Clinically significant delusion is a symptom of a number of mental illnesses. We rely on what a person says and how she behaves in order to identify if she has this symptom and it is clear from the literature that delusions are heterogeneous and extremely difficult to define. People with active delusions were interviewed to explore what it is like to develop and experience delusion. The transcribed interview data was analysed to identify themes and narrative trajectories that help to explain the phenomenon. Results showed that delusions can sometimes provide pragmatic (protective) benefits and that the genesis of some delusions can be characterised in terms of the enactivist notion of affective framing. Affective framing is a term that captures the background emotions that enable know-how in terms of goal directed action and cognition. If a person’s affective frame alters the world is no longer understood and know-how is lost. The way in which a person relates to her environment can be highly anomalous thus requiring her to find an extraordinary explanation. I argue that delusions arise as a result of a breakdown in affective framing and offer a conceptualisation of delusion supported by empirical findings.

Methodological naturalists generally believe that science is the best and only method for discovering the properties of reality and what exists. A central tenet of methodological naturalism is that science is limited to evaluating only natural things. Science cannot allow for the possibility of supernatural objects because doing so would irreparably damage the scientific method. Or, it may be that evaluating the supernatural is beyond the capabilities of science. In this thesis, I challenge these assumptions. I defend a form of naturalism known as Provisory Methodological Naturalism which holds that science can, at least theoretically, evaluate supernatural claims. Provisory methodological naturalists believe the notion that science only evaluates natural things is provisional and subject to being overruled. Should supernatural objects exist, science would be able to observe them.

This thesis proceeds from an attempt to articulate the body. At its core, however, is not the attempt to offer a definition of the body but instead to articulate a problem of touching on it. As such, it is motivated by a question at once banal and impossible: ‘Are we nearly here yet?’ Following Jean-Luc Nancy’s engagement with the account of space and being-there proposed by Martin Heidegger, it relates the materiality of the body to a broader role of touch and sense in constructing a world of engagements in which the body is never “here” but always “there”, always exposed in its touch upon the other. Following Nancy, this thesis begins by opening an ontological formulation of space and embodiment in which the materiality of the body allows for sense to pattern a world of bodies always separated from each other but situated in relation to each other. Sense, on Nancy’s account, is both bodily and conceptual; sense is the touch of vision, of the hands, of the body, and of understanding. Emphasising this multiple formulation of touch, this thesis offers an ontology of space as both material and transparent, in which this transparency figures the potential of the world to be continually re-spaced according to the touches and relationships enacted within it. After establishing this ontology of body and touch, the thesis enacts a series of attempts to approach the body, conducted in relation to encounters with bodies through photographs, painting and self-portraiture, as well as encounters with bodies that reveal aspects of their particular embodiment at moments of disruption or in their pathological relationships to the world. In each case, what is explored are figures of approach and withdrawal, turn and return, in which the body is nearly available to touch, but always elusive.

No description available.

Volcanic earthquakes can provide significant insight into physical processes acting at volcanoes, such as magma accumulation and the mechanisms of deformation of the volcanic edifice. At the same time a statistical analyses of volcanic seismicity prior to an eruption (for example variations in the Gutenberg-Richter b-value – a measure of the proportion of large and small events) are a key component of the practical problem of forecasting eruptions. This thesis aims to tackle two key areas of research that are closely related to these important overall goals, by comparing seismic data obtained from currently-active volcanoes with direct field observation of faulting and fracturing from an exhumed extinct volcano. First I introduce a new approach that improves the accuracy and reliability of calculating spatial and temporal variations of the seismic b-value for frequency-magnitude distributions at active volcanoes, and apply it to several test cases. An extensive literature review highlights a large variability and lack of standardisation of methodology used to analyse frequency-magnitude distributions in the past. Motivated by this, I introduce and test a new workflow to standardise calculating completeness magnitudes of seismic catalogues. The review also highlights the fact that uncertainties in estimating the threshold magnitude of complete reporting have been ignored to date. Here I use synthetic catalogues to quantify this previously unidentified source of error, and provide a template to estimate the total error in b-value. In standard analysis it is also common to sample time windows subjectively, although this can introduce bias. Here I develop a new objective, iterative sampling method that calculates the b-value as a full probability density function which need not have a Gaussian error structure. Application of this method reveals ‘mode-switching’ behaviour for the first time in volcanic seismic catalogues. The results also show b-values often do have a value indistinguishable from that of tectonic seismicity (b=1 within error). Nevertheless there are also several robust examples of real high b-values, as high as 3.3. The second part of the study is based on a field campaign to investigate the fracture zones from an exhumed volcanic setting on the Isle of Rum, NW Scotland. Lithological and structural mapping is used to collect structural data that is then used to quantify and explain complex fracture patterns and the underlying intra-magma chamber processes that occurred there in the geological past. In particular I identify a singular collapse event within the youngest volcanic unit, the Central Intrusion. This is responsible for forming the observed igneous breccias and the lineaments on satellite images that I interpret as contemporaneous faults. Using appropriate scaling relations, I infer the b-value for the Rum lineaments data. This would have been relatively high, at a value of approximately 1.9. The final part of the study compares the fracture data on Rum to earthquake distributions at El Hierro volcano, Canary Islands. Here I show the level of fractal clustering is similar in both an extinct (60 Ma) and a currently active volcano. Both show similar high levels of clustering. However, in both cases there is a difference between the capacity and correlation dimensions (D₀≠D₂), implying the set of rupture sources or mapped fault traces form a multi-fractal set. Broadly, the scaling of fracture sets in an ancient volcano has similar properties to those observed in a modern volcano, except that the Rum data imply a greater absolute degree of spatial clustering of deformation than that for the recent unrest at El Hierro.

