| 1. |
- Abed Abud, A., et al.
(författare)
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Searching for solar KDAR with DUNE
- 2021
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2021:10, s. 065-065
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Andersen, T. C. B., et al.
(författare)
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The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell?specific adapter protein
- 2019
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 294:42, s. 15480-15494
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Tidskriftsartikel (refereegranskat)abstract
- T-cell activation requires stimulation of specific intracellular signaling pathways in which protein-tyrosine kinases, phosphatases, and adapter proteins interact to transmit signals from the T-cell receptor to the nucleus. Interactions of LCK proto-oncogene, SRC family tyrosine kinase (LCK), and the IL-2?inducible T cell kinase (ITK) with the T cell-specific adapter protein (TSAD) promotes LCK-mediated phosphorylation and thereby ITK activation. Both ITK and LCK interact with TSAD's proline-rich region (PRR) through their Src homology 3 (SH3) domains. Whereas LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3 domain. To begin to understand on a molecular level how the LCK SH3 and ITK SH3 domains interact with TSAD in human HEK293T cells, here we combined biochemical analyses with NMR spectroscopy. We found that the ITK and LCK SH3 domains potentially have adjacent and overlapping binding sites within the TSAD PRR amino acids (aa) 239?274. Pulldown experiments and NMR spectroscopy revealed that both domains may bind to TSAD aa 239?256 and aa 257?274. Co-immunoprecipitation experiments further revealed that both domains may also bind simultaneously to TSAD aa 242?268. Accordingly, NMR spectroscopy indicated that the SH3 domains may compete for these two adjacent binding sites. We propose that once the associations of ITK and LCK with TSAD promote the ITK and LCK interaction, the interactions among TSAD, ITK, and LCK are dynamically altered by ITK phosphorylation status.
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| 4. |
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| 5. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Cooperative merging strategy between connected autonomous vehicles in mixed traffic
- 2022
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Ingår i: IEEE Open Journal of Intelligent Transportation Systems. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2687-7813. ; 3, s. 825-837
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Tidskriftsartikel (refereegranskat)abstract
- In this work we propose a new cooperation strategy between connected autonomous vehicles in on-ramps merging scenarios and we implement the cut-in risk indicator (CRI) to investigate the safety effect of the proposed strategy. The new cooperation strategy considers a pair of vehicles approaching an on-ramp. The strategy then makes decisions on the target speeds/accelerations of both vehicles, possible lane changing, and a dynamic decision-making approach in order to reduce the risk during the cut-in manoeuvre. In this work, the CRI was first used to assess the risk during the merging manoeuvre. For this purpose, scenarios with penetration rates of autonomous vehicles from 20% to 100%, with step of 10%, both connected and non-connected autonomous vehicles were evaluated. As a result, on average a 35% reduction of the cut-in risk manoeuvres in connected autonomous vehicles compared to non-connected autonomous vehicles is obtained. It is shown through the analysis of probability density functions characterising the CRI distribution that the reduction is not homogeneous across all indicator values, but depends on the penetration rate and the severity of the manoeuvre.
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| 6. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Equivalence between spectral properties of graphs with and without loops
- 2018
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper we introduce a spectra preserving relation between graphs with loops and graphs without loops. This relation is achieved in two steps. First, by generalizing spectra results got on (m, k)-stars to a wider class of graphs, the (m, k, s)-stars with or without loops. Second, by defining a covering space of graphs with loops that allows to remove the presence of loops by increasing the graph dimension. The equivalence of the two class of graphs allows to study graph with loops as simple graph without loosing information.
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| 7. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Mathematical Definitions of Scene and Scenario for Analysis of Automated Driving Systems in Mixed-Traffic Simulations
- 2021
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Ingår i: IEEE Transactions on Intelligent Vehicles. - 2379-8858. ; 6:2, s. 366-375
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Tidskriftsartikel (refereegranskat)abstract
- This paper introduces a unified mathematical definition for describing commonly used terms encountered in systematical analysis of automated driving systems in mixed-traffic simulations. The most significant contribution of this work is in translating the terms that are clarified previously in literature into a mathematical set and function based format. Our work can be seen as an incremental step towards further formalisation of Domain-Specific-Language (DSL) for scenario representation. We also extended the previous work in the literature to allow more complex scenarios by expanding the model-incompliant information using set-theory to represent the perception capacity of the road-user agents. With this dynamic perception definition, we also support interactive scenarios and are not limited to reactive and pre-defined agent behavior. Our main focus is to give a framework to represent realistic road-user behavior to be used in simulation or computational tool to examine interaction patterns in mixed-traffic conditions. We believe that, by formalising the verbose definitions and extending the previous work in DSL, we can support automatic scenario generation and dynamic/evolving agent behavior models for simulating mixed traffic situations and scenarios. In addition, we can obtain scenarios that are realistic but also can represent rare-conditions that are difficult to extract from field-tests and real driving data repositories.
