Epidemiological studies on comorbidity, heritability and co-aggregation in organ-specific autoimmune diseases

Autoimmunity is caused by loss of tolerance, whereby the immune system fails to distinguish self from non-self. The autoimmune panorama entails more than 100 diseases that collectively affect close to 5% of the total population, with a higher prevalence in women than in men. Depending on which tissues are targeted, autoimmunity is classified as organ-specific or systemic. For unknown reasons, organ-specific autoimmunity often targets the endocrine system, leading to organ failure and lifelong need of hormone replacement. Most autoimmune diseases show familial clustering, but co-aggregation of different disorders in family members, and co-occurrence of multiple diseases in a single individual, is also common. This points to shared etiologies in autoimmunity. Twin studies can help explain to what extent genetic and environmental influences contribute to differences in traits, and can thus provide a framework for genetic studies. In autoimmunity, twin studies have helped explain genetic contributions (heritability) for some diseases, but for many they are still lacking. In other scientific fields, twin studies have also been used to shed light on disease overlap, but no attempts of explaining clustering of autoimmunity using twins have been published. In this thesis we explore different aspects of organ-specific autoimmunity. In Study I, we use the Swedish Twin Registry to demonstrate that the heritability for Addison’s disease is very high, making it suitable for further genetic studies. In Study II we use national health registries to explore cardiovascular morbidity for Addison’s disease, and show that women are at increased risk of cardiac events. We also demonstrate a dose-dependent correlation between adrenal hormone replacement-therapy and risk of cardiovascular disease. Study III addresses genetic versus non-genetic components to clustering in seven autoimmune diseases, and we find evidence of genetic factors explaining co-aggregation. In Study III we also validate previous estimates of heritability in autoimmunity by using a larger cohort of twins than ever before used. In Study IV, we take a closer look at Hashimoto’s thyroiditis and Graves’ disease, again using twins. Results imply that they are distantly related diseases, in contrast with current dogma. We also find that heritability is higher in men than in women, most notably for Hashimoto’s thyroiditis. This could mean that the mechanisms leading to disease differ between the sexes

EN VIRKELIGHED BAG VIRKELIGHEDEN – UTOPIEN SET FRA ET FÆNOMENOLOGISK PERSPEKTIV

Der sigtes i artiklen mod en dybere forståelse af tid og dens rolle i menneskets daglige liv. En traditionel forståelse af utopi som noget negativt udfordres, og det forsøges belyst, hvordan en konstant ‘forudgriben’ af mere eller mindre realistisk karakter forekommer som en naturlig del af ens orientering i verden (her benævnt som mikro-utopiske projekter). Og at denne forudgriben endda virker åbnende for muligheder i fremtiden, som ellers ikke ville have manifesteret sig. Til dette formål benyttes to cases – terapi og religiøsitet. Inden for begge disse områder ses der måder at orientere sig og gribe tingene an på, som bliver befordrende for, at nye muligheder i fremtiden bliver synlige eller åbner sig. Muligheder, som ellers ville være forblevet usynlige eller umulige – forstået på den måde, at de først opstår som muligheder, efter at en ny orientering mod fremtiden er begyndt. Der argumenteres ved hjælp af Kierkegaard for, at netop denne oscillation – denne uophørlige refleksion – mellem det, der er, det, der kunne ske, og det, som allerede er sket – hvor alle tre tidslige domæner hele tiden påvirker hinanden – er den menneskelige eksistens’ udgangspunkt og på den måde kilde til både alle vores muligheder og vores udfordringer. Således giver en dybere forståelse af utopi-begrebet forøgede muligheder for at forstå den menneskelige væren

DET HELLIGE ER LIVETS SVAR PÅ ET PASSENDE STILLET SPØRGSMÅL

Spørgsmålet om det helliges eksistens knyttes sammen med spørgsmålet om erkendelsen og beskrivelsen af det hellige, og det hævdes, at det ikke giver mening at beskrive eksistensen uden at have afklaret, hvad sproget kan og ikke kan indfange. Universet beskrives som et system af ufattelig kompleksitet, der kan reflektere over sig selv, og på den måde »ganger« sin kompleksitet op. Gennem en redegørelse for Batesons tænkning beskrives det hellige som det fænomen at gensidigt uafhængige dele, som ellers ikke kan hænge sammen, bliver afhængige af hinanden, midlertidigt eller permanent. Til sidst foreslås det, at det religiøse kan forstås som mulige svar på passende henvendelser, ligesom frø, der spirer under passende omstændigheder. På den måde bliver forholdet mellem eksistensen af det religiøse og beskrivelsen af det endnu mere central, da dette forhold både kan slippe det religiøse fri og spærre det inde. Det hellige blomstrer kun, hvis der er nogen til at vande det – ligesom kærligheden

Adaptive Layer Height During DLP Materials Processing

The aim of this research is to show how manufacturing speeds during vat polymerisation can be vastly increased through an adaptive layer heightstrategy that takes the geometry into account through analysis of the relationship between layer height, cross-section variability and surface structure. This allows for considerable process speedup during the Additive Manufacture of components that contain areas of low cross-section variability, at no loss of surface quality. The adaptive slicing strategy was tested with a purpose built vat polymerisation system and numerical engine designed and constructed to serve as a Next-Gen technology platform. By means of assessing hemispherical manufactured test specimen and through 3D surface mapping with variable-focus microscopy and confocal microscopy, a balance between minimal loss of surface quality with a maximal increase of manufacturing rate has been identified as a simple angle-dependent rule. The achievable increase in manufacturing rate was above 38% compared to conventional part slicing.Published versio

A Self-Peeling Vat for Improved Release Capabilities During DLP Materials Processing

This paper describe research to increase the competitiveness of vat polymerisation by increasing the manufacturing rate while lowering the normal forces that induce part stress during the lift procedure of vat based systems. This is achieved through introducing a polymerisation vat that allows for an eased release of the manufactured part from the vat by means of a flexible membrane system. A membrane of fluorinated ethylene polymer will through elastic deformation automatically peel off the part as the part is lifted during layer changes. Peeling has been qualified by means of a truncated inverted cone as test geometry. As the cross-sectional diameter of the cone increase throughout the build-job, the geometry will release from the glass based build platform at the point where the peeling force exceed the adhesion force between platform and part. At failure point the lateral surface area of the top and bottom of the truncated cone is used as a measure of the performance of the vat with respect to release-capability. This has been tested at increasing manufacturing rates. The new self-peeling vat outperformed industrial state-of-the-art vats by 814% percent.Published versio