La phospholipase A2 liée aux lipoprotéines (Lp-PLA2) est une biomarqueur de plusieurs maladies inflammatoires et une niveau sérique élevé est associé à l’instabilité de la plaque artérioscléreuse. Comme son nom l’indique, la Lp-PLA2 est liée aux lipoprotéines plasmatiques (LDL et HDL) et son rôle est de prévenir l’accumulation de phospholipides oxidés a la surface des lipoprotéines. Toutefois, les produits de dégradation des phospholipides oxidés par la Lp-PLA2 - le lysophosphatidyl choline par les acides gras oxidés peuvent aussi promouvoir l’inflammation. Mieux comprendre le métabolisme de la Lp-PLA2 pourrait nous permettre de mieux apprécier son rôle dans la formation d’une plaque artérioscléreuse instable, car des études antérieures ont démontré une forte expression de la Lp-PLA2 dans la plaque. De plus, il existe une forte corrélation entre les niveaux et l’activité plasmatiques de la Lp-PLA2 et la maladie coronarienne, les accidents cérébraux-vasculaires et la mortalité cardiaque. L’inhibition de la Lp-PLA2 avec une petite molécule, le darapladib, n’a pas démontré de bénéfice sur les évènements cardiovasculaires dans deux études cliniques. Cette thèse présentera d’abord une revue de la littérature sur la Lp-PLA2 et les maladies cardiovasculaires et les deuxième et troisième chapitres, une étude clinique réalisée sur des patients avec un syndrome coronarien aigu. / Lipoprotein associated phospholipase A2 (Lp-PLA2) is a biomarker of several inflammatory diseases and syndromes. An elevated Lp-PLA2 level is associated with unstable atherosclerotic plaques. Bound to plasma lipoproteins (LDL and HDL), Lp-PLA2 prevents the formation of biologically active oxidized phospholipids on their surface such as oxidized phosphatidylcholine (oxPC). Nevertheless, the products of Lp-PLA2 action, lysophosphatidylcholine (LPC) and non-esterified fatty acids (NEFA) are both known to aggravate inflammation. Thus, understanding the metabolism of Lp-PLA2 could help us better understand its role in plaque formation, as studies have shown high expression of Lp-PLA2 and LPCs in unstable plaques. Moreover, studies showed correlation between increased Lp-PLA2 mass and activity and increased risk of coronary artery disease, stroke, and death. The inhibition of Lp-PLA2 with a small molecule, Darapladib, has not demonstrated benefit in reduction of cardiovascular events in two clinical studies. Here, the first chapter will focus on Lp-PLA2 and cardiovascular disease in man, highlighting the latest updates in the literature. The second and third chapters will introduce experimental work on Lp-PLA2 in the setting of acute coronary syndrome.

No description available.

Reduction in dopamine receptor D2, has been associated with insufficient brain reward, food addiction, obesity, and type 2 diabetes (T2D). Our aim was to assess whether the genetic variability responsible for this reduction is associated with poor dietary compliance and life style habits in T2D patients. Genetic-analysis was done for 109 T2D individuals who completed a 24-week randomized clinical trial and were assigned to follow either a low-GI or a high-fibre diet. Polymorphisms of TaqIA and C957T were compared with physical and biochemical measures. Regardless of dietary treatments, individuals with the C957T-T allele and the TaqIA-A2 allele were significantly associated with blood pressure reduction. Carriers of the T allele significantly lowered their body mass index (BMI) over the 24-week trial. Our findings suggest that the presence of the TaqIA-A2 allele is associated with a decrease in blood pressure. The C957T-T allele was associated with decrease in pressure and body weight.

Reduction in dopamine receptor D2, has been associated with insufficient brain reward, food addiction, obesity, and type 2 diabetes (T2D). Our aim was to assess whether the genetic variability responsible for this reduction is associated with poor dietary compliance and life style habits in T2D patients. Genetic-analysis was done for 109 T2D individuals who completed a 24-week randomized clinical trial and were assigned to follow either a low-GI or a high-fibre diet. Polymorphisms of TaqIA and C957T were compared with physical and biochemical measures. Regardless of dietary treatments, individuals with the C957T-T allele and the TaqIA-A2 allele were significantly associated with blood pressure reduction. Carriers of the T allele significantly lowered their body mass index (BMI) over the 24-week trial. Our findings suggest that the presence of the TaqIA-A2 allele is associated with a decrease in blood pressure. The C957T-T allele was associated with decrease in pressure and body weight.

