Statistical methods for multi-marker testing in genetic association studies

As the development of genotyping and next-generation sequencing technologies, multi-marker testing in genome-wide association study and rare variant association study became active research areas in statistical genetics. This dissertation contains three methodologies for association study by exploring different genetic data features and demonstrates how to use those methods to test genetic association hypothesis. The methods can be categorized into in three scenarios: 1) multi-marker testing for strong Linkage Disequilibrium regions, 2) multi-marker testing for family-based association studies, 3) multi-marker testing for rare variant association study. I also discussed the advantage of using these methods and demonstrated its power by simulation studies and applications to real genetic data.

Is perioperative point-of-care prothrombin time testing accurate compared to the standard laboratory test?

There is no accepted way of measuring prothrombin time without time loss for patients undergoing major surgery who are at risk of intraoperative dilution and consumption coagulopathy due to bleeding and volume replacement with crystalloids or colloids. Decisions to transfuse fresh frozen plasma and procoagulatory drugs have to rely on clinical judgment in these situations. Point-of-care devices are considerably faster than the standard laboratory methods. In this study we assessed the accuracy of a Point-of-care (PoC) device measuring prothrombin time compared to the standard laboratory method. Patients undergoing major surgery and intensive care unit patients were included. PoC prothrombin time was measured by CoaguChek XS Plus (Roche Diagnostics, Switzerland). PoC and reference tests were performed independently and interpreted under blinded conditions. Using a cut-off prothrombin time of 50%, we calculated diagnostic accuracy measures, plotted a receiver operating characteristic (ROC) curve and tested for equivalence between the two methods. PoC sensitivity and specificity were 95% (95% CI 77%, 100%) and 95% (95% CI 91%, 98%) respectively. The negative likelihood ratio was 0.05 (95% CI 0.01, 0.32). The positive likelihood ratio was 19.57 (95% CI 10.62, 36.06). The area under the ROC curve was 0.988. Equivalence between the two methods was confirmed. CoaguChek XS Plus is a rapid and highly accurate test compared with the reference test. These findings suggest that PoC testing will be useful for monitoring intraoperative prothrombin time when coagulopathy is suspected. It could lead to a more rational use of expensive and limited blood bank resources.

Can a novel web-based computer test predict poor simulated driving performance? A pilot study with healthy and cognitive-impaired participants

BACKGROUND Driving a car is a complex instrumental activity of daily living and driving performance is very sensitive to cognitive impairment. The assessment of driving-relevant cognition in older drivers is challenging and requires reliable and valid tests with good sensitivity and specificity to predict safe driving. Driving simulators can be used to test fitness to drive. Several studies have found strong correlation between driving simulator performance and on-the-road driving. However, access to driving simulators is restricted to specialists and simulators are too expensive, large, and complex to allow easy access to older drivers or physicians advising them. An easily accessible, Web-based, cognitive screening test could offer a solution to this problem. The World Wide Web allows easy dissemination of the test software and implementation of the scoring algorithm on a central server, allowing generation of a dynamically growing database with normative values and ensures that all users have access to the same up-to-date normative values. OBJECTIVE In this pilot study, we present the novel Web-based Bern Cognitive Screening Test (wBCST) and investigate whether it can predict poor simulated driving performance in healthy and cognitive-impaired participants. METHODS The wBCST performance and simulated driving performance have been analyzed in 26 healthy younger and 44 healthy older participants as well as in 10 older participants with cognitive impairment. Correlations between the two tests were calculated. Also, simulated driving performance was used to group the participants into good performers (n=70) and poor performers (n=10). A receiver-operating characteristic analysis was calculated to determine sensitivity and specificity of the wBCST in predicting simulated driving performance. RESULTS The mean wBCST score of the participants with poor simulated driving performance was reduced by 52%, compared to participants with good simulated driving performance (P<.001). The area under the receiver-operating characteristic curve was 0.80 with a 95% confidence interval 0.68-0.92. CONCLUSIONS When selecting a 75% test score as the cutoff, the novel test has 83% sensitivity, 70% specificity, and 81% efficiency, which are good values for a screening test. Overall, in this pilot study, the novel Web-based computer test appears to be a promising tool for supporting clinicians in fitness-to-drive assessments of older drivers. The Web-based distribution and scoring on a central computer will facilitate further evaluation of the novel test setup. We expect that in the near future, Web-based computer tests will become a valid and reliable tool for clinicians, for example, when assessing fitness to drive in older drivers.

