在本文中，分別就四種不同參數組合（包括六個模式）的二維交叉實驗設計，採用一般線性模式法及二樣本t檢定法予以分析，並探討模式間與分析方法間的異同。此外，在二維重覆測量交叉實驗設計方面，我們也分別以單變量分裂區集變異數分析法及多變量變異數分析法進行探討。 / Four possible parametrizations ( including six models ) are considered in this study to clearify some ambigous issues related to a 2*2 cross-over design. Each model is analyzed using both the GLM procedure and two-sample t test. In addition, we also discuss issues related to the 2*2 repeated measurements cross-over design by using the univariate split-plot and multivariate analysis of variance techniques.

No description available.

Bioequivalence determines if two drugs are alike. The three kinds of bioequivalence are Average, Population, and Individual Bioequivalence. These Bioequivalence criteria can be evaluated using aggregate and disaggregate methods. Considerable work assessing bioequivalence in a frequentist method exists, but the advantages of Bayesian methods for Bioequivalence have been recently explored. Variance parameters are essential to any of theses existing Bayesian Bioequivalence metrics. Usually, the prior distributions for model parameters use either informative priors or vague priors. The Bioequivalence inference may be sensitive to the prior distribution on the variances. Recently, there have been questions about the routine use of inverse gamma priors for variance parameters. In this paper we examine the effect that changing the prior distribution of the variance parameters has on Bayesian models for assessing Bioequivalence and the carry-over effect. We explore our method with some real data sets from the FDA.

Avian cholera, caused by infection with Pasteurella multocida, is an important infectious disease of wild birds in North America Since it was first confirmed in 2005, annual outbreaks of avian cholera have had a dramatic effect on common eiders on East Bay Island, Nunavut, one of the largest breeding colonies of northern common eiders (Somateria mollissima borealis) in the eastern Arctic. I investigated potential avian and environmental reservoirs of P. multocida on East Bay Island and other locations in the eastern Canadian Arctic by collecting cloacal and oral swabs from live or harvested, apparently healthy, common eiders, lesser snow geese, Ross’s geese, king eiders, herring gulls, and snow buntings. Water and sediment from ponds on East Bay Island were sampled before and during outbreaks. Avian and environmental samples were tested using a real-time polymerase chain reaction (PCR) assay to detect P. multocida. PCR positive birds were found in every species except for snow buntings, and PCR positive common eiders were found in most locations, supporting the hypothesis that apparently healthy wild birds can act as a reservoir for avian cholera. In all years, P. multocida DNA was detected in ponds both before and after the avian cholera outbreak began each year, suggesting that the environment also plays a role in outbreak dynamics. Contrary to our expectations, model results revealed that ponds were generally more likely to be positive earlier in the season, before the outbreaks began. Whereas average air temperature at the beginning of the breeding season was not an important predictor for detecting P. multocida in ponds, eiders were more likely to be PCR positive under cooler conditions, pointing to an important link between disease and weather. Potential origins of P. multocida causing avian cholera in Arctic eider colonies were investigated by comparing eastern Arctic isolates of P. multocida to isolates from wild birds across Canada, and the central flyway in the United States. Using repetitive extragenic palindromic-PCR (REP-PCR) and multi-locus sequence typing (MLST), we detected a low degree of genetic diversity among isolates, and P. multocida genotypes were correlated with somatic serotype. Isolates from East Bay Island were distinct from P. multocida from eider colonies in the St. Lawrence Estuary, Quebec, however, East Bay Island isolates were indistinguishable from isolates collected from a 2007 pelagic avian cholera outbreak on the east coast of Canada. Isolates from East Bay Island and Nunavik shared sequence types, indicating possible transmission of isolates among eider colonies in the eastern Arctic. Previously, feather corticosterone in eiders was found to be significantly associated with environmental temperature during the moulting period. In my study, path analysis revealed that environmental conditions experienced during the moulting period had direct impacts on arrival date and pre-breeding body condition of common eiders during the subsequent breeding period on East Bay Island, with indirect impacts on both reproductive success and survival. Higher temperatures experienced during the fall moulting period appear to impose significant costs to eiders, with subsequent carry-over effects on both survival and reproduction many months later during avian cholera outbreaks. This thesis describes several important features of the host, agent and environmental dynamics of avian cholera in North America with a particular focus on the disease in the eastern Canadian Arctic. Continued exploration of infectious wildlife disease dynamics is needed to better predict, detect, manage, and mitigate disease emergence that can threaten human and animal health and species conservation.

