The advent of Next Generation Sequencing (NGS), a little over a decade ago, has led to a vast and rapid increase in the generation of genomic data. The drastically reduced cost has in turn enabled powerful modifications that can be used to investigate not just genetic, but epigenetic, phenomena. Epigenetics refers to the study of mechanisms effecting gene expression other than the genetic code itself and thus, at the transcription level, incorporates DNA methylation, transcription factor binding and histone modifications amongst others. This thesis outlines and tackles two major challenges in the computational analysis of such data using techniques from machine learning. Firstly, I address the problem of testing for differential methylation between groups of bisulfite sequencing data sets. DNA methylation plays an important role in genomic imprinting, X-chromosome inactivation and the repression of repetitive elements, as well as being implicated in numerous diseases, such as cancer. Bisulfite sequencing provides single nucleotide resolution methylation data at the whole genome scale, but a sensitive analysis of such data is difficult. I propose a solution that uses a powerful kernel-based machine learning technique, the Maximum Mean Discrepancy, to leverage well-characterised spatial correlations in DNA methylation, and adapt the method for this particular use. I use this tailored method to analyse a novel data set from a study of ageing in three different tissues in the mouse. This study motivates further modifications to the method and highlights the utility of the underlying measure as an exploratory tool for methylation analysis. Secondly, I address the problem of predictive and explanatory modelling of chromatin immunoprecipitation sequencing data (ChIP-Seq). ChIP-Seq is typically used to assay the binding of a protein of interest, such as a transcription factor or histone, to the DNA, and as such is one of the most widely used sequencing assays. While peak callers are a powerful tool in identifying binding sites of sparse and clean ChIPSeq profiles, more broad signals defy analysis in this framework. Instead, generative models that explain the data in terms of the underlying sequence can help uncover mechanisms that predicting binding or the lack thereof. I explore current problems with ChIP-Seq analysis, such as zero-inflation and the use of the control experiment, known as the input. I then devise a method for representing k-mers that enables the use of longer DNA sub-sequences within a flexible model development framework, such as generalised linear models, without heavy programming requirements. Finally, I use these insights to develop an appropriate Bayesian generative model that predicts ChIP-Seq count data in terms of the underlying DNA sequence, incorporating DNA methylation information where available, fitting the model with the Expectation-Maximization algorithm. The model is tested on simulated data and real data pertaining to the histone mark H3k27me3. This thesis therefore straddles the fields of bioinformatics and machine learning. Bioinformatics is both plagued and blessed by the plethora of different techniques available for gathering data and their continual innovations. Each technique presents a unique challenge, and hence out-of-the-box machine learning techniques have had little success in solving biological problems. While I have focused on NGS data, the methods developed in this thesis are likely to be applicable to future technologies, such as Third Generation Sequencing methods, and the lessons learned in their adaptation will be informative for the next wave of computational challenges.

Den här studien har tittat närmare på vilka informationskvalitativa faktorer som påverkar användarens upplevelse av informationskvalité i en e-handelskontext. Studien bygger på vetenskapliga artiklar och litteratur inom områdena informationskvalité och e-handel. Det gjordes även en egen datainsamling där sex informanter deltog. Dessa fick svara på intervjufrågor och genomföra ett användartest på en befintlig e-handelswebbplats. Uppgifterna i användartesterna presenterades i form av scenarios där informanten fick genomföra olika handlingar som är vanliga vid e-handel. Svaren från den egna datainsamlingen mappades sedan för att kunna identifiera vilka faktorer som påverkar användarens upplevelse av informationskvalité. Dessa jämfördes sedan med de faktorer som identifierats i tidigare studier. Resultatet från den egna datainsamlingen visar på att Förtroende, Informationsarkitektur, Information och Användbarhet är viktiga informationskvalitativa faktorer. Ett resultat som går i linje med tidigare forskning. / This study has looked into which information quality factors that affect the users’ experience in the context of e-commerce. The study is based on scientific articles and literature within the areas of information quality and e-commerce. There were also a separate data collection where six informants participated. These were asked to answer interview questions and carry out a user test on an existing e-commerce website. The tasks in the user test were presented in the form of scenarios were the informant had to carry out various actions that are common within e-commerce. The answers from the own data collection was then mapped to be able to identify which factors that affect the user's experience of information quality. These were then compared to the factors identified in previous studies. The result of the data collection in question shows that Trust, Informations architecture, Information and Usability are important information quality factors. A result that is in line with previous research.

