BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is a widely used imaging modality in HNSCC.PurposeTo provide evident data about associations between 18F-FDG PET and histopathology in HNSCC.Material and MethodsThe MEDLINE database was screened for associations between maximum standard uptake values (SUVmax) derived from 18F-FDG PET and histopathological features in HNSCC up to May 2020. Only papers containing correlation coefficients between SUVmax and histopathology were acquired. Overall, 23 publications were collected.ResultsThe following correlations were calculated: KI 67: 12 studies (345 patients), pooled correlation coefficient (PCC): 0.23 (95% confidence interval [CI] 0.06–0.40); hypoxia-inducible factor-1α: eight studies (240 patients), PCC: 0.24 (95% CI 0.06–0.42); microvessel density: three studies (64 patients), PCC: 0.33 (95% CI 0.02–0.65); vascular endothelial growth factor: two studies (59 cases), PCC: 0.27 (95% CI 0.02–0.51); tumor suppressor protein p53: four studies (159 patients), PCC: 0.05 (95% CI –0.41 to 0.51); epidermal growth factor receptor: two studies (124 patients), PCC: 0.21 (95% CI 0.05–0.37); tumor cell count: three studies (67 patients), PCC: 0.18 (95% CI –0.06 to 0.42); tumor cell apoptosis: two studies (40 patients), PCC: 0.07 (95% CI = –0.85 to 0.99); B-cell lymphoma-2 protein: two studies (118 patients); PCC: 0.04 (95% CI –0.65 to 0.74); glucose-transporter 1: 10 studies (317 patients), PCC: 0.20 (95% CI 0.10–0.30).ConclusionSUVmax derived from 18F-FDG PET cannot reflect relevant histopathological features in HNSCC.

A common task in data science at internet companies is to develop metrics that capture aspects of the user experience. In this thesis, we are interested in systems of measurement variables without direct causal relations such that covariance is explained by unobserved latent common causes. A framework for modeling the data generating process is given by Neuro-Causal Factor Analysis (NCFA). The graphical model consists of a directed graph with edges pointing from the latent common causes to the measurement variables; its functional relations are approximated with a constrained Variational Auto-Encoder (VAE). We refine the estimation of the graphical model by developing an MCMC algorithm over Bayesian networks from which we read marginal independence relations between the measurement variables. Unlike standard independence testing, the method is guaranteed to yield an identifiable graphical model. Our algorithm is competitive with the benchmark, and it admits additional flexibility via hyperparameters that are natural to the approach. Tuning these parameters yields superior performance over the benchmark. We train the improved NCFA model on Spotify user behavior data. It is competitive with the standard VAE on data reconstruction with the benefit of causal interpretability and model identifiability. We use the learned latent space representation to characterize clusters of Spotify users. Additionally, we train an NCFA model on data from a randomized control trial and observe treatment effects in the latent space. / En vanlig uppgift för en data scientist på ett internetbolag är att utveckla metriker som reflekterar olika aspekter av användarupplevelsen. I denna uppsats är vi intresserade av system av mätvariabler utan direkta kausala relationer, så till vida att kovarians förklaras av latenta gemensamma orsaker. Ett ramverk för att modellera den datagenererande processen ges av Neuro-Causal Factor Analysis (NCFA). Den grafiska modellen består av en riktad graf med kanter som pekar från de latenta orsaksvariablerna till mätvariablerna; funktionssambanden uppskattas med en begränsad Variational Auto-Encoder (VAE). Vi förbättrar uppskattningen av den grafiska modellen genom att utveckla en MCMC algoritm över Bayesianska nätverk från vilka vi läser de obetingade beroendesambanden mellan mätvariablerna. Till skillnad från traditionella oberoendetest så garanterar denna metod en identifierbar grafisk modell. Vår algoritm är konkurrenskraftig jämfört med referensmetoderna, och den tillåter ytterligare flexibilitet via hyperparametrar som är naturliga för metoden. Optimal justering av dessa hyperparametrar resulterar i att vår metod överträffar referensmetoderna. Vi tränar den förbättrade NCFA modellen på data om användarbeteende på Spotify. Modellen är konkurrenskraftig jämfört med en standard VAE vad gäller rekonstruktion av data, och den tillåter dessutom kausal tolkning och identifierbarhet. Vi analyserar representationen av Spotify-användarna i termer av de latenta orsaksvariablerna. Specifikt så karakteriserar vi grupper av liknande användare samt observerar utfall av en randomiserad kontrollerad studie.

