Objectives/Goals: Primary sclerosing cholangitis (PSC) manifests with an inflammatory milieu that leads to fibrotic scarring of the liver. Human PSC liver bile ducts are enriched with neutrophils; however, their infiltration and functional role is unexplored. Our goal is to investigate the mechanism and impact of peribiliary neutrophil infiltration observed in PSC. Methods/Study Population: Primary cholangiocytes (bile duct cells) isolated from WT and mouse models of PSC (3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice and Mdr2-/- mice) were analyzed by RNA-sequencing. Immunofluorescence (IF) was performed on liver tissues from PSC patients and mouse models of PSC for markers of bile ducts and neutrophils (KRT19 and MPO). Intrahepatic leukocytes (IHL) isolated from mice livers were evaluated for neutrophil abundance and activation state. Anti-Ly6G antibody-mediated neutrophil depletion in Mdr2-/- mice was analyzed by IF, histology, and cytometry by time-of-flight (CyTOF). Cholangiocytes stimulated with TNFα (to induce an inflammatory phenotype) were analyzed for neutrophil chemoattractants with genetic and pharmacological interventions. Results/Anticipated Results: RNA-seq analysis of primary cholangiocytes from PSC mouse models revealed enrichment in inflammatory and neutrophil degranulation pathways. Flow cytometry and RT-PCR analysis revealed an increase in the neutrophil population in PSC mice with activated phenotype. Peripheral depletion of neutrophils in Mdr2-/- mice alleviated liver injury and inflammation, along with a reduction in peribiliary neutrophil infiltration and attenuated bridging fibrosis. CyTOF analysis showed a significant reduction in CD8+ T cells upon neutrophil depletion, implying neutrophils sustain CD8+ T cells in PSC liver. Mechanistically in cholangiocytes, TNFα mediates expression of neutrophil chemoattractants, CXCL1 and CXCL8, through the cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway. Discussion/Significance of Impact: Our findings suggest that activation of the STING pathway in cholangiocytes in cholestatic liver disease triggers an immune response resulting in peri-portal neutrophil infiltration via CXC chemokines. The sustained presence of these activated neutrophils engages the adaptive immune system to perpetuate the inflammation and fibrosis seen in PSC.

In September 2023, the UK Health Security Agency’s (UKHSA) South West Health Protection Team received notification of patients with Pseudomonas aeruginosa perichondritis. All five cases had attended the same cosmetic piercing studio and a multi-disciplinary outbreak control investigation was subsequently initiated. An additional five cases attending the same studio were found. Seven of the ten cases had isolates available for Variable Number Tandem Repeat (VNTR) typing at the UKHSA national reference laboratory. Clinical and environmental P. aeruginosa isolates from the patients, handwash sink, tap water and throughout the wall-mounted point-of-use water heater (including outlet water) were indistinguishable by VNTR typing (11,6,2,2,1,3,6,3,11). No additional cases were identified after control measures were implemented, which included replacing the sink and point-of-use heater.

The lack of specific recommendations to control for P. aeruginosa within Council-adopted ear-piercing byelaws or national guidance means that a cosmetic piercing artist could inadvertently overlook the risks from this bacterial pathogen despite every intention to comply with the law and follow industry best practice advice. Clinicians, Environmental Health Officers and public health professionals should remain alert for single cases of Pseudomonas perichondritis infections associated with piercings and have a low threshold for notification to local health protection teams.

The present paper proposes a hierarchical, multi-unidimensional two-parameter logistic item response theory (2PL-MUIRT) model extended for a large number of groups. The proposed model was motivated by a large-scale integrative data analysis (IDA) study which combined data (N = 24,336) from 24 independent alcohol intervention studies. IDA projects face unique challenges that are different from those encountered in individual studies, such as the need to establish a common scoring metric across studies and to handle missingness in the pooled data. To address these challenges, we developed a Markov chain Monte Carlo (MCMC) algorithm for a hierarchical 2PL-MUIRT model for multiple groups in which not only were the item parameters and latent traits estimated, but the means and covariance structures for multiple dimensions were also estimated across different groups. Compared to a few existing MCMC algorithms for multidimensional IRT models that constrain the item parameters to facilitate estimation of the covariance matrix, we adapted an MCMC algorithm so that we could directly estimate the correlation matrix for the anchor group without any constraints on the item parameters. The feasibility of the MCMC algorithm and the validity of the basic calibration procedure were examined using a simulation study. Results showed that model parameters could be adequately recovered, and estimated latent trait scores closely approximated true latent trait scores. The algorithm was then applied to analyze real data (69 items across 20 studies for 22,608 participants). The posterior predictive model check showed that the model fit all items well, and the correlations between the MCMC scores and original scores were overall quite high. An additional simulation study demonstrated robustness of the MCMC procedures in the context of the high proportion of missingness in data. The Bayesian hierarchical IRT model using the MCMC algorithms developed in the current study has the potential to be widely implemented for IDA studies or multi-site studies, and can be further refined to meet more complicated needs in applied research.

Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.

This editorial considers the value and nature of academic psychiatry by asking what defines the specialty and psychiatrists as academics. We frame academic psychiatry as a way of thinking that benefits clinical services and discuss how to inspire the next generation of academics.

The idea that some abilities might be enhanced by adversity is gaining traction. Adaptation-based approaches have uncovered a few specific abilities enhanced by particular adversity exposures. Yet, for a field to grow, we must not dig too deep, too soon. In this paper, we complement confirmatory research with principled exploration. We draw on two insights from adaptation-based research: 1) enhanced performance manifests within individuals, and 2) reduced and enhanced performance can co-occur. Although commonly assumed, relative performance differences are rarely tested. To quantify them, we need a wide variety of ability measures. However, rather than using adaptive logic to predict which abilities are enhanced or reduced, we develop statistical criteria to identify three data patterns: reduced, enhanced, and intact performance. With these criteria, we analyzed data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development to investigate how adversity shapes within-person performance across 10 abilities in a cognitive and achievement battery. Our goals are to document adversity-shaped cognitive performance patterns, identify drivers of reduced performance, identify sets of “intact” abilities, and discover new enhanced abilities. We believe principled exploration with clear criteria can help break new theoretical and empirical ground, remap old territory, and advance theory development.

The diagnosis of functional constipation (FC) relies on patient-reported outcomes evaluated as criteria based on the clustering of symptoms. Although the ROME IV criteria for FC diagnosis is relevant for a multicultural population(1), how an individual’s lifestyle, environment and culture may influence the pathophysiology of FC remains a gap in our knowledge. Building on insights into mechanisms underpinning disorders of gut-brain interactions (formerly functional gastrointestinal disorders) in the COMFORT Cohort(2), this study aimed to investigate the differences in gastrointestinal (GI) symptom scores among participants with FC in comparison to healthy controls between Chinese and non-Chinese New Zealanders. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal cohort study, which aimed to determine a comprehensive profile of characteristics and biological markers of FC between Chinese and non-Chinese New Zealanders. Chinese (classified according to maternal and paternal ethnicity) or non-Chinese (mixed ethnicities) adults living in Auckland classified as with or without FC based on ROME IV were enrolled. Monthly assessment (for 3 months) of GI symptoms, anthropometry, quality of life, diet, and biological samples were assessed monthly over March to June 2023. Demographics were obtained through a self-reported questionnaires and GI symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). This analysis is a cross-sectional assessment of patient-reported outcomes of GI symptoms. Of 78 enrolled participants, 66 completed the study (male, n = 10; female, n = 56) and were distributed across: Chinese with FC (Ch-FC; n = 11), Chinese control (Ch-CON; n = 19), non-Chinese with FC (NCh-FC; n = 16), non-Chinese control (NCh-CON; n = 20). Mean (SD) age, body mass index, and waist circumference were 40 ± 9 years, 22.7 ± 2.5 kg/m2, and 78.0 ± 7.6 cm, respectively. Ethnicity did not impact SAGIS domain scores for GI symptoms (Ethnicity x FC severity interaction p>0.05). Yet, the constipation symptoms domain of the GSRS was scored differently depending on ethnicity and FC status (Ethnicity x FC interaction p<0.05). In post hoc comparison, NCh-FC tended to have higher GSRS constipation severity scores than Ch-FC (3.4 ± 1.0 versus 3.8 ± 0.8 /8, p<0.1) Although constipation symptom severity tended to be higher in NCh-FC, on the whole, ethnicity did not explain variation in this cohort. FC status was a more important predictor of GI symptoms scores. Future research will assess differences in symptom burden to explore ethnicity-specific characteristics of FC.

