50 research outputs found
Labeling poststorm coastal imagery for machine learning: measurement of interrater agreement
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Goldstein, E. B., Buscombe, D., Lazarus, E. D., Mohanty, S. D., Rafique, S. N., Anarde, K. A., Ashton, A. D., Beuzen, T., Castagno, K. A., Cohn, N., Conlin, M. P., Ellenson, A., Gillen, M., Hovenga, P. A., Over, J.-S. R., Palermo, R., Ratliff, K. M., Reeves, I. R. B., Sanborn, L. H., Straub, J. A., Taylor, L. A., Wallace E. J., Warrick, J., Wernette, P., Williams, H. E. Labeling poststorm coastal imagery for machine learning: measurement of interrater agreement. Earth and Space Science, 8(9), (2021): e2021EA001896, https://doi.org/10.1029/2021EA001896.Classifying images using supervised machine learning (ML) relies on labeled training data—classes or text descriptions, for example, associated with each image. Data-driven models are only as good as the data used for training, and this points to the importance of high-quality labeled data for developing a ML model that has predictive skill. Labeling data is typically a time-consuming, manual process. Here, we investigate the process of labeling data, with a specific focus on coastal aerial imagery captured in the wake of hurricanes that affected the Atlantic and Gulf Coasts of the United States. The imagery data set is a rich observational record of storm impacts and coastal change, but the imagery requires labeling to render that information accessible. We created an online interface that served labelers a stream of images and a fixed set of questions. A total of 1,600 images were labeled by at least two or as many as seven coastal scientists. We used the resulting data set to investigate interrater agreement: the extent to which labelers labeled each image similarly. Interrater agreement scores, assessed with percent agreement and Krippendorff's alpha, are higher when the questions posed to labelers are relatively simple, when the labelers are provided with a user manual, and when images are smaller. Experiments in interrater agreement point toward the benefit of multiple labelers for understanding the uncertainty in labeling data for machine learning research.The authors gratefully acknowledge support from the U.S. Geological Survey (G20AC00403 to EBG and SDM), NSF (1953412 to EBG and SDM; 1939954 to EBG), Microsoft AI for Earth (to EBG and SDM), The Leverhulme Trust (RPG-2018-282 to EDL and EBG), and an Early Career Research Fellowship from the Gulf Research Program of the National Academies of Sciences, Engineering, and Medicine (to EBG). U.S. Geological Survey researchers (DB, J-SRO, JW, and PW) were supported by the U.S. Geological Survey Coastal and Marine Hazards and Resources Program as part of the response and recovery efforts under congressional appropriations through the Additional Supplemental Appropriations for Disaster Relief Act, 2019 (Public Law 116-20; 133 Stat. 871)
SMC complexes differentially compact mitotic chromosomes according to genomic context
Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes
The Sariçiçek Howardite Fall in Turkey: Source Crater of HED Meteorites on Vesta and İmpact Risk of Vestoids
The Sariçiçek howardite meteorite shower consisting of 343 documented stones
occurred on 2 September 2015 in Turkey and is the first documented howardite fall. Cosmogenic
isotopes show that Sariçiçek experienced a complex cosmic ray exposure history, exposed during
~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid
was launched by an impact 22 ± 2 Ma ago to Earth (as did one third of all HED meteorites). SIMS
dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages
for the basaltic magma clasts. The apatite U-Pb age of 4525 ± 17 Ma, K-Ar age of ~3.9 Ga, and
the U,Th-He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic
and impact-related resetting ages, respectively. Petrographic, geochemical and O-, Cr- and Tiisotopic
studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic
observations and analysis of organic material indicate a small portion of carbonaceous chondrite
material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on
soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 kms-1 from NW,
fragmentations at 37, 33, 31 and 27 km altitude, and provide a pre-atmospheric orbit that is the
first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data
indicate the similarity of Sariçiçek with the Vesta asteroid family (V-class) spectra, a group of
asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of
meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family
asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4
m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antonia
impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of
Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was
formed ~22 Ma ago
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers
The somatic genomic landscape of glioblastoma
We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer
The Somatic Genomic Landscape of Glioblastoma
We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Venous Sinus Stent Placement Reduces Dosage Requirements for Carbonic Anhydrase Inhibitors in Patients with Idiopathic Intracranial Hypertension
This study evaluates how the dosage (Acetazolamide and Topiramate) and need for medication changes pre and post venous sinus stent placement (VSS) for Idiopathic Intracranial Hypertension (IIH). This is a retrospective single center study. Adults diagnosed with IIH who failed optimized medical management treated with VSS were included. This study comprised 55 patients who underwent VSS for the diagnosis of IIH. The median preprocedural dosage of Acetazolamide and Topiramate was 1000.0 (500-4000) mg and 100.0 (0-200) mg among patients able to tolerate the medication. The median postprocedural dosage of Acetazolamide and Topiramate was 375 mg (0-4000) with a mean reduction of 52.9% (P=0.001) and 0.0 mg (0-200) with a mean reduction of 45.9% (P=0.005). Patients who underwent VSS on Acetazolamide and or Topiramate required a significantly reduced dosage post procedure which has the potential to reduce the morbidity secondary to medication side effects
Decompressive craniectomy for severe traumatic brain injury: clinical study, literature review and meta-analysis.
OBJECTIVE: To examine the clinical and neurological outcome of patients who sustained a severe non-penetrating traumatic brain injury (TBI) and underwent unilateral decompressive craniectomy (DC) for refractory intracranial hypertension.
DESIGN: Single center, retrospective, observational.
SETTING: Level I Trauma Center in Portland, Maine.
PATIENTS: 31 patients aged 16-72 of either sex who sustained a severe, non-penetrating TBI and underwent a unilateral DC for evacuation of parenchymal or extra-axial hematoma or for failure of medical therapy to control intracranial pressure (ICP).
INTERVENTIONS: Review of the electronic medical record of patients undergoing DC for severe TBI and assessment of extended Glasgow Outcome Score (e-GOS) at 6-months following DC.
MEASUREMENTS AND MAIN RESULTS: The mean age was 39.3y ± 14.5. The initial GCS was 5.8 ± 3.2, and the ISS was 29.7 ± 6.3. Twenty-two patients underwent DC within the first 24 h, two within the next 24 h and seven between the 3rd and 7th day post injury. The pre-DC ICP was 30.7 ± 10.3 and the ICP was 12.1 ± 6.2 post-DC. Cranioplasty was performed in all surviving patients 1-4 months post-DC. Of the 29 survivors following DC, the e-GOS was 8 in seven patients, and 7 in ten patients. The e-GOS was 5-6 in 6 others. Of the 6 survivors with poor outcomes (e-GOS = 2-4), five were the initial patients in the series.
CONCLUSIONS: In patients with intractable cerebral hypertension following TBI, unilateral DC in concert with practice guideline directed brain resuscitation is associated with good functional outcome and acceptable-mortality