Ultra-processed foods and cardiometabolic health

The overall aim of my thesis was to investigate the associations between ultra-processed food consumption (UPF) and cardiometabolic health at the individual and the population-level while adhering to methodological principles such as incorporating and presenting a multiverse of statistical results and interpreting statistical hypothesis testing in a non-dichotomous way. I addressed these aims in three studies: a systematic review and meta-analysis of 41 prospective cohort studies, an ecological, longitudinal cross-country comparison, and a prospective analysis in the UK EPIC-Norfolk cohort. The research presented in this dissertation revealed consistent associations between UPFs and adverse cardiometabolic health. The results of the systematic review and meta-analyses of chapter 2 provided the first systematic analysis of published nutritional epidemiology studies from the perspective of food processing. I defined UPF consumption more broadly and identified studies in which UPF consumption had been termed in several different but related ways, such as fast, convenience, or Western foods. I combined those diets and dietary pattern studies that were characterized by a higher relative intake of UPFs in non-linear and summary random-effects meta-analysis estimates. Higher intakes of UPFs were associated with both an increased risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM). Higher sales of UPF were associated with an increased risk of adiposity and diabetes mellitus in the country-level analysis in chapter 3, using data from 76 countries across all five continents over 16 years. The panel analysis demonstrated that a strong and consistent association existed between the sales of UPFs at the food system level and adiposity and diabetes prevalence in low-to-middle-income countries (LMICs) for children, adolescent, and adult populations, as well as for both sexes separately. This finding adds value to the literature because no previous study had systematically investigated these associations in countries in which often a lack of individual data exists and had estimated associations for LMICs and high-income countries (HICs) separately. However, the analysis did not establish an association between UPF and adiposity in HICs, which was surprising, given that previous studies indicating an association at the individual level were mostly from HICs. The lack of variability in UPF data from HICs during the study period were likely a key reason for the lack of estimated associations in HICs. As a consequence of the many combinations of data processing and analytical methods and the variability of point estimates and P-values, no particular set of point estimates was emphasized, but the consistency of findings indicate that the expansion of global adiposity and diabetes since 2000 can partially be attributed to the increased sales of UPFs, at the level of the food system or country. The associations that were found in the meta-analysis and the panel study were replicated in prospective analyses of detailed data from over 17,000 individuals in the EPIC-Norfolk cohort, yielding associations between increased UPF intake and adiposity as well as risk of T2DM and CVD. This study demonstrated that the way UPF intake is operationalized can fundamentally influence results. Previous UPF studies had only expressed UPFs as weight or the proportion of food weight, with the justification that energy measures would not capture the non-calorific components of UPFs with potentially adverse effects on health. Guided by previous nutritional epidemiological research to adjust for total energy intake, I modelled UPF and disease risks in five different ways. The analyses revealed that these different approaches affect the statistical results, but also that they affect the results differently for different diseases. For example, the differences between measures of UPF intake based on energy and weight were much more pronounced for T2DM as an outcome than for CVD, suggesting that potentially different mechanisms relating to dietary energy and other factors common to UPFs might be responsible for different outcomes. Chapter four was also the first research to comprehensively test the associations between UPF and three important cardiometabolic disease outcomes (adiposity, T2DM, and CVD) in a prospective cohort with a long follow-up period. The findings of an almost consistent positive association provide the strongest evidence to date that UPFs are positively associated with adverse risk of cardiometabolic health. The secondary analyses of eight different food groups and outcomes indicated that greater consumption of ultra-processed meat, fish, and eggs; fast foods; and SSBs are associated with an increased risk of T2DM and CVD, whereas consumption of ultra-processed fruits and vegetables, milk and diary, fats, and breads and cereals might not be associated with an increased risk of disease. Bodyweight is likely a very important mediator of the association between UPF and T2DM and CVD, while increased total energy intake through UPFs is likely the most important driver of the UPF-adiposity association

Measuring environmental policy change: conceptual alternatives and research implications

"The study of policy change has been receiving increasing scholarly attention. Despite the growing number of empirical studies on policy change, the definition and measurement of the concept has made limited progress. In comparative environmental policy research, for instance, most existing large n studies rely on impact data such as pollutant emissions to approximate processes of policy change, often without discussing the conceptual implications of this measurement approach. Against this background, this article proposes a new measurement concept for empirically assessing environmental policy change, which conceives of policy change in terms of changes in policy outputs. We illustrate our measurement concept on the basis of an original dataset covering the evolution of clean air policies in 24 advanced democracies over a period of almost three decades (1976-2003). In a second step, we evaluate the relationship between our measurement of environmental policy change and standard emission data representing the most widely used proxy in the literature. Our findings suggest that clean air policies cannot be consistently associated with emission levels, therefore calling into question the viability of environmental impact data for the study of the determinants of policy change." [author's abstract

