Mycolic acids are long chain lipids from the cell walls of Mycobacterium tuberculosis. The Nkuku phage display library was previously used to obtain monoclonal antibody binders to mycolic acids. In total 11 binders were obtained of which one was selected (MAC10) for further investigation by genetic engineering as presented in this dissertation. The antibodies of the Nkuku phage display library are in the format of single chain variable fragments (scFv). ScFv’s constitute only the epitope binding domains of an antibody consisting of the VH and VL domains fused into a single chain by a flexible linker protein. The selected anti-mycolic acid scFv is referred to as mycolic acid clone 10 (MAC10). Genes encoding the scFv’s of the Nkuku phage display library were cloned into the plasmid pHEN-1, a phage display vector. This vector is not commercially available or ideally suited for expression of scFv proteins. Therefore two vectors were investigated as possible targets for subcloning. The plasmids pGE20 and pAK400 were previously used for the expression of scFv antibody proteins. Subcloning into plasmid pAK400 proved to be the more efficient of the two investigated for subcloning. This subcloning yielded the recombinant plasmid pAKJS. Following the subcloning scFv protein expression was attempted using the plasmids pMAC10 (derived from pHEN-1) and pAKJS (derived from pAK400). Expression of MAC10 using plasmid pMAC10 in both Escherichia coli TG-1 and HB2151 was constitutive. This demonstrates that plasmid pHEN-1 is a non ideal vector as expression should not occur unless induced. Expression of MAC10 did not occur when pAKJS and Escherichia coli HB2151 were used. This was due to both the vector and expression host producing inhibitor protein for the Lac Z promoter controlling expression of the scFv. The MAC10 gene was subsequently randomized using the directed evolution method, error prone PCR. Sequence analysis of the five selected mutants indicated an average mutation rate of 8.6 mutations per 1000 base pairs. From the combined total of all five mutants, transversions made up the majority of substitutions. The majority of transversion mutations occurred at A-T base pairs. Transition substation mutations that made up the minority of total mutations occurred mostly at G-C base pairs. / Dissertation (MSc)--University of Pretoria, 2012. / Biochemistry / unrestricted

Title: Relation between aerobic endurance and static strength of elderly female athletes to selected anthropometric parameters. Objectives: The purpose of this study is to analyse an aerobic endurance, tested by 2 km walk test and static strength tested by prone bridge maneuver and to investigate any existing association to selected anthropometric parameters. These tests were undertaken by elderly female athletes studying U3A at the UK FTVS. Methods: 48 elderly female athletes (age 66,1±2,35, body height 1,67±0,064cm, body weight 69,80±10,42kg, waist circumference 88,82±10,64cm, body mass index (BMI) 25,10±3,62), studying U3V of UK FTVS at the time of taking the part in the research. The original sample of elderly athletes accounted for 86, but elderly athletes over age of 70 and athletes under heart - rate medication were excluded. Male athletes were also excluded for greater group compatibility. Measurement of aerobic endurance was realized by a 2 km walk test at the athletic stadium of UK FTVS according to Mr. Stejskal. Time and heart rate were scanned by sporttesters (PolarS610i). Static strength was measured by isometric method of prone bridge maneuver. Selected anthropometric parameters to the aerobic endurance and prone bridge maneuver were investigated. All data was processed using the...

