Browse Articles

Abstract P1099: A Daily Diary Examination of the Associations of Adverse Childhood Experiences, Anticipated Discrimination, and Blood Pressure among Sexual and Gender Minority Adults

Background: Chronic psychosocial stressors, such as anticipated discrimination and adverse childhood experiences, have been shown to influence hypertension risk among stigmatized adults. Emerging research suggests that individuals exposed to adverse childhood experiences later report greater discrimination as adults. Researchers theorize that exposure to adverse childhood experiences likely moderate the association between discrimination and blood pressure (BP); however, this remains underexplored. Therefore, we sought to examine whether adverse childhood experiences moderated the associations of anticipated discrimination and BP in a diverse sample of adults. Methods: Data were obtained from a 30-day online diary study of sexual and gender minority (SGM; e.g., gay/lesbian, bisexual, transgender) adults in the United States. Participants completed daily electronic diaries that assessed anticipated discrimination every morning. Home BP was assessed every day at awakening and before bedtime. Adverse childhood experiences, including childhood physical, emotional, and sexual abuse, were assessed at baseline using a validated questionnaire. Mixed-effects linear models, adjusted for demographic factors, estimated the associations between daily anticipated discrimination and BP and the moderating role of adverse childhood experiences. Results: The sample included 31 SGM adults with a mean age of 27.1 years (±7.50). Approximately 83% of participants were Latinx and 49% were multiracial. We found that 39% of the sample reported exposure to 4 or more adverse childhood experiences. Results of mixed-effects linear models suggested that daily anticipated discrimination was not significantly associated with BP. However, we did find evidence that childhood physical abuse significantly strengthened the association between daily anticipated discrimination and morning diastolic BP (β(SE) = 2.36 (0.88), p = 0.01). Childhood emotional and sexual abuse were not significant moderators. Conclusions: Our findings highlight the importance of considering the moderating effects of adverse childhood experiences on the association between daily anticipated discrimination and BP among SGM people. Future research is needed with larger samples to understand the role that adverse childhood experiences (particularly childhood physical abuse) may play in sensitizing individuals to greater exposure to psychosocial stress and subsequent hypertension risk in adulthood.

Abstract P1165: Dietary Quality Among Pregnant People With Overweight/Obesity: Comparison Between Randomized Controlled Trial Participants in Early Pregnancy With Non-Pregnant NHANES Matched Participants

Background: Poor dietary quality is associated with perinatal obesity, including excess gestational weight gain, a risk factor for future cardiometabolic disease. Despite the need to assess and intervene on dietary quality in pregnancy, few studies have identified screeners that are easy to use and have comparable performance in research as well as the general population. We sought to describe the dietary patterns of participants in early pregnancy using the Dietary Screener Questionnaire (DSQ) and compare the results with a matched non-pregnant sample from the 2009-2010 wave of the National Health and Nutrition Examination Survey (NHANES) who also completed the screener to demonstrate the external validity of our DSQ results. Methods: We compared the baseline dietary quality data from an ongoing randomized controlled trial (RCT) to assess the effectiveness of a remote lifestyle intervention targeting dietary quality on gestational weight gain with matched controls from non-pregnant NHANES participants. Baseline DSQ responses were collected from the RCT participants at ≤ 15 weeks of gestation. We selected a non-pregnant NHANES sample matched for age (20-44), sex (female), BMI (≥ 25), and complete DSQ data. We estimated daily intake of added sugar (total and from sweetened beverages), fiber, fruits and vegetables, and dairy using the standard scoring procedures and compared the samples using the Mann-Whitney U test. Results: At baseline, 383 RCT participants completed the DSQ with a mean age of 34.2 years (SD = 5.0). The NHANES sample included 651 people (mean age = 32.9 years, SD = 7.4 years). Pregnant RCT participants had a significantly lower consumption of daily total sugar (median = 13.2 tsp, IQR = [11.6, 15.0]) and sugar from beverages (median = 4.5 tsp, IQR = [3.9, 6.1]) compared to matched NHANES non-pregnant participants (total: median = 15.3 tsp, IQR = [12.9, 19.8]; beverages: median = 6.6 tsp, IQR = [4.4, 11.0]; both p < 0.001). Other dietary quality measures were comparable between samples (Figure 1). Conclusion: Dietary patterns of RCT participants in early pregnancy and matched non-pregnant NHANES 2009-2010 participants were similar, except for sugar intake, indicating that the DSQ results may be generalizable to a broader population like people in NHANES. The lower intake of added sugar, particularly from sweetened beverages, may reflect decreased intake in early pregnancy or secular changes in the last 15 years.

