Indiana University-Purdue University Indianapolis (IUPUI) / Background: Tobacco use is associated with an increased risk of developing Alzheimer's disease (AD). 14% of the incidence of AD is associated with various types of tobacco exposure. Additional real-world evidence is warranted to reveal the association between tobacco use and AD in age/gender-specific subpopulations. Method: In this thesis, the relationships between diagnoses related to tobacco use and diagnoses of AD in gender- and age-specific subgroups were investigated, using health information exchange data. The non-parametric Kaplan-Meier method was used to estimate the incidence of AD. Furthermore, the log-rank test was used to compare incidence between individuals with and without tobacco related diagnoses. In addition, we used semi-parametric Cox models to examine the association between tobacco related diagnoses and diagnoses of AD, while adjusting covariates. Results: Tobacco related diagnosis was associated with increased risk of developing AD comparing to no tobacco related diagnosis among individuals aged 60-74 years (female hazard ratio [HR] =1.26, 95% confidence interval [CI]: 1.07 – 1.48, p-value = 0.005; and male HR =1.33, 95% CI: 1.10 - 1.62, p-value =0.004). Tobacco related diagnosis was associated with decreased risk of developing AD comparing to no tobacco related diagnosis among individuals aged 75-100 years (female HR =0.79, 95% CI: 0.70 - 0.89, p-value =0.001; and male HR =0.90, 95% CI: 0.82 - 0.99, p-value =0.023). Conclusion: Individuals with tobacco related diagnoses were associated with an increased risk of developing AD in older adults aged 60-75 years. Among older adults aged 75-100 years, individuals with tobacco related diagnoses were associated with a decreased risk of developing AD.

Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation—if any—remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and -sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and -sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.

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Nanocellulose is a sustainable material and has shown interesting properties in various applications. One such application is Pickering emulsion, where the nanocellulose stabilizes the oil and water interface. Thus, this project aimed to evaluate a new type of nanocellulose, cellulose oxalate (COX), derived from different sources, dissolving pulp and bark, as a potential emulsifier. The properties of the nanocellulose, such as the chemical composition, morphology, aspect ratio, viscosity, and surface tension, are analyzed to determine how it affects the Pickering emulsion. Pectin has reported having emulsifying properties. Therefore, pectin derived from the bark was also studied as a potential emulsifier.  The emulsion capacity and emulsion stability of the Pickering emulsion were estimated. Additionally, the emulsions were observed and visualized in an optical microscope, and it showed that all Pickering emulsions were successful. The COX and pectin particles were successfully adsorbed at the interface to form individual droplets which were stable enough not to coalescence. With the images from AFM, the aspect ratio and morphology of the particles were measured. COX pulp had an average width of 5.5 nm and an average length of 372 nm. COX bark had an average width of 3.9 nm and an average length of 257 nm. Notably, COX pulp does have a slightly higher aspect ratio than COX bark. DLS was another way the particle size was measured. However, it was not a suitable technique because both COX did indicate a relatively polydisperse system and are therefore not suitable to be measured by DLS. Furthermore, the viscosity of the COX pulp and COX bark suspensions were measured with an Ubbelohde capillary viscometer which was not an ideal method because the COX suspensions were too thick and gel-like for the instrument and got clogged constantly. As expected, the surface tension decreased steadily, more so for COX pulp than COX bark with increasing concentration. Then again, this means that COX has a hydrophobic property that does reduce the surface tension of water. Lastly, the carbohydrate analysis did indicate that both COX do have a high amount of glucose. Moreover, both COX did also show a significant amount of other components.  Overall, this study does conclude that COX pulp, COX bark, and pectin did stabilize the Pickering emulsion to some degree, despite being inconsistent and can therefore be considered effective emulsifiers. / Nanocellulosa är ett hållbart material som har visat intressanta egenskaper i olika applikationer. En specifik applikation är Pickering emulsion, där nanocellulosan stabiliserar gränsytan mellan olje-och vatten fasen. Därav var syftet med detta projekt att utvärdera en ny typ av nanocellulosa, cellulosaoxalat (COX) producerad från olika källor såsom förhandlad pappersmassa och bark som ett potentiellt emulgeringsmedel. De olika egenskaperna hos nanocellulosan dvs. den kemiska sammansättningen, morfologin, partikelstorlek, viskositet och ytspänning undersöktes för att bestämma hur de påverkar Pickering emulsionen. Pektin har också rapporterats att ha emulgerande egenskaper. Därför studerades även pektin producerad från bark som ett potentiellt emulgeringsmedel.  Emulsionskapaciteten och emulsionsstabiliteten hos Pickering emulsionen uppskattades. Dessutom observerades och visualiserades emulsionerna i ett optiskt mikroskop som visade att alla Pickering emulsioner var successiva. Det innebär att COX- och pektinpartiklarna adsorberades successivt vid gränsytan för att bilda individuella droppar som var stabila nog att inte koalescensera. Med hjälp av bilderna från AFM mättes storleken på partiklarna och dess morfologi bestämdes. COX-massa hade en genomsnittlig bredd på 5,5 nm en medellängd på 372 nm. COX-bark hade en genomsnittlig bredd på 3,9 nm och en medellängd på 257 nm. Från resultatet, kan det noteras att COX-massa har något större partikelstorlek är COX-bark. DLS var ett annat sätt att mäta partikelstorleken. Dock, var det inte en lämplig teknik eftersom både COX-massa och COX-bark visade ett relativt polydisperst system och är därav inte lämplig att mättas i DLS. Vidare så mättes viskositeten för COX-massa och COX-bark med en Ubbelohde kapillärviskometer, vilket inte heller var en idealisk metod att mäta med eftersom COX lösningen var för tjock och gel-liknande och täppte till instrumentet. Däremot, som förväntad minskades ytspänningen stadigt med ökande koncentration. Detta var mer tydligt hos COX- massa än COX-bark. Oavsett så betyder det att COX har en hydrofob egenskap som minskar ytspänningen hos vatten. Sist men inte minst så indikerade kemiska sammansättningsanalysen att båda COX har en stor mängd glukos. De har även en betydande mängd av andra komponenter.  Sammantaget drar denna studie slutsatsen att COX-massa, COX-bark och pektin stabiliserade Pickering emulsionen till en viss del relativt väl, trots att det var inkonsekvent så anses de vara effektiva emulsionsmedel.

Indiana University-Purdue University Indianapolis (IUPUI) / The counting process is the fundamental of many real-world problems with event data. Poisson process, used as the background intensity of Hawkes process, is the most commonly used point process. The Hawkes process, a self-exciting point process fits to temporal event data, spatial-temporal event data, and event data with covariates. We study the Hawkes process that fits to heterogeneous drug overdose data via a novel semi-parametric approach. The counting process is also related to survival data based on the fact that they both study the occurrences of events over time. We fit a Cox model to temporal event data with a large corpus that is processed into high dimensional covariates. We study the significant features that influence the intensity of events.