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Sökning: WFRF:(Valkonen M)

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  • Bulten, W, et al. (författare)
  • Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge
  • 2022
  • Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:1, s. 154-
  • Tidskriftsartikel (refereegranskat)abstract
    • Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge—the largest histopathology competition to date, joined by 1,290 developers—to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840–0.884) and 0.868 (95% CI, 0.835–0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.
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  • Atilaw, Yoseph, et al. (författare)
  • Prenylated Flavonoids from the Roots of Tephrosia rhodesica
  • 2020
  • Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 83:8, s. 2390-2398
  • Tidskriftsartikel (refereegranskat)abstract
    • Five new compounds-rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)-along with 16 known secondary metabolites, were isolated from the CH2Cl2-CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2-5, 9, 15, and 21 showed activity (100% at 10 mu g and IC50 = 5-15 mu M) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
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  • Shkolnikov, Vladimir M., et al. (författare)
  • Increasing absolute mortality disparities by education in Finland, Norway and Sweden, 1971-2000
  • 2012
  • Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 66:4, s. 372-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objectives Studies on socioeconomic health disparities often suffer from a lack of uniform data and methodology. Using high quality, census-linked data and sensible inequality measures, this study documents the changes in absolute and relative mortality differences by education in Finland, Norway and Sweden over the period 1971 to 2000.Methods The age-standardised mortality rates and the population exposures for three educational categories were computed from detailed data provided by the national statistical offices. Mortality disparities by education were assessed using two range measures (rate differences and rate ratios), and two Gini-like measures (the average inter-group difference (AID) and the Gini coefficient (G)). The formulae for the decomposition of the change in the AID into (1) the contribution of change in population composition by education, and (2) the contribution of mortality change were introduced.Results Mortality decreases were often greater for high than for medium and low education. Both relative and absolute mortality disparities tend to increase over time. The magnitude and timing of the increases in absolute disparities vary by country. Both the rate differences and the AIDs have increased since the 1970s in Norway and Sweden, and since the 1980s in Finland. The contributions of the changes in population composition to the total AID increase were substantial in all countries, and for both sexes. The mortality contributions were substantial for males in Norway and Sweden.Conclusions The study reports increases in absolute mortality disparity, and its components. This trend needs to be further studied and addressed by policies.
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  • Suutari, T. J., et al. (författare)
  • IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in cow's milk allergic patients
  • 2006
  • Ingår i: J Investig Allergol Clin Immunol. - 1018-9068. ; 16:5, s. 296-302
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Allergic reactions to cow's milk are common in small children. One of the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg). Reindeer and bovine milk both contain related beta-Lg proteins, but the allergenicity of reindeer beta-Lg has not previously been studied. The purpose of this study was to analyze the immunological cross-reactivity of IgE antibodies from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS: Sera from 17 children and a serum pool of 4 patients with elevated cow's milk-specific IgE were investigated. Beta-Lg from bovine and reindeer milk was isolated in native form and an enzyme-linked immunosorbent inhibition assay was developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS: Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg varied among patients. In general, reindeer beta-Lg showed significantly lower inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta-Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests that it lacks important bovine epitopes and those that are recognized are only weakly bound.
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  • Pekkanen, Juha, et al. (författare)
  • Indoor bacteria and asthma in adults : a multicentre case-control study within ECRHS II
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation. A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays. 15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs, Clostridium cluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22-0.84) for the fourth versus first quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used. In this large international study, the level of Clostridium cluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies.
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  • Suutari, T.J., et al. (författare)
  • IgE cross reactivity between reindeer and bovine milk ?-lactoglobulins in cow's milk allergic patients
  • 2006
  • Ingår i: Journal of investigational allergology & clinical immunology. - 1018-9068 .- 1698-0808. ; 16:5, s. 296-302
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic reactions to cow's milk are common in small children. One of the main protein allergens found in cow's milk is ?-lactoglobulin (?-Lg). Reindeer and bovine milk both contain related ?-Lg proteins, but the allergenicity of reindeer ?-Lg has not previously been studied. The purpose of this study was to analyze the immunological cross-reactivity of IgE antibodies from children with cow's milk allergy to reindeer and bovine ?-Lg. Methods: Sera from 17 children and a serum pool of 4 patients with elevated cow's milk-specific IgE were investigated. ?-Lg from bovine and reindeer milk was isolated in native form and an enzyme-linked immunosorbent inhibition assay was developed. Bovine ?-Lg was used as a capturing antigen and the inhibiting effects of reindeer and bovine ?-Lg on the IgE binding were measured. Results: Cross-reactivity patterns of bovine milk ?-Lg specific IgE to reindeer ?-Lg varied among patients. In general, reindeer ?-Lg showed significantly lower inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine ?-Lg (mean 89%). In some patients, even high concentrations of reindeer ?-Lg only partly eliminated the IgE binding to bovine ?-Lg. Conclusions: The partial cross-reactivity of human anti-bovine IgE with reindeer ?-Lg suggests that it lacks important bovine epitopes and those that are recognized are only weakly bound. © 2006 Esmon Publicidad.
