The Autocratic Trust Bias: Politically Sensitive Survey Items and Self-censorship

Because of the perceived risk of repression some survey questions are likely sensitive in more autocratic countries while less so in more democratic countries. Yet, survey data on potentially sensitive topics are frequently used in comparative research despite concerns about comparability. In a novel approach to test the comparability of politically sensitive questions I employ a multilevel-analysis with more than 80 000 respondents in 36 African countries to test for systematic bias when the survey respondents believe (fear) that the government has commissioned the survey, as opposed to an independent research institute. The findings indicate that fear of the government induces a substantial and significant bias on questions regarding the citizen-state relationship in more autocratic countries, but not in more democratic countries. This has practical implications for the comparative use of survey data.I am grateful to Staffan I. Lindberg, Ellen Lust, Beth Simmons, Anja Neundorf, Mattias Agerberg and participants of the 2017 V-Dem Research Conference for valuable comments and suggestions. This research project was supported by Riksbankens Jubileumsfond, Grant M13-0559:1, PI: Staffan I. Lindberg, V-Dem Institute, University of Gothenburg, Sweden; by Knut and Alice Wallenberg Foundation to Wallenberg Academy Fellow Staffan I. Lindberg, Grant 2013.0166, V-Dem Institute, University of Gothenburg, Sweden; by European Research Council, Grant 724191, PI: Staffan I. Lindberg, V-Dem Institute, University of Gothenburg, Sweden; by the Swedish Research Council, Grant 439-2014-38, PI: Pam Fredman, Vice-Chancellor, University of Gothenburg, Sweden; as well as by internal grants from the Vice-Chancellor’s office, the Dean of the College of Social Sciences, and the Department of Political Science at University of Gothenburg. We performed simulations and other computational tasks using resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Center in Sweden, SNIC 2016/1-382 and 2017/1-68. We specifically acknowledge the assistance of In-Saeng Suh at CRC and Johan Raber at SNIC in facilitating our use of their respective systems

Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease

Glutamate-mediated toxicity has been implicated in the neurodegeneration observed in Alzheimer's disease. In particular, glutamate transport dysfunction may increase susceptibility to glutamate toxicity, thereby contributing to neuronal cell injury and death. In this study, we examined the cellular localization of the glial glutamate transporter excitatory amino acid transporter 1 (EAAT1) in the cerebral cortex of control, Alzheimer's disease, and non-Alzheimer dementia cases. We found that EAAT1 was strongly expressed in a subset of cortical pyramidal neurons in dementia cases showing Alzheimer-type pathology. In addition, tau (which is a marker of neurofibrillary pathology) colocalized to those same pyramidal cells that expressed EAAT1. These findings suggest that EAAT1 changes are related to tau expression (and hence neurofibrillary tangle formation) in dementia cases showing Alzheimer-type pathology. This study implicates aberrant glutamate transporter expression as a mechanism involved in neurodegeneration in Alzheimer's disease

ST-T segments analysis of ECG signals with focusing on T-wave alternance

Kardiovaskulární onemocnění způsobují vysoké procento úmrtí po celém světě. V řadě vyspělých zemích je toto procento úmrtí dokonce vyšší než úmrtí způsobená onemocněním rakovinou. V současné době je používáno mnoho metod pro predikci náhlé srdeční smrti se zaměřením na segment ST-T signálu EKG, zejména TWA. Cílem disertační práce bylo prohloubit vztahy a spolupráci s Interní kardiologickou klinikou Fakultní nemocnice Brno Bohunice na analýze rizik náhlé srdeční smrti, seznámit se a ověřit metody používané k detekci a kvantifikaci simulované TWA. Nalézt vhodná vylepšení metod detekce TWA a na závěr metody vyhodnotit na reálných datech získaných na IKK FN Brno. První část práce je zaměřena na souhrn patologických artefaktů v signálu EKG při určování rizik (stratifikaci) náhlé srdeční smrti, dále jsou popsány metody analýzy, detekce a klasifikace TWA. Mezi stěžejní zajímavé poznatky pro klinickou praxi patří analýza trendu změny TWA v čase a nalezení nejvhodnější metody pro zjišťování krátkodobé TWA. Druhá část práce popisuje vývoj a výsledky nových vylepšení a metod pro detekci TWA. Poslední část práce je zaměřena na metodiku určení pravděpodobnosti výroku o přítomnosti a nepřítomnosti TWA v signálu EKG.The Cardiovascular diseases may evocated the high percentual risk of sudden cardiac death in whole world. In several western countries is the number of death higher then number of cancer death. In this time is used a lot of methods for prediction of sudden cardiac death with focus on ECG T-wave alternance. The aim of the theses was to do stronger relation and cooperation with Internal Cardiac Clinic of Faculty Hospital Brno Bohunice on the risk analysis of sudden cardiac death. Secondly, we met the methods used for detection and quantification of simulated TWA. Last but not least was necessary to find TWA detection methods improvement and process the data on real signals obtained from Faculty Hospital Brno Bohunice. First part of the Thesis is focused on summary of pathologic artifacts in ECG signal, which are important for sudden cardiac risk stratification. There are described further known detection and quantification methods for TWA analysis. An interesting part for clinical practice is analysis of TWA trend in time and looking for the best method, which is able to catch and track the short TWA trend changes. Second part describes the new methods improvements, which were tested with interesting outputs. Further, there was developed method for TWA presence statement probability evaluation.

