Measuring the Efficiency Effect of Banning Anti-Microbial Growth Promoters: The Case of Danish Pig Production

This study examines the effect of banning antimicrobial growth promoters on efficiency in the production of weaned and slaughter (finishing) pigs. We focus on the reaction of producers and production efficiency. We evaluate the estimated output and input shadow prices relative to market prices to analyse producer reactions and capture the impact on production efficiency by evaluating the effects of the ban changes on total factor productivity. To this end we model a multi product shadow profit function and incorporate output and input related shadow prices by using a second order flexible functional form. The development in total factor productivity is subsequently measured by calculating the Malmquist index on the farm level. To make infer-ences on the effect of banning growth promoters over time we regress in a second estimation step the changes in total factor productivity on potential explanatory factors by applying a bootstrapped censored regression procedure. Our results suggest that there was no effect of the ban on total factor productivity due to outputs and inputs substitution. Breeding pigs are pro-duced at the expense of weaned and finisher pigs. Feed input is over utilised relative to other inputs. The high shadow prices for substituting outputs are associated with better export mar-ket prices. These findings may have critical implications for the slaughtering plants with over capacity.animal health economics, food economics, shadow prices, efficiency, antimicrobial growth promoters, pig production, Livestock Production/Industries, Q1, Q11, Q12, Q24,

Nonlinear resonant tunneling in systems coupled to quantum reservoirs

An adiabatic approximation in terms of instantaneous resonances is developed to study the steady-state and time-dependent transport of interacting electrons in biased resonant tunneling heterostructures. The resulting model consists of quantum reservoirs coupled to regions where the system is described by nonlinear ordinary differential equations and has a general conceptual interest.Comment: 4 pages, 3 postscript figure

Highly variable pharmacokinetics of tyramine in humans and polymorphisms in OCT1, CYP2D6, and MAO-A

Tyramine, formed by the decarboxylation of tyrosine, is a natural constituent of numerous food products. As an indirect sympathomimetic, it can have potentially dangerous hypertensive effects. In vitro data indicated that the pharmacokinetics of tyramine possibly depend on the organic cation transporter OCT1 genotype and on the CYP2D6 genotype. Since tyramine is a prototypic substrate of monoamine oxidase A (MAO-A), genetic polymorphisms in MAO-A may also be relevant. The aims of this study were to identify to what extent the interindividual variation in pharmacokinetics and pharmacodynamics of tyramine is determined by genetic polymorphisms in OCT1, CYP2D6, and MAO-A. Beyond that, we wanted to evaluate tyramine as probe drug for the in vivo activity of MAO-A and OCT1. Therefore, the pharmacokinetics, pharmacodynamics, and pharmacogenetics of tyramine were studied in 88 healthy volunteers after oral administration of a 400 mg dose. We observed a strong interindividual variation in systemic tyramine exposure, with a mean AUC of 3.74 min*µg/ml and a high mean CL/F ratio of 107 l/min. On average, as much as 76.8% of the dose was recovered in urine in form of the MAO-catalysed metabolite 4-hydroxyphenylacetic acid (4-HPAA), confirming that oxidative deamination by MAO-A is the quantitatively most relevant metabolic pathway. Systemic exposure of 4-HPAA varied only up to 3-fold, indicating no strong heritable variation in peripheral MAO-A activity. Systolic blood pressure increased by more than 10 mmHg in 71% of the volunteers and correlated strongly with systemic tyramine concentration. In less than 10% of participants, individually variable blood pressure peaks by >40 mmHg above baseline were observed at tyramine concentrations of >60 µg/l. Unexpectedly, the functionally relevant polymorphisms in OCT1 and CYP2D6, including the CYP2D6 poor and ultra-rapid metaboliser genotypes, did not significantly affect tyramine pharmacokinetics or pharmacodynamics. Also, the MOA-A genotypes, which had been associated in several earlier studies with neuropsychiatric phenotypes, had no significant effects on tyramine pharmacokinetics or its metabolism to 4-HPAA. Thus, variation in tyramine pharmacokinetics and pharmacodynamics is not explained by obvious genomic variation, and human tyramine metabolism did not indicate the existence of ultra-low or -high MAO-A activity

Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver

Abstract Background With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO2, ZnO, Ag, BaSO4 and CeO2) would have a significantly different toxicological outcome (cytotoxicity, (pro-)inflammatory and genotoxic response) upon 3D human HepG2 liver spheroids. In addition, this study evaluated whether a more realistic, prolonged fractionated and repeated ENM dosing regime induces a significantly different toxicity outcome in liver spheroids as compared to a single, bolus prolonged exposure. Results Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO2. Interestingly, the DNA damage effects observed following acute exposures, were not mirrored in the prolonged exposures, where only 0.2–5.0 µg/mL of ZnO ENMs were found to elicit significant (p ≤ 0.05) genotoxicity. When fractionated, repeated exposure regimes were performed with the test ENMs, no significant (p ≥ 0.05) difference was observed when compared to the single, bolus exposure regime. There was < 5.0% cytotoxicity observed across all exposures, and the mean difference in IL-8 cytokine release and genotoxicity between exposure regimes was 3.425 pg/mL and 0.181%, respectively. Conclusion In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner

Multiparametric Magnetic Resonance Imaging Allows Non-Invasive Functional and Structural Evaluation of Diabetic Kidney Disease

BackgroundWe sought to develop a novel non-contrast multi-parametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD).MethodsIn the cross-sectional part of this prospective observational study, 38 subjects aged 18‒79 years with type 2 diabetes and DKD (estimated glomerular filtration rate [eGFR] 15‒60 ml/min/1.73 m2), and 20 age- and gender-matched healthy volunteers (HV) underwent mpMRI. Repeat mpMRI was performed in 23 DKD subjects and 10 HV. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3, and 20 stage G4/5. A wide range of MRI-biomarkers associated with kidney hemodynamics, oxygenation, and macro/micro-structure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys, and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed.ResultsSeveral MRI-biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/5); mean arterial flow (MAF) was the strongest predictor (sensitivity = 0.94 and 1.0, specificity = 1.00 and 0.69, p = 0.04 and 0.004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney hemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92, p<0.0001).ConclusionsA comprehensive and repeatable non-contrast mpMRI protocol was developed that as a single, non-invasive tool allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Dickkopf1 - A New Player in Modelling the Wnt Pathway

The Wnt signaling pathway transducing the stabilization of β-catenin is essential for metazoan embryo development and is misregulated in many diseases such as cancers. In recent years models have been proposed for the Wnt signaling pathway during the segmentation process in developing embryos. Many of these include negative feedback loops where Axin2 plays a key role. However, Axin2 null mice show no segmentation phenotype. We therefore propose a new model where the negative feedback involves Dkk1 rather than Axin2. We show that this model can exhibit the same type of oscillations as the previous models with Axin2 and as observed in experiments. We show that a spatial Wnt gradient can consistently convert this temporal periodicity into the spatial periodicity of somites, provided the oscillations in new cells arising in the presomitic mesoderm are synchronized with the oscillations of older cells. We further investigate the hypothesis that a change in the Wnt level in the tail bud during the later stages of somitogenesis can lengthen the time period of the oscillations and hence the size and separation of the later somites

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Mobility Data Science (Dagstuhl Seminar 22021)

This report documents the program and the outcomes of Dagstuhl Seminar 22021 "Mobility Data Science". This seminar was held January 9-14, 2022, including 47 participants from industry and academia. The goal of this Dagstuhl Seminar was to create a new research community of mobility data science in which the whole is greater than the sum of its parts by bringing together established leaders as well as promising young researchers from all fields related to mobility data science. Specifically, this report summarizes the main results of the seminar by (1) defining Mobility Data Science as a research domain, (2) by sketching its agenda in the coming years, and by (3) building a mobility data science community. (1) Mobility data science is defined as spatiotemporal data that additionally captures the behavior of moving entities (human, vehicle, animal, etc.). To understand, explain, and predict behavior, we note that a strong collaboration with research in behavioral and social sciences is needed. (2) Future research directions for mobility data science described in this report include a) mobility data acquisition and privacy, b) mobility data management and analysis, and c) applications of mobility data science. (3) We identify opportunities towards building a mobility data science community, towards collaborations between academic and industry, and towards a mobility data science curriculum