Characterization of structure and dynamics of submicrometric systems via fluorescence correlation spectroscopy

The presented thesis revolves around the study of thermally-responsive PNIPAAm-based hydrogels in water/based environments, as studied by Fluorescence Correlation Spectroscopy (FCS).rnThe goal of the project was the engineering of PNIPAAm gels into biosensors. Specifically, a gamma of such gels were both investigated concerning their dynamics and structure at the nanometer scale, and their performance in retaining bound bodies upon thermal collapse (which PNIPAAm undergoes upon heating above 32 ºC).rnFCS’s requirements, as a technique, match the limitations imposed by the system. Namely, the need to intimately probe a system in a solvent, which was also fragile and easy to alter. FCS, on the other hand, both requires a fluid environment to work, and is based on the observation of diffusion of fluorescents at nanomolar concentrations. FCS was applied to probe the hydrogels on the nanometer size with minimal invasivity.rnVariables in the gels were addressed in the project including crosslinking degree; structural changes during thermal collapse; behavior in different buffers; the possibility of decreasing the degree of inhomogeneity; behavior of differently sized probes; and the effectiveness of antibody functionalization upon thermal collapse.rnThe evidenced results included the heightening of structural inhomogeneities during thermal collapse and under different buffer conditions; the use of annealing to decrease the inhomogeneity degree; the use of differently sized probes to address different length scale of the gel; and the successful functionalization before and after collapse.rnThe thesis also addresses two side projects, also carried forward via FCS. One, diffusion in inverse opals, produced a predictive simulation model for diffusion of bodies in confined systems as dependent on the bodies’ size versus the characteristic sizes of the system. The other was the observation of interaction of bodies of opposite charge in a water solution, resulting in a phenomenological theory and an evaluation method for both the average residence time of the different bodies together, and their attachment likelihood.

Population based screening - the difficulty of how to do more good than harm and how to achieve it

Screening people without symptoms of disease is an attractive idea. Screening allows early detection of disease or elevated risk of disease, and has the potential for improved treatment and reduction of mortality. The list of future screening opportunities is set to grow because of the refinement of screening techniques, the increasing frequency of degenerative and chronic diseases, and the steadily growing body of evidence on genetic predispositions for various diseases. But how should we decide on the diseases for which screening should be done and on recommendations for how it should be implemented? We use the examples of prostate cancer and genetic screening to show the importance of considering screening as an ongoing population-based intervention with beneficial and harmful effects, and not simply the use of a test. Assessing whether screening should be recommended and implemented for any named disease is therefore a multi-dimensional task in health technology assessment. There are several countries that already use established processes and criteria to assess the appropriateness of screening. We argue that the Swiss healthcare system needs a nationwide screening commission mandated to conduct appropriate evidence-based evaluation of the impact of proposed screening interventions, to issue evidence-based recommendations, and to monitor the performance of screening programmes introduced. Without explicit processes there is a danger that beneficial screening programmes could be neglected and that ineffective, and potentially harmful, screening procedures could be introduced.

Development, feasibility and performance of a health risk appraisal questionnaire for older persons

BACKGROUND: Health risk appraisal is a promising method for health promotion and prevention in older persons. The Health Risk Appraisal for the Elderly (HRA-E) developed in the U.S. has unique features but has not been tested outside the United States. METHODS: Based on the original HRA-E, we developed a scientifically updated and regionally adapted multilingual Health Risk Appraisal for Older Persons (HRA-O) instrument consisting of a self-administered questionnaire and software-generated feed-back reports. We evaluated the practicability and performance of the questionnaire in non-disabled community-dwelling older persons in London (U.K.) (N = 1090), Hamburg (Germany) (N = 804), and Solothurn (Switzerland) (N = 748) in a sub-sample of an international randomised controlled study. RESULTS: Over eighty percent of invited older persons returned the self-administered HRA-O questionnaire. Fair or poor self-perceived health status and older age were correlated with higher rates of non-return of the questionnaire. Older participants and those with lower educational levels reported more difficulty in completing the HRA-O questionnaire as compared to younger and higher educated persons. However, even among older participants and those with low educational level, more than 80% rated the questionnaire as easy to complete. Prevalence rates of risks for functional decline or problems were between 2% and 91% for the 19 HRA-O domains. Participants' intention to change health behaviour suggested that for some risk factors participants were in a pre-contemplation phase, having no short- or medium-term plans for change. Many participants perceived their health behaviour or preventative care uptake as optimal, despite indications of deficits according to the HRA-O based evaluation. CONCLUSION: The HRA-O questionnaire was highly accepted by a broad range of community-dwelling non-disabled persons. It identified a high number of risks and problems, and provided information on participants' intention to change health behaviour.