Ill-posed sets of linear equations typically arise when discretizing certain types of integral transforms. A well known example is image reconstruction, which can be modeled using the Radon transform. After expanding the solution into a finite series of basis functions a large, sparse and ill-conditioned linear system occurs. We consider the solution of such systems. In particular we study a new class of iteration methods named DROP (for Diagonal Relaxed Orthogonal Projections) constructed for solving both linear equations and linear inequalities. This class can also be viewed, when applied to linear equations, as a generalized Landweber iteration. The method is compared with other iteration methods using test data from a medical application and from electron microscopy. Our theoretical analysis include convergence proofs of the fully-simultaneous DROP algorithm for linear equations without consistency assumptions, and of block-iterative algorithms both for linear equations and linear inequalities, for the consistent case. When applying an iterative solver to an ill-posed set of linear equations the error usually initially decreases but after some iterations, depending on the amount of noise in the data, and the degree of ill-posedness, it starts to increase. This phenomenon is called semi-convergence. We study the semi-convergence performance of Landweber-type iteration, and propose new ways to specify the relaxation parameters. These are computed so as to control the propagated error. We also describe a class of stopping rules for Landweber-type iteration for solving linear inverse problems. The class includes the well known discrepancy principle, and the monotone error rule. We unify the error analysis of these two methods. The stopping rules depend critically on a certain parameter whose value needs to be specified. A training procedure is therefore introduced for securing robustness. The advantages of using trained rules are demonstrated on examples taken from image reconstruction from projections. Kaczmarz's method, also called ART (Algebraic Reconstruction Technique) is often used for solving the linear system which appears in image reconstruction. This is a fully sequential method. We examine and compare ART and its symmetric version. It is shown that the cycles of symmetric ART, unlike ART, converge to a weighted least squares solution if and only if the relaxation parameter lies between zero and two. Further we show that ART has faster asymptotic rate of convergence than symmetric ART. Also a stopping criterion is proposed and evaluated for symmetric ART. We further investigate a class of block-iterative methods used in image reconstruction. The cycles of the iterative sequences are characterized in terms of the original linear system. We define symmetric block-iteration and compare the behavior of symmetric and non-symmetric block-iteration. The results are illustrated using some well-known methods. A stopping criterion is offered and assessed for symmetric block-iteration.

Sexual health is an important component to overall well-being and quality of life. Yet so much of sexual health research is focused solely on the negative consequences of sexuality, such as unintended pregnancy and transmission of sexually transmitted infections. Recently, the need for a positive, health promotion focused framework for research and understanding sexual health has received attention, including from the World Health Organization and the Centers for Disease Control and Prevention. This transition of public health research and practice from a disease-based framework to a positive, health promotion framework necessitates exploring what factors are associated with positive sexuality and how it is experienced. This study contributed to fulfilling this need. This study focused on healthy sexuality in young college women. Specifically, this study sought to explore what young women find sexually satisfying in different types of sexual relationships (e.g., casual and committed partners). Next, this study identified variables that are important to the healthy sexuality of young college women, including sexual self-concept, communication with sexual partners, sexual satisfaction, and condom use. Lastly, this study aimed to understand the statistical relationship between these variables. This was a two-phase mixed methods study. Phase one consisted of thirty face to face individual interviews with college women aged 18-25 years, and took place in the fall semester of 2011 and the spring semester 2012 at a large public urban university located in the southeastern United States. Phase two took place in the spring semester 2012 and consisted of an online quantitative survey measuring sexual self-concept, communication with partners, sexual satisfaction and condom use. Analyses for the quantitative data included bivariate correlations and structural equation modeling. Qualitative results indicated that these young college women experienced sexual satisfaction with both committed and casual sexual partners, although they identified different reasons why each type of partnership was satisfying. Specifically, the