This thesis aims to study the role, function, and responsibility of municipalities in the Swedish total defence during periods of heightened preparedness. The method used in this thesis is a qualitative text analysis, and the material consists of public documents from state actors. The research question formulated is as follows: What role, function, and responsibility are municipalities expected to have within the future total defence during periods of heightened preparedness? To answer the research question, resilience has been used as a theoretical framework. The results show that municipalities are expected to take on a proactive role by working with anticipation and identification, as well as by preventing, mitigating, and preparing for crises. Additionally, municipalities are expected to have an adaptive capability and act reactively by implementing measures and restoring society to normalcy. Furthermore, although the concept of resilience is not explicitly mentioned in the analyzed documents, it is evident that municipalities are expected to have a role, function, and responsibility characterized by resilience within the framework of future total defence. By contributing new knowledge and insights in this area, the study aims to fill the knowledge gaps that previous research has not addressed, while also aspiring to provide ideas for further research and development in the field of total defence and municipal resilience.

Syftet med denna studie var att studera hur förskollärare upplever sin roll inom totalförsvaret och hur deras försvarsvilja ser ut. Totalt har tio förskollärare intervjuats genom semistrukturerade intervjuer och en tematisk analys utfördes på intervjumaterialet. Detta resulterade i två teman och sju subteman som redogör för gynnsamma samt ogynnsamma aspekter för förskollärares syn på sin roll inom totalförsvaret och deras försvarsvilja. Slutsatserna från denna studie var att förskollärare anser att de har en viktig roll inom totalförsvaret och att det finns en hög försvarsvilja. Studien visar dock att kunskapen och informationen om vad deras roll innebär är bristande, inte bara internt utan även stort i samhället och att ledare utgör en viktig roll i att sprida den kunskapen. Slutligen visadestudien på att den mest ogynnsamma aspekten är det som står oss närmast - familjen. Behovet att skydda sin egen familj och veta att den är trygg är det viktigaste och det visar i sig hur viktig förskolan är som aktör inom det civila försvaret för att tillgodose det behovet. / The aim of this study was to study how preschool teachers perceive their role within the total defence and what their willingness to defend one’s own country looks like. A total of tenpreschool teachers have been interviewed through semi-structured interviews and the interview material has been data-processed through a thematic analysis. This resulted in two themes and seven subthemes that included favorable and unfavorable aspects of preschool teachers view of their role in total defence and their willingness to defend. The conclusions of this study were that preschool teachers think that they have an important role in the total defence and that there is a high willingness to defend, but that the knowledge and information about what their role entails is lacking, not only internally but also widely in society and that leaders plays an important role to spread this knowledge. Finally this study shows that the most unfavorable aspect, for the willingness to defend one’s country, is what we have closestto us - the family. The need to protect the own family is the most important thing and that itself shows how important preschool is as an actor in the civil defence.

Just as packet switched networks constituted a major breakthrough in our perception of the information exchange in computer networks so have the decoupling properties of publish/subscribe systems revolutionized the way we look at networking in the context of large scale distributed systems. The decoupling of the components of publish/subscribe systems in time, space and synchronization has created an appealing platform for the asynchronous information exchange among anonymous information producers and consumers. Moreover, the content-based nature of publish/subscribe systems provides a great degree of flexibility and expressiveness as far as construction of data flows is considered. However, a number of challenges and not yet addressed issued still exists in the area of the publish/subscribe systems. One active area of research is directed toward the problem of the efficient content delivery in the content-based publish/subscribe networks. Routing of the information based on the information itself, instead of the explicit source and destination addresses poses challenges as far as efficiency and processing times are concerned. Simultaneously, due to their decoupled nature, publish/subscribe systems introduce new challenges with respect to issues related to dependability and fail-awareness. This thesis seeks to advance the field of research in both directions. First it shows the design and implementation of routing algorithms based on the end-to-end systems design principle. Proposed routing algorithms obsolete the need to perform content-based routing within the publish/subscribe network, pushing this task to the edge of the system. Moreover, this thesis presents a fail-aware approach towards construction of the content-based publish/subscribe system along with its application to the creation of the soft state publish/subscribe system. A soft state publish/subscribe system exposes the self stabilizing behavior as far as transient timing, link and node failures are concerned. The result of this thesis is a family of the XSiena content-based publish/subscribe systems, implementing the proposed concepts and algorithms. The family of the XSiena content-based publish/subscribe systems has been a subject to rigorous evaluation, which confirms the claims made in this thesis.