Graphics Processor Unit Based Parallelization of Optimized Baseline Wander Filtering Algorithms for Long-term Electrocardiography

Long-term electrocardiogram (ECG) often suffers from relevant noise. Baseline wander in particular is pronounced in ECG recordings using dry or esophageal electrodes, which are dedicated for prolonged registration. While analog high-pass filters introduce phase distortions, reliable offline filtering of the baseline wander implies a computational burden that has to be put in relation to the increase in signal-to-baseline ratio (SBR). Here we present a graphics processor unit (GPU) based parallelization method to speed up offline baseline wander filter algorithms, namely the wavelet, finite, and infinite impulse response, moving mean, and moving median filter. Individual filter parameters were optimized with respect to the SBR increase based on ECGs from the Physionet database superimposed to auto-regressive modeled, real baseline wander. A Monte-Carlo simulation showed that for low input SBR the moving median filter outperforms any other method but negatively affects ECG wave detection. In contrast, the infinite impulse response filter is preferred in case of high input SBR. However, the parallelized wavelet filter is processed 500 and 4 times faster than these two algorithms on the GPU, respectively, and offers superior baseline wander suppression in low SBR situations. Using a signal segment of 64 mega samples that is filtered as entire unit, wavelet filtering of a 7-day high-resolution ECG is computed within less than 3 seconds. Taking the high filtering speed into account, the GPU wavelet filter is the most efficient method to remove baseline wander present in long-term ECGs, with which computational burden can be strongly reduced.

Comparison of 2.5D and 3D Quantification of Femoral Head Coverage in Normal Control Subjects and Patients with Hip Dysplasia.

Hip dysplasia is characterized by insufficient femoral head coverage (FHC). Quantification of FHC is of importance as the underlying goal of the surgery to treat hip dysplasia is to restore a normal acetabular morphology and thereby to improve FHC. Unlike a pure 2D X-ray radiograph-based measurement method or a pure 3D CT-based measurement method, previously we presented a 2.5D method to quantify FHC from a single anteriorposterior (AP) pelvic radiograph. In this study, we first quantified and compared 3D FHC between a normal control group and a patient group using a CT-based measurement method. Taking the CT-based 3D measurements of FHC as the gold standard, we further quantified the bias, precision and correlation between the 2.5D measurements and the 3D measurements on both the control group and the patient group. Based on digitally reconstructed radiographs (DRRs), we investigated the influence of the pelvic tilt on the 2.5D measurements of FHC. The intraclass correlation coefficients (ICCs) for absolute agreement was used to quantify interobserver reliability and intraobserver reproducibility of the 2.5D measurement technique. The Pearson correlation coefficient, r, was used to determine the strength of the linear association between the 2.5D and the 3D measurements. Student's t-test was used to determine whether the differences between different measurements were statistically significant. Our experimental results demonstrated that both the interobserver reliability and the intraobserver reproducibility of the 2.5D measurement technique were very good (ICCs > 0.8). Regression analysis indicated that the correlation was very strong between the 2.5D and the 3D measurements (r = 0.89, p < 0.001). Student's t-test showed that there were no statistically significant differences between the 2.5D and the 3D measurements of FHC on the patient group (p > 0.05). The results of this study provided convincing evidence demonstrating the validity of the 2.5D measurements of FHC from a single AP pelvic radiograph and proved that it could serve as a surrogate for 3D CT-based measurements. Thus it may be possible to use this method to avoid a CT scan for the purpose of estimating 3D FHC in diagnosis and post-operative treatment evaluation of patients with hip dysplasia.