The increase in competition amongst companies that produce complex or large product portfolios has created a need to utilise modularity strategies not only to flexibly manage technical complexity in a costeffective manner but also for visual appearance. This research aims to understand how the visual appearance of products is affected by modular product development strategies. Specifically, the aim is to understand how such strategies induce constraints and generate possibilities for management of visual appearance in the design process. Five studies have been conducted during the course of this licentiate thesis. Two were conducted with professionals and students in design, while the remaining three are theoretical studies based on findings in the literature, theory building, and experimental research. The goal has been to investigate how designers work when they are put to the task of changing and developing the designs of complex products that are part of a portfolio. The challenge has been to study what suitable strategies exist that manage complex products and product brands, then investigate how these influence designers’ practices. The first study examined how coherence towards a product category influences the design of new products. The outcome of the study was a method to explore visual coherence and diversity in the appearance of a product category. The remaining four studies investigated how modularity, brand management and the redesign of product portfolios influence a design process. The second study described a design phenomenon known as aesthetic flexibility, which was further explored in studies three and five. The outcome from these studies was a proposal for four aesthetic flexibility strategies. The fourth study investigated in what way portfolio extension strategies found in brand management and design research are related, and how such strategies influence aesthetic flexibility. The results from study four were illustrated as a model. The main contribution of this work is the phenomenon of ‘aesthetic flexibility’, which helps understand the factors that influence designers when working with branded modular products. Understanding visual flexibility serves as a starting point in further investigations of how different development strategies affect the possibilities for visual product design. The findings of this work serve to illustrate and explain a complex and multi-facetted design phenomenon which many designers manage more or less intuitively today, thus advancing academics’, teachers’ and professional designers’ understanding of the field.

No description available.

Two studies were conducted to determine the effect of panelist participation frequency and specific aspects of questionnaire design on overall acceptance scoring in consumer central location tests. Regarding participation frequency, research subjects who participate frequently in some survey types are known to provide responses that differ from subjects who participate less frequently, known as panel conditioning. With respect to questionnaire design, overall acceptance (OA) question placement and usage of pre-evaluation instructions (PEI) in questionnaires for food sensory analysis may bias consumers' scores via carry-over effects. To investigate these concerns, data from consumer sensory panels previously conducted at a central location, spanning 11 years and covering a broad range of food product categories, was extracted, compiled, and analyzed. For the first study, data was analyzed to determine evidence of panel conditioning by measuring the effect of participation frequency on mean consumer OA scoring among frequent, moderate, and infrequent participants. Practical significance and occurrence of panel conditioning, defined as mean scoring differences of ≥ 0.50 on a discrete 9-point scale hedonic point, were examined. Results indicate that for overall acceptance, in general, mean scoring differences were not practically significant and did not signify occurrence of panel conditioning. For the second study, OA question placement was studied with categories designated as first (the first evaluation question following demographic questions), after non-gustation questions (immediately following questions that do not require panelists to taste the product), and later (following all other hedonic and just-about-right questions, but occasionally before ranking, open-ended comments, and/or intent to purchase questions). Additionally, each panel was categorized as having or not having PEI in the questionnaire; PEI are instructions that appear immediately before the first evaluation question and show panelists all attributes they will evaluate prior to receiving test samples. Post-panel surveys were administered regarding the self-reported effect of PEI on panelists' evaluation experience. OA scores were analyzed and compared (1) between OA question placement categories and (2) between panels with and without PEI. For most product categories, OA scores tended to be lower when asked later in the questionnaire, suggesting evidence of a carry-over effect. Usage of PEI increased OA scores by 0.10 of a 9-point hedonic scale point, which is not practically significant. Post-panel survey data showed that presence of PEI typically improved the panelists' experience. Using PEI does not appear to introduce a meaningful carry-over effect.

No description available.

