The primary purpose of this doctoral dissertation was to investigate the effect of body temperature responses at physiologically relevant sites during an incremental exercise test on the phenomenon of exercise-induced hypoxemia (EIH). This phenomenon has been considered as an important limitation to physical performance with a prevalence of ~50 % in trained male athletes, but described in both sexes, across the range of both age and physical fitness in more recent literature. Previously this phenomenon has been described as a decrement in both arterial oxygen partial pressure (PaO₂) and oxy-haemoglobin saturation (SaO₂or SpO₂) with, particularly important for PaO₂, a lack of or inappropriate correction made for the change in body temperature during intense exercise. The initial study of this thesis determined the thermal response within the body at physiologically relevant sites measured simultaneously during an incremental exercise test. The results demonstrated the inadequacy of rectal temperature as an indicator of the acute temperature changes occurring during an incremental exercise test due to its slow response rate and relative thermal inertia. Radial arterial blood and oesophageal temperatures were shown to behave almost identically during the exercise test, albeit with an offset of approximately 1.3ºC, and were considered much more appropriate and relevant indicators of thermal changes during exercise. As an extension of the initial work active muscle temperature (vastus lateralis) was measured during the exercise test, demonstrating a significantly lower resting temperature than the oft-reported “core” temperatures (rectal and oesophageal) as well as a significantly greater increase in temperature in comparison to all other measurement sites. Overall, the results of this first study indicated that the physiologically relevant temperatures measured at the oesophageal and muscle sites differed markedly to the outdated rectal temperature measurement site and should be used as measures of thermal response when evaluating oxygen loading (oesophageal) or unloading (active muscle). Utilising the definition of EIH as a decrease in PaO₂ of ≥ 10 mmHg, the effect of temperature correcting PaO₂ was evaluated in the second study. Arterial blood gases measured simultaneously to the temperature measurements during the incremental exercise test were adjusted for the temperature changes at each site (every 1ºC increase in temperature will increase a PaO₂ value by ~5 mmHg). Whilst uncorrected PaO₂ values indicated an almost 100% prevalence of EIH in this group, oesophageal temperature corrected PaO₂ values decreased this prevalence to ~50% while muscle temperature corrections resolved all cases of EIH and demonstrated an HYPEROXAEMIA (i.e. the reverse of the well-established phenomenon) in the majority of subjects. Further investigation of arterial oxygen content during the exercise test indicates that there is no disruption in the delivery of oxygen to the active muscles and therefore any performance decrement should be attributed to another mechanism. Whilst the phenomenon of EIH is determined by the definition applied and the use of temperature corrections in the case of PaO₂, its reproducibility in a test-retest situation had not previously been determined. Utilising a subset of previously tested subjects, the reproducibility of both temperature and PaO₂ were determined with results indicating that the blood gas response was highly reproducible, especially the minimum PaO₂ value noted during each exercise test. However, comparing a more statistically relevant definition of a change in PaO₂ of ± 2 standard deviations from the mean resting PaO₂ to the previous delimiter of 10 mmHg indicated a lesser reproducibility of the prevalence of EIH. In summary, this thesis exposes the inadequacies of previous research into EIH with regard to the expected reproducibility of the phenomenon and the need to correctly adjust PaO₂ values for exercise-induce hyperthermia as well as demonstrating the difference in thermal responses to acute exercise in physiologically significant areas of the body. Furthermore, previously described correlations between the change in PaO₂ and VO₂ max were not evident in the subjects tested within this thesis, nor was there any indication of a diffusion limitation based on reduced pulmonary capillary transit time (by association with VO₂ max) or pulmonary oedema (rebuked by a rapid return of PaO₂ to above resting levels following exercise cessation). / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320633 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008

Proteins are a highly diversified group of molecules, andfor their study, advanced analytical tools are required. Inparticular, a need for high-throughput techniques has emergedin order to enable the characterization of large sets ofproteins. In this thesis, improved techniques for proteinseparations as well as new tools for the mass spectrometricanalysis of proteins are described. In the work, presented in the first part of the thesis, arefined extract containing proteases from Antarctic krill (Euphausia superba) was separated and characterized bymeans of capillary electrophoresis (CE) and mass spectrometry(MS). Tailored CE separations of the krill extract revealed thepresence of approximately 50 components. In addition, adetailed CE and MS analysis of fractions, containing individualkrill proteases has been carried out. Trypsin-like proteasesfrom krill exhibited a 12-fold and a 60-fold higher digestionefficiency at 37 °C and 2 °C respectively compared todigests performed with bovine trypsin. Furthermore, thecleavage specificity of the trypsin-like proteases wasstudied. In the last part of the thesis, novel concepts forchip-based nanoelectrospray (nanoESI) and matrix-assisted laserdesorption/ionization (MALDI) mass spectrometry are described.First, a micromachined silicon chip with a two-dimensionalmatrix of out-ofplane nanoESI needles for high-throughputanalysis was fabricated. A two-fold improvement insignal-to-noise reproducibility was obtained. Second, achip-based target for MALDI was developed, which featured pairsof elevated 50×50 µm anchors in close proximity. Theanchors were individually addressable with sample solution. Theminiaturized sample preparations at close distance to eachother allowed a simultaneous ionization of a physicallyseparated sample and standard by one single laser pulse. Thisresulted in a twofold reduction of relative mass errors.Moreover, ion suppression of the analyte was significantlyreduced. The effective utilization of the sample resulted in adetection limit of ca 200 zeptomole of angiotensin I. Key words:Proteins, peptides, proteases, Antarctickrill,Euphausia superba, capillary electrophoresis,fluorosurfactants, mass spectrometry, nanoelectrospray, ESI,MALDI, chip, high-throughput, reproducibility, sensitivity andmass accuracy.

