Proteínas FtsH são metaloproteases pertencentes à família AAA (ATPases Associadas a Diversas Atividades Celulares), e estão presentes em todos os reinos dos seres vivos. Estas proteases utilizam a energia liberada da hidrólise do ATP para desempenhar suas diversas atividades celulares. Em Escherichia coli, as proteases FtsH se organizam em um homohexamero na membrana plasmática, sendo que este complexo atua na degradação de proteínas mal dobradas. Em Arabidopsis, o hetero-complexo FtsH localizado na membrana dos tilacóides é formados por isômeros do tipo A (FtsH1/FtsH5) e do tipo B (FtsH2/FtsH8). Sua atividade proteolítica está relacionada ao controle de qualidade organelar, degradando proteínas mal dobradas e de vida curta. O complexo está envolvido também na degradação da proteína D1 do PSII, danificada por danos foto-oxidativo. Embora as FtsH cloroplastidiais sejam bem caracterizadas em termos genéticos e moleculares, o mecanismo de regulação do complexo ainda não foi esclarecido, o que torna interessante a busca por fatores proteicos adicionais. Em investigações anteriores nosso grupo de pesquisa encontrou um candidato potencial, denominado FIP (FtsH5 Interacting Protein), que pode modular a atividade ATPásica e/ou proteásica do complexo. Fip está presente na membrana dos tilacóides e mostrou interação com FtsH5 in vivo e in vitro. Neste trabalho foram realizados ensaios de duplo híbrido de leveduras, utilizando deleções da proteína FIP, bem como substituições de resíduos de cisteína por alanina. Os resultados revelaram que a interação entre FIP e FtsH5 é mantida somente quando duas regiões ricas em cisteína estão presentes na sequência de FIP. Essa região compreende 46 aminoácidos, com 4 resíduos de cisteína conservados, e ensaios com 7 diferentes substituições desses resíduos por alanina não mostraram interação com FtsH5, o que corrobora a hipótese de que os resíduos de cisteína são necessários para a interação. Experimentos de análise de expressão utilizando PCR em tempo real, sob condições de estresse salino e estresse a frio, revelaram que os genes que codificam FIP e FtsH5 têm sua expressão regulada de modo antagônico, o que sugere que FIP possa atuar como modulador negativo da atividade proteásica do complexo FtsH. / Metalloprotease FtsH proteins are members of the AAA family (ATPases Associated with Diverse Cellular Activities), and are present in all kingdoms of living organisms. These proteases use energy of ATP hydrolysis to perform its various cellular activities. In Escherichia coli, FtsH proteases are organized in a homo-hexamer in the cytoplasmic membrane, and this complex acts in the degradation of misfolded proteins. In Arabidopsis, the FtsH hetero-complex located in the thylakoid membrane is formed by type A (FtsH1/FtsH5) and type B (FtsH2/FtsH8) isomers. Its proteolytic activity is involved in organellar quality control by degrading misfolded and short-lived proteins. The complex is also involved in the degradation of the D1 protein of PSII, damaged by photo-oxidative damage. Although the chloroplast FtsH are well characterized genetically and molecularly, the regulatory mechanism of the complex remains unclear, which makes it interesting to search for additional protein factors. In earlier studies our research group has found a potential candidate called FIP (FtsH5 Interacting Protein), which can modulate the ATPase and/or protease activity of the complex. FIP is present in the membrane of the thylakoids and showed interaction with FtsH5 in vivo and in vitro. In this study yeast two-hybrid assays were performed using FIP protein deletions, and substitutions of cysteine to alanine residues. The results showed that the interaction between FIP and FtsH5 is maintained only when two cysteine rich regions are present in the sequence of FIP. This region contains 46 amino acids with four conserved cysteine residues and 7 different assays with alanine replacements of these residues showed no interaction with FtsH5, which corroborates the hypothesis that the cysteine residues are required for the interaction. Expression experiments analysis using realtime PCR, under conditions of salt stress and cold stress, revealed that the genes encoding FtsH5 and FIP have its expression regulated in an antagonistic way, suggesting that FIP can act as a negative modulator of the activity FtsH protease of the complex.

