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Statistical Estimation of Physiologically-based Pharmacokinetic Models: Identifiability, Variation, and Uncertainty with an Illustration of Chronic Exposure to Dioxin and Dioxin-like-compounds.Thompson, Zachary John 01 January 2012 (has links)
Assessment of human exposure to environmental chemicals is inherently subject to uncertainty and variability. There are data gaps concerning the inventory, source, duration, and intensity of exposure
as well as knowledge gaps regarding pharmacokinetics in general. These gaps result in uncertainties in exposure assessment.
The uncertainties compound further with variabilities due to population variations regarding stage of life, life style, and susceptibility,
etc. Use of physiologically-based pharmacokinetic (PBPK) models promises to reduce the uncertainties and enhance extrapolation between species, between routes, from high to low dose, and from acute to chronic exposure. However, fitting PBPK models is challenging because of a large number of biochemical and physiological parameters to be estimated. Many of these model parameters are non-identifiable in that their estimates cannot be uniquely determined using statistical criteria. In practice some parameters are fixed in value and some determined through mathematical calibration or computer simulation.
These estimated values are subject to substantial uncertainties. The first part of this paper illustrates the use of iteratively-reweighted-nonlinear-least-squares for fitting pharmacokinetic (PK) models, highlighting some common difficulties in obtaining statistical estimates of non-identifiable parameters and use bootstrap confidence interval to quantify uncertainties.
Statistical estimation of parameters in physiologically based pharmacokinetic (PBPK) models is a relatively new area of research. Over the past decade or so PBPK models have become important and valuable tools in risk assessment as these models are used to describe the absorption, distribution, metabolism, and excretion of xenobiotics in a biological system such as the human or rat. Because these models incorporate information on biological processes, they are well equipped to describe the kinetic behaviors of chemicals and are useful for extrapolation across dose routes, between species, from high-to-low-doses, and across exposure scenarios.
A PBPK model has been developed based on published models in the literature to describe the absorption, distribution, metabolism, and excretion of Dioxin and dioxin like compounds (DLCs) in the rat. Data from the National Toxicology Program (NTP) two year experiment TR-526 is used to illustrate model fitting and statistical estimation of the parameters. Integrating statistical methods into risk assessments is the most efficient way to characterize the variation in parameter values. In this dissertation a Markov Chain Monte Carlo (MCMC) method is used to estimate select parameters of the system and to describe the variation of the select parameters.
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Systémy bezpečnosti a ochrany zdraví při práci - analýza bezpečnostních rizik / Occupational safety and health systems - safety risks analysisŠmejkal, Jakub January 2007 (has links)
The thesis deals with occupational safety and health systems at work. In theory is about risk assesment methods. The practical part of the thesis is concerned with methods application on my distinguished firm.
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Mapping dynamic exposure: constructing GIS models of spatiotemporal heterogeneity in artificial stream systemsWeighman, Kristi Kay 07 May 2019 (has links)
No description available.
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Distribution Parameters of Dendroctonus frontalis in a Georgia LandscapeChristel, Lynne M. January 2011 (has links)
A three-phase study was performed to examine abiotic and biotic metrics at southern pine beetle infestation sites in northern Georgia in 2002 to find early indicators that can be leveraged by forest managers to mitigate the effects of future outbreaks: creation of a 2003 Final Impact Map, determining if MODIS MOD13Q1 EVI 16-day image composites can distinguish differences in biomass indicators among healthy and infested loblolly pine and hardwood forests, and creation of an Infestation Risk Map derived from significant climate and physical variables at known infestation sites.Three land cover classification techniques (change vector analysis, enhanced wetness differencing index and standard land cover classification analysis of Landsat 5 TM) were compared to determine which would provide the best estimate of final infestation damage. Classification accuracy results indicated that the latter provided the most reliable site damage information and it became the reference map against which outbreak model results were compared.Using time series analysis of MODIS composites acquired March 2000 - December 2006 to measure 11 phenology metrics for infested and healthy loblolly and hardwood stands showed that the imagery differentiated between forest classes. Results indicated the lowest base vegetation biomass in 2001 for infested loblolly, relative to healthy loblolly, with many metrics trending towards hardwood values following infestation.Abiotic influences included those related to landscape position and climate. Statistical testing showed increased beetle success: 1) along ridge tops at maximum solar exposure, 2) in areas with canopy density>60%, 3) in areas experiencing cooler summers and warmer winters, and 4) where precipitation was significantly lower at infested sites in the 2 years preceding outbreak.The Infestation Risk Map was developed from significant physical and climate indicator variables using the fuzzy theory modeling approach. Comparison of model output to infestation sites resulted in Chi-squared and Cramér's V values of 55.4 and 0.16, respectively, indicating that infestation risk distributions strongly paralleled site infestation. Comparison of model output and low, medium and high infestation density clusters resulted in Chi-squared and Cramér's V values of 241.24 and 0.66, respectively, indicating a more substantive relationship between infestation density and risk classes.