Timely follow-up of abnormal diagnostic imaging test results in an outpatient setting: are electronic medical records achieving their potential?

BACKGROUND: Given the fragmentation of outpatient care, timely follow-up of abnormal diagnostic imaging results remains a challenge. We hypothesized that an electronic medical record (EMR) that facilitates the transmission and availability of critical imaging results through either automated notification (alerting) or direct access to the primary report would eliminate this problem. METHODS: We studied critical imaging alert notifications in the outpatient setting of a tertiary care Department of Veterans Affairs facility from November 2007 to June 2008. Tracking software determined whether the alert was acknowledged (ie, health care practitioner/provider [HCP] opened the message for viewing) within 2 weeks of transmission; acknowledged alerts were considered read. We reviewed medical records and contacted HCPs to determine timely follow-up actions (eg, ordering a follow-up test or consultation) within 4 weeks of transmission. Multivariable logistic regression models accounting for clustering effect by HCPs analyzed predictors for 2 outcomes: lack of acknowledgment and lack of timely follow-up. RESULTS: Of 123 638 studies (including radiographs, computed tomographic scans, ultrasonograms, magnetic resonance images, and mammograms), 1196 images (0.97%) generated alerts; 217 (18.1%) of these were unacknowledged. Alerts had a higher risk of being unacknowledged when the ordering HCPs were trainees (odds ratio [OR], 5.58; 95% confidence interval [CI], 2.86-10.89) and when dual-alert (>1 HCP alerted) as opposed to single-alert communication was used (OR, 2.02; 95% CI, 1.22-3.36). Timely follow-up was lacking in 92 (7.7% of all alerts) and was similar for acknowledged and unacknowledged alerts (7.3% vs 9.7%; P = .22). Risk for lack of timely follow-up was higher with dual-alert communication (OR, 1.99; 95% CI, 1.06-3.48) but lower when additional verbal communication was used by the radiologist (OR, 0.12; 95% CI, 0.04-0.38). Nearly all abnormal results lacking timely follow-up at 4 weeks were eventually found to have measurable clinical impact in terms of further diagnostic testing or treatment. CONCLUSIONS: Critical imaging results may not receive timely follow-up actions even when HCPs receive and read results in an advanced, integrated electronic medical record system. A multidisciplinary approach is needed to improve patient safety in this area.

An investigation into the mechanical and aesthetic properties of new generation coated nickel-titanium wires in the as-received state and after clinical use.

BACKGROUND/OBJECTIVES The purpose of this study was to compare the mechanical, structural, and aesthetic properties of two types of aesthetic coated nickel-titanium (NiTi) wires compared with comparable regular NiTi wires in the as-received state and after clinical use. MATERIALS/METHODS Sixty one subjects were randomly assigned to four groups (N = 61), two groups of coated wires and two groups of comparable, non-coated controls (n = 15/group). The period in the mouth ranged from 4 to 12 weeks after insertion. In total, 121 wires (61 retrieved and 60 as-received) were used in the study. The percentages of coating retention and loss were extrapolated from scans. A brief survey of five questions with three choices was given to all patients. Differential scanning calorimetry (DSC) and three-point bending tests were done on as-received and used wires. RESULTS The surface characterization by the percentage of resin remaining indicated that most wires in both test groups lost a significant amount of coating. A patient survey indicated that this was a noticeable feature for patients. DSC analysis of the wires indicated that the metallurgical properties of the coated wires were not similar to the uncoated wires in the as-received condition. Three-point bending results indicate a wide variation in test results with large standard deviations among all the groups. LIMITATIONS The extent of coating loss requires investigating, as do the biological properties of the detached coating. CONCLUSIONS Both wires lost a significant amount of aesthetic coating after varying periods in the mouth. The metallurgical testing of these findings may indicate that these wires perform differently in the mouth.

Venepuncture during head-up tilt testing in patients with suspected vasovagal syncope - implications for the test protocol.