Background: Low back pain (LBP) is often associated with lumbar spinal instability (LSI). The multifidus muscle is considered a stabilizer of the spine and has been studied extensively with Rehabilitative Ultrasound Imaging (RUSI). There may be a relationshipbetween clinical signs of LSI, decreased cross-sectional area (CSA) of the multifidus and weakness. Having the ability to detect multifidus weakness without the use of RUSI may serve to be invaluable to the clinician in detecting multifidus weakness.Purpose: To investigate the relationship between the modified prone straight leg raise test (MPSLR) and CSA of the multifidusmuscle as measured by RUSI and to investigate the relationship between MPSLR and RUSI findings with the presence of low back pain symptoms that interfere with regular daily activities. Subjects: Participants consisted of two groups of subjects. One group (n=30, 87% male) comprised individuals in general good health, aged 18-55, without history of back pain. The second group (n=36, 56% male) comprised individuals aged 18-55, with history of low back pain within the past 12 months. Methodology: Subjects performed a MPSLR test to identify multifidus weakness. All subjects repeated the same test with concurrent RUSI to visualize the multifidusand measure its CSA. Results: A significant association between a positive MPSLR, asymmetry of the multifidus, and pain was observed (p r = .049, p = .696) was not observed. A sensitivity of 94% and a specificity of 63% was also discovered in the ability of the MPSLR test to detect asymmetry of themultifidus muscle within subjects. A positive MPSLR combined with a high Oswestry score of 25-30 further reinforced the probability of pain (p < .001) Conclusion: The MPSLR test demonstrated a strong association between a positive test and asymmetry of themultifidus muscle within subjects. Clinical Relevance: The MPSLR test can be used to identify patients at risk for LBP symptoms due to asymmetrical changes in the multifidus muscle of the lumbar spine, and aid in directing an appropriate rehabilitation approach to those patients in need of specific multifidus exercise prescription.

The problem of this study was first year student retention at a private university. The purpose of the study was to identify high risk students (dropout prone) by use of the Stratil Counseling Inventory -_ College Form (SCI-C) in order to initiate early intervention counseling and advising. Intrusive counseling was started within the first six weeks of the 1984 fall semester to facilitate the students' transition to college. The population of the study was first-time full-time freshmen students in attendance at Freshmen Orientation the week prior to the beginning of the 1984 academic year. SCI-C instrument consisted of six scales designed to elicit attrition-related information about the firsttime, freshmen students. The scales identified students who were in need of assistance, and they provided a profile of their problem areas. This information, available within ten days after the beginning of classes enabled Student Development personnel to select the students out of the freshman class who needed help and to refer them to university resources for assistance. The conclusions drawn from the analysis of the SCI-C data were: (1) students who needed assistance to integrate into the academic and social envrionment of the university were identified by the SCI-C; (2) students at Hardin-Simmons University value adult/student relationship outside of the classroom; (3) attitudes of caring service creates a "staying environment;1* (4) although the SCI-C indicates students' interests in support services, not all students who request assistance, avail themselves of the opportunities provided for them; (5) a relationship seems to exist between the intervention strategies provided particular freshmen and their succesful performance in the classroom (CPA of 1.60 or greater) and their persistence at the university for their second year; (6) the SCI-C provides attrition-related counseling information about students rather than predicting college academic success; and (7) the SCI-C i s a valid instrument to use to facilitate student retention at Hardin-Simmons University,