Im Rahmen der EU-Richtlinie REACH müssen industrierelevante Chemikalien bezüglich des Risikos für Mensch und Umwelt (neu) untersucht und bewertet werden, wobei die Anzahl an Tierversuchen zu minimieren ist und neue toxikologische Prüfmethoden, Bewertungsstrategien sowie alternative Testsysteme entwickelt und optimiert werden sollen. Ubiquitär vorkommende Testorganismen, welche ähnliche Eigenschaften und eine vergleichbare Sensitivität bezüglich äußerer Einflüsse wie komplexere Organismen (Fisch, Säugetier, Mensch) besitzen, sind hier besonders gefragt um die Belastung abzuschätzen und Trendaussagen über die Wirkung zu formulieren. Durch den Einsatz vieler dieser Testorganismen sowie durch die Ermittlung der chemischen Reaktivität und der Strukturmerkmale einer Verbindung kann ein globales Bild über die Wirkung erhalten werden. Ein Organismus, der diese Charakteristika aufweist, ist der eukaryotische Einzeller Tetrahymena pyriformis GL. In der vorliegenden Dissertation wird zum einen die jeweilige Toxizität elektrophiler Substanzen unterschiedlicher Stoffklassen und Reaktions-mechanismen (α,β-ungesättigte Carbonyl- und Carboxylverbindungen, heterozyklische Drei- und Vierringe, α-halogenierte Carbonyle, Harnstoffe und Thioharnstoffe, aromatische Disulfide sowie aliphatische und aromatische Nitroverbindungen) nach den Expositionszeiten 24 h, 48 h und 72 h mit Hilfe eines etablierten Wachstumshemmtests (Müller, 2001) bestimmt und Struktur-Toxizitäts-Beziehungen bzw. Strukturalarme abgeleitet. Neben der methodischen Optimierung werden die substanzspezifischen Eigenschaften, Flüchtigkeit und Sorptionsfähigkeit, quantitativ erfasst und durch neu aufgestellten Modellgleichungen für jede Substanz ermittelt. Mit der Bestimmung der Toxizitätserhöhung, Te, welche auch als ein Maß für die Reaktivität angesehen werden kann, werden Organismen-spezifische Narkose-Basis-Geraden generiert, exzesstoxische Verbindungen identifiziert und Strukturalarme für die jeweiligen Stoffklassen aufgestellt. Zum anderen werden binäre Mischungen untersucht, welche aus den Einzelstoffen bestehen, deren Toxizität im ersten Abschnitt der Arbeit ermittelt wurden und bei denen theoretische Annahmen über die Reaktionsmechanismen bestehen. Dieser Abschnitt identifiziert, ob gleiche bzw. unähnliche primäre Wechselwirkungen zweier Substanzen mit den biologischen Targets vorliegen und welcher Mechanismus, der reaktive Mechanismus exzesstoxischer Substanzen oder die Wechselwirkungen mit Membran-Bestandteilen, dominierend ist. Für die Auswertung der Mischungsergebnisse werden die etablierten biometrischen Modelle Konzentrations-Additivität und Unabhängigen Wirkung verwendet. Es wird dargestellt, dass die Mischungstoxizitäten der binären Mischungen ähnlich wirkender Substanzen zwar relativ genau mithilfe beider Modelle berechnet werden, jedoch keine eindeutige Charakterisierung der Mechanismen möglich ist. Die Ergebnisse der untersuchten binären Mischungen unterschiedlich wirkender Substanzen zeigen dagegen, dass die Mischungstoxizitäten unähnlicher Substanzen relativ genau mithilfe des Modells der Unabhängigen Wirkung berechnet werden und eine Charakterisierung der Mechanismen möglich ist.

The aim of this thesis is to define the basic parameters of balance of trade between the Czech Republic and Poland in agri-food production. Attention is focused on assessing qualitative aspects of Polish origin food, especially with the findings of supervisory authorities in the Czech market. The thesis also deals with agrarian foreign trade in terms of territorial and commodity structure. Another issue is the import of Polish food focusing on the market for poultry. Poland joined the awareness of consumers and professionals in connection with undesirable practices negatively affecting food safety.

