Submitted by Patricia Barros (patricia.barros@ufes.br) on 2017-06-14T14:44:09Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Fabiana Florio Domingues_completa.pdf: 1401159 bytes, checksum: 574681450ad51d8136df5de85e2435b3 (MD5) / Approved for entry into archive by Patricia Barros (patricia.barros@ufes.br) on 2017-06-14T14:46:36Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Fabiana Florio Domingues_completa.pdf: 1401159 bytes, checksum: 574681450ad51d8136df5de85e2435b3 (MD5) / Made available in DSpace on 2017-06-14T14:46:38Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Fabiana Florio Domingues_completa.pdf: 1401159 bytes, checksum: 574681450ad51d8136df5de85e2435b3 (MD5) / Fapes / A presente dissertação tem por objetivo compreender os aspectos simbólicos relacionados ao espaço da feira de artesanato e artes da Praça dos Namorados, nas perspectivas de passantes e expositores que compartilham o local. Por conseguinte, buscou-se então desenvolver interpretações a respeito das dinâmicas dos aspectos simbólicos entre as perspectivas captadas, que transformaram a feira no que ela é hoje. Para tal tarefa, inicialmente foi desenvolvida uma investigação exploratória que desse suporte para expandir o olhar sobre o lócus escolhido, possibilitando a identificação de questões relevantes a expositores e passantes. Foi nessa fase que se levantou como tema a mudança de leiaute da feira, que mudou tanto a apropriação do espaço físico da feira como a noção do espaço simbólico entre as pessoas que compartilham aquele lugar. A fim de prosseguir e completar esta pesquisa qualitativa, utilizou-se o método etnográfico. A apreensão dos dados de campo se deu por meio de observação sistemática e participante, fazendo uso de diários de campo, entrevista em profundidade com representantes da prefeitura e entrevistas semiestruturadas com passantes. A permanência em campo da pesquisadora ocorreu entre maio e outubro de 2015, no qual participou das rotinas organizacionais dos expositores, resultando em 40 diários de campo. Os dados coletados foram analisados por meio da análise de conteúdo, a partir de categorias êmicas, primeiramente classificadas em seis categorias temáticas e correlacionadas às três categorias teóricas de espaço propostas por Lefebvre. Os resultados obtidos apontam para uma feira em constante mudança, que enquanto fenômeno social, não pode ser compreendida de maneira isolada, apenas fazendo sentido quando vista como um espaço simbólico em constante resignificação, a partir do cotidiano vivo de seus sujeitos. Desta forma, abre-se ainda a possibilidade a novos olhares, tanto em perspectivas teóricas como conceituais, em estudos que busquem a compreensão de fenômenos sociais e organizacionais presentes nos espaços das cidades. / This study had its goal set on understanding the symbolic aspects related to the craft and art fair space at Praça dos Namorados, through the perspectives of passers-by and exhibitors sharing the site. Therefore, the author develop interpretations about the dynamics of the symbolic aspects through the perspectives apprehended, which made the fair what it is today. In the intent of completing this task, an exploratory investigation was initially developed to support the expanding of the overlook of the chosen locus, enabling the identification of relevant issues to exhibitors and passers-by. In this stage, the change layout of the fair rose as the focus of the study, which has changed the appropriation of the physical space of the fair as well as the notion of symbolic space among people who share that site. In order to continue and complete this qualitative study, the author chose to use the ethnographic method. The apprehension of field data occurred through systematic and participant observation, the usage of field diaries, in-depth interviews with city Hall representatives and semi-structured interviews with passers-by. The period of time spent on field research was comprehended between May and October of 2015, in which the researcher participated in the organizational routine of exhibitors, resulting in 40 field diaries. The collected data were analyzed using content analysis, developed from emic categories, primarily classified into six thematic categories and then linked to the three theoretical categories of space proposed by Lefebvre. The results point towards a fair that is constantly changing, which as a social phenomenon, cannot be understood if isolated from others. It could only make sense when seen as a symbolic space constantly reframing, from everyday life experiences of that people. Thus, it would also make new understandings possible, both in theoretical and conceptual perspectives, for studies that seek the comprehension of social and organizational phenomena existent in all the spaces of the cities.

