People with disabilities are a ‘disadvantaged’ group, not only due to their impairment, but also due to the formal and informal institutional inertia that they contend with in Western Societies. This disadvantage has been recognised and acknowledged in the social model of disability. This model understands that disability is a social construction placed on people with impairments. The Health Impact Assessment (HIA) is a tool which identifies inequities in policy, and is potentially a useful tool to aid the response of policy makers to the needs of people with disabilities. Arguably, the New Zealand HIA guidelines reflect the underlying principles of the social model of disability. Using a mixed methods research strategy, this thesis sets out to understand in a global context using a top-down quantitative analysis, to what extent the New Zealand HIA guidelines which acknowledge the social model of disability are translated into practice. It then subsequently investigates from a bottom-up qualitative perspective, what factors influence this relationship. It is argued in this thesis that there are barriers to translating the rhetoric about people with disabilities found in the HIA guidelines into practice. Three sets of inter-related barriers identified include attitudinal barriers to people with disabilities, generic HIA barriers, and barriers related to the feminist interpretation of the construction of disability. In this thesis, the research findings conclude that it is difficult to operationalise the disability awareness present in the HIA guidelines due to barriers which are related to the ‘othering’ of people with disabilities. This is discussed in relation to feminist analyses of the construction of people with disabilities, and it needs to be addressed by wider societal reforms. The thesis makes the recommendation that a national awareness-raising campaign about people with disabilities be undertaken in New Zealand in an attempt to rectify this situation.

<p>Nontypeable Haemophilus influenzae (NTHi) is a common commensal in the human nasopharynx that can cause localized respiratory tract diseases such as otitis media, bronchitis, and pneumonia. NTHi adheres to respiratory epithelial cells, a critical step in the process of colonization enabled by bacterial surface adhesive structures called adhesins. One group of NTHi adhesins are autotransporters, proteins that have an N-terminal signal sequence, a C-terminal &#946;-barrel domain, and an internal passenger domain with effector function. The goal of this work was to increase our understanding of two NTHi autotransporters, Hap and Hia.</p><p>Hap is a monomeric autotransporter that mediates adherence to epithelial cells and extracellular matrix (ECM) proteins. Hap also self-associates with protein on neighboring bacteria, resulting in bacterial aggregation and microcolony formation. The Hap passenger domain contains the regions responsible for adhesive activity. To define the molecular mechanism of Hap adhesive activity, we crystallized the Hap passenger domain. Characterization of the crystal structure revealed an N-terminal globular domain and a more ordered, prism-like C-terminal domain. Interestingly, Hap crystallized as a multimer, suggesting that Hap-Hap interactions occurred in the passenger domain. Progressive deletions of the &#946;-loops that comprise the C-terminal region disrupted Hap-Hap interactions and led to a defect in bacterial settling. To further support that the C-terminal domain was responsible for Hap-Hap interactions,</p><p>7</p><p>we purified the wild type and truncated passenger domains and conjugated the proteins to latex beads. By light microscopy we visualized bead aggregation when the wild type passenger domain was conjugated to the beads, but not when the truncated passenger domain was conjugated. These results show that the C-terminal portion of the Hap passenger domain is responsible for Hap-Hap interactions leading to multimerization. Hap multimerization could be important in microcolony formation that leads to biofilm formation in vivo.</p><p>The ECM binding domain in located in the final 511 amino acids of the Hap passenger domain. To pin-point the region of the ECM protein fibronectin that is recognized by Hap, we spotted small fragments of fibronectin onto nitrocellulose membranes and incubated the membrane with purified Hap passenger domain. Far Western analysis using Hap antibody revealed that the smallest fibronectin region necessary for binding was comprised of the first two type III repeats, FNIII(1-2). To define the regions of Hap responsible for interaction with fibronectin, we mutated motifs in the Hap passenger domain that are important for fibronectin binding in other bacterial proteins. Based on assessment by ELISA, many of the mutations located between amino acids 525-725 caused reduced bacterial binding to fibronectin. However, no mutation totally ablated binding, suggesting that a larger Hap region is involved in fibronectin binding.