Proteínas FtsH são metaloproteases pertencentes à família AAA (ATPases Associadas a Diversas Atividades Celulares), e estão presentes em todos os reinos dos seres vivos. Estas proteases utilizam a energia liberada da hidrólise do ATP para desempenhar suas diversas atividades celulares. Em Escherichia coli, as proteases FtsH se organizam em um homohexamero na membrana plasmática, sendo que este complexo atua na degradação de proteínas mal dobradas. Em Arabidopsis, o hetero-complexo FtsH localizado na membrana dos tilacóides é formados por isômeros do tipo A (FtsH1/FtsH5) e do tipo B (FtsH2/FtsH8). Sua atividade proteolítica está relacionada ao controle de qualidade organelar, degradando proteínas mal dobradas e de vida curta. O complexo está envolvido também na degradação da proteína D1 do PSII, danificada por danos foto-oxidativo. Embora as FtsH cloroplastidiais sejam bem caracterizadas em termos genéticos e moleculares, o mecanismo de regulação do complexo ainda não foi esclarecido, o que torna interessante a busca por fatores proteicos adicionais. Em investigações anteriores nosso grupo de pesquisa encontrou um candidato potencial, denominado FIP (FtsH5 Interacting Protein), que pode modular a atividade ATPásica e/ou proteásica do complexo. Fip está presente na membrana dos tilacóides e mostrou interação com FtsH5 in vivo e in vitro. Neste trabalho foram realizados ensaios de duplo híbrido de leveduras, utilizando deleções da proteína FIP, bem como substituições de resíduos de cisteína por alanina. Os resultados revelaram que a interação entre FIP e FtsH5 é mantida somente quando duas regiões ricas em cisteína estão presentes na sequência de FIP. Essa região compreende 46 aminoácidos, com 4 resíduos de cisteína conservados, e ensaios com 7 diferentes substituições desses resíduos por alanina não mostraram interação com FtsH5, o que corrobora a hipótese de que os resíduos de cisteína são necessários para a interação. Experimentos de análise de expressão utilizando PCR em tempo real, sob condições de estresse salino e estresse a frio, revelaram que os genes que codificam FIP e FtsH5 têm sua expressão regulada de modo antagônico, o que sugere que FIP possa atuar como modulador negativo da atividade proteásica do complexo FtsH. / Metalloprotease FtsH proteins are members of the AAA family (ATPases Associated with Diverse Cellular Activities), and are present in all kingdoms of living organisms. These proteases use energy of ATP hydrolysis to perform its various cellular activities. In Escherichia coli, FtsH proteases are organized in a homo-hexamer in the cytoplasmic membrane, and this complex acts in the degradation of misfolded proteins. In Arabidopsis, the FtsH hetero-complex located in the thylakoid membrane is formed by type A (FtsH1/FtsH5) and type B (FtsH2/FtsH8) isomers. Its proteolytic activity is involved in organellar quality control by degrading misfolded and short-lived proteins. The complex is also involved in the degradation of the D1 protein of PSII, damaged by photo-oxidative damage. Although the chloroplast FtsH are well characterized genetically and molecularly, the regulatory mechanism of the complex remains unclear, which makes it interesting to search for additional protein factors. In earlier studies our research group has found a potential candidate called FIP (FtsH5 Interacting Protein), which can modulate the ATPase and/or protease activity of the complex. FIP is present in the membrane of the thylakoids and showed interaction with FtsH5 in vivo and in vitro. In this study yeast two-hybrid assays were performed using FIP protein deletions, and substitutions of cysteine to alanine residues. The results showed that the interaction between FIP and FtsH5 is maintained only when two cysteine rich regions are present in the sequence of FIP. This region contains 46 amino acids with four conserved cysteine residues and 7 different assays with alanine replacements of these residues showed no interaction with FtsH5, which corroborates the hypothesis that the cysteine residues are required for the interaction. Expression experiments analysis using realtime PCR, under conditions of salt stress and cold stress, revealed that the genes encoding FtsH5 and FIP have its expression regulated in an antagonistic way, suggesting that FIP can act as a negative modulator of the activity FtsH protease of the complex.