Distinct pathophysiology has been identified with disorders of gut-brain interactions (DGBI), including functional constipation (FC)(1,2), yet the causes remain unclear. Identifying how modifiable factors (i.e., diet) differ depending on gastrointestinal health status is important to understand relationships between dietary intake, pathophysiology, and disease burden of FC. Given that dietary choices are culturally influenced, understanding ethnicity-specific diets of individuals with FC is key to informing appropriate symptom management and prevention strategies. Despite distinct genetic and cultural features of Chinese populations with increasing FC incidence(3), DGBI characteristics are primarily described in Caucasian populations(2). We therefore aimed to identify how dietary intake of Chinese individuals with FC differs to non-Chinese individuals with FC, relative to healthy controls. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal case-control study using systems biology to investigate the multi-factorial aetiology of FC. Here we conducted a cross-sectional dietary intake assessment, comparing Chinese individuals with FC (Ch-FC) against three control groups: a) non-Chinese with FC (NCh-FC) b) Chinese without FC (Ch-CON) and c) non-Chinese without FC (NCh-CON). Recruitment from Auckland, New Zealand (NZ) identified Chinese individuals based on self-identification alongside both parents self-identifying as Chinese, and FC using the ROME IV criteria. Dietary intake was captured using 3-day food diaries recorded on consecutive days, including one weekend day. Nutrient analysis was performed by Foodworks 10 and statistical analysis with SPSS using a generalised linear model (ethnicity and FC status as fixed factors). Of 78 enrolled participants, 66 completed the study and 64 (39.4 ± 9.2 years) completed a 3-day food diary at the baseline assessment. More participants were female (84%) than male (16%). FC and ethnicity status allocated participants into 1 of 4 groups: Ch-FC (n = 11), Ch-CON (n = 18), NCh-FC (n = 16), NCh-CON (n = 19). Within NCh, ethnicities included NZ European (30%), non-Chinese Asian (11%), Other European (11%), and Latin American (2%). Fibre intake did not differ between Ch-FC and NCh-FC (ethnicity × FC status interaction p>0.05) but was independently lower overall for FC than CON individuals (21.8 ± 8.7 versus 27.0 ± 9.7 g, p<0.05) and overall for Ch than NCh (22.1 ± 8.0 versus 27.0 ± 10.4 g, p<0.05). Carbohydrate, protein, and fat intakes were not different across groups (p>0.05 each, respectively). In the context of fibre and macronutrient intake, there is no difference between Ch-FC and NCh-FC. Therefore, fibre and macronutrients are unlikely to contribute to potential pathophysiological differences in FC between ethnic groups. A more detailed assessment of dietary intake concerning micronutrients, types of fibre, or food choices may be indicated to ascertain whether other dietary differences exist.

Child care environments offer an ideal setting for feeding interventions. CELEBRATE Feeding is an approach implemented in child care environments in two Maritime Provinces in Canada to support responsive feeding (RF) to foster children’s self-efficacy, self-regulation, and healthy relationships with food. This study aimed to describe RF in child care using established and enhanced scoring frameworks.

The Environment and Policy Assessment and Observation (EPAO) was modified to reflect RF environments and practices, resulting in our modified EPAO and a CELEBRATE scale. Observations were conducted in 18 child care rooms. Behaviours and environments were scored on both scales, creating 21 RF scores, with a score of ‘3’ indicating the most responsiveness. Descriptive analyses of the scores were conducted. The overall room averages were Mean (M) = 41.00, Standard Deviation (SD) = 7.07 (EPAO), and M = 37.92 SD = 6.50 (CELEBRATE). Most responsive scores among rooms within our EPAO and CELEBRATE scales, respectively, were ‘educators not using food to calm or encourage behaviour’ (M = 2.94, SD = 0.24; M = 2.98, SD = 0.06) and ‘not requiring children to sit at the table until finished’ (M = 2.89, SD = 0.47; M = 2.97, SD = 0.12). The least responsive scores within the EPAO were ‘educator prompts for children to drink water’ (M = 0.78, SD = 0.94) and ‘children self-serving’ (M = 0.83, SD = 0.38). The least responsive in the CELEBRATE scale were ‘enthusiastic role modelling during mealtime’ (M = 0.70, SD = 0.68) and ‘praise of mealtime behaviour unrelated to food intake’ (M = 0.74, SD = 0.55). The CELEBRATE scale captured unique observation information about RF to allow documenting change over time with detailed measurement to inform and support nutrition interventions within child care environments.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel–Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

The Critically Endangered African wild ass Equus africanus is one of the most threatened equids, with fewer than 400 individuals persisting in the Danakil Desert (Eritrea), and fewer than 600 globally. To effectively conserve the species, it is essential to determine the extent of available suitable habitats and understand the environmental factors that most influence its current distribution. During 2016–2019 we observed African wild asses, recorded their locations during both the wet and dry seasons and analysed the bioclimatic data and topography using the maximum entropy species distribution model. Distance from water sources and precipitation of the driest month were the top predictors of suitable habitat for the dry season, whereas seasonal temperature variability and precipitation during the warmest quarter were the top predictors for the wet season. Model performances were high, with area under the curve values of 0.97 and 0.98 for the dry and wet seasons, respectively. In the Danakil Desert of Eritrea, the extent of optimal habitat for African wild asses is estimated to be 130 km2 in the dry season and 739 km2 in the wet season, with a potential range of 11,000 km2 for both seasons. Our model results also indicate that in the dry season 89 km2 of the Messir Plateau is optimal habitat, and the entire plateau area of 124 km2 provides optimal habitat during the wet season. These findings provide wildlife management authorities with substantive information and rationale for the establishment of a protected area on the Messir Plateau for African wild asses in Eritrea.