nÃo hà / O trabalho tem como objetivo avaliar a dinÃmica da evoluÃÃo no valor das empresas, descrita pelas variÃveis Equity e Entreprise Value, das Companhias de capital aberto do setor de mineraÃÃo e siderurgia listadas na BOVESPA, entre janeiro de 2002 a dezembro de 2012, o qual contribui com a literatura ao utilizar como ferramenta de anÃlise um modelo autoregressivo com valor limite endÃgeno, e ajuda a captar se existe mudanÃa de padrÃo do valor das empresas ante as alteraÃÃes no cenÃrio e na polÃtica econÃmica, para prever um valor mais justo das empresas no futuro, uma vez que sua utilizaÃÃo à de extrema importÃncia para tomada de decisÃes empresariais e outras finalidades. Indicadores quantitativos para essas duas variÃveis foram calculados e a metodologia permitiu investigar, simultaneamente, a linearidade e estacionaridade de suas trajetÃrias. Os resultados mostraram, atravÃs das variÃveis selecionadas, ocorreram trÃs situaÃÃes diferentes entre as empresas: i) dinÃmicas lineares, nÃo estacionaridade para o Equity e Enterprise Value, atinge a Ferbasa e Equity a Vale; porÃm o Enterprise Value da Vale segue uma dinÃmica estacionÃria; ii) dinÃmicas nÃo lineares, o que segue uma mudanÃa de padrÃo nas variÃveis selecionadas, para Equity e o Enterprise Value, adicionalmente, nÃo estacionaridade nos dois regimes, para o Equity e Enterprise Value, atingem a Gerdau e Usiminas, e iii) dinÃmica nÃo linear para o Equity e dinÃmica linear para o Enterprise Value para a companhia SiderÃrgica Nacional, que adicionalmente, apresenta para o Equity com raiz unitÃria parcial e globalmente estacionÃria, e para o Enterprise Value apresenta nÃo estacionaridade. / The study aims to evaluate the dynamics of evolution of corporate value; described by the variables Equity and Enterprise Value, the publicly traded companies in the mining and steel sector listed on the BOVESPA, between January 2002 and December 2012, which contributes with to the literature to use as a tool to analyze an autoregressive model with endogenous threshold value, and helps to capture changes on the default value of the companies placed on our current scenario and economic policy, to provide a more fair value of companies in the future since their use is of utmost importance to business decision-making and other purposes. Quantitative indicators for these two variables were calculated and the methodology allowed to investigate both the linearity and stationarity of their trajectories. The results showed, through the selected variables, three different situations among the selected companies: i) linear dynamics, non-stationarity for Equity and Enterprise Value, reaches Ferbasa and Equity the Vale; but the Enterprise Value of the Vale follows a stationary dynamics;ii) non-linear dynamics, which follows a pattern change in selected variables for Equity and Enterprise Value additionally non-stationarity in the two regimes, for Equity and Enterprise Value reaches Gerdau and Usiminas; and iii) non-linear dynamic for Equity and linear for the Enterprise Value for the National Steel Company, which additionally presents for Equity partial and globally stationary unit root, dynamic and Enterprise Value presents non-stationarity.

The aim of this diploma thesis is the valuation of the company Daruma spol. s r.o through determining the threshold values for the seller and buyer in the case that current owners would consider the sale of the company. The valuation date is 31st December 2015. The first part of the diploma thesis is focused on the theoretical information about valuation of small and medium enterprise. The second part is devoted to the valuation as such, the threshold values are calculated and then the potential arbitration value under the terms of the transaction is estimated.