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / IntroduÃÃo: A ventilaÃÃo nÃo invasiva com pressÃo positiva (VNI) vem tendo uma crescente utilidade na prÃtica clÃnica e o seu uso està bem estabelecido em casos de edema agudo de pulmÃo e nas exacerbaÃÃes da doenÃa pulmonar obstrutiva crÃnica (DPOC), diminuindo a necessidade de intubaÃÃo orotraqueal e melhorando a sobrevida. AlÃm disso, a pressÃo positiva contÃnua em vias aÃreas (CPAP) â modo de VNI â constitui o tratamento de escolha para pacientes portadores da sÃndrome de apnÃia obstrutiva do sono (SAOS), onde geralmente nÃo hà alteraÃÃo no parÃnquima pulmonar. Ainda a aplicaÃÃo de nÃveis elevados de pressÃo positiva expiratÃria final (PEEP) no manejo da sÃndrome do desconforto respiratÃrio agudo (SDRA) està associada tanto ao recrutamento alveolar como à hiperdistensÃo de Ãreas previamente normoaeradas, com resultados ainda indefinidos quanto ao impacto na sobrevida. Um dos recursos para melhora da oxigenaÃÃo nestes pacientes à a posiÃÃo prona e os efeitos da associaÃÃo desta manobra com pressÃo positiva permanecem controversos. A tomografia computadorizada de alta resoluÃÃo (TCAR) constitui um excelente mÃtodo de imagem para avaliaÃÃo qualitativa e quantitativa do parÃnquima pulmonar. O emprego da TCAR pode auxiliar na investigaÃÃo dos efeitos da CPAP de modo nÃo invasivo sobre o parÃnquima pulmonar, contribuindo para a elucidaÃÃo dos efeitos fisiolÃgicos da pressÃo positiva e da posiÃÃo prona. Objetivos: Avaliar e comparar os efeitos de diferentes nÃveis de CPAP de modo nÃo invasivo sobre o parÃnquima pulmonar em indivÃduos sadios nas posiÃÃes supina e prona. CasuÃstica e mÃtodos: Estudo intervencionista com oito voluntÃrios sadios, sem doenÃa cardiopulmonar. Foram realizados cortes tomogrÃficos de alta resoluÃÃo em trÃs regiÃes: Ãpice (2 cm acima do arco aÃrtico), hilo (1 cm abaixo da carina) e base (2 cm acima do diafragma) na posiÃÃo supina, sem CPAP (basal) e com CPAP de 5, 10 e 15 cmH2O; e na posiÃÃo prona, corte em base, sem CPAP e com CPAP de 10 cmH2O. A seqÃÃncia das posiÃÃes e da ordem das pressÃes aplicadas foi randomizada. Aguardava-se um perÃodo de no mÃnimo 5 minutos apÃs completa adaptaÃÃo da mÃscara para realizaÃÃo do exame e o mesmo perÃodo de tempo entre um nÃvel de pressÃo e outro. Os dados foram analisados agrupando-se os cortes tomogrÃficos das trÃs regiÃes e por subdivisÃes em regiÃes ventral, medial e dorsal, sendo calculadas as mÃdias das densidades pulmonares e o percentual do nÃmero de unidades com densidade menor que -950 UH (hiperaeradas) para cada uma das regiÃes. Resultados: NÃo houve diferenÃa das mÃdias das densidades pulmonares entre Ãpice, hilo e base para o mesmo nÃvel de pressÃo. Na posiÃÃo supina, houve reduÃÃo da densidade pulmonar e aumento do percentual de pixels nas Ãreas hiperaeradas com nÃveis crescentes de pressÃo: basal -761 UH e 7,25%; CPAP 5: -780 UH e 8,57%; CPAP 10: -810 UH e 11,62%; CPAP 15: -828 UH e 14,65% (p < 0,05). O mesmo foi observado na posiÃÃo prona: basal -759 UH e 6,30%; CPAP 10: -803 UH e 9,94% (p < 0,05). Este aumento da aeraÃÃo tambÃm foi observado nas regiÃes ventral, medial e dorsal. Foi encontrado um gradiente crescente no sentido ventro-dorsal de densidades pulmonares na posiÃÃo supina e o inverso na posiÃÃo prona. A CPAP de 10 cmH2O, na posiÃÃo prona, ocasionou menor aumento do percentual de pixels nas Ãreas hiperaeradas em relaÃÃo à supina. Nas regiÃes nÃo dependentes do pulmÃo (ventral em supina e dorsal em prona), observou-se um menor percentual de pixels nas Ãreas hiperaeradas e aumento nas normoaeradas na posiÃÃo prona em relaÃÃo à supina, praticamente sem diferenÃa nas regiÃes dependentes. ConclusÃes: A aplicaÃÃo de diferentes nÃveis de CPAP, de modo nÃo