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Abstract Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson’s disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic “Parkinson-Disease-related-Pattern (PDRP)”-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient’s FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.

Abstract Background The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. Methods Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. Results Youth with an eating disorder (n = 65, M age = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, M age = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). Conclusions These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.

Abstract Purpose This study investigated the association between childhood eating behaviors and cortical morphology, in relation to sex and age, in a community sample. Methods Neuroimaging data of 71 children (mean age = 9.9 ± 1.4 years; 39 boys/32 girls) were obtained from the Nathan Kline Institute-Rockland Sample. Emotional overeating, food fussiness, and emotional undereating were assessed using the Children’s Eating Behavior Questionnaire. Cortical thickness was obtained at 81,924 vertices covering the entire cortex. Generalized Linear Mixed Models were used for statistical analysis. Results There was a significant effect of sex in the association between cortical thickness and emotional overeating (localized at the right postcentral and bilateral superior parietal gyri). Boys with more emotional overeating presented cortical thickening, whereas the opposite was observed in girls (p

Background Suboptimal treatment outcomes contribute to the high disease burden of mood, anxiety or psychotic disorders. Clinical prediction models could optimise treatment allocation, which may result in better outcomes. Whereas ample research on prediction models is performed, model performance in other clinical contexts (i.e. external validation) is rarely examined. This gap hampers generalisability and as such implementation in clinical practice. Aims Systematically appraise studies on externally validated clinical prediction models for estimated treatment outcomes for mood, anxiety and psychotic disorders by (1) reviewing methodological quality and applicability of studies and (2) investigating how model properties relate to differences in model performance. Method The review and meta-analysis protocol was prospectively registered with PROSPERO (registration number CRD42022307987). A search was conducted on 8 November 2021 in the databases PubMED, PsycINFO and EMBASE. Random-effects meta-analysis and meta-regression were conducted to examine between-study heterogeneity in discriminative performance and its relevant influencing factors. Results Twenty-eight studies were included. The majority of studies (n = 16) validated models for mood disorders. Clinical predictors (e.g. symptom severity) were most frequently included (n = 25). Low methodological and applicability concerns were found for two studies. The overall discrimination performance of the meta-analysis was fair with wide prediction intervals (0.72 [0.46; 0.89]). The between-study heterogeneity was not explained by number or type of predictors but by disorder diagnosis. Conclusions Few models seem ready for further implementation in clinical practice to aid treatment allocation. Besides the need for more external validation studies, we recommend close examination of the clinical setting before model implementation.

Abstract Background The impact of the COVID-19 pandemic on young people with eating disorders (EDs) and their families was profound, with surging rates of hospitalizations and referrals reported internationally. This paper provides an account of the additional health and social costs of ED care for young people living in Canada incurred during the COVID-19 pandemic, drawing attention to the available data to inform these estimates while noting gaps in data capacities to account for a full view of the ED system of care. Methods Three methodologies were used to capture costs: (1) provincial administrative data holdings available at the Canadian Institute of Health Information (CIHI) were used by Deloitte Access Economics to conduct analyses on costs related to hospitalizations, emergency room visits, outpatient visits with physicians and loss of well-being from being on a waitlist. These were examined across three fiscal years (April 1 to March 31, 2019–2022) to compare costs from one year before to two years after the onset of the pandemic, (2) data collected on support-based community ED organizations and, (3) costs identified by young people, caregivers and health care professionals. Results Estimates of additional health care costs and social costs arising from ED care waitlists were estimated to have increased by 21% across the two years after the onset of the pandemic and is likely to represent an underestimate of costs. Costs related to some standard ED care services (e.g. day treatment programs) and support-based community ED organizations that saw a 118% increase in services during this time, are some examples of costs not captured in the current cost estimate. Conclusions This paper provides a first account of the additional health and social ED care costs associated with the pandemic, which indicate at minimum, a 21% increase. The results invite discussion for more investments in ED services for young people in Canada, as it is unclear if needs are expected to remain elevated. We suggest a call for a national surveillance strategy to improve data holdings to aid in managing services and informing policy. A robust strategy could open the door for much-needed, data-informed, system transformation efforts that can improve ED care for youth, families and clinicians.