A universal, scalable quantum computer will require the use of quantum error correction in order to achieve fault tolerance. The assessment and comparison of error-correcting strategies is performed by classical simulation. However, due to the prohibitive exponential scaling of general quantum circuits, simulations are restrained to specific subsets of quantum operations. This creates a gap between accuracy and efficiency which is particularly problematic when modeling noise, because most realistic noise models are not efficiently simulable on a classical computer. We have introduced extensions to the Pauli channel, the traditional error channel employed to model noise in simulations of quantum circuits. These expanded error channels are still computationally tractable to simulate, but result in more accurate approximations to realistic error channels at the single qubit level. Using the Steane [[7,1,3]] code, we have also investigated the behavior of these expanded channels at the logical error-corrected level. We have found that it depends strongly on whether the error is incoherent or coherent. In general, the Pauli channel will be an excellent approximation to incoherent channels, but an unsatisfactory one for coherent channels, especially because it severely underestimates the magnitude of the error. Finally, we also studied the honesty and accuracy of the expanded channels at the logical level. Our results suggest that these measures can be employed to generate lower and upper bounds to a quantum code's threshold under the influence of a specific error channel.

本研究使用含外生多變數為門檻值之TAR模型，分析並預測103年到105年的台股指數。建構多變量之門檻自迴歸模式較傳統以時變或自變數自動控制值更能反映出時間數列結構改變的過程與趨勢。這對於模式分析與預測有更優的解釋能力。且含外生多變數為門檻值之多變量門檻模式的可適用範圍很廣，尤其是當時間數列中的結構改變的現象，來自於外在多個變數衝擊，或非線性現象。此時加入多個外生變數作為考量，更能精準分析資料和做預測。我們以台股指數為例，實證結果顯示，我們所提出之模型，較傳統預測方法有更高之準確度。 / In this research, we use exogenous multi-variables as threshold values to construct a threshold autoregressive model in order to analysis and forecast TAIEX index between 103 years and 105 years. Constructing the threshold autoregressive model with multi-variables is better to reflect the process and trend of the change in time series structure than traditional model. This provides the better explanatory ability for model analysis and forecast. Also, the threshold autoregressive model with multi-variables containing exogenous multi-variables can apply more range, especially, as the structure change in time series due to the exogenous multi-variables shock. Through adding more exogenous variables, one can analyze data and forecast accurately. In this paper, the empirical results of TAIEX index shows that the threshold autoregressive model with multi-variables containing exogenous multi-variables is more precise than the traditional way.

Ett av EU:s främsta syfte är att skapa fri rörelse av kapital. Genom att kontinuerligt reducera handelshinder strävar de efter att skapa lika förutsättningar mellan medlemsstaterna. I och med den globalisering som skett och fortfarande sker blir det allt mer vanligt förekommande att svenska bolag konkurrerar och samverkar med andra europeiska bolag. Mycket har hänt på redovisnings- och revisionsområdet det senaste decenniet vilket har gjort att den svenska lagstiftningen delvis har skrivits om och anpassats efter EG:s direktiv. Internationella redovisningsstandarder har fått stort inflytande på framförallt de stora svenska bolagen. Dessa standarder var ursprungligen anpassade för börsnoterade bolag vilket har medfört att mindre svenska bolag under de senaste åren ålagts orimligt omfattande redovisningsskyldigheter. I november 2004 presenterade Justitiedepartementet en promemoria vilken bland annat avsåg förenklade redovisningsregler. Deras bedömning var att de två gränsvärdena som i dag benämns i ÅRL och BFN bör samordnas till ett gemensamt. Motiveringen till detta var att små och medelstora bolag i större utsträckning bör undantas från betungade regler gällande bokföring och bokslut. Under vintern 2005/2006 har en lag-rådsremiss och en proposition offentliggjorts där remissinstanserna BFN, FAR, SRS m.fl. givit uttryck för sina åsikter. Detta resulterade i att delvärdena i den samordnade gränsvärdet fastställdes till 50 anställda, 25 miljoner kronor i balansomslutning samt 50 miljoner kronor i totala intäkter. Syftet med denna uppsats är att utreda vilka konsekvenser detta får för de små och medelstora bolagen i Sverige. Undersökningen har genomförts ur två perspektiv, dels för att återspegla de generella konsekvenserna med harmoniseringen och dels vilka konsekvenser det samordnade gränsvärdet blir redovisningsmässigt. För att uppnå syftet genomfördes fyra expertintervjuer. Resultatet av dessa var att redovisningsprinciperna blir något förenklade men eftersom förslaget ej trätt i laga kraft ännu är det svårt att peka på konkreta konsekvenser. Dock kan man förutse vissa skillnader avseende bland annat delårsrapportering, balansering av egenupparbetade immateriella anläggningstillgångar och restvärdesavskrivningar. Efter att ha tagit del av respondenternas svar samt vad