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Abstract Background Few randomized trials of public health and social measures were carried out during the COVID-19 pandemic. We report on the major barriers we faced when we tried to run such trials. Methods We reviewed all randomized trials proposed and initiated by the Centre for Epidemic Interventions Research in Norway during the COVID-19 pandemic. Results Of the 18 proposed trials, 11 trials were not implemented. One of the key legal and ethical barriers to conducting the trials was the Norwegian Health Research Act, which demands informed consent from all participants who are exposed to an intervention. A lack of sufficient political support was also a challenge, as was unpredictability, due to shifting disease incidence and changing recommendations from the authorities. Conclusion Strengthening the evidence base for public health and social measures in pandemics will require political and public understanding and support and a legal framework that allows for the conduct of such trials.

Abstract Background Eating disorders (EDs), such as (atypical) Anorexia (AN) and Bulimia Nervosa (BN), are difficult to treat, causing socioeconomic impediments. Although enhanced cognitive behavioral therapy (CBT-E) is widely considered clinically effective, it may not be the most beneficial treatment for (atypical) AN and BN patients who do not show a rapid response after the first 4 weeks (8 sessions) of a CBT-E treatment. Alternatively, group schema therapy (GST) may be a valuable treatment for this ED population. Even though GST for EDs has yielded promising preliminary findings, the current body of evidence requires expansion. On top of that, data on cost-effectiveness is lacking. In light of these gaps, we aim to describe a protocol to examine whether GST is more (1) clinically effective and (2) cost-effective than CBT-E for (atypical) AN and BN patients, who do not show a rapid response after the first 4 weeks of treatment. Additionally, we will conduct (3) process evaluations for both treatments. Methods Using a multicenter RCT design, 232 Dutch (atypical) AN and BN patients with a CBT-E referral will be recruited from five treatment centers. Clinical effectiveness and cost-effectiveness will be measured before treatment, directly after treatment, at 6 and at 12 months follow-up. In order to rate process evaluation, patient experiences and the degree to which treatments are implemented according to protocol will be measured. In order to assess the quality of life and the achievement of personalized goals, interviews will be conducted at the end of treatment. Data will be analyzed, using a regression-based approach to mixed modelling, multivariate sensitivity analyses and coding trees for qualitative data. We hypothesize GST to be superior to CBT-E in terms of clinical effectiveness and cost-effectiveness for patients who do not show a rapid response to the first 4 weeks of a CBT-E treatment. Discussion To our knowledge, this is the first study protocol describing a multicenter RCT to explore the three aforementioned objectives. Related risks in performing the study protocol have been outlined. The expected findings may serve as a guide for healthcare stakeholders to optimize ED care trajectories. Trial registration clinicaltrials.gov (NCT05812950).

This discussion of the fourth-century commentary of Marius Victorinus on Paul’s epistle to the Galatians serves as a critical witness to late ancient understanding of Paul’s self-identification with the stigmata of Christ (of Gal 6:17), as the marks of his humiliating death on the cross. Echoing Paul on “being crucified with Christ”, Victorinus exhorted Christians to follow that example in suffering for their faith, warning them that suffering is inevitable. The present textual study uses linguistic, grammatical, rhetorical, and socio-historical analysis, particularly on the key terms, stigmata and mysterium. It concludes that Victorinus associated these terms to give meaning to trauma and suffering for Christians. The term mysterium in Victorinus’ work is closely associated with central aspects of Christ’s life and work, especially his crucifixion and death. While rejecting the “history of religions” school of thought on Christian liturgy borrowing from mystery religions, this study concludes that Victorinus’ use of the term mysterium reflects a move in fourth century Christianity to adapt language of the mysteries for the sacraments; more particularly, baptism is understood as a symbolic reenactment of Christ’s crucifixion, death and resurrection. Such an approach enhances the meaning of suffering in terms of service to Christ, for in baptism Christians share not only in Christ’s death, as suffering “with Christ”, but also in his resurrection, as victory over sin, suffering and death.

