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The alignment of shapes has been a crucial step in statistical shape analysis, for example, in calculating mean shape, detecting locational differences between two shape populations, and classification. Procrustes alignment is the most commonly used method and state of the art. In this work, we uncover that alignment might seriously affect the statistical analysis. For example, alignment can induce false shape differences and lead to misleading results and interpretations. We propose a novel hierarchical shape parameterization based on local coordinate systems. The local parameterized shapes are translation and rotation invariant. Thus, the inherent alignment problems from the commonly used global coordinate system for shape representation can be avoided using this parameterization. The new parameterization is also superior for shape deformation and simulation. The method's power is demonstrated on the hypothesis testing of simulated data as well as the left hippocampi of patients with Parkinson's disease and controls., Comment: 25 pages, 20 figures

Statistical analysis of the skeletal structure of slabular objects like groups of hippocampi is valuable for medical researchers as it can be useful for diagnoses and understanding diseases. This work proposes a novel object representation based on model fitting and analysis of the locally parameterized discrete swept skeletal representation of such entities where the model fitting procedure is based on boundary division and surface flattening. The goodness of the model fitting is demonstrated according to the skeletal symmetry, the volume of the implied boundary, and skeletal perturbation. The power of the method is demonstrated by visual inspection and statistical analysis of a synthetic and an actual data set in comparison with an available skeletal representation.

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Skeletal models that are structurally medial provide effective object representations. This is because they include not only locations but also boundary directions and object widths. We present a skeletal object representation that we call “quasimedial” because geometric properties associated with Blum's [1] medial axis are relaxed to allow the skeleton to have a pre-specified amount of branching and thus to support statistical analysis. We call this form of object representation the s-rep. We explain how such models can be automatically determined from object boundary data in a way that a) avoids boundary noise, b) implies a boundary that closely fits the input boundary, and c) well recognizes shape correspondences across cases. We also explain how to use Riemannian geometry to estimate probability distributions from a sample of s-reps and to find ways to classify s-reps between two categories as trained from s-reps in each class. Finally, we describe various evidence that shows the relative strengths of s-reps vs. other object representations; we also discuss shortcomings of s-reps.

Birth asphyxia, defined as 5-minute Apgar score7 in apneic newborns, is a major cause of newborn mortality. Heart rate (HR) response to ventilation is considered an important indicator of effective resuscitation.To describe the relationship between initial HR in apneic newborns, HR responses to ventilation and 24-h survival or death.In a Tanzanian hospital, data on all newborns ≥34 weeks gestational age resuscitated between June 2013-January 2017 were recorded using self-inflating bags containing sensors measuring ventilation parameters and expired CO757 newborns of gestational age 38 ± 2 weeks and birthweight 3131 ± 594 g were included; 706 survived and 51 died. Fetal HR abnormalities (abnormal, undetectable or not assessed) increased the risk of death almost 2-fold (RR = 1.77; CI: 1.07, 2.96, p = 0.027). For every beat/min increase in first detected HR after birth the risk of death was reduced by 2% (RR = 0.98; CI: 0.97, 0.99, p 0.001). A decrease in HR to100 beats/minute when ventilation was paused increased the risk of death almost 2-fold (RR = 1.76; CI: 0.96, 3.20, p = 0.066). An initial rapid increase in HR to100 beats/min in response to treatment reduced the risk of dying by 75% (RR = 0.25; CI: 0.14, 0.44, p 0.001). A 1% increase in expired COThe risk of death in apneic newborns can be predicted by the fetal HR (absent or abnormal), initial newborn HR (bradycardia), and the HR response to ventilation. These findings stress the importance of reliable fetal HR monitoring during labor and providing effective ventilation following birth to enhance survival.

