Ichnology and paleoecology of the Jurassic Aztec Sandstone

In this study I describe and interpret tracks and trackways of the Jurassic Aztec Sandstone of southern Nevada and southern California. This study involved mapping of all known tracks and trackways, including foot length, stride length, and trackway width. Photogrammetric data, collected by Bureau of Land Management scientists, were utilized for several trackways in Red Rock Canyon National Conservation Area. More than three hundred tracks belonging to five ichnotaxa were documented within the Aztec Sandstone, including about 165 tridactylGrallator, 250 tetradactyl (four-toed)Brasilichniumtracks, and 7 arthropod trackways ofOctopodichnusandPaleohelcura. Four of the five ichnotaxa were not previously reported from the Aztec Sandstone. The trackway finds are similar to the most common tracks found in the correlative Navajo Sandstone, although the diversity of tracks is much higher in the Navajo. One type of track examined in this study has not been reported from the Navajo Sandstone. The higher diversity within the Navajo is almost certainly partly due to the much longer history of systematic investigation. All but one of the discovered tracksites in the Aztec were unknown prior to October 2011. Where possible, in the case of the Grallator trackways I calculated the speed of the trackmaker. Speeds range from 0.7 mph (0.35 m/sec) to 8.5 mph (3.8 m/sec). In one trackway, pauses in the animal\u27s steps are also recorded. Several of the tracksites contain multiple ichnotaxa on the same bedding plane, and sometimes trackways of different ichnotaxa overlap each other. From details such as these, some aspects of the paleoecology of the Aztec Sandstone can be inferred. The Grallator trackmakers were carnivorous theropod dinosaurs, which probably preyed on the herbivorous Brasilichnium trackmakers. The Brasilichnium trackmakers fed on unknown plants. Some tracksites reveal evidence that the trackmakers resided near or visited the same area repeatedly over an extended period of time, which implies the sustained availability of food

On the Nonexistence of Singular Equilibria in the Four-vortex Problem

In this paper we provide a partial answer to a question recently posed by Hassan Aref et. al. in their article Vortex Crystals, namely whether there are certain singular equilibria of point vortices. We prove that there are no such equilibria in the four-vortex case

QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract Long-term neurocognitive deficits in pediatric brain tumor survivors are challenging to both predict and treat. In a previous cohort analysis, we identified the genetic variant for ApoE4 reliably correlates with decreased neurocognitive function over time. Herein, we present case-control analyses comparing neurocognitive outcomes of ApoE4 carriers versus non-carriers in a group of pediatric brain tumor survivors. Utilizing an existing cohort of pediatric brain tumor patients from a diverse population, we isolated cases heterozygous for ApoE4 and matched these to controls carrying ApoE3. Priority was placed on matching cases and controls along variables previously identified to impact neurocognition – time from radiation and hydrocephalus or seizures at diagnosis. Student t-tests and lowess smoothing regression were used to compare outcomes in 6 neurocognitive domains over multiple time points. Twenty matched cases and controls were included in the analyses. At baseline, there were no statistically significant differences between cases and controls in any domain. Over time, ApoE3 controls performed statistically significantly higher across an increasing number of neurocognitive domains than ApoE4 carriers. Using smoothing regression, cases visibly performed worse over time as compared to controls and as seen by decreasing neurocognitive scores across all domains. ApoE4 carrier status strongly correlates with neurocognition function over time in pediatric brain tumor survivors. This effect appears across multiple domains and may show evidence of progressive deterioration with each year from treatment. Our results identify ApoE4 as a possible genetic predictor for neurocognitive outcomes in pediatric brain tumor survivors and support further investigation of this genetic variant

An Integrated Analysis of Clinical, Genomic, and Imaging Features Reveals Predictors of Neurocognitive Outcomes in a Longitudinal Cohort of Pediatric Cancer Survivors, Enriched with CNS Tumors (Rad ART Pro).

BackgroundNeurocognitive deficits in pediatric cancer survivors occur frequently; however, individual outcomes are unpredictable. We investigate clinical, genetic, and imaging predictors of neurocognition in pediatric cancer survivors, with a focus on survivors of central nervous system (CNS) tumors exposed to radiation.MethodsOne hundred eighteen patients with benign or malignant cancers (median diagnosis age: 7; 32% embryonal CNS tumors) were selected from an existing multi-institutional cohort (RadART Pro) if they had: 1) neurocognitive evaluation; 2) available DNA; 3) standard imaging. Utilizing RadART Pro, we collected clinical history, genomic sequencing, CNS imaging, and neurocognitive outcomes. We performed single nucleotide polymorphism (SNP) genotyping for candidate genes associated with neurocognition: COMT, BDNF, KIBRA, APOE, KLOTHO. Longitudinal neurocognitive testing were performed using validated computer-based CogState batteries. The imaging cohort was made of patients with available iron-sensitive (n = 28) and/or T2 FLAIR (n = 41) sequences. Cerebral microbleeds (CMB) were identified using a semi-automated algorithm. Volume of T2 FLAIR white matter lesions (WML) was measured using an automated method based on a convolutional neural network. Summary statistics were performed for patient characteristics, neurocognitive assessments, and imaging. Linear mixed effects and hierarchical models assessed patient characteristics and SNP relationship with neurocognition over time. Nested case-control analysis was performed to compare candidate gene carriers to non-carriers.ResultsCMB presence at baseline correlated with worse performance in 3 of 7 domains, including executive function. Higher baseline WML volumes correlated with worse performance in executive function and verbal learning. No candidate gene reliably predicted neurocognitive outcomes; however, APOE ϵ4 carriers trended toward worse neurocognitive function over time compared to other candidate genes and carried the highest odds of low neurocognitive performance across all domains (odds ratio 2.85, P=0.002). Hydrocephalus and seizures at diagnosis were the clinical characteristics most frequently associated with worse performance in neurocognitive domains (5 of 7 domains). Overall, executive function and verbal learning were the most frequently negatively impacted neurocognitive domains.ConclusionPresence of CMB, APOE ϵ4 carrier status, hydrocephalus, and seizures correlate with worse neurocognitive outcomes in pediatric cancer survivors, enriched with CNS tumors exposed to radiation. Ongoing research is underway to verify trends in larger cohorts

QOL-53. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract OBJECTIVE To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors. METHODS Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/. RESULTS APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p<0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p<5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing. CONCLUSION Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance

NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract OBJECTIVE To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors. METHODS Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/. RESULTS APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p< 0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p< 5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing. CONCLUSION Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance