Age-Dependent Variations in Kawasaki Disease Incidence in Japan.

Importance: The etiology of Kawasaki disease (KD) remains elusive, with immunologic and epidemiologic data suggesting different triggers in individuals who are genetically susceptible. KD remains the most common cause of acquired heart disease in pediatric patients, and Japan is the country of highest incidence, with an increasing number of cases. Objective: To investigate whether an analysis of the epidemiologic KD record in Japan stratified by age and prefecture (subregion) may yield new clues regarding mechanisms of exposure to etiologic agents associated with KD. Design, Setting, and Participants: This cross-sectional study was conducted using a dataset of patients with KD with detailed information on location and age at onset created through nationwide surveys of hospitals caring for pediatric patients with KD throughout Japan. Pediatric patients hospitalized in Japan for KD from 1970 to 2020 were included. Data were analyzed from January 2022 to January 2024. Exposure: Pediatric patients with KD. Main Outcomes and Measures: The KD dataset was analyzed by patient age (infants [aged <6 months], toddlers [aged 6 to <24 months], children aged 2 years [aged 24 to <36 months], and children and adolescents aged 3 years or older [aged ≥36 months]), with investigations of seasonal cycles, interannual variations, and correlations across regions. Results: Among 422 528 pediatric patients (243 803 males [57.7%] and 178 732 females [42.3%]; median [IQR] age, 23.69 [11.96-42.65] months), infants, toddlers, and patients aged 3 years or older exhibited different rates of increase in KD incidence, seasonality, and degrees of coherence of seasonality across prefectures. Although the mean (SD) incidence of KD among infants remained relatively stable over the past 30 years compared with older patients (1.00 [0.07] in 1987-1992 to 2.05 [0.11] in 2011-2016), the mean (SD) incidence rate for children and adolescents aged 3 years or older increased 5.2-fold, from 1.00 (0.08) in 1987 to 1992 to 5.17 (0.46) in 2014 to 2019. Patients aged 3 years or older saw a reduction in mean (SD) incidence, from peaks of 5.71 (0.01) in October 2014 through June 2015 and July 2018 through March 2019 to 4.69 (0.11) in 2016 to 2017 (17.8% reduction) not seen in younger children. The seasonal cycle varied by age group; for example, mean (SD) incidence peaked in July and August (5.63 [0.07] cases/100 000 individuals) for infants and in December and January (4.67 [0.13] cases/100 000 individuals) for toddlers. Mean (SD) incidence changed dramatically for toddlers beginning in the early 2010s; for example, the normalized mean (SD) incidence among toddlers for October was 0.74 (0.03) in 1992 to 1995 and 1.10 (0.01) in 2016 to 2019. Across Japan, the seasonal cycle of KD incidence of older children and adolescents exhibited mean (SD) correlation coefficients between prefectures as high as 0.78 (0.14) for prefecture 14 among patients aged 3 years or older, while that of infants was much less (highest mean [SD] correlation coefficient, 0.43 [0.23]). Conclusions and Relevance: This study found distinct temporal signatures and changing spatial consistency of KD incidence across age groups, suggesting different age-related mechanisms of exposure. Some results suggested that social factors may modulate exposure to etiologic agents of KD; however, the increase in KD incidence in older children coupled with the correlation across prefectures of KD incidence suggest that the intensity of an environmental exposure that triggers KD in this age group may have increased over time.

Exposures and behavioural responses to wildfire smoke.

Pollution from wildfires constitutes a growing source of poor air quality globally. To protect health, governments largely rely on citizens to limit their own wildfire smoke exposures, but the effectiveness of this strategy is hard to observe. Using data from private pollution sensors, cell phones, social media posts and internet search activity, we find that during large wildfire smoke events, individuals in wealthy locations increasingly search for information about air quality and health protection, stay at home more and are unhappier. Residents of lower-income neighbourhoods exhibit similar patterns in searches for air quality information but not for health protection, spend less time at home and have more muted sentiment responses. During smoke events, indoor particulate matter (PM2.5) concentrations often remain 3-4× above health-based guidelines and vary by 20× between neighbouring households. Our results suggest that policy reliance on self-protection to mitigate smoke health risks will have modest and unequal benefits.

Globally ubiquitous negative effects of nitrogen dioxide on crop growth.

Nitrogen oxides (NOx) are among the most widely emitted pollutants in the world, yet their impacts on agriculture remain poorly known. NOx can directly damage crop cells and indirectly affect growth by promoting ozone (O3) and aerosol formation. We use satellite measures of both crop greenness and NOx during 2018-2020 to evaluate crop impacts for five major agricultural regions. We find consistent negative associations between NO2 and greenness across regions and seasons. These effects are strongest in conditions where O3 formation is NOx limited but remain significant even in locations where this pathway is muted, suggesting a role for direct NOx damage. Using simple counterfactuals and leveraging published relationships between greenness and growth, we estimate that reducing NOx levels to the current fifth percentile in each region would raise yields by ~25% for winter crops in China, ~15% for summer crops in China, and up to 10% in other regions.

Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States.

Importance: Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology. Objectives: To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD. Design, Setting, and Participants: This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]). Main Outcomes and Measures: For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence. Results: A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates. Conclusions and Relevance: In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Land-use emissions embodied in international trade.

International trade separates consumption of goods from related environmental impacts, including greenhouse gas emissions from agriculture and land-use change (together referred to as "land-use emissions"). Through use of new emissions estimates and a multiregional input-output model, we evaluated land-use emissions embodied in global trade from 2004 to 2017. Annually, 27% of land-use emissions and 22% of agricultural land are related to agricultural products ultimately consumed in a different region from where they were produced. Roughly three-quarters of embodied emissions are from land-use change, with the largest transfers from lower-income countries such as Brazil, Indonesia, and Argentina to more industrialized regions such as Europe, the United States, and China. Mitigation of global land-use emissions and sustainable development may thus depend on improving the transparency of supply chains.

Temporal clustering of Kawasaki disease cases around the world.

In a single-site study (San Diego, CA, USA), we previously showed that Kawasaki Disease (KD) cases cluster temporally in bursts of approximately 7 days. These clusters occurred more often than would be expected at random even after accounting for long-term trends and seasonality. This finding raised the question of whether other locations around the world experience similar temporal clusters of KD that might offer clues to disease etiology. Here we combine data from San Diego and nine additional sites around the world with hospitals that care for large numbers of KD patients, as well as two multi-hospital catchment regions. We found that across these sites, KD cases clustered at short time scales and there were anomalously long quiet periods with no cases. Both of these phenomena occurred more often than would be expected given local trends and seasonality. Additionally, we found unusually frequent temporal overlaps of KD clusters and quiet periods between pairs of sites. These findings suggest that regional and planetary range environmental influences create periods of higher or lower exposure to KD triggers that may offer clues to the etiology of KD.

Characterization of Groundwater Recharge and Flow in California's San Joaquin Valley From InSAR-Observed Surface Deformation.

Surface deformation in California's Central Valley (CV) has long been linked to changes in groundwater storage. Recent advances in remote sensing have enabled the mapping of CV deformation and associated changes in groundwater resources at increasingly higher spatiotemporal resolution. Here, we use interferometric synthetic aperture radar (InSAR) from the Sentinel-1 missions, augmented by continuous Global Positioning System (cGPS) positioning, to characterize the surface deformation of the San Joaquin Valley (SJV, southern two-thirds of the CV) for consecutive dry (2016) and wet (2017) water years. We separate trends and seasonal oscillations in deformation time series and interpret them in the context of surface and groundwater hydrology. We find that subsidence rates in 2016 (mean -42.0 mm/yr; peak -345 mm/yr) are twice that in 2017 (mean -20.4 mm/yr; peak -177 mm/yr), consistent with increased groundwater pumping in 2016 to offset the loss of surface-water deliveries. Locations of greatest subsidence migrated outwards from the valley axis in the wetter 2017 water year, possibly reflecting a surplus of surface-water supplies in the lowest portions of the SJV. Patterns in the amplitude of seasonal deformation and the timing of peak seasonal uplift reveal entry points and potential pathways for groundwater recharge into the SJV and subsequent groundwater flow within the aquifer. This study provides novel insight into the SJV aquifer system that can be used to constrain groundwater flow and subsidence models, which has relevance to groundwater management in the context of California's 2014 Sustainable Groundwater Management Act (SGMA).

Global and regional drivers of land-use emissions in 1961-2017.

