Browse Articles

Abstract P1042: Effects of urban greenspace on time to major adverse cardiovascular events among women with breast cancer: Insights from the Greater Milwaukee Area

Background: Cardiovascular disease (CVD) remains a significant concern among breast cancer (BC) survivors, particularly following potentially cardiotoxic treatments, such as anthracyclines and anti-HER2 drugs, which increase the risk of major adverse cardiovascular events (MACE). Social determinants of health (SDOH) and environmental factors influence health outcomes, including those related to CVD. Greenspace has been associated with cardiovascular and cancer-related health benefits, yet its specific impact on MACE among BC survivors remains unknown. Objective: This study aims to investigate the association between urban greenspace and time to first MACE incidence among individuals with BC after being treated with cardiotoxic therapies in the greater Milwaukee, WI area. Methods: A retrospective cohort study was conducted using electronic medical records from the Froedtert Health System, linked to the National Death Index. Cox proportional hazards regression models were used to assess the association between percent tree canopy cover and MACE-specific hazards, adjusting for sociodemographic, clinical, and neighborhood-level factors. Results: Among the 849 women included, 44.6% experienced a MACE. Non-Hispanic Black (NHB) women had a higher proportion of MACE incidence. Adjusted models indicated a 18% and 20% lower MACE-specific hazard for women in the second and third quartiles of percent tree canopy cover, as compared to the women in the first (lowest) quartile, respectively. Racial/ethnic disparities in MACE incidence were evident, with the NHB group having a higher proportion of MACE (61.9%) compared to NHW women (41.6%). Discussion: Our findings suggest a protective effect of urban tree canopy on time to incident MACE among BC survivors receiving cardiotoxic treatments. These results underscore the importance of considering environmental factors in Cardio-Oncology care and highlight the benefits of greenspace in mitigating cardiovascular complications among individuals with BC. Future research should delve into environmental factors, behavioral factors, and biological mechanisms that underlie these associations. Additionally, longitudinal studies should be conducted to evaluate greenspace-based interventions for BC survivors, aiming to advance precision Cardio-Oncology interventions. Observed racial/ethnic disparities in MACE incidence underscore the urgent need for equity-focused interventions addressing greenspace access and MACE-related disparities.

Tick-borne encephalitis virus seroprevalence and infection incidence in Switzerland, 2020–2021

EGFR-induced lncRNA <i>TRIDENT</i> promotes drug resistance in non–small cell lung cancer via phospho-TRIM28-mediated DNA damage repair

Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript ( TRIDENT ), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non–small cell lung cancer. Knocking down TRIDENT leads to decreased tumor-cell proliferation in both in vitro and in vivo model systems and induces sensitization to chemotherapeutic drugs. Using ChIRP-MS analysis we identified TRIM28 as a protein interactor of TRIDENT . TRIDENT promotes phosphorylation of TRIM28 and knocking down TRIDENT leads to accumulation of DNA damage in cancer cells via decreased TRIM28 phosphorylation. Altogether, our results reveal a molecular pathway in which TRIDENT regulates TRIM28 phosphorylation to promote tumor cell growth and drug resistance. Our findings suggest that TRIDENT can be developed as a biomarker or therapeutic target for EGFR mutant non–small cell lung cancer.

Abstract P3150: Age-standardized trends in Incidence Rates of Noncommunicable diseases among Adults Aged 30 to 79 in Senegal from 2000 to 2019

