Cyclic variation of the common carotid artery structure in relation to prior atherosclerotic burden and physical activity

Background and aims: Cardiovascular disease (CVD) accounts for the most deaths of non-communicable diseases worldwide. It begins with structural and functional changes of the arterial system commonly known as the atherosclerotic process, starting asymptomatically in early childhood, adapting arterial structure and function with advancing age depending on genetic and environmental exposures and finally resulting in CVD events such as myocardial infarction or stroke. CVD risk prediction today is generally based on risk scores, but substantial disadvantages occur since they account only for specific risk factors at one time point. Carotid structure and function (also called carotid stiffness) parameters measured by ultrasound may overcome this disadvantage, since they can provide information on structural and elastic carotid properties and reflect therefore vascular damage accumulated over time. Thus, the aims of this thesis were to summarize the state of the art of ultrasound measurements, to validate the new developed ultrasound analysis system, to assess the variability and reproducibility within the study sample and to investigate the long- and short-term associations of cardiovascular risk factors and carotid stiffness with main focus on physical activity in elderly participants of the SAPALDIA cohort. Methods: The SAPALDIA cohort study is an ongoing multicenter study with a population-based random sample of adults from eight rural and urban areas started in 1991 (SAPALDIA 1), with a first follow-up in 2001-2003 (SAPALDIA 2) and a second follow-up in 2010-2011 (SAPALDIA 3). In SAPALDIA 3, sequential B-mode ultrasound images of the common carotid artery were examined in 3489 participants (51% women) aged between 50-81 years at the time of examination. Expert readers analyzed these ultrasound images with a new analysis system called DYARA (DYnamic ARtery Analysis) according to the state of the art assessed in the review. Thereof, carotid structure parameters were measured and carotid stiffness indices were derived considering blood pressure at time of ultrasound assessment. Validation of the ultrasound analysis program DYARA and reproducibility of carotid parameters were performed in subgroup within the SAPALDIA 3 survey. The presented studies within this thesis comprise cardiovascular risk factor data from the first and second follow-up and therefore, long- and short-term associations with carotid stiffness could be investigated. Results: The intra- and inter-reader results of the validation study were highly consistent with slightly higher bias for analyses with manual interactions compared to the automatic detection. Among the carotid structure parameters, average values across heart cycle showed lower variability than single images in diastole and systole, whereby the relative difference was smaller in lumen diameter values compared to the carotid intima media thickness (CIMT). Based on different statistical approaches, reproducibility values within SAPALDIA 3 were consistently good to excellent for carotid structure and function indices. Findings additionally revealed that subjects itself were the greatest source of variability between two measurements. Multivariate regression analyses suggested that most single cardiovascular risk factors in SAPALDIA 2 were long-termly associated with increased carotid stiffness in SAPALDIA 3 except physical activity and high-density lipoprotein cholesterol (HDL-C). HDL-C was the only protective vascular determinant and no relation was observed for physical activity. Most carotid stiffness parameters were similar strong associated within each cardiovascular risk factor (except compliance showed main deviances among several risk factors). Estimating sex-specific associations of atherosclerotic risk factors and carotid stiffness indicated that increased heart rate was more strongly associated with stiffer arteries across all carotid stiffness parameters in men than in women. Low-density lipoprotein cholesterol (LDL-C) was significantly associated with carotid stiffness only in men and triglyceride only in women. Multifactorial pathway analyses of cardiovascular risk factors in SAPALDIA 3 showed that age was the strongest predictor of carotid stiffness, followed by mean arterial blood pressure and heart rate. Age strongly confounded the association of physical activity and carotid stiffness in multiple regression analyses and therefore, only an univariate association of physical activity and carotid stiffness could be observed. Conclusion: DYARA tackles the challenge of being able to analyze varying ultrasound image qualities with high precision. The high reproducibility and the feasible application in a large sample size suggest that this program can be recommended for epidemiological research, diagnostics and clinical practice. Long- and short-term cardiovascular exposures have added important information to the overall vascular damage assessed by carotid stiffness for both sexes. Although age was the strongest predictor, sex-differences in long-term associations may indicate a certain differentiated susceptibility to cardiovascular risk factors among men and women, which should be investigated in more detail. The presented studies within this thesis provide an important basis towards future investigations targeting the early and late consequences of atherosclerosis, its progression and possible implementations of preventive and/or personalized interventions

The art of compromise: an analysis of the discourse that led to the creation of article 15bis of the Rome Statute.

This Sociology of Law thesis looks at the negotiation process that took place within the Special Working Group on the Crime of Aggression between 2004 and 2009 and which led to the creation of article 15bis of the Rome Statute. The article sets out the rules regarding the International Criminal Court’s jurisdiction over crime of aggression cases, referred to it by States or initiated by the Prosecutor of the Court. Foucauldian theories on the effects of power on the production of knowledge and the productivity of discourse were used to analyse the process, in order to gain an understanding for how the debate on this issue developed in the way it did. It was found that the negotiation process contained many conflicting views on what the Court’s jurisdiction should be. Power was used in a strategic way by delegations to work towards their specific aim, and the visibility of different institutions shaped the way in which the discourse could be conducted. This meant that many compromises had to be made throughout the process in order to finally be able to reach an agreement regarding the Court’s jurisdiction on the crime, in time for the Review Conference held in 2010