Background During delivery room resuscitation of depressed newborns, provision of appropriate tidal volume (TV) with establishment of functional residual capacity (FRC) is essential for circulatory recovery. Effective positive pressure ventilation (PPV) is associated with a rapid increase in heart rate (HR). The relationship between delivery of TV and HR responses remains unclear. Objectives The study objectives were to determine (1) the relationship between a given TV during initial PPV and HR responses of depressed newborns, and (2) the optimal delivered TV associated with a rapid increase in HR. Methods In a Tanzanian rural hospital, ventilation and ECG signals were recorded during neonatal resuscitation and stored in Neonatal Resuscitation Monitors. Resuscitators without positive end-expiratory pressure were used for PPV. No oxygen was used. Perinatal events were observed and recorded by research assistants. Results 215 newborns of gestational age 37.3 ± 1.9 weeks and birth weight 3115 ± 579 g were included. There was a non-linear relationship between delivered TV and HR increase. TV of 9.3 ml/kg produced the largest increase in HR during PPV. Frequent interruptions of PPV sequences to provide stimulation/suctioning occurred in all cases and were associated with further HR increases, especially for newborns with initial HR Conclusions There was a consistent positive relationship between HR increase and delivered TV. The unanticipated finding of a further increase in HR with PPV pauses to provide stimulation/suctioning suggests that most newborns were in primary rather than secondary apnea.

The objective of this study is to examine the frequency, development, concomitants, and risk factors of falls in a population-based incident Parkinson’s disease (PD) cohort. One hundred eighty-one drug-naive patients with incident PD and 173 normal controls recruited from the Norwegian ParkWest study were prospectively monitored over 7 years. Information on falls was obtained biannually from patients, and at baseline and after 1, 3, 5, and 7 years of follow-up in control subjects. Generalized estimating equation models for correlated data were applied to investigate concomitant features of falls and risk factors for incident falls during 7 years of follow-up in PD. Overall, 64.1% of patients reported falling during the study period. The 7-year cumulative incidence of falls in non-falling patients at baseline (n = 153) was 57.5%, with a relative risk to controls of at least 3.1 (95% confidence interval 1.5–6.3; p

Objective:To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis.Methods:One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures.Results:The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness.Conclusions:The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD.

This article considers the analysis of complex monitored health data, where often one or several signals are reflecting the current health status that can be represented by a finite number of states, in addition to a set of covariates. In particular, we consider a novel application of a non-parametric state intensity regression method in order to study time-dependent effects of covariates on the state transition intensities. The method can handle baseline, time varying as well as dynamic covariates. Because of the non-parametric nature, the method can handle different data types and challenges under minimal assumptions. If the signal that is reflecting the current health status is of continuous nature, we propose the application of a weighted median and a hysteresis filter as data pre-processing steps in order to facilitate robust analysis. In intensity regression, covariates can be aggregated by a suitable functional form over a time history window. We propose to study the estimated cumulative regression parameters for different choices of the time history window in order to investigate short- and long-term effects of the given covariates. The proposed framework is discussed and applied to resuscitation data of newborns collected in Tanzania.

Classifying medically imaged objects, e.g., into diseased and normal classes, has been one of the important goals in medical imaging. We propose a novel classification scheme that uses a skeletal representation to provide rich non-Euclidean geometric object properties. Our statistical method combines distance weighted discrimination (DWD) with a carefully chosen Euclideanization which takes full advantage of the geometry of the manifold on which these non-Euclidean geometric object properties (GOPs) live. Our method is evaluated via the task of classifying 3D hippocampi between schizophrenics and healthy controls. We address three central questions. 1) Does adding shape features increase discriminative power over the more standard classification based only on global volume? 2) If so, does our skeletal representation provide greater discriminative power than a conventional boundary point distribution model (PDM)? 3) Especially, is Euclideanization of non-Euclidean shape properties important in achieving high discriminative power? Measuring the capability of a method in terms of area under the receiver operator characteristic (ROC) curve, we show that our proposed method achieves strongly better classification than both the classification method based on global volume alone and the s-rep-based classification method without proper Euclideanization of non-Euclidean GOPs. We show classification using Euclideanized s-reps is also superior to classification using PDMs, whether the PDMs are first Euclideanized or not. We also show improved performance with Euclideanized boundary PDMs over non-linear boundary PDMs. This demonstrates the benefit that proper Euclideanization of non-Euclidean GOPs brings not only to s-rep-based classification but also to PDM-based classification.

A test of modality of rotationally symmetric distributions on hyperspheres is proposed. The test is based on a modified multivariate kurtosis defined for directional data on S d . We first reveal a relationship between the multivariate kurtosis and the types of modality for Euclidean data. In particular, the kurtosis of a rotationally symmetric distribution with decreasing sectional density is greater than the kurtosis of the uniform distribution, while the kurtosis of that with increasing sectional density is less. For directional data, we show an asymptotic normality of the modified spherical kurtosis, based on which a large-sample test is proposed. The proposed test of modality is applied to the problem of preventing overfitting in non-geodesic dimension reduction of directional data. The proposed test is superior than existing options in terms of computation times, accuracy and preventing overfitting. This is highlighted by a simulation study and two real data examples.

