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Please read the abstract in the section 00front of this document / Thesis (PhD)--University of Pretoria, 2009. / Civil Engineering / unrestricted

Railway transportation plays a vital role in modern societies. Due to increasing demands for transportation of passengers and goods, higher speed trains with heavier axle loads are introduced to the railway system, and it is expected to continue in the future. Therefore, track geometry bears huge static and dynamic forces that accelerate degradation process. As a result, railway track should be inspected regularly to detect geometry faults and to plan for maintenance actions in advance. Track geometry inspection has a profound impact on railway track availability and maintenance cost. Although there have been improvements in safety performance and maintenance planning of railway tracks, still infrastructure managers expect a more effective maintenance planning and scheduling regime. This thesis proposes a simulation-based model for optimization of track geometry inspection intervals. To simulate the track geometry evolution a linear model is used to model track geometry degradation in a maintenance cycle. It is assumed that the parameters of degradation model are random variables following lognormal distribution. Using the proposed model, the track geometry behaviour is simulated under different inspection intervals. Later, different inspection intervals are compared with respect to the cost function and the optimal range of inspection intervals is obtained.

Syfte: Beskriva ambulanssjuksköterskors erfarenhet av att använda snabbspår. Bakgrund: Inom ambulanssjukvården används begreppet snabbspår. Det är en arbetsmodellsom arbetats fram för att effektivisera vårdprocessen av patienterna. Där snabbspår används,ses ett snabbare omhändertagande av patienterna genom hela vårdkedjan, snabbare återhämtningoch minskad återinläggning. Ambulanssjuksköterskor arbetar på vetenskaplig grund ochefter beprövad erfarenhet, och ska efter undersökning av patientens hälsotillstånd bedöma ompatienter skall inkluderas i något snabbspår. Design: En kvalitativ intervjustudie. Metod: Hösten 2015 genomfördes nio intervjuer bland yrkesverksamma ambulanssjuksköterskorinom en region. Intervjuerna granskades med hjälp av kvalitativ innehållsanalys. Resultat: Två kategorier identifierades: Patientsäker vård och risk för vårdlidande. Subkategoriernavar; tydliga rutiner och riktlinjer, arbetslivserfarenhet, tydlig patientinformation, bristpå helhetssyn, fördröjd vårdtid, resurs och kompetensbrist och kommunikationsbrist. I berättelsernalyftes perspektiv utifrån ambulanssjuksköterskors, patienters och sjukvårdens synvinklar .Brister i användandet identifierades både regionalt och nationellt. Resultatet kundestort delas in i patientsäker vård och risker för att vårdlidande kunde uppstå för patienterna. Förbättringsförslag på sjukdomar/ skador som inte omfattas av snabbspår lyftes även fram. Slutsats: Snabbspår som ett arbetsverktyg för ambulanspersonalen ansågs vara en säkerhet,eftersom det garanterar likabehandling av personer med liknande sjukdomar/skador. Mennationella riktlinjer efterlystes, då dessa kan skilja sig mellan olika sjukhus och regioner. Efterfråganpå förbättringar för både regional och nationell nivå efterfrågades.

