Recent developments in statistical methods for detecting genetic loci affecting phenotypic variability

A number of recent works have introduced statistical methods for detecting genetic loci that affect phenotypic variability, which we refer to as variability-controlling quantitative trait loci (vQTL). These are genetic variants whose allelic state predicts how much phenotype values will vary about their expected means. Such loci are of great potential interest in both human and non-human genetic studies, one reason being that a detected vQTL could represent a previously undetected interaction with other genes or environmental factors. The simultaneous publication of these new methods in different journals has in many cases precluded opportunity for comparison. We survey some of these methods, the respective trade-offs they imply, and the connections between them. The methods fall into three main groups: classical non-parametric, fully parametric, and semi-parametric two-stage approximations. Choosing between alternatives involves balancing the need for robustness, flexibility, and speed. For each method, we identify important assumptions and limitations, including those of practical importance, such as their scope for including covariates and random effects. We show in simulations that both parametric methods and their semi-parametric approximations can give elevated false positive rates when they ignore mean-variance relationships intrinsic to the data generation process. We conclude that choice of method depends on the trait distribution, the need to include non-genetic covariates, and the population size and structure, coupled with a critical evaluation of how these fit with the assumptions of the statistical model.

Continuous Delivery : Utmaningar ett förvaltningsuppdrag kan stå inför vid en övergång till Continuous Delivery

Continuous delivery (CD) is a software engineering approach where the focus lays on creating a short delivery cycle by automating parts of the deployment pipeline which includes build, deploy-, test and release process. CD is based on that during development should be possible to always automatically generate a release based on the source code in its current state. One of CD's many advantages is that through continuous releases it allows you to get a quick feedback loop leading to faster and more efficient implementation of new functions, at the same time fixing errors. Although CD has many advantages, there are also several challenges a maintenance management project must manage in the transition to CD. These challenges may differ depending on the maturity level for a maintenance management project and what strengths and weaknesses the project has. Our research question was: "What challenges can a maintenance management project face in transition to Continuous delivery?" The purpose of this study is to describe Continuous delivery and the challenges a maintenance management project may face during a transition to Continuous delivery. A descriptive case study has been carried out with the data collection methods of interviews and documents. A situation analysis was created based on the collected data in a shape of a process model that represent the maintenance management projects release process. The processmodel was used as the basis of SWOT analysis and analysis by Rehn et al's Maturity Model. From these analyzes we found challenges of a maintenance management project may face in the transition to CD. The challenges are about customers and the management's attitude towards a transition to CD. But the biggest challenge is about automation of the deployment pipeline steps.

Automatiserade regressionstester avseende arbetsflöden och behörigheter i ProjectWise. : En fallstudie om ProjectWise på Trafikverket

Test av mjukvara görs i syfte att se ifall systemet uppfyller specificerade krav samt för att hitta fel. Det är en viktig del i systemutveckling och involverar bland annat regressionstestning. Regressionstester utförs för att säkerställa att en ändring i systemet inte medför att andra delar i systemet påverkas negativt. Dokumenthanteringssystem hanterar ofta känslig data hos organisationer vilket ställer höga krav på säkerheten. Behörigheter i system måste därför testas noggrant för att säkerställa att data inte hamnar i fel händer. Dokumenthanteringssystem gör det möjligt för flera organisationer att samla sina resurser och kunskaper för att nå gemensamma mål. Gemensamma arbetsprocesser stöds med hjälp av arbetsflöden som innehåller ett antal olika tillstånd. Vid dessa olika tillstånd gäller olika behörigheter. När en behörighet ändras krävs regressionstester för att försäkra att ändringen inte har gjort inverkan på andra behörigheter. Denna studie har utförts som en kvalitativ fallstudie vars syfte var att beskriva utmaningar med regressionstestning av roller och behörigheter i arbetsflöden för dokument i dokumenthanteringssystem. Genom intervjuer och en observation så framkom det att stora utmaningar med dessa tester är att arbetsflödens tillstånd följer en förutbestämd sekvens. För att fullfölja denna sekvens så involveras en enorm mängd behörigheter som måste testas. Det ger ett mycket omfattande testarbete avseende bland annat tid och kostnad. Studien har riktat sig mot dokumenthanteringssystemet ProjectWise som förvaltas av Trafikverket. Beslutsunderlag togs fram för en teknisk lösning för automatiserad regressionstestning av roller och behörigheter i arbetsflöden åt ProjectWise. Utifrån en kravinsamling tillhandahölls beslutsunderlag som involverade Team Foundation Server (TFS), Coded UI och en nyckelordsdriven testmetod som en teknisk lösning. Slutligen jämfördes vilka skillnader den tekniska lösningen kan utgöra mot manuell testning. Utifrån litteratur, dokumentstudie och förstahandserfarenheter visade sig testautomatisering kunna utgöra skillnader inom ett antal identifierade problemområden, bland annat tid och kostnad.

Improvement of Routine Test Process of High Voltage Power Capacitors

The capacitor test process at ABB Capacitors in Ludvika must be improved to meet future demands for high voltage products. To find a solution to how to improve the test process, an investigation was performed to establish which parts of the process are used and how they operate. Several parts which can improves the process were identified. One of them was selected to be improved in correlation with the subject, mechanical engineering. Four concepts were generated and decision matrixes were used to systematically select the best concept. By improving the process several benefits has been added to the process. More units are able to be tested and lead time is reduced. As the lead time is reduced the cost for each unit is reduced, workers will work less hours for the same amount of tested units, future work to further improve the process is also identified. The selected concept was concept 1, the sway stop concept. This concept is used to reduce the sway of the capacitors as they have entered the test facility, the box. By improving this part of the test process a time saving of 20 seconds per unit can be achieved, equivalent to 7% time reduction. This can be compared to an additional 1400 units each year.

