The warm, equable, and ice-free early Eocene Epoch permits investigation of ecosystem function and macro-ecological patterns during a very different climate regime than exists today. It also provides insight into what the future may entail, as anthropogenic CO2 release drives Earth toward a comparable hothouse condition. Studying plant–insect herbivore food webs during hothouse intervals is warranted, because these account for the majority of nonmicrobial terrestrial biodiversity. Here, we report new plant and insect herbivore damage census data from two floodplain sites in the Wind River Basin of central Wyoming, one in the Aycross Formation (50–48.25 Ma) at the basin edge (WRE) and the second in the Wind River Formation in the interior of the basin (WRI). The WRI site is in stratigraphic proximity to a volcanic ash that is newly dated to 52.416 ± 0.016/0.028/0.063 (2σ). We compare the Wind River Basin assemblages to published data from a 52.65 Ma floodplain flora in the neighboring Bighorn (BH) Basin and find that only 5.6% of plant taxa occur at all three sites and approximately 10% occur in both basins. The dissimilar floras support distinct suites of insect herbivores, as recorded by leaf damage. The relatively low-diversity BH flora has the highest diversity of insect damage, contrary to hypotheses that insect herbivore diversity tracks floral diversity. The distinctiveness of the WRE flora is likely due to its younger age and cooler reconstructed paleotemperature, but these factors are nearly identical for the WRI and BH floras. Site-specific microenvironmental factors that cannot be measured easily in deep time may account for these differences. Alternatively, the Owl Creek Mountains between the two basins may have provided a formidable barrier to the thermophilic organisms that inhabited the basin interiors, supporting Janzen's hypothesis that mountain passes appear higher in tropical environments.

Understanding the properties of time averaging (age mixing) in a stratigraphic layer is essential for properly interpreting the paleofauna preserved in the geologic record. This work assesses the age and quantifies the scale and structure of time averaging of land snail-rich colluvial sediments from the Madeira Archipelago (Portugal) by dating individual shells using amino acid racemization calibrated with graphite-target and carbonate-target accelerator mass spectrometry radiocarbon methods. Gastropod shells of Actinella nitidiuscula were collected from seven sites on the volcanic islands of Bugio and Deserta Grande (Desertas Islands), where snail shells are abundant and well preserved in Quaternary colluvial deposits. Results show that the shells ranged in age from modern to ~48 cal ka BP (calibrated radiocarbon age), covering the last glacial and present interglacial periods. Snail shells retrieved from two of the colluvial sites exhibit multimillennial age mixing (>6 ka), which significantly exceeds the analytical error from dating methods and calibration. The observed multimillennial mixing of these assemblages should be taking into consideration in upcoming paleoenvironmental and paleoecological studies in the region. The extent of age mixing may also inform about the time span of colluvial deposition, which can be useful in future geomorphological studies. In addition, this study presents the first carbonate-target radiocarbon results for land snail shells and suggests that this novel, rapid, and more affordable dating method offers reliable age estimates for small land snail shells younger than ~20 cal ka BP.

