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Abstract The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance.

Abstract Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

Abstract Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.

Abstract Adolescence is a period of dynamic brain remodeling and susceptibility to psychiatric risk factors, mediated by the protracted consolidation of association cortices. Here, we investigated whether longitudinal variation in adolescents’ resilience to psychosocial stressors during this vulnerable period is associated with ongoing myeloarchitectural maturation and consolidation of functional networks. We used repeated myelin-sensitive Magnetic Transfer (MT) and resting-state functional neuroimaging (n = 141), and captured adversity exposure by adverse life events, dysfunctional family settings, and socio-economic status at two timepoints, one to two years apart. Development toward more resilient psychosocial functioning was associated with increasing myelination in the anterolateral prefrontal cortex, which showed stabilized functional connectivity. Studying depth-specific intracortical MT profiles and the cortex-wide synchronization of myeloarchitectural maturation, we further observed wide-spread myeloarchitectural reconfiguration of association cortices paralleled by attenuated functional reorganization with increasingly resilient outcomes. Together, resilient/susceptible psychosocial functioning showed considerable intra-individual change associated with multi-modal cortical refinement processes at the local and system-level.

Abstract Introduction Rates of substance use are high among youth involved in the legal system (YILS); however, YILS are less likely to initiate and complete substance use treatment compared to their non legally-involved peers. There are multiple steps involved in connecting youth to needed services, from screening and referral within the juvenile legal system to treatment initiation and completion within the behavioral health system. Understanding potential gaps in the care continuum requires data and decision-making from these two systems. The current study reports on the development of data dashboards that integrate these systems’ data to help guide decisions to improve substance use screening and treatment for YILS, focusing on end-user feedback regarding dashboard utility. Methods Three focus groups were conducted with n = 21 end-users from juvenile legal systems and community mental health centers in front-line positions and in decision-making roles across 8 counties to gather feedback on an early version of the data dashboards; dashboards were then modified based on feedback. Results Qualitative analysis revealed topics related to (1) important aesthetic features of the dashboard, (2) user features such as filtering options and benchmarking to compare local data with other counties, and (3) the centrality of consistent terminology for data dashboard elements. Results also revealed the use of dashboards to facilitate collaboration between legal and behavioral health systems. Conclusions Feedback from end-users highlight important design elements and dashboard utility as well as the challenges of working with cross-system and cross-jurisdiction data.

Abstract Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well as after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent with the repression of genes enabling mitotic expansion, concurrent with the onset of aging-associated transcriptional programs. Adult hGPCs develop a repressive transcription factor network centered on MYC, and regulated by ZNF274, MAX, IKZF3, and E2F6. Individual over-expression of these factors in iPSC-derived hGPCs lead to a loss of proliferative gene expression and an induction of mitotic senescence, replicating the transcriptional changes incurred during glial aging. miRNA profiling identifies the appearance of an adult-selective miRNA signature, imposing further constraints on the expansion competence of aged GPCs. hGPC aging is thus associated with acquisition of a MYC-repressive environment, suggesting that suppression of these repressors of glial expansion may permit the rejuvenation of aged hGPCs.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Thioredoxin Reductase (TrxR) functions to recycle thioredoxin (Trx) during hydroperoxide metabolism mediated by peroxiredoxins and is currently being targeted using the FDA-approved anti-rheumatic drug, auranofin (AF), to selectively sensitize cancer cells to therapy. AF treatment decreased TrxR activity and clonogenic survival in small cell lung cancer (SCLC) cell lines (DMS273 and DMS53) as well as the H727 atypical lung carcinoid cell line. AF treatment also significantly sensitized DMS273 and H727 cell lines in vitro to sorafenib, an FDA-approved multi-kinase inhibitor that depleted intracellular glutathione (GSH). The pharmacokinetic, pharmacodynamic, and safety profile of AF was examined in nude mice with DMS273 xenografts administered AF intraperitoneally at 2 mg/kg or 4 mg/kg (IP) once (QD) or twice daily (BID) for 1−5 d. Plasma levels of AF were 10–20 μM (determined by mass spectrometry of gold), and the optimal inhibition of TrxR activity was obtained at 4 mg/kg once daily, with no effect on glutathione peroxidase 1 activity. This AF treatment extended for 14 d, inhibited TrxR (>75%), and resulted in a significant prolongation of median overall survival from 19 to 23 d (p = .04, N = 30 controls, 28 AF). In this experiment, there were no observed changes in animal bodyweight, complete blood counts (CBCs), bone marrow toxicity, blood urea nitrogen, or creatinine. These results support the hypothesis that AF effectively inhibits TrxR both in vitro and in vivo in SCLC, sensitizes NETs and SCLC to sorafenib, and could be repurposed as an adjuvant therapy with targeted agents that induce disruptions in thiol metabolism.

Abstract The OPRM1 gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in OPRM1 is adenine (A) substituted by guanine (G) at position 118 (118A>G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A>G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N‐ and C‐terminal regions of MOR‐1. Using molecular docking and post‐docking energy minimizations with morphine, we show that the extracellular substitution of Asn at position 40 alters the cytoplasmic C‐terminal conformation, while leaving the G‐protein binding interface unaffected. A real‐time BRET assay measuring G‐protein and β‐arrestin association with MOR r generated data that tested this prediction. Consistent with this in silico prediction, we show changes in morphine‐mediated β‐arrestin association with receptor variants with little change in morphine‐mediated G‐protein association comparing MOR‐1 wild type (WT) to MOR‐1118A>G. We tested the system with different opioid agonists, the OPRM1 118A>G SNP, and different MOR splice variants (MOR‐1 and MOR‐1O). These results are consistent with the observation that patients with the 118A>G OPRM1 allele respond more readily to fentanyl than to morphine. In conclusion, the 118A>G substitution alters receptor responses to opioids through variable C‐terminal domain movements that are agonist and splice variant dependent.

