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Dissolving microneedle arrays for enhanced transcutaneous delivery of a model antigen
No full textVaccination remains the most important approach to offering protection from infectious diseases. However, using needles and syringes for vaccine administration continues to be a matter of concern, especially in developing countries. Re-use of needles, needle stick injuries and improper disposal of needles in these regions of the world increase the risk of spreading blood-borne pathogens among health care workers, patients and the wider community. The concerns about the safe vaccination practice have led to an intensive effort to develop safe delivery methods for vaccines and replace hypodermic injections. The opportunity to develop a safe and effective method of vaccination using a minimally invasive method is becoming real. The most promising approaches is microneedle (MN) array which has proven to be a safe and cost effective method for vaccination. The current thesis was focus on dissolvable MNs fabricated from 20%w/w poly(methyl vinyl ether/maleic acid) loaded with a model antigen, ovalbumin (OVA). Various experiments were carried out during this thesis to investigate the feasibility and efficacy of using MNs for vaccine delivery. The in vitro studies showed that MNs loaded with OVA were strong enough to avoid breaking under high compression force. The integrity of the primary and secondary structure of OVA loaded into MN arrays successfully ensured. Further, MNs enhanced the release of OVA into the skin compared to passive permeation. In in vivo studies, the OVA released from the MNs' matrix upon insertion into mouse skin targeted dendrite cells (DCs). This thesis showed that av A was engulfed by DCs, processed and migrated to the lymph nodes. Consequently, the processed antigen encountered naive T cells, which led to initiation of robust humoral and cellular immune responses indicated by production of IgG, IgG 1, IgG2a, IFN-γ and IL-4. Interestingly, the PMVE/MA copolymer used to fabricate MNs seems to have adjuvant effects, indicated by the higher IgG level of mice immunized using MNs fabricated from PMVE/MA loaded with OVA compared with MNs fabricated from PMVE/MA and loaded with OVA plus adjuvant imiquimod.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Is the use of brewery spent grain in bioremediation of diesel contaminated soil sustainable
No full textRemediation of contaminated land needs to be carried out using methods that are both cost effective and minimise environmental pollution. However, the remediation option currently chosen by practitioners is often based upon limited economic information with the true environmental costs not being considered. This can result in the least sustainable option being chosen. This study has developed a methodology to evaluate the sustainability, in terms of economic and environmental costs, for a range of treatments available for the remediation of diesel contaminated land, including bioremediation (with and without the addition of brewery spent grain), disposal to landfill and thermal treatment. Initial laboratory investigations indicated that the use of brewery spent grain decreased the time taken for the clean-up of soil contaminated with diesel, suggesting that bioremediation augmented by the addition of this organic material was a viable option. A costing model was then developed that included all of the costs associated with the remediation options chosen. This included both direct and indirect costs. The results show that considering the indirect costs of remediation such as costs associated with delayed development the land, make bioremediation in this study an economically feasible option. Finally environmental costs were considered with a focus on the release of carbon dioxide a known greenhouse gas. Respirometry was used to determine the volume of carbon dioxide released during the bioremediation process. This information was then combined with data collected from a range of other sources and the impact of the chosen remediation options on atmospheric greenhouse gas release was evaluated. Other environmental impacts were also determined including land and water pollution. The results indicate that bioremediation with brewery spent grain has one of the lowest environmental costs and showed that emission from pollutants such as NOx, PMl.O, PM2.5, NH3 and S02 could contribute to the limit values in the area covered by remediation work. The model developed in this study has indicated that the use of bioremediation with and without the use of brewery spent grain is a sustainable remediation option providing both direct and indirect economic costs are included. The results have indicated that, the strategy of using brewery spent grain to augment bioremediation process promotes the re-use of by-product material, reduces waste and conserve resources. There is a need for the remediation industry to adopt similar models in order that decisions made, as to the remediation option chosen, are based upon accurate costings of their sustainability.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Characterization of the clinical phenotype of tuberculous meningitis in children with TB meningitis in Vietnam
No full textTuberculosis, caused by the bacterium Mycobacterium tuberculosis, kills 1.4 million people each year. Tuberculous meningitis (TBM) is the most severe manifestation of disease caused by M.tuberculosis with high mortality, and disabling neurological sequelae common among those who survive. Early diagnosis and initiation of antituberculous chemotherapy are the strongest prognostic factors for a successful outcome, yet diagnosis of TBM remains challenging, with conventional microbiological techniques for detection of M.tuberculosis either slow or insensitive. Standardised treatment regimens use the same drugs and dosages as pulmonary TB, despite the variability in CSF penetration of these drugs. Treatment regimens for TBM have never been optimized through randomized controlled trials and little is known about the long-term outcomes of those who survive. In addition children with TBM may require different dosages to adults.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Quantifying monetary benefits of intermittent generators to electrical power networks