Quantification of extrusion-induced excavation volume in shield tunnelling through squeezing cohesive-frictional ground

Abstract When tunnelling through weak and highly deformable ground, relevant deformations occur ahead of the tunnel face and result in face displacements that are opposite to the advance direction (“extrusion”). In mechanised tunnelling, the cutterhead continuously removes the ground extruding at the tunnel face during advance. Therefore, the total excavation volume is higher than the volume that corresponds to the tunnel cross-section area. Previous investigations by the authors showed that the additional, extrusion-induced excavation volume may be considerable in the case of purely cohesive ground. This paper extends this work for the case of cohesive-frictional ground. Firstly, we quantify the extrusion-induced excavation volume for a wide parameter range by means of a numerical model that uses re-meshing to consider the continuous re-profiling taking place at the tunnel face during advance. The results of the performed parametric study are summarised in a single dimensionless design chart. Secondly, we derive a simple closed-form expression, which, despite the underlying simplifications, allows for an accurate and rapid quantification of the extrusion-induced excavation volume. The results show that face extrusion has an effect on excavation volume in the cohesive-frictional case, although less pronounced than when tunnelling through low-permeability clays with purely cohesive short-term strength. The study suggests that if the additional excavation volume due to face extrusion is not taken into account in the design of the mechanised advance, it may (a) pose logistical and disposal challenges and (b) lead to erroneous conclusions about the stability of the tunnel face, both of which affect the rate of tunnel advance.

TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice

Sperm morphogenesis is a tightly regulated differentiation process, disruption of which leads to sperm malfunction and male infertility. Here, we show that Tex38 knockout (KO) male mice are infertile. Tex38 KO spermatids exhibit excess retention of residual cytoplasm around the head, resulting in abnormal sperm morphology with backward head bending. TEX38 interacts and colocalizes with ZDHHC19, a testis-enriched acyltransferase catalyzing protein S-palmitoylation, at the plasma membrane of spermatids. ZDHHC19 and TEX38 are each downregulated in mouse testes lacking the other protein. TEX38 stabilizes and localizes ZDHHC19 to the plasma membrane of cultured cells and vice versa, consolidating their interdependence. Mice deficient in ZDHHC19 or harboring a C142S mutation that disables the palmitoyltransferase activity of ZDHHC19 display phenotypes resembling those of Tex38 KO mice. Strikingly, ZDHHC19 palmitoylates ARRDC5, an arrestin family protein regulating sperm differentiation. Overall, our findings indicate that TEX38 forms a stable complex with ZDHHC19 at the plasma membrane of spermatids, which governs downstream S-palmitoylation of proteins essential for morphological transformation of spermatids.

Abstract P1108: Plasma metabolome of a cholesterol-lowering plant-based diet and cardiometabolic disease risk

