From adsorption to crystallization of proteins: Evidence for interface-assisted nucleation.

Protein crystallization is among the key processes in biomolecular research, but the underlying mechanisms are still elusive. Here, we address the role of inevitable interfaces for the nucleation process. Quartz crystal microbalance with dissipation monitoring (QCM-D) with simultaneously optical microscopy, confocal microscopy, and grazing-incidence small angle X-rays scattering (GISAXS) were employed to investigate the temporal behavior from the initial stage of protein adsorption to crystallization. Here we studied the crystallization of the Human Serum Albumin (HSA), the most abundant blood protein, in the presence of a charged surface and a trivalent salt. We found evidence for interface-assisted nucleation of crystals. The kinetic stages involved are initial adsorption followed by enhanced adsorption after longer times, subsequent nucleation, and finally crystal growth. The results highlight the importance of interfaces for protein phase behavior and in particular for nucleation.

Elevated accuracy in recognition of subliminal happy facial expressions in patients with panic disorder after psychotherapy.

Background: Individuals with anxiety disorders (ADs) often display hypervigilance to threat information, although this response may be less pronounced following psychotherapy. This study aims to investigate the unconscious recognition performance of facial expressions in patients with panic disorder (PD) post-treatment, shedding light on alterations in their emotional processing biases. Methods: Patients with PD (n=34) after (exposure-based) cognitive behavior therapy and healthy controls (n=43) performed a subliminal affective recognition task. Emotional facial expressions (fearful, happy, or mirrored) were displayed for 33 ms and backwardly masked by a neutral face. Participants completed a forced choice task to discriminate the briefly presented facial stimulus and an uncovered condition where only the neutral mask was shown. We conducted a secondary analysis to compare groups based on their four possible response types under the four stimulus conditions and examined the correlation of the false alarm rate for fear responses to non-fearful (happy, mirrored, and uncovered) stimuli with clinical anxiety symptoms. Results: The patient group showed a unique selection pattern in response to happy expressions, with significantly more correct "happy" responses compared to controls. Additionally, lower severity of anxiety symptoms after psychotherapy was associated with a decreased false fear response rate with non-threat presentations. Conclusion: These data suggest that patients with PD exhibited a "happy-face recognition advantage" after psychotherapy. Less symptoms after treatment were related to a reduced fear bias. Thus, a differential facial emotion detection task could be a suitable tool to monitor response patterns and biases in individuals with ADs in the context of psychotherapy.

Depression, Contraception, and Ambivalence Concerning Fertility.

Individuals suffering from depression exhibit a higher rate of unintended pregnancies, which are associated with negative outcomes for both parents and children. Often, unintended pregnancies result from contraceptive mistakes. Here, we examine the relationship between depression and the consistency of contraceptive behavior, testing ambivalence as a possible mediator. The analyses were based on cross-sectional data from the second and third waves of the German Relationship and Family Panel Pairfam. A German-speaking sample without children (N = 190; 117 female, 73 male), who reported not attempting to conceive or become pregnant during the last 12 months, was analyzed in comparison with a propensity score matched sample. Ambivalence was operationalized as the difference between the ideal and realistic number of children in wave 2. Data from wave 3 were used to assess contraceptive behavior. Depressed mood in wave 2 and consistency of contraceptive behavior in wave 3 were negatively correlated. After including ambivalence in wave 2 as a mediator in the model, the direct path between depressed mood and consistency of contraceptive behavior remained significant, with no significant mediation found. For men only, we observed a significant negative association of ambivalence with the consistency of contraceptive behavior in the last 3 months. No significant relationship was found between depressed mood and ambivalence. We conclude that future research aiming to better understand the consistency of contraceptive behavior should incorporate measures of ambivalence.

Neural network analysis of neutron and X-ray reflectivity data incorporating prior knowledge.

