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1. The haemodynamic mechanisms underlying the antihypertensive effect of guanfacine during chronic oral administration were studied. 2. Ten patients with essential hypertension were submitted to haemodynamic measurements at rest and during exercise, before and after 12 weeks' treatment with guanfacine alone at a daily dose of between 3 and 15 mg orally. 3. The relevant haemodynamic values were obtained by means of an arterial catheter in the aorta, a venous catheter in the right atrium, and the measurement of cardiac output using the thermodilution method. 4. The antihypertensive efficacy of guanfacine was confirmed. 5. In the seven patients with a high peripheral resistance the main effect of guanfacine was a marked decrease in total peripheral resistance. In three patients with hypertension characterized by high stroke volume and cardiac output, the main effect of guanfacine was to reduce these variables. [ABSTRACT FROM AUTHOR]

We compared the assemblages of bark beetles and associated beetle species among mature and overmature managed, and old-growth Picea abies(L.) Karst. dominated mesic forests in southern Finland. We established 10, 11 and 9 sample plots in these categories, respectively, within an area of 35x 80km. We took the beetle samples by 10 window-flight traps in each 1ha plot (total number of traps=300). The species richness of bark beetles was highest in old-growth, lowest in mature, and intermediate in overmature forests. This was due to the greater amount and diversity of decaying wood in old-growth forests. Bark beetles which are dependent on deciduous trees, especially Trypodendron signatum (F.), were significantly more abundant in old-growth than in mature forests, obviously because deciduous trees have decreased in managed forests. The overall abundance of bark beetles was 23% higher inovermature and 30% higher in old-growth than in mature forests, but the differences were not statistically significant. Primary bark beetles comprised only 1% of the total catch, indicating that in non-epidemic conditions secondary scolytids are much more abundant than primary ones in old spruce forests. The abundance of bark beetles was bestcorrelated with the amount of recently dead wood of the stand characteristics studied. Species associated with bark beetles showed patterns similar to those in bark beetles. The number of species was significantly higher in old-growth than in mature forests. The abundance ofassociated species was 61% higher in overmature and 89% higher in old-growth than in mature forests, although these differences were not statistically significant because of large inter-stand variation. It is thus likely that in the absence of major disturbances, the populations of primary bark beetles will stay at non-epidemic levels in old-growth forests. The species spectrum of bark beetles and their enemies could be broadened by promoting a deciduous mixture and improving the s [ABSTRACT FROM AUTHOR]

Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety., (© 2024. The Author(s).)

