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Abstract Functional neuroimaging has contributed substantially to understanding brain function but is dominated by group analyses that index only a fraction of the variation in these data. It is increasingly clear that parsing the underlying heterogeneity is crucial to understand individual differences and the impact of different task manipulations. We estimate large-scale (N = 7728) normative models of task-evoked activation during the Emotional Face Matching Task, which enables us to bind heterogeneous datasets to a common reference and dissect heterogeneity underlying group-level analyses. We apply this model to a heterogenous patient cohort, to map individual differences between patients with one or more mental health diagnoses relative to the reference cohort and determine multivariate associations with transdiagnostic symptom domains. For the face>shapes contrast, patients have a higher frequency of extreme deviations which are spatially heterogeneous. In contrast, normative models for faces>baseline have greater predictive value for individuals’ transdiagnostic functioning. Taken together, we demonstrate that normative modelling of fMRI task-activation can be used to illustrate the influence of different task choices and map replicable individual differences, and we encourage its application to other neuroimaging tasks in future studies.

Abstract Background Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people’s feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples. Methods In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns. Results We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment. Limitations Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations. Conclusions Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.

Abstract Background Immune checkpoint inhibitors (ICI) show remarkable results in cancer treatment, but at the cost of immune‐related adverse events (irAE). irAE can be difficult to differentiate from infections or tumor progression, thereby challenging treatment, especially in the emergency department (ED) where time and clinical information are limited. As infections are traceable in blood, we were interested in the added diagnostic value of routinely measured hematological blood cell characteristics in addition to standard diagnostic practice in the ED to aid irAE assessment. Methods Hematological variables routinely measured with our hematological analyzer (Abbott CELL‐DYN Sapphire) were retrieved from Utrecht Patient Oriented Database (UPOD) for all patients treated with ICI who visited the ED between 2013 and 2020. To assess the added diagnostic value, we developed and compared two models; a base logistic regression model trained on the preliminary diagnosis at the ED, sex, and gender, and an extended model trained with lasso that also assessed the hematology variables. Results A total of 413 ED visits were used in this analysis. The extended model showed an improvement in performance (area under the receiver operator characteristic curve) over the base model, 0.79 (95% CI 0.75–0.84), and 0.67 (95% CI 0.60–0.73), respectively. Two standard blood count variables (eosinophil granulocyte count and red blood cell count) and two advanced variables (coefficient of variance of neutrophil depolarization and red blood cell distribution width) were associated with irAE. Conclusion Hematological variables are a valuable and inexpensive aid for irAE diagnosis in the ED. Further exploration of the predictive hematological variables could yield new insights into the pathophysiology underlying irAE and in distinguishing irAE from other inflammatory conditions.

PurposeA lifestyle front office (LFO) in the hospital is a not yet existing, novel concept that can refer patients under treatment in the hospital to community-based lifestyle interventions (CBLI). The aim of this study was to identify implementation barriers and facilitators regarding the implementation of an LFO in the hospital from the perspective of CBLI-professionals and to develop evidence-based implementation strategies to reduce these identified barriers.MethodsWe conducted semi-structured interviews until data saturation, with 23 lifestyle professionals working in the community. A semi-structured topic guide was used, inquiring about (1) community-based lifestyle interventions; (2) their views about referral from the LFO; and (3) their preferences, needs and recommendations for collaboration with the LFO in the hospital. The online interviews lasted on average 46 minutes, were audio-recorded and transcribed verbatim. A thematic content analysis was conducted. Found barriers and facilitators regarding the LFO where mapped using the consolidated framework for implementation research (CFIR) whereafter evidence based strategies were developed using the CFIR-Expert Recommendations for Implementing Change Strategy Matching Tool V.1.0 (CFIR-ERIC).ResultsBarriers and facilitators were divided into two main themes: 1) barriers and facilitators related to the referral from LFO to CBLI (i.e. financial, cultural, geographical, quality) and 2) barriers and facilitators related to the collaboration between LFO and CBLI (i.e. referral, communication platform and partnership). Thirty-seven implementation strategies concerning 15 barriers were developed and clustered into six overarching strategies: identify referral options, determine qualifications lifestyle professionals, develop support tools, build networks, facilitate learning collaboratives, and optimize workflow.ConclusionsIn this study, barriers and facilitators for the development of the LFO were found and matching implementation strategies were developed. Practical improvements, like identifying specific referral options or develop support tools, can be implemented immediately. The implementation of other strategies, like connecting care pathways in basic services, primary, secondary and tertiary care, will take more time and effort to come to full potential. Future research should evaluate all implemented strategies.

