Application of mathematical models to mycotoxins children risk assessment: a case study of Portuguese children exposure to co-occurring mycotoxins in processed cereal-based foods

People, animals and the environment can be exposed to multiple chemicals at once from a variety of sources, but current risk assessment is usually carried out based on one chemical substance at a time. In human health risk assessment, ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins, a wide group of fungal secondary metabolites that are known to potentially cause toxicity and carcinogenic outcomes. Mycotoxins are commonly found in a variety of foods including those intended for consumption by infants and young children and have been found in processed cereal-based foods available in the Portuguese market. The use of mathematical models, including probabilistic approaches using Monte Carlo simulations, constitutes a prominent issue in human health risk assessment in general and in mycotoxins exposure assessment in particular. The present study aims to characterize, for the first time, the risk associated with the exposure of Portuguese children to single and multiple mycotoxins present in processed cereal-based foods (CBF). Portuguese children (0-3 years old) food consumption data (n=103) were collected using a 3 days food diary. Contamination data concerned the quantification of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) were evaluated in 20 CBF samples marketed in 2014 and 2015 in Lisbon; samples were analyzed by HPLC-FLD, LC-MS/MS and GC-MS. Daily exposure of children to mycotoxins was performed using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) to the aflatoxin exposure. The magnitude of the MoE gives an indication of the risk level. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (ratio between exposure and a reference dose, HQ). For the cumulative risk assessment of multiple mycotoxins, the concentration addition (CA) concept was used. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. 71% of CBF analyzed samples were contaminated with mycotoxins (with values below the legal limits) and approximately 56% of the studied children consumed CBF at least once in these 3 days. Preliminary results showed that children exposure to single mycotoxins present in CBF were below the TDI. Aflatoxins MoE and MoET revealed a reduced potential risk by exposure through consumption of CBF (with values around 10000 or more). HQ and HI values for the remaining mycotoxins were below 1. Children are a particularly vulnerable population group to food contaminants and the present results point out an urgent need to establish legal limits and control strategies regarding the presence of multiple mycotoxins in children foods in order to protect their health. The development of packaging materials with antifungal properties is a possible solution to control the growth of moulds and consequently to reduce mycotoxin production, contributing to guarantee the quality and safety of foods intended for children consumption.

Visualisation of numerical models for paper damage mechanics

Abstract not available

Towards the systematic simplification of mechanistic models

Mechanistic models used for prediction should be parsimonious, as models which are over-parameterised may have poor predictive performance. Determining whether a model is parsimonious requires comparisons with alternative model formulations with differing levels of complexity. However, creating alternative formulations for large mechanistic models is often problematic, and usually time-consuming. Consequently, few are ever investigated. In this paper, we present an approach which rapidly generates reduced model formulations by replacing a model’s variables with constants. These reduced alternatives can be compared to the original model, using data based model selection criteria, to assist in the identification of potentially unnecessary model complexity, and thereby inform reformulation of the model. To illustrate the approach, we present its application to a published radiocaesium plant-uptake model, which predicts uptake on the basis of soil characteristics (e.g. pH, organic matter content, clay content). A total of 1024 reduced model formulations were generated, and ranked according to five model selection criteria: Residual Sum of Squares (RSS), AICc, BIC, MDL and ICOMP. The lowest scores for RSS and AICc occurred for the same reduced model in which pH dependent model components were replaced. The lowest scores for BIC, MDL and ICOMP occurred for a further reduced model in which model components related to the distinction between adsorption on clay and organic surfaces were replaced. Both these reduced models had a lower RSS for the parameterisation dataset than the original model. As a test of their predictive performance, the original model and the two reduced models outlined above were used to predict an independent dataset. The reduced models have lower prediction sums of squares than the original model, suggesting that the latter may be overfitted. The approach presented has the potential to inform model development by rapidly creating a class of alternative model formulations, which can be compared.

The use of animal models in multiple myeloma

International audience

A Fuzzy Decision Strategy for Topic Identification and Dynamic Selection of Language Models

International audience

An analysis of the effects of preferential trade policies through the estimation of quantitative models: the case of Portugal.

Doutoramento em Economia.

Application of Mixture Models to Survival Data

Survival models are being widely applied to the engineering field to model time-to-event data once censored data is here a common issue. Using parametric models or not, for the case of heterogeneous data, they may not always represent a good fit. The present study relays on critical pumps survival data where traditional parametric regression might be improved in order to obtain better approaches. Considering censored data and using an empiric method to split the data into two subgroups to give the possibility to fit separated models to our censored data, we’ve mixture two distinct distributions according a mixture-models approach. We have concluded that it is a good method to fit data that does not fit to a usual parametric distribution and achieve reliable parameters. A constant cumulative hazard rate policy was used as well to check optimum inspection times using the obtained model from the mixture-model, which could be a plus when comparing with the actual maintenance policies to check whether changes should be introduced or not.