This thesis argues for a move beyond the division of contemporary western experiences into separate social and political spheres. This includes a comparative study of the theories of Hannah Arendt and Michel Foucault alongside historical and contemporary examples in support of the relevance of their theories and that of this thesis. The synthesis between Arendt and Foucault made here corrects the respective weaknesses in each theory by using the strengths of the other. Furthermore, this synthesis informs a move beyond the social and political referred to above. The critique of sovereignty, the defence of plurality and the critique of instrumental reason are shown here as the most important parallels between the two thinkers and the central ways that people in contemporary western society are disempowered. This thesis argues for a reconsideration of these issues in order to redress this disempowerment. The thesis also looks at the major divergence between the two thinkers which is shown to rest on their respective treatment of the social and political. This argument rejects the Arendtian argument for the separation of the social and political to favour Foucauldian resistance located on and within the everyday experiences of western individuals. This shown to be political action rooted in the social aspects of the individuals' lives and stands in opposition to the claims of Arendt regarding the social. However, this retains the political strengths of her vision. The synthesis of the strengths of both theorists alongside the ultimate rejection of the Arendtian separation of the social and political that this Foucauldian resistance exemplifies is concluded as constituting a move beyond the social and political to have more relevance, meaning and ultimate empowerment for individuals because it more accurately reflects the realities of their everyday lives.

As polimixinas são antibióticos polipeptídicos com potente ação sobre várias bactérias Gram-negativas. Seu uso foi abandonado na década de 1960 devido a relatos de nefrotoxicidade e neurotoxicidade. No entanto, o aumento progressivo das infecções nosocomiais por bactérias Gram-negativas multirresistentes, como Pseudomonas aeruginosa e Acinetobacter baumannii, e a ausência de novos antimicrobianos para combater esses patógenos, desencadearam a sua reintrodução nos últimos anos. Somente as polimixinas B e E são utilizadas na prática clínica. As publicações referem-se, na grande maioria, à polimixina E. Encontramos poucos estudos clínicos sobre polimixina B, o que despertou o interesse para o desenvolvimento deste trabalho. Mais recentemente, um crescente número de publicações sobre a farmacocinética (FC) e a farmacodinâmica (FD), efetividade e segurança, das polimixinas, sobretudo, da colistina (polimixina E) tem sido publicado. Por exemplo, demonstrou-se em modelo experimental que o padrão FC/FD da colistina associado com sua atividade bactericida é a área sob a curva/ concentação inibitória mínima. Esse achado corrobora os resultados de um único estudo clínico com essa droga, demonstrando que doses maiores estão associadas a melhores desfechos clínicos. No presente estudo, de coorte retrospectivo, avaliaram-se os fatores de risco associados à mortalidade hospitalar em pacientes tratados com polimixina B endovenosa, com especial ênfase para o efeito da dose nesse desfecho. Os pacientes ≥ 18 anos que receberam polimixina B por ≥72 horas foram incluídos no estudo. O desfecho foi mortalidade hospitalar. Análise de subgrupos foi realizada em pacientes com infecções microbiologicamente confirmados e os com bacteremia. Toxicidade renal também foi avaliada. Para análise dos grupos e subgrupos utilizou-se Modelos de Regressão Logística (MRL). A mortalidade hospitalar global foi de 60,5%. Sepse grave ou choque séptico (Odds Ratio ajustado (ORa) 4,07; [Intervalo de Confiança] IC 95% 2,22-7,46), ventilação mecânica (ORa 3,14; IC 95% 1,73-5,71), escore de Charlson (ORa 1,25; IC 95% 1,09-1,44) e idade (ORa 1,02; IC 95% 1,01-1,04) foram independentemente associados com aumento da mortalidade intrahospitalar, enquanto doses ≥ 200mg/dia de polimixina B foram associadas com menor risco para o desfecho mortalidade (ORa 0,43; IC 95% 0,23-0,79). A dose ≥ 200mg/dia de polimixina B sobre a mortalidade foi maior no subgrupo de pacientes com infecções microbiologicamente documentadas e bacteremia. Os pacientes com ≥ 200mg/dia de polimixina B apresentaram um risco significativamente maior de insuficiência renal grave. O estudo demonstrou que polimixina B em doses ≥ 200mg/dia foi associada com menor mortalidade hospitalar, e o benefício destas doses mais elevadas sobrepõe o risco de disfunção renal grave durante o tratamento.