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During viral infection, the accumulation of RNA replication intermediates or viral proteins imposes major stress on the host cell. In response, cellular stress pathways can rapidly impose defence mechanisms by shutting off the protein synthesis machinery, which viruses depend on, and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Previously we showed that murine norovirus (MNV) regulates the activity of eukaryotic initiation factors (eIFs). Here we examined how MNV interacts with the eIF2α signaling axis controlling translation and stress granules accumulation. We show that while MNV infection represses host cell translation, it results in the assembly of virus-specific granules rather than stress granules. Further mechanistic analyses revealed that eIF2α signaling is uncoupled from translational stalling. Moreover the interaction of the RNA-binding protein G3BP1 with viral factors together with a redistribution of its cellular interacting partners could explain norovirus evasion of stress granules assembly. These results identify novel strategies by which norovirus ensure efficient replication propagation by manipulating the host stress response.

Recently there has been a growing interest in covalent protease inhibitors in both industry and academia, caused by their longer residence times, their higher potency and their high ligand efficiency. Covalently reactive moieties which interact with activated amino acid residues such as serine or cysteine in enzymes like proteases or esterases mostly act through nucleophilic addition, substitution or ring opening. In contrast, nucleophilic aromatic substitution (SNAr) is rarely employed. In our previous work, we prepared and investigated electrophilic “warheads”, which contain aromatic, heteroaromatic or quinoid fragments. Some of them show potent inhibition constants for cathepsin L, cathepsin B, rhodesain or dengue-protease, and depending on the exact nature of the electrophile they exhibit reversible covalent or irreversible inhibition modes. In the present work, we demonstrate the synthesis of fluorescent “warhead” candidates based on 2,1,3-benzoxadiazoles and the investigation of their physicochemical and photophysical properties. These molecules shall serve as probes for the detailed analysis of association/dissociation mechanism and of the kinetic parameters of the bond forming event.

Background: Major depressive Disorder (MDD) is a severe mental disorder associated with considerable disability and high costs. Over the last decades, various psychotherapies for MDD have been developed and researched, among others Behavioral Activation (BA) and Metacognitive Therapy (MCT). MCT and BA target different maintaining factors of MDD and have not been compared to date. The PRO*MDD randomized controlled trial will compare MCT and BA in the routine clinical setting of an outpatient clinic. Methods and Design: We aim to recruit 128 MDD patients, who will be randomly assigned to either MCT or BA. In both conditions, patients will receive one individual therapy session and one group therapy session per week for a maximum of 6 months. Assessments will take place at baseline, pre-treatment, mid-treatment, post-treatment as well as at 12, 18, and 30 months after start of treatment as follow-up. The primary outcome is reduction of depression severity assessed with the Hamilton Rating Scale for Depression; secondary outcomes address quality of life, psychosocial functioning and participation as well as comorbidity. Discussion: The PRO*MDD study is the first randomized controlled trial to compare the effectiveness of MCT and BA. The outcome of this trial will increase our knowledge on the effectiveness and applicability of both treatment modalities and therefore contribute to the improvement of treatment for depressive patients. Ethics and dissemination: The study has been reviewed and approved on 11 August 2016 by the Ethics Committee of the Lubeck University (reference number: 16-176). The results will be discussed through peer-reviewed publications. Trial registration: German Clinical Trials Register DRKS-ID: DRKS00011536 (retrospectively registered).

Objective: Childhood maltreatment, interpersonal fear and a specific kind of interpersonal skills deficit (preoperational thinking) have all been associated with persistent depressive disorder (PDD...

Introduction: Borderline Personality Disorder (BPD) is a prevalent condition that is often under-treated. This is partly because very few psychotherapists offer treatment for this disabling disorder. Internet-based self-management interventions could contribute to reducing the treatment gap but-mainly due to safety concerns-these have never been tested for BPD in controlled trials. Methods: Patients with BPD will be recruited primarily via the internet and randomized to two groups: care as usual (CAU) alone) or the self-management intervention priovi® in addition to CAU. At the end of the diagnostic interview, all participants will discuss an emergency plan. The main outcome measure is the clinician-rated symptom severity using the BPD Severity Index (BPDSI). Secondary outcome measures include a range of self-reported scales, an SCID-diagnosis of BPD and several safety parameters including serious adverse events (e.g., a life-threatening event, hospitalization or suicide attempt). Discussion: This trial will evaluate the effectiveness of the self-management intervention, priovi, in reducing symptoms of BPD. It will also assess the safety of its use in this target population. If successful, this intervention would be the first comprehensive internet intervention for the treatment of BPD and complement the wide range of internet interventions effective in treating other mental disorders, particularly depression and anxiety disorders. Trial Registration: NCT03418142 (clinicaltrials.gov) on January 23rd 2018. Trial status: recruiting, currently N = 108 (July 2018).