Introduction: Noncommunicable diseases (NCD) represent a significant global health burden in Sub-Saharan Africa (SSA). However, most SSA countries lack reliable data despite the need for surveillance of NCD trends to inform targeted preventive strategies. Objective: To analyze trends over two decades in the incidence of NCD (cancers, cardiovascular diseases, chronic respiratory diseases, diabetes, and chronic kidney diseases) among adults in Senegal Methods: Data were sourced from the WHO Health Inequality Data Repository data. Using the Cox-Stuart test for trend, we compared trends of age-standardized incidence of NCD (cancers, cardiovascular diseases, chronic respiratory diseases, diabetes, and chronic kidney diseases) among adults aged 30-79 in Senegal from 2000 to 2019. Results: From 2000 to 2019, there was a non-significant increase in NCD incidence among adults in Senegal (p-value 0.08). The age-standardized incidence rate per 100,000 population increased steadily from 351,478 cases to 358,419 cases per 100,000 population from 2000 to 2019 (Figure 1). Incidence rates in females were consistently higher than in males. Rates in females increased from 190,856 cases to 194,619 cases per 100,000 population between 2000 and 2019 (p-value 0.33) as compared to 160,622 cases to 163,799 cases per 100,000 population in males (p-value 0.33). There were differences in the trends by sex among NCD subtypes (Figure 2). Incidence rates were higher in females for neoplasm (p-value 0.08), chronic respiratory diseases (p-value 0.08), and diabetes and chronic kidney diseases (p-value 0.08), while cardiovascular disease incidence was higher in males (p-value 0.08). Conclusion: There was a non-significant increase in age-standardized NCD incidence among adults in Senegal. Reliable epidemiological data, as well as targeted interventions focusing on risk factors, early detection, and access to quality health care, are crucial to improving health outcomes in Senegal.

Abstract P2119: MESA Heart Failure Risk Score: Trajectory and LE8 Healthy Behavior Impact in Brazilian Adults

Background: Heart failure (HF) is a leading cause of mortality, particularly among older adults. HF risk scores developed in high-income Western countries are being incorporated into national guidelines in low- and middle-income countries (LMICs) without a systematic evaluation of their performance in these populations. Existing HF risk scores, including those recalibrated for LMICs, fail to accurately capture risk in Brazilian population. Objective: To evaluate the trajectory of the Multi-Ethnic Study of Atherosclerosis (MESA) heart failure (HF) risk score in a representative Brazilian sample over 10 years and its association with the Life’s Essential 8 health behaviors (LE8HB). Methods: We analyzed 13,664 Brazilian adults (54.4% women) from six cities, followed from 2008-2010 (W1), 2012-2014 (W2), and 2017-2019 (W3) from the ELSA-Brasil study. The primary outcome was the 10-year MESA HF risk score trajectory, composed of age, sex, smoking status, BMI categories, systolic blood pressure, heart rate, and diabetes status. LE8HB was evaluated based on diet, physical activity, nicotine exposure, and sleep, with scores categorized as high (80-100), moderate (50-79), and low (0-49). Multivariate regression models adjusted for alcohol intake, waist circumference, creatinine, income, and city assessed LE8HB's association with HF risk. Results: At W1, the mean age was 52.1 years, increasing to 59.6 years at W3. Over this period, the mean heart failure (HF) risk score significantly increased from 4.2 at W1 to 5.0 at W3. Concurrently, the proportion of participants with high adherence to LE8HB increased from 16.0% to 20.3%. We identified three distinct HF risk trajectory groups: low HF risk (W1 mean = 2.1, W2 = 2.3, W3 = 3.0), moderate HF risk (W1 = 4.6, W2 = 4.7, W3 = 5.4), and High HF risk (W1 = 7.7, W2 = 7.8, W3 = 8.6). Participants with higher LE8HB adherence had a significantly lower HF risk score (mean = 5.6, 95% CI: 5.4–5.8) compared to those with low LE8HB adherence (mean = 4.1, 95% CI: 3.9–4.3). Conclusion: The Multi-Ethnic Study of Atherosclerosis effectively stratified heart failure risk trajectories in Brazilian adults. Although heart failure risk increased across all groups, individuals with healthier behaviors consistently showed lower risk trajectories. The MESA score is a promising tool for recalibration, accounting for lifestyle patterns in the Brazilian population.

