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.

[Truncated abstract] The present thesis is devoted to the development of new methods for transient stability-constrained optimal power flow, probabilistic transient stability assessment and security-constrained ancillary services allocation. The key objective of the thesis is to develop novel dispatch and assessment methods for power systems operation in the new environment of electricity markets to ensure power systems security, particularly transient stability. A new method for economic dispatch together with nodal price calculations which includes transient stability constraints and, at the same time, optimises the reference inputs to the Flexible AC Transmission System (FACTS) devices for maintaining power systems transient stability and reducing nodal prices is developed. The method draws on the sensitivity analysis of time-domain transient stability simulation results to derive a set of linearised stability constraints expressed in terms of generator active powers and FACTS devices input references. '...' The low computing time requirement of the two-point estimate method allows online applications, and the use of detailed power systems dynamic model for time-domain simulation which offers high accuracy. The two-point estimate method is integrated in a straightforward manner with the existing transient stability analysis tools. The integrated software facility has potential applications in control rooms to assist the system operator in decision making process based on instability risks. The software system when implemented on a cluster of processors also makes it feasible to re-assess online transient stability for any change in system configuration arising from switching control. The method proposed has been tested on a representative power system and validated using the Monte Carlo simulation. In conjunction with the energy market, by which forecasted load demand is met by generator dispatch, ancillary services are required in relation to control for secure system operation and power quality. The final part of the thesis has a focus on the key aspect of allocating these ancillary services, subject to an important constraint that the dispatch of the ancillary services will not impair the system security achieved in the load dispatch. With this focus and requirement, the thesis develops a new dispatch formulation in which the network security constraints are represented in the optimal determination of generator active power schedule and allocation of ancillary services. Contingencies considered include power demand variations at individual load nodes from the values specified for the current dispatch calculation. The required changes in generator active powers to meet the new load demands are represented by additional control variables in the new dispatch formulation which augment those variables in the traditional OPF dispatch calculation. Based on the Lagrange function which includes the extended set of security constraints, the formulation derives the optimality condition to be satisfied by the dispatch solution, together with the marginal prices for individual ancillary service providers and LMPs. The effects of the security constraints are investigated and discussed. Case studies for representative power systems are presented to verify the new dispatch calculation procedure.

Thesis (Ph.D.)--Indiana University, 2009. / Title from screen (viewed on December 1, 2009). Department of Anatomy and Cell Biology, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Zao C. Xu, Feng C. Zhou, Charles R. Yang, Theodore R. Cummins. Includes vitae. Includes bibliographical references (leaves 115-135).

Context: As one of the major causes of death and disability in Canada, research into the treatment and prevention of acute cerebrovascular syndrome (ACVS) remains a priority for clinicians, researchers and the general public. Understanding the relationship between current treatment practices of a rapid stroke clinic and patient outcomes is an essential part of measuring success and considering opportunities for quality improvement. Objective: This study compared the 90-day and 1-year hospital admission and mortality outcomes of patients who were referred to and seen in a rapid stroke clinic (the shows) following an initial transient neurological event (TNE) with those who were referred to but not seen in the same clinic (the no-shows). The specific outcomes examined were stroke events, cardiovascular events and all other hospital events. Methods: In this post-test only non-equivalent group design, data on patient outcomes was collected in the Victoria-based Stroke Rapid Assessment Unit (SRAU) between 2007 and 2013. Analysis included an assessment of group equivalency for possible confounders (age, sex and severity score) and two sets of multivariate logistic regressions were conducted on nine outcomes. Results: An independent t-test revealed there was a statistically significant difference between the mean age of the shows (mean= 68.26) and no-shows (mean= 69.90) (p<0.01). While the proportion of males and females in each of the groups was similar (Fisher’s Exact test, p = 0.831, ns), the severity score of the treatment group (mean= 3.64) was statistically more severe in the show group than the no-show group (mean= 3.50; t = 2.137, p<0.05). Controlling for age, sex and severity score, the odds ratios (ORs) were calculated to compare the odds of various outcomes in the treated (shows) versus the untreated (no-shows) patients groups. ORs for the 90-day and 1-year hospital admissions for stroke-related events were 0.071 (p<0.01) and 0.091 (p<0.01), respectively; the OR for 1-year stroke deaths was 0.167 (p<0.01), indicating a strong protective factor related to attending the clinic appointment. For the cardiovascular outcomes, the ORs for hospitalizations were 0.967 (ns) at 90-days and 0.978 (ns) within 1-year and the OR for the 1-year cardiac-related deaths was 0.391 (ns). For all other outcomes, the ORs were 0.525 (p<0.01) for hospitalizations within 90-days, 0.579 (p<0.01) for hospitalizations within 1-year and 0.299 (p<0.01) for deaths within 1-year. These findings remained consistent with re-analysis excluding subjects who had an event within 5.4 days of their initial TNE. These latter finding largely rules out the possibility that the primary reason the no-shows did not make their clinic appointment, was due to a subsequent hospital event. Conclusion: The ORs for the outcomes show a protective effect of stroke and all other hospital outcomes (but not cardiac events) for patients treated in the rapid assessment clinic. The exclusion of patients who experienced an outcome while waiting for a clinic appointment, lowered the protective effect of the treatment and emphasized the need for rapid assessment but did not alter the main study conclusions. Future research that explores factors influencing appointment adherence and patient attitudes towards acute treatment of TNEs might reveal strategies that could help to reduce the number of patients that remain untreated and at a higher risk for poor outcomes. / Graduate