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2015-02-04T09:24:45Z No. of bitstreams: 2 Dissertação - Leandro Nascimento da Silva - 2014.pdf: 6086146 bytes, checksum: 75f020e70d97640ac095871c4913b275 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-02-05T14:16:04Z (GMT) No. of bitstreams: 2 Dissertação - Leandro Nascimento da Silva - 2014.pdf: 6086146 bytes, checksum: 75f020e70d97640ac095871c4913b275 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-05T14:16:04Z (GMT). No. of bitstreams: 2 Dissertação - Leandro Nascimento da Silva - 2014.pdf: 6086146 bytes, checksum: 75f020e70d97640ac095871c4913b275 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-09-09 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Crack is considered a public health problem in Brazil and in the world because of its impact on social relationships, physical and mental integrity of the user, and the risk associated with infections, such as those caused by the hepatitis B virus (HBV). This study investigated the epidemiology of infection with the hepatitis B virus and immunization status among users of crack institutionalized in Goiania, Brazil. During August 2012 to April 2013, a total of 600 individuals were interviewed, and blood samples collected for the detection of serological markers of HBV (HBsAg, total anti HBc and anti-HBs) by enzyme-linked immune sorbent assay (ELISA). Subsequently a cohort of individuals susceptible to hepatitis B was formed to assess compliance, completion of the vaccination series, and vaccine response against hepatitis B, using an accelerated scheme. Prior exposure to HBV (anti-HBc) was 7.0% (95% CI: 5.22 to 9.32), and 17.7% (95% CI: 14.8 to 20.9) were anti -HBs isolated, suggesting previous vaccination against hepatitis B. The use of crack cocaine through improvised pipes, history of sexually transmitted disease, and exchanging sex for drugs or money were significantly associated with exposure to HBV (p < 0.05). Of the total of individuals who received the first dose of hepatitis B vaccine and eligible to complete the full vaccine scheme (n = 406), 229 (56.4%) and 96 (26.6%) received the second and third doses, respectively. It was possible to evaluate the vaccine response in only 23/96 subjects, and 78% responded with protective titers. The high frequency of risk behaviors, the low frequency of vaccinations, and improper compliance with the vaccination schedule, even using the accelerated scheme, highlights the need for strategies for health education and prevention to reach this population so vulnerable to sexually transmitted infections and parenteral transmission of hepatitis B. / O crack é considerado um problema de saúde pública no Brasil e no mundo devido ao seu impacto nas relações sociais, na integridade física e mental do usuário e no risco associado às infecções, como a causada pelo vírus da hepatite B (HBV). Este estudo investigou a epidemiologia da infecção pelo vírus da Hepatite B e situação vacinal em usuários de crack institucionalizados em Goiânia – Goiás. Durante agosto de 2012 a abril de 2013 um total de 600 indivíduos foram entrevistados e amostras sanguíneas coletadas para detecção dos marcadores sorológicos do HBV (HBsAg, anti-HBc total e anti-HBs) pelo ensaio imunoenzimático (ELISA). Posteriormente foi formada uma coorte de indivíduos suscetíveis a hepatite B para avaliação da adesão, completude do esquema e resposta vacinal contra hepatite B, utilizando-se um esquema super acelerado. A exposição prévia ao HBV (anti-HBc) foi de 7,0% (IC 95%: 5,22-9,32), e 17,7% (IC 95%: 14,8-20,9) apresentaram positividade isolada para o anti-HBs, sugerindo vacinação prévia contra hepatite B. O consumo de crack por meio de lata improvisada como cachimbo, história de doença sexualmente transmissível e troca de sexo por droga ou dinheiro foram significativamente associados à exposição ao HBV (p< 0,05). Do total de indivíduos que recebeu a primeira dose da vacina contra hepatite B e elegíveis para completar o esquema (n=406), 229 (56,4%) e 96 (26,6%) receberam a segunda e terceira doses, respectivamente. Em somente 23/96 indivíduos foi possível avaliar a resposta vacinal, sendo que 78% responderam com títulos protetores. A frequência elevada de comportamentos de risco, a baixa frequência de indivíduos vacinados e adesão ao esquema vacinal, mesmo com esquema super acelerado, evidencia a necessidade de estratégias de educação em saúde e prevenção que alcancem essa população vulnerável as doenças de transmissão sexual e parenteral como a hepatite B.