Introduction: The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C), however, less is known about its long-term impact on cardiometabolic disease. Objective metabolic response to diet using metabolomics can provide additional insight into how diet affects disease risk. Objective: To investigate whether a metabolomic signature can characterize adherence to the portfolio diet and whether this signature is associated with cardiometabolic disease. Methods and Results: The metabolomic signature discovery cohort included 633 plasma samples from four previously conducted randomized controlled trials (RCTs) on the portfolio diet. The validation cohorts included 11,985 participants from the Nurses’ Health Studies (NHS) I&II and Health Professionals Follow-up Study (HPFS). Adherence to the portfolio diet was assessed using a portfolio diet score, and the plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. Using elastic net regression, a metabolomic signature of 56 metabolites was found, most of which were amino acids and amines (34%), glycerophosphocholines (14%), glycerophosphoethanolamines (7%), and indoles (7%). The signature was highly correlated with portfolio diet adherence in the RCTs (r=0.87, p<0.001). In the NHS/HPFS cohorts, a simplified signature showed an attenuated relationship with the portfolio diet score (r=0.26, p<0.001). In the RCTs, using linear mixed models, the signature was associated with lower total cholesterol, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, triglycerides, and systolic blood pressure. In the NHS/HPFS cohorts, using multivariable linear regression, the signature was associated with lower total cholesterol, LDL-C, non-HDL-C, and HDL-C. In multivariable Cox regressions in the NHS/HPFS cohorts, the signature was inversely associated with total mortality (HR: 0.94 [95% CI: 0.89, 0.99]) and type 2 diabetes (0.92 [0.84, 0.99]), but not cardiovascular disease (0.96 [0.86, 1.08]). Conclusions: A metabolomic signature that reflects adherence and metabolic response to the cholesterol-lowering plant-based portfolio diet was identified, which was then associated with several cardiovascular disease risk factors in both the RCTs and cohorts, and lower risk of mortality and type 2 diabetes in the cohorts. Further research on this dietary pattern and replication in other cohort studies is warranted.

Abstract 055: Gestational Diabetes and Risk of Type 2 Diabetes: Exploring the Role of Gut microbiome and Blood Metabolome in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

Introduction: Women with a history of gestational diabetes mellitus (GDM) have a higher risk of type 2 diabetes (T2D), but the underlying mechanisms, particularly the roles of gut microbiota and blood metabolites, remain unclear. Hypothesis: Women with history of GDM have an altered gut microbiota and blood metabolites, which may lead to a higher T2D risk. Methods: Among parous women from HCHS/SOL, gut microbiome was assessed by shotgun sequencing (visit 2, 2014-17). We identified microbial species associated with presence vs. absence of history of GDM (visit 2, n=1525), and serum metabolites associated with both history of GDM (baseline, 2008-11, n=2968) and GDM-related microbiota (visit 2, n=391). We also examined prospective associations of the GDM-related microbiome (visit 2, n=798) with incident T2D over 6 years follow-up, and of microbial-related metabolites (baseline, n=2341) with incident T2D over 12 years. Results: Seven species showed differential abundance between women with and without history of GDM, including higher abundance of 4 species (e.g., Parabacteroides merdae CAG:48 ), and lower abundance of 3 species (e.g., Dialister sp. CAG:588 ). A GDM-related microbiome score, generated via linear combination of 7 species, was associated with higher T2D risk (RR=1.08 [95% CI: 1.00, 1.18] per SD). Fifteen metabolites (e.g., saturated sphingomyelins) were associated with both history of GDM and the microbiome score in consistent direction, 9 of which were prospectively associated with incident T2D (Fig. 1A). Proxy association analysis based on these metabolites suggested a positive relationship between the GDM-related microbiome and T2D (Fig. 1B). A metabolite score derived from the 9 microbial-related metabolites partially mediated the relationship between GDM and T2D risk (21.8%, 95% CI: 8.1%, 54%). Conclusion: Among U.S. Hispanic/Latino women, history of GDM is associated with an unfavorable gut microbiota and related metabolites, suggesting a potential role of gut microbiota in GDM-T2D relationship.

Respiratory compliance related to prognostic of lung transplant patients with veno‑venous extracorporeal membrane oxygenation support

Archaeology and traversing America’s pre-Columbian fault line

Abstract MP47: Cardiovascular risk factors for dementia: Causal estimates on individual-level data

