How do people make decisions between an immediate but small reward and a delayed but large one? The outcome of such decisions indicates that people discount rewards by their delay and hence these outcomes are well described by discounting functions. However, to understand irregular decisions and dysfunctional behavior one needs models which describe how the process of making the decision unfolds dynamically over time: how do we reach a decision and how do sequential decisions influence one another? Here, we present an attractor model that integrates into and extends discounting functions through a description of the dynamics leading to a final choice outcome within a trial and across trials. To validate this model, we derive qualitative predictions for the intra-trial dynamics of single decisions and for the inter-trial dynamics of sequences of decisions that are unique to this type of model. We test these predictions in four experiments based on a dynamic delay discounting computer game where we study the intra-trial dynamics of single decisions via mouse tracking and the inter-trial dynamics of sequences of decisions via sequentially manipulated options. We discuss how integrating decision process dynamics within and across trials can increase our understanding of the processes underlying delay discounting decisions and, hence, complement our knowledge about decision outcomes.

Following the 2008 financial crisis, austerity measures have been introduced in many national contexts to reorganise public sector work and redesign labour laws and labour policies. At the same time, right-populist discourses and movements have arisen in ways that give both legitimacy and voice to the politics of austerity. Toronto, Canada, provides a world-renowned case of populist experimentation at the metropolitan scale, as the actions of Mayor Rob Ford typified this nexus of austerity and populism. Set in the context of Ford’s term as Mayor of Toronto (2010–2014), this article asks how the combined rise of austerity and right populism creates both new challenges and new opportunities for public sector labour in urban spaces. We argue that public sector unions are central in both the making and unmaking of populist austerity and identify potential trajectories for organised labour in the face of the continuation of austerity-driven politics.

The fluvial geomorphology and stratigraphy on the middle Snake River at Bancroft Springs, Idaho, provide evidence for numerous episodes of Snake River aggradation and incision since the Bonneville Flood at ca. 18 ka. A suite of seven terraces ranging from 20–1 m above modern bankfull elevation records multiple cut-and-fill cycles during the latest Pleistocene and Holocene in response to local base-level controls, variations in sediment supply, and hydroclimate change. Radiocarbon and luminescence dating show that the ages of fluvial aggradation generally coincide with increased sediment supply and likely wetter hydroclimate during onset of the Younger Dryas stadial (ca. 13.2 ka), deglaciation and termination of the Younger Dryas stadial (ca. 11.3 ka), Early Holocene cooling (ca. 8.8 ka), and Neoglacial (ca. 4.5, 2.9, 1.1 ka). Six intervening periods of incision and channel stability may also reflect either reduced sediment supply, drier hydroclimate, or both. The terrace chronology can be correlated to a variety of local and regional paleoclimate proxy records and corresponds well with periods of continental- and global-scale rapid climate change during the Holocene. The fluvial record demonstrates the geomorphic response and sensitivity of large river systems to changes in hydroclimate variability, which has important implications for inferring paleoenvironmental conditions in the region.

The first generation of Ethiopian filmmakers produced significant fictional and documentary films inside Ethiopia from the 1960s to 1990s, but access to these films has been limited. Drawing on interviews with filmmakers, Kassahun and Thomas analyze this early production in its cultural context and compare it with Haile Gerima’s internationally celebrated Harvest: 3000 Years (1975), produced in the United States, to complicate the meta-narrative of Ethiopia’s film history. In the context of debates by intellectuals about art and politics, early Ethiopian filmmakers participated in an internationally conscious Ethiopian modernism across the political revolutions of 1974 and 1991.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