emotional connection and comfort felt with committed relationship partners made sex satisfaction. With more casual or uncommitted partners, these women identified the benefits of maintaining their freedom and not having an obligation to another person. These young women shared their thoughts on how sex could be more satisfying for women and they indicated that communicating sexual desires and needs to partners as one of the most important factors. The quantitative portion of this study found that sexual self-concept was directly positively associated with communication with sexual partners (B=1.45, 95% CI=1.05 1.84, beta=.72), and directly positively related to sexual satisfaction (B=.49, 95% CI= .70, 2.35, beta=.49). Communication with partners was associated with lower discrepancies between wanted and experienced sexual activities (B=-3.96, 95% CI=-4.96, -2.95, beta=-.41). For respondents reporting on committed partnerships, communication with partners was directly related to higher sexual satisfaction (B=.74, 95% CI=.17, 1.32, beta=.43). For those reporting on casual sexual partners, communication was related to sexual satisfaction only through lower sexual activity discrepancy scores (B=.07, 95% CI=.01, .13, beta=.04). Overall the findings from this study suggest that communicating with casual sexual partners impacts sexual satisfaction partially through decreasing the discrepancies between wanted and experienced sexual activities. However, for committed partners, discrepancies were not significantly related to sexual satisfaction, directly or indirectly, although communication was directly associated with sexual satisfaction. This suggests that communication is impacting sexual satisfaction through a different mechanism for committed partners than casual partners. The significance of this study lies in its contribution to the positive sexuality literature, which is currently still in its infancy. This study has implications for public health practice in the improvement of health promotion/sex education programs. This study identified sexual self-concept and communication between partners as important factors for achieving authentic sexual experiences. The implications of this study for public health research include the identification of variables important to understanding women's experience of positive sexuality. Specifically, this study found sexual self-concept to be important to communication and sexual satisfaction, and identified communication as important for both risk reduction (e.g., condom use) and sexual health promotion (e.g., sexual satisfaction).

Femoral neck fracture (FNF) is a great challenge for today´s health care and is associated with high mortality and morbidity in the elderly.  In the short term several studies in the literature have demonstrated improved hip function, quality of life and fewer re-operations in elderly patients treated with total hip arthroplasty (THA) instead of internal fixation (IF). There are few reports on the long-term outcome comparing IF and THA. The vast majority of orthopaedic departments in Sweden use the direct lateral (DL) or posteriolateral (PL) approaches for hip arthroplasty. The PL approach has been linked to an increased risk of dislocation of the prosthesis and a higher rate of revision surgery in comparison to the DL approach. There are few reports focusing on radiological risk factors for prosthetic dislocation and patient reported hip function comparing the two surgical approaches for hip arthroplasty in FNF. The randomized controlled trial (RCT) is the gold standard for evaluating medical or surgical interventions. An RCT of high quality has to be internally and externally valid. Internal validity refers to a correct study design to avoid bias skewing the results. External validity (EV) refers to whether the results will be clinically relevant to a definable group of patients and can be extrapolated to the general health care situation. There are only a few reports in the orthopaedic literature focusing on the EV of published studies and none in the field of hip fractures. Study I: This is a RCT of 100 patients with a displaced FNF comparing THA and IF. Follow-up evaluations were performed at three months and 1, 2, 4, 11 and 17 years. It was found that the Harris hip score (HHS) was higher and the rate of reoperations lower for patients treated with THA. Study II: This is a prospective cohort study of 185 hips, comparing the DL and the PL approaches in patients treated with a hemiarthroplasty (HA) for a displaced FNF. Follow-up was after 1 year. There was no difference in patient reported outcome between the groups measured with the HHS and WOMAC index. The PL approach resulted in a higher re-operation rate while the DL approach in a higher incidence of limping. Study III: This is a retrospective cohort study of 373 patients with a cemented bipolar HA using a PL approach for a FNF with a follow-up ranging from 6 months to 7 years. Radiographs and all surgical records were reviewed regarding femoral offset (FO), leg length discrepancy (LLD) and Wiberg angle. Patients with recurrent dislocations had a decreased postoperative FO, LLD