som sägs i lagrådsremissen kan vi konstatera att förändringarna på flera plan går mot att uppgifter ej är lagstadgade utan snarare styrs av intressenterna. Delårsrapporter är en sådan uppgift, då det ej åligger revisionsplikt på dem ser vi det som en naturlig utveckling att ta bort den lagstadgade uppgiftsskyldigheten för K3 – bolagen. Vidare diskuteras huruvida K2 – blocket kommer innefatta bolag med allt för stora skillna-der i omfattning av verksamhet och hur detta skulle kunna undvikas. Vi föreslår en höjning av K1-blocket från tre till fem miljoner kronor i nettoomsättning där aktiebolag ej ska in-kluderas. Anledningen till detta är att få bort de minsta bolagen ur K2 – blocket genom att fler bolag bör överväga alternativa bolagsformer för att undvika allt för omfattande redovisningsmässiga skyldigheter. Från och med den första januari 2007 träder ett nytt regelverk beträffande redovisningsprinciper i kraft i Sverige. Regelverket är delvis utformat efter EU:s redovisningsdirektiv och är ett steg i harmoniseringen. De bolag som vid årsskiftet skall till-lämpa det nya regelverket är de som ej överskrider det nya 50/25/50 - värdet, dvs. K1 och K2 - bolagen. För större bolag, K3 samt K4, kommer reglerna träda i kraft med det räkenskapsår som påbörjas första januari 2010. / One of EU:s primary purposes is to create freedom of movement for capital. Through continuous reducing of trade obstacles they strive to create equal conditions between the member nations. Through the globalization that has taken place and still is taking place it is increasingly common for Swedish companies to compete and cooperate with European companies. A lot has happened in the accounting and auditor area during the last decade which has forced the Swedish legislation partly to be rewritten and adjusted to EG directives. International accounting standards has had a great deal of influence on the major Swedish companies. These standards are originally adapted for stock exchange introduced companies which in the last couple of years have resulted in unreasonable extensive accounting obligations for smaller Swedish companies. In November 2004 the ministry of Justice presented a memorandum which among other things intended to simplify accounting obligations. Their assessment was that the two threshold values that today are termed in ÅRL and BFN should be coordinated into one common threshold. The motivation for this was that small and medium companies in a greater extent should be able to make exceptions from onerous rules concerning bookkeeping and closure. During the winter 2005/2006 a referral and a government bill was made public where BFN, FAR and SRS gave expression of their opinions. This resulted in that the partial value in the coordinated threshold was established to 50 employees, 25 million in balanced turnover and 50 million in total reve-nue. The purpose of this paper is to investigate which consequences this will have to the small and medium companies in Sweden. The investigation has been carried out through two perspectives, one to reflect the general consequences with the harmonious and also which consequences the coordinated threshold value will bring to the accounts. To reach the pur-pose four expert interviews were carried out. The conclusion of these interviews was that the accounting standards will be a bit more simplified but since the proposal has not yet become legally binding it is hard to point to concrete consequences. We can still predict to a certain extend with respect to among other things; quarterly reports, balancing of non-material internally acquired inventory and depreciation of residual values. After studying the respondents’ answers and the referral we can establish that the changes on several levels will progress to the point of information not being statutory but rather controlled by interest organisations. Quarterly reports are that sort of task, when it is not mandatory audit on this sort of report we can not see any reason not to remove the statu-tory information obligation for the K – 3 companies. The thesis further discusses whether the K2 – block will include companies with much too large differences in the extent of activity and how this should be avoided. We suggest a raise of the K-1 block from three too five million in net turnover, where joint-stock companies not will be included. The reason for this is to get rid of the smallest companies in the K-2 block; more companies should consider alternative company forms to avoid all too extensive accounting obligations. Starting on the first of January 2007, the new regulation concerning accounting principles will take effect in Sweden. The regulations are partly designed according to the EU:s ac-counting directives and are a step in the harmonious direction. Those companies who will apply the new regulation at the turn of the year are those which do not exceed the new 50/25/50 value i.e. K-1 and K-2 companies. For the bigger companies, K-3 and K-4, the new regulation takes effect with the accounting year that starts on the first of January 2010.