Automatic spiral analysis for objective assessment of motor symptoms in Parkinson's disease

Objective: To develop a method for objective quantification of PD motor symptoms related to Off episodes and peak dose dyskinesias, using spiral data gathered by using a touch screen telemetry device. The aim was to objectively characterize predominant motor phenotypes (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Background: A retrospective analysis was conducted on recordings from 65 patients with advanced idiopathic PD from nine different clinics in Sweden, recruited from January 2006 until August 2010. In addition to the patient group, 10 healthy elderly subjects were recruited. Upper limb movement data were collected using a touch screen telemetry device from home environments of the subjects. Measurements with the device were performed four times per day during week-long test periods. On each test occasion, the subjects were asked to trace pre-drawn Archimedean spirals, using the dominant hand. The pre-drawn spiral was shown on the screen of the device. The spiral test was repeated three times per test occasion and they were instructed to complete it within 10 seconds. The device had a sampling rate of 10Hz and measured both position and time-stamps (in milliseconds) of the pen tip. Methods: Four independent raters (FB, DH, AJ and DN) used a web interface that animated the spiral drawings and allowed them to observe different kinematic features during the drawing process and to rate task performance. Initially, a number of kinematic features were assessed including ‘impairment’, ‘speed’, ‘irregularity’ and ‘hesitation’ followed by marking the predominant motor phenotype on a 3-category scale: tremor, bradykinesia and/or choreatic dyskinesia. There were only 2 test occasions for which all the four raters either classified them as tremor or could not identify the motor phenotype. Therefore, the two main motor phenotype categories were bradykinesia and dyskinesia. ‘Impairment’ was rated on a scale from 0 (no impairment) to 10 (extremely severe) whereas ‘speed’, ‘irregularity’ and ‘hesitation’ were rated on a scale from 0 (normal) to 4 (extremely severe). The proposed data-driven method consisted of the following steps. Initially, 28 spatiotemporal features were extracted from the time series signals before being presented to a Multilayer Perceptron (MLP) classifier. The features were based on different kinematic quantities of spirals including radius, angle, speed and velocity with the aim of measuring the severity of involuntary symptoms and discriminate between PD-specific (bradykinesia) and/or treatment-induced symptoms (dyskinesia). A Principal Component Analysis was applied on the features to reduce their dimensions where 4 relevant principal components (PCs) were retained and used as inputs to the MLP classifier. Finally, the MLP classifier mapped these components to the corresponding visually assessed motor phenotype scores for automating the process of scoring the bradykinesia and dyskinesia in PD patients whilst they draw spirals using the touch screen device. For motor phenotype (bradykinesia vs. dyskinesia) classification, the stratified 10-fold cross validation technique was employed. Results: There were good agreements between the four raters when rating the individual kinematic features with intra-class correlation coefficient (ICC) of 0.88 for ‘impairment’, 0.74 for ‘speed’, 0.70 for ‘irregularity’, and moderate agreements when rating ‘hesitation’ with an ICC of 0.49. When assessing the two main motor phenotype categories (bradykinesia or dyskinesia) in animated spirals the agreements between the four raters ranged from fair to moderate. There were good correlations between mean ratings of the four raters on individual kinematic features and computed scores. The MLP classifier classified the motor phenotype that is bradykinesia or dyskinesia with an accuracy of 85% in relation to visual classifications of the four movement disorder specialists. The test-retest reliability of the four PCs across the three spiral test trials was good with Cronbach’s Alpha coefficients of 0.80, 0.82, 0.54 and 0.49, respectively. These results indicate that the computed scores are stable and consistent over time. Significant differences were found between the two groups (patients and healthy elderly subjects) in all the PCs, except for the PC3. Conclusions: The proposed method automatically assessed the severity of unwanted symptoms and could reasonably well discriminate between PD-specific and/or treatment-induced motor symptoms, in relation to visual assessments of movement disorder specialists. The objective assessments could provide a time-effect summary score that could be useful for improving decision-making during symptom evaluation of individualized treatment when the goal is to maximize functional On time for patients while minimizing their Off episodes and troublesome dyskinesias.

Response process and test-retest reliability of the Context Assessment for Community Health tool in Vietnam

BACKGROUND: The recently developed Context Assessment for Community Health (COACH) tool aims to measure aspects of the local healthcare context perceived to influence knowledge translation in low- and middle-income countries. The tool measures eight dimensions (organizational resources, community engagement, monitoring services for action, sources of knowledge, commitment to work, work culture, leadership, and informal payment) through 49 items. OBJECTIVE: The study aimed to explore the understanding and stability of the COACH tool among health providers in Vietnam. DESIGNS: To investigate the response process, think-aloud interviews were undertaken with five community health workers, six nurses and midwives, and five physicians. Identified problems were classified according to Conrad and Blair's taxonomy and grouped according to an estimation of the magnitude of the problem's effect on the response data. Further, the stability of the tool was examined using a test-retest survey among 77 respondents. The reliability was analyzed for items (intraclass correlation coefficient (ICC) and percent agreement) and dimensions (ICC and Bland-Altman plots). RESULTS: In general, the think-aloud interviews revealed that the COACH tool was perceived as clear, well organized, and easy to answer. Most items were understood as intended. However, seven prominent problems in the items were identified and the content of three dimensions was perceived to be of a sensitive nature. In the test-retest survey, two-thirds of the items and seven of eight dimensions were found to have an ICC agreement ranging from moderate to substantial (0.5-0.7), demonstrating that the instrument has an acceptable level of stability. CONCLUSIONS: This study provides evidence that the Vietnamese translation of the COACH tool is generally perceived to be clear and easy to understand and has acceptable stability. There is, however, a need to rephrase and add generic examples to clarify some items and to further review items with low ICC.