invasivo, em voluntÃrios sadios, resultou em maior aeraÃÃo com nÃveis crescentes de pressÃo e maior homogeneizaÃÃo da aeraÃÃo pulmonar, tanto na posiÃÃo supina como na prona. Houve menor hiperaeraÃÃo nas regiÃes nÃo dependentes na posiÃÃo prona, em relaÃÃo à supina, sem CPAP e com CPAP de 10 cmH2O, com melhor distribuiÃÃo da aeraÃÃo pulmonar naquela posiÃÃo. / Introduction: Noninvasive positive-pressure ventilation (NIPPV) is an effective means of treating patients with acute respiratory failure and its use has been well established in cardiogenic pulmonary edema and in exacerbations of chronic obstructive pulmonary disease (COPD), reducing the need for endotracheal intubation and improving survival. Furthermore the continuous positive airway pressure (CPAP) â a mode of NIPPV â is the recommended treatment for obstructive sleep apnea syndrome (OSAS), where frequently there is no abnormality in pulmonary parenchyma. Also in the acute respiratory distress syndrome (ARDS), the application of positive end-expiratory pressure (PEEP) may result in alveolar recruitment of nonaerated units as well as in overinflation of the aerated lung areas. Alveolar overinflation is considered an important factor related to ventilator-induced lung injury causing higher mortality. The prone position has beneficial effects on oxygenation in these patients and the additive effect of PEEP with this maneuver is debatable. High resolution computed tomography (HRCT) is an excellent imaging method to evaluate the effects of positive pressure and prone position on pulmonary parenchyma. Objectives: To evaluate the effects of CPAP applied by a nasal mask on pulmonary inflation in normal subjects in supine and prone positions. Patients and methods: This is an interventionist study that evaluated eight healthy volunteers. A protocol of HRCT of the lung was performed in three regions: at the apex (2 cm above the aortic level), hilum (1 cm below the carina) and basis (2 cm above the right diaphragm) in the supine position, without and with CPAP of 5, 10 and 15 cmH2O. Also HRCT slices were performed in the prone position at the lung basis, without and with CPAP of 10 cmH2O. All HRCT slices were obtained at the functional residual capacity. Each CPAP level was maintened at least five minutes and the period between the different levels of CPAP was similar. For analysis the results were divided into regions ventral, medial and dorsal and with slices of apex, hilum and basis together. The mean lung densities (MLD) and the percentual of units with densities lower than -950 UH (overinflated) were calculated for each region. Results: There was no difference between the MLD of apex, hilum and basis for the same level pressure. In the supine position, there were a MLD reduction and an increase of the number of pixels on hyperinflated areas according to CPAP levels: without CPAP -761 HU e 7,25%; CPAP 5: -780 HU e 8,57%; CPAP 10: -810 HU e 11,62%; CPAP 15: -828 UH e 14,65% (p< 0,05). The same occurred in the prone position without CPAP: -759 UH e 6,30% and with CPAP 10: -803 UH e 9,94% (p < 0,05). It was observed a crescent ventro-dorsal density gradient in supine position that was inverse in prone position. At CPAP of 10 cmH2O there was lower percentage of pixels on hyperinflated areas in the prone position than in supine. In the non dependent lung regions (ventral in supine and dorsal in prone) there were lower percentage of pixels on hyperinflated areas and higher on normoaerated areas in the prone position than in supine with little differences in the dependent regions. Conclusions: Non invasive CPAP in normal subjects induces progressive overdistension with increase of pressure levels in supine and prone positions. CPAP of 10 cmH2O causes less overdistension of the non dependent regions than the same level of CPAP in supine position, without inducing significant overinflation of the dependent regions. So that the prone position causes a more homogeneous air distribution through the lungs.