<p>Ett av EU:s främsta syfte är att skapa fri rörelse av kapital. Genom att kontinuerligt reducera handelshinder strävar de efter att skapa lika förutsättningar mellan medlemsstaterna. I och med den globalisering som skett och fortfarande sker blir det allt mer vanligt förekommande att svenska bolag konkurrerar och samverkar med andra europeiska bolag.</p><p>Mycket har hänt på redovisnings- och revisionsområdet det senaste decenniet vilket har gjort att den svenska lagstiftningen delvis har skrivits om och anpassats efter EG:s direktiv. Internationella redovisningsstandarder har fått stort inflytande på framförallt de stora svenska bolagen. Dessa standarder var ursprungligen anpassade för börsnoterade bolag vilket har medfört att mindre svenska bolag under de senaste åren ålagts orimligt omfattande redovisningsskyldigheter. I november 2004 presenterade Justitiedepartementet en promemoria vilken bland annat avsåg förenklade redovisningsregler. Deras bedömning var att de två gränsvärdena som i dag benämns i ÅRL och BFN bör samordnas till ett gemensamt. Motiveringen till detta var att små och medelstora bolag i större utsträckning bör undantas från betungade regler gällande bokföring och bokslut. Under vintern 2005/2006 har en lag-rådsremiss och en proposition offentliggjorts där remissinstanserna BFN, FAR, SRS m.fl. givit uttryck för sina åsikter. Detta resulterade i att delvärdena i den samordnade gränsvärdet fastställdes till 50 anställda, 25 miljoner kronor i balansomslutning samt 50 miljoner kronor i totala intäkter.</p><p>Syftet med denna uppsats är att utreda vilka konsekvenser detta får för de små och medelstora bolagen i Sverige. Undersökningen har genomförts ur två perspektiv, dels för att återspegla de generella konsekvenserna med harmoniseringen och dels vilka konsekvenser det samordnade gränsvärdet blir redovisningsmässigt. För att uppnå syftet genomfördes fyra expertintervjuer. Resultatet av dessa var att redovisningsprinciperna blir något förenklade men eftersom förslaget ej trätt i laga kraft ännu är det svårt att peka på konkreta konsekvenser. Dock kan man förutse vissa skillnader avseende bland annat delårsrapportering, balansering av egenupparbetade immateriella anläggningstillgångar och restvärdesavskrivningar.</p><p>Efter att ha tagit del av respondenternas svar samt vad som sägs i lagrådsremissen kan vi konstatera att förändringarna på flera plan går mot att uppgifter ej är lagstadgade utan snarare styrs av intressenterna. Delårsrapporter är en sådan uppgift, då det ej åligger revisionsplikt på dem ser vi det som en naturlig utveckling att ta bort den lagstadgade uppgiftsskyldigheten för K3 – bolagen.</p><p>Vidare diskuteras huruvida K2 – blocket kommer innefatta bolag med allt för stora skillna-der i omfattning av verksamhet och hur detta skulle kunna undvikas. Vi föreslår en höjning av K1-blocket från tre till fem miljoner kronor i nettoomsättning där aktiebolag ej ska in-kluderas. Anledningen till detta är att få bort de minsta bolagen ur K2 – blocket genom att fler bolag bör överväga alternativa bolagsformer för att undvika allt för omfattande redovisningsmässiga skyldigheter.</p><p>Från och med den första januari 2007 träder ett nytt regelverk beträffande redovisningsprinciper i kraft i Sverige. Regelverket är delvis utformat efter EU:s redovisningsdirektiv och är ett steg i harmoniseringen. De bolag som vid årsskiftet skall till-lämpa det nya regelverket är de som ej överskrider det nya 50/25/50 - värdet, dvs. K1 och K2 - bolagen. För större bolag, K3 samt K4, kommer reglerna träda i kraft med det räkenskapsår som påbörjas första januari 2010.