Comparison of Sales From Vending Machines With 4 Different Food and Beverage Messages: A Randomized Trial.

Importance: Point-of-sale food messaging can encourage healthier purchases, but no studies have directly compared multiple interventions in the field. Objective: To examine which of 4 food and beverage messages would increase healthier vending machine purchases. Design, Setting, and Participants: This randomized trial assessed 13 months (February 1, 2019, to February 29, 2020) of vending sales data from 267 machines and 1065 customer purchase assessments from vending machines on government property in Philadelphia, Pennsylvania. Data analysis was performed from March 5, 2020, to November 8, 2022. Interventions: Study interventions were 4 food and beverage messaging systems: (1) beverage tax posters encouraging healthy choices because of the Philadelphia tax on sweetened drinks; (2) green labels for healthy products; (3) traffic light labels: green (healthy), yellow (moderately healthy), or red (unhealthy); or (4) physical activity equivalent labels (minutes of activity to metabolize product calories). Main Outcomes and Measures: Sales data were analyzed separately for beverages and snacks. The main outcomes analyzed at the transaction level were calories sold and the health status (using traffic light criteria) of each item sold. Additional outcomes were analyzed at the monthly machine level: total units sold, calories sold, and units of each health status sold. The customer purchase assessment outcome was calories purchased per vending trip. Results: Monthly sales data came from 150 beverage and 117 snack vending machines, whereas 1065 customers (558 [52%] male) contributed purchase assessment data. Traffic light labels led to a 30% decrease in the mean monthly number of unhealthy beverages sold (mean ratio [MR], 0.70; 95% CI, 0.55-0.88) compared with beverage tax posters. Physical activity labels led to a 34% (MR, 0.66; 95% CI, 0.51-0.87) reduction in the number of unhealthy beverages sold at the machine level and 35% (MR, 0.65; 95% CI, 0.50-0.86) reduction in mean calories sold. Traffic light labels also led to a 30-calorie reduction (b = -30.46; 95% CI, -49.36 to -11.56) per customer trip in the customer purchase analyses compared to physical activity labels. There were very few significant differences for snack machines. Conclusions and Relevance: In this 13-month randomized trial of 267 vending machines, the traffic light and physical activity labels encouraged healthier beverage purchases, but no change in snack sales, compared with a beverage tax poster. Corporations and governments should consider such labeling approaches to promote healthier beverage choices. Trial Registration: ClinicalTrials.gov Identifier: NCT06260176.

Anti-tumor activity of a novel LAIR1 antagonist in combination with anti-PD-1 to treat collagen-rich solid tumors.

We recently reported that resistance to PD-1-blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and thus we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. Here, we report LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer. NGM438, a novel humanized LAIR1 antagonist monoclonal antibody, elicits myeloid inflammation and allogeneic T cell responses by binding to LAIR1 and blocking collagen engagement. Further, a mouse-reactive NGM438 surrogate antibody sensitized refractory KP mouse lung tumors to anti-PD-1 therapy and resulted in increased intratumoral CD8+ T cell content and inflammatory gene expression. These data place LAIR1 at the intersection of stroma and suppressive myeloid cells and support the notion that blockade of the LAIR1/collagen axis can potentially address resistance to checkpoint inhibitor therapy in the clinic.

Impact of the Philadelphia Beverage Tax on Perceived Beverage Healthfulness, Tax Awareness, and Tax Opinions.