Pupae of numerous Papilionidae and Nymphalidae produce twitter sounds when wriggling in response to mechanical stimulation. The structural basis comprises distinct pairs of sound-producing organs (SPOs) located at intersegmental membranes of the abdomen. They differ—as the twitters do—in sampled taxa of Papilioninae, Epicaliini, and Heliconiini. The opposing sculptured cuticular sound plates (SPs) of each SPO appear structurally the same but are actually mirror-images of each other. Results suggest that sounds are not generated by stridulation (friction of a file and a scraper) but when these inversely sculptured and interlocking surfaces separate during pupal wriggling, representing a stick-slip mechanism. Twitter sounds comprise series of short broadband pulses with the main energy in the frequency range 3–13 kHz; they can be heard by humans but extend into ultrasonic frequencies up to 100 kHz.

Bei der Behandlung mit Antipsychotika der zweiten Generation treten Spätdyskinesien seltener auf als bei der Behandlung mit den älteren Antipsychotika der ersten Generation. Das berichten Maren Carbon und Kollegen vom Zucker Hillside Hospital im US-Bundesstaat New York jetzt im Fachjournal World Psychiatry.

Background: The self-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) is a well-established measure of depression severity. This study aimed to evaluate the psychometric properties of the German translation of the QIDS-SR16. Methods: 332 depressed German adults awaiting psychotherapy were assessed with the German translations of the QIDS-SR16, the Beck Depression Inventory (BDI-II) and the 24-item Hamilton Rating Scale for Depression (HRSD-24). Results: Internal consistency for the QIDS-SR16 was acceptable (Cronbach’s alpha = .77). Corrected item-total correlations indicated adequate discriminatory power of all the items. The QIDS-SR16 highly correlated with the BDI-II (r = .810) but only moderately correlated with the HRSD-24 (r = .581). Regarding discriminant validity, the QIDS-SR16 discriminated between patients with and without a depressive episode but not between patients with and without panic disorder. Conclusion: The German translation of the QIDS-SR16 has adequate psychometric properties. Our results support the usefulness of the German version of the QIDS-SR16 as a brief depression rating scale in clinical and research settings.

Chronic depression is assumed to be caused and maintained by interpersonal deficits. We describe the development and psychometric evaluation of the Interactive Test of Interpersonal Behavior (ITIB) that we developed for self-assessment of these deficits. Participants with chronic depression (CD, N = 15), episodic depression (ED, N = 15) and healthy controls (HC, N = 15) participated in this pilot study. They completed the ITIB and a number of pen and paper questionnaires including the Lübeck Questionnaire of Preoperational Thinking (LQPT) and the inventory of interpersonal problems (IIP). The ITIB was highly acceptable for use in these participants. Internal consistency for the ITIB was adequate for group comparisons (Cronbach's alpha = 0.649). Item-total correlations indicated adequate discriminatory power of five of the six items. The ITIB correlated moderately with the LQPT (r = 0.524) and the IIP (r = -0.568). The ITIB score differed significantly between the diagnostic groups (ANOVA F(2,42) = 6.22, p = 0.004). It was the only measure that - albeit at a trend level - was associated with diagnostic group (CD vs. ED) on multinomial logistic regression analysis (B = 0.049 ± 0.029; OR 1.051; p = 0.088). We found preliminary evidence that the ITIB is an acceptable and psychometrically adequate measure of interpersonal behavior that distinguishes between patients with CD and patients with ED. If replicated with an improved version of the test, our results could support the hypothesis that having interpersonal problems is a core deficit in patients with CD.

Hintergrund Die Finanzierung psychiatrisch-psychotherapeutischer Krankenhausleistungen in Deutschland wird seit 1991 unverandert durch die Psychiatrie-Personalverordnung (Psych-PV) bestimmt. Psychotherapie hat sich nach 1991 als eine wirksame und unverzichtbare Behandlungsform in der Versorgung von psychischen Storungen und Verhaltensstorungen etabliert.

Background Types of maltreatment often co-occur and it is unclear how maltreatment patterns impact on comorbidity in depressed patients. Methods We analysed associations of maltreatment patterns with a broad range of comorbidities assessed with diagnostic interviews in 311 treatment-seeking depressed outpatients. Results Latent class analyses identified a “no maltreatment class” (39%), a “mild to moderate abuse and neglect class” (34%), a “severe abuse and neglect class” (14%) and a “severe neglect class” (13%). We found a dose-response association for the first three classes with comorbid disorders, a general psychopathology factor and an interpersonal insecurity factor. Patients in the “severe abuse and neglect” class had increased odds ratios (OR) of suffering from an anxiety disorder (OR 3.58), PTSD (OR 7.09), Borderline personality disorder (OR 7.97) and suicidality (OR 10.04) compared to those without child maltreatment. Patients in the “severe neglect” class did not have a higher risk for comorbidity than those in the “no maltreatment” class. Limitations Class sizes in the “severe abuse and neglect” and the “severe neglect” classes were small and findings should be replicated with other clinical and population samples. Conclusions A higher severity rather than the constellation of types of child abuse and neglect was associated with more comorbid disorders. An exception were patients reporting solely severe emotional and physical neglect who had a similar risk for comorbidity as patients without a history of child maltreatment. This may be associated with distinct learning experiences and may inform treatment decisions.

BackgroundLittle is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration.MethodsRandomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates.ResultsThirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates.ConclusionsSelf-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Using a sample of almost 300 European banks, we show that the concentration of ownership leads to larger capital buffers, consistent with theories of interest alignment and the charter value theory. Mixed empirical findings of previous literature suggest that external factors may affect the disciplinary role of controlling owners. In this paper, we demonstrate that the stabilizing impact of concentrated ownership is weaker when the level of regulatory discipline is higher. We also observe a weaker stabilizing impact when the level of market discipline is higher, while this effect seems to be less robust. Moreover, we find evidence for the too-big-to-fail phenomenon, since the stabilizing impact of ownership concentration on capital buffers is significantly weaker for systemically important institutions. Our findings indicate that bank owners are aware of the risk of losing charter value when external monitoring is lower and underline that internal governance of banks should not be discussed in isolation from external governance factors.

Background Psychological online interventions (POIs) for depression have demonstrated promising effects. However, there are fewer randomized controlled studies on POIs among older adults with depression. The goal of the present study was to compare the use and efficacy of Deprexis, an online intervention for depression, among Millennials (18–35 years) and Baby Boomers (50–65 years). Methods We completed a secondary data analysis on a subset (N = 577) of participants in the EVIDENT trial, a parallel-groups, pragmatic, randomized, controlled single-blind study, which compared a 12-week POI (Deprexis) to care as usual (CAU). Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The main outcome of interest was change on self-rated depression severity (PHQ-9). Results Compared to Millennials, Boomers used the intervention significantly more often (d = 0.45) and for a longer duration (d = 0.46), and endorsed more positive attitudes towards POIs (d = 0.14). There was no significant Age Group by Intervention Group interaction for change in PHQ-9. The post-assessment between-group effect size (intervention vs. CAU control) for Millennials and Boomers were d = 0.26 and d = 0.39, respectively, and were stable at follow-up (d = 0.37 and d = 0.39). Limitations Age-based dichotomization may not accurately represent participants’ experiences with and use of technology. Conclusions The POI examined in this trial was superior to CAU and was comparably effective among groups of adults defined as Millennials and Baby Boomers. Adults of the Baby Boomer generation who participate in POIs may have more positive attitudes towards POIs compared to their younger counterparts.

Background While the efficacy of Internet interventions for depression has been demonstrated in numerous studies, there is concern that the participants in these studies may systematically differ from depressed subjects in the general population. The goal of this study was to compare participants in a large trial of an Internet intervention for depression with a population-based sample that reported depressive symptomatology in the same range of severity. Methodology The analysis is based on a sample of participants of a randomized controlled trial testing the effectiveness of an Internet intervention for depression in mild to moderate depression (EVIDENT, N = 1013) and a subsample of participants in a representative population-based sample (DEGS1, n = 1978). The DEGS1 subsample was chosen based on the score in the Patient Health Questionnaire-9 (PHQ-9, score 5–14) as this was the main inclusion criterion for the EVIDENT study. Both samples were compared with respect to a range of demographic and clinical variables. Results Compared with the DEGS1 subsample, participants in the EVIDENT sample were significantly more often female (68.6% vs. 56.3%), slightly older (mean age 42.9 vs. 40.4 years), had more often completed highest secondary education (51.3% vs. 22.4%), were clinically more severely affected (moderate depressive symptoms in 62.6% vs. 18.3%) and reported a lower quality of life. Conclusion These findings indicate that participants in this Internet trial were not just internet savvy young males without significant impairment. Future studies should aim to recruit participants with lower educational status to increase the reach of Internet interventions., Highlights • The present study consists of a large sample size with participants from multiple sources. • Differences in characteristics between depressed participants in an Internet trial and in a population-based sample were found. • Participants in the Internet trial were older, more often female, single/divorced, more highly educated and more depressed. • Mild to moderately depressed individuals seeking help in the Internet are substantially impaired.

