Climate change could negate U.S. forest ecosystem service benefits gained through reductions in nitrogen and sulfur deposition.

Climate change and atmospheric deposition of nitrogen (N) and sulfur (S) impact the health and productivity of forests. Here, we explored the potential impacts of these environmental stressors on ecosystem services provided by future forests in the contiguous U.S. We found that all stand-level services benefitted (+ 2.6 to 8.1%) from reductions in N+S deposition, largely attributable to positive responses to reduced S that offset the net negative effects of lower N levels. Sawtimber responded positively (+ 0.5 to 0.6%) to some climate change, but negatively (- 2.4 to - 3.8%) to the most extreme scenarios. Aboveground carbon (C) sequestration and forest diversity were negatively impacted by all modelled changes in climate. Notably, the most extreme climate scenario eliminated gains in all three services achieved through reduced deposition. As individual tree species responded differently to climate change and atmospheric deposition, associated services unique to each species increased or decreased under future scenarios. Our results suggest that climate change should be considered when evaluating the benefits of N and S air pollution policies on the services provided by U.S. forests.

Future climate change effects on US forest composition may offset benefits of reduced atmospheric deposition of N and S.

Climate change and atmospheric deposition of nitrogen (N) and sulfur (S) are important drivers of forest demography. Here we apply previously derived growth and survival responses for 94 tree species, representing >90% of the contiguous US forest basal area, to project how changes in mean annual temperature, precipitation, and N and S deposition from 20 different future scenarios may affect forest composition to 2100. We find that under the low climate change scenario (RCP 4.5), reductions in aboveground tree biomass from higher temperatures are roughly offset by increases in aboveground tree biomass from reductions in N and S deposition. However, under the higher climate change scenario (RCP 8.5) the decreases from climate change overwhelm increases from reductions in N and S deposition. These broad trends underlie wide variation among species. We found averaged across temperature scenarios the relative abundance of 60 species were projected to decrease more than 5% and 20 species were projected to increase more than 5%; and reductions of N and S deposition led to a decrease for 13 species and an increase for 40 species. This suggests large shifts in the composition of US forests in the future. Negative climate effects were mostly from elevated temperature and were not offset by scenarios with wetter conditions. We found that by 2100 an estimated 1 billion trees under the RCP 4.5 scenario and 20 billion trees under the RCP 8.5 scenario may be pushed outside the temperature record upon which these relationships were derived. These results may not fully capture future changes in forest composition as several other factors were not included. Overall efforts to reduce atmospheric deposition of N and S will likely be insufficient to overcome climate change impacts on forest demography across much of the United States unless we adhere to the low climate change scenario.

Above-ground tree carbon storage in response to nitrogen deposition in the U.S. is heterogeneous and may have weakened.

Changes in nitrogen (N) availability affect the ability for forest ecosystems to store carbon (C). Here we extend an analysis of the growth and survival of 94 tree species and 1.2 million trees, to estimate the incremental effects of N deposition on changes in aboveground C (dC/dN) across the contiguous U.S. (CONUS). We find that although the average effect of N deposition on aboveground C is positive for the CONUS (dC/dN=+9 kg C per kg N), there is wide variation among species and regions. Furthermore, in the Northeastern U.S. where we may compare responses from 2000-2016 with those from the 1980s-90s, we find the recent estimate of dC/dN is weaker than from the 1980s-90s due to species-level changes in responses to N deposition. This suggests that the U.S. forest C-sink varies widely across forests and may be weakening overall, possibly necessitating more aggressive climate policies than originally thought.

Empirical nitrogen and sulfur critical loads of U.S. tree species and their uncertainties with machine learning.

Critical loads (CLs) of atmospheric deposition for nitrogen (N) and sulfur (S) are used to support decision making related to air regulation and land management. Frequently, CLs are calculated using empirical methods, and the certainty of the results depends on accurate representation of underlying ecological processes. Machine learning (ML) models perform well in empirical modeling of processes with non-linear characteristics and significant variable interactions. We used bootstrap ensemble ML methods to develop CL estimates and assess uncertainties of CLs for the growth and survival of 108 tree species in the conterminous United States. We trained ML models to predict tree growth and survival and characterize the relationship between deposition and tree species response. Using four statistical methods, we quantified the uncertainty of CLs in 95 % confidence intervals (CI). At the lower bound of the CL uncertainty estimate, 80 % or more of tree species have been impacted by nitrogen deposition exceeding a CL for tree survival over >50 % of the species range, while at the upper bound the percentage is much lower (<20 % of tree species impacted across >60 % of the species range). Our analysis shows that bootstrap ensemble ML can be effectively used to quantify critical loads and their uncertainties. The range of the uncertainty we calculated is sufficiently large to warrant consideration in management and regulatory decision making with respect to atmospheric deposition.