Entwicklung eines Biosensors für das online-Monitoring des akuten Koronarsyndroms

Herz-Kreislauf-Erkrankungen sind weltweit die häufigste Todesursache. Im Falle eines akuten myokardialen Infarkts ist eine schnelle und präzise Diagnostik notwendig, um ggf. die entsprechend überlebenswichtigen Maßnahmen in die Wege zu leiten. Einer der wichtigsten Biomarker für die Herzinfarkt-Diagnostik ist das kardiale Troponin I (cTnI), welches durch das Absterben der Myokardzellen (Herzmuskel) in den Blutkreislauf gelangt und sich dessen Konzentration über die Zeit ändert. Diese Konzentrationsänderung ist entscheidend für die Diagnostik und letztendlich für weitere lebensrettende medizinische Schritte. Entsprechend wurden in dieser Arbeit verschiedene Messmethoden entwickelt, um cTnI-Konzentrationen zu bestimmen. Zunächst wurden mehrere Enzyme-linked Immunosorbent Assays (ELISA) im Sandwich-Format entwickelt, um eine höchstmögliche Sensitivität zur Detektion von cTnI zu ermöglichen. Um eine schnelle und kostengünstige Detektion von cTnI zu ermöglichen, wurde außerdem ein Lateral-Flow-Assay (LFA) entwickelt. Dabei wurden Gold-Nanoshells für die optische Auswertung verwendet, welche eine empfindlichere Detektion als übliche Gold-Nanopartikel ermöglichen. Des Weiteren wurden verschiedene Immunisierungen mit unterschiedlichen Strategien durchgeführt, um neue Antikörper gegen humanes cTnI zu entwickeln. Für das Online-Monitoring von cTnI wurde der Prototyp eines Biosensors entwickelt, welcher auf Chemilumineszenz-Detektion basiert. Für cTnI wurde mit dem Biosensor eine Nachweisgrenze von 0,6 μg/L (25 pM) in Puffer, 1,8 μg/L (73 pM) in Serum und 1,5 μg/L (63 pM) erzielt.Cardiovascular diseases are the most common cause of death worldwide. In the event of an acute myocardial infarction, rapid and precise diagnostics are necessary in order to initiate the appropriate vital measures if necessary. One of the most important biomarkers for heart attack diagnostics is cardiac troponin I (cTnI), which enters the bloodstream when the myocardial cells (heart muscle) undergo necrosis after an infarction and whose concentration changes over time. This change in concentration is crucial for diagnostics and ultimately for further lifesaving medical steps. Accordingly, various measurement methods were developed in this work to determine cTnI concentrations. Initially, several enzyme-linked immunosorbent assays (ELISA) were developed in a sandwich format to enable the highest possible sensitivity for the detection of cTnI. A lateral flow assay (LFA) was also developed to enable rapid and cost-effective detection of cTnI. Gold nanoshells were used for optical evaluation, which enable more sensitive detection than conventional gold nanoparticles. Furthermore, different immunizations with different strategies were performed to develop new antibodies against human cTnI. A prototype biosensor based on chemiluminescence detection was developed for the online monitoring of cTnI. For cTnI, a detection limit of 0.6 μg/L (25 pM) in buffer, 1.8 μg/L (73 pM) in serum and 1.5 μg/L (63 pM) was achieved with the biosensor

Regimes of the World (RoW): Opening New Avenues for the Comparative Study of Political Regimes

