Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

Measuring and attributing greenhouse gas (GHG) emissions remains a challenging problem as the world strives toward meeting emissions reductions targets. As a significant portion of total global emissions, the road transportation sector represents an enormous challenge for estimating and tracking emissions at a global scale. To meet this challenge, we have developed a hybrid approach for estimating road transportation emissions that combines the strengths of machine learning and satellite imagery with localized emissions factors data to create an accurate, globally scalable, and easily configurable GHG monitoring framework.

A retrospective cohort of children admitted to the pediatric intensive care unit (PICU) with cerebral palsy was matched 1:3 by age and admission year to determine odds of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization. Adjusted odds of MRSA nasal colonization at PICU admission were 2.6-fold higher among children with cerebral palsy.

OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.

Inadequate sleep and poor eating behaviours are associated with higher risk of childhood overweight and obesity. Less is known about the influence sleep has on eating behaviours and consequently body composition. Furthermore, whether associations differ in boys and girls has not been investigated extensively. We investigate associations between sleep, eating behaviours and body composition in cross-sectional analysis of 5-year-old children. Weight, height, BMI, mid upper arm circumference (MUAC), abdominal circumference (AC) and skinfold measurements were obtained. Maternal reported information on child’s eating behaviour and sleep habits were collected using validated questionnaires. Multiple linear regression examined associations between sleep, eating behaviours and body composition. Sleep duration was negatively associated with BMI, with 1-h greater sleep duration associated with 0·24 kg/m2 (B = 0·24, CI −0·42, −0·03, P = 0·026) lower BMI and 0·21 cm lower (B = –0·21, CI −0·41, −0·02, P = 0·035) MUAC. When stratified by sex, girls showed stronger inverse associations between sleep duration (h) and BMI (kg/m2) (B = –0·32; CI −0·60, −0·04, P = 0·024), MUAC (cm) (B = –0·29; CI −0·58, 0·000, P = 0·05) and AC (cm) (B = –1·10; CI −1·85, −0·21, P = 0·014) than boys. Positive associations for ‘Enjoys Food’ and ‘Food Responsiveness’ with BMI, MUAC and AC were observed in girls only. Inverse associations between sleep duration and ‘Emotional Undereating’ and ‘Food Fussiness’ were observed in both sexes, although stronger in boys. Sleep duration did not mediate the relationship between eating behaviours and BMI. Further exploration is required to understand how sleep impacts eating behaviours and consequently body composition and how sex influences this relationship.

ABSTRACT IMPACT: This work identifies host immune perturbations in sepsis mortality that suggests targets for a precision medicine paradigm in the host response to infection. OBJECTIVES/GOALS: To compare the early whole blood transcriptome during sepsis between 30-day survivors and non-survivors in the Intensive Care Unit (ICU), and to evaluate for pathway enrichment that might explain sepsis lethality. METHODS/STUDY POPULATION: We enrolled 162 sepsis patients in the first 24 hours of ICU admission, particularly targeting individuals requiring vasopressors. Peripheral whole blood was collected in PAXgene vacutainers. Isolated RNA was analyzed with Affymetrix Human Genome ST 2.0 microarray. Differential gene expression was performed with Bioconductor/R/limma using log2 fold-change +/-0.6 as a threshold for differential expression, and a Benjamini-Hochberg adjusted p-value <0.05 to declare significance. Functional gene enrichment was performed using the Gene Ontology (GO) database with PANTHER overrepresentation test (Fisher’s Exact) on all transcripts with adjusted p-value <0.05. Pathways analysis was performed with the Reactome Project using the raw fold change and significance data to identify dysregulated pathways. RESULTS/ANTICIPATED RESULTS: There were 58 non-survivors (36% mortality). We identified 39 genes as differentially expressed between sepsis non-survivors and survivors; 31 were upregulated in non-survivors and 8 had reduced expression. Several of the most overexpressed transcripts are neutrophil-specific, including LCN, MPO, OLF4M4, DEFA3, and DEFA4. A functional gene overrepresentation test further supports this finding, as the most enriched gene ontologies were neutrophil-mediated killing, neutrophil cytotoxicity, neutrophil extravasation, and respiratory burst, all demonstrating higher than 10-fold enrichment and FDR < 0.02. Pathway analysis of the peripheral blood transcriptome was notable for immune response derangement, specifically downregulation of both innate and adaptive immune pathways (FDR < 0.00001). DISCUSSION/SIGNIFICANCE OF FINDINGS: We identified increased expression of neutrophil-related genes in sepsis non-survivors, replicating candidates previously identified in pediatric sepsis mortality and ARDS. These immune perturbations in sepsis mortality may represent key targets for eventually employing precision medicine strategies in sepsis.

Specialised rehabilitation units offer inpatient multi-disciplinary rehabilitation for individuals with severe and enduring mental illness. A cornerstone of therapy is the work in the community through further education and community organisations. However, coronavirus restrictions have meant that such external supports are no longer available for the duration of the crisis. This has led to opportunities for developing new ways of offering rehabilitation within hospital environments. This article describes some of the new initiatives developed. The benefits of the lockdown for service users are also discussed. Many found the cessation of visits from family members with whom they had an ambivalent relationship helpful. The lockdown improved relationships between patients on the unit and encouraged a greater feeling of community. The lockdown has also emphasised the importance of team self-awareness and an awareness of the nature of the treatments offered.

Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.

We explored whether supported (SJE) or coordinated joint engagement (CJE) between mothers recruited from the community and their 24-month-old children who were slow-to-talk at 18 months old were associated with child language scores at ages 24, 36, and 48 months (n = 197). We further explored whether SJE or CJE modified the concurrent positive associations between maternal responsive behaviours and language scores. Previous research has shown that SJE, maternal expansions, imitations, and responsive questions were associated with better language scores. Our main finding was that SJE but not CJE was consistently positively associated with 24- and 36-month-old expressive and receptive language scores, but not with 48-month-old language scores. SJE modified how expansions and imitations, but not responsive questions, were associated with language scores; the associations were evident in all but the highest levels of SJE. Further research is necessary to test these findings in other samples before clinical recommendations can be made.

Validation of the number of central line–days by hospitals is required by the National Healthcare Safety Network. A prospective study that compared a daily report of such days generated by an electronic medical record with observational audits by nurses revealed that the report was 100% sensitive and 99.9% specific.

Infect. Control Hosp. Epidemiol. 2015;36(9):1098–1099