ABSTRACT The demand of healthier products is increasing, and more people are more interested of what they eat. Statistics show that the consumption of snacks is rising. Hyperglycemia leads to an increased risk for complications in type II diabetes mellitus. Increased levels of postprandial plasma glucose may also lead to equal or maybe more harmful effects than fasting hyperglycemia. When the levels of postprandial plasma glucose are decreased, the development of cardiovascular complications is delayed, why it is important to lower the snacks consumption especially snacks that brings hunger quickly after they are eaten. Because of these factors, healthier products were developed in this study. The aim was to develop a wafer chocolate product that gives higher satiating effect and healthier blood glucose levels compared to one of Cloetta’s chocolate products. Two raw materials were used, a new carbohydrate and a new fat. The new carbohydrate is a healthier sugar alternative than sucrose, since it leads to lower and prolonged increase in blood glucose and insulin levels. The new fat is based on natural oil that is believed to be healthy, mainly due to its satiating effect. The effects of these two materials on blood glucose response and satiety were examined in two products. Furthermore, the products were made of fat reduced milk chocolate in which sucrose in the chocolate mass was 100 % replaced with the new carbohydrate, dietary fibre and fruit concentrate. Only one of the products contained the new fat. The products, together with Cloetta’s chocolate product were consumed by 17 healthy subjects. Blood glucose response and satiating effect after product intake were examined during a period of 3 days. When blood glucose response was analyzed, a slight indication that the products were relatively healthier than placebo, due to placebo’s unhealthy fluctuations, was found. No clear differences regarding blood sugar maxima were found. Placebo showed, as expected, the highest blood glucose maxima and the largest incremental area under curve, but the maxima of the new fat-lacking product was less than half as high as that of the new fatcontaining product and the area was smaller too, which was not expected. The results regarding the hunger levels were not as expected either since the new fat-lacking product was most satiating while the new fatcontaining product was the least satiating. Despite that, 57 % of the subjects reported they would by such products in the future. Several biases may have played a role in the results, for example whether or not subjects followed the criteria (e.g. lunch time, exercise), stress, worry, individual energy requirement and how serious and focused the subjects were. However, for further research, increasing the new fat content to 3 g, a bigger sized product, different filling, more subjects and more repeats of same measurements is recommended. / SVENSK SAMMANFATTNING Efterfrågan på hälsosammare produkter ökar, och fler människor blir mer intresserade av vad de äter. Statistik visar att konsumtionen av mellanmål ökar. Hyperglykemi leder till en ökad risk för komplikationer i typ II-diabetiker. Ökade nivåer av postprandiell plasmaglukos kan leda till lika eller mer skadliga effekter än fastande hyperglykemi. När nivåerna av postprandiell plasmaglukos är lägre reduceras utvecklingen av kardiovaskulära komplikationer, därför är det viktigt att minska småätandet, speciellt av mellanmål som leder till hunger snart efter att de har ätits. På grund av dessa faktorer har hälsosammare produkter utvecklats i denna studie. Syftet var att utveckla en kexchokladprodukt som har högre mättnadseffekt samt hälsosammare blodsockernivåer jämfört med en av Cloettas chokladprodukter. Två produkter som alternativ till Cloettas chokladprodukter utvecklades. I dessa användes en ny kolhydrat och ett nytt fett. Den nya kolhydraten är ett hälsosammare sockeralternativ än sukros, då den leder till en lägre och förlängd ökning av blodglukos- och insulinnivåer. Det nya fettet är baserat på en naturlig olja som är hälsosam på grund av dess mättande effekt. Effekten av dessa två ämnen undersöktes. Vidare så gjordes de två produkterna av fettreducerad mjölkchoklad i vilken sukros i chokladmassan var 100 % ersatt med den nya kolhydraten, kostfiber samt fruktkoncentrat. endast en av produkterna innehöll det nya fettet. Produkterna, tillsammans med Cloettas chokladprodukt (placebo) konsumerades av 17 friska personer. Blodsockerresponsen och den mättande effekten efter produktintaget undersöktes under 3 timmars period per dag i totalt 3 dagar. När blodglukosrespons analyserades hittades en svag indikation på att produkterna var relativt hälsosammare än placebo, på grund av de ohälsosamma fluktuationerna. Inga klara skillnader med avseende på blodsockermaxima hittades. Placebo visade, som väntat, det högsta blodglukosmaximum och den största arean under kurvan, men maximum för produkten utan det nya fettet var mindre än hälften så högt som det för produkten med det nya fettet och även arean under kurvan var mindre, vilket inte var förväntat. De upplevda hungernivåerna var inte heller som förväntat då produkten som saknar det nya fettet mättade flest personer medan produkten innehållande nya fettet mättade minst antal personer. Trots det så kunde 57 % av deltagarna tänka sig köpa sådana produkter i framtiden. Flera faktorer kan ha påverkat resultatet, till exempel huruvida försökspersonerna följde kriterierna (t.ex. lunchtid, träning), stress, oro, individuella energibehov samt hur allvarliga och fokuserade personerna var när de angav hungernivåerna. För vidare studier rekommenderas ett högre innehåll av det nya fettet (3 g), en större produkt, annorlunda fruktbaserad fyllning och fler deltagare och flera upprepningar av samma mätningar.