The primary objective of this dissertation is to revisit the CAPM and the Fama-French multi-factor models with a view to evaluate the validity of the probabilistic assumptions imposed (directly or indirectly) on the particular data used. By thoroughly testing the assumptions underlying these models, several departures are found and the original linear regression models are respecified. The respecification results in a family of heterogeneous Student's t models which are shown to account for all the statistical regularities in the data. This family of models provides an appropriate basis for revisiting the empirical adequacy of the CAPM and the Fama-French multi-factor models, as well as other models, such as alternative asset pricing models and risk evaluation models. Along the lines of providing a sound basis for reliable inference, the respecified models can serve as a coherent basis for selecting the relevant factors from the set of possible ones. The latter contributes to the enhancement of the substantive adequacy of the CAPM and the multi-factor models. / Ph. D. / The primary objective of this dissertation is to revisit the CAPM and the FamaFrench multi-factor models with a view to evaluate the validity of the probabilistic assumptions imposed (directly or indirectly) on the particular data used. By probing for potential departures from the Normality, Linearity, Homoskedasticity, Independence, and t-invariance assumptions, it is shown that the assumptions implicitly imposed on these empirical asset pricing models are inappropriate. In light of these results, the probabilistic assumptions underlying the CAPM and the Fama-French multi-factor models are replaced with the Studentís t, Linearity, Heteroskedasticity, Markov Dependence, and t-heterogeneity assumptions. The new probabilistic structure results in a family of heterogeneous Studentís t models which are shown to account for all the statistical regularities in the data. This family of models provides an appropriate basis for revisiting the empirical adequacy of the CAPM and the Fama-French multifactor models, as well as other models, such as alternative asset pricing models and risk evaluation models. Along the lines of providing a sound basis for reliable statistical inference results, the proposed models can serve as a coherent basis for selecting the potential sources of risk from a set of possible ones. The latter contributes to the enhancement of the substantive adequacy of the CAPM and the multi-factor models.

Insulin-like growth factor-I is a small growth factor known to signal in a variety of mammalian cells through the IGF-I cell surface receptor (IGF-IR). A unique feature of the IGF-I system is the regulation of this binding by soluble IGF binding proteins. Recent studies from our laboratory show that there is a pH dependence in the association of IGF-I with the cell surface in the presence of IGFBP-3 which suggested increased association of IGF-I with IGFBP-3 at low pH. We studied cell free interaction of IGF-I and IGFBP-3 as a function of pH using surface plasmon resonance (SPR) in order to understand the mechanism that causes the increased association. In our studies three different SPR instruments with different surfaces for immobilization of one of the binding partners were used: a Leica Bio-SPR 9000 with a low molecular weight carboxymethylated dextran (CMD) surface, a BIAcore 2000 with a high molecular weight CMD surface and a Leica SPR 2001 Alpha with a planar mixed self-assembled monolayer (mSAM) surface. Since the experimental system we used was transport sensitive, only the mSAM surface, under optimized conditions, produced results that fit to a single site model. Results suggest that use of CMD layers for immobilization of one partner of a high-affinity binding complex can result in transport limited binding for which simple analysis is inappropriate. Future studies are planned to expand the work with the mSAM surface to elucidate whether a significant difference between the binding parameters as a function of pH exists. / Master of Science

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Factor VIII, a component of the intrinsic pathway of blood coagulation, has yet to be purified to homogeneity. It appears that, in vivo, the factor VIII coagulant protein is closely associated with one or more other proteins (factor VHI-related antigen and platelet aggregating factor). The material normally isolated from bovine plasma as 'factor VIII' possesses all three activities and is therefore either a mixture or a complex of the various proteins. In the present study, bovine factor VIII:C was purified approximately fivethousand- fold by a combination of ion-exchange chromatography and fractional precipitation. The factor VIII coagulant activity can be separated from the other activities of the 'factor VIII complex' but the procedures involved are not suitable for preparative use as the factor VIII:C which is obtained is unstable. During coagulation, factor VIII:C is required during the activation of factor X. Studies with purified bovine clotting factors indicate that factor IX_a is the enzyme responsible for the cleavage of factor X, in a calcium-dependent reaction which is stimulated by phospholipid. Factor VIII:C further accelerates the rate at which factor X_a is generated. Preliminary investigations of the kinetic parameters of the reaction indicate that the stimulation by factor VIII:C occurs through a marked increase in the V_max of the reaction; factor VIII:C does not affect the K_m for factor X. The coagulant activity of factor VIII is enhanced by exposure to thrombin, but the 'activated' factor VIII:C which is produced is not itself capable of activating factor X in the absence of factor IX_a. Thus, the 'activation' of factor VIII:C, in contrast to the activation of, for example, factors IX and X, does not appear to result in the formation of an enzyme. That is, factor VIII:C is a non-enzymic, high molecular weight cofactor for factor IX_a.