OBJECTIVES/SPECIFIC AIMS: Negative symptoms of schizophrenia, including motivational deficits, social withdrawal, poverty of speech, decreased emotional reactivity, and psychomotor retardation, have been shown to be most predictive of functional impairment and poor outcome in patients with schizophrenia. Furthermore, these symptoms tend not to be responsive to antipsychotic medications. Inflammation could be one mechanism underlying these difficult to treat symptoms. METHODS/STUDY POPULATION: Three cohorts of patients, reflecting different phases of disease, were studied. One cohort was comprised of a sample of patients with deficit schizophrenia (characterized by primary and enduring negative symptoms; n=17), nondeficit patients (n=39), and healthy controls (n=28). ANOVA and multivariate general linear models were used to compare groups, and linear regression models were used to examine relationships between inflammatory cytokines and negative symptoms. The second cohort was comprised of 80 individuals at clinical high risk for psychosis from the North American Prodromal Longitudinal Study. Linear regression models examined the relationship between baseline inflammatory markers and subsequent negative symptoms at follow-up visits up to 2 years. The third cohort consisted of patients with treatment-resistant schizophrenia (TRS) on clozapine (n=10). Correlations were performed to examine relationships between inflammatory markers and negative symptoms. In a subgroup of patients from this third sample, resting state functional connectivity analyses were performed on fMRI data to explore relationships between inflammatory markers and connectivity in brain reward circuitry. RESULTS/ANTICIPATED RESULTS: In a sample of patients with the deficit syndrome of schizophrenia (n=17), a subtype of the disorder characterized by primary and enduring negative Symptoms, tumor necrosis factor (TNF) was significantly increased relative to nondeficit patients (n=39) and healthy controls (n=28; F2,57=3.51, p=0.036), and predicted total negative symptoms (β=0.31, p=0.012), alogia (β=0.30, p=0.024), and blunted affect (β=0.31, p=0.018) items of the Positive and Negative Symptom Scale in linear regression models while controlling for antipsychotics. In another sample of individuals at clinical-high risk for psychosis (n=80), baseline concentrations of TNF significantly predicted negative symptoms, including anhedonia, apathy, and loss of interest in linear regression models, at the 6-month (β=0.25, p=0.011) and 12-month follow-up (β=0.39, p=0.001). Interleukin (IL)-1 receptor antagonist also predicted these symptoms at the 6-month follow-up (β=0.21, p=0.037). In a third sample (n=10) of patients with TRS treated with clozapine, IL-1β was correlated with passive/apathetic social withdrawal (r=0.657, p=0.039) and disturbance of volition (r=0.686, p=0.029) items of the Positive and Negative Symptom Scale and the global avolition-apathy scores of the Scale for the Assessment of Negative Symptoms (r=0.751, p=0.012). Finally, in a small subsample (n=5) of patients from this TRS cohort for whom we collected fMRI data, we found resting-state functional connectivity from a right nucleus accumbens seed to a cluster in medial prefrontal cortex. We found relationships between higher inflammation and decreased connectivity for TNF (r=−0.64) and CRP (r=−0.89). DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together, these preliminary data show the predicted relationship between inflammatory markers and negative symptoms and demonstrate the reproducibility of TNF and other monocytic-derived cytokines as reliably elevated in schizophrenia and associated with negative symptoms across samples of patients with schizophrenia and individuals at high risk for psychosis. Cytokines may exert their effects via their impact on brain reward circuitry, and could represent novel treatment targets for motivational deficits and negative symptoms of schizophrenia.

Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.

Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days–12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30–132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15–100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.

Florpyrauxifen-benzyl is a new herbicide under development in rice that will provide an alternative mode of action to control barnyardgrass. Multiple greenhouse experiments evaluated florpyrauxifen-benzyl efficacy on barnyardgrass accessions collected in rice fields across Arkansas, and to evaluate its efficacy on herbicide-resistant biotypes. In one experiment, florpyrauxifen-benzyl was applied at the labeled rate of 30 g ai ha−1 to 152 barnyardgrass accessions collected from 21 Arkansas counties. Florpyrauxifen-benzyl at 30 g ai ha−1 effectively controlled barnyardgrass and subsequently reduced plant height and aboveground biomass. In a dose-response experiment, susceptible-, acetolactate synthase (ALS)-, propanil-, and quinclorac-resistant barnyardgrass biotypes were subjected to nine rates of florpyrauxifen-benzyl ranging from 0 to 120 g ai ha−1. The effective dose required to provide 90% control, plant height reduction, and biomass reduction of the susceptible and resistant biotypes fell below the anticipated labeled rate of 30 g ai ha−1. Based on these results, quinclorac-resistant barnyardgrass as well as other resistant biotypes can be controlled with florpyrauxifen-benzyl at 30 g ai ha−1. Overall, results from these studies indicate that florpyrauxifen-benzyl can be an effective tool for controlling susceptible and currently existing herbicide-resistant barnyardgrass biotypes in rice. Additionally, the unique auxin chemistry of florpyrauxifen-benzyl will introduce an alternative mechanism of action in rice weed control thus acting as an herbicide-resistance management tool.