Due to the ambiguity related to the lack of phase information, determining the physical parameters of multilayer thin films from measured neutron and X-ray reflectivity curves is, on a fundamental level, an underdetermined inverse problem. This ambiguity poses limitations on standard neural networks, constraining the range and number of considered parameters in previous machine learning solutions. To overcome this challenge, a novel training procedure has been designed which incorporates dynamic prior boundaries for each physical parameter as additional inputs to the neural network. In this manner, the neural network can be trained simultaneously on all well-posed subintervals of a larger parameter space in which the inverse problem is underdetermined. During inference, users can flexibly input their own prior knowledge about the physical system to constrain the neural network prediction to distinct target subintervals in the parameter space. The effectiveness of the method is demonstrated in various scenarios, including multilayer structures with a box model parameterization and a physics-inspired special parameterization of the scattering length density profile for a multilayer structure. In contrast to previous methods, this approach scales favourably when increasing the complexity of the inverse problem, working properly even for a five-layer multilayer model and a periodic multilayer model with up to 17 open parameters.

Closing the loop: autonomous experiments enabled by machine-learning-based online data analysis in synchrotron beamline environments.

Recently, there has been significant interest in applying machine-learning (ML) techniques to the automated analysis of X-ray scattering experiments, due to the increasing speed and size at which datasets are generated. ML-based analysis presents an important opportunity to establish a closed-loop feedback system, enabling monitoring and real-time decision-making based on online data analysis. In this study, the incorporation of a combined one-dimensional convolutional neural network (CNN) and multilayer perceptron that is trained to extract physical thin-film parameters (thickness, density, roughness) and capable of taking into account prior knowledge is described. ML-based online analysis results are processed in a closed-loop workflow for X-ray reflectometry (XRR), using the growth of organic thin films as an example. Our focus lies on the beamline integration of ML-based online data analysis and closed-loop feedback. Our data demonstrate the accuracy and robustness of ML methods for analyzing XRR curves and Bragg reflections and its autonomous control over a vacuum deposition setup.

Respiratory Interoception and Pathological Illness Anxiety: Disentangling Bias.

OBJECTIVE: Biased interoception decoupled from physiology might be relevant in the etiology of pathological illness anxiety (PIA). Empirical evidence for interoceptive deviations in illness anxiety is scarce but potentially informative to optimize treatments. We hypothesized that persons with PIA differ fundamentally in the classification of bodily sensations from those without PIA. METHODS: In a respiratory categorization task, participants breathed into a pulmonary training device. Inspiration effort was varied by eight resistive loads. The lower/higher four loads were introduced as belonging to arbitrary categories "A"/"B," respectively. Participants memorized respiratory sensations in a first experimental block and were asked to label the resistances in a second block. We calculated the sensitivity of resistance classification according to category and response bias in terms of categorical misclassification. Data of 39 participants with PIA and 35 controls were compared with regard to sensitivity and response bias by group, resistive load, and their interaction in a multiple regression. RESULTS: With similar sensitivity, patients more often labeled loads above the categorical border erroneously as belonging to category A, thus underestimating their resistance ( ß = -0.06, p = .001; η2 = 0.02). CONCLUSIONS: Individuals with PIA showed a systematic "wait and see" approach. Altered respiroception in PIA might stem from biased perception during training phase, the recognition phase, biased memory, or a combination of these. Its exact characteristics remain unknown, and future research must address the challenge of developing reliable and valid paradigms accounting for the variability of interoceptive biases. REGISTRATION: This work was preregistered on OSF ( https://osf.io/9shcw ).

Vagally-mediated heart rate variability and depression in children and adolescents - A meta-analytic update.