The virome investigation of the globally endangered Eld’s deer (Rucervus eldii) on Hainan Island, China

The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8 ⁺ T cells

Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction of cancer, requiring a substantial amount of proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role of transcriptional regulation in this process, paired transcriptomic and proteomic analyses reveal that the RNA profile is poorly correlated with protein levels. This discrepancy underscores the importance of post-translational modifications (PTMs) in controlling protein abundance during activation. However, the impact of PTMs on the CD8+ T cell protein dynamic remains underexplored. We identify that neddylation, a recently discovered PTM, is activated in response to T cell receptor (TCR) stimulation and enriched in effector CD8+ T cells from colon cancer patients. Mechanistically, we found the rate-limiting enzyme of neddylation, neural precursor cell expressed developmentally down-regulated protein 8 activating enzyme E1 (NAE1), is induced by the NFATc1, a critical transcription factor downstream of TCR signaling. Our observation revealed that genetic ablation of NAE1 significantly disturbed the proteomic landscape related to activation and mitochondrial function. As a result, CD8+ T cells lacking NAE1 exhibited severely compromised activation, proliferation, and survival, which was accompanied by impaired mitochondrial function. Consistently, deletion of NAE1 in CD8+ T cells abolished their antitumor function and promoted tumor progression. By contrast, the overexpression of NAE1 significantly improved the function of tumor-infiltrating CD8+ T cells. Overall, we uncovered neddylation, a previously underappreciated PTM, as a proteomic checkpoint for CD8+ T cell activation. Enforced expression of NAE1 offers promising therapeutic potential for boosting the antitumor CD8+ T cell responses.

Abstract P2091: Relations Between Plasma and Digitally-Obtained Neuropsychological Biomarkers: Data from the Disparities and Equity in Childhood Cardiovascular Exposures and Alzheimer’s Dementia (DECADE) Study

Background: Plasma proteins associated with Alzheimer’s disease (AD) include β-amyloid-42 (Aβ 42 ), phosphorylated -tau at threonine-181 (p-tau 181 ), and neurofilament light chain (NfL). This study assessed the relationship between these biomarkers and digital neuropsychological test performance. Methods: Middle-aged participants in the DECADE study had blood drawn and completed the Rowan Digital Cancellation Test (RDCT) consisting of 64 targets embedded among foils. Within 90 seconds, participants circled as many targets as possible, alternating between letters and symbols. RDCT outcomes included correct targets; ‘think’ time between correct targets; ‘ink’ time to circle correct targets; total pen strokes; commission errors; and total pen stroke distance and were summarized using factor analysis. Their association with AD biomarkers was done using linear regression. Results: The first 77 participants (age=55.3±8.7; 81.6% female) were included, with serum Aβ 42 (mean±SD: 7.8 + 2.7 pg/ml), p-Tau 181 (17.2 + 11.1 pg/ml), and NfL (10.5 + 13.8 pg/ml) assessed. Factor analysis identified 2 factors (Table). Higher scores on Factor 1 (49.2% variance) correspond to fewer correct responses, more think time, commission errors, and pen strokes. Higher scores on Factor 2 (27.9% variance) correspond to more correct responses, fewer commission errors, ink time, and pen strokes. Adjusting for age, sex, education, and both RDCT factor scores, NfL was negatively associated with Factor 2 (R 2 = 0.176, β= -0.445[JW1] , SE=2.57; p&lt; 0.01 ) suggesting worse RDCT test performance with increasing biomarker level. In contrast, Aβ42 was positively associated with Factor 1 (R 2 =0.268, β= 0.503, SE= p&lt; 0.003. Analyses involving p-Tau 181 were not significant. Conclusion: In this community-dwelling, middle-aged sample, plasma levels of AD-related proteins are associated with digital measures of neurocognitive performance. Middle-age assessment of serum AD-related proteins and digital neuropsychological performance have the potential to help identify emergent neurodegenerative illness.