Background Adherence to Internet interventions is often reported to be rather low and this might adversely impact the effectiveness of these interventions. We investigated if patient characteristics are associated with adherence, and if adherence is associated with treatment outcome in a large RCT of an Internet intervention for depression, the EVIDENT trial. Methods Patients were randomized to either care as usual (CAU) or CAU plus the Internet intervention Deprexis. A total of 509 participants with mild to moderate depressive symptoms were included in the intervention group and of interest for the present study. We assessed depression symptoms pre and post intervention (12 weeks). Patient characteristics, a self-rating screening for mental disorders, attitudes towards online interventions, and quality of life were assessed before randomization. Results Adherence in this study was good with on average seven hours of usage time and eight number of sessions spent with the intervention. Some of the patient characteristics (age, sex, depressive symptoms, and confidence in the effectiveness of the program) predicted higher number of sessions in different models (explaining in total between 15 and 25% of variance). Older age (β = .16) and higher depressive symptoms (β = .15) were associated with higher usage duration. Higher adherence to the program predicted a greater symptom reduction in depressive symptoms over 12 weeks (number of sessions: β = .13, usage duration: β = .14), however, this prediction could mostly be explained by receiving guidance (β = .27 and .26). Limitations Receiving guidance and symptom severity at baseline were confounded since only participants with a moderate symptom severity at baseline received e-mail support. Therefore no firm conclusions can be drawn from the association we observed between baseline symptom severity and usage intensity. Conclusions We conclude that older age was associated with adherence and adherence was positively associated with outcome. The effects we have found were small however suggesting that adherence might also be influenced by further variables.

BackgroundMost original studies and all meta-analyses conducted to date converge on the conclusion that patients with schizophrenia display rather generalized neurocognitive deficits. For the present study, we reopen this seemingly closed chapter and examine whether important influences, such as lack of motivation and negative attitudes towards cognitive assessment, result in poorer secondary neuropsychological performance.MethodA sample of 50 patients with an established diagnosis of schizophrenia were tested for routine neurocognitive assessment and compared to 60 nonclinical volunteers. Before and after the assessment, subjective momentary influences were examined (e.g. motivation, concerns about assessment, fear about poor outcome) for their impact on performance using a new questionnaire called theMomentary Influences, Attitudes and Motivation Impact(MIAMI)on Cognitive Performance Scale.ResultsAs expected, patients performed significantly worse than controls on all neurocognitive domains tested (large effect size, on average). However, patients also displayed more subjective momentary impairment, as well as more fears about the outcome and less motivation than controls. Mediation analyses indicated that these influences contributed to (secondary) poorer neurocognitive performance. Differences in neurocognitive scores shrank to a medium effect size, on average, when MIAMI scores were accounted for.ConclusionsThe data argue that performance on measures of neurocognition in schizophrenia are to a considerable extent due to secondary factors. Poor motivation, fears and momentary impairments distinguished patients from controls and these variables heavily impacted performance. Before concluding that neurocognitive deficits in psychiatric patients are present, clinicians should take these confounding influences into account. Although patients with schizophrenia achieved, on average, worse test scores than controls, a large subgroup displayed spared performance.

As obligate parasites, viruses strictly depend on host cell translation for the production of new progeny, yet infected cells also synthesize antiviral proteins to limit virus infection. Modulation of host cell translation therefore represents a frequent strategy by which viruses optimize their replication and spread. Here we sought to define how host cell translation is regulated during infection of human cells with dengue virus (DENV) and Zika virus (ZIKV), two positive-strand RNA flaviviruses. Polysome profiling and analysis of de novo protein synthesis revealed that flavivirus infection causes potent repression of host cell translation, while synthesis of viral proteins remains efficient. Selective repression of host cell translation was mediated by the DENV polyprotein at the level of translation initiation. In addition, DENV and ZIKV infection suppressed host cell stress responses such as the formation of stress granules and phosphorylation of the translation initiation factor eIF2α (α subunit of eukaryotic initiation factor 2). Mechanistic analyses revealed that translation repression was uncoupled from the disruption of stress granule formation and eIF2α signaling. Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was essential for the efficient production of virus particles. Together, these results identify the uncoupling of translation suppression from the cellular stress responses as a conserved strategy by which flaviviruses ensure efficient replication in human cells.For efficient production of new progeny, viruses need to balance their dependency on the host cell translation machinery with potentially adverse effects of antiviral proteins produced by the infected cell. To achieve this, many viruses evolved mechanisms to manipulate host cell translation. Here we find that infection of human cells with two major human pathogens, dengue virus (DENV) and Zika virus (ZIKV), leads to the potent repression of host cell translation initiation, while the synthesis of viral protein remains unaffected. Unlike other RNA viruses, these flaviviruses concomitantly suppress host cell stress responses, thereby uncoupling translation suppression from stress granule formation. We identified that the p38-Mnk1 cascade regulating phosphorylation of eIF4E is a target of DENV infection and plays an important role in virus production. Our results define several molecular interfaces by which flaviviruses hijack host cell translation and interfere with stress responses to optimize the production of new virus particles.