A via permanente representa um elemento imprescindível na composição do transporte ferroviário e seu desempenho deve ser adequado, de forma a garantir tanto segurança quanto conforto. Assim, diversos aspectos devem ser analisados ainda na fase de projeto, através de dimensionamentos que confrontem diferentes parâmetros da resposta da via e os limites estabelecidos. Dessa forma, o conhecimento do comportamento mecânico da via, devido aos esforços impostos pela passagem do material rodante, passa a ser essencial no projeto de uma estrutura que garanta os requisitos necessários, sem ser inviável economicamente. Visto que esse comportamento mecânico é muito sensível à rigidez vertical da estrutura, o presente trabalho apresenta análises da influência desse parâmetro na resposta da via e, consequentemente, no seu dimensionamento. Nesse contexto, o trabalho abrange tanto o caso de vias em lastro solicitadas por trens de carga, quanto o caso de vias em laje solicitadas por trens de passageiros em meios urbanos. No primeiro caso são realizados estudos paramétricos, por meio de modelos clássicos e um modelo mecanicista, para a análise de momentos fletores e deflexões nos trilhos, bem como tensões verticais nas camadas de lastro, sub-lastro e subleito. Já no segundo caso, são realizados estudos paramétricos relativos à transmissibilidade e à atenuação de vibrações causadoras de ruído secundário. Também é feita uma análise da influência da rigidez vertical na amplificação dinâmica das cargas estáticas, que pode ser aplicada a ambos os casos citados e até extrapolada para casos de vias de alta velocidade. Os resultados mostraram que aumentos de rigidez vertical resultam em ganhos do ponto de vista de momentos fletores e deflexões nos trilhos, além de maior resistência e capacidade de dissipação de tensões verticais nas camadas de lastro, sub-lastro e subleito. Por outro lado, esses aumentos também levaram a maiores tensões nas camadas subjacentes à grade citadas, além de atenuações de vibrações em menores intervalos de frequência e maiores amplificações dinâmicas das cargas estáticas em vias de alta velocidade. Assim, é mostrado que a influência da rigidez vertical, tanto da via como um todo quanto de alguns elementos específicos, não deve ser analisada de forma genérica, pois, dependendo do parâmetro da resposta da via considerado no dimensionamento, seu aumento pode representar uma influência positiva ou negativa. / The railway track is an essential element in the composition of rail transport and its performance should be adequate to ensure both safety and comfort. Therefore, several aspects should be analyzed still in the project phase, through project designs that compare the response of the track from the point of view of different parameters and some stablished limits. Thus, the knowledge of the mechanical behavior of the track due to stresses imposed by the passage of rolling stock becomes essential to the design of a structure which ensures the necessary requirements, without being uneconomic. Since this mechanical behavior is very sensitive to vertical stiffness of the structure, this thesis presents some analyses about the influence of this parameter in the track response and, consequently, in its design. In this context, the research covers both the case of ballasted tracks with freight trains and the case of slab tracks with passenger trains in urban areas. In the first case, parametric studies are performed by means of classical and mechanistic models with analyses of bending moments and deflections in rails, as well as the vertical stresses on ballast, sub-ballast and subgrade layers. In the second, it was analyzed in the parametric studies the transmission and attenuation of vibrations causing ground borne vibration. In addition to these, there is also an analysis of the influence of the vertical stiffness in dynamic amplification of the static loads, which can be applied to both the mentioned cases and even extrapolated to cases of high-speed railways. The results showed that stiffness increases result in positive gains from the point of view of bending moments and deflections in rails, as well as higher strength and dissipation of vertical stresses on ballast, sub-ballast and subgrade layers. On the other hand, this increase of stiffness also lead to higher pressures on the layers cited, in addition to attenuation of vibrations in lower frequency ranges and higher dynamic amplifications of static loads in the case of high-speed operation. Thus, the influence of vertical stiffness should not be analyzed in a generic way, because, depending on the parameter of the track response considered, it can represent a positive or negative influence.

