Hand, foot, and mouth disease (HFMD) shows spatiotemporal heterogeneity in China. A spatiotemporal filtering model was constructed and applied to HFMD data to explore the underlying spatiotemporal structure of the disease and determine the impact of different spatiotemporal weight matrices on the results. HFMD cases and covariate data in East China were collected between 2009 and 2015. The different spatiotemporal weight matrices formed by Rook, K-nearest neighbour (KNN; K = 1), distance, and second-order spatial weight matrices (SO-SWM) with first-order temporal weight matrices in contemporaneous and lagged forms were decomposed, and spatiotemporal filtering model was constructed by selecting eigenvectors according to MC and the AIC. We used MI, standard deviation of the regression coefficients, and five indices (AIC, BIC, DIC, R2, and MSE) to compare the spatiotemporal filtering model with a Bayesian spatiotemporal model. The eigenvectors effectively removed spatial correlation in the model residuals (Moran’s I < 0.2, p > 0.05). The Bayesian spatiotemporal model’s Rook weight matrix outperformed others. The spatiotemporal filtering model with SO-SWM was superior, as shown by lower AIC (92,029.60), BIC (92,681.20), and MSE (418,022.7) values, and higher R2 (0.56) value. All spatiotemporal contemporaneous structures outperformed the lagged structures. Additionally, eigenvector maps from the Rook and SO-SWM closely resembled incidence patterns of HFMD.

Exposure to adversity during the perinatal period has been associated with cognitive difficulties in children. Given the role of the nucleus accumbens (NAcc) in attention and impulsivity, we examined whether NAcc volume at age six mediates the relations between pre- and postnatal adversity and subsequent attention problems in offspring. 306 pregnant women were recruited as part of the Growing Up in Singapore Towards Healthy Outcomes Study. Psychosocial stress was assessed during pregnancy and across the first 5 years postpartum. At six years of age, children underwent structural MRI and, at age seven years, mothers reported on their children’s attention problems. Separate factor analyses conducted on measures of pre- and postnatal adversity each yielded two latent factors: maternal mental health and socioeconomic status. Both pre- and postnatal maternal mental health predicted children’s attention difficulties. Further, NAcc volume mediated the relation between prenatal, but not postnatal, maternal mental health and children’s attention problems. These findings suggest that the NAcc is particularly vulnerable to prenatal maternal mental health challenges and contributes to offspring attention problems. Characterizing the temporal sensitivity of neurobiological structures to adversity will help to elucidate mechanisms linking environmental exposures and behavior, facilitating the development of neuroscience-informed interventions for childhood difficulties.

We study household fuel choice in rural China through the lens of social interactions, deploying a structural discrete choice interaction model to explain peer-dependence in household fuel choice. The data comes from the China Family Panel Studies 2010–2020, and we use multiple strategies to examine the robustness of the social interaction effects. We find a significant endogenous social effect, meaning that whether a household chooses non-solid clean fuel for cooking is directly affected by the choice in cooking fuel made by its neighbors in the village. Households with lower non-farm income are more sensitive to the choices of others, and the fuel choices of households with a higher education and/or a higher income attracts more attention from others. Modern communication technologies facilitate information exchange among rural residents, thereby strengthening the endogenous social effect. We suggest that public policies can accelerate rural energy transition by stimulating positive social spillovers.

We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

We conducted a retrospective cohort study in Ontario, Canada between December 1, 2020 and June 31, 2021 to compare the incidence of neurological events (hospitalization or emergency room visit) within six weeks of COVID-19 vaccination in Chinese, South Asian and Other ethnic groups. Compared to Others, the crude rates after the first dose for Bell’s palsy, ischemic stroke and intracerebral hemorrhage were lower in Chinese (34, 159 and 48 per 1,000,000 doses) and in South Asians (44, 148 and 32), but similar after adjusting for age, sex and vaccine type. Our findings should help encourage vaccination for all, irrespective of ethnicity.

The proto-Milky Way epoch forms the earliest stars in our galaxy and sets the initial conditions for the subsequent disk formation. Recent observations showed that the [$\alpha$/Fe] ratio among in situ metal-poor stars declined between [Fe/H] $=-3$ and $-1.3$ until it reached the lowest value ($\sim$0.25) and rose to the traditional value associated with the high-[$\alpha$/Fe] thick disk ($\sim$0.3) at [Fe/H] $\approx$ -1.0. It was suggested that the rise in [$\alpha$/Fe] could be caused by an increase in the star formation efficiency (SFE), known as the ‘simmering’ phase scenario. However, gas inflow also plays a vital role in shaping the star formation history and chemical evolution of galaxies, especially during the earliest epoch of the universe. We investigate this unexpected [$\alpha$/Fe]-rise with an experiment involving a galactic chemical evolution model. Our model has five free parameters: the mass of the initial reservoir of the cold interstellar medium (ISM) at birth, the frequency of Type Ia supernovae (SNe Ia), the cooling timescale of the warm ISM, the SFE, and the inflow rate of fresh gas. The last two free parameters were allowed to change after [$\alpha$/Fe] reached its lowest value, dividing the proto-Galaxy epoch into two phases. The models that reproduced the observed [Fe/H]-[$\alpha$/Fe]-track provided estimates for these fundamental parameters of the proto-Milky Way. We find that the rise in [$\alpha$/Fe] could also be caused by a large inflow of high-[$\alpha$/Fe] gas and conclude that the [$\alpha$/Fe]-rise could be a signature of the gas accretion that fuelled the formation of the Milky Way disk.

There is a relative lack of research, targeted models and tools to manage beaches in estuaries and bays (BEBs). Many estuaries and bays have been highly modified and urbanised, for example port developments and coastal revetments. This paper outlines the complications and opportunities for conserving and managing BEBs in modified estuaries. To do this, we focus on eight diverse case studies from North and South America, Asia, Europe, Africa and Australia combined with the broader global literature. Our key findings are as follows: (1) BEBs are diverse and exist under a great variety of tide and wave conditions that differentiate them from open-coast beaches; (2) BEBs often lack statutory protection and many have already been sacrificed to development; (3) BEBs lack specific management tools and are often managed using tools developed for open-coast beaches; and (4) BEBs have the potential to become important in “nature-based” management solutions. We set the future research agenda for BEBs, which should include broadening research to include greater diversity of BEBs than in the past, standardising monitoring techniques, including the development of global databases using citizen science and developing specific management tools for BEBs. We must recognise BEBs as unique coastal features and develop the required fundamental knowledge and tools to effectively manage them, so they can continue providing their unique ecosystem services.

This study aimed to understand the population and contact tracer uptake of the quick response (QR)-code-based function of the New Zealand COVID Tracer App (NZCTA) used for digital contact tracing (DCT). We used a retrospective cohort of all COVID-19 cases between August 2020 and February 2022. Cases of Asian and other ethnicities were 2.6 times (adjusted relative risk (aRR) 2.58, 99 per cent confidence interval (95% CI) 2.18, 3.05) and 1.8 times (aRR 1.81, 95% CI 1.58, 2.06) more likely than Māori cases to generate a token during the Delta period, and this persisted during the Omicron period. Contact tracing organization also influenced location token generation with cases handled by National Case Investigation Service (NCIS) staff being 2.03 (95% CI 1.79, 2.30) times more likely to generate a token than cases managed by clinical staff at local Public Health Units (PHUs). Public uptake and participation in the location-based system independent of contact tracer uptake were estimated at 45%. The positive predictive value (PPV) of the QR code system was estimated to be close to nil for detecting close contacts but close to 100% for detecting casual contacts. Our paper shows that the QR-code-based function of the NZCTA likely made a negligible impact on the COVID-19 response in New Zealand (NZ) in relation to isolating potential close contacts of cases but likely was effective at identifying and notifying casual contacts.

Coreference resolution is the task of identifying and clustering mentions that refer to the same entity in a document. Based on state-of-the-art deep learning approaches, end-to-end coreference resolution considers all spans as candidate mentions and tackles mention detection and coreference resolution simultaneously. Recently, researchers have attempted to incorporate document-level context using higher-order inference (HOI) to improve end-to-end coreference resolution. However, HOI methods have been shown to have marginal or even negative impact on coreference resolution. In this paper, we reveal the reasons for the negative impact of HOI coreference resolution. Contextualized representations (e.g., those produced by BERT) for building span embeddings have been shown to be highly anisotropic. We show that HOI actually increases and thus worsens the anisotropy of span embeddings and makes it difficult to distinguish between related but distinct entities (e.g., pilots and flight attendants). Instead of using HOI, we propose two methods, Less-Anisotropic Internal Representations (LAIR) and Data Augmentation with Document Synthesis and Mention Swap (DSMS), to learn less-anisotropic span embeddings for coreference resolution. LAIR uses a linear aggregation of the first layer and the topmost layer of contextualized embeddings. DSMS generates more diversified examples of related but distinct entities by synthesizing documents and by mention swapping. Our experiments show that less-anisotropic span embeddings improve the performance significantly (+2.8 F1 gain on the OntoNotes benchmark) reaching new state-of-the-art performance on the GAP dataset.

Background: Nonprescription antibiotic use includes taking an antibiotic without medical guidance (eg, leftover antibiotics, antibiotics from friends or relatives, or antibiotics purchased without a prescription). Nonprescription use contributes to antimicrobial resistance, adverse drug reactions, interactions, and superinfections such as Clostridioides difficile colitis. Qualitative studies exploring perspectives regarding nonprescription use among Hispanic patients are lacking. We used the Kilbourne Framework for Advancing Health Disparities Research to identify factors influencing Hispanic patients’ nonprescription use and to organize our findings. Methods: Our study includes Hispanic primary-care clinic patients with different types of health coverage in the Houston metroplex who endorsed nonprescription use in a previous quantitative survey. Semistructured interviews explored the factors promoting nonprescription use in Hispanic adults. Interviews were conducted remotely, in English or Spanish, between May 2020 and October 2021. We used inductive coding and thematic analysis to identify the factors and motives for nonprescription use. Results: Of the 35 Hispanic participants surveyed, 69% were female and between the ages of 27 and 66. All participants had some form of healthcare coverage (eg, Medicare or private insurance, Medicaid, or the county financial assistance program). Participants reported obtaining antibiotics from their own leftover prescriptions and through trusted persons (eg, herbalists, pharmacists, friends/relatives, and others), buying them under the counter in US markets, and purchasing them without a prescription outside the United States. Thematic analysis revealed the factors contributing to nonprescription use (Fig. 1). Themes included beliefs that the ‘doctor visit was unnecessary,’ ‘limited direct access to healthcare’ in the United States (due to limited insurance coverage, high costs of the doctor’s visits and medications, and long clinic wait times), ‘more open indirect access to healthcare’ abroad and under the counter in the United States, and communication difficulties (eg, language barriers with clinicians, perceived staff rudeness, and gaps in health literacy). Figure 2 shows representative quotes across thematic domains. Participants expressed having confidence in medical recommendations from pharmacists and trusted community members in their social networks. Conclusions: Antibiotic stewardship interventions that include pharmacist-driven patient education regarding appropriate antibiotic use may decrease nonprescription antibiotic use in Hispanic communities. Additionally, improving access to care while addressing communication barriers and cultural competency in clinics may improve primary care delivery and reduce potentially unsafe antibiotic use.

Disclosure: None

While grain farming has seen a major shift toward organic production in recent years, the USA continues to lag behind with domestic demand continuing to outpace domestic supply, making the USA an all-around net importer. The Midwestern USA is poised to help remedy this imbalance; however, farmers continue to slowly transition to organic production systems. Existing literature has identified three prevalent narratives that farmers use to frame their organic transition: environmentalism, farm-family legacy and economic factors, in addition to a four and untested religiosity narrative. This study sought to better understand how these different narratives frame grain farmers’ thought processes for transitioning from conventional production systems to certified organic production systems. We co-created narratives around organic production with farmers, which resulted in four passages aligned with the literature: farm-family legacy, economic values, environmental values and Christianity and stewarding Eden. Then, we mailed a paper survey to conventional, in transition and certified organic Indiana grain farmers in order to test how these different narratives motivated organic production. We found that the most prevalent narrative around organic production is the farm-family legacy, which specifically resonated with midsize farmers. We also found that the religious stewardship narrative resonated with a substantial number of organic and mixed practice farmers, which is likely due to Amish farmers within the sample. These results shed light on the role that narratives and associated values play in organic practice use and can inform the organic efforts of agricultural professionals.

Since the discovery of Legionnaires’ disease (LD), limited progress has been made in understanding the epidemiology of sporadic cases of LD. Outbreaks have confirmed that air conditioning and potable water systems can be sources of community-acquired LD. However, studying the association between water quality and LD incidence has been challenging due to the heterogeneity of water systems across large geographic areas. Furthermore, although seasonal trends in incidence have been linked to increased rainfall and temperatures, the large geographic units have posed similar difficulties. To address this issue, a retrospective ecological study was conducted in Washington, DC, from 2001 to 2019. The study identified aseasonal pattern of LD incidence, with the majority of cases occurring between June and December, peaking in August, October, and November. Increased temperature was found to be associated with LD incidence. In surface water, higher concentrations of manganese, iron, and strontium were positively associated with LD, while aluminum and orthophosphate showed a negative association. Intreatment plant water, higher concentrations of total organic carbon, aluminum, barium, and chlorine were positively associated with LD, while strontium, zinc, and orthophosphate showed a negative association. The results for orthophosphates and turbidity were inconclusive, indicating the need for further research.

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.