Medical researchers are increasingly prioritizing the inclusion of underserved communities in clinical studies. However, mere inclusion is not enough. People from underserved communities frequently experience chronic stress that may lead to accelerated biological aging and early morbidity and mortality. It is our hope and intent that the medical community come together to engineer improved health outcomes for vulnerable populations. Here, we introduce Health Equity Engineering (HEE), a comprehensive scientific framework to guide research on the development of tools to identify individuals at risk of poor health outcomes due to chronic stress, the integration of these tools within existing healthcare system infrastructures, and a robust assessment of their effectiveness and sustainability. HEE is anchored in the premise that strategic intervention at the individual level, tailored to the needs of the most at-risk people, can pave the way for achieving equitable health standards at a broader population level. HEE provides a scientific framework guiding health equity research to equip the medical community with a robust set of tools to enhance health equity for current and future generations.

Background: Burkholderia multivorans are gram-negative bacteria typically found in water and soil. B. multivorans outbreaks among patients without cystic fibrosis have been associated with exposure to contaminated medical devices or nonsterile aqueous products. Acquisition can also occur from exposure to environmental reservoirs like sinks or other hospital water sources. We describe an outbreak of B. multivorans among hospitalized patients without cystic fibrosis at 2 hospitals within the same healthcare system in California (hospitals A and B) between August 2021 and July 2022. Methods: We defined confirmed case patients as patients without cystic fibrosis hospitalized at hospital A or hospital B between January 2020 to July 2022 with B. multivorans isolated from any body site matching the outbreak strain. We reviewed medical records to describe case patients and to identify common exposures. We evaluated infection control practices and interviewed staff to detect exposures to nonsterile water. Select samples from water, ice, drains, and sink splash zone surfaces were collected and cultured for B. multivorans in March 2022 and July 2022 from both hospitals. Common aqueous products used among case patients were tested for B. multivorans. Genetic relatedness between clinical and environmental samples was determined using random amplified polymorphic DNA (RAPD) and repetitive extragenic palindromic polymerase chain reaction (Rep-PCR). Results: We identified 23 confirmed case patients; 20 (87%) of these were identified at an intensive care unit (ICU) in hospital A. B. multivorans was isolated from respiratory sources in 18 cases (78%). We observed medication preparation items, gloves, and patient care items stored within sink splash zones in ICU medication preparation rooms and patient rooms. Nonsterile water and ice were used for bed baths, swallow evaluations, and ice packs. B. multivorans was cultured from ice and water dispensed from an 11-year-old ice machine in the ICU at hospital A in March 2022 but no other water sources. Additional testing in July 2022 yielded B. multivorans from ice and a drain pan from a new ice machine in the same ICU location at hospital A. All products were negative. Clinical and environmental isolates were the same strain by RAPD and Rep-PCR. Conclusions: The use of nonsterile water and ice from a contaminated ice machine contributed to this outbreak. Water-related fixtures can serve as reservoirs for Burkholderia, posing infection risk to hospitalized and immunocompromised patients. During outbreaks of water-related organisms, such as B. multivorans , nonsterile water and ice use should be investigated as potential sources of transmission and other options should be considered, especially for critically ill patients.

Disclosures: None

Pb–Zr–Ti–O (PZT) perovskites span a large solid-solution range and have found widespread use due to their piezoelectric and ferroelectric properties that also span a large range. Crystal structure analysis via Rietveld refinement facilitates materials analysis via the extraction of the structural parameters. These parameters, often obtained as a function of an additional dimension (e.g., pressure), can help to diagnose materials response within a use environment. Often referred to as “in-situ” studies, these experiments provide an abundance of data. Viewing structural changes due to applied pressure conditions can give much-needed insight into materials performance. However, challenges exist for viewing/presenting results when the details are inherently three-dimensional (3D) in nature. For PZT perovskites, the use of polyhedra (e.g., Zr/Ti–O6 octahedra) to view bonding/connectivity is beneficial; however, the visualization of the octahedra behavior with pressure dependence is less easily demonstrated due to the complexity of the added pressure dimension. We present a more intuitive visualization by projecting structural data into virtual reality (VR). We employ previously published structural data for Pb0.99(Zr0.95Ti0.05)0.98Nb0.02O3 as an exemplar for VR visualization of the PZT R3c crystal structure between ambient and 0.62 GPa pressure. This is accomplished via our in-house CAD2VR™ software platform and the new CrystalVR plugin. The use of the VR environment enables a more intuitive viewing experience, while enabling on-the-fly evaluation of crystal data, to form a detailed and comprehensive understanding of in-situ datasets. Discussion of methodology and tools for viewing are given, along with how recording results in video form can enable the viewing experience.