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Ανάλυση κινδύνου σε φωτοβολταϊκά συστήματα λόγω πληγμάτων κεραυνούΜπουγιούκος, Παναγιώτης 19 October 2012 (has links)
Το θέμα της παρούσας διπλωματικής είναι η αντικεραυνική προστασία σε κατασκευές που περιέχουν φωτοβολταϊκές διατάξεις και η λήψη κατάλληλων μέτρων προστασίας ώστε το πλήγμα ενός κεραυνού να μην προκαλέσει ανθρώπινες ή οικονομικές και υλικές απώλειες. Στα πλαίσια αυτής της διπλωματικής εργασίας αναπτύχθηκε μια εφαρμογή υπολογισμού του κινδύνου μιας κατασκευής. Το περιβάλλον του προγράμματος είναι κατανοητό από τον χρήστη και απαλλαγμένο όσο κατέστη δυνατό από ανάγκη εισαγωγής αριθμητικών παραμέτρων που αφορούν σε τεχνικά χαρακτηριστικά. Το πρόγραμμα δίνει την δυνατότητα επιλογής στον χρήστη γενικών αλλά και ειδικών χαρακτηριστικών της κατασκευής και του συστήματος αντικεραυνικής προστασίας και εκτελεί πράξεις για τον υπολογισμό του κινδύνου με αντιστοίχιση των χαρακτηριστικών αυτών με αριθμητικές τιμές σύμφωνα με το πρότυπο IEC 62305.
Το πρώτο μέρος αποτελείται από μια απαραίτητη θεωρητική μελέτη και ορισμένες γενικές πληροφορίες για το φαινόμενο του κεραυνού.
Στο δεύτερο μέρος αναλύονται τα χαρακτηριστικά και οι προδιαγραφές που οφείλει να καλύπτει ένα σύστημα αντικεραυνικής προστασίας σύμφωνα με το πρότυπο IEC 62305-2 του οργανισμού IEC. Γίνεται ανάλυση όλων των παραγόντων που συντελούν στον υπολογισμό του κινδύνου , το πώς τα τεχνικά χαρακτηριστικά ενός συστήματος αντικεραυνικής προστασίας επηρεάζουν τους παράγοντες αυτούς καθώς και μια βήμα προς βήμα μέθοδος για τον υπολογισμό του κινδύνου. Με την ολοκλήρωση της μελέτης και την ανάλυση αυτή δίνονται τα αποτελέσματα περί επάρκειας ή μη του συστήματος αντικεραυνικής προστασίας . Σε περίπτωση αρνητικού πορίσματος ο εξοικειωμένος με το πρότυπο IEC 62305 χρήστης καλείται να μεταβάλει παραμέτρους του συστήματος αντικεραυνικής προστασίας και να προσθέσει νέα μέτρα προστασίας για την μείωση του κινδύνου σε ανεκτά επίπεδα. Για την λήψη μέτρων προστασίας προσφέρεται κατάλληλος αλγόριθμος ώστε να υπάρχει αποτελεσματική εφαρμογή τους και ικανοποιητική μείωση του κινδύνου.
