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The political history of U.S. commercial remote sensing began in 1984 when the U.S. government first attempted to commercialize its civil earth observation satellite system " Landsat. Since then, the high technology of earth imaging satellite systems has generated intense debates and policy conflicts, primarily centered on U.S. government concerns over the national security and foreign policy implications of high-resolution commercial satellite systems. Conversely, proponents of commercial observation satellites have urged U.S. policymakers to recognize the scientific and socio-economic utility of commercial remote sensing and thus craft and implement regulatory regimes that allow for a greater degree of information openness and transparency in using earth observation satellite imagery. This dissertation traces and analyzes that tumultuous political history and examines the policy issues and social construction of commercial remote sensing to determine the role of knowledge in the effective crafting and execution of commercial remote sensing laws and policies. Although individual and organizational perspectives, interests, missions, and cultures play a significant role in the social construction of commercial observation satellite systems and programs, the problem of insufficient knowledge of the myriad dimensions and complex nature of commercial remote sensing is a little studied but important component of this social construction process. Knowledge gaps concerning commercial remote sensing extend to various dimensions of the subject matter, such as the global, economic, technical, and legal/policy aspects. Numerous examples of knowledge voids are examined to suggest a connection between deficient knowledge and divergent policy perceptions as they relate to commercial remote sensing. Relevant knowledge voids are then structurally categorized to demonstrate the vastness and complexity of commercial remote sensing policy issues and to offer recommendations on how to fill such knowledge gaps to effect increased collaboration between the US government and the U.S. commercial remote sensing industry. Finally, the dissertation offers suggestions for future STS studies on policy issues, particularly those that focus on the global dimensions of commercial remote sensing or on applying the knowledge gap concept advanced by this dissertation to other areas of science and technology policymaking. / Ph. D.

Background: Warfarin is an anticoagulant that is used for the prophylactic and therapeutic treatment for a wide range of thrombo-embolic disorders. The prescribing and monitoring of warfarin therapy is challenging due to the fact that warfarin exhibits numerous interactions with other drugs and a variety of factors that influence the dosing of warfarin. Objective: The general objective of this study was to investigate the prevalence of drugs prescribed with warfarin that may have a potential drug-drug interaction (DDI) with warfarin. Methods: This was a cross-sectional, observational or qualitative study that was conducted on medicine claims data of a pharmaceutical benefit management company for patients receiving warfarin therapy for a six year period, ranging from 1 January 2005 to 31 December 2010. Drug products that were co-prescribed with warfarin were also identified from the medicine claims database. The total number of prescriptions for all drug products during the study period were analysed and compared to the warfarin dataset. This was done by means of the SAS 9.1® computer package (SAS Institute, 2004). The total number of prescriptions and medicine items claimed from the database during the study period were respectively 49 523 818 and 118 305 941. Potential DDls between warfarin and coprescribed drugs were identified and classified according to a clinically significant rating. The clinically significance ratings of potential DDls are described in three degrees of severity, identified as major, moderate and minor (Tatro, 2011 :xiv). Results: The database consisted of 427 238 warfarin prescriptions and 427 744 warfarin medicine items, which represented 0.9% of the total number of prescriptions and 0.4% of total number of medicine items. The total number of patients who claimed warfarin prescriptions through the