OBJECTIVE: To assess the impact of the Philadelphia Beverage Tax on perceived beverage healthfulness, and awareness and opinions of the tax. DESIGN: Natural experiment SETTING: Small independent stores in Philadelphia (n = 61) and Baltimore (untaxed control site; n = 65) PARTICIPANTS: Shoppers in Philadelphia (n = 2,731) and Baltimore (n = 4,600) pre- and post-tax implementation. MAIN OUTCOME MEASURES: Perceptions of 4 beverages (unhealthy vs healthy/neutral), tax awareness, and tax opinions (oppose vs favor/neutral). ANALYSIS: Mixed-effects linear probability models estimated changes in perceived beverage healthfulness in Philadelphia, relative to Baltimore, following a difference-in-differences approach. Mixed-effects linear probability models estimated pre-post changes in tax awareness and opinions in Philadelphia-only. RESULTS: The probability of perceiving taxed beverages as unhealthy increased 2-years post-tax relative to Baltimore (regular soda: 5.7% [95% confidence interval (CI), 0.9-10.6], P = 0.02; diet soda: 7.7% [95% CI, 1.5-13.8], P < 0.001; sports drinks: 6.4% [95% CI, 0.4-12.4], P = 0.04), with similar changes at 1-year post-tax, whereas perceived healthfulness of untaxed 100% fruit juice did not change. Tax awareness was high at baseline (72%) and increased post-implementation; however, the probability of opposing the tax (22%) also increased over time. CONCLUSIONS AND IMPLICATIONS: Decreases in the perceived healthfulness of taxed beverages suggest the tax had a health-signaling effect. Consumer awareness and health education efforts could complement tax policies to enhance understanding of health risks.

Congenital Cytomegalovirus Testing Outcomes From the ValEAR Trial.

OBJECTIVE: To determine the positivity rate of congenital cytomegalovirus (cCMV) testing among universal, hearing-targeted CMV testing (HT-cCMV) and delayed targeted dried blood spot (DBS) testing newborn screening programs, and to examine the characteristics of successful HT-cCMV testing programs. STUDY DESIGN: Prospective survey of birth hospitals performing early CMV testing. SETTING: Multiple institutions. METHODS: Birth hospitals participating in the National Institutes of Health ValEAR clinical trial were surveyed to determine the rates of cCMV positivity associated with 3 different testing approaches: universal testing, HT-cCMV, and DBS testing. A mixed methods model was created to determine associations between successful HT-cCMV screening and specific screening protocols. RESULTS: Eighty-two birth hospitals were surveyed from February 2019 to December 2021. Seven thousand six hundred seventy infants underwent universal screening, 9017 infants HT-cCMV and 535 infants delayed DBS testing. The rates of cCMV positivity were 0.5%, 1.5%, and 7.3%, respectively. The positivity rate for universal CMV screening was less during the COVID-19 pandemic than that reported prior to the pandemic. There were no statistically significant drops in positivity for any approach during the pandemic. For HT-cCMV testing, unique order sets and rigorous posttesting protocols were associated with successful screening programs. CONCLUSION: Rates of cCMV positivity differed among the 3 approaches. The rates are comparable to cohort studies reported in the literature. Universal CMV prevalence decreased during the pandemic but not significantly. Institutions with specific order set for CMV testing where the primary care physician orders the test and the nurse facilitates the testing process exhibited higher rates of HT-cCMV testing.

Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection.

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.IMPORTANCEWe detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.

Advertising and Stocking at Small Retailers: A Sweetened Beverage Excise Tax in Philadelphia.

INTRODUCTION: In 2017, Philadelphia enacted a $0.015 per ounce excise tax on SBs that covered both sugar-sweetened beverages and artificially-sweetened beverages, which reduced purchasing and consumption. This study assessed whether the tax also changed beverage advertising or stocking practices that could influence consumer behavior among stores in Philadelphia, Baltimore, and Philadelphia-adjacent counties not subject to the tax. METHODS: Using a longitudinal difference-in-differences approach, beverage advertising and availability changes were evaluated from 4-month pretax to 6-, 12-, and 24-month post-implementation in small independent stores in Philadelphia (n=34) and Philadelphia-adjacent counties (n=38) versus Baltimore (n=43), a demographically similar city without a tax. Mixed effects models tested whether beverage advertising/availability increased in Philadelphia and surrounding counties after implementation versus Baltimore, included store-level random intercepts, and were stratified by beverage tax status, type, size, and store ZIP code income. Data were collected from 2016 to 2018, and analyses were performed in 2022-2023. RESULTS: SB advertising increased post-tax in Philadelphia (6 months= +1.04 advertisements/store [95% CI=0.27, 1.80]; 12 months= +1.54 [95% CI=0.57, 2.52]; 24 months= +0.91 [95% CI=0.09, 1.72]) relative to Baltimore. This was driven by increased advertising of sweetened beverages in low-income ZIP codes. Marketing of SBs increased significantly in Philadelphia-adjacent counties relative to Baltimore. Although SB availability in Philadelphia did not change, it increased in surrounding county stores (6 months= +0.20 [95% CI=0.15, 0.25]; 12 months= +0.08 [95% CI=0.03, 0.12]) relative to Baltimore. CONCLUSIONS: Marketing of SBs, especially in low-income neighborhoods and in surrounding counties, increased following Philadelphia's beverage tax among small, independent retailers. These increases in advertising might have dampened the tax's effect on purchasing behaviors, although estimated effects on sales remained large.

Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes.

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins infrequently detected as targets of T cell responses may contain important vaccine antigens. Using an extant dataset from a T cell profiling study, we tested whether HCMV proteins recognized by only a small minority of participants encompass any T cell epitopes. Our analyses demonstrate a prominent skewing of T cell responses away from most viral proteins-although they contain robust predicted CD8 T cell epitopes-in favor of a more restricted set of proteins. Our findings raise the possibility that HCMV may benefit from evading the T cell recognition of certain key proteins and that, contrary to current vaccine design approaches, including them as vaccine antigens could effectively take advantage of this vulnerability.

Effects of 4 Interpretive Front-of-Package Labeling Systems on Hypothetical Beverage and Snack Selections: A Randomized Clinical Trial.

Importance: Policymakers and researchers have proposed a variety of interpretative front-of-package food labeling systems, but it remains unclear which is most effective at encouraging people to choose healthier foods and beverages, including among people with less education. Objective: To test the effects of 4 interpretative front-of-package food labeling systems on the healthfulness of beverage and snack selections, overall and by education level. Design, Setting, and Participants: This randomized clinical trial of a national sample of US adults 18 years and older was conducted online from November 16 to December 3, 2022. Intervention: Participants were randomized to view products with 1 of 5 food labeling systems, including control (calorie labels only) or 1 of 4 interpretative labeling systems: green ("choose often") labels added to healthy foods; single traffic light labels added to healthy, moderately healthy, and unhealthy foods; physical activity calorie equivalent labels added to all products; and nutrient warning labels added to products high in calories, sugar, saturated fat, or sodium. All conditions had calorie labels on all products. Main Outcomes and Measures: Participants selected 1 of 16 beverages and 1 of 16 snacks that they wanted to hypothetically purchase. The primary outcomes were calories selected from beverages and from snacks. Secondary outcomes included label reactions and perceptions. Results: A total of 7945 participants completed the experiment and were included in analyses (4078 [51%] female, 3779 [48%] male, and 88 [1%] nonbinary or another gender; mean [SD] age, 47.5 [17.9 years]). Compared with the control arm, exposure to the green (average differential effect [ADE], -34.2; 95% CI, -42.2 to -26.1), traffic light (ADE, -31.5; 95% CI, -39.5 to -23.4), physical activity (ADE, -39.0; 95% CI, -47.0 to -31.1), or nutrient warning labels (ADE, -28.2; 95% CI, -36.2 to -20.2) led participants to select fewer calories from beverages (all P < .001). Similarly, compared with the control label, exposure to the green (ADE, -12.7; 95% CI, -17.3 to -8.2), traffic light (ADE, -13.7; 95% CI, -18.2 to -9.1), physical activity (ADE, -18.5; 95% CI, -23.1 to -13.9), or nutrient warning labels (ADE, -14.2; 95% CI, -18.8 to -9.6) led participants to select fewer calories from snacks (all P < .001). These effects did not differ by education level. The green labels were rated as less stigmatizing than the other interpretative systems but otherwise generally received the least favorable label reactions and perceptions (eg, elicited less attention, were perceived as less trustworthy), while the nutrient warnings and physical activity labels received the most favorable ratings. Conclusions and Relevance: In this randomized clinical trial of front-of-package food labeling systems, all 4 interpretative labeling systems reduced calories selected from beverages and from snacks compared with calorie labels, with no differences by education level. Trial Registration: ClinicalTrials.gov Identifier: NCT05432271.

Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study.

BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.

Philadelphia Beverage Tax and Association With Prices, Purchasing, and Individual-Level Substitution in a National Pharmacy Chain.

Importance: Taxes on sweetened beverages are being implemented around the globe; an understanding of these taxes on individual-level behavior is necessary. Objective: To evaluate the degree to which the sweetened beverage tax in Philadelphia, Pennsylvania, was associated with changes in beverage prices and individual-level purchasing over time at a national pharmacy chain in Philadelphia compared with Baltimore, Maryland. Design, Setting, and Participants: Using a difference-in-differences approach and generalized linear mixed models, this cohort study examined beverage purchases made by loyalty cardholders at a national chain pharmacy retailer with stores in Philadelphia and Baltimore (control city) from before tax to after tax. Beverage sales (in US dollars) were linked by unique loyalty card numbers to enable longitudinal analyses. Data were collected from January 1, 2015, through December 31, 2017 (2 years before tax and 1 year after tax); data analyses were conducted from January through October 2022. Exposure: Implementation of Philadelphia's 1.5 cents/oz tax on sweetened beverages. Main Outcomes and Measures: The outcomes were the change in mean beverage price per-ounce and mean beverage volume purchased per cardholder transaction. Individual-level point-of-sale scanner data from all beverage purchases were analyzed. Results: A total of 1188 unique beverages were purchased from the same stores before tax and after tax. There were 231 065 unique cardholders in Philadelphia and 82 517 in Baltimore. Mean prices of taxed beverages (n = 2 094 220) increased by 1.6 (95% CI, 1.3-2.0) cents/oz (106.7% pass-through) in Philadelphia compared with Baltimore from before tax to after tax. Philadelphia cardholders purchased 7.8% (95% CI -8.1% to -7.5%) fewer ounces of taxed beverages and 1.1% (95% CI, 0.6%-1.7%) more ounces of nontaxed beverages per transaction. Taxed beverages made up a smaller percentage of cardholders' overall beverage purchases after tax (-13.4% [95% CI, -14.2% to -12.6%]), while nontaxed beverages made up a larger share (9.3% [95% CI, 7.7%-10.7%]). Conclusions and Relevance: In this longitudinal cohort study of the Philadelphia beverage tax, the tax was completely passed through to prices and was associated with a 7.8% decline in ounces of taxed beverages purchased at a national pharmacy chain.

A Qualitative Assessment of Clinical Practice Guidelines and Patterns for Congenital Cytomegalovirus in the United States.

Cytomegalovirus (CMV) infection during pregnancy may result in long-term health problems for children with congenital CMV (cCMV). Currently, no prevention or treatment interventions are approved by the Food and Drug Administration for a cCMV indication. Healthcare provider and public awareness is low, and formal clinical practice guidelines and local practice patterns vary. A pilot study of eight cCMV experts was performed using qualitative semi-structured interviews to better understand clinical practice guidelines and patterns in the United States. Results from participant interviews highlighted the need for better prenatal diagnostic techniques, broader neonatal screening opportunities, and more robust evidence supporting intervention strategies. Healthcare provider and public partnerships are essential for advancing cCMV guidelines and improving care delivery. Our results provide a preliminary knowledge base and framework for developing a consensus cCMV research agenda to address evidence gaps that limit the revision of clinical practice guidelines. The changes in clinical practice patterns that may arise as a result of further research have the potential to reduce risk during pregnancy and improve care for children with cCMV infection.

Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance.

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way to improve response to ICB therapy. Results: Our results show that combination anti-PD-1/CTLA-4 produces an initial antitumor effect with evidence of an activated immune response. Upon extended treatment with anti-PD-1/CTLA-4 acquired resistance developed with an increase of the immunosuppressive populations, including T-regulatory cells, neutrophils and monocytes. Addition of anti-Ly6C blocking antibody to anti-PD-1/CTLA-4 was capable of completely reversing treatment resistance and restoring CD8 T cell activity in multiple KP lung cancer models and in the autochthonous lung cancer KrasLSL-G12D/p53fl/fl model. We found that there were higher classical Ly6C+ monocytes in anti-PD-1/CTLA-4 combination resistant tumors. B7 blockade illustrated the importance of dendritic cells for treatment efficacy of anti-Ly6C/PD-1/CTLA-4. We further determined that classical Ly6C+ monocytes in anti-PD-1/CTLA-4 resistant tumors are trafficked into the tumor via IFN-γ and the CCL2-CCR2 axis. Mechanistically we found that classical monocytes from ICB resistant tumors were unable to differentiate into antigen presenting cells and instead differentiated into immunosuppressive M2 macrophages or myeloid-derived suppressor cells (MDSC). Classical Ly6C+ monocytes from ICB resistant tumors had a decrease in both Flt3 and PU.1 expression that prevented differentiation into dendritic cells/macrophages. Conclusions: Therapeutically we found that addition of anti-Ly6C to the combination of anti-PD-1/CTLA-4 was capable of complete tumor eradication. Classical Ly6C+ monocytes differentiate into immunosuppressive cells, while blockade of classical monocytes drives dendritic cell differentiation/maturation to reinvigorate the anti-tumor T cell response. These findings support that immunotherapy resistance is associated with infiltrating monocytes and that controlling the differentiation process of monocytes can enhance the therapeutic potential of ICB.

Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The digital site-less approach employed in the "Test Us At Home" study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Changes in Dental Outcomes After Implementation of the Philadelphia Beverage Tax.

INTRODUCTION: Beverage taxes are associated with declines in sugar-sweetened beverage sales and consumption, but few studies have evaluated the associations of these taxes with health outcomes. This study analyzed changes in dental decay after the implementation of the Philadelphia sweetened beverage tax. METHODS: Electronic dental record data were obtained on 83,260 patients living in Philadelphia and control areas from 2014 to 2019. Difference-in-differences analyses compared the number of new Decayed, Missing, and Filled Teeth with that of new Decayed, Missing, and Filled Surfaces before (January 2014-December 2016) and after (January 2019-December 2019) tax implementation in Philadelphia and control patients. Analyses were conducted in older children/adults (aged ≥15 years) and younger children (aged <15 years). Subgroup analyses stratified by Medicaid status. Analyses were conducted in 2022. RESULTS: The number of new Decayed, Missing, and Filled Teeth did not change after tax implementation in Philadelphia in panel analyses of older children/adults (difference-in-differences= -0.02, 95% CI= -0.08, 0.03) or younger children (difference-in-differences=0.07, 95% CI= -0.08, 0.23). There were similarly no post-tax changes in the number of new Decayed, Missing, and Filled Surfaces. However, in cross-sectional samples of patients on Medicaid, the number of new Decayed, Missing, and Filled Teeth was lower after tax implementation in older children/adults (difference-in-differences= -0.18, 95% CI= -0.34, -0.03; -22% decline) and younger children (difference-in-differences= -0.22, 95% CI= -0.46, 0.01; -30% decline), with similar results for number of new Decayed, Missing, and Filled Surfaces. CONCLUSIONS: The Philadelphia beverage tax was not associated with reduced tooth decay in the general population, but it was associated with reduced tooth decay in adults and children on Medicaid, suggesting potential health benefits for low-income populations.

Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study.