Les polyphénols sont des bioproduits générés par le métabolisme des végétaux. Récemment, ils ont attiré l’attention par leur impact potentiellement positif sur la santé, en grande partie lié à leur capacité antioxydante. Ils interviennent également dans les arômes de vin, café, thé… et intéressent donc l’industrie agroalimentaire. Le développement de biocapteurs adaptés à ces molécules est donc nécessaire, tout en respectant certains critères (simplicité d’utilisation, rapidité de la mesure, faible coût). Dans le cas des biocapteurs enzymatiques, l’étape déterminante est l'immobilisation de l’enzyme sur la surface du transducteur sans affecter ses performances.Dans cette thèse nous avons utilisé des matériaux de type « hydroxyde double lamellaires » (HDLs) comme matrice d’immobilisation de la tyrosinase, enzyme reconnaissant spécifiquement les polyphénols, afin de fonctionnaliser la surface d’électrodes d’or sérigraphiées. L’objectif était d’élaborer des microbiocapteurs pour détecter les polyphénols extraits du thé vert.Les HDLs ont été synthétisés par la méthode de coprécipitation directe, puis caractérisés par différentes méthodes physiques (spectroscopies Raman et infrarouge, diffraction des RX) afin de confirmer leur composition et de définir leur structure cristalline. Puis, des films minces bidimensionnels de HDL de différentes compositions ont été réalisés en faisant varier différents paramètres comme la nature du substrat, la concentration de la solution initiale de HDL et la méthode de dépôt (auto-assemblage « SAM » ou spin coating). L’étude morphologique de ces films a été réalisée par microscopie de force atomique (AFM) afin d’optimiser l’état de surface avant l’immobilisation de la tyrosinase. Le greffage de cette dernière a également été étudié par AFM. Enfin, une étude électrochimique (par voltammétrie cyclique et chronoampérométrie) nous a permis de déterminer les caractéristiques analytiques des microbiocapteurs ampérométriques ainsi élaborés. Les résultats ont montré que nos systèmes présentent une grande sensibilité aux polyphénols et sont capables de détecter ces molécules grâce à leur oxydation et aussi à la réduction des composés enzymatiquement générés par la réaction catalytique. Ils sont dynamiques dans une large gamme linéaire de détection (jusqu'à 1000 ng.mL-1) et peuvent également détecter des traces de polyphénols (de m’ordre de quelques pg.mL-1). / Polyphenols are in abundance in diet, being present in various fruits or vegetables, but also in tea or wine. Their antioxidant properties attracted an increasing interest of different researchers in the field of medicine and food manufacturers. Consequently, very intensive studies have been conducted to develop efficient polyphenols biosensors, while respecting certain criteria (simplicity of use, speed of measurement, low cost). In the case of enzymatic biosensors, the decisive step is the immobilization of the enzyme on the transducer surface without affecting its performances.In this thesis, we used layered double hydroxides (LDHs) as a host matrix to immobilize tyrosinase, an enzyme recognizing specifically polyphenols, at the surface of screen printed gold electrodes. Polyphenols used to study the biosensors were extracted from green tea.LDHs nanosheets were prepared by the co-precipitation method. In a first step, their structural properties were characterized by X-ray powder diffraction, Raman and Infra-Red spectroscopies, confirming crystalline phase and chemical composition of LDHs. In a second step, LDHs-thin films were prepared by self-assembly and spin coating deposition under various experimental conditions (nature and concentration of LDHs …), and studied by Atomic Force Microscopy (AFM) to obtain information about the surface morphology of the host matrix before enzyme immobilization. The presence of tyrosinase after the immobilization step was also confirmed by AFM. Electrochemical characteristics of the amperometric biosensors, whose design is based on this study, were determined by cyclic voltammetry and chronoamperometry. This study showed that these systems are highly sensitive to polyphenols, detecting them by their oxidation but also by the reduction of compounds enzymatically generated. They exhibit also other very attractive characteristics for the detection of complex mixture of polyphenols: a large dynamic range (up to 1000 ng.mL-1)and a very low detection limit (few pg.mL-1).

