Genetic Heteroscedasticity for Domestic Animal Traits

Animal traits differ not only in mean, but also in variation around the mean. For instance, one sire’s daughter group may be very homogeneous, while another sire’s daughters are much more heterogeneous in performance. The difference in residual variance can partially be explained by genetic differences. Models for such genetic heterogeneity of environmental variance include genetic effects for the mean and residual variance, and a correlation between the genetic effects for the mean and residual variance to measure how the residual variance might vary with the mean. The aim of this thesis was to develop a method based on double hierarchical generalized linear models for estimating genetic heteroscedasticity, and to apply it on four traits in two domestic animal species; teat count and litter size in pigs, and milk production and somatic cell count in dairy cows. The method developed is fast and has been implemented in software that is widely used in animal breeding, which makes it convenient to use. It is based on an approximation of double hierarchical generalized linear models by normal distributions. When having repeated observations on individuals or genetic groups, the estimates were found to be unbiased. For the traits studied, the estimated heritability values for the mean and the residual variance, and the genetic coefficients of variation, were found in the usual ranges reported. The genetic correlation between mean and residual variance was estimated for the pig traits only, and was found to be favorable for litter size, but unfavorable for teat count.

Kvinnors upplevelser av fosterrörelser i slutet av graviditeten

Bakgrund: Det finns begränsad kunskap om hur kvinnor upplever fosterrörelser i slutet av graviditeten. Ökad kunskap om fosterrörelser kan bidra till bättre möjligheter att identifiera foster som riskerar att dö intrauterint. Syfte: Att utforska hur gravida kvinnor upplever fosterrörelser i slutet av en okomplicerad graviditet samt hur mammor som mist ett barn i livmodern upplevt kontakten med barnet tiden före beskedet att barnet hade dött. Metod: Delstudie I, djupintervjuer med 26 mammor vars barn dött före födelsen, efter 28 fullgångna graviditetsveckor. Delstudie II, frågeformulär till 393 kvinnor med okomplicerad graviditet som besvarades i graviditetsvecka 37 till 42. Svaren analyserades i båda studierna med kvalitativ innehållsanalys. Resultat: 22 mammor i delstudie I beskrev att de hade haft en föraning om att något kunde ha hänt deras barn innan de fick besked att barnet dött intrauterint. Föraningen grundades på att mammorna hade upplevt minskade eller uteblivna fosterrörelser. Det är något som inte stämmer; formulerades som ett sammanfattande tema på mammornas föraning. Processen mot insikten om att deras barn dött beskrivs i olika steg; Inte känna kontakt med barnet; Känna oro; Känna att något är fel; Inte begripa det ofattbara; Vilja få besked; Vara säker på att barnet har dött. I delstudie II beskrev 383 (96 %) kvinnor i fullgången okomplicerad graviditet olika rörelser som klassificerades som kraftfulla rörelser. De flesta kvinnorna beskrev flera typer av rörelser, tio (4 %) kvinnor beskrev fosterrörelser som inte inkluderade någon rörelse i kategorin kraftfulla rörelser. Konklusion: Mammor som mist sitt barn före födelsen hade känt en föraning om att deras väntade barn kunde må dåligt, de hade upplevt att de tappat kontakten med barnet innan de fick besked att barnet hade dött i livmodern men normaliserade känslan. De flesta kvinnor med okomplicerad, fullgången graviditet, beskriver att barnet rör sig med kraft och tryck, få kvinnor beskriver rörelser som inte kan kategoriseras som kraftfulla. Implikationer: Blivande mammor bör uppmanas att lita på sin upplevelse av att det är något som inte stämmer och kontakta sjukvården direkt om de är bekymrade över sitt ofödda barns rörelser. Bedömning av fosterrörelser i fullgången graviditet kan inkludera: förekomst, frekvens och intensitet. Nyckelord: Innehållsanalys, fosterdöd, fosterrörelser, fullgången graviditet, upplevelser

Computerized identification of motor complications in Parkinson's disease

Objective: To investigate whether spirography-based objective measures are able to effectively characterize the severity of unwanted symptom states (Off and dyskinesia) and discriminate them from motor state of healthy elderly subjects. Background: Sixty-five patients with advanced Parkinson’s disease (PD) and 10 healthy elderly (HE) subjects performed repeated assessments of spirography, using a touch screen telemetry device in their home environments. On inclusion, the patients were either treated with levodopa-carbidopa intestinal gel or were candidates for switching to this treatment. On each test occasion, the subjects were asked trace a pre-drawn Archimedes spiral shown on the screen, using an ergonomic pen stylus. The test was repeated three times and was performed using dominant hand. A clinician used a web interface which animated the spiral drawings, allowing him to observe different kinematic features, like accelerations and spatial changes, during the drawing process and to rate different motor impairments. Initially, the motor impairments of drawing speed, irregularity and hesitation were rated on a 0 (normal) to 4 (extremely severe) scales followed by marking the momentary motor state of the patient into 2 categories that is Off and Dyskinesia. A sample of spirals drawn by HE subjects was randomly selected and used in subsequent analysis. Methods: The raw spiral data, consisting of stylus position and timestamp, were processed using time series analysis techniques like discrete wavelet transform, approximate entropy and dynamic time warping in order to extract 13 quantitative measures for representing meaningful motor impairment information. A principal component analysis (PCA) was used to reduce the dimensions of the quantitative measures into 4 principal components (PC). In order to classify the motor states into 3 categories that is Off, HE and dyskinesia, a logistic regression model was used as a classifier to map the 4 PCs to the corresponding clinically assigned motor state categories. A stratified 10-fold cross-validation (also known as rotation estimation) was applied to assess the generalization ability of the logistic regression classifier to future independent data sets. To investigate mean differences of the 4 PCs across the three categories, a one-way ANOVA test followed by Tukey multiple comparisons was used. Results: The agreements between computed and clinician ratings were very good with a weighted area under the receiver operating characteristic curve (AUC) coefficient of 0.91. The mean PC scores were different across the three motor state categories, only at different levels. The first 2 PCs were good at discriminating between the motor states whereas the PC3 was good at discriminating between HE subjects and PD patients. The mean scores of PC4 showed a trend across the three states but without significant differences. The Spearman’s rank correlations between the first 2 PCs and clinically assessed motor impairments were as follows: drawing speed (PC1, 0.34; PC2, 0.83), irregularity (PC1, 0.17; PC2, 0.17), and hesitation (PC1, 0.27; PC2, 0.77). Conclusions: These findings suggest that spirography-based objective measures are valid measures of spatial- and time-dependent deficits and can be used to distinguish drug-related motor dysfunctions between Off and dyskinesia in PD. These measures can be potentially useful during clinical evaluation of individualized drug-related complications such as over- and under-medications thus maximizing the amount of time the patients spend in the On state.

Visualization of spirography-based objective measures in Parkinson's disease

Objective: To investigate whether advanced visualizations of spirography-based objective measures are useful in differentiating drug-related motor dysfunctions between Off and dyskinesia in Parkinson’s disease (PD). Background: During the course of a 3 year longitudinal clinical study, in total 65 patients (43 males and 22 females with mean age of 65) with advanced PD and 10 healthy elderly (HE) subjects (5 males and 5 females with mean age of 61) were assessed. Both patients and HE subjects performed repeated and time-stamped assessments of their objective health indicators using a test battery implemented on a telemetry touch screen handheld computer, in their home environment settings. Among other tasks, the subjects were asked to trace a pre-drawn Archimedes spiral using the dominant hand and repeat the test three times per test occasion. Methods: A web-based framework was developed to enable a visual exploration of relevant spirography-based kinematic features by clinicians so they can in turn evaluate the motor states of the patients i.e. Off and dyskinesia. The system uses different visualization techniques such as time series plots, animation, and interaction and organizes them into different views to aid clinicians in measuring spatial and time-dependent irregularities that could be associated with the motor states. Along with the animation view, the system displays two time series plots for representing drawing speed (blue line) and displacement from ideal trajectory (orange line). The views are coordinated and linked i.e. user interactions in one of the views will be reflected in other views. For instance, when the user points in one of the pixels in the spiral view, the circle size of the underlying pixel increases and a vertical line appears in the time series views to depict the corresponding position. In addition, in order to enable clinicians to observe erratic movements more clearly and thus improve the detection of irregularities, the system displays a color-map which gives an idea of the longevity of the spirography task. Figure 2 shows single randomly selected spirals drawn by a: A) patient who experienced dyskinesias, B) HE subject, and C) patient in Off state. Results: According to a domain expert (DN), the spirals drawn in the Off and dyskinesia motor states are characterized by different spatial and time features. For instance, the spiral shown in Fig. 2A was drawn by a patient who showed symptoms of dyskinesia; the drawing speed was relatively high (cf. blue-colored time series plot and the short timestamp scale in the x axis) and the spatial displacement was high (cf. orange-colored time series plot) associated with smooth deviations as a result of uncontrollable movements. The patient also exhibited low amount of hesitation which could be reflected both in the animation of the spiral as well as time series plots. In contrast, the patient who was in the Off state exhibited different kinematic features, as shown in Fig. 2C. In the case of spirals drawn by a HE subject, there was a great precision during the drawing process as well as unchanging levels of time-dependent features over the test trial, as seen in Fig. 2B. Conclusions: Visualizing spirography-based objective measures enables identification of trends and patterns of drug-related motor dysfunctions at the patient’s individual level. Dynamic access of visualized motor tests may be useful during the evaluation of drug-related complications such as under- and over-medications, providing decision support to clinicians during evaluation of treatment effects as well as improve the quality of life of patients and their caregivers. In future, we plan to evaluate the proposed approach by assessing within- and between-clinician variability in ratings in order to determine its actual usefulness and then use these ratings as target outcomes in supervised machine learning, similarly as it was previously done in the study performed by Memedi et al. (2013).