Abstract P2108: Longitudinal Changes of Chemical Exposome on Blood Pressure after Bariatric Surgery among Adolescents

Background: The heterogeneous response in cardiometabolic outcomes following obesity treatment, such as bariatric surgery, is well documented, yet the underlying environmental contributors remain unclear. One potential factor is the chemical exposome which can have an obesogenic effect. To date, no prior studies have examined the longitudinal changes in chemical exposures after obesity treatment and their influence on cardiometabolic outcomes. This study aimed to assess the associations between chemical exposome trajectories and blood pressure after bariatric surgery among adolescents. Methods: We quantified the plasma chemical exposome in 5 classes (polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFAS), phthalates, pyrethroid pesticides and other pesticides) in plasma collected prior to surgery and post-surgery at 6-months, 1 year and 3 years using gas and liquid chromatography with high-resolution mass spectrometry. The cohort included 149 adolescents from the prospective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Outcomes were systolic and diastolic blood pressure measurements (SBP, DBP), mean arterial pressure (MAP) and pulse pressure at 3 years and 5 years following surgery. We used linear mixed models with random intercepts and slopes to estimate exposure trajectories, and model-based clustering based on each chemical exposure trajectories to generate aggregate exposure trajectory profiles. Linear regression was used to assess the associations of these profiles with blood pressure, adjusting for baseline age, race, sex, parents’ annual income, BMI and blood pressure medications. Results: Two distinct exposure trajectory profiles were generated based on longitudinal changes in individual chemicals. Profile 1 (100 participants) showed a decrease in pesticides and an increase in phthalates. Profile 2 (49 participants) showed the opposite trend. Compared with profile 1, profile 2 was statistically significantly lower for the association in MAP (b = -3.91 mmHg, 95%CI: -7.41, -0.41) and DBP (b = -3.41 mmHg, 95%CI: -6.68, -0.14) three years after bariatric surgery. The associations with blood pressure at five years were weaker. Conclusion: This study identified chemical exposome trajectory profiles after bariatric surgery and highlighted how longitudinal changes in these exposures may play an important role in explaining the heterogeneity in cardiometabolic outcomes after bariatric surgery.

Experimental study on gas permeability and radon control performance of red clay covering layer on uranium mill tailings pond

Dynamic investigation of hypoxia-induced L-lactylation

The recently identified histone modification lysine lactylation can be stimulated by L-lactate and glycolysis. Although the chemical group added upon lysine lactylation was originally proposed to be the L-enantiomer of lactate (K L-la ), two isomeric modifications, lysine D-lactylation (K D-la ) and N-ε-(carboxyethyl) lysine (K ce ), also exist in cells, with their precursors being metabolites of glycolysis. The dynamic regulation and differences among these three modifications in response to hypoxia remain poorly understood. In this study, we demonstrate that intracellular K L-la , but not K D-la or K ce , is up-regulated in response to hypoxia. Depletion of glyoxalase enzymes, GLO1 and GLO2, had minimal impact on K D-la , K ce , or hypoxia-induced K L-la . Conversely, blocking glycolytic flux to L-lactate under hypoxic conditions by knocking out lactate dehydrogenase A/B completely abolished the induction of K L-la but increased K D-la and K ce . We further observed a correlation between the level of K L-la and hypoxia-inducible factor 1 alpha (HIF-1α) expression under hypoxic conditions and when small molecules were used to stabilize HIF-1α in the normoxia condition. Our result demonstrated that there is a strong correlation between HIF-1α and K L-la in lung cancer tissues and that patient samples with higher grade tend to have higher K L-la levels. Using a proteomics approach, we quantified 66 K L-la sites that were up-regulated by hypoxia and demonstrated that p300/CBP contributes to hypoxia-induced K L-la . Collectively, our study demonstrates that K L-la , rather than K D-la or K ce , is the prevailing lysine lactylation in response to hypoxia. Our results therefore demonstrate a link between K L-la and the hypoxia-induced adaptation of tumor cells.

