Für die Ätiopathogenese der Atherosklerose spielen eine Vielzahl von Mediatoren eine Rolle. Dabei werden durch das Endothel sowohl protektive als auch schädliche Mediatoren sezerniert. High Density Lipoproteine (HDL) stellen einen bedeutenden protektiven Marker für das kardiovaskuläre Risiko dar, u.a. durch die Aktivierung der endothelialen NO-Synthase (eNOS). HDL besteht zu 50 % aus Proteinen und zu 50 % aus Lipiden. Welche Komponenten des HDL für die eNOS Aktivierung verantwortlich sind, ist nicht bekannt gewesen. Im ersten Abschnitt dieser Promotionsarbeit konnte erfolgreich gezeigt werden, dass die Lysophospholipide, Sphingosin-1-Phosphat (S1P) und Sphinsosylphosphorylcholin (SPC), die strukturelle Bestandteile der Lipidfraktion von HDL darstellen, für einen Teil der HDL induzierten eNOS Aktivierung durch Stimulation des S1P3-Rezeptors verantwortlich sind. Diese eNOS Aktivierung wird durch den intrazellulären Einstrom von Calcium und durch die Aktivierung der Akt-Kinase induziert. Im zweiten Abschnitt dieser Promotionsarbeit konnte nachgewiesen werden, dass das oral verfügbare Lysophospholipid-basierte Medikament, FTY720, das ein strukturelles Analogon des S1P ist, den HDL induzierten Signaltransduktionsweg der eNOS Aktivierung in gleicher Weise induziert. Im dritten Abschnitt dieser Promotionsarbeit konnte ein neuartiges endothelabhängig sezerniertes gemischtes Dinukleosidpolyphosphat, Uridin-Adenosin-Tetraphosphat (Up4A), identifiziert werden. Up4A ist ein Agonist an den P2X- und P2Y-Purinrezeptoren. Up4A induziert bei Applikation in eine isoliert perfundierte Rattenniere hauptsächlich über die Aktivierung des P2X1-Rezeptors und des P2Y2/P2Y4-Rezeptors eine starke Vasokonstriktion im renalen Perfusionsgebiet mit einhergehender Erhöhung des mittleren renalen Perfusionsdrucks. Die direkte Infusion von Up4A in vivo in eine WKY-Ratte führt zu einer signifikanten Erhöhung des mittleren arteriellen Blutdrucks. / In the pathogenesis of atherosclerosis many mediators are included. Therefore the endothelium plays a crucial part by secreting protective but also deleterious factors. High density lipoproteins are an established protective factor in the risk profile of cardiovascular events especially by activating the endothelial NO synthase (eNOS). HDL is composed of 50 % proteins and 50 % lipids. Which component of HDL is responsible for the eNOS activation was not known. In the first part of this dissertation it could be shown, that the lysophospholipids, sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), which are structural compounds of the lipid fraction of HDL, are responsible for a significant part of the HDL induced eNOS activation by stimulating the specific S1P3 receptor. In the signal transduction mechanism the activation of Akt kinase and an influx of calcium is involved. In the second part of this dissertation it could be shown, that the orally active lysophospholipide based drug FTY720, which is a structural analogue of S1P, is able to induce the same signal transduction mechanism activated by HDL including the stimulation of the S1P3 receptor. In the last part of this dissertation a new endothelium dependent vasoconstrictor, the dinucleoside polyphosphate uridine-adenosine-tetraphosphate (Up4A), could be for the first time identified. Up4A is a potent agonist of the P2X- and P2Y-purinoceptors. Via activating the P2X1 receptor and the P2Y2/P2Y4 receptor Up4A induce a strong vasoconstriction in the renal perfusion system in the model of the isolated perfused rat kidney with an adjacent increase of the mean perfusion pressure. By injection of Up4A in vivo in a Wistar Kyoto rat the mean arterial pressure also increase significantly.

