Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, and yttrium-stabilized zirconia, Y$_{0.095}$Zr$_{0.905}$O$_2$, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

OBJECTIVES/GOALS: Decongestion, or fluid removal, is an important goal in the management of acute heart failure (AHF) among patients with heart failure with reduced ejection fraction (HFrEF). We sought to examine whether the rate of decongestion is associated with mortality and cardiovascular (CV) outcomes. METHODS/STUDY POPULATION: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial (n=4133), we evaluated the rate of decongestion by using linear mixed models to derive the in-hospital slope of b-type natriuretic peptide (BNP) and hematocrit as proxies of volume overload and hemoconcentration, respectively. A propensity score was developed to match patients from the quartile with most rapid rates of decongestion to the three quartiles with slower rates. Cox proportional hazards regression models were fitted to assess the association between rate of decongestion with risk of all-cause mortality and a composite of CV mortality or AHF hospitalization. RESULTS/ANTICIPATED RESULTS: Slower rates of in-hospital decongestion were associated with increased risk of both outcomes over a median 10-month follow-up. Those with slower rates of BNP decline, in comparison to the propensity-score matched patients with the most rapid rates of BNP decline, had higher hazards of mortality (HR=1.73 [1.23, 2.42]) and the composite outcome (HR=1.48 [1.18, 1.86]). Those with slower rates of hematocrit increase, in comparison to the propensity-score matched patients with the most rapid rates of hematocrit increase, showed a trend toward higher hazard of mortality (HR=1.17 [0.95, 1.43]) and an increased risk of the composite outcome (HR=1.26 [1.08, 1.47]). DISCUSSION/SIGNIFICANCE: Among patients with HFrEF admitted for AHF, slower rates of decongestion are associated with increased risk of mortality, CV mortality and AHF hospitalization. It remains unknown whether more rapid decongestion provides cardiovascular benefit or if it serves as a proxy for less treatment resistant heart failure.

The Centers for Medicare and Medicaid mandated that nursing homes implement antibiotic stewardship programs (ASPs) by November 2017. We conducted surveys of Wisconsin nursing-home stewardship practices before and after this mandate. Our comparison of these surveys shows an overall increase in ASP implementation efforts, but it also highlights areas for further improvement.

About 800 foodborne disease outbreaks are reported in the United States annually. Few are associated with food recalls. We compared 226 outbreaks associated with food recalls with those not associated with recalls during 2006–2016. Recall-associated outbreaks had, on average, more illnesses per outbreak and higher proportions of hospitalisations and deaths than non-recall-associated outbreaks. The top confirmed aetiology for recall-associated outbreaks was Salmonella. Pasteurised and unpasteurised dairy products, beef and molluscs were the most frequently implicated foods. The most common pathogen−food pairs for outbreaks with recalls were Escherichia coli-beef and norovirus-molluscs; the top pairs for non-recall-associated outbreaks were scombrotoxin-fish and ciguatoxin-fish. For outbreaks with recalls, 48% of the recalls occurred after the outbreak, 27% during the outbreak, 3% before the outbreak, and 22% were inconclusive or had unknown recall timing. Fifty per cent of recall-associated outbreaks were multistate, compared with 2% of non-recall-associated outbreaks. The differences between recall-associated outbreaks and non-recall-associated outbreaks help define the types of outbreaks and food vehicles that are likely to have a recall. Improved outbreak vehicle identification and traceability of rarely recalled foods could lead to more recalls of these products, resulting in fewer illnesses and deaths.

No form of English popular protest has been subject to such close scholarly analysis as the eighteenth-century food riot, a response not just to the understanding that food riots comprised two out of every three crowd actions but also to the influence of E. P. Thompson's seminal paper ‘The moral economy of the English crowd’. If the food riot is now understood as an event of considerable complexity, one assertion remains unchallenged: that riots remained a tradition of the towns, with agrarian society all but unaffected by food rioting. This article offers a new interpretation in which the rural is not just the backdrop to food protests but instead a locus and focus of collective actions over the marketing of provisions, with agricultural workers taking centre stage. It is shown that agricultural workers often took the lead in market town riots as well as well as in instigating riots in the countryside. Further, such episodes of collective protest were neither rare nor unusual but instead formed an integral part of the food rioting repertoire. It is also shown that rural industrial workers – notoriously active in market town riots – were often joined or even led by agricultural workers in their protests.

Invasive plants are expanding their ranges due to climate change, creating new challenges for invasive species management. Early detection and rapid response could address some nascent invasions, but limited resources make it impossible to monitor for every range-shifting species. Here, we aimed to create a more focused watch list by evaluating the impacts of 87 plant species projected to shift into northern New England (the states of Maine, New Hampshire, and/or Vermont). We used the Environmental Impact Classification for Alien Taxa (EICAT) protocol to evaluate all ecological impacts reported in the scientific literature, scoring ecological impacts from 1 (minimal concern) to 4 (major) depending on the level of reported impact. For each species, we also recorded any reported impacts on socioeconomic systems (agriculture, human health, or economics) as “present.” We found 24 range-shifting species with impacts on ecological communities, of which 22 have reported impacts in ecosystems common to northern New England. Almost all of these species also had impacts on socioeconomic systems and were available for purchase at ornamental plant retailers or online. Thus, these species can be considered high risk to northern New England with climate change based on their large negative impacts and potential to arrive quickly with deliberate human introduction. Our study demonstrates the use of impact assessments for creating targeted priority lists for invasive species monitoring and management.