database represented 0.9% (n=68 575) of the total number of patients who claimed prescriptions in the total database (2005-2010). General practitioners prescribed the highest frequency of warfarin medicine items, representing 58.3% (n=249 202) of the total number prescribed. The age group that claimed the highest frequency of warfarin prescriptions (n=327 592, 76.6%) and the highest frequency of warfarin medicine items (n=327 984, 76.7%) was age group 4 (consisting of patients 59 years and older). The distribution between females and males regarding warfarin prescriptions claimed (n=205 999, 48.2%; n=221 117, 51.8%) and warfarin medicine items claimed (n=206 232, 48.2%; n=221 390, 51.8%) were almost equal. General practitioners prescribed the highest average PDD (7.01 mg ± 9.86 mg) of warfarin medicine items. Paediatric cardiologists prescribed the lowest average PDD (4.61 mg ± 1.29 mg) of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDD between general practitioners and paediatric cardiologists. The average PDD of warfarin medicine items between females (6.60 mg ± 9.06 mg) and males (6.74 mg± 8.41 mg) was almost equal. The age group who was prescribed the highest average PDD was age group 2 (consisting of patients 20 years to 39 years old) (7.42 mg± 7.42 mg). Age group 4 (consisting of patients 59 years and older) (6.50 mg± 8.90 mg) was prescribed the lowest average PDD of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDDs of warfarin medicine items between these two age groups. The results revealed that drugs with a significance rating (SR) of 1 (n=155 066, 43.3%), 2 (n=30128, 8.4%), 4 (n=137144, 38.3%), and 5 (n=36144, 10.1%) were co-prescribed with warfarin in the six year study period. The five drugs that was co-prescribed with warfarin most frequently was aspirin (n=48 903, 13.6%), thyroxine (n=33 954, 9.5%), amiodarone (n=25 056, 7.0%), simvastatin (n=19 070, 5.3%) and celecoxib (n=10 794, 3.0%). These five drugs have a SR of 1. Conclusions: This study showed that the top five drugs most frequently prescribed with warfarin are aspirin, thyroxine, amiodarone, simvastatin and celecoxib. These drugs can potentially interact with warfarin. The potential interactions of these drugs are rated with a significance rating of 1. This concludes that drugs that can potentially cause life threatening effects and permanent damage are commonly co-prescribed with warfarin. Clinical data concerning the INR or PT must be obtained in order to evaluate whether or not warfarin therapy is changed when a potentially interacting drug is co-prescribed. The age of the patients as well as the duration of warfarin treatment should also be obtained in order to assess whether warfarin treatment is changed with the progression of age. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2013

Background: Warfarin is an anticoagulant that is used for the prophylactic and therapeutic treatment for a wide range of thrombo-embolic disorders. The prescribing and monitoring of warfarin therapy is challenging due to the fact that warfarin exhibits numerous interactions with other drugs and a variety of factors that influence the dosing of warfarin. Objective: The general objective of this study was to investigate the prevalence of drugs prescribed with warfarin that may have a potential drug-drug interaction (DDI) with warfarin. Methods: This was a cross-sectional, observational or qualitative study that was conducted on medicine claims data of a pharmaceutical benefit management company for patients receiving warfarin therapy for a six year period, ranging from 1 January 2005 to 31 December 2010. Drug products that were co-prescribed with warfarin were also identified from the medicine claims database. The total number of prescriptions for all drug products during the study period were analysed and compared to the warfarin dataset. This was done by means of the SAS 9.1® computer package (SAS Institute, 2004). The total number of prescriptions and medicine items claimed from the database during the study period were respectively 49 523 818 and 118 305 941. Potential DDls between warfarin and coprescribed drugs were identified and classified according to a clinically significant rating. The clinically significance ratings of potential DDls are described in three degrees of severity, identified