Historically, human uses of land have transformed and fragmented ecosystems1,2, degraded biodiversity3,4, disrupted carbon and nitrogen cycles5,6 and added prodigious quantities of greenhouse gases (GHGs) to the atmosphere7,8. However, in contrast to fossil-fuel carbon dioxide (CO2) emissions, trends and drivers of GHG emissions from land management and land-use change (together referred to as 'land-use emissions') have not been as comprehensively and systematically assessed. Here we present country-, process-, GHG- and product-specific inventories of global land-use emissions from 1961 to 2017, we decompose key demographic, economic and technical drivers of emissions and we assess the uncertainties and the sensitivity of results to different accounting assumptions. Despite steady increases in population (+144 per cent) and agricultural production per capita (+58 per cent), as well as smaller increases in emissions per land area used (+8 per cent), decreases in land required per unit of agricultural production (-70 per cent) kept global annual land-use emissions relatively constant at about 11 gigatonnes CO2-equivalent until 2001. After 2001, driven by rising emissions per land area, emissions increased by 2.4 gigatonnes CO2-equivalent per decade to 14.6 gigatonnes CO2-equivalent in 2017 (about 25 per cent of total anthropogenic GHG emissions). Although emissions intensity decreased in all regions, large differences across regions persist over time. The three highest-emitting regions (Latin America, Southeast Asia and sub-Saharan Africa) dominate global emissions growth from 1961 to 2017, driven by rapid and extensive growth of agricultural production and related land-use change. In addition, disproportionate emissions are related to certain products: beef and a few other red meats supply only 1 per cent of calories worldwide, but account for 25 per cent of all land-use emissions. Even where land-use change emissions are negligible or negative, total per capita CO2-equivalent land-use emissions remain near 0.5 tonnes per capita, suggesting the current frontier of mitigation efforts. Our results are consistent with existing knowledge-for example, on the role of population and economic growth and dietary choice-but provide additional insight into regional and sectoral trends.

Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers.

OBJECTIVE: To test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters. STUDY DESIGN: We designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-year period (2002-2019) from a single clinical site and compared the cluster characteristics with those of 2 control groups of synthetic Kawasaki disease clusters. We defined a "true" Kawasaki disease cluster as at least 5 patients within a 7-day moving window. The observed and synthetic Kawasaki disease clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, rotated empirical orthogonal function analysis. RESULTS: In a univariate analysis, the median values for age, coronary artery z-score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true Kawasaki disease clusters exceeded the 95th percentile for the 2 synthetic clusters. REOF analyses revealed distinct patterns of demographic and clinical measures within clusters. CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensities of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of Kawasaki disease.

Author Correction: Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers.

Kawasaki Disease (KD) is the most common cause of pediatric acquired heart disease, but its etiology remains unknown. We examined 1164 cases of KD treated at a regional children's hospital in San Diego over a period of 15 years and uncovered novel structure to disease incidence. KD cases showed a well-defined seasonal variability, but also clustered temporally at much shorter time scales (days to weeks), and spatiotemporally on time scales of up to 10 days and spatial scales of 10-100 km. Temporal clusters of KD cases were associated with strongly significant regional-scale air temperature anomalies and consistent larger-scale atmospheric circulation patterns. Gene expression analysis further revealed a natural partitioning of KD patients into distinct groups based on their gene expression pattern, and that the different groups were associated with certain clinical characteristics that also exhibit temporal autocorrelation. Our data suggest that one or more environmental triggers exist, and that episodic exposures are modulated at least in part by regional weather conditions. We propose that characterization of the environmental factors that trigger KD in genetically susceptible children should focus on aerosols inhaled by patients who share common disease characteristics.

The case for distributed irrigation as a development priority in sub-Saharan Africa.

Distributed irrigation systems are those in which the water access (via pump or human power), distribution (via furrow, watering can, sprinkler, drip lines, etc.), and use all occur at or near the same location. Distributed systems are typically privately owned and managed by individuals or groups, in contrast to centralized irrigation systems, which tend to be publicly operated and involve large water extractions and distribution over significant distances for use by scores of farmers. Here we draw on a growing body of evidence on smallholder farmers, distributed irrigation systems, and land and water resource availability across sub-Saharan Africa (SSA) to show how investments in distributed smallholder irrigation technologies might be used to (i) use the water sources of SSA more productively, (ii) improve nutritional outcomes and rural development throughout SSA, and (iii) narrow the income disparities that permit widespread hunger to persist despite aggregate economic advancement.

Greenhouse gas mitigation by agricultural intensification.

As efforts to mitigate climate change increase, there is a need to identify cost-effective ways to avoid emissions of greenhouse gases (GHGs). Agriculture is rightly recognized as a source of considerable emissions, with concomitant opportunities for mitigation. Although future agricultural productivity is critical, as it will shape emissions from conversion of native landscapes to food and biofuel crops, investment in agricultural research is rarely mentioned as a mitigation strategy. Here we estimate the net effect on GHG emissions of historical agricultural intensification between 1961 and 2005. We find that while emissions from factors such as fertilizer production and application have increased, the net effect of higher yields has avoided emissions of up to 161 gigatons of carbon (GtC) (590 GtCO(2)e) since 1961. We estimate that each dollar invested in agricultural yields has resulted in 68 fewer kgC (249 kgCO(2)e) emissions relative to 1961 technology ($14.74/tC, or approximately $4/tCO(2)e), avoiding 3.6 GtC (13.1 GtCO(2)e) per year. Our analysis indicates that investment in yield improvements compares favorably with other commonly proposed mitigation strategies. Further yield improvements should therefore be prominent among efforts to reduce future GHG emissions.