Kokzidiostatika werden in der Kleintiermast als Futtermittelzusatzstoffe zur Vorbeugung der Kokzidiose eingesetzt. Die Verwendung der Wirkstoffe ist in der Europäischen Union gesetzlich geregelt und unterliegt der amtlichen Lebens- und Futtermittelkontrolle. In der vorliegenden Arbeit wurden Methoden zur flüssigchromatographisch tandem-massen¬spektro¬metrischen (LC-MS/MS-) Bestimmung von Kokzidiostatika in Futtermitteln und in Ei entwickelt. Durch Bestandteile des Probenmaterials traten Störungen des Analytsignals auf. Die Untersuchung solcher Matrixeffekte ist in der pharmazeutischen und der Pestizidanalytik üblich. Zu Matrixeffekten bei der LC-MS/MS-Analytik in Futtermitteln gibt es kaum Daten. Ein Schwerpunkt dieser Arbeit war daher die Untersuchung der Einflussfaktoren auf Matrixeffekte bei der Analyse von Kokzidiostatika. Aufgrund der gewonnenen Erkenntnisse wurde eine Methode zur Bestimmung von Verschleppungen von Kokzidiostatika in Futtermittel für Nichtzieltierarten entwickelt und validiert. Weitere LC-MS/MS-Methoden wurden zur Bestimmung Maduramicins in Futtermittel, Eiweiß und Eigelb optimiert. Diese wurden zur wurden zur Untersuchung des Übergangs des Kokzidiostatikums aus dem Futtermittel in das Ei benötigt. Dazu wurde eine Fütterungsstudie mit Legehennen durchgeführt. Futtermittel mit drei Konzentrationen von Maduramicin bis zum Höchstgehalt in Futtermittel für Nichtzieltierarten wurden hergestellt und je einer Gruppe von Legehennen verabreicht. Das aufgenommene Maduramicin ging ausschließlich ins Eigelb über, es ergab sich eine Carry-over-Rate von 8 %. Der für Eier festgelegte Höchstgehalt von 2 µg/kg wurde überschritten, obwohl die Konzentrationen Maduramicins in den verfütterten Futtermitteln unterhalb des Höchstgehaltes für Futtermittel lagen. Als Folge dieser Ergebnisse wurde der Maduramicin-Höchstgehalt in Ei auf 12 µg/kg angepasst. Der in Verordnung (EG) Nr. 124/2009 festgelegte Höchstgehalt wurde durch die Verordnung (EU) 610/2012 geändert. / Prevention of coccidosis by anticoccidial feed additives is of great economic importance in poultry farming. Application of these substances is regulated by European law and is a matter of official feed and food control requiring appropriate determination methods for coccidiostats. In this study, liquid chromatographic tandem mass spectrometric (LC-MS/MS-) methods for the quantification of coccidiostats in feed and eggs were developed. The influence of the sample material resulted in poor method performance. These matrix effects are intensively investigated in other analytical fields like drug or pesticide analysis. In contrast, there are limited data concerning matrix effects in LC-MS/MS analysis in feedingstuffs. This study therefore focussed on the systematic investigation of factors influencing matrix effects during analysis of coccidiostats. The findings were implemented in the development and validation of a method for the determination of cross-contamination levels of authorized coccidiostats in feed for non-target animals. This method was optimized for the determination of the anticoccidial feed additive maduramicin in feed, egg white, and egg yolk for a carry-over study. By means of the conducted feeding trial with laying hens the carry-over of maduramicin from feed into eggs was comprehensively characterized. Three feedingstuffs containing different levels of maduramicin up to the maximum tolerable level in non-target animal feed were prepared and fed to groups of ten laying hens. Maduramicin is exclusively transferred into egg yolk, and a carry-over rate into whole eggs of 8 % was calculated. Although the applied diets were in compliance with the maximum level in feed, resulting concentrations in whole eggs exceeded the maximum level in eggs. As a consequence of these findings, the maximum permitted level of maduramicin in eggs was adapted to 12 µg/kg. The maximum level assigned by Regulation (EC) No. 124/2009 was amended in Regulation (EU) 610/2012.

La tesi è divisa in quattro manoscritti. Lo scopo è lo studio di tre aspetti, come casi-studio indipendenti, all’interno della gestione della catena alimentare dai mangimi al latte. Il primo manoscritto riguarda la fortificazione del latte bovino con iodio e selenio allo scopo di migliorare la qualità del latte e dei suoi derivati; il secondo riguarda la contaminzione dei mangimi con melamina come fattore di rischio per l’industria lattiero-casearia e la salute pubblica. Gli ultimi due lavori sono corollari alla qualità del latte derivante dallo iodio: ovvero un confronto analitico tra procedure di determinazione dello iodio in latte crudo, e uno studio di speciazione dello iodio inorganico nel latte crudo fortificato. Il primo lavoro offre informazioni per meglio comprendere i fattori coinvolti nel miglioramento della concentrazione dello iodio e del selenio nel latte a seguito di una fortificazione della dieta animale. Riguardo la melamina, lo studio conferma il passaggio di essa dai mangimi al latte e la sua rapida escrezione anche a livelli bassi di ingestione da parte dell’animale; uno scarso passaggio dal latte al formaggio. Il terzo lavoro mostra che, per analisi dello iodio con ICP-MS, l’estrazione dell’elemento con soluzione d’ammoniaca è una valida alternativa al metodo ufficiale con TMAH. La speciazione dello iodio inorganico nel latte scremato è un’operazione possibile utilizzando delle diluizioni con soluzione d’ammoniaca (quarto manoscritto). / The thesis is divided into 4 manuscripts. The aim is to study three aspects, as independent case studies, within the quality management of feed-for-food system. The first manuscript is about the fortification of feeds with iodine and selenium to improve the quality of cow’s milk and derivatives; the second one investigates the contamination of feeds with melamine as risk factor for dairy industries and human health. The last two works are corollaries to the iodine-linked quality of milk: i.e. a comparison between analytical procedures for the determination of iodine in raw milk, and a speciation study of iodine in fortified milk. The first work helps to better understand factors involved in improvement of milk iodine and selenium concentration and CO following supplementation with inorganic sources. Regarding melamine, the study confirmed the pathway for its transmission from feed to milk and its rapid excretion, also at a very low level of melamine ingestion by cows; and a low transfer from milk to cheese. The third study shows that the ammonia extraction of iodine is a valid alternative to the official method with TMAH for iodine determination in milk, by using ICP-MS. The speciation of inorganic iodine in skimmed milk is feasible by using ammonia dilution (fourth manuscript).