Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL). FL is clinically designated as an indolent disease with a long median survival of 8-10 years. However, the clinical and biological behavior of FL shows considerable variability, with some patients showing aggressive disease progression and very short survival. Because defects in the regulation of apoptotic cell death are fundamental in FL pathogenesis, we hypothesized that deregulated expression of components of the pRb signaling pathway may promote cell proliferation, thereby complementing antecedent anti-apoptotic mutations and producing more aggressive disease. In the present study we undertook an immunohistochemical (IHC) evaluation of expression of key cell-cycle regulatory proteins in diagnostic biopsies from 127 cases of FL using formalin-fixed, paraffin-embedded tissues (FFPE) in tissue microarray (TMA) sections immunostained for p53, pRb, p16INK4A and cyclin D3. Data analysis revealed that increased abundance of p53 or p16INK4A is associated with reduced overall survival (OS) (p=0.005 and p=0.014 respectively), and with conventional pathological markers of tumour aggressiveness including high histologic grade. Encouraged by this remarkable finding of a counterintuitive association between p16INK4A expression and clinical outcome, we analyzed CDKN2A gene deletion and methylation, as these are the most frequent mechanisms of the CDKN2A gene inactivation in NHL including FL. We determined the deletion and methylation status of CDKN2A in 105 FL cases. Laser-capture microdissection was used to enrich the samples for lymphoma cells. CDKN2A was deleted in 9 cases and methylated in 22 cases. The 29 cases (28%) with CDKN2A deletion or methylation had decreased overall survival (OS) (p=0.046) in all cases and in cases treated with rituximab (p<0.001). Our findings indicate that deleterious alterations of CDKN2A are relatively prevalent in FL at diagnosis and can predict poor clinical outcome. In summary, our data reveal novel insights into the pathogenesis of FL and suggest a relationship between increased p16INK4A expression and CDKN2A deletion or methylation and unfavorable clinical outcome in FL. We hope that the work presented herein will provide a useful prognostic tool for predicting the prognosis and choosing optimal treatment approaches to help patients suffering from FL. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2013-03-12 23:49:44.541

Personalized medicine can be an approach to address the unsatisfactory treatment outcomes in inflammatory conditions such as cancer, arthritis, and cardiovascular diseases. A common feature of chronic diseases is the infiltration of pro-inflammatory macrophages at the disease loci. Infiltrating macrophages have been previously utilized for disease diagnosis. These features suggest that macrophages can be broadly applicable targets for simultaneous therapy and diagnosis. Cyclooxygenase-2 (COX-2), an enzyme involved in the biosynthesis of a lipid inflammatory mediator, prostaglandin E2 (PGE2), is over expressed in macrophages infiltrating the pathological site. Inhibition of PGE2 leads to reduced inflammation, pain and macrophage infiltration. To utilize macrophages for the purpose of simultaneous therapy and diagnosis, we proposed to integrate therapeutic and imaging capabilities on a single nanomedicine platform, referred as theranostics. A stable 19F MRI visible nanoemulsion platform was developed, incorporating celecoxib for COX-2 inhibition and near-infrared fluorescent dye(s) for fluorescence imaging. We hypothesized that inhibition of COX-2 in macrophages using a theranostic nanoemulsion will reduce the inflammation (and pain), and that this response can be visualized by monitoring changes in macrophage infiltration. In vitro characterization demonstrated that the theranostic displays excellent stability with no toxicity, and significant uptake in macrophages. Furthermore, it delivers celecoxib to macrophages and reduces PGE2 production from these cells. In vivo studies in a murine paw inflammation model showed nanoemulsion presence at the inflamed site, specifically in COX-2 expressing macrophages compared to neutrophils. Supporting our hypothesis, celecoxib delivered through a nanoemulsion demonstrated time-dependent reduction in fluorescence from the inflamed paw, indicative of reduced macrophage infiltration. In a neuropathic pain model, celecoxib delivered to macrophages led to reduced pain concomitant with reduced macrophage infiltration at the inflamed site compared to free drug control (cross reference: Kiran Vasudeva, Dissertation, 2015). In conclusion, inhibition of COX-2 in macrophages using theranostic nanoemulsions proves to be an effective and generalized strategy facilitating simultaneous therapy and diagnosis, which can be applied to many chronic diseases. The diagnostic information during therapy can be used to tailor the treatment and reduce patient variability leading to personalized medicine. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences; / Pharmaceutics / PhD; / Dissertation;

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research. (C) 2017 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