Background Osteoarthritis (OA) of the hip is a common disease among elderly adults and its prevalence increases with age. Hip OA is presumed to be a group of diseases resulting in the same pathological pathway, but its etiology is not completely understood. The major symptoms are joint pain, joint stiffness, impaired range of motion, and muscle weakness resulting in increased levels of physical disability (PD) and reduced quality of life. Besides the impairments of the individual subject a heavy economic burden goes along with the disease and is expected to increase due to aging societies in western countries throughout the upcoming years. Exercise therapy (ET), including elements to strengthen the hip muscles, is a common treatment in hip OA and considered to reduce pain and PD. Currently, there is only silver-level scientific evidence regarding the effectiveness of ET in hip OA due to a limited number of high quality studies. Furthermore, the optimal content and dosage, as well as the mode of delivery of ET need to be evaluated. This doctoral thesis deals with three specific aspects of hip muscle strength (HMS) in patients with hip OA: the precision of measuring HMS, training HMS, and the relevance of HMS to physical disability (PD). Three studies and one study protocol provide the scientific program of this thesis, referring to these aspects of HMS. Methods The first study (S1) investigated the reproducibility of isokinetic and isometric HMS measures in patients with hip OA. 16 subjects with unilateral or bilateral hip OA and 13 healthy subjects were tested twice, 7 days apart. A subpopulation of 11 hip OA patients was tested a third time to evaluate familiarization to these measurements. The standard error of measurement (SEM) served as the reproducibility outcome parameter. The second study (S2) investigated the feasibility of strengthening exercises and their effect on HMS in hip patients. 36 participants from an institutional training group for hip patients were allocated randomly to an intervention or control group. While the intervention group completed an eight-week progressive home-based strengthening exercise program (PHSEP) in addition to the weekly institutional supervised group-based exercise therapy (ISET), the control group continued weekly ISET, only. Exercise logs were used to monitor adherence, pain, and the applied exercise intensity of the PHSEP. Before and after the intervention period, HMS was determined using isokinetic concentric and isometric HMS measurements. Additionally, health-related quality of life was assessed by the SF36 questionnaire. These two studies served as a basis for developing strength-specific aspects of a study design for a randomized controlled trial (RCT), which was in progress at the writing of this thesis. This RCT addresses the above-mentioned lack of scientific evidence about the effectiveness of ET in hip OA. A study protocol (P1) describes this RCT, which evaluates the effectiveness of ET on pain and PD in patients with hip OA. 217 patients with hip OA were recruited from the community and allocated to one of the four groups: (1) exercise group, n = 70 (2) non-intervention group, n = 70, (3) “Sham” ultrasound group, n = 70, and (4) ultrasound group, n = 7. The main outcome measure is the change in the subscale bodily pain of the SF36. Secondary outcomes are PD assessed by the SF36 and the WOMAC questionnaire, isometric HMS, several gait variables and postural control. Finally, the relationship of HMS and PD in hip OA was investigated in a third (cross-sectional) study (S3). A stepwise regression model was applied with data from 149 subjects suffering from hip OA. The outcome variable was the self-reported physical disability, assessed with the physical function subscale of the WOMAC questionnaire. Age, gender, body mass index BMI , HMS, pain, stiffness, and range of motion were included in the statistical model as associated factors of PD. Results The results of S1 showed high variability in HMS measurements between days. The highest SEM values, indicating poorest reproducibility, were obtained for hip extension, followed by hip adduction and hip flexion measures, while the smallest values were found for hip abduction measures. Lower reproducibility occurred in patients with hip OA in comparison to healthy controls during the isometric measures of hip abduction, adduction, and flexion. Reproducibility of 11 hip OA patients was lower for the second test sequence (test-day 2 and 3) than for the first test sequence (test-day 1 and 2). The findings of S2 indicated high exercise adherence (99%) of the intervention group to the applied PHSEP. Furthermore, exercise logs reported that pain resulting from the PHSEP was low. HMS improved about 7-11% in comparison to the control group. The SF36 variables did not change throughout the exercise period. In S3, the statistical model revealed stiffness, pain, and HMS to be significant factors of self-reported physical disability in hip OA. Conclusion In conclusion, the precision of several HMS measures may be affected by hip OA and clinicians should be aware of a higher measurement error in patients with hip OA under isometric test conditions than for healthy subjects. A familiarization measurement may be an approach to diminish the measurement error. The applied PHSEP amended to an ISET is feasible for hip patients to carry out and can be applied to improve HMS. Furthermore, a significant cross-sectional relationship between HMS and PD has been evaluated, indicating that HMS may be an important factor to stimulate