Abstract P2138: Childhood Parental Incarceration and Adverse Pregnancy Outcomes

Background: Adverse childhood experiences (ACEs) are associated with adverse pregnancy outcomes (APOs). However, the association between specific ACEs, such as parental incarceration, with APOs is not well understood. We examined whether: (1) childhood parental incarceration and its duration are associated with APOs and (2) if the association differed by race and ethnicity. Methods: Parous participants ≥ 18 years without: (1) history of CVD or diabetes and (2) did not have a pregnancy prior to age 18 in Wave V (2016-2018) of the US National Longitudinal Survey of Adolescent to Adult Health were analyzed. Childhood parental incarceration was defined as incarceration of the respondent’s parent/parental figure before age 18. Duration of parental incarceration was calculated by taking the difference of the age of respondents when the parent started and ended incarceration. Our outcome was defined as the self-reported occurrence of any APO (gestational diabetes, hypertensive disorder of pregnancy, small for gestational age, and pre-term birth). Multivariable logistic regression models assessed associations between parental incarceration and APOs. Covariates included age, difficulty paying bills, marital status, and smoking status during pregnancy. Models were stratified to assess interaction by race and ethnicity. Results: Among 2,088 participants, 234 (11.2%) reported a history of parental incarceration. Women with a history of parental incarceration were younger at first pregnancy, disproportionately Black, more likely to struggle paying bills, and had a higher prevalence of APOs. In unadjusted models, women who experienced childhood parental incarceration had 45% increased odds of experiencing an APO (OR 1.45; 95% CI: 1.10-1.92) but was nonsignificant after adjustment (OR 1.16; 95% CI: 0.83-1.62). Duration of incarceration was not associated with occurrence of APOs though the association differed by race such that a one-year increase in duration of parental incarceration was associated with 6% increased odds of having an APO among Black women (OR 1.06; 95% CI: 1.001-1.12). Conclusions: Longer duration of childhood parental incarceration was associated with higher odds of APOs for Black women. Future research should examine biological pathways by which parental incarceration contributes to deleterious health outcomes, particularly in minoritized communities.

Abstract P2131: The Association between Leisure Activities and the Risk of Cardiometabolic Multimorbidity among Older Chinese Adults

Background: Cardiometabolic multimorbidity (CMM) is becoming increasingly common in prehypertension patients and hypertension patients. Leisure activities play a vital role in preventing hypertension. However, its effect on CMM risk is unknown. Hypothesis: I hypothesized that leisure activities lower the risk of CMM among Chinese older adults. Methods: I included participants aged 65 and over from five waves (2002–2014) of the Chinese Longitudinal Healthy Longevity Survey, with follow-up until 2018. Participants diagnosed with CMM at baseline year were excluded. CMM was identified as having at least two of the four diseases: hypertension, diabetes, heart disease, or cardiovascular disease. Leisure activities were measured by the frequency (never, sometimes, and almost daily) of eight activities, including housework, fieldwork, reading books or newspapers, playing cards and/or mahjong, TV and/or radio watching, gardening, petting, and social activities. Cox proportional hazard models were used to estimate hazard ratio (HR), adjusting for demographics, lifestyles, and comorbidities. Results: Among 9,895 participants (mean age: 83.8 years; 55.3% female), 1,528 participants developed CMM during a median follow-up of 3.4 years (IQR: 3.0–6.2). Frequent participation in housework was associated with a lower risk of CMM (sometimes: HR 0.77, 95% CI 0.68–0.87; almost daily: HR 0.73, 95% CI 0.66–0.82), as was petting (sometimes: HR 0.73, 95% CI 0.63–0.86; almost every day: HR 0.68, 95% CI 0.60–0.76). In contrast, frequent TV and/or radio watching was associated with a higher risk of CMM (almost every day: HR 1.24, 95% CI 1.10–1.41). No significant associations were found between the risk of CMM and activities such as fieldwork, reading books or newspapers, playing cards and/or mahjong, gardening, or social activities. In the stratified analysis, the effect of almost daily housework and petting in reducing the risk of CMM was more pronounced among participants who frequently engage in physical exercise, while the effect of sometimes doing housework and petting was more pronounced among participants who never exercise. Conclusion: Frequent participation in housework and petting is associated with a lower risk of CMM among older Chinese adults, whereas activities such as TV and/or radio watching are linked to an increased risk. These findings underscore the importance of promoting healthy lifestyles by encouraging beneficial leisure activities in the older population.