Introduction: To characterize the impact of rural patients’ travel time to obtain healthcare on their reported utilization of preventive healthcare services and personal health outcomes. Methods: Online survey data from rural adults ages 50+ years living in the Northeastern United States were collected from February to August 2021. Study measures included self-reported travel time to obtain healthcare, use of preventive healthcare, and health outcomes. The associations between travel time with use of preventive care and health outcomes were assessed using linear, Poisson, and logistic regression analyses controlling for demographic variables. Results: Our study population included 1052 rural adults, with a mean travel time of 18.5 min (range: 0-60). Travel time was greater for racial/ethnic minority participants and for higher-income participants (both P

Tibiotalar arthrodesis is a common procedure performed in patients with ankle arthritis to relieve pain, restore function, and improve the quality of life. Obtaining proper bone-to-bone apposition is crucial to obtaining a solid fusion. Therefore, adequate joint preparation is critical. Open-joint preparation is the standard of care, but arthroscopic arthrodesis is becoming increasingly popular, as it can decrease tissue trauma, postoperative pain, hospital stay, and complications. The addition of bone matrix allograft and autograft also improves healing rates. Use of an arthroscopic autologous tissue collector through standard arthroscopic portals allows harvesting of bone matrix autograft without having to perform additional invasive bone harvesting outside of the affected joint. We present our technique for tibiotalar arthrodesis using an arthroscopic approach with an arthroscopic autologous tissue collector.

Abstract Here we present a sample of 12 massive quiescent galaxy candidates at $$z\sim 3-4$$ z ∼ 3 - 4 observed with the James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec). These galaxies were pre-selected from the Hubble Space Telescope imaging and 10 of our sources were unable to be spectroscopically confirmed by ground based spectroscopy. By combining spectroscopic data from NIRSpec with multi-wavelength imaging data from the JWST Near Infrared Camera (NIRCam), we analyse their stellar populations and their formation histories. We find that all of our galaxies classify as quiescent based on the reconstruction of their star formation histories but show a variety of quenching timescales and ages. All our galaxies are massive ( $$\sim 0.1-1.2\times 10^{11}$$ ∼ 0.1 - 1.2 × 10 11 M $$_\odot$$ ⊙ ), with masses comparable to massive galaxies in the local Universe. We find that the oldest galaxy in our sample formed $$\sim 1.0\times 10^{11}$$ ∼ 1.0 × 10 11 M $$_\odot$$ ⊙ of mass within the first few hundred million years of the Universe and has been quenched for more than a billion years by the time of observation at $$z\sim 3.2$$ z ∼ 3.2 ( $$\sim 2$$ ∼ 2 billion years after the Big Bang). Our results point to very early formation of massive galaxies requiring a high conversion rate of baryons to stars in the early Universe.

Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Multimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT.

Intervertebral disc (IVD) degeneration is a common pathological condition associated with low back pain. Recent evidence suggests that mesenchymal signaling cells (MSCs) promote IVD regeneration, but underlying mechanisms remain poorly defined. One postulated mechanism is via modulation of macrophage phenotypes. In this manuscript, we tested the hypothesis that MSCs produce trophic factors that alter macrophage subsets. To this end, we collected conditioned medium from human, bone marrow-derived STRO3+ MSCs. We then cultured human bone marrow-derived macrophages in MSC conditioned medium (CM) and performed single cell RNA-sequencing. Comparative analyses between macrophages cultured in hypoxic and normoxic MSC CM showed large overlap between macrophage subsets; however, we identified a unique hypoxic MSC CM-induced macrophage cluster. To determine if factors from MSC CM simulated effects of the anti-inflammatory cytokine IL-4, we integrated the data from macrophages cultured in hypoxic MSC CM with and without IL-4 addition. Integration of these data sets showed considerable overlap, demonstrating that hypoxic MSC CM simulates the effects of IL-4. Interestingly, macrophages cultured in normoxic MSC CM in the absence of IL-4 did not significantly contribute to the unique cluster within our comparison analyses and showed differential TGF-β signaling; thus, normoxic conditions did not approximate IL-4. In addition, TGF-β neutralization partially limited the effects of MSC CM. In conclusion, our study identified a unique macrophage subset induced by MSCs within hypoxic conditions and supports that MSCs alter macrophage phenotypes through TGF-β-dependent mechanisms.

We present a sample of 88 candidate z ∼ 8.5–14.5 galaxies selected from the completed NIRCam imaging from the Cosmic Evolution Early Release Science survey. These data cover ∼90 arcmin ^2 (10 NIRCam pointings) in six broadband imaging filters and one medium-band imaging filter. With this sample we confirm at higher confidence early JWST conclusions that bright galaxies in this epoch are more abundant than predicted by most theoretical models. We construct the rest-frame ultraviolet luminosity functions at z ∼ 9, 11, and 14 and show that the space density of bright ( M _UV = −20) galaxies changes only modestly from z ∼ 14 to z ∼ 9, compared to a steeper increase from z ∼ 8 to z ∼ 4. While our candidates are photometrically selected, spectroscopic follow-up has now confirmed 13 of them, with only one significant interloper, implying that the fidelity of this sample is high. Successfully explaining the evidence for a flatter evolution in the number densities of UV-bright z > 10 galaxies may thus require changes to the dominant physical processes regulating star formation. While our results indicate that significant variations of dust attenuation with redshift are unlikely to be the dominant factor at these high redshifts, they are consistent with predictions from models that naturally have enhanced star formation efficiency and/or stochasticity. An evolving stellar initial mass function could also bring model predictions into better agreement with our results. Deep spectroscopic follow-up of a large sample of early galaxies can distinguish between these competing scenarios.