Neste trabalho estuda-se a interação, através de choques, entre um oscilador harmônico e um carro de trilho de ar inclinado, análogo ao sistema descrito na literatura como \"bouncing-ball\". A análise teórica e a simulação prevêem estabilidade e bifurcação nas fases do oscilador em que ocorrem os choques, confirmados pela experiência. As simulações indicam a ocorrência de caos, fato que foi confirmado experimentalmente. O sistema experimental de aquisição de dados produzido permite a utilização no ensino de graduação. Os dados experimentais gerados pelo sistema são coletados por uma interface de aquisição, que trabalha acoplada a um microcomputador Apple II, e transferidos para um microcomputador tipo IBM-PC, possibilitando uma análise rápida dos resultados obtidos. Para a visualização das regiões de estabilidade, de bifurcação e do atrator estranho, que surge na região de caos, foram desenvolvidos programas gráficos e de cálculo, que permitem, também, realizar uma avaliação da dimensão do atrator. Os programas de simulação permitem ao aluno realizar cálculos e gerar gráficos, variando os parâmetros de controle do sistema. No experimento foi utilizado coeficiente de restituição E de 0,22 e a dimensão fractal encontrada para o atrator foi 1,2. / In the present dissertation the interaction between an harmonic oscillator and an air track\'s glider is studied, analogous to the system described in literature as the bouncing-ball. Theoretical analysis and simulation predict stability and bifurcation in the phases of the oscillator in which occur collisions. The simulations indicate the occurrence of chaos, a fact confirmed experimentally. The built up experimental data acquisition system can be used in undergraduate teaching. Experimental data generated by the system are collected by na acquisition interface, which works linked to an Apple II microcomputer, and are transferred to an IBM-PC type microcomputer, allowing quick analysis of the obtained results. To visualize the regions of stability, of bifurcation and of the strange attractor, graphic and calculation programs were developed, which also permit an evaluation of the attractor\'s dimension. The simulation programs allow the student to do calculations and generate graphs, while varying the system\'s control parameters. In the experiment a restitution coefficient E of 0.22 was used and the found fractal dimension for the attractor was 1.2.

Class of 2007 Abstract / Objectives: In this paper we analyzed the time frame for oncology drugs that were designated as a fast track drug and the time transition from a phase II to phase III clinical trial completion. Methods In our study we utilized oncology drugs that were approved between the years of 2000-2006 (FDA.gov). We then analyzed the CDER data base that provided information to Fast Track drugs that have been approved within the time period as determined by the FDA selection criteria (21 CFR 312.81(a)). Under certain circumstances, the FCA may consider reviewing portions of a marketing application in advance of the complete New Drug Application (NDA) or Biologic License Application (BLA). We will evaluate fast track designated products which may also be eligible to participate in FDA’s Continuous Marketing Applications Pilot 1 or Pilot 2 programs. For our analysis, we specifically selected oncology drugs. In particular, we analyzed 32 drugs from the stated time period. Each fast track drug was then selected and analyzed for its clinical phase development time period based on news announcements during clinical trails. For each announcement we conducted an event study analysis through lexis Nexus with respect to the announcement of a clinical trial enrollment, clinical trials news (Phase I, II, III). Results: The results of our preliminary study show that there was a shorter time to development transition for the fast track oncology drugs. The oncology clinical phase transition from II to three on average lasted 12 months with a range of 2 - 29 months The average length of the phase development had to excludes 4 drugs due to the lack of information provided from the LexisNexis database. The current timeline for fats track drugs has shown a decrease in transition from clinical trials to the market. In the example of Spyrcel, the data from our study had to be excluded, there was a definitive difference in the time to approval process for the drug as compared to other standard review entities. The approvals for dasatinib, or Sprycel, for refractory CML was shown to move through the development to approval in one of the fastest timeframes in modern development. Since its first clinical study on in Gleevec-resistant patients, the medication was decided on entering an accelerated timeline. It took us just 25 months to bring Sprycel from first-in-human dosing to a regulatory submission. In contrast, the industry average for this cycle time is 6.4 years which is three times greater than the cycle time for Sprycel. Conclusions: The new Subpart H regulations state that post-marketing studies to confirm clinical benefit that would consist usually by "studies underway” at the time of accelerated approval, this has not always been the case and is not a requirement (Dagher R, Johnson J, Williams G et al). In conclusion, the accelerated approval program in oncology has been successful in making 18 different products available to patients for 22 different cancer treatment indications since the inception of the fast track program. From the current data and transition information, there is a comparative difference between the clinical phase transitions from phase II to Phase III clinical trials. However, this preliminary data needs to be further evaluated against the standard FDA review process from oncology drugs. Moreover, further studies will be needed to interpret whether the average length of oncology studies biases the value of our study.