Background: The performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) in temporal relation to symptom onset or exposure is unknown, as is the impact of vaccination on this relationship. Objective: To evaluate the performance of Ag-RDT compared with RT-PCR based on day after symptom onset or exposure in order to decide on 'when to test'. Design Setting and Participants: The Test Us at Home study was a longitudinal cohort study that enrolled participants over 2 years old across the United States between October 18, 2021 and February 4, 2022. All participants were asked to conduct Ag-RDT and RT-PCR testing every 48 hours over a 15-day period. Participants with one or more symptoms during the study period were included in the Day Post Symptom Onset (DPSO) analyses, while those who reported a COVID-19 exposure were included in the Day Post Exposure (DPE) analysis. Exposure: Participants were asked to self-report any symptoms or known exposures to SARS-CoV-2 every 48-hours, immediately prior to conducting Ag-RDT and RT-PCR testing. The first day a participant reported one or more symptoms was termed DPSO 0, and the day of exposure was DPE 0. Vaccination status was self-reported. Main Outcome and Measures: Results of Ag-RDT were self-reported (positive, negative, or invalid) and RT-PCR results were analyzed by a central laboratory. Percent positivity of SARS-CoV-2 and sensitivity of Ag-RDT and RT-PCR by DPSO and DPE were stratified by vaccination status and calculated with 95% confidence intervals. Results: A total of 7,361 participants enrolled in the study. Among them, 2,086 (28.3%) and 546 (7.4%) participants were eligible for the DPSO and DPE analyses, respectively. Unvaccinated participants were nearly twice as likely to test positive for SARS-CoV-2 than vaccinated participants in event of symptoms (PCR+: 27.6% vs 10.1%) or exposure (PCR+: 43.8% vs. 22.2%). The highest proportion of vaccinated and unvaccinated individuals tested positive on DPSO 2 and DPE 5-8. Performance of RT-PCR and Ag-RDT did not differ by vaccination status. Ag-RDT detected 78.0% (95% Confidence Interval: 72.56-82.61) of PCR-confirmed infections by DPSO 4. For exposed participants, Ag-RDT detected 84.9% (95% CI: 75.0-91.4) of PCR-confirmed infections by day five post-exposure (DPE 5). Conclusions and Relevance: Performance of Ag-RDT and RT-PCR was highest on DPSO 0-2 and DPE 5 and did not differ by vaccination status. These data suggests that serial testing remains integral to enhancing the performance of Ag-RDT.

Effects of Sugary Beverage Text and Pictorial Warnings: A Randomized Trial.

INTRODUCTION: Multiple U.S. localities have introduced legislation requiring sugar-sweetened beverage (SSB) warnings. This study effects of different warning designs on beverage selections and perceptions. STUDY DESIGN: The study was an RCT. SETTING/PARTICIPANTS: An online virtual convenience store and survey were used with a nationally representative sample of primary caregivers of 6-11-year-olds (n=961). Data were collected in January 2020 and analyzed in May-July 2020. INTERVENTION: Participants were randomized to view SSBs with 1 of 4 front-of-package label designs: (1) no-warning control, (2) health-related text warning, (3) sugar pictorial warning (image of beverage sugar content in cubes/teaspoons/packets with health-related warning text), or (4) health pictorial warning (image of possible health consequences of overconsuming SSBs with health-related warning text). MAIN OUTCOME MEASURES: Outcomes included participants' beverage choice for their child and perceptions of beverages, their assigned labels, and warning policies. RESULTS: Proportionally fewer participants chose a SSB in the sugar pictorial warning condition (-13.4 percentage points; 95% CI= -21.6 to -0.1 percentage points; p=0.007) and in the health pictorial warning condition (-14.7 percentage points; 95% CI= -22.8 to -0.1 percentage points; p=0.004) compared to the control. Sugar pictorial warnings led to more accurate added-sugar content estimates than all conditions and greater label trust and support for sugar-sweetened beverage warning policies than health pictorial warnings. CONCLUSIONS: SSB warning policies may be most effective if they mandate images of beverages' added sugar content accompanied by warning text. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov NCT03648138.

