What explains right-wing radicalization in the United States? Existing research emphasizes demographic changes, economic insecurity, and elite polarization. This paper highlights an additional factor: the impact of foreign wars on society at home. We argue communities that bear the greatest costs of foreign wars are prone to higher rates of right-wing radicalization. To support this claim, we present robust correlations between activity on Parler, a predominantly right-wing social media platform, and fatalities among residents who served in U.S. wars in Iraq and Afghanistan, at both the county and census tract level. The findings contribute to understanding right-wing radicalization in the US in two key respects. First, it examines widespread, nonviolent radical-right activity that, because it is less provocative than protest and violence, has eluded systematic measurement. Second, it highlights that U.S. foreign wars have important implications for domestic politics beyond partisanship and voting, to potentially include radicalization.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

The IntCal family of radiocarbon (14C) calibration curves is based on research spanning more than three decades. The IntCal group have collated the 14C and calendar age data (mostly derived from primary publications with other types of data and meta-data) and, since 2010, made them available for other sorts of analysis through an open-access database. This has ensured transparency in terms of the data used in the construction of the ratified calibration curves. As the IntCal database expands, work is underway to facilitate best practice for new data submissions, make more of the associated metadata available in a structured form, and help those wishing to process the data with programming languages such as R, Python, and MATLAB. The data and metadata are complex because of the range of different types of archives. A restructured interface, based on the “IntChron” open-access data model, includes tools which allow the data to be plotted and compared without the need for export. The intention is to include complementary information which can be used alongside the main 14C series to provide new insights into the global carbon cycle, as well as facilitating access to the data for other research applications. Overall, this work aims to streamline the generation of new calibration curves.

Water is often referred to as our most precious resource, and for a good reason – drinking water and wastewater services sustain core functions of the critical infrastructure, communities, and human life itself. Our water systems are threatened by aging infrastructure, floods, drought, storms, earthquakes, sea level rise, population growth, cyber-security breaches, and pollution, often in combination. Marginalized communities inevitably feel the worst impacts, and our response continues to be hampered by fragmented and antiquated governance and management practices. This paper focuses on the resilience of water sector (drinking water, wastewater, and stormwater [DWS]) to three major hazards (Sea-Level Rise, Earthquake, and Cyberattack). The purpose of this paper is to provide information useful for creating and maintaining resilient water system services. The term resilience describes the ability to adapt to changing conditions and to withstand and recover from disruptions. The resilience of DWS systems is of utmost importance to modern societies that are highly dependent on continued access to these water sector services. This review covers the terminology on water sector resilience and the assessment of a broad landscape of threats mapped with the proposed framework. A more detailed discussion on two areas of resilience is given: Physical Resilience, which is currently a major factor influencing disruptions and failures in DWS systems, and Digital Resilience, which is a rapidly increasing concern for modern infrastructure systems. The resilience of DWS systems should be considered holistically, inclusive of social, digital, and physical systems. The framework integrates various perspectives on water system threats by showcasing interactions between the parts of the DWS systems and their environment. While the challenges of change, shock and stresses are inevitable, embracing a social–ecological–technical system-of-systems and whole-life approach will allow us to better understand and operationalize resilience.

Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.

OBJECTIVES/GOALS: Glioblastoma (GBM) is the most common and aggressive adult primary brain malignancy. Clinically, GBM is refractory to T cell immune checkpoint blockade (ICB), in part due to its dense immune suppressive myeloid stroma. Here we show that myeloid-targeting STING agonists can repolarize the GBM microenvironment to cure ICB-refractory GBM models. METHODS/STUDY POPULATION: Using the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803) we treated orthotopic ICB-refractory QPP8 orthotopic murine GBM tumors intratumorally. We then analyzed survival and performed high parameter flow cytometry profiling of the tumor immune microenvironment following STING agonist treatment. To assess the contribution of adaptive immunity to STING agonist therapeutic efficacy, we treated orthotopic QPP8 tumors implanted in RAG1 KO mice and monitored survival. RESULTS/ANTICIPATED RESULTS: We found that STING agonist therapy cured murine orthotopic QPP8 tumors, in contrast to ICB that showed no survival benefit. In RAG1-/- mice bearing QPP8 tumors STING agonist therapy extended survival, however, the curative effect observed in wild-type mice was lost in the absence of adaptive immunity. STING agonist-treated QPP8 tumors displayed increased counts of CD8 T cells and NK cells, and decreased CD8 T cell PD1 expression. Infiltration of STING-treated gliomas by Ly6C+ F4/80+ Mono-MDSC substantially increased; however, these cells expressed reduced CD206 and CD163, suggestive of reduced immuno-suppression. Finally, in the cervical LN of QPP8-treated mice the frequency and CD80/CD86 expression of cDC1 cells increased.​ DISCUSSION/SIGNIFICANCE: ICB has failed in GBM, and the suppressive myeloid stroma remains a major barrier to generating anti-GBM T cell responses. Our work shows that STING activation, which primarily targets innate immunity myeloid cells 'upstream' of T cells in the antitumor immunity cycle, can cure ICB-refractory GBM tumors in an adaptive immunity-dependent manner.

A theoretical and experimental framework for novel metamaterial with programmable damping properties is presented. This material system is able to switch between elastic-dominated and damping-dominated regimes with different overall stiffness under dynamic loading depending on the external stimulus. The unit cell combines an auxetic and a bellow-like layer separated by an interface through which the amount of media flow can be tuned depending on the lateral strain. A simplified analytical model is derived to analyse the programmable damping effect. The model is further extended with a fluid-dynamics approach to link the effective damping properties with geometrical parameters to aid with the practical design of the metamaterial. Afterward, experiments are conducted on a macroscopic level using laser-sintered unit cells to validate the functionality of the concept both with air and water as media within the unit cells. To conclude the work, initial results on microscopic-level unit cells fabricated by two-photon lithography are introduced to showcase the scalability of the concept. This work provides an experimentally validated theoretical framework for future investigations to design unit cells with programmable damping on different length scales for applications requiring tailored dynamic energy dissipation.

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2–17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0–22.0) in May 2021 to 54.1% (95% CrI 46.7–61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12–17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.

We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log10 with XF-73 compared to 0.4 log10 CFU/mL for those who received placebo (95% CI, −2.7 to −1.5; P < .0001).

Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.