during exercise therapy in hip OA. The upcoming results of the RCT (P1) described in the study protocol will help to reduce the shortcomings in scientific evidence regarding the effectiveness of strengthening exercise regimes to reduce pain and PD in patients with hip OA. / Hintergrund Coxarthrose ist eine weit verbreitete Krankheit in der älteren Bevölkerung westlicher Industrienationen. Die Bedeutung und Zahl der Neuerkrankungen nehmen mit steigendem Lebensalter zu. Schmerz, Steifheit, Bewegungseinschränkungen und Muskelschwäche zählen zu den Leitsymptomen dieser Krankheit, die sich in einer zunehmenden körperlichen Funktionseinschränkung und eingeschränkten Lebensqualität der Patienten äußern. Neben der Bedeutung für die betroffenen Patienten selbst wachsen in westlichen Industrienationen aufgrund der demographischen Entwicklung hin zu einer alternden Gesellschaft der Druck und die finanzielle Belastung auf die Renten- und Gesundheitssysteme. Die Sporttherapie wird häufig in frühen Stadien der Krankheit eingesetzt und zählt zu den konservativen Therapieverfahren. Nach aktuellem Stand der Wissenschaft scheinen sporttherapeutische Interventionen mit Trainingselementen zur Kräftigung der hüftumgebenden Muskulatur sinnvoll. Dennoch wurde die Wirksamkeit von Sporttherapie bei Coxarthrose bisher nur in einzelnen Studien nachgewiesen (Silver-level Evidence). Es fehlen qualitativ hochwertige randomisierte Kontrollgruppenstudien (RCTs). Zudem ist bislang ungeklärt, wie ein optimales Trainingsprogramm bei Coxarthrose hinsichtlich der Inhalte, Dosierung und Durchführungsmodalität zu gestalten ist, um Schmerz und körperliche Funktionseinschränkungen bestmöglich zu therapieren. Vor diesem Hintergrund beschäftigt sich die vorliegende Dissertation mit drei Aspekten der Hüftmuskelkraft bei Patienten mit Coxarthrose. Drei entsprechende Studien, die in vier wissenschaftlichen Artikeln aufgearbeitet wurden, bilden den wissenschaftlichen Schwerpunkt der Arbeit. Methode Die erste Studie (S1) befasst sich mit der Messgenauigkeit von Hüftkraftmessungen bei Coxarthrosepatienten. Unter diesem Aspekt wurden isometrische und isokinetische Kraftmessgrößen an der Hüfte bei 16 Coxarthrosepatienten und 13 gesunden Personen zwei Mal im Abstand von sieben Tagen erhoben. Bei einer Teilstichprobe von 11 Coxarthrosepatienten wurden die Messungen ein drittes Mal durchgeführt, um mögliche Gewöhnungseffekte zu evaluieren. Der Standard Error of Measurement (SEM) wurde verwendet, um den Messfehler zu quantifizieren. Die zweite Studie (S2) greift einen weiteren Aspekt auf, der sich auf das Training der Hüftmuskelkraft bei Hüftpatienten bezieht. Hier wurde die Machbarkeit eines ergänzenden Heimtrainingsprogramms zur Kräftigung der hüftumgebenden Muskulatur evaluiert sowie mögliche Auswirkungen auf die Hüftmuskelkraft untersucht. 36 Teilnehmer einer Hüftsportgruppe mit Coxarthrose und/oder einer Total-Endoprothese (TEP) wurden randomisiert in zwei Untersuchungsgruppen aufgeteilt. Während die Patienten der Kontrollgruppe im Untersuchungszeitraum weiterhin wöchentliche institutionelle sporttherapeutische Trainingseinheiten wahrnahmen, führten die Patienten der Interventionsgruppe zusätzlich Heimtrainingseinheiten zur Kräftigung der Hüftmuskeln durch. Vor und nach der Intervention wurden isometrische und isokinetische Maximalkraftmessungen durchgeführt. Die Patienten der Trainingsgruppe haben ein Trainingstagebuch geführt, um die Teilnahme am Heimtrainingsprogramm und mögliche Schwierigkeiten damit zu dokumentieren. Der SF36 Fragebogen wurde eingesetzt, um die gesundheitsbezogene Lebensqualität im Verlauf zu kontrollieren. Die Erkenntnisse der beiden beschriebenen Studien wurden verwendet, um kraftspezifische Aspekte eines Studiendesigns zu entwickeln. Dieses Studiendesign entspricht einem RCT und soll die Effektivität eines sporttherapeutischen Trainingskonzepts hinsichtlich Schmerzreduktion und Verbesserung der körperlichen Funktionsfähigkeit überprüfen. 217 Hüftarthrosepatienten werden rekrutiert und randomisiert auf eine der folgenden Untersuchungsgruppen aufgeteilt: (1) Trainingsgruppe, n = 70 (2) Kontrollgruppe ohne Intervention, n = 70, (3) “Schein” Ultraschallgruppe, n = 70, und (4) Ultraschallgruppe, n = 7. Die primäre Zielgröße ist Veränderung in der Subskala „Körperliche Schmerzen“ des SF36-Fragebogens. Sekundäre Zielgrößen sind Schmerz und Körperliche Funktionsfähigkeit aus dem WOMAC-Fragebogen, weiteren Subskalen des SF36-Fragebogens, isometrische Hüftmuskelkraft, verschiedene Variablen des Gangs und posturale Kontrolle. Die Bedeutung der Hüftmuskelkraft auf die alltagsrelevante körperliche Funktionsfähigkeit stellt den dritten Aspekt dieser Dissertation dar und wurde in Studie 3 (S3), einer Querschnittsuntersuchung an 149 Coxarthrosepatienten behandelt. Ziel der Studie war die Untersuchung des Zusammenhangs verschiedener Variablen und der alltagsbezogenen körperlichen Funktionsfähigkeit. In einem statistisches Modell wurde die Beziehung zwischen den Variablen: Hüftmuskelkraft, Body Mass Index (BMI), Alter, Geschlecht, Schmerz, Steifheit und Beweglichkeit der Hüfte und der Subskala „Körperliche Funktionsfähigkeit“ des WOMAC-Fragebogens als Maß für die alltagsbezogene körperlichen Funktionsfähigkeit berechnet. Ergebnisse In der ersten Studie (S1) wurden die größten Messfehler in den Messgrößen Hüftextension ermittelt. Danach folgten die Messgrößen Hüftadduktion und -flexion. Der geringste Messfehler wurde für Hüftabduktion ermittelt. Unter isometrischen Bedingungen wurden in den Kraftmessgrößen Hüftabduktion, -adduktion und -flexion