Evaluating a Speech Communication System for deaf people

This paper describes the development of an Advanced Speech Communication System for Deaf People and its field evaluation in a real application domain: the renewal of Driver’s License. The system is composed of two modules. The first one is a Spanish into Spanish Sign Language (LSE: Lengua de Signos Española) translation module made up of a speech recognizer, a natural language translator (for converting a word sequence into a sequence of signs), and a 3D avatar animation module (for playing back the signs). The second module is a Spoken Spanish generator from sign-writing composed of a visual interface (for specifying a sequence of signs), a language translator (for generating the sequence of words in Spanish), and finally, a text to speech converter. For language translation, the system integrates three technologies: an example-based strategy, a rule-based translation method and a statistical translator. This paper also includes a detailed description of the evaluation carried out in the Local Traffic Office in the city of Toledo (Spain) involving real government employees and deaf people. This evaluation includes objective measurements from the system and subjective information from questionnaires. Finally, the paper reports an analysis of the main problems and a discussion about possible solutions.

Interval-based ranking in noisy evolutionary multiobjective optimization

As one of the most competitive approaches to multi-objective optimization, evolutionary algorithms have been shown to obtain very good results for many realworld multi-objective problems. One of the issues that can affect the performance of these algorithms is the uncertainty in the quality of the solutions which is usually represented with the noise in the objective values. Therefore, handling noisy objectives in evolutionary multi-objective optimization algorithms becomes very important and is gaining more attention in recent years. In this paper we present ?-degree Pareto dominance relation for ordering the solutions in multi-objective optimization when the values of the objective functions are given as intervals. Based on this dominance relation, we propose an adaptation of the non-dominated sorting algorithm for ranking the solutions. This ranking method is then used in a standardmulti-objective evolutionary algorithm and a recently proposed novel multi-objective estimation of distribution algorithm based on joint variable-objective probabilistic modeling, and applied to a set of multi-objective problems with different levels of independent noise. The experimental results show that the use of the proposed method for solution ranking allows to approximate Pareto sets which are considerably better than those obtained when using the dominance probability-based ranking method, which is one of the main methods for noise handling in multi-objective optimization.

Design and development of compact optical systems = Diseño y desarrollo de sistemas ópticos compactos

Esta tesis considera dos tipos de aplicaciones del diseño óptico: óptica formadora de imagen por un lado, y óptica anidólica (nonimaging) o no formadora de imagen, por otro. Las ópticas formadoras de imagen tienen como objetivo la obtención de imágenes de puntos del objeto en el plano de la imagen. Por su parte, la óptica anidólica, surgida del desarrollo de aplicaciones de concentración e iluminación, se centra en la transferencia de energía en forma de luz de forma eficiente. En general, son preferibles los diseños ópticos que den como resultado sistemas compactos, para ambos tipos de ópticas (formadora de imagen y anidólica). En el caso de los sistemas anidólicos, una óptica compacta permite tener costes de producción reducidos. Hay dos razones: (1) una óptica compacta presenta volúmenes reducidos, lo que significa que se necesita menos material para la producción en masa; (2) una óptica compacta es pequeña y ligera, lo que ahorra costes en el transporte. Para los sistemas ópticos de formación de imagen, además de las ventajas anteriores, una óptica compacta aumenta la portabilidad de los dispositivos, que es una gran ventaja en tecnologías de visualización portátiles, tales como cascos de realidad virtual (HMD del inglés Head Mounted Display). Esta tesis se centra por tanto en nuevos enfoques de diseño de sistemas ópticos compactos para aplicaciones tanto de formación de imagen, como anidólicas. Los colimadores son uno de los diseños clásicos dentro la óptica anidólica, y se pueden utilizar en aplicaciones fotovoltaicas y de iluminación. Hay varios enfoques a la hora de diseñar estos colimadores. Los diseños convencionales tienen una relación de aspecto mayor que 0.5. Con el fin de reducir la altura del colimador manteniendo el área de iluminación, esta tesis presenta un diseño de un colimador multicanal. En óptica formadora de imagen, las superficies asféricas y las superficies sin simetría de revolución (o freeform) son de gran utilidad de cara al control de las aberraciones de la imagen y para reducir el número y tamaño de los elementos ópticos. Debido al rápido desarrollo de sistemas de computación digital, los trazados de rayos se pueden realizar de forma rápida y sencilla para evaluar el rendimiento del sistema óptico analizado. Esto ha llevado a los diseños ópticos modernos a ser generados mediante el uso de diferentes técnicas de optimización multi-paramétricas. Estas técnicas requieren un buen diseño inicial como punto de partida para el diseño final, que será obtenido tras un proceso de optimización. Este proceso precisa un método de diseño directo para superficies asféricas y freeform que den como resultado un diseño cercano al óptimo. Un método de diseño basado en ecuaciones diferenciales se presenta en esta tesis para obtener un diseño óptico formado por una superficie freeform y dos superficies asféricas. Esta tesis consta de cinco capítulos. En Capítulo 1, se presentan los conceptos básicos de la óptica formadora de imagen y de la óptica anidólica, y se introducen las técnicas clásicas del diseño de las mismas. El Capítulo 2 describe el diseño de un colimador ultra-compacto. La relación de aspecto ultra-baja de este colimador se logra mediante el uso de una estructura multicanal. Se presentará su procedimiento de diseño, así como un prototipo fabricado y la caracterización del mismo. El Capítulo 3 describe los conceptos principales de la optimización de los sistemas ópticos: función de mérito y método de mínimos cuadrados amortiguados. La importancia de un buen punto de partida se demuestra mediante la presentación de un mismo ejemplo visto a través de diferentes enfoques de diseño. El método de las ecuaciones diferenciales se presenta como una herramienta ideal para obtener un buen punto de partida para la solución final. Además, diferentes técnicas de interpolación y representación de superficies asféricas y freeform se presentan para el procedimiento de optimización. El Capítulo 4 describe la aplicación del método de las ecuaciones diferenciales para un diseño de un sistema óptico de una sola superficie freeform. Algunos conceptos básicos de geometría diferencial son presentados para una mejor comprensión de la derivación de las ecuaciones diferenciales parciales. También se presenta un procedimiento de solución numérica. La condición inicial está elegida como un grado de libertad adicional para controlar la superficie donde se forma la imagen. Basado en este enfoque, un diseño anastigmático se puede obtener fácilmente y se utiliza como punto de partida para un ejemplo de diseño de un HMD con una única superficie reflectante. Después de la optimización, dicho diseño muestra mejor rendimiento. El Capítulo 5 describe el método de las ecuaciones diferenciales ampliado para diseños de dos superficies asféricas. Para diseños ópticos de una superficie, ni la superficie de imagen ni la correspondencia entre puntos del objeto y la imagen pueden ser prescritas. Con esta superficie adicional, la superficie de la imagen se puede prescribir. Esto conduce a un conjunto de tres ecuaciones diferenciales ordinarias implícitas. La solución numérica se puede obtener a través de cualquier software de cálculo numérico. Dicho procedimiento también se explica en este capítulo. Este método de diseño da como resultado una lente anastigmática, que se comparará con una lente aplanática. El diseño anastigmático converge mucho más rápido en la optimización y la solución final muestra un mejor rendimiento. ABSTRACT We will consider optical design from two points of view: imaging optics and nonimaging optics. Imaging optics focuses on the imaging of the points of the object. Nonimaging optics arose from the development of concentrators and illuminators, focuses on the transfer of light energy, and has wide applications in illumination and concentration photovoltaics. In general, compact optical systems are necessary for both imaging and nonimaging designs. For nonimaging optical systems, compact optics use to be important for reducing cost. The reasons are twofold: (1) compact optics is small in volume, which means less material is needed for mass-production; (2) compact optics is small in size and light in weight, which saves cost in transportation. For imaging optical systems, in addition to the above advantages, compact optics increases portability of devices as well, which contributes a lot to wearable display technologies such as Head Mounted Displays (HMD). This thesis presents novel design approaches of compact optical systems for both imaging and nonimaging applications. Collimator is a typical application of nonimaging optics in illumination, and can be used in concentration photovoltaics as well due to the reciprocity of light. There are several approaches for collimator designs. In general, all of these approaches have an aperture diameter to collimator height not greater than 2. In order to reduce the height of the collimator while maintaining the illumination area, a multichannel design is presented in this thesis. In imaging optics, aspheric and freeform surfaces are useful in controlling image aberrations and reducing the number and size of optical elements. Due to the rapid development of digital computing systems, ray tracing can be easily performed to evaluate the performance of optical system. This has led to the modern optical designs created by using different multi-parametric optimization techniques. These techniques require a good initial design to be a starting point so that the final design after optimization procedure can reach the optimum solution. This requires a direct design method for aspheric and freeform surface close to the optimum. A differential equation based design method is presented in this thesis to obtain single freeform and double aspheric surfaces. The thesis comprises of five chapters. In Chapter 1, basic concepts of imaging and nonimaging optics are presented and typical design techniques are introduced. Readers can obtain an understanding for the following chapters. Chapter 2 describes the design of ultra-compact collimator. The ultra-low aspect ratio of this collimator is achieved by using a multichannel structure. Its design procedure is presented together with a prototype and its evaluation. The ultra-compactness of the device has been approved. Chapter 3 describes the main concepts of optimizing optical systems: merit function and Damped Least-Squares method. The importance of a good starting point is demonstrated by presenting an example through different design approaches. The differential equation method is introduced as an ideal tool to obtain a good starting point for the final solution. Additionally, different interpolation and representation techniques for aspheric and freeform surface are presented for optimization procedure. Chapter 4 describes the application of differential equation method in the design of single freeform surface optical system. Basic concepts of differential geometry are presented for understanding the derivation of partial differential equations. A numerical solution procedure is also presented. The initial condition is chosen as an additional freedom to control the image surface. Based on this approach, anastigmatic designs can be readily obtained and is used as starting point for a single reflective surface HMD design example. After optimization, the evaluation shows better MTF. Chapter 5 describes the differential equation method extended to double aspheric surface designs. For single optical surface designs, neither image surface nor the mapping from object to image can be prescribed. With one more surface added, the image surface can be prescribed. This leads to a set of three implicit ordinary differential equations. Numerical solution can be obtained by MATLAB and its procedure is also explained. An anastigmatic lens is derived from this design method and compared with an aplanatic lens. The anastigmatic design converges much faster in optimization and the final solution shows better performance.