BACKGROUND: Depression is one of the most common mental disorders and a leading cause of disability worldwide. In adults, depression is characterized by decreased vagal activity (vagally-mediated heart rate variability; vmHRV), while vmHRV is inversely correlated with depressive symptoms. In children/adolescents, a 2016 synthesis (4 studies, 259 individuals) found similarly decreased vmHRV in clinical depression, but no significant association between depressive symptoms and vmHRV (6 studies, 2625 individuals). Given the small number of studies previously considered for synthesis and the rapidly growing evidence base in this area, a meta-analytic update was warranted. METHOD: A previous review was updated by a systematic literature search to identify studies that (a) compared vmHRV in clinically depressed children/adolescents with non-depressed controls and (b) reported associations between vmHRV and depression severity. RESULTS: The search update identified 5 additional studies for group comparison (k = 9 studies in total, n = 608 individuals in total) and 15 additional studies for correlational meta-analysis (k = 21 studies in total, n = 4224 individuals in total). Evidence was found for lower resting-state vmHRV in clinically depressed children/adolescents compared to healthy controls (SMD = -0.593, 95 % CI [-1.1760; -0.0101], I2 = 90.92 %) but not for a significant association between vmHRV and depressive symptoms (r = -0.053, 95 % CI [-0.118; 0.012], I2 = 65.77 %). Meta-regression revealed a significant association between depressive symptoms and vmHRV as a function of sex. LIMITATIONS: The samples considered are highly heterogeneous. Data on the longitudinal association between vmHRV and depression are currently lacking. CONCLUSION: The present findings support the use of vmHRV as a biomarker for clinical depression in children/adolescents.

Interoception and Premonitory Urges in Children and Adolescents With Tic Disorders.

Background: Compared to healthy controls (HCs), adult Tic Disorder (TD) patients exhibit a lower interoceptive accuracy (IAcc) in heartbeat perception. Since the lower IAcc is not evident in children, the age at which tics develop, but in adults only (Pile et al., 2018, https://doi.org/10.1007/s10803-018-3608-8), lower IAcc may reflect a pathological mechanism relevant with regard to tics, premonitory urges (PUs) or the resulting impairment. Although tics are a motor phenomenon, up to date, IAcc has been assessed only with a heartbeat-counting task. This study aims at comparing cardiac and muscular IAcc using two different paradigms and investigates how IAcc is related to premonitory urges in youth. Method: Interoceptive measures (heartbeat-counting task, muscle tension paradigm) of 28 youth with TD were compared to 23 control participants and related to self-rated premonitory urges and tic symptoms. Results: TD patients did not differ from HCs in any IAcc measures. However, within TD patients, IAcc explained additional variance in PUs when controlling for tic severity. Muscular IAcc in TD patients is related to urges and tics, but the direction of this association is unclear. IAcc is lower in TD patients than in HCs, indicating imprecise sensory input which is more easily overcome by priors within the predictive coding framework. Conclusions: Muscle tension feedback tasks could extend interoceptive trainings aimed at improving IAcc to improve accuracy of urge perception (more precise sensory input) to foster the ability to control tics via HRT. Longitudinal studies could provide further insights in causal relationships between IAcc, premonitory urges and tics.

Machine learning for scattering data: strategies, perspectives and applications to surface scattering.

Machine learning (ML) has received enormous attention in science and beyond. Discussed here are the status, opportunities, challenges and limitations of ML as applied to X-ray and neutron scattering techniques, with an emphasis on surface scattering. Typical strategies are outlined, as well as possible pitfalls. Applications to reflectometry and grazing-incidence scattering are critically discussed. Comment is also given on the availability of training and test data for ML applications, such as neural networks, and a large reflectivity data set is provided as reference data for the community.

Screening and assessment for cancer patients' psychosocial support needs: Development and validation of the psychosocial risk questionnaire.