We present the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) Survey, a deep slitless spectroscopic and imaging Cycle 1 JWST treasury survey designed to constrain feedback mechanisms in low-mass galaxies across cosmic time. NGDEEP targets the Hubble Ultra Deep Field (HUDF) with NIRISS slitless spectroscopy ( ${f}_{\mathrm{lim},\mathrm{line},5\sigma }\approx 1.2\,\times \,$ 10 ^−18 erg s ^−1 cm ^−2 ) to measure metallicities and star formation rates (SFRs) for low-mass galaxies through the peak of the cosmic SFR density (0.5 < z < 4). In parallel, NGDEEP targets the HUDF-Par2 parallel field with NIRCam ( ${m}_{\mathrm{lim},5\sigma }=30.6-30.9$ ) to discover galaxies to z > 12, constraining the slope of the faint end of the rest-ultraviolet luminosity function. NGDEEP overlaps with the deepest HST Advanced Camera for Surveys optical imaging in the sky, F435W in the HUDF ( ${m}_{\mathrm{lim},{\rm{F}}435{\rm{W}}}=29.6$ ) and F814W in HUDF-Par2 ( ${m}_{\mathrm{lim},{\rm{F}}814{\rm{W}}}=30$ ), making this a premier HST+JWST deep field. As a treasury survey, NGDEEP data are public immediately, and we will rapidly release data products and catalogs in the spirit of previous deep-field initiatives. In this paper we present the NGDEEP survey design, summarize the science goals, and detail plans for the public release of NGDEEP reduced data products.

Abstract Background For youth involved in the juvenile justice (JJ) system, caregiver involvement and engagement in the system is crucial for youth development and outcomes of JJ cases; however, there are challenges to establishing positive/productive partnerships between caregivers and JJ representatives. The current project examines perspectives of caregivers and JJ personnel regarding facilitators and barriers to establishing JJ-caregiver partnerships, as well as their perceptions of the use of a caregiver navigator program to support caregivers of system-involved youth. Results are used to inform development of a caregiver navigator program to support caregivers and help them navigate the JJ system. Results Semi-structured interviews were conducted with caregivers of youth involved in JJ (n = 15, 53% White, 93% female), JJ personnel (n = 7, 100% White, 50% female), and JJ family advisory board members (n = 5, 100% Black, 100% female). Caregivers reported varying experiences across intake/arrest, court, and probation processes. Positive experiences were characterized by effective communication and feeling supported by JJ. Negative experiences related to feeling blamed and punished for their child’s system involvement and feeling unsupported. JJ interviews corroborated caregiver sentiments and also illustrated facilitators and barriers to JJ-caregiver partnerships. Both JJ personnel and caregivers endorsed potential benefits of a peer-based caregiver navigator program to provide social, informational, and emotional support. Conclusion Continued work is needed to improve JJ-caregiver partnerships and use of a peer-based navigator program has the potential to address barriers to caregiver engagement in the JJ system.

A crucial yet challenging task in galaxy evolution studies is the identification of distant merging galaxies, a task that suffers from a variety of issues ranging from telescope sensitivities and limitations to the inherently chaotic morphologies of young galaxies. In this paper, we use random forests and convolutional neural networks to identify high-redshift JWST Cosmic Evolution Early Release Science Survey (CEERS) galaxy mergers. We train these algorithms on simulated 3 < z < 5 CEERS galaxies created from the IllustrisTNG subhalo morphologies and the Santa Cruz SAM light cone. We apply our models to observed CEERS galaxies at 3 < z < 5. We find that our models correctly classify ∼60%–70% of simulated merging and nonmerging galaxies; better performance on the merger class comes at the expense of misclassifying more nonmergers. We could achieve more accurate classifications, as well as test for a dependency on physical parameters such as gas fraction, mass ratio, and relative orbits, by curating larger training sets. When applied to real CEERS galaxies using visual classifications as ground truth, the random forests correctly classified 40%–60% of mergers and nonmergers at 3 < z < 4 but tended to classify most objects as nonmergers at 4 < z < 5 (misclassifying ∼70% of visually classified mergers). On the other hand, the CNNs tended to classify most objects as mergers across all redshifts (misclassifying 80%–90% of visually classified nonmergers). We investigate what features the models find most useful, as well as the characteristics of false positives and false negatives, and also calculate merger rates derived from the identifications made by the models.

Ostechondritis dissecans (OCD) is an orthopaedic disease characterized by formation of osteochondral defects in developing joints. Epiphyseal cartilage necrosis (osteochondrosis [OC]) caused by focal failure of vascular supply is the known precursor lesion of OCD, but it remains to be established how the severity of vascular failure drives lesion healing or progression. In the current study we have implemented a novel piglet model of induced osteochondrosis of the lateral trochlear ridge of the femur to determine the role that the extent of ischemia plays in the development and progression of OC/OCD lesions. Ten 4-week-old Yorkshire piglets underwent surgical interruption of the vascular supply to the entirety (n = 4 pigs) or the distal half (n = 6 pigs) of the lateral trochlear ridge of the femur. At 2, 6, and 12 weeks postoperatively, distal femora were evaluated by magnetic resonance imaging (MRI) to determine the fate of induced OC lesions. At 12 weeks, piglets were euthanized, and the surgical sites were examined histologically. After complete devascularization, lesion size increased between the 6- and 12-week MRI by an average of 24.8 mm2 (95% CI: [-2.2, 51.7]; p = 0.071). During the same period, lesion size decreased by an average of 7.6 mm2 (95% CI: [-24.5, 19.4]; p = 0.83) in piglets receiving partial devascularization. At 12 weeks, average ± SD lesion size was larger (p