Laparoscopic common bile duct exploration (LCBDE) utility in management of choledocholithiasis may decrease length of stay and patient cost, but postoperative management remains widely debated. We examined periprocedural LFTs for patients undergoing LCBDE and endoscopic retrograde cholangiopancreatography (ERCP) speculating for trend existence after successful LCBDE. We hypothesized that postoperative LCBDE LFTs would not downtrend even after successful ductal clearance. We identified 99 patients under 18 who underwent ERCP or LCBDE with at least one pre- and post-procedural LFT. Periprocedural LFTs between groups were compared using Wilcoxon signed-rank tests. The 22 ERCP patients demonstrated a significant downtrend across Tbili ( P < .001), AST ( P = .001), ALT ( P = .002), and ALP ( P < .001). The 27 LCBDE patients demonstrated a significant downtrend in Tbili ( P = .002) only, while AST ( P > .05), ALT ( P > .05), and ALP ( P > .05) were nonsignificant. Lack of consistent downtrend in the LCBDE group raises doubt regarding the utility of postoperative LFTs for post-procedural management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Quality measurement in the German statutory program for quality in health care follows a two-step process. For selected areas of health care, quality is measured via performance indicators (first step). Providers failing to achieve benchmarks in these indicators subsequently enter into a peer review process (second step) and are asked by the respective regional authority to provide a written statement regarding their indicator results. The statements are then evaluated by peers, with the goal to assess the provider's quality of care. In the past, similar peer review-based approaches to the measurement of health care quality in other countries have shown a tendency to lack reliability. So far, the reliability of this component of the German statutory program for quality in health care has not been investigated., Method: Using logistic regression models, the influence of the respective regional authority on the peer review component of health care quality measurement in Germany was investigated using three exemplary indicators and data from 2016., Results: Both the probability that providers are asked to provide a statement as well as the results produced by the peer review process significantly depend on the regional authority in charge. This dependence cannot be fully explained by differences in the indicator results or by differences in case volume., Conclusions: The present results are in accordance with earlier findings, which show low reliability for peer review-based approaches to quality measurement. Thus, different results produced by the peer review component of the quality measurement process may in part be due to differences in the way the review process is conducted. This heterogeneity among the regional authorities limits the reliability of this process. In order to increase reliability, the peer review process should be standardized to a higher degree, with clear review criteria, and the peers should undergo comprehensive training for the review process. Alternatively, the future peer review component could be adapted to focus rather on identification of improvement strategies than on reliable provider comparisons., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Cognitive reappraisal is an essential emotion regulation skill for social life and psychological health. However, individuals with major depressive disorder (MDD) cannot use this skill effectively. Successful cognitive reappraisal in healthy controls (HC) has been shown to be associated with theta activity in a frontal and subcortical network. In the present study, we investigated whether MDD patients are characterized by altered theta power and connectivity pattern during cognitive reappraisal compared to HC., Methods: Using EEG and eLORETA, we examined both theta activity and connectivity when 25 controls and 24 patients with MDD were asked to complete the emotion cognitive reappraisal task of viewing neutral and negative pictures and reappraise negative pictures. Habitual use of emotion regulation skills was collected using the Cognitive Emotion Regulation Questionnaire (CERQ)., Results: The results showed that MDD patients had (1) reduced theta activity in the left dorsolateral (dlPFC), dorsomedial prefrontal (dmPFC), and rostral-ventral cingulate cortices (rvACC), as well as (2) reduced dlPFC-rvACC theta connectivity than HC during reappraisal. In addition, left dlPFC-rvACC theta connectivity was positively correlated with self-reported cognitive reappraisal in HC. This relation was not observed in MDD. In contrast, CERQ revealed significantly greater use of inadequate regulations skills and significantly lower use of adaptive skills in MDD., Limitation: Sample size, limited solution space to cortical grey matter excluding regions such as the amygdala., Conclusion: This study may indicate a putative frontocingulate dysfunction leading either to an increased use of inadequate emotion regulation or a decreased use of skills that serve to boost positive emotion., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials., Methods: Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels., Results: We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival., Conclusion: First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAS reports personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Roche, personal fees from BMS, personal fees from Amgen, personal fees from LEO pharma, personal fees from Novartis, personal fees from Takeda, outside of the submitted work. FCA has received a research grant from Novartis, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA.PD has nothing to disclose. JR has nothing to disclose. AT has nothing to disclose. ANH has nothing to disclose. NF reports personal fees from AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, Boehringer Ingelheim, Bristol Myers&Squibb, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, outside of the submitted work. HY has nothing to disclose. PC has received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. OB has nothing to disclose. CMB has nothing to disclose. ABVD has nothing to disclose. JA has nothing to disclose. SPA as nothing to disclose. MW has nothing to disclose. SK has nothing to disclose. MU has nothing to disclose. GT has nothing to disclose. CFW has nothing to disclose. AR reports grants from AbbVie, grants from AstraZeneca, grants from BMS, grants from Boehringer Ingelheim, grants from Daichi Sankyo, grants from Eli Lilly, grants from GSK, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, outside the submitted work. PH has nothing to disclose. JB has nothing to disclose. HGK has nothing to disclose. CG has nothing to disclose. MSch has nothing to disclose. CSch has nothing to disclose. FG reports personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, Ariad, Abbvie, Tesaro / GSK, Sanofi, Daiichi-Sankyo, Beigene, outside of the submitted work. MSch has nothing to disclose. MS reports personal fees from Lilly, Astra-Zeneca, Bristol-Myers & Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Roche, AbbVie, Boehringer-Ingelheim, Celgene, Novartis, grants from Astra Zeneca outside the submitted work. NR reports personal fees from Amgen, personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, personal fees from Daiichi Sankyo, personal fees from GSK, personal fees from Hoffmann-La Roche, personal fees from Janssen, personal fees from MSD, personal fees from Merck, personal fees from Lilly, personal fees from Pfizer, personal fees from Takeda, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Borderline personality disorder (BPD) is a severe psychiatric disorder conceptualised as a disorder of emotion regulation. Emotion regulation has been linked to a frontolimbic network comprising the dorsolateral prefrontal cortex and the amygdala, which apparently synchronises its activity via oscillatory coupling in the theta frequency range., Aims: To analyse whether there are distinct differences in theta oscillatory coupling in frontal brain regions between individuals with BPD and matched controls during emotion regulation by cognitive reappraisal., Method: Electroencephalogram (EEG) recordings were performed in 25 women diagnosed with BPD and 25 matched controls during a cognitive reappraisal task in which participants were instructed to downregulate negative emotions evoked by aversive visual stimuli. Between- and within-group time-frequency analyses were conducted to analyse regulation-associated theta activity (3.5-8.5 Hz)., Results: Oscillatory theta activity differed between the participants with BPD and matched controls during cognitive reappraisal. Regulation-associated theta increases were lower in frontal regions in the BPD cohort compared with matched controls. Functional connectivity analysis for regulation-associated changes in the theta frequency band revealed a lower multivariate interaction measure (MIM) increase in frontal brain regions in persons with BPD compared with matched controls., Conclusions: Our findings support the notion of alterations in a frontal theta network in BPD, which may be underlying core symptoms of the disorder such as deficits in emotion regulation. The results add to the growing body of evidence for altered oscillatory brain dynamics in psychiatric populations, which might be investigated as individualised treatment targets using non-invasive stimulation methods.

