Development of the German social attitude barriers and facilitators to participation-scales: an analysis according to the Rasch model.

BACKGROUND: Social attitudes experienced by people with disabilities can strongly impact upon their health and quality of life. The extent to which social attitude measurement transcends specific cultures is unknown. Thus, the aim of the study was to develop German item banks to assess social attitude barriers and facilitators to participation and compare the construct definition with that developed in the United States. METHODS: The American version of the two item banks assessing social attitudes that act as barriers and facilitators in persons with disabilities was translated into German and culturally adapted. The sample consisted of 410 in- and outpatients treated for spinal diseases at a German University Hospital. The psychometric properties of the resulting 53 items-item pool were evaluated using Rasch analysis. A special focus was placed on the investigation of unidimensionality, local independence, differential item functioning (DIF) and targeting. To evaluate convergent and divergent validity correlations with perceived social support, depression and pain interference were calculated. RESULTS: Unlike the American version, both the barriers and facilitators item banks had to be divided into two subscales assessing attitudes that individuals with disabilities experience as being directed towards them (individual perception) or attitudes that respondents experience as being directed towards people with disabilities as a social group (societal perception). Four unidimensional scales were constructed. Fit to the Rasch model required item deletion and forming testlets to account for extensive local dependence. There was no evidence of DIF with regard to gender or age. Targeting of the subscales was moderate to good. CONCLUSIONS: Results support a distinction between social attitudes at the individual and societal level, allowing a more specific assessment than is possible when this distinction is ignored.

Selective ABO immunoadsorption in hematopoietic stem cell transplantation with major ABO incompatibility.

OBJECTIVE: ABO mismatch between donor and recipient occurs in 40% of allogeneic hematopoietic stem cell transplantations (HCT). Different strategies have been described to reduce isohemagglutinins (IHA) before HCT. We describe the effect of selective ABO immunoadsorption (ABO IA) on erythrocyte transfusion rate and the development of post-transplant pure red cell aplasia (ptPRCA). METHODS: 63 patients with major ABO incompatibility were retrospectively analyzed. Nine patients with major ABO incompatibility and high-IHA titer were treated by ABO IA before HCT. We analyzed the need for transfusion and the occurrence of ptPRCA. We compared the outcome with patients treated by other methods to reduce IHA. RESULTS: In all nine patients treated by ABO IA, IHA decreased in a median four times. PtPRCA occurred in one patient. The median number of transfusions was 8 (range: 0-36) between d0 and d100. In 25 patients with high-IHA titer without treatment or treated by other methods to reduce IHA, the need for transfusions was comparable. No difference in the incidence of ptPRCA was observed. CONCLUSIONS: Selective ABO IA is a feasible, safe, and effective method to reduce IHA before HCT in major ABO incompatibility. No effect on transfusion rate or ptPRCA compared to other strategies could be observed.

Development of a short scale for assessing economic environmental aspects in patients with spinal diseases using Rasch analysis.

BACKGROUND: Economic environmental factors represent important barriers to participation and have deleterious effects on quality of life (QOL) in persons with spinal diseases (SpD). While economic factors are anchored in the International Classification of Functioning, Disability and Health, their influence on QOL and participation from patients' perspectives is an infrequent focus of research. The aim of the present research is to calibrate a culturally adapted Rasch-based questionnaire assessing economic QOL in patients with SpD. METHODS: The 11-items of the German economic-QOL-scale were answered by 325 patients with SpD on a four-point Likert-scale. Fit to the Rasch measurement model was investigated by testing for stochastic ordering of the items, unidimensionality, local independence, and differential item functioning (DIF). RESULTS: After adjusting for local dependency, fit to the Rasch model was achieved with a non-significant item-trait interaction (chi-squaredf = 20 = 34.8, p = 0.021). The person separation reliability equaled 0.88, the scale was free from age- or gender-related DIF, and unidimensionality could be verified. CONCLUSIONS: The Rasch-based German version of the economic-QOL-scale represents a suitable instrument to investigate the influences of economic factors on patients' QOL at a group and individual level. It can be easily applied in research and practice and may be administered quickly in combination with other instruments. The short test duration implies a low test burden for patients and a minimum of time expenditure by clinicians when evaluating the results.