IntroductionPsychosis often develops gradually along a continuum of severity. Little is known about the role of protective factors such as positive affect (PA) in the development of psychotic experiences (PEs). This study investigated i) the temporal (between-day) and contemporaneous (within-day) daily associations between PA and PEs in individuals at different early clinical stages for psychosis and ii) whether these associations differed per clinical stage.MethodsDaily diary data for 90 days came from 96 individuals at risk for psychosis, distributed over four subgroups defined according to the clinical staging model (stages 0–1b). We constructed multilevel models with PA as a predictor of PEs and vice versa. We investigated within- and between-person temporal and contemporaneous associations and tested whether these associations differed among early stages with multilevel moderation analyses.ResultsWe found no within-person temporal effects between PA and PEs in either direction. Contemporaneously, current-day PA predicted current-day PEs (B = −0.14, p < 0.001) and vice versa (B = −0.61, p < 0.001). Between persons, more 90-day PA predicted fewer PEs in the temporal model (B = −0.14, p = 0.03). In addition, more 90-day PEs predicted PA in the temporal (B = −0.26, p < 0.001) and contemporaneous (B = −0.36, p < 0.001) models. The contemporaneous association between PA and PEs was stronger in individuals at ultra-high risk (UHR) for psychosis than in earlier stages.DiscussionOur study supported a significant within-day, bidirectional relationship between PA and PEs. This suggests that a focus on PA and methods to improve PA may be an important addition to early intervention practices, particularly in those at UHR for psychosis.

Abstract Background The onset of the COVID-19 pandemic has had an adverse impact on children, youth, and families with eating disorders (EDs). The COVID-19 pandemic exacerbated pre-existing personal and financial costs to youth, caregivers, and health professionals accessing or delivering ED services. The objectives of this mixed methods study were to (1) understand the indirect, direct medical and non-medical costs reported by youth, caregivers, and clinicians; (2) understand how the COVID-19 pandemic may have impacted these costs, and (3) explore implications of these costs with regards to barriers and resources to inform future decisions for the ED system of care. Methods Youth (aged 16–25 years) with lived/living experience, primary caregivers, clinicians, and decision-makers were recruited with support from various partners across Canada to complete group specific surveys. A total of 117 participants responded to the survey. From those respondents, 21 individuals volunteered to further participate in either a discussion group or individual interview to provide additional insights on costs. Results Youth and primary caregivers reported costs relating to private services, transportation and impacts of not attending school or work. Additionally, primary caregivers reported the top direct medical cost being special food or nutritional supplements (82.8%). In discussion groups, youth and caregivers elaborated further on the challenges with long waitlists and cancelled services, impact on siblings and effect on family dynamics. Clinicians and decision-makers reported increased work expectations (64.3%) and fear/isolation due to COVID-19 in the workplace (58.9%). Through discussion groups, clinicians expanded further on the toll these expectations took on their personal life. Approximately 1 in 3 health professionals reported contemplating leaving their position in 1–2 years, with greater than 60% of this group stating this is directly related to working during the pandemic. Conclusions Findings demonstrate the need for increased support for youth and caregivers when accessing ED services both during crisis and non-crisis times. Additionally, attention must be given to acknowledging the experience of health professionals to support better retention and resource management as they continue to navigate challenges in the health care system.

Abstract Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The “body-first subtype” is associated with a prodrome of isolated REM-sleep Behavior Disorder (iRBD) and a relatively symmetric brain degeneration. The “brain-first subtype” is suggested to have a more asymmetric degeneration and a prodromal stage without RBD. This study aims to investigate the proposed difference in symmetry of the degeneration pattern in the presumed body and brain-first PD subtypes. We analyzed 123I-FP-CIT (DAT SPECT) and 18F-FDG PET brain imaging in three groups of patients (iRBD, n = 20, de novo PD with prodromal RBD, n = 22, and de novo PD without RBD, n = 16) and evaluated dopaminergic and glucose metabolic symmetry. The RBD status of all patients was confirmed with video-polysomnography. The PD groups did not differ from each other with regard to the relative or absolute asymmetry of DAT uptake in the putamen (p = 1.0 and p = 0.4, respectively). The patient groups also did not differ from each other with regard to the symmetry of expression of the PD-related metabolic pattern (PDRP) in each hemisphere. The PD groups had no difference in symmetry considering mean FDG uptake in left and right regions of interest and generally had the same degree of symmetry as controls, while the iRBD patients had nine regions with abnormal left–right differences (p

Abstract The water footprint of a crop (WF) is a common metric for assessing agricultural water consumption and productivity. To provide an update and methodological enhancement of existing WF datasets, we apply a global process-based crop model to quantify consumptive WFs of 175 individual crops at a 5 arcminute resolution over the 1990–2019 period. This model simulates the daily crop growth and vertical water balance considering local environmental conditions, crop characteristics, and farm management. We partition WFs into green (water from precipitation) and blue (from irrigation or capillary rise), and differentiate between rainfed and irrigated production systems. The outputs include gridded datasets and national averages for unit water footprints (expressed in m3 t−1 yr−1), water footprints of production (m3 yr−1), and crop water use (mm yr−1). We compare our estimates to other global studies covering different historical periods and methodological approaches. Provided outputs can offer insights into spatial and temporal patterns of agricultural water consumption and serve as inputs for further virtual water trade studies, life cycle and water footprint assessments.