Value Assessment of Orphan Drugs and Treatments for Rare Diseases

Thesis (Master's)--University of Washington, 2016-06

GIS-Based Suitability Analysis and Planning of Green Infrastructure: A Case of the PPCOD, Capitol Hill

Thesis (Master's)--University of Washington, 2016-06

Fitness assessment of document model

Document classification is a supervised machine learning process, where predefined category labels are assigned to documents based on the hypothesis derived from training set of labelled documents. Documents cannot be directly interpreted by a computer system unless they have been modelled as a collection of computable features. Rogati and Yang [M. Rogati and Y. Yang, Resource selection for domain-specific cross-lingual IR, in SIGIR 2004: Proceedings of the 27th annual international conference on Research and Development in Information Retrieval, ACM Press, Sheffied: United Kingdom, pp. 154-161.] pointed out that the effectiveness of document classification system may vary in different domains. This implies that the quality of document model contributes to the effectiveness of document classification. Conventionally, model evaluation is accomplished by comparing the effectiveness scores of classifiers on model candidates. However, this kind of evaluation methods may encounter either under-fitting or over-fitting problems, because the effectiveness scores are restricted by the learning capacities of classifiers. We propose a model fitness evaluation method to determine whether a model is sufficient to distinguish positive and negative instances while still competent to provide satisfactory effectiveness with a small feature subset. Our experiments demonstrated how the fitness of models are assessed. The results of our work contribute to the researches of feature selection, dimensionality reduction and document classification.

ICA based steganography

A domain independent ICA-based watermarking method is introduced and studied by numerical simulations. This approach can be used either on images, music or video to convey a hidden message. It relies on embedding the information in a set of statistically independent sources (the independent components) as the feature space. For the experiments the medium has arbritraly chosen to be digital images.