and shallower acetabulum on the operated side compared with their controls. Study IV: This is a prospective cohort study of 840 hips comparing patients included in a RCT with those that did not give their informed consent (NC) or did not fulfill the criteria for participating in the trial (MS). Patients in the NC and MS groups had an increased mortality rate in comparison to those included in the study. We did not find any differences in hip function between these groups. The main conclusions of this thesis are: Healthy and lucid elderly patients with good hip function preoperatively, should be treated with THA for a displaced FNF. The DL approach is favourable in treating displaced FNF with HA due to its decreased risk of reoperation but with an identical hip function outcome as the PL approach. Care should be taken to restore the LLD and FO otherwise this may increase the risk of recurrent dislocation of a HA. Our findings suggest that trial participants had a lower mortality rate than non-participants but the functional outcome of non-participants appeared to be satisfactory. This is important to take into consideration when extrapolating study results to a health care system. / Lårbenshalsfrakturer (FNF) är en utmaning för dagens sjukvård och förknippad med hög mortalitet i den äldre befolkningen. FNF orsakas främst av lågenergitrauma efter fall i samma plan hos patienter med benskörhet. Total höftledsprotes (THA) har visat sig ge en bättre höftfunktion, livskvalitet med färre omoperationer hos äldre patienter än sluten reposition samt fixering med skruvar (IF) under de första två-fyra åren efter operation. Få studier har publicerats med långtidsuppföljning av THA jämfört med IF. Vid behandling av felställd FNF med halv höftledsplastik (HA) eller THA finns olika kirurgiska metoder (snittföring) för implantation av protesen. Majoriteten av ortopedkliniker i Sverige använder direkt lateral (DL) eller posteriolateral (PL) snittföring. PL har kopplats till en ökad risk för luxation av protesen (urledsvridning), vilket i sin tur genererat en högre risk för omoperation jämfört med DL. Få studier har utvärderat höftfunktion med avseende på snittföring. Detsamma gäller vilka radiologiska faktorer som påverkar risken förprotesluxation. Det finns olika typer av studiedesigner för utvärdering av medicinska och kirurgiska behandlingsmetoder. Studiedesignen med högst bevisvärde anses vara den randomiserade kontrollerade studien (RCT). För att en RCT skall hålla hög kvalitet krävs intern och extern validitet. Intern validitet syftar på ett korrekt studieupplägg som mäter det som avses och undviker påverkan av icke önskvärda faktorer. Extern validitet (EV) innebär att erhållna resultat från studien är generaliserbara och kan extrapoleras till andra grupper än den studerade. Det inga rapporter i ortopediska litteraturen med fokus på EV med patienter som drabbats av FNF. Studie I: Prospektiv randomiserad studie av 100 patienter med en felställd FNF jämförs THA med IF med avseende på höftfunktion och reoperationer. Uppföljning gjordes efter tre månader samt 1, 2, 4, 11 och 17 år. HHS som mått på höftfunktion var högre och andelen reoperationer lägre för patienter som behandlades med THA. Studie II: Prospektiv kohortstudie med 183 patienter med felställd FNF behandlade med HA och antingen DL eller PL. Vi fann ingen skillnad i patientrapporterad höftfunktion utvärderat med HHS och WOMAC efter 1 år men en ökad förekomst av hälta vid DL. Studie III: Retrospektiv kohortstudie av 373 patienter opererade med en cementerad bipolär HA och PL. Postoperativa röntgenbilder granskades avseende femoral offset (FO), postoperativ benlägdsskillnad (LLD) samt acetabulär Wibergvinkel och relaterades till återkommande protesluxationer. Detta relaterades till återkommande luxationer. Uppföljningstiden varierade mellan 6 månader och 7 år. Patienter med återkommande luxationer hade en minskad postoperativ global FO, förkortad LLD och grundare acetabulum på den opererade sidan jämfört med kontroller. Studie IV: Prospektiv kohortstudie av 840 patienter med felställd FNF där patienter som ingick i en RCT jämförs med de som inte gav sitt samtycke för deltagande eller ej inkluderats i screeningprocessen. De patienterna som inte gav sitt samtycke hade ökad dödlighet, men ingen skillnad i höftfunktion jämfört med deltagare. Slutsatser • Friska och kognitivt vitala äldre patienter med god höftfunktion innan en felställd lårbenshalsfraktur bör behandlas med total höftledsprotes. • DLsnittföring ger ett lika bra patientrapporterad höftfunktion men en ökad förekomst av hälta jämfört med PL snitt vid behandling med halvprotes på grund av en felställd lårbenshalsfraktur. • Ansträngning bör göras för att återställa benlängdsskillnad samtfemoral offset och därigenom minska risken för återkommande luxation. • Våra resultat tyder på att patienter som deltar i en randomiserad studie har lägre dödlighet än patienter som avböjt att delta samt de som missats i screeningprocessen. Det är viktigt att ta hänsyn till när extrapolerar studieresultat till ett hälso-och sjukvårdssystem. Detta bör vägas in i värderingen av studieresultatens externa validitet.

