Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA)

OBJECTIVE Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). METHODS We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle grading of MS-lesions.

Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging

Purpose. The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). Methods. We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions () were prestratified into enhancing lesions with increased permeability (EL+; ) and enhancing lesions with subtle permeability (EL−; ). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. Results. Significant differences () were found between EL+ and EL− and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL− and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL− and EL+ versus NEL), while EL− and NEL differed only in their SD during outflow. Conclusion. DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL− were similar to NEL, while EL+ differed significantly from EL− and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration.

Patterns of psychological adaptation to divorce

Despite the increase in divorces after a long relationship, this trend remains a neglected research topic. The present contribution seeks to identify patterns of psychological adaptation to divorce after a long-term marriage. Data from a questionnaire study with 308 persons aged 45–65 years, who divorced after having been married for an average of 25 years, are presented. Exploratory latent profile analysis with various well-being outcomes revealed five groups: one with average adapted, one with resilients, and three small groups with seriously affected individuals. Discriminant variables between the groups were personality, time since separation, a new relationship, and financial situation. Age, gender, and length of marriage played a marginal role; satisfaction with the former marriage and initiator status were not relevant.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

Patterns of Psychological Adaptation to Spousal Bereavement in Old Age

Background: While the negative effects of spousal bereavement on well-being are well documented in empirical research, the large individual differences in psychological adaptation are still not well understood. Objective: This contribution aims to identify patterns of psychological adaptation to spousal loss in old age and to shed light on the role of intra- and interpersonal resources and contextual factors as discriminant variables among these patterns. Methods: The data stem from a cross-sectional questionnaire study of 402 widowed individuals (228 women, 174 men) aged between 60 and 89 years (mean age 74.41 years), who lost their partner within the last 5 years, and 618 married individuals, who served as controls (312 women, 306 men; mean age 73.82 years). Results: The exploratory latent profile analysis of the well-being outcomes of depressive symptoms, hopelessness, loneliness, life satisfaction and subjective health revealed three different groups in the widowed sample: ‘resilients' (54% of the sample), ‘copers' (39%) and ‘vulnerables' (7%). The most important variables for group allocation were intrapersonal resources - psychological resilience and the Big Five personality traits - but also the quality of the former relationship and how the loss was experienced. Conclusion: Successful adaptation to spousal loss is primarily associated with high scores in psychological resilience and extraversion and low scores in neuroticism. Our results shed light on the variability in psychological adaptation and underline the important role of intrapersonal resources in facing spousal loss in old age.

Trajectories of psychological adaptation to marital breakup after a long-term marriage

While the negative effects of divorce on well-being are well documented in research literature, the large individual differences in psychological adaptation over time are still not well understood. This is especially the case for marital breakup after long-term marriage, which is still a neglected research topic. Against this background, the aim of the present contribution is to shed light on the various trajectories of psychological adaptation to marital breakup after a long-term relationship. Data stem from a longitudinal survey study, which is part of the Swiss National Centre of Competence in Research ‘LIVES – Overcoming vulnerability: life course perspectives’ (funded by the Swiss National Science Foundation). Our analyses are based on results of an exploratory latent profile analysis performed at the first assessment in 2012 among 308 divorced participants aged 45 – 65 years, who divorced after an average of 25 years of marriage (Perrig-Chiello, Hutchison, & Morselli, 2014). Five different groups regarding psychological adaptation to marital breakup (i.e. life satisfaction, depression, hopelessness, subjective health, and mourning) were identified. They were composed of two larger groups of individuals that adapted quite well or very well (“average copers”, n=151 and “resilients”, n=90) and of three smaller groups with major difficulties to adjust to the new situation (“vulnerables”, n= 18; “malcontens”, n= 37 and “resigned ones”, n=12). Clusters differed statistically significant regarding personality variables, time since separation, current relationship status, and financial situation. In the present contribution, we want to investigate the course of adaptation of the five classes two years later by using latent transition analysis. Furthermore, we aim to examine which variables in terms of personality, relationship status, variables of the context of the separation and socio-demographic variables are crucial for change or stability in levels of adaptation in the different classes. The evaluation of the trajectories of adaptation to this critical life event and the identification of variables that enhance the adaptation over time is essential for developing more differentiated measures in counselling as well as intervention techniques in clinical and social services.