Load-following capability of German nuclear power plants. Summary

How flexibly can nuclear power plants be operated? Is their operation compatible with high fluctuating feed-in from from renewable energies? These questions wer Against this background, TAB was commissioned in 2010 to review and concisely summarise the state of scientific knowledge and the current debate. The disaster in Fukushima in spring 2011 and the subsequent upheavals in the German energy system considerably reduced the priority of this study and made the original schedule obsolete. Nevertheless, the results are still interesting: On the one hand, the analyses presented here on the requirements that a dynamic expansion of fluctuating renewable energy generation places on the conventional power plant fleet are still highly relevant. On the other hand, the questions examined here arise with great urgency in other countries (e.g. France, England). e the subject of a controversial debate in politics, science and the public from 2010 onwards. The occasion was the energy concept of the then Federal Government, which envisaged an extension of the operating lives of German nuclear power plants

Coherent phonon dynamics at the martensitic phase transition of Ni_2MnGa

We use time-resolved optical reflectivity to study the laser stimulated dynamics in the magnetic shape memory alloy Ni_2MnGa. We observe two coherent optical phonons, at 1.2 THz in the martensite phase and at 0.7 THz in the pre-martensite phase, which we interpret as a zone-folded acoustic phonon and a heavily damped amplitudon respectively. In the martensite phase the martensitic phase transition can be induced by a fs laser pulse on a timescale of a few ps.Comment: 3 figure

Energy consumption of ICT infrastructure

Due to omnipresent digitisation, the energy consumption of information and communication technology (ICT), i. e. of digital end devices, data centres and telecommunications networks, is becoming more and more important. Between 2015 and 2020, the annual energy demand of data centres and transmission grids in Germany increased by around 5.4 TWh. This corresponds to an increase of 30 %. Existing efficiency and saving potentials must be consistently tapped in order to slow down the current growth in consumption. In the TAB report, blockchain applications, private internet use and smart energy management in buildings have been examined in depth

Climate Engineering. TAB-Fokus

Climate change is widely seen as the central environmental issue of our time. However, climate protection measures implemented to date are showing little impact. The question has been raised of whether direct technological interventions in the climate system – termed climate engineering – could be a suitable means of limiting the rise in temperature. Policy-makers and society would face major challenges with regard to decisions about the development and application of climate engineering, especially as the entire world population would potentially have to deal with the possible consequences of these measures. Decisions on the benefits of climate engineering therefore cannot be based solely on technological and scientific criteria or economic considerations. Assessment must also include ethical, legal and societal criteria

Assessment of daylight saving time. TAB-Fokus

The Directive 2000/84/EC stipulates the application of daylight saving time arrangements as mandatory for all EU Member States for an unspecified period. Any change with regard to daylight saving time requires an amendment of this directive. In 2007, the European Commission concluded that daylight saving time would have only little impact. With regard to energetic aspects and based on the current state of knowledge, this conclusion still can be considered to be valid. Moreover, there are no indications to question this conclusion with regard to economic aspects. In view of health-related aspects, further research is required for an in-depth examination and evaluation of the short-term and long-term implications related to the time change. An amendment of the Directive 2000/84/EC can be proposed in different ways. Whether or not a corresponding legislative procedure will be initiated is at the discretion of the European Commission

On Classical de Sitter Vacua in String Theory

We review the prospect of obtaining tree-level de Sitter (dS) vacua and slow-roll inflation models in string compactifications. Restricting ourselves to the closed string sector and assuming the absence of NSNS-sources, we classify the minimal classical ingredients that evade the simplest no-go theorems against dS vacua and inflation. Spaces with negative integrated curvature together with certain combinations of low-dimensional orientifold planes and low-rank RR-fluxes emerge as the most promising setups of this analysis. We focus on two well-controlled classes that lead to an effective 4D, N=1 supergravity description: Type IIA theory on group or coset manifolds with SU(3)-structure and O6-planes, as well as type IIB compactifications on SU(2)-structure manifolds with O5- and O7-planes. While fully stabilized AdS vacua are generically possible, a number of problems encountered in the search for dS vacua are discussed.Comment: 4 pages, proceedings of the 9th Hellenic School on Elementary Particle Physics and Gravity, Corfu 200

Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1

Male F-344 rats were given [3H]aflatoxin B1 (AFB 1) in the drinking water at three exposure levels (0.02, 0.6, 20 μg/l, resulting in average dose levels of 2.2, 73, 2110 ng/kg per day). After 4, 6 and 8 weeks, DNA was isolated from the livers and analyzed for aflatoxin- DNA adducts. The level of DNA adducts did not increase significantly after 4 weeks, indicating that a steady-state for adduct formation and removal had nearly been reached. At 8 weeks, the adduct levels were 0.91, 32 and 850 nucleotide-aflatoxin adducts per 109 nucleotides, i.e. clearly proportional ot the dose. At the high dose level, a near 50% tumor incidence would be expected in a 2-year bioassay with F-344 rats while the low dose used is within the range of estimated human dietary exposures to aflatoxin in Western countries. The proportionality seen between exposure and steady-state DNA adduct level is discussed with respect to a linear extrapolation of the turnor risk to low dos