We present measurements of the rest-frame UV spectral slope, β , for a sample of 36 faint star-forming galaxies at z ∼ 9–16 discovered in one of the deepest JWST NIRCam surveys to date, the Next Generation Deep Extragalactic Exploratory Public Survey. We use robust photometric measurements for UV-faint galaxies (down to M _UV ∼ −16), originally published in Leung et al., and measure values of the UV spectral slope via photometric power-law fitting to both the observed photometry and stellar population models obtained through spectral energy distribution (SED) fitting with Bagpipes . We obtain a median and 68% confidence interval for β from photometric power-law fitting of ${\beta }_{\mathrm{PL}}=-{2.7}_{-0.5}^{+0.5}$ and from SED fitting, ${\beta }_{\mathrm{SED}}=-{2.3}_{-0.1}^{+0.2}$ for the full sample. We show that when only two to three photometric detections are available, SED fitting has a lower scatter and reduced biases than photometric power-law fitting. We quantify this bias and find that after correction the median ${\beta }_{\mathrm{SED},\mathrm{corr}}=-{2.5}_{-0.2}^{+0.2}$ . We measure physical properties for our galaxies with Bagpipes and find that our faint ( ${M}_{\mathrm{UV}}=-{18.1}_{-0.9}^{+0.7}$ ) sample is low in mass ( $\mathrm{log}[{M}_{* }/{M}_{\odot }]={7.7}_{-0.5}^{+0.5}$ ), fairly dust-poor ( ${A}_{{\rm{v}}}={0.1}_{-0.1}^{+0.2}$ mag), and modestly young ( $\mathrm{log}[\mathrm{age}]={7.8}_{-0.8}^{+0.2}$ yr) with a median star formation rate of $\mathrm{log}(\mathrm{SFR})=-{0.3}_{-0.4}^{+0.4}{M}_{\odot }\,{\mathrm{yr}}^{-1}$ . We find no strong evidence for ultrablue UV spectral slopes ( β ∼ −3) within our sample, as would be expected for exotically metal-poor ( Z / Z _⊙ < 10 ^−3 ) stellar populations with very high Lyman continuum escape fractions. Our observations are consistent with model predictions that galaxies of these stellar masses at z ∼ 9–16 should have only modestly low metallicities ( Z / Z _⊙ ∼ 0.1–0.2).

We study the H α equivalent width (EW(H α )) maps of 19 galaxies at 0.6 < z < 2.2 in the Hubble Ultra Deep Field using NIRISS slitless spectroscopy as part of the Next Generation Deep Extragalactic Exploratory Public Survey. Our galaxies mostly lie on the star formation main sequence with stellar masses between 10 ^9 and 10 ^11 M _⊙ , characterized as “typical” star-forming galaxies at these redshifts. Leveraging deep Hubble Space Telescope and JWST images, spanning 0.4–4.8 μ m, we perform spatially resolved fitting of the spectral energy distributions for these galaxies and construct specific star formation rate (sSFR) and stellar-mass-weighted age maps with a spatial resolution of ∼1 kpc. The pixel-to-pixel EW(H α ) increases with increasing sSFR and with decreasing age. The average trends are slightly different from the relations derived from integrated fluxes of galaxies from the literature, suggesting complex evolutionary trends within galaxies. We quantify the radial profiles of EW(H α ), sSFR, and age. The majority (84%) of galaxies show positive EW(H α ) gradients, in line with the inside-out quenching scenario. A few galaxies (16%) show inverse (and flat) EW(H α ) gradients, possibly due to merging or starbursts. We compare the distributions of EW(H α ) and sSFR to star formation history (SFH) models as a function of galactocentric radius. We argue that the central regions of galaxies have experienced at least one rapid star formation episode, which leads to the formation of the bulge, while their outer regions (e.g., disks) grow via more smoothly varying SFHs. These results demonstrate the ability to study resolved star formation in distant galaxies with JWST NIRISS.

Abstract Background Intravenous nitrates are a primary therapy for hypertensive congestive heart failure (CHF) with acute pulmonary edema (APE) in the hospital setting. Historically, sublingual nitrates are the mainstay of emergency medical services (EMS) pharmacologic therapy for these patients. We aimed to evaluate the safety of prehospital bolus dose intravenous nitroglycerin in patients with APE. Methods This is a retrospective evaluation of EMS data between March 15, 2018, and March 15, 2022, where CHF with APE was suspected and bolus‐dose intravenous nitroglycerin was administered. Protocol inclusion criteria were hypertension (systolic blood pressure [SBP] >160 mmHg) and acute respiratory distress, with a presumption of decompensated CHF with APE. These patients received 1 mg intravenous nitroglycerin, with the option to repeat once for ongoing distress if the SBP remained >160 mmHg. The primary outcomes were adverse events, defined as hypotension (SBP

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Unlike university classrooms, academic support services provide students opportunities for enactive mastery of a skill with immediate feedback in a low-risk learning environment. Given that this environment likely alters affective states, this study tracked support-seekers’ perception (n=107) of their anxiety and confidence before and after repeated 1 hour academic skill development sessions (n=384). Results showed that academic-support environment had a robust, immediate, and long-lasting effect on decreasing anxiety and increasing confidence. Positive outcomes such as reduced anxiety and increased confidence during an academic skill development session were associated with increased academic performance. There was a high rate of participants (98%) persisting into the next year of their program. Together this study demonstrates that the academic-support environment can provide intervention in the form of enhancing affective states in situations of high anxiety and low confidence to potentially affect academic outcomes and retention rates.

The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function.

Abstract Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

Social determinants of health are an important aspect of improving health outcomes. Militaries have deployed global health engagement activities to meet security objectives from peacetime through post-conflict. Two frameworks, the Social Model of Health and the U.S. Institute of Peace Strategic Framework for Stabilisation and Reconstruction, have similarities and are reviewed in this paper. Drawing similarities between the two presents opportunities for targeted, well-planned global health engagement activities that may bring stronger health outcomes. Military global health efforts must work with civil affairs experts and civilian partners within the host nation health context to target the most amenable social determinants of health elements that may enhance security and stability in that society.

Substantial populations of massive quiescent galaxies at z ≥ 3 challenge our understanding of rapid galaxy growth and quenching over short timescales. In order to piece together this evolutionary puzzle, more statistical samples of these objects are required. Established techniques for identifying massive quiescent galaxies are increasingly inefficient and unconstrained at z > 3. As a result, studies report that as much as 70% of quiescent galaxies at z > 3 may be missed from existing surveys. In this work, we propose a new empirical color selection technique designed to select massive quiescent galaxies at 3 ≲ z ≲ 6 using JWST NIRCam imaging data. We use empirically constrained galaxy spectral energy distribution (SED) templates to define a region in the F277W − F444W versus F150W − F277W color plane that captures quiescent galaxies at z > 3. We apply these color selection criteria to the Cosmic Evolution Early Release Science (CEERS) Survey and use SED fitting on sources in the region to identify 44 candidate z ≳ 3 quiescent galaxies. Over half of these sources are newly discovered and, on average, exhibit specific star formation rates of poststarburst galaxies. Most of these sources would not be discovered using canonical UVJ diagrams. We derive volume density estimates of n ∼ 1–4 × 10 ^−5 Mpc ^−3 at 3 < z < 5, finding excellent agreement with existing reports on similar populations in the CEERS field. Thanks to NIRCam’s wavelength coverage and sensitivity, this technique provides an efficient tool to search for large samples of these rare galaxies.