Submitted by Patricia Barros (patricia.barros@ufes.br) on 2017-10-27T11:11:25Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_11207_Dissertação Thiago.pdf: 3081235 bytes, checksum: 8b08c67ba5bb6c783eb0ffd7069c9c6f (MD5) / Approved for entry into archive by Patricia Barros (patricia.barros@ufes.br) on 2017-10-27T12:43:20Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_11207_Dissertação Thiago.pdf: 3081235 bytes, checksum: 8b08c67ba5bb6c783eb0ffd7069c9c6f (MD5) / Made available in DSpace on 2017-10-27T12:43:20Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_11207_Dissertação Thiago.pdf: 3081235 bytes, checksum: 8b08c67ba5bb6c783eb0ffd7069c9c6f (MD5) / Existe uma extensa agenda pesquisa para entendimento do comprometimento organizacional. No entanto, há também muita imprecisão para sua conceituação. Embora não haja total consenso sobre o conceito, a maioria das pesquisas concorda que o comprometimento organizacional envolve características como a forte crença e aceitação de valores e metas da organização, do desejo de permanecer na organização e pelo empenho extra despendido para contribuir para organização (MOWDAY; STEERS; PORTE, 1979). O presente estudo teve como objetivo compreender a relação ente as Representações Sociais de comprometimento organizacional para os gestores públicos e suas práticas sociais desenvolvidas no processo de gestão na figura dos Diretores Gerais dos campi e do Reitor do Instituto Federal de Educação do Espírito Santo (Ifes). A Teoria das Representações Sociais (TRS) é a lente teórica que contribui para compreender as representações sociais e sua dinâmica em seus diversos contextos ou numa determinada situação. Segundo Jodelet (2001), as representações sociais são constituídas de saberes que se articulam na vida cotidiana. Foram utilizados procedimentos qualitativos de coleta e análise, diferenciando-se da maioria das pesquisas nessa área. Foram realizadas entrevistas semiestruturadas com 12 gestores do Ifes que exercem os cargos de Diretor Geral e Reitor. Os dados obtidos foram avaliados por meio de procedimentos de análise de conteúdo. Observou-se que a representação social dos gestores do Ifes, no que diz respeito ao comprometimento organizacional, remete à base afetiva desse vínculo, bem como suas práticas sociais, que propiciam a afetividade do comprometimento organizacional. A pesquisa contribui para a delimitação do conceito de comprometimento organizacional no sentido de que mostra que tal conceito, no contexto da presente pesquisa, está ligado à afetividade, ou seja, ao desejo de empenharem e de contribuírem em prol da organização. / There is an extensive research agenda for the understanding the organizational commitment. Nevertheless, there are also imprecision related to its conceptualization. Although there is no consensus about the concept, most research agrees that the organizational commitment involves features such as the belief and the acceptance of organizational values and goals, the desire to remain in the organization and the extra commitment to contribute to the organization (MOWDAY; STEERS; PORTE, 1979). This study aimed to comprehend the relationship between the social representations of organizational commitment to the public managers and their social practices developed in the management process, in the figure of the general directors of the campuses and the rector of the Instituto Federal de Educação do Espírito Santo (Ifes). The Social Representations Theory (SRT) is a theoretical lens that contributes to comprehend the social representations and their dynamics in their different contexts or in a given situation. According to Jodelet (2001), the social representations are constituted of knowledge that is articulated to the daily life. It was used qualitative procedures of data gathering and analysis, differing from most of the research in this area. Semi-structured interviews were conducted with 12 Ifes' managers that held positions of general director and rector. The data obtained were evaluated through content analysis procedures. It was observed that the social representation of the Ifes' managers, mainly regarding the organizational commitment, refer to the emotional basis of this link, as well as to the social practices of the Ifes' managers, which favor the affectionateness of the organizational commitment. The research contributes to the delimitation of the concept of organizational commitment in the sense that shows that this concept, in the context of the present research, is linked to affectionateness, that is, to managers’ desiƌes to strive and to contribute for the benefit of the organization.