This thesis examines attentional and cognitive biases for particular facial expressions in delusion-prone and deluded individuals. The exploration of cognitive biases in delusion-prone individuals provides one means of elucidating psychological processes that might be involved in the genesis of delusions. Chapter 1 provides a brief review of the continuum approach to schizophrenia, and outlines recent theoretical conceptualisations of delusions. The study of schizophrenia phenomena at the symptom level has become a popular method of inquiry, given the heterogeneous phenotypic expression of schizophrenia, and the uncertainty surrounding the existence of a core neuropathology. Delusions are one of the most commonly experienced symptoms of schizophrenia, and have traditionally been regarded as fixed, false beliefs that are pathognomonic of an organic disease process. However, recent phenomenological evidence of delusional ideation in the general population has led to the conceptualisation of delusions as multi-dimensional entities, lying at the extreme end of a continuum from normal through to maladaptive beliefs. Recent investigations of the information processing abnormalities in deluded individuals are reviewed in Chapter 2. This strand of research has revealed evidence of various biases in social cognition, particularly in relation to threat-related material, in deluded individuals. These biases are evident in probabilistic reasoning, attribution style, and attention, but there has been relatively little investigation of cognitive aberrations in delusion-prone individuals. In the present thesis, social-cognitive biases were examined in relation to a standard series of faces that included threat-related (anger, fear) and non-threatening (happy, sad) expressions, in both delusion-prone and clinically deluded individuals. Chapters 3 and 4 present the results of behavioural (RT, affect recognition accuracy) and visual scanpath investigations in healthy participants assessed for level of delusion- proneness. The results indicate that delusion-prone individuals are slower at processing angry faces, and show a general (rather than emotion-specific) impairment in facial affect recognition, compared to non-prone healthy controls. Visual scanpath studies show that healthy individuals tend to direct more foveal fixations to the feature areas (eyes, nose, mouth) of threat-related facial expressions (anger, fear). By contrast, delusion-prone individuals exhibit reduced foveal attention to threat-related faces, combined with �extended� scanpaths, that may be interpreted as an attentional pattern of �vigilance-avoidance� for social threat. Chapters 5 and 6 extend the work presented in Chapters 3 and 4, by investigating the presence of similar behavioural and attentional biases in deluded schizophrenia, compared to healthy control and non-deluded schizophrenia groups. Deluded schizophrenia subjects exhibited a similar delay in processing angry faces, compared to non-prone control participants, while both deluded and non-deluded schizophrenia groups displayed a generalised affect recognition deficit. Visual scanpath investigations revealed a similar style of avoiding a broader range of negative (anger, fear, sad) faces in deluded schizophrenia, as well as a common pattern of fewer fixations with shorter duration, and reduced attention to facial features of all faces in both deluded and non-deluded schizophrenia. The examination of inferential biases for emotions displayed in facial expressions is presented in Chapter 7 in a study of causal attributional style. The results of this study provide some support for a �self-serving� bias in deluded schizophrenia, as well as evidence for an inability to appreciate situational cues when making causal judgements in both delusion-prone and deluded schizophrenia. A theoretical integration of the current findings is presented in Chapter 8, with regard to the implications for cognitive theories of delusions, and neurobiological models of schizophrenia phenomena, more generally. Visual attention biases for threat-related facial expressions in delusion-prone and deluded schizophrenia are consistent with proposals of neural dysconnectivity between frontal-limbic networks, while attributional biases and impaired facial expression perception may reflect dysfunction in a broader �social brain� network encompassing these and medial temporal lobe regions. Strong evidence for attentional biases and affect recognition deficits in delusion-prone individuals implicates their role in the development of delusional beliefs, but the weaker evidence for attributional biases in delusion-prone individuals suggests that inferential biases about others� emotions may be relevant only to the maintenance of delusional beliefs (or that attributional biases for others� emotional states may reflect other, trait-linked difficulties related to mentalising ability). In summary, the work presented in this thesis demonstrates the utility of adopting a single-symptom approach to schizophrenia within the continuum framework, and attests to the importance of further investigations of aberrant social cognition in relation to the development of delusions.