Probing the effect of minor groove interactions on the catalytic efficiency of DNAzymes 8–17 and 10–23

DNAzymes (Dz) 8–17 and 10–23 are two widely studied and well-characterized RNA-cleaving DNA catalysts. In an effort to further improve the understanding of the fragile interactions and dynamics of the enzymatic mechanism, this study examines the catalytic efficiency of minimally modified DNAzymes. Five single mutants of Dz8–17 and Dz10–23 were prepared by replacing the adenine residues in the corresponding catalytic cores with 3-deazaadenine units. Kinetic assays were used to assess the effect on the catalytic activity and thereby identify the importance of hydrogen bonding that arises from the N3 atoms. The results suggest that modifications at A15 and A15.0 of Dz8–17 have a significant influence and show a reduction in catalytic activity. Modification at each location in Dz10–23 results in a decrease of the observed rate constants, with A12 appearing to be the most affected with a reduction of ∼80% of kobs and ∼25% of the maximal cleavage rate compared to the wild-type DNAzyme. On the other hand, modification of A12 in Dz8–17 showed an ∼130% increase in kobs, thus unraveling a new potential site for the introduction of chemical modifications. A pH-profile analysis showed that the chemical cleavage step is rate-determining, regardless of the presence and/or location of the mutation. These findings point towards the importance of the N3-nitrogens of certain adenine nucleotides located within the catalytic cores of the DNAzymes for efficient catalytic activity and further suggest that they might directly partake in maintaining the appropriate tertiary structure. Therefore, it appears that minor groove interactions constitute an important feature of DNAzymes as well as ribozymes.

Career adaptability profiles and their relationship to adaptivity and adapting

Research on career adaptability predominantly uses variable-centered approaches that focus on the average effects in terms of the predictors and outcomes within a given sample. Extending this research, the present paper used a person-centered approach to determine whether subgroups with distinct adaptability profiles in terms of concern, control, curiosity and confidence can be identified. We also explored the relationship between the various adaptability profiles and adapting (career planning, career decision-making difficulties, career exploration, and occupational self-efficacy beliefs) and adaptivity (core self-evaluations and proactivity). Using latent profile analysis, we found distinct adaptability profiles among 350 German university students. Students with different profiles differed significantly in their levels of adapting. This finding was confirmed in a second study of 1226 students selected from the same population. In both samples, the adaptability profiles differed mainly in terms of their adaptability levels but not their shape. Moreover, in both samples, the students whose profiles indicated generally higher adaptability showed more adapting compared with the students whose profiles indicated generally lower adaptability. Study 2 also showed that students with higher-adaptability profiles showed significantly higher adaptivity. The results suggest that level effects dominate adaptability profiles, implying the existence of a general adaptability factor within university students that is meaningfully related to adapting and adaptivity.

Latent profiles of work motivation in adolescents in relation to work expectations, goal engagement, and changes in work experiences

Motivation plays a key role in successful entry into working life. Based on a cross-sectional and a one-year longitudinal study, we used a person-centered approach to explore work-related motivation (i.e., autonomous goals, positive affect, and occupational self-efficacy) among 577 students in 8th grade (Study 1) and 949 adolescents in vocational training (Study 2). Based on latent profile analysis, in both studies we identified four groups that were characterized by different levels of overall motivation and one group characterized by low positive affect and mean levels in autonomous goals and self-efficacy. Profiles characterized by high levels of motivation showed the highest levels of positive work expectations and goal engagement and the lowest levels of negative work expectations in Study 1 and the highest levels of person-job fit, work engagement, and job satisfaction in Study 2. Moreover, latent difference score analysis showed that motivational profiles predicted changes in person-job fit and work engagement across one year but not in job satisfaction. The results imply that career counselors should be aware of characteristic motivational patterns of clients that may require specific counseling approaches.

Chance Events and Career Decidedness: Latent Profiles in Relation to Work Motivation

Research has shown that chance events affect careers but has not established the nature of their effects. Moreover, the relationship between chance and career decidedness is not well understood. The present study used a person-centered approach with latent profile analysis to examine 312 Swiss adolescents in their first year of vocational training. We identified five qualitatively differing profiles according to levels of perceived chance events and career decidedness: balanced scorers, undecided with mean chance, undecided with high chance, decided with chance, and decided without chance. The groups differed significantly in work motivation (i.e., occupational self-efficacy beliefs, perceived person-job fit, and work engagement). Decided adolescents reported more favorable work motivation regardless of their level of perceived chance events. The results imply that promoting decidedness remains a valuable goal in career counseling despite the occurrence of unpredicted events.

Pemphigus herpetiformis: analysis of the autoantibody profile during the disease course with changes in the clinical phenotype

Pemphigus herpetiformis (PH) is a rare dapsone-responsive variant of pemphigus, characterized by annular and vesiculopustular cutaneous lesions. Most PH serum samples contain autoantibodies against desmoglein (Dsg)1, but not Dsg3, and the presence of the latter is almost invariably associated with mucosal involvement, as predicted based on the 'Dsg compensation theory'. We describe a patient with features characteristic of PH with histologically eosinophilic spongiosis who repeatedly tested positive for anti-Dsg3 but not anti-Dsg1 autoantibodies by ELISA. To investigate whether the peculiar clinical phenotype was due to a distinct immunological profile, the patient's serum was tested by ELISA and immunoblotting using recombinant forms of Dsg3. Serum samples were found to have low and high reactivity against the EC1 and the EC4 domains of Dsg3, respectively, whereas the autoantibodies belonged predominantly to the IgG1 and IgG4 subclasses. The overall immunological profile was typical of pemphigus vulgaris. The patient finally developed isolated oral erosions 22 months after initial presentation, without significant changes in the autoantibody profile and of the targeted antigenic sites. Our patient presented features characteristic of PH. Although circulating anti-Dsg3 antibodies were present, the patient had only cutaneous involvement for a long period. Our findings indicate that the proposed Dsg compensation theory cannot always explain the clinical phenotype, changes in which may occur without apparent modification of the autoantibody profile and antibody specificity. Hence, additional factors, such as Fcgamma-dependent neutrophil activation, may critically affect the clinical presentation of pemphigus.