Sustainability has a molecular basis that suggests a central role for chemistry in addressing today's challenges to Earth and societal systems, and this role requires educators to see chemical reactions and processes as integral parts of dynamic and interconnected systems. Despite this prospect, few accessible resources are available for students and educators to facilitate systems thinking in chemistry for sustainability. We have developed an interactive digital learning tool (https://planetaryboundaries.kcvs.ca) based on the Planetary Boundaries framework, which uses interactive visualizations to help users better understand Earth system sustainability challenges and helps chemists and educators connect substances, reactions, and chemistry concepts to sustainability science. The tool highlights the fundamental role that chemistry plays in regulating the individual biophysical Earth system processes and in determining their control variables. It incorporates key features of a systems thinking framework by illustrating the dynamic interconnections among the processes and their control variables and demonstrates change of the Earth system over time. Finally, the interactive tool provides educators with accessible entry points to support the integration of chemistry curriculum content with sustainability considerations.

Abstract Background Despite concern about migrant children’s mental health and their access to mental healthcare services during the COVID-19 pandemic, this topic has attracted little research attention. This study aimed to examine the impact of the COVID-19 pandemic on the use primary and specialist healthcare services for mental health problems among children and adolescents with migrant background. Methods Using event study models, we investigated the impact of lockdown and subsequent COVID-19 infection control measures on children’s health service use for mental health problems according to migrant background. Drawing on reimbursement data from Norwegian public healthcare providers we observe consultations in a pre-pandemic (2017–2019) and pandemic cohort (2019–2021) in primary and specialised care. Results The pre-pandemic cohort included 77 324 migrants, 78 406 descendants of migrants and 746 917 non-migrants and the pandemic cohort included 76 830 migrants, 88 331 descendants and 732 609 non-migrants (age 6–19). The full cohorts were observed for mental healthcare use in primary care while a subsample (age 6–16) was observed for health care use in specialist care. Lockdown resulted in a dip in consultation volumes for mental disorders for all children, but this dip was relatively larger and more persistent for children with migrant background. After lockdown, consultation volumes rose more for non-migrant children than for children with migrant background. Consultations in primary healthcare peaked during January to April 2021 for non-migrants and descendants of migrants, but not for migrants (4%, 95% CI -4 to 11). In specialist care during the same period, consultations dropped by 11% for migrants (95% CI -21 to -1). By October 2021, all mental health consultations in specialist care were up with 8% for non-migrants (95% CI 0 to 15), and down with -18% for migrants and -2% for descendants (95% CIs -31 to -5 and -14 to 10). Migrant males experienced the largest reduction in consultations. Conclusions Changes in consultation volumes among children with migrant background after lockdown were not as pronounced as for non-migrants, and at times actually decreased. This suggests that an increase in barriers to care emerged during the pandemic for children with a migrant background.

Objective: To provide an overview of the development of the Preparing Heart and Mind™ (PHM™) care program designed for parents with a prenatal diagnosis of critical congenital heart disease (CCHD) and describe issues of parental concern, caregiving competencies, and type and timing of PHM™ topics. Methods: Guided participation theory underpinned intervention development and a mixed methods pilot of a novel, nurse-guided mHealth intervention. Parents were enrolled from the third trimester of pregnancy–12 weeks postnatally. Online surveys, session transcripts, and app use were descriptively analyzed. Results: The sample included 19 mothers/birthing persons and 15 caregiving partners randomized to the intervention group. In 49 sessions, mental health/wellbeing (94%) and condition-specific information (86%) were top issues. Many caregiving competencies were developed, with mothers/birthing persons often focused on feeding (86%). Regulating emotions and co-parenting consistently needed support. PHM™ topics of preparing for hospitalization (47%) and handling uncertainty (45%) were most discussed. Two cases further characterize findings. Conclusion: Nurse-parent collaborative understanding of issues emphasized the need for mental health assessments. Prenatal intervention opportunities were underscored through discussions of caregiving issues and PHM™ topics. Innovation: PHM™ represents an innovative approach that holds promise for supporting parents' mental health and caregiving needs outside the healthcare setting.

IntroductionThermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating the inflammatory processes following burn injuries, thereby impeding the development of more effective therapies to improve burn wound healing in patients.MethodsIn this study, we established a human full skin equivalent (FSE) burn wound model and incorporated human peripheral blood-derived monocytes and T cells.ResultsUpon infiltration into the FSEs, the monocytes differentiated into macrophages within a span of 7 days. Burn-injured FSEs exhibited macrophages with increased expression of HLA-DR+ and elevated production of IL-8 (CXCL8), in comparison to uninjured FSEs. Among the T cells that actively migrated into the FSEs, the majority were CD4+ and CD25+. These T cells demonstrated augmented expression of markers associated with regulatory T cell, Th1, or Th17 activity, which coincided with significant heightened cytokine production, including IFN-γ, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10 (CXCL10), and TGF-β1. Burn injury did not impact the studied effector T cell subsets or cytokine levels.DiscussionCollectively, this study represents a significant advancement in the development of an immunocompetent human skin model, specifically tailored for investigating burn-induced innate or adaptive immune reactions at the site of burn injury.

Background Infants with single ventricle congenital heart disease undergo 3 staged surgeries/interventions, with risk for morbidity and mortality. We estimated the effect of human milk (HM) and direct breastfeeding on outcomes including necrotizing enterocolitis, infection‐related complications, length of stay, and mortality. Methods and Results We analyzed the National Pediatric Cardiology Quality Improvement Collaborative (NPC‐QIC) registry (2016–2021), examining HM/breastfeeding groups during stage 1 and stage 2 palliations. We calculated propensity scores for feeding exposures, then fitted Poisson and logistic regression models to compare outcomes between propensity‐matched cohorts. Participants included 2491 infants (68 sites). Estimates for all outcomes were better in HM/breastfeeding groups. Infants fed exclusive HM before stage 1 palliation (S1P) had lower odds of preoperative necrotizing enterocolitis (odds ratio [OR], 0.37 [95% CI, 0.17–0.84]; P=0.017) and shorter S1P length of stay (rate ratio [RR], 0.87 [95% CI, 0.78–0.98]; P=0.027). During the S1P hospitalization, infants with high HM had lower odds of postoperative necrotizing enterocolitis (OR, 0.28 [95% CI, 0.15–0.50]; P

Abstract Individuals with Neurofibromatosis type 1 (NF1) experience a high degree of motor problems. The cerebellum plays a pivotal role in motor functioning and the NF1 gene is highly expressed in cerebellar Purkinje cells. However, it is not well understood to what extent NF1 affects cerebellar functioning and how this relates to NF1 motor functioning. Therefore, we subjected global Nf1 +/− mice to a cerebellum-dependent associative learning task, called Pavlovian eyeblink conditioning. Additionally, we assessed general motor function and muscle strength in Nf1 +/− mice. To our surprise, we found that Nf1 +/− mice showed a moderately increased learning rate of conditioned eyeblink responses, as well as improved accuracy in the adaptive timing of the eyeblink responses. Locomotion, balance, general motor function, and muscle strength were not affected in Nf1 +/− mice. Together, our results support the view that cerebellar function in Nf1 +/− mice is unimpaired.

Abstract Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS—in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12–15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS.