Submitted by Maykon Nascimento (maykon.albani@hotmail.com) on 2014-10-01T18:16:34Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertacao.Diego de Marchi.texto.pdf: 1448546 bytes, checksum: c0c8a83bd89eb2d12f651379827de693 (MD5) / Approved for entry into archive by Elizabete Silva (elizabete.silva@ufes.br) on 2014-11-24T18:24:23Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertacao.Diego de Marchi.texto.pdf: 1448546 bytes, checksum: c0c8a83bd89eb2d12f651379827de693 (MD5) / Made available in DSpace on 2014-11-24T18:24:23Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertacao.Diego de Marchi.texto.pdf: 1448546 bytes, checksum: c0c8a83bd89eb2d12f651379827de693 (MD5) Previous issue date: 2014 / Esta dissertação tem como objetivo descrever e analisar como o fenômeno da governança corporativa articula mecanismos de gestão e impacta na dinâmica de uma pequena organização familiar. Para isso, utilizou-se as perspectivas de Fan (2001) e Silva Junior (2006), que tratam da governança corporativa, e de Chandler (1994), para empresas familiares. Através de abordagem qualitativa com ênfase em um estudo de caso, uma triangulação de dados foi realizada, utilizando a entrevista semiestruturada, observação assistemática ou livre e pesquisa de documentos, e a análise dos dados foi realizada por análise de conteúdo. Verificou-se a presença do fenômeno da governança por intermédio da identificação dos fatores de diferenciação, resultando na implantação de mecanismos de governança ao longo do ciclo de vida da organização familiar, o que possibilitou mudanças em seu controle, no seu processo sucessório e na sua profissionalização. Quanto ao controle, foram verificados que os mecanismos de “manutenção do status quo”, “aconselhamento profissional”, “sinergia de interesses”, “regulamentação financeira da sociedade”, “atribuições e responsabilidades”, “alinhamento de interesses do negócio” e “proteção do empreendimento familiar” possibilitaram a modificação e manutenção do controle da empresa com os sócios. Quanto ao eixo da profissionalização, foi verificado que os mecanismos de “regulamentação financeira da sociedade”, “atribuições e responsabilidades”, “alinhamento de interesses do negócio”, “proteção do empreendimento familiar” e “atenção aos interesses dos stakeholders” foram responsáveis por prover as modificações neste quesito e indicar que a empresa caminha no sentido de se profissionalizar. Quanto ao processo sucessório, verificou-se que a terceira geração não tem interesse na empresa, o que podem resultar na contratação de um profissional externo para gerir a mesma, respeitando a questão dos valores familiares e a cultura organizacional ou conduzir à sucessão recursiva. Aparentemente, observou-se que a segunda questão foi mais evidente, visto que a saída do último irmão do negócio culmina com a venda da empresa familiar, gerando duas alternativas: a compra da empresa por um grupo de sócios ou outra empresa não familiar, o que resultaria na “morte” da empresa enquanto empresa familiar; ou a sua compra por outra família ou empresa familiar, preservando sua classificação inicial. / This thesis aims to describe and analyze how the phenomenon of corporate governance articulates management mechanisms and impacts the dynamics of a small family organization. For this, we used the perspectives of Fan (2001) and Silva Junior (2006), dealing with corporate governance, and Chandler (1994), for family businesses. Through qualitative approach with emphasis on a case study, triangulation of data was performed using a semi-structured interview, unsystematic or free observation and document research, and data analysis was performed by content analysis. There was the presence of the phenomenon of governance through the identification of differentiation factors, resulting in the deployment of governance mechanisms throughout the life cycle of the family organization, which enabled changes in your control, in its succession process and its professionalization. As the control, were observed that the mechanisms of "status quo", "professional advice", "synergy of interests", "financial rules of society", "duties and responsibilities", "alignment of interests of the business" and "protection of the family business "allowed the modification and maintenance of control of the company with partners. For axis of professionalization, it was found that the mechanisms of "financial rules of society", "duties and responsibilities", "alignment of interests of the business", "protection of the family business" and "attention to the interests of stakeholders" were responsible for provide changes in this regard and indicate that the company moves towards becoming professional. As to the succession process, it was found that the third generation has no interest in the company, which can result in hiring an outside professional to manage the same, respecting the issue of family values and organizational culture or lead to recursive sequence. Apparently, it was observed that the second question was more evident as the output of the last brother of the business culminating in the sale of the family business, generating two alternatives: the purchase of the company by a group of partners or other non-family business, the would result in the "death" of the company as a family business; or your purchase by another family or family business, preserving its original classification.

Aging is an underlying risk factor for many major diseases including cancer, cardiovascular disease, and neurodegeneration. Yet we still do not know the full extent of how our bodies age and what determines our lifespan. One mechanism that may play an important role are telomeres, which are protective caps at the end of chromosomes. Telomeres are directly linked to longevity and can be lengthened by the enzyme telomerase. Early life telomere length is critical for lifespan, but we do not know how telomerase performs during this period. Whether variation in telomerase levels can influence telomere length and loss during development with consequences to longevity is still unknown. This thesis focuses on the role of telomerase during post-natal development and its response to stressors and activators with effects on telomeres. Taken together this research enhances our understanding of how telomerase acts and influences telomere during post-natal development.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第19639号 / 社医博第72号 / 新制||社医||9(附属図書館) / 32675 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 今中 雄一, 教授 佐藤 俊哉, 教授 木原 正博 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

The friction stir welding of steel has produced a hard zone in several different alloys. Despite its detrimental effects on weld toughness, the reasons behind neither its formation nor a method of reducing its size or effects have been explored. Recent advances in process control allow for direct heat input control, which combined with the use of backing plates of different thermal conductivity allows for an expansion of the process window. These control methods also affect the HAZ cooling rate by providing greater range (a 60% increase compared to a fixed backing plate) and control (five welds within 16 °C/s). This increased range produced microstructures consisting of various forms of ferrite at lower cooling rates and bainite at higher cooling rates. The hard zone was determined to be the result of the formation of the bainite at higher cooling rates and was avoided by keeping the cooling rate below 20 °C/s in HSLA-65.

