Psychologists and other behavioral scientists are frequently interested in whether a questionnaire measures a latent construct. Attempts to address this issue are referred to as construct validation. We describe and extend nonparametric hypothesis testing procedures to assess matrix structures, which can be used for construct validation. These methods are based on a quadratic assignment framework and can be used either by themselves or to check the robustness of other methods. We investigate the performance of these matrix structure tests through simulations and demonstrate their use by analyzing a big five personality traits questionnaire administered as part of the Health and Retirement Study. We also derive rates of convergence for our overall test to better understand its behavior.

OBJECTIVES/GOALS: The objective is to describe the process for developing two measurement tools to measure confidence (self-efficacy) of the anti-racist advocate in an academic setting. METHODS/STUDY POPULATION: We proposed five spheres encountered by the academic trainees: Academic/Research, Clinical, Policy, Interpersonal, and Intrapersonal. We evaluated a book, by Shereen Daniels, used in anti-racism literature: The Anti-Racist Organization - Dismantling Systemic Racism in the Workplace. Using the proposed metric of RACE framework, Recognize the problem, Analyze the impact, Commit to action, Empower for change, we sought to establish readiness on the spectrum of anti-racism advocacy. We developed a list of anti-racism and anti-bias advocacy skills based on: 1) Informational interviews with anti-racism and anti-bias experts, 2) Scoping literature review and 3) Academic trainees’ and faculty lived experience. RESULTS/ANTICIPATED RESULTS: The first assessment, “5-Spheres”, consists of 10 items that perform, 1) Analysis of readiness on the spectrum of anti-racism advocacy using RACE framework (Figure 1 [https://drive.google.com/file/d/1A3nMArEn7ZSxZSuSgDkYl_row-VOhOXf/view?usp=drive_link]), 2) Assessment of workplace environment. The second assessment, “Skills”, consists of 25 items (Figure 2 [https://drive.google.com/file/d/1GTdfSgn0-mPu-flSUVSN-vIKTxBCkFW3/view?usp=drive_link]) that perform assessment of confidence of specific skills within each of the five spheres using the following scale: 1 – Not confident at all, 2 – Lacking some confidence, 3 – Somewhat confident, 4 – Completely confident DISCUSSION/SIGNIFICANCE: This proposed measurement tool can extend to anti-bias as well as anti-racism. Potential uses of the self-assessment includes: 1) Measurement and 2) Gap-spotting.

K-Ar measurements were used in this study of upland Savannah River Site soils to distinguish between sorbed K and the K remaining in remnants of primary minerals. Study of sorbed K contributes to understanding further the interaction of alkali metals (Cs in particular) with the soils. Primary mineral K and the associated radiogenic Ar were studied to characterize soil mica with respect to its provenance and its relationship to hydroxy-interlayered vermiculite. K-Ar age values of Na-saturated clay fractions from five samples of these soils range in age from 270 to 370 Ma. After a moderate acid treatment (6% HNO3 v/v, ~1 mol dm-3, 3 h, 80°C) of the clay fractions, K-Ar age values (270-325 Ma) were little changed on the whole, but they were more closely grouped near 300 Ma. Earlier work had shown that most of the K in these soils is found in material resistant to moderate acid extraction. The K-Ar age values show that this acid-resistant material is much older than any pedogenic minerals could be, even much older than the sedimentary parent rocks from which the soils were derived. These observations support earlier inferences by others that the K in these well leached soils is largely in remnants of primary muscovite from the parent sediments. Age values near 300 Ma suggest that the muscovite is largely from proximal Piedmont terranes of the Appalachian orogen, where the K-Ar relationship in most micas was set by Alleghanian tectonic processes late in the Paleozoic Era. The structural location of the K within mica, shown by the retention of the associated radiogenic Ar, is in contrast to the sorption-dominated behavior of the Cs and most of the Rb in these soils during pedogenesis. Stronger acid treatment (~6 mol dm-3 HNO3, 3 h, 100°C) extracted substantial fractions of both the K and the radiogenic Ar from bulk-soil portions, indicating destruction of some of the primary mica. K-Ar age values for the sand-rich bulk soils were not useful for this study because the sand contains excess radiogenic Ar, probably in sand-sized vein quartz.