A web-based system for visualizing upper limb motor performance of Parkinson’s disease patients

Objective To design, develop and set up a web-based system for enabling graphical visualization of upper limb motor performance (ULMP) of Parkinson’s disease (PD) patients to clinicians. Background Sixty-five patients diagnosed with advanced PD have used a test battery, implemented in a touch-screen handheld computer, in their home environment settings over the course of a 3-year clinical study. The test items consisted of objective measures of ULMP through a set of upper limb motor tests (finger to tapping and spiral drawings). For the tapping tests, patients were asked to perform alternate tapping of two buttons as fast and accurate as possible, first using the right hand and then the left hand. The test duration was 20 seconds. For the spiral drawing test, patients traced a pre-drawn Archimedes spiral using the dominant hand, and the test was repeated 3 times per test occasion. In total, the study database consisted of symptom assessments during 10079 test occasions. Methods Visualization of ULMP The web-based system is used by two neurologists for assessing the performance of PD patients during motor tests collected over the course of the said study. The system employs animations, scatter plots and time series graphs to visualize the ULMP of patients to the neurologists. The performance during spiral tests is depicted by animating the three spiral drawings, allowing the neurologists to observe real-time accelerations or hesitations and sharp changes during the actual drawing process. The tapping performance is visualized by displaying different types of graphs. Information presented included distribution of taps over the two buttons, horizontal tap distance vs. time, vertical tap distance vs. time, and tapping reaction time over the test length. Assessments Different scales are utilized by the neurologists to assess the observed impairments. For the spiral drawing performance, the neurologists rated firstly the ‘impairment’ using a 0 (no impairment) – 10 (extremely severe) scale, secondly three kinematic properties: ‘drawing speed’, ‘irregularity’ and ‘hesitation’ using a 0 (normal) – 4 (extremely severe) scale, and thirdly the probable ‘cause’ for the said impairment using 3 choices including Tremor, Bradykinesia/Rigidity and Dyskinesia. For the tapping performance, a 0 (normal) – 4 (extremely severe) scale is used for first rating four tapping properties: ‘tapping speed’, ‘accuracy’, ‘fatigue’, ‘arrhythmia’, and then the ‘global tapping severity’ (GTS). To achieve a common basis for assessment, initially one neurologist (DN) performed preliminary ratings by browsing through the database to collect and rate at least 20 samples of each GTS level and at least 33 samples of each ‘cause’ category. These preliminary ratings were then observed by the two neurologists (DN and PG) to be used as templates for rating of tests afterwards. In another track, the system randomly selected one test occasion per patient and visualized its items, that is tapping and spiral drawings, to the two neurologists. Statistical methods Inter-rater agreements were assessed using weighted Kappa coefficient. The internal consistency of properties of tapping and spiral drawing tests were assessed using Cronbach’s α test. One-way ANOVA test followed by Tukey multiple comparisons test was used to test if mean scores of properties of tapping and spiral drawing tests were different among GTS and ‘cause’ categories, respectively. Results When rating tapping graphs, inter-rater agreements (Kappa) were as follows: GTS (0.61), ‘tapping speed’ (0.89), ‘accuracy’ (0.66), ‘fatigue’ (0.57) and ‘arrhythmia’ (0.33). The poor inter-rater agreement when assessing “arrhythmia” may be as a result of observation of different things in the graphs, among the two raters. When rating animated spirals, both raters had very good agreement when assessing severity of spiral drawings, that is, ‘impairment’ (0.85) and irregularity (0.72). However, there were poor agreements between the two raters when assessing ‘cause’ (0.38) and time-information properties like ‘drawing speed’ (0.25) and ‘hesitation’ (0.21). Tapping properties, that is ‘tapping speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’ had satisfactory internal consistency with a Cronbach’s α coefficient of 0.77. In general, the trends of mean scores of tapping properties worsened with increasing levels of GTS. The mean scores of the four properties were significantly different to each other, only at different levels. In contrast from tapping properties, kinematic properties of spirals, that is ‘drawing speed’, ‘irregularity’ and ‘hesitation’ had a questionable consistency among them with a coefficient of 0.66. Bradykinetic spirals were associated with more impaired speed (mean = 83.7 % worse, P < 0.001) and hesitation (mean = 77.8% worse, P < 0.001), compared to dyskinetic spirals. Both these ‘cause’ categories had similar mean scores of ‘impairment’ and ‘irregularity’. Conclusions In contrast from current approaches used in clinical setting for the assessment of PD symptoms, this system enables clinicians to animate easily and realistically the ULMP of patients who at the same time are at their homes. Dynamic access of visualized motor tests may also be useful when observing and evaluating therapy-related complications such as under- and over-medications. In future, we foresee to utilize these manual ratings for developing and validating computer methods for automating the process of assessing ULMP of PD patients.