BAKGRUND: De som drabbats av svåra livshändelser (här begränsade till skilsmässa eller make/makas död) betraktas som en riskgrupp när det gäller både allmän hälsa och munhälsa. SYFTE: Att undersöka om och i vilken mån svåra livshändelser (skilsmässa eller make/makas död) påverkar den allmänna hälsan och munhälsan, samt vilka aspekter av munhälsa som en global munhälsofråga kan fånga upp. MATERIAL OCH METOD: Studien utfördes som en kvantitativ studie med en enkät om munhälsa som delades ut till samtliga födda 1942 i Örebro och Östergötlands län under 2007. Svarsfrekvensen var 73,1% av totalt 8313 individer. Både allmän hälsa och munhälsa mättes med hjälp av en global fråga. Munhälsan mättes dessutom med sex ytterligare frågor. Deskriptiv analys gjordes, skillnader mellan grupper testades och kompletterades med logistiska regressionsanalyser. RESULTAT: Det finns en statistiskt signifikant skillnad mellan dem som är frånskilda och/eller änka/änkling jämfört med dem som är gifta/sambo. De som inte drabbats av skilsmässa eller make/makas död hade bättre allmän hälsa och munhälsa. Skillnaden är systematisk och signifikant. Skillnaden mellan grupperna är statistisk signifikant även vid användandet av endast en fråga, den globala munhälsofrågan. Den globala munhälsofrågan förefaller i första hand spegla de delar av munhälsan som anknyter till patientens uppfattning om utseende och tuggförmåga. Studien antyder också att den försämrade hälsan kvarstår lång tid efter händelsen. SLUTSATSER OCH REKOMMENDATIONER: Den här studien påvisar vikten av en adekvat anamnes som även inkluderar frågor om civilstånd. En global fråga om självupplevd munhälsa är också ett möjligt komplement för att bättre kunna bedöma såväl patientens munhälsa som behov av preventiva insatser. / BACKGROUND: Individuals who have experienced difficult life events, limited here todivorce or death of a spouse, show elevated risk regarding general and oral health. AIM: This study investigated how and to what extent difficult life events, i.e., divorce ordeath of a spouse, affect general and oral health. I also sought to determine whether a globalquestion can identify different aspects of oral health. MATERIALS AND METHOD: This cross-sectional quantitative study used an existingquestionnaire already distributed to all (8,313) 65-year-old citizens in two Swedish counties.Within the questionnaire, a global question measured general as well as oral health, and sixadditional questions assessed oral health. Descriptive analysis sought to determinedifferences between groups, and logistic regressions were used to compare them further. RESULTS: The questionnaire response rate was 73.1%. The results showed statisticallysignificant differences in general and oral health among individuals who experienceddivorce or death of a spouse compared with individuals without such experiences. Thedifferences among groups, i.e., better general and oral health among individuals withoutdivorce or death of a spouse, were significant and systemic, p&lt;0.05. Further, differencesremained statistically significant even when using a global question on oral health. However,this global question focused mainly on chewing capacity and appearance. CONCLUSIONS: This study shows the importance of accurate anamnesis, includingquestions on civil status. A global question about self-perceived oral health providesimportant information for judging patients’ oral health and determining preventive actions.The study also suggests that risk for deteriorating oral health lingers long after difficult lifeevents have occurred. / <p>ISBN 978-91-85721-48-1</p>