</p> / <p>One of EU:s primary purposes is to create freedom of movement for capital. Through continuous reducing of trade obstacles they strive to create equal conditions between the member nations. Through the globalization that has taken place and still is taking place it is increasingly common for Swedish companies to compete and cooperate with European companies.</p><p>A lot has happened in the accounting and auditor area during the last decade which has forced the Swedish legislation partly to be rewritten and adjusted to EG directives. International accounting standards has had a great deal of influence on the major Swedish companies. These standards are originally adapted for stock exchange introduced companies which in the last couple of years have resulted in unreasonable extensive accounting obligations for smaller Swedish companies. In November 2004 the ministry of Justice presented a memorandum which among other things intended to simplify accounting obligations. Their assessment was that the two threshold values that today are termed in ÅRL and BFN should be coordinated into one common threshold. The motivation for this was that small and medium companies in a greater extent should be able to make exceptions from onerous rules concerning bookkeeping and closure. During the winter 2005/2006 a referral and a government bill was made public where BFN, FAR and SRS gave expression of their opinions. This resulted in that the partial value in the coordinated threshold was established to 50 employees, 25 million in balanced turnover and 50 million in total reve-nue.</p><p>The purpose of this paper is to investigate which consequences this will have to the small and medium companies in Sweden. The investigation has been carried out through two perspectives, one to reflect the general consequences with the harmonious and also which consequences the coordinated threshold value will bring to the accounts. To reach the pur-pose four expert interviews were carried out. The conclusion of these interviews was that the accounting standards will be a bit more simplified but since the proposal has not yet become legally binding it is hard to point to concrete consequences. We can still predict to a certain extend with respect to among other things; quarterly reports, balancing of non-material internally acquired inventory and depreciation of residual values.</p><p>After studying the respondents’ answers and the referral we can establish that the changes on several levels will progress to the point of information not being statutory but rather controlled by interest organisations. Quarterly reports are that sort of task, when it is not mandatory audit on this sort of report we can not see any reason not to remove the statu-tory information obligation for the K – 3 companies.</p><p>The thesis further discusses whether the K2 – block will include companies with much too large differences in the extent of activity and how this should be avoided. We suggest a raise of the K-1 block from three too five million in net turnover, where joint-stock companies not will be included. The reason for this is to get rid of the smallest companies in the K-2 block; more companies should consider alternative company forms to avoid all too extensive accounting obligations.</p><p>Starting on the first of January 2007, the new regulation concerning accounting principles will take effect in Sweden. The regulations are partly designed according to the EU:s ac-counting directives and are a step in the harmonious direction. Those companies who will apply the new regulation at the turn of the year are those which do not exceed the new 50/25/50 value i.e. K-1 and K-2 companies. For the bigger companies, K-3 and K-4, the new regulation takes effect with the accounting year that starts on the first of January 2010.</p>