SfbI, Fibronektin bindendes Protein von Streptococcus pyogenes: Vielversprechender Impfstoffkandidat und mukosales Adjuvans

Streptococcus pyogenes stellt ein Humanpathogen dar, welches leichte Erkrankungen wie Pharyngitis, Tonsillitis, oder Scharlach, aber auch schwere Erkrankungen wie nekrotisierende Fasciitis oder das Toxischer-Schock-Syndrom verursacht. Ferner können aus Streptokokkeninfektionen Autoimmunerkrankungen wie rheumatisches Fieber (RF) oder Glomerulonephritis hervorgehen. 10-20 Millionen neuen Fälle von RF jährlich und 400000 Todesfälle weltweit durch damit verbundene rheumatische Herzerkrankungen machen diese Folgeerkrankungen zu einem bedeutenden Gesundheitsproblem. Impfungen stellen die geeignetste Ansatz zur Vorbeugung von Infektionen mit S. pyogenes dar. Obwohl bereits verschiedene Impfstoffkandidaten beschrieben wurden, hat sich das Fibronektin Bindungsprotein I (SfbI) von S. pyogenes als ein vielversprechender Impfstoffkandidat erwiesen. Das Protein ist oberflächengebunden und dient den Bakterien als Adhäsin und Invasin. Anhand von Immunisierungsstudien wurden die immunologischen Eigenschaften von SfbI charakterisiert und die kleinste, für die Stimulierung eines Impfschutzes benötigte Proteindomäne identifiziert. Es konnte gezeigt werden, dass zur Stimulation einer schützenden Immunantwort gegen S. pyogenes lediglich die Fibronektin-Bindungsdomäne (FnB) notwendig ist, dass die induzierte Immunität über einen langen Zeitraum bestehen bleibt und dass dies auch ohne Koadministration eines mukosalen Adjuvans erzielt wird. Ferner konnte gezeigt werden, dass die FnB darüber hinaus auch als mukosales Adjuvans wirken kann. Schließlich ließen sich innerhalb der FnB B- und T-Zellepitope identifizieren, welche die Entwicklung eines Kombinationsimpfstoffes gegen S. pyogenes ermöglichen könnten.Streptococcus pyogenes is an important human pathogen able to cause self-limiting infectious diseases such as pharyngitis, tonsillitis or scarlet fever and also very severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Autoimmune sequelae such as acute rheumatic fever (RF) and glomerulonephritis can also develop after streptococcal infections. The 10-20 million new cases of RF per year and the mortality rate of rheumatic heard disease of 400000 people worldwide makes these streptococcal sequelae a health problem of particular importance. Vaccination provides the most suitable approach to prevent infection with S. pyogenes. Although several vaccines have been proposed, the fibronectin-binding protein I (SfbI) of S. pyogenes, a surface bound protein acting as adhesin and invasin, represents a promising vaccine candidate. Therefore, the immunological properties of SfbI protein were characterized with the identification of the minimal domain needed for protection. Immunization studies showed that the fibronectin-binding domain was the smallest fragment of SfbI able to stimulate protective and long-lasting immune responses against S. pyogenes even in the absence of a co-administered mucosal adjuvant. In addition, the fibronectin-binding domain was also able to act as mucosal adjuvant when co-administered with model antigens. Finally, B and T cell epitopes were identified within the fibronectin-binding domain which could facilitate the generation of a combined vaccine against S. pyogenes

Methoden und Möglichkeiten der hochpräzisen Röntgenpolarimetrie

Die Polarimetrie ist im sichtbaren Spektralbereich aus einer Vielzahl von Anwendungen in der Physik, Chemie und in den Lebenswissenschaften nicht mehr wegzudenken. Aber auch im Röntgenbereich hat sich die Messung von Polarisationsänderungen in einer Reihe von Anwendungsfeldern etabliert. Diese Arbeit stellt zwei Methoden vor, mit denen solche Änderungen im Röntgenspektralbereich hochpräzise analysiert werden können. Dabei wird die Erzeugung und Messung von hochreinen linear polarisierten Zuständen zum einen mit Hilfe von Channel-Cut-Kristallen und zum anderen auf der Basis des Borrmann-Effektes theoretisch und experimentell untersucht. Diese Methoden ermöglichen durch ihre sehr hohe Polarisationsreinheit von bis zu zehn Größenordnungen eine genaue Analyse von Doppelbrechung, Dichroismus und optischer Aktivität, was in der Arbeit durch verschiedene Messungen gezeigt wird. So konnten Polarisationsdrehungen von unter einer Bogensekunde beim Durchgang von Röntgenstrahlung durch eine Zuckerlösung nachgewiesen werden. Verschiedene Eigenschaften der Polarisatoren werden mit Hilfe von Berechnungen, die auf der dynamischen Theorie der Röntgenbeugung beruhen, erläutert. Zudem zeigen diese Simulationen, dass vor allem bei hohen Photonenenergien die Reinheit der Polarisationszustände durch Umweganregungen begrenzt wird. Die hohe Polarisationsreinheit des Röntgenpolarimeters kann nicht nur genutzt werden, um Polarisationsänderungen präzise zu messen, es erlaubt auch eine Selektion von Photonen, die durch resonante Kernstreuung eine Änderung der Polarisation erfahren, während der nicht-resonant gestreute Untergrund um zahlreiche Größenordnungen unterdrückt wird. Durch diese Methode können Kernspektren nahezu unverfälscht gemessen werden, was zum Nachweis verschiedener quantenoptischer Phänomene im Röntgenspektralbereich führte