Background: Patients with choledocholithiasis are often treated with endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Upfront LC, intraoperative cholangiogram (IOC), and possible transcystic laparoscopic common bile duct exploration (LCBDE) could potentially avoid the need for ERCP. We hypothesized that upfront LC + IOC ± LCBDE will decrease length of stay (LOS) and the total number of interventions for children with suspected choledocholithiasis., Methods: A multicenter, retrospective cohort study was performed on pediatric patients (<18 years) between 2018 and 2022 with suspected choledocholithiasis. Demographic and clinical data were compared for upfront LC + IOC ± LCBDE and possible postoperative ERCP (OR1st) versus preoperative ERCP prior to LC (OR2nd). Complications were defined as postoperative pancreatitis, recurrent choledocholithiasis, bleeding, or abscess., Results: Across four centers, 252 children with suspected choledocholithiasis were treated with OR1st (n = 156) or OR2nd (n = 96). There were no differences in age, gender, or body mass index. Of the LCBDE patients (72/156), 86% had definitive intraoperative management with the remaining 14% requiring postoperative ERCP. Complications were fewer and LOS was shorter with OR1st (3/156 vs. 15/96; 2.39 vs 3.84 days, p < 0.05)., Conclusion: Upfront LC + IOC ± LCBDE for children with choledocholithiasis is associated with fewer ERCPs, lower LOS, and decreased complications. Postoperative ERCP remains an essential adjunct for patients who fail LCBDE. Further educational efforts are needed to increase the skill level for IOC and LCBDE in pediatric patients with suspected choledocholithiasis., Level of Evidence: Level III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

For evaluating the quality of care provided by hospitals, special interest lies in the identification of performance outliers. The classification of healthcare providers as outliers or non-outliers is a decision under uncertainty, because the true quality is unknown and can only be inferred from an observed result of a quality indicator. We propose to embed the classification of healthcare providers into a Bayesian decision theoretical framework that enables the derivation of optimal decision rules with respect to the expected decision consequences. We propose paradigmatic utility functions for two typical purposes of hospital profiling: the external reporting of healthcare quality and the initiation of change in care delivery. We make use of funnel plots to illustrate and compare the resulting optimal decision rules and argue that sensitivity and specificity of the resulting decision rules should be analyzed. We then apply the proposed methodology to the area of hip replacement surgeries by analyzing data from 1,277 hospitals in Germany which performed over 180,000 such procedures in 2017. Our setting illustrates that the classification of outliers can be highly dependent upon the underlying utilities. We conclude that analyzing the classification of hospitals as a decision theoretic problem helps to derive transparent and justifiable decision rules. The methodology for classifying quality indicator results is implemented in an R package (iqtigbdt) and is available on GitHub., (© 2022 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Mesothelial inclusion cysts are rare benign tumors not frequently reported in the literature. When reported, they are primarily found in adults. One report from 2006 reports an association with Beckwith-Weideman syndrome, but no other reported cases discuss this correlation. We describe a case of an infant with Beckwith-Weideman syndrome who, in the setting of omphalocele repair, was found to have hepatic cysts with pathology revealing mesothelial inclusion cysts.

In Germany, the use of quality data to support hospital capacity planning was introduced in 2017. On behalf of the Federal Joint Committee, IQTIG suggested 11 quality indicators and developed a program on how to collect, evaluate and report data for the clinical areas gynaecological surgery, obstetrics and breast surgery. By analysing data from 2015 to 2021, effects of the introduction of the program on indicator results, statistical discrepancies and impact on care quality are examined. Effects on capacity planning are discussed. Since the program started, indicator results improved in all clinical areas, and statistical discrepancies and the number of assessments with insufficient quality decreased due to enhanced adherence to quality standards and data validity. Effects on capacity planning or the allocation of hospitals have not occurred. Thus, a change of the legal basis to allow a better link between quality and hospital planning is recommended. The approach to use quality data on hospital regulation in Germany is evolving. The current hospital reform in Germany also addresses other approaches to quality-based regulation. Already now, there have been clear improvements in specific indicators as well as lessons for quality assurance and its link to capacity planning provided by the program, which are also applicable to other countries., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD., Methods: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity., Results: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention., Conclusions: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: One of the most important cognitive functions in our everyday life is the working memory (WM). In several neuropsychiatric diseases such as ADHD or schizophrenia WM deficits can be observed, making it an attractive target for non-invasive brain stimulation methods like transcranial electrical stimulation (tES). However, the literature shows rather heterogeneous results of tES effects on WM performance. fMRI meta-analyses have identified a WM network including frontoparietal brain areas such as the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Neurophysiological studies revealed oscillatory activity in the theta band frequency range to be of crucial functional relevance for WM processes. Based on this, transcranial alternating current stimulation (tACS) in the theta frequency range targeting DLPFC and PPC in a spatially optimized way might further improve effects of tES on WM performance., Methods: Sixteen healthy subjects were stimulated with varying stimulation settings on four different days in a counterbalanced within-subject design. These setups included the application of (1) tACS with a frequency of 5 Hz (theta frequency range) over the left DLPFC and (2) the right superior parietal cortex, (3) transcranial direct current stimulation (tDCS) of the DLPFC and (4) a sham stimulation condition during the online performance of a visual delayed-match-to-sample task with varying working memory load. We introduce a procedure to calculate an optimal tES model revealing optimized high-density setups for the present study for 3 cathodes and 1 anode and stimulation currents of 1.5 mA., Results: A significant interaction effect of stimulation type and load condition on working memory capacity was found. This was reflected by a significant improvement of WM performance in the high load condition during tACS over the left DLPFC compared with sham stimulation, which was not the case for our parietal tACS or tDCS setup., Discussion: Working memory performance can be improved with optimized high-definition tACS with a frequency of 5 Hz over the left DLPFC. The conception of different mechanisms underlying transcranial electrical stimulation with alternating and direct currents is supported by these results. Patients suffering from working memory impairments due to neuropsychiatric diseases might potentially benefit from this brain stimulation approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rauh, Müller, Nolte, Haaf, Mußmann, Steinmann, Mulert and Leicht.)