Exploiting spectrally resolved satellite observations to assess the performance of climate models

The accurate representation of the Earth Radiation Budget by General Circulation Models (GCMs) is a fundamental requirement to provide reliable historical and future climate simulations. In this study, we found reasonable agreement between the integrated energy fluxes at the top of the atmosphere simulated by 34 state-of-the-art climate models and the observations provided by the Cloud and Earth Radiant Energy System (CERES) mission on a global scale, but large regional biases have been detected throughout the globe. Furthermore, we highlighted that a good agreement between simulated and observed integrated Outgoing Longwave Radiation (OLR) fluxes may be obtained from the cancellation of opposite-in-sign systematic errors, localized in different spectral ranges. To avoid this and to understand the causes of these biases, we compared the observed Earth emission spectra, measured by the Infrared Atmospheric Sounding Interferometer (IASI) in the period 2008-2016, with the synthetic radiances computed on the basis of the atmospheric fields provided by the EC-Earth GCM. To this purpose, the fast σ-IASI radiative transfer model was used, after its validation and implementation in EC-Earth. From the comparison between observed and simulated spectral radiances, a positive temperature bias in the stratosphere and a negative temperature bias in the middle troposphere, as well as a dry bias of the water vapor concentration in the upper troposphere, have been identified in the EC-Earth climate model. The analysis has been performed in clear-sky conditions, but the feasibility of its extension in the presence of clouds, whose impact on the radiation represents the greatest source of uncertainty in climate models, has also been proven. Finally, the analysis of simulated and observed OLR trends indicated good agreement and provided detailed information on the spectral fingerprints of the evolution of the main climate variables.

Incompressible limit and well-posedness of PDE models of tissue growth

Both compressible and incompressible porous medium models are used in the literature to describe the mechanical aspects of living tissues. Using a stiff pressure law, it is possible to build a link between these two different representations. In the incompressible limit, compressible models generate free boundary problems where saturation holds in the moving domain. Our work aims at investigating the stiff pressure limit of reaction-advection-porous medium equations motivated by tumor development. Our first study concerns the analysis and numerical simulation of a model including the effect of nutrients. A coupled system of equations describes the cell density and the nutrient concentration and the derivation of the pressure equation in the stiff limit was an open problem for which the strong compactness of the pressure gradient is needed. To establish it, we use two new ideas: an L3-version of the celebrated Aronson-Bénilan estimate, and a sharp uniform L4-bound on the pressure gradient. We further investigate the sharpness of this bound through a finite difference upwind scheme, which we prove to be stable and asymptotic preserving. Our second study is centered around porous medium equations including convective effects. We are able to extend the techniques developed for the nutrient case, hence finding the complementarity relation on the limit pressure. Moreover, we provide an estimate of the convergence rate at the incompressible limit. Finally, we study a multi-species system. In particular, we account for phenotypic heterogeneity, including a structured variable into the problem. In this case, a cross-(degenerate)-diffusion system describes the evolution of the phenotypic distributions. Adapting methods recently developed in the context of two-species systems, we prove existence of weak solutions and we pass to the incompressible limit. Furthermore, we prove new regularity results on the total pressure, which is related to the total density by a power law of state.

Development of multicomponent models for the prediction of lubricant oil-fuel dilution in internal combustion engines

The current environmental crisis is forcing the automotive industry to face tough challenges for the Internal Combustion Engines development in order to reduce the emissions of pollutants and Greenhouse gases. In this context, in the last decades, the main technological solutions adopted by the manufacturers have been the direct injection and the engine downsizing, which led to the rising of new concerns related to the fuel-cylinder walls physical interaction. The fuel spray possibly impacts the cylinder liner wall, which is wetted by the lubricant oil thus causing the derating of the lubricant properties, increasing the oil consumption, and contaminating the lubricant oil in the crankcase. Also, concerning hydrogen fuelled internal combustion engines, it is likely that the high near-wall temperature, which is typical of the hydrogen flame, results in the evaporation of a portion of the lubricant oil, increasing its consumption. With regards on the innovative combustion systems and their control strategies, optical accessible engines are fundamental tools for experimental investigations on such combustion systems. Though, due to the optical measurement line, optical engines suffer from a high level of blow-by, which must be accounted for. In light of the above, this thesis work aims to develop numerical methodologies with the aim to build useful tools for supporting the design of modern engines. In particular, a one-dimensional modelling of the lubricant oil-fuel dilution and oil evaporation has been performed and coupled with an optimization algorithm to achieve a lubricant oil surrogate. Then, a quasi-dimensional blow-by model has been developed and validated against experimental data. Such model, has been coupled with CFD 3D simulations and directly implemented in CFD 3D. Finally, CFD 3D simulations coupled with the VOF method have been performed in order to validate a methodology for studying the impact of a liquid droplet on a solid surface.