A governance framework for development and assessment of national action plans on antimicrobial resistance

Strengthening governance is an essential strategy to tackling antimicrobial resistance (AMR) at all levels: global, national, regional, and local. To date, no systematic approach to governance of national action plans on AMR exists. To address this issue, we aimed to develop the first governance framework to offer guidance for both the development and assessment of national action plans on AMR. We reviewed health system governance framework reviews to inform the basic structure of our framework, international guidance documents from WHO, the Food and Agriculture Organization, the World Organisation for Animal Health, and the European Commission, and sought the input of 25 experts from international organisations, government ministries, policy institutes, and academic institutions to develop and refine our framework. The framework consists of 18 domains with 52 indicators that are contained within three governance areas: policy design, implementation tools, and monitoring and evaluation. To consider the dynamic nature of AMR, the framework is conceptualised as a cyclical process, which is responsive to the context and allows for continuous improvement and adaptation of national action plans on AMR

an experimental study in the rat osteoarthritis model

Background Anti-inflammatory nanoparticular compounds could represent a strategy to diminish osteoarthritis (OA) progression. The present study was undertaken to prove the uptake of nanoparticular dendritic polyglycerol sulfates (dPGS) by rat-derived articular chondrocytes and to answer the question of whether dPGS could modulate knee joint cartilage degradation in a rat OA model and whether complications could arise. Methods dPGS uptake and cytotoxicity was assessed in cultured primary rat-derived articular chondrocytes. Subsequently, OA was induced in the right knee joints of 12 male Wistar rats by medial collateral ligament and meniscus transection. Unoperated left knees remained as controls. Six weeks post surgery six rats were either treated daily (14 days) with 30 mg/kg dPGS (s.c.) or a similar volume of physiological saline. Animals were analyzed clinically for gait alterations. Explanted knee joints were studied histologically using OA scores according to Mankin (1971), Glasson et al., (2010) and the synovitis score according to Krenn et al., (2006). Liver, spleen and kidneys were analyzed for degenerative changes due to dPGS accumulation. Results dPGS was taken up after 2 hours by the chondrocytes. Whereas no significant clinical signs of OA could be detected, at the histological level, all operated rat knee joints revealed features of OA in the medial compartment. The values produced by both OA score systems were lower in rats treated with dPGS compared with saline-treated animals. Synovitis score did not significantly differ between the groups. The analyzed organs revealed no degenerative changes. Conclusions dPGS presented overall cyto- and biocompatibility, no accumulation in metabolizing organs and chondroprotective properties in the osteoarthritic knee joint

Measuring climate change adaptation policy output: Toward a two‐dimensional approach

As jurisdictions across the globe step up their efforts to adapt to climate change, it is important to assess progress by taking stock of and comparing adaptation policy. However, scholars and practitioners are struggling to conceptualize and measure adaptation policy. In this article, we propose a new two-dimensional framework to measure public adaptation policy output, namely, the Climate Adaptation Policy Index (CAPI). The index combines multiple indicators from two core interdependent dimensions, namely, an institutionalization dimension focusing on strategic plans and administrative capacities for adaptation; and a measures dimension capturing concrete adaptation measures in relevant action areas such as in green and open spaces, transport infrastructure, buildings, public education, and disaster management. Our approach is extensive but feasible and may be adjusted for use in different contexts and policy areas. We probe our approach at the local level using original survey data from a diverse sample of 211 municipalities located in the state of Hessen in central Germany. A factor analysis suggests that the two dimensions constitute a meaningful measurement of municipal adaptation policy output. A cluster analysis identifies five groups of municipalities representing different stages of adaptation policy progress in Hessen. Finally, a regression analysis examines potential determinants of local adaptation policy making such as the size and wealth of municipalities. The results highlight the potential of the CAPI for analyzing both the state and the making of municipal adaptation policy