Connus sous le nom de Systèmes d’Alerte Avancés, ou Early Warning Systems (EWS), les modèles de prévision des crises financières sont appelés à jouer un rôle déterminant dans l’orientation des politiques économiques tant au niveau microéconomique qu’au niveau macroéconomique et international. Or,dans le sillage de la crise financière mondiale, des questions majeures se posent sur leur réelle capacité prédictive. Deux principales problématiques émergent dans le cadre de cette littérature : comment évaluer les capacités prédictives des EWS et comment les améliorer ?Cette thèse d’économétrie appliquée vise à proposer (i) une méthode d’évaluation systématique des capacités prédictives des EWS et (ii) de nouvelles spécifications d’EWS visant à améliorer leurs performances. Ce travail comporte quatre chapitres. Le premier propose un test original d’évaluation des prévisions par intervalles de confiance fondé sur l’hypothèse de distribution binomiale du processus de violations. Le deuxième chapitre propose une stratégie d’évaluation économétrique des capacités prédictives des EWS. Nous montrons que cette évaluation doit être fondée sur la détermination d’un seuil optimal sur les probabilités prévues d’apparition des crises ainsi que sur la comparaison des modèles.Le troisième chapitre révèle que la dynamique des crises (la persistance) est un élément essentiel de la spécification économétrique des EWS. Les résultats montrent en particulier que les modèles de type logit dynamiques présentent de bien meilleurs capacités prédictives que les modèles statiques et que les modèles de type Markoviens. Enfin, dans le quatrième chapitre nous proposons un modèle original de type probit dynamique multivarié qui permet d’analyser les schémas de causalité intervenant entre différents types crises (bancaires, de change et de dette). L’illustration empirique montre clairement que le passage à une modélisation trivariée améliore sensiblement les prévisions pour les pays qui connaissent les trois types de crises. / Known as Early Warning Systems (EWS), financial crises forecasting models play a key role in definingeconomic policies at microeconomic, macroeconomic and international level. However, in the wake ofthe global financial crisis, numerous questions with respect to their forecasting abilities have been raised,as very few signals were drawn prior to the starting of the turmoil. Two questions arise in this context:how to evaluate EWS forecasting abilities and how to improve them?The broad goal of this applied econometrics dissertation is hence (i) to propose a systematic model-free evaluation methodology for the forecasting abilities of EWS as well as (ii) to introduce new EWSspecifications with improved out-of-sample performance. This work has been concretized in four chapters.The first chapter introduces a new approach to evaluate interval forecasts which relies on the binomialdistributional assumption of the violations series. The second chapter proposes an econometric evaluationmethodology of the forecasting abilities of an EWS. We show that adequate evaluation must take intoaccount the cut-off both in the optimal crisis forecast step and in the model comparison step. The thirdchapter points out that crisis dynamics (persistence) is essential for the econometric specification of anEWS. Indeed, dynamic logit models lead to better out-of-sample forecasting probabilities than those oftheir main competitors (static model and Markov-switching one). Finally, a multivariate dynamic probitEWS is proposed in the fourth chapter to take into account the causality between different types of crises(banking, currency, sovereign debt). The empirical application shows that the trivariate model improvesforecasts for countries that underwent the three types of crises.

Pickling is a unit operation within stainless steel production, which means treating the steel with hydrofluoric acid (HF) and nitric acid (HNO3), also called mixed acid. The whole process generates waste water streams which have to be treated before released to recipient. The aim of this degree thesis was to make an evaluation of different possibilities for reduction of emissions from the pickling process with China as a possible future market. The work consisted of two different parts; the first was to describe and evaluate different treatment methods for waste pickling acid, with emphasis on denitrification technologies. The second and main part was to make a fundamental description of the neutralisation process and outline important parameters. The work was performed by gathering information from literature but also from industry in both Sweden and China. The work has been a collaboration between the Royal Institute of Technology (KTH), the Swedish Environmental Institute (IVL) and the company Scanacon. A review of the different acid recovery methods; ionic exchange, diffusion dialysis and extraction was made. The study showed that ionic exchange is a robust method with relatively low cost and