Dispensing activity in a community pharmacy-based repeat dispensing pilot project

Objective: To measure changes in dispensing activity in a UK repeat dispensing pilot study and to estimate any associated cost savings. Method: Patients were provided with two successive three-monthly repeat prescriptions containing all of the items on their "repeat medicines list" and valid at a study pharmacy. Pharmacists consulted with patients at the time of supply and completed a patient-monitoring form. Prescriptions with pricing data were returned by the UK Prescription Pricing Authority. These data were used to calculate dispensing activity, the cost of dispensed items and an estimate of cost savings on non-dispensed items. A retrospective identification of items prescribed during the six months prior to the project was used to provide a comparison with those dispensed during the project and thus a more realistic estimate of changes. Setting: 350 patients from two medical practices in a large English City, with inner city and suburban locations, and served by seven pharmacies. Key findings: There were methodological challenges in establishing a robust framework for calculating changes. Based on all of the items that patients could have obtained from their repeat list, 23.8% were not dispensed during the intervention period. A correction was then made to allow for a comparison with usage in the six months prior to the study. Based on the corrected data, there was an estimated 11.3% savings in drug costs compared with the pre-intervention period. There was a marked difference in changes between the two practices, the pharmacies and individual patients. The capitation-based remuneration method was acceptable to all but one of the community pharmacists. Conclusion: The repeat dispensing system reduced dispensing volume in comparison with the control period. A repeat dispensing system with a focus on patients' needs and their use of medicines might be cost neutral.

The Evaluation of health and safety auditing systems

The specific objective of the research was to evaluate proprietary audit systems. Proprietary audit systems comprise question sets containing approximately 500 questions dealing with selected aspects of health and safety management. Each question is allotted a number of points and an organisation seeks to judge its health and safety performance by the overall score achieved in the audit. Initially it was considered that the evaluation method might involve comparing the proprietary audit scores with other methods of measuring safety performance. However, what appeared to be missing in the first instance was information that organisations could use to compare the contrast question set content against their own needs. A technique was developed using the computer database FileMaker Pro. This enables questions in an audit to be sorted into categories using a process of searching for key words. Questions that are not categorised by word searching can be identified and sorted manually. The process can be completed in 2-3 hours which is considerably faster than manual categorisation of questions which typically takes about 10 days. The technique was used to compare and contrast three proprietary audits: ISRS, CHASE and QSA. Differences and similarities between these audits were successfully identified. It was concluded that in general proprietary audits need to focus to a greater extent on identifying strengths and weaknesses in occupational health and safety management systems. To do this requires the inclusion of more probing questions which consider whether risk control measures are likely to be successful.

Exploring the effectiveness of similarity-based visualisations for colour-based image retrieval

In April 2009, Google Images added a filter for narrowing search results by colour. Several other systems for searching image databases by colour were also released around this time. These colour-based image retrieval systems enable users to search image databases either by selecting colours from a graphical palette (i.e., query-by-colour), by drawing a representation of the colour layout sought (i.e., query-by-sketch), or both. It was comments left by readers of online articles describing these colour-based image retrieval systems that provided us with the inspiration for this research. We were surprised to learn that the underlying query-based technology used in colour-based image retrieval systems today remains remarkably similar to that of systems developed nearly two decades ago. Discovering this ageing retrieval approach, as well as uncovering a large user demographic requiring image search by colour, made us eager to research more effective approaches for colour-based image retrieval. In this thesis, we detail two user studies designed to compare the effectiveness of systems adopting similarity-based visualisations, query-based approaches, or a combination of both, for colour-based image retrieval. In contrast to query-based approaches, similarity-based visualisations display and arrange database images so that images with similar content are located closer together on screen than images with dissimilar content. This removes the need for queries, as users can instead visually explore the database using interactive navigation tools to retrieve images from the database. As we found existing evaluation approaches to be unreliable, we describe how we assessed and compared systems adopting similarity-based visualisations, query-based approaches, or both, meaningfully and systematically using our Mosaic Test - a user-based evaluation approach in which evaluation study participants complete an image mosaic of a predetermined target image using the colour-based image retrieval system under evaluation.