Made available in DSpace on 2014-12-17T14:44:18Z (GMT). No. of bitstreams: 1 LuizFFJ_DISSERT.pdf: 561001 bytes, checksum: d3e0298e76c38d08d3b0c195db8c91b5 (MD5) Previous issue date: 2014-04-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The complex human behavior related to exercise involves cognitive, physical and emotional processing. The recent theories about exercise s intensity regulation have highlighted the role played by psychophysics aspects in controlling exercise s intensity. In this regard, recent evidences have shown that there is variability in human capacity in perceiving interoceptives clues. Thus, subjects more sensitive show higher physiological arousal to physical and/or emotional stress, and sensations with higher intensity. In fact, studies have evidenced that interoceptive feedback modifies behavior in exercise with free load. However, exercise recommendations are based in a constant load standard. Therefore, we aimed to analyze the influence of interoceptive sensibility on psychophysics responses during dynamic exercise performed with constant load. Twenty-four adult males were allocated into two groups accordingly with their interoceptive sensibility: high sensibility (n=11) and low sensibility (13). They underwent to an incremental test (IT) and then randomly to two sections of moderate and severe exercise intensity for 20 minutes. Heart rate (HR), rating of perceived exertion (RPE), affective feelings (AF), alert state (AS), and percentage of associative thoughts were collect during exercise. A two-way ANOVA with repeated measures was used to assess differences between psychophysics responses. There were differences between group in RPE, AF, and AS in moderate intensity. There was no difference in any measure in severe intensity. We conclude that subjects with high interoceptive sensibility feel dynamic moderate exercise more intense than the subjecs with low interoceptive sensibility / INTRODU??O: O complexo comportamento humano de realizar exerc?cio f?sico envolve processamento cognitivo, f?sico e emocional. As recentes teorias sobre fadiga e reposta afetivas ao exerc?cio f?sico atribuem importante papel na regula??o da intensidade do esfor?o aos fatores interoceptivos. Al?m disso, Evid?ncias recentes tem apontado haver variabilidade na capacidade humana em perceber esses est?mulos interoceptivos. Dessa forma, pessoas mais sens?veis apresentam excita??o fisiol?gica mais acentuada ao estresse f?sico e/ou emocional, e maior intensifica??o dessas sensa??es. Adicionalmente, estudos tem relatado que feedback interoceptivo diminui a intensidade do esfor?o exercida, e que pessoas com maior sensibilidade interoceptiva controlam melhor a intensidade de esfor?o em tarefas com ritmo livre. Contudo, os modelos de prescri??o de exerc?cio f?sico din?mico apresentam padr?o de intensidade de esfor?o fechado, e n?o ? conhecida as repostas psicofisiol?gicas entre os grupos de variabilidade interoceptiva durante a realiza??o de exerc?cio f?sico. OBJETIVO: O presente estudo verificou a influ?ncia da sensibilidade interoceptiva sobre as repostas psicofisiol?gicas em exerc?cio din?mico com carga constante. M?TODOS: A amostra foi composta por 24 homens jovens adultos, insufientemente ativos, que foram designados a dois grupos de acordo com seus n?veis de sensibilidade interoceptiva: Alta sensibilidade (n=11) e Baixa sensibilidade (n=13). Todos foram submetidos a um teste incremental (TI) em cicloerg?metro para identifica??o do limiar de variabilidade da frequ?ncia card?aca (LiVFC) e da pot?ncia pico (PP). Posteriormente, os sujeitos foram submetidos (em ordem aleat?ria e cruzada) a dois protocolos experimentais de exerc?cio f?sico em cicloerg?metro durante 20 minutos com intensidade correspondente a 20% abaixo e 20% acima LiVFC. Durante os protocolos experimentais as respostas de Frequ?ncia Card?aca (FC), Percep??o Subjetiva de Esfor?o (PSE), Val?ncia Afetiva (VA), Estado de Alerta e N?vel de pensamento Dissociativo-Associativo ao exerc?cio f?sico foram registradas. O teste de Shapiro-Wilk e as an?lises da m?dia, assimetria e curtose verificaram a normalidade de distribui??o dos dados. O Teste de Mauchly verificou a esfericidade dos dados de medidas repetidas. O Teste t para amostra independente e o Teste de Mann Whitney verificaram as igualdade dos dados descritivos entre os grupos. A ANOVA two away (grupo x momentos) para medidas repetidas verificou as poss?veis diferen?as entre as respostas psicofisiol?gicas. RESULTADOS: Houve diferen?a estatisticamente significante entre os grupos na PSE (F(3,36)=18,50, p=0,000), VA (F(3,36)=4,14, p=0,01) e no Estado de Alerta (F(3,36)=4,03, p=0,01) no exerc?cio realizado em intensidade correspondente a 80% LiVFC. Na intensidade correspondente a 120% LiVFC n?o houve diferen?a entre os grupos, somente entre os momentos em cada grupo. CONCLUS?O: A sensibilidade interoceptiva modifica as respostas psicofisiol?gicas durante a realiza??o de exerc?cio f?sico din?mica com intensidade moderada (abaixo do LiVFC)

