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Das Cognitive Behavioral Analysis System of Psychotherapy (CBASP) wurde von James McCullough speziell für die Behandlung der chronischen Depression entwick-elt. Patientinnen und Patienten mit einer chronischen Depression haben häufig bei der Bewältigung von interpersonellen Situationen Schwierigkeiten. Beim Vorgehen nach dem CBASP-Ansatz lassen sich Therapeut:innen persönlich und ganz individuell auf ihre Patient:innen ein, um mit ihnen zusammen interpersonelle Fertigkeiten zu trainieren. Das evidenzbasierte Buch vermittelt praxisnah und anhand zahlreicher Beispiele das therapeutische Vorgehen. Die 2., vollständig überarbeitete Auflage liefert zunächst eine Beschreibung des Störungsbildes und fasst den aktuellen Forschungsstand zu CBASP zusammen. Anschließend vermittelt das Buch Schritt für Schritt alle Techniken des CBASP und die therapeutische Haltung im Umgang mit chronisch depressiven Patient:innen. Der Ablauf der Therapie, beginnend mit der Vermittlung des Krankheitsmodells, der Fallkonzeptualisierung und dem Training interpersoneller Fertigkeiten bis hin zur Rückfallprohylaxe, wird praxisorientiert erläutert. Vorgestellt werden zudem neue Entwicklungen des Ansatzes, wie z. B. der Umgang mit komorbiden psychischen Störungen und die Anwendung des CBASP in der Gruppe oder im stationären Setting. Anhand zahlreicher Fallbeispiele wird außerdem der Umgang mit schwierigen Therapiesituationen aufgezeigt. Die zahlreichen im Buch enthaltenen Arbeitsmaterialien für die Diagnostik, zur Psychoedukation und für die Arbeit mit den Patient:innen können nach erfolgter Registrierung von der Hogrefe Website heruntergeladen werden.

Background: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for Sustainable Development Goals, including Universal Health Coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. Methods: In a cross-sectional study we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1,482 adult participants at three primary health-care centers in north-western and central areas of Madagascar. Results: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, respectively. Higher prevalence was observed among males and main contributors to the family income. Not working as a farmer and higher age were found to be protective factors for infection. Conclusions: Our findings provide evidence that adults are a high-risk group for schistosomiasis. The general focus on children and the exclusion of adults from control strategies for schistosomiasis in high endemic countries may hamper the achievement of both the schistosomiasis elimination goal and UHC. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

Leasing provides a fundamental source of firm funding, especially for small and medium-sized enterprises. A crucial difference from loans and bonds is that the lessor retains ownership rights of the leased asset during the lease term. This facilitates the asset utilization and work-out process and leads to higher liquidation proceeds. Hence, previous findings on the loan and bond loss given default (LGD) are not transferable to the leasing industry. Our analysis is based on a very granular data set covering a great variety of information on the lessee, the leased asset, as well as contractual and transactional characteristics. We examine novel LGD determinants such as an external credit rating, the lessee’s limited liability, and the number of leased assets and collaterals. Moreover, new results on previously explored factors question earlier findings, for example, on the lease contract type. Most importantly, as proposed by Miller and Töws (J Bank Finance 91:189–201, 2018), we analyze two different LGDs, one based on the asset utilization proceeds, the other on repayments. Our results clearly indicate the crucial importance of this separation when analyzing the drivers of the leasing LGD in detail because several determinants affect these LGDs in different ways. Our study assists both lessors and regulators in assessing the effective risk of lease contracts and enables lessors to enhance their risk management and work-out processes.

Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 μM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.

This survey provides an extensive overview of the state-of-the-art model-based online semi-supervised and unsupervised anomaly detection algorithms used on multivariate time series. It also outlines the most popular benchmark datasets used in literature, as well as a novel taxonomy where a distinction between online and offline, and training and inference is made. To achieve this, almost 50 peer-reviewed publications are surveyed and categorised into different model families to paint a clear picture of the anomaly detection landscape for the reader. Then, where possible, a comparison of the anomaly detection performance of the surveyed approaches is provided and the key research gaps are highlighted. It is concluded that few approaches propose any enhancements that involve the user feedback. In addition to that, transformer-based models seem to have found little application in anomaly detection so far, though this is most likely due to the novelty of the model type, not necessarily due to the lack of potential. Moreover, there is no standard benchmark procedure to assess anomaly detection performance. A variety of different datasets and evaluation metrics used for evaluation are used hence it is difficult to draw conclusions from comparisons between papers. Lastly, the rarity of approaches trained and inferred in an online manner is also pointed out, possibly explained by the lower performance compared to offline trained approaches.

BackgroundInternet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.MethodsWe did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.FindingsWe identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.InterpretationThe individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.FundingJapan Society for the Promotion of Science.