Feasibility of texture analysis for the assessment of biochemical changes in meniscal tissue on T1 maps calculated from delayed gadolinium-enhanced magnetic resonance imaging of cartilage data: comparison with conventional relaxation time measurements

To (1) establish the feasibility of texture analysis for the in vivo assessment of biochemical changes in meniscal tissue on delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and (2) compare textural with conventional T1 relaxation time measurements calculated from dGEMRIC data ("T1(Gd) relaxation times").

In search of the "why" behind campaign professionalisation: explaining the degree and profile of campaign professionalisation by an empirical analysis of 23 Swiss cantonal election campaigns

Die Organisation und die strategische Kommunikation von Wahlkämpfen haben sich in den letzten Jahrzehnten in den meisten westeuropäischen Staaten gewandelt, so auch in der Schweiz. Die Kommunikationswissenschaft hat dafür den Begriff der „Professionalisierung“ geprägt und Eigenschaften zusammengetragen, die zu einem „professionalisierten“ Wahlkampf gehören – wie z.B. die Beauftragung von externen Expertinnen und Experten oder die direkte Ansprache von Wählerinnen und Wählern („narrowcasting“). Welche Hintergründe diese Professionalisierung aber hat und wie das Phänomen nicht nur praktisch zu beschreiben, sondern auch theoretisch zu begründen ist, wurde bisher kaum diskutiert. Hier setzt die vorliegende Dissertation an. Basierend auf einer Analyse von 23 Wahlkämpfen aus den Kantonen Aargau, Appenzell Ausserrhoden, Bern, Neuchâtel und Zürich mithilfe der Methode Fuzzy Set Qualitative Comparative Analysis (fsQCA) kommt sie zum Schluss, dass die Professionalisierung der Wahlkämpfe vor dem theoretischen Hintergrund des soziologischen Neo-Institutionalismus als Anpassung von Wahlkämpfen an sich verändernde Bedingungen, Erwartungen und Anforderungen in den wichtigsten Anspruchsgruppen oder „Umwelten“ für den Wahlkampf (Wählerinnen und Wähler, Mitglieder, Medien, andere Parteien) definiert werden kann. Daraus folgt, dass es nicht nur „die“ Professionalisierung gibt, sondern dass jeder Wahlkampf an jene Umwelten angepasst wird, wo diese Anpassung den Wahlkampfverantwortlichen am dringlichsten erscheint. Daher sollte Professionalisierung mit vier einzelnen Messinstrumenten bzw. Professionalisierungsindices – einem pro Umwelt – gemessen werden. Misst man Professionalisierung wie bisher üblich nur mit einem einzigen Messinstrument, gibt der resultierende Wert nur ein ungenaues Bild vom Grad der Professionalisierung des Wahlkampfs wieder und verschleiert, als Anpassung an welche Umwelt die Professionalisierung geschieht. Hat man ermittelt, wie professionalisiert ein Wahlkampf im Hinblick auf jede der vier relevantesten Umwelten ist, können dann auch zuverlässiger die Gründe analysiert werden, die zur jeweiligen Professionalisierung geführt haben. Die empirische Analyse der kantonalen Wahlkämpfe bestätigte, dass hinter der Professionalisierung in Bezug auf jede der vier Umwelten auch tatsächlich unterschiedliche Gründe stecken. Wahlkämpfe werden in Bezug auf die Ansprache der Wähler angepasst („professionalisiert“), wenn sie in urbanen Kontexten stattfinden. Den Wahlkampf im Hinblick auf die Mitglieder zu professionalisieren ist besonders wichtig, wenn die Konkurrenz zwischen den Parteien gross ist oder wenn eine Ansprache der Gesamtwählerschaft für eine Partei wenig gewinnbringend erscheint. Die Professionalisierung des Wahlkampfes in Bezug auf die Medien erfolgt dann, wenn er eine grosse, regional stark verteilte oder aber eine urbane Wählerschaft ansprechen muss. Für die Professionalisierung der Wahlkämpfe gegenüber anderen Parteien kann kein aussagekräftiger Schluss gezogen werden, da nur wenige der untersuchten Kantonalparteien ihre Wahlkämpfe überhaupt im Hinblick auf andere Parteien professionalisierten, indem sie die gegnerischen Wahlkämpfe beobachteten und den eigenen wenn nötig entsprechend anpassten.

Radiomic Texture Analysis Mapping Predicts Areas of True Functional MRI Activity.

Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.