, progestogens, corticosteroids, thyroids, s2-agonists, and growth hormones (GH).

Numerous studies conducted to assess welfare of domestic dogs housed in kennel facilities have reported that these dogs experience suboptimal living conditions. One important goal of improving welfare of kennelled dogs is to reduce their stress levels, and one recommended approach for improving welfare of kennelled dogs is group or social housing. The beneficial effects of management changes designed to achieve this goal should be measurable in individual animals. Stress is evident through behaviours exhibited, as well as via the concentration of cortisol, a key hormone reflecting stress. Using behavioural and hair cortisol measures, we conducted a pilot study to measure the impact of switching dogs housed in a long-term kennels facility from solitary to pair housing, using both within-subjects and between-groups comparisons. Considerable individual variation in dog responses was noted, with only two of eight pair-housed dogs showing significant declines in multiple stress-related behaviours once in pair housing. The most sensitive behaviours were active vigilance and repetitive movements (such as jumping and pacing). Barking was reduced overall in the facility following the housing change, even among dogs still in solitary housing. The long-term stress as reflected in hormone deposition in hair also provided encouraging indications that the dogs experienced lower stress levels when in paired housing; dogs showed a significant decline in hair cortisol levels from the first (prehousing change) to second (postintervention) samples. Domestic dogs are social animals, and numerous indications of potential benefit were recorded with no negative impacts seen. Based on our findings, we recommend pair or group housing of compatible dogs as a promising addition to the strategies available to those seeking to improve welfare of kennelled dogs. Future studies using higher numbers of animals and that include tracking of hair cortisol, vigilance behaviour, repetitive movements and barking would be desirable.

Recombinant bovine somatotropin (rbST) can be used to enhance milk production in dairy cattle. This is permitted in several countries but unauthorized in the European Union. Antibodies, which are produced endogenously in response to rbST administration, can be detected as a biomarker for indicating rbST (ab)use. For the first time, a fast and easy-to-perform screening assay for anti-rbST antibodies has been developed and applied to raw milk samples. This flow cytometric immunoassay (FCIA) is capable of discriminating between milk from rbST-treated animals and untreated animals. In accordance with literature, 67% of the rbST-treated animals responded positively with antibody production, whereas 94% of the untreated animals did not. The analysis of simulated tank milk samples showed more than 95% of the milk mixtures as truly positive for rbST treatment, indicating that the 33% physiologically non-responding cows will not be a problem when pooled tank milk samples are considered. FCIA biomarker responses in raw milk were specific for rbST and also obtained in pasteurized milk of rbST-treated animals. Using milk as a sample matrix for detection has the advantages of non-invasive sampling, and for tank milk analysis at the farm only one milk sample is needed to screen the whole farm for rbST (ab)use.