BACKGROUND AND PURPOSE Head-up tilt (HUT) testing is a widely used diagnostic tool in patients with suspected vasovagal syncope (VVS). However, no gold standard exists for this examination and the various protocols used have a limited sensitivity and specificity. Our aim was to determine the sensitivity of a sequential HUT testing protocol including venepuncture (VP) and sublingual nitroglycerin application. METHODS This was a retrospective analysis of the diagnostic gain of a sequential HUT testing protocol including VP applied 10 min after the start of HUT testing and sublingual application of nitroglycerin 20 min after the start of the test protocol in 106 patients with a final diagnosis of VVS. The sensitivity of the test protocol was compared between patients with positive and negative history for VP induced VVS. RESULTS Overall, pre-syncope or syncope occurred in 68 patients (64.2%). Only 17% of all patients fainted spontaneously within 10 min of passive HUT. Another 39.6% fainted within 20 min. Application of nitroglycerin after 20 min of HUT evoked syncope in another 7.5% until the end of 45 min of HUT. The sensitivity of the test protocol for evoking (pre-)syncope was 94.4% in patients with a positive history for VP associated VVS and 58% in patients with a negative history (P < 0.01**); 85.7% of patients with a positive history and 42.9% of patients with a negative history fainted within 20 min of HUT testing (P < 0.01**). CONCLUSIONS Implementation of VP in sequential HUT testing protocols allows the sensitivity of HUT testing to be increased, especially in patients with a positive history for VP associated VVS.

Physical data acquisition and PWM signal generation using a microcontroller allowing control for DC motor rotation speed

El objetivo de este proyecto es diseñar un sistema capaz de controlar la velocidad de rotación de un motor DC en función del valor de temperatura obtenido de un sensor. Para ello se generará con un microcontrolador una señal PWM, cuyo ciclo de trabajo estará en función de la temperatura medida. En lo que respecta a la fase de diseño, hay dos partes claramente diferenciadas, relativas al hardware y al software. En cuanto al diseño del hardware puede hacerse a su vez una división en dos partes. En primer lugar, hubo que diseñar la circuitería necesaria para adaptar los niveles de tensión entregados por el sensor de temperatura a los niveles requeridos por ADC, requerido para digitalizar la información para su posterior procesamiento por parte del microcontrolador. Por tanto hubo que diseñar capaz de corregir el offset y la pendiente de la función tensión-temperatura del sensor, a fin de adaptarlo al rango de tensión requerido por el ADC. Por otro lado, hubo que diseñar el circuito encargado de controlar la velocidad de rotación del motor. Este circuito estará basado en un transistor MOSFET en conmutación, controlado mediante una señal PWM como se mencionó anteriormente. De esta manera, al variar el ciclo de trabajo de la señal PWM, variará de manera proporcional la tensión que cae en el motor, y por tanto su velocidad de rotación. En cuanto al diseño del software, se programó el microcontrolador para que generase una señal PWM en uno de sus pines en función del valor entregado por el ADC, a cuya entrada está conectada la tensión obtenida del circuito creado para adaptar la tensión generada por el sensor. Así mismo, se utiliza el microcontrolador para representar el valor de temperatura obtenido en una pantalla LCD. Para este proyecto se eligió una placa de desarrollo mbed, que incluye el microcontrolador integrado, debido a que facilita la tarea del prototipado. Posteriormente se procedió a la integración de ambas partes, y testeado del sistema para comprobar su correcto funcionamiento. Puesto que el resultado depende de la temperatura medida, fue necesario simular variaciones en ésta, para así comprobar los resultados obtenidos a distintas temperaturas. Para este propósito se empleó una bomba de aire caliente. Una vez comprobado el funcionamiento, como último paso se diseñó la placa de circuito impreso. Como conclusión, se consiguió desarrollar un sistema con un nivel de exactitud y precisión aceptable, en base a las limitaciones del sistema. SUMMARY: It is obvious that day by day people’s daily life depends more on technology and science. Tasks tend to be done automatically, making them simpler and as a result, user life is more comfortable. Every single task that can be controlled has an electronic system behind. In this project, a control system based on a microcontroller was designed for a fan, allowing it to go faster when temperature rises or slowing down as the environment gets colder. For this purpose, a microcontroller was programmed to generate a signal, to control the rotation speed of the fan depending on the data acquired from a temperature sensor. After testing the whole design developed in the laboratory, the next step taken was to build a prototype, which allows future improvements in the system that are discussed in the corresponding section of the thesis.

Grid-connected roof solar plants in educational institutions for testing and electricity generation: a case in Spain.

