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Sökning: WFRF:(Kovac A)

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1.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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  • Bousquet, J., et al. (författare)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Tidskriftsartikel (refereegranskat)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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  • Potapov, Anton M., et al. (författare)
  • Globally invariant metabolism but density-diversity mismatch in springtails
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.
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  • Potapov, Anton M., et al. (författare)
  • Global fine-resolution data on springtail abundance and community structure
  • 2024
  • Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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  • Abazajian, Kevork, et al. (författare)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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  • Cunningham, A. L., et al. (författare)
  • Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older
  • 2016
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 375:11, s. 1019-1032
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01(B) adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1: 1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.govnumbers, NCT01165177 and NCT01165229.)
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  • Kalokairinou, L, et al. (författare)
  • Legislation of direct-to-consumer genetic testing in Europe: : a fragmented regulatory landscape
  • 2018
  • Ingår i: Journal of Community Genetics. - : Springer Science and Business Media LLC. - 1868-310X .- 1868-6001. ; 9:2, s. 117-132
  • Forskningsöversikt (refereegranskat)abstract
    • Despite the increasing availability of direct-to-consumer (DTC) genetic testing, it is currently unclear how such services are regulated in Europe, due to the lack of EU or national legislation specifically addressing this issue. In this article, we provide an overview of laws that could potentially impact the regulation of DTC genetic testing in 26 European countries, namely Austria, Belgium, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, the Netherlands and the United Kingdom. Emphasis is placed on provisions relating to medical supervision, genetic counselling and informed consent. Our results indicate that currently there is a wide spectrum of laws regarding genetic testing in Europe. There are countries (e.g. France and Germany) which essentially ban DTC genetic testing, while in others (e.g. Luxembourg and Poland) DTC genetic testing may only be restricted by general laws, usually regarding health care services and patients’ rights.
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  • Heikinheimo, K, et al. (författare)
  • The Mutational Profile of Unicystic Ameloblastoma.
  • 2018
  • Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 98:1, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence ( P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis.
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11.
  • López-Fauqued, M., et al. (författare)
  • Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
  • 2019
  • Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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12.
  • Berisa, Aldin, et al. (författare)
  • Comparative Evaluation of Various Generations of Controller Area Network Based on Timing Analysis
  • 2023
  • Ingår i: IEEE Int. Conf. Emerging Technol. Factory Autom., ETFA. - : Institute of Electrical and Electronics Engineers Inc.. - 9798350339918
  • Konferensbidrag (refereegranskat)abstract
    • This paper performs a comparative evaluation of various generations of Controller Area Network (CAN), including the classical CAN, CAN Flexible Data-Rate (FD), and CAN Extra Long (XL). We utilize response-time analysis for the evaluation. In this regard, we identify that the state of the art lacks the response-time analysis for CAN XL. Hence, we discuss the worst-case transmission times calculations for CAN XL frames and incorporate them to the existing analysis for CAN to support response-time analysis of CAN XL frames. Using the extended analysis, we perform a comparative evaluation of the three generations of CAN by analyzing an automotive industrial use case. In crux, we show that using CAN FD is more advantageous than the classical CAN and CAN XL when using frames with payloads of up to 8 bytes, despite the fact that CAN XL supports higher bit rates. For frames with 12-64 bytes payloads, CAN FD performs better than CAN XL when running at the same bit rate, but CAN XL performs better when running at a higher bit rate. Additionally, we discovered that CAN XL performs better than the classical CAN and CAN FD when the frame payload is over 64 bytes, even if it runs at the same or higher bit rates than CAN FD.
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  • Kovac, E., et al. (författare)
  • Association of Baseline Prostate-Specific Antigen Level With Long-term Diagnosis of Clinically Significant Prostate Cancer Among Patients Aged 55 to 60 Years: A Secondary Analysis of a Cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
  • 2020
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: The use of prostate-specific antigen (PSA) screening for prostate cancer is controversial because of the risk of overdiagnosis and overtreatment of indolent cancers. Optimal screening strategies are highly sought. Objective: To estimate the long-term risk of any prostate cancer and clinically significant prostate cancer based on baseline PSA levels among men aged 55 to 60 years. Design, Setting, and Participants: This secondary analysis of a cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial uses actuarial analysis to analyze the association of baseline PSA levels with long-term risk of any prostate cancer and of clinically significant prostate cancer among men aged 55 to 60 years enrolled in the screening group of the trial between 1993 and 2001. Exposure: Single PSA measurement at study entry. Main Outcomes and Measures: Long-term risk of any prostate cancer and clinically significant prostate cancer diagnoses. Results: There were 10968 men aged 55 to 60 years (median [interquartile range] age, 57 [55-58] years) at study enrollment in the screening group of the PLCO Cancer Screening Trial who had long-term follow-up. Actuarial 13-year incidences of clinically significant prostate cancer diagnosis among participants with a baseline PSA of 0.49 ng/mL or less was 0.4% (95% CI, 0%-0.8%); 0.50-0.99 ng/mL, 1.5% (95% CI, 1.1%-1.9%); 1.00-1.99 ng/mL, 5.4% (95% CI, 4.4%-6.4%); 2.00-2.99 ng/mL, 10.6% (95% CI, 8.3%-12.9%); 3.00-3.99 ng/mL, 15.3% (95% CI, 11.4%-19.2%); and 4.00 ng/mL and greater, 29.5% (95% CI, 24.2%-34.8%) (all pairwise log-rank P≤.004). Only 15 prostate cancer-specific deaths occurred during 13 years of follow-up, and 9 (60.0%) were among men with a baseline PSA level of 2.00 ng/mL or higher. Conclusions and Relevance: In this secondary analysis of a cohort from the PLCO Cancer Screening Trial, baseline PSA levels among men aged 55 to 60 years were associated with long-term risk of clinically significant prostate cancer. These findings suggest that repeated screening can be less frequent among men aged 55 to 60 years with a low baseline PSA level (ie, <2.00 ng/mL) and possibly discontinued among those with baseline PSA levels of less than 1.00 ng/mL.
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  • Pruner, I, et al. (författare)
  • The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor
  • 2020
  • Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 66:2, s. 379-389
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C&gt;T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases.MethodsTo determine the frequency of the FII c.1824C&gt;T variant we have sequenced patients’ DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C&gt;T variant. Scanning electron microscopy was used to examine the structure of fibrin clots.ResultsFrequency of the FII c.1824C&gt;T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C&gt;T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis.ConclusionOur data indicate that FII c.1824C&gt;T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C&gt;T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
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