This paper presents a novel method to test mean differences of geometric object properties (GOPs). The method is designed for data whose representations include both Euclidean and non-Euclidean elements. It is based on advanced statistical analysis methods such as backward means on spheres. We develop a suitable permutation test to find global and simultaneously individual morphological differences between two populations based on the GOPs. To demonstrate the sensitivity of the method, an analysis exploring differences between hippocampi of first-episode schizophrenics and controls is presented. Each hippocampus is represented by a discrete skeletal representation (s-rep). We investigate important model properties using the statistics of populations. These properties are highlighted by the s-rep model that allows accurate capture of the object interior and boundary while, by design, being suitable for statistical analysis of populations of objects. By supporting non-Euclidean GOPs such as direction vectors, the proposed hypothesis test is novel in the study of morphological shape differences. Suitable difference measures are proposed for each GOP. Both global and simultaneous GOP analyses showed statistically significant differences between the first-episode schizophrenics and controls.

Objective: To examine the frequency, development, and risk factors of excessive daytime sleepiness (EDS) in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. Methods: One hundred fifty-three drug-naive patients with early PD derived from a population-based incident cohort and 169 control participants were assessed for EDS and reevaluated after 1, 3, and 5 years on medication. EDS was diagnosed according to the Epworth Sleepiness Scale. Cutoff score above 10 was applied. Generalized estimating equation models for correlated data were used to examine associated and risk factors for EDS. Results: Patients reported EDS more often than control participants at the time of diagnosis and during follow-up. The frequency of EDS in PD increased from 11.8% at baseline to 23.4% after 5 years. Associated factors were male sex, the use of dopamine agonists, and higher Montgomery-Asberg Depression Rating Scale and Unified Parkinson9s Disease Rating Scale–activities of daily living scores. Main risk factor for developing EDS was an increased Epworth Sleepiness Scale score at baseline. Conclusion: EDS is more frequent in PD even before treatment initiation compared with control participants and increases in occurrence with disease progression. The main risk factor for developing EDS with time is an early predisposition for sleepiness. In addition, the use of dopamine agonists was associated with the development of EDS. These findings necessitate caution in patients with PD and early increased sleep propensity and when using dopamine agonists.

This article discusses a novel framework to analyze rotational deformations of real three-dimensional objects. The rotational deformations such as twisting or bending have been observed as the major variation in some medical applications, where the features of the deformed three-dimensional objects are directional data. We propose modeling and estimation of the global deformations in terms of generalized rotations of directions. The proposed method can be cast as a generalized small circle fitting on the unit sphere. We also discuss the estimation of descriptors for more complex deformations composed of two simple deformations. The proposed method can be used for a number of different three-dimensional object models. Two analyses of three-dimensional object data are presented in detail: one using skeletal representations in medical image analysis and the other from biomechanical gait analysis of the knee joint. Supplementary materials for this article are available online.

The increasing demand for more agility and flexibility in innovation development projects also sets new requirements for market and user experience (UX) researchers. In this chapter, we discuss several challenges and issues inherent in the liaison between agile innovation development and the claim for user centricity. We outline one specific approach to agile market and UX research in the project field User Driven Innovation at the Telekom Innovation Laboratories. By introducing two different types of user researchers, the UX consultant and the UX tester, who are deployed in different stages of an innovation project and who operate in different working modes, we offer a hands-on solution based on experience for the issues described. Two short case studies exemplify more agile and flexible methods that are tailored for fast but yet profound market and UX research. We argue that Rapid Ethnography and the Customer Advisory Board are ideal for the new requirements mentioned. In conclusion, we list critical success criteria for user integration in agile innovation development projects.