Enhancing energy efficiency in buildings using sawdust-based insulation in hot arid climates

Brain aging shows nonlinear transitions, suggesting a midlife “critical window” for metabolic intervention

Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal “landmarks” of brain aging starting in midlife (40s). Comparison of metabolic, vascular, and inflammatory biomarkers implicate dysregulated glucose homeostasis as the driver mechanism for these transitions. Correlation between the brain’s regionally heterogeneous patterns of aging and gene expression further supports these findings, selectively implicating GLUT4 (insulin-dependent glucose transporter) and APOE (lipid transport protein). Notably, MCT2 (a neuronal, but not glial, ketone transporter) emerges as a potential counteracting factor by facilitating neurons’ energy uptake independently of insulin. Consistent with these results, an interventional study of 101 participants shows that ketones exhibit robust effects in restabilizing brain networks, maximized from ages 40 to 60, suggesting a midlife “critical window” for early metabolic intervention.

Abstract P3014: Night shift work and markers of cardiovascular health in workers from Spain, Denmark and Sweden: Findings from the Exposome Project for Health and Occupational Research

Objective: Night shift work disrupts normal circadian rhythms, which is hypothesized to lead to negative impacts on cardiovascular health. The underlying mechanisms remain poorly understood. We examined the associations between night shift work and cardiovascular risk factors, including blood pressure (BP), body mass index (BMI) and waist-to-hip ratio (WHR). Materials and Methods: We used data from the Exposome Project for Health and Occupational Research study (EPHOR), which included night and day shift workers from Spain, Sweden, and Denmark. We included participants with complete data on BP, BMI, and WHR. We used linear regression for the continuous outcomes and logistic regression for the binary outcomes, adjusting for relevant confounders. We conducted sex-stratified analyses, since sex may modify the relationship between night shift work exposure and cardiometabolic outcomes. Results: The analytic sample comprised 805 participants, 58% of whom were night shift workers with a mean age of 42 years (SD 11). The majority were female (87%). Compared to day workers, night shift workers had a higher BMI (β coeff. 1.10, 95%CI 0.37, 1.83), a higher odds of overweight/obesity (OR 1.39, 95%CI 1.03, 1.88), and a higher odds of moderate-high risk WHR (OR 1.39, 95%CI 1.00, 1.93). Blood pressure and the odds of hypertension were also elevated among night shift workers, but 95% CIs overlapped with the null. In the sex-stratified analyses, the point estimates were elevated among women (Table 1). Conclusion: Compared with day workers, night shift workers showed a worse cardiometabolic profile, particularly among women, indicating that cardiometabolic problems may be compounded among female night shift workers. These findings are in line with earlier research indicating that night shift work is associated with an increased cardiometabolic risk. We plan to further explore whether shift work characteristics, for example intensity of night shifts, may influence these findings.

Abstract P3013: Left Ventricular Diastolic to Systolic Wall Stress Ratio and Mortality Following Transcatheter Aortic Valve Replacement

Background: Most studies of left ventricular wall stress in patients with aortic stenosis (AS) focus on the end systolic (LVESWS) component with suggestion of an inverse association with adverse outcomes. LV end diastolic wall stress (LVEDWS) is less characterized and LVEDWS to LVESWS ratio, which may provide a combined measure of diastolic and systolic dysfunction and remodeling, has not been previously reported in patients with severe AS undergoing transcatheter aortic valve replacement (TAVR). Hypothesis: Higher LVEDWS to LVESWS ratio assessed by echocardiography prior to TAVR associates with greater risk of post-TAVR death. Methods: From a multicenter registry of patients with severe AS undergoing TAVR, we examined 637 participants (median age 84 years, 43% female, 95% white) who underwent pre-TAVR echocardiogram from which LVEDWS and LVESWS could be calculated from chamber dimensions, wall thicknesses, aortic valve gradient, blood pressure, and E/e’. Multivariable-adjusted Cox regression was used to examine associations between LVEDWS, LVESWS, their ratio, and the risk of post-TAVR mortality. Results: Median LVEDWS, LVESWS, and LVEDWS/LVESWS ratio were 22.1 (IQR: 16.2, 29.7) kdynes/cm2, 64.7 (IQR: 50.0, 90.7) kdynes/cm2, and 0.32 (IQR: 0.24, 0.43), respectively. Correlates of higher LVEDWS/LVESWS included: female gender, non-white race, hypertension medication use, higher natriuretic peptide and LV ejection fraction, and lower systolic and diastolic BP and hemoglobin. Over a median follow-up of 3 years post-TAVR, 262 (41%) individuals died. Higher LVEDWS tended towards greater risk of death (aHR: 1.013; 95% CI 0.999 – 1.027, p=0.071), while higher LVESWS associated with lower mortality risk (aHR: 0.993; 95% CI 0.988-0.998, p=0.008). Higher LVEDWS/LVESWS ratio associated with greater risk of death (aHR: 1.130, 95% CI 1.043-1.224, p=0.003, per 0.1 unit) (Figure), independent of age, comorbidities, LVEF, mass index, natriuretic peptide, and troponin. Conclusion: Among patients with severe aortic stenosis, higher LVEDWS to LVESWS ratio prior to TAVR associated with greater risk of post-TAVR mortality.