Hintergrund: Die ambulant erworbene Pneumonie (CAP) ist bei Patienten mit schwerer Immunsuppression häufig und mit einer schlechten Prognose assoziiert. Scores zur Risikoprädiktion bei Sepsis oder CAP sind bei diesen Patienten kaum untersucht. Fragestellung: Ziel der Studie war die Evaluation der prognostischen Prädiktion der qSOFA- und CRB-65-Scores bei Patienten mit Pneumonie und schwerer Immunsuppression. Methoden: Es handelt sich um eine retrospektive Kohortenstudie am Uniklinikum Dresden zwischen 2014 und 2017 mit Einschluss konsekutiver Patienten mit CAP und schwerer Immunsuppression (u.a. Neutropenie, aktive hämatologische Neoplasie, Z.n. allogener Stammzell- oder Organtransplantation, HIV–Infektion mit CD4-Zellen < 200/µl, zytostatische oder rheumatologische immunsuppressive Therapie innerhalb der letzten 3 Monate, Prednisolon-Äquivalent >10mg/d > 3 Monate). Patienten mit dokumentierter Therapielimitation oder direkter Aufnahme auf die Intensivstation wurden ausgeschlossen. Die CRB-65- und qSOFA-Kriterien wurden bei Erstvorstellung dokumentiert. Der primäre Endpunkt war definiert als Notwendigkeit mechanischer Beatmung oder von Vasopressoren (MVVS) und/oder Krankenhausletalität. Um die prognostischen Eigenschaften der Scores, der einzelnen Score- Parameter, sowie der darüber hinaus erhobenen Parameter zu untersuchen, wurden univariate und multivariate Regressionsanalysen sowie ROC-Kurvenanalysen durchgeführt. Ergebnisse: Von 198 eingeschlossenen Patienten erfüllten 41 (21%) den primären Endpunkt, 19 (10%) verstarben. Das Alter war kein unabhängiger Prädiktor, dagegen waren sowohl der CRB- als auch der qSOFA-Score in der Kaplan-Meier-Analyse sowie in der multivariaten Analyse unabhängig von anderen Prädiktoren mit dem primären Endpunkt assoziiert (jeweils p < 0.001). In der ROC-Analyse erreichten beide Scores eine moderate Prädiktion (AUC 0,70 bzw. 0,69), bei 0 vorliegenden Kriterien zeigte sich ein NPV von jeweils 89% (13/120 bzw. 12/105 Patienten „übersehen“). Bei ≥ 2 Kriterien resultierten PPVs von 44 bzw. 58%. Diskussion: Sowohl die CRB- als auch die qSOFA-Kriterien zeigten eine moderate, aber signifikante prognostische Aussagekraft. Das Alter ist dagegen in dieser Population kein geeigneter prädiktiver Parameter. Auch bei den Scores ohne Alterskriterium ist der NPV jedoch nicht ausreichend zum Ausschluss von Komplikationen. Daher sollten alle schwer immunsupprimierten Patienten mit Pneumonie zumindest initial stationär, bei > 1 positivem Score-Kriterium auch intensiv hinsichtlich einer akuten Organdysfunktion, überwacht werden.:ABBILDUNGSVERZEICHNIS V TABELLENVERZEICHNIS VI ABKÜRZUNGS- UND SYMBOLVERZEICHNIS VIII 1 EINLEITUNG 1 1.1 DIE AMBULANT ERWORBENE PNEUMONIE 1 1.1.1 Definition und Einteilung 1 1.1.2 Epidemiologie 2 1.1.3 Diagnosestellung 3 1.1.4 Erregerspektrum bei CAP ohne Immunsuppression 4 1.1.5 Therapie der CAP ohne Immunsuppression 5 1.1.6 Verlauf, klinische Stabilitätskriterien und Therapiedauer 6 1.2 RISIKOSTRATIFIZIERUNG DER CAP OHNE IMMUNSUPPRESSION 7 1.2.1 Bedeutung der korrekten und schnellen Risikostratifizierung 7 1.2.2 Risikostratifizierung der CAP ohne Immunsuppression 8 1.2.3 Aktuelle Studien zur Risikostratifizierung mittels CRB-65/qSOFA 13 1.3 CAP BEI IMMUNSUPPRESSION 15 1.3.1 Aufbau des Immunsystems 15 1.3.2 Immunsuppression 16 1.3.3 Ursachen der Immunsuppression 17 1.3.4 Bedeutung der CAP bei Immunsuppression 19 1.3.5 Verändertes Erregerspektrum und Therapie bei CAP-Patienten mit Immunsuppression 20 1.3.6 Risikostratifizierung bei CAP und Immunsuppression 23 1.4 RATIONALE UND STUDIENZIEL 26 2 METHODEN 28 2.1 ÜBERBLICK 28 2.2 STUDIENDESIGN 28 2.3 SELEKTION DER STUDIENPOPULATION 28 2.3.1 Datenbasis 28 2.3.2 Einschlusskriterien 29 2.3.3 Ausschlusskriterien 30 2.3.4 Studienpopulation 31 2.4 ENDPUNKTE 33 2.5 DATENERFASSUNG 33 2.5.1 Erhobene Parameter 33 2.5.2 Berechnete Scores und Parameter 34 2.6 FALLZAHLSCHÄTZUNG 34 2.7 STATISTISCHE ANALYSE 34 3 ERGEBNISSE 36 3.1 PATIENTENCHARAKTERISTIKA 36 3.2 MIKROBIOLOGIE 39 3.3 UNIVARIATE ANALYSEN 41 3.3.1 Primärer Endpunkt 41 3.3.2 Sekundärer Endpunkt 45 3.4 MULTIVARIATE ANALYSEN 48 3.5 KAPLAN-MEIER-ANALYSE 54 3.6 ROC-KURVENANALYSE FÜR QSOFA-, CRB-65-, QSOFA-65- UND CRB- SCORE 56 4 DISKUSSION 61 4.1 WICHTIGSTE ERGEBNISSE DER ARBEIT 61 4.2 REPRÄSENTATIVITÄT DER PATIENTENKOHORTE 61 4.2.1 Patientencharakteristika 61 4.2.2 Mikrobiologie 65 4.2.3 Endpunkte 66 4.3 PRÄDIKTIVE PARAMETER 67 4.3.1 CRB-65-Einzelkriterien und -Score 67 4.3.2 qSOFA-Einzelkriterien und -Score 69 4.3.3 Neuer Score 70 4.3.4 qSOFA-Score und CRB-65-Score im direkten Vergleich 70 4.3.5 Komorbiditäten 71 4.3.6 Laborchemische Prognoseparameter 72 4.3.7 Weitere