No full textTo meet the renewable targets set by the government's renewables portfolio, an increasing penetration of distributed generation, mainly wind energy conversion systems, is expected to connect to the UK power system networks. Since a significant proportion of these generators will connect to distribution networks, it is important for the network owners to evaluate how distributed generators will benefit them. From the distribution network operator's point of view, the understanding of the benefits which different wind developments can bring about is crucial in strategic planning to earn some performance incentives in a more efficient system. This work aims at providing a platform for system operators to evaluate the long-term benefits of connecting intermittent generation to typical UK power system networks, and help decide the most economically viable expansion option. Factors considered in this cost benefit analysis are the network investment deferral, the capacity credit, the reliability improvement and the reduction in system losses brought about by intermittent generation. Each of the factors mentioned were analysed with different wind penetration scenarios, and the magnitude of their benefits quantified. A common test system was then utilised to perform a cost benefit analysis including all the factors and it was seen that an indefinitely increasing wind penetration does not inexorably increase the benefits, unless the network is properly reinforced to accommodate increased generation levels. The largest contributor to benefits brought about by DGs is reliability improvement when wind penetrations of 9, 18 and 26% were considered on the IEEE reliability test system. This is translated into around 68-83% of the benefits due to a reduction in costs associated with interruptions and outages when DGs are allowed to work in islanding mode and additional future reinforcements are disregarded.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
The adaptive reference-state minimal control synthesis algorithm : with application to the control of shaking-tables
No full textLessons learnt from the recent catastrophic earthquakes and tsunami across the world motivate research testing using full -scale earthquake shaking-tables. Through this testing avenue, the effects of an earthquake can be reproduced. The dynamic tests involved play significant roles in ensuring the reliability, durability and functionality of engineering systems. This in turn has an impact on lives of people. The fidelity of the results obtained from shaking-tab le tests are largely influenced by the accuracy of the control system. Currently. conventional linear control schemes are widely used on many shaking-tables, but their control performance can significantly deteriorate in the face of dynamic uncertainties, non-linearities and external disturbances. Generally, a feedback control strategy is employed to compensate such disturbances and improve the closed-loop stability of the system. In practice, however, many shaking-tab le facilities have some controller design restrictions: primarily, performance enhancement with in the feedback-loops is explicitly not allowed due to confidentiality and/or safety reasons. Beside these issues, a shaking-tab le system which can generate a large amplitude acceleration (more than -20m/s2)) earthquake wave is in a high demand, due to recent earthquakes recorded in Japan being at such levels of intensity. Nevertheless, most large shaking-tab les cannot reproduce this level of acceleration due to the mechanical limitations in their actuation systems. This thesis describes how a conventional linear controller can be enhanced by a novel, feed forward adaptive control strategy, called the reference-state minimal control synthesis algorithm and its application to the control of shaking-tab les. Furthermore, the development of a new shaking-table configuration. called a multi-stage shaking-table which is used to generate a high-acceleration table motion, is also presented. Comparative simulation and implementation tests show that significant performance improvements are achieved with the new control scheme, in spite of non- linearities and parameter changes in the controlled system.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Life and death : a study of the wills and testaments of men and women in London and Bury St. Edmunds in the late fourteenth and early fifteenth centuries
No full textThe aim of this thesis is to investigate the lives of men and women living in London and Bury St. Edmunds in the late fourteenth - early fifteenth centuries. Sources studied include the administrative and legal records of the City of London and of the Abbot and Convent of St. Edmund's abbey; legislation and court records of royal government and the wills and testaments of Londoners and Bury St. Edmunds' inhabitants. Considerable research on a wide range of topics on London. but for less work on Bury St. Edmunds, has already been undertaken; however, this thesis is the first systematic comparative study of these two towns. The introduction discusses the historiography and purpose of the thesis; the methodology used, and the shortcomings of using medieval wills and the probate process. Chapter One discusses the testamentary jurisdiction in both towns: who was involved in the will making process, and the role that clerics played as both executors and scribes and how the church courts operated. Chapter Two focuses on testators' preparations for the afterlife, their choices concerning burial location, funeral arrangements and the provisions made for prayers for their souls. Chapter Three examines in detail their pious and charitable bequests and investigates what 'good works' testators chose to support apart from 'forgotten tithes'. The family and household relationships, including servants and apprentices, are examined in Chapter Four, exploring -the differences in bequests mode depending on the testators ' marital status. together with evidence for close friendships and social networks. Chapter Five discusses the ownership and types of books referred to in wills and the inter-relationship between the donors and the recipients. Testators' literacy and the provision for education are also investigated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Stress and creep damage evolution in materials for ultra-supercritical power plants