We present the first results from the Web Epoch of Reionization Ly α Survey (WERLS), a spectroscopic survey of Ly α emission using Keck I/MOSFIRE and LRIS. WERLS targets bright ( J < 26) galaxy candidates with photometric redshifts of 5.5 ≲ z ≲ 8 selected from pre-JWST imaging embedded in the Epoch of Reionization (EoR) within three JWST deep fields: CEERS, PRIMER, and COSMOS-Web. Here, we report 11 z ∼ 7–8 Ly α emitters (LAEs; three secure and eight tentative candidates) detected in the first five nights of WERLS MOSFIRE data. We estimate our observed LAE yield is ∼13%, which is broadly consistent with expectations assuming some loss from redshift uncertainty, contamination from sky OH lines, and that the Universe is approximately half-ionized at this epoch, whereby observable Ly α emission is unlikely for galaxies embedded in a neutral intergalactic medium. Our targets are selected to be UV-bright, and span a range of absolute UV magnitudes with −23.1 < M _UV < −19.8. With two LAEs detected at z = 7.68, we also consider the possibility of an ionized bubble at this redshift. Future synergistic Keck+JWST efforts will provide a powerful tool for pinpointing beacons of reionization and mapping the large-scale distribution of mass relative to the ionization state of the Universe.

The Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey program was designed specifically to include Near Infrared Slitless Spectroscopic observations (NGDEEP-NISS) to detect multiple emission lines in as many galaxies as possible and across a wide redshift range using the Near Infrared Imager and Slitless Spectrograph. We present early results obtained from the first set of observations (Epoch 1, 50% of the allocated orbits) of this program (NGDEEP-NISS1). Using a set of independently developed calibration files designed to deal with a complex combination of overlapping spectra, multiple position angles, and multiple cross filters and grisms, in conjunction with a robust and proven algorithm for quantifying contamination from overlapping dispersed spectra, NGDEEP-NISS1 has achieved a 3 σ sensitivity limit of 2 × 10 ^−18 erg s ^−1 cm ^−2 . We demonstrate the power of deep wide field slitless spectroscopy (WFSS) to characterize the star formation rates, and metallicity ([O iii ]/H β ), and dust content, of galaxies at 1 < z < 3.5. The latter showing intriguing initial results on the applicability and assumptions made regarding the use of Case B recombination. Further, we identify the presence of active galactic nuclei and infer the mass of their supermassive black holes using broadened restframe Mg ii and H β emission lines. The spectroscopic results are then compared with the physical properties of galaxies extrapolated from fitting spectral energy distribution models to photometry alone. The results clearly demonstrate the unique power and efficiency of WFSS at near-infrared wavelengths over other methods to determine the properties of galaxies across a broad range of redshifts.

We analyze rest-frame ultraviolet to optical spectra of three z ≃ 7.47–7.75 galaxies whose Ly α emission lines were previously detected with Keck/MOSFIRE observations, using the JWST/NIRSpec observations from the Cosmic Evolution Early Release Science survey. From NIRSpec data, we confirm the systemic redshifts of these Ly α emitters, and emission-line ratio diagnostics indicate these galaxies were highly ionized and metal-poor. We investigate Ly α line properties, including the line flux, velocity offset, and spatial extent. For the one galaxy where we have both NIRSpec and MOSFIRE measurements, we find a significant offset in their flux measurements (∼1.3–5× greater in MOSFIRE) and a marginal difference in the velocity shifts. The simplest interpretation is that the Ly α emission is extended and not entirely encompassed by the NIRSpec slit. The cross-dispersion profiles in NIRSpec reveal that Ly α in one galaxy is significantly more extended than the nonresonant emission lines. We also compute the expected sizes of ionized bubbles that can be generated by the Ly α sources and discuss viable scenarios for the creation of sizable ionized bubbles (>1 physical Mpc). The source with the highest-ionization condition is possibly capable of ionizing its own bubble, while the other two do not appear to be capable of ionizing such a large region, but require additional sources of ionizing photons. Therefore, the fact that we detect Ly α from these galaxies suggests diverse scenarios for the escape of Ly α during the epoch of reionization. High-spectral-resolution spectra with JWST/NIRSpec will be extremely useful for constraining the physics of patchy reionization.

Abstract Background Symbionts provide a variety of reproductive, nutritional, and defensive resources to their hosts, but those resources can vary depending on symbiont community composition. As genetic techniques open our eyes to the breadth of symbiont diversity within myriad microbiomes, symbiosis research has begun to consider what ecological mechanisms affect the identity and relative abundance of symbiont species and how this community structure impacts resource exchange among partners. Here, we manipulated the in hospite density and relative ratio of two species of coral endosymbionts (Symbiodinium microadriaticum and Breviolum minutum) and used stable isotope enrichment to trace nutrient exchange with the host, Briareum asbestinum. Results The patterns of uptake and translocation of carbon and nitrogen varied with both density and ratio of symbionts. Once a density threshold was reached, carbon acquisition decreased with increasing proportions of S. microadriaticum. In hosts dominated by B. minutum, nitrogen uptake was density independent and intermediate. Conversely, for those corals dominated by S. microadriaticum, nitrogen uptake decreased as densities increased, and as a result, these hosts had the overall highest (at low density) and lowest (at high density) nitrogen enrichment. Conclusions Our findings show that the uptake and sharing of nutrients was strongly dependent on both the density of symbionts within the host, as well as which symbiont species was dominant. Together, these complex interactive effects suggest that host regulation and the repression of in hospite symbiont competition can ultimately lead to a more productive mutualism. Video Abstract