therefore it has been largely implemented both in Swedish and Chinese industry. The outflow however still requires neutralisation. Nitrate reduction can be performed as “end of pipe”, those methods investigated in this study were; biological treatment, reverse osmosis and nanofiltration. Meanwhile, internal solutions such as evaporation and electro-dialysis are two interesting technologies which reduce nitrates in combination with acid recovery. It was found that slaked lime (Ca(OH)2) is the most suitable neutralisation agent for pickling waste and, besides the choice of chemicals, many important parameters influence the process, such as the optimal pH, mixing and conditions during lime slaking. Based on information from one of the visited sites in Sweden a mass balance of the neutralisation facility was made and from that the required amount of Ca(OH)2 was calculated. The calculations were verified by an experimental part performed by IVL, using pickling acids from the same site. The amount of metals in the outgoing water was calculated using software “Medusa” but also by equilibrium equations. However, the results differed somewhat; this is probably due to the fact that Medusa takes other complexes and their interaction, besides the formed metal hydroxides, into consideration. Within the mining industry research has been made on different methods for neutralisation and some have been tested in field. An example is the High Density Sludge process (HDS), were an amount of sludge is recycled back to the neutralisation tank. It was shown that this gave improved sludge properties and decreased lime consumption. This could perhaps also be implemented for waste water in the stainless steel industry, and the method was also tested during the experimental part of this project. The dry content increased after a number of cycles but further investigation is required before any conclusion can be drawn. / Betning är en enhetsprocess inom tillverkningen av rostfritt stål då godset behandlas med fluorväte syra (HF) och salpetersyra (HNO3), också kallad blandsyra. Betningen ger upphov till vatten strömmar som måste behandlas innan de släpps ut till recipienten. Syftet med det här examensarbetet var att göra en utvärdering av olika tekniker för att reducera utsläpp till vatten från betningen med Kina som potentiell framtida marknad. Arbetet bestod av två delar; den första delen var att beskriva och utvärdera olika behandlingsmetoder av förbrukade betbad med betoning på denitrifikationstekniker. Den andra och största delen var att göra en grundläggande beskrivning av neutralisationsprocessen. Studien utfördes genom att inhämta information från litteratur samt från industrin i både Sverige och Kina. Arbetet har varit ett samarbetsprojekt mellan Kungliga Tekniska Högskolan (KTH), Svenska miljöinstitutet (IVL) och företaget Scanacon.    Arbetet behandlar syraåtervinningsystemen; jonbytare, diffusions dialys samt extraktion. Nitrat reduktion kan ske internt eller externt där de externa åtgärder som behandlas i denna rapport är biologisk rening, omvänd osmos och nanofiltrering. De interna metoderna avdunstning och elektrodialys är intressanta eftersom de återvinner syran samtidigt som de reducerar nitraterna avsevärt. Studien visade att jonbyte, på grund av dess robusthet och relativt låga kostnad är den mest implementerade metoden för syraåtervinning i både svensk och kinesisk industri idag. Restprodukten från jonbytaren kräver dock fortsatt behandling, där det traditionella valet är neutralisation. Studien visade att släckt kalk (Ca(OH)2) är det mest passande kemikalien för neutralisation av betsyror. Förutom kemikalieval så finns det många parametrar som påverkar effektiviteten hos processen så som pH, omrörning och förhållanden under kalksläckningen. Baserat på information ifrån ett av de besökta stålverken i Sverige, gjordes en massbalans över dess neutralisationanläggning. Utifrån de flöden som denna gav kunde den teoretiska mängden kalk som krävdes för utfällning räknas ut. Beräkningarna verifierades med en experimentell del som utfördes av IVL på betsyror från samma verk. Resthalterna av metall i utgående vatten beräknades med programmet ”Medusa” men också med jämviktsekvationer. Resultaten mellan de två skiljde sig, detta beror förmodligen på att Medusa förutom hydroxidutfällning tar hänsyn till andra utfällningskomplex och dess interaktioner. Inom gruvvatten industrin har det forskats en del kring olika neutralisationsmetoder, en i litteraturen föreslagen sådan är ”High Density Sludge process (HDS)”. Här återförs en del av slammet tillbaka till neutralisationssteget, vilket visade sig ge förbättrade slamegenskaper och minskad kalkåtgång. Det var intressant att undersöka om denna metod också gick att implementera på förbrukade betbad och därför prövades metoden i den experimentella delen av detta projekt. Detta gav efter ett antal återföringscykler högre torrhalt på slammet, dock krävs fortsatta undersökningar innan någon slutsats kan dras.