No full textThe so-called creep strength enhanced ferritic (CSEF) 9-12% Cr steels have been identified as the most promising class of materials for some of the key components in ultra-supercritical fossil-fired power plants, including the main steam pipes, headers and superheater tubings. These steels are less costly, and they have a lower coefficient of thermal expansion and a higher thermal conductivity when compared with austenitic stainless steels, making them less susceptible to degradation through thermal fatigue. However, experience has shown that the weldments in these steels are particularly prone to premature creep failure, due to a localised form of cracking in the heat-affected zone {HAZl, which is referred to as Type IV cracking. The work presented in this thesis is concerned with the effects of residual stresses and constraint on Type IV cracking. In the first part of this work, the residual stresses in a 25.4 mm thick, 324 mm diameter pipe girth weld, made in a P91 steel pipe, have been measured in both the as-welded and post weld heat treated (PWHT) conditions using neutron diffraction, and compared with the corresponding metallurgical zones across each weld. It was found that the highest as-welded tensile stresses resided near the outer boundary of the HAZ, and towards t he weld root region and these were not fully relieved by the applied PWHT. In both conditions substantial tensile direct and hydrostatic stresses existed across the HAZ, including the fine-grained and intercritically-annealed regions, where premature Type IV creep failures manifest in 9-12% Cr steel welds. Compressive stresses were found in the weld metal coinciding with the last weld bead to be deposited. In the second part of the work, creep tests were conducted at 625°C on cross-weld and simulated fine-grained HAZ specimens. The contributions of specific influences on creep performance (such as residual stress, constraint and creep damage associated with relaxation of residual stresses during PWHT) were then systematically examined. It was found that the geometric constraint (introducing a triaxial stress state) was beneficial in improving creep rupture life and that residual stresses (of the order of 50 MPa) showed a. clear reduction in life. Moreover there was some evidence that residual stress relaxation associated with PWHT may introduce some creep damage. The digital image correlation (DIC) technique was applied to resolve tensile and time• dependent creep deformation properties along the length of P91 cross-weld samples. The results demonstrated the capability of the Die technique for full field measurement of strain during both room-temperature-tensile and high temperature creep tests in the vicinity of welded joints, where the gradients in microstructure and mechanical properties can be steep.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Nouvelle prise en charge des patients âgés atteints d hémopathie maligne (Place du médecin généraliste dans l évaluation gériatrique pré-thérapeutique dans le service d Hématologie de l Hôpital d Instruction des Armées Percy )
No full textLE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF
La consommation de cannabis facteur pronostique un an après un premier épisode psychotique? (étude prospective sur un an portant sur 121 patients hospitalisés pour un premier épisode psychotique)
No full textContexte: l.'usage de cannabis concerne en moyenne, dans les populations qui souffrent de schizophrénie. un patient sur deux. Une abondante littérature suggère qu'à long terme, le cannabis peut constituer un élément déclenchant de troubles psychotiques, tout au moins chez les consommateurs vulnérables. En revanche, peu de recherches ont évalué l'impact de la consommation sur la progression d'une psychose d'éclosion récente. Objectifs: l'objectif de notre étude vise à déterminer si l'usage de cannabis avant la survenue d'un premier épisode psychotique, constitue un facteur prédictif de son évolution. Nous avons réalisé une étude prospective sur une période d'un an, auprès de 121 patients, hospitalisés au CHU de Montpellier pour un premier épisode psychotique. Résultats: à l'admission, près de la moitié des sujets a déclaré un usage de cannabis. Ces patients sont significativement plus souvent des hommes (p = 0.0127), plus jeunes (p = 0.0408) que les non-consommateurs. Les taux de rémission à un an, de l'ordre de 60%, sont comparables, selon que les patients faisaient ou non usage de cannabis avant l'hospitalisation. De même, la consommation ne semble pas assombrir le pronostic, en termes de symptomatologie psychotique, conscience des troubles, qualité de vie ni fonctionnement cognitif. Conclusion: l'ambiguïté des données publiées à ce jour requiert la réalisation d'études complémentaires à grande échelle, afin de déterminer si la consommation de cannabis doit devenir une cible prioritaire en termes de santé publique et, si tel est le cas, de mettre en oeuvre des stratégies d'intervention précoces, déterminantes dans le cadre d'un premier épisode psychotiqueBackground: Cannabis use affects, in people who suffer from schizophrenia, about one in two patients. Many articles suggest that long-term cannabis use may induce psychosis, at least among vulnerable users. Nevertheless, few research did assess the impact of consumption on recent-onset psychosis outcome. Aims : our study aims to ascertain whether cannabis use, before a first- episod e psychosis, predicts its evolution. A one year prospective study was realized among 121 patients, admitted ln the CHU de Montpellier for a first-episode psychosis. Results: when admitted, nearly haIf subjects reported a cannabis consumption. These patients are more often men (p = 0.0127), younger (p = 0.0408) than non-users. Remission rates after one year, about 60%, are similar, depending on whether the patients did or didn't use cannabis before hospitalization. Likewise, consumption doesn't appear to worsen the prognosis, concerning psychotic symptoms, awareness of the disorder, quality of life or cognitive functioning. Conclusion: The ambigulty of publlshed data requires further, large-scale studies, to determine whether cannabis use has to become a public health concern and, in this case, to Implement early intervention strategies, essential in first-episode psychosisMONTPELLIER-BU Médecine UPM (341722108) / SudocSudocFranceF
Sécurisation de la prise en charge médicamenteuse en Etablissement d'Hébergement pour Personnes Agées Dépendantes (une démarche régionale et pluridisciplinaire)
No full textREIMS-BU Santé (514542104) / SudocSudocFranceF