Abstract As coral reefs face warming oceans and increased coral bleaching, a whitening of the coral due to loss of microalgal endosymbionts, the possibility of evolutionary rescue offers some hope for reef persistence. In tightly linked mutualisms, evolutionary rescue may occur through evolution of the host and/or endosymbionts. Many obligate mutualisms are composed of relatively small, fast-growing symbionts with greater potential to evolve on ecologically relevant time scales than their relatively large, slower growing hosts. Numerous jellyfish species harbor closely related endosymbiont taxa to other cnidarian species such as coral, and are commonly used as a model system for investigating cnidarian mutualisms. We examined the potential for adaptation of the upside-down jellyfish Cassiopea xamachana to increased temperature via evolution of its microalgal endosymbiont, Symbiodinium microadriaticum. We quantified trait variation among five algal genotypes in response to three temperatures (26 °C, 30 °C, and 32 °C) and fitness of hosts infected with each genotype. All genotypes showed positive growth rates at each temperature, but rates of respiration and photosynthesis decreased with increased temperature. Responses varied among genotypes but were unrelated to genetic similarity. The effect of temperature on asexual reproduction and the timing of development in the host also depended on the genotype of the symbiont. Natural selection could favor different algal genotypes at different temperatures, affecting host fitness. This eco-evolutionary interaction may be a critical component of understanding species resilience in increasingly stressful environments.

Measurement(s) Brain anatomy • Brain activity • Diffusion • Brain microstructure • Functional connectivity • Structural connectivity Technology Type(s) magnetic resonance imaging (MRI) • Functional Magnetic Resonance Imaging • Diffusion Weighted Imaging • magnetic resonance imaging (MRI) • Resting State Functional Connectivity Magnetic Resonance Imaging • Diffusion Weighted Imaging Sample Characteristic - Organism Homo sapiens

Abstract Background Advances in health equity rely on representation of diverse groups in population health research samples. Despite progress in the diversification of research samples, continued expansion to include systematically excluded groups is needed to address health inequities. One such group that is infrequently represented in population health research are adults with intellectual disability. Individuals with intellectual disability experience pervasive health disparities. Representation in population health research is crucial to determine the root causes of inequity, understand the health of diverse populations, and address health disparities. The purpose of this paper was to develop recommendations for researchers to increase the accessibility of university health research and to support the inclusion of adults with intellectual disability as participants in health research. Methods A comprehensive literature review, consultation with the university ethics review board, and review of United States federal regulations was completed to identify barriers to research participation for individuals with intellectual disability. A collaborative stakeholder working group developed recommendations and products to increase the accessibility of university research for participants with intellectual disability. Results Eleven key barriers to research participation were identified including gaps in researchers’ knowledge, lack of trust, accessibility and communication challenges, and systematic exclusion among others. Together the stakeholder working group compiled seven general recommendations for university health researchers to guide inclusion efforts. Recommendations included: 1) address the knowledge gap, 2) build community partnerships, 3) use plain language, 4) simplify consent and assent processes, 5) establish research capacity to consent, 6) offer universal supports and accommodations, and 7) practice accessible dissemination. In addition, four products were created as part of the stakeholder working group to be shared with researchers to support the inclusion of participants with intellectual disability. 1) Supports I Need Checklist, 2) Plain language glossary of health and research terms, 3) Understanding Consent and Assent in Plain Language, 4) Easy-Read Paper Template. Conclusion Community members and individuals with intellectual disability want to be included in research and are eager to engage as research participants. It is the responsibility of the researcher to open the door to university health research. The recommendations discussed in this paper could increase accessibility for a broader range of research participants and, in particular, promote the inclusion of individuals with intellectual disability to advance health equity in population health research.

Individuals across six major psychiatric conditions from the ENIGMA consortium reveals a shared morphological effect, following a sensory-fugal axis, which is related to microstructural gradient and neurotransmitter axes.

In this paper we describe the survey design for the Ultradeep NIRSpec and NIRCam Observations before the Epoch of Reionization (UNCOVER) Cycle 1 JWST Treasury program, which executed its early imaging component in 2022 November. The UNCOVER survey includes ultradeep (∼29–30AB) imaging of ∼45 arcmin ^2 on and around the well-studied A2744 galaxy cluster at z = 0.308 and will follow up ∼500 galaxies with extremely deep low-resolution spectroscopy with the NIRSpec/PRISM during the summer of 2023, with repeat visits in summer 2024. We describe the science goals, survey design, target selection, and planned data releases. We also present and characterize the depths of the first NIRCam imaging mosaic, highlighting previously unparalleled resolved and ultradeep 2–4 μ m imaging of known objects in the field. The UNCOVER primary NIRCam mosaic spans 28.8 arcmin ^2 in seven filters (F115W, F150W, F200W, F277W, F356W, F410M, and F444W) and 16.8 arcmin ^2 in our NIRISS parallel (F115W, F150W, F200W, F356W, and F444W). To maximize early community use of the Treasury data set, we publicly release the full reduced mosaics of public JWST imaging including 45 arcmin ^2 NIRCam and 17 arcmin ^2 NIRISS mosaics on and around the A2744 cluster, including the Hubble Frontier Field primary and parallel footprints.

We present a sample of 1165 extreme emission-line galaxies (EELGs) at 4 < z < 9 selected using James Webb Space Telescope (JWST) NIRCam photometry in the Cosmic Evolution Early Release Science (CEERS) program. We use a simple method to photometrically identify EELGs with H β + [O iii ] (combined) or H α emission of observed-frame equivalent width (EW) > 5000 Å. JWST/NIRSpec spectroscopic observations of a subset (34) of the photometrically selected EELGs validate our selection method: All spectroscopically observed EELGs confirm our photometric identification of extreme emission, including some cases where the spectral-energy-distribution-derived photometric redshifts are incorrect. We find that the medium-band F410M filter in CEERS is particularly efficient at identifying EELGs, both in terms of including emission lines in the filter and in correctly identifying the continuum between H β + [O iii ] and H α in the neighboring broadband filters. We present examples of EELGs that could be incorrectly classified as ultrahigh redshift ( z > 12) as a result of extreme H β + [O iii ] emission blended across the reddest photometric filters. We compare the EELGs to the broader (subextreme) galaxy population in the same redshift range and find that they are consistent with being the bluer, high-EW tail of a broader population of emission-line galaxies. The highest-EW EELGs tend to have more compact emission-line sizes than continuum sizes, suggesting that active galactic nuclei are responsible for at least some of the most extreme EELGs. The photometrically inferred emission-line ratios are consistent with interstellar medium conditions with high ionization and moderately low metallicity, consistent with previous spectroscopic studies.