The European Project for Ice Coring in Antarctica (EPICA) includes a comprehensive pre-site survey on the inland ice plateau of Dronning Maud Land. This paper focuses on the investigation of the 18O content of shallow firn and ice cores. These cores were dated by profiles derived from dielectric-profiling and continuous flow analysis measurements. the individual records were stacked in order to obtain composite chronologies of 18O contents and accumulation rates with enhanced signal-to-noise variance ratios. These chronologies document variations in the last 200 and 1000 years. The18O contents and accumulation rates decreased in the 19th century and increased during the 20th century. Using the empirical relationships between stable isotopes, accumulation rates and the 10 m firn temperature, the variation of both parameters can be explained by the same temperature history. But other causes for these variations, such as the build-up of the snow cover, cannot be excluded. A marked feature of the 1000 year chronology occurs during the period AD 1180–1530 when the 18Ocontents remains below the long-term mean. Cross-correlation analyses between five cores from the Weddell Sea region and Dronning Maud Land show that 18O records can in some periods be positively correlated and in others negatively correlated, indicating a complex climatic history in time and space.

OBJECTIVES/SPECIFIC AIMS: Enhancing Patient Safety for hospitalized patients is a priority for healthcare facilities, providers, and federal funding agencies. Multidisciplinary partnerships in clinical and translational research better defines the scope of complex patient-safety issues, and is part of more effectively developing interventions. The discipline represented by engineering-trained partners brings valuable perspective to patient safety problems through their training background in human factors and systems analysis. The objective of this education program was to create and implement a collaboration between engineering students and clinical providers. Through the Johns Hopkins Institute for Clinical and Translational Research, a multidisciplinary partnership was created, to identify contributing factors, and suggest novel solutions, to key patient safety problems using an ethnographic research approach. METHODS/STUDY POPULATION: The collaboration was formed between the following Johns Hopkins (JH) groups: (1) The Institute for Clinical and Translational Research (ICTR), (2) The Armstrong Institute for Patient Safety, (3) The JH Hospital Clinical Engineering Services, (4) The Homecare Group, (5) The Masters of Science in Engineering Management Program at the Whiting School of Engineering, and (6) The JH Hospital Risk Management. All 6 provided representation to contribute to the planning, structure, and implementation of the project. The initial cohort was 24 masters students enrolled in the JHU Whiting School of engineering, and included 46% men, 54% women, and 75% international students. Students were placed in teams of 2–3 to work on 9 distinct patient safety concerns, as provided by the Armstrong Institute as priority. Potential clinical hosts from the appropriate clinical departments were vetted for feasibility and scope before students were assigned to them. Students and clinical hosts were oriented to the process. The students then spent 3–6 hours a week, for 7 weeks, observing and interacting with patients and health professionals at their specific clinical sites, conducting ethnographic research under the guidance of their hosts. Ethnographic research is the systematic investigation of a culture or system; in our application, teams were looking at the environment, culture, and its contributing factors, with respect to patient safety issues. Teams made observations, then formulated hypothesis and collected data relevant to what systems factors may be contributing to the patient safety issue. Following data collection and analyses, teams made recommendations for culture and/or systems shifts that could impact change and improve patient safety. Ethnography research process training is a tenet of the training undertaken by all Masters of Science in Engineering Management Students. RESULTS/ANTICIPATED RESULTS: At the end of the 7-week project, each team generated a comprehensive report suggesting potential solutions for each problem, and gave presentations on their findings to their peers, clinical hosts, and JHU steering committee representatives. Requirements on the student side included a midterm, final presentation, and report. Both students and site leaders submitted mid- and final program evaluations. Based on follow-up survey data, 71% of students said that the course may impact their career choice, 57% said the collaboration changed the way they viewed themselves, and 28% elected to continue working or were planning to work with their site in some fashion after the course ended. Nearly 60% of students believed additional funding or resources would benefit the course and 71% thought they would benefit from more or similar experiences with their clinical partners. Furthermore, 85% wanted to see the course expanded. Of the clinical hosts, 71% said that students added value, 86% believed students changed their perspective on their problem, unveiled new areas of investigation, and improved or likely would improve patient safety in their department. Seventy-one percent of hosts were actively acting on the students’ findings, and over 86% shared findings with their colleagues. Following the 7-week program, 2 teams also presented their findings to committees within the hospital departments, 2 patient-safety projects are being continued with engineering teams, and 2 new collaborative projects have been initiated. Based on the popularity of this program with the students, hosts, and teaching faculty, this will be implemented within the engineering curriculum for a second time next year. Additional outcomes data collection are currently ongoing, and we plan to continue to monitor and analyze results. DISCUSSION/SIGNIFICANCE OF IMPACT: In its first year our engineering collaboration exceeded expectations. Engineering students and clinical providers successfully worked toward tangible solutions that were directly applicable to patient care. Furthermore, interactions were both personally and professionally beneficial for students while simultaneously adding value to clinical hosts. Beyond the collaboration, this initiative allowed for secondary connections between engineers and clinicians that are also have great potential for resulting in translational innovation. Despite the overwhelming success of this project, it highlighted the need for increased resources for sustainability. Our pilot highlighted a role for funding with regards to: (1) students in the execution of their projects (eg, transportation to sites, prototype materials); (2) clinical hosts, particularly protecting time to interact with and lead student teams; (3) the Armstrong Institute—to aid the identification and prioritization of high impact, patient safety projects; and (4) the ICTR for staff to facilitate placements, student orientation to the hospital setting, and program execution and maintenance. Ultimately, this collaboration addressed an unmet need for the clinical providers as well as the engineering students: thus, all partners agree that (1) the impact of this pilot would be greatly magnified by more time, longer duration, and additional resources; and (2) this collaboration could provide a useful model for approaching other complex health care problems. In terms of larger and longer-term impact, engaging engineers at the training level together with clinicians provides early exposure, and could potentially prime them to continue collaborations with clinical and translational science, across their careers.

