@phdthesis{Wittenbecher2017,
  author    = {Wittenbecher, Clemens},
  title     = {Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404592},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XII, 194, ii},
  year      = {2017},
  abstract  = {Background: Consumption of whole-grain, coffee, and red meat were consistently related to the risk of developing type 2 diabetes in prospective cohort studies, but potentially underlying biological mechanisms are not well understood. Metabolomics profiles were shown to be sensitive to these dietary exposures, and at the same time to be informative with respect to the risk of type 2 diabetes. Moreover, graphical network-models were demonstrated to reflect the biological processes underlying high-dimensional metabolomics profiles. Aim: The aim of this study was to infer hypotheses on the biological mechanisms that link consumption of whole-grain bread, coffee, and red meat, respectively, to the risk of developing type 2 diabetes. More specifically, it was aimed to consider network models of amino acid and lipid profiles as potential mediators of these risk-relations. Study population: Analyses were conducted in the prospective EPIC-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2731, including 692 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Concentrations of 126 metabolites (acylcarnitines, phosphatidylcholines, sphingomyelins, amino acids) were determined in baseline-serum samples. Incident type 2 diabetes cases were assed and validated in an active follow-up procedure. The median follow-up time was 6.6 years. Analytical design: The methodological approach was conceptually based on counterfactual causal inference theory. Observations on the network-encoded conditional independence structure restricted the space of possible causal explanations of observed metabolomics-data patterns. Given basic directionality assumptions (diet affects metabolism; metabolism affects future diabetes incidence), adjustment for a subset of direct neighbours was sufficient to consistently estimate network-independent direct effects. Further model-specification, however, was limited due to missing directionality information on the links between metabolites. Therefore, a multi-model approach was applied to infer the bounds of possible direct effects. All metabolite-exposure links and metabolite-outcome links, respectively, were classified into one of three categories: direct effect, ambiguous (some models indicated an effect others not), and no-effect. Cross-sectional and longitudinal relations were evaluated in multivariable-adjusted linear regression and Cox proportional hazard regression models, respectively. Models were comprehensively adjusted for age, sex, body mass index, prevalence of hypertension, dietary and lifestyle factors, and medication. Results: Consumption of whole-grain bread was related to lower levels of several lipid metabolites with saturated and monounsaturated fatty acids. Coffee was related to lower aromatic and branched-chain amino acids, and had potential effects on the fatty acid profile within lipid classes. Red meat was linked to lower glycine levels and was related to higher circulating concentrations of branched-chain amino acids. In addition, potential marked effects of red meat consumption on the fatty acid composition within the investigated lipid classes were identified. Moreover, potential beneficial and adverse direct effects of metabolites on type 2 diabetes risk were detected. Aromatic amino acids and lipid metabolites with even-chain saturated (C14-C18) and with specific polyunsaturated fatty acids had adverse effects on type 2 diabetes risk. Glycine, glutamine, and lipid metabolites with monounsaturated fatty acids and with other species of polyunsaturated fatty acids were classified as having direct beneficial effects on type 2 diabetes risk. Potential mediators of the diet-diabetes links were identified by graphically overlaying this information in network models. Mediation analyses revealed that effects on lipid metabolites could potentially explain about one fourth of the whole-grain bread effect on type 2 diabetes risk; and that effects of coffee and red meat consumption on amino acid and lipid profiles could potentially explain about two thirds of the altered type 2 diabetes risk linked to these dietary exposures. Conclusion: An algorithm was developed that is capable to integrate single external variables (continuous exposures, survival time) and high-dimensional metabolomics-data in a joint graphical model. Application to the EPIC-Potsdam cohort study revealed that the observed conditional independence patterns were consistent with the a priori mediation hypothesis: Early effects on lipid and amino acid metabolism had the potential to explain large parts of the link between three of the most widely discussed diabetes-related dietary exposures and the risk of developing type 2 diabetes.},
  language  = {en}
}
@phdthesis{Muehlenhoff2017,
  author    = {M{\"u}hlenhoff, Judith},
  title     = {Culture-driven innovation},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-104626},
  school      = {Universit{\"a}t Potsdam},
  pages     = {143},
  year      = {2017},
  abstract  = {This cumulative dissertation deals with the potential of underexplored cultural sources for innovation. Nowadays, firms recognize an increasing demand for innovation to keep pace with an ever-growing dynamic worldwide competition. Knowledge is one of the most crucial sources and resource, while until now innovation has been foremost driven by technology. But since the last years, we have been witnessing a change from technology's role as a driver of innovation to an enabler of innovation. Innovative products and services increasingly differentiate through emotional qualities and user experience. These experiences are hard to grasp and require alignment in innovation management theory and practice. This work cares about culture in a broader matter as a source for innovation. It investigates the requirements and fundamentals for "culture-driven innovation" by studying where and how to unlock cultural sources. The research questions are the following: What are cultural sources for knowledge and innovation? Where can one find cultural sources and how to tap into them? The dissertation starts with an overview of its central terms and introduces cultural theories as an overarching frame to study cultural sources for innovation systematically. Here, knowledge is not understood as something an organization owns like a material resource, but it is seen as something created and taking place in practices. Such a practice theoretical lens inheres the rejection of the traditional economic depiction of the rational Homo Oeconomicus. Nevertheless, it also rejects the idea of the Homo Sociologicus about the strong impact of society and its values on individual actions. Practice theory approaches take account of both concepts by underscoring the dualism of individual (agency, micro-level) and structure (society, macro-level). Following this, organizations are no enclosed entities but embedded within their socio-cultural environment, which shapes them and is also shaped by them. Then, the first article of this dissertation acknowledges a methodological stance of this dualism by discussing how mixed methods support an integrated approach to study the micro- and macro-level. The article focuses on networks (thus communities) as a central research unit within studies of entrepreneurship and innovation. The second article contains a network analysis and depicts communities as central loci for cultural sources and knowledge. With data from the platform Meetup.com about events etc., the study explores which overarching communities and themes have been evolved in Berlin's start up and tech scene. While the latter study was about where to find new cultural sources, the last article addresses how to unlock such knowledge sources. It develops the concept of a cultural absorptive capacity, that is the capability of organizations to open up towards cultural sources. Furthermore, the article points to the role of knowledge intermediaries in the early phases of knowledge acquisition. Two case studies on companies working with artists illustrate the roles of such intermediaries and how they support firms to gain knowledge from cultural sources. Overall, this dissertation contributes to a better understanding of culture as a source for innovation from a theoretical, methodological, and practitioners' point of view. It provides basic research to unlock the potential of such new knowledge sources for companies - sources that so far have been neglected in innovation management.},
  language  = {en}
}