</p><p>8</p><p>In an additional study, we identified a relationship between Hap levels in the outer membrane and the expression of lipopolysaccharide (LPS) biosynthesis enzymes. Through Western and qPCR analysis, we found that mutation of the rfaF, pgmB, lgtC, kfiC, orfE, rfbP, lsgB and lsgD genes involved in the synthesis of LPS oligosaccharide core in H. influenzae strain Rd/HapS243A resulted in loss of Hap in the bacterial outer membrane and a decrease in hap transcript. In contrast, the same mutations had no effect on outer membrane localization of H. influenzae P5 and IgA1 protease or levels of the p5 or iga1 transcripts, suggesting a Hap-specific effect. Elimination of the HtrA periplasmic protease resulted in a return of Hap to the outer membrane and restoration of wild type levels of hap transcript. We speculate that the lack of certain LPS biosynthesis enzymes causes Hap to mislocalize and accumulate in the periplasm, where it is degraded by HtrA. This degradation then leads to a decrease in hap transcript. lgtC is one of several phase variable LPS biosynthesis genes. Using an antibody against the epitope formed in part by the lgtC gene product, we identified lgtC phase-off bacteria by Western analysis of colony blots. Consistent with our previous observations, in lgtC phase off bacteria Hap was absent from the outer membrane and hap transcript was reduced. By analyzing a lgtC/lic2A double mutant, we found that Hap localization in the outer membrane and hap transcript levels were not related to LPS size but instead to the functions of the LPS synthesis enzymes themselves. This relationship could be beneficial to bacteria in vivo as a way to regulate Hap expression.</p><p>9</p><p>Early models suggested that autotransporters do not require accessory factors for folding and OM insertion. However, mounting recent evidence has suggested that the Bam complex is required for OM localization of most &#946;-barrel proteins, including autotransporters. We studied the role of the Bam complex in OM localization of the trimeric autotransporter Hia. We expressed Hia in E. coli strains with mutations in the Bam complex and found that BamA and BamD were needed for Hia localization, while BamB, BamC, and BamE were not necessary. In further studies, we mutated the C-terminus of Hia and found that the final and third-to-last amino acids were the most important for outer membrane localization.</p><p>In summary, this work provides insights into the regulation and adhesive activity of Hap and the outer membrane localization of Hia. We have learned important details about these factors that shed light on aspects of H. influenzae disease and could lead to new antimicrobial therapies.</p> / Dissertation

Introdução: A Avaliação de Impactos à Saúde (AIS) é adotada em vários países como estratégia para abordar os potenciais impactos à saúde relacionados a políticas, planos, programas ou projetos, mas não é ainda utilizada no Brasil. Objetivo: Identificar as condições brasileiras que podem corroborar com vantagens e limitações da AIS já descritas na literatura internacional, considerando sua aplicação futura no Brasil, especialmente no caso de projetos. Métodos: Revisão da literatura científica e de outros documentos internacionais sobre AIS, identificados através de bases de dados (Pub Med e Science Direct), e de portais especializados, para entender o contexto e compilar vantagens e limitações da AIS. Revisão da literatura científica nacional e de outros documentos sobre avaliação de impactos e saúde, identificados através das bases de dados LILACS, SCIELO e outros portais brasileiros que tratam desses temas. Pesquisa qualitativa complementar com profissionais e pesquisadores brasileiros. Resultados e discussão: A AIS ainda está se desenvolvendo no mundo, por isso há vantagens e limitações igualmente importantes associadas aos seus indutores; ao objeto da avaliação (políticas, planos, programas ou projetos); à fase em que é conduzida (prospectiva ou retrospectiva); aos patrocinadores e avaliadores; ao tipo de AIS adotada; à sua institucionalização; à integração a outras formas de avaliação de impactos (AIA ou AAE); à abordagem em saúde, ao escopo e aos métodos adotados; à participação das partes afetadas e a sua influência no processo de tomada de decisão. No Brasil, os estudos que abordam os impactos à saúde são frequentemente retrospectivos e a abordagem de saúde na AIA apresenta lacunas. Os poucos estudos prospectivos ainda não utilizam as ferramentas e passos da AIS. O Ministério da Saúde vem articulando o processo de introdução da AIS no país. Conclusões e Recomendações: Há oportunidades para introduzir a AIS de projetos no país. Entretanto, é urgente o engajamento dos profissionais brasileiros da área de saúde e de avaliação de impactos com as redes de profissionais nacionais e internacionais, visando aprimorar a discussão e prepará-los para enfrentar questionamentos à AIS eventualmente levantados por aqueles que veem no processo de avaliação de impactos obstáculos para a eficiência e rapidez da tomada de decisão sobre projetos. É também preciso organizar padrões mínimos para que não sejam reproduzidos no Brasil problemas já vivenciados e solucionados em outras localidades / Introduction: Health Impact Assessment (HIA) is adopted as a strategy to address the potential health impacts associated with policies, plans, programs or projects in various countries, but not yet in Brazil. Objective: To identify the Brazilian conditions that can contribute to HIA advantages and constraints already described in the literature, considering its future adoption in Brazil, particularly in the case of projects. Method: Review of scientific literature and other documents on HIA, identified in Pub Med and Science Direct, as well as in HIA websites, in order to understand the context and compile HIA advantages and constraints already described in the literature. Review of Brazilian scientific literature and other Brazilian documents on impact assessment and health, identified through LILACS and SCIELO databases as well as other Brazilian web sites that address the subject. Additional qualitative research with Brazilian stakeholders. Results and discussion: HIA is still developing worldwide. Due to that, there are equally important advantages and limitations associated to its drivers, its object (policies, plans, programs or projects), when it is conducted (prospective or retrospective), HIA sponsors and assessors, HIA types, if HIA is institutionalized, if it is integrated with other forms of impact assessment (AIA, SEA), its approach to health, its scope and methods, the participation of affected parties and its influence to decision making. In Brazil, health impact assessments are frequently retrospective and do not adopt HIA tools and its steps. The Brazilian Ministry of Health is working to introduce HIA in the country. Conclusions and recommendations: There are opportunities to introduce HIA of projects in the country. However, it is urgent to engage Brazilian health and impact assessment professionals with national and international networks, in order to deepen and improve the discussion and to prepare them to face future questioning to HIA eventually raised by those that view the impact assessment process as an obstacle to efficiency in the context of project decision making. It is also necessary to develop minimum standards so that some issues already faced and solved elsewhere are not repeated in Brazil