Introduction: Evidence on effects of Internet-based interventions to treat subthreshold depression (sD) and prevent the onset of major depression (MDD) is inconsistent. Objective: We conducted an individual participant data meta-analysis to determine differences between intervention and control groups (IG, CG) in depressive symptom severity (DSS), treatment response, close to symptom-free status, symptom deterioration and MDD onset as well as moderators of intervention outcomes. Methods: Randomized controlled trials were identified through systematic searches via PubMed, PsycINFO, Embase and Cochrane Library. Multilevel regression analyses were used to examine efficacy and moderators. Results: Seven trials (2,186 participants) were included. The IG was superior in DSS at all measurement points (posttreatment: 6–12 weeks; Hedges’ g = 0.39 [95% CI: 0.25–0.53]; follow-up 1: 3–6 months; g = 0.30 [95% CI: 0.15–0.45]; follow-up 2: 12 months, g = 0.27 [95% CI: 0.07–0.47], compared with the CG. Significantly more participants in the IG than in the CG reached response and close to symptom-free status at all measurement points. A significant difference in symptom deterioration between the groups was found at the posttreatment assessment and follow-up 2. Incidence rates for MDD onset within 12 months were lower in the IG (19%) than in the CG (26%). Higher initial DSS and older age were identified as moderators of intervention effect on DSS. Conclusions: Our findings provide evidence for Internet-based interventions to be a suitable low-threshold intervention to treat individuals with sD and to reduce the incidence of MDD. This might be particularly true for older people with a substantial symptom burden.

Although abnormal resting state connectivity within several brain networks has been repeatedly reported in depression, little is known about connectivity in patients with early onset chronic depression. We compared resting state connectivity in a homogenous sample of 32 unmedicated patients with early onset chronic depression and 40 healthy control participants in a seed-to-voxel-analysis. According to previous meta-analyses on resting state connectivity in depression, 12 regions implicated in default mode, limbic, frontoparietal and ventral attention networks were chosen as seeds. We also investigated associations between connectivity values and severity of depression. Patients with chronic depression exhibited stronger connectivity between precuneus and right pre-supplementary motor area than healthy control participants, possibly reflecting aberrant information processing and emotion regulation deficits in depression. Higher depression severity scores (Hamilton Rating Scale for Depression) were strongly and selectively associated with weaker connectivity between the precuneus and the subcallosal anterior cingulate. Our findings correspond to results obtained in studies including both episodic and chronic depression. This suggests that there may be no strong differences between subtypes of depression regarding the seeds analyzed here. To further clarify this issue, future studies should directly compare patients with different courses of depression.

Introduction: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. Methods: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. Results: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). Discussion: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.

Background Childhood maltreatment (CM) predicted poorer outcomes in acute depression treatment with CBT, IPT and Supportive Psychotherapy (SP). The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) fared well in patients with chronic depression and CM during acute treatment, yet there is a considerable lack of empirical evidence for long-term outcomes. Methods We analyzed one and two-year follow-up data of 268 patients randomized to 24 sessions (20 weeks) of acute and 8 sessions (28 weeks) of extended treatment with CBASP or SP. Primary outcome was the number of well weeks as measured by the Longitudinal Interval Follow-Up Evaluation Interview (LIFE). Secondary outcomes included self- and clinician-rated depression symptoms. We investigated this moderating effect for any CM and for specific subtypes of CM. Results Intent-to-treat analyses revealed that the presence of CM did not significantly moderate long-term effects of CBASP compared to SP. The analysis of trauma subtypes revealed that patients with childhood emotional abuse had statistically significant worse outcomes than patients without (main effect, p=.015) and that the advantage of CBASP over SP was larger in patients with childhood emotional abuse than in patients without (interaction effect, p=.045) after 1 year. No significant effects were found for other trauma subtypes. Limitations The measurement of CM was limited to retrospective self-assessment. Conclusions The presence of CM did not significantly moderate long-term treatment effects of CBASP compared to SP. When trauma subtypes were considered, CBASP was more effective than SP after one year in patients who retrospectively reported emotional abuse.