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| 8. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Measuring stability of spectral clustering
- 2019
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Ingår i: Linear Algebra and Its Applications. - : Elsevier BV. - 0024-3795. ; 610, s. 673-697
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Tidskriftsartikel (refereegranskat)abstract
- As an indicator of the stability of spectral clustering of an undirected weighted graph into k clusters, the kth spectral gap of the graph Laplacian is often considered. The k-th spectral gap is characterized here as an unstructured distance to ambiguity, namely as the minimal distance of the Laplacian to arbitrary symmetric matrices with vanishing kth spectral gap. As a more appropriate measure of stability, the structured distance to ambiguity of the k-clustering is introduced as the minimal distance of the Laplacian to Laplacians of the same graph with weights that are perturbed such that the k-th spectral gap vanishes. To compute a solution to this matrix nearness problem, a two-level iterative algorithm is proposed that uses a constrained gradient system of matrix differential equations in the inner iteration and a one-dimensional optimization of the perturbation size in the outer iteration. The structured and unstructured distances to ambiguity are compared on some example graphs. The numerical experiments show, in particular, that selecting the number k of clusters according to the criterion of maximal stability can lead to different results for the structured and unstructured stability indicators.
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| 9. |
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| 10. |
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| 11. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Potential impact of autonomous vehicles in mixed traffic from simulation using real traffic flow
- 2023
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Ingår i: Journal of Intelligent and Connected Vehicles. - 2399-9802. ; 6:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- This work focuses on the potential impacts of the autonomous vehicles in a mixed traffic condition represented in traffic simulator Simulation of Urban MObility (SUMO) with real traffic flow. Specifically, real traffic flow and speed data collected in 2002 and 2019 in Gothenburg were used to simulate daily flow variation in SUMO. In order to predict the most likely drawbacks during the transition from a traffic consisting only manually driven vehicles to a traffic consisting only fully-autonomous vehicles, this study focuses on mixed traffic with different percentages of autonomous and manually driven vehicles. To realize this aim, several parameters of the car following and lane change models of autonomous vehicles are investigated in this paper. Along with the fundamental diagram, the number of lane changes and the number of conflicts are analyzed and studied as measures for improving road safety and efficiency. The study highlights that the autonomous vehicles' features that improve safety and efficiency in 100% autonomous and mixed traffic are different, and the ability of autonomous vehicles to switch between mixed and autonomous driving styles, and vice versa depending on the scenario, is necessary.
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| 12. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Safety-centred analysis of transition stages to traffic with fully autonomous vehicles
- 2020
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Ingår i: IEEE Conference on Intelligent Transportation Systems, Proceedings, ITSC.
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Konferensbidrag (refereegranskat)abstract
- The aim of this paper is to highlight and investigate the effects of increasing presence rate of autonomous vehicles (AVs) in terms of traffic safety and traffic flow characteristics. For this purpose, using existing driver models in traffic simulator software SUMO we identify and analyze those parameters that characterize and distinguish AVs' driving from manual driving in a heterogeneous traffic context. While it is essential to identify the parameters for traffic flow characteristics of heterogeneous fleets compared to homogeneous ones comprising manually driven vehicles (MV) only (i.e. current status), the safety aspects must be also accounted for. In order to combine these two fundamental aspects of heterogeneous traffic, we used a complete description of a highway driving scenario. The scenario integrates the perceptions of different type of vehicles (i.e. AV and MV) involved and the reaction times of human drivers and decision-making units of autonomous vehicles, to explore the impact of both the rate of AV presence and the perturbation in perception capabilities in highway scenarios.