Melanome zählen zu den zehn häufigsten Tumorentitäten weltweit. Bei frühzeitiger Diagnose ist eine Exzision im Gesunden kurativ. Sobald eine Resektion im Gesunden jedoch nicht mehr möglich ist, sinken die Heilungschancen drastisch. Maligne Melanome sprechen wenig auf konventionelle Tumortherapien wie Radiatio und zytostatische Chemotherapie an. Daher werden neue Therapieoptionen in der Melanomtherapie getestet. Neueste Ansätze beziehen sich auf die Modulation von Immunzellen mittels monoklonaler Antikörper sowie die Modifikation der Signaltransduktion über die Mitogen-aktivierte Protein Kinase Kinase (MAPKK = MEK), BRAF und c-KIT. Auch Ionenkanäle stellen eine vielversprechende, zukünftige Option in der Behandlung maligner Melanome dar. Ich konnte zeigen, dass neben der bereits beschriebenen funktionellen Expression des „transient receptor potential“ Kanals TRPM8 in Melanomzelllinien auch TRPA1 in verschiedenen Melanomzelllinien exprimiert und funktionell ist. Die Phytopharmaka Senföl (Allylisothiozyanat; AITC) und Zimtaldehyd zeigen in Melanom-Modellen antitumoröse Effekte. Zudem sind beide Substanzen potente Stimulatoren von TRPA1. In dieser Arbeit wurde untersucht, ob AITC und Zimtaldehyd TRPA1-vermittelt die Proliferation, Apoptose und Migration von Melanomzellen beeinflussen. Das Vorkommen von TRPA1 in verschiedenen Melanomzelllinien wurde auf molekularbiologischer Ebene, mit fluorometrischen Bestimmungen des TRPA1-vermittelten Ca2+-Einstroms sowie in elektrophysiologischen Messungen nachgewiesen. Anschließend wurde die funktionelle Relevanz von TRPA1 bezüglich tumorhemmender Eigenschaften geprüft. Durch die Anwendung von TRPA1-Blockern konnte die AITC- und Zimtaldehyd-induzierte Verminderung der Proliferation nicht aufgehoben werden. Auch bezüglich der Migration und Apoptose konnte keine Korrelation zu einer TRPA1-Modulation festgestellt werden. Daher scheinen die durch AITC und Zimtaldehyd induzierten Effekte höchstwahrscheinlich nicht durch TRPA1 vermittelt zu werden.