Self-reported symptoms and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial

Objective To investigate if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression. Background Seventy-seven patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study at 10 clinics in Sweden and Norway; 40 of them were treated with levodopa-carbidopa intestinal gel (LCIG) and 37 patients were candidates for switching from oral PD treatment to LCIG. They utilized a mobile device test battery, consisting of self-assessments of symptoms and objective measures of motor function through a set of fine motor tests (tapping and spiral drawings), in their homes. Both the LCIG-naïve and LCIG-non-naïve patients used the test battery four times per day during week-long test periods. Methods Assessments The LCIG-naïve patients used the test battery at baseline (before LCIG), month 0 (first visit; at least 3 months after intraduodenal LCIG), and thereafter quarterly for the first year and biannually for the second and third years. The LCIG-non-naïve patients used the test battery from the first visit, i.e. month 0. Out of the 77 patients, only 65 utilized the test battery; 35 were LCIG-non-naïve and 30 LCIG-naïve. In 20 of the LCIG-naïve patients, assessments with the test battery were available during oral treatment and at least one test period after having started infusion treatment. Three LCIG-naïve patients did not use the test battery at baseline but had at least one test period of assessments thereafter. Hence, n=23 in the LCIG-naïve group. In total, symptom assessments in the full sample (including both patient groups) were collected during 379 test periods and 10079 test occasions. For 369 of these test periods, clinical assessments including UPDRS and PDQ-39 were performed in afternoons at the start of the test periods. The repeated measurements of the test battery were processed and summarized into scores representing patients’ symptom severities over a test period, using statistical methods. Six conceptual dimensions were defined; four subjectively-reported: ‘walking’, ‘satisfied’, ‘dyskinesia’, and ‘off’ and two objectively-measured: ‘tapping’ and ‘spiral’. In addition, an ‘overall test score’ (OTS) was defined to represent the global health condition of the patient during a test period. Statistical methods Change in the test battery scores over time, that is at baseline and follow-up test periods, was assessed with linear mixed-effects models with patient ID as a random effect and test period as a fixed effect of interest. The within-patient variability of OTS was assessed using intra-class correlation coefficient (ICC), for the two patient groups. Correlations between clinical rating scores and test battery scores were assessed using Spearman’s rank correlations (rho). Results In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. However, there were no significant changes in mean OTS scores of LCIG-non-naïve patients, except for worse mean OTS at month 36 (p<0.01, n=16). The mean scores of all subjectively-reported dimensions improved significantly throughout the course of the study, except ‘walking’ at month 36 (p=0.41, n=4). However, there were no significant differences in mean scores of objectively-measured dimensions between baseline and other test periods, except improved ‘tapping’ at month 6 and month 36, and ‘spiral’ at month 3 (p<0.05). The LCIG-naïve patients had a higher within-subject variability in their OTS scores (ICC=0.67) compared to LCIG-non-naïve patients (ICC=0.71). The OTS correlated adequately with total UPDRS (rho=0.59) and total PDQ-39 (rho=0.59). Conclusions In this 3-year follow-up study of advanced PD patients treated with LCIG we found that it is possible to monitor PD progression over time using a home environment test battery. The significant improvements in the mean OTS scores indicate that the test battery is able to measure functional improvement with LCIG sustained over at least 24 months.

Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

Novel Statistical Methods in Quantitative Genetics : Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation

This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion : a study protocol

Background. Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. Omitting bolus insulin doses using CSII may cause reduced glycaemic control among adolescents. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrolment. Methods. This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used to evaluate perceived health and QoL: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment. Results and discussion. In this study, we will assess the effect of starting an insulin pump together with the model of Guided Self-Determination to determine whether this approach leads to retention of improved glycaemic control, QoL, responsibility distribution and reduced diabetes-related conflicts in the family. Trial registration: Current controlled trials: ISRCTN22444034

The effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants : study protocol for a randomized controlled trial

Background: Although breast milk has numerous benefits for infants' development, with greater effects in those born preterm (at < 37 gestational weeks), mothers of preterm infants have shorter breastfeeding duration than mothers of term infants. One of the explanations proposed is the difficulties in the transition from a Neonatal Intensive Care Unit (NICU) to the home environment. A person-centred proactive telephone support intervention after discharge from NICU is expected to promote mothers' sense of trust in their own capacity and thereby facilitate breastfeeding. Methods/design: A multicentre randomized controlled trial has been designed to evaluate the effectiveness and cost-effectiveness of person-centred proactive telephone support on breastfeeding outcomes for mothers of preterm infants. Participating mothers will be randomized to either an intervention group or control group. In the intervention group person-centred proactive telephone support will be provided, in which the support team phones the mother daily for up to 14 days after hospital discharge. In the control group, mothers are offered a person-centred reactive support where mothers can phone the breastfeeding support team up to day 14 after hospital discharge. The intervention group will also be offered the same reactive telephone support as the control group. A stratified block randomization will be used; group allocation will be by high or low socioeconomic status and by NICU. Recruitment will be performed continuously until 1116 mothers (I: 558 C: 558) have been included. Primary outcome: proportion of mothers exclusively breastfeeding at eight weeks after discharge. Secondary outcomes: proportion of breastfeeding (exclusive, partial, none and method of feeding), mothers satisfaction with breastfeeding, attachment, stress and quality of life in mothers/partners at eight weeks after hospital discharge and at six months postnatal age. Data will be collected by researchers blind to group allocation for the primary outcome. A qualitative evaluation of experiences of receiving/providing the intervention will also be undertaken with mothers and staff. Discussion: This paper presents the rationale, study design and protocol for a RCT providing person-centred proactive telephone support to mothers of preterm infants. Furthermore, with a health economic evaluation, the cost-effectiveness of the intervention will be assessed. Trial registration: NCT01806480

Automatic and objective assessment of alternating tapping performance in Parkinson’s disease

This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson’s disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson’s Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