as major, moderate and minor (Tatro, 2011 :xiv). Results: The database consisted of 427 238 warfarin prescriptions and 427 744 warfarin medicine items, which represented 0.9% of the total number of prescriptions and 0.4% of total number of medicine items. The total number of patients who claimed warfarin prescriptions through the database represented 0.9% (n=68 575) of the total number of patients who claimed prescriptions in the total database (2005-2010). General practitioners prescribed the highest frequency of warfarin medicine items, representing 58.3% (n=249 202) of the total number prescribed. The age group that claimed the highest frequency of warfarin prescriptions (n=327 592, 76.6%) and the highest frequency of warfarin medicine items (n=327 984, 76.7%) was age group 4 (consisting of patients 59 years and older). The distribution between females and males regarding warfarin prescriptions claimed (n=205 999, 48.2%; n=221 117, 51.8%) and warfarin medicine items claimed (n=206 232, 48.2%; n=221 390, 51.8%) were almost equal. General practitioners prescribed the highest average PDD (7.01 mg ± 9.86 mg) of warfarin medicine items. Paediatric cardiologists prescribed the lowest average PDD (4.61 mg ± 1.29 mg) of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDD between general practitioners and paediatric cardiologists. The average PDD of warfarin medicine items between females (6.60 mg ± 9.06 mg) and males (6.74 mg± 8.41 mg) was almost equal. The age group who was prescribed the highest average PDD was age group 2 (consisting of patients 20 years to 39 years old) (7.42 mg± 7.42 mg). Age group 4 (consisting of patients 59 years and older) (6.50 mg± 8.90 mg) was prescribed the lowest average PDD of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDDs of warfarin medicine items between these two age groups. The results revealed that drugs with a significance rating (SR) of 1 (n=155 066, 43.3%), 2 (n=30128, 8.4%), 4 (n=137144, 38.3%), and 5 (n=36144, 10.1%) were co-prescribed with warfarin in the six year study period. The five drugs that was co-prescribed with warfarin most frequently was aspirin (n=48 903, 13.6%), thyroxine (n=33 954, 9.5%), amiodarone (n=25 056, 7.0%), simvastatin (n=19 070, 5.3%) and celecoxib (n=10 794, 3.0%). These five drugs have a SR of 1. Conclusions: This study showed that the top five drugs most frequently prescribed with warfarin are aspirin, thyroxine, amiodarone, simvastatin and celecoxib. These drugs can potentially interact with warfarin. The potential interactions of these drugs are rated with a significance rating of 1. This concludes that drugs that can potentially cause life threatening effects and permanent damage are commonly co-prescribed with warfarin. Clinical data concerning the INR or PT must be obtained in order to evaluate whether or not warfarin therapy is changed when a potentially interacting drug is co-prescribed. The age of the patients as well as the duration of warfarin treatment should also be obtained in order to assess whether warfarin treatment is changed with the progression of age. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2013

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Submitted by LUIS OTAVIO PAVAN HATAMOTO (luis_hatamoto@hotmail.com) on 2017-01-10T18:35:12Z No. of bitstreams: 1 LuisHatamoto-TeseMestrado.pdf: 1852048 bytes, checksum: bc6eb8138880413b55d2b36836dc2d21 (MD5) / Rejected by Fabiana da Silva Segura (fabiana.segura@fgv.br), reason: Boa Tarde, Prezado Luis Por favor corrigir os seguintes itens: Tirar o acento de Getulio Titulo em letras maiúsculas - alterar nas página que houver o titulo No fim da página fica apenas São Paulo tirar o - SP Campo de Conhecimento: Finanças e Economia de Empresas (alterar nas páginas que houver campo de conhecimento) Peço proceder com as alterações e submeter novamente o trabalho Atenciosamente on 2017-01-10T18:48:54Z (GMT) / Submitted by LUIS OTAVIO PAVAN HATAMOTO (luis_hatamoto@hotmail.com) on 2017-01-11T12:50:13Z No. of bitstreams: 2 LuisHatamoto-TeseMestrado.pdf: 1852048 bytes, checksum: bc6eb8138880413b55d2b36836dc2d21 (MD5) Financ¸as-Hatamoto-Tese-Final_v4 - entrega.pdf: 1507861 bytes, checksum: cf32b9fd2a3bdc2b7a9dff998a04a9fc (MD5) / Approved for entry into archive by Fabiana da Silva Segura (fabiana.segura@fgv.br) on 2017-01-11T15:14:18Z (GMT) No. of bitstreams: 2 LuisHatamoto-TeseMestrado.pdf: 1852048 bytes, checksum: bc6eb8138880413b55d2b36836dc2d21 (MD5) Financ¸as-Hatamoto-Tese-Final_v4 - entrega.pdf: 1507861 bytes, checksum: cf32b9fd2a3bdc2b7a9dff998a04a9fc (MD5) / Made available in DSpace on 2017-01-12T11:47:23Z (GMT). No. of bitstreams: 2 LuisHatamoto-TeseMestrado.pdf: 1852048 bytes, checksum: bc6eb8138880413b55d2b36836dc2d21 (MD5) Financ¸as-Hatamoto-Tese-Final_v4 - entrega.pdf: 1507861 bytes, checksum: cf32b9fd2a3bdc2b7a9dff998a04a9fc (MD5) Previous issue date: 2016-12-13 / This study seeks to assess whether the provision method for doubtful accounts (PDD, or 'Provisão para Devedores Duvidosos') adopted by financial institutions is applicable in retail companies and if there are adjustments needed to improve the use of these methods in this sector. Banks and other financial institutions have unique characteristics in the composition of its loan portfolio, which require the adoption of different procedures in the PDD composition against those charged by other sectors (i.e. trade, industry or services), which are free to actualize the loss provisioning. Financial companies are regulated by the Central Bank of Brazil through the Resolution of the National Monetary Council No. 2682 of December 21th 1999 which determines percentage, terms and minimum levels of classification, and which leaves the task of developing risk models for the institutions. Based on the Resolution by Central Bank of Brazil, this study evaluate the adoption of provisioning models used by financial institutions in the receivables’ portfolio from suppliers in a Brazilian retail company, and through an academic work applied to propose a model for allowance for doubtful accounts of this portfolio. The main objective is achieved due to the risk model developed fits better the provision in the losses. This benefit has two effects: first in the profits, as it reduces the expenses with allowances, and second since it smooths impacts of bad debts. / O estudo visa avaliar se o método de provisão para devedores duvidosos (PDD) adotado pelas instituições financeiras é aplicável em empresas varejistas e se há necessidade de adequações para melhorar o uso deste método neste setor. Bancos e demais instituições financeiras têm características singulares na composição de sua carteira de crédito, que obrigam a adoção de procedimentos diferenciados na composição da PDD em relação aos praticados pelos demais setores (comerciais, indústria ou de prestação de serviços), os quais são livres para realizar o provisionamento de perdas. Empresas do setor financeiro são regulamentadas pelo Banco Central do Brasil através da Resolução do Conselho Monetário Nacional de n° 2.682 de 21 de dez de 1999, que determina percentuais, prazos e níveis mínimos de classificação, deixando a cargo das instituições fazerem a classificação de risco de suas operações. Considerando esta norma do Banco Central do Brasil, este trabalho avalia a adoção do modelo de provisionamento utilizado pelas instituições financeiras, na carteira de trade allowances, que são recebíveis de fornecedores com origem em negociações comerciais realizadas entre a empresa varejista e seus fornecedores, utilizados para fomentar a venda de produtos, por exemplo, desconto no preço final, exposição diferenciada, entre outras ações e, através de um trabalho acadêmico aplicado propõe um modelo de avaliação de risco para constituição da PDD desta carteira. O principal objetivo é atingido, pois o modelo de avaliação de risco se mostra satisfatório e o método de provisionamento, seguindo a Resolução 2.682, gerou benefício a medida que melhor se adequou à perda observada. Este benefício tem efeito tanto no resultado, a medida que reduz a despesa com a provisão, como na gestão do capital de giro, pois suaviza impactos de não recebimento.