L'objectif principal de cette thèse est d'étudier la valeur pronostique de la qualité de vie (QdV) en cancérologie etd'explorer son utilité tant pour la pratique clinique que pour la planification des essais.Pour ce faire, nous évaluerons la significativité statistique et clinique de rapport d'un modèle de prédiction composé defacteurs cliniques et de la Qdv par rapport à un modèle de prédiction composé uniquement de facteurs cliniques.La validation statistique et clinique de cette plus-value de la Qdv en oncologie, permettrait de construire des index plusprécis en termes de pronostic vital, et mieux adapter les traitements. En fonction de sa valeur pronostic, la Qdv pourraitservir de critère de stratification dans les essais randomisés en oncologie.Pour les différentes localisations et le stade concernés, la recherche des facteurs pronostics sera réalisée selon lesrecommandations publiées dans la littérature. La procédure suivante sera utilisée :> Sélection des facteurs pronostics par un modèle univarié.> Construction d'un modèle multivarié par sélection « forward », « backward » ou « stepwise » en respectant aumieux la « règle de 10 événements par variable ».> Si existence de scores pronostics étudier l'apport de la Qdv à ces scores.> Vérifications à posteriori des hypothèses du modèle.> Mesure de la concordance entre les valeurs prédites et les valeurs observées à l'aided'indicateurs comme le C-index d'Harell, la statistique de Schemper, le NR1 (Net Reclassification Improvement) et l'IDI (Integrated Discrimation Improvement) de d'Agostino. Analyse de sensibilité par rapport aux données manquantes dans les différentes dimensions de la qualité de vie.Validation interne et/ou externe du modèle. Recherche de valeurs seuil pour les différents scores de qualité de vie dans le but d'une meilleure applicationclinique.Trois localisations seront étudiées : Carcinome hépatocellulaire en situation palliative. Cancer du pancréas métastatique. Cancer colorectal métastatique / The primary objective of this thesis is to evaluate the added prognostic value of health-related quality of life (QoL) inoncology and to explore ils utility for routine clinical practice as well as for design of clinical trials.In a methodological point of view, we will fïrst compare statistical and clinical performances of a model based onclinico-biological variables and a model based on clinico-biological variables and QoL scores.After validation of ils prognostic value, optimal cut-off points for QoL scores will be explored and revised prognosticclassifications including QoL measures will be built. QoL could then be used to guide treatment assignment and asinclusion/exclusion criteria or as stratification criteria in randomized clinical trials.For the different types of cancer, the validation of the prognostic value of QoL for advanced cancer patients will beperformed according to standard recommendations. The following steps will be performed:> Selection of prognostic factors based on univariable Cox models.> Multivariable Cox models using stepwise procedure. The number of variables entering the multivariable modelwill be selected in such a way that the thumb rule (10 events per variable) will be respected.> If a prognostic System exists, compare its performance alone with ils performance after addition of QoL factorsas well as other clinico-biological factors not included in the prognostic System.> Verify model hypotheses.> Assess model performance using HarreH"s C-index, Schempers V statistic, The NRI (Net ReclassificationImprovement) and the IDI (Integrated Discrimination Improvement). Perform sensitivity analysis after imputation of missing QoL data. Internai validation ofnew models. Find cut-off values for QoL scales to facilitate their use in daily practice.Three type of cancer will be studied: Advanced hepatocellular carcinoma. Metastatic pancreatic adenocarcinoma. Metastatic colorectal cancer.

No description available.

