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Sökning: WFRF:(Georgiadis P)

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  • Chatziioannou, Aristotelis, et al. (författare)
  • Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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  • Chockalingam, P. S., et al. (författare)
  • Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor
  • 2011
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 315-323
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate aggrecanase activity after traumatic knee injury in a rat model by measuring the level of aggrecanase-generated Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments in synovial fluid, and compare with ARG-aggrecan release into joint fluid following human knee injury. To evaluate the effect of small molecule inhibitors on induced aggrecanase activity in the rat model. Method: An enzyme-linked immunosorbent assay (ELISA) was developed to measure ARG-aggrecan levels in animal and human joint fluids. A rat model of meniscal tear (MT)-induced joint instability was used to assess ARG-aggrecan release into joint fluid and the effects of aggrecanase inhibition. Synovial fluids were also obtained from patients with acute joint injury or osteoarthritis and assayed for ARG-aggrecan. Results: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG-aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG-aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. Conclusions: Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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  • Georgiadis, N. J., et al. (författare)
  • Large-Eddy Simulation: Current Capabilities, Recommended Practices, and Future Research
  • 2010
  • Ingår i: AIAA Journal. - 1533-385X .- 0001-1452. ; 48:8, s. 1772-1784
  • Tidskriftsartikel (refereegranskat)abstract
    • Usage of large-eddy simulation (LES) methods for calculation of turbulent flows has increased substantially in recent years. This paper attempts to 1) provide an assessment of the current capabilities of LES, 2) outline some recommended practices for using LES, and 3) identify future research needs. The assessment considers flow problems for which LES can be successfully applied today and flow problems for which LES still has limitations. The availability of LES and hybrid Reynolds-averaged Navier-Stokes (RANS)/LES in general-purpose codes is discussed. Several important issues for which the LES community has not yet reached a consensus are discussed. These include grid sensitivity studies, application of unstructured grid methods, upwind-biased solvers, and turbulence (subgrid) modeling including continuous hybrid RANS/LES approaches. A section on recommended practices and key considerations tries to provide guidance on some of the important items that need to be addressed in using LES. The paper concludes with a discussion of future research directions, with a focus on work needed to advance the capabilities and reliability of LES for analysis of turbulent flows.
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  • Georgiadis, S, et al. (författare)
  • CAN SINGLE IMPUTATION TECHNIQUES FOR BASDAI COMPONENTS RELIABLY CALCULATE THE COMPOSITE SCORE IN AXIAL SPONDYLOARTHRITIS PATIENTS?
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 212-213
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In axial spondyloarthritis (axSpA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a key patient-reported outcome. However, one or more of its components may be missing when recorded in clinical practice.ObjectivesTo determine whether an individual patient’s BASDAI at a given timepoint can be reliably calculated with different single imputation techniques and to explore the impact of the number of missing components and/or differences between missingness of individual components.MethodsReal-life data from axSpA patients receiving tumour necrosis factor inhibitors (TNFi) from 13 countries in the European Spondyloarthritis (EuroSpA) Research Collaboration Network were utilized [1]. We studied missingness in BASDAI components based on simulations in a complete dataset, where we applied and expanded the approach of Ramiro et al. [2]. After introducing one or more missing components completely at random, BASDAI was calculated from the available components and with three different single imputation techniques: possible middle value (i.e. 50) of the component and mean and median of the available components. Differences between the observed (original) and calculated scores were assessed and correct classification of patients as having BASDAI<40 mm was additionally evaluated. For the setting with one missing component, differences arising between missing one of components 1-4 versus 5-6 were explored. Finally, the performance of imputations in relation to the values of the original score was investigated.ResultsA total of 19,894 axSpA patients with at least one complete BASDAI registration at any timepoint were included. 59,126 complete BASDAI registrations were utilized for the analyses with a mean BASDAI of 38.5 (standard deviation 25.9). Calculating BASDAI from the available components and imputing with mean or median showed similar levels of agreement (Table 1). When allowing one missing component, >90% had a difference of ≤6.9 mm between the original and calculated scores and >95% were correctly classified as BASDAI<40 (Table 1). However, separate analyses of components 1-4 and 5-6 as a function of the BASDAI score suggested that imputing any one of the first four BASDAI components resulted in a level of agreement <90% for specific BASDAI values while imputing one of the stiffness components 5-6 always reached a level of agreement >90% (Figure 1, upper panels). As expected, it was observed that regardless of the BASDAI component set to missing and the imputation technique used, correct classification of patients as BASDAI<40 was less than 95% for values around the cutoff (Figure 1, lower panels).Table 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAI<40 mmLevel of agreement with Dif≤6.9 mm* (%)Correct classification for BASDAI<40 mm** (%)1 missing componentAvailable93.996.9Value 