nÃo hà / Neonatos internados em unidade de terapia intensiva neonatal (UTIN) sÃo expostos a uma grande variedade de medicamentos, a maioria sem dados de seguranÃa e eficÃcia. Descrever o perfil de uso de medicamentos em neonatos em UTIN de um hospital pÃblico no Brasil de acordo com dados de registro do medicamento e potencial nocivo destes, foi o objetivo do trabalho. Trata-se de um estudo descritivo retrospectivo sobre uso de medicamentos em UTIN, envolvendo neonatos internados por mais de 24 horas e dados de prescriÃÃo coletados em prontuÃrio eletrÃnico durante o perÃodo de janeiro a junho do ano de 2012. InformaÃÃes sobre os medicamentos, com base nas bulas, foram comparadas com o British National Formulary for Children 2012-2013 e a base de dados Thomson Micromedex. O potencial nocivo de medicamentos e excipientes foi avaliado conforme a literatura. Neonatos foram categorizados em grupos de idade gestacional (IG). Os dados foram submetidos à anÃlise descritiva e testes de distribuiÃÃo (ANOVA, Teste U de Mann-Whitney, Kruskal-Wallis, qui-quadrado de Pearson) por IG com o nÃvel de significÃncia de p < 0,05. IncluÃram-se 192 neonatos, a maioria prÃ-termo, com mediana de 33 semanas de IG, totalizando 3.617 neonatos-dia. Registraram-se 3.290 prescriÃÃes, mÃdia 17,1 prescriÃÃes/neonato (DP  17,9) e 8,8 medicamentos/neonato (DP  5,9), maiores em neonatos mais imaturos (p < 0,05). Anti-infecciosos de uso sistÃmico, medicamentos para o sangue e ÃrgÃos formadores do sangue, trato alimentar e metabolismo apresentaram maior utilizaÃÃo, variando conforme a IG. Neonatos apresentaram maior exposiÃÃo a gentamicina seguido por ampicilina, heparina e fitomenadiona. A maioria dos neonatos (99,5%) foi exposta a medicamentos nÃo licenciados (NL) e de uso nÃo padronizado (NP), mais frequentes em neonatos com IG < 28 semanas (p < 0,05). Mais de 70% dos RN estiveram expostos a algum medicamento potencialmente perigoso (MPP), com maior frequÃncia em neonatos com IG < 31 semanas (p < 0,05). Praticamente todos os neonatos estiveram expostos a excipientes nocivos (EN) e potencialmente nocivos, sendo maior o nÃmero de formulaÃÃes prescritas a neonatos mais imaturos. Metilparabeno, propilparabeno e polissorbato 80 foram os EN aos quais os neonatos estiveram mais expostos, principalmente nas formulaÃÃes de domperidona soluÃÃo oral, polivitamÃnicos soluÃÃo oral e fentanila soluÃÃo injetÃvel. Neonatos em UTIN no Brasil, tal como em outras realidades, estÃo expostos a uma variedade de medicamentos NL, NP e com potencial nocivo, uma situaÃÃo preocupante. Alternativas seguras e estudos sÃo necessÃrios sobre esse tema. / Neonates admitted to neonatal intensive care unit (NICU) are exposed to a wide variety of drugs most without data on safety and efficacy. To describe the drug use profile of neonates in NICU of a public hospital in Brazil according to the drugs records and harmful potential of drugs and pharmaceutical excipients. Descriptive and retrospective study of drug use in NICU, with neonate inpatients for over 24 hours and prescription data from electronic medical records over the period from January to June, 2012. Drug information found in the package leaflets were compared with information in the British National Formulary for Children 2012-2013 and in the Thomson Micromedex database. The drug and excipients harmful potential was evaluated according to the literature. Neonates were categorized into groups of gestational age (GA). The data were analyzed using descriptive analysis and Distribution tests tests (ANOVA Mann-Whitney U, Kruskal-Wallis and Pearson's chi-squared) by GA, with a significance level of p <0.05. Were included 192 neonates, most preterm with median 33 weeks of GA and a total of 3.617 neonates-day. Were registered 3,290 prescriptions, average 