Multiplicity issues arise prevalently in a variety of situations in clinical trials and statistical methods for multiple testing have gradually gained importance with the increasing number of complex clinical trial designs. In general, two types of multiple testing can be performed (Dmitrienko et al., 2009): union-intersection testing (UIT) and intersection-union testing (IUT). The UIT is of the interest in this dissertation. Thus, the familywise error rate (FWER) is required to be controlled in the strong sense. A number of methods have been developed for controlling the FWER, including single-step and stepwise procedures. In single-step approaches, such as the simple Bonferroni method, the rejection decision of a hypothesis does not depend on the decision of any other hypotheses. Single-step approaches can be improved in terms of power through stepwise approaches, while also controlling for the desired error rate. Besides, it is also possible to improve those procedures by a parametric approach. In the first project, we developed a new and powerful single-step progressive parametric multiple (SPPM) testing procedure for correlated normal test statistics. Through simulation studies, we demonstrate that SPPM improves power substantially when the correlation is moderate and/or the magnitude of eect sizes are similar. Group sequential designs (GSD) are clinical trials allowing interim looks with the possibility of early terminations due to ecacy, harm or futility, which can reduce the overall costs and timelines for the development of a new drug. However, repeated looks of data also have multiplicity issues and could inflate the type I error rate. The proper treatments to the error inflation have been discussed widely (Pocock, 1977), (O'Brien and Fleming, 1979), (Wang and Tsiatis, 1987), (Lan and DeMets, 1983). Most literature about GSD focuses on a single endpoint. GSD with multiple endpoints however, has also received considerable attention. The main focus of our second project is a GSD with multiple primary endpoints, in which the trial is to evaluate whether at least one of the endpoints is statistically signicant. In this study design, multiplicity issues arise from repeated interims and multiple endpoints. Therefore, the appropriate adjustments must be made to control the Type I error rate. Our second purpose here is to show that the combination of multiple endpoint and repeated interim analyses can lead to a more powerful design. Via the multivariate normal distribution, a method that allows for simultaneously consideration of interim analyses and all clinical endpoints was proposed. The new approach is derived from the closure principle, thus it can control type I error rate strongly. We evaluate the power under dierent scenarios and show that it compares favorably to other methods when correlation among endpoints is non-zero. In the group sequential design framework, another interesting topic is multiple arm multiple stage design (MAMS), where multiple arms are involved in the trial at the beginning with the flexibility about treatment selection or stopping decisions during the interim analyses. One of major hurdles of MAMS is the computational cost with the increasing number of arms and interim looks. Various designs were implemented to overcome this diculty (Thall et al., 1988; Schaid et al., 1990; Follmann et al., 1994; Stallard and Todd, 2003; Stallard and Friede, 2008; Magirr et al., 2012; Wason et al., 2017), but also control the FWER with the potential inflation from the multiple arm comparisons and multiple interim tests. Here, we consider a more flexible drop-the-loser design allowing the safety information in the treatment selection without a pre-specied dropping-arms mechanism and it still retains reasonable high power. The two dierent types of stopping boundaries are proposed for such a design. A sample size is also adjustable if the winner arm is dropped due to the safety considerations.