PURPOSE: Psychosocial factors can negatively influence the ability to cope with cancer-specific therapy. To identify high-risk patients and to offer need-based care concerning social issues, valid, reliable, and economic instruments are needed. This study aims to develop a tool assessing psychosocial support needs and analyze its psychometric properties. METHODS: Based on an extensive literature search, items for the scale of psychosocial risks (PSR) were developed to assess the need for psychosocial support. Overall, N = 343 participants with cancer took part in the study to investigate the psychometric properties of the PSR. The factor structure was examined by using a principal component analysis. Correlations with criteria-related constructs determined the convergent validity. Cut-off scores for the PSR were selected based on receiver-operating characteristics and the calculation of Youden indices. RESULTS: The principal component analysis suggests a two-factor structure: (1) Psychosocial support need to ensure medical and social care services, and (2) Support need for coping with problems. The predicted correlations confirm the convergent validity. Both scales showed excellent internal consistency (Ensure medical and social care services: Omega = 0.94) and (Coping with problems: Omega = 0.90). CONCLUSION: The newly developed scale can provide helpful information regarding psychosocial support needs to professionals (psychotherapists, psychologists, physicians, and social workers) in the psycho-oncological field. Based on this information, specific and personalized interventions for cancer patients can be offered. The PSR is appropriate for assessing specific psychosocial needs to support cancer patients.

Symptom Perception in Pathological Illness Anxiety: Tactile Sensitivity and Bias.

OBJECTIVE: Symptom perception in pathological illness anxiety (PIA) might be biased so that somatic signals are overreported. In the somatic signal detection task (SSDT), performance in detecting weak tactile stimuli gives information on overreporting or underreporting of stimuli. This task has not yet been applied in PIA. METHODS: Participants with PIA (n = 44) and healthy controls (n = 40) underwent two versions of the SSDT in randomized order. In the original version, tactile and auxiliary light-emitting diode (LED) stimuli were each presented in half of the trials. In the adapted version, illness or neutral words were presented alongside tactile stimuli. Participants also conducted a heartbeat mental tracking task. RESULTS: We found significantly higher sensitivity and a more liberal response bias in LED versus no-LED trials, but no significant differences between word types. An interaction effect showed a more pronounced increase of sensitivity from no LED to LED trials in participants with PIA when compared with the adapted SSDT and control group (F(1,76) = 5.34, p = .024, η2 = 0.066). Heartbeat perception scores did not differ between groups (BF01 of 3.63). CONCLUSIONS: The increase in sensitivity from no LED to LED trials in participants with PIA suggests stronger multisensory integration. Low sensitivity in the adapted SSDT indicates that attentional resources were exhausted by processing word stimuli. Word effects on response bias might have carried over to the original SSDT when the word version was presented first, compromising group effects regarding bias. TRIAL REGISTRATION: The study was preregistered on OSF (https://osf.io/sna5v/).

[Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan]. / Metakognitionen und interozeptive Sensibilität bei der Wahrnehmung des Vorgefühls bei Tic-Störungen über die Lebensspanne.

Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan Abstract. Objective: Depending on contextual factors, the prevalence of premonitory urges (PU) in patients with tic disorders (TD) increases with age and varies both intra- and interindividually. In youth, PUs correlate with metacognitions. In both youth and adults, interoceptive sensibility is altered compared to healthy controls. We examined the relationship between PUs, tics, metacognitions, and interoceptive sensibility across the lifespan regarding tic severity. Method: In an online survey, 53 participants reported their PUs on the Premonitory Urge for Tics Scale (PUTS) and tic severity on the Symptom Checklist for Tic Disorders (SBB-TIC). We assessed interoceptive sensibility via the Body Perception Questionnaire (BPQ-A) and metacognitions regarding tics with the Belief About Tics Scale (BATS). Results: Adults scored higher on the PUTS than youth. In youth, interoceptive sensibility increased with age; interoceptive sensibility correlated with PUTS. Metacognitions and interoceptive sensibility explained a significant amount of variance in premonitory urges, even after controlling for tic severity and age. Conclusions: The presumed cause of age-dependent development of PUs in youth lies in their neurophysiological maturing processes. However, negative metacognitions and interoceptive abilities also play an important role in the development and maintenance of PU and might be of therapeutic use in the treatment of TD.

Interoceptive accuracy and bias in somatic symptom disorder, illness anxiety disorder, and functional syndromes: A systematic review and meta-analysis.

