Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Good judgment is often gauged against two gold standards – coherence and correspondence. Judgments are coherent if they demonstrate consistency with the axioms of probability theory or propositional logic. Judgments are correspondent if they agree with ground truth. When gold standards are unavailable, silver standards such as consistency and discrimination can be used to evaluate judgment quality. Individuals are consistent if they assign similar judgments to comparable stimuli, and they discriminate if they assign different judgments to dissimilar stimuli. We ask whether “superforecasters”, individuals with noteworthy correspondence skills (see Mellers et al., 2014) show superior performance on laboratory tasks assessing other standards of good judgment. Results showed that superforecasters either tied or out-performed less correspondent forecasters and undergraduates with no forecasting experience on tests of consistency, discrimination, and coherence. While multifaceted, good judgment may be a more unified than concept than previously thought.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0–18 years in Qatar. We conducted a cross-sectional study of all children aged 0–18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3–13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7–37.5), and it was similar between children aged <5 years (37.8%), 5–9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20–0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45–0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02–0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02–0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.

Patient safety is a complex systems issue. In this study, we used a scoping review of peer-reviewed literature and a case study of provincial and territorial legislation in Canada to explore the influence of mandatory reporting legislation on patient safety outcomes in hospital settings. We drew from a conceptual model that examines the components of mandatory reporting legislation that must be in place as a part of a systems governance approach to patient safety and used this model to frame our results. Our results suggest that mandatory reporting legislation across Canada is generally designed to gather information about – rather than respond to and prevent – patient safety incidents. Overall, we found limited evidence of impact of mandatory reporting legislation on patient safety outcomes. Although legislation is one lever among many to improve patient safety outcomes, there are nonetheless several considerations for patient safety legislation to assist in broader system improvement efforts in Canada and elsewhere. Legislative frameworks may be enhanced by strengthening learning systems, accountability mechanisms and patient safety culture.

A weakly nonlinear time-dependent theory for the evolution of superharmonics generated by the nonlinear self-interaction of a mode-1 internal tide in non-uniform stratification is developed and compared to numerical simulations. The forcing by the internal tide is found to excite near-pure mode-1 superharmonics whose natural frequency is moderately different from twice the internal tide frequency. Consequently, the superharmonics undergo a slow periodic growth and decay that is comparable to an acoustic ‘beat’. At low latitudes the beat frequency is smaller and the superharmonics can grow to larger amplitude, allowing for the possibility of a superharmonic cascade.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.