bei Coxarthrosepatienten größere Messfehler quantifiziert als bei gesunden Personen. Zudem war die Reproduzierbarkeit in der ersten Test-Sequenz (Messtag 1 und 2) im Vergleich zur zweiten Test-Sequenz reduziert (Messtag 2 und 3). In der zweiten Studie (S2) konnte gezeigt werden, dass das verwendete Heimtrainingsprogramm sicher und selbstständig von den Hüftpatienten durchgeführt werden konnte. Die Trainingstagebücher ließen auf eine nahezu hundertprozentige Teilnahme am ergänzenden Heimtrainingsprogramm schließen und zeigten außerdem, dass das Heimtrainingsprogramm keine schmerzverursachende Wirkung hatte. Nach der Intervention war die Kraft der hüftumgebenden Muskulatur im Vergleich zur Kontrollgruppe um 7-9% gesteigert. Befunde hinsichtlich einer veränderten Lebensqualität konnten nicht registriert werden. Das statistische Modell, das in der dritten Studie (S3) eingesetzt wurde, erkannte Schmerz, Steifheit und Hüftmuskelkraft als die drei bedeutsamsten Faktoren für die alltagsbezogene körperliche Funktionsfähigkeit bei Patienten mit Coxarthrose. Schlussfolgerungen Kraftmessungen an der Hüfte scheinen erheblichen Tagesschwankungen ausgesetzt zu sein. Bei Coxarthrosepatienten und gesunden Personen scheint sich die Wiederholbarkeit von isokinetischen Kraftmessungen zu ähneln. Unter isometrischen Testbedingungen muss mit höheren Messfehlern bei Coxarthrosepatienten gerechnet und entsprechend bei der Interpretation von Ergebnissen berücksichtigt werden. Eine Gewöhnungsmessung kann den Messfehler reduzieren, birgt allerdings einen erheblich höheren finanziellen und personellen Aufwand. Das ergänzende Heimtrainingsprogramm wurde von den Patienten gut angenommen, so dass lediglich kleinere Modifikationen vorgenommen werden mussten, um es in dem geplanten RCT zu evaluieren. Zudem konnte gezeigt werden, dass die Hüftmuskelkraft zu den drei bedeutsamsten Faktoren zählt, die Einfluss auf die alltagsbezogene körperliche Funktionsfähigkeit bei Patienten mit Coxarthrose haben können. Ob diese Beziehung tatsächlich kausaler Natur ist, werden zukünftige Verlaufsstudien aufzeigen, in denen gezielt solche Faktoren der alltagsrelevanten körperliche Funktionsfähigkeit durch sporttherapeutische Maßnahmen modifiziert werden. Die ausstehenden Ergebnisse des RCT sollen die noch unzureichende wissenschaftliche Beweislage bezüglich der Wirksamkeit sporttherapeutischer Interventionen bei Coxarthrose verbessern. Dabei soll gezeigt werden, ob und in welchem Maß eine Schmerzreduktion und Verringerung der körperlichen Funktionseinschränkung erzielt werden kann.

<p>Proteins are a highly diversified group of molecules, andfor their study, advanced analytical tools are required. Inparticular, a need for high-throughput techniques has emergedin order to enable the characterization of large sets ofproteins. In this thesis, improved techniques for proteinseparations as well as new tools for the mass spectrometricanalysis of proteins are described.</p><p>In the work, presented in the first part of the thesis, arefined extract containing proteases from Antarctic krill (<i>Euphausia superba</i>) was separated and characterized bymeans of capillary electrophoresis (CE) and mass spectrometry(MS). Tailored CE separations of the krill extract revealed thepresence of approximately 50 components. In addition, adetailed CE and MS analysis of fractions, containing individualkrill proteases has been carried out. Trypsin-like proteasesfrom krill exhibited a 12-fold and a 60-fold higher digestionefficiency at 37 °C and 2 °C respectively compared todigests performed with bovine trypsin. Furthermore, thecleavage specificity of the trypsin-like proteases wasstudied.</p><p>In the last part of the thesis, novel concepts forchip-based nanoelectrospray (nanoESI) and matrix-assisted laserdesorption/ionization (MALDI) mass spectrometry are described.First, a micromachined silicon chip with a two-dimensionalmatrix of out-ofplane nanoESI needles for high-throughputanalysis was fabricated. A two-fold improvement insignal-to-noise reproducibility was obtained. Second, achip-based target for MALDI was developed, which featured pairsof elevated 50×50 µm anchors in close proximity. Theanchors were individually addressable with sample solution. Theminiaturized sample preparations at close distance to eachother allowed a simultaneous ionization of a physicallyseparated sample and standard by one single laser pulse. Thisresulted in a twofold reduction of relative mass errors.Moreover, ion suppression of the analyte was significantlyreduced. The effective utilization of the sample resulted in adetection limit of ca 200 zeptomole of angiotensin I.</p><p><b>Key words:</b>Proteins, peptides, proteases, Antarctickrill,<i>Euphausia superba</i>, capillary electrophoresis,fluorosurfactants, mass spectrometry, nanoelectrospray, ESI,MALDI, chip, high-throughput, reproducibility, sensitivity andmass accuracy.</p>