A performance analysis of mesh models for cloud-based workflows

Nell'ambito della loro trasformazione digitale, molte organizzazioni stanno adottando nuove tecnologie per supportare lo sviluppo, l'implementazione e la gestione delle proprie architetture basate su microservizi negli ambienti cloud e tra i fornitori di cloud. In questo scenario, le service ed event mesh stanno emergendo come livelli infrastrutturali dinamici e configurabili che facilitano interazioni complesse e la gestione di applicazioni basate su microservizi e servizi cloud. L’obiettivo di questo lavoro è quello di analizzare soluzioni mesh open-source (istio, Linkerd, Apache EventMesh) dal punto di vista delle prestazioni, quando usate per gestire la comunicazione tra applicazioni a workflow basate su microservizi all’interno dell’ambiente cloud. A questo scopo è stato realizzato un sistema per eseguire il dislocamento di ognuno dei componenti all’interno di un cluster singolo e in un ambiente multi-cluster. La raccolta delle metriche e la loro sintesi è stata realizzata con un sistema personalizzato, compatibile con il formato dei dati di Prometheus. I test ci hanno permesso di valutare le prestazioni di ogni componente insieme alla sua efficacia. In generale, mentre si è potuta accertare la maturità delle implementazioni di service mesh testate, la soluzione di event mesh da noi usata è apparsa come una tecnologia ancora non matura, a causa di numerosi problemi di funzionamento.

A Comparative Analysis of Dynamical Models for Tidal Dissipation in Natural Satellite Ephemerides

The study of the tides of a celestial bodies can unveil important information about their interior as well as their orbital evolution. The most important tidal parameter is the Love number, which defines the deformation of the gravity field due to an external perturbing body. Tidal dissipation is very important because it drives the secular orbital evolution of the natural satellites, which is even more important in the case of the the Jupiter system, where three of the Galilean moons, Io, Europa and Ganymede, are locked in an orbital resonance where the ratio of their mean motions is 4:2:1. This is called Laplace resonance. Tidal dissipation is described by the dissipation ratio k2/Q, where Q is the quality factor and it describes the dampening of a system. The goal of this thesis is to analyze and compare the two main tidal dynamical models, Mignard's model and gravity field variation model, to understand the differences between each model with a main focus on the single-moon case with Io, which can help also understanding better the differences between the two models without over complicating the dynamical model. In this work we have verified and validated both models, we have compared them and pinpointed the main differences and features that characterize each model. Mignard's model treats the tides directly as a force, while the gravity field variation model describes the tides with a change of the spherical harmonic coefficients. Finally, we have also briefly analyzed the difference between the single-moon case and the two-moon case, and we have confirmed that the governing equations that describe the change of semi-major axis and eccentricity are not good anymore when more moons are present.

Validation of microFE models of human metastatic vertebrae

La colonna vertebrale è uno dei principali siti per lo sviluppo delle metastasi ossee. Esse modificano le proprietà meccaniche della vertebra indebolendo la struttura e inducendo l’instabilità spinale. La medicina in silico e i modelli agli elementi finiti (FE) hanno trovato spazio nello studio del comportamento meccanico delle vertebre, permettendo una valutazione delle loro proprietà meccaniche anche in presenza di metastasi. In questo studio ho validato i campi di spostamento predetti da modelli microFE di vertebre umane, con e senza metastasi, rispetto agli spostamenti misurati mediante Digital Volume Correlation (DVC). Sono stati utilizzati 4 provini da donatore umano, ognuno composto da una vertebra sana e da una vertebra con metastasi litica. Per ogni vertebra è stato sviluppato un modello microFE omogeneo, lineare e isotropo basato su sequenze di immagini ad alta risoluzione ottenute con microCT (voxel size = 39 μm). Sono state imposte come condizioni al contorno gli spostamenti ottenuti con la DVC nelle fette prossimali e distali di ogni vertebra. I modelli microFE hanno mostrato buone capacità predittive degli spostamenti interni sia per le vertebre di controllo che per quelle metastatiche. Per range di spostamento superiori a 100 μm, il valore di R2 è risultato compreso tra 0.70 e 0.99 e il valore di RMSE% tra 1.01% e 21.88%. Dalle analisi dei campi di deformazione predetti dai modelli microFE sono state evidenziate regioni a maggior deformazione nelle vertebre metastatiche, in particolare in prossimità delle lesioni. Questi risultati sono in accordo con le misure sperimentali effettuate con la DVC. Si può assumere quindi che il modello microFE lineare omogeneo isotropo in campo elastico produca risultati attendibili sia per le vertebre sane sia per le vertebre metastatiche. La procedura di validazione implementata potrebbe essere utilizzata per approfondire lo studio delle proprietà meccaniche delle lesioni blastiche.

Solutions to higher Hamiltonians in the Toda hierarchies

A method is presented for constructing the general solution to higher Hamiltonians (nonquadratic in the momenta) of the Toda hierarchies of integrable models associated with a simple Lie group G. The method is representation independent and is based on a modified version of the Lax operator. It constitutes a generalization of the method used to construct the solutions of the Toda molecule models. The SL(3) and SL(4) cases are discussed in detail. © 1990 American Institute of Physics.