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  • Valkonen, J., et al. (författare)
  • Formal Verification of Safety I&C System Designs : Two Nuclear Power Plant Related Applications
  • 2008
  • Ingår i: Proceedings Man-Technology-Organisation Session, Enlarged Halden Programme Group Meeting. - Norway : Institt for energiteknikk.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Instrumentation and control (I&C) systems play a crucial role in the operation of nuclear power plants(NPP) and other safety critical processes. An important change is the replacement of the old analogue I&Csystems with new digitalised ones. The programmable digital logic controllers enable more complicatedcontrol tasks than the old analogue systems and thus the validation of the control logic designs against safetyrequirements has become more important. In order to diminish the subjective component of the evaluationthere is a need to develop new formal verification methods. A promising approach is a method called modelchecking, which enables the complete verification of requirements when a finite state machine model of thesystem is available. The use of model checking to verify two nuclear power plant related systems isdescribed: an arc protection system and a reactor emergency cooling system. For the verification, it was alsonecessary to model the operation environment of the device and the larger system it is part of. Theenvironment models could be kept relatively simple, but it is important that the essential behaviour of theenvironment is covered. The reactor emergency cooling system is in use in an operating nuclear power plantand the arc protection system model included a typical realistic operation environment. The results showedthat it was possible to reliably verify the presence of desired behaviour as well as the absence of anundesired behaviour of the system. The possibility for complete verification makes model checking differentfrom simulation-based testing where only a number of selected scenarios can be simulated and one can neverbe sure that all the possible behaviour is covered. The challenges for future research are to develop morededicated methods for the verification of safety critical automation and safety critical embedded software.
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  • Valkonen, J., et al. (författare)
  • Model-Based Analysis of an Arc Protection and an Emergency Cooling System
  • 2008
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Instrumentation and control (I&C) systems play a crucial role in the operation of nuclearpower plants and other safety critical processes. An important change that will be going on inthe near future is the replacement of the old analogue I&C systems by new digitalised ones.The programmable digital logic controllers enable more complicated control tasks than the oldanalogue systems and thus the verification of the control logic designs against safetyrequirements has become more important. In order to diminish the subjective component ofthe evaluation, there is a need to develop new formal verification methods.This report summarizes the work done in the MODSAFE 2007 project on two case studieswhere model checking techniques have been used to study an arc protection system and anemergency cooling system. Model checking tools offer typically a finite state machine basedmodelling language for modelling the system to be verified, a specification language(temporal logic) for expressing the properties to be verified and a set of analysis tools to checkthat the system satisfies the given properties. A state of the art open source model checkingsystem NuSMV was employed and using a reasonable effort it was possible to (i) model bothsystems on an adequate level, (ii) to formulate required safety properties in the specificationlanguage, and (iii) to perform a full verification of the properties using the NuSMV system.This indicates that current model checking techniques are applicable in the analysis of safetyI&C systems in NPPs.
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  • Yaouba, Souaibou, et al. (författare)
  • Crystal structures and cytotoxicity of ent-kaurane-type diterpenoids from two Aspilia species
  • 2018
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 23:12
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 by the authors. A phytochemical investigation of the roots of Aspilia pluriseta led to the isolation of ent-kaurane-type diterpenoids and additional phytochemicals (1–23). The structures of the isolated compounds were elucidated based on Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric analyses. The absolute configurations of seven of the ent-kaurane-type diterpenoids (3–6, 6b, 7 and 8) were determined by single crystal X-ray diffraction studies. Eleven of the compounds were also isolated from the roots and the aerial parts of Aspilia mossambicensis. The literature NMR assignments for compounds 1 and 5 were revised. In a cytotoxicity assay, 12α-methoxy-ent-kaur-9(11),16-dien-19-oic acid (1) (IC50 = 27.3 ± 1.9 µM) and 9β-hydroxy-15α-angeloyloxy-ent-kaur-16-en-19-oic acid (3) (IC50 = 24.7 ± 2.8 µM) were the most cytotoxic against the hepatocellular carcinoma (Hep-G2) cell line, while 15α-angeloyloxy-16β,17-epoxy-ent-kauran-19-oic acid (5) (IC50 = 30.7 ± 1.7 µM) was the most cytotoxic against adenocarcinomic human alveolar basal epithelial (A549) cells.
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