Objectives: Disrupted auditory networks play an important role in the pathophysiology of psychosis, with abnormalities already observed in individuals at clinical high-risk for psychosis (CHR). Here, we examine structural and functional connectivity of an auditory network in CHR utilising state-of-the-art electroencephalography and diffusion imaging techniques., Methods: Twenty-six CHR subjects and 13 healthy controls (HC) underwent diffusion MRI and electroencephalography while performing an auditory task. We investigated structural connectivity, measured as fractional anisotropy in the Arcuate Fasciculus (AF), Cingulum Bundle, and Superior Longitudinal Fasciculus-II. Gamma-band lagged-phase synchronisation, a functional connectivity measure, was calculated between cortical regions connected by these tracts., Results: CHR subjects showed significantly higher structural connectivity in the right AF than HC ( p < .001). Although non-significant, functional connectivity between cortical areas connected by the AF was lower in CHR than HC ( p = .078). Structural and functional connectivity were correlated in HC ( p = .056) but not in CHR ( p = .29)., Conclusions: We observe significant differences in structural connectivity of the AF, without a concomitant significant change in functional connectivity in CHR subjects. This may suggest that the CHR state is characterised by a decoupling of structural and functional connectivity, possibly due to abnormal white matter maturation.

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30-100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation.

Endocannabinoids (eCBs) are involved in buffering threat and stress responses. Elevation of circulating eCBs in humans was reported to strengthen inhibition (i.e., extinction) of threat responses and to reduce effects of stressors. However, it remains unclear whether the acquisition of threat responses involves a physiological change in circulating eCBs. Here, we demonstrate in male human volunteers that the plasma concentration of the eCB N-arachidonoylethanolamine (AEA) and its metabolite arachidonic acid (AA) are increased during acquisition of threat responses. Furthermore, elevated responses to a learned threat cue (e.g., rating of fear) were associated with individual increases in plasma concentration of the eCB 2-arachidonoylglycerol (2-AG). In complementing these observations, we found individual increases in AEA associated with elevated neural responses during threat learning in the amygdala. Our results thereby suggest that physiological increases in circulating eCB levels are part of a response mechanism to learned threats., (© 2022. The Author(s).)

While the place of birth plays a crucial role for women's birth experiences, the interest in out-of-hospital births has increased during the Covid-19 pandemic. Related to this, various international policies recommend enabling women to choose where to give birth. We aimed to analyze Swiss women's choice between birth hospitals and birth centers. Employing spatial accessibility analysis, we incorporated four data types: highly disaggregated population data, administrative data, street network data, addresses of birth hospitals and birth centers. 99.8% of Swiss women of childbearing age were included in the analysis (N = 1.896.669). We modelled car travel times from a woman's residence to the nearest birth hospital and birth center. If both birth settings were available within 30 minutes, a woman was considered to have a true choice. Only 58.2% of women had a true choice. This proportion varied considerably across Swiss federal states. The main barrier to a true choice was limited accessibility of birth centers. Median travel time to birth hospitals was 9.8 (M = 12.5), to birth centers 23.9 minutes (M = 28.5). Swiss women are insufficiently empowered to exercise their reproductive autonomy as their choice of place of birth is significantly limited by geographical constraints. It is an ethical and medical imperative to provide women with a true choice. We provide high-resolution insights into the accessibility of birth settings and strong arguments to (re-)examine the need for further birth centers (and birth hospitals) in specific geographical areas. Policy-makers are obligated to improve the accessibility of birth centers to advance women's autonomy and enhance maternal health outcomes after childbirth. The Covid-19 pandemic offers an opportunity to shift policy., Competing Interests: The authors have declared that no competing interests exist.

Smoking is highly prevalent among patients with anxiety disorders. Previous studies suggest that smokers show altered fear learning as compared to non-smokers. To test the effect of acute smoking on fear learning and generalization, we conducted a fear learning experiment online. 202 healthy subjects learned to differentiate a danger and a safe cue on day 1 and were tested for generalization of threat responses 24 h later. To see if the timing of smoking impacts fear learning, we formed three smoker groups with manipulations of acute smoking and withdrawal at different time-points (each group: n = 46) and one non-smoker control group (n = 64). Smoking manipulations contained a 6 h withdrawal after fear learning, smoking directly before or after fear learning. We found no group differences between smoker manipulation groups for fear learning or generalization. However, we found differences in fear generalization between smokers and non-smokers. Smokers showed increased fear ratings towards the stimulus that has been learned as safe and higher US expectancy to stimuli similar to the safe stimulus, when compared to non-smokers. Smoking might constitute a risk factor for impaired discrimination between danger and safety and smoking restrictions could be an effective way to reduce the risks of development or maintenance of anxiety disorders., (© 2022. The Author(s).)

Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease. Moreover, this oscillatory change can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR, through NMDA-receptor co-agonism, accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the PANSS. S-Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants' threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants' treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders., (© 2022. The Author(s).)