A central component of modern computing is the idea that computation requires determinism. Contrary to this belief, the primary contribution of this work shows that useful computation can be accomplished in an error-prone fashion. Focusing on low-power computing and the increasing push toward energy conservation, the work seeks to sacrifice accuracy in exchange for energy savings. Probabilistic computing forms the basis for this error-prone computation by diverging from the requirement of determinism and allowing for randomness within computing. Implemented as probabilistic CMOS (PCMOS), the approach realizes enormous energy sav- ings in applications that require probability at an algorithmic level. Extending probabilistic computing to applications that are inherently deterministic, the biased voltage overscaling (BIVOS) technique presented here constrains the randomness introduced through PCMOS. Doing so, BIVOS is able to limit the magnitude of any resulting deviations and realizes energy savings with minimal impact to application quality. Implemented for a ripple-carry adder, array multiplier, and finite-impulse-response (FIR) filter; a BIVOS solution substantially reduces energy consumption and does so with im- proved error rates compared to an energy equivalent reduced-precision solution. When applied to H.264 video decoding, a BIVOS solution is able to achieve a 33.9% reduction in energy consumption while maintaining a peak-signal-to-noise ratio of 35.0dB (compared to 14.3dB for a comparable reduced-precision solution). While the work presented here focuses on a specific technology, the technique realized through BIVOS has far broader implications. It is the departure from the conventional mindset that useful computation requires determinism that represents the primary innovation of this work. With applicability to emerging and yet to be discovered technologies, BIVOS has the potential to contribute to computing in a variety of fashions.

This thesis describes the construction and characterisation of an insulin-like growth factor (IGF-I)-binding single chain Fv (scFv) and the utilisation of this scFv as a model protein for the study of the application of DNA shuffling and ribosome display to antibody engineering. The variable domain genes were isolated from the hybridoma cell line producing the monoclonal antibody and successfully joined by PCR for the construction of the scFv, named anti-GPE. Sequencing of the gene revealed an unusually short heavy chain CDR2 region. The cloned scFv was expressed in E. coli and purified. Expression levels were low and the protein has poor solubility, most likely due to a reduction in folding efficiency caused by the abbreviated CDR2. The purified monomeric form of the protein was analysed for binding to IGF-I using surface plasmon resonance on the BIAcore 1000 with the specificity of the IgG version of the antibody for the three N-terminal residues of IGF-I - Gly-Pro-Glu - reproduced. The scFv's calculated dissociation constant of 3.68 µM is a low affinity for an antibody and is approximately 36-fold weaker than was calculated for the Fab version of the antibody, but it is concluded that the calculated affinity for the scFv was an apparent affinity that may be an underestimation of true affinity due to the presence of non-functional or misfolded scFv species within the gel-filtration purified monomer peaks. A mutant version of anti-GPE with residues inserted in the CDR2 to restore it to normal length produced a protein with improved expression and solubility characteristics while retaining IGF-I-binding. It was concluded that the short CDR2 was due to deletions generated during the somatic mutation process and a model for this is described. A ribosome display method using a rabbit reticulocyte lysate as a source of ribosomes was developed for specific selection of anti-GPE against IGF-I. Error prone PCR was used to produce a random point mutated library of anti-GPE (EPGPE). This was taken through several cycles of display and selection but selection for non-specifically binding scFvs was commonly observed. This was probably due to poor folding of ribosome-displayed proteins in the system used, possibly caused by the presence of DTT in the lysate and/or the low capacity of the anti-GPE framework to tolerate mutation while retaining stability. It is assumed misfolds, exposing hydrophobic regions, would have a tendency to non-specifically interact with the selection surface. Of the 64 EPGPE clones screened from four rounds of display and selection, many were shown to have poor or non-specific binding, but one scFv was characterised that was affinity matured 2.6-fold over anti-GPE wild type affinity for IGF-I. A DNA shuffling method was developed to produce libraries of chimaeric scFvs between anti-GPE and NC10 (anti-neuraminidase scFv) with the objective of isolating functional IGF-I-binding chimaeras. The NC10 scFv had its CDRs replaced with the anti-GPE CDRs prior to the shuffling to increase the likelihood of isolating IGF-I binders. Ribosome display was used for selection from the chimaera libraries. Selection strategies included elution of specific binders by GPE peptide and a GPE 10-mer peptide. Selection was also performed using IGF-I immobilised on a BIAcore sensorchip as a selection surface. Again, much non-specific selection was observed as seen for display of EPGPE, for what was expected to be the same reasons. Selected scFvs were genuinely chimaeric but with poor expression and solubility and mostly non-specific in their binding. One characterised selected chimaera, made up of three segments of each of the parental scFvs, was shown to bind specifically to IGF-I by BIAcore. Steps to improve the efficiency of the ribosome display system have been identified and are discussed.