5073.996.3Mean94.296.8Median93.196.82 missing componentsAvailable83.794.8Value 5040.792.8Mean83.594.8Median82.894.73 missing componentsAvailable71.992.6Value 5028.187.3Mean72.292.6Median69.792.2* The levels of agreement with a difference (Dif) of ≤6.9 mm between the original and calculated scores were based on the half of the smallest detectable change. Agreement of >90% was considered as acceptable. ** Correct classification of >95% was considered as acceptable.Figure 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAI<40 mm as a function of the original scoreConclusionBASDAI calculation with available components gave similar results to single imputation of missing components with mean or median. Only when missing one of BASDAI components 5 or 6, single imputation techniques can reliably calculate individual BASDAI scores. However, missing any single component value results in misclassification of patients with original BASDAI scores close to 40.References[1]Ørnbjerg et al. (2019). Ann Rheum Dis, 78(11), 1536-1544.[2]Ramiro et al. (2014). Rheumatology, 53(2), 374-376.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsStylianos Georgiadis Grant/research support from: Novartis, Myriam Riek Grant/research support from: Novartis, Christos Polysopoulos Grant/research support from: Novartis, Almut Scherer Grant/research support from: Novartis, Daniela Di Giuseppe: None declared, Gareth T. Jones Speakers bureau: Janssen, Grant/research support from: AbbVie, Pfizer, UCB, Amgen, GSK, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Simon Horskjær Rasmussen Grant/research support from: Novartis, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Merih Birlik: None declared, Ayten Yazici Grant/research support from: Roche, Brigitte Michelsen Grant/research support from: Novartis, Eirik kristianslund: None declared, Adrian Ciurea Speakers bureau: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Ana Maria Rodrigues Speakers bureau: Abbvie, Amgen, Consultant of: Abbvie, Amgen, Grant/research support from: Novartis, Pfizer, Amgen, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, UCB, Viatris, Consultant of: Abbvie, Celgene, Pfizer, UCB, Viatris, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Corina Mogosan: None declared, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Björn Gudbjornsson Speakers bureau: Amgen, Novartis, Consultant of: Amgen, Novartis, Arni Jon Geirsson: None declared, Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Consultant of: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Grant/research support from: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Isabel Castrejon: None declared, Manuel Pombo-Suarez Consultant of: Abbvie, MSD, Roche, Bruno Frediani: None declared, Florenzo Iannone Speakers bureau: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis
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  • Ruesink, Gerben B., et al. (författare)
  • A psychophysical and neuroimaging analysis of genital hedonic sensation in men
  • 2022
  • Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Current understanding of human genital-brain interactions relates primarily to neuroendocrine and autonomic control, whereas interactions during sexual stimulation remain largely unexplored. Here we present a systematic approach towards identifying how the human brain encodes sensory genital information. Using a validated affective touch paradigm and functional magnetic resonance imaging, we found that hedonic responses to discriminatory versus affective tactile stimulation were distinctly different for both penile shaft and forearm. This suggests that, as with other body sites, genital skin contains small diameter mechanoreceptive nerve fibres that signal pleasant touch. In the brain, secondary somatosensory cortex (S2) distinguished between affective and discriminative touch for the penile shaft, but not for the forearm. Frenulum stimulation induced the greatest reports of subjective pleasure and led to the greatest deactivation of the default-mode network. This study represents a first pass at investigating, in humans, the relationship between innervation of genital surfaces, hedonic feelings, and brain mechanisms, in a systematic way.
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  • Susilo, Yusak O., et al. (författare)
  • Findings from measuring door-to-door travellers’ travel satisfaction with traditional and smartphone app survey methods in eight European cities
  • 2017
  • Ingår i: European Journal of Transport and Infrastructure Research. - : Editorial Board EJTIR. - 1567-7133 .- 1567-7141. ; 17:3, s. 384-410
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates how different travel satisfaction survey methods influence the reported level of door-to-door travel satisfaction among travellers. The travel satisfaction measurement survey tools tested consisted of two types of smartphone applications (a satellite navigation app and a game app), an on-line survey, a paper-based semi-structured questionnaire and a focus group. Each of the measurement tools comprised of a similar set of questions, but in different formats, aimed at exploring the pros and cons of each tool among different group of travellers. In total, 5,275 valid responses were collected during the survey period from eight European cities and five FIA (Federation Internationale de I’Automobile) national motorist networks. The analysis results, with ordered logit model of travellers’ reported overall satisfaction, showed that the travel satisfaction reported by different survey methods and different travel modes and user groups, correlated with distinct groups of key determinants. The relationship between and within these key determinants, however, was far from straight forward. Some were more complex than others. Some issues, such as parking availability and security, that are mostly discussed by policy makers and users may not be the ones that directly correlate with the users’ overall travel satisfactions. Consistent with previous studies, the travellers’ mood and previous experience influenced the reported overall journey satisfaction.
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