Το τρίτο μέρος περιλαμβάνει μια αναλυτική παρουσίαση του προγράμματος με οδηγίες χρήσης και εξήγηση των βασικών λειτουργιών του. Στο μέρος αυτό ο χρήστης μπορεί να βρει αναλυτικές πληροφορίες για κάθε μεταβαλλόμενη παράμετρο που υπάρχει στις σελίδες εισαγωγής στοιχείων. Αφού ολοκληρωθεί η παρουσίαση του προγράμματος και όλων των σελίδων που αυτό περιέχει ακολουθεί ένα αναλυτικό παράδειγμα χρήσης του και σύγκριση των αποτελεσμάτων του με μια θεωρητική μελέτη για μια ρεαλιστική κατασκευή που περιέχει διατάξεις φωτοβολταϊκών στην οροφή. / The subject of this project is the protection against lightning in constructions that contain photovoltaic systems and also taking the necessary ways of protection, in order for the blow of lightning not to cause human or economical and material losses. Within this project ,an application which calculates the danger of one construction ,in an environment has developed. The environment of the program is understandable of its user and free as far as possible of need for introduction of arithmetical parameters that concern technical characteristics. The program gives the user the opportunity to choose among general and specific characteristics of the construction and the lightning protection system and also performs calculations in order to calculate the danger by matching these characteristics with arithmetical prices according to the standard IEC 62305.
The first part is consisted of a necessary theoretical study and some general information about the lightning phenomenon.
In the second part, the characteristics and the standards that a lightning protection system should cover according to the standard IEC 62305-2 of the organization IEC, are being analyzed. There is an analysis of all the factors that are contracting to the calculation of danger , about how the technical characteristics of a lightning system affect those factors and also , one step by step method in order to calculate danger. With the completion of the study and this analysis , the results about the adequacy or not of the lightning system . In the situation of a negative result , the familiar with the standard IEC 62305 user ,has the opportunity to change the lightning system’s parameters and to add new protection measures in order to decrease the danger in tolerable levels. When it comes to take protection measures, the most suitable algorithm is being offered in order to attain an effective application of them and a satisfying decrease of danger.
The third part ,contains a detailed feature of the program with use instructions and explanation of its basic operations. In this part, the user can find detailed information about each and every one changing parameter that exists in the pages that data have been introduced. When the feature of the program and all of its contained pages will come to the end , then it comes a detailed example of its use and comparison of its results by one theoretical study referring to a realistic construction that contains photovoltaic systems in its roof.
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Psykiatrisjuksköterskans arbeta med suicidala patienter / The psychiatric nurses´ work with suicidal patientsSturk, Maria, Persson, Dennis January 2018 (has links)
Cirka 800 000 människor världen över avslutade sina liv genom suicid 2014. En psykiatrisk diagnos är en vanligt förekommande bakomliggande orsak. De vanligaste diagnoserna är depression, bipolär sjukdom, post traumatiskt stressyndrom samt substansmissbruk. Tidigare suicidförsök är den enskilt största riskfaktorn för ett fullbordat suicid. Det är komplext att arbeta med suicidnära patienter i öppenvården och det ställs höga krav på specialistkompetens inom psykiatrisk omvårdnad och goda kunskaper kring det suicidpreventiva arbetet. Syftet med studien var att beskriva psykiatrisjuksköterskans erfarenhet av att bedöma suicidrisk på patienter på en vuxenpsykiatriskmottagning. En kvalitativ metod användes med induktiv ansats där fyra intervjuer med psykiatrisjuksköterskor genomfördes. I resultatet framkom att psykiatrisjuksköterskan dagligen möter och behandlar suicidnära patienter på en öppenvårdsmottagning. Resultatet visade att psykiatrisjuksköterskan trots år av erfarenhet upplevde arbetet med suicidnära patienter som komplext och ansvarsfullt. Det framkom att psykiatrisjuksköterskan arbetade självständigt och stod ofta ensam med att bedöma suicidrisken och vidta åtgärder. Psykiatrisjuksköterskan har en viktig del i det suicidpreventiva arbetet och behöver känna sig trygga och säkra i omvårdnaden kring suicidnära patienter och i att bedöma suicidrisken. Vidare forskning skulle kunna ge fördjupad kunskap om psykiatrisjuksköterskan roll och behov för att ge omvårdnad till suicidnära patienter.
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Development of Mechanically Stabilized Earth (MSE) Wall Inspection Plan and Procedure For Failure Mode Analysis and Risk AssesmentMaw, Ryan Bruce 01 May 2009 (has links)
A large component of the State of Utah's transportation network involves the use of MSE walls, which have proven useful in infrastructure for their reduced costs and footprint compared to other alternatives. As effective as MSE walls have been in responding to demands in transportation, they also have inherent challenges. For the majority of MSE walls the structure is limited in observation as structural components are buried as part of the soils mass. This inability to observe at can lead to the development of complex failure mechanisms, which can be difficult to assess and anticipate. As society becomes increasingly reliant on the transportation networks for goods, services, and security, properly understanding the potential failure mechanisms of MSE walls also increases in importance. This thesis discusses the development of an inspection procedure, data collection, geotechnical asset management database, and an evaluation of gathered information to be used in a reliability analysis of MSE walls for the State of Utah. The findings suggest areas of improvement in the design, specifications, maintenance, and further investigation of MSE walls.