This thesis investigates a newly developed term coined by the author called generalized identification, which is the tendency that people who identify high with one group tend to identify high with other groups as well, and how personality variables from the Five-Factor model may relate to this tendency. A common component of identification towards 10 preselected groups was calculated (N = 148), with a principal component analysis. The result reveal that the generalized identification account for 41 % of the total variance. A stepwise multiple regression analysis further showed that Openness to Experience and Agreeableness from the Five-Factor model explained 26 % of the variance in the generalized identification. However, due to low reliability when measuring personality traits, the relationship between personality and generalized identification could not be interpreted in a satisfying way, and it needs to be further explored before drawing firm conclusions.

Roundabout installations are becoming common practice among DOTs and other local governments due to their superior safety attributes compared to other conventional at-grade intersections, especially stop-control and uncontrolled intersections. Current U.S. national guidelines for roundabout illumination recommend systematic illumination for all roundabouts. This recommendation might become a potential hindrance to desired widespread installations due to implied financial costs, especially in rural areas because the competing stop-control and uncontrolled intersections can be kept unlit. Interestingly rural roundabouts in most countries around the world are not illuminated as indicated by a recent survey of international roundabout illumination policies and standards from 45 countries. Also, review of intersection safety literature does not identify any publication that supports a systematic illumination policy of U.S. roundabouts. In fact, despite this recommendation there is no quantitative research on influence of illumination levels on nighttime safety at roundabouts and little on conventional intersections. Conversely, the literature shows a significant number of published studies which have indicated that currently recommended illumination levels on roadways can be reduced without compromising nighttime safety. This dissertation evaluates the link between roundabout crashes and different illumination levels. At the beginning of this dissertation research, there was no available repository of quantitative intersection illumination levels which could be used in highway safety research. Also, existing protocols for measurement require expensive light meters and are extremely time consuming to follow, making them impractical to use to study a large number of intersections. Consequently, this dissertation first evaluates the relationship with the best available data. The best available intersection illumination data was obtained from the Minnesota data contained in the Highway Safety Information System (HSIS). Minnesota crash and illumination data from 2003 to 2010 were analyzed. This illumination data was a qualitative description of intersection illuminating schemes and/or luminaire arrangement. Therefore, this dissertation also developed a cost-effective, accurate, and rapid method for measurement of quantitative intersection illumination data, and applied the developed protocol to a case study in Georgia. The measured intersection illumination was analyzed together with crash data obtained from GDOT for 2009 to 2014. The results of a naive analysis on the best available data indicated among other findings that the presence of lighting can provide approximately 61 percent lower total nighttime crash rate compared to the unlit condition. Also, providing illumination to the roundabout circle alone can yield about 80 percent of the benefits (55 percent reduction from unlit condition) of illuminating both the roundabout circle and approaches (66 percent reduction from unlit condition). Field test results for the camera calibration indicate that the average intersection illuminance derived from the protocol is within 4 percent difference of the actual average intersection illumination estimated from following the existing protocols. Next, despite limited roundabout data and potential issues of selection bias which could not be addressed in this dissertation, a cautious roundabout illumination specific crash modification factor was estimated with a negative binomial regression model. The model results showed that an increase of 1 lux in average roundabout illuminance will result in a 4.72 percent reduction in expected number nighttime crashes. The results of this work are useful in creating a sound framework for DOTs and other transportation agencies to determine the most appropriate level of illumination for roundabouts. This study also makes a number of significant contributions to highway safety research. First, this work is the first quantitative study on the impact of illumination on safety at roundabouts. The status-quo for highway safety research regarding the impacts of illumination had been to treat road lighting as a binary (Lit/Unlit) variable. However, even in most places without purposely-built road lighting there is usually ambient lighting from abutting facilities such as a gas stations or a store. Second, this dissertation is the first documented application of the photographic method to roundabouts. It is also the first documented application of the photographic method’s camera specific constant calibration approach to transportation field measurements. Previous documented application of the photographic method to transportation field measurements used an exposure specific calibration approach. Unlike the camera specific constant calibration approach, the exposure specific approach is rigid and field measurements must always be done at the exposure settings used in calibrating the camera. Thirdly, this work demonstrates the first developed procedure to developing uniformity (contour) plots from the photographic method. Next, this work can serve as the basis for initial efforts to create an illumination specific quantitative crash modification factor. Currently, the Highway Safety Manual is lacking in this important safety parameter. Last, but not the least this work offers procedures for collecting luminance data from the field and also documents a database of intersection illumination levels and intersection characteristics which can be used by future research.

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