Acetaminophen causes neurodevelopmental injury in susceptible babies and children: no valid rationale for controversy.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

A gap in nitrous oxide emission reporting complicates long-term climate mitigation.

Nitrous oxide (N2O) is an important greenhouse gas (GHG) that also contributes to depletion of ozone in the stratosphere. Agricultural soils account for about 60% of anthropogenic N2O emissions. Most national GHG reporting to the United Nations Framework Convention on Climate Change assumes nitrogen (N) additions drive emissions during the growing season, but soil freezing and thawing during spring is also an important driver in cold climates. We show that both atmospheric inversions and newly implemented bottom-up modeling approaches exhibit large N2O pulses in the northcentral region of the United States during early spring and this increases annual N2O emissions from croplands and grasslands reported in the national GHG inventory by 6 to 16%. Considering this, emission accounting in cold climate regions is very likely underestimated in most national reporting frameworks. Current commitments related to the Paris Agreement and COP26 emphasize reductions of carbon compounds. Assuming these targets are met, the importance of accurately accounting and mitigating N2O increases once CO2 and CH4 are phased out. Hence, the N2O emission underestimate introduces additional risks into meeting long-term climate goals.

Nitrification, denitrification, and competition for soil N: Evaluation of two Earth System Models against observations.

Earth System Models (ESMs) have implemented nitrogen (N) cycles to account for N limitation on terrestrial carbon uptake. However, representing inputs, losses, and recycling of N in ESMs is challenging. Here, we use global rates and ratios of key soil N fluxes, including nitrification, denitrification, mineralization, leaching, immobilization, and plant uptake (both NH4 + and NO3 - ), from the literature to evaluate the N cycles in the land model components of two ESMs. The two land models evaluated here, E3SM Land Model version 1 (ELMv1)-ECA and CLM5.0, originated from a common model but have diverged in their representation of plant-microbe competition for soil N. The models predict similar global rates of gross primary productivity (GPP) but have approximately two-fold to three-fold differences in their underlying global mineralization, immobilization, plant N uptake, nitrification, and denitrification fluxes. Both models dramatically underestimate the immobilization of NO3 - by soil bacteria compared with literature values and predict dominance of plant uptake by a single form of mineral nitrogen (NO3 - for ELM, with regional exceptions, and NH4 + for CLM5.0). CLM5.0 strongly underestimates the global ratio of gross nitrification:gross mineralization and both models are likely to substantially underestimate the ratio of nitrification:denitrification. Few experimental data exist to evaluate this last ratio, in part because nitrification and denitrification are quantified using different techniques and because denitrification fluxes are difficult to measure at all. More observational constraints on soil nitrogen fluxes such as nitrification and denitrification, as well as greater scrutiny of the functional impact of introducing separate NH4 + and NO3 - pools into ESMs, could help to improve confidence in present and future simulations of N limitation on the carbon cycle.

Nitrification and denitrification in the Community Land Model compared with observations at Hubbard Brook Forest.

Models of terrestrial system dynamics often include nitrogen (N) cycles to better represent N limitations on terrestrial carbon (C) uptake, but simulating the fate of N in ecosystems has proven challenging. Here, key soil N fluxes and flux ratios from the Community Land Model version 5.0 (CLM5.0) are compared with an extensive set of observations from the Hubbard Brook Forest Long-Term Ecological Research site in New Hampshire. Simulated fluxes include microbial immobilization and plant uptake, which compete with nitrification and denitrification, respectively, for available soil ammonium (NH4 + ) and nitrate (NO3 - ). In its default configuration, CLM5.0 predicts that both plant uptake and immobilization are strongly dominated by NH4 + over NO3 - , and that the model ratio of nitrification:denitrification is ~1:1. In contrast, Hubbard Brook observations suggest that NO3 - plays a more significant role in plant uptake and that nitrification could exceed denitrification by an order of magnitude. Modifications to the standard CLM5.0 at Hubbard Brook indicate that a simultaneous increase in the competitiveness of nitrifying microbes for NH4 + and reduction in the competitiveness of denitrifying bacteria for NO3 - are needed to bring soil N flux ratios into better agreement with observations. Such adjustments, combined with evaluation against observations, may help to improve confidence in present and future simulations of N limitation on the C cycle, although C fluxes, such as gross primary productivity and net primary productivity, are less sensitive to the model modifications than soil N fluxes.

Autism Tsunami: the Impact of Rising Prevalence on the Societal Cost of Autism in the United States.

The cost of ASD in the U.S. is estimated using a forecast model that for the first time accounts for the true historical increase in ASD. Model inputs include ASD prevalence, census population projections, six cost categories, ten age brackets, inflation projections, and three future prevalence scenarios. Future ASD costs increase dramatically: total base-case costs of $223 (175-271) billion/year are estimated in 2020; $589 billion/year in 2030, $1.36 trillion/year in 2040, and $5.54 (4.29-6.78) trillion/year by 2060, with substantial potential savings through ASD prevention. Rising prevalence, the shift from child to adult-dominated costs, the transfer of costs from parents onto government, and the soaring total costs raise pressing policy questions and demand an urgent focus on prevention strategies.

Century-long changes and drivers of soil nitrous oxide (N2 O) emissions across the contiguous United States.

The atmospheric concentration of nitrous oxide (N2 O) has increased by 23% since the pre-industrial era, which substantially destructed the stratospheric ozone layer and changed the global climate. However, it remains uncertain about the reasons behind the increase and the spatiotemporal patterns of soil N2 O emissions, a primary biogenic source. Here, we used an integrative land ecosystem model, Dynamic Land Ecosystem Model (DLEM), to quantify direct (i.e., emitted from local soil) and indirect (i.e., emissions related to local practices but occurring elsewhere) N2 O emissions in the contiguous United States during 1900-2019. Newly developed geospatial data of land-use history and crop-specific agricultural management practices were used to force DLEM at a spatial resolution of 5 arc-min by 5 arc-min. The model simulation indicates that the U.S. soil N2 O emissions totaled 0.97 ± 0.06 Tg N year-1 during the 2010s, with 94% and 6% from direct and indirect emissions, respectively. Hot spots of soil N2 O emission are found in the US Corn Belt and Rice Belt. We find a threefold increase in total soil N2 O emission in the United States since 1900, 74% of which is from agricultural soil emissions, increasing by 12 times from 0.04 Tg N year-1 in the 1900s to 0.51 Tg N year-1 in the 2010s. More than 90% of soil N2 O emission increase in agricultural soils is attributed to human land-use change and agricultural management practices, while increases in N deposition and climate warming are the dominant drivers for N2 O emission increase from natural soils. Across the cropped acres, corn production stands out with a large amount of fertilizer consumption and high-emission factors, responsible for nearly two-thirds of direct agricultural soil N2 O emission increase since 1900. Our study suggests a large N2 O mitigation potential in cropland and the importance of exploring crop-specific mitigation strategies and prioritizing management alternatives for targeted crop types.

California Autism Prevalence by County and Race/Ethnicity: Declining Trends Among Wealthy Whites.

County-level ASD prevalence was estimated using an age-resolved snapshot from the California Department of Developmental Services (DDS) for birth years 1993-2013. ASD prevalence increased among all children across birth years 1993-2000 but plateaued or declined thereafter among whites from wealthy counties. In contrast, ASD rates increased continuously across 1993-2013 among whites from lower income counties and Hispanics from all counties. Both white ASD prevalence and rate of change in prevalence were inversely correlated to county income from birth year 2000-2013 but not 1993-2000. These disparate trends within the dataset suggest that wealthy white parents, starting around 2000, may have begun opting out of DDS in favor of private care and/or making changes that effectively lowered their children's risk of ASD.

Race/Ethnicity-Resolved Time Trends in United States ASD Prevalence Estimates from IDEA and ADDM.

Race-specific time trends in Autism Spectrum Disorder prevalence are tracked among 3-5 year-olds and 8 year-olds identified by the U.S. Individuals with Disabilities Education Act (IDEA) and the Autism and Developmental Disabilities Monitoring (ADDM) Network, respectively. White ASD prevalence historically has been higher than other racial groups but plateaued for IDEA birth cohorts from ~ 2004 to 2007 before resuming its increase. Black and Hispanic IDEA prevalence increased continuously and caught up to whites by birth year ~ 2008 and ~ 2013, respectively, with black prevalence subsequently exceeding white prevalence in the majority of states. Plateaus in white prevalence occurred in some ADDM states for birth years 2002-2006, but IDEA trends suggest prevalence will increase across all racial groups in ADDM's birth year 2008 report.

California Autism Prevalence Trends from 1931 to 2014 and Comparison to National ASD Data from IDEA and ADDM.

Time trends in U.S. autism prevalence from three ongoing datasets [Individuals with Disabilities Education Act, Autism and Developmental Disabilities Monitoring Network, and California Department of Developmental Services (CDDS)] are calculated using two different methods: (1) constant-age tracking of 8 year-olds and (2) age-resolved snapshots. The data are consistent across methods in showing a strong upward trend over time. The prevalence of autism in the CDDS dataset, the longest of the three data records, increased from 0.001% in the cohort born in 1931 to 1.2% among 5 year-olds born in 2012. This increase began around ~ 1940 at a rate that has gradually accelerated over time, including notable change points around birth years 1980, 1990 and, most recently, 2007.