The objectives of this thesis are: a) To examine racial/ethnic differences in coronary artery calcification (CAC) and CAD, between symptomatic South Asians and Caucasians, matched for age, gender and conventional cardiovascular risk factors, b) To assess, using a meta-analysis model, the natural history of and stability of measurements of coronary artery calcium scoring (CACs) based on data collected from two large published trials: St Francis and EBEAT, c) To investigate the prevalence of coronary artery calcification in individuals with CT evidence for AVC, mitral valve calcification (MAC) or of both of them (AVC+MAC), d) To assess any potential association between premature CAD (&lt;55 years in first-degree male relatives and &lt;65 years in first-degree female relatives) and CAC in a large cohort of asymptomatic individuals. We found that coronary artery calcification is more extensive and diffuse in symptomatic patients of South Asian ethnic origin as compared to Caucasians, despite similar conventional risk factors for CAD. This is more evident in those &gt;50 years of age, suggesting potential genetic or other risk factors yet to be determined. The natural history of coronary artery calcification was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA brances are influenced by the branch allocation of the CACs. Valve calcification is not isolated but involve also and the coronary arteries. The presence of calcification in the aortic valve or combined aortic and mitral valves predicted coronary artery calcification. Additionally patients in whom both valves have become calcified tend to have severe coronary artery calcification. And finally, there is no relationship between the prevalence and extent of coronary artery calcification and the presence of family history of coronary heart disease in asymptomatic individuals with none of the conventional risk factors for atherosclerosis.

The primary purpose of this doctoral dissertation was to investigate the effect of body temperature responses at physiologically relevant sites during an incremental exercise test on the phenomenon of exercise-induced hypoxemia (EIH). This phenomenon has been considered as an important limitation to physical performance with a prevalence of ~50 % in trained male athletes, but described in both sexes, across the range of both age and physical fitness in more recent literature. Previously this phenomenon has been described as a decrement in both arterial oxygen partial pressure (PaO₂) and oxy-haemoglobin saturation (SaO₂or SpO₂) with, particularly important for PaO₂, a lack of or inappropriate correction made for the change in body temperature during intense exercise. The initial study of this thesis determined the thermal response within the body at physiologically relevant sites measured simultaneously during an incremental exercise test. The results demonstrated the inadequacy of rectal temperature as an indicator of the acute temperature changes occurring during an incremental exercise test due to its slow response rate and relative thermal inertia. Radial arterial blood and oesophageal temperatures were shown to behave almost identically during the exercise test, albeit with an offset of approximately 1.3ºC, and were considered much more appropriate and relevant indicators of thermal changes during exercise. As an extension of the initial work active muscle temperature (vastus lateralis) was measured during the exercise test, demonstrating a significantly lower resting temperature than the oft-reported “core” temperatures (rectal and oesophageal) as well as a significantly greater increase in temperature in comparison to all other measurement sites. Overall, the results of this first study indicated that the physiologically relevant temperatures measured at the oesophageal and muscle sites differed markedly to the outdated rectal temperature measurement site and should be used as measures of thermal response when evaluating oxygen loading (oesophageal) or unloading (active muscle). Utilising the definition of EIH as a decrease in PaO₂ of ≥ 10 mmHg, the effect of temperature correcting PaO₂ was evaluated in the second study. Arterial blood gases measured simultaneously to the temperature measurements during the incremental exercise test were adjusted for the temperature changes at each site (every 1ºC increase in temperature will increase a PaO₂ value by ~5 mmHg). Whilst uncorrected PaO₂ values indicated an almost 100% prevalence of EIH in this group, oesophageal temperature corrected PaO₂ values decreased this prevalence to ~50% while muscle temperature corrections resolved all cases of EIH and demonstrated an HYPEROXAEMIA (i.e. the reverse of the well-established phenomenon) in the majority of subjects. Further investigation of arterial oxygen content during the exercise test indicates that there is no disruption in the delivery of oxygen to the active muscles and therefore any performance decrement should be attributed to another mechanism. Whilst the phenomenon of EIH is determined by the definition applied and the use of temperature corrections in the case of PaO₂, its reproducibility in a test-retest situation had not previously been determined. Utilising a subset of previously tested subjects, the reproducibility of both temperature and PaO₂ were determined with results indicating that the blood gas response was highly reproducible, especially the minimum PaO₂ value noted during each exercise test. However, comparing a more statistically relevant definition of a change in PaO₂ of ± 2 standard deviations from the mean resting PaO₂ to the previous delimiter of 10 mmHg indicated a lesser reproducibility of the prevalence of EIH. In summary, this thesis exposes the inadequacies of previous research into EIH with regard to the expected reproducibility of the phenomenon and the need to correctly adjust PaO₂ values for exercise-induce hyperthermia as well as demonstrating the difference in thermal responses to acute exercise in physiologically significant areas of the body. Furthermore, previously described correlations between the change in PaO₂ and VO₂ max were not evident in the subjects tested within this thesis, nor was there any indication of a diffusion limitation based on reduced pulmonary capillary transit time (by association with VO₂ max) or pulmonary oedema (rebuked by a rapid return of PaO₂ to above resting levels following exercise cessation). / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320633 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008

