Stroke is the second most common cause of death worldwide and the commonest cause of dependency, creates a huge societal burden and is responsible for billions of pounds in health and social care costs. About 30% of strokes occur in individuals with a previous transient ischaemic attack (TIA) or minor stroke. Effective prevention would minimise the consequences. However, the diagnosis of TIA is difficult, particularly by non-experts. About 50% of patients with a suspected TIA or minor stroke have atypical TIAs or a non-vascular diagnosis (TIA/minor stroke mimics). Although there is some evidence that non-specific Transient Neurological Attacks (TNAs) have an increased risk of acute vascular events, the evidence is still both thin and controversial. The aim of my thesis has been to evaluate the burden of TIA/minor stroke mimics, TNAs and all acute cerebrovascular events among all referrals from the general population to a TIA clinic; to determine the reliability of clinical diagnosis of TIA and non-specific TNA; to improve the classification of non-specific TNAs; and to predict the risk of stroke and other major vascular events after a non-specific TNA and TNA syndromes. I have collected and analysed data from a population-based study, the Oxford Vascular Study (OXVASC). OXVASC is an ongoing prospective, population-based incidence study of all vascular diseases in all territories in Oxfordshire, UK, which started in 2002. The study population comprises approximately 92,728 individuals registered with nine GP practices and uses multiple overlapping methods of "hot" and "cold" pursuit to identify patients with acute vascular events. The research described in this thesis has several clinically relevant findings which can contribute to improving the diagnosis and treatment of patients with suspected TIAs. First, I highlighted that TIA/minor stroke mimics (mimics) were responsible for one quarter of all suspected TIAs, had similar short- and long-term risk of acute cardiac events as did TIAs, and that the majority (70%) of mimics were complex neurological conditions. Second, I showed that TIA/minor ischaemic strokes are each more common than major ischaemic strokes and that TIA/minor ischaemic stroke patients together had two-thirds of all recurrent strokes and two-thirds of all myocardial infarctions and sudden cardiac deaths. Moreover, the 10 years' cumulative risk of stroke in patients with TIA, minor stroke and major stroke was very high and the risk of death among all cerebrovascular events was greater than 50%. Third, I found that the crude incidence rate of TNAs per 1000 people in OXVASC was slightly higher than the crude incidence rate of TIAs (0.73 versus 0.67) and increased with age. In addition, I reported that among TNA syndromes, transient isolated vertigo, unilateral sensory symptoms, migraine-aura like events and transient confusion had high incidence rates, whereas transient total paralysis and transient speech arrest had low incidence rates. Fourth, I showed that about one-third of TIAs seen in the first 10 years of OXVASC did not fulfil the classical criteria (NINDS-negative TIA) and had the same short- and long-term risk of stroke as NINDS-positive TIAs. Fifth, although the 90 days stroke risk after a TNA was lower than after a NINDS-positive TIA, in the post 90 days up to 10 years period the risk of recurrent stroke was not significantly different between the two groups. Sixth, the risks of stroke were higher than expected in the background population in all TNA categories (focal-TNA, non-focal TNA and focal plus non-focal TNA) and all TNA syndromes (isolated brainstem syndrome, migraine-like syndrome, isolated sensory syndromes, isolated visual disturbance, isolated speech disturbance, transient confusion and transient unresponsiveness) except transient amnesia. Moreover, non-focal TNAs and focal plus non-focal TNAs had a six times higher risk of stroke than expected and a similar risk to NINDS-positive TIAs. Finally, transient confusion and transient unresponsiveness had a relative risk of stroke nine times higher than expected and twice the risk of NINDS-positive TIAs.

<p> </p><p>The European Union has lead to higher collaboration between the European countries, more exchange of information and a tendency to centralize more political decisions. There is also a tendency to try to create legislations that are more similar in each nation.</p><p> </p><p>This paper aims at giving an idea about the challenges that the nations might meet when working towards higher archival collaboration within the European Union. The report by the European Commission “<em>Report on archives in the enlarged European Union - Increased archival collaboration in Europe: action plan” </em>from 2005<em> </em>states that there is a need for higher European collaboration within the field of archives. The goal is to create a gateway for the citizens to have easy access to archival information from the different member states.</p><p> </p><p>There are some obstacles for this to easily work. To start with the member nations have different cultural traditions and legislations when it comes to freedom of information. It has also got to do with technical issues such as which computer systems, file types and structures et c that are allowed.</p><p> </p><p>This paper takes its starting point in the field of digital deliveries to the national archives of Sweden and The United Kingdom. A comparison has been made to show the difference of how these countries proceed with their archival work to give an idea about how these differences can affect the wish for higher collaboration within the European Union.</p><p> </p><p> </p>