We analyze the evolution of massive (log _10 [ M _⋆ / M _⊙ ] > 10) galaxies at z ∼ 1–4 selected from JWST Cosmic Evolution Early Release Survey (CEERS). We infer the physical properties of all galaxies in the CEERS NIRCam imaging through spectral energy distribution (SED) fitting with dense basis to select a sample of high-redshift massive galaxies. Where available we include constraints from additional CEERS observing modes, including 18 sources with MIRI photometric coverage, and 28 sources with spectroscopic confirmations from NIRSpec or NIRCam WFSS. We sample the recovered posteriors in stellar mass from SED fitting to infer the volume densities of massive galaxies across cosmic time, taking into consideration the potential for sample contamination by active galactic nuclei. We find that the evolving abundance of massive galaxies tracks expectations based on a constant baryon conversion efficiency in dark matter halos for z ∼ 1–4. At higher redshifts, we observe an excess abundance of massive galaxies relative to this simple model, resulting in a shallower decline of observed volume densities of massive galaxies. These higher abundances can be explained by modest changes to star formation physics and/or the efficiencies with which star formation occurs in massive dark matter halos, and are not in tension with modern cosmology.

Ultraviolet (UV; rest-frame ∼1200–2000 Å) spectra provide a wealth of diagnostics to characterize fundamental galaxy properties, such as their chemical enrichment, the nature of their stellar populations, and their amount of Lyman-continuum (LyC) radiation. In this work, we leverage publicly released JWST data to construct the rest-frame UV-to-optical composite spectrum of a sample of 63 galaxies at 5.6 < z < 9, spanning a wavelength range from 1500 to 5200 Å. Based on the composite spectrum, we derive an average dust attenuation $E{(B-V)}_{\mathrm{gas}}\,=\,{0.10}_{-0.11}^{+0.10}$ from H β /H γ , an electron density ${n}_{e}={570}_{-290}^{+510}$ cm ^−3 from the [O ii ] doublet ratio, an electron temperature ${T}_{e}={16700}_{-1500}^{+1500}$ K from the [O iii ] λ 4363/[O iii ] λ 5007 ratio, and an ionization parameter $\mathrm{log}(U)=-{2.15}_{-0.03}^{+0.03}$ from the [O iii ]/[O ii ] ratio. Using a direct T _e method, we calculate an oxygen abundance $12+\mathrm{log}({\rm{O}}/{\rm{H}})\,=\,7.67\pm 0.08$ and a carbon-to-oxygen (C/O) abundance ratio $\mathrm{log}({\rm{C}}/{\rm{O}})\,=\,-{0.86}_{-0.10}^{+0.13}$ . This C/O ratio is smaller than compared to z = 0 and z = 2–4 star-forming galaxies, albeit with moderate significance. This indicates the reionization-era galaxies might be undergoing a rapid buildup of stellar mass with high specific star formation rates. A UV diagnostic based on the ratios of C iii ] λ λ 1907, 1909/He ii λ 1640 versus O iii ] λ 1666/He ii λ 1640 suggests that the star formation is the dominant source of ionization, similar to the local extreme dwarf galaxies and z ∼ 2–4 He ii –detected galaxies. The [O iii ]/[O ii ] and C iv /C iii ] ratios of the composite spectrum are marginally larger than the criteria used to select galaxies as LyC leakers, suggesting that some of the galaxies in our sample are strong contributors to the reionizing radiation.

We test the relationship between UV-derived star formation rates (SFRs) and the 7.7 μ m polycyclic aromatic hydrocarbon luminosities from the integrated emission of galaxies at z ∼ 0–2. We utilize multiband photometry covering 0.2–160 μ m from the Hubble Space Telescope, CFHT, JWST, Spitzer, and Herschel for galaxies in the Cosmic Evolution Early Release Science (CEERS) Survey. We perform spectral energy distribution (SED) modeling of these data to measure dust-corrected far-UV (FUV) luminosities, L _FUV , and UV-derived SFRs. We then fit SED models to the JWST/MIRI 7.7–21 μ m CEERS data to derive rest-frame 7.7 μ m luminosities, L _770 , using the average flux density in the rest-frame MIRI F770W bandpass. We observe a correlation between L _770 and L _FUV , where $\mathrm{log}{L}_{770}\propto (1.27\pm 0.04)\mathrm{log}{L}_{\mathrm{FUV}}$ . L _770 diverges from this relation for galaxies at lower metallicities, lower dust obscuration, and for galaxies dominated by evolved stellar populations. We derive a “single-wavelength” SFR calibration for L _770 that has a scatter from model estimated SFRs ( σ _ΔSFR ) of 0.24 dex. We derive a “multiwavelength” calibration for the linear combination of the observed FUV luminosity (uncorrected for dust) and the rest-frame 7.7 μ m luminosity, which has a scatter of σ _ΔSFR = 0.21 dex. The relatively small decrease in σ suggests this is near the systematic accuracy of the total SFRs using either calibration. These results demonstrate that the rest-frame 7.7 μ m emission constrained by JWST/MIRI is a tracer of the SFR for distant galaxies to this accuracy, provided the galaxies are dominated by star formation with moderate-to-high levels of attenuation and metallicity.

