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Sökning: WFRF:(Hieronymus J.)

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2.
  • Hieronymus, M., et al. (författare)
  • On the Application of Machine Learning Techniques to Regression Problems in Sea Level Studies
  • 2019
  • Ingår i: Journal of Atmospheric and Oceanic Technology. - : American Meteorological Society. - 0739-0572 .- 1520-0426. ; 36:9, s. 1889-1902
  • Tidskriftsartikel (refereegranskat)abstract
    • Long sea level records with high temporal resolution are of paramount importance for future coastal protection and adaptation plans. Here we discuss the application of machine learning techniques to some regression problems commonly encountered when analyzing such time series. The performance of artificial neural networks is compared with that of multiple linear regression models on sea level data from the Swedish coast. The neural networks are found to be superior when local sea level forcing is used together with remote sea level forcing and meteorological forcing, whereas the linear models and the neural networks show similar performance when local sea level forcing is excluded. The overall performance of the machine learning algorithms is good, often surpassing that of the much more computationally costly numerical ocean models used at our institute.
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3.
  • Blattner, Mirjam, et al. (författare)
  • SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
  • 2014
  • Ingår i: Neoplasia. - New York : Elsevier. - 1522-8002 .- 1476-5586. ; 16:1, s. 14-U34
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
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4.
  • de Rouw, Nikki, et al. (författare)
  • Rethinking the Application of Pemetrexed for Patients with Renal Impairment : A Pharmacokinetic Analysis
  • 2021
  • Ingår i: Clinical Pharmacokinetics. - : ADIS INT LTD. - 0312-5963 .- 1179-1926. ; 60:5, s. 649-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Pemetrexed is used for the treatment for non-small cell lung cancer and mesothelioma. Patients with renal impairment are withheld treatment with this drug as it is unknown what dose is well tolerated in this population. Objective The purpose of our study was to investigate the pharmacokinetics (PK) of pemetrexed in patients with renal impairment. Methods A population PK analysis of pemetrexed was performed using non-linear mixed-effects modelling with phase I data obtained from the manufacturer. Additionally, the impact of renal function on pemetrexed PK was assessed with a simulation study using the developed PK model and a previously developed PK model lacking the phase I data. Results The dataset included 548 paired observations of 47 patients, with a wide range of estimated glomerular filtration rates (eGFR; 14.4-145.6 mL/min). Pemetrexed PK were best described by a three-compartment model with eGFR (calculated using the Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] formula) as a linear covariate on renal pemetrexed clearance. Using the developed model, we found that renal clearance accounts for up to 84% (95% confidence interval 69-98%) of total pemetrexed clearance, whereas the manufacturer previously reported a 50% contribution of renal clearance. Conclusion Renal function is more important for the clearance of pemetrexed than previously thought and this should be taken into account in patients with renal impairment. Furthermore, a third compartment may contribute to prolonged exposure to pemetrexed during drug washout.
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5.
  • Walin, Gösta, 1938, et al. (författare)
  • Source-related variables for the description of the oceanic carbon system
  • 2014
  • Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 15:9, s. 3675-3687
  • Tidskriftsartikel (refereegranskat)abstract
    • The oceanic carbon system is commonly described in terms of the two state variables total carbon, DIC, and alkalinity, Alk. Here we suggest the use of alternative source adapted state variables, Acidic Carbon, AC and Basic Carbon, BC, defined by and related to (DIC, Alk) with a simple linear transformation. (AC, BC) can be interpreted as representing respectively the supply to the system of carbon dioxide and dissolved carbonate, keeping in mind that supply of hydrogen ions acts to transform from basic carbon to acidic carbon. Accordingly these variables tell us how much carbon dioxide or dissolved carbonate we actually have in the water, despite the fact that the major part of the carbon resides in bicarbonate ions. We claim that using these source-related variables as a compliment to the traditional variables, offers a number of advantages in the formulation of continuity equations, as well as in the interpretation of observations and modeling results. The traditional definition of alkalinity is related to a measuring procedure rather than to the supply of material to the system. Here we demonstrate that alkalinity, though defined in the traditional way, may be interpreted in terms of sources and sinks acting on the system. In the case of ocean water this amounts to twice the supply of dissolved carbonate minus the net supply of free hydrogen ions. We argue that this interpretation is a useful complement to the traditional definition. Every process that affects the state of the carbon system may be quantified in terms of supply of carbon dioxide, F-a, carbonate ions, F-b, or hydrogen ions, E.
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  • Bergbauer, S., et al. (författare)
  • Thermal stress evolution in cooling pluton environments of different geometries
  • 1998
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 25:5, s. 707-71-
  • Tidskriftsartikel (refereegranskat)abstract
    • Thermoelastic displacement potentials and fast Fourier transforms can be combined to rapidly calculate the thermal stresses in 2-D for plutons that cool by conduction. First, temperature distributions over time are computed by solving the diffusion equation. Thermal stresses are then obtained using thermoelastic stress potentials. This method can be applied to a broad range of pluton geometries and initial conditions, and requires far less computation time than finite difference or finite element analyses. Results of 2-D analyses show that pluton geometry strongly influences the thermal stresses that occur in a cooling pluton. Thermal stresses of several tens of MPa arise during cooling and are highest at the corners or where the intrusion is thin. The most tensile stress is greater inside a pluton than in the host rock. Moreover, the orientation of the most tensile stress in a cooling pluton generally changes over time. This could result in multiple fracture sets, which would significantly affect the mechanical and hydraulic behavior of a pluton.
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9.
  • Chen, Deliang, 1961, et al. (författare)
  • Summary of a workshop on extreme weather events in a warming world organized by the Royal Swedish Academy of Sciences
  • 2020
  • Ingår i: Tellus Series B-Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 72:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate change is not only about changes in means of climatic variables such as temperature, precipitation and wind, but also their extreme values which are of critical importance to human society and ecosystems. To inspire the Swedish climate research community and to promote assessments of international research on past and future changes in extreme weather events against the global climate change background, the Earth Science Class of the Royal Swedish Academy of Sciences organized a workshop entitled 'Extreme weather events in a warming world' in 2019. This article summarizes and synthesizes the key points from the presentations and discussions of the workshop on changes in floods, droughts, heat waves, as well as on tropical cyclones and extratropical storms. In addition to reviewing past achievements in these research fields and identifying research gaps with a focus on Sweden, future challenges and opportunities for the Swedish climate research community are highlighted.
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10.
  • Döscher, Ralf, et al. (författare)
  • The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6
  • 2022
  • Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 15:7, s. 2973-3020
  • Tidskriftsartikel (refereegranskat)abstract
    • The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.
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