Student Research Assistant Acknowledgements: The authors thank Manik Arora, Alexandra Morani, and Thomas Cornish -- Johns Hopkins University.

We present results from a study to identify the globular cluster systems of six of the brightest galaxies of the Sculptor Group. From Mosaic II CMR images of the area surrounding the galaxies NGC 45, NGC 55, NGC 247, NGC 253, NGC 300, and NGC 7793, we identify cluster candidates through their morphology, luminosity, and color. We show that many of the Milky Way's globular clusters would appear extended in our images if placed in the Sculptor Group; only in the two most distant galaxies, NGC 45 and NGC 7793, is the discrimination difficult. We find 50–100 candidates per galaxy with integrated properties similar to Milky Way clusters. Published spectroscopic identifications of candidates in NGC 253 lead us to expect that ∼50% of the candidates are true clusters, while the remainder are background galaxies. Study of the Sculptor Group galaxies increases the sample of late-type spiral and Magellanic-type galaxies with known globular cluster systems from 2 to ∼10.

For the first time, valence electron energy-loss spectroscopy (VEELS) was applied to individual single-crystalline SnO2 nanowires to investigate the dielectric function, band gap, and optical absorption coefficient. The results are compared with data from optical techniques such as spectroscopic ellipsometry and UV-Vis, and theoretical calculations from variations of density functional theory. The data obtained agree well with the standard optical and theoretical techniques. The dielectric function and optical absorption coefficient are given up to 20 eV, which otherwise requires a synchrotron source and large single crystals via optical methods. The energy loss function is given up to 40 eV, which gives a useful comparison to previous theoretical studies in an energy range that cannot be achieved via optical measurements. The comparison gives confidence in the accuracy of this method for exploring spatially-resolved measurements in individual nanoparticles or more complex nanostructures that are otherwise difficult to measure accurately using optical techniques.

We present liquid-cell transmission electron microscopy (liquid-cell TEM) imaging of fixed and non-fixed prostate cancer cells (PC3 and LNCaP) with high resolution in a custom developed silicon nitride liquid cell. Fixed PC3 cells were imaged for 90–120 min without any discernable damage. High contrast on the cellular structures was obtained even at low electron doses (~2.5 e−/nm2 per image). The images show distinct structures of cell compartments (nuclei and nucleoli) and cell boundaries without any further sample embedding, dehydration, or staining. Furthermore, we observed dynamics of vesicles trafficking from the cell membrane in consecutive still frames in a non-fixed cell. Our findings show that liquid-cell TEM, operated at low electron dose, is an excellent tool to investigate dynamic events in non-fixed cells with enough spatial resolution (few nm) and natural amplitude contrast to follow key intracellular processes.