Competing Interests: G. Heller und T. Thomas: berufliche Tätigkeit für das IQTIG. Diese Arbeit wurde außerhalb der beruflichen Tätigkeit für das IQTIG erstellt. R. Rossi: Berater für den GKV-SV in der AG QFR-RL und AG Mindestmengen beim G-BA. R. F. Maier: Berater für den GKV-SV in der AG QFR-RL beim G-BA, Mitglied in den Fachgruppen auf Bundes- und Landesebene. M. Gutzeit, J. Rauh und J. Cederbaum geben keine Interessenskonflikte an.

Neural oscillations are fundamental mechanisms of the human brain that enable coordinated activity of different brain regions during perceptual and cognitive processes. A frontotemporal network generated by means of gamma oscillations and comprising the auditory cortex (AC) and the anterior cingulate cortex (ACC) has been shown to be involved in the cognitively demanding auditory information processing. This study aims to reveal patterns of functional and effective connectivity within this network in healthy subjects by means of simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We simultaneously recorded EEG and fMRI in 28 healthy subjects during the performance of a cognitively demanding auditory choice reaction task. Connectivity between the ACC and AC was analysed employing EEG and fMRI connectivity measures. We found a significant BOLD signal correlation between the ACC and AC, a significant task-dependant increase of fMRI connectivity (gPPI) and a significant increase in functional coupling in the gamma frequency range between these regions (LPS), which was increased in top-down direction (granger analysis). EEG and fMRI connectivity measures were positively correlated. The results of these study point to a role of a top-down influence of the ACC on the AC executed by means of gamma synchronisation. The replication of fMRI connectivity patterns in simultaneously recorded EEG data and the correlation between connectivity measures from both domains found in our study show, that brain connectivity based on the synchronisation of gamma oscillations is mirrored in fMRI connectivity patterns., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Previous studies using imaging techniques such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) have identified neurophysiological markers of impaired feedback processing in patients with Borderline Personality Disorder (BPD). These mainly include reduced oscillatory activity in the theta frequency range in the EEG and altered activations in frontal and striatal regions in fMRI studies. The aim of the present study is to integrate these results using a coupling of simultaneously recorded EEG and fMRI. Simultaneous EEG (64-channel) and fMRI (3-Tesla Siemens Prisma) was recorded whilst participants (19 BPD patients and 18 controls) performed a gambling task. Data was analysed for the two imaging techniques separately as well as in a single-trial coupling of both modalities. Evoked theta oscillatory power as a response to loss feedback was reduced in BPD patients. EEG-fMRI coupling revealed an interaction between feedback valence and group in prefrontal regions centering in the dorsolateral prefrontal cortex (dlPFC), with healthy controls showing stronger modulation by theta responses during loss when compared to gain feedback and the opposite effect in BPD patients. Our results show multiple alterations in the processing of feedback in BPD, which were partly linked to impulsivity. The dlPFC was identified as the seed of theta-associated activation differences., (© 2021. The Author(s).)

Restless leg syndrome (RLS) is a common cause of lower extremity discomfort. We hypothesized that patients with RLS symptoms have higher rates of deep and superficial venous reflux (SVR). Retrospective review of patients ≥18 years of age evaluated in a venous center from December 2018 to February 2019. Differences in rates of RLS symptoms, demographics, comorbidities, and clinical and radiologic presence of venous disease were analyzed. Overall, 207 patients were analyzed; 140 (67.6%) reported RLS symptoms ( n  = 25 with prior RLS diagnosis). RLS symptoms were more common with superficial or combined superficial and deep venous reflux (DVR) compared with those without reflux ( p  < 0.001). Patients with RLS symptoms as opposed to those without had similar demographics and comorbidities (all p  > 0.05) but increased rates of venous pain, phlebitis, family history of venous disease, lower extremity swelling and SVR, and combined SVR and DVR (all p  < 0.05). Our multivariable logistic regression found presence of SVR, and family history of venous reflux was associated with RLS symptomatology (all p  < 0.001). Ninety-nine patients with RLS underwent ablation; of them, 93 had duplex-proven reflux resolution of which 81 (87%) reported RLS symptom improvement. This included 13 of 16 (81.3%) with prior RLS diagnosis. SVR is associated with increased rates of RLS symptoms in a vein center population. Therefore, RLS symptoms should trigger a targeted venous evaluation. Our results suggest that venous ablation may lead to resolution of RLS symptoms in patients with SVR, but randomized prospective trials with strict RLS definition criteria are warranted to confirm these outcomes., Competing Interests: Conflict of Interest None declared., (International College of Angiology. This article is published by Thieme.)

Background: Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care., Methods: Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof-of-concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population-based Cancer Registry of Bavaria were linked at the district level., Results: Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho-oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes., Conclusions: Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high-quality health care to all inhabitants, regardless of residence., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Rapid accessibility of (intensive) medical care can make the difference between life and death. Initial care in case of strokes is highly dependent on the location of the patient and the traffic situation for supply vehicles. In this methodologically oriented paper we want to determine the inequivalence of the risks in this respect., Methods: Using GIS we calculate the driving time between Stroke Units in the district of Münster, Germany for the population distribution at day- & nighttime. Eight different speed scenarios are considered. In order to gain the highest possible spatial resolution, we disaggregate reported population counts from administrative units with respect to a variety of factors onto building level., Results: The overall accessibility of urban areas is better than in less urban districts using the base scenario. In that scenario 6.5% of the population at daytime and 6.8% at nighttime cannot be reached within a 30-min limit for the first care. Assuming a worse traffic situation, which is realistic at daytime, 18.1% of the population fail the proposed limit., Conclusions: In general, we reveal inequivalence of the risks in case of a stroke depending on locations and times of the day. The ability to drive at high average speeds is a crucial factor in emergency care. Further important factors are the different population distribution at day and night and the locations of health care facilities. With the increasing centralization of hospital locations, rural residents in particular will face a worse accessibility situation.

Objective: Sexual dimorphism has been investigated in schizophrenia, although sex-specific differences among individuals who are at clinical high-risk (CHR) for developing psychosis have been inconclusive. This study aims to characterize sexual dimorphism of language areas in the brain by investigating the asymmetry of four white matter tracts relevant to verbal working memory in CHR patients compared to healthy controls (HC). HC typically show a leftward asymmetry of these tracts. Moreover, structural abnormalities in asymmetry and verbal working memory dysfunctions have been associated with neurodevelopmental abnormalities and are considered core features of schizophrenia. Methods: Twenty-nine subjects with CHR (17 female/12 male) for developing psychosis and twenty-one HC (11 female/10 male) matched for age, sex, and education were included in the study. Two-tensor unscented Kalman filter tractography, followed by an automated, atlas-guided fiber clustering approach, were used to identify four fiber tracts related to verbal working memory: the superior longitudinal fasciculi (SLF) I, II and III, and the superior occipitofrontal fasciculus (SOFF). Using fractional anisotropy (FA) of tissue as the primary measure, we calculated the laterality index for each tract. Results: There was a significantly greater right>left asymmetry of the SLF-III in CHR females compared to HC females, but no hemispheric difference between CHR vs. HC males. Moreover, the laterality index of SLF-III for CHR females correlated negatively with Backward Digit Span performance, suggesting a greater rightward asymmetry was associated with poorer working memory functioning. Conclusion: This study suggests increased rightward asymmetry of the SLF-III in CHR females. This finding of sexual dimorphism in white matter asymmetry in a language-related area of the brain in CHR highlights the need for a deeper understanding of the role of sex in the high-risk state. Future work investigating early sex-specific pathophysiological mechanisms, may lead to the development of novel personalized treatment strategies aimed at preventing transition to a more chronic and difficult-to-treat disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Steinmann, Lyall, Langhein, Nägele, Rauh, Cetin-Karayumak, Zhang, Mussmann, Billah, Makris, Pasternak, O'Donnell, Rathi, Kubicki, Leicht, Shenton and Mulert.)

Disturbed functional connectivity is assumed to cause neurocognitive deficits in patients suffering from schizophrenia. A Glutamate N-methyl-D-aspartate receptor (NMDAR) dysfunction has been suggested as a possible mechanism underlying altered connectivity in schizophrenia, especially in the gamma- and theta-frequency range. The present study aimed to investigate the effects of the NMDAR-antagonist ketamine on resting-state power, functional connectivity, and schizophrenia-like psychopathological changes in healthy volunteers. In a placebo-controlled crossover design, 25 healthy subjects were recorded using resting-state 64-channel-electroencephalography (EEG) (eyes closed). The imaginary coherence-based Multivariate Interaction Measure (MIM) was used to measure gamma and theta connectivity across 80 cortical regions. The network-based statistic was applied to identify involved networks under ketamine. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC). Ketamine caused an increase in all PANSS ( p < 0.001) as well as 5D-ASC scores ( p < 0.01). Significant increases in resting-state gamma and theta power were observed under ketamine compared to placebo ( p < 0.05). The source-space analysis revealed two distinct networks with an increased mean functional gamma- or theta-band connectivity during the ketamine session. The gamma-network consisted of midline regions, the cuneus, the precuneus, and the bilateral posterior cingulate cortices, while the theta-band network involved the Heschl gyrus, midline regions, the insula, and the middle cingulate cortex. The current source density (CSD) within the gamma-band correlated negatively with the PANSS negative symptom score, and the activity within the gamma-band network correlated negatively with the subjective changed meaning of percepts subscale of the 5D-ASC. These results are in line with resting-state patterns seen in people who have schizophrenia and argue for a crucial role of the glutamate system in mediating dysfunctional gamma- and theta-band-connectivity in schizophrenia. Resting-state networks could serve as biomarkers for the response to glutamatergic drugs or drug development efforts within the glutamate system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Curic, Andreou, Nolte, Steinmann, Thiebes, Polomac, Haaf, Rauh, Leicht and Mulert.)

