Bakgrund: Postoperativa sårinfektioner orsakar ett lidande för patienten och medför stora kostnader för samhället. En central del i operationssjuksköterskans arbete är att ge en säker vård och undvika patientskador i samband med operation. Operationssjuksköterskans kompetens inom hygien och att upprätthålla det sterila fältet under operation behövs för att förhindra uppkomsten av postoperativa sårinfektioner. Syfte: Att belysa operationssjuksköterskans erfarenheter av situationer när det sterila fältet äventyras intraoperativt och vilka åtgärder som då vidtas. Metod: Kvalitativ design med semistrukturerade intervjuer av 12 operationssjuksköterskor från ett sjukhus i södra Sverige. Induktiv innehållsanalys av Elo och Kyngäs (2008) användes för analys av data. Resultat: Studien visar att kommunikation och teamsamverkan är viktigt för att operationssjuksköterskan ska kunna upprätthålla det sterila fältet. Operationssjuksköterskan måste hela tiden hålla koll på allt som händer i operationssalen för att kunna uppmärksamma om det sterila fältet äventyras. Vid akuta operationer är steriliteten sekundär då patientens liv är i fara vilket gör att det gäller att prioritera. Oförutsägbara händelser kräver kreativitet för att återställa det sterila fältet men med åren blir det lättare i alla situationer.  Slutsats:Operationssjuksköterskan har många erfarenheter av situationer där det sterila fältet äventyras. Flera faktorer spelar in i arbetet med att upprätthålla det sterila fältet. Forskning som underlättar för operationssjuksköterskan i arbetsuppgifterna med att upprätthålla det sterila fältet bör studeras vidare. / Background: Surgical site infections increase suffering for the patient and entails great cost for society. The theatre nurse should work to make sure patient safety and to avoid patient injuries correlated to the surgery. The theatre nurse competence in hygiene and adherence to conduct the sterile field is needed to prevent surgical site infections. Aim: To describe the theatre nurse experiences of situations where the sterile field is jeopardized intraoperative and the actions to prevent it. Method: Qualitative design, semi structured interviews with 12 theatre nurses from a hospital in southern Sweden. Inductive content analysis by Elo and Kyngäs (2008) was used to analyze the data. Results: The study shows that communication and teamwork is necessary for the theatre nurse to maintain the sterile field. For the same reason the theatre nurse needs to be observant of everything going on in the operating room. When the patient's life is in danger, sterility comes in second place, and makes it necessary to prioritize. Unpredicted situations demands creativity to restore the sterile field but it gets easier with work experience Conclusion: The theatre nurse has a lot of experiences regarding situations where the sterile field is jeopardized. Several factors play a role in maintaining the sterile field. Research that facilitates the theatre nurse tasks in maintaining the sterile field should be further studied.

A linhagem tsl (temperature sensitive lethal) - Vienna 8 da espécie Ceratitis capitata, por apresentar mutações que facilitam a criação e a liberação de apenas machos estéreis no campo, vem sendo utilizada em programas de controle da mosca-do-mediterrâneo com o uso da técnica do inseto estéril. O objetivo deste trabalho foi determinar a dose de radiação gama que proporciona o maior índice de esterilidade para machos da espécie C. capitata - linhagem tsl Vienna 8, avaliando seus parâmetros biológicos que indicam a qualidade dos machos estéreis a serem liberados. Pupas marrons (machos) da linhagem tsl, provenientes da criação do laboratório de Irradiação de Alimentos e Radioentomologia do CENA/USP, foram submetidas à radiação gama (60Co) 24 horas antes da emergência nas doses de 0, 30, 60, 90 e 120 Gy. A determinação da dose esterilizante foi baseada na fertilidade de fêmeas sexualmente maduras, da linhagem bissexual e não irradiadas, acasaladas com machos dos diferentes tratamentos. A coleta dos ovos foi realizada diariamente por 6 dias, sendo possível contabilizar e estimar a fecundidade, e obter a taxa de eclosão. A determinação da porcentagem de emergência e da capacidade de voo seguiram o protocolo de controle de qualidade do manual da FAO/IAEA/USDA (2003). Para avaliar a longevidade sob estresse nutricional, os insetos ficaram um período de 48h após a emergência na ausência de água e alimento, e após este período, a mortalidade foi registrada. O tamanho dos testículos (esquerdo e direito) foi obtido ao dissecar machos irradiados e não-irradiados no 8o dia de vida, e mensurar os testículos em uma ocular micrométrica, considerando os maiores comprimento e largura de cada amostra. Para determinar o número de espermatozoides foi necessário dissecar os machos e romper seus testículos. Não houve diferença na taxa de emergência, capacidade de voo e longevidade entre machos irradiados e não-irradiados, e nem na fecundidade das fêmeas acasaladas com os machos dos diferentes tratamentos. A dose esterilizante que resultou na menor fertilidade das fêmeas foi de 120 Gy, com 1,5% de eclosão. Considerando os parâmetros de porcentagem de emergência, capacidade de vôo, longevidade sob estresse, e a esterilidade recomendada para a técnica do inseto estéril que consiste em, aproximadamente, 99% dos ovos serem inviáveis, a dose esterilizante a ser utilizada é a de 120 Gy. O tamanho dos testículos e o número de espermatozoides foram afetados pela radiação, havendo diferença entre os tratamentos. Os machos irradiados com 120 Gy apresentaram uma redução de cerca de 25% no tamanho dos testículos, comparando com os do controle (0 Gy). Os testículos dos machos normais continham uma média de 41910 espermatozoides, e esse valor foi decrescendo ao aumentar a dose de radiação, de maneira que machos irradiados