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The need to quantify distance between two groups of objects is prevalent throughout the signal processing world. The difference of group means computed using the Euclidean, or L2 distance, is one of the predominant distance measures used to compare feature vectors and groups of vectors, but many problems arise with it when high data dimensionality is present. Maximum mean discrepancy (MMD) is a recent unsupervised kernel-based pattern recognition method which may improve differentiation between two distinct populations over many commonly used methods such as the difference of means, when paired with the proper feature representations and kernels. MMD-based distance computation combines many powerful concepts from the machine learning literature, such as data distribution-leveraging similarity measures and kernel methods for machine learning. Due to this heritage, we posit that dissimilarity-based classification and changepoint detection using MMD can lead to enhanced separation between different populations. To test this hypothesis, we conduct studies comparing MMD and the difference of means in two subareas of image analysis and understanding: first, to detect scene changes in video in an unsupervised manner, and secondly, in the biomedical imaging field, using clinical ultrasound to assess tumor response to treatment. We leverage effective computer vision data descriptors, such as the bag-of-visual-words and sparse combinations of SIFT descriptors, and choose from an assessment of several similarity kernels (e.g. Histogram Intersection, Radial Basis Function) in order to engineer useful systems using MMD. Promising improvements over the difference of means, measured primarily using precision/recall for scene change detection, and k-nearest neighbour classification accuracy for tumor response assessment, are obtained in both applications.

Specific Learning Disabilities (SLD) have historically been difficult to define and measure which has led to uncertainty and controversy. The current study explored the practices of identifying specific learning disabilities in Kentucky by surveying school psychologist practitioners in the state. Information was obtained about current practices with regard to RTI implementation and methods and data used for SLD identification as well as the roles that school psychologists take in the response to intervention (RTI) process. The sample consisted of 97 current or recently (within the past year) practicing school psychologists from 45 districts across the state. It was predicted that the use of RTI data for SLD identification would be associated with the length of time a district had been implementing RTI. The data did not support such a relationship. The majority of the districts represented by respondents were noted to be beyond an initial implementation of RTI practices. Responses to questions regarding the implementation of core features of RTI were grouped into High Implementation (HI; n = 45) and Low Implementation (LI; n = 41) groups. An independent samples t-test found a significant difference between the HI and LI groups for the quality of implementation. The HI group evidenced higher quality ratings than the LI. The use of RTI data as the most frequent method for SLD determination was noted for 30.9% of respondents as opposed to 0% prior to 2007. However, severe discrepancy was the most preferred method (59.3%) used for determining placement followed by RTI (28.4%) and a pattern of strengths and weaknesses (4.9%). Districts were also not likely to utilize non-preferred types of data if a student transferred into their district with that non-preferred data. Finally, the roles of school psychologists in the RTI process were explored. Great variability was found across practitioners with regard to the roles they actively have in the RTI process; however, practitioners in the HI group generally were more involved in the RTI process than those in the LI group. The findings are discussed with regard to the current national SLD identification practices and the limitations of the current findings.

Thesis (Ed. D.)--Miami University, Dept. of Educational Leadership, 2007. / Title from first page of PDF document. Includes bibliographical references (p. 89-94).