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany., Patients and Methods: A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany. Details on treatment, best response, and outcome were analyzed for patients with KRAS wildtype, G12C, and non-G12C mutations., Results: Within the study population, 160 (15.4 %) patients presented with KRAS G12C, 251 (24.2 %) with non-G12C mutations, 628 (60.4 %) with KRAS wildtype. High PD-L1 expression (Tumor Proportion Score, TPS > 50 %) was documented for 28.0 %, 43.5 %, and 28.9 % (wildtype, G12C, non-G12C) of the tested patients; 68.8 %, 89.3 %, and 87.7 % of the patients received first-line treatment combined with an immune checkpoint-inhibitor in 2019. TPS > 50 % vs. TPS < 1 % was associated with a significantly decreased risk of mortality in a multivariate Cox model (HR 0.39, 95 % CI 0.26-0.60, p=<0.001). There were no differences in clinical outcome between KRAS wildtype, G12C or non-G12C mutations and KRAS mutational status was not prognostic in the model., Conclusion: Here we describe the so far largest prospectively recruited cohort of patients with advanced NSCLC and KRAS mutations, with special focus on the G12C mutation. These data constitute an extremely valuable historical control for upcoming clinical studies that employ KRAS inhibitors., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP)., Methods: Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FA T ), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed., Results: There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP ( p FWE < 0.05). FA changes in CHR-P were associated with significantly lower FA T and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP., Conclusions: Our study suggests that cellular (FA T ) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.

Objectives: Reward system dysfunctions are considered to be a pathophysiological mechanism in schizophrenia. Electrophysiological studies of reward system functions have identified frequency-specific brain networks for the processing of positive (high-beta frequency) and negative (theta frequency) events. Remarkably, midbrain dopaminergic signalling also includes theta and high-beta frequency modes, which have been assumed to reflect tonic and phasic dopamine responses, respectively. The aim of the present study was to identify alterations of oscillatory responses to reward feedback in patients with schizophrenia., Methods: Seventeen patients with schizophrenia and 18 healthy controls performed a gambling task during recording of 64-channel electroencephalography. The theta and high-beta band total power were investigated in response to feedback events depending on feedback valence (loss or gain) and magnitude (5 vs. 25 points)., Results: Both the increase of theta oscillatory activity in response to loss feedback (compared to gain feedback) and the increase of high-beta oscillatory activity in response to gain feedback (compared to loss feedback) were reduced in patients. The difference in high-beta responses to gain versus loss feedback in patients was associated with the severity of negative symptoms., Conclusions: Our findings are consistent with current models of reward system dysfunction in schizophrenia, and indicate deficits in both cortical tonic and subcortical phasic dopamine activity, consistent with the complex dopaminergic abnormalities in schizophrenia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard therapy for patients with previously untreated diffuse large B-cell lymphomas (DLBCL). Dose-dense two-weekly 'R-CHOP-14' was not superior over three-weekly 'R-CHOP-21' in randomised clinical trials (RCTs). We present real-world data on effectiveness of R-CHOP-14 and R-CHOP-21 in patients with DLBCL treated in German routine practice., Methods: We identified 582 patients with DLBCL treated with R-CHOP-14 or R-CHOP-21 in 92 sites from the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms. Patients' schedules were classified by (a) length of the initial first cycle and (b) length of cycles 1-4., Results: About 55% of patients received R-CHOP-21, 45% R-CHOP-14, in median 6 cycles. 51% and 55% of patients, respectively, were able to continue their initial R-CHOP-14 and R-CHOP-21 schedule. While most characteristics between the patient cohorts were similar, patients receiving R-CHOP-21 presented slightly more often with tumour stage I and lower IPI risk. 3-year overall survival of patients with R-CHOP-14 and R-CHOP-21 did not differ: 84% vs 84% (first cycle), 87% vs 89% (cycles 1-4)., Conclusions: Patients with DLBCL in Germany are slightly more likely to receive R-CHOP-21 than R-CHOP-14. Both schedules are similarly effective in routine practice confirming the results from RCTs., (© 2019 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Purpose: Improving the outcome of patients with HER2-negative metastatic breast cancer experiencing tumour progression following first-line chemotherapy remains an urgent medical need. The purpose of the VicTORia trial was to show superiority of everolimus in combination with vinorelbine versus vinorelbine monotherapy as second-line chemotherapy for patients with advanced HER2 negative breast cancer., Methods: In this randomised phase II trial, 133 patients were recruited in 32 centres in Germany. Patients were randomised 1:1 to second-line chemotherapy either with vinorelbine plus everolimus (arm1) or vinorelbine alone (arm2). Primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS rate at 6 months, overall survival (OS), overall response rate (ORR) and safety. Baseline PI3 K mutational status was determined in plasma samples., Results: Median progression-free survival was not different between arms (arm1 vs. arm2: 4.01 months, 95% CI 2.40-6.09 vs. 4.08, 95% CI 2.80-5.33). PFS rate at 6 months (arm1 vs. arm2: 39.4%, 95% CI 27.6-50.9% vs. 36.6%, 95% CI 24.6-48.6%), median OS (arm1 vs. arm2: 16.3 months, 95% CI 11.4-19.0 vs. 13.8 months, 95% CI 10.2-19.1) and ORR were not different between arms. Most frequent grade 3/4 adverse events were neutropenia (50% vs. 40%), gastrointestinal toxicities (19.1% vs. 6.1%), and infections (19.1% vs. 7.7%). PI3 K mutational status was neither associated with PFS nor with OS., Conclusion: Although well tolerated, the efficacy of everolimus and vinorelbine combination therapy was not superior to vinorelbine monotherapy. There was no correlation between PI3 K mutational status and efficacy. EudracCT No 2011-001024-38, ClinicalTrials.gov No NCT01520103.