[ES] La electrofisiología extracelular es una técnica ampliamente usada en investigación neurocientífica, la cual estudia el funcionamiento del cerebro mediante la medición de campos eléctricos generados por la actividad neuronal. Esto se realiza a través de electrodos implantados en el cerebro y conectados a dispositivos electrónicos para amplificación y digitalización de las señales. De los muchos modelos animales usados en experimentación, las ratas y los ratones se encuentran entre las especies más comúnmente utilizadas. Actualmente, la experimentación electrofisiológica busca condiciones cada vez más complejas, limitadas por la tecnología de los dispositivos de adquisición. Dos aspectos son de particular interés: Realimentación de lazo cerrado y comportamiento en condiciones naturales. En esta tesis se presentan desarrollos con el objetivo de mejorar diferentes facetas de estos dos problemas. La realimentación en lazo cerrado se refiere a todas las técnicas en las que los estímulos son producidos en respuesta a un evento generado por el animal. La latencia debe ajustarse a las escalas temporales bajo estudio. Los sistemas modernos de adquisición presentan latencias en el orden de los 10ms. Sin embargo, para responder a eventos rápidos, como pueden ser los potenciales de acción, se requieren latencias por debajo de 1ms. Además, los algoritmos para detectar los eventos o generar los estímulos pueden ser complejos, integrando varias entradas de datos en tiempo real. Integrar el desarrollo de dichos algoritmos en las herramientas de adquisición forma parte del diseño experimental. Para estudiar comportamientos naturales, los animales deben ser capaces de moverse libremente en entornos emulando condiciones naturales. Experimentos de este tipo se ven dificultados por la naturaleza cableada de los sistemas de adquisición. Otras restricciones físicas, como el peso de los implantes o limitaciones en el consumo de energía, pueden también afectar a la duración de los experimentos, limitándola. La experimentación puede verse enriquecida cuando los datos electrofisiológicos se ven complementados con múltiples fuentes distintas. Por ejemplo, seguimiento de los animales o miscroscopía. Herramientas capaces de integrar datos independientemente de su origen abren la puerta a nuevas posibilidades. Los avances tecnológicos presentados abordan estas limitaciones. Se han diseñado dispositivos con latencias de lazo cerrado inferiores a 200us que permiten combinar cientos de canales electrofisiológicos con otras fuentes de datos, como vídeo o seguimiento. El software de control para estos dispositivos se ha diseñado manteniendo la flexibilidad como objetivo. Se han desarrollado interfaces y estándares de naturaleza abierta para incentivar el desarrollo de herramientas compatibles entre ellas. Para resolver los problemas de cableado se siguieron dos métodos distintos. Uno fue el desarrollo de headstages ligeros combinados con cables coaxiales ultra finos y conmutadores activos, gracias al seguimiento de animales. Este desarrollo permite reducir el esfuerzo impuesto a los animales, permitiendo espacios amplios y experimentos de larga duración, al tiempo que permite el uso de headstages con características avanzadas. Paralelamente se desarrolló un tipo diferente de headstage, con tecnología inalámbrica. Se creó un algoritmo de compresión digital especializado capaz de reducir el ancho de banda a menos del 65% de su tamaño original, ahorrando energía. Esta reducción permite baterías más ligeras y mayores tiempos de operación. El algoritmo fue diseñado para ser capaz de ser implementado en una gran variedad de dispositivos. Los desarrollos presentados abren la puerta a nuevas posibilidades experimentales para la neurociencia, combinando adquisición elextrofisiológica con estudios conductuales en condiciones naturales y estímulos complejos en tiempo real. / [CA] L'electrofisiologia extracel·lular és una tècnica àmpliament utilitzada en la investigació neurocientífica, la qual permet estudiar el funcionament del cervell mitjançant el mesurament de camps elèctrics generats per l'activitat neuronal. Això es realitza a través d'elèctrodes implantats al cervell, connectats a dispositius electrònics per a l'amplificació i digitalització dels senyals. Dels molts models animals utilitzats en experimentació electrofisiològica, les rates i els ratolins es troben entre les espècies més utilitzades. Actualment, l'experimentació electrofisiològica busca condicions cada vegada més complexes, limitades per la tecnologia dels dispositius d'adquisició. Dos aspectes són d'especial interès: La realimentació de sistemes de llaç tancat i el comportament en condicions naturals. En aquesta tesi es presenten desenvolupaments amb l'objectiu de millorar diferents aspectes d'aquestos dos problemes. La realimentació