com 120 Gy tinham um número médio de 27921 espermatozoides, e isto, possibilita a recomendação do uso de macho transgênico para controle de C. capitata / The Vienna-8, tsl (temperature sensitive lethal) strain of Ceratitis capitata, by presenting mutations that facilitate the mass rearing and release only of sterile males in the field, has been used in medfly SIT (Sterile Insect Technique) programmes. The objective of this study was to determine the radiation dose that provides the highest level of sterility for Vienna-8, tsl males assessing their biological parameters that indicate the quality of sterile males to be released. Brown pupae (males) of the tsl strain were obtained from the mass rearing of the Food Irradiation and Radioentomologia laboratory of CENA/USP, and they were irradiated (with gamma radiation - 60Co) 24 hours before the emergence at rates of 0, 30, 60, 90 and 120 Gy. The determination of the sterilizing dose was based on fertility of sexually mature females of the bisexual strain and not irradiated, mated with males of different treatments. Eggs were collected daily during 6 days, were counted and it was possible to estimate fecundity, and assess the hatching rate. The emergence and flight ability were determined by following the protocol of quality control manual for FAO/IAEA/USDA (2003). To assess the longevity under nutritional stress, the insects were kept a period of 48 h after emergence in the absence of water and food, and after this period, mortality was recorded. The size of the testes (left and right) was obtained by dissecting irradiated and non-irradiated males at the eighth day of life, and measure the testes in an ocular micrometer, considering the maximum length and width of each sample. To determine the sperm number was necessary to dissect the males and break their testicles. No difference was observed in emergence rate, flight ability and longevity of irradiated and non-irradiated males, nor in the fecundity of females mated with males of different treatments. The sterilizing dose that resulted in lower fertility of females was 120 Gy, with 1.5% hatching. Considering the parameters of emergence, flight ability, longevity under stress and sterility recommended for the sterile insect technique which consists of approximately 99%, the sterilizing dose to be used is 120 Gy. The size of the testes and the sperm number were affected by radiation. Males irradiated with 120 Gy presented a reduction about 25% in size of the testes, compared with the control (0 Gy). The testes of normal males contained an average of 41.910 sperm, and this value was decreased by increasing the dose of radiation, so that males irradiated with 120 Gy had a median of 27.921 sperm, and this allowed to recommend the use of GM male to control C. capitata

Die intrazelluläre Weiterleitung von Interferonsignalen von der Zytoplasmamembran zum Zellkern wird vermittelt über den Signaltransduktor und Aktivator der Transkription 1 (STAT1), welcher in seiner tetrameren Form als Transkriptionsfaktor an Immunantworten beteiligt ist. In diesem Projekt wurde der Protomerenaustausch zwischen STAT1-Dimeren unter kinetischen Gesichtspunkten untersucht und dabei dieser Prozess als ein potentiell geschwindigkeitsbestimmender Schritt des Aktivierungs-/Inaktivierungs-Zyklus von STAT1 identifiziert. Die Daten unterstützen einen alternativen Mechanismus für den Wechsel zwischen der parallelen und antiparallelen Konformation von STAT1-Dimeren basierend auf der Dissoziation und nachfolgenden Reassoziation von Protomeren, bei dem reziproke Interaktionen innerhalb des N-terminalen Domänendimers zur Stabilisierung eines intermediären Konformationsübergangs nicht benötigt werden. Durch Bindung an spezifische DNA-Zielbereiche, als Gamma-aktivierte Sequenzen (GAS) bezeichnet, wird die Dynamik des Protomerenaustauschs wesentlich beeinträchtigt. In der Sequenz des für das zytoskelettale Strukturprotein Ezrin kodierenden humanen EZR-Gens wurde mittels in silico Analyse ein doppeltes GAS-Motiv als mögliche STAT1-Zielsequenz identifiziert und die Bindung von STAT1-Dimeren an jedes der beiden Elemente sowie eine moderate Geninduktion bestätigt. Allerdings zeigen Mäuse mit einer N-terminalen Substitutionsmutation von STAT1, welche die kooperative DNA-Bindung beeinträchtigt, sowie auch ein kompletter funktioneller Knockout des Stat1-Gens keine veränderte Expression von Ezrin und Moesin in Knochenmarkszellen verglichen mit Mäusen, die das Wildtyp-Molekül exprimieren. In einem Myokardinfarktmodell durch Ligatur des Ramus interventricularis anterior zeigen männliche Mäuse mit Expression der Interferon-γ-irresponsiven STAT1-Mutante höhere Überlebensraten, während weibliche Tiere vor den nachteiligen Effekten des kardialen Remodellings in der frühen Phase geschützt sind. In entzündlichen myokardialen Infiltraten dieser Tiere wurde ein geringfügig höheres Expressionsniveau an tyrosinphosphoryliertem STAT1 nachgewiesen, während die Gesamtproteinmenge an STAT1 gegenüber dem Wildtyp reduziert war. Zellen aus lymphatischen Organen STAT1-defizienter Tiere mit experimenteller autoimmuner Enzephalomyelitis, die als Modell einer T-Helfer-Zell-vermittelten Autoimmunerkrankung verwendet wurde, zeigten einen hyperproliferativen Phänotyp und sezernierten größere Mengen an IFNγ und IL-17A. Injektion dieser Mäuse mit Lipopolysaccharid während der Induktionsphase der experimentellen autoimmunen Enzephalomyelitis hob den hyperproliferativen Phänotyp vollständig auf. Zusammenfassend demonstrieren die Ergebnisse aus dieser Arbeit die Bedeutung einer kooperativen DNA-Bindung und Tetramerstabilisierung von STAT1 im Zusammenspiel komplexer immunologischer Prozesse auch in Abwesenheit infektiöser Pathogene und unterstreichen zudem die Schlüsselrolle von tyrosinphosphoryliertem STAT1 bei der Verknüpfung zwischen angeborenem und erworbenem Immunsystem.