Somatic symptom disorder, illness anxiety disorder, and functional syndromes are characterized by burdensome preoccupation with somatic symptoms. Etiological models propose either increased interoceptive accuracy through hypervigilance to the body, or decreased and biased interoception through top-down predictions about sensory events. This systematic review and meta-analysis summarizes findings of 68 studies examining interoceptive accuracy and 8 studies examining response biases in clinical or non-clinical groups. Analyses yielded a medium population effect size for decreased interoceptive accuracy in functional syndromes, but no observable effect in somatic symptom disorder and illness anxiety disorder. The overall effect size was highly heterogeneous. Regarding response bias, there was a small significant effect in somatic symptom disorder and illness anxiety disorder. Our findings strengthen the notion of top-down factors that result in biased rather than accurate perception of body signals in somatic symptom disorder and illness anxiety disorder.

Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits.

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

Linking Depression with Negative Alcohol-Related Consequences: A Structural Equation Model Among a Clinically Depressed Population.

Background and Objectives: Previous research suggests that rumination acts as a mediating mechanism in the association between depression and drinking motives, particularly drinking to cope, as well as negative alcohol-related consequences. In this study, we tested the connections between depressive symptoms, rumination, drinking motives, alcohol consumption, and alcohol-related problems in a clinically depressed population (N = 209). Methods: Structural equation modeling was used to test the models. Specifications were based on the results of a previously evaluated model in a sample of college students. Results: The complex model showed a significant positive association between depressive symptoms and rumination. Drinking motives (enhancement and coping) were linked to more negative alcohol-related consequences. In a simplified model, pronounced depressive symptoms were associated with both increased ruminative thinking and more negative alcohol-related problems. Rumination was connected with stronger drinking motives (combined in one general factor), which were again associated with alcohol consumption and alcohol-related problems. Limitations: The use of self-report measures to determine diagnostic validity. Conclusions: In a clinically depressed sample, depressive symptoms were linked to increased negative alcohol-related consequences. This association was partially explained by rumination and drinking motives. However, rumination was less relevant than previous studies suggested.

Psychometric evaluation of the Positive Mental Health (PMH) scale using item response theory.

BACKGROUND: The investigation of patient-reported outcomes and psycho-oncological interventions mainly focuses on psychological distress or psychopathology. However, the recognition of the equal importance of positive mental health (PMH) has increased lately. The PMH-scale is a brief questionnaire allowing to assess well-being in individuals in the general population and in patients. Previous studies evaluated the psychometric properties of the PMH-scale using classical test theory (CTT). This study is the first to investigate the PMH-scale in patients with cancer using item analysis according to the Rasch model. METHODS: In total, N = 357 cancer patients participated in the study. A Rasch analysis of the PMH-scale was conducted including testing of unidimensionality, local independence, homogeneity and differential item functioning (DIF) with regard to age, gender, type of cancer, the presence of metastases, psycho-oncological support, and duration of disease. Additionally, the ordering of the item thresholds as well as the targeting of the scale were investigated. RESULTS: After excluding one misfitting item and accounting for local dependence by forming superitems, a satisfactory overall fit to the Rasch model was established (χ2 = 30.34, p = 0.21). The new PMH-8 scale proved to be unidimensional, and homogeneity of the scale could be inferred. All items showed ordered thresholds, there was no further item misfit. DIF was found for age, but as the impact of DIF was not substantial, no adjustment related to the age-DIF had to be made. The Person Separation Index (PSI = 0.89) was excellent, indicating excellent discriminatory power between different levels of positive mental health. Overall, the targeting of the PMH-8 was good for the majority of the present sample. However, at both ends of the scale item thresholds are missing as indicated by a slight floor effect (1.4%) and a considerable ceiling effect (9.8%). CONCLUSIONS: Overall, the results of the analysis according to the Rasch model support the use of the revised PMH-scale in a psycho-oncological context.

Embodied feelings-A meta-analysis on the relation of emotion intensity perception and interoceptive accuracy.