Abstract Background A healthy lifestyle is indispensable for the prevention of noncommunicable diseases. However, lifestyle medicine is hampered by time constraints and competing priorities of treating physicians. A dedicated lifestyle front office (LFO) in secondary/tertiary care may provide an important contribution to optimize patient-centred lifestyle care and connect to lifestyle initiatives from the community. The LOFIT study aims to gain insight into the (cost-)effectiveness of the LFO. Methods Two parallel pragmatic randomized controlled trials will be conducted for (cardio)vascular disorders (i.e. (at risk of) (cardio)vascular disease, diabetes) and musculoskeletal disorders (i.e. osteoarthritis, hip or knee prosthesis). Patients from three outpatient clinics in the Netherlands will be invited to participate in the study. Inclusion criteria are body mass index (BMI) ≥25 (kg/m2) and/or smoking. Participants will be randomly allocated to either the intervention group or a usual care control group. In total, we aim to include 552 patients, 276 in each trial divided over both treatment arms. Patients allocated to the intervention group will participate in a face-to-face motivational interviewing (MI) coaching session with a so-called lifestyle broker. The patient will be supported and guided towards suitable community-based lifestyle initiatives. A network communication platform will be used to communicate between the lifestyle broker, patient, referred community-based lifestyle initiative and/or other relevant stakeholders (e.g. general practitioner). The primary outcome measure is the adapted Fuster-BEWAT, a composite health risk and lifestyle score consisting of resting systolic and diastolic blood pressure, objectively measured physical activity and sitting time, BMI, fruit and vegetable consumption and smoking behaviour. Secondary outcomes include cardiometabolic markers, anthropometrics, health behaviours, psychological factors, patient-reported outcome measures (PROMs), cost-effectiveness measures and a mixed-method process evaluation. Data collection will be conducted at baseline, 3, 6, 9 and 12 months follow-up. Discussion This study will gain insight into the (cost-)effectiveness of a novel care model in which patients under treatment in secondary or tertiary care are referred to community-based lifestyle initiatives to change their lifestyle. Trial registration ISRCTN ISRCTN13046877 . Registered 21 April 2022.

Abstract Background A longer emergency department length of stay (EDLOS) is associated with poor outcomes. Shortening EDLOS is difficult, due to its multifactorial nature. A potential way to improve EDLOS is through shorter turnaround times for diagnostic testing. This study aimed to investigate whether a shorter laboratory turnaround time (TAT) and time to testing (TTT) were associated with a shorter EDLOS. Methods A retrospective cohort study was performed, including all visits to the emergency department (ED) of an academic teaching hospital from 2017 to 2020 during which a standardized panel of laboratory tests had been ordered. TTT was calculated as the time from arrival in the ED to the ordering of laboratory testing. TAT was calculated as the time from test ordering to the reporting of the results, and was divided into a clinical and a laboratory stage. The outcome was EDLOS in minutes. The effect of TTT and TAT on EDLOS was estimated through a linear regression model. Results In total, 23,718 ED visits were included in the analysis. Median EDLOS was 199.0 minutes (interquartile range [IQR] 146.0–268.0). Median TTT was 7.0 minutes (IQR 2.0–12.0) and median TAT was 51.1 minutes (IQR 41.1–65.0). Both TTT and TAT were positively associated with EDLOS. The laboratory stage comprised a median of 69% (IQR 59–78%) of total TAT. Conclusion Longer TTT and TAT are independently associated with longer EDLOS. As the laboratory stage predominantly determines TAT, it provides a promising target for interventions to reduce EDLOS and ED crowding.

Abstract Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum—a central hub in motor, cognitive, affective and reward-related brain circuits—and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

Abstract Negative memory bias refers to the enhanced recall of negative memories and is a prominent cognitive factor causing and maintaining depression. Surprisingly few studies modify this negative recall. The current study used a smartphone-based autobiographical memory training to increase positive memory recall and thereby alter negative memory bias. A total of 96 dysphoric (≥ 13 BDI-II) participants were randomly allocated to a positive, sham or no-training condition, conducted over a period of 6 days. Positive memory bias (i.e., recalled event evaluation) significantly increased from pre- to post-training after positive and sham intervention, suggesting an unspecific training effect. No transfer to memory specificity, implicit memory bias or depressive symptoms was found, nor was the training effect modulated by pre-existing level of positive memory bias. A post-hoc follow-up measurement during the initial COVID-19 crisis revealed that subjects who benefitted most from either of the trainings maintained their stress levels better during a natural stressful period, compared to those who responded least to the training. Future studies should carefully consider the impact of sham training design. Moreover, it is important to examine transfer effects of bias training as practice in daily life.