This thesis examines attentional and cognitive biases for particular facial expressions in delusion-prone and deluded individuals. The exploration of cognitive biases in delusion-prone individuals provides one means of elucidating psychological processes that might be involved in the genesis of delusions. Chapter 1 provides a brief review of the continuum approach to schizophrenia, and outlines recent theoretical conceptualisations of delusions. The study of schizophrenia phenomena at the symptom level has become a popular method of inquiry, given the heterogeneous phenotypic expression of schizophrenia, and the uncertainty surrounding the existence of a core neuropathology. Delusions are one of the most commonly experienced symptoms of schizophrenia, and have traditionally been regarded as fixed, false beliefs that are pathognomonic of an organic disease process. However, recent phenomenological evidence of delusional ideation in the general population has led to the conceptualisation of delusions as multi-dimensional entities, lying at the extreme end of a continuum from normal through to maladaptive beliefs. Recent investigations of the information processing abnormalities in deluded individuals are reviewed in Chapter 2. This strand of research has revealed evidence of various biases in social cognition, particularly in relation to threat-related material, in deluded individuals. These biases are evident in probabilistic reasoning, attribution style, and attention, but there has been relatively little investigation of cognitive aberrations in delusion-prone individuals. In the present thesis, social-cognitive biases were examined in relation to a standard series of faces that included threat-related (anger, fear) and non-threatening (happy, sad) expressions, in both delusion-prone and clinically deluded individuals. Chapters 3 and 4 present the results of behavioural (RT, affect recognition accuracy) and visual scanpath investigations in healthy participants assessed for level of delusion- proneness. The results indicate that delusion-prone individuals are slower at processing angry faces, and show a general (rather than emotion-specific) impairment in facial affect recognition, compared to non-prone healthy controls. Visual scanpath studies show that healthy individuals tend to direct more foveal fixations to the feature areas (eyes, nose, mouth) of threat-related facial expressions (anger, fear). By contrast, delusion-prone individuals exhibit reduced foveal attention to threat-related faces, combined with �extended� scanpaths, that may be interpreted as an attentional pattern of �vigilance-avoidance� for social threat. Chapters 5 and 6 extend the work presented in Chapters 3 and 4, by investigating the presence of similar behavioural and attentional biases in deluded schizophrenia, compared to healthy control and non-deluded schizophrenia groups. Deluded schizophrenia subjects exhibited a similar delay in processing angry faces, compared to non-prone control participants, while both deluded and non-deluded schizophrenia groups displayed a generalised affect recognition deficit. Visual scanpath investigations revealed a similar style of avoiding a broader range of negative (anger, fear, sad) faces in deluded schizophrenia, as well as a common pattern of fewer fixations with shorter duration, and reduced attention to facial features of all faces in both deluded and non-deluded schizophrenia. The examination of inferential biases for emotions displayed in facial expressions is presented in Chapter 7 in a study of causal attributional style. The results of this study provide some support for a �self-serving� bias in deluded schizophrenia, as well as evidence for an inability to appreciate situational cues when making causal judgements in both delusion-prone and deluded schizophrenia. A theoretical integration of the current findings is presented in Chapter 8, with regard to the implications for cognitive theories of delusions, and neurobiological models of schizophrenia phenomena, more generally. Visual attention biases for threat-related facial expressions in delusion-prone and deluded schizophrenia are consistent with proposals of neural dysconnectivity between frontal-limbic networks, while attributional biases and impaired facial expression perception may reflect dysfunction in a broader �social brain� network encompassing these and medial temporal lobe regions. Strong evidence for attentional biases and affect recognition deficits in delusion-prone individuals implicates their role in the development of delusional beliefs, but the weaker evidence for attributional biases in delusion-prone individuals suggests that inferential biases about others� emotions may be relevant only to the maintenance of delusional beliefs (or that attributional biases for others� emotional states may reflect other, trait-linked difficulties related to mentalising ability). In summary, the work presented in this thesis demonstrates the utility of adopting a single-symptom approach to schizophrenia within the continuum framework, and attests to the importance of further investigations of aberrant social cognition in relation to the development of delusions.