17.1 prescriptions/neonate (SD  17.9) and 8.8 drugs/neonate (SD  5.9), higher in most immature neonates (p < 0.05). The anti-infectives for systemic use, blood and blood forming organs, alimentary tract and metabolism drugs groups showed increased use among the neonates, varying according to the GA. Neonates had higher exposure to gentamicin followed by ampicillin, heparin and phytomenadione. Most neonates (99.5%) were exposed to unlicensed drugs (UL) and off label use (OL), more frequently those with GA < 28 weeks (p < 0.05). More than 70% of the neonates were exposed to any high-alert medications, with higher frequency among neonates with GA < 31 weeks (p < 0.05). Almost all neonates were exposed to harmful and potentially harmful excipients, being greater the number of formulations prescribed to more immature neonates. Gentamicin (sulfate) injectable Solution 10 mg/mL (1 mL), fentanyl solution injectable 0.05 mg/mL (10 mL) and sodium heparin injectable solution were the containing harmful excipients formulations to which neonates were most exposed. Neonates in Brazilian NICU, as in other settings, are exposed to a variety of OL, UL and potentially harmful drugs and harmful excipients, an alarming situation. Safety alternatives and more studies are needed on this topic.

The Canadian Arctic is a region that greatly contrasts with the remainder of Canada, particularly the main area of settlement: the thin strip of land in southern Canada along the United States boundary. Since Canadian military personnel come primarily from southern Canada, being sent to an arctic installation places them in an unfamiliar, confined, isolated and potentially threatening environment that may expose them to social and psychological stresses that they are unprepared to encounter. Planning of an arctic military installation must consider physical design constraints such as construction in areas of permafrost and physical protection from the harsh natural environment. However, planning should also consider the social and psychological needs of the inhabitants. The purpose of this thesis is to identify measures that should be considered in planning a Canadian arctic military installation in order to alleviate the social and psychological stresses of this unique environment. The scope is limited to investigating primarily the military environment, although relevant material is drawn from other sources through a literature review. In order to identify the stresses of this environment, to understand their potential effects, and to suggest measures to alleviate these effects, a explicit concept of stress is required. A literature review is used to discuss the concept of stress and define a model of stress that is applied in the subsequent analysis in the thesis. This model, the transactional or interactional model, emphasizes the individuality of the experience of stress. Stress is a dynamic phenomenon that includes the capacity of an individual to not only cope with stress, but also learn from the coping experience. The experience of stress is a process affected by the characteristics of the environment, the characteristics of the individual and the relationship between the individual and his natural, man-made and social environment. A second literature review is conducted to discuss the potential social and psychological stresses that could apply to military personnel posted to the unique environment of a Canadian arctic military installation. The more salient characteristics of this environment that imply social and psychological stresses are those of isolation and confinement. Efforts suggested in the literature aimed at either avoiding or ameliorating the incidence of stress in an isolated and confined environment include actions that would be taken: a. in the design of the station built environment; b. in the screening and selection of station personnel; c. during the indoctrination training of personnel prior to deployment; and d. throughout the operation of the station. These measures were applied, via a case study of Canadian Forces Station Alert, to gauge their relevancy in planning a Canadian arctic military installation. Many of these measures are currently in practice; however, particular characteristics of the Canadian military and an arctic military station make changes in specific emphasis. Characteristics which apply are those of: a. the differences