O estágio larval do Echinococcus granulosus é o agente etiológico da hidatidose. O antígeno B (AgB) é um dos principais componentes antigênicos do liquído hidático do metacestódeo e foi caracterizado como uma lipoproteína imunogêncica de 120-160 kDa. Na presença de agentes redutores, dissocia-se em 8, 16, 24 e 32 kDa, sugerindo que é composto de multímeros de subunidades de 8 kDa. Embora a função biológica do AgB ainda não seja totalmente clara, muitos estudos demonstraram sua atuação junto à processos importantes na relação parasito-hospedeiro, por exemplo, a evasão da resposta imune do hospedeiro. Nosso laboratório já clonou e expressou em Escherichia coli cinco cDNAs que codificam subunidades do AgB, EgB8/1, EgB8/2 e EgB8/3, EgB8/4 e EgB8/5. Um trabalho recente realizado em nosso laboratório demonstrou que as subunidades recombinantes do AgB, rAgB8/1, rAgB8/2 e rAgB8/3, são capazes de autoassociarem em solução formando homo-oligômeros com características estruturais semelhantes ao AgB nativo. Entretanto, neste trabalho não foi testada a heterooligomerização das subunidades recombinantes do AgB, visto que as proteínas recombinantes purificadas foram obtidas já sob a forma de homo-oligômeros, não sendo possível a mistura destas subunidades para este fim. Este trabalho tem como objetivo investigar a possível hetero-oligomerização das subunidades recombinantes do AgB através de experimentos de co-expressão. As sequências codificadoras do AgB (EgB8/2) e (EgB8/3) de E. granulosus foram amplificadas por PCR e os produtos de PCR de ambas as sequências foram clonados no vetor de expressão (pCDF-Duet), o qual possui duas regiões com múltiplos sítios de clonagem (MCS). A fidelidade das sequências clondadas foi confirmada por sequenciamento de DNA. As proteínas recombinantes foram expressas em Escherichia coli e pela copurificação em coluna de níquel, foi possível verificar experimentalmente que as subunidades rAgB8/2 e rAgB8/3 estão interagindo entre si. A interação entre as subunidades foi confirmada pela análise por imunoblot e espectrometria de massas. Nossos resultados demostram a hetero-oligomerização das subunidades recombinantes rAgB8/2 e rAgB8/3 de E. granulosus e os dados podem fornecer um possível mecanismo de regulação na oligomerização destas subunidades. É necessário um melhor entendimento da estrutura e dos mecanismos de oligomerização do AgB para usá-lo como um importante alvo na elaboração de novas estratégias de prevenção, controle e tratamento de cestodíases. / The larval stage of Echinococcus granulosus is the etiologic agent of hydatidosis. Antigen B (AgB) is a major protein component of the metacestode hydatid fluid and was characterized as a immunogenic lipoprotein of 120-160 kDa. In presence of reducing agents, dissociates into 8, 16, 24 and 32 kDa, suggesting that their consists of multimers of 8kDa subunits. Although the biological function of AgB is still not entirely clear, numerous studies have demonstrated it engagement in important processes in the host-parasite relationship such as evasion of host immune response. Our laboratory has already cloned and expressed five cDNA encode EgB8/1, EgB8/2 e EgB8/3, EgB8/4 e EgB8/5 antigen B subunits in E. coli. Previous studies from our group demonstrated that recombinant AgB subunits are able to self-associate in solution to form homo-oligomers, presenting similar properties to native AgB. However the hetero-oligomerization of the recombinant AgB subunits were not investigated. Since purified recombinant proteins were already obtained in the form of homo-oligomers and, it was not possible to combine these subunits for this purpose. In this work we aim to investigate the possible hetero-oligomerization of the AgB subunits through co-expression experiments. The cDNA sequences enconding E. granulosus EgAgB8/2 and EgAgB8/3 by PCR and the PCR products of both sequences have been cloned in the expression vector (pCDF-Duet), which has two multiple cloning site (MCS). The fidelity of the cloned sequences was confirmed by DNA sequencing. Afterwards the recombinant proteins rAgB8/2 and rAgB8/3 expressed in Escherichia coli. By co-purification in the nickel column, it was possible to verify experimentally that the two subunits rAgB8/2 and rAgB8/3 are interacting one each other. The interaction between the subunits was confirmed by immunoblotting and mass spectrometry. Our results demonstrated the heterooligomerization of recombinant subunits rAgB8/2 and rAgB8/3 of E. granulosus and these data may help to elucidate a possible mechanism for regulation of the subunits oligomerization process. A better understanding of the structure and mechanisms of oligomerization is necessary since that the AgB as an important target in the development of new strategies for prevention, control and treatment of cestodiasis.