Made available in DSpace on 2015-12-06T23:01:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2000 / O reconhecimento e a evolucao da Terapia Ocupacional em paises como Estados Unidos, Canada, Inglaterra e Continente Europeu estao centrados na pratica clinica. Definicoes da profissao, metodos e tecnicas tem sido desenvolvidos em funcao ou consequencia dessa pratica. Grande enfase tem sido dada na construcao de instrumentos de avaliacao desses construtos, na expectativa de alcancar medidas de eficacia da Terapia Ocupacional. Na Area da Saúde Mental, apos levantamento e resumo de instrumentos de avaliacao, destaca-se o Self Assessment of Occupational Functioning - SAOF - (Baron et Curtin, 1990), como objeto de estudo. O SAOF e um instrumento de auto-avaliacao do funcionamento ocupacional com caracteristicas semelhantes aos instrumentos especificos desenvolvidos por terapeutas ocupacionais nos EUA. Sua construcao permite a aplicacao de 23 itens subdivididos em sete areas, permitindo uma analise dos itens ou das areas. O objetivo do presente trabalho foi o estudo da traducao para o portugues e obtencao dos indices de validade de criterio e de contabilidade. A traducao foi realizada atraves da tecnica da retrotraducao, enfocando-se principalmente uma equivalencia conceitual. Para o estudo de validade de criterio, considerou-se como um padrao-ouro a avaliadora, que detem um amplo conhecimento do embasamento teorico do instrumento e a fornacao especifica na area de avaliacao em Terapia Ocupacional. Para atingir esse objetivo, foi realizado um estudo da comparacao das respostas entre tres avaliadoras, atraves do teste de Kappa, obtendo-se bons indices de concordancia. O estudo de contabilidade teste-reteste foi realizado em amostra clinica sugerindo baixos indices de correlacao na analise dos itens e bons indices na analise das areas. Os resultados obtidos neste estudo sugerem a necessidade de ampliacao do estudo de escalas de avaliacao de Terapia Ocupacional no nosso meio e o cuidado na aplicacao de escalas desenvolvidas em outra cultura / BV UNIFESP: Teses e dissertações

Evidências indicam a relação entre o consumo excessivo de açúcar pela população mundial e o desenvolvimento de doenças crônicas como cárie, obesidade, diabetes e câncer. Para verificar a relação entre dieta e processo saúde-doença, estudos epidemiológicos utilizam instrumentos válidos, reprodutíveis e confiáveis, sendo o mais utilizado o questionário de frequência alimentar (QFA). Este estudo tratou de desenvolver, reproduzir e validar um instrumento de pesquisa (QFA-açúcar) que permita quantificar em gramas o consumo de açúcar em amostra da população adulta de Porto Alegre/RS. Para a determinação da lista de alimentos e do modelo de registro do QFA-açúcar, foi realizada a abordagem de pesquisa qualitativa denominada grupo focal, baseada na adaptação do QFA desenvolvido para a população adolescente, adulta e idosa de Porto Alegre (QFA-Porto Alegre). A quantificação do açúcar dos alimentos seguiu o método físico-químico de análise de alimentos de Fehling, ou a leitura da tabela de composição de alimentos do Departamento de Agricultura dos Estados Unidos (USDA). O QFA-açúcar foi avaliado por juízes com experiência na elaboração e aplicação de QFA. O resultado final desta etapa apresenta o QFA-açúcar com 94 itens. Para testar a reprodutibilidade e medir a validade do QFA-açúcar, foi empregada a abordagem quantitativa de pesquisa, utilizando uma amostra de 81 indivíduos, residentes em Porto Alegre, com idade entre 18 e 60 anos, selecionada através da amostragem por estágios múltiplos. O estudo aconteceu de julho a novembro de 2011 e os participantes responderam dois inquéritos recordatórios de 24 horas e 2 QFA-açúcar, num intervalo de 15 a 30 dias. A reprodutibilidade foi testada através do coeficiente de correlação intraclasse por ponto e por intervalo de 95% de confiança, por meio do teste das diferenças das médias pareadas (t-student) e pelo coeficiente alfa de Cronbach. A validade foi medida através dos coeficientes de correlação de Pearson e Spearman brutos e deatenuados e da classificação dos indivíduos segundo suas distribuições em quartos de consumo de sacarose de cada método. Os resultados apontaram que, para a reprodutibilidade, o teste t-student indicou que não há diferença significativa entre os dois questionários (p>0,01). O valor obtido para o coeficiente de alfa de Cronbach foi 0,903. Quanto à validade, diversamente do QFA-açúcar2, o teste t pareado entre o QFA-açúcar1 e a média dos dois IR24h mostrou diferença estatisticamente significativa para a ingestão de sacarose (p<0,05). Os coeficientes de correlação de Pearson e Spearman deatenuados para o QFA-açúcar 1 foram de 0,18 e 0,21 e para o QFA-açúcar2 de 0,36 e 0,44. A concordância exata média entre os QFA-açúcar1 e 2 foi de 30,25% e o percentual médio de indivíduos classificados em quartos adjacentes foi 61,11%. Concluindo, o QFA-açúcar possui relevâncias e limitações, contudo pode ser aprimorado. Mostrou reprodutibilidade e validade satisfatórias e poderá ser utilizado em estudos epidemiológicos para investigar a associação entre consumo de açúcar, doenças crônicas não-transmissíveis e cárie na população adulta de Porto Alegre. / Evidence indicates the relationship between