Background: Stenotrophomonas maltophilia is a gram-negative, biofilm-producing bacterium that is ubiquitous in water environments and often associated with healthcare-associated infections (HAIs). Outbreaks of S. maltophilia bloodstream infections are a rare event and raise the suspicion of a common source. We used whole-genome sequencing (WGS) for an investigation of a cluster of S. maltophilia HAIs at a single hospital. Methods: A patient was defined as an intensive care unit (ICU) patient with fever and S. maltophilia isolated from a culture and who was treated for an HAI from May to October 2022. The response to the cluster included an epidemiologic investigation, water infection control risk assessments (WICRA), and environmental sampling. We also conducted WGS to characterize and assess relatedness between clinical and environmental S. maltophilia isolates. Results: From May 5 to October 1, 2022, we identified 11 HAIs due to S. maltophilia: 9 bloodstream infections and 2 ventilator-associated pneumonia cases. The initial epidemiological investigation did not identify common medical products, procedures, or personnel as an exposure source. The WICRA identified several breaches that may have exposed patients to contaminated water from sink backsplashes in the ICU, computerized tomography (CT) rooms, and the emergency department. In the CT rooms, saline bags were sometimes used for multiple patients, as were single-use intravenous contrast solution bottles. No additional cases were identified once infection control breaches were mitigated by installing sink splashguards, disinfecting drains, dedicating sink use for handwashing, and adhering to single-patient use of pharmaceutical products in the CT rooms. Of 46 environmental water samples, 19 were culture-positive for S. maltophilia. Isolates available for WGS included 7 clinical isolates (6 blood and 1 respiratory) and 17 environmental isolates. Among the 24 isolates sequenced, 16 unique multilocus sequence types (MLSTs) were identified. The 6 blood isolates sequenced were highly related (ST239, 0–4 high-quality, single-nucleotide variants [hqSNV] over 98.99% core genome), suggesting a common source. Two clusters of related environmental isolates were identified; however, overall MLST and hqSNV analyses suggested no relatedness between clinical and environmental isolates. Conclusions: An ICU cluster of S. maltophilia bloodstream infections was likely associated with water contamination of room surfaces and use of single-use intravenous products for multiple patients in the setting of a national pharmaceutical product shortage. This investigation highlights the importance of strong surveillance and water infection control, including routine assessment of ancillary areas in which intravenous products are administered and interdisciplinary collaboration to properly mitigate nosocomial transmission.

Disclosures: None

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

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.

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 Tonle Sap is the largest wetland in South-east Asia and the heart of the largest inland fishery in the world. Its unique flood pulse system and annual flow reversal is a hotspot for biodiversity and productivity, as well as an essential habitat for many endangered fishes and birds. Despite predicted changes to the wetland's hydrology due to climate change and hydropower development in the Mekong, the consequent impacts on the fauna of the lake are poorly understood. A spatial modelling framework was developed to simulate the impact of potential scenarios of change using relationships between fauna and biophysical characteristics. Potential impacts on 61 animal species with documented nutritional, conservation or ecological value were examined. A large number of species rely on gallery forest to provide important habitats for their life history, yet this area is likely to be highly impacted by permanent inundation. There is a strong synchronicity between life histories and the flood pulse; consequently continued hydrological disruptions will have a significant impact on ecosystem dynamics, imposing further challenges to conservation. Protecting areas that may become suitable for gallery forests and shrublands under a modified flood regime will be crucial to management planning and the maintenance of a diverse and healthy ecosystem.

The tribunals system in England and Wales has been transformed by the entry into force of the Tribunals, Courts and Enforcement Act 2007; among other things, tribunals are now located more firmly and explicitly than ever before within the judicial branch. Questions concerning the relationship between tribunals and regular courts fall to be confronted afresh within this new institutional landscape. Those questions form the focus of this article, which is particularly concerned with the issue recently considered by the Supreme Court in Cart whether, and if so to what extent, decisions taken within the tribunals system (by the Upper Tribunal) should be susceptible to judicial review by the High Court. In Cart, emphasis was placed upon the concept of “proportionate dispute resolution” as a means by which to delimit regular courts' oversight of tribunals' decisions, raising fundamental questions both of legal doctrine (relating to the relevance of the orthodox doctrinal tools of administrative law) and legal policy (concerning the degree of error on the part of a tribunal that a higher court should tolerate in the interests of the efficient, or proportionate, use of judicial resources).