A macieira (Malus x domestica) é uma das mais importantes frutíferas do mundo, e sua produção tem destaque na região sul do Brasil. Comparações entre padrões de expressão gênica de diferentes variedades constituem uma estratégia de alto valor científico para seu melhoramento genético. Contudo, a acurácia das análises é dependente de genes de referência estáveis para a normalização dos dados. A escolha de controles inapropriados pode resultar em determinações estatísticas e conclusões incorretas. Pelo presente trabalho, teve-se como objetivo selecionar os melhores genes-referência para estudos de expressão gênica em macieiras, via reação em cadeia da DNA polimerase quantitativa precedida de transcrição reversa (RT-qPCR). A expressão de 21 genes, incluindo tradicionais “housekeeping genes” ou genes sugeridos como constitutivos por dados de microarranjos disponíveis na literatura, foram avaliados em diferentes tecidos vegetativos e reprodutivos da cultivar ‘Gala’ de macieira. Para todos os genes, as combinações de primers testadas permitiram amplificações específicas e curvas de eficiência apropriadas. A estabilidade dos genes foi determinada por dois diferentes algoritmos estatísticos, geNorm e NormFinder. Os resultados permitiram concluir que, para os tecidos e condições avaliadas, EF1β, MDH, SAND, THFS e WD40 são os melhores genes normalizadores para quantificação relativa da abundância de transcritos de interesse em diferentes tecidos-alvos de macieira. A expressão de PAL foi utilizada para validação dos controles selecionados. Combinações específicas de dois ou três genes-referência demonstraram ser suficientes para a normalização dos dados em cada conjunto de amostras analisado. Finalmente, a expressão do gene MDP0000232313 ou MdDAM6, potencial gene MADS-box associado à dormência em macieira, foi avaliada em gemas da cultivar ‘Fuji Standard’, amostradas durante o ciclo vegetativo e de dormência das plantas ao longo do ano 2009. As análises foram conduzidas via RT-qPCR e de forma relativa aos genes EF1β e WD40. Observou-se um nível basal de expressão de MdDAM6 durante o verão e um aumento de cerca de 10 vezes no inverno, refletindo sua possível função no estabelecimento e/ou manutenção do estado endodormente das gemas de macieira, uma vez que este tenha sido estabelecido. / Apple (Malus x domestica) is one of the most important fruit tree crop in the world, and its production is prominent in southern Brazil. Comparisons among profiles of gene expression from different cultivars are valuable scientific tools for apple genetic breeding. However, the accuracy of the analyses is dependent on the evaluation of stable reference genes for data normalization. The inappropriate choice of controls may result in statistical significance undue or incorrect conclusions. In the present work, the objective was to select the best reference genes for gene expression studies by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in apple trees. The expression of 21 genes, including traditional housekeeping or genes suggested as constitutive by microarray data available in the literature, was evaluated in different vegetative and reproductive tissues of the apple ‘Gala’ cultivar. For all genes, tested combinations of primers allowed specific amplification and suitable efficiency curves. The stability of the genes was determined by two different statistical algorithms, geNorm and NormFinder. The results allowed us to conclude that, for tissues and conditions evaluated, EF1β, MDH, SAND, THFS and WD40 are the best normalizing genes for relative quantification of interest transcript abundance in different target tissues of apple. PAL expression was used to validate the selected normalizers. Specific combinations of two or three reference genes were shown to be sufficient to normalize each apple sample set analyzed. Finally, the MDP0000232313 or MdDAM6 gene expression, a potential MADS-box gene associated with dormancy in apple, was evaluated in buds of the apple 'Fuji' cultivar, sampled in the vegetative and dormant cycle of plants during the year of 2009. The analysis was performed by RT-qPCR and quantified in relation to the EF1β and WD40 normalizing genes. It a basal level of expression was observed during summer and a ten fold increase during winter, reflecting its possible function associated with the establishment and/or maintenance of the endodormant state of apple buds, once it has been established.