Motivation Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular consequences that include injury, risky sexual behaviour, violent crime and family dysfunction among black South Africans, contributing to high mortality. Moreover, the highest number of individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable to high intake of alcohol. HIV remains a major concern in South Africa with significant funding diverted to address the pandemic. The continued increases in mortality from preventable outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation, poverty and dysfunctional health systems working with limited budgets. These are some of the factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although there is enough evidence that links excessive drinking with hypertension and CVD, the markers of alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate deficient transferrin – are still not specific enough to isolate other confounding factors in the association of alcohol intake with CVD. The markers of alcohol that independently predict CVD and mortality need to be explored. Finally, the severe lack of longitudinal investigations on alcohol-related hypertension development and total mortality in black South Africans has compromised the early identification of risk factors associated with these outcomes. This study will therefore attempt to address the limited availability of longitudinal studies and stimulate interest for continued investigation. Aim The aim of this study was to investigate whether alcohol intake of black South Africans is related to specific measures of cardiovascular function (change in blood pressure (BP), hypertension development) and mortality over a period of 5 years. Methodology This study was based on the international Prospective Urban and Rural Epidemiology (PURE) study which includes 26 countries, investigating the cause and development of cardiovascular risk factors in low, middle and high income countries. This South African leg of the PURE study started in 2005 in which the baseline data was collected from 2021 black South Africans from rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven participants presented with missing data, leaving 2010 participants with complete datasets at baseline. However, data from these 11 participants was useful, especially for Chapter 4. All participants gave informed consent and the Ethics committee of the North-West University (Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010. General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular measurements were taken both at baseline and follow-up using appropriate methods. We also collected blood samples and performed biochemical analyses for lipid markers, liver enzymes, inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and death certificates. We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline and follow-up variables. Furthermore, we employed single and partial linear regression analyses to correlate alcohol markers with each other and with the cardiovascular measures. Multiple regression analyses were used to correlate dependent variables in the study with various independent variables as required. Finally, we employed multivariable-adjusted Cox regression analyses to assess the association of the selected alcohol markers with mortality while adjusting for several independent variables. Results and Conclusions of each manuscript - With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake estimates with GGT and %CDT, considering their relationship with percentage change in brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The results indicated that only self-reported alcohol intake independently predicted % change in brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT. Self-reported alcohol intake seems to be an important measure to implement by health systems in low income areas of sub-Saharan Africa, where honest reporting is expected. - Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the cardiovascular and metabolic characteristics of excessive alcohol users and individuals with suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex and cardiometabolic profiles characterised excessive alcohol users and individuals suspected with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up the higher proportion of this group. In excessive alcohol users systolic blood pressure and pulse pressure were independently associated with high-density lipoprotein cholesterol. Diastolic blood pressure showed a significant correlation with waist circumference. These disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These results emphasise the importance of modifiable risk factors as the main contributors to CVD and that lifestyle change should be the main focus in developing countries such as South Africa. - The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported alcohol intake, GGT and %CDT) that related best with hypertension development, cardiovascular and all-cause mortality over 5 years in the same population of black South Africans. We found that GGT was the only independent predictor of hypertension development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol intake predicted incident hypertension, confirming our findings from Chapter 4. The third marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in low-resource primary healthcare settings, measurement of GGT is encouraged due to its predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic steatohepatitis and obesity - all known to have severe cardiovascular consequences. Discussion and Conclusions Excessive alcohol intake remains a major concern in the development of hypertension, CVD and premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity, self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers that independently predicted 5-year change in BP, hypertension development and total mortality in this population. Serum %CDT did not show any association with the mentioned cardiovascular markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e. with high GGT levels who do not consume alcohol) are typically obese women, whereas lean men were more likely to have high alcohol consumption. Further prospective investigations are encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular consequences that include injury, risky sexual behaviour, violent crime and family dysfunction among black South Africans, contributing to high mortality. Moreover, the highest number of individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable to high intake of alcohol. HIV remains a major concern in South Africa with significant funding diverted to address the pandemic. The continued increases in mortality from preventable outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation, poverty and dysfunctional health systems working with limited budgets. These are some of the factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although there is enough evidence that links excessive drinking with hypertension and CVD, the markers of alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate deficient transferrin – are still not specific enough to isolate other confounding factors in the association of alcohol intake with CVD. The markers of alcohol that independently predict CVD and mortality need to be explored. Finally, the severe lack of longitudinal investigations on alcohol-related hypertension development and total mortality in black South Africans has compromised the early identification of risk factors associated with these outcomes. This study will therefore attempt to address the limited availability of longitudinal studies and stimulate interest for continued investigation. Aim The aim of this study was to investigate whether alcohol intake of black South Africans is related to specific measures of cardiovascular function (change in blood pressure (BP), hypertension development) and mortality over a period of 5 years. Methodology This study was based on the international Prospective Urban and Rural Epidemiology (PURE) study which includes 26 countries, investigating the cause and development of cardiovascular risk factors in low, middle and high income countries. This South African leg of the PURE study started in 2005 in which the baseline data was collected from 2021 black South Africans from rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven participants presented with missing data, leaving 2010 participants with complete datasets at baseline. However, data from these 11 participants was useful, especially for Chapter 4. All participants gave informed consent and the Ethics committee of the North-West University (Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010. General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular measurements were taken both at baseline and follow-up using appropriate methods. We also collected blood samples and performed biochemical analyses for lipid markers, liver enzymes, inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and death certificates. We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline and follow-up variables. Furthermore, we employed single and partial linear regression analyses to correlate alcohol markers with each other and with the cardiovascular measures. Multiple regression analyses were used to correlate dependent variables in the study with various independent variables as required. Finally, we employed multivariable-adjusted Cox regression analyses to assess the association of the selected alcohol markers with mortality while adjusting for several independent variables. Results and Conclusions of each manuscript - With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake estimates with GGT and %CDT, considering their relationship with percentage change in brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The results indicated that only self-reported alcohol intake independently predicted % change in brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT. Self-reported alcohol intake seems to be an important measure to implement by health systems in low income areas of sub-Saharan Africa, where honest reporting is expected. - Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the cardiovascular and metabolic characteristics of excessive alcohol users and individuals with suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex and cardiometabolic profiles characterised excessive alcohol users and individuals suspected with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up the higher proportion of this group. In excessive alcohol users systolic blood pressure and pulse pressure were independently associated with high-density lipoprotein cholesterol. Diastolic blood pressure showed a significant correlation with waist circumference. These disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These results emphasise the importance of modifiable risk factors as the main contributors to CVD and that lifestyle change should be the main focus in developing countries such as South Africa. - The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported alcohol intake, GGT and %CDT) that related best with hypertension development, cardiovascular and all-cause mortality over 5 years in the same population of black South Africans. We found that GGT was the only independent predictor of hypertension development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol intake predicted incident hypertension, confirming our findings from Chapter 4. The third marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in low-resource primary healthcare settings, measurement of GGT is encouraged due to its predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic steatohepatitis and obesity - all known to have severe cardiovascular consequences. Discussion and Conclusions Excessive alcohol intake remains a major concern in the development of hypertension, CVD and premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity, self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers that independently predicted 5-year change in BP, hypertension development and total mortality in this population. Serum %CDT did not show any association with the mentioned cardiovascular markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e. with high GGT levels who do not consume alcohol) are typically obese women, whereas lean men were more likely to have high alcohol consumption. Further prospective investigations are encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

高密度發展的都市型態已成為世界各國為追求永續發展的都市規劃方式。對政策規劃者來說，他們關心的議題之一為高密度都市發展後房價的變動是否會影響居民對住的福利水準，過去文獻之實證研究亦發現高密度發展將產生房價上漲或下跌的效果，此引發本研究欲得知高密度指標對台北市房價將如何影響之動機。然而高密度都市發展政策的實施對各所得階層居民的影響為何若以普通最小平方迴歸分析將無法得知，所以本研究以分量迴歸進行分析，增加變數的可解釋能力。 因此本研究以台北市十二個行政區為空間範圍，利用民國九十三年至九十六年間共1268筆房屋交易實例案例，作為實證研究之樣本。主題變數方面以容積率、是否為住宅大樓及人口密度來分析各變數對房價之影響。藉由普通最小平方迴歸及分量迴歸分析結果發現，高密度之都市發展將造成住宅平均價格下跌，對中低總價住宅亦產生價格下跌的效果，因此高密度都市發展型態將增加居民福利水準，增進都市整體效益。 / Nowadays, most nations in the world has thought of the urban form of high density development as a mean to pursue sustainable development. For policy planner, what they care is whether high density development would influence residents about the variation of welfare for living. Literatures of past empirical research also show that high density development will have the effects of rising or falling on housing prices, which leads to the motive of this study and also leads to a better understanding of how high density indicators would impact housing prices in Taipei City. However, what’s the impact for every income class through the implication of this urban development policy is impossible to know if we use OLS models, therefore, our study adopts Quantile Regression to enhance the interpretable abilities for every variable. Accordingly, our study uses 1268 property-trading-records from 2004 to 2007 as samples, which all locate within 12 districts in Taipei City. We use floorage ratio, residential building and population density as main variables to analyze their impacts on housing prices. The result shows that high density development will both lead to falling of average housing prices and middle and low housing prices. Consequently, the urban form of high density development will enhance the level of residents’ welfare and improve the benefits for all urban area.

Introdução: estudos recentes demonstram que o aumento do colesterol na lipoproteína de alta densidade (HDL-C), induzido por medicamentos ou mutações genéticas, não é associado à redução de eventos coronarianos. A lipoproteína de alta densidade (HDL) apresenta aspectos funcionais distintos em relação ao seu papel cardioprotetor. Objetivo: desenvolver um escore de funcionalidade da HDL (EFH) e avaliar a sua associação com algoritmos de predição de risco cardiovascular e aterosclerose subclínica em indivíduos brasileiros. Metodologia: trata-se de um estudo transversal composto por duas etapas. Na 1ª etapa, o EFH preditor de risco cardiovascular (EFH-RCV) foi desenvolvimento e validado a partir de uma subamostra do estudo CARDIONUTRI (n=354). Na 2ª etapa, o EFH preditor de aterosclerose subclínica (EFH-AS) foi desenvolvido e validado com dados de uma subamostra do estudo ELSA-Brasil (n=4549). No estudo CARDIONUTRI foram avaliadas a atividade da paraoxonase 1 (PON1) e da proteína de transferência de ésteres de colesterol (CETP), a concentração da apolipoproteína AI (APOAI), a capacidade antioxidante da HDL (lag time) e as subfrações da HDL pelo método Lipoprint®. O estudo ELSA-Brasil avaliou as subfrações da HDL pelo método Vertical Auto Profile (VAP) e Ressonância Magnética Nuclear (RMN), e a aterosclerose subclínica por tomografia computadorizada, quantificação da calcificação da artéria coronária (CAC) e calculo do escore da CAC. Resultados: no desenvolvimento do EFH-RCV, a HDL grande apresentou maior força de associação com o risco cardiovascular no modelo múltiplo final (OR = 0,797; p <0,001). O EFH-RCV demonstrou bom desempenho em relação ao escore de risco de Framingham (AUC = 0,899; p <0,001), escore de risco de Reynolds (AUC = 0,722; p <0,001) e Adult Treatment Panel III/2013 (AUC = 0,864; p <0,001). Além disso, apresentou boa reprodutibilidade e correlação com aterosclerose subclínica, quando testado na amostra do estudo ELSA-Brasil, utilizando medidas da HDL grande derivadas do método VAP (AUC = 0,864; p <0,001 e r = 0,252 p <0,001) ou do método de RMN (AUC = 0,876; p <0,001 e r = 0,277; p <0,001). O EFH-AS foi desenvolvido a partir do tamanho da HDL (nm), que apresentou a associação mais forte com aterosclerose subclínica no modelo múltiplo final (OR = 0,549; p <0,001) e demonstrou bom desempenho (AUC = 0,769; p <0,001). Conclusão: o EFH apresentou associações mais fortes com o risco cardiovascular e a aterosclerose subclínica, independente do HDL-C, com destaque para a HDL grande. Os resultados controversos entre as subfrações da HDL e o risco cardiovascular parecem manter relação com as metodologias distintas utilizadas nas análises. Portanto, a validação dos métodos e a inclusão do tamanho da HDL como marcador de risco cardiovascular revela um futuro promissor como adjuvante na estimativa do risco cardiovascular, manejo de medicamentos e tomada de decisões na prática clínica. / Introduction: current studies have not presented association between high density-lipoprotein cholesterol (HDL-C) increase, induced by drugs or genetic mutations, and coronary events reduction. HDL plays different functional cardioprotective role. Objective: to develop a HDL functionality score (HFS) and to assessment its association with predictive cardiovascular risk algorithms and subclinical atherosclerosis outcomes in Brazilian subjects. Methods: cross-sectional study based in two steps. In the first step, the HFS predictor of cardiovascular risk disease (HFS-CVR) was developed and validated on CARDIONUTRI study subsample (n=354). In second step the HFS predictor of subclinical atherosclerosis (HFS-SA) was developed and validated on ELSA-Brasil study subsample (n=4549). CARDIONUTRI study evaluated paraoxonase 1(PON1) and cholesterol ester transfer protein (CETP) activity, apolipoprotein AI (APOAI) concentration, HDL antioxidant capacity, and HDL subfractions by standard Lipoprint® method. ELSA-Brasil study evaluated the size of HDL and subfractions by Vertical Auto Profile (VAP) and Nuclear Magnetic Resonance (NMR) method, and the diagnosis of subclinical atherosclerosis by computed tomography, quantifying coronary artery calcification (CAC) and CAC score. Results: in the development of HFS-CVR, the large HDL presented greater strength of association with cardiovascular risk in the multiple final model (OR = 0.797; p <0.001). The HFS-CVR showed satisfactory performance by Framingham risk score (AUC = 0.899; p <0.001), Reynolds risk score (AUC = 0.722; p <0.001) and Adult Treatment Panel III/2013 guidelines (AUC = 0.864; p <0.001). In addition, HFS-CVR presented satisfactory