Background: The 2024 Lancet Commission report highlights 14 modifiable risk factors that if eliminated can prevent nearly half of dementia, of which most are cardiovascular risk factors. The causal aspects remain however unclear, hence we aimed to establish causal estimates for these cardiovascular risk factors. Methods: We used individual-level data from 408,788 European participants from the UK Biobank. We computed polygenetic risk scores of individual risk factors for each participant, exploiting independent instrumental variants from the largest genomic consortia for each risk factor. We conducted univariable and multivariable linear Mendelian randomization analyses and assessed genetic shapes by nonlinear approaches. Findings: Genetically predicted high BMI (OR, 95% CI: 1.04, 1.02-1.07), smoking (1.18, 1.06-1.32), high systolic (1.14, 1.09-1.20) and diastolic (1.10, 1.02-1.19) blood pressure, type 2 diabetes (1.04, 1.00-1.09), high LDL cholesterol (1.12, 1.01-1.23) and high triglycerides (1.19, 1.01-1.41) were associated with increased risk of all-cause dementia. Results for Alzheimer’s disease and vascular dementia were in the same direction. Moreover, genetically predicted high physical activity was associated with reduced risk of Alzheimer’s disease (0.58, 0.33-0.99), and longer education was associated with all-cause dementia (0.72, 0.65-0.79), Alzheimer’s disease (0.71, 0.62-0.81), and vascular dementia (0.64, 0.52-0.77) Sensitivity analyses supported the main results, and no nonlinear shapes were detected. Interpretation: These findings provide causal insights into cardiovascular risk factors for dementia, underscore the importance of more targeted interventions to mitigate these risk factors for dementia prevention, and give hope for maintaining brain health by timely treatment of high cholesterol and triglycerides alongside hypertensive medication, smoking cessation and maintenance of normal weight.

Abstract P1028: Prospective associations of optimism and cynicism with Life’s Essential 8: The Study of Women’s Health Across the Nation (SWAN) Study

Introduction: Hostility and Optimism are traits known to be associated with the risk of cardiovascular disease (CVD). However, important gaps remain in understanding the behavioral and biological mechanisms of these associations among multi-ethnic midlife women transitioning through menopause. We aim to assess the associations of optimism and cynicism with Life’s Essential 8 (LE8) and its components. Methods: Participants were from the SWAN study, a multi-ethnic longitudinal study of the menopause transition. Optimism and cynicism were assessed at baseline and visit 1 via the Life Orientation Test (0[low]-18[high]) and the Cook-Medley Cynicism scale (0 [low] – 13 [high]), respectively. The total and component-specific LE8 scores (0[worst]– 100[best]), including dietary health, physical activity, sleep quality, nicotine exposure, blood pressure, blood glucose, blood lipids and body mass index (BMI), were measured 5 years after baseline. Linear regression models adjusting for demographics and menopause related variables (listed in figure) were used to test the associations of quartiles of optimism or hostility in relation with each LE8 outcome separately. Results: A total of 1,907 women (mean (SD) baseline age: 45.9 (2.7) years; 48% White, 27%% Black, 9% Chinese, 7% Hispanics, 10% Japanese) with available data on main predictors and outcomes were included in the analysis. Compared women with the lowest quartile of the optimism scores, women in the highest quartile had 3.3 (95% CI: 1.1-5.3) points higher total LE8 scores (p-trend= 0.0005). Conversely, women in the highest quartile of hostility had 2.2 (0.4-4.1) points lower total LE8 scores (p-trend= 0.075) than women with the lowest quartile of hostility. Of the 8 components, higher optimism scores were associated with better sleep and physical activity scores, whereas higher hostility scores were associated with lower physical activity and diet scores, Figure 1. An analysis accounted for both traits together showed similar results compared to the analysis of the two traits separately. Conclusion: Optimism was positively associated with total LE8 scores, while cynicism was negatively associated with total LE8 scores. Optimism and cynicism play more important roles in health behavior components than health measures components. Supported by NIH/DHHS {Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720}.