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In situ performance and numerical analysis of lining systems for waste containmentZamara, Katarzyna A. January 2013 (has links)
Growing environmental awareness has led to developments within landfill engineering, increasing the amount of research with the aim of constructing safe, stable landfills with optimal geometry. EU member states are forced to improve waste disposal policies through directives (Council of the European Union 1999) enforced in member countries through local legislation (in the UK, The Landfill (England and Wales) Regulations 2002). This research focuses on several aspects of waste barrier in situ performance. A field study was conducted on a landfill side slope to investigate geosynthetics mechanical behaviour in service conditions and on a landfill capping to investigate capping geosynthetic drainage system performance in situ conditions and pore water distributions along the capping. Further site derived data were collected in order to validate numerical modelling approaches, to increase confidence in a design processes and to investigate mechanisms incorporated in the liner s performance. The side slope studies revealed an additional factor affecting lining components displacement along the slope: geomembrane and geotextile response to atmospheric conditions. The capping study allowed production of recommendations for future capping designs. These can be used to considerably enhance capping stability.
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Riziková analýza v projektech dopravních staveb / Risk Analysis in Transport Infrastructure ProjectsHašek, Jiří January 2019 (has links)
The subject of the master’s thesis is a risk analysis in transport infrastructure projects. In the theoretical part, I deal with public sector, life cycle of the project, evaluation of public projects, conception of risk, clasification of risk, risk analysis and valuation of the risk. In the practical section I process risk analysis of the project in transport infrastucture.
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Étude du rôle des émotions sur les traitements différentiels mis en œuvre par des pilotes d'avions lors de la gestion de situations à risques sur simulateur de vol / Review of role of emotions on differential processing implemented by pilots of aircraft in the management of risk situations in flight simulatorMegret, Lise 18 February 2016 (has links)
Cette recherche porte sur l’impact des émotions sur les réponses des pilotes d’avion dans la gestion de situations dynamiques et ambiguës. A l’inverse des théories selon lesquelles les émotions dégradent les performances des pilotes, nous défendons la thèse selon laquelle les processus émotionnels ont une fonction adaptative et vont donc favoriser des réponses appropriées à la situation. Afin de vérifier cette hypothèse, des pilotes volontaires sont mis en situation de devoir gérer une fuite d’essence sur un simulateur de vol. Nous avons construit un scénario réaliste d’une durée d’une heure. Les pilotes ne sont donc pas confrontés à un problème ponctuel, s’apparentant à une situation de résolution de problèmes, mais doivent traiter l’anomalie de consommation d’essence pendant toute la durée du vol simulé. Ils ont donc la possibilité, en cours du vol, de corriger des choix qu’ils jugent inadaptés. Le relevé des fréquences cardiaques de chaque pilote pendant leur vol nous permet de repérer les épisodes émotionnels. Nous montrons que loin de dégrader les réponses des pilotes, les émotions sont positivement liées à la fois à leur expertise et à leurs performances : les pilotes ayant mis en œuvre les décisions les plus adaptées à la situation sont aussi ceux qui ont ressenti le plus d’émotions lors de la découverte et du traitement de la fuite d’essence. / This research centers on the impact of emotions on a pilot who's dealing with dynamic and/or ambiguous situations. Contrary to theories that state pilots' performances are diminished by emotions, we believe that an emotional process actually has an adaptive function which subsequently helps give appropriate answers to a given situation. To verify this hypothesis, volunteer pilots are confronted with having to deal with a fuel leakage on a flight simulator. We have built a realistic 1h long scenario. The pilots are not faced with a punctual situation, akin to problem solving, but have to treat the fuel consumption anomaly during the whole length of the flight simulation. Consequently they have the possibility, in flight, to recover inappropriate responses. The readings of the pilots' heartbeat allows us to identify the emotional episodes. We show that, far from diminishing the pilots' responses, emotions are linked positively not only to the pilots' expertise, but also their performances: The pilots who have devised the best responses to the situation are also those who've registered the most emotions whilst discovering and treating the fuel leakage.
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