reproducibility and was associated with subclinical atherosclerosis on ELSA-Brasil sample using large HDL measurements derived from the VAP method (AUC = 0.864; p <0.001 and r = 0,252; p <0,001) or the NMR method (AUC = 0.876; p <0.001 and r = 0.277; p <0,001). HFS-AS was developed from the HDL size (nm), because presented greater association with subclinical atherosclerosis in the final multiple model (OR = 0.549; p <0.001). HFS-AS demonstrated satisfactory performance (AUC = 0.769; p <0.001). Conclusion: the HFS demonstrates strong association with cardiovascular risk and subclinical atherosclerosis, independent of HDL-C, with emphasis on large HDL. Controversial results, between HDL subfractions and cardiovascular irsk seem to maintain a relation with the different methodologies used in analysis. Therefore, the validation of the methods and the inclusion of the HDL size as a cardiovascular risk marker reveal a promising future as an adjunct in the estimation of cardiovascular risk, drug management and decision making in clinical practice.

No description available.

LIBS é um método baseado na espectrometria de emissão óptica que emprega a microamostragem por ablação por laser e formação de um microplasma para a determinação dos elementos químicos presentes na amostra. Neste trabalho, o método foi avaliado para a análise de embalagens plásticas produzidas com polietileno de alta densidade e polipropileno. A construção de curvas de calibração com amostras dos polímeros contendo diferentes concentrações de Cd, Cr e Pb e a determinação desses analitos, assim como os efeitos da taxa de repetição do laser, número de pulsos, fluência e diâmetro de focalização foram estudados. O sistema LIBS utilizado foi composto por um laser pulsado de Nd:YAG operando a 064 nm, com pulsos de 5 ns e máxima energia de 360 mJ/pulso. Os sinais de emissão foram coletados por um conjunto de lentes acoplado por fibra óptica ao espectrômetro com montagem Echelle e detector ICCD. Os parâmetros instrumentais foram ajustados em 10 pulsos acumulados, 2 \'mü\'s de atraso e 6 \'mü\'s de integração. O software ESAWIN, o banco de dados de espectros atômicos e iônicos do NIST e algoritmo desenvolvido em ambiente MATLAB® foram utilizados para aquisição e tratamento dos dados. A avaliação da topografia das crateras nas placas dos polímeros foi feita por perfilometria e microscopia eletrônica de varredura, que proporcionaram informações úteis para a caracterização das crateras. As massas removidas das placas de polietileno de alta densidade e de polipropileno foram calculadas a partir dos volumes das crateras obtidos pelas análises perfilométricas. A taxa de repetição e número de pulsos do laser tiveram efeitos marcantes na ablação dos polímeros, e as principais causas foram atribuídas ao grau de cristalinidade, à temperatura de fusão cristalina (Tm) e à temperatura de transição vítrea (Tg). Os resultados desta tese indicaram que diâmetros de focalização da ordem de 600 \'mü\'m e fluências entre 50 e 85 J cm-2 podem ser recomendados para análises de PEAD e PP por LIBS com laser de Nd:YAG@1064 nm (pulsos de 5 ns) e taxa de repetição de 10Hz. Nessas condições, as curvas de calibração obtidas apresentaram boa correlação. Identificaram-se três amostras contaminadas por Cd, Cr e Pb dentre 60 embalagens plásticas analisadas. A comparação dos resultados obtidos por LIBS e ICP OES apresentou concordâncias e algumas diferenças significativas (teste t ao nível de 95% de probabilidade) que foram associadas a efeitos de matriz observados na análise dos polímeros por LIBS / LIBS is an optical emission spectroscopy technique that employs a laser for micro sampling and induction of a plasma for determination of chemical elements in a sample. In this work, LIBS was evaluated for the analysis of plastic packaging produced with high density polyethylene (HDPE) and polypropylene (PP). Plates of these polymers with different concentrations of Cd, Cr and Pb were prepared for evaluating the effects of laser repetition rate, number of pulses, fluence and laser focusing as well as for building the analytical calibration curves. The LIBS system was designed by using a Q-Switch Nd:YAG laser operating at 1064 nm (5 ns, 360 mJ/pulse) and the emission signals were collected by lenses into an optical fiber coupled to a high-resolution echelle spectrometer equipped with ICCD. Instrumental parameters consisted of 10 accumulated laser pulses, 2 \'mü\'s delay time and 6 \'mü\'s integration time gate. Software ESAWIN, NIST atomic database and an algorithm develop in MATLAB® were used for acquisition and data processing. The evaluation of topographical