La reconnaissance des expressions faciales émotionelles dans les Troubles Envahissants du Développement (TED) est atypique, contribuant à des difficultés socio-adaptatives y compris dans les TED sans déficience intellectuelle (TED-SDI). Hypothèse : il existe des facteurs de risque ou de protection dans les capacités de reconnaissance des expressions faciales émotionnelles des TED-SDI. Objectifs : 1) caractériser les capacités de 32 enfants et adolescents de 8 à 14 ans avec TED-SDI ; 2) identifier des facteurs de risque ou de protection, comparer nos observations à un groupe contrôle de 37 sujets typiques. Notre étude est transversale, descriptive et analytique. Le critère de jugement principal utilisé est le nombre d'erreurs au DANVA2F, qui évalue les capacités de reconnaissance des expressions faciales émotionnelles de base. Résultats : un nombre significatif d'erreurs plus élevé est observé dans le groupe TED-SDI comparativement à la population normée et à la population contrôle. L'intensité des troubles socio-communicatifs actuels mesurés par l'ADOS constitue un facteur de risque (ORa=2,08 ; IC 95%= [1,02/4,22] ; p=0,006). D'autre part, une faible intensité des comportements stéréotypés et des schémas répétitifs inférieurs mesurée à l'aire 3 de l'ADI apparaît être un facteur de protection (DANVA AF : ORa=0,078 ; IC 95%= [0,007/0,883] ; p=0,02. DANVA CF : ORa : 0,05 ; IC 95%= [0,005/0,44] ; p=0,0004). Conclusion : nos résultats vont dans le sens d'un trouble de la capacité à reconnaitre les expressions faciales dans les TED-SDI et permettent d'identifier des facteurs de risque cliniques de plus grandes vulnérabilités. Perspectives : utiliser un échantillon plus large et développer sur le plan clinique des interventions précoces et multimodales. / Facial emotionanl expression recognition in Pervasive Developpemental Disorders (PDD) are atypic and contribute to social skills difficulties for children and adolescents with PDD, including without intellectual disabilities. Hypothesis: predictiv factors exist in facial emotional expression recognition in PDD. Objectives: 1) characterize the abilities of facial emotional expressions recognition of 32 children and adolescents; 2) identify risk or protective factors in the development of these abilities. Compare our results with a control group of 37 typical peers. Our study is cross-sectional, descriptive and analytical. The primary point was the number of errors in the Danva 2F, which is a validated and standardized assessment tool (basic emotional expression). Results: show that our clinical group made significantly more errors in the recognition of facial emotional expressions than what is observed in population and standardized in our control population. Risk factors of the number of errors made in the Danva are highlighted: the intensity of socio-communicative disorders present as measured by the ADOS (ORa=2,08 ; IC 95%= [1,02/4,22] ; p=0,006). Protective factors are identified, linked to a low of stereotyped and repetitive patterns score below the threshold of the area 3 of the ADI (DANVA AF: ORa=0,078 ; IC 95%= [0,007/0,883] ; p=0,02. DANVA CF: ORa: 0,05 ; IC 95%= [0,005/0,44] ; p=0,0004). Conclusion: results allow us to observe a disorder of the ability to recognize facial expressions in our clinical group and the presence of risk factors and protective factors related to it. Perspectives: use a larger sample to study clinical parameters more related to emotional processing, our clinical work emphasizes the importance of early intervention multimodal, to improve the capacity of emotional processing.

The thesis is aimed at understanding of molecular mechanisms of autophagic degradation of peroxisomes (pexophagy) in the yeast Yarrowia lipolytica. This microorganism has been extensively used to explore peroxisome biogenesis (Titorenko and Rachubinski, 2000). Gunkel et al. (1999) intoduced Y. lypolitica into pexophagy studies. However, the field of pexophagic research on this yeast remains quite unexplored. This work involved following tasks: (1) the development and optimization of Y. lipolytica as a model system to study peroxisome degradation; (2) Y. lipolytica genes and proteins implicated in pexophagy should be found and characterized; (3) a proper easy-to-handle selection procedure to isolate novel peroxisome degradation-deficient(pdd) mutants of Y. lipolytica should be devised.

