Psychopathology assessed across the lifespan often can be summarized with a few broad dimensions: internalizing, externalizing, and psychosis/thought disorder. Extensive overlap between internalizing and externalizing symptoms has garnered interest in bifactor models comprised of a general co-occurring factor and specific internalizing and externalizing factors. We focus on internalizing and externalizing symptoms and compare a bifactor model to a correlated two-factor model of psychopathology at three timepoints in a large adolescent community sample (N = 387; 55 % female; 83% Caucasian; M age = 12.1 at wave 1) using self- and parent-reports. Each model was tested within each time-point with 25–28 validators. The bifactor models demonstrated better fit to the data. Child report had stronger invariance across time. Parent report had stronger reliability over time. Cross-informant correlations between the factors at each wave indicated that the bifactor model had slightly poorer convergent validity but stronger discriminant validity than the two-factor model. With notable exceptions, this pattern of results replicated across informants and waves. The overlap between internalizing and externalizing pathology is systematically and, sometimes, non-linearly related to risk factors and maladaptive outcomes. Strengths and weaknesses to modeling psychopathology as two or three factors and clinical and developmental design implications are discussed.

Compared with other areas of mental health research that are focused on the active and early management of youth presenting in the early stages of major mental disorders, there has been a relative lack of focus on young people with emerging or established bipolar disorders. Recently, this has stimulated both international professional societies (e.g., International Society for Bipolar Disorders [ISBD] Early Intervention Task Force) and funding agencies from Canada, UK, Australia, and the USA – including the Daymark Foundation (Jain et al. 2023), Wellcome Trust (2022), National Health and Medical Research Council, and BD2 – to promote a focus on identifying the major challenges in this field and gathering support for novel research and clinical service programmes.

We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.

Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.

Although knowledge of their fossil record continues to improve, multituberculates nonetheless remain one of the more poorly understood mammalian clades, which can be attributed to a record comprised of isolated teeth and fragmentary jaws. Fortunately, the p4 of multituberculates is the most common form of remains for this group and is a principal source of diagnostic characters in systematic studies, the p4 of cimolodontan multituberculates is both common and a source of diagnostic characters in systematic studies. The results of a recent morphometric study on the neoplagiaulacid Mesodma suggest that p4 size may be more useful than shape in diagnosing the various species referred to this genus. We tested this hypothesis by applying two different morphometric methods (2D geometric morphometrics and linear measurements) to two samples: (1) one including the p4s of four known species of Mesodma (M. ambigua, M. thompsoni, M. formosa, and M. pygmaea), and (2) a sample of unidentified p4s of Mesodma from the Bug Creek Anthills locality of northeastern Montana. Our results indicate that while form explains most of the morphological variation in p4s of the various species of Mesodma, linear-measurement data support differences in p4 morphology that are not recovered by form data alone. Depending on the methods used, we found evidence for the presence of one or more species of Mesodma in the Bug Creek Anthills fauna. Although shape and size both contribute to morphological variation in the p4 of Mesodma, our results suggest that the diagnostic power of each varies with the type of methodology employed.

The Australian SKA Pathfinder (ASKAP) radio telescope has carried out a survey of the entire Southern Sky at 887.5 MHz. The wide area, high angular resolution, and broad bandwidth provided by the low-band Rapid ASKAP Continuum Survey (RACS-low) allow the production of a next-generation rotation measure (RM) grid across the entire Southern Sky. Here we introduce this project as Spectral and Polarisation in Cutouts of Extragalactic sources from RACS (SPICE-RACS). In our first data release, we image 30 RACS-low fields in Stokes I, Q, U at 25$^{\prime\prime}$ angular resolution, across 744–1032 MHz with 1 MHz spectral resolution. Using a bespoke, highly parallelised, software pipeline we are able to rapidly process wide-area spectro-polarimetric ASKAP observations. Notably, we use ‘postage stamp’ cutouts to assess the polarisation properties of 105912 radio components detected in total intensity. We find that our Stokes Q and U images have an rms noise of $\sim$80 $\unicode{x03BC}$Jy PSF$^{-1}$, and our correction for instrumental polarisation leakage allows us to characterise components with $\gtrsim$1% polarisation fraction over most of the field of view. We produce a broadband polarised radio component catalogue that contains 5818 RM measurements over an area of $\sim$1300 deg$^{2}$ with an average error in RM of $1.6^{+1.1}_{-1.0}$ rad m$^{-2}$, and an average linear polarisation fraction $3.4^{+3.0}_{-1.6}$ %. We determine this subset of components using the conditions that the polarised signal-to-noise ratio is $>$8, the polarisation fraction is above our estimated polarised leakage, and the Stokes I spectrum has a reliable model. Our catalogue provides an areal density of $4\pm2$ RMs deg$^{-2}$; an increase of $\sim$4 times over the previous state-of-the-art (Taylor, Stil, Sunstrum 2009, ApJ, 702, 1230). Meaning that, having used just 3% of the RACS-low sky area, we have produced the 3rd largest RM catalogue to date. This catalogue has broad applications for studying astrophysical magnetic fields; notably revealing remarkable structure in the Galactic RM sky. We will explore this Galactic structure in a follow-up paper. We will also apply the techniques described here to produce an all-Southern-sky RM catalogue from RACS observations. Finally, we make our catalogue, spectra, images, and processing pipeline publicly available.

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.