excessive consumption of sugar by the population and the development of non communicable chronic diseases such as caries, obesity, diabetes and cancer. To investigate the relationship between diet and health-disease process, epidemiological studies use valid and reproducible instruments, and the most widely used is the Food Frequency Questionnaire (FFQ). The objective of this study was to develop, reproduce and validate a survey instrument (FFQ-sugar) to quantify in grams the sugar consumption in a sample of the adult population from Porto Alegre / RS. To determine the list of foods and the model's log of the FFQ-sugar, was carried out a qualitative research approach called focus group. It was based on the adaptation of the FFQ developed for adolescents, adults and elderly from Porto Alegre (FFQ-Porto Alegre). The food sugar quantification followed the Fehling method of food physical-chemical analysis or the reading of the food composition table from the American United States Department of Agriculture (USDA). The FFQ-sugar was evaluated by judges with experience in FFQ developing and implementing. The final result of this step shows the FFQ sugar with 94 items. To test the reproducibility and to measure the validity of the FFQ-sugar, was used the quantitative research approach. A sample of 81 individuals living in Porto Alegre, from 18 and 60 years of age were selected by multistage sampling. The study happened from July to November of 2011. The participants answered two 24-hour dietary recall questionnaire and two FFQ-sugar, in a interval of 15 to 30 days. The reproducibility was tested by the intra-class correlation coefficient by point and 95% confidence interval, through the test of paired differences of means (student-t test) and by the Cronbach's alpha. The validity was measured by the brute and de-attenuated correlation coefficients of Pearson and Spearman and by the classification of the individuals according to their distributions in sucrose consumption quartile of each method. The results showed that, for the reproducibility, the student-t test indicated that there is no significant difference between the two questionnaires (p> 0,01). The value of the coefficient of Cronbach's alpha was 0.903. As for validity, unlike the FFQ-açúcar2, the student-t test between the FFQ-açúcar1 and the two IR24h average demonstrated statistically significant difference for sucrose intake (p <0,05). The de-attenuated correlation coefficients of Pearson and Spearman for the FFQ-sugar1 were 0,18 and 0,21 and for the FFQ-sugar2 were 0,36 and 0,44. The exact average concordance between the FFQ- sugar 1 and 2 was 30,25% and the the average percentage of individuals classified in adjacent quartiles was 61,11%. The FFQ-sugar has relevance and limitations, but can be improved. It showed reasonable reproducibility and validity. As such, it may be used in epidemiological studies to investigate the association between sugar consumption, non communicable chronic diseases and dental caries in the adult population from Porto Alegre.

Made available in DSpace on 2015-07-22T20:49:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-27 / Objetivo: Avaliar os métodos biométricos do olho humano em pacientes portadores de catarata e com indicação de implante de lente intra-ocular. Métodos: Oitenta e quatro pacientes com média de idade de 58,82 ± 10,03 anos foram submetidos às biometrias óptica e ultra-sônica (imersão e contato) em ambos os olhos (n = 168). Os dados do comprimento axial, profundidade da câmara anterior, espessura do cristalino, profundidade da câmara vítrea e curvatura da córnea foram analisados. Foi avaliada a diferença das médias de cada método biométrico usado e a concordância foi investigada pela análise gráfica intra-individual de Bland-Altman de um método em relação ao outro. Resultados: Não houve diferença estatisticamente significante para as médias do comprimento axial (P=0,245), profundidade da câmara anterior (P=0,073), espessura do cristalino (P=0,8794) e profundidade da câmara vítrea (P=0,7640) entre os métodos usados. A diferença das médias da curvatura da córnea entre o IOLMaster® e o ceratômetro manual OM-4® foi estatisticamente significante (P<0,0001). Apesar da boa reprodutibilidade dos resultados, os gráficos de Bland- Altman mostraram algumas medidas fora dos limites de concordância estabelecidos em todas as variáveis analisadas. Houve menor concordância das medidas ceratométricas na comparação entre o IOLMaster® e o ceratômetro OM- 4®. Conclusões: Não houve diferença das médias dos métodos biométricos usados nesse estudo, exceto a curvatura da córnea que apresentou uma diferença estatisticamente significante entre as médias apresentadas. Os métodos demonstraram boa concordância, entretanto algumas medidas se apresentaram discordantes e podem ocasionar erros no cálculo do poder dióptrico da lente intraocular. / TEDE / BV UNIFESP: Teses e dissertações