The use of photovoltaic experimental plants in engineering educational buildings contributes to an increase in acceptance of this technology by future engineers. There are some photovoltaic (PV) systems in educational buildings in Spain, but they are usually limited to buildings in relation to electrical technologies or research areas. They are not common in other educational or official buildings. This paper presents the project of a grid-connected solar plant with two main objectives. First, different PV module technologies will be compared. Second, an emphasis on agronomical areas in educational settings will be reviewed in an attempt to facilitate student engagement in the use of the power plant. The system is grid-connected in order to pay-back the investment in the plant. In fact the electricity generated by the plant will be used by the installations of the building, as it is the closest consumer. This work intends to approximate photovoltaic technology to university degrees not directly related with it and at the same time research in comparison of systems with different technologies. This is a good example of an solar plant for both optimum production and educational purposes.

Practical issues for testing thin film PV modules at standard test conditions.

Thin film photovoltaic (TF) modules have gained importance in the photovoltaic (PV) market. New PV plants increasingly use TF technologies. In order to have a reliable sample of a PV module population, a huge number of modules must be measured. There is a big variety of materials used in TF technology. Some of these modules are made of amorphous or microcrystalline silicon. Other are made of CIS or CdTe. Not all these materials respond the same under standard test conditions (STC) of power measurement. Power rates of the modules may vary depending on both the extent and the history of sunlight exposure. Thus, it is necessary a testing method adapted to each TF technology. This test must guarantee repeatability of measurements of generated power. This paper shows responses of different commercial TF PV modules to sunlight exposure. Several test procedures were performed in order to find the best methodology to obtain measurements of TF PV modules at STC in the easiest way. A methodology for indoor measurements adapted to these technologies is described.

Generation of human computational models with machine learning

Services in smart environments pursue to increase the quality of people?s lives. The most important issues when developing this kind of environments is testing and validating such services. These tasks usually imply high costs and annoying or unfeasible real-world testing. In such cases, artificial societies may be used to simulate the smart environment (i.e. physical environment, equipment and humans). With this aim, the CHROMUBE methodology guides test engineers when modeling human beings. Such models reproduce behaviors which are highly similar to the real ones. Originally, these models are based on automata whose transitions are governed by random variables. Automaton?s structure and the probability distribution functions of each random variable are determined by a manual test and error process. In this paper, it is presented an alternative extension of this methodology which avoids the said manual process. It is based on learning human behavior patterns automatically from sensor data by using machine learning techniques. The presented approach has been tested on a real scenario, where this extension has given highly accurate human behavior models,

Cognitive test-bed for wireless sensor networks

Cognitive Wireless Sensor Networks are an emerging technology with a vast potential to avoid traditional wireless problems such as reliability, interferences and spectrum scarcity in Wireless Sensor Networks. Cognitive Wireless Sensor Networks test-beds are an important tool for future developments, protocol strategy testing and algorithm optimization in real scenarios. A new cognitive test-bed for Cognitive Wireless Sensor Networks is presented in this paper. This work in progress includes both the design of a cognitive simulator for networks with a high number of nodes and the implementation of a new platform with three wireless interfaces and a cognitive software for extracting real data. Finally, as a future work, a remote programmable system and the planning for the physical deployment of the nodes at the university building is presented.

Identification and correction of besouro's faults: impact on test‐driven development experiments

Context. This thesis is framed in experimental software engineering. More concretely, it addresses the problems arisen when assessing process conformance in test-driven development experiments conducted by UPM's Experimental Software Engineering group. Process conformance was studied using the Eclipse's plug-in tool Besouro. It has been observed that Besouro does not work correctly in some circumstances. It creates doubts about the correction of the existing experimental data which render it useless. Aim. The main objective of this work is the identification and correction of Besouro's faults. A secondary goal is fixing the datasets already obtained in past experiments to the maximum possible extent. This way, existing experimental results could be used with confidence. Method. (1) Testing Besouro using different sequences of events (creation methods, assertions etc..) to identify the underlying faults. (2) Fix the code and (3) fix the datasets using code specially created for this purpose. Results. (1) We confirmed the existence of several fault in Besouro's code that affected to Test-First and Test-Last episode identification. These faults caused the incorrect identification of 20% of episodes. (2) We were able to fix Besouro's code. (3) The correction of existing datasets was possible, subjected to some restrictions (such us the impossibility of tracing code size increase to programming time. Conclusion. The results of past experiments dependent upon Besouro's data could no be trustable. We have the suspicion that more faults remain in Besouro's code, whose identification requires further analysis.