ABSTRACT IMPACT: Improved radiation treatment will yield higher doses at the tumor site, while reducing damage to healthy tissue, which will improve clinical outcomes. OBJECTIVES/GOALS: Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized and the mechanism uncovered. The efficacy of these particles will be tested in a murine system. METHODS/STUDY POPULATION: Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol then covalently conjugated to chlorin e6, a known, FDA approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species following X-irradiation was measured. Enhanced cell killing was measured clonogenically and in vivo efficacy and tumor pathology was assessed in a murine system. Further studies will determine the optimum combination of particle shape, photosensitizer structure, and ratio of components, as well as the optimal dosing schedule. RESULTS/ANTICIPATED RESULTS: Conjugation of the particle to the photosensitizer was successfully achieved, and the molecule was detectable by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates significantly increased cell killing during radiation treatment, while neither the particle alone or the photosensitizer significantly affected clonogenic survival at the same concentrations. Pathology of breast tumors grown in immunocompetent mice showed a significant increase in necrotic tissue following a single 20 gy treatment when the conjugate was present. DISCUSSION/SIGNIFICANCE OF FINDINGS: Radiation therapy is widely used clinically and it is a highly localized form of treatment. However, the total dose of radiation is limited largely to prevent injury to adjacent normal tissue. This conjugate has the potential to increase the effective dose in the tumor thereby reducing damage to healthy tissue and providing a more effective therapy.

OBJECTIVES/GOALS:

• Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized structurally and mechanistically. The gold particles should enhance radiation activity by closer proximity to the photosensitizer and by increasing particle accumulation in the tumor.

METHODS/STUDY POPULATION:

• Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol, then covalently conjugated to chlorin e6, a known FDA-approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species was measured after X-irradiation. Enhanced cell killing was evaluated clonogenically in addition to assessment of in vivo efficacy and tumor pathology.

RESULTS/ANTICIPATED RESULTS:

• Conjugation of the particle to the photosensitizer was achieved, and the molecule was detected by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates increased cell killing during radiation treatment, whereas neither the particle alone nor the photosensitizer significantly affected clonogenic survival at the same concentrations. Breast tumors grown in immunocompetent mice showed increased necrotic tissue after a single 20 gy treatment in the presence of the conjugate.

DISCUSSION/SIGNIFICANCE OF IMPACT: Radiation therapy is widely used clinically, but dosage is limited largely to prevent injury to adjacent normal tissue. By increasing the local effect of radiation therapy, our gold conjugate has the potential to augment the effective radiation dose in the tumor, thereby reducing damage to healthy tissue and providing a more effective therapy.

This paper examines the work and lives of black female activist intellectuals in the years before the formation of the National Association of Colored Women's Clubs (NACWC) in 1896. Looking deeper at arguments originally made by Maria Stewart concerning the denial of black women's ambitions and limiting potential in their working lives, the analysis employs the work of the Italian Marxist Antonio Gramsci, in particular his notion of the intellectual, to help reflect on the centrality of these black women in the development of an early counterhegemonic movement.

Methods to stimulate appetite in the sick or elderly remains a challenge with few safe therapeutic options. Ghrelin is an orexigenic hormone, increasing appetite and subsequent food intake. It has received considerable attention as a therapeutic target to stimulate food intake in patients with anorexia. The identification of food-grade bioactives with proven orexigenic effects would mark significant progress in the treatment of disease-related malnutrition. This study therefore investigated the effects of two milk-derived ghrelinergic peptides on appetite and energy intake in healthy humans.

A single-blind, placebo-controlled, 3-arm (placebo, casein bioactive MF1145 and whey bioactive UL-2-141) cross-over trial was conducted in healthy male volunteers. Participants received 26 mg/kg of both the bioactives and placebo. The main outcome measures were energy & protein intake from a set breakfast and ad libitum lunch and subjective appetite sensations as assessed by visual analogue scale (VAS). Basal and postprandial levels of active ghrelin (AG) were measured. Dietary intakes were analysed using Nutritics software. Statistical analyses were performed in R.

Overall, 22 male participants (mean age 27 years) were included, average BMI was 24.6 kg/m2, (19.8 to 30.2 kg/m2). Mean energy and protein intakes at lunch when treated with placebo were 1343 kcal (95% CI: 1215–1471 kcal) and 74 g (95% CI: 66–81 g), respectively. Energy and protein intakes were not significantly different from placebo for either treatment (p = 0.918, p = 0.319 for UL-2-141 and p = 0.889, p = 0.959 for MF1145, respectively). Similarly, appetite, hunger and satiety responses on VAS were not significantly different from placebo for either treatment. AG peak post-lunch on placebo was 653 pg/ml (95% CI: 511–794 pg/ml). Treatment with UL-2-141 resulted in 139 pg/ml reduction in post-prandial AG compared to placebo and treatment with MF1145 resulted in 114 pg/ml reduction compared to placebo. This pattern was significant for both treatments (p = 0.021 and p = 0.045, respectively) however when controlling for fasting-AG, the pattern was no longer significant (p = 0.590 and p = 0.877 respectively). Pre-prandial AG peaks were not significantly different across treatments.

While these peptides have previously demonstrated ghrelinergic effects in rats, no effect on appetite or food intake in humans was identified by this study. This may be attributable to the small sample size or low dose. However, since healthy adults are often not in tune with their own physiological hunger, they may not respond strongly to simple physiological modulators and repeating the study in subjects with established anorexia may be prudent.