TNMpBC-NeoBCSS model: a breast cancer specific survival prediction model for triple-negative metaplastic breast carcinoma patients with neoadjuvant therapy

Copy number variation contributes to parallel local adaptation in an invasive plant

Adaptation is a critical determinant of the diversification, persistence, and geographic range limits of species. Yet the genetic basis of adaptation is often unknown and potentially underpinned by a wide range of mutational types—from single nucleotide changes to large-scale alterations of chromosome structure. Copy number variation (CNV) is thought to be an important source of adaptive genetic variation, as indicated by decades of candidate gene studies that point to CNVs underlying rapid adaptation to strong selective pressures. Nevertheless, population-genomic studies of CNVs face unique logistical challenges not encountered by other forms of genetic variation. Consequently, few studies have systematically investigated the contributions of CNVs to adaptation at a genome-wide scale. We present a genome-wide analysis of CNV contributing to the adaptation of an invasive weed, Ambrosia artemisiifolia . CNVs show clear signatures of parallel local adaptation between North American (native) and European (invaded) ranges, implying widespread reuse of CNVs during adaptation to shared heterogeneous patterns of selection. We used a local principal component analysis (PCA) to genotype CNV regions in whole-genome sequences of samples collected over the last two centuries. We identified 16 large CNV regions of up to 11.85 megabases in length, eight of which show signals of rapid evolutionary change, with pronounced frequency shifts between historic and modern populations. Our results provide compelling genome-wide evidence that CNV underlies rapid adaptation over contemporary timescales of natural populations.

Abstract P1097: Geographic Variation of Healthcare Expenditures Among U.S. Adults with Heart Failure, 2012-2022

Introduction: Heart failure is a public health burden that currently affects over 6 million individuals in the United States and is estimated to continue to increase over the coming decade. Despite improvements in clinical outcomes, heart failure is associated with increased morbidity and mortality that place a significant financial strain on individuals and the healthcare system. However, little is known about the geographic variation in healthcare expenditures for heart failure. Methods: Data from the Medical Expenditure Panel Survey (MEPS) from 2012-2022 were used to estimate the national and regional (Northeast, Midwest, South, West) heart failure-attributable healthcare expenditures. A two-part model, adjusted for demographics, comorbidities, and time, was applied to estimate the total healthcare expenditures for individuals with heart failure, as well as service-specific expenditures, including inpatient stays, outpatient care, emergency room visits, physician office visits, home care visits, and prescription medication. Results: In the final sample, 1,180 adults (0.80%) were identified as having heart failure. After adjusting for demographics and clinical comorbidities, the estimated incremental cost of heart failure in adults was $7,586 ± 1571 per person. There was significant regional variation in total heart failure-related expenditures: the Midwest exhibited the highest total incremental costs at $10,309 ± 2,974, followed by the Northeast ($7,303 ± 1,530), the South ($6,467 ± 18.92), and the West ($6,371 ± 3,388), which had the lowest expenditures. Similar differences in incremental costs by geographic regions throughout the nation were exhibited in service-specific expenditures. Conclusion: Heart failure related healthcare expenditures varied throughout the nation, with the Midwest region experiencing higher expenditures. This variation highlights the need for target interventions in these specific states. Understanding the geographic differences in overall and service-specific expenditures will have important implications for resource allocation and healthcare policy, with the ultimate goal of reducing the financial burden on affected individuals.

Abstract MP62: Health Behaviors Among Nulliparas With Planned and Unplanned Pregnancies

Introduction: The relationship between pregnancy planning and health behaviors in the preconception and antepartum periods remains unclear. This study aimed to compare health behaviors before and during pregnancy between nulliparous individuals with planned and unplanned pregnancies. Methods: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be. The present study included nulliparas who indicated whether their pregnancy was planned or unplanned. Preconception and antepartum health behaviors were compared between planned and unplanned pregnancies using bivariate and multivariate analyses. Results: Among the 8,765 participants included, 5,202 (59.3%) had planned pregnancies, and 3,563 (40.7%) had unplanned pregnancies. Planned pregnancies were associated with older age, lower body mass index, white race, college education, higher income, and commercial insurance (p≤.001). Participants with unplanned pregnancies were more likely to have chronic hypertension and pregestational diabetes, and to be Hispanic or Latino, unmarried or unpartnered, and unemployed (p≤.001). In bivariate analysis, tobacco use, secondhand smoke exposure, and illicit drug use were more frequent among unplanned pregnancies three months preconception and throughout all three trimesters whereas engagement in physical activity was higher among planned pregnancies. Healthy Eating Index-2010 scores were also higher pre-pregnancy among planned pregnancies (Table). After adjusting for maternal age, education, marital status, income, commercial insurance, employment, chronic hypertension, and pregestational diabetes, these associations persisted (Table). Conclusion: Nulliparas with planned pregnancies demonstrated healthier behaviors that included less tobacco use, secondhand smoke exposure, and illicit drug use and greater engagement in physical activity and healthy eating. These associations persisted beyond the preconception period throughout pregnancy. This underscores the importance of preconception counseling and interventions as they not only improve health behaviors before pregnancy but also sustain these healthy practices throughout pregnancy.