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| 13. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Signless normalized Laplacian for hypergraphs
- 2022
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Ingår i: Electronic Journal of Graph Theory and Applications. - : The Institute for Research and Community Services (LPPM) ITB. - 2338-2287. ; 10:2, s. 485-500
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Tidskriftsartikel (refereegranskat)abstract
- The spectral theory of the normalized Laplacian for chemical hypergraphs is further investigated. The signless normalized Laplacian is introduced and it is shown that its spectrum for classical hypergraphs coincides with the spectrum of the normalized Laplacian for bipartite chemical hypergraphs. Furthermore, the spectra of special families of hypergraphs are established.
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| 14. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Simulation-based impact projection of autonomous vehicle deployment using real traffic flow
- 2021
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this work we focus on future projected impacts of the autonomous vehicles in a realistic condition representing mixed traffic. By using real flow and speed data collected in 2002 and 2019 in the city of Gothenburg, we replicated and simulated the daily flow variation in SUMO. The expansion of the city in recent years was reflected in an increase in road users, and it is reasonable to expect it will increase further. Through simulations, it was possible to project this increase and to predict how this will impact the traffic in future. Furthermore, the composition of vehicle types in the future traffic can be expected to change through the introduction of autonomous vehicles. In order to predict the most likely drawbacks during the transition from a traffic consisting only manually driven vehicles to a traffic consisting only fully-autonomous vehicles, we focus on mixed traffic with different percentages of autonomous and manually driven vehicles. To realize this aim, several parameters of the car following and lane change models of autonomous vehicles are investigated in this paper. Along with the fundamental diagram, the number of lane changes and the number of conflicts are analyzed and studied as measures for improving road safety and efficiency.
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| 15. |
- Andreotti, Eleonora, 1988
(författare)
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Spectra of hyperstars
- 2022
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Ingår i: Australasian Journal of Combinatorics. - 1034-4942 .- 2202-3518. ; 82, s. 74-94
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is to introduce a model to study structures which are widely present in public transportation networks. We show that, through hypergraphs, one can describe these structures and investigate the relation between their spectra. To this aim, we extend the structure of (m, k)-stars on graphs to hypergraphs: the (m, k)-hyperstars on hypergraphs. Also, by giving suitable conditions on the hyperedge weights, we prove the existence of matrix eigenvalues of computable values and multiplicities, where the matrices considered are Laplacian, adjacency and transition matrices. By considering separately the case of generic hypergraphs and uniform hypergraphs, we prove that two kinds of vertex set reductions on hypergraphs with (m, k)-hyperstars are feasible, keeping the same eigenvalues with reduced multiplicity. Finally, some useful eigenvector properties are derived up to a product with a suitable matrix, and we relate these results to Fiedler spectral partitioning on the hypergraph.
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| 16. |
- Andreotti, F, et al.
(författare)
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Acute, periprocedural and longterm antithrombotic therapy in older adults: 2022 Update by the ESC Working Group on Thrombosis
- 2023
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 44:4, s. 262-279
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Tidskriftsartikel (refereegranskat)abstract
- The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Bazzani, Armando, et al.
(författare)
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NETWORK STRUCTURES DYNAMICS. An ecological application
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The network theory succeeded to apply the mathematical results of graph theory to describe the complex structures of big dataset provided by biological, economic and social systems. Recently the dynamical nature of the empirical observations has pointed out the necessity of introducing a dynamical structure on the considered interaction networks both to study the features of equilibrium solutions and to define new dynamical observables which allow to measure the resilience or frailty of the observed systems. We present a mathematical description of a network structure starting from the concept of landscape potential. Then we introduce a dynamics into this network structure by means of a Master Equation and we characterize some properties of the network using the eigenvalue spectral distribution of the associated stochastic matrix. In particular we are interested in the resilience of the stationary states and in the estimate relaxation time scales. Afterward we give some biological applications to understand the emergence of universal statistical laws as the relative species abundance distribution and the resilience of ecosystems.
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| 23. |
- Berge, Tone, et al.
(författare)
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T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9761-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The chemokine CXCL12/SDF-1alpha interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd's effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd's ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses. CONCLUSION: We propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements.
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| 24. |
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| 25. |
- Billnert, Robert, 1981, et al.
(författare)
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New information on the characteristics of 1 in. x 1 in. cerium bromide scintillation detectors
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 647:1, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- In view of highly demanded new and accