Background: Antibiotic use without a prescription (nonprescription use) leads to antibiotic overuse, with negative consequences for patient and public health. We studied whether screening patients for prior nonprescription antibiotic use in the past 12 months predicted their intentions to use them in the future. Methods: A survey asking respondents about prior and intended nonprescription antibiotic use was performed between January 2020 and June 2021 among patients in waiting rooms of 6 public clinics and 2 private emergency departments in economically and socially diverse urban and suburban areas. Respondents were classified as prior nonprescription users if they reported previously taking oral antibiotics without contacting a doctor, dentist, or nurse. Intended use was defined as answering “yes” or “maybe” to the question, “Would you use antibiotics without contacting a doctor, nurse, or dentist?” We calculated the sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of prior nonprescription antibiotic use in the past 12 months for future intended nonprescription use. Bayes PPV and NPV were also calculated, considering the prevalence of nonprescription antibiotic use (24.8%) in our study. Results: Of the 564 patients surveyed, the median age was 51 years (SD, 19–92), with 72% of patients identifying as female. Most were from the public healthcare system (72.5%). Most respondents identified as Hispanic or Latino(a) (47%) or African American (33%), and 57% received Medicaid or the county financial assistance program. Prior nonprescription use was reported by 246 (43%) of 564 individuals, with 91 (16%) reporting nonprescription use within the previous 12 months. Intention to use nonprescription antibiotics was reported by 140 participants (25%). The sensitivity and specificity of prior nonprescription use in the past 12 months to predict the intention to use nonprescription antibiotics in the future were 75.9% (95% CI, 65.3–84.6) and 91.4% (95% CI, 87.8–94.2), respectively. After the Bayes’ adjustment, the PPV and NPV of prior use to predict future intention were 74.5% (95% CI, 66.7–80.9) and 92.0% (95% CI, 88.7–94.4) (Table 1). Conclusions: These results show that prior nonprescription antibiotic use in the past 12 months predicted the intention to use nonprescription antibiotics in the future (PPV of 75%). As a stewardship effort, we suggest clinicians use a simple question about prior nonprescription antibiotic use in primary-care settings as a screening question for patients at high risk for future nonprescription antibiotic use.

Financial support: HSQR-R 5R01HS026901-04

Disclosure: None

Valproate is widely used in psychiatry and neurology, including off-label use. Here we consider its potential benefits and risks, particularly for women of childbearing potential, and the evidence that clinical guidelines are adhered to. Finally, we consider the implications for clinical practice and research into its efficacy in off-label indications.

Large-scale archaeogenetic studies of people from prehistoric Europe tend to be broad in scope and difficult to resolve with local archaeologies. However, accompanying supplementary information often contains useful finer-scale information that is comprehensible without specific genetics expertise. Here, we show how undiscussed details provided in supplementary information of aDNA papers can provide crucial insight into patterns of ancestry change and genetic relatedness in the past by examining details relating to a >90 per cent shift in the genetic ancestry of populations who inhabited Chalcolithic and Early Bronze Age Britain (c. 2450–1600 bc). While this outcome was certainly influenced by movements of communities carrying novel ancestries into Britain from continental Europe, it was unlikely to have been a simple, rapid process, potentially taking up to 16 generations, during which time there is evidence for the synchronous persistence of groups largely descended from the Neolithic populations. Insofar as genetic relationships can be assumed to have had social meaning, identification of genetic relatives in cemeteries suggests paternal relationships were important, but there is substantial variability in how genetic ties were referenced and little evidence for strict patrilocality or female exogamy.