Quand un stimulus visuel de haut contraste précède et puis succède à la présentation d'une cible de faible contraste à la même position, la cible peut devenir non-reconnaissable ou même non-détectable. Cet effet de masquage a été étudié en profondeur et beaucoup de ses paramètres sont bien définis. Mais en utilisant une nouvelle méthode avec une séquence de masques et de cibles en mouvement, il est maintenant possible de séparer de manière perceptuelle et attentionnelle la cible des masques tout en conservant l'ordre d'apparition des masques et de la cible à chaque endroit. Cette thèse utilise cette technique de stimuli en mouvement pour répondre à trois questions qui ne pourraient pas être résolu en utilisant une méthode de masquage conventionnelle. Dans la première série d'expériences on a testé si l'attention portée au masque influence l'impact de celle-ci sur la cible. Nous avons utilisé un écran où une séquence masque-cible-masque apparaît à une position puis à chaque 'frame' suivant elle apparaît à la position adjacente. Cette méthode permet à l'observateur de suivre attentionellement la cible sur son trajet, tout en évitant les masques distracteurs qui paraissent être à côté de la cible spatialement et non temporellement. Quand les masques sont efficaces, la position de la cible paraît être vide. Nous comparons l'efficacité du masquage quand l'attention n'est pas dirigée vers les masques, à l'efficacité du masquage quand l'attention ne peut pas éviter les masques, comme dans le masquage conventionnel. Nous n'avons trouvé aucune différence significative entre les deux conditions attentionnelles, ce qui indique que l'attention portée sur les masques ne module pas leur efficacité. Ensuite nous avons testé l'importance de l'espacement dans la séquence masque-cible-masque. Il n'y avait pas plus de masquage quand les espacements étaient réduits, ce qui suggère que le masquage n'est pas le résultat de masquage latéral ou de 'crowding' (encombrement spatial) aux distances testées. Enfin nous avons comparé la contribution de chaque masque: celui qui précède la cible (le pré-masque) et celui qui suit la cible (post-masque). Nous avons trouvé que le pré-masque génère la majorité de l'effet de masquage tandis que le post-masque a peu d'influence. Dans la seconde série d'expériences nous avons étudié ce qu'il advient du stimulus masqué. En baissant le contraste de la cible juste en dessous de son seuil de détection et en lui donnant une couleur saillante, nous avons découvert un stade intermédiaire où les caractéristiques ('features') de la cible sont reportées à la position d'un des masques. Avec une série d'expérience nous avons montré que la cible est intégrée avec le masque qui la suit directement et temporellement à la même position. Finalement nous avons étudié si un stimulus qui est masqué à un niveau invisible peut quand même exercer une influence sur une cible proche dans un arrangement de crowding. Nous avons comparé la détection d'une cible avec deux flankers (distracteurs adjacent) dans la zone de crowding, à la détection d'une cible quand les deux flankers sont masqué et que leur position paraît être vide. Pour conclure, la méthode de séquence en mouvement a révélé de nouvelles caractéristiques du masquage qui ne pouvaient pas être examinées en utilisant des techniques de masquage conventionnelles. Premièrement nous avons découvert que l'efficacité du masque est comparable que l'attention soit dirigée sur le masque ou non. Deuxièmement nous avons montré que les caractéristiques d'une cible qui est supprimée à sa position physique peuvent apparaître à la position du masque qui la suit temporellement. Et finalement, nous avons examiné l'effet de flankers masqués sur une cible dans un arrangement de crowding. / When high contrast visual stimuli precede and follow a low contrast target at the same location, the target may become unrecognizable and even undetectable. This masking effect has been extensively studied and many of its parameters are well characterized. However, using a new technique with a moving sequence of masks and targets it is now possible to perceptually and attentionally separate the target from the masks while retaining the same temporal order of masks and target at each location. This thesis exploits this moving stimulus technique to ask three questions that could not be addressed in standard masking paradigms. In the first series of experiments we looked at whether attention to the mask affected its impact on the target. We used a display where the mask-target-mask sequence appears at one location and on each subsequent frame it appears in the adjacent location. This allows observers to attentively track the target across locations without attending to the masks which appear perceptually adjacent in space rather than in time. When the masks are effective, the observer sees a blank space at the target location. We compare the effectiveness of this masking when the masks are unattended to the effectiveness when the masks are attended as in standard masking. We found no significant difference between the two attentional conditions suggesting that attention to the masks does not modulate their effectiveness. We next examined the importance of the spacing within the mask-target-mask sequences. There was no increase in the masking effect as spacing was reduced, suggesting that the masking was not a consequence of lateral masking or crowding at the spacings we tested. Finally, we compared the contributions of each mask individually: the one that preceded the target (pre-mask) and the one that followed (post-mask). We found that the pre-mask generated the majority of the masking effect while the post-mask was of little influence. In the second series of studies we investigated the fate of a masked stimulus. By lowering the target contrast just below its detection threshold and giving it a salient color, we found an intermediate, "lurking" stage where the target's features migrate to one of the mask locations. Through a succession of experiments we found that the target is integrated with the mask directly following it in time at the same location. Finally we looked at whether a stimulus that is masked to invisibility can still exert influence over nearby targets in a crowding array. We compared the detection of a crowded target with two flankers, compared to the detection of a target when the two adjacent flankers are masked so that their locations appear empty. In conclusion, the moving sequence technique revealed new characteristics of masking that could not be examined in standard masking paradigms. First, we found that the effectiveness of a mask was the same whether it is attended or not. Second, we showed that once a masked target has been suppressed from its physical location, its features can be found "lurking" at the location of the mask that follows the target in time. Finally, we examined the effect of masked flankers on a target in a crowding paradigm.