Emotion theories emphasize the relevance of (predicted) bodily changes for the construction of one's own emotions and an extensive overlap of brain regions involved during emotion intensity perception and somatosensory processing. The ability to accurately perceive bodily changes and its impact on the perception of emotion intensity has been studied for at least 40 years. The results of previous studies were summarized in a meta-analysis to examine how closely interoceptive accuracy and emotion intensity are related. After a systematic literature search, 4036 studies were screened for eligibility. Only studies assessing adults from general population samples were considered. Samples recruited to examine mental disorders or neurological conditions were excluded. Thirty studies with a quantifiable measure for the relation of interoceptive accuracy and emotion intensity perception were included in the meta-analysis. Interoceptive accuracy was significantly related with emotion intensity perception, when emotions were experimentally induced (k= 22, r= 0.15). However, the relationship was only found when IAPS images (k= 9, r= 0.33) or facial expressions (k= 3, r= 0.24) were used for emotion induction. No significant relation was found in studies without emotion induction (k= 19, r = -0.007). There was considerable bias, varying dependent on bias assessment method, study protocol and examined risk of bias dimension. We discuss the impact of differences in study protocols, review the operationalization of interoceptive accuracy critically and derive directions for future research.

Neural network analysis of neutron and X-ray reflectivity data: automated analysis using mlreflect, experimental errors and feature engineering.

The Python package mlreflect is demonstrated, which implements an optimized pipeline for the automated analysis of reflectometry data using machine learning. The package combines several training and data treatment techniques discussed in previous publications. The predictions made by the neural network are accurate and robust enough to serve as good starting parameters for an optional subsequent least-mean-squares (LMS) fit of the data. For a large data set of 242 reflectivity curves of various thin films on silicon substrates, the pipeline reliably finds an LMS minimum very close to a fit produced by a human researcher with the application of physical knowledge and carefully chosen boundary conditions. The differences between simulated and experimental data and their implications for the training and performance of neural networks are discussed. The experimental test set is used to determine the optimal noise level during training. The extremely fast prediction times of the neural network are leveraged to compensate for systematic errors by sampling slight variations in the data.

Integrated, cross-sectoral psycho-oncology (isPO): a new form of care for newly diagnosed cancer patients in Germany.