We present the construction of a deep multiwavelength point-spread-function-matched photometric catalog in the Ultra-Deep Survey (UDS) field following the final UKIDSS UDS release. The catalog includes photometry in 24 filters, from the MegaCam- uS 0.38 μ m band to the Spitzer-IRAC 8 μ m band, over ∼0.9 deg ^2 and with a 5 σ depth of 25.3 AB in the K -band detection image. The catalog, containing ≈188,564 (136,235) galaxies at 0.2 < z < 8.0 with stellar mass $\mathrm{log}({M}_{* }/{M}_{\odot })\gt 8$ and K -band total magnitude K < 25.2 (24.3) AB, enables a range of extragalactic studies. We also provide photometric redshifts, corresponding redshift probability distributions, and rest-frame absolute magnitudes and colors derived using the template-fitting code eazy-py . Photometric redshift errors are less than 3%−4% at z < 4 across the full brightness range in the K band and stellar mass range $8\lt \mathrm{log}({M}_{* }/{M}_{\odot })\lt 12$ . Stellar population properties (e.g., stellar mass, star formation rate, dust extinction) are derived from the modeling of the spectral energy distributions using the codes FAST and Dense Basis.

Using more than 100 galaxies in the MUSE Ultra Deep Field with spectroscopy from the Hubble Space Telescope’s (HST) Wide Field Camera 3 and the Very Large Telescope’s Multi Unit Spectroscopic Explorer, we extend the gas-phase mass–metallicity relation (MZR) at z ≈ 1–2 down to stellar masses of M _⋆ ≈ 10 ^7.5 M _⊙ . The sample reaches 6 times lower in stellar mass and star formation rate (SFR) than previous HST studies at these redshifts, and we find that galaxy metallicities decrease to log(O/H) + 12 ≈ 7.8 ± 0.1 (15% solar) at log( M _⋆ / M _⊙ ) ≈ 7.5, without evidence of a turnover in the shape of the MZR at low masses. We validate our strong-line metallicities using the direct method for sources with [O iii ] λ 4363 and [O iii ] λ 1666 detections, and find excellent agreement between the techniques. The [O iii ] λ 1666-based metallicities double existing measurements with a signal-to-noise ratio ≥ 5 for unlensed sources at z > 1, validating the strong-line calibrations up to z ∼ 2.5. We confirm that the MZR resides ∼0.3 dex lower in metallicity than local galaxies and is consistent with the fundamental metallicity relation if the low-mass slope varies with SFR. At lower redshifts ( z ∼ 0.5) our sample reaches ∼0.5 dex lower in SFR than current calibrations and we find enhanced metallicities that are consistent with extrapolating the MZR to lower SFRs. Finally, we detect only an ∼0.1 dex difference in the metallicities of galaxies in groups versus isolated environments. These results are based on robust calibrations and reach the lowest masses and SFRs that are accessible with HST, providing a critical foundation for studies with the Webb and Roman Space Telescopes.

The James Webb Space Telescope is revealing a new population of dust-reddened broad-line active galactic nuclei (AGN) at redshifts z ≳ 5. Here we present deep NIRSpec/Prism spectroscopy from the Cycle 1 Treasury program Ultradeep NIRSpec and NIRCam ObserVations before the Epoch of Reionization (UNCOVER) of 15 AGN candidates selected to be compact, with red continua in the rest-frame optical but with blue slopes in the UV. From NIRCam photometry alone, they could have been dominated by dusty star formation or an AGN. Here we show that the majority of the compact red sources in UNCOVER are dust-reddened AGN: 60% show definitive evidence for broad-line H α with a FWHM > 2000 km s ^−1 , 20% of the current data are inconclusive, and 20% are brown dwarf stars. We propose an updated photometric criterion to select red z > 5 AGN that excludes brown dwarfs and is expected to yield >80% AGN. Remarkably, among all z _phot > 5 galaxies with F277W – F444W > 1 in UNCOVER at least 33% are AGN regardless of compactness, climbing to at least 80% AGN for sources with F277W – F444W > 1.6. The confirmed AGN have black hole masses of 10 ^7 –10 ^9 M _⊙ . While their UV luminosities (−16 > M _UV > −20 AB mag) are low compared to UV-selected AGN at these epochs, consistent with percent-level scattered AGN light or low levels of unobscured star formation, the inferred bolometric luminosities are typical of 10 ^7 –10 ^9 M _⊙ black holes radiating at ∼10%–40% the Eddington limit. The number densities are surprisingly high at ∼10 ^−5 Mpc ^−3 mag ^−1 , 100 times more common than the faintest UV-selected quasars, while accounting for ∼1% of the UV-selected galaxies. While their UV faintness suggests they may not contribute strongly to reionization, their ubiquity poses challenges to models of black hole growth.

We study a new population of extremely red objects (EROs) recently discovered by the James Webb Space Telescope (JWST) based on their NIRCam colors F277W − F444W > 1.5 mag. We find 37 EROs in the Cosmic Evolution Early Release Science Survey (CEERS) field with F444W < 28 mag and photometric redshifts between 5 < z < 7, with median $z={6.9}_{-1.6}^{+1.0}$ . Surprisingly, despite their red long-wavelength colors, these EROs have blue short-wavelength colors (F150W − F200W ∼ 0 mag) indicative of bimodal spectral energy distributions (SEDs) with a red, steep slope in the rest-frame optical, and a blue, flat slope in the rest-frame UV. Moreover, all these EROs are unresolved, point-like sources in all NIRCam bands. We analyze the SEDs of eight of them with MIRI and NIRSpec observations using stellar population models and active galactic nucleus (AGN) templates. We find that dusty galaxies or obscured AGNs provide similarly good SED fits but different stellar properties: massive and dusty, $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ∼ 10 and A _V ≳ 3 mag, or low mass and obscured, $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ∼ 7.5 and A _V ∼ 0 mag, hosting an obscured quasi-stellar object (QSO). SED modeling does not favor either scenario, but their unresolved sizes are more suggestive of AGNs. If any EROs are confirmed to have $\mathrm{log}{M}_{\star }/{M}_{\odot }$ ≳ 10.5, it would increase the pre-JWST number density at z > 7 by up to a factor ∼60. Similarly, if they are QSOs with luminosities in the L _bol > 10 ^45–46 erg s ^−1 range, their number would exceed that of bright blue QSOs by more than three orders of magnitude. Additional photometry at mid-infrared wavelengths will reveal the true nature of the red continuum emission in these EROs and will place this puzzling population in the right context of galaxy evolution.