de sistemes de llaç tancat es refereix a totes aquestes tècniques on els estímuls es produeixen en resposta a un esdeveniment generat per l'animal. La latència ha d'ajustar-se a les escales temporals sota estudi. Els sistemes moderns d'adquisició presenten latències en l'ordre dels 10ms. No obstant això, per a respondre a esdeveniments ràpids, com poden ser els potencials d'acció, es requereixen latències per davall de 1ms. A més a més, els algoritmes per a detectar els esdeveniments o generar els estímuls poden ser complexos, integrant varies entrades de dades a temps real. Integrar el desenvolupament d'aquests algoritmes en les eines d'adquisició forma part del disseny dels experiments. Per a estudiar comportaments naturals, els animals han de ser capaços de moure's lliurement en ambients emulant condicions naturals. Aquestos experiments es veuen limitats per la natura cablejada dels sistemes d'adquisició. Altres restriccions físiques, com el pes dels implants o el consum d'energia, poden també limitar la duració dels experiments. L'experimentació es pot enriquir quan les dades electrofisiològiques es complementen amb dades de múltiples fonts. Per exemple, el seguiment d'animals o microscòpia. Eines capaces d'integrar dades independentment del seu origen obrin la porta a noves possibilitats. Els avanços tecnològics presentats tracten aquestes limitacions. S'han dissenyat dispositius amb latències de llaç tancat inferiors a 200us que permeten combinar centenars de canals electrofisiològics amb altres fonts de dades, com vídeo o seguiment. El software de control per a aquests dispositius s'ha dissenyat mantenint la flexibilitat com a objectiu. S'han desenvolupat interfícies i estàndards de naturalesa oberta per a incentivar el desenvolupament d'eines compatibles entre elles. Per a resoldre els problemes de cablejat es van seguir dos mètodes diferents. Un va ser el desenvolupament de headstages lleugers combinats amb cables coaxials ultra fins i commutadors actius, gràcies al seguiment d'animals. Aquest desenvolupament permet reduir al mínim l'esforç imposat als animals, permetent espais amplis i experiments de llarga durada, al mateix temps que permet l'ús de headstages amb característiques avançades. Paral·lelament es va desenvolupar un tipus diferent de headstage, amb tecnologia sense fil. Es va crear un algorisme de compressió digital especialitzat capaç de reduir l'amplada de banda a menys del 65% de la seua grandària original, estalviant energia. Aquesta reducció permet bateries més lleugeres i majors temps d'operació. L'algorisme va ser dissenyat per a ser capaç de ser implementat a una gran varietat de dispositius. Els desenvolupaments presentats obrin la porta a noves possibilitats experimentals per a la neurociència, combinant l'adquisició electrofisiològica amb estudis conductuals en condicions naturals i estímuls complexos en temps real. / [EN] Extracellular electrophysiology is a technique widely used in neuroscience research. It can offer insights on how the brain works by measuring the electrical fields generated by neural activity. This is done through electrodes implanted in the brain and connected to amplification and digitization electronic circuitry. Of the many animal models used in electrophysiology experimentation, rodents such as rats and mice are among the most popular species. Modern electrophysiology experiments seek increasingly complex conditions that are limited by acquisition hardware technology. Two particular aspects are of special interest: Closed-loop feedback and naturalistic behavior. In this thesis, we present developments aiming to improve on different facets of these two problems. Closed-loop feedback encompasses all techniques in which stimuli is produced in response of an event generated by the animal. Latency, the time between trigger event and stimuli generation, must adjust to the biological timescale being studied. While modern acquisition systems feature latencies in the order of 10ms, response to fast events such as high-frequency electrical transients created by neuronal activity require latencies under $1ms$. In addition, algorithms for triggering or generating closed-loop stimuli can be complex, integrating multiple inputs in real-time. Integration of algorithm development into acquisition tools becomes an important part of experiment design. For electrophysiology experiments featuring naturalistic behavior, animals must be able to move freely in ecologically meaningful environments, mimicking natural conditions. Experiments featuring elements such as large arenaa, environmental objects or the presence of another animals are, however, hindered by the wired nature of acquisition systems. Other physical constraints, such as implant weight or power restrictions can also affect experiment time, limiting their duration. Beyond