Purpose: Quality of life (QoL) plays an important role in recovery-especially after an incisive diagnosis such as breast cancer. Here, we present a comprehensive assessment of QoL for pre- and postmenopausal patients, starting from initial systemic treatment of early breast cancer until 3 years later, in patients from a so-called "real-world" setting., Methods: 251 premenopausal and 478 postmenopausal patients with early breast cancer have been recruited into the longitudinal MaLife project within the prospective, multicentre, German Tumour Registry Breast Cancer between 2011 and 2015. The questionnaires FACT-G, FACT-Taxane, FACT-ES, EORTC QLQ-BR23, BFI and HADS were filled in at start of treatment (T0), 6, 12, 24 and 36 months later. The proportion of patients with clinically meaningful changes at 36 months was determined., Results: This first interim analysis shows that the FACT-G global QoL improved over time regardless of the menopausal status. However, clinically meaningful decrease of social/family well-being (48-51%), arm symptoms (44-49%) and symptoms of neurotoxicity (55-56%) was frequently reported 3 years after start of treatment. Many premenopausal patients also reported a clinically meaningful worsening of endocrine symptoms (64%), emotional well-being (36%) and fatigue intensity (37%). Additionally, 3 years after start of treatment, 15% of the patients were classified as doubtful cases and 18% as definite cases of anxiety., Conclusions: Despite improvements in global QoL, breast cancer survivors report worsened ailments 3 years after start of therapy. Follow-up care should distinguish between premenopausal patients needing special attention for emotional/menopausal issues, and postmenopausal patients needing particular care regarding physical concerns.

Several studies using electroencephalography (EEG) demonstrate that the processing of feedback in patients suffering from borderline personality disorder (BPD) is altered in comparison to healthy controls. Differences occur in the theta (ca. 5 Hz) and high-beta frequency-ranges (ca. 20 Hz) of oscillations in response to negative and positive feedback, respectively. However, alpha (ca. 10 Hz) and low-beta (ca. 15 Hz) oscillations have also been shown to be involved in feedback processing. We hypothesized that additional alterations might occur in these frequency ranges in BPD. Eighteen patients with BPD and twenty-two healthy controls performed a gambling task while 64-channel-EEG was recorded. Induced oscillatory responses to positive (i.e. gain) and negative (i.e. loss) feedback in the alpha and low-beta frequency range were investigated. No significant differences were found in the alpha frequency range. Regarding the low-beta frequency range a significant Group (i.e. BPD vs. healthy controls) × Valence (i.e. gain vs. loss) interaction in the time frame between 600 and 700 milliseconds after feedback was found. This effect showed a significant correlation with symptom severity (assessed with the BSL-23). The results indicate that feedback processing in BPD could be more heavily altered than previously expected, with more severe symptomatology being linked to stronger alterations in oscillatory responses to feedback in the low-beta range.

This paper aims to investigate the temporal dynamics within the dorsal anterior cingulate cortex (dACC) and the rostral-ventral (rv) ACC during the interaction of emotional valence and arousal with cognitive control in patients with Schizophrenia (SZ). Although cognitive deficits in SZ are highly relevant and emotional disturbances are common, the temporal relationship of brain regions involved in the interaction of emotional and cognitive processing in SZ is yet to be determined. To address this issue, the reaction time (RT), event-related potential (ERP) and temporal dynamics of the dACC and rvACC activity were compared between SZ subjects and healthy controls (HC), using a modified emotional Stroop experiment (with factors namely congruence, arousal and valence). EEG was recorded with 64 channels and source localisation was performed using the sLORETA software package. We observed slower initial increase and lower peaks of time course activity within the dACC and rvACC in the SZ group. In this particular group, the dACC activity during late negativity was negatively correlated with a significantly higher RT in the high arousal conflict condition. In contrast to HC subjects, at the N450 window, there was no significant valence (ERP and rvACC ROI) modulation effect in the SZ subjects. Using high density EEG and source localisation, it was possible to distinguish various disturbances within the dACC and rvACC in patients with SZ, during emotion-cognition processing.

Reports linking a 'jumping-to-conclusions' bias to delusions have led to growing interest in the neurobiological correlates of probabilistic reasoning. Several brain areas have been implicated in probabilistic reasoning; however, findings are difficult to integrate into a coherent account. The present study aimed to provide additional evidence by investigating, for the first time, effective connectivity among brain areas involved in different stages of evidence gathering. We investigated evidence gathering in 25 healthy individuals using fMRI and a new paradigm (Box Task) designed such as to minimize the effects of cognitive effort and reward processing. Decisions to collect more evidence ('draws') were contrasted to decisions to reach a final choice ('conclusions') with respect to BOLD activity. Psychophysiological interaction analysis was used to investigate effective connectivity. Conclusion events were associated with extensive brain activations in widely distributed brain areas associated with the task-positive network. In contrast, draw events were characterized by higher activation in areas assumed to be part of the task-negative network. Effective connectivity between the two networks decreased during draws and increased during conclusion events. Our findings indicate that probabilistic reasoning may depend on the balance between the task-positive and task-negative network, and that shifts in connectivity between the two may be crucial for evidence gathering. Thus, abnormal connectivity between the two systems may significantly contribute to the jumping-to-conclusions bias., (Copyright © 2018 Elsevier Inc. All rights reserved.)