Metacognitive monitoring of attention performance and its influencing factors.

Metacognitive monitoring is a central element of metacognitive processing exerting widespread influences on information processing. Albeit being subject to numerous empirical investigations referring to memory performance, there is little research investigating metacognitive monitoring in other cognitive domains. The present study investigated in 45 healthy students whether factors that are known to influence monitoring of memory performance, i.e., task difficulty, time of assessment, and practice, also exhibit a significant impact on monitoring of attention performance. A multivariate analysis of variance with three within-subject repeated measures factors on two dependent variables (monitoring of (a) time, and (b) errors in an attention task) was conducted. Results showed that monitoring ability significantly decreased with increasing task difficulty, was significantly better for post than for pre-assessment, and significantly increased with practice. Therefore, results suggest that the examined factors influenced monitoring of attention performance equivalent to the influence of these factors found in metamemory research.

Measuring decentering in self-reports: Psychometric properties of the experiences questionnaire in a German sample.

Decentering is described as referring to one's current mental experiences from an objective perspective. This study presents a psychometric evaluation of a German version of the Experiences Questionnaire (EQ-D), a self-report instrument designed to measure decentering. Confirmatory factor analysis on a sample of 506 university students indicates acceptable-to-good model fit (χ(2)=58.3; TLI=.92; CFI=.95; RMSEA=.067) for a second-order factor Overall Decentering comprising the two first-order factors Accepting Self-Perception and Distanced Perspective. Preliminary evidence for the validity of the EQ-D was demonstrated via negative correlations with measures of depression and depressive rumination. The present results stress the multidimensional nature of decentering and provide important suggestions for future research on how to investigate and operationalize the decentering construct.

Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry.

Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60-89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

Telomerase Is a Prognostic Marker of Poor Outcome and a Therapeutic Target in Neuroblastoma.

PURPOSE: Telomere maintenance is a hallmark of high-risk neuroblastoma; however, the contribution of telomerase and alternative lengthening of telomeres (ALT) to clinical phenotypes has remained unclear. We aimed to determine the clinical relevance of telomerase activation versus ALT as biomarkers in pretreatment neuroblastoma and to assess the potential value of telomerase as a therapeutic target. MATERIALS AND METHODS: The genomic status of TERT and MYCN was assessed in 457 pretreatment neuroblastomas by fluorescence in situ hybridization. ALT was examined in 273 of 457 tumors by detection of ALT-associated promyelocytic leukemia nuclear bodies, and TERT expression was determined by microarrays in 223 of these. Cytotoxic effects of telomerase-interacting compounds were analyzed in neuroblastoma cell lines in vitro and in vivo. RESULTS: We detected TERT rearrangements in 46 of 457 cases (10.1%), MYCN amplification in 93 of 457 cases (20.4%), and elevated TERT expression in tumors lacking TERT or MYCN alterations in 10 of 223 cases (4.5%). ALT activation was found in 49 of 273 cases (17.9%). All these alterations occurred almost mutually exclusively and were associated with unfavorable prognostic variables and adverse outcome. The presence of activated telomerase (ie, TERT rearrangements, MYCN amplification, or high TERT expression without these alterations) was associated with poorest overall survival and was an independent prognostic marker in multivariable analyses. We also found that the telomerase-interacting compound 6-thio-2'-deoxyguanosine effectively inhibited viability and proliferation of neuroblastoma cells bearing activated telomerase. Similarly, tumor growth was strongly impaired upon 6-thio-2'-deoxyguanosine treatment in telomerase-positive neuroblastoma xenografts in mice. CONCLUSION: Our data suggest telomerase activation and ALT define distinct neuroblastoma subgroups with adverse outcome and that telomerase may represent a promising therapeutic target in many high-risk neuroblastomas.

LDHA in Neuroblastoma Is Associated with Poor Outcome and Its Depletion Decreases Neuroblastoma Growth Independent of Aerobic Glycolysis.