Background: The NHSN parameter estimate for predicted number of central-line–associated bloodstream infection (CLABSI) is the same for gastroenterology wards as other specialty wards, such as behavioral health and gerontology. We conducted this study to contribute to the body of knowledge surrounding the risk for hospital-acquired bloodstream infection (HABSI) in patients with and without hepatic failure. The Cleveland Clinic is a 1,200-bed, multispecialty hospital with a solid-organ transplant service. Patients with hepatic failure who do not require critical care are housed on 36-bed unit A. On unit A, 43% of patients are under hepatology or gastroenterology service, although 51% of patients are under general internal medicine. Overall, unit A has a high incidence of HABSI. Methods: Surveillance for HABSI and CLABSI is performed at the Cleveland Clinic per NHSN protocol. All patients with a midnight stay on unit A from January 2019 through September 2021 were dichotomized as having hepatic failure (yes or no) if they ever received the International Classification of Diseases Tenth Revision code for “hepatic failure, not elsewhere classified.” We joined the diagnostic code to patient days and central-line-days databases and summarized the data using Microsoft Excel software. We stratified the number of patients, patient days, device days, infection classification, and hospital length of stay by whether the patient had hepatic failure, and we compared the incidence of HABSI and CLABSI between the 2 groups using OpenEpi version 3.01 software. Results: We identified 72 HABSIs among 4,285 patients who stayed on unit A for 30,910 patient days during the study period. The incidences of HABSI in patients with and without hepatic failure were 39.0 and 13.9 per 10,000 patient days, respectively (P < .001). The incidence of CLABSI was 5.4 and 1.9 per 1,000 line days, respectively (P = .01). Patients with hepatic failure stayed longer (11.5 vs 5.9 days), yet the central-line utilization ratios were not substantially different (0.25 vs 0.24). Enterococcus was the most common pathogen involved in CLABSI in both groups (Table 2). Conclusions: Patients with hepatic failure experienced CLABSI more frequently than patients without hepatic failure, stayed longer in the hospital, and were less likely have HABSI attributed to another primary focus of infection according to NHSN definitions. Although hepatic failure may be among the most severe conditions among patients in a gastroenterology ward, we have demonstrated that these units house a population uniquely susceptible to HABSI and CLABSI.

Funding: None

Disclosures: None

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

Analysis of patterns of faulting and hydrogeology, stratigraphic and sedimentologic studies, and luminescence dating of aeolian deposits in China Lake basin provide new perspectives on the origins and development of Late Holocene dunes and sand ramps in the seismically active Indian Wells Valley of eastern California. Aeolian dune and sand sheet deposits were sourced from alluvial material derived from granitic rocks of the south-eastern Sierra Nevada and are concentrated in areas with sand-stabilizing phreatophyte vegetation influenced by high groundwater levels along the active oblique-normal Little Lake and Paxton Ranch faults, which locally form barriers to groundwater flow. Three episodes of sand accumulation are recognized (2.1 ± 0.1 to 2.0 ± 0.1 ka, 1.8 ± 0.2 to 1.6 ± 0.2 ka, and 1.2 ± 0.1 to 0.9 ± 0.1 ka) during conditions in which sediment supplied to the basin during periods of enhanced rainfall and runoff was subsequently reworked by wind into dunes and sand ramps at the transition to more arid periods. Understanding the role tectonics plays in influencing the hydrogeology of seismically active lake basins provides insights to accurately interpret landscape evolution and any inferences made on past hydroclimate variability in a region.

High-throughput grain mapping with sub-nanometer spatial resolution is demonstrated using scanning nanobeam electron diffraction (also known as 4D scanning transmission electron microscopy, or 4D-STEM) combined with high-speed direct-electron detection. An electron probe size down to 0.5 nm in diameter is used and the sample investigated is a gold–palladium nanoparticle catalyst. Computational analysis of the 4D-STEM data sets is performed using a disk registration algorithm to identify the diffraction peaks followed by feature learning to map the individual grains. Two unsupervised feature learning techniques are compared: principal component analysis (PCA) and non-negative matrix factorization (NNMF). The characteristics of the PCA versus NNMF output are compared and the potential of the 4D-STEM approach for statistical analysis of grain orientations at high spatial resolution is discussed.

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.