Prognoseparameter 73 4.4 LIMITATIONEN 75 4.5 SCHLUSSFOLGERUNG UND KLINISCHE BEDEUTUNG 75 4.6 AUSBLICK 77 5 ZUSAMMENFASSUNG 78 6 SUMMARY 79 7 LITERATURVERZEICHNIS 80 8 ANHANG 93 9 DANKSAGUNG 101 10 SELBSTSTÄNDIGKEITSERKLÄRUNG 102 / Background: Community-acquired pneumonia (CAP) in immunocompromised patients is a common issue and often associated with poor prognosis. Scores for risk prediction used in immunocompetent patients with sepsis or CAP are poorly evaluated for these patients. Aim: The purpose of the study was to evaluate the prognostic value of the qSOFA- and CRB-65-criteria for risk stratification of immunocompromised patients with CAP. Methods: The retrospective cohort study including 198 consecutive patients hospitalized in the university hospital of Dresden with CAP and severe immunosuppression (neutropenia, active haematological neoplasia, stem cell transplantation, solid organ transplantation, HIV-infection with CD4-cells < 200/µl, immunosuppressive treatment within the last 3 months, prednisolone equivalent > 10 mg/d > 3 months) was conducted between 2014 and 2017. Patients that were admitted directly to the intensive care unit and those with treatment restrictions were excluded. The CRB- and qSOFA-criteria were documented when patients entered the emergency department. Primary outcome was defined as need of mechanical ventilation (MV) or vasopressor support (VS) and/or hospital-mortality. Univariate and multivariate regression analysis as well as ROC curve analysis were performed to investigate the prognostic properties of all scores, the single score parameters and other predictive parameters. Results: 41 (21 %) of 198 included patients reached the primary endpoint and 19 (10 %) of the patients died. Age was not an independent predictive parameter. Using Kaplan-Meier and multivariate logistic regression analysis, both the CRB- and qSOFA-scores were independently associated with the primary endpoint (each p < 0,001). However, after ROC curve analysis both scores only showed moderate prediction (AUC 0,70 and 0,69). With a score of 0, the negative predictive value (NVP) was about 89% in both scores (13/120 and 12/105 missed patients, respectively). When 2 or more parameters were positive the positive predictive values (PPV) were 44 and 58%, respectively. Conclusion: Both, the qSOFA as well as the CRB score, showed moderate but significant prognostic properties. In this population, age was an inappropriate predictive parameter. Even without the age criterion the NPV was inadequate to exclude the possibility of organ failure and complications. Therefore, all immunocompromised patients, especially those with a score > 1, should be monitored intensively concerning organ failure when having a CAP.:ABBILDUNGSVERZEICHNIS V TABELLENVERZEICHNIS VI ABKÜRZUNGS- UND SYMBOLVERZEICHNIS VIII 1 EINLEITUNG 1 1.1 DIE AMBULANT ERWORBENE PNEUMONIE 1 1.1.1 Definition und Einteilung 1 1.1.2 Epidemiologie 2 1.1.3 Diagnosestellung 3 1.1.4 Erregerspektrum bei CAP ohne Immunsuppression 4 1.1.5 Therapie der CAP ohne Immunsuppression 5 1.1.6 Verlauf, klinische Stabilitätskriterien und Therapiedauer 6 1.2 RISIKOSTRATIFIZIERUNG DER CAP OHNE IMMUNSUPPRESSION 7 1.2.1 Bedeutung der korrekten und schnellen Risikostratifizierung 7 1.2.2 Risikostratifizierung der CAP ohne Immunsuppression 8 1.2.3 Aktuelle Studien zur Risikostratifizierung mittels CRB-65/qSOFA 13 1.3 CAP BEI IMMUNSUPPRESSION 15 1.3.1 Aufbau des Immunsystems 15 1.3.2 Immunsuppression 16 1.3.3 Ursachen der Immunsuppression 17 1.3.4 Bedeutung der CAP bei Immunsuppression 19 1.3.5 Verändertes Erregerspektrum und Therapie bei CAP-Patienten mit Immunsuppression 20 1.3.6 Risikostratifizierung bei CAP und Immunsuppression 23 1.4 RATIONALE UND STUDIENZIEL 26 2 METHODEN 28 2.1 ÜBERBLICK 28 2.2 STUDIENDESIGN 28 2.3 SELEKTION DER STUDIENPOPULATION 28 2.3.1 Datenbasis 28 2.3.2 Einschlusskriterien 29 2.3.3 Ausschlusskriterien 30 2.3.4 Studienpopulation 31 2.4 ENDPUNKTE 33 2.5 DATENERFASSUNG 33 2.5.1 Erhobene Parameter 33 2.5.2 Berechnete Scores und Parameter 34 2.6 FALLZAHLSCHÄTZUNG 34 2.7 STATISTISCHE ANALYSE 34 3 ERGEBNISSE 36 3.1 PATIENTENCHARAKTERISTIKA 36 3.2 MIKROBIOLOGIE 39 3.3 UNIVARIATE ANALYSEN 41 3.3.1 Primärer Endpunkt 41 3.3.2 Sekundärer Endpunkt 45 3.4 MULTIVARIATE ANALYSEN 48 3.5 KAPLAN-MEIER-ANALYSE 54 3.6 ROC-KURVENANALYSE FÜR QSOFA-, CRB-65-, QSOFA-65- UND CRB- SCORE 56 4 DISKUSSION 61 4.1 WICHTIGSTE ERGEBNISSE DER ARBEIT 61 4.2 REPRÄSENTATIVITÄT DER PATIENTENKOHORTE 61 4.2.1 Patientencharakteristika 61 4.2.2 Mikrobiologie 65 4.2.3 Endpunkte 66 4.3 PRÄDIKTIVE PARAMETER 67 4.3.1 CRB-65-Einzelkriterien und -Score 67 4.3.2 qSOFA-Einzelkriterien und -Score 69 4.3.3 Neuer Score 70 4.3.4 qSOFA-Score und CRB-65-Score im direkten Vergleich 70 4.3.5 Komorbiditäten 71 4.3.6 Laborchemische Prognoseparameter 72 4.3.7 Weitere Prognoseparameter 73 4.4 LIMITATIONEN 75 4.5 SCHLUSSFOLGERUNG UND KLINISCHE BEDEUTUNG 75 4.6 AUSBLICK 77 5 ZUSAMMENFASSUNG 78 6 SUMMARY 79 7 LITERATURVERZEICHNIS 80 8 ANHANG 93 9 DANKSAGUNG 101 10 SELBSTSTÄNDIGKEITSERKLÄRUNG 102

Background: Type 1 Diabetes mellitus (TIDM) is a chronic disorder in which the insulin producing beta cells are selectively self-destroyed. Although the etiology of the disease has not been determined, genetic dispositions such as SLC11A1 polymorphism in suffering patients have been reported. The role of pathogenic microorganisms such as Mycobacterium avium subspecies paratuberculosis (MAP) in TIDM has also been recently debated. MAP is already known to cause paratuberculosis in cattle and now it is a strong suspect of causing autoimmune diseases in humans such as Crohn’s disease, multiple sclerosis, autoimmune Thyroiditis, rheumatoid arthritis and autoimmune diabetes. We hypothesis that molecular mimicry between MAP Heat shock protein 65K (Hsp65) and human Glutamic Acid Decarboxylase 65K (GAD65) can be the trigger which leads to the autoimmune destruction of beta cell in patients exposed to MAP . Method: To test the hypothesis, peptide sequences of MAP Hsp65 and human GAD65 were investigated using BLAST and PyMOL bioinformatics tools. Moreover, 18 blood samples from humans with TIDM and controls, and 100 sera samples from cattle with paratuberculosis and controls were evaluated for the presence of MAP, MAP DNA and its antibodies. Glucose, insulin and GAD65 antibodies were also determined in some of the clinical samples. Results: Peptide BLAST analysis revealed 44% identity between the two proteins with 75% positive identities in a 16 amino acid region. PyMOL structural analysis identified possible shared epitope regions of the proteins in its 3D conformation. Immunoblot analysis revealed a strong cross reactivity between lysate of E.coli recombinant of MAP Hsp65 and plasma from human subject with TIDM. A weak cross reactivity was also observed between healthy rat pancreatic homogenate and rabbit anti MAP IgG. Nested PCR using IS900-specific iv oligonucleotide primers did not detect MAP DNA in peripheral blood from 18 subjects with Type I Diabetes, Type II Diabetes and non-diabetic controls. Long term culture of leukocytes from blood samples from same subjects resulted in the presence of MAP in 3/10 (30%) TIDM and 4/8 (50%) control subjects. However anti MAP IgG were detected in 5/10 (50 %) TIDM samples compared to 3/8 (37.5 %) controls. Insulin level was measured in sera from paratuberculosis cattle and controls. In MAP infected cattle, insulin level ranged from below 0.1ng/ml to 2.456 ng/ml with an average of 0.36 +/- 0.57ng/ml compared to below 0.1ng/ml to 13.47ng/ml with an average of 2.86 +/- 3.00ng/ml in healthy cattle. Conclusion: Bioinformatics analysis between MAP Hsp65 and human GAD65 through BLAST and PyMOL analysis revealed a homology of 16 amino acid motif and possible shared epitope regions; immunohistochemistry analysis revealed a cross reactivity between rabbit antiMAP IgG and pancreatic cell homogenate from a healthy rat. Moreover, plasma from patient with TIDM (TD8), who was confirmed to be positive for MAP DNA and MAP IgG, reacted strongly with MAP Hsp65 in MAP protein lysate and MAP Hsp65 recombinant clone pmptb20. Culture of MAP from human leukocytes is significant despite the lack of correlation between MAP in samples from TIDM and controls. It