Orientador: José Roberto Fioretto / Resumo: A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta morbi-mortalidade apesar dos avanços no entendimento de sua fisiopatologia e tratamento. A terapia ventilatória baseia-se na proteção pulmonar, sendo a ventilação oscilatória de alta frequência (VOAF) uma opção de método protetor. A posição prona (PP) é terapia adjuvante que possibilita homogeneização da distribuição do volume corrente (VC) e promove recrutamento alveolar. O objetivo do estudo foi investigar o efeito da posição prona associada à VOAF e ventilação mecânica convencional (VMC) protetora sobre a oxigenação, inflamação, dano oxidativo e histologia pulmonares, comparando-a à posição supina em ambos os modos ventilatórios. Foram instrumentados 75 coelhos com traqueostomia e acessos vasculares. A lesão pulmonar aguda (LPA) foi induzida por lavagem traqueal de salina aquecida (30mL/Kg, 38°C). Os animais foram então aleatorizados em cinco grupos (n=15): 1) GC (Controle): animais sadios em VMC protetora basal; 2) GVMS: animais com LPA em VMC protetora e posição supina; 3) GVMP: animais com LPA em VMC protetora e posição prona; 4) GVAFS: animais com LPA em VOAF e posição supina; 5) GVAFP: animais com LPA em VOAF e posição prona. Após, foram submetidos a quatro horas de VMC protetora (modo pressão regulada-volume controlado, PEEP 10 cmH2O, VC 6mL/kg, Ti 0,5s, FR 40 rpm e FiO2 1) ou VOAF (MAP 15 mmHg, FR 10Hz, amplitude 22 e FiO2 1). O nível de significância foi de 5%. Após a indução, os grupos apresentaram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acute Respiratory Distress Syndrome (ARDS) presents with high morbidity and mortality despite advances in the understanding of its pathophysiology and treatment. Ventilatory therapy is based on the intention of injuring less, with high frequency oscillatory ventilation (HFOV) being a protective method option. Prone position (PP) is an adjuvant therapy that enables homogenization of volume tidal (VT) distribution and promotes alveolar recruitment. The aim of this study was to investigate the effects of prone position associated with HFOV and protective conventional mechanical ventilation (CMV) on oxygenation and lung inflammation, oxidative damage and histology, comparing it with the supine position in both ventilatory modes. Seventy five rabbits were submitted to tracheostomy and vascular accesses. ALI was induced by tracheal infusion of heated saline (30mL/kg, 38° C). The subjects were then ramdomized in five groups (n=15): 1) CG (Control): healthy animals in basal protective CMV; 2) MVSG: animals with ALI in protective CMV and supine position; 3) MVPG animals with ALI in protective CMV and prone position; 4) HFSG: animals with ALI in HFOV and supine position; 5) HFPG: animals with ALI in HFOV and prone position. After that, they were submitted to four hours of protective VMC (PRV mode, PEEP 10 cmH2O, VC 6ml/kg, Ti 0,5s, FR=40 rpm and FiO2 1) or HFOV (MAP 15 mmHg, FR 10 Hz, amplitude 22 and FiO2 1). The level of significance was 5%. After induction, the groups presented simi... (Complete abstract click electronic access below) / Doutor