Chemotherapeutic Activity of Pitavastatin in Vincristine Resistant B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (ALL) is derived from an accumulation of malignant, immature B cells in the bone marrow and blood. Relapse due, in part, to the emergence of tumor cells that are resistant to front line standard chemotherapy is associated with poor patient outcomes. This challenge highlights the need for new treatment strategies to eliminate residual chemoresistant tumor cells. Based on the use of pitavastatin in acute myeloid leukemia (AML), we evaluated its efficacy in an REH ALL cell line derived to be resistant to vincristine. We found that pitavastatin inhibited the proliferation of both parental and vincristine-resistant REH tumor cells at an IC50 of 449 nM and 217 nM, respectively. Mitochondrial bioenergetic assays demonstrated that neither vincristine resistance nor pitavastatin treatment affected cellular oxidative phosphorylation, beta-oxidation, or glycolytic metabolism in ALL cells. In a co-culture model of ALL cells with bone marrow stromal cells, pitavastatin significantly decreased cell viability more robustly in the vincristine-resistant ALL cells compared with their parental controls. Subsequently, NSG mice were used to develop an in vivo model of B-cell ALL using both parental and vincristine-resistant ALL cells. Pitavastatin (10 mg/kg i.p.) significantly reduced the number of human CD45+ REH ALL cells in the bone marrow of mice after 4 weeks of treatment. Mechanistic studies showed that pitavastatin treatment in the vincristine-resistant cells led to apoptosis, with increased levels of cleaved PARP and protein-signaling changes for AMP-activated protein kinase/FoxO3a/Puma. Our data suggest the possible repurposing of pitavastatin as a chemotherapeutic agent in a model of vincristine-resistant B-cell ALL.

Impact of Privacy Messaging on COVID-19 Exposure Notification App Downloads: Evidence From a Randomized Experiment.

Introduction: Digital contact-tracing smartphone apps have the potential to slow the spread of disease but are not widely used. We tested whether messages describing how a COVID-19 digital contact-tracing app protects users' privacy led to increased or decreased intentions to download the app by either calming privacy concerns or increasing their saliency. Design: Randomized controlled trial. Setting/participants: We recruited adult smartphone owners in the U.S. (oversampled for younger adults aged 18-34 years) in November 2020 through an online panel. Intervention: Survey software randomly assigned 860 participants to 1 of 2 parallel messaging conditions (n=430 privacy assured, n=430 no privacy described). Main outcome measures: 4-point scale of intention to use the app "if public health officials released a COVID Exposure Notification app in their state" that averaged likelihood to (1) download and install the app on their phone; (2) keep the app active on their phone; and (3) keep Bluetooth active on their phone (needed for the app to work). Results: After removing incompletes, those who failed the manipulation checks, or those who had already downloaded a COVID-19 digital contact-tracing app, we analyzed 671 participants (n=330 privacy, n=341 no privacy) in 2021. There was no relationship between privacy condition and download intention (meanprivacy=2.69, meannoprivacy=2.69, b=0.01, 95% CI= -0.13, 0.15, p=0.922) but also no evidence that describing the app's security increased context-dependent privacy concerns (measured 3 ways). Instead, we found increased endorsement of data security in the privacy condition using a scale of beliefs about the app keeping privacy secure (meanprivacy=2.74, meannoprivacy=2.58, b=0.16, 95% CI=0.04, 0.28, p=0.009, small effect ω2=0.009). Conclusions: This study provides some evidence that people developing contact-tracing messaging campaigns do not need to worry that describing a digital contact-tracing app's privacy protections will backfire. Future mixed methods testing of messages about who has access to information-and for how long-may uncover new communication strategies to increase public trust in contact-tracing apps. Trial registration: This study is registered with AsPredicted#51826.

Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection.

Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting: Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants: Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements: Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations: New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the 'Test Us At Home' study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.