Gamma titanium aluminide alloys are emerging as a lightweight replacement to nickel superalloys, with current application in turbine stages of aero-engines, as well as in high performance automobiles and potentially the nuclear industry. The lack of toughness of its two constitutive intermetallic phases, γ-TiAl and α2-Ti3Al, prevents a conventional damage tolerant approach to fatigue lifing. To gain confidence in the use of γ-TiAl alloys and extend the temperature-stress envelope of applicability, the present work aims to achieve an understanding of the development of plasticity and flaw formation during cyclic loading. The general plasticity of a γ-TiAl alloy, Ti-45Al-2Nb-2Mn(at.%)-0.8vol.%TiB2, in compression was investigated by mapping the development of localised strain at the specimen surface. Methods were developed to produce speckle patterns for high resolution digital image correlation that were stable at test temperatures of 700 °C in air, in order to study the extent of plasticity generated by differing deformation mechanisms at application-relevant temperatures, with nano-scale resolution. At the colony scale (i.e. single stacks of co-planar α2-Ti3Al and γ-TiAl lamellae, where each stack is formed from a single high temperature disordered α-TiAl grain), macroscopic deformation bands were observed to develop at only a few percent strain. Within such bands, which propagated across many colonies of differing lamellar orientations, considerable lattice curvature and localised slip and twin operation occurred. This correlated with colony boundary failure in such bands. Twinning of the γ-TiAl phase parallel to the lamellar interfaces, longitudinal twinning, has rarely been studied, despite generalised twinning in equiaxed γ-TiAl grains being known to cause boundary decohesion. Here, the occurrence of longitudinal twinning in both microcompression and polycrystalline testpieces was investigated up to 700 °C by electron backscatter diffraction. The strength of constraint by surrounding lamellar domains was found to be the determining factor in the increased prominence of twinning at 700 °C, and hence determined whether twinning shear-induced flaws formed at colony boundaries. Using the high temperature digital image correlation strain mapping and electron backscatter diffraction techniques developed, along with transmission electron microscopy, the onset of plasticity at temperatures up to 700 °C was studied in both micro-scale and macro-scale test specimens for different lamellar thicknesses. Testpieces were loaded below the macroscopic yield stress in both monotonic and high cycle fatigue regimes, to 107 cycles, at a tensile stress ratio of R = 0.1. Longitudinal plasticity occurred in most colonies with soft mode lamellar orientations, and was located just 30 - 50 nm from lamellar interfaces. Lamellar refinement caused an increased number of slip bands to develop. In most cases, plastic strains decreased to zero by the colony boundary and strain transfer across such boundaries in high cycle fatigue was rare. At room temperature, the maximum applied stress was found to influence the number of slip bands more than the number of loading cycles.

Submitted by Daniele Santos (danielesantos.htl@gmail.com) on 2017-01-18T19:26:37Z No. of bitstreams: 1 Martin Cottard, v28 (1).docx: 628181 bytes, checksum: 5982513672c7342dff2d897820eb08f0 (MD5) / Approved for entry into archive by Janete de Oliveira Feitosa (janete.feitosa@fgv.br) on 2017-02-23T17:42:59Z (GMT) No. of bitstreams: 1 Martin Cottard, v28 (1).docx: 628181 bytes, checksum: 5982513672c7342dff2d897820eb08f0 (MD5) / Made available in DSpace on 2017-02-24T18:41:57Z (GMT). No. of bitstreams: 1 Martin Cottard, v28 (1).docx: 628181 bytes, checksum: 5982513672c7342dff2d897820eb08f0 (MD5) Previous issue date: 2016-11-11 / The currency markets are dominated by the few greatest currencies (as $, €, ¥, £ …). Their strong influence is gathering many currencies around them. From the outside, it looks like a large group of correlated currencies. - How many large groups of correlated currencies exists? What currencies are included? When considering all the currencies of the world, there are thousands of possible influences. This means a huge number of correlations to study. This is not convenient. - Is there a visual tool that can helps us to find our way, among all the numerous correlations? We propose here a simple tool to answer to those questions: the currency map. This map is a plot of more than 100 currencies. It’s easy to locate a specific currency and to find its close neighbors. And close neighbors often have similar fluctuations. We provide several examples of using this map: - An example explains how to share equally the currency risks between parties, in an import/export business. - An example explains how to create an optimum currency basket, which perfectly minimized the fluctuations over the last 10 Years. - An example to inform about the risks of contagion, in case of a local currency crisis.