Les femelles moustiques peuvent être vectrices de nombreux agents infectieux (virus, protozoaires, helminthes) pour l'Homme, qui peuvent être la cause de maladies graves comme le paludisme et la dengue. Ces maladies menacent respectivement 50 et 40% de la population mondiale ; le paludisme étant responsable de près d'un million de décès par an. Les méthodes de lutte anti-vectorielle destinées à limiter les populations vectrices et stopper la transmission de maladies, se heurtent au développement incessant de résistances de la part des moustiques et des agents infectieux vis-à-vis des traitements employés. Bien que certaines régions du monde aient réussi à stopper efficacement la transmission de certaines de ces maladies, une grande partie des régions tropicales reste menacée. De plus l'expansion rapide de certaines espèces vectrices, telles qu'Aedes albopictus, accroît les risques sanitaires dans de nouvelles régions du globe. La technique de l'insecte stérile (TIS), qui a permis l'éradication ou la suppression des populations de nombreux insectes nuisibles aux cultures et à l'Homme, représente un moyen de lutte prometteur contre les moustiques. Cette technique s'appuie sur le lâcher en masse de mâles stérilisés par rayonnements ionisants qui, en transférant un sperme stérile aux femelles sauvages, vont permettre une diminution progressive de la population cible. Suite à l'épidémie de chikungunya à l'île de la Réunion en 2005 et face aux menaces permanentes de recrudescence de la dengue et du paludisme, les services de lutte anti-vectorielle réunionnais mettent en place d'importants moyens de lutte contre les populations de moustiques concernées. Toutefois, ces mesures ne permettant pas une diminution durable des densités de vecteurs, une étude de faisabilité est en cours quant à l'utilisation de la TIS pour diminuer et contrôler les populations d’Aedes albopictus, vecteur de la dengue et du chikungunya, et d’Anopheles arabiensis, vecteur du paludisme.Ce travail de thèse s'inscrit dans le cadre du projet TIS Réunion, dans le but d'étudier la biologie et le comportement des souches destinées aux lâchers de mâles stériles. Dans un premier temps, cette étude s'intéresse à la comparaison entre les souches d'élevage d’Anopheles arabiensis et les souches sauvages, ainsi qu'aux modalités de stérilisation des mâles de la souche à sexage génétique. Une seconde partie est consacrée à l'étude de l'effet de l'irradiation sur les mâles d’Aedes albopictus, en étudiant plus particulièrement leur stratégie de reproduction, leur capacité d'insémination en laboratoire, ainsi que leur compétitivité sexuelle et longévité face aux mâles sauvages en conditions semi-contrôlées. / Mosquito females are potential vectors of numerous pathogens (viruses, protozoa, helminths), which can cause serious diseases such as malaria and dengue in humans. These two infectious diseases are threatening 50 and 40% of the world population respectively. Malaria is responsible for nearly one million deaths per year, and is considered by many experts as the most important insect-transmitted disease. Antivectorial control methods, intended to limit the vector populations and to stop the disease transmission have to face many challenges such as the development of mosquitoes' and pathogens' resistance to the treatments employed to control them. Although various regions of the world have succeeded in efficiently stopping the transmission of some diseases, most of the tropical regions remain under threat. In addition, the rapid expansion of some vector species, such as Aedes albopictus, increases the risks in previously safe areas of the world. The sterile insect technique (SIT) has allowed the eradication or suppression of various insect pest populations threatening crops, animal, and human health, and could offer a promising control tool against mosquitoes. The classical SIT relies on the mass releases of males sterilized by ionizing radiation;they transfer sterile sperm to wild females, which results in a progressive reduction of the target population.Following the chikungunya outbreak in Reunion Island in 2005 and considering the constant threat of arecrudescence of dengue and malaria, the anti-vectorial services in Reunion Island are deploying important means to control the relevant mosquito populations. However, these measures do not confer a permanent, or long-lasting reduction of vector densities. A feasibility study is ongoing, evaluating the use of the SIT to diminish and control the populations of Ae. albopictus, a vector of dengue and chikungunya, and Anopheles arabiensis, a vector of malaria. This PhD work was developed in the context of the SIT Reunion project, with the aim of studying the biology and the behaviour of some strains intended for the sterile male releases. Firstly, this study endeavours to compare colonized and wild strains of An. arabiensis, and to determine the sterilisation procedures of the genetic sexing strain males. The second part of this work studies the effect of irradiation on male Ae. albopictus, and most notably their reproductive strategy, the insemination capacity in laboratory, and finally their sexual competitiveness and longevity against wild males under semi-field conditions.

As moscas-das-frutas se constituem no maior obstáculo para a produção, processamento e comércio de frutas frescas em todo o mundo. O Brasil não é exceção e, embora as condições brasileiras sejam bastante adequadas à produção de frutas tropicais e temperadas, a fruticultura enfrenta, continuamente, o problema das moscas-das-frutas. Dentre as espécies de maior importância econômica e quarentenária, destaca-se a mosca-do-mediterrâneo Ceratitis capitata (Wied., 1824) que tem, como centro de origem, a África Equatorial, e é uma das pragas mais destrutivas, causando elevados prejuízos à fruticultura mundial. No Brasil, onde sua presença foi registrada no início do século passado, esta praga se encontra amplamente distribuída em todo o território nacional. Os processos integrados de controle de pragas e doenças, com emprego de controle biológico, monitoramento populacional da praga, sistema de informação geográfica e aplicação de técnicas de controle das populações têm se desenvolvido significativamente nos últimos anos, permitindo a obtenção de frutas de alta qualidade. Com o sucesso da aplicação da Técnica do Inseto Estéril (TIE) na erradicação da Cochliomyia hominivorax (Coquerel, 1858) da Ilha de Curaçao e da região Sudeste dos Estados Unidos, houve um estímulo para o uso de programa contra várias espécies de moscas-das-frutas. A necessidade de se buscar respostas para o uso de fontes alternativas na esterilização de insetos, notadamente o uso de raios X, em escala industrial e a busca de novos modelos que possam inovar desde o ponto de vista tecnológico a TIE, com métodos que dispensem, por completo, o uso de radiação ionizante é o desafio do presente estudo, que teve como objetivo avaliar, através de testes em laboratório e em gaiola de campo, a linhagem transgênica de Ceratitis capitata (Wied.), OX3864A, comparada à linhagem tsl Vienna 8 da mesma espécie, esterilizada por raios X, visando a sua possível aplicação em programas de controle de moscas-dasfrutas, com foco na TIE. Os resultados obtidos mostram que a criação massal da linhagem transgênica esta dominada e que a dieta adotada pela BIOFÁBRICA MOSCAMED BRASIL (BMB), para a linhagem tsl Vienna 8, pode ser usada para a criação da linhagem transgênica OX3864A sem afetar o rendimento e os padrões de qualidade requeridos para o uso da linhagem na TIE. No que diz respeito aos bioensaios em gaiola de campo, os machos de ambas linhagens apresentaram uma boa performance sexual sendo capazes de competir com machos coespécificos selvagens pela cópula com fêmeas selvagens virgens. O desempenho dos machos transgênicos OX3864A não deferiu do desempenho dos machos irradiados de tsl Vienna 8. A fim de aprofundar os estudos, necessário se faz a realização de novas pesquisas para avaliar o desempenho de linhagens transgênicas em campo aberto / Fruit flies are within the main barriers to fresh fruit production, processing and trade throughout the world. In that sense, Brazil is not an exception, and although Brazilian conditions are favorable to the production of tropical and temperate fruits, this industry continually faces problems related to the fruit fly. From an economical and quarantine point of view, Ceratitis capitata (Wied., 1824) can be considered the most important fruit fly specie, which has the Equatorial Africa as center of origin, is also one of the most destructive pests, causing high losses to the world fruit industry. In Brazil, where its presence has been first noticed in the beginning of the past century, nowadays this pest is widespread throughout the whole national territory. With the latest developments on biological control, pest monitoring, geographical information systems and application of population control techniques it is seen that the integrated pest management systems are allowing the production of high quality fruits. Since the successful application of the sterile insect technique on the eradication of Cochliomyia hominivorax (Coquerel, 1858) in Curaçao and in the US Southeast region, there has been an incentive to the use of this technique in programs against various fruit fly species. On the search for alternative sources for insect sterilization especially the use of X-ray in high scale and the search for new models able to innovate the sterile insect technique from a technological point of view with methods that exempt the use of ionizing irradiation is the challenge of the present study, whose aim was to evaluate through lab and field cage tests the transgenic OX3864A RIDL of Ceratitis capitata (Wied.) strain, compared to X-ray sterilized tsl Vienna 8 strain, looking for a possible application on fruit fly control programs focused on the Sterile Insect Technique (SIT). Results obtained show that the mass rearing of the transgenic strain is dominated and the diet adopted by MOSCAMED BRAZIL rearing facility, for tsl Vienna 8 can also be used for the OX3864A transgenic strain without affecting its yield and quality standards required for its use in SIT. Regarding the field cage bioassays, males from both strains presented a good sexual performance, being able to compete with wild co-specific to mate with virgin wild females. Transgenic males did not differ from irradiated tsl Vienna 8 males. Further studies on sexual performance evaluation on open field of transgenic strain is recommended in order to provide more knowledge

As moscas-das-frutas se constituem no maior obstáculo para a produção, processamento e comércio de frutas frescas em todo o mundo. O Brasil não é exceção e, embora as condições brasileiras sejam bastante adequadas à produção de frutas tropicais e temperadas, a fruticultura enfrenta, continuamente, o problema das moscas-das-frutas. Dentre as espécies de maior importância econômica e quarentenária, destaca-se a mosca-do-mediterrâneo Ceratitis capitata (Wied., 1824) que tem, como centro de origem, a África Equatorial, e é uma das pragas mais destrutivas, causando elevados prejuízos à fruticultura mundial. No Brasil, onde sua presença foi registrada no início do século passado, esta praga se encontra amplamente distribuída em todo o território nacional. Os processos integrados de controle de pragas e doenças, com emprego de controle biológico, monitoramento populacional da praga, sistema de informação geográfica e aplicação de técnicas de controle das populações têm se desenvolvido significativamente nos últimos anos, permitindo a obtenção de frutas de alta qualidade. Com o sucesso da aplicação da Técnica do Inseto Estéril (TIE) na erradicação da Cochliomyia hominivorax (Coquerel, 1858) da Ilha de Curaçao e da região Sudeste dos Estados Unidos, houve um estímulo para o uso de programa contra várias espécies de moscas-das-frutas. A necessidade de se buscar respostas para o uso de fontes alternativas na esterilização de insetos, notadamente o uso de raios X, em escala industrial e a busca de novos modelos que possam inovar desde o ponto de vista tecnológico a TIE, com métodos que dispensem, por completo, o uso de radiação ionizante é o desafio do presente estudo, que teve como objetivo avaliar, através de testes em laboratório e em gaiola de campo, a linhagem transgênica de Ceratitis capitata (Wied.), OX3864A, comparada à linhagem tsl Vienna 8 da mesma espécie, esterilizada por raios X, visando a sua possível aplicação em programas de controle de moscas-dasfrutas, com foco na TIE. Os resultados obtidos mostram que a criação massal da linhagem transgênica esta dominada e que a dieta adotada pela BIOFÁBRICA MOSCAMED BRASIL (BMB), para a linhagem tsl Vienna 8, pode ser usada para a criação da linhagem transgênica OX3864A sem afetar o rendimento e os padrões de qualidade requeridos para o uso da linhagem na TIE. No que diz respeito aos bioensaios em gaiola de campo, os machos de ambas linhagens apresentaram uma boa performance sexual sendo capazes de competir com machos coespécificos selvagens pela cópula com fêmeas selvagens virgens. O desempenho dos machos transgênicos OX3864A não deferiu do desempenho dos machos irradiados de tsl Vienna 8. A fim de aprofundar os estudos, necessário se faz a realização de novas pesquisas para avaliar o desempenho de linhagens transgênicas em campo aberto / Fruit flies are within the main barriers to fresh fruit production, processing and trade throughout the world. In that sense, Brazil is not an exception, and although Brazilian conditions are favorable to the production of tropical and temperate fruits, this industry continually faces problems related to the fruit fly. From an economical and quarantine point of view, Ceratitis capitata (Wied., 1824) can be considered the most important fruit fly specie, which has the Equatorial Africa as center of origin, is also one of the most destructive pests, causing high losses to the world fruit industry. In Brazil, where its presence has been first noticed in the beginning of the past century, nowadays this pest is widespread throughout the whole national territory. With the latest developments on biological control, pest monitoring, geographical information systems and application of population control techniques it is seen that the integrated pest management systems are allowing the production of high quality fruits. Since the successful application of the sterile insect technique on the eradication of Cochliomyia hominivorax (Coquerel, 1858) in Curaçao and in the US Southeast region, there has been an incentive to the use of this technique in programs against various fruit fly species. On the search for alternative sources for insect sterilization especially the use of X-ray in high scale and the search for new models able to innovate the sterile insect technique from a technological point of view with methods that exempt the use of ionizing irradiation is the challenge of the present study, whose aim was to evaluate through lab and field cage tests the transgenic OX3864A RIDL of Ceratitis capitata (Wied.) strain, compared to X-ray sterilized tsl Vienna 8 strain, looking for a possible application on fruit fly control programs focused on the Sterile Insect Technique (SIT). Results obtained show that the mass rearing of the transgenic strain is dominated and the diet adopted by MOSCAMED BRAZIL rearing facility, for tsl Vienna 8 can also be used for the OX3864A transgenic strain without affecting its yield and quality standards required for its use in SIT. Regarding the field cage bioassays, males from both strains presented a good sexual performance, being able to compete with wild co-specific to mate with virgin wild females. Transgenic males did not differ from irradiated tsl Vienna 8 males. Further studies on sexual performance evaluation on open field of transgenic strain is recommended in order to provide more knowledge

L’expérience Double Chooz a pour but la mesure précise de l’angle de mélange θ₁₃. Son évaluation repose sur l’étude de la disparition des antineutrinos produits par les réacteurs de la centrale de Chooz, disparition due au phénomène d’oscillation des neutrinos. Deux détecteurs identiques composés de liquide scintillant permettent d’effectuer une mesure relative, diminuant ainsi les incertitudes systématiques. Le détecteur proche, qui fournit la normalisation du flux de neutrinos émis, est en cours d’installation, son achèvement est prévu pour le printemps 2014. Le détecteur lointain, sensible à l’effet de θ₁₃, est situé à un kilomètre environ et prend des données depuis 2011. Dans cette première phase de l’expérience, les données acquises par le détecteur lointain sont comparées à une prédiction du flux de neutrinos émis par les réacteurs pour estimer le paramètre θ₁₃. Au sein de cette thèse, l’expérience Double Chooz et son analyse sont présentées. Une attention particulière est portée à l’étude des bruits de fond et au rejet de signaux parasites constitués de flashs lumineux émis par les photo-multiplicateurs. Les flux de neutrons aux interfaces entre les différents volumes du détecteur affectent la définition du volume d’interaction et partant l’efficacité de détection. L’étude détaillée de ces effets de bord est présentée. Dans le cadre de l’expérience Double Chooz, des études ont été menées afin d’améliorer la prédiction des flux de neutrinos émis par les réacteurs. Ces travaux ont mis à jour un déficit des taux de neutrinos observés dans les expériences passées à courtes distances des réacteurs. Ce déficit pourrait s’expliquer par une oscillation vers une saveur stérile. Le projet Stereo a pour but d’observer la distorsion — caractéristique de l’oscillation — du spectre des neutrinos en énergie et en distance de propagation. Cette thèse s’attache à présenter le concept du détecteur, les simulations réalisées, ainsi que les études de sensibilité. Les différents bruits de fond et les blindages envisagés pour s’en prémunir sont enfin discutés. / The Double Chooz experiment aims to measure the θ₁₃ mixing angle through the disappearance—induced by the oscillation phenomenon—of anti-neutrinos produced by the Chooz nuclear reactors. In order to reduce systematic uncertainties, the experiment relies on the relative comparison of detected signals in two identical liquid scintillator detectors. The near one, giving the normalization of the emitted flux, is currently being built and will be delivered in spring 2014. The far detector, sensitive to θ₁₃, is located at about one kilometer and is taking data since 2011. In this first phase of the experiment, the far detector data are compared to a prediction of the emitted neutrino flux to estimate θ₁₃. In this thesis, the Double Chooz experiment and its analysis are presented, especially the background studies and the rejection of parasitic signals due to light emitted by photo-multipliers. Neutron fluxes between the different detector volumes impact the definition of the fiducial volume of neutrino interactions and the efficiency of detection. Detailed studies of these effects are presented. As part of the Double Chooz experiment, studies were performed to improve the prediction of neutrino flux emitted by reactors. This work revealed a deficit of observed neutrino rates in the short baseline experiments of last decades. This deficit could be explained by an oscillation to a sterile state. The Stereo project aims to observe a typical signature of oscillations: the distortion of neutrino spectra both in energy and baseline. This thesis presents the detector concept and simulations as well as sensitivity studies. Background sources and the foreseen shielding are also discussed.

Interagissant très peu avec leur environnement, les neutrinos peuvent aujourd'hui être clairement détectés à l'aide d'une technologie largement éprouvée reposant sur l'utilisation de liquide scintillant et de photo-multiplicateurs. Les progrès réalisés ces dernières années permettent de réduire la taille et la complexité des détecteurs et laissent ainsi entrevoir les premières applications à ces particules. Première expérience placée à 7,2 m d'un coeur de réacteur nucléaire, le détecteur Nucifer démontre la possibilité de compter les antineutrinos venant du combustible à cette faible distance induisant un environnement très défavorable en terme de bruits de fond. Dans cette thèse, nous présentons l'analyse ayant permis de rejeter les différents bruits de fond venant du réacteur et de son circuit de désactivation mais aussi des muons atmosphériques. Une prédiction du taux d'antineutrinos avec différentes simulations Monte-Carlo a également été réalisée et se trouve en accord avec le taux mesuré dans la limite des incertitudes statistiques et systématiques. Sur près d'un an de prise de données, nous avons pu suivre l'évolution en puissance du réacteur Osiris. Une étude de sensibilité a montré que la présence de plutonium dans le coeur d'Osiris était détectable à 95 % CL dès que cet isotope contribue à hauteur de 10 % de la masse fissile (1,5 kg dans Osiris). En outre, le détecteur a montré une grande stabilité tout au long de la prise de données prouvant que le contrôle à distance des réacteurs nucléaires est possible. Cette expérience ouvre donc la voie à de nouveaux modes de contrôle des réacteurs nucléaires pour les autorités de sûreté. Dans le cadre des travaux sur les spectres d'antineutrinos émis par les réacteurs nucléaires, un déficit a récemment été mis en évidence dans le taux des antineutrinos mesurés pour les expériences à courte distance des réacteurs. Ce déficit, appelé anomalie réacteur, pourrait trouver son origine dans une nouvelle oscillation à travers un état stérile du neutrino à l'électronvolt. L'expérience Stéréo a pour but de trancher sur l'existence ou non de cette oscillation en se plaçant à 10 m du réacteur nucléaire de l'ILL. En observant une distorsion à la fois en énergie et en distance, le détecteur permettra en effet d'apporter une conclusion solide sur ce phénomène. Nous revenons ici sur le développement du projet et sur les différents choix technologiques réalisés pour améliorer la sensibilité de l'expérience. Une attention particulière est portée sur l'estimation des bruits de fond provenant du réacteur nucléaire ainsi que des expériences voisines utilisant des faisceaux de neutrons. Des mesures expérimentales alliées à des simulations ont permis de quantifier les flux de rayons gammas et de neutrons ainsi que leur direction afin de prévoir les blindages nécessaires. Enfin, nous présentons les performances du prototype correspondant à une cellule du détecteur final. / In spite of a faint interaction with their environment, neutrinos can be now clearly detected thanks to a proven technology based on liquid scintillators and photomultiplier tubes. The advances made these last years allow to reduce the size and the complexity of the detectors and therefore naturally lead to the first applications with these particles. As the first experiment to be placed at 7.2 m of a nuclear core, the Nucifer detector demonstrates the possibility of counting antineutrinos coming from the nuclear fuel at such a short baseline despite the very unfavourable environment in term of the background noises. In this thesis, we present an analysis which rejects the various background noises coming from the reactor and its deactivation circuit but also from the atmospheric muons. A prediction of the antineutrino rate with several Monte-Carlo simulations was also performed and is in good agreement with the measured rate, within statistical and systematic uncertainties. After nearly one year of data taking, we were able to follow the power evolution of the reactor Osiris. A sensibility study showed that the presence of plutonium in the Osiris core was detectable at 95 % CL as soon as this isotope contributes at the level of 10 % of the fissile mass (1,5 kg in Osiris). Besides, the detector was very stable throughout the data taking proving that the remote control of nuclear reactor with a neutrino detector is possible. Thus, this experiment opens the way to new control modes of nuclear reactors by the nuclear safety authorities. As part of the work on the antineutrino spectra emitted by nuclear reactors, a deficit was recently highlighted in the observed antineutrino rate for the experiments at short baseline. This deficit, called the reactor anomaly, could be explain by a new oscillation into a sterile state of the neutrino at the electronvolt scale. The Stereo experiment aims to test the existence of this oscillation by performing measurements 10 m away from the ILL nuclear reactor. By observing a distortion pattern of the energy and distance dependence of the neutrino spectrum, the detector will be able to provide a solid proof of this phenomenon. We present here the project development and the various technological choices that we have done to improve the experiment sensibility. The estimation of the background noise coming from the nuclear reactor as well as the nearby experiments using neutron beams has been performed with on-site measurements and simulations to design the shielding of the detector. Eventually we present the performances of the prototype which corresponds to one cell of the final detector.

Purpose: Prescription and illicit opioid abuse have disproportionately impacted the Central Appalachian Region. Centers for Disease Control and Prevention (CDC) data indicate the region is home to many of the 220 counties most vulnerable to rapid dissemination of Hepatitis C Virus (HCV) and HIV related to injection drug use. Growing evidence supports the role of community pharmacies in HCV/HIV prevention by providing access to non-prescription sterile syringes; however, research has largely been confined to major metropolitan areas. The objective of this study is to evaluate the feasibility of community pharmacies in Central Appalachia serving as access points for sterile syringes. Methods: This study was approved by the Institutional Review Board. Using state directories of health professionals, community pharmacists from Northeast Tennessee, Western North Carolina, and Southwest Virginia were randomly selected to participate in key informant interviews to inform understanding of the impact of attitudes, beliefs, and state-level policies on pharmacists’ syringe dispensing behaviors (N=15). Informed consent was obtained prior to initiating the interviews and participants were provided modest compensation for their time. The semi-structured interviews were guided by Theory of Planned Behavior constructs to focus the interview on evidence-based predictors of behaviors. Interviews were audio-recorded, de-identified, transcribed, and are currently being thematically analyzed by the research team with NVivo software. The results of this study are expected to inform development of a survey instrument for a larger quantitative evaluation of pharmacists' perceptions on syringe dispensing in the region. Results: Not applicableConclusion: Not applicable

Μελέτες στη Μεσογειακή μύγα έχουν οδηγήσει στον χαρακτηρισμό πέντε άρρενο-ειδικών πρωτεϊνών (MSSPs) οι οποίες είναι ομο- και ετερο- διμερή δύο συγγενών, τύπου α και β, πολυπεπτιδίων (MSSP-α και –β). Τα πολυπεπτίδια αυτά κωδικοποιούνται από τουλάχιστον 7 γονίδια τα οποία με βάση την ομοιότητα των αλληλουχιών τους κατατάσσονται σε 3 ομάδες: msspα (α1 και α2), msspβ (β1, β2 και β3) και msspγ (γ1 και γ2). Λειτουργική ανάλυση των υποκινητών των γονιδίων msspα2 και msspβ2 έδειξε ότι το γονίδιο msspα2 εκφράζεται σε υψηλά επίπεδα στο λιπώδη ιστό των ενήλικων αρσενικών ατόμων ενώ το γονίδιο msspβ2 εκφράζεται σε χαμηλά επίπεδα στο έντερο και των δύο φύλων. Με στόχο την αρρενο- ειδική υπερέκφραση τής αλκοολικής αφυδρογονάσης τής D. melanogaster σε άτομα C. Capitata για την κατασκευή ενός Στελέχους Διαλογής Φύλου στη Μεσογεική μύγα στο οποίο παρουσία υψηλών επιπέδων αλκοόλης θα πεθαίνουν τα θηλυκά άτομα, ενώ τα αρσενικά θα επιβιώνουν, κατασκευάστηκαν διαγονιδιακά στελέχη τα οποία έφεραν το γονίδιο DmadhFAST υπό τον έλεγχο της περιοχής -522/+37 (α2PL) του γονιδίου msspα2. Η κατασκευή των διαγονιδιακών στελεχών έγινε με γενετικό μετασχηματισμό χρησιμοποιώντας το σύστημα μετασχηματισμού Minos. Από την ανάλυση 9 μετασχηματισμένων σειρών σε επίπεδο RNA (Northern ανάλυση και RT-PCR) και σε επίπεδο πρωτεΐνης (Western ανάλυση και Adh assay) προέκυψαν τα εξής συμπεράσματα: α) Ο υποκινητής α2PL είναι κατάλληλος για υψηλή φύλο-ειδική έκφραση διαγονιδίων στα ενήλικα αρσενικά άτομα της Μεσογειακής μύγας και β) Το γονίδιο της ADH της D. melanogaster πιθανόν δεν είναι το κατάλληλο γονίδιο επιλογής για τη δημιουργία στελεχών γενετικού διαχωρισμού του φύλου στη Μεσογειακή μύγα. Επιπλέον, στην παρούσα διατριβή επιλέχθηκε να μελετηθεί ο τρόπος έκφρασης του γονιδίου msspβ1. Όπως και με το msspα2 γονίδιο μελετήθηκε η λειτουργία του msspβ1 γονιδίου, in vivo, σε μετασχηματισμένες σειρές χρησιμοποιώντας το τμήμα -485/+35 (β1PL) του υποκινητή και το γονίδιο lacZ ως γονίδιο αναφοράς. Οι αναλύσεις έκφρασης του διαγονιδίου lacZ, τόσο στο επίπεδο του RNA (RT-PCR) όσο και στο επίπεδο της πρωτεΐνης (β-gal assay), σε 7 διαφορετικές σειρές έδειξαν ότι το τμήμα β1PL είναι αρκετό για την ορθή χρονο- ειδική έκφραση του διαγονιδίου σύμφωνα με το φυσιολογικό πρότυπο έκφρασης των mssp-α και -β γονιδίων, εντούτοις, δεν παρουσιάζει αυστηρά άρρενο-ειδικό πρότυπο έκφρασης, αν και η έκφραση στα αρσενικά άτομα ήταν εντονότερη από ότι στα θηλυκά. Από τη σύγκριση των επιπέδων μεταγραφής του διαγονιδίου lacZ υπό τον έλεγχο του υποκινητή β1PL με εκείνα του διαγονιδίου DmadhFAST υπό τον έλεγχο του υποκινητή α2PL, φαίνεται ότι η ισχύς του υποκινητή του γονιδίου msspβ1 είναι εκατοντάδες φορές μικρότερη από εκείνη του msspα2. Τα αποτελέσματα αυτά σε συνδυασμό με προηγούμενη μελέτη υποδηλώνουν ότι το δεύτερο γονίδιο mssp που εκφράζεται σε υψηλά επίπεδα και με αρρενο-ειδικό τρόπο θα πρέπει να είναι το msspβ3 γονίδιο ή κάποιο άλλο mssp γονίδιο του οποίου το προϊόν είναι ένα MSSP πολυπεπτίδιο τύπου β. / Studies in the medfly have led to the characterization of five male-specific serum proteins (MSSPs) that are homo- and hetero- dimmers of two major polypeptide types, MSSP-α and –β. These polypeptides are coded by at least 7 distinct genes which, based on their homology, are classified in three subgroups, MSSP-α (α1 and α2), MSSP-β (β1, β2 and β3) and MSSP-γ (γ1 and γ2). Functional analysis of the msspa2 and msspβ2 promoters showed that msspa2 is expressed in high levels in the fat body of adult male individuals, whereas msspβ2 is expressed in low levels in the midgut of both sexes. In order to overexpress in a male-specific manner the D. melanogaster alcohol dehydrogenase (ADH) in C. capitata for the construction of a Genetic Sexing Strain (GSS) in the medfly, which in the presence of high alcohol concentration will lead to the death of female and the survival of the male individuals, we constructed transgenic medfly strains using DmadhFAST under the control of the -522/+37 fragment (α2PL) of the msspa2 promoter, via Minos-mediated germline transformation. The RNA analysis (Northern and RT-PCR) and the protein analysis (Western and Adh assay) of 9 transgenic strains showed that: a) The α2PL fragment is sufficient for high levels of male-specific expression of transgenes in the medfly and b) The D. melanogaster ADH gene may not be the appropriate gene for the construction of GSS strains in the medfly. In addition in the present study we performed functional analysis of the msspβ1promoter in vivo in medfly transgenic adults generated by Minos-mediated germ line transformation. For this analysis we used the -485/+37 fragment of the msspβ1 promoter and the lacZ reporter gene. The RNA analysis (RT-PCR) and the protein analysis (b-gal assay) performed on 7 transgenic strains showed that the β1PL fragment is sufficient for the proper time-specific expression of the transgene in accordance to the expression pattern of mssp-a and –β genes, not in male-specific manner, although the level of expression in males was higher than in females. The comparison of the expression levels of the lacZ and the DmadhFAST transgenes showed that the α2PL promoter fragment is a hundred time stronger than the β1PL. These results indicate that msspβ3 or another β type mssp gene may be expressed in high levels in the male adults of the medfly.