Imaging markers of cerebral small vessel disease

Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment in the elderly population and it very often co-occurs with impairment resulting from other neurodegenerative pathologies. Cognitive impairment due to vascular pathology is potentially treatable; i.e. the progression could be slowed or even stopped by managing the underlying vascular disease. However, there is no specific treatment available for VCI up to date. One of the main reasons for this is an insufficient understanding of the disease pathophysiology. Cerebral small vessel disease is the primary pathology leading to VCI and therefore its study provides the chance to elucidate the mechanisms leading from vascular pathology to cognitive impairment. Understanding the underlying disease mechanisms is crucial for diagnosis, prevention and managing the disease. For this purpose, markers play an important role, as they indicate which disease processes are at play within the brain. This PhD-work aimed at finding optimal imaging markers for diagnosing cerebral small vessel diseases and estimating the vascular disease burden in the brain. Advances in brain imaging tools, in particular diffusion tensor imaging (DTI), have enabled the exploration of microstructural changes in the human brain, which precede the occurrence of lesions that are visible on conventional MRI. The first project focused on developing and establishing a DTI-based imaging marker for small vessel disease that is quantitative, reliable, and fully automated. This marker (peak width of skeletonized mean diffusivity, PSMD) was then systematically investigated - along with conventional imaging markers - in patients with hereditary and sporadic SVD, memory clinic patients as well as in patients with Alzheimer pathology. The results showed that PSMD outperformed the conventional markers in explaining the cognitive impairment scores. Furthermore, in longitudinal analysis, PSMD was more sensitive to disease related changes than any other imaging markers, which resulted in low sample size estimations for a hypothetical clinical trial. Additionally. PSMD showed very high interscanner reproducibility suggesting that it might be especially useful in multicenter studies. Interestingly, increases in PSMD were mostly linked to vascular but not to neurodegenerative disease. Therefore, PSMD could be a valuable tool to disentangle effects caused by these different pathologies, a common challenge in understanding cognitive impairment. This suggests that the newly established marker PSMD could be easily applied to large samples and may be of great utility for both research studies and clinical use. The second project focused on the evaluation of cortical superficial siderosis (cSS) as a potential new marker for cerebral small vessel diseases. cSS emerged recently as a marker for cerebral amyloid angiopathy (CAA). However, the presence of cSS is associated with many other signs of cSVD, such as cerebral microbleeds (CMB) and white matter hyperintensities (WMH), and therefore its specificity for CAA was questionable. The results of the second project revealed that the distribution patterns and frequency of CMB and WMH overlap between different subtypes of cSVD. This clearly demonstrated that these imaging features have limited discriminative value. More importantly, the presence of cSS was found to be strongly indicative of CAA. To summarize, the key findings reported in this PhD-work have important implications for diagnosing patients with cerebral small vessel disease, disentangling underlying pathologies, as well as for managing and treating the disease. The newly established imaging marker PSMD can be utilized to select the target population for clinical studies and may function as a surrogate marker for treatment effects. PSMD can be further used to identify patients who have a low disease burden as targets for prevention and early treatment

Asya Türk Kültürünün Bir Unsuru Olarak Mezar Taşı

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Tarihi Hamamlar

Taha Toros Arşivi, Dosya No: 106-Hamamlarİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Vakfın Gelişme ve Gerilemesindeki Etkenler

[No Abstract Available

Effective Road To Quantification Of Damages In EU Antitrust Law : Actions For Damages: A Hinder Or A Facilitator?

The competitiveness in and of the internal market of the EU is one of the main objectives of the Treaty of the European Union. In the EU, private enforcement is seen as a complimentary mechanism of public enforcement to attain the goals of competition law policy. Following the publication of Regulation 1/2003, the private enforcement of EU competition law has gained steady pace for development. During the past decade multiple legal instruments have been produced by the EU legislators to facilitate actions for damages, however, with limited accuracy and clarity for the victims of competition law infringements. The latest legislative piece, the Damages Directive, does not provide harmonization of the procedures leading up to the quantification phase or the methods for quantification .The procedural elements of the actions for damages are greatly left to the discretion of the national courts as long as the application of the twin EU principles of effectiveness and equality are ensured. The lack of clear guidelines in these aspects of the damages actions often create ambiguity and contrasting outcomes in different member states. Furthermore, the interplay between the tasks assigned to EU competition law combined with the application of “concept of effectiveness” often puts the parties in confusing situations in the hands of the national courts. This study focuses on the possibility of a victim of competition law infringement to effectively bring an action for damages by demonstrating the shortcomings of the various elements of the claim process and assesses whether the legal instruments and applicable other sources of law provide sufficient relief for the claimants. Furthermore, the policy choices of the EU are assessed to their compatibility from the potential victim’s and defendant’s perspective. The methods of quantification, which is the last phase of the claim is also reviewed from both economic and legal perspective. regarding The claim friendliness of the processes is also reviewed through its application, which remains in the hands of recent national case law. The study concludes that the policy choices are the main reason behind the inefficiencies and that effective application of competition law can be found by a more concentrated approach between the deterrence and corrective tasks assigned to private enforcement and advises the claimants to pursue a number of procedural reliefs

Structural lubricity under ambient conditions.

Despite its fundamental importance, physical mechanisms that govern friction are poorly understood. While a state of ultra-low friction, termed structural lubricity, is expected for any clean, atomically flat interface consisting of two different materials with incommensurate structures, some associated predictions could only be quantitatively confirmed under ultra-high vacuum (UHV) conditions so far. Here, we report structurally lubric sliding under ambient conditions at mesoscopic (∼4,000-130,000 nm(2)) interfaces formed by gold islands on graphite. Ab initio calculations reveal that the gold-graphite interface is expected to remain largely free from contaminant molecules, leading to structurally lubric sliding. The experiments reported here demonstrate the potential for practical lubrication schemes for micro- and nano-electromechanical systems, which would mainly rely on an atomic-scale structural mismatch between the slider and substrate components, via the utilization of material systems featuring clean, atomically flat interfaces under ambient conditions

Vakıf Kültür Varlıklarının Yaşatılması Gerekliliği ve Batı Anadolu'dan Birkaç Örnek

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Vakıflar Genel Müdürlüğü Arşivi'ndeki Bir Deftere Göre XVIII. Yüzyıl Başlarında Varna

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Türkiye Selçuklularında İdari Birim ve Bununla İlgili Meseleler

[No Abstract Available