the technical limits, complex experiments are enriched when electrophysiology data is integrated with multiple sources, for example animal tracking or brain microscopy. Tools allowing mixing data independently of the source open new experimental possibilities. The technological advances presented on this thesis addresses these topics. We have designed devices with closed-loop latencies under 200us while featuring high-bandwidth interfaces. These allow the simultaneous acquisition of hundreds of electrophysiological channels combined with other heterogeneous data sources, such as video or tracking. The control software for these devices was designed with flexibility in mind, allowing easy implementation of closed-loop algorithms. Open interface standards were created to encourage the development of interoperable tools for experimental data integration. To solve wiring issues in behavioral experiments, we followed two different approaches. One was the design of light headstages, coupled with ultra-thin coaxial cables and active commutator technology, making use of animal tracking. This allowed to reduce animal strain to a minimum allowing large arenas and prolonged experiments with advanced headstages. A different, wireless headstage was also developed. We created a digital compression algorithm specialized for neural electrophysiological signals able to reduce data bandwidth to less than 65.5% its original size without introducing distortions. Bandwidth has a large effect on power requirements. Thus, this reduction allows for lighter batteries and extended operational time. The algorithm is designed to be able to be implemented in a wide variety of devices, requiring low hardware resources and adding negligible power requirements to a system. Combined, the developments we present open new possibilities for neuroscience experiments combining electrophysiology acquisition with natural behaviors and complex, real-time, stimuli. / The research described in this thesis was carried out at the Polytechnic University of Valencia (Universitat Politècnica de València), Valencia, Spain in an extremely close collaboration with the Neuroscience Institute - Spanish National Research Council - Miguel Hernández University (Instituto de Neurociencias - Consejo Superior de Investigaciones Cientí cas - Universidad Miguel Hernández), San Juan de Alicante, Spain. The projects described in chapters 3 and 4 were developed in collabo- ration with, and funded by, Open Ephys, Cambridge, MA, USA and OEPS - Eléctronica e produção, unipessoal lda, Algés, Portugal. / Cuevas López, A. (2021). Development of Advanced Closed-Loop Brain Electrophysiology Systems for Freely Behaving Rodents [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/179718 / TESIS

This thesis aims to create effective and comprehensive learning materials for students enrolled in the Switching Theory and Digital Design course. The lab is designed to enable students to program an FPGA using VHDL in the Quartus programming environment to control traffic intersections with sensors and traffic signals. This laboratory aims to provide students with practical experience in digital engineering design and help them develop the necessary skills to program and implement state machines for regulating traffic environments

Model predictive control is a popular research focus in electric motor control as it allows designers to specify optimization goals and exhibits fast transient response. Availability of faster and more affordable computers makes it possible to implement these algorithms in real-time. Real-time implementation is not without challenges however as these algorithms exhibit high computational complexity. Field-programmable gate arrays are a potential solution to the high computational requirements. However, they can be time-consuming to develop for. In this thesis, we present a methodology that reduces the size and development time of field-programmable gate array based fixed-point model predictive motor controllers using automated numerical analysis, optimization and code generation. The methods can be applied to other domains where model predictive control is used. Here, we demonstrate the benefits of our methodology by using it to build a motor controller at various sampling rates for an interior permanent magnet synchronous motor, tested in simulation at up to 125 kHz. Performance is then evaluated on a physical test bench with sampling rates up to 35 kHz, limited by the inverter. Our results show that the low latency achievable in our design allows for the exclusion of delay compensation common in other implementations and that automated reduction of numerical precision can allow the controller design to be compacted. / Thesis / Master of Applied Science (MASc)

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.