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.

Correlation between FDG-PET uptake and survival in patients with primary brain tumors.

This study evaluates F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) semi-quantitative analysis as biomarker of tumor aggressiveness and predictor of survival in patients with primary brain tumors. Semi-quantitative analyses (SUVmax, SUVmean) were derived from FDG PET images in 78 patients with suspected recurrence of primary brain tumors based on MRI. SUVmax and the ratio of lesion SUVmax to the SUVmean of contralateral white matter (SUVmax/WM) were measured. A one-way Analysis of Variance (ANOVA), Kaplan-Meier analyses and the log rank test for evaluating statistical significance were utilized. There was statistical significance for time between FDG-PET and patient death. There was a significant difference with respect to FDG-PET time to death between patients with glioblastoma and patients with anaplastic oligodendroglioma, oligodendroglioma, and other histological subtypes. There is significant correlation with SUVmax/WM and patient survival following FDG-PET when a cut-point ratio of 1.90 is used. A 1.90 cut-point ratio of SUVmax/WM was associated with a difference in survival. GBM was associated with a significant difference in terms of reduced survival following FDG PET compared to most other histological sub-types. These results may inform current treatment and counseling strategies for patients with primary brain tumors.

Reliability of Quantitative 18F-FDG PET/CT Imaging Biomarkers for Classifying Early Response to Chemoradiotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE OF THE REPORT: We evaluated the reliability of 18F-FDG PET imaging biomarkers to classify early response status across observers, scanners, and reconstruction algorithms in support of biologically adaptive radiation therapy for locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Thirty-one patients with unresectable locally advanced non-small cell lung cancer were prospectively enrolled on a phase 2 trial (NCT02773238) and underwent 18F-FDG PET on GE Discovery STE (DSTE) or GE Discovery MI (DMI) PET/CT systems at baseline and during the third week external beam radiation therapy regimens. All PET scans were reconstructed using OSEM; GE-DMI scans were also reconstructed with BSREM-TOF (block sequential regularized expectation maximization reconstruction algorithm incorporating time of flight). Primary tumors were contoured by 3 observers using semiautomatic gradient-based segmentation. SUVmax, SUVmean, SUVpeak, MTV (metabolic tumor volume), and total lesion glycolysis were correlated with midtherapy multidisciplinary clinical response assessment. Dice similarity of contours and response classification areas under the curve were evaluated across observers, scanners, and reconstruction algorithms. LASSO logistic regression models were trained on DSTE PET patient data and independently tested on DMI PET patient data. RESULTS: Interobserver variability of PET contours was low for both OSEM and BSREM-TOF reconstructions; intraobserver variability between reconstructions was slightly higher. ΔSUVpeak was the most robust response predictor across observers and image reconstructions. LASSO models consistently selected ΔSUVpeak and ΔMTV as response predictors. Response classification models achieved high cross-validated performance on the DSTE cohort and more variable testing performance on the DMI cohort. CONCLUSIONS: The variability FDG PET lesion contours and imaging biomarkers was relatively low across observers, scanners, and reconstructions. Objective midtreatment PET response assessment may lead to improved precision of biologically adaptive radiation therapy.

The contribution of wildland fire emissions to deposition in the U S: implications for tree growth and survival in the Northwest.

Ecosystems require access to key nutrients like nitrogen (N) and sulfur (S) to sustain growth and healthy function. However, excessive deposition can also damage ecosystems through nutrient imbalances, leading to changes in productivity and shifts in ecosystem structure. While wildland fires are a known source of atmospheric N and S, little has been done to examine the implications of wildland fire deposition for vulnerable ecosystems. We combine wildland fire emission estimates, atmospheric chemistry modeling, and forest inventory data to (a) quantify the contribution of wildland fire emissions to N and S deposition across the U S, and (b) assess the subsequent impacts on tree growth and survival rates in areas where impacts are likely meaningful based on the relative contribution of fire to total deposition. We estimate that wildland fires contributed 0.2 kg N ha-1 yr-1 and 0.04 kg S ha-1 yr-1 on average across the U S during 2008-2012, with maxima up to 1.4 kg N ha-1 yr-1 and 0.6 kg S ha-1 yr-1 in the Northwest representing over ~30% of total deposition in some areas. Based on these fluxes, exceedances of S critical loads as a result of wildland fires are minimal, but exceedances for N may affect the survival and growth rates of 16 tree species across 4.2 million hectares, with the most concentrated impacts occurring in Oregon, northern California, and Idaho. Understanding the broader environmental impacts of wildland fires in the U S will inform future decision making related to both fire management and ecosystem services conservation.