A Computer Vision Framework For Finger-Tapping Evaluation In Parkinson's Disease

Objective: To define and evaluate a Computer-Vision (CV) method for scoring Paced Finger-Tapping (PFT) in Parkinson's disease (PD) using quantitative motion analysis of index-fingers and to compare the obtained scores to the UPDRS (Unified Parkinson's Disease Rating Scale) finger-taps (FT). Background: The naked-eye evaluation of PFT in clinical practice results in coarse resolution to determine PD status. Besides, sensor mechanisms for PFT evaluation may cause patients discomfort. In order to avoid cost and effort of applying wearable sensors, a CV system for non-invasive PFT evaluation is introduced. Methods: A database of 221 PFT videos from 6 PD patients was processed. The subjects were instructed to position their hands above their shoulders besides the face and tap the index-finger against the thumb consistently with speed. They were facing towards a pivoted camera during recording. The videos were rated by two clinicians between symptom levels 0-to-3 using UPDRS-FT. The CV method incorporates a motion analyzer and a face detector. The method detects the face of testee in each video-frame. The frame is split into two images from face-rectangle center. Two regions of interest are located in each image to detect index-finger motion of left and right hands respectively. The tracking of opening and closing phases of dominant hand index-finger produces a tapping time-series. This time-series is normalized by the face height. The normalization calibrates the amplitude in tapping signal which is affected by the varying distance between camera and subject (farther the camera, lesser the amplitude). A total of 15 features were classified using K-nearest neighbor (KNN) classifier to characterize the symptoms levels in UPDRS-FT. The target ratings provided by the raters were averaged. Results: A 10-fold cross validation in KNN classified 221 videos between 3 symptom levels with 75% accuracy. An area under the receiver operating characteristic curves of 82.6% supports feasibility of the obtained features to replicate clinical assessments. Conclusions: The system is able to track index-finger motion to estimate tapping symptoms in PD. It has certain advantages compared to other technologies (e.g. magnetic sensors, accelerometers etc.) for PFT evaluation to improve and automate the ratings

MAPfastR : quantitative trait loci mapping in outbred line crosses

MAPfastR is a software package developed to analyze QTL data from inbred and outbred line-crosses. The package includes a number of modules for fast and accurate QTL analyses. It has been developed in the R language for fast and comprehensive analyses of large datasets. MAPfastR is freely available at: http://www.computationalgenetics.se/?page_id=7.

Simplified follow-up after medical abortion using a low-sensitivity urinary pregnancy test and a pictorial instruction sheet in Rajasthan, India : study protocol and intervention adaptation of a randomised control trial

The World Health Organisation suggests that simplification of the medical abortion regime will contribute to an increased acceptability of medical abortion, among women as well as providers. It is expected that a home-based follow-up after a medical abortion will increase the willingness to opt for medical abortion as well as decrease the workload and service costs in the clinic. Trial design The study is a randomised, controlled, non-superiority trial . Methods Women screened to participate in the study are those with unwanted pregnancies and gestational ages equal to or less than nine weeks. Eligible women randomised to the home-based assessment group will use a low-sensitivity pregnancy test and a pictorial instruction sheet at home, while the women in the clinic follow-up group will return to the clinic for routine follow-up carried out by a doctor. The primary objective of the study is to evaluate the effectiveness of home-based assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet 10-14 days after an early medical abortion. Providers or research assistants will not be blinded during outcome assessment. To ensure feasibility of the self-assessment intervention an adaption phase took place at the selected study sites before study initiation. This was to optimise and tailor-make the intervention and the study procedures and resulted in the development of the pictorial instruction sheet for how to use the low-sensitivity pregnancy test and the danger signs after a medical abortion. Discussion In this paper, we will describe the study protocol for a randomised control trial investigating the efficacy of simplified follow-up in terms of home-based assessment, 10-14 days after a medical abortion. Moreover, a description of the adaptation phase is included for a better understanding of the implementation of the intervention in a setting where literacy is low and the road-connections are poor. Trial registration: Clinicaltrials.gov NCT01827995. Registered 04 May 2013

"Ja, denna stig är stigarnas stig" : Taoistiska influenser i Vilhelm Ekelunds verk

In this article I show how Taoist philosophy has influenced the Swedish poet, essayist and aphorist Vilhelm Ekelund. I note that the author mentions the Taoist philosophers Lao Tzu and Chuang Tzu and discusses their ideas on a couple of occasions in his later works (Atticism – Humanism, 1943; Plus salis–, 1945). Examples of such explicit influence can also be found in Ekelund’s private notebooks, posthumously published in two volumes: Hemkomst och flykt (1972) and Ur en scholaris’ verkstad (1974). I argue that Taoist philosophy implicitly influenced the Swedish author as early as the second part of the 1910’s – when he started to emphasize such principles as moderation, composure, dispassion and non-desire in his writing. I also discuss other important ideals which Ekelund shared with the Taoist philosophers, such as poverty, humility, simplicity and dishonour. Finally, I see a parallel in the anti-intellectual aspects of Taoist thinking and Ekelund’s use of the term misologi (misology), a word which often has positive connotations in his works. In Ekelund’s prose, as well as in the famous Taoist text Tao Te Ching, excessive intellectualism is frequently criticized.