Deletion of pcnB affects antibiotic susceptibility in resistant Escherichia coli by reducing copy number of ColE1-family plasmids

Prediction of carbon nanostructure mechanical properties and the role of defects using machine learning

Graphene-based nanostructures hold immense potential as strong and lightweight materials, however, their mechanical properties such as modulus and strength are difficult to fully exploit due to challenges in atomic-scale engineering. This study presents a database of over 2,000 pristine and defective nanoscale CNT bundles and other graphitic assemblies, inspired by microscopy, with associated stress–strain curves from reactive molecular dynamics (MD) simulations using the reactive INTERFACE force field (IFF-R). These 3D structures, containing up to 80,000 atoms, enable detailed analyses of structure-stiffness-failure relationships. By leveraging the database and physics- and chemistry-informed machine learning (ML), accurate predictions of elastic moduli and tensile strength are demonstrated at speeds 1,000 to 10,000 times faster than efficient MD simulations. Hierarchical Graph Neural Networks with Spatial Information (HS-GNNs) are introduced, which integrate chemistry knowledge. HS-GNNs as well as extreme gradient boosted trees (XGBoost) achieve forecasts of mechanical properties of arbitrary carbon nanostructures with only 3 to 6% mean relative error. The reliability equals experimental accuracy and is up to 20 times higher than other ML methods. Predictions maintain 8 to 18% accuracy for large CNT bundles, CNT junctions, and carbon fiber cross-sections outside the training distribution. The physics- and chemistry-informed HS-GNN works remarkably well for data outside the training range while XGBoost works well with limited training data inside the training range. The carbon nanostructure database is designed for integration with multimodal experimental and simulation data, scalable beyond 100 nm size, and extendable to chemically similar compounds and broader property ranges. The ML approaches have potential for applications in structural materials, nanoelectronics, and carbon-based catalysts.

Abstract 072: Plasma Metabolome Predicts Long-term Body Weight Gain and Type 2 Diabetes in Non-Obese Individuals

Introduction: Body weight is known to modulate the human blood metabolome, although whether certain plasma metabolomic profiles predict long-term weight change remains unknown. Hypothesis: We hypothesize that there are inter-relationships between plasma metabolome, current weight, weight change, and incident type 2 diabetes (T2D). Methods: We measured 260 annotated metabolites among 7, 499 participants in Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study using nontargeted LC-MS. We assessed the associations of these metabolites and BMI trajectory since blood draw during 26.0 years of follow-up using a mixed-effect model, also by BMI groups at blood draw (lean: 18.5-24.9 kg/m 2 , overweight: 25.0-29.9 kg/m 2 , and obese: ≥30 kg/m 2 ). A metabolomic score reflecting BMI change slope was identified using elastic net regression with a training/testing approach. Associations between the metabolomic scores and T2D were evaluated using Cox proportional hazards regression. Results: Cross-sectionally, metabolites associated with current BMI level among lean, overweight, and obese individuals minimally overlapped (of 260 metabolites, 2 overlapping among the three groups). Distinct metabolomic profiles associated with BMI trajectories were also identified among the three groups. While 46 metabolites significantly predicted BMI change slope in the lean group, only 20 and 13 metabolites predicted the slope among overweight and obese groups, respectively, with no metabolites overlapping among the three groups. Among lean individuals, the elastic net regression identified 82 metabolites, predominantly lipids and organic acids, to construct a score that reflected faster BMI gain. The score was significantly associated with the BMI slope in lean group (training: Spearman r = 0.33; testing: Spearman r = 0.20), but the correlation was weaker among overweight, and obese groups (Spearman r = 0.15, and 0.08, respectively). The metabolomic score was significantly associated with a higher risk of T2D in the lean group (aHR per 1SD: 1.41 [95% CI 1.25-1.59]) and overweight group (aHR per 1SD: 1.29 [95% CI 1.17-1.42]) groups, but not in the obese group. Conclusions: Metabolomic profiles associated with current BMI and BMI trajectory differ significantly among lean, overweight, and obese individuals. A metabolomic score that predicts BMI change is associated with higher T2D risk in lean and overweight individuals, but not among obese individuals.

