TopoRoot: a method for computing hierarchy and fine-grained traits of maize roots from 3D imaging.

BACKGROUND: 3D imaging, such as X-ray CT and MRI, has been widely deployed to study plant root structures. Many computational tools exist to extract coarse-grained features from 3D root images, such as total volume, root number and total root length. However, methods that can accurately and efficiently compute fine-grained root traits, such as root number and geometry at each hierarchy level, are still lacking. These traits would allow biologists to gain deeper insights into the root system architecture. RESULTS: We present TopoRoot, a high-throughput computational method that computes fine-grained architectural traits from 3D images of maize root crowns or root systems. These traits include the number, length, thickness, angle, tortuosity, and number of children for the roots at each level of the hierarchy. TopoRoot combines state-of-the-art algorithms in computer graphics, such as topological simplification and geometric skeletonization, with customized heuristics for robustly obtaining the branching structure and hierarchical information. TopoRoot is validated on both CT scans of excavated field-grown root crowns and simulated images of root systems, and in both cases, it was shown to improve the accuracy of traits over existing methods. TopoRoot runs within a few minutes on a desktop workstation for images at the resolution range of 400^3, with minimal need for human intervention in the form of setting three intensity thresholds per image. CONCLUSIONS: TopoRoot improves the state-of-the-art methods in obtaining more accurate and comprehensive fine-grained traits of maize roots from 3D imaging. The automation and efficiency make TopoRoot suitable for batch processing on large numbers of root images. Our method is thus useful for phenomic studies aimed at finding the genetic basis behind root system architecture and the subsequent development of more productive crops.

Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model.

BACKGROUND: Medulloblastomas with chromothripsis developing in children with Li-Fraumeni Syndrome (germline TP53 mutations) are highly aggressive brain tumors with dismal prognosis. Conventional photon radiotherapy and DNA-damaging chemotherapy are not successful for these patients and raise the risk of secondary malignancies. We hypothesized that the pronounced homologous recombination deficiency in these tumors might offer vulnerabilities that can be therapeutically utilized in combination with high linear energy transfer carbon ion radiotherapy. METHODS: We tested high-precision particle therapy with carbon ions and protons as well as topotecan with or without PARP inhibitor in orthotopic primary and matched relapsed patient-derived xenograft models. Tumor and normal tissue underwent longitudinal morphological MRI, cellular (markers of neurogenesis and DNA damage-repair), and molecular characterization (whole-genome sequencing). RESULTS: In the primary medulloblastoma model, carbon ions led to complete response in 79% of animals irrespective of PARP inhibitor within a follow-up period of 300 days postirradiation, as detected by MRI and histology. No sign of neurologic symptoms, impairment of neurogenesis or in-field carcinogenesis was detected in repair-deficient host mice. PARP inhibitors further enhanced the effect of proton irradiation. In the postradiotherapy relapsed tumor model, median survival was significantly increased after carbon ions (96 days) versus control (43 days, P < .0001). No major change in the clonal composition was detected in the relapsed model. CONCLUSION: The high efficacy and favorable toxicity profile of carbon ions warrants further investigation in primary medulloblastomas with chromothripsis. Postradiotherapy relapsed medulloblastomas exhibit relative resistance compared to treatment-naïve tumors, calling for exploration of multimodal strategies.

Barcodes of Towers and a Streaming Algorithm for Persistent Homology.

A tower is a sequence of simplicial complexes connected by simplicial maps. We show how to compute a filtration, a sequence of nested simplicial complexes, with the same persistent barcode as the tower. Our approach is based on the coning strategy by Dey et al. (SoCG, 2014). We show that a variant of this approach yields a filtration that is asymptotically only marginally larger than the tower and can be efficiently computed by a streaming algorithm, both in theory and in practice. Furthermore, we show that our approach can be combined with a streaming algorithm to compute the barcode of the tower via matrix reduction. The space complexity of the algorithm does not depend on the length of the tower, but the maximal size of any subcomplex within the tower. Experimental evaluations show that our approach can efficiently handle towers with billions of complexes.

Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage*.

OBJECTIVES: Acute respiratory distress syndrome develops commonly in critically ill patients in response to an injurious stimulus. The prevalence and risk factors for development of acute respiratory distress syndrome after spontaneous intracerebral hemorrhage have not been reported. We sought to determine the prevalence of acute respiratory distress syndrome after intracerebral hemorrhage, characterize risk factors for its development, and assess its impact on patient outcomes. DESIGN: Retrospective cohort study at two academic centers. PATIENTS: We included consecutive patients presenting from June 1, 2000, to November 1, 2010, with intracerebral hemorrhage requiring mechanical ventilation. We excluded patients with age less than 18 years, intracerebral hemorrhage secondary to trauma, tumor, ischemic stroke, or structural lesion; if they required intubation only during surgery; if they were admitted for comfort measures; or for a history of immunodeficiency. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected both prospectively as part of an ongoing cohort study and by retrospective chart review. Of 1,665 patients identified by database query, 697 met inclusion criteria. The prevalence of acute respiratory distress syndrome was 27%. In unadjusted analysis, high tidal volume ventilation was associated with an increased risk of acute respiratory distress syndrome (hazard ratio, 1.79 [95% CI, 1.13-2.83]), as were male sex, RBC and plasma transfusion, higher fluid balance, obesity, hypoxemia, acidosis, tobacco use, emergent hematoma evacuation, and vasopressor dependence. In multivariable modeling, high tidal volume ventilation was the strongest risk factor for acute respiratory distress syndrome development (hazard ratio, 1.74 [95% CI, 1.08-2.81]) and for inhospital mortality (hazard ratio, 2.52 [95% CI, 1.46-4.34]). CONCLUSIONS: Development of acute respiratory distress syndrome is common after intubation for intracerebral hemorrhage. Modifiable risk factors, including high tidal volume ventilation, are associated with its development and in-patient mortality.