OBJECTIVES/SPECIFIC AIMS: The goal of this research is to use circulating tumor cells (CTC) enumeration and characterization to monitor anticancer treatment response. Emerging evidence strongly suggests the implications that epithelial-to-mesenchymal transition may have in cancer metastasis. Consequently, we hope to elucidate the significance of mesenchymal and stem-like CTCs in the peripheral blood of metastatic pancreatic cancer patients by analyzing the prevalence and frequency trends of CD133+ CTCs, as they relate to clinical events. We also hope to determine if there is a correlation between EpCAM+ CTCs and CD133+ CTCs numbers with tumor size, disease stage, and patient clinical outcome. METHODS/STUDY POPULATION: Blood samples of patients with metastatic pancreatic cancer (stage IV) were obtained from the University of Florida Health Cancer Center after informed consent through an IRB-approved protocol. CTC capture, characterization, and enumeration was performed on the blood of these cancer patients during their anticancer treatment. Patients had blood drawn for this purpose at time points aligned with clinical phlebotomy (every 2 weeks). CTC capture was performed by introducing treated patient blood samples into antibody-functionalized microdevices. The PDMS devices were functionalized by immobilizing either anti-EpCAM or anti-CD133, through an avidin-biotin complex. After capture, cells were fixated and permeabilized with 4% paraformaldehyde and 0.2% Triton X-100, respectively. Three-color immunocytochemistry (anti-cytokeratin-FITC, anti-CD45-PE, and DAPI) was performed to identify CTCs from nonspecifically captured blood cells. To be counted as a CTC, based on the FDA-approved technical definition, a cell with the appropriate cell size and morphology must be nucleated (DAPI+), express cytokeratin (CK+), and lack the leukocytic CD45 marker (CD45−). RESULTS/ANTICIPATED RESULTS: We tested the clinical utility of the device for monitoring the response of patients with advanced pancreatic cancer to a chemotherapy treatment consisting of anticancer drugs including 5-fluorouracil, leucovorin, oxaliplatin, and dasatinib. We have detected EpCAM+ CTCs in 47/47 (100%) and CD133+ CTCs in 41/47 (87.2%) of blood samples, coming from a cohort of 16 patients. We studied the correlation between the CTC numbers and the clinical result of patients in the study. We found that the size and changes in the size of the primary tumor (confirmed by CT scans) correlated with the frequency and increase/decrease trends in the number of CTCs detected. We expect to find some relationship between the number of detected CD133+ CTCs, or rather stem-like CTCs, and the clinical outcome of patients (eg, disease progression leading to withdrawal from study). DISCUSSION/SIGNIFICANCE OF IMPACT: Enumeration of patient CTCs and stem-like CTCs at different stages of a patient’s treatment may correlate with disease stage and prognosis, and prove useful in monitoring early recurrence, patient-specific treatment response, and newly acquired resistances; all of which would aid in providing guidance for the next step in clinical intervention. This type of liquid biopsy technology has great potential to make an impact in the future of personalized medicine and point-of-care diagnostics, as well as become a sturdy tool for translational research.

The United States has been a leader in the creation of disability rights law, providing a policy template for other nations. Yet the social model, the animating philosophy behind the disability rights movement, has had little effect on the wide range of welfare programs that serve people with disabilities. These programs, whose creation preceded the modern disability rights movement, reflect a medical model of disability that is at odds with the social model. Analysing the Americans with Disabilities Act (which embodies the social model) and Social Security Disability Insurance (the largest welfare program for people with disabilities), we explore how and why this layering of contradictory disability rights and welfare programs developed and how it has been maintained. We argue that the tension between these policies engendered a series of patches, or ‘kludges’, that allow the policies to coexist without meaningful synthesis. We contend that the United States is particularly prone to this layering of ‘tense policies’, but that it is likely characteristic of disability policy in many nations. Finally we argue that accurate benchmarking of disability rights regimes across nations requires analysts to dig through all the layers of disability policy.

Effective methods are needed to eradicate tall fescue (Festuca arundinacea) and convert tall fescue fields into habitats more suitable to wildlife species. The objectives of this study were to determine the efficacy of (1) a single glyphosate application during the spring or fall and (2) AC 263,222, alone and in combination with glyphosate, applied during four different tall fescue growth stages for control of established tall fescue. Studies were conducted during 1996 to 1998 in fields dominated by tall fescue located in central Kentucky. Pre- and posttreatment plant communities were described to quantify differences in vegetative characteristics due to herbicide applications. Glyphosate at 2.2 kg ai/ha applied during the spring or fall was effective in reducing tall fescue to less than 12% cover. AC 263,222 at 0.2 kg ai/ha, AC 263,222 at 0.2 kg/ha plus glyphosate at 0.6 kg/ha, or AC 263,222 at 0.2 kg/ha plus glyphosate at 1.1 kg/ha applied during the spring growth, boot, summer dormancy, and fall growth stages were equally effective, reducing tall fescue cover to less than 3% at 2 to 7 mo after treatment. Glyphosate and AC 263,222 are effective tools for the initial removal of tall fescue.

Two field experiments were conducted to evaluate the effects of selected herbicides on Italian ryegrass, combined Italian ryegrass plus wheat forage production, and returns from hard red winter wheat grain. Herbicides included BAY FOE 5043 + metribuzin (4:1 w/w premix), BAY MKH 6562, chlorsulfuron, chlorsulfuron + metsulfuron (5:1 w/w premix), diclofop, MON 37560, pendimethalin, ICIA 0604, and triasulfuron. Italian ryegrass was controlled 80% or more by 28 of 34 treatments. Grain dockage was reduced by 33 of 34 treatments at both sites, and grain yield was improved at both sites by 29 of 34 treatments. No herbicide treatment decreased forage protein content, but forage yield was frequently decreased by controlling Italian ryegrass. Gross returns from wheat grain were improved over the untreated check by all but six treatments at site 1, and by all but one treatment at site 2. The data did not support the hypothesis that returns from forage plus grain could be maximized by delaying Italian ryegrass control until grazing termination.