Abstract P1062: Pre-Pandemic Thrombo-inflammatory Biomarkers and Risk of Severe Covid-19: the Collaborative Cohort of Cohorts for Covid-19 Research (C4R)

Background: Thrombo-inflammation is a hallmark of acute Covid-19, with higher thrombo-inflammatory markers during infection associated with adverse outcomes. We hypothesized that higher pre-pandemic biomarkers, reflecting a higher thrombo-inflammatory setpoint, might identify people at greater risk of severe manifestations of Covid-19. Hypothesis: Pre-pandemic inflammation markers are associated with risk of hospitalized or fatal (hereafter, “severe”) Covid-19 in a multi-ethnic US sample. Methods: From 2020-2023, C4R harmonized pre-pandemic measures and ascertained Covid-19 across 14 longstanding cohort studies. In 12 cohorts, we assessed biomarker data and covariates from the study visit closest to the pandemic for 6 analytes shown in the Table. HRs of severe Covid-19 by pre-pandemic biomarkers were estimated using cause-specific Cox regression, treating non-severe Covid-19 as a competing risk, and adjusting for pre-pandemic sociodemographic and clinical characteristics. Results: Biomarkers were measured a mean of 20 years before the pandemic with different sample sizes for each (Table footnote). Mean age at the start of the pandemic was in the 60s or 70s depending on the biomarker. The most represented race or ethnic groups were White and Black. The largest sample was for C-reactive protein, and there were 1,001 severe Covid-19 cases among 38,784 participants. In the adjusted models, considered individually, higher CRP, leukocyte count, factor VIII and fibrinogen, but not other markers, were associated with greater risk of severe Covid-19 (Table).Associations were robust across subgroups and time since biomarker measurement (example for C-reactive protein in Figure). Conclusions: In this prospective multi-study analysis of a multi-ethnic population, higher basal levels of thrombo-inflammation markers were associated with greater risk of severe Covid-19. Since we considered non-severe Covid-19 as a competing risk, associations may reflect factors related to progression to more serious Covid-19 illness.

Multiple item representations in visual working memory simultaneously guide attention

Resilient tree-planting strategies for carbon dioxide removal under compounding climate and economic uncertainties

To meet decarbonization targets, nations around the globe have made ambitious commitments to expand forested land. Operationalizing these commitments requires choosing a planting strategy: How many trees should be planted, of which species, and where? Given those choices must be made now but have long-term consequences, such decisions are plagued by uncertainty. For example, species that are well suited to present conditions may perform poorly under future climates, yet those future climates are themselves highly uncertain. Using the exemplar of the United Kingdom, a nation committed to achieving net zero emissions by midcentury, we quantify key uncertainties pertaining to coevolving climate and economic conditions and examine how modern methods of decision-making under uncertainty can advise on planting choices. Our analysis reveals that the best planting strategy assuming a “high-emissions” future is radically different to that for a future that remains on a “near-historic” path. Planting for the former while experiencing the latter results in substantial net costs to UK society. Assimilating uncertainty into decision-making identifies planting strategies that diversify risk and significantly reduce the probability of high-cost outcomes. Importantly, our research reveals that the scope for mitigating risk through choice of planting strategy is relatively limited. Despite this persistent risk, we find that tree planting remains a highly cost-effective carbon removal solution when compared to alternative technologies, even when those alternatives are assumed to be riskless.