A general tribo-dynamic model for lubricated clearance joints in spatial multibody systems

Dynamic and context-dependent keystone species effects in kelp forests

Sea otters are an iconic keystone predator that can maintain kelp forests by preying on grazing invertebrates such as sea urchins. However, the effects of sea otters on kelp forests vary over their geographic range. Here, we analyze two 30-y datasets on kelp forest communities during the reintroduction of sea otters along the west coast of Vancouver Island, BC, Canada, and around San Nicolas Island, CA. We developed a community model to estimate species interactions as dynamic rates, varying with community state. We find evidence of a classic trophic cascade off Vancouver Island; the arrival of otters quickly led to depletion of urchins and recovery of kelp. However, this cascade was muted around San Nicolas Island, with otters, urchins, and kelp all coexisting at intermediate densities for multiple years. Our models show that this difference came from a pulse of strong otter impacts on urchins following recolonization off Vancouver Island, but not off San Nicolas Island. The mean effects of otters on urchins and urchins on kelp were not stronger in the north, indicating that interaction dynamics and not average interaction strength are key to explaining differences in community trajectories. We also find stronger multistep interaction chains in the south, arising from competitive interactions that indirectly buffered otter effects. These findings shed light on long-standing hypotheses about how interspecific interactions can alter the function of keystone species across community contexts. More broadly, we show how community change can be more accurately predicted by considering dynamic interaction strengths.

Abstract P2099: Higher Carotid IMT Related to Lower Cognitive Function in Healthy Adults: the i3C DECADE Study

Introduction: As the US population ages, the prevalence of Alzheimer’s disease and related dementias (ADRD) is expected to increase. Cardiovascular risk factors an accelerated vascular aging increase risk for ADRD. Therefore, we examined the relationship between carotid intima-media thickness (IMT) and neurocognitive function in a longitudinal study of the effect of CV risk factors on brain health. Methods: Participants had CV risk factors (BMI, BP, Lipids, high sensitivity CRP), IMT (mean R&amp;L, common, bulb, internal) and Rowan Digital Cancellation Tests (RDCT) collected which consists of 3 tests administered on an iPAD that varied in stimulus complexity. For Letter, participants were asked to circle the letter A on a sheet of letters where there were 16 targets (the letter ‘A’) in each of the 4 quadrants of the paper, for Symbol, they were to circle a specific symbol, and for Mixed they were to alternate between A and the symbol. A Summary outcome measure was calculated for each test condition by combining correct hits, average time between correct hits, and drawing time for correct targets. Mean values for CV risk factors, IMT and RDCT were calculated; and general linear models were constructed to determine if IMT remained associated with RDCT after adjustment for demographics, age, BP, lipids, and hsCRP. Results: Forty-nine participants had data available (mean age 60.7 + 6.3 yr, 68% female, 73% white). Higher IMT was associated with reduced neurocognitive functioning (lower RDCT) independently of CV risk factors for all 3 RDCT outcomes (TABLE). Summary: In these preliminary findings among middle-aged adults, accelerated vascular aging was associated with poorer cognitive function. Additional research with a greater number of participants with replication in populations who are older, have known mild cognitive impairment, and dementia are needed to determine the utility of IMT as a biomarker for age-related neurodegenerative disease.