Heightened attention towards negative information is characteristic of depression. Evidence is emerging for a negative attentional bias in Autism spectrum disorder (ASD), perhaps driven by the high comorbidity between ASD and depression. We investigated whether ASD is characterised by a negative attentional bias and whether this can be explained by comorbid (sub) clinical depression. Participants (n = 116) with current (CD) or remitted depression (RD) and/or ASD, and 64 controls viewed positively and negatively valenced (non-)social pictures. Groups were compared on three components of visual attention using linear mixed models. Both CD individuals with and without ASD, but not remitted depressed and never-depressed ASD individuals showed a negative bias, suggesting that negative attentional bias might be a depressive state-specific marker for depression in ASD.

In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health-related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus, and thalamus across the different modalities of this component may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems, and sensitivity to sensory stimuli, respectively. Taken together, the findings from our extensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.

Case summary A 12-year-old neutered female domestic shorthair cat was presented with bilateral progressive forelimb lameness that was unresponsive to anti-inflammatory drugs. Bilateral carpal flexural deformity with hyperflexion of multiple toes of the right forelimb was observed. In the absence of abnormalities detected on radiographs and ultrasound, a bilateral contracture of the carpal and digital flexor muscles was diagnosed. Treatment consisted of single-session bilateral selective tenectomies (5 mm) of the flexor carpi ulnaris, flexor carpi radialis and superficial digital flexor muscle tendons on the left forelimb and tendons of the flexor carpi ulnaris muscle, and branches of the third and fourth digit of the deep digital flexor muscle on the right forelimb. Two months postoperatively, selective tenectomies (10 mm) were performed due to contracture recurrence on the left forelimb. The subjective outcome was rated as good 6 months postoperatively. Relevance and novel information Digital and/or carpal contractures are rarely described in (feline) veterinary medicine and are limited to a few case reports. The exact aetiology remains unknown. A traumatic/iatrogenic origin seems to be the most likely cause. Surgery is indicated, consisting of selective tenectomy and/or tenotomy, and is associated with minor complications and an excellent outcome. This case report describes the presence, treatment and successful outcome of a cat with bilateral carpal and digital flexor muscle contractures resulting in carpal flexural deformity with valgus deviation treated with selective tenectomies.

Childhood adversity (CA), including childhood adverse life events, increases the risk for development of psychiatric disorders later in life. Both CA and psychiatric disorders are associated with structural brain changes and dysfunctional hypothalamic–pituitary–adrenal‐axis. However, many studies investigated single diagnostic and single regions of interest of the brain, and did not take stress reactivity into account. We investigated associations of CA and cortisol levels with gray matter volume and cortical thickness, in a whole‐brain manner. Primary analysis constituted of a transdiagnostic approach, followed by a moderation analysis to investigate the influence of diagnosis. Patients with stress‐related and/or neurodevelopmental disorders and matched healthy controls underwent an magnetic resonance imaging scan, next to assessing hair cortisol levels and CA/life events. CA was reported by 62–72% of the patients versus 33% of the controls. Primary transdiagnostic linear regression analyses revealed that CA was not associated with gray matter volume, while childhood life events were associated with lower right thalamic volume. Hair cortisol was not associated with any lobe volume. None of the associations were moderated by diagnosis. In conclusion, CA is a risk factor that needs to be taken into account when investigating psychiatric disorders. Yet the relationship with structural brain changes and stress reactivity is less clear than postulated on the basis of more seed‐based studies. [ABSTRACT FROM AUTHOR]

Cryogenic environments benefit ion trapping experiments by offering lower motional heating rates, collision energies, and an ultrahigh vacuum (UHV) environment for maintaining long ion chains for extended periods of time. Mechanical vibrations caused by compressors in closed-cycle cryostats can introduce relative motion between the ion and the wavefronts of lasers used to manipulate the ions. Here, we present a novel ion trapping system where a commercial low-vibration closed-cycle cryostat is used in a custom monolithic enclosure. We measure mechanical vibrations of the sample stage using an optical interferometer, and observe a root-mean-square relative displacement of 2.4 nm and a peak-to-peak displacement of 17 nm between free-space beams and the trapping location. We packaged a surface ion trap in a cryopackage assembly that enables easy handling while creating a UHV environment for the ions. The trap cryopackage contains activated carbon getter material for enhanced sorption pumping near the trapping location, and source material for ablation loading. Using $^{171}$Yb$^{+}$ as our ion, we estimate the operating pressure of the trap as a function of package temperature using phase transitions of zig-zag ion chains as a probe. We measured the radial mode heating rate of a single ion to be 13 quanta/s on average. The Ramsey coherence measurements yield 330-ms coherence time for counter-propagating Raman carrier transitions using a 355-nm mode-locked pulse laser, demonstrating the high optical stability.