Classifying political regimes has never been more difficult. Most contemporary regimes hold de-jure multiparty elections with universal suffrage. In some countries, elections ensure that political rulers are - at least somewhat - accountable to the electorate whereas in others they are a mere window dressing exercise for authoritarian politics. Hence, regime types need to be distinguished based on the de-facto implementation of democratic institutions and processes. Using V-Dem data, we propose with Regimes of the World (RoW) such an operationalization of four important regime types - closed and electoral autocracies; electoral and liberal democracies - with vast coverage (almost all countries from 1900 to 2016). We also contribute a solution to a fundamental weakness of extant typologies: The unknown extent of misclassification due to uncertainty from measurement error. V-Dem's measures of uncertainty (Bayesian highest posterior densities) allow us to be the first to provide a regime typology that distinguishes cases classified with a high degree of certainty from those with "upper" and "lower" bounds in each category. Finally, a comparison of disagreements with extant datasets (7%-12% of the country-years), demonstrates that the RoW classification is more conservative, classifying regimes with electoral manipulation and infringements of the political freedoms more frequently as electoral autocracies, suggesting that it better captures the opaqueness of contemporary autocracies

Pulmonary hypertension : the role and place of PDGF

Pulmonary hypertension is a severe condition, leading to right heart dysfunction and preterm death. For pulmonary arterial hypertension (PAH), a disease group in which the primary pathology resides within the pulmonary pre-capillary vessels, several specific therapies are in clinical use, but unfortunately the prognosis is still grim. Available PAH therapy mainly targets vasoconstriction and the progressive vascular remodeling is not adequately suppressed. Considering biological similarities to malignancies, hypotheses and therapies from cancer research have been tested in PAH. An example of this is imatinib, originally designed to target a mutated receptor in chronic myeloid leukemia, and found to also inhibit platelet-derived growth factor (PDGF) signaling. Albeit to some extent efficient, imatinib is unspecific and leads to severe side effects in PAH patients. Previous studies have found PDGF receptor b and its ligand, PDGF-B, to be implicated in PAH. PDGF signaling is known to induce cell proliferation, migration, and extracellular matrix deposition. Additionally, PDGF-B contains a retention motif that binds to matrix proteoglycans, such as perlecan. Perlecan, which has previously been shown to affect vascular remodeling in the systemic circulation, has here been investigated in the pulmonary circulation. Further, the role of PDGF-D, the other known ligand of PDGF receptor b, has in this thesis been characterized in physiology as well as in pulmonary hypertension. Paper I and II combined describes how pulmonary vascular remodeling could be altered by either targeting the PDGF-B retention motif or perlecan heparan sulfate (HS). In development, perivascular smooth muscle cells and pericytes propagate towards an extracellular PDGF-B gradient. Our findings support previous reports on similar mechanisms also in hypoxia-induced pulmonary vascular remodeling. Further, we show that perlecan HS promotes fibroblast growth factor signaling, another important mitogen for smooth muscle cells and pericytes. In paper III, effects of PDGF-D deletion were thoroughly characterized. Pdgfd-/- mice were shown to be viable and healthy, however a mild cardiovascular phenotype, including discrete alterations in pericyte attachment to cardiac microvessels, was found. In Paper IV the role of PDGF-D in PH was explored. It was shown to be present in vascular lesions of PAH patients and recombinant PDGF-D potently induced proliferation of human and mouse pulmonary arterial smooth muscle cells in vitro. This suggested that PDGF-D could be a driver of pulmonary vascular remodeling. However, Pdgfd-/- mice were not protected against disease and hence, PDGF-D seems to be a redundant mitogen in hypoxia-induced PH. The collected work of this thesis highlights the importance of spatial distribution of growth factors and prompts future PAH studies to take the extracellular matrix into consideration

Regimes of the World (RoW): Opening New Avenues for the Comparative Study of Political Regimes

Classifying political regimes has never been more difficult. Most contemporary regimes hold de-jure multiparty elections with universal suffrage. In some countries, elections ensure that political rulers are—at least somewhat—accountable to the electorate whereas in others they are a mere window dressing exercise for authoritarian politics. Hence, regime types need to be distinguished based on the de-facto implementation of democratic institutions and processes. Using V-Dem data, we propose with Regimes of the World (RoW) such an operationalization of four important regime types—closed and electoral autocracies; electoral and liberal democracies—with vast coverage (almost all countries from 1900 to 2016). We also contribute a solution to a fundamental weakness of extant typologies: The unknown extent of misclassification due to uncertainty from measurement error. V-Dem’s measures of uncertainty (Bayesian highest posterior densities) allow us to be the first to provide a regime typology that distinguishes cases classified with a high degree of certainty from those with “upper” and “lower” bounds in each category. Finally, a comparison of disagreements with extant datasets (7%–12% of the country-years), demonstrates that the RoW classification is more conservative, classifying regimes with electoral manipulation and infringements of the political freedoms more frequently as electoral autocracies, suggesting that it better captures the opaqueness of contemporary autocracies