La fitness et a fortiori la survie d'une population dépendent de la stratégie et des performances de reproduction façonnées par son environnement. Par conséquent, les biomarqueurs traduisant une altération de la fonction de reproduction présentent un intérêt particulier. L'atteinte de la fertilité mâle au sein de la faune sauvage a notamment été adressée comme une problématique majeure susceptible de représenter une menace pour le maintien des populations. Toutefois, peu de méthodologies sont aujourd'hui disponibles chez des espèces pertinentes pour aborder cette problématique dans le cadre de programmes de biosurveillance environnementale, notamment chez les crustacés en dépit de leur représentativité au sein du règne animal et de leurs indispensables fonctions au sein des écosystèmes. Dans ce contexte, les présents travaux avaient pour objectif de proposer une ou plusieurs méthodologies basées sur la mesure de marqueurs de fonctionnalité et d'intégrité spermatique chez des crevettes Palaemonidae. Les investigations se sont portées sur deux espèces, une estuarienne, Palaemon longirostris, et une côtière, Palaemon serratus, pour leur complémentarité vis-à-vis du continuum estuaire - littoral. Compte tenu des nombreuses spécificités structurelles et fonctionnelles des spermatozoïdes de crustacés, I nombre de marqueurs transposables vers ces espèces s'est finalement avéré limité. Aussi, après une brève prospection, l'effort de recherche a rapidement été recentré sur la mesure de l'intégrité de l'ADN. Dès lors, la démarche scientifique a été construite de sorte à évaluer, point par point, la pertinence de la méthodologie développée dans une perspective d'application de l'outil dans le cadre de la surveillance environnementale. Une étape préliminaire d'optimisation et de validation méthodologique du test Cornet a démontré que, contrairement à une grande majorité de type spermatique, l'adaptation de ce test sur les spermatozoïdes de Palaemonidae ne nécessite aucune modification particulière du protocole. La dynamique de la réponse biologique en termes d'apparitions, de rémanence et d'effets possibles sur la fitness a été évaluée en conditions contrôlées au laboratoire. Ainsi, des expositions ex vivo et in vivo ont été conduites en utilisant une variété de génotoxiques modèles présentant différents modes d'actions. Les résultats ont attesté de la sensibilité, de la reproductibilité et du caractère intégrateur de la réponse. En revanche, aucun lien entre un ADN spermatique endommagé et une altération du succès de reproduction pré-éclosion n'a pu être établi. Parallèlement, une approche in situ a été conduite en vue de caractériser la valeur basale de la réponse mesurée. Différentes stratégies ont dû être adoptées en fonction des contraintes propres au milieu de vie de chacune des deux espèces. Un référentiel et une valeur seuil, communs aux deux espèces, ont pu être définis, soulignant le potentiel de transférabilité inter-espèces de l'outil. La méthodologie ainsi finalisée, a été éprouvée dans le cadre de plusieurs campagnes de suivi de différentes populations indigènes de l'estuaire et de la baie de Seine en 2015 et 2016. Les résultats se sont révélés très cohérents au regard de la pression de contamination et de la dynamique hydro-sédimentaire de la baie de Seine. En définitive, l'intégrité de l'ADN spermatique chez les Palaemonidae est opérationnelle en l'état pour un déploiement in situ en tant que biomarqueur d'exposition à un stress génotoxique. De futurs études devront néanmoins être conduites (1) pour mieux discerner les implications de ces dommages spermatiques en termes d'impact sur le recrutement des nouvelles cohortes et (2) éprouver la transférabilité de la méthodologie à d'autres espèces de crevettes et sur une plus large échelle géographique. / The environment shapes the reproduction's strategy and performance of a population, influencing its fitness and a fortiori its survival. Therefore, biomarkers that alter reproductive functions represent a great interest in ecotoxicology. The reduction of male fertility in wildlife can represent a threat to the population's survival. Moreover, fcw methodologies are available for species that are relevant to address this issue on envimnmental biomonitoring programs, especially for crustaceans, despite their representativeness in the wildlife and their essential functions within ecosysterns. The present work aimed to propose methodologies based on the measurement of functionality and integrity spermatic biomarkers on Palaemonidae shrimps. We studied two species, an estuarine, Palaemon longirostris, and a coastal species. Palaemon serratus. due to their complementaiity on the continuum estuary-littoral ecosystem. Howevcr, crustaceans' sperm has many structuraI and functional characteristics, the number of transposable markers is limited. Thereafter, the research effort was refocused on the measurement of the DNA integrity and this inethod was evaluated for its adequacy for a biomonitoring study. We optitrtized and validate the Cornet assay for the Palaemonidae species, and the dynamic of the biological response in ternis of appearances, persistence, and possible effects on fitness was evaluated under controlled conditions in the laboratoiy. Furthermore, ex-vivo and in-vivo exposures were conducted using genotoxic models with different modes of action. On the one hand, results attested to the sensibility, the reproducibility and the integrating character of the response, on the other hand, no correlation between damaged sperm DNA and an altération of the pre-hatch stage of development was established. In paralIel, an in-situ approach was conducted to characterize the baseline level of the measured response, taking into consideration the specific constraints of each species' habitat. We were able to define a common baseline level and a threshold value for both species, highlighting the potential of the tool for inter-species transferability. This method was tested with native populations from the estuary and from the Seine Bay in 2015 and 20] 6. And, the results proved to be consistent with the contamination pressure and the hydro-sedimentary dynamics of the Seine Bay. Ultimately, the DNA integrity of sperm in Palaemonidae seems to be functional for in-situ deploytnents as a biomarker of exposure to genotoxic stress. Nevertheless, future studies should be conducted (1) to botter discern the implications of this spermatic damage on the recruitment of new cohorts and, (2) to test the transferability of the methodology to other shrimp species and on a wider geographical scale.