Spiralian Genomes Reveal Gene Family Expansions Associated with Adaptation to Freshwater.

The colonization of freshwater habitats by marine-adapted organisms represents a major transition that has only occurred a few times in the evolution of animals. Only around half of the extant animal phyla have representatives in both marine and freshwater environments and even within those phyla some major clades are restricted to marine environments. Moving from marine to freshwater environments can create severe osmotic and ionic stresses and the mechanisms that animals have used to adapt to those stresses are still not well understood. In this study, we downloaded amino acid sequence data from 11 spiralian animal genomes (four freshwater taxa representing four different phyla as well as 7 marine taxa) and identified a number of gene family expansions that have occurred exclusively in the freshwater lineages. Further investigation of these gene families and the timing and nature of their expansions will illuminate one of the major evolutionary transitions in the history of life on Earth.

Nitrogen deposition and climate change effects on tree species composition and ecosystem services for a forest cohort.

The composition of forests in the northeastern United States and the ecosystem services they provide to future generations will depend on several factors. In this paper, we isolate the effects of two environmental drivers, nitrogen (N) deposition and climate (temperature and precipitation) change, through an analysis of a single cohort of 24 dominant tree species. We assembled a tree database using data from U.S. Forest Service Forest Inventory and Analysis monitoring plots. Applying observed species-specific growth and survival responses, we simulated how forest stands in a 19-state study area would change from 2005 to 2100 under 12 different future N deposition-climate scenarios. We then estimated implications for three selected forest ecosystem services: merchantable timber, aboveground carbon sequestration, and tree diversity. Total tree biomass (for 24 species combined) was positively associated with both increased N deposition and temperatures; however, due to differences in the direction and magnitude of species-specific responses, forest composition varied across scenarios. For example, red maple (Acer rubrum) trees gained biomass under scenarios with more N deposition and more climate change, whereas biomass of yellow birch (Betula alleghaniensis) and red pine (Pinus resinosa) was negatively affected. Projections for ecosystem services also varied across scenarios. Carbon sequestration, which is positively associated with biomass accumulation, increased with N deposition and increasing climate change. Total timber values also increased with overall biomass; however, scenarios with increasing climate change tended to favor species with lower merchantable value, whereas more N deposition favored species with higher merchantable value. Tree species diversity was projected to decrease with greater changes in climate (warmer temperatures), especially in the northwestern, central, and southeastern portions of the study area. In contrast, the effects of N deposition on diversity varied greatly in magnitude and direction across the study area. This study highlights species-specific and regional effects of N deposition and climate change in northeastern U.S. forests, which can inform management decision for air quality and forests in the region, as well as climate policy. It also provides a foundation for future studies that may incorporate other important factors such as multiple cohorts, sulfur deposition, insects, and diseases.

Na+ /K+ -ATPase gene duplications in clitellate annelids are associated with freshwater colonization.

Major habitat transitions, such as those from marine to freshwater habitats or from aquatic to terrestrial habitats, have occurred infrequently in animal evolution and may represent a barrier to diversification. Identifying genomic events associated with these transitions can help us better understand mechanisms that allow animals to cross these barriers and diversify in new habitats. Study of the Capitella telata and Helobdella robusta genomes allows examination of one such habitat transition (marine to freshwater) in Annelida. Initial examination of these genomes indicated that the freshwater leech H. robusta contains many more copies (12) of the sodium-potassium pump alpha-subunit (Na+ /K+ -ATPase) gene than does the marine polychaete C. telata (2). The sodium-potassium pump plays a key role in maintenance of cellular ionic balance and osmoregulation, and Na+ /K+ -ATPase duplications may have helped annelids invade and diversify in freshwater habitats. To assess whether the timing of Na+ /K+ -ATPase duplications coincided with the marine-to-freshwater transition in Clitellata, we used transcriptomic data from 18 annelid taxa, along with the two genomes, to infer a species phylogeny and identified Na+ /K+ -ATPase gene transcripts in order to infer the timing of gene duplication events using tree-based methods. The inferred timing of Na+ /K+ -ATPase duplication events is consistent with the timing of the initial marine-to-freshwater transition early in the history of clitellate annelids, supporting the hypothesis that gene duplications may have played a role in the annelid diversification into freshwater habitats.