Zusammenfassung. Hintergrund: In der Behandlung der persistierenden depressiven Störung (PDD) werden Psychotherapien mit interpersonellem Schwerpunkt empfohlen. Ein Beispiel dafür ist das Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was davon ausgeht, dass Menschen mit PDD zu einem präoperatorischen Denkstil neigen. Das Ziel dieser Arbeit ist herauszufinden, ob dieser Denkstil auch bei Menschen mit einer Panikstörung oder einem chronischen Rückenschmerz beobachtet werden kann. Methodik: In einer Studie wurden Patient_innen mit einer Panikstörung ( n = 20) verglichen mit Patient_innen mit einer depressiven Störung ( n = 20) und gesunden Kontrollen ( n = 20). In einer weiteren Studie wurden Patient_innen mit chronischem Rückenschmerz ( n = 30) verglichen mit gesunden Kontrollen ( n = 32). Alle Proband_innen wurden mit dem Lübecker Fragebogen Präoperatorisches Denken (LFPD) befragt. Daneben wurden die Angehörigen der Proband_innen gebeten, das Interaktionsverhalten der Probandin bzw. des Probanden mit dem Interpersonal Message Inventory (IMI) zu beurteilen. Ergebnis: Die erste Studie kam zu dem Ergebnis, dass sich nur die depressiven Patient_innen im LFPD signifikant von den gesunden Kontrollen unterschieden ( p < .001). In der Subskala „feindselig“ des IMI unterschieden sich die Kontrollen von beiden Patient_innengruppen, allerdings war nur der Befund für die Panikstörung signifikant ( p = .008). In der zweiten Studie unterschieden sich die Patient_innen mit der Schmerzstörung von den gesunden Kontrollen nur im Bezug auf die IMI Subskala „feindselig“ ( p = .005), aber nicht im LFPD. Schlussfolgerung: Das präoperatorische Denken wurde nur bei Patient_innen mit depressiver Störung beobachtet, obwohl die anderen beiden Patient_innengruppen von ihren Angehörigen ebenfalls als feindselig wahrgenommen wurden. Diese Befunde sprechen dafür, dass interpersonelle Defizite bei psychischen Störungen nicht immer auf das dem CBASP zugrundeliegende Modell des präoperatorischen Denkens zurückzuführen sind.

Very few reports exist on serious cardiac complications associated with intake of serotonin-noradrenaline reuptake inhibitors. This paper describes and discusses the case of a patient who ingested a dose of 17.5 g venlafaxine. She developed a full serotonergic syndrome leading to multi-organ failure, including refractory cardiovascular shock, which was managed by early implantation of an extracorporeal life support (ECLS) system as a bridging strategy. This intervention was successful and resulted in full recovery of the patient.

The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of 19F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area., A systematic QM/MM study for predicting 19F NMR chemical shifts of a fluorinated inhibitor covalently bound to the essential oxidoreductase tryparedoxin from Trypanosoma brucei is reported. Sampling over protein–inhibitor conformations of monomeric and dimeric inhibitor–protein complexes enables the prediction of the inhibitor binding mode. This is currently the largest computational study on 19F chemical shifts in a biological context.

BACKGROUND: Music performance anxiety (MPA) is an issue concerning musicians from all levels but is still a rather neglected topic in the education and employment of musicians. This study investigated the link between self-esteem, MPA, and depression within a German-speaking sample of musicians of different professions. The underlying question of this study was generated during psychotherapy treatment of musicians with depression and MPA. Thus, we investigated whether musicians with low self-esteem had MPA or depression. METHODS: An online questionnaire on self-esteem, performance anxiety, and depression was sent to a sample (n=295) of German musicians of different professions and levels of education. The assessment tools in the online questionnaire included the Rosenberg-Self-Esteem-Scale, the Kenny Music-Performance-Anxiety-Inventory, and the Beck-Depression-Inventory. RESULTS: Music students had a significantly lower self-esteem scores compared to employed professionals and amateurs and a higher MPA compared to employed musicians. Regression analyses showed a significant prediction of depression by self-esteem and MPA. Specifically, low self-esteem and the cognitive and behavioral aspects of MPA were significant predictors of depression. Partial mediation by MPA between self-esteem and depression was found. CONCLUSION: Low self-esteem and MPA could predict depression. The scores of the entire sample of musicians regarding their MPA and depression were higher than in the general German population. These results highlight the importance of education and removal of negativity regarding performance anxiety in order to improve psychotherapy methods and ensure musicians’ health in general.

Stress granules (SGs) are formed in the cytosol as an acute response to environmental cues and activation of the integrated stress response (ISR), a central signaling pathway controlling protein synthesis. Using chronic virus infection as stress model, we previously uncovered a unique temporal control of the ISR resulting in recurrent phases of SG assembly and disassembly. Here, we elucidate the molecular network generating this fluctuating stress response, by integrating quantitative experiments with mathematical modeling, and find that the ISR operates as a stochastic switch. Key elements controlling this switch are the cooperative activation of the stress-sensing kinase PKR, the ultrasensitive response of SG formation to the phosphorylation of the translation initiation factor eIF2α, and negative feedback via GADD34, a stress-induced subunit of protein phosphatase 1. We identify GADD34 mRNA levels as the molecular memory of the ISR that plays a central role in cell adaptation to acute and chronic stress.