Introdução: A Avaliação de Impactos à Saúde (AIS) é adotada em vários países como estratégia para abordar os potenciais impactos à saúde relacionados a políticas, planos, programas ou projetos, mas não é ainda utilizada no Brasil. Objetivo: Identificar as condições brasileiras que podem corroborar com vantagens e limitações da AIS já descritas na literatura internacional, considerando sua aplicação futura no Brasil, especialmente no caso de projetos. Métodos: Revisão da literatura científica e de outros documentos internacionais sobre AIS, identificados através de bases de dados (Pub Med e Science Direct), e de portais especializados, para entender o contexto e compilar vantagens e limitações da AIS. Revisão da literatura científica nacional e de outros documentos sobre avaliação de impactos e saúde, identificados através das bases de dados LILACS, SCIELO e outros portais brasileiros que tratam desses temas. Pesquisa qualitativa complementar com profissionais e pesquisadores brasileiros. Resultados e discussão: A AIS ainda está se desenvolvendo no mundo, por isso há vantagens e limitações igualmente importantes associadas aos seus indutores; ao objeto da avaliação (políticas, planos, programas ou projetos); à fase em que é conduzida (prospectiva ou retrospectiva); aos patrocinadores e avaliadores; ao tipo de AIS adotada; à sua institucionalização; à integração a outras formas de avaliação de impactos (AIA ou AAE); à abordagem em saúde, ao escopo e aos métodos adotados; à participação das partes afetadas e a sua influência no processo de tomada de decisão. No Brasil, os estudos que abordam os impactos à saúde são frequentemente retrospectivos e a abordagem de saúde na AIA apresenta lacunas. Os poucos estudos prospectivos ainda não utilizam as ferramentas e passos da AIS. O Ministério da Saúde vem articulando o processo de introdução da AIS no país. Conclusões e Recomendações: Há oportunidades para introduzir a AIS de projetos no país. Entretanto, é urgente o engajamento dos profissionais brasileiros da área de saúde e de avaliação de impactos com as redes de profissionais nacionais e internacionais, visando aprimorar a discussão e prepará-los para enfrentar questionamentos à AIS eventualmente levantados por aqueles que veem no processo de avaliação de impactos obstáculos para a eficiência e rapidez da tomada de decisão sobre projetos. É também preciso organizar padrões mínimos para que não sejam reproduzidos no Brasil problemas já vivenciados e solucionados em outras localidades / Introduction: Health Impact Assessment (HIA) is adopted as a strategy to address the potential health impacts associated with policies, plans, programs or projects in various countries, but not yet in Brazil. Objective: To identify the Brazilian conditions that can contribute to HIA advantages and constraints already described in the literature, considering its future adoption in Brazil, particularly in the case of projects. Method: Review of scientific literature and other documents on HIA, identified in Pub Med and Science Direct, as well as in HIA websites, in order to understand the context and compile HIA advantages and constraints already described in the literature. Review of Brazilian scientific literature and other Brazilian documents on impact assessment and health, identified through LILACS and SCIELO databases as well as other Brazilian web sites that address the subject. Additional qualitative research with Brazilian stakeholders. Results and discussion: HIA is still developing worldwide. Due to that, there are equally important advantages and limitations associated to its drivers, its object (policies, plans, programs or projects), when it is conducted (prospective or retrospective), HIA sponsors and assessors, HIA types, if HIA is institutionalized, if it is integrated with other forms of impact assessment (AIA, SEA), its approach to health, its scope and methods, the participation of affected parties and its influence to decision making. In Brazil, health impact assessments are frequently retrospective and do not adopt HIA tools and its steps. The Brazilian Ministry of Health is working to introduce HIA in the country. Conclusions and recommendations: There are opportunities to introduce HIA of projects in the country. However, it is urgent to engage Brazilian health and impact assessment professionals with national and international networks, in order to deepen and improve the discussion and to prepare them to face future questioning to HIA eventually raised by those that view the impact assessment process as an obstacle to efficiency in the context of project decision making. It is also necessary to develop minimum standards so that some issues already faced and solved elsewhere are not repeated in Brazil

In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele. In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p&lt;0.001), which could be of importance since an SDC &gt;1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders). In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.