OBJECTIVES/GOALS: We developed a non-invasive test of ocular alignment (OA) as a measure of otolith asymmetry, which impacts vestibular function. This test has also been administered on commercial astronauts to study the effect of microgravity on vestibular function. We will assess OA test performance in ground subjects, which has not yet been characterized. METHODS/STUDY POPULATION: Subjects were recruited from visitors to Space Center Houston from June to October 2022. Participants wore red-blue glasses in a darkened room and aligned two vertically or torsionally misaligned line segments, one red and one blue, on a tablet. Each subject underwent 11 vertical and torsional trials. The remaining misalignment was used to calculate ocular misalignment. Subjects self-reported demographic and health data. We calculated descriptive statistics and explored the distribution of overall vertical and torsional OA and distributions by age. Next steps will establish the reliability of the outcome measures with intraclass correlation coefficients and analyze associations between demographic variables and health status with OA performance using linear regression analysis. RESULTS/ANTICIPATED RESULTS: A total of 143 participants (67 female) with a median age of 21 (range 5-74 years old) completed OA testing. Of participants, 64% identified as white, 10% as black, 14% as Asian, 3% as Native American, and 8% as unknown. This test battery was feasible to implement in this mixed-age sample, with a 95% completion rate. Median absolute vertical OA was 0.08 degrees (IQR = 0.17 degrees), and median absolute torsional OA was 0.80 degrees (IQR = 1.20 degrees). Visual analysis of plots of OA by trial number reveals no apparent learning effect within subjects, though some individuals had considerable variation in performance. Average absolute vertical ocular misalignment increased modestly when plotted by age (fitted regression line b = 0.0032 degrees per year of age, p = 0.004), unadjusted for potential confounders. DISCUSSION/SIGNIFICANCE: Ocular alignment testing was feasible in a mixed-age general population sample. Our findings will expand understanding of how OA varies with age. These results will be used to create a normative database to compare and inform analysis of OA results from commercial spaceflights, which include individuals of varying age and health statuses.

One in six nursing home residents and staff with positive SARS-CoV-2 tests ≥90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.

Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6–8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure–volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.

Infective endocarditis is a microbial infection of the endothelial surface of the heart, predominantly the heart valves, that is associated with high mortality and morbidity. Few contemporary data exist regarding affected children in our context.

The thickness of varves in the sediments of Skilak Lake, Alaska, are correlated with the mean annual temperature (r = 0.574), inversely correlated with the mean annual cumulative snowfall (r = −0.794), and not correlated with the mean annual precipitation (r = 0.202) of the southern Alaska climatological division for the years 1907–1934 A.D. Varve thickness in Skilak Lake is sensitive to annual temperature and snowfall because Skilak Glacier, the dominant source of sediment for Skilak Lake, is sensitive to these climatic parameters. Trends of varve thickness are well correlated with trends of mean annual cumulative snowfall ( = −0.902) of the southern Alaska climatological division and with trends of mean annual temperature of the southern ( = 0.831) and northern ( = 0.786) Alaska climatological divisions. Trends of varve thickness also correlate with trends of annual temperature in Seattle and North Head, Washington ( = 0.632 and 0.850, respectively). Comparisons of trends of varve thickness with trends of annual temperature in California, Oregon, and Washington suggest no widespread regional correlation. Trends of annual snowfall in the southern Alaska climatological division and trends of annual temperature in the southern and northern Alaska climatological divisions are reconstructed for the years 1700–1906 A.D. Climatic reconstructions on the basis of varve thickness in Skilak Lake utilize equations derived from the regression of series of smoothed climatological data on series of smoothed varve thickness. Reconstruction of trends of mean annual cunulative snowfall in the southern Alaska climatological division suggests that snowfall during the 1700s and 1800s was much greater than that during the early and mid-1900s. The periods 1770–1790 and 1890–1906 show marked decreases in the mean annual snowfall. Reconstructed trends of the annual temperature of the northern and southern Alaska climatological divisions suggest that annual temperatures during the 1700s and 1800s were lower than those of the early and mid-1900s. Two periods of relatively high annual temperatures coincide with the periods of low annual snowfall thus determined.

A controversy currently exists regarding the number of Toba eruptive events represented in the tephra occurrences across peninsular India. Some claim the presence of a single bed, the 75,000-yr-old Toba tephra; others argue that dating and archaeological evidence suggest the presence of earlier Toba tephra. Resolution of this issue was sought through detailed geochemical analyses of a comprehensive suite of samples, allowing comparison of the Indian samples to those from the Toba caldera in northern Sumatra, Malaysia, and importantly, the sedimentary core at ODP Site 758 in the Indian Ocean—a core that contains several of the earlier Toba tephra beds. In addition, two samples of Toba tephra from western India were dated by the fission-track method. The results unequivocally demonstrate that all the presently known Toba tephra occurrences in peninsular India belong to the 75,000 yr B.P. Toba eruption. Hence, this tephra bed can be used as an effective tool in the correlation and dating of late Quaternary sedimentary sequences across India and it can no longer be used in support of a middle Pleistocene age for associated Acheulian artifacts.