Diagnostic Substitution for Intellectual Disability: A Flawed Explanation for the Rise in Autism.

Time trends in autism spectrum disorder (ASD) and intellectual disability (ID) prevalence from the United States Individuals with Disabilities Education Act data were computed from 2000 to 2011 for each state and each age from 6 to 17. These trends did not support the hypothesis that diagnostic substitution for ID can explain the ASD rise over recent decades, although the hypothesis appeared more plausible when the data were aggregated across all states and ages. Nationwide ID prevalence declined steeply over the last two decades, but the decline was driven mainly by ~15 states accounting for only one-fourth of the U.S. school population. More commonly, including in the most populous states, ID prevalence stayed relatively constant while ASD prevalence rose sharply.

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism.

The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.

Effects of sea ice cover on satellite-detected primary production in the Arctic Ocean.

The influence of decreasing Arctic sea ice on net primary production (NPP) in the Arctic Ocean has been considered in multiple publications but is not well constrained owing to the potentially large errors in satellite algorithms. In particular, the Arctic Ocean is rich in coloured dissolved organic matter (CDOM) that interferes in the detection of chlorophyll a concentration of the standard algorithm, which is the primary input to NPP models. We used the quasi-analytic algorithm (Lee et al 2002 Appl. Opti. 41, 5755-5772. (doi:10.1364/AO.41.005755)) that separates absorption by phytoplankton from absorption by CDOM and detrital matter. We merged satellite data from multiple satellite sensors and created a 19 year time series (1997-2015) of NPP. During this period, both the estimated annual total and the summer monthly maximum pan-Arctic NPP increased by about 47%. Positive monthly anomalies in NPP are highly correlated with positive anomalies in open water area during the summer months. Following the earlier ice retreat, the start of the high-productivity season has become earlier, e.g. at a mean rate of -3.0 d yr-1 in the northern Barents Sea, and the length of the high-productivity period has increased from 15 days in 1998 to 62 days in 2015. While in some areas, the termination of the productive season has been extended, owing to delayed ice formation, the termination has also become earlier in other areas, likely owing to limited nutrients.

A model for the induction of autism in the ecosystem of the human body: the anatomy of a modern pandemic?

BACKGROUND: The field of autism research is currently divided based on a fundamental question regarding the nature of autism: Some are convinced that autism is a pandemic of modern culture, with environmental factors at the roots. Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood. OBJECTIVE: In this review, two lines of reasoning are examined which suggest that autism is indeed a pandemic of modern culture. First, given the widely appreciated derailment of immune function by modern culture, evidence that autism is strongly associated with aberrant immune function is examined. Second, evidence is reviewed indicating that autism is associated with 'triggers' that are, for the most part, a construct of modern culture. In light of this reasoning, current epidemiological evidence regarding the incidence of autism, including the role of changing awareness and diagnostic criteria, is examined. Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture. CONCLUSIONS: It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors.

BACKGROUND: The prevalence of diagnosed autism has increased rapidly over the last several decades among U.S. children. Environmental factors are thought to be driving this increase and a list of the top ten suspected environmental toxins was published recently. METHODS: Temporal trends in autism for birth years 1970-2005 were derived from a combination of data from the California Department of Developmental Services (CDDS) and the United States Individuals with Disabilities Education Act (IDEA). Temporal trends in suspected toxins were derived from data compiled during an extensive literature survey. Toxin and autism trends were compared by visual inspection and computed correlation coefficients. Using IDEA data, autism prevalence vs. birth year trends were calculated independently from snapshots of data from the most recent annual report, and by tracking prevalence at a constant age over many years of reports. The ratio of the snapshot:tracking trend slopes was used to estimate the "real" fraction of the increase in autism. RESULTS: The CDDS and IDEA data sets are qualitatively consistent in suggesting a strong increase in autism prevalence over recent decades. The quantitative comparison of IDEA snapshot and constant-age tracking trend slopes suggests that ~75-80% of the tracked increase in autism since 1988 is due to an actual increase in the disorder rather than to changing diagnostic criteria. Most of the suspected environmental toxins examined have flat or decreasing temporal trends that correlate poorly to the rise in autism. Some, including lead, organochlorine pesticides and vehicular emissions, have strongly decreasing trends. Among the suspected toxins surveyed, polybrominated diphenyl ethers, aluminum adjuvants, and the herbicide glyphosate have increasing trends that correlate positively to the rise in autism. CONCLUSIONS: Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s. In contrast, children's exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame. Environmental factors with increasing temporal trends can help suggest hypotheses for drivers of autism that merit further investigation.