@phdthesis{Polemiti2022,
  author    = {Polemiti, Elli},
  title     = {Identifying risk of microvascular and macrovascular complications of type 2 diabetes},
  doi       = {10.25932/publishup-57103},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-571038},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xii, 292},
  year      = {2022},
  abstract  = {Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors - mainly related to lifestyle - of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications. To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals' complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95\% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95\% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95\% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication. The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95\% CI 1.07, 1.36), kidney disease (HR 1.39; 95\% CI 1.21, 1.60) and neuropathy (HR 1.12; 95\% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95\% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1\% indicated a decreased risk of total microvascular complications (HR 0.62; 95\% CI 0.47, 0.80), kidney disease (HR 0.57; 95\% CI 0.40, 0.81) and neuropathy (HR 0.73; 95\% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95\% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers. The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications. In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.},
  language  = {en}
}
@phdthesis{Voroshnin2023,
  author    = {Voroshnin, Vladimir},
  title     = {Control over spin and electronic structure of MoS₂ monolayer via interactions with substrates},
  doi       = {10.25932/publishup-59070},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-590709},
  school      = {Universit{\"a}t Potsdam},
  pages     = {viii, 125},
  year      = {2023},
  abstract  = {The molybdenum disulfide (MoS2) monolayer is a semiconductor with a direct bandgap while it is a robust and affordable material. It is a candidate for applications in optoelectronics and field-effect transistors. MoS2 features a strong spin-orbit coupling which makes its spin structure promising for acquiring the Kane-Mele topological concept with corresponding applications in spintronics and valleytronics. From the optical point of view, the MoS2 monolayer features two valleys in the regions of K and K' points. These valleys are differentiated by opposite spins and a related valley-selective circular dichroism. In this study we aim to manipulate the MoS2 monolayer spin structure in the vicinity of the K and K' points to explore the possibility of getting control over the optical and electronic properties. We focus on two different substrates to demonstrate two distinct routes: a gold substrate to introduce a Rashba effect and a graphene/cobalt substrate to introduce a magnetic proximity effect in MoS2. The Rashba effect is proportional to the out-of-plane projection of the electric field gradient. Such a strong change of the electric field occurs at the surfaces of a high atomic number materials and effectively influence conduction electrons as an in-plane magnetic field. A molybdenum and a sulfur are relatively light atoms, thus, similar to many other 2D materials, intrinsic Rashba effect in MoS2 monolayer is vanishing small. However, proximity of a high atomic number substrate may enhance Rashba effect in a 2D material as it was demonstrated for graphene previously. Another way to modify the spin structure is to apply an external magnetic field of high magnitude (several Tesla), and cause a Zeeman splitting, the conduction electrons. However, a similar effect can be reached via magnetic proximity which allows us to reduce external magnetic fields significantly or even to zero. The graphene on cobalt interface is ferromagnetic and stable for MoS2 monolayer synthesis. Cobalt is not the strongest magnet; therefore, stronger magnets may lead to more significant results. Nowadays most experimental studies on the dichalcogenides (MoS2 included) are performed on encapsulated heterostructures that are produced by mechanical exfoliation. While mechanical exfoliation (or scotch-tape method) allows to produce a huge variety of structures, the shape and the size of the samples as well as distance between layers in heterostructures are impossible to control reproducibly. In our study we used molecular beam epitaxy (MBE) methods to synthesise both MoS2/Au(111) and MoS2/graphene/Co systems. We chose to use MBE, as it is a scalable and reproducible approach, so later industry may adapt it and take over. We used graphene/cobalt instead of just a cobalt substrate because direct contact of MoS2\ monolayer and a metallic substrate may lead to photoluminescence (PL) quenching in the metallic substrate. Graphene and hexagonal boron nitride monolayer are considered building blocks of a new generation of electronics also commonly used as encapsulating materials for PL studies. Moreover graphene is proved to be a suitable substrate for the MBE growth of transitional metal dichalcogenides (TMDCs). In chapter 1, we start with an introduction to TMDCs. Then we focus on MoS2 monolayer state of the art research in the fields of application scenario; synthesis approaches; electronic, spin, and optical properties; and interactions with magnetic fields and magnetic materials. We briefly touch the basics of magnetism in solids and move on to discuss various magnetic exchange interactions and magnetic proximity effect. Then we describe MoS2 optical properties in more detail. We start from basic exciton physics and its manifestation in the MoS2 monolayer. We consider optical selection rules in the MoS2 monolayer and such properties as chirality, spin-valley locking, and coexistence of bright and dark excitons. Chapter 2 contains an overview of the employed surface science methods: angle-integrated, angle-resolved, and spin-resolved photoemission; low energy electron diffraction and scanning tunneling microscopy. In chapter 3, we describe MoS2 monolayer synthesis details for two substrates: gold monocrystal with (111) surface and graphene on cobalt thin film with Co(111) surface orientation. The synthesis descriptions are followed by a detailed characterisation of the obtained structures: fingerprints of MoS2 monolayer formation; MoS2 monolayer symmetry and its relation to the substrate below; characterisation of MoS2 monolayer coverage, domain distribution, sizes and shapes, and moire structures. In chapter~4, we start our discussion with MoS2/Au(111) electronic and spin structure. Combining density functional theory computations (DFT) and spin-resolved photoemission studies, we demonstrate that the MoS2 monolayer band structure features an in-plane Rashba spin splitting. This confirms the possibility of MoS2 monolayer spin structure manipulation via a substrate. Then we investigate the influence of a magnetic proximity in the MoS2/graphene/Co system on the MoS2 monolayer spin structure. We focus our investigation on MoS2 high symmetry points: G and K. First, using spin-resolved measurements, we confirm that electronic states are spin-split at the G point via a magnetic proximity effect. Second, combining spin-resolved measurements and DFT computations for MoS2 monolayer in the K point region, we demonstrate the appearance of a small in-plane spin polarisation in the valence band top and predict a full in-plane spin polarisation for the conduction band bottom. We move forward discussing how these findings are related to the MoS2 monolayer optical properties, in particular the possibility of dark exciton observation. Additionally, we speculate on the control of the MoS2 valley energy via magnetic proximity from cobalt. As graphene is spatially buffering the MoS2 monolayer from the Co thin film, we speculate on the role of graphene in the magnetic proximity transfer by replacing graphene with vacuum and other 2D materials in our computations. We finish our discussion by investigating the K-doped MoS2/graphene/Co system and the influence of this doping on the electronic and spin structure as well as on the magnetic proximity effect. In summary, using a scalable MBE approach we synthesised MoS2/Au(111) and MoS2/graphene/Co systems. We found a Rashba effect taking place in MoS2/Au(111) which proves that the MoS2 monolayer in-plane spin structure can be modified. In MoS2/graphene/Co the in-plane magnetic proximity effect indeed takes place which rises the possibility of fine tuning the MoS2 optical properties via manipulation of the the substrate magnetisation.},
  language  = {en}
}