We analyzed the recent (< 25 yr) spread in New Hampshire, USA, of the exotic tree Kalopanax septemlobus, native to Asia. The invasion was likely initiated by a single tree planted ca. 1972. Our objective was to assess the viability of the invasion, especially in light of the small propagule size. We tallied, mapped, aged, and measured the height and growth of K. septemlobus individuals at two sites, the University of New Hampshire campus (UC) and Thompson Farm (TF), both in Durham. We found over 3,800 plants at UC and 270 at TF in < 120 ha (296 ac) total area. Plant age ranged from 0 to 22 yr, and UC plants were as far as 775 m (2,543 ft) from the purported parent tree. Annual height growth was comparable to midtolerant native trees. Plants occurred in both open and forested habitats, and the mean level of photosynthetically active radiation incident on understory plants was 4 to 6% of full sun. The large population size, shade tolerance, rapid height growth, and ability to sprout from damaged stems suggest potential for K. septemlobus to invade and persist in forests, the most common natural ecosystem in the northeastern United States. We further suggest that small propagule size, likely a single tree, has not prevented K. septemlobus from initiating a spatially extensive and vigorous population. Kalopanax septemlobus has been planted as an ornamental in the northeastern United States, and prevention of region-wide invasion might depend on removal of these trees, even when they occur as single individuals.

Alluvial and lacustrine sediments exposed beneath late Pleistocene glaciolacustrine silt and clay at two sites along the Old Crow River, northern Yukon Territory, are rich in fossils and contain tephra beds. Surprise Creek tephra (SZt) occurs in the lower part of the alluvial sequence at CRH47 and Little Timber tephra (LTt) is present near the base of the exposure at CRH94. Surprise Creek tephra has a glass fission-track age of 0.17 ± 0.07 Ma and Little Timber tephra is 1.37 ± 0.12 Ma. All sediments at CRH47 have a normal remanent magnetic polarity and those near LTt at CRH94 have a reversed polarity — in agreement with the geomagnetic time scale. Small mammal remains from sediments near LTt support an Early Pleistocene age but the chronology is not so clear at CRH47 because of the large error associated with the SZt age determination. Tephrochronological and paleomagnetic considerations point to an MIS 7 age for the interglacial beds just below SZt at CRH47 and at Chester Bluffs in east-central Alaska, but mammalian fossils recovered from sediments close to SZt suggest a late Irvingtonian age, therefore older than MIS 7. Further studies are needed to resolve this problem.

Silver nanowire-based contacts represent one of the major new directions in transparent contacts for opto-electronic devices with the added advantage that they can have Indium-Tin-Oxide-like properties at substantially reduced processing temperatures and without the use of vacuum-based processing. However, nanowires alone often do not adhere well to the substrate or other film interfaces; even after a relatively high-temperature anneal and unencapsulated nanowires show environmental degradation at high temperature and humidity. Here we report on the development of ZnO/Ag-nanowire composites that have sheet resistance below 10 Ω/sq and >90% transmittance from a solution-based process with process temperatures below 200 °C. These films have significant applications potential in photovoltaics and displays.

Beta-gallium oxide (β-Ga2O3) is of increasing interest to the optoelectronic community for transparent conductor and power electronic applications. Considerable variability exists in the literature on the growth and doping of Ga2O3 films, especially as a function of growth approach, temperature, and oxygen partial pressure. Here pulsed laser deposition (PLD) was used to grow high-quality β-Ga2O3 films on (0001) sapphire and (−201) Ga2O3 single crystals and to explore the growth, stability, and dopability of these films as function of temperature and oxygen partial pressure. There is a strong temperature dependence to the phase formation, morphology, and electronic properties of β-Ga2O3 from 350 to 550 °C.

Five patients with progressive supranuclear palsy are described, in whom the ophthalmoplegia developed late in the course of the disease. In two, an internuclear component was identified in the ophthalmoplegia, and one patient had an alternating nystagmus of a type not previously described in this condition.

The late appearance of the ophthalmoplegia, with a corresponding delay in establishing the diagnosis, is compared to the similar experience of Pfaffenbach et al (1972) in six patients.

Other clinical features, previously seldom described, have been encountered. Dysphasia was seen in two cases, both of whom had evidence of cortical atrophy on neuro-radiological investigation. The evidence that cortical changes, in particular the presence of neurofibrillary tangles, may be a specific morphological characteristic of the disease rather than a chance association is discussed. Disorders of respiratory rhythm in four patients were similar to those described by Mastaglia et al. (1973), and indistinguishable from those occurring after encephalitis lethargica.

A review of cases resembling progressive supranuclear palsy in the early part of the century fails to show any with post-encephalitic features, nor does a search of reviews of eye movement disorders in encephalitis lethargica and post-encephalitic Parkinsonism provide comparable cases. None of the forty patients with post encephalitic Parkinsonism examined at the Highlands Hospital had a clinical picture resembling progressive supranuclear palsy.

It is suggested that neither on clinical nor pathological grounds is it justifiable to equate this disorder with known postencephalitic syndromes.