The European Union has lead to higher collaboration between the European countries, more exchange of information and a tendency to centralize more political decisions. There is also a tendency to try to create legislations that are more similar in each nation.   This paper aims at giving an idea about the challenges that the nations might meet when working towards higher archival collaboration within the European Union. The report by the European Commission “Report on archives in the enlarged European Union - Increased archival collaboration in Europe: action plan” from 2005 states that there is a need for higher European collaboration within the field of archives. The goal is to create a gateway for the citizens to have easy access to archival information from the different member states.   There are some obstacles for this to easily work. To start with the member nations have different cultural traditions and legislations when it comes to freedom of information. It has also got to do with technical issues such as which computer systems, file types and structures et c that are allowed.   This paper takes its starting point in the field of digital deliveries to the national archives of Sweden and The United Kingdom. A comparison has been made to show the difference of how these countries proceed with their archival work to give an idea about how these differences can affect the wish for higher collaboration within the European Union.

abstract: A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable helical structures with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Another alternative genetic system, glycerol nucleic acid (GNA) undergoes intrasystem pairing with superior thermalstability compared to that of DNA. Inspired by this property, I demonstrated a minimal nanostructure composed of both left- and right-handed mirro image GNA. This work suggested that GNA could be useful as promising orthogonal material in structural DNA nanotechnology. / Dissertation/Thesis / Ph.D. Chemistry 2011

The 'RNA World' hypothesis states that RNA was the first living system on the primitive Earth, where it carried out dual genotypic and phenotypic functions. Therefore, RNA must have self-assembled by purely chemical means from small prebiotic feedstock molecules. A plausible demonstration of the synthesis of RNA with the natural [5'→3'] phosphodiester linkage, and its self-replication has not been achieved so far. Some have speculated a 'simpler' informational polymer preceded it, and biology based on this polymer subsequently 'invented' RNA. The structurally simpler L-α-threofuranosyl nucleic acid (TNA) has been proposed as a primordial ancestor to RNA. A study into the potential self-assembly of TNA nucleotides was carried out. It is shown that as a direct result of TNA's structural simplicity, its generational chemistry is more difficult than RNA. The tetrose aminooxazolines are unstable under the conditions of its formation. The tetrose anhydronucleosides efficiently incorporate phosphate to form activated tetrose cytidine-2',3'-cyclic phosphates, but with the wrong stereochemistry. Strong support for the 'RNA world' hypothesis came from a report in 2009 of the prebiotic synthesis of activated pyridimine ribonucleoside-2',3'-cyclic phosphates. Oligomerisation studies were carried out on these activated monomers with various catalysts, and NMR studies were carried out to determine the aspects of their reactivity. It was found that only short oligomers are formed. However, nucleoside-2',3'-cyclic phosphates were found to selectively hydrolyse to a 2:1 mixture of 3' and 2'-monophosphates, and this observation was considered as etiologically relevant. Nucleoside-2' and 3'-monophosphates cyclise back to nucleoside-2',3'-cyclic phosphates upon phosphate activation, and so cannot be considered as direct candidates for oligomerisation. A chemistry that selectively uses the nucleoside-3'-phosphate for the synthesis of RNA, and recycles the unwanted 2'-phosphate would be highly desirable. Thus, a regio- and chemoselective reaction that selectively acetylates monomer and oligomer nucleoside-3'-phosphates at the 2'-hydroxyl in water is presented. Nucleoside-2'-phosphates are shown to acetylate less efficiently, and show a greater propensity to recyclise back to nucleoside-2',3'-cyclic phosphates. Purine nucleotides were also found to acetylate better than pyrimidines. This potentially primordial protecting group chemistry approach towards the prebiotic synthesis of RNA is conceptually novel, and has the potential to give a natural [5'→3'] phosphodiester linkage isomer. It is considered as a major step towards solving the long-standing problem of non-enzymatic self-replication of RNA.

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