Importance: Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment. - Objectives: To estimate the effect of self-guided iCBT in treating adults with depressive symptoms compared with controls and evaluate the moderating effects of treatment outcome and response. - Data Sources: A total of 13 384 abstracts were retrieved through a systematic literature search in PubMed, Embase, PsycINFO, and Cochrane Library from database inception to January 1, 2016. - Study Selection: Randomized clinical trials in which self-guided iCBT was compared with a control (usual care, waiting list, or attention control) in individuals with symptoms of depression. - Data Extraction and Synthesis: Primary authors provided individual participant data from 3876 participants from 13 of 16 eligible studies. Missing data were handled using multiple imputations. Mixed-effects models with participants nested within studies were used to examine treatment outcomes and moderators. - Main Outcomes and Measures: Outcomes included the Beck Depression Inventory, Center for Epidemiological Studies–Depression Scale, and 9-item Patient Health Questionnaire scores. Scales were standardized across the pool of the included studies. - Results: Of the 3876 study participants, the mean (SD) age was 42.0 (11.7) years, 2531 (66.0%) of 3832 were female, 1368 (53.1%) of 2574 completed secondary education, and 2262 (71.9%) of 3146 were employed. Self-guided iCBT was significantly more effective than controls on depressive symptoms severity (β = −0.21; Hedges g = 0.27) and treatment response (β = 0.53; odds ratio, 1.95; 95% CI, 1.52-2.50; number needed to treat, 8). Adherence to treatment was associated with lower depressive symptoms (β = −0.19; P = .001) and greater response to treatment (β = 0.90; P

Does the pre-treatment profile of individuals with persistent depressive disorder (PDD) moderate their benefit from disorder-specific Cognitive Behavioral System of Psychotherapy (CBASP) versus supportive psychotherapy (SP)? We investigated this question by analyzing data from a multi-center randomized clinical trial comparing the effectiveness of 48 weeks of CBASP to SP in n = 237 patients with early-onset PDD who were not taking antidepressant medication. We statistically developed an optimal composite moderator as a weighted combination of 13 preselected baseline variables and used it for identifying and characterizing subgroups for which CABSP may be preferable to SP or vice versa. We identified two distinct subgroups: 58.65% of the patients had a better treatment outcome with CBASP, while the remaining 41.35% had a better outcome with SP. At baseline, patients responding more favorably to CBASP were more severely depressed and more likely affected by moderate-to-severe childhood trauma including early emotional, physical, or sexual abuse, as well as emotional or physical neglect. In contrast, patients responding more favorably to SP had a higher pre-treatment global and social functioning level, a higher life quality and more often a recurrent illness pattern without complete remission between the episodes. These findings emphasize the relevance of considering pre-treatment characteristics when selecting between disorder-specific CBASP and SP for treating PDD. The practical implementation of this approach would advance personalized medicine for PDD by supporting mental health practitioners in their selection of the most effective psychotherapy for an individual patient.

On December 7th 2017, the Basel Committee on Banking Supervision (BCBS) published the first completed draft of the finalisation of the Basel III regulation for credit institutions. One of the BCBS's main focuses in this revision was on the calculation of capital requirements for credit risk using internal models. In order to limit that part of the risk-weighted asset variability which is not intended from a regulatory perspective, banks will have to consider input floors and an output floor. These rules are attributed to significant - partly intended, partly unintended - consequences, especially for traditionally low-risk financing. Using the example of real estate and lease financing, this study illustrates that, in addition to the intended consequences, the new regulatory requirements can also incentivize banks to shift their business in favor of riskier financing.

Background Neurofunctional deficits in chronic depression (CD) have been understudied. Specifically there is no known published study of the effects of a specialized psychotherapy for CD (CBASP) on neurofunctional deficits. Methods Ten patients with a DSM-IV diagnosis of CD received a 12 week specialised psychotherapy (CBASP). Controls were healthy matched volunteers. All subjects participated in a prospective study with functional magnetic resonance imaging (fMRI) at baseline and after 12 weeks. During the fMRI scans, subjects performed an implicit and explicit emotional processing task while watching dynamic displays of neutral, positive (happy) and negative (fearful and sad) facial expressions. Effects of treatment were analyzed in a repeated measures design. The analysis was restricted to two anatomically defined regions of interest (ROI): the amygdala and the cingulum. Results 60% of patients responded to treatment. Patients with CD reported increased arousal to negative emotional expressions. They also showed an increase in left amygdala reactivity during implicit processing of emotional expressions following psychotherapy. We found no significant effect for the cingulum. Limitations The main limitation of our study is the small sample size. Due to the lack of a control group it is also unclear whether the demonstrated effect is specific to the psychotherapy used in this study. Conclusions For the first time our study demonstrates an effect of CBASP on neural processing of facial emotions in CD. It therefore adds to the growing evidence supporting this treatment.

Donor–acceptor polymers can store both a positive and negative charge allowing them to function as both the positive and negative charge storage material in a supercapacitor device, however few have been explored for this application. Here, we describe the synthesis of several donor–acceptor polymers and their electrodeposited polymer electrodes. We use differing molecular structures to examine the effect of electron acceptor concentration and show that device stability can be improved significantly by increasing the acceptor concentration. Further, we provide computational insight into the important chemical requirements for achieving even higher performance supercapacitors based on donor–acceptor conjugated polymers. Supercapacitor devices with specific energy and specific power as high as 11 Wh kg–1 (at 0.5 A g–1) and 20 kW kg–1 (at 50 A g–1 with an energy of 3.6 Wh kg–1) are reported, which are some of the highest values achieved to date.

Patienten, die an einer Migräne und an einer Depression leiden, können sowohl Triptane als auch viele gängige Antidepressiva nehmen. Zu diesem Ergebnis kommen Yulia Orlova von der Universität Florida und Kollegen auf Grundlage einer Auswertung von umfangreichen Patientenunterlagen. Das berichten sie jetzt im Fachjournal JAMA Neurology.

ZusammenfassungInternetbasierte psychologische Behandlung gewinnt zunehmend an Bedeutung und wird intensiv beforscht. Vorteile dieser Form der Behandlung sind die leichte Verfügund Vervielfältigbarkeit. Grenzen werden beispielsweise in Krisensituationen der Patienten erreicht. Internetbasierte psychologische Interventionen werden eingeteilt nach der Intensität des therapeutischen Kontaktes, dem zugrunde liegenden Therapieansatz und der medialen Gestaltung der Intervention. Es liegen zahlreiche Studien und Metaanalysen zur Wirksamkeit internetbasierter psychologischer Behandlungen bei Angststörungen und Depression vor. Allerdings wurden die meisten Studien bei selbstselegierten Patientenstichproben außerhalb der Routineversorgung durchgeführt. Bei diesen Patienten haben sich insbesondere internetbasierte Interventionen, die einen therapeutischen Kontakt beinhalten (z. B. therapeutengeleitete Selbsthilfeprogramme), in vielen Studien als wirksam erwiesen. In Zukunft sollte vermehrt der Einsatz internetbasierter Interventionen in der Routineversorgung erforscht werden.

Dieses Kapitel vermittelt praxisorientiert alle wichtigen rechtlichen Grundlagen fur die psychiatrische Notfallbehandlung. Das Vorgehen wird im Sinne eines Leitfadens Schritt fur Schritt dargestellt. Schwerpunkte sind das Vorgehen bei Unterbringung und das Vorgehen bei arztlichen Zwangsmasnahmen. Der Leser lernt dabei, wann das Betreuungsrecht und wann das PsychKG zum Einsatz kommt und wie in jedem der beiden Falle vorgegangen werden sollte. Abgerundet wird das Kapitel durch eine Entscheidungshilfe zur Feststellung der Einwilligungsfahigkeit.

In diesem Kapitel wird das CognitiveBehavioral Analysis System ofPsychotherapy (CBASP) sowohl wissenschaftlich fundiert als auch praxisorientiert dargestellt. CBASP ist die erste Psychotherapie, welche spezifisch fur die Behandlung chronischer Depression entwickelt wurde. Die Techniken wurden ursprunglich von James McCullough beschrieben und anschliesend von ihm und anderen weiterentwickelt. Zu Beginn des Kapitels wird anhand des Fallbeispiels das Storungsmodell der chronischen Depression eingefuhrt und die empirischen Belege fur dieses Modell zusammengefasst. Dann werden anhand dieses Fallbeispiels Schritt fur Schritt die Struktur der Behandlung und die einzelnen CBASP-Techniken erlautert. Den Schwerpunkt bilden dabei die Situationsanalyse und die Techniken der Beziehungsgestaltung. Zum Abschluss des Kapitels wird dargestellt, warum CBASP auf Grundlage der mittlerweile vorliegenden klinischen Studien als evidenzbasierte Psychotherapie gelten kann.

As obligate parasites, viruses strictly depend on host cell translation for the production of new progeny, yet infected cells also synthesize antiviral proteins to limit virus infection. Modulation of host cell translation therefore represents a frequent strategy by which viruses optimize their replication and spread. Here we sought to define how host cell translation is regulated during infection of human cells with dengue virus (DENV) and Zika virus (ZIKV), two positive-strand RNA flaviviruses. Polysome profiling and analysis of de novo protein synthesis revealed that flavivirus infection causes potent repression of host cell translation, while synthesis of viral proteins remains efficient. Selective repression of host cell translation was mediated by the DENV polyprotein at the level of translation initiation. In addition, DENV and ZIKV infection suppressed host cell stress responses such as the formation of stress granules and phosphorylation of the translation initiation factor eIF2α (α subunit of eukaryotic initiation factor 2). Mechanistic analyses revealed that translation repression was uncoupled from the disruption of stress granule formation and eIF2α signaling. Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was essential for the efficient production of virus particles. Together, these results identify the uncoupling of translation suppression from the cellular stress responses as a conserved strategy by which flaviviruses ensure efficient replication in human cells., IMPORTANCE For efficient production of new progeny, viruses need to balance their dependency on the host cell translation machinery with potentially adverse effects of antiviral proteins produced by the infected cell. To achieve this, many viruses evolved mechanisms to manipulate host cell translation. Here we find that infection of human cells with two major human pathogens, dengue virus (DENV) and Zika virus (ZIKV), leads to the potent repression of host cell translation initiation, while the synthesis of viral protein remains unaffected. Unlike other RNA viruses, these flaviviruses concomitantly suppress host cell stress responses, thereby uncoupling translation suppression from stress granule formation. We identified that the p38-Mnk1 cascade regulating phosphorylation of eIF4E is a target of DENV infection and plays an important role in virus production. Our results define several molecular interfaces by which flaviviruses hijack host cell translation and interfere with stress responses to optimize the production of new virus particles.

Objective: This study aims to examine whether the effects of internet interventions for depression generalise to participants recruited in clinical settings. Design: This study uses subgroup analysis of the results of a randomised, controlled, single-blind trial. Setting: The study takes place in five diagnostic centres in Germany. Participants: A total of 1013 people with mild to moderate depressive symptoms were recruited from clinical sources as well as internet forums, statutory insurance companies and other sources. Interventions: This study uses either care-as-usual alone (control) or a 12-week internet intervention (Deprexis) plus usual care (intervention). Main outcome measures: The primary outcome measure was self-rated depression severity (Patient Health Questionnaire-9) at 3 months and 6 months. Further measures ranged from demographic and clinical parameters to a measure of attitudes towards internet interventions (Attitudes towards Psychological Online Interventions Questionnaire). Results: The recruitment source was only associated with very few of the examined demographic and clinical characteristics. Compared with participants recruited from clinical sources, participants recruited through insurance companies were more likely to be employed. Clinically recruited participants were as severely affected as those from other recruitment sources but more sceptical of internet interventions. The effectiveness of the intervention was not differentially associated with recruitment source (treatment by recruitment source interaction=0.28, p=0.84). Conclusion: Our results support the hypothesis that the intervention we studied is effective across different recruitment sources including clinical settings. Trial registration number: ClinicalTrials.gov NCT01636752.

Background: Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. Objective: The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. Methods: We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. Results: Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P

Worldwide, Gerhard Andersson is one of the most influential researchers working on internet-based psychological treatments. Moreover, he is also one of the leading researchers in the field of psychologically oriented tinnitus research. He is full professor of clinical psychology at Linkoping University and affiliated professor at the Karolinska Institute in Stockholm at the Department of Clinical Neuroscience, Section Psychiatry. Professor Andersson has been highly productive, having produced more the 300 scientific papers. During his whole career he has worked part-time with patients. Apart from his own research and clinical work, Professor Andersson has editorial responsibilities for several journals including Cognitive Behaviour Therapy, Plos One, BMC Psychiatry, and Scandinavian Journal of Psychology. The interview was conducted by Professor Thomas Berger.

This manuscript describes the design considerations, implementation, and laboratory validation of an odor sensing module whose purpose is to support people that suffer from incontinence. Because of the requirements expressed by the affected end-users the odor sensing unit is realized as a portable accessory that may be connected to any pre-existing smart device. We have opted for a low-cost, low-power consuming metal oxide based gas detection approach to highlight the viability of developing an inexpensive yet helpful odor recognition technology. The system consists of a hotplate employing, inkjet-printed p-type semiconducting layers of copper(II) oxide, and chromium titanium oxide. Both functional layers are characterized with respect to their gas-sensitive behavior towards humidity, ammonia, methylmercaptan, and dimethylsulfide and we demonstrate detection limits in the parts-per-billion range for the two latter gases. Employing a temperature variation scheme that reads out the layer’s resistivity in a steady-state, we use each sensor chip as a virtual array. With this setup, we demonstrate the feasibility of detecting odors associated with incontinence.