in station size; b. the differences in climate and natural environment; c. the need to maintain continuous station operation without the disruption of complete member rotation; d. the limited source population from which to select members for service in the Arctic; e. a station composed of service persons of the Canadian military is typically more homogeneous in composition; f. the differences in the circumstances under which the members are employed, as Canadian service members in the Arctic are less likely to be volunteers; g. the members of the Canadian Forces have already had some experience in postings to isolated environments; and h. the marital status of members has particular importance due to the added difficulities for service families. / Applied Science, Faculty of / Community and Regional Planning (SCARP), School of / Graduate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / INTRODUCTION: Although patient safety institutions define High-Alert Medications (MAVs) as those that are at increased risk of causing significant harm to patients as a result of a failure to use, there are few scientific studies to prove the prevalence of harm due to MAVs. OBJECTIVES: To determine the prevalence of harm to patients involving MAVs due to medications errors (MEs) in hospitals. Make recommendations for conducting studies that identify harm caused by MEs and for the preparation of lists of MAVs. METHODOLOGY: Chapter 1 was carried out through a systematic review of the PubMed, Scopus, Web of Science and Lilacs databases, considering the studies published until April 2017, using descriptors and their synonyms in different combinations. Then, titles, abstracts and full texts were evaluated by two authors independently, according to the previously established inclusion criteria. In case of discrepancies, a third evaluator was consulted. The articles were included when they determined or allowed the determination of the rates of harm caused by MAVs as a result of MEs in hospitals. Chapter 2 comprised recommendations for patient safety from the studies found in chapter one. RESULTS: In the systematic review, five articles met the inclusion criteria. The overall prevalence of harm resulting from MEs involving MAVs was 16.3%. Less than 0.01% of MEs involving MAVs resulted in death. Hypotension, hypoglycemia, hyperglycemia, hemorrhage, cardiac arrest, stroke, prolonged hospitalization, coma, permanent injury, death have been reported. The drugs most related to the damages were 15% potassium chloride, insulin, anticoagulants, epoprostenol, anesthetics. The recommendations proposed in chapter two include methods for conducting studies that identify MEs harm and emphasize the importance of hospital units to create their own lists of MAVs. CONCLUSION: Two-thirds of the medications on the ISMP list of MEs from the United States and Brazil did not provide evidence of potential harm. In general, few studies - characterized by methodological and conceptual heterogeneity - were performed to determine the prevalence of harm resulting from errors involving these drugs. / INTRODUÇÃO: Embora instituições de segurança do paciente definam os Medicamentos Alta Vigilância (MAVs) como aqueles que apresentam risco aumentado de provocar danos significativos aos pacientes em decorrência de falha no processo de utilização, há poucos estudos científicos que comprovem a prevalência dos danos devidos erros com MAVs. OBJETIVOS: Determinar a prevalência dos danos aos pacientes envolvendo MAVs em decorrência de erros de medicação (EMs) em hospitais. Realizar recomendações para realização de estudos que identifiquem danos causados por EM e para elaboração das listas de MAVs. METODOLOGIA: O Capítulo 1 foi realizado através de uma revisão sistemática nas bases PubMed, Scopus, Web of Science e Lilacs, sendo considerados os estudos publicados até abril de 2017, usando descritores e seus sinônimos em diferentes combinações. Em seguida foram avaliados títulos, resumos e textos completos por dois autores de forma independente, de acordo com os critérios de inclusão previamente estabelecidos. Em caso de discrepâncias, um terceiro avaliador foi consultado. Os artigos foram incluídos quando determinaram ou possibilitaram a determinação das taxas de danos causados por medicamentos de alta vigilância em decorrência de erros de medicação em hospitais. O Capítulo 2 compreendeu recomendações