Correction: Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

[This corrects the article DOI: 10.1371/journal.pone.0205296.].

Long-term Changes in 18F-Flutemetamol Uptake in Nondemented Older Adults.

PURPOSE: Longitudinal studies into the variability of F-Flutemetamol uptake are lacking. METHODS/PATIENTS: Therefore, the current study examined change in F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. RESULTS: Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0.002). For the total sample, the average difference over this time period when using the composite SUVR was 6.8%. Similar results were seen in subsets of the total sample (MCI vs. cognitively intact, amyloid positive vs. negative). Finally, a Reliable Change Index that exceeded ±0.046 SUVR units would indicate a significant change of F-Flutemetamol. CONCLUSIONS: The current results extend the limited literature on longitudinal variability of F-Flutemetamol uptake across 3.6 years, which should give clinicians and researchers more confidence in the stability of this amyloid imaging agent in longer therapeutic and prevention trials in cognitive decline in MCI and Alzheimer disease.

Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

Atmospheric deposition of nitrogen (N) influences forest demographics and carbon (C) uptake through multiple mechanisms that vary among tree species. Prior studies have estimated the effects of atmospheric N deposition on temperate forests by leveraging forest inventory measurements across regional gradients in deposition. However, in the United States (U.S.), these previous studies were limited in the number of species and the spatial scale of analysis, and did not include sulfur (S) deposition as a potential covariate. Here, we present a comprehensive analysis of how tree growth and survival for 71 species vary with N and S deposition across the conterminous U.S. Our analysis of 1,423,455 trees from forest plots inventoried between 2000 and 2016 reveals that the growth and/or survival of the vast majority of species in the analysis (n = 66, or 93%) were significantly affected by atmospheric deposition. Species co-occurred across the conterminous U.S. that had decreasing and increasing relationships between growth (or survival) and N deposition, with just over half of species responding negatively in either growth or survival to increased N deposition somewhere in their range (42 out of 71). Averaged across species and conterminous U.S., however, we found that an increase in deposition above current rates of N deposition would coincide with a small net increase in tree growth (1.7% per Δ kg N ha-1 yr-1), and a small net decrease in tree survival (-0.22% per Δ kg N ha-1 yr-1), with substantial regional and among-species variation. Adding S as a predictor improved the overall model performance for 70% of the species in the analysis. Our findings have potential to help inform ecosystem management and air pollution policy across the conterminous U.S., and suggest that N and S deposition have likely altered forest demographics in the U.S.

Lipopolysaccharide endotoxemia induces amyloid-ß and p-tau formation in the rat brain.

Amyloid beta (Aß) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aß may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aß production are associated with Aß plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1ß, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aß and p-tau were compared and Aß plaques were quantified and characterized. Brain uptake of [18F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated rats relative to controls. LPS resulted in increased soluble Aß and in p-tau levels in whole brain. Progressive increases in morphologically-diffuse Aß plaques occurred throughout the interval of observation (to 7-9 days post LPS). LPS endotoxemia resulted in increased [18F]flutemetamol in the cortex and increased cortex: white matter ratios of activity. In conclusion, LPS endotoxemia causes neuroinflammation, increased soluble Aß and Aß diffuse plaques in the brain. Aß PET tracers may inform this neuropathology. Increased p-tau in the brain of LPS treated animals suggests that downstream consequences of Aß plaque formation may occur. Further mechanistic and neurocognitive studies to understand the causes and consequences of LPS-induced neuropathology are warranted.

Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic Resonance, and Positron Emission Tomography Imaging.

Gliomas are the most common type of primary, malignant brain tumor and significantly impact patients, who have a median survival of ~1 year depending on mutational background. Novel imaging modalities such as luciferase bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized tomography (micro-CT), and micro-positron emission tomography (micro-PET) have expanded the portfolio of tools available to study this disease. Hypoxia, a key oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by the concomitant use of noninvasive MRI and PET imaging. We present a protocol involving stereotactic injection of syngenic F98 luciferase-expressing glioma cells generated by our laboratory into Fischer 344 rat brains and imaging using luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F-fluorothymidine PET imaging are compared with quantified luciferase flux. These tools can potentially be used for assessing tumor growth characteristics, hypoxia, mutational effects, and treatment effects.