Tidigare studier har visat att det finns en övervägande nytta för samhället som helhet vid införandet och användandet av förstainsatsaktörer. I Sverige har nyttjandet av förstainsatsperson, FIP, inom räddningstjänsten visat på en kortare responstid än övrig styrka vid en olycka. Vid en byggnadsbrand är det enligt räddningstjänstens lagföreskrift ett rökdykarpar som utför livräddningen med resterande styrka (släckbil) verkande i bakgrunden. Den här studien utvärderar på nationell nivå tidsbesparingen (den kortare responstiden för två FIP-enheter jämfört med nästkommande enhet) samt den nytta som införandet och användandet av två FIP-enheter resulterar i för samhället som helhet vid en byggnadsbrand. Metoden för att analysera den minskning i skadevärde som en tidigare påbörjad insats medför genom nyttjandet av två FIP-enheter är en kostnadsnyttometod, även kallad CBA (Cost- benefit analysis). Kostnadsnyttoanalysen ställer den merkostnad som investeringen i FIP- enheter medför i kontrast till den nytta som FIP-enheter bidrar med, har nyttan ett större värde än kostnaden så är projektet samhällsekonomiskt lönsamt. Efter sortering av analysunderlaget genomförts återstod 210 stycken fall med fatal utkomst vid brand i byggnad mellan åren 2010 – 2014. Datamaterialet är från räddningstjänstens insats- samt dödsrapporter som ifyllts vid en olyckshändelse som räddningstjänsten larmats till. Resultatet från analysen visar att den genomsnittliga årliga nyttan av FIP-enheterna är beroende på hur stor andel av den avsedda populationen som återfinns inom stationsområde (benämns som täckningsgrad i studien) samt om stationen väljer att investera i en FIP-enhet eller två FIP-enheter. Täckningsgraden för att det ska vara lönsamt att investera i en FIP-enhet är 5311 stycken individer, för att det ska vara samhällsekonomiskt lönsamt att investera i två FIP-enheter måste stationen täcka 10 621 stycken individer. Investeringsalternativen är till följd av att utgångsläget för räddningstjänstens stationer är av olika art, d.v.s. en del stationer har redan en verksam FIP-enhet. För att stationen i fråga ska kunna ta del av den tänkta åtgärden med tidsbesparingen av två stycken FIP-enheter presenteras därav ett case scenario med investeringsalternativet om en FIP-enhet. Slutsatsen som dras är att det är samhällsekonomiskt lönsamt att implementera och nyttja två FIP-enheter för Sveriges räddningstjänster beroende på hur stor andel av Sveriges befolkning som den aktuella stationen täcker och vilket investeringsalternativ som är av intresse. / Previous studies have shown that there is an overwhelming benefit to society as a whole for the introduction and use of first responders. In Sweden, the use of first responders, FIP, for the civil protection demonstrated a shorter response time than the other rescue force when an accident occurred. When there is a fire in a building, according to rescue services regulations a smoke-diving couple performs the lifesaving operation with the residual rescue force (fire engine) acting in the background. This study evaluates if the national time savings; the shorter response time for two FIP units compared with the next unit arriving at the scene of an accident. If the introduction and use of two FIP units and the time saved results in a benefit to the society as a whole when there is a fire in a building. The method for analyzing the reduction in the damaged value as a previously initiated effort involving the use of two FIP units is a cost-benefit approach, also called CBA. Cost-benefit analysis makes the extra cost an investment in FIP units brings in contrast to the benefits that FIP units contributes, is the benefit of greater value than the cost the project is said to be economically viable. After sorting the analytical framework remained 210 cases, with fatal outcomes, for the variable fire in building between the years 2010 - 2014. The data material obtained is from the emergency input and death reports completed after an accident occurred that the rescue services were alerted to. The results of the analysis show that the average annual benefit of FIP units is dependent on the proportion of the intended population found in the station area (referred to as coverage in the study) and if the station chooses to invest in one FIP unit or two FIP units. Adequacy for it to be profitable to invest in one FIP unit requires that the station covers 5311 individuals, for it to be economically profitable to invest in two FIP units the station must cover 10 621 individuals. The investment options are due to the starting position for the rescue stations are of different kinds, i.e. some stations already have an effective FIP unit. For the station in question to take part of the division and time savings with two FIP units therefore a case scenario is presented with the investment option of one FIP unit. The conclusion is that it is economically viable to implement and use two FIP units for Sweden's emergency services depending on the proportion of the population of Sweden that the current station covers and what investment options that are of interest.

Är införande och nyttjande av förstainsatsperson (FIP) samhällsekonomiskt lönsamt? En FIP är, i normalfallet, en deltidsbrandman som inte behöver inställa sig vid brandstationen när en olycka har inträffat då denne har ett eget utryckningsfordon och kan på så sätt fortare komma fram till olycksplats. Den här uppsatsen gör en utvärdering av fyra stationsområden i Jönköpings kommun som för FIP-verksamhet. Tidigare studier framställer att FIP har kortare responstid än nästkommande räddningsenhet. Om så är fallet är följden att räddningsarbetet kan påbörjas i ett tidigare skede och således kan det slutliga räddade värdet i en olyckssituation vara av större omfattning än vad som annars vore möjligt. Enligt teorin bör det finnas ett sätt att värdera denna effekt, vilket sedan kan ställas i förhållande till merkostnaden av införande av FIP. Är fördelarna av FIP-verksamhet av större magnitud än nackdelarna är projektet samhällsekonomiskt lönsamt. Metoden använd för att utvärdera FIP i Jönköpings kommun är kostnadsnyttoanalys (CBA), vari analysunderlaget består av 1150 insatser där FIP-rapport ifyllts. Resultatet visar att den årliga nyttan per FIP-enhet, det vill säga per stationsområde, är mellan 242,8 och 652,0 TSEK (ej extrapolerat värde). Den årliga kostnaden är cirka 76,5 TSEK och nettonuvärdet uppgår därför till mellan 166,2 och 509,1 TSEK. Nyttokostnadskvoten är mellan 3,17 och 8,52. Slutsatsen är att införande och nyttjande av FIP är samhällsekonomiskt lönsamt. / Is introduction of first responder economically beneficial to society? A first responder is, most commonly, a part-time firefighter who can directly head for the scene of an accident since he has his own emergency vehicle. This means that the first responder does not have to first go by the fire department, like other part-time firefighters, and thus will be able to help people, or other, in an early stage of the situation. This thesis evaluates four fire departments (areas) in the municipality of Jönköping, which have adopted the concept of first responders into their organizations. Previous studies have shown that first responders have, on average, a shorter response time than the next emergency unit called to a rescue scene. If this is a fact, the rescue work can begin at an earlier stage and thus the final value saved during a rescue operation will be of greater scope than otherwise would be possible. In theory there should be a way to evaluate this effect, which then can be compared with the additional cost of introducing first responders. If the benefits of first responders are of greater magnitude than the disadvantages, the project is economically beneficial to society. The method used to evaluate the project of first responders in the municipality of Jönköping is a cost-benefit analysis (CBA), where the analytical framework consists of 1150 emergency rescues where a first-responder report has been completed. The results show that the annual benefits per first-responder unit, i.e. per station area, is between SEK 242.8 thousand and SEK 652.0 thousand (with no extrapolation). The annual cost is approximately SEK 76.5 thousand. The net present value therefore is between SEK 166.2 thousand and SEK 509.1 thousand. The cost-benefit ratio is between 3.17 and 8.52. The con-clusion is that introduction and use of first responders in the municipality of Jönköping is economic-ally beneficial to society. / Effektsamband i samhället

Die Nekrotisierende Enterokolitis (NEK) und die Fokale Intestinale Perforation (FIP) sind schwere Erkrankungen, die in den ersten Lebenswochen von Frühgeborenen auftreten können und durch den Grad der Unreife (niedriges Gestationsalter und Geburtsgewicht) gefördert werden. Als weitere Einflussfaktoren werden insbesondere die Ernährung, Medikamente (prä- und postnatale Steroide, Antibiotika, H2-Blocker, Morphin, Indometacin, Ibuprofen) sowie perinatale Faktoren (Tokolyse, vorzeitiger Blasensprung, AIS und andere Infektionen der Mutter) kontrovers diskutiert. Diese Variablen und das resultierende Outcome wurden anhand der am UKL im Zeitraum von Januar 2008 bis Dezember 2014 geborenen Frühgeborenen mit einem Geburtsgewicht von unter 750 g retrospektiv untersucht. In die Analyse eingeschlossen wurden 168 Kinder, von denen 21 Kinder (12,5 %) eine NEK und 9 Kinder (5,4 %) eine FIP entwickelten. Die Analyse der Einflussfaktoren auf die Kinder und ihr weiteres Leben wurde in die Analyse der Gesamtpopulation (alle 138 gesunden Kinder gegenüber den 30 erkrankten Kindern), sowie mehrere Subpopulationen (alle vor der vollendeten 25. SSW geborenen Kinder und ein Vergleich der an NEK mit den an FIP erkrankten Kindern) aufgeteilt. Ein niedriges Geburtsgewicht sowie ein jüngeres Gestationsalter zur Geburt sind entscheidende Einflussfaktoren auf die untersuchten Erkrankungen. Ebenso zeigt sich ein vermehrtes Auftreten von NEK/FIP bei niedrigem Nabelschnur-pH-Wert (Mittelwert NEK/FIP: 7,22; Mittelwert gesund: 7,28), niedrigem Hämatokritwert (Mittelwert NEK/FIP: 40,5; Mittelwert gesund: 46,4), schlechter respiratorischer Situation sowie Ibuprofen- und Opioideinsatz. Kein Einfluss ließ sich durch die pränatale