para segurança do paciente apartir dos estudos encontrados no capítulo um. RESULTADOS: Na revisão sistemática, cinco artigos atenderam os critérios de inclusão. A prevalência geral de danos decorrentes de EMs envolvendo MAVs foi de 16,3%. Menos de 0,01% dos EMs envolvendo MAVs resultaram em morte. Foram reportados danos como hipotensão, hipoglicemia, hiperglicemia, hemorragia, parada cardíaca, acidente vascular cerebral, hospitalização prolongada, coma, lesão permanente, morte. Os medicamentos mais relacionados aos danos foram cloreto de potássio a 15%, insulina, anticoagulantes, epoprostenol, anestésicos. As recomendações propostas no capítulo dois incluem métodos para realização de estudos que identifiquem danos provocados por EMs e refoça a importância das unidades hospitalares criarem suas próprias listas de MAVs. CONCLUSÃO: Dois terços do medicamentos presentes na lista de MAVs do ISMP dos Estados Unidos e do Brasil não apresentaram evidências quanto ao potencial de provocar danos. Em geral, poucos estudos - caracterizados por heterogeneidade metodológica e conceitual - foram realizados para determinar a prevalência de danos decorrentes de erros envolvendo esses medicamentos. / São Cristóvão, SE

Im Rahmen der EU-Richtlinie REACH müssen industrierelevante Chemikalien bezüglich des Risikos für Mensch und Umwelt (neu) untersucht und bewertet werden, wobei die Anzahl an Tierversuchen zu minimieren ist und neue toxikologische Prüfmethoden, Bewertungsstrategien sowie alternative Testsysteme entwickelt und optimiert werden sollen. Ubiquitär vorkommende Testorganismen, welche ähnliche Eigenschaften und eine vergleichbare Sensitivität bezüglich äußerer Einflüsse wie komplexere Organismen (Fisch, Säugetier, Mensch) besitzen, sind hier besonders gefragt um die Belastung abzuschätzen und Trendaussagen über die Wirkung zu formulieren. Durch den Einsatz vieler dieser Testorganismen sowie durch die Ermittlung der chemischen Reaktivität und der Strukturmerkmale einer Verbindung kann ein globales Bild über die Wirkung erhalten werden. Ein Organismus, der diese Charakteristika aufweist, ist der eukaryotische Einzeller Tetrahymena pyriformis GL. In der vorliegenden Dissertation wird zum einen die jeweilige Toxizität elektrophiler Substanzen unterschiedlicher Stoffklassen und Reaktions-mechanismen (α,β-ungesättigte Carbonyl- und Carboxylverbindungen, heterozyklische Drei- und Vierringe, α-halogenierte Carbonyle, Harnstoffe und Thioharnstoffe, aromatische Disulfide sowie aliphatische und aromatische Nitroverbindungen) nach den Expositionszeiten 24 h, 48 h und 72 h mit Hilfe eines etablierten Wachstumshemmtests (Müller, 2001) bestimmt und Struktur-Toxizitäts-Beziehungen bzw. Strukturalarme abgeleitet. Neben der methodischen Optimierung werden die substanzspezifischen Eigenschaften, Flüchtigkeit und Sorptionsfähigkeit, quantitativ erfasst und durch neu aufgestellten Modellgleichungen für jede Substanz ermittelt. Mit der Bestimmung der Toxizitätserhöhung, Te, welche auch als ein Maß für die Reaktivität angesehen werden kann, werden Organismen-spezifische Narkose-Basis-Geraden generiert, exzesstoxische Verbindungen identifiziert und Strukturalarme für die jeweiligen Stoffklassen aufgestellt. Zum anderen werden binäre Mischungen untersucht, welche aus den Einzelstoffen bestehen, deren Toxizität im ersten Abschnitt der Arbeit ermittelt wurden und bei denen theoretische Annahmen über die Reaktionsmechanismen bestehen. Dieser Abschnitt identifiziert, ob gleiche bzw. unähnliche primäre Wechselwirkungen zweier Substanzen mit den biologischen Targets vorliegen und welcher Mechanismus, der reaktive Mechanismus exzesstoxischer Substanzen oder die Wechselwirkungen mit Membran-Bestandteilen, dominierend ist. Für die Auswertung der Mischungsergebnisse werden die etablierten biometrischen Modelle Konzentrations-Additivität und Unabhängigen Wirkung verwendet. Es wird dargestellt, dass die Mischungstoxizitäten der binären Mischungen ähnlich wirkender Substanzen zwar relativ genau mithilfe beider Modelle berechnet werden, jedoch keine eindeutige Charakterisierung der Mechanismen möglich ist. Die Ergebnisse der untersuchten binären Mischungen unterschiedlich wirkender Substanzen zeigen dagegen, dass die Mischungstoxizitäten unähnlicher Substanzen relativ genau mithilfe des Modells der Unabhängigen Wirkung berechnet werden und eine Charakterisierung der Mechanismen möglich ist.