Abstract Background Evidence-based parenting programmes have strong evidence in preventing and mitigating violence, but in-person programmes are challenging to deliver at scale. ParentApp is an open-source, offline-first app-based adaptation of the Parenting for Lifelong Health for Parents and Teens programme to promote playful and positive parenting, reduce risks for sexual violence victimisation, and prevent violence against adolescents. This study aims to evaluate the effectiveness and cost-effectiveness of ParentApp compared to an attention-control group. Methods This study is a two-arm pragmatic cluster-randomised controlled trial to test whether ParentApp reduces adolescent physical abuse, emotional abuse, and sexual violence risks and victimisation at 1 month and 12 months post-intervention. Caregivers of adolescents aged 10–17 years and their adolescent children (N = 2400 caregiver-adolescent dyads) will be recruited in urban and peri-urban communities in the Mwanza region of Tanzania. A total of 80 study clusters will be stratified and randomised (1:1) to the intervention group, who will receive ParentApp with support through a WhatsApp group, or to an attention-control group, who will receive a water, sanitation, and hygiene app. Quantitative data will be collected through outcomes questionnaires with caregivers and adolescents, administered at baseline, 4 months post-baseline, and 16 months post-baseline, as well as through routine implementation data and ParentApp engagement data. Qualitative data will be collected through individual interviews and focus groups with caregivers, adolescents, and implementing partner staff. Discussion App-based interventions have the potential to expand access to evidence-based parenting support, but currently lack rigorous evidence in low- and middle-income countries. This is the first known randomised control trial of a hybrid digital parenting programme to prevent the abuse of adolescents in low- and middle-income settings. Trial registration The trial was registered on the Open Science Framework on 14 March 2023, registration: OSF.IO/T9FXZ .

Abstract Group-level studies showed associations between depressive symptoms and circadian rhythm elements, though whether these associations replicate at the within-person level remains unclear. We investigated whether changes in circadian rhythm elements (namely, rest-activity rhythm, physical activity, and sleep) occur close to depressive symptom transitions and whether there are differences in the amount and direction of circadian rhythm changes in individuals with and without transitions. We used 4 months of actigraphy data from 34 remitted individuals tapering antidepressants (20 with and 14 without depressive symptom transitions) to assess circadian rhythm variables. Within-person kernel change point analyses were used to detect change points (CPs) and their timing in circadian rhythm variables. In 69% of individuals experiencing transitions, CPs were detected near the time of the transition. No-transition participants had an average of 0.64 CPs per individual, which could not be attributed to other known events, compared to those with transitions, who averaged 1 CP per individual. The direction of change varied between individuals, although some variables showed clear patterns in one direction. Results supported the hypothesis that CPs in circadian rhythm occurred more frequently close to transitions in depression. However, a larger sample is needed to understand which circadian rhythm variables change for whom, and more single-subject research to untangle the meaning of the large individual differences.

The number of women and underrepresented individuals working in science, technology, engineering and mathematics (STEM) fields does not reflect the diversity of our societies. Even if children have an interest in STEM, they may not consider choosing a study or career in that direction if their perception is that they would not belong in science. This study examines the effects of a STEM lesson series aimed at inclusivity and diversity on children's perception and sense of belonging in space science. Before and after the lesson series, children filled out a questionnaire aimed at eliciting their perception of space science and space scientists. After the lessons, a subsample of children was interviewed about the effects of the lesson series on the children's perception and sense of belonging regarding space science. Six months after the last lesson took place, children from two classes filled out a short survey with open questions to measure retention. The results of this study showed that the lesson series had a significant impact on children's perception of space scientists, and that the implementation of the lessons facilitated thinking about (a future in) space science. This lesson series has succeeded in changing children's perception of space scientists as a diverse and international group of people.

IntroductionStudies have consistently demonstrated increased stress sensitivity in individuals with psychosis. Since stress sensitivity may play a role in the onset and maintenance of psychosis, this could potentially be a promising target for treatment. The current study was the first to investigate whether reactivity to and recovery from daily-life stressors in psychosis change in response to treatment, namely virtual-reality-based cognitive behavioral therapy (VR-CBT).Methods116 patients were randomized to either VR-CBT or the waiting list control group (WL). Pre-treatment and post-treatment participants completed a diary ten times a day during six to ten days. Multilevel analyses were used to model the time-lagged effects of daily stressful events on negative affect (NA) and paranoia symptoms to examine reactivity and recovery.ResultsThere was a significant difference in NA reactivity. VR-CBT showed higher NA at post-treatment compared to pre-treatment than WL (bpre=0.14; bpost=0.19 vs bpre=0.18; bpost=0.14). There was a significant difference in NA recovery and paranoia recovery between the groups at lag 1: VR-CBT showed relatively lower negative affect (bpre=0.07; bpost=-0.06) and paranoia (bpre= 0.08; bpost=-0.10) at post-treatment compared to pre-treatment than WL (bpre=0.08; bpost=0.08; bpre=0.04; bpost=0.03).ConclusionNegative affect and paranoia recovery improved in response to treatment. Increased NA reactivity may be explained by a decrease in safety behavior in the VR-CBT group. The discrepancy between reactivity and recovery findings may be explained by the inhibitory learning theory that suggests that an original threat reaction may not erase but can be inhibited as a consequence of exposure therapy.

Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.

Abstract Background Cross-sectional studies have shown that hyperactivity and impaired executive functioning are associated with symptoms of eating disorders in adolescence and adulthood. Whether hyperactivity and executive functions in early life can prospectively predict the emergence of eating disorder symptoms in adolescence remains unknown. The present study relies on a longitudinal design to investigate how hyperactivity at age 3, eating behaviours at age 3.5 and cognition at ages 3–6 were associated with the development of eating-disorder symptoms from 12 to 20 years old. Methods Using archival data collected since 1997 from the Quebec Longitudinal Study of Child Development cohort (N = 2, 223), we used Latent Curve Models to analyse predictors of youth’s trajectories of eating-disorder symptoms at four timepoints. Results A quadratic (curvilinear) trajectory of eating-disorder symptoms was found to be most representative of the data. Higher hyperactivity at age 3 was associated with higher levels of eating-disorder symptoms at age 12, and this association was partially mediated by higher levels of overeating and cognitive inflexibility in childhood. Cognitive inflexibility in childhood also mediated the association between hyperactivity at age 3 and increases in eating-disorder symptoms during adolescence. Furthermore, working memory was indirectly related to eating-disorder symptoms via the mediational role of cognitive flexibility. Conclusions Hyperactivity, overeating, cognitive inflexibility, and working memory early in life might precede the onset of eating-disorder symptoms in adolescence. Early behavioural and cognitive screening may help to identify children who are most at risk for eating disorders. This, in turn, could guide preventive interventions.

Abstract Background Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change. The aim of the present study was to describe the development and examine the psychometric properties, user satisfaction and rated potentials for practical use of our application. Methods The content of our application was based on concepts derived from self-determination theory, the transtheoretical model of change, and cognitive theory. The application was developed by a multidisciplinary team of clinicians, researchers, staff members and individuals with lived ED experience, each being involved in all steps of the application’s development. We tested validity, reliability, satisfaction and perceived feasibility for clinical implementation in an independent sample of 15 patients with an ED and 13 clinicians specialized in ED treatment. Psychometric properties were evaluated using descriptive statistics, correlations, content validity indices and intraclass coefficients. Differences in satisfaction ratings and perceived potential for clinical implementation of the application between clinicians and patients were examined using Mann–Whitney U tests. Results The digital application showed excellent validity (mean i-CVI: .93, range: .86–.96) and internal reliability (all Cronbach alpha’s > .88). Patients and clinicians both considered the application acceptable, appropriate, and feasible for use in clinical practice. Conclusions Findings suggest that our transdiagnostic interactive application has excellent psychometric properties. Furthermore, patients and clinicians alike were positive about the possible use of the application in clinical practice. The next step will be to investigate the application's effectiveness as an intervention to promote autonomous motivation and to facilitate remission in people on the waitlist for specialized ED treatment.

IntroductionThe COVID-19 outbreak disrupted regular health care, including the Emergency Department (ED), and resulted in insufficient ICU capacity. Lockdown measures were taken to prevent disease spread and hospital overcrowding. Little is known about the relationship of stringency of lockdown measures on ED utilization.ObjectiveThis study aimed to compare the frequency and characteristics of ED visits during the COVID-19 outbreak in 2020 to 2019, and their relation to stringency of lockdown measures.Material and methodsA retrospective multicentre study among five Dutch hospitals was performed. The primary outcome was the absolute number of ED visits (year 2018 and 2019 compared to 2020). Secondary outcomes were age, sex, triage category, way of transportation, referral, disposition, and treating medical specialty. The relation between stringency of lockdown measures, measured with the Oxford Stringency Index (OSI) and number and characteristics of ED visits was analysed.ResultsThe total number of ED visits in the five hospitals in 2019 was 165,894, whereas the total number of visits in 2020 was 135,762, which was a decrease of 18.2% (range per hospital: 10.5%-30.7%). The reduction in ED visits was greater during periods of high stringency lockdown measures, as indicated by OSI.ConclusionThe number of ED visits in the Netherlands has significantly dropped during the first year of the COVID-19 pandemic, with a clear association between decreasing ED visits and increasing lockdown measures. The OSI could be used as an indicator in the management of ED visits during a future pandemic.