Steroidgabe, ein AIS, den Einsatz von Tokolyse, einen vorzeitigen Blasensprung, den Apgar-Wert sowie durch eine Pantoprazol- oder Antibiotikaverabreichung nachweisen. Erkrankte Kinder hatten eine um 7 % erhöhte Mortalität, verbrachten eine längere Zeit im Krankenhaus (im Schnitt 36 Tage länger), hatten ein höheres Entlassungsgewicht (rund 630 g mehr) und wurden erst später voll enteral ernährt (im Mittel 21 Tage später) als nicht erkrankte Kinder. Die erste Fütterung erhielten die später erkrankten Kinder 6 Stunden später als Kinder, die nicht erkrankten. Ebenso erhielten die später an einer NEK/FIP erkrankten Kinder länger Glucose, bevor sie Frauenmilch gefüttert bekamen und schieden seltener aus (Stuhlgang und Erbrechen/Spucken). Der Einsatz postnataler Steroide hatte einen Einfluss auf die Auftretenswahrscheinlichkeit einer FIP (67 %), aber nicht einer NEK (19 %). Weitere Studien zur klareren Differenzierung der neu gefundenen Faktoren Nabelschnur-pH-Wert und Hämatokritwert sind nötig, um die Erkrankungen gegebenenfalls früher zu erkennen, entsprechend zu therapieren und damit die Mortalität zu reduzieren. Die vorliegenden Daten verdeutlichen, dass die FIP und die NEK im Hinblick auf das klinische Management zusammen analysiert werden können.

Measles is one of the most contagious diseases known to mankind. Despite the availability of a safe and effective vaccine, approximately 164,000 measles-related deaths were recorded in 2008. The inherent restricted host tropism of MV means that the development of authentic rodent models will be a valuable research tool in testing new vaccines and antivirals. In addition to the receptor requirement, mouse innate immunity has been shown to inhibit MV growth. In this thesis, the contributions of several key components of the mouse innate immune system on the inhibition of MV replication were examined. The transcription factor interferon regulatory factor 3 (IRF3), which normally plays a key role in mediating innate immune signaling, contributed relatively little in inhibiting MV replication both in vitro and in vivo. In contrast, the JAK/STAT pathway and the double-stranded RNA inducible protein kinase, PKR, played more important roles in controlling virus replication. The resurgence of measles in areas where the virus was once thought to be eradicated makes the development of anti-MV treatments essential. Concurrent to the development of an animal model to better study its pathogenesis, we wanted to look at the effect of MV inhibitors on its replication. The MV fusion inhibitor, carbobenzoxy-D-phenylalanine-L-phenylalanine-glycine (ZfFG), was developed in the past to study fusion; however, its mechanism of action has not yet been elucidated. To examine this, spontaneous ZfFG-resistant mutants were generated and characterized. Mutations were found in the HRB region of the fusion (F) protein, and when these were modeled using published paramyxovirus F crystal structures, data suggested that ZfFG targeted a small pocket present between the head and stalk regions of its pre-fusion conformation. An authentic mouse model of measles developed from findings in this study may allow for in vivo efficacy testing of ZfFG in the future.

Measles is one of the most contagious diseases known to mankind. Despite the availability of a safe and effective vaccine, approximately 164,000 measles-related deaths were recorded in 2008. The inherent restricted host tropism of MV means that the development of authentic rodent models will be a valuable research tool in testing new vaccines and antivirals. In addition to the receptor requirement, mouse innate immunity has been shown to inhibit MV growth. In this thesis, the contributions of several key components of the mouse innate immune system on the inhibition of MV replication were examined. The transcription factor interferon regulatory factor 3 (IRF3), which normally plays a key role in mediating innate immune signaling, contributed relatively little in inhibiting MV replication both in vitro and in vivo. In contrast, the JAK/STAT pathway and the double-stranded RNA inducible protein kinase, PKR, played more important roles in controlling virus replication. The resurgence of measles in areas where the virus was once thought to be eradicated makes the development of anti-MV treatments essential. Concurrent to the development of an animal model to better study its pathogenesis, we wanted to look at the effect of MV inhibitors on its replication. The MV fusion inhibitor, carbobenzoxy-D-phenylalanine-L-phenylalanine-glycine (ZfFG), was developed in the past to study fusion; however, its mechanism of action has not yet been elucidated. To examine this, spontaneous ZfFG-resistant mutants were generated and characterized. Mutations were found in the HRB region of the fusion (F) protein, and when these were modeled using published paramyxovirus F crystal structures, data suggested that ZfFG targeted a small pocket present between the head and stalk regions of its pre-fusion conformation. An authentic mouse model of measles developed from findings in this study may allow for in vivo efficacy testing of ZfFG in the future.

Feline coronavirus (FCoV) is endemic in cat populations worldwide. Persistently, subclinically infected cats play a significant role in spreading the infection. Testing fecal samples of cats may facilitate efforts to decrease the viral burden within a population. Real-time RT-PCR is highly sensitive and specific for the detection of FCoV but must be performed in a fully equipped laboratory. A simple and accurate assay is needed to identify FCoV at the point-of-need. The aim of this study was to develop a rapid FCoV detection assay based on isothermal amplification technology, i.e., reverse transcription-recombinase polymerase amplification (RT-RPA). Primers were designed to target the highly conserved 3′ untranslated region of the 7b gene. Running on a constant temperature of 42 °C, reverse transcription as well as DNA amplification and detection was achieved in a maximum of 15 min. A probit analysis revealed a detection limit of 58.5 RNA copies/reaction. For cross-detection, nucleic acids from 19 viruses were tested. Both RT-RPA and real-time RT-PCR showed cross-detection with canine coronavirus and transmissible gastroenteritis virus, but not with other pathogens. To evaluate clinical performance, RNA was extracted from 39 fecal samples from cats. All samples were tested simultaneously with real-time RT-PCR resulting in a RT-RPA sensitivity and specificity of 90.9% and 100%, respectively. RT-RPA can be considered a promising simple method for rapid detection of FCoV.

L’information des patients est devenue un enjeu de santé publique et une composante essentielle de la relation médecin patient. De nombreux auteurs s’accordent à dire que l’information écrite est un complément indispensable à l’obligation d’information orale car elle améliore la qualité des soins et l’adhérence du patient à sa prise en charge. Malgré l’existence de nombreuses Fiches d’Information Patient (FIP), le médecin a du mal à se les approprier. Elles sont souvent non validées, peu lisibles, difficiles à stocker, sans références, sources ni dates de rédaction. La première étape de notre travail a consisté à proposer une méthode pour élaborer des fiches d’information du patient (FIP) et à partir d’elle, 125 FIP concernant des motifs de consultation les plus fréquents en soins primaires. Une étude observationnelle réalisée dans 26 cabinets de médecine générale auprès de 350 patients, a montré d’une part que les patients sont demandeurs de FIP et qu’elles sont appréciées des patients. Et d’autre part, que la compréhension des maladies aiguës est plus limitée que celles des maladies chroniques ou situations de prescription chez les patients à faible niveau scolaire. Une étude interventionnelle randomisée en clusters réalisée dans 24 cabinets de médecine générale auprès de 400 patients, nous a permis de montrer que les FIP permettaient aux patients d’améliorer leur niveau de connaissances sur les pathologies et de modifier positivement leur comportements de santé, y compris pour les patients à faible niveau scolaire. Néanmoins, il n’était pas possible de comparer ces résultats à ceux de la littérature, les protocoles de recherche étant trop hétérogènes (critères de jugement spécifiques d’une situation clinique donnée).Pour surmonter cette difficulté, nous basant sur une « revue des revues » de la littérature, nous avons proposé un modèle théorique décrivant les modalités d’action des FIP au cours de la consultation, à partir duquel nous avons élaboré trois scores génériques utilisables pour tout type de consultation : un score de Communication Médecin Malade (CMM), un score de satisfaction et un score d’adhérence globale. Une fois les propriétés psychométriques de ces scores validés, nous avons étudié leurs déterminants. En situation aiguë, le seul déterminant de la CMM était la qualité de l’information reçu (quoi et que faire multipliant la probabilité d’une bonne communication par 11.9), les caractéristiques du patient n’influençant pas la CMM. L’adhérence globale est déterminée par le type de pathologie (paramètre inflexible) et par la qualité de la CMM. Enfin, la satisfaction, bien que tout autant liée à l’infrastructure, à l’équipe paramédicale et à l’équipe médicale, est également améliorée par une CMM de bonne qualité. En situation aiguë, la CMM est donc primordiale et impacte sur les indicateurs santé usuels que sont la satisfaction et l’adhérence des patients.Enfin, nous avons évalué avec ces nouveaux outils l’impact de 6 FIP sur la CMM, l’adhérence globale du patient et la satisfaction dans deux services d’urgences auprès de 324 patients. Cette étude interventionnelle avant-après nous a permis de montrer que les FIP améliorent: la CMM, la satisfaction vis-à-vis des professionnels de santé, le comportement des