Background: English media have reported that many unvaccinated individuals took the COVID-19 vaccine after receiving a phone call from their GP. Aim: To determine whether phone calls from GPs to unvaccinated patients at increased risk of severe COVID-19 improves uptake of the COVID-19 vaccine. Design & setting: Randomised trial where 202 participants were allocated to receive a phone call from their GP, and 452 participants were allocated to not get the call. Twenty-five GPs at 11 medical centres in Norway took part. The post-trial focus group discussion was with five GPs. Method: Participants were sourced from the GP electronic medical record system, which communicates with the Norwegian Immunisation Registry and can generate a list of the GPs’ unvaccinated patients at increased risk of severe COVID-19. Results: The GPs managed to speak over the phone with 154 (76%) patients allocated to receiving a phone call. At follow-up (average 7.5 weeks), 8.9% in the intervention group and 5.3% in the control group had been vaccinated (odds ratio [OR] 1.72; 95% confidence interval [CI] = 0.90 to 3.28). Findings from the focus group discussion suggested the timing of the intervention as a likely key reason for its limited success. Conclusion: An increase in the proportion of patients who took the COVID-19 vaccine in the intervention group was observed, but the difference was smaller than anticipated, and may be a chance finding. The effect of this type of intervention will likely vary across contexts and may have proved more effective if a larger proportion of the population were unvaccinated.

Summary: With the recent findings that mutations in the gene encoding the α-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2A) causes a neurodevelopmental disorder (NDD), it is of great therapeutic relevance to know if there exists a critical developmental time window in which CAMK2A needs to be expressed for normal brain development, or whether expression of the protein at later stages is still beneficial to restore normal functioning. To answer this question, we generated an inducible Camk2a mouse model, which allows us to express CAMK2A at any desired time. Here, we show that adult expression of CAMK2A rescues the behavioral and electrophysiological phenotypes seen in the Camk2a knock-out mice, including spatial and conditional learning and synaptic plasticity. These results suggest that CAMK2A does not play a critical irreversible role in neurodevelopment, which is of importance for future therapies to treat CAMK2A-dependent disorders.

Background: Few randomized trials of public health and social measures were carried out during the COVID-19 pandemic. We report on the major barriers we faced when we tried to run such trials. Methods: We reviewed all randomized trials proposed and initiated by the Centre for Epidemic Interventions Research in Norway during the COVID-19 pandemic. Results: Of the 18 proposed trials, 11 trials were not implemented. One of the key legal and ethical barriers to conducting the trials was the Norwegian Health Research Act, which demands informed consent from all participants who are exposed to an intervention. A lack of sufficient political support was also a challenge, as was unpredictability, due to shifting disease incidence and changing recommendations from the authorities. Conclusion: Strengthening the evidence base for public health and social measures in pandemics will require political and public understanding and support and a legal framework that allows for the conduct of such trials. [ABSTRACT FROM AUTHOR]

While the influence of canopy trees on soils in natural and restored forest environments is well studied, the influence of understory species is not. Here, we evaluate the effects of outplanted native woody understory on invasive grass biomass and soil nutrient properties in heavily grass-invaded 30 + year-old plantations of a native N-fixing tree Acacia koa in Hawai'i. We analyze soils from under A. koa trees with versus without planted woody understory and compare these to soils from under remnant pasture trees of the pre-deforestation dominant, Metrosideros polymorpha where passive recruitment of native woody understory has occurred since the cessation of grazing. Simultaneously, we experimentally planted understory species at three times the density used by managers to see if this could quickly decrease grass biomass and change soil nutrient dynamics. We found that invasive grass biomass declined with understory planting in surveyed and experimental sites. Yet, woody understory abundance had no effect on N cycling. Short-term N availability and nitrification potential were higher under A. koa than M. polymorpha trees regardless of understory. Net N mineralization either did not differ (~ 1 mo) between canopy species or was higher (171 day incubations) under remnant M. polymorpha where organic matter was also higher. The only influence of understory on soil was a positive correlation with loss-on-ignition (organic matter) under M. polymorpha. We also demonstrate differential controls over N cycling under the two canopy tree species. Overall, understory restoration has not changed soil characteristics even as invasive grass biomass declines. [ABSTRACT FROM AUTHOR]