Abstract Background Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change. Methods In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli). Discussion The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD. Trial registration This trial is registered in the Netherlands Trial Register (code: NL7639 ). Registered 3 april 2019.

BackgroundThe chronic nature of depression and limited availability of evidence-based treatments emphasize the need for complementary recovery-oriented services, such as peer support interventions (PSIs). Peer support is associated with positive effects on clinical and personal recovery from mental illness, but little is known about the processes of engagement that foster change, and studies targeting individuals with depression specifically are limited. ObjectiveThis study aimed to evaluate whether the level of user engagement, assessed on several dimensions, in an online peer support community for individuals with depression promotes empowerment and the use of self-management strategies and reduces symptom severity and disability. MethodsIn a longitudinal survey conducted from June 2019 to September 2020, we analyzed the data of the users of Depression Connect (DC), an online peer support community hosted by the Dutch Patient Association for Depression and the Pro Persona Mental Health Care institute, on measures of empowerment, self-management, depression, and disability. Of the 301 respondents, 49 (16.3%) respondents completed the survey again after 3 months and 74 (24.6%) respondents, after 6 months. Analysis of 3 parameters (ie, total time spent on the platform, number of page views, and number of posts) derived from their data logs yielded 4 engagement profiles. Linear mixed models were fitted to determine whether the outcomes had significantly changed over time and differed for the various profiles. ResultsBaseline engagement with the online peer support community was “very low” (177/301, 58.8%) or “low” (87/301, 28.9%) for most of the participants, with few showing “medium” (30/301, 9.9%) or “high” engagement patterns (7/301, 2.3%), while user profiles did not differ in demographic and clinical characteristics. Empowerment, self-management, depressive symptoms, and disability improved over time, but none were associated with the intensity or nature of user engagement. ConclusionsWith most DC members showing very low to low engagement and only a few being identified as high-engaged users, it is likely that this flexibility in use frequency is what provides value to online PSI users. In other more formal supportive environments for depression, a certain level of engagement is predetermined either by their organizational or by their societal context; at DC, users can adapt the intensity and nature of their engagement to their current needs on their personal road to recovery. This study added to the current knowledge base on user engagement for PSIs because previous studies targeting depression with an online format focused on active users, precluding passive and flexible engagement. Future studies should explore the content and quality of the interactions in online PSIs to identify optimal user engagement as a function of current, self-reported clinical parameters and reasons to engage in the PSI.

Abstract Background Individuals with a parental family history of dementia have an increased risk of developing dementia because they share their genes as well as their psychosocial behaviour. Due to this increased risk and their experience with dementia, they may be particularly eager to receive information regarding dementia risk reduction (DRR). This study evaluated the knowledge, beliefs and attitudes towards dementia and DRR among descendants of people with dementia. Method Using a semi-structured topic guide, three focus group discussions were conducted consisting of 12 female (80%) and 3 male (20%) descendants of people with dementia with a mean (± SD) age of 48.8 (± 12) years. Focus group discussions were audio recorded and transcribed. Each transcript was analysed thoroughly, and where appropriate, a code was generated and assigned by two researchers independently. Then, similar codes were grouped together and categorized into themes. Results The items in the topic guide could only be addressed after participants had been given the opportunity to share their experiences of having a parent with dementia. Participants were unaware or uncertain about the possibility of reducing the risk of developing dementia and therefore hesitant to assess their dementia risk without treatment options in sight. Moreover, participants indicated that their general practitioner only gave some information on heritability, not on DRR. Although participants identified a large number of modifiable risk factors as a group during the group discussions, they were eager to receive more information on dementia and DRR. In the end, participants adopted a more positive attitude towards a DRR programme and provided suggestions for the development of future DRR programmes. Conclusions Although the research aim was to evaluate the knowledge, beliefs and attitudes towards dementia and DRR, sharing experiences of having a parent with dementia seemed a prerequisite for considering participants’ own risk of developing dementia and participating in a DRR programme. Knowledge of dementia and DRR was limited. Due to unawareness of the possibility of reducing dementia risk, participants were hesitant about assessing their dementia risk. Group discussions positively changed the perception of dementia risk assessment and participants’ willingness to participate in a DRR programme.