Background: It is often difficult to differentiate early melanomas from benign melanocytic nevi even by expert dermatologists, and the task is even more challenging for primary care physicians untrained in dermatology and dermoscopy. A computer system can provide an objective and quantitative evaluation of skin lesions, reducing subjectivity in the diagnosis. Objective: Our objective is to make a low-cost computer aided diagnostic tool applicable in primary care based on a consumer grade camera with attached dermatoscope, and compare its performance to that of experienced dermatologists. Methods and materials: We propose several new image-derived features computed from automatically segmented dermoscopic pictures. These are related to the asymmetry, color, border, geometry, and texture of skin lesions. The diagnostic accuracy of the system is compared with that of three dermatologists. Results: With a data set of 206 skin lesions, 169 benign and 37 melanomas, the classifier was able to provide competitive sensitivity (86%) and specificity (52%) scores compared with the sensitivity (85%) and specificity (48%) of the most accurate dermatologist using only dermoscopic images. Conclusion: We show that simple statistical classifiers can be trained to provide a recommendation on whether a pigmented skin lesion requires biopsy to exclude skin cancer with a performance that is comparable to and exceeds that of experienced dermatologists.

Background: GPs’ individual decisions to refer and the various ways of working when they refer are important determinants of secondary care use. The objective of this study was to explore and describe potential characteristics of GPs’ referral practice by investigating their opinions about referring and their self-reported experiences of what they do when they refer. Methods: Observational cross-sectional study using data from 128 Norwegian GPs who filled in a questionnaire with statements on how they regarded the referral process, and who were invited to collect data when they actually referred to hospital during one month. Only elective referrals were recorded. The 57 participants (44,5 %) recorded data from 691 referrals. The variables were included in a principal component analysis. A multiple linear regression analysis was conducted to identify typologies with GP’s age, gender, specialty in family medicine and location as independent variables. Results: Eight principal components describe the different ways GPs think and work when they refer. Two typologies summarize these components: confidence characterizing specialists in family medicine, mainly female, who reported a more patient-centred practice making priority decisions when they refer, who confer easily with hospital consultants and who complete the referrals during the consultation; uncertainty characterizing young, mainly male non-specialists in family medicine, experiencing patients’ pressure to be referred, heavy workload, having reluctance to cooperate with the patient and reporting sparse contact with hospital colleagues. Conclusions: Training specialists in family medicine in patient-centred method, easy conference with hospital consultant and cooperation with patients while making the referral may foster both self-reflections on own competences and increased levels of confidence. publishedVersion

Background: There is limited evidence regarding the heart rate (HR) during the first minutes of life. Nonetheless, resuscitative actions within the first minute are partly guided by different HR levels. The advent of an electrocardiographic (ECG) HR sensor with early HR detection has provided the opportunity to study changes immediately following delivery. Objective: The objectives were to determine immediately following delivery: (i) the time to achievement of reliable ECG signals using dry electrodes, (ii) changes in HR, and (iii) the influence of the onset of breathing and cord clamping on the HR. Methods: Healthy term neonates were randomly included between July and October 2013. The HR was recorded by the ECG sensor, placed over the abdomen immediately after birth. Results: Fifty-five newborns were included. The median time from birth to placement of the HR sensor was 3 s (quartiles: 2 and 5), and the median time to the start of breathing was 6 s (quartiles: 2 and 15). The HR was around 120 beats/min (bpm) in the first seconds of life. As determined via breakpoint analysis, the HR increased by 1 beat in the first 40 s to 149 ± 33 bpm, followed by a moderate increase until 130 s and stabilization thereafter. After the onset of breathing, the HR decreased for 10 s and then increased. Minimal HR changes were observed after cord clamping. Conclusion: A dry-electrode ECG sensor detected reliable ECG signals almost immediately after birth. The normal HR increased significantly in spontaneously breathing infants during the first minute, influenced by the onset of breathing. Delayed cord clamping had a minimal impact on the HR, likely reflecting an earlier onset of breathing.

INTRODUCTION A protocol including judicious use of oxytocin augmentation was investigated to determine whether it would change how oxytocin was used and eventually influence labor and fetal outcomes. MATERIAL AND METHODS The population of this cohort study comprised 20 227 delivering women with singleton pregnancies ≥37 weeks, cephalic presentation, spontaneous or induced onset of labor, without previous cesarean section. Women delivering from 2009 to 2013 at Stavanger University Hospital, Norway, were included. Data were collected prospectively. Before implementing the protocol in 2010, oxytocin augmentation was used if progression of labor was perceived as slow. After implementation, oxytocin could only be started when the cervical dilation had crossed the 4-h action line in the partograph. RESULTS The overall use of oxytocin augmentation was significantly reduced from 34.9% to 23.1% (p < 0.01). The overall frequency of emergency cesarean sections decreased from 6.9% to 5.3% (p < 0.05) and the frequency of emergency cesarean sections performed due to fetal distress was reduced from 3.2% to 2.0% (p = 0.01). The rate of women with duration of labor over 12 h increased from 4.4% to 8.5% (p < 0.01) and more women experienced severe estimated postpartum hemorrhage (2.6% vs. 3.7%; p = 0.01). The frequency of children with pH