Background\ud \ud Depression is common in schizophrenia. Whereas the improvement of mood and self-esteem represents a subjective treatment priority for many patients, depression is rarely a primary target for clinical intervention. The present trial examined whether an online intervention for depression can ameliorate depressive symptoms in schizophrenia.\ud \ud Methods\ud \ud A total of 58 individuals with schizophrenia were invited to participate in an online survey which encompassed the Center for Epidemiologic Studies-Depression Scale (CES-D, primary outcome), the Patient-Health-Questionnaire-9 (PHQ-9) and the Paranoia Checklist. Subsequently, telephone interviews were conducted to verify diagnostic status and assess symptoms (Positive and Negative Syndrome Scale, PANSS). Participants were randomized either to the experimental condition (online depression intervention) or to a waitlist control condition. Three months after inclusion, a reassessment was carried out (self-report and telephone interview blind for group condition). The trial was registered (registration: DRKS00007888).\ud \ud Results\ud \ud Participants in the treatment group showed a significant decline of depressive symptoms at a medium-to-large effect size, as assessed with the CES-D and the PANSS depression item, in comparison to the waitlist control group (completer (CC) and intention-to-treat analyses (ITT)). For the PHQ-9 (CC and ITT) and the PANSS distress subscale (CC only) significance was bordered at a medium effect size. Completion at the post-assessment after three months was 84%.\ud \ud Discussion\ud \ud Depression in schizophrenia is both underdiagnosed and undertreated. To reduce the large treatment gap in the disorder, low threshold strategies are urgently needed. Online treatment and bibliotherapy may represent valuable tools to address patients' needs beyond the treatment of the core positive syndrome.

Objective: This pilot study was a comparison of dimensional models assessing personality traits and personality pathology in a clinical sample of adults diagnosed with ADHD and adults diagnosed with borderline personality disorder (BPD), and a nonclinical control sample of healthy adults. Method: Personality traits were assessed using the NEO–Personality Inventory–Revised (NEO-PI-R) and dimensional personality pathology with the Dimensional Assessment of Personality Pathology–Basic Questionnaire (DAPP-BQ). Results: Adults with ADHD and BPD produced higher Emotional Dysregulation/Neuroticism and Dissocial Behavior scores than controls. For the Extraversion/Inhibitedness scale, adults with BPD produced significantly lower scores than adults with ADHD and controls. On the Conscientiousness/Compulsivity domains, Conscientiousness scores were lower for both disorders, whereas low Compulsivity values were specific to adult ADHD. Conclusion: Our results suggest that patients with adult ADHD and BPD have distinguishable profiles of personality traits and personality pathology.

This paper describes a robot head platform which holds a pair of event-based Dynamic Vision Sensor (DVS) retinas and microphones connected to an event-based binaural AEREAR2 VLSI cochlea system. The platform has 6 degrees of freedom (DOF): 2 for the neck, and 2 for each of the DVS retinas. Two applications using this platform are described: the first is image stitching of a scene larger than the field of view of the individual retinas as the head pans and tilts and the second is selective image painting of the local visual scene around spatially displaced sound sources. This platform allows for the investigation of event-driven sensory-action models that use the information from multiple event-based sensor modalities in real-time scenarios.

Background Only a minority of people suffering from depression receive adequate treatment. Psychological Online Interventions (POIs) could help bridge existing treatment gaps and augment the effectiveness of current treatments. Apart from effectiveness, user acceptance of POIs must be achieved if such interventions are to be broadly implemented in existing health-care. Valid measurement tools examining attitudes towards POIs are lacking. Therefore, we examined the dimensionality of attitudes towards POIs, developed a novel questionnaire, the Attitudes towards Psychological Online Interventions Questionnaire (APOI), and gathered data to examine its reliability. Methods We recruited a sample of 1004 adults with mild to moderate depressive symptoms from a range of sources. We constructed a set of 35 items based on literature review as well as expert and patient queries. The initial items were subjected to an exploratory factor analysis (EFA) in a randomly selected subsample. A final set of 16 items was subjected to a confirmatory factor analysis (CFA) to cross-validate the factor structure in a separate subsample. Results The EFA revealed four dimensions: “Scepticism and Perception of Risks”, “Confidence in Effectiveness”, “Technologization Threat” and “Anonymity Benefits”. The model fit in the CFA was excellent relating to all applied indices (χ2=105.816, p=.651; SRMR=.042; RMSEA=.013; CFI=.994) and the APOI total scale showed acceptable to good internal consistency. Conclusions Further research with the APOI might facilitate the development and dissemination of POIs and, ultimately, help improve the quality of care for people experiencing depressive symptoms.

Zusammenfassung: Bei der Kombination von Psychotherapie und Pharmakotherapie sind Wechselwirkungen zu beachten. Psychopharmaka können den Verlauf der Psychotherapie begünstigen oder behindern. Benzodiazepine beispielsweise beeinträchtigen in Tierexperimenten und klinischen Studien den Lernerfolg. Bei einigen Störungen ist eine Pharmakotherapie in der Regel unerlässlich (Depression, Manie, Schizophrenie). Durch eine Kombination von Pharmakotherapie mit Psychotherapie kann die Rückfallrate gesenkt und die Remissionsrate erhöht werden. Bei anderen Störungen ist die Psychotherapie das Mittel der Wahl (Angst- und Zwangsstörungen). Eine Kombination mit Psychopharmaka kann den Therapieerfolg beschleunigen, besonders bei therapierefraktären Patienten oder sekundären Depressionen.