A voltage disturbances prototype for testing electrical generators connected to microgrids

The search for new energy models arises as a necessity to have a sustainable power supply. The inclusion of distributed generation sources (DG) allows to reduce the cost of facilities, increase the security of the grid or alleviate problems of congestion through the redistribution of power flows. In remote microgrids it is needed in a particular way a safe and reliable supply, which can cover the demand for a low cost; due to this, distributed generation is an alternative that is being widely introduced in these grids. But the remote microgrids are especially weak grids because of their small size, low voltage level, reduced network mesh and distribution lines with a high ratio R/X. This ratio affects the coupling between grid voltages and phase shifts, and stability becomes an issue of greater importance than in interconnected systems. To ensure the appropriate behavior of generation sources inserted in remote microgrids -and, in general, any electrical equipment-, it is essential to have devices for testing and certification. These devices must, not only faithfully reproduce disturbances occurring in remote microgrids, but also to behave against the equipment under test (EUT) as a real weak grid. This also makes the device commercially competitive. To meet these objectives and based on the aforementioned, it has been designed, built and tested a voltage disturbances generator, in order to provide a simple, versatile, full and easily scalable device to manufacturers and laboratories in the sector.

Implantación de técnicas de QA en un proyecto de desarrollo software

Hoy en día existe una preocupación creciente por la calidad del software entregado en los proyectos que se realizan a lo largo del mundo. El trabajo de fin de grado que va a ser desarrollado en estas páginas pretende demostrar la importancia de la realización de tests funcionales durante el proceso de desarrollo de software para que el proyecto alcance la calidad requerida tan demandada en estos días. Para ello, después de una pequeña introducción a la historia del software, se presentarán y compararán diversos tipos de metodologías de desarrollo de software, tanto pesadas (cascada, espiral, etc.) como ágiles (Extreme Programming y Scrum), se enfatizará en dichas metodologías ágiles y cómo el proceso de testing y control de calidad encaja perfectamente con la filosofía de las citadas metodologías ágiles. Se desarrollará una explicación del papel de QA en el desarrollo de software, asi como una explicación de los tipos de test existentes, y las herramientas, tecnologías y patrones que existen a disposición de aquellos que quieran desempeñar el papel de QA. Para complementar el punto de vista teórico de este trabajo se presentará un caso práctico real realizado en la empresa bq bajo una metodología Scrum. Dicho caso práctico muestra el uso de ciertas herramientas y su aporte para el control de calidad del proyecto bajo desarrollo, demostrando su importancia. Se realizará énfasis en el proceso de automatización de ciertas baterías de test (llamadas test suites), mostrando desde el planteamiento inicial de las diferentes historias de usuario y la batería de test, pasando por la elección de las tecnologías más adecuadas para la elaboración de los test hasta llegar al lanzamiento de dicha batería de pruebas y la comprobación de éstas. El punto de vista práctico quedará complementado por una explicación del framework nightwatch.js, framework utilizado en el desarrollo del proyecto en bq para la automatización de test funcionales. Esta explicación comprenderá tanto la configuración y uso del framework como el uso de patrones y la estructura de las pruebas. ABSTRACT Nowadays there is a growing concern about the Quality of the software delivered in the projects that are made all around the world. This final project will try to prove the importance of performing functional tests during the Software Development Process in order to be able to reach the demanded Quality. To fulfill this objective, different types of Software Development methodologies will be presented and compared. Heavy methodologies (waterfall, spiral methodologies, etc.) as well as agile methodologies (Extreme Programming and Scrum). There will be an emphasis in the second kind (agile methodologies) and how the testing and quality assurance process fits perfectly in their philosophy. A deep explanation of the role that Quality Assurance holds on software development will be presented, as well as an explanation on the current types of testing and an explanation of the different tools; technologies and patrons that exist to help anyone who wants to perform the role of QA. To complement the theoretical perspective of this work a real case study, performed at the company bq under a Scrum methodology, will be presented. The mentioned study covers the use of certain tools and their input for the quality assurance of the project under development, proving its relevance. Emphasis will be made in the process of conducting a set of tests (called test suite), showing from the initial approach of the different users stories and the set of tests, going through the choosing of the most suitable technologies for the tests development, and ending with the performance of this battery of tests and their checkout. The practical point of view will be complemented by a deep explanation of the creation process using the nightwatch.js automated test framework, used in the project in bq. This explanation will cover both the configuration and use of the framework as the use of patterns and structure of the tests.