The aim of this study was to investigate a productivity measurement at the South African Minting Company and evaluate the relationship between productivity and quality. Special emphasis was given to profit-linked total factor model as the tool for measurement. This was encouraged by their ability to separate productivity, profitability and price recovery. Three models were selected and evaluated. These models American Productivity Center (APC) Model, “Profitability = productivity + price recovery” (PPP) model and multi-factor productivity measurement model (MFPMM). APC model was selected as the suitable model because of its simplicity, easy to set up, its ability to produce both financial and non financial data, and allow for route cause analysis with expert system, and more insight for the manager with Microsoft Excels’ What if analysis “Goal seek”. APC model was set up for four periods, from 1 April 2004 to 30 September 2007. The overall profitability results of the circulation coins profit center show an overall positive contribution. There was a break-even of the price recovery for 2006 financial year (period 2). In 2007 financial year (period 3), there was a negative contribution, and this improved to almost break-even in the six month period during this 2008 financial year (period 4). This means there was much more inflation on input resources and the recovery was not fully realised in the price of goods sold. Individual input costs show that the negative price recovery is culminating from material, labour and energy costs contributions. There is a plausible explanation for material and labour, but not for energy. The metal volatility is the underlying cause of the price variation. Labour variation was a company strategy to adjust employee to higher percentiles. Productivity was always positive with the highest contribution in the current financial year (period 4). This means that the profitability at SA Mint has been driven by productivity in the past two financial years. iv Survey of the questionnaire shows average scores for productivity and quality. It is noteworthy, that the lowest mean score for productivity is for the statement “Products are produced in error-free process”. This is a productivity quality measure. In addition, the same variable shows r2 value of 0.42. A conclusion is that even though productivity and quality are highly correlated and show a highly positive relationship, there is a concern on quality in the company. A link can be made that low price recovery becomes more difficult when the quality is not always good. Defective product is a cost, because the product does not reach the customer and if the product is reworked it is still a cost, though low, but more importantly it decreases the available capacity. This study was successful in setting up APC model and producing data that is worthy to the company and academic world. Finally, this study was successful in its quest to establish the relationship between productivity and quality.

Advanced composite materials are widely used for many structural applications in the aerospace/aircraft industries today. Joining of composite structures using adhesive bonding offers several advantages over traditional fastening methods. However, this technique is not yet employed for fastening the primary structures of aircrafts or space vehicles. There are several reasons for this: There are not any reliable non-destructive evaluation (NDE) methods that can quantify the strength of the bonds, and there are no certifications of quality assurance for inspecting the bond quality. Therefore, there is a significant need for an effective, reliable, easy to use NDE method for the analysis of composite adhesive joints. This research aimed to investigate an adhesively bonded composite-aluminum joints of variable bond strength using digital image correlation (DIC). There are many future possibilities in continuing this research work. As the application of composite materials and adhesive bond are increasing rapidly, the reliability of the composite structures using adhesive bond should quantified. Hence a lot of similar research using various adhesive bonds and materials can be conducted for characterizing the behavior of adhesive bond. The results obtained from this research will set the foundation for the development of ultrasonic DIC as a nondestructive approach for the evaluation of adhesive bond line.

Scientific studies have suggested an increase in the frequency and intensity of flooding. The research presented herein is focused on a small watershed, which has experienced intense flooding of a downstream, urbanized area. For emergency response and preparedness, it is pertinent to have the ability to predict intensity and peak flows of a flood. The Town of Dyer, Indiana has been severely impacted by flooding in the last twenty years. A 37.6 square mile watershed begins in a rural section of Illinois with tributaries draining into Plum Creek. The creek crosses into Indiana and becomes Hart Ditch, a straight, narrow, deep channel through the urbanized Town of Dyer. A HEC-HMS hydrologic model was used and calibrated based on USGS gage data. Storm events ranging from short, high intensity to long, intermittent precipitation provided a vast representation of possible scenarios within the watershed. The hydrologic model was paired with an unsteady HEC-RAS hydraulic model to allow for different lateral inflows to the creek providing variations of flow. A comparison between upstream and downstream stream gage readings was utilized to create a working model that predicts downstream water surface elevations for previous real-time storm and hypothetical storms. These conditions were analyzed by two stream gages and a correlation between the two gages was developed. This correlation was used to predict downstream water surface elevations. The correlation was also used to determine the time to crest based on readings at the upstream gage for many different storm events. The ability to know downstream water surface elevations for real-time storm events allows a window of time to implement emergency response in areas where flooding is imminent. The downstream area of concern has known flood elevations that represent various damage levels.