Phylogenomic analyses of Crassiclitellata support major Northern and Southern Hemisphere clades and a Pangaean origin for earthworms.

BACKGROUND: Earthworms (Crassiclitellata) are a diverse group of annelids of substantial ecological and economic importance. Earthworms are primarily terrestrial infaunal animals, and as such are probably rather poor natural dispersers. Therefore, the near global distribution of earthworms reflects an old and likely complex evolutionary history. Despite a long-standing interest in Crassiclitellata, relationships among and within major clades remain unresolved. METHODS: In this study, we evaluate crassiclitellate phylogenetic relationships using 38 new transcriptomes in combination with publicly available transcriptome data. Our data include representatives of nearly all extant earthworm families and a representative of Moniligastridae, another terrestrial annelid group thought to be closely related to Crassiclitellata. We use a series of differentially filtered data matrices and analyses to examine the effects of data partitioning, missing data, compositional and branch-length heterogeneity, and outgroup inclusion. RESULTS AND DISCUSSION: We recover a consistent, strongly supported ingroup topology irrespective of differences in methodology. The topology supports two major earthworm clades, each of which consists of a Northern Hemisphere subclade and a Southern Hemisphere subclade. Divergence time analysis results are concordant with the hypothesis that these north-south splits are the result of the breakup of the supercontinent Pangaea. CONCLUSIONS: These results support several recently proposed revisions to the classical understanding of earthworm phylogeny, reveal two major clades that seem to reflect Pangaean distributions, and raise new questions about earthworm evolutionary relationships.

Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults.

Little research exists examining the relationship between beta-amyloid neuritic plaque density via [18F]flutemetamol binding and cognition; consequently, the purpose of the current study was to compare cognitive performances among individuals having either increased amyloid deposition (Flute+) or minimal amyloid deposition (Flute-). Twenty-seven nondemented community-dwelling adults over the age of 65 underwent [18F]flutemetamol amyloid-positron emission tomography imaging, along with cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and select behavioral measures. Analysis of variance was used to identify the differences among the cognitive and behavioral measures between Flute+/Flute- groups. Flute+ participants performed significantly worse than Flute- participants on RBANS indexes of immediate memory, language, delayed memory, and total scale score, but no significant group differences in the endorsed level of depression or subjective report of cognitive difficulties were observed. Although these results are preliminary, [18F]flutemetamol accurately tracks cognition in a nondemented elderly sample, which may allow for better prediction of cognitive decline in late life.

A 2D threshold of the condylar-C1 interval to maximize identification of patients at high risk for atlantooccipital dislocation using computed tomography.

OBJECTIVE Measurement of the occipital condyle-C1 interval (CCI) is important in the evaluation of atlantooccipital dislocation (AOD) in pediatric trauma patients. The authors studied a large cohort of children with and without AOD to identify a 2D measurement threshold that maximizes the diagnostic yield of the CCI on cervical spine CT scans obtained in trauma patients. METHODS This retrospective, single-center study included all children who underwent CT of the cervical spine at Primary Children's Hospital from January 1, 2011, through December 31, 2014, for trauma evaluation. Bilateral CCI measurements in the coronal (3 measurements per side) and sagittal (4 measurements per side) planes were recorded. Using an iterative method, the authors determined optimal cutoffs for the maximal CCI in each plane in relation to AOD. The primary outcome was AOD requiring occipitocervical fusion. RESULTS A total of 597 pediatric patients underwent cervical spine CT for trauma evaluation: 578 patients without AOD and 19 patients with AOD requiring occipitocervical fusion. The authors found a statistically significant correlation between CCI and age (p < 0.001), with younger patients having higher CCIs. Using a 2D threshold requiring a sagittal CCI ≥ 2.5 mm and a coronal CCI ≥ 3.5 mm predicted AOD with a sensitivity of 95%, a specificity of 73%, positive predictive value of 10.3%, and negative predictive value of 99%. The accuracy of this 2D threshold was 84%. CONCLUSIONS In the present study population, age-dependent differences in the CCI were found on CT scans of the cervical spine in a large cohort of patients with and without AOD. A 2D CCI threshold as a screening method maximizes identification of patients at high risk for AOD while minimizing unnecessary imaging studies in children being evaluated for trauma.