is worth noting that some of the control subjects have not been evaluated for other autoimmune diseases possible MAP role. Additionally, antiMAP IgG levels in TIDM subjects compared to controls have raised a suspicion on the involvement of MAP in TIDM. The poor correlation of MAP in blood versus either the antiMAP IgG or the insulin level may be related with the fastidious nature of MAP and in vitro cultivation. Since MAP is the sole causative agent of Johne’s disease, it is significant that the insulin level is 8 folds less in MAP infected cattle compared to MAP free cattle. Overall, the data v is mixed and suggest that further study is needed to investigate the intriguing question to whether MAP is involved in TIDM or not.

Syfte: Syftet med studien var att beskriva om aktivitetskorten i I-HOPE motsvarar äldre personers aktiviteter i hemmet utifrån svenska förhållanden samt identifiera behov av att komplettera med ytterligare aktiviteter. Metod: Datainsamling utfördes med en kvantitativ standardiserad webbenkät med kvalitativt inslag. Totalt deltog 41 personer mellan 65 och 87 år med en medelåldern av 73.3 år och standardavvikelse på 5.1 år. Samtliga deltagare bodde i ordinärt boende i Södra Norrland kust- och inland i Sverige. Datamaterialet bearbetades med kvantitativ analysmetod, resultatet presenterades i löptext med tabeller och figurer. Svaren från webbänktens öppna fråga angående saknade aktiviteter kategoriserades i grupper utifrån de faktiska svaren. Resultat: Resultatet från studien visade att samtliga deltagare kunde identifiera 18 av de 44 aktivitetskorten utan vägledning och 16 aktivitetskort kunde 75-99% av deltagarna identifiera utan vägledning.Vidare var det 10 aktivitetskort som färre än 50% av studiens deltagare identifierade utan vägledning. På flertalet aktivitetskort kunde deltagarna identifiera aktiviteten men de identifierade sig sedan inte med miljön, utrustningen eller hur aktiviteten utfördes. Resultatet visade även att 10 av de 44 aktiviteterna inte utfördes av samtliga deltagare i studien. Vidare framkom behov av att komplettera I-HOPE med ytterligare aktivitetskort för att svara mot svenska förhållande. Slutsats: Utifrån studiens resultat finner författarna ett behov av att komplettera med fler aktivitetskort samt att revidera ett antal av bilderna på de befintliga aktivitetskorten i bedömningsinstrumentet I-HOPE. / Purpose: The purpose of the study was to describe whether the activity cards in I-HOPE correspond to older people's activities in the home based on Swedish conditions and identify the need to supplement additional activities. Method: Data collection was performed with a quantitative standardized web quote with qualitative elements. In total, 41 participants participated between 65 and 87 years with an average age of 73.3 years and a standard deviation of 5.1 years. All participants lived in Ordinary accommodation in southern Norway, coastal and inland in Sweden. The data was processed using quantitative analysis method, the result was presented in running text with tables and figures. The answers from the web site's open question about missing activities were categorized into groups based on the actual answers. Results: The result of the study showed that it was 18 of the 44 activity cards that all participants could identify without guidance. 16 activity cards were 75-99% of the participants who could identify. In addition, there were 10 activity cards that fewer than 50% of the study participants were able to Identify without guidance. On most activity cards, participants were able to identify the activity without guidance but they could not identify with the environment, equipment or how the activity was performed. The result also showed that 10 of the 44 activities were not performed by all participants in the study. Furthermore, there was a need to supplement I-HOPE with additional activity cards to respond to Swedish conditions. Conclusion: Based on the results of the study, the authors find a need to supplement more activity cards and to revise a number of the pictures on the existing activity cards in the I-HOPE assessment tool.