Large aspiny neurons are the only non-GABAergic neurons in the striatum. After transient cerebral ischemia, large aspiny neurons survive while medium spiny neurons die. Previous studies have shown that differential changes in the intrinsic membrane properties and excitatory synaptic transmission play a role in this selective vulnerability. However, the role of inhibitory synaptic transmission in this selective vulnerability is still unknown. Since inhibitory tone is very important in the control of neuronal excitability, the present study is aimed at examining if there are any changes in inhibitory synaptic transmission in striatal neurons after ischemia and the possible mechanisms. We also examined if facilitation of inhibitory synaptic transmission by muscimol could attenuate ischemic neuronal injury in the striatum after ischemia. Results from this study will improve the understanding of the mechanisms underlying selective neuronal injury after transient cerebral ischemia. We hope this study could contribute to the translational studies for the stroke patients after cardiac arrest. / Indiana University-Purdue University Indianapolis (IUPUI) / In the striatum, large aspiny (LA) interneurons survive transient cerebral ischemia while medium spiny (MS) neurons die. Excitotoxicity is believed to be the major cause for neuronal death after ischemia. Since inhibitory tone plays an important role in the control of neuronal excitability, the present study is aimed at examining if there are any changes in inhibitory synaptic transmission in striatal neurons after ischemia and the possible mechanisms. Transient forebrain ischemia was induced in male Wistar rats using the four-vessel occlusion method. Inhibitory postsynaptic currents (IPSCs) were evoked intrastriatally and whole-cell voltage-clamp recording was performed on striatal slices. The expression of glutamate decarboxylase65 (GAD65) was analyzed using immunohistochemical studies and Western blotting. Muscimol (a specific GABAA receptor agonist) was injected intraperitoneally to the rats (1 mg/kg) to observe ischemic damage, evaluated by counting the survived cells in the striatum after hematoxylin & eosin (HE) staining. The amplitudes of evoked IPSCs were significantly increased in LA neurons while depressed in MS neurons after ischemia. This enhancement was due to the increase of presynaptic release. Muscimol (1 μM) presynaptically facilitated inhibitory synaptic transmission in LA neurons at 24 h after ischemia. The optical density of GAD65-positive terminals and the number of GAD65-positive puncta was significantly increased in the striatum at both 1 day and 3 days after ischemia. Consistently, data from western blotting suggested an increased expression of GAD65 in the striatum after ischemia. For the rats treated with muscimol, the number of survived cells in the striatum was greatly increased compared to the non-treatment group. The present study demonstrates an enhancement of inhibitory synaptic transmission in LA neurons after ischemia, which is contributed by two mechanisms. One is the increased presynaptic release of GABA mediated by presynaptic GABAA receptors. The other is the increased expression of GAD. Facilitation of inhibitory synaptic transmission by muscimol protects striatal neurons against ischemia. Therefore, the enhancement of inhibitory synaptic transmission might reduce excitotoxicity and contribute to the selective survival of LA neurons after ischemia.

No description available.

Transient Liquid phase bonding (TLP) has evolved as a viable method of joining difficult-to-weld superalloys with potential of producing joints with comparable mechanical properties to the base material. Although the high temperature properties of aerospace superalloys have been studied extensively, there is little information on the corrosion behaviour of these special class of materials that had been subjected to TLP bonding. In this work, electrochemical assessment of the corrosion behaviour of TLP bonded nickel-based superalloy was performed. Microstructural evaluation of the TLP bonded joint revealed the presence of a centreline eutectic when isothermal solidification was not completed and the corrosion resistance increased with a decrease in this eutectic width. The use of a composite interlayer produces TLP joints with smaller eutectic size and results in complete isothermal solidification in shorter processing time. Complete isothermal solidification, achieved with the composite interlayer, results in a uniform chromium distribution in the joint centre and produced a corrosion performance similar to the as-received cast base metal. It was found that aside from the mere presence of chromium, which is widely recognised as necessary for corrosion resistance, its uniform distribution within the joint region is imperative for achieving adequate corrosion resistance in TLP joints. / May 2016

International Telemetering Conference Proceedings / October 25-28, 1993 / Riviera Hotel and Convention Center, Las Vegas, Nevada / In order to reduce the measuring channels for the single-transient signals, the author propose the time division multiplex technique and introduce the method of SAW delay line in this paper. That used method of SAW tap-delay line in this system is different from previous methods consists in making traditional method, which is one-path signal input different delayed multi- path signals output, alter new method, which is simultaneous multi-path signal inputs that are respectively delayed and one-path signal serial output.