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

International Competition and Environmental Expenditures: Empirical Evidence from Indonesian Manufacturing Plants

This paper analyzes environmental expenditures in Indonesia – a significant newly industrializing economy – reported at the plant level comprising all 23 thousand manufacturing establishments with more than 20 employees. Since compliance is barely enforced, pollution abatement expenditures are effectively voluntary in nature. This allows us to test whether foreign owned firms expend more due to a technology that adheres to stricter Western standards or whether the predominant effect is that both foreign and domestic exporting companies are more environmentally conscious due to better technology transfer or green consumerism in the Western countries. If so, this would contradict conventional wisdom that environmental expenditures reduce competitiveness and that increased levels of foreign direct investment or export-orientation in manufacturing will necessarily pre-empt firms from behaving in a ?greener? fashion

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

Household clusters reveal household- and variant-specific properties of SARS-CoV-2

It is unclear if – after symptom onset of a primary case of coronavirus disease-2019 (COVID-19) in a household – ensuing chains of transmissions among household members occur and if household epidemiology of COVID-19 is modified by the different circulating variants. We analysed data of 52 774 household clusters to investigate the day of symptom onset of ensuing cases in households relative to the symptom onset of the primary case within the household. Irrespective of cluster size or age of the primary case, 95% of all secondary household cases had symptom onset within 14 days after the symptom onset of the primary case. Stratification by variant showed that the mean interval from symptom onset of the primary case to the symptom onset of secondary cases decreased significantly from 4.8 days (wildtype) to 4.5 days (alpha) and 4.0 days (delta). Similarly, the cumulative proportion of 95% of secondary cases occurred within 14 days (wild type), 12 days (alpha) and 10 days (delta). Our findings suggest that during dominant delta circulation – apart from rare individual constellations – a 10-day household quarantine after symptom onset of the primary case is sufficient for household contacts who remain COVID-free.Peer Reviewe

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