A via permanente representa um elemento imprescindível na composição do transporte ferroviário e seu desempenho deve ser adequado, de forma a garantir tanto segurança quanto conforto. Assim, diversos aspectos devem ser analisados ainda na fase de projeto, através de dimensionamentos que confrontem diferentes parâmetros da resposta da via e os limites estabelecidos. Dessa forma, o conhecimento do comportamento mecânico da via, devido aos esforços impostos pela passagem do material rodante, passa a ser essencial no projeto de uma estrutura que garanta os requisitos necessários, sem ser inviável economicamente. Visto que esse comportamento mecânico é muito sensível à rigidez vertical da estrutura, o presente trabalho apresenta análises da influência desse parâmetro na resposta da via e, consequentemente, no seu dimensionamento. Nesse contexto, o trabalho abrange tanto o caso de vias em lastro solicitadas por trens de carga, quanto o caso de vias em laje solicitadas por trens de passageiros em meios urbanos. No primeiro caso são realizados estudos paramétricos, por meio de modelos clássicos e um modelo mecanicista, para a análise de momentos fletores e deflexões nos trilhos, bem como tensões verticais nas camadas de lastro, sub-lastro e subleito. Já no segundo caso, são realizados estudos paramétricos relativos à transmissibilidade e à atenuação de vibrações causadoras de ruído secundário. Também é feita uma análise da influência da rigidez vertical na amplificação dinâmica das cargas estáticas, que pode ser aplicada a ambos os casos citados e até extrapolada para casos de vias de alta velocidade. Os resultados mostraram que aumentos de rigidez vertical resultam em ganhos do ponto de vista de momentos fletores e deflexões nos trilhos, além de maior resistência e capacidade de dissipação de tensões verticais nas camadas de lastro, sub-lastro e subleito. Por outro lado, esses aumentos também levaram a maiores tensões nas camadas subjacentes à grade citadas, além de atenuações de vibrações em menores intervalos de frequência e maiores amplificações dinâmicas das cargas estáticas em vias de alta velocidade. Assim, é mostrado que a influência da rigidez vertical, tanto da via como um todo quanto de alguns elementos específicos, não deve ser analisada de forma genérica, pois, dependendo do parâmetro da resposta da via considerado no dimensionamento, seu aumento pode representar uma influência positiva ou negativa. / The railway track is an essential element in the composition of rail transport and its performance should be adequate to ensure both safety and comfort. Therefore, several aspects should be analyzed still in the project phase, through project designs that compare the response of the track from the point of view of different parameters and some stablished limits. Thus, the knowledge of the mechanical behavior of the track due to stresses imposed by the passage of rolling stock becomes essential to the design of a structure which ensures the necessary requirements, without being uneconomic. Since this mechanical behavior is very sensitive to vertical stiffness of the structure, this thesis presents some analyses about the influence of this parameter in the track response and, consequently, in its design. In this context, the research covers both the case of ballasted tracks with freight trains and the case of slab tracks with passenger trains in urban areas. In the first case, parametric studies are performed by means of classical and mechanistic models with analyses of bending moments and deflections in rails, as well as the vertical stresses on ballast, sub-ballast and subgrade layers. In the second, it was analyzed in the parametric studies the transmission and attenuation of vibrations causing ground borne vibration. In addition to these, there is also an analysis of the influence of the vertical stiffness in dynamic amplification of the static loads, which can be applied to both the mentioned cases and even extrapolated to cases of high-speed railways. The results showed that stiffness increases result in positive gains from the point of view of bending moments and deflections in rails, as well as higher strength and dissipation of vertical stresses on ballast, sub-ballast and subgrade layers. On the other hand, this increase of stiffness also lead to higher pressures on the layers cited, in addition to attenuation of vibrations in lower frequency ranges and higher dynamic amplifications of static loads in the case of high-speed operation. Thus, the influence of vertical stiffness should not be analyzed in a generic way, because, depending on the parameter of the track response considered, it can represent a positive or negative influence.