Our research investigated the correlations of five key contaminants in drinking water in the State of Illinois with the incidence rates of three different categories of negative reproductive outcomes: birth defects, adverse pregnancy outcomes and preterm births. The five water contaminants included three agrichemical-based contaminants (atrazine, nitrate and nitrite) and two disinfectant byproducts (total trihalomethanes and haloacetic acids). We obtained nearly 38,000 measurements of the individual concentrations of these five contaminants from the Illinois Environmental Protection Agency (IEPA). These data, spanning over a five-year period (1998-2002), were collected from nearly 1,800 community water supplies (CWS) located in all 102 Illinois counties. The county-specific incidence rate data for the same time period for preterm births, seven groups of birth defects and seven groups of adverse pregnancy outcomes were collected from the Illinois Department of Public Health (IDPH). The traditional approach of establishing correlation of one explanatory variable at a time indicated that nitrate concentration in drinking water was statistically correlated to the incidence rate of only one category of negative reproductive outcome, i.e., birth defects. However, multiple regression analysis, which took into consideration all water contaminant data simultaneously, established statistical significance of the correlation between nitrate and all three categories of negative reproductive outcomes. Total trihalomethanes (TTHM) and haloacetic acids (HAA5) were also found to be the statistically significant explanatory variables for all three types of negative reproductive outcomes. Nitrite was found to be associated with adverse pregnancy outcomes and preterm births only; its correlation with birth defect rates could not be established at 80% confidence level. Atrazine was found to be among the significant explanatory variables for all three negative reproductive outcomes. However, its correlations with birth defect model developed using censored data and preterm birth model developed based on observed data were not statistically significant. Nearly 21.5%, 35.8% and 16.6% of the variabilities in incidence rates of different types of birth defects, adverse pregnancy outcomes and preterm births, respectively, were correlated to average concentrations of above mentioned five contaminants in community drinking water supplies. The monthly average concentrations of two of three agrichemical-based contaminants, i.e., atrazine and nitrate were significantly higher in SW(surface water)-based than GW(ground water)-based community water supplies. On the other hand, concentrations of both disinfectant byproducts and the other agrichemical-based contaminant, i.e., nitrite were significantly higher in GW-based water supplies. Further correlation analysis based on the actual observed concentration (excluding all 0 detections) was conducted utilizing SW-based atrazine and nitrate data and GW-based nitrite, TTHM and HAA5 data. All categories of negative reproductive outcomes were found significantly correlated with at least one type of water contaminants. The overall negative reproductive outcomes were correlated with nitrate, nitrite and atrazine. Birth defects specifically correlated with nitrate and TTHM, whereas adverse pregnancy outcomes were correlated with nitrate, nitrite and HAA5; preterm birth was correlated with the concentrations of nitrite, atrazine and TTHM. Further investigation indicated significant correlations among the explanatory variables (drinking water contaminants data), which is referred as multicollinearity. In such case, multiple linear regression based analysis may not provide reliable results. Partial least squares (PLS) approach of regression analysis was introduced into our study to overcome the multicollinearity problem. As much as 65.5% of the variability in the county-wide average concentrations of five contaminants in public drinking water supplies was explained by the 4 component PLS regression model, whereas only 7.7% of the incidence rates of different types of birth defects, adverse pregnancy outcomes and preterm births in various Illinois counties, were explained by PLS regression. Although, individual negative reproductive outcome model could be generated, the low R2 values indicated the poor reliability of these models. We attempted to corroborate our statistical analysis findings with the physiological effects of various water contaminants reported in the literature. It is well known that excessive exposure to any of the five key water contaminants may cause malfunction of organism or the immune system, reproduction, nervous and endocrine system and others, which may further result in potential risk of developing adverse effects. Nitrate and nitrite in drinking water associate to a certain extent with congenital malformations, such as central nervous system abnormalities, in human offsprings. Excessive exposure to atrazine is known to increase the risk of potential cardiovascular or reproductive system problems. A certain type of TTHM, i.e., BDCM are known to be associated with an increased risk of spontaneous miscarriage in pregnant women. It also may result in an increased risk of reproductive problem, such as fetal growth restriction.

This thesis examines the feasibility of combining Digital Image Correlation (DIC) with laser speckle based methods to form a new hybrid deformation measurement method called Digital Laser Speckle Image Correlation (DilSIC). Consequently, this method does not require any sample preparation and allows for the measurement of displacement of micro structures in addition to large displacements. In this technique, a coherent 30mW-632nm laser beam is expanded with 40X lens and then illuminated on the target surface to produce a fine, homogenous laser speckle pattern. Images were captured before and after deformation due to external load and the whole field displacement and strain were determined by the DIC method. This technique could measure displacement less than 30-μm with high accuracy when a 120mm × 80mm area of the surface was inspected. Up to 10% strain was measured by this technique with high accuracy during the whole range. Eventually the sub-surface crack was located successfully, which is a revolutionary achievement in NDT optical methods. This method was tested in different material, with different roughness. Aluminum sheet and rubber material were used mostly. This method could broaden the capability of displacement measurement and subsurface crack detection in wide range of materials.