Bakgrund: Studier visar att hundar har en positiv effekt på den fysiska hälsan. De kan också öka det sociala samspelet, minska depression, öka självförtroende och självbestämmande samt reducera ångest genom hundassisterad aktivitet eller hundassisterad intervention. Syfte: Syftet med denna studie är att undersöka om hundar inom ramen för omvårdnad på en rättspsykiatrisk avdelning kan påverka patienternas välbefinnande. Metod: För att undersöka patienternas upplevelser användes en kvalitativ studiedesign. För att besvara syfte och frågeställningar gjordes semistukturerade intervjuer som analyserades med en kvalitativ innehållsanalys.   Resultat: Hundar på avdelningen upplevdes både positivt och negativt. De inverkade på välbefinnandet genom att de genererade glädje och välmående men också irritation och ilska. De gav också en känsla av att bli sedd som människa, ökade den fysiska aktiviteten, förbättrade sömnen och påverkade självkänslan och självförtroendet. Vårdmiljön påverkades också genom ett förbättrat klimat på avdelningen. De gav en meningsfullhet i vardagen, en möjlighet till närhet, en känsla av mindre kontrollerande miljö samt att de hade en inverkan på hur patienterna rörde sig på avdelningen. Det identifierades en ståndpunkt för hundar på avdelningen, men också en emot att ha hundar på avdelningen. Slutsats: Resultaten tyder på att det positiva överväger det negativa då majoriteten av resultatet belyser aspekter som ökar välbefinnandet hos patienterna. Hundar inom vården anses därför vara en bra komplementär omvårdnadsform för att som sjuksköterska på en rättspsykiatrisk avdelning. Detta för att kunna utföra god omvårdnad, främja välbefinnande och upprätthålla ett samhällsskydd och samtidigt reducera känslan hos patienten av att vara underordnad och kontrollerad. Det är dock viktigt att beakta olika individers åsikter för att hitta en form som passar. / Background: Studies have shown that dogs have a positive effect on humans physical health. They may also increase social interactions, decrease depression, increase peoples selfconfidence and autonomy and reduce anxiety trough animal-assisted interventions. Aim: The aim of this studie is to investigate if dogs can effect well-being in patients within forensic psychiatric care. Method: To investigate the patients experiences a qalitative reserch method were used. Semi-structured interviews were used to answer to the aim of the studie, and analysed with a content analysis. Result: The patients had both positive and negative experiences regarding the presence of the dogs at the unit. The dogs had an impact on the patients well-being by generating joy as well as anger and irritation. They gave a sense of being perceived as an individual, they increased physical activity, improved quality of sleep and had an inpact on self-esteem and self-confidence. The dogs also had an impact on the health facility environment trough an inprovement of the atmosphere at the unit. The dogs gave sense of mening in the everday life, an opportunity for intimacy, a sense of a less controlling environment and they also had an impact on how the patients moved at the unit. Some where proponents and some opponents to the impementation of dogs at the unit. Conclusion: The results shows that the positive experiences tops the negative because the majority of the results shows aspects of improved well-being. Dogs within healthcare facilities are therefore concidered to be a good complementary form of care for nurses working in forensic psychiatric care. This to perform good nursing care, promote well-being and maintain the civil protection and at the same time reduce feelings of being inferior, subordinated and controlled. It is however important to pay regards to the different idividual opinions and find a resolution that suits best.