Είναι γνωστό ότι η άνοια σχετίζεται με την απώλεια μνήμης, έκπτωση γλωσσικών ικανοτήτων, έλλειψη αυτονομίας και απώλεια της προσωπικής ταυτότητας του ασθενούς. Στόχος της παρούσας εργασίας είναι να αναδείξει τη σχέση αμφισημίας- άνοιας και να διερευνηθεί η σκοπιμότητα ύπαρξης ενός μεθοδολογικού εργαλείου για την εκτίμηση και τη διερεύνηση της γλωσσικής έκπτωσης στη άνοια μέσα από την γλωσσική επεξεργασία των λεξικών σχέσεων (μεταφορών –ομωνυμίας- μετωνυμιών) και να παρουσιάζει το προφίλ των ασθενών αυτών. Στην πρώτη ενότητα παρουσιάζω γενικά στοιχεία για την νόσο της άνοιας αλλά και στοιχεία για τους κυριότερους τύπους της νόσου όσον αφορά την γλωσσική συμπεριφορά των ασθενών. Στην ενότητα αυτή αναφέρω επίσης βασικά διαγνωστικά εργαλεία που χρησιμοποιούνται ευρέως για τον προσδιορισμό της νόσου, ενώ αναλυτικότερα στοιχεία για τα εργαλεία που χρησιμοποιούνται και τις δομές που εξετάζουν παρατίθενται στο παράρτημα. Κλείνοντας την ενότητα καταλήγω στα οφέλη και την αναγκαιότητα ύπαρξης πρώιμης διάγνωσης. Στην δεύτερη ενότητα αναφέρομαι κυρίως στο νοητικό λεξικό και στην δυσκολία πρόσβασης των ασθενών με πιθανή άνοια σε αυτό. Επιπλέον υπάρχουν στοιχεία για την λεξική κατάκτηση, επιλογή και ανάκτηση των πληροφοριών και φαίνεται η σχέση νοητικού λεξικού – αμφισημίας. Στην τρίτη ενότητα παρουσιάζω το φαινόμενο της αμφισημίας από την θεωρητική άποψη αρχικά της γλωσσολογίας, πως κατακτώνται οι αμφίσημες λέξεις και επεξεργάζονται σε σχέση με την ηλικία και καταλήγω στην νευρική συσχέτιση των λεξικών αμφισημιών με συγκεκριμένες εγκεφαλικές περιοχές. Στο τέλος της παρούσας ενότητας παρουσιάζω ευρήματα/ συμπεράσματα από πλήθος ερευνών που αφορούν την λεξική αμφισημία με διαφορετικές μεθόδους για κάθε τύπο άνοιας. Στην τελευταία ενότητα παρουσιάζω τις βασικές υποθέσεις μου πως η χρήση των λεξικών σχέσεων θα μπορεί να αποτελέσει διαγνωστικό εργαλείο στην άνοια. Επίσης παρουσιάζω την κατασκευή και τα αποτελέσματα της πειραματικής διαδικασίας ανάμεσα σε τέσσερα διαφορετικά υποκείμενα (πασχόντων –υγειών) διαφορετικής παθολογίας και σοβαρότητας. Ακολουθεί τέλος το παράρτημα με στοιχεία που αφορούν την διαφοροδιάγνωση της νόσου βάσει αλγορίθμων με τα γνωστικά ελλείμματα όπως παρουσιάζονται από τους φροντιστές των ασθενών αλλά και παθολογικών συμπτωμάτων που παρουσιάζουν, ενώ σε πίνακα υπάρχουν τα γλωσσικά στοιχεία που βοηθούν επίσης στην διαφοροδιάγνωση των κυριότερων τύπων άνοιας και τα αποτελέσματα της πειραματικής διαδικασίας. / It is well known that dementia is associated with memory loss, impaired language skills, lack of autonomy and loss of patients’ independence. The aim of this paper is to highlight the connection between ambiguity and dementia, and to investigate the feasibility of a methodological tool to assess and investigate the linguistic deduction in dementia through the linguistic processing of lexical relations (metaphor-homonymy-metonymy) and present the profile of such patients. In the first section I present general information as well as the linguistic features of the main types of dementia. In this section there is also a report on the diagnostic tools which are widely used to identify the disease. More detailed information about the use of these diagnostic tools is listed in the Annex. At the end of this section there is evidence about the benefits and the importance of early diagnosis. The second section is mainly referred to the mental lexicon and the difficulty patients with probable dementia face in accessing it. Furthermore there is evidence for lexical acquisition, selection and retrieval of information which shows the mental lexicon – ambiguity connection. In the third section I present the phenomenon of ambiguity, starting from the theoretical linguistic view; how the ambiguous words are conquered and processed in relation to age and lead to neural correlation of lexical ambiguity with specific brain regions. At the end of this section I present findings / conclusions of several researches, using different methods, on the lexical ambiguity on each type of dementia. The last section presents my basic assumptions concerning how the use of lexical relations can be a diagnostic tool in dementia. Furthermore, I present the construction and the results of the experimental process between four different subjects (patient-healthy) with different pathology and severity of the disease. Finally, at the annex, I present data on the differential diagnosis of the disease based on algorithms with cognitive deficits reported by caregivers of patients as well as pathology features. Also there is a board with differential linguistic elements which help distinguish the main types of dementia, along with the experimental material used and the results of the procedure.