The primary objective of this research is to conduct further evaluation of ultrasonic digital image correlation (UT-DIC) on strain map analysis and defect detection of adhesive joints with embedded speckle pattern. UT-DIC is a non-destructive evaluation method that utilized ultrasonic C-scan images for whole field strain and displacement analysis. Acrylic glass, epoxy resin system and metal shavings with high acoustic impedance of a specific weight were used to create the samples which were loaded under tension. Defects with varying shapes and sizes were implemented by surface preparation to understand the limits of this approach. UT-DIC and optical DIC strain map results were compared, and it was found that each approach detected certain shapes of defect better than the other.

Gengivite é um achado comum em diferentes populações, com alta prevalência em todas as idades. A principal etiologia da inflamação gengival tem sido estabelecida como o biofilme bacteriano. Devido ao fato de que a gengivite impreterivelmente precede a periodontite, o diagnóstico dessa doença é de suma importância no contexto da saúde periodontal do paciente. Para identificar esta condição, diversos índices têm sido propostos na literatura para acuradamente definir o estado dos tecidos gengivais, considerando sangramento como sendo o sinal pioneiro e mais significativo da inflamação. O objetivo geral desta tese foi avaliar a correlação entre dois diferentes índices, o de sangramento à sondagem da margem (ISM) e o de sangramento à sondagem do sulco (ISS). Ainda, a correlação de ambos os índices em relação à presença de biofilme na superfície dos dentes foi avaliada. Para tanto, uma amostra de 260 adultos jovens sistemicamente saudáveis foi examinada. Os índices de sangramento e de placa foram medidos em seis sítios por dente, por examinadores treinados, cada um responsável por um único índice ao longo de todo o estudo. Dados de ISM, ISS e placa foram descritos em nível ecológico e analisados em nível de indivíduo e de sítio. Para a análise em nível de sítio, as associações foram sumarizadas através de correlações policóricas, e uma metanálise de efeitos fixos e aleatórios foi realizada. Os resultados demonstraram que quando da sondagem do sulco, mais sangramento foi elicitado se comparado à sondagem da margem gengival (51.2% CI: 49.3 – 53, e 19.9% CI: 18.4 – 21.3, respectivamente). Além disso, em nível de sítio, uma baixa correlação foi verificada entre placa e sangramento de ambos os índices empregados (ISM 0,19 CI: 0.17 – 0.21, ISS 0,20 CI: 0,19 – 0,23). Pode ser concluído que, aparentemente, além do biofilme bacteriano, outros fatores podem estar envolvidos no processo que leva o estado de saúde gengival à inflamação. O sangramento à sondagem da margem parece ser o índice de escolha para o diagnóstico de gengivite. / Gingivitis is a common finding among different populations, with a high prevalence in all ages. The primary etiology of gingival inflammation has been established to be bacterial biofilm. Due to the fact that gingivitis imperatively precedes periodontitis, the diagnosis of the disease is of utmost importance. To assess this condition, several indices have been proposed in the literature to accurately define the state of the gingival tissues, considering bleeding as being the most meaningful and earliest sign of inflammation. The general aim of this thesis was to evaluate the correlation between two different indices, bleeding on marginal probing (BOMP) and bleeding upon pocket probing (BOPP). Moreover, the correlation of both indices as related to the presence of plaque was also evaluated. A sample of 260 systemically healthy young adults was examined. Bleeding and plaque indices were measured by single examiners, each responsible for one index, in six sites per tooth. Data regarding BOMP, BOPP and plaque were described at individual level and analysed at both individual and site-level. At site level, the associations were summarized using polychoric correlations, and a metanalysis of fixed and random effects was performed. The results demonstrated that more bleeding was elicited when probing the pocket than when the gingival margin was evaluated (51.2% CI: 49.3 – 53, e 19.9% CI: 18.4 – 21.3, respectively). Also, a low correlation was verified between plaque and the bleeding indices (BOMP 0,19 CI: 0.17 – 0.21, BOPP 0,20 CI: 0,19 – 0,23). It can be concluded that, apparently, besides plaque, other factors may be involved in the process that leads the healthy gingivae to an inflammation. Bleeding the gingival margin should be the index of choice for the diagnosis of gingivitis.