patients (qui respectent mieux les modalités de prises des médicaments et reconsultent moins dans les services d’urgences pour une même pathologie) et le comportement des médecins (qui prescrivent moins médicaments et davantage d’examens complémentaires). En situation aiguë, un outil simple pour améliorer la CMM est l’usage de FIP délivrée en complément de l’information orale.La CMM est un critère de jugement fondamental qu’il conviendra à l’avenir d’utiliser plus souvent, notamment pour évaluer les interventions thérapeutiques non pharmacologiques en plein essor, et pour lesquelles la communication est probablement un déterminant majeur de l’efficacité. / Patient information has become a public health issue and an essential component of Doctor-Patient communication (DPC). Many authors agree that written information is an indispensable complement to the obligatory oral information, since it improves the quality of care and the patient adherence. Despite the existence of numerous Patient Information Leaflets (PILs), physicians have difficulty appropriating them; they are often not validated, hard to read, difficult to store, without references, sources and dates of writing. The first step in our work was to propose a methodology for developing PILs and from there, design 125 PILs for the most common reasons for consultation in primary care. An observational study carried out in 26 general practice offices with 350 patients showed that patients appreciate PILs. On the other hand, the understanding of Acute Conditions (AC) is more limited than that of chronic diseases or prescription situations, particularly patients with a low school level. A cluster randomized interventional study performed in 24 general practice offices with 400 patients showed that PILs allowed patients to improve their knowledge about pathologies and modify their health behaviors positively, independently of their level of education. Nevertheless, the heterogeneity of the research protocols made it impossible to compare our results with those of the literature.To overcome this scientific hurdle and continue our work on the assessment of PILs, we performed a review of the literature on the subject, constructed a theoretical model describing the various effects of PILs and created three generic scales usable for evaluating the impact of PILs on any type of condition (scales of Doctor-Patient Communication, satisfaction and overall adherence). An observational study carried out in 2 Emergency Departments (ED) allowed us to validate the 3 scores, assess the psychometric properties and elucidate their determinants. In the context of AC, the only determinant of the DPC was the quality of the information received (both information "what to do" and "when to reconsult" have an adjusted Odds Ratio 11.9. Characteristics of the patient did not influence the DPC score. The overall adhesion is determined by the type of pathology (inflexible parameter) and by the quality of the DPC. Finally, although satisfaction was strongly associated with the hospital infrastructure and the attitude of the paramedical and medical staff, a high DPC score multiplied the probability of having a good satisfaction score. In a context of emergency consultations, the DPC is paramount and has an impact on the usual health indicators: satisfaction and adherence.Finally, a before-after intervention study conducted in two ED showed that PILs improve DPC, satisfaction with healthcare professionals, and adherence to medication regimens. PILs decrease the number of reconsultations for the same pathology, in particular return to the ED. They reduce the number of drug prescriptions given by the doctor in favor of complementary examinations and specialized advice. In a context of AC, a PIL given by the doctor improves DPC, the patient’s satisfaction with healthcare professionals and improves both the doctor’s and the patient’s behaviors.The DPC is a fundamental outcome that will need to be measured more frequently in the future, including in acute situations.

Master's thesis deals with influence of various factors on the concrete compressive strength and modulus of elasticity. This work concentrates mainly on the influence of early curing and air entrainment of concrete. One part of this work is the evaluation of laboratory measurement, which was carried out on cubes of standard and norm prisms. The development of elastic moduli was monitored in time to 730 days of age with respect to air entrainment and curing conditions. The second part of the experiment deals with a comparison of theoretical creep curves depending on the value of the modulus of elasticity based on different standards. Again, the air entrainment effect and influence of initial conditions are reflected.