Submitted by Priscila Nascimento (pnascimento@icict.fiocruz.br) on 2012-12-10T13:43:12Z No. of bitstreams: 1 marisol-simoes.pdf: 2202112 bytes, checksum: 3f9f53685909ddd3fdd381f8f3692f14 (MD5) / Made available in DSpace on 2012-12-10T13:43:12Z (GMT). No. of bitstreams: 1 marisol-simoes.pdf: 2202112 bytes, checksum: 3f9f53685909ddd3fdd381f8f3692f14 (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil. / A febre amarela é causada pelo vírus protótipo do gênero Flavivirus e é transmitida ao homem através da picada de mosquitos hematófagos infectados com o agente viral. A doença permanece endêmica em regiões das florestas tropicais da África e América do Sul, apesar da disponibilidade de vacinas eficazes contra o vírus da FA – 17D-204 e 17DD – consideradas seguras e altamente imunogênicas, capazes de induzir uma rápida resposta imune específica, com a formação de anticorpos neutralizantes que aparecem precocemente, são protetores e de longa duração. O teste de neutralização por redução de placas de lise (PRNT) é considerado o teste mais sensível e mais específico para a detecção e quantificação dos anticorpos neutralizantes, sendo o método de referência para a avaliação da resposta imune protetora após a vacinação. Este estudo avaliou a confiabilidade e a acurácia do micro PRNT50 (aplicado em placas de 96 poços) tomando como referência o PRNT 50 (aplicado em placas de 6 poços) e comparou o desempenho do micro PRNT50 com o micro PRNT90 (redução de 50% e 90% das placas de lise, respectivamente). Foram selecionados 200 soros de indivíduos brasileiros que participaram de um estudo clínico de dose-resposta da vacina 17DD produzida em Bio-Manguinhos. A repetibilidade foi aferida a partir de três repetições independentes do teste para cada um dos 200 soros por uma dupla operadora e o mesmo procedimento foi realizado pelas outras duas duplas operadoras, com a finalidade de determinar a reprodutibilidade do micro PRNT50 . Foram determinados o Coeficiente de Correlação Intraclasse (CCI) e o Coeficiente de Correlação de Pearson. As medidas de acurácia determinadas neste estudo foram sensibilidade, especificidade, acurácia global, prevalência e valores preditivos positivo (VPP) e negativo (VPN). A curva ROC também foi utilizada para determinar o melhor ponto de corte do micro PRNT50 . Na avaliação da repetibilidade, os CCIs das duplas operadoras variaram entre 0,62 e 0,76; e os coeficientes de correlação de Pearson apresentaram-se entre 0,62 e 0,78. Para a reprodutibilidade, o CCI obtido foi de 0,72 e os coeficientes de correlação de Pearson variaram entre 0,70 e 0,76. As melhores medidas de acurácia foram alcançadas considerando o ponto de corte para o micro PRNT50 de 2,9 Log 10 mUI/mL, o qual apresentou sensibilidade de 91,1%, especificidade de 72,9% e acurácia global de 78%. O melhor desempenho do micro PRNT50 com este ponto de corte foi ratificado pela análise da curva ROC. Considerando um cenário hipotético de surto de FA, a prevalência seria de 28%, com VPP de 56,7% e VPN de 95,5%. O micro PRNT50 apresentou níveis satisfatórios de confiabilidade e de acurácia, mas o micro PRNT90 mostrou desempenho superior com sensibilidade de 100%, especificidade de 94,7% e acurácia global de 95%. Modificações na metodologia do teste e alterações nos critérios de classificação nas leituras dos resultados obtidos serão importantes para melhorar a acurácia do micro PRNT. / Yellow fever is caused by the prototype virus of the genus Flavivirus and it is transmitted to humans through the bite of bloodsucking mosquitoes infected with the viral agent. The disease remains endemic in tropical forest regions from Africa and South America, despite the availability of effective vaccines against yellow fever virus - 17D-204 and 17DD - considered safe and highly immunogenic, capable of inducing a rapid specific immune response, with the formation of neutralizing antibodies that appear early, are protective and long lasting. The plaque reduction neutralization test (PRNT) is considered the most sensitive and most specific test for detection and quantification of neutralizing antibodies, and the reference method for assessing the protective immune response after vaccination. This study evaluated the reliability and accuracy of micro PRNT50 (applied in 96-well plates) with reference to the PRNT50 (applied in 6-well plates) and compared the performance of the micro PRNT50 with the micro PRNT90. Two-hundred serum samples from Brazilian individuals who participated in a clinical study of dose-response of 17DD vaccine produced in Bio-Manguinhos were selected. The repeatability was measured from three independent repetitions of the test for each of the 200 sera by a dual operator and the same procedure was performed by the other two dual operators, in order to determine the reproducibility of the micro PRNT50. The intraclass correlation coefficient (ICC) and Pearson correlation coefficient were determined. Accuracy measures determined in this study were sensitivity, specificity, overall accuracy, prevalence and positive predictive values (PPV) and negative (NPV). The ROC curve was also used to determine the best cut-off point of micro PRNT50 . In the assessment of repeatability, ICCs for dual operators ranged from 0.62 to 0.76, and Pearson correlation coefficients were between 0.62 and 0.78. For reproducibility, the ICC obtained was 0.72 and the Pearson correlation coefficients ranged between 0.70 and 0.76. The best measures of accuracy were achieved considering the cut-off point for the micro PRNT50 of 2.9 log10 mIU/mL, which had a sensitivity of 91.1%, specificity of 72.9% and overall accuracy of 78%. The best performance of micro PRNT50 with this cut-off point was ratified by the ROC curve analysis. Considering a hypothetical scenario of an outbreak of YF, the prevalence would be 28%, with PPV of 56.7% and NPV of 95.5%. The micro PRNT50 showed satisfactory levels of reliability and accuracy, however the micro PRNT90 showed higher performance with sensitivity of 100%, specificity of 94.7% and overall accuracy of 95%. Modifications in the test methodology and changes in the classification criteria in the readings of the results obtained will be important to improve the accuracy of micro PRNT.