ABSTRACT IMPACT: Identifying an important pathway in treatment resistant TNBC will allow for the future development of clinical therapeutics specific for this disease. OBJECTIVES/GOALS: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer characterized by negative expression of estrogen receptor, progesterone receptor, and HER2/neu amplification. It resists therapies and has a high recurrence rate after resection. The goal of my research is to identify & characterize a TNBC pathway for future development of therapies. METHODS/STUDY POPULATION: The project uses a combination of cell lines, patient derived xenograft (PDX) models, as well as patient databases. Standard cellular and molecular biology techniques will be used including: Cell culture, qPCR, western blotting, and flow cytometry. RESULTS/ANTICIPATED RESULTS: LKB1 is a master kinase that activates 14 possible downstream kinases. The signaling pathway has been demonstrated to play a role in energy homeostasis and metabolism. Mutation of LKB1 signaling results in Peutz-Jeghers Syndrome and is associated with neoplasias of the lung, pancreas, and breast. Based on preliminary analysis, overexpression of LKB1 by shRNA in TNBC cell lines results in suppression of EMT and reduction of the cancer stem cell population. Additional studies show that LKB1 overexpression has no effect on growth rate in 2D culture while significant reduction in 3D mammosphere formations can be seen. Downstream studies using commercially available SIK1 inhibitor HG-9-91-01 is able to induce a larger fraction of CSC from reduced LKB1 overexpression as well as from baseline levels. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, our results suggest that LKB1 acts through SIK1 to suppress EMT and the generation of cancer stem cells. This results in reduced cancer functionality, as evidenced by inhibition of mammosphere formation. These results establishes a foundation for future mechanistic studies on the LKB1 axis and its mechanisms in TNBC.

The remnant phase of a radio galaxy begins when the jets launched from an active galactic nucleus are switched off. To study the fraction of radio galaxies in a remnant phase, we take advantage of a $8.31$ deg$^2$ subregion of the GAMA 23 field which comprises of surveys covering the frequency range 0.1–9 GHz. We present a sample of 104 radio galaxies compiled from observations conducted by the Murchison Widefield Array (216 MHz), the Australia Square Kilometer Array Pathfinder (887 MHz), and the Australia Telescope Compact Array (5.5 GHz). We adopt an ‘absent radio core’ criterion to identify 10 radio galaxies showing no evidence for an active nucleus. We classify these as new candidate remnant radio galaxies. Seven of these objects still display compact emitting regions within the lobes at 5.5 GHz; at this frequency the emission is short-lived, implying a recent jet switch off. On the other hand, only three show evidence of aged lobe plasma by the presence of an ultra-steep-spectrum ($\alpha<-1.2$) and a diffuse, low surface brightness radio morphology. The predominant fraction of young remnants is consistent with a rapid fading during the remnant phase. Within our sample of radio galaxies, our observations constrain the remnant fraction to $4\%\lesssim f_{\mathrm{rem}} \lesssim 10\%$; the lower limit comes from the limiting case in which all remnant candidates with hotspots are simply active radio galaxies with faint, undetected radio cores. Finally, we model the synchrotron spectrum arising from a hotspot to show they can persist for 5–10 Myr at 5.5 GHz after the jets switch of—radio emission arising from such hotspots can therefore be expected in an appreciable fraction of genuine remnants.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

Two phases of archaeological investigation were performed in the Novi Sad City Museum at Petrovaradin Fortress. In this study, we summarize the results of geo-archaeological investigations of the second period of excavation inside the Novi Sad City Museum building. The fortress is situated on a Danube terrace with the top of the bedrock at ca.123 m asl. The investigated section consists of undisturbed fine-sandy silt. The grain-size distribution of the sediments indicates clearly its alluvial reworking but shows also a general similarity with typical primary loess in the region. All analyzed proxies indicate slightly stronger weathering in the upper part of the profile. Luminescence ages suggest that the investigated sequence covers the last glacial period and the terrace presumably formed during MIS 4. Subsequently, the Danube started its incision at the start of the next warmer period (MIS 3) onward. This terrace age and elevation enable us to derive an uplift rate of the terrace of ca. 0.73 mm/a for the last 60 ka, which seems to increase towards the present. Basal loessic material, in which artifacts occur, likely in the reworked position, indicate that the area close to today's Petrovaradin Fortress was already inhabited in MIS 5.