features of craters on the plates of the polymers was carried out by perfilometry and scanning electron microscopy, and provides useful information for the characterization of the craters. The mass removal of HDPE and PP were calculated using craters volume obtained in perfilometric analysis. The repetition rate and number of laser pulses affect the ablation process in polymers. Moreover, the main properties of polymers that affect the ablation are degree of crystallinity, crystalline melting temperature (Tm) and glass transition temperature (Tg). The results indicated that laser focusing of 610 \'mü\'m and fluences between 50 and 85 J cm-2 can be indicated for LIBS analysis of HDPE and PP with Nd:YAG@1064 nm, 5 ns and 10 Hz. Under these conditions the calibration curves obtained presented good correlations and 3 samples containing Cd, Cr and Pb were identified from 60 samples from the local market. LIBS results compared well with ICP OES but some data presented significant differences by applying a t-test at 95 % confidence level, which were mainly associated to matrix effects observed in the analysis of polymers by LIBS

O alto consumo de energia para a produção de metais e de cimento, a pressão em relação à utilização de madeira tropical e a abundância de material plástico vêm contribuindo para o desenvolvimento de pesquisas e a aplicação dos termoplásticos na construção civil, em elementos estruturais que, em sua grande maioria, são constituídos de madeira, de aço e de concreto. O progresso dos materiais poliméricos pode ser comprovado pelos diversos produtos que estão sendo projetados, principalmente na Europa e nos Estados Unidos, como passarelas, dormentes, marinas, etc. Foi escolhido o polietileno de alta densidade (PEAD) reciclado, por ser um dos materiais poliméricos rígidos mais disponíveis para reciclagem. Nesse contexto, o objetivo deste trabalho foi a caracterização do PEAD reciclado. Foi determinada a composição do material polimérico (PEAD) reciclado obtido no mercado, por meio dos ensaios termoanalíticos: calorimetria exploratória diferencial e análise termogravimétrica. Os resultados mostraram que o material fornecido pela empresa de reciclagem é isento dos contaminantes comumente encontrados nos materiais reciclados e apresenta um grau de pureza bastante significativo. A determinação das propriedades mecânicas, por meio dos ensaios de tração, de compressão, de flexão e de impacto Izod, finaliza o estudo do material analisado. Nesses ensaios, a resistência obtida foi próxima dos valores encontrados na literatura, para o PEAD virgem, e pouco inferior à do concreto e à da madeira. Entretanto, a rigidez do PEAD reciclado foi bem menor que a dos materiais de construção tradicionais, sendo essa sua maior deficiência. Concluiu-se que o PEAD reciclado pode ser aplicado em elementos estruturais, desde que sejam estudadas possíveis formas de controlar sua deformabilidade, como a incorporação de nervuras, a utilização de blendas poliméricas e adição de cargas minerais e de fibras de elevado módulo de elasticidade e resistência. / The use of thermoplastics in civil engineering has been increasing considerably in the last decades. The latter is due to large amount of plastic material and high cost on a production of metals and cement for reinforced concrete, besides the lack of wood. This could be proved by the development of new thermoplastics products, especially in Europe and United States, like bridges, railway sleepers, posts, etc. Recycled high density polyethylene (HDPE) was chosen due to the fact that it is one of the most rigid recycled polymers available on the recycling industry. In this study, recycled polymer has been characterized in order to determinate the recycled material composition available in the market. The characterization of recycled HDPE samples was made by thermo gravimetric analysis and differential scanning calorimetry. Consequently, mechanical properties were determinated by tensile test, compression test, flexural test and impact Izod. The results of thermal analysis showed that the recycled material is exempt from possible contaminants and has a significant pureness degree. Under tension, compression, bending and impact conditions, the strength was around the pure polymer and little smaller of the concrete and wood. In contrast, the stiffness was much lower in comparison to traditional materials, their worst characteristic. These problems could be overcome through the study of polymeric blends, adding high modulus and strength fibers and charges and adding ribs. Then the recycled polymer could be applied as a structural element.