The use of online personalized advertisements has drawn attention among firms, in efforts of acquiring and maintaining competitive advantage. By collecting individual consumer information, firms are able to personalize advertisements to specific individuals in online contexts. The collection and use of individuals’ personal information have given rise to privacy concerns among consumers. However, contemporary research displays disparate conclusions regarding the extent to which these privacy concerns influence the effectiveness of online personalized advertisements. In order to provide insights regarding this discrepancy, this study explored the theoretical foundations of consumer perceived benefits and risks, upon which contemporary research was based. Two focus groups were conducted to explore how consumers perceive benefits and risks of online personalized advertisements. Using pattern matching, the interpretation of the empirically gathered material implied that consumer perceived benefits, in form of perceived relevance, appears to be insufficient in appealing to the interests and preferences of consumers. Instead, consumers’ perceptions of relevance appear to be dependent on several elements. Furthermore, the findings imply that consumers are aware of the risks through personal information disclosure, yet appear to be unconcerned by them. Instead, consumers seem to possess a sense of hopelessness in online environments, that attempts to restrict the availability of their personal information are pointless.

In recent years, personalized learning has become a buzzword in the field of education and an approach that schools across the United States have adopted in their attempts to account for the diverse interests, aspirations, and needs of their students. Despite the growing interest in personalized learning, there is a dearth of empirical research on this educational approach, particularly as it relates to the student experience. Given the paucity of research in this area, little is known about the extent to which personalized learning can offer students a more beneficial quality of experience than traditional educational methods. This question is further complicated by the fact that personalized learning has been defined and put into practice in diverse ways. Given these conditions, the purpose of this study was to explore students' experiences with more humanistic forms of personalized learning at three high schools in Vermont. A pragmatic approach to qualitative research was used along with self-determination theory (SDT) as a framework to investigate students' perceptions of their autonomy, competence, relatedness, motivation, and well-being within the context of personalized learning. SDT was used as framework because it offers a lens for analyzing how social contexts affect people's experiences and proposes that individuals experience higher qualities of motivation, engagement, and performance when their basic psychological needs for autonomy, competence, and relatedness are met. Study findings, which are based on interviews with 28 students from three Vermont high schools, suggest participants generally felt autonomous, competent, and related in their personalized learning environments, which contributed to their intrinsic motivation, engagement, and well-being within these settings. Some features of personalized learning that supported multiple facets of students' basic psychological needs were the individualized nature of instruction, student-driven curriculum, and structures that enabled and supported community-based learning. Although many students suggested personalized learning supported their basic psychological needs, some struggled to direct and manage their own learning, which diminished their feelings of competence while others indicated that the individualized nature of their projects undermined their sense of relatedness to their peers. Overall, the findings indicate that humanistic approaches to personalized learning have the potential to contribute to a more beneficial quality of experience for high school students than traditional educational methods. The study has implications for educational policy and practice as it suggests personalization may be an effective approach for engaging a variety of students with their education and promoting the skills and dispositions for lifelong learning.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Jeřábková Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Interaction of selected anthocyanidins with farnesoid X receptor Human farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that act as ligand-activated transcription factors. FXR binds to specific regulatory DNA regions and induces expression of many target genes. These regulated genes are involved in bile acid metabolism and transport, maintaining blood lipids, liporoteins and glucose homeostasis and also contribute to maintain intestinal bacterial balance, hepatoprotection and liver regeneration. The interest of recent studies is to test the range of FXR ligands for treatment and prevention of many diseases such as cholestais, cholesterol gallstone disease, steato-hepatitis, dyslipidemia, atherosclerosis, type 2 diabetes mellitus, metabolic syndrome, liver cancer and other forms of cancer such as breast cancer. In this experimental diploma thesis we are focused on testing of potencial ligands of human farnesoid X receptor from the group of natural plant pigments anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin) using the human hepatoma cell line...

Usefulness of a particular clinical assay is directly correlated with its ability to extract highest possible signal from available data. This is particularly relevant for personalized radiation therapy since early plan modifications confer greater benefits to treatment outcome. Recent studies have demonstrated capability of single-cell Raman microscopy to detect cellular radiation response at clinical (below 10Gy) doses, but only in certain strongly responding cell lines and after at least two day incubation. One possible cause is rather unoptimized signal processing used. This work investigates application of several advanced multivariate methods - weighted principal component analysis (WPCA), robust PCA, probabilistic PCA, and nonlinear PCA to increase radiation response signal. Representative datasets from strongly (H460 - human lung) and weakly (LNCaP - human prostate) responding cell lines were analysed in 0-50Gy and 0-10Gy dose ranges and results quantified to determine relative and absolute algorithm performance. It was found that with careful tuning, significant improvements in sensitivity and better signal separation could be achieved as compared to conventional PCA. / Graduate