BACKGROUND: The annual incidence of new cancer cases has been increasing worldwide for many years, and is likely to continue to rise. In Germany, the number of new cancer cases is expected to increase by 20% until 2030. Half of all cancer patients experience significant emotional and psychosocial distress along the continuum of their disease, treatment, and aftercare, and also as long-term survivors. Consequently, in many countries, psycho-oncological programs have been developed to address this added burden at both the individual and population level. These programs promote the active engagement of patients in their cancer therapy, aftercare and survivorship planning and aim to improve the patients' quality of life. In Germany, the "new form of care isPO" ("nFC-isPO"; integrated, cross-sectoral psycho-oncology/integrierte, sektorenübergreifende Psycho-Onkologie) is currently being developed, implemented and evaluated. This approach strives to accomplish the goals devised in the National Cancer Plan by providing psycho-oncological care to all cancer patients according to their individual healthcare needs. The term "new form of care" is defined by the Innovation Fund (IF) of Germany's Federal Joint Committee as "a structured and legally binding cooperation between different professional groups and/or institutions in medical and non-medical care". The nFC-isPO is part of the isPO project funded by the IF. It is implemented in four local cancer centres and is currently undergoing a continuous quality improvement process. As part of the isPO project the nFC-isPO is being evaluated by an independent institution: the Institute for Medical Sociology, Health Services Research, and Rehabilitation Science (IMVR), University of Cologne, Germany. The four-year isPO project was selected by the IF to be eligible for funding because it meets the requirements of the federal government's National Cancer Plan (NCP), in particular, the "further development of the oncological care structures and quality assurance" in the psycho-oncological domain. An independent evaluation is required by the IF to verify if the new form of care leads to an improvement in cross-sectoral care and to explore its potential for permanent integration into the German health care system. METHODS: The nFC-isPO consists of six components: a concept of care (C1), care pathways (C2), a psycho-oncological care network (C3), a care process organization plan (C4), an IT-supported documentation and assistance system (C5) and a quality management system (C6). The two components concept of care (C1) and care pathways (C2) represent the isPO clinical care program, according to which the individual cancer patients are offered psycho-oncological services within a period of 12 months after program enrolment following the diagnosis of cancer. The remaining components (C3-C6) represent the formal-administrative aspects of the nFC-isPO that are intended to meet the legally binding requirements of patient care in the German health care system. With the aim of systematic development of the nFC-isPO while at the same time enabling the external evaluators to examine its quality, effectiveness and efficiency under conditions of routine care, the project partners took into consideration approaches from translational psycho-oncology, practice-based health care research and program theory. In order to develop a structured, population-based isPO care program, reference was made to a specific program theory, to the stepped-care approach, and also to evidence-based guideline recommendations. RESULTS: The basic version, nFC-isPO, was created over the first year after the start of the isPO project in October 2017, and has since been subject to a continuous quality improvement process. In 2019, the nFC-isPO was implemented at four local psycho-oncological care networks in the federal state North Rhine-Westphalia, in Germany. The legal basis of the implementation is a contract for "special care" with the German statutory health insurance funds according to state law (§ 140a SCB V; Social Code Book V for the statutory health insurance funds). Besides the accompanying external evaluation by the IMVR, the nFC-isPO is subjected to quarterly internal and cross-network quality assurance and improvement measures (internal evaluation) in order to ensure continuous quality improvement process. These quality management measures are developed and tested in the isPO project and are to be retained in order to ensure the sustainability of the quality of nFC-isPO for later dissemination into the German health care system. DISCUSSION: Demands on quality, effectiveness and cost-effectiveness of in the German health care system are increasing, whereas financial resources are declining, especially for psychosocial services. At the same time, knowledge about evidence-based screening, assessment and intervention in cancer patients and about the provision of psychosocial oncological services is growing continuously. Due to the legal framework of the statutory health insurance in Germany, it has taken years to put sound psycho-oncological findings from research into practice. Ensuring the adequate and sustainable financing of a needs-oriented, psycho-oncological care approach for all newly diagnosed cancer patients, as required by the NCP, may still require many additional years. The aim of the isPO project is to develop a new form of psycho-oncological care for the individual and the population suffering from cancer, and to provide those responsible for German health policy with a sound basis for decision-making on the timely dissemination of psycho-oncological services in the German health care system. TRIAL REGISTRATION: The study was pre-registered at the German Clinical Trials Register (https://www.drks.de/DRKS00015326) under the following trial registration number: DRKS00015326 ; Date of registration: October 30, 2018.

The Influence of Alcohol on Rumination and Metacognitions in Major Depressive Disorder.

Background and Objectives: Comorbidity between major depressive disorder (MDD) and alcohol use disorder (AUD) is highly prevalent but reasons for this association are unclear. Rumination may activate metacognitive beliefs that contribute to the development and maintenance of rumination and depression. Negative metacognitions can further lead to other dysfunctional coping strategies (i.e., consumption of alcohol). We examined whether alcohol reduces (state) metacognitions, rumination and other disorder-specific processes in a group of individuals suffering from MDD. Method: In an experiment with three randomized conditions we investigated whether the consumption of alcohol, placebo or no alcohol (orange juice) affects (meta-)cognitions, depressive symptoms and / or psychophysiological variables while participants ruminate. Results: Voluntary rumination increased self-reported sadness, tension and rumination, tensed facial muscles and increased heart rate, but did not affect (state) metacognitions and heart rate variability. The consumption of alcohol did not influence rumination, metacognitions, depressive or psychophysiological measures. Limitations: We recruited a depressed population but excluded pathological alcohol use due to ethical considerations. Conclusions: We found no evidence that alcohol consumption affects rumination, metacognitions and other disorder-specific processes in MDD. However, rumination had a negative effect on various depression-specific processes, although it did not activate (negative state) metacognitions.