Background: Delineation of the target volume is a time-consuming task in radiotherapy treatment planning, yet essential for a successful treatment of cancers such as prostate cancer. To facilitate the delineation procedure, the paper proposes an intuitive approach for 3D modeling of the prostate by slice-wise best fitting ellipses. Methods: The proposed estimate is initialized by the definition of a few control points in a new patient. The method is not restricted to particular image modalities but assumes a smooth shape with elliptic cross sections of the object. A training data set of 23 patients was used to calculate a prior shape model. The mean shape model was evaluated based on the manual contour of 10 test patients. The patient records of training and test data are based on axial T1-weighted 3D fast-field echo (FFE) sequences. The manual contours were considered as the reference model. Volume overlap (Vo), accuracy (Ac) (both ratio, range 0-1, optimal value 1) and Hausdorff distance (HD) (mm, optimal value 0) were calculated as evaluation parameters. Results: The median and median absolute deviation (MAD) between manual delineation and deformed mean best fitting ellipses (MBFE) was Vo (0.9 ± 0.02), Ac (0.81 ± 0.03) and HD (4.05 ± 1.3)mm and between manual delineation and best fitting ellipses (BFE) was Vo (0.96 ± 0.01), Ac (0.92 ± 0.01) and HD (1.6 ± 0.27)mm. Additional results show a moderate improvement of the MBFE results after Monte Carlo Markov Chain (MCMC) method. Conclusions: The results emphasize the potential of the proposed method of modeling the prostate by best fitting ellipses. It shows the robustness and reproducibility of the model. A small sample test on 8 patients suggest possible time saving using the model.

Good running shoe tests combine biomechanical and subjective evaluation procedures. Biomechanical tests identify the influence of the footwear on shock attenuation, subtalar joint pronation and pla...

2-chloro-(4-Cl), 3,3-dichloro- (4-Cl 2 ), and 2,3,3-trichlorodiazopropene (4-Cl 3 ) can easily be prepared in up to 70% yield by thermal fragmentation (Bamford-Stevens reaction), at 60 o C in tetrahydrofuran, of the corresponding chloroacrolein tosylhydrazone sodium salts 3-Cl n . Tetrahydrofuran solutions of (chlorovinyl)diazomethanes 4-Cl n thus obtained are used for cyclopropanation reactions of a large variety of alkenes

Background GPs’ individual decisions to refer and the various ways of working when they refer are important determinants of secondary care use. The objective of this study was to explore and describe potential characteristics of GPs’ referral practice by investigating their opinions about referring and their self-reported experiences of what they do when they refer. Methods Observational cross-sectional study using data from 128 Norwegian GPs who filled in a questionnaire with statements on how they regarded the referral process, and who were invited to collect data when they actually referred to hospital during one month. Only elective referrals were recorded. The 57 participants (44,5 %) recorded data from 691 referrals. The variables were included in a principal component analysis. A multiple linear regression analysis was conducted to identify typologies with GP’s age, gender, specialty in family medicine and location as independent variables. Results Eight principal components describe the different ways GPs think and work when they refer. Two typologies summarize these components: confidence characterizing specialists in family medicine, mainly female, who reported a more patient-centred practice making priority decisions when they refer, who confer easily with hospital consultants and who complete the referrals during the consultation; uncertainty characterizing young, mainly male non-specialists in family medicine, experiencing patients’ pressure to be referred, heavy workload, having reluctance to cooperate with the patient and reporting sparse contact with hospital colleagues. Conclusions Training specialists in family medicine in patient-centred method, easy conference with hospital consultant and cooperation with patients while making the referral may foster both self-reflections on own competences and increased levels of confidence. Electronic supplementary material The online version of this article (doi:10.1186/s12875-016-0495-y) contains supplementary material, which is available to authorized users.