Purpose: To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB).Experimental Design: Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated with survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity, and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model.Results: Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity, and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed.Conclusions: High expression of LDHA is independently associated with outcome of NB, and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells. Clin Cancer Res; 24(22); 5772-83. ©2018 AACR.

A mechanistic classification of clinical phenotypes in neuroblastoma.

Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance-negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.

Exploring the relationship of decentering to health related concepts and cognitive and metacognitive processes in a student sample.

BACKGROUND: Decentering, a central change strategy of Mindfulness-Based Cognitive Therapy, is a process of stepping outside of one's own mental events leading to an objective and non-judging stance towards the self. The study aimed at investigating associated mechanisms of decentering. METHOD: The present study investigated the relation of decentering, operationalized by means of the German Version of the Experiences Questionnaire, to severity of depressive symptoms, assessed by the adaptive Rasch-based depression screening, and self-focussed attention, assessed by the Questionnaire of Dysfunctional and Functional Self-Consciousness. Furthermore, the relationship between decentering and a) the ability to shift and allocate attention by means of the Stroop test, and b) metacognitive monitoring, i.e. the absolute difference between judged and real task performance, was investigated. These relationships were examined in 55 healthy students using Pearson's correlations. RESULTS: In line with our assumptions, higher decentering scores were significantly associated with lower scores on severity of depressive symptoms, with higher functional- and lower dysfunctional self-focussed attention. Contrary to our expectations, results neither indicated a relationship between decentering and attention ability, nor between decentering and metacognitive monitoring. CONCLUSIONS: The present results suggest that decentering is associated with concepts of mental health (i.e. less severity of depressive symptoms and higher functional self-focussed attention). Overall, the concept decentering seems to be mainly composed of self-focussed aspects when investigated in a healthy sample without intervention. Further investigations of associated concepts of decentering should consider aspects of self-relevance and emotional valence.

[Fearlessness about Death and Suicidal Behavior: Psychometric Properties of the German Version of the Revised Acquired Capability for Suicide Scale (ACSS-FAD)]. / Furchtlosigkeit vor dem Tod und Suizidalität: Psychometrische Eigenschaften der deutschen Version der revidierten Acquired Capability for Suicide Scale (ACSS-FAD).

OBJECTIVES: The Acquired Capability of Suicide Scale (ACSS-FAD) assesses fearlessness about death according to the Interpersonal Theory of Suicide. Psychometric properties of the German version of the ACSS-FAD are investigated. METHODS: Dimensionality and validity were analysed in a sample of N=268 undergraduate students. RESULTS: Confirmatory factor analysis replicated the unidimensionality of the measure. Correlations with suicidal ideation (r= .05) and self-reported capability for suicide (r= .14) supported the validity of the scale, while the association with depression (r= - .20) is not in line with the theory. Male participants and participants reporting past self-injurious behaviour/suicidal attempts did not show higher levels of fearlessness about death. CONCLUSION: The study demonstrates good psychometric properties of the German ACSS-FAD and largely supports the validity of the measure. However, future research needs to further investigate the validity of the ACSS-FAD (i.e. testing the utility of the instrument in predicting suicidal behaviour in patients at risk).

A mediation model of mindfulness and decentering: sequential psychological constructs or one and the same?

BACKGROUND: Mindfulness and decentering are closely related processes both assumed to promote well-being. While some researchers claim that mindfulness and decentering can be clearly differentiated others suggest to use these concepts interchangeably. The precise relation between mindfulness and decentering remains unclear and therefore the present study aims to determine the relation between mindfulness and decentering. METHODS: In a structural equation modeling framework, a mediation model was tested among a sample group of 495 university students (average age 20.8 years, 30.3% female). RESULTS: The identified model shows an acceptable fit to the data and illustrates the role of decentering as a mediator of the relationship between mindfulness and depressive symptoms by complementary mediation and indirect-only mediation. CONCLUSION: The present results cannot sustain previous research, which converted mindfulness and decentering into one single variable. Rather the data suggests to treat mindfulness and decentering as two separable concepts and to regard decentering as an important working mechanism of mindfulness.