Background: Quantitative susceptibility mapping (QSM) is an MR sequence that has potential as a biomarker in concussion. We compared QSM in pediatric concussion patients versus a comparison group of children with orthopedic injuries (OI) and assessed QSM’s performance relative to the current clinical benchmark (5P risk score) for predicting persistent postconcussion symptoms (PPCS). Methods: Children (N=967) aged 8-16.99 years with either concussion or OI were prospectively recruited from 5 Canadian centers. Participants completed QSM at a post-acute assessment 2-33 days post-injury. QSM z-score metrics for 9 regions of interest (ROI) were derived from 371 children (concussion=255, OI=116). PPCS at 1-month post-injury was defined using reliable change methods. Results: The concussion and OI groups did not differ significantly in QSM across ROI. Increased frontal white matter (WM) susceptibility predicted reliable increases in parent-rated cognitive symptoms (p=0.001). Together, frontal WM susceptibility and the 5P risk score were better at predicting persistent cognitive symptoms than the 5P risk score alone (p=0.0021). AUC were 0.71 (95%CI: 0.62-0.80) for frontal WM susceptibility, 0.67 (95%CI: 0.56-0.78) for the 5P risk score, and 0.73 (95%CI: 0.64-0.82) for both. Conclusions: This is the first study to demonstrate a potential imaging biomarker that predicts persistent symptoms in children with concussion compared to the current clinical benchmark.

Maternal experiences of childhood adversity can increase the risk of emotional and behavioural problems in their children. This systematic review and meta-analysis provide the first narrative and quantitative synthesis of the mediators and moderators involved in the link between maternal childhood adversity and children's emotional and behavioural development. We searched EMBASE, PsycINFO, Medline, Cochrane Library, grey literature and reference lists. Studies published up to February 2021 were included if they explored mediators or moderators between maternal childhood adversity and their children's emotional and behavioural development. Data were synthesised narratively and quantitatively by meta-analytic approaches. The search yielded 781 articles, with 74 full-text articles reviewed, and 41 studies meeting inclusion criteria. Maternal mental health was a significant individual-level mediator, while child traumatic experiences and insecure maternal–child attachment were consistent family-level mediators. However, the evidence for community-level mediators was limited. A meta-analysis of nine single-mediating analyses from five studies indicated three mediating pathways: maternal depression, negative parenting practices and maternal insecure attachment, with pooled indirect standardised effects of 0.10 [95% CI (0.03–0.17)), 0.01 (95% CI (−0.02 to 0.04)] and 0.07 [95% CI (0.01–0.12)], respectively. Research studies on moderators were few and identified some individual-level factors, such as child sex (e.g. the mediating role of parenting practices being only significant in girls), biological factors (e.g. maternal cortisol level) and genetic factors (e.g. child's serotonin-transporter genotype). In conclusion, maternal depression and maternal insecure attachment are two established mediating pathways that can explain the link between maternal childhood adversity and their children's emotional and behavioural development and offer opportunities for intervention.

Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.

OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.

Multifetal pregnancies are at risk of adverse maternal, neonatal and long-term health outcomes, and gestational weight gain (GWG) is a potentially modifiable risk factor for several of these. However, studies assessing the associations of GWG with long-term health in twins are rare, and studies which do assess these associations in twins often do not account for gestational age. Since longer gestations are likely to lead to larger GWG and lower risk of adverse outcomes, adjusting for gestational age is necessary to better understand the association of GWG with twin health outcomes. We aimed to explore long-term associations of GWG-for-gestational-age with twin anthropometric measures. The Peri/Postnatal Epigenetic Twins Study (PETS) is a prospective cohort study, which recruited women pregnant with twins from 2007 to 2009. Twins were followed-up at 18 months and 6 years of age. GWG-for-gestational-age z-scores were calculated from pre-pregnancy weight and weight at delivery. We fitted regression models to assess associations of GWG with twin weight, height and BMI at birth, 18 months, and 6 years. Of the 250 women in the PETS, 172 had GWG measured throughout pregnancy. Overall, higher GWG-for-gestational-age z-scores were associated with higher birthweight (β: 0.32 z-scores, 95% Confidence Interval (95% CI): 0.19, 0.45), BMI (β: 0.29 z-scores, 95% CI: 0.14, 0.43) and length (β: 0.27 z-scores, 95% CI: 0.09, 0.45). However, these associations were not observed at 18 months or 6 years of age. GWG was associated with twin length, weight and BMI at birth but not during childhood. Further research is needed to determine the long-term effects of GWG on twin health outcomes.

Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

Background: Quantitative susceptibility mapping (QSM) is an MR sequence that has potential as a biomarker in concussion. We compared QSM in pediatric concussion patients versus a comparison group of children with orthopedic injuries (OI) and assessed QSM’s performance relative to the current clinical benchmark (5P risk score) for predicting persistent postconcussion symptoms (PPCS). Methods: Children (N=967) aged 8-16.99 years with either concussion or OI were prospectively recruited from 5 Canadian centers. Participants completed QSM at a post-acute assessment 2-33 days post-injury. QSM z-score metrics for 9 regions of interest (ROI) were derived from 371 children (concussion=255, OI=116). PPCS at 1-month post-injury was defined using reliable change methods. Results: The concussion and OI groups did not differ significantly in QSM across ROI. Increased frontal white matter (WM) susceptibility predicted reliable increases in parent-rated cognitive symptoms (p=0.001). Together, frontal WM susceptibility and the 5P risk score were better at predicting persistent cognitive symptoms than the 5P risk score alone (p=0.0021). AUC were 0.71(95%CI: 0.62-0.80) for frontal WM susceptibility, 0.67(95%CI: 0.56-0.78) for the 5P risk score, and 0.73(95%CI: 0.64-0.82) for both. Conclusions: This is the first study to demonstrate a potential imaging biomarker that predicts persistent symptoms in children with concussion compared to the current clinical benchmark.