De nombreux tests de dépistage des troubles cognitifs légers ont été élaborés ces dernières années afin d'identifier des personnes plus à risque de développer une maladie neurodégénérative telle que la maladie d'Alzheimer. Plusieurs indices (sensibilité, spécificité, valeurs de prédiction et rapports de vraisemblance) permettent d'évaluer la performance et l'utilité d'un test en pratique. L'objectif de cette thèse était d'évaluer le degré de variation de la performance d'un outil de dépistage des troubles cognitifs légers et ses conséquences sur la prise de décision clinique. Nos résultats montrent une variation importante de la performance de l'outil étudié en fonction des caractéristiques démographiques des individus, de la nature et la sévérité du trouble cognitif La performance globale d'un test ne serait donc pas constante et exposerait à un risque de sous-estimer ou de surestimer la présence de troubles cognitifs dans certains sous-groupes de l'échantillon d'étude. La mesure de ce phénomène de variation (ou effet de spectre) devrait faire partie des étapes obligatoires de la validation d'un test de dépistage des troubles cognitifs. Elle implique l'analyse de grands échantillons permettant de rendre compte de la complexité de l'interprétation d'un test et son application au niveau pratique. L'utilisation de valeurs seuils ajustées selon l'âge et le niveau scolaire, est proposée afin d'améliorer la prise de décision clinique. Nous discutons également de l'intérêt d'utiliser le concept épidémiologique de dépistage dans la recherche et l'identification de troubles cognitifs et proposons le terme plus approprié de repérage qui ne préjuge pas de leur étiologie. / In recent years, numerous tests have been proposed to screen Mild Cognitive Impairment (MCI) in order to identify individuals who are at risk for developing a neurodegenerative pathology such as Alzheimer's disease. Severa! indices (sensitivity, specificity, predictive values and likelihood ratios) enable to assess the performance and the utility of a test in clinical practice. The main objective of this thesis was to determine the degree of variation of an MCI screening test performance and its impact on clinical decision. Our results showed that performance indices of the study test may vary depending on the demographic characteristics of the individuals, the type and the degree of cognitive impairment. They also highlight that the overall performance of a screening test is not fixed and may result in failure to identify cognitive impairment in true cases and misclassified non cases as cognitively impaired in some subgroups of the study sample. These findings support the perspective that this subgroup variation ( or spectrum effect) should routinely be taken into account to assess the quality of a cognitive screening test. One way to minimize the impact of this phenomena would be to focus the assessment on broad and well defined subgroups of patients. The use of adjusted eut-offs values could help clinicians to increase their level of certainty regarding whether a cognitive impairment is present. We also discuss the interest of using the epidemiological concept of screening in the identification of cognitive impairments and propose a more appropriate term of cognitive impairment detection without prejudging its aetiology