The traditional type of marketing is more directed towards big customer segments in specified areas. Due to technological improvement marketing has evolved into an extreme form of segmentation where marketing target the individual consumer based on their personal needs and preferences. This has led to a discussion of whether personalized marketing is something that create privacy concerns or benefits in the eyes of the consumer.     The purpose of this thesis is to explore the consumer perception of personalized marketing and how the perception affects the purchase decision-making process.   A conceptual framework was developed based on earlier research within personalized marketing. A qualitative method with an abductive approach has been used. Our primary data was collected through 8 different semi-structured interviews and consisted of men and women in the age span of 40-59 years’ old who had engaged in e-commerce at least once during the last six months.   Our empirical data has been analyzed out of the literature review, which founds the basis for our findings. Our findings show that the consumer perception of personalized marketing affect the consumer decision-making process in varying ways. A positive perception of the personalized marketing makes the consumer more susceptible to it, which further impacts the different stages in the process.

Recent trends and developments in the fields of Big Data, Machine Learning, and Artificial Intelligence are completely transforming the way brands are engaging and communicating with their audience, allowing more personalized communications than ever. With the spread of social networking sites, such as Facebook, YouTube or Instagram a new opportunity arises for companies to connect to their consumers. However, since social media personalization implies the collection and analysis of highly personal data, consumers may develop negative reactions, attitudes or perceptions towards personalized advertising. Research covers extensively issues such as privacy concerns, invasiveness, forced exposure or irritation, which can lead to advertising avoidance. Though understanding the user perspective is crucial, the topic advertising avoidance in the context of personalization, especially in social media environments, hasn’t been discussed at great length. The purpose of this thesis is to understand how YouTube users experience personalized advertising while using the platform. The empirical findings of this thesis contribute to the ongoing research on personalized advertising within a social media setting. In addition, by understanding what can influence personalized ad avoidance on YouTube and describing how consumers express ad avoidance on the platform, this thesis aims to nurture a deeper understanding of the phenomenon. This study is based on an interpretative, abductive as well as a qualitative research design. It uses semi-structured interviews to explore the views, experiences, beliefs, and motivations of individual participants as well as focus groups that can leverage group dynamics to generate new qualitative data. The results of this thesis show that YouTube users experience ad avoidance in relationship with personalized ads for several reasons linked to prior negative attitudes, perceived goal impediment or ad irritation. The analysis of the findings revealed that users can experience cognitive, affective and behavioral ad avoidance as presented in the literature, but a theoretical model which can perfectly explain the phenomena of personalized ad avoidance on social media is currently not existent. While some antecedents claimed by the previously mentioned theoretical frameworks were also visible in the study, additional aspects may have an impact on how consumers experience personalized advertising avoidance in the social media environment, and more specifically on YouTube.

Abstract Background The advancement of Internet technology and the ability of companies to process large amounts of information has made it possible for marketers to communicate with their customers through customized measures, namely personalized advertising. One of the primary aspects that differentiates personalized advertising from traditional advertising is the collection and use of consumers’ personal information, which have presented marketers with numerous benefits and opportunities. However, this has also raised concerns among consumers regarding their privacy and the handling of their personal information. In this study, the attitudes of Generation Z will be examined regarding data privacy, personalization, and the commercial usage of their personal information, as well as how these attitudes may impact consumer behavior. Purpose                   The purpose of this study is to examine the attitudes of consumers towards personalized advertising and the commercial usage of personal consumer data, with the focus on consumers belonging to Generation Z. Issues regarding data privacy and personalization is explored, as well as how consumer attitudes towards the personalization of advertisements may impact consumer behavior in the digital environment. Method The positivistic approach was applied with the intention to draw conclusions about a population of people, namely Generation Z. A deductive approach was implemented to test an existing theory, the Theory of Planned Behavior (TPB) with the intention to examine whether Generation Z follows the trend found in the literature; namely that younger consumers (Millennials) are more positive towards personalized advertising and the sharing of personal data for commercial purposes than older generations. The empirical data was collected through a survey, which was later analyzed through statistical measures.           Conclusion              The results suggested a predominantly neutral attitude among the survey participants regarding personalized advertising and the sharing of personal data for commercial purposes. Moreover, a positive correlation between consumer attitudes and behavioral intention to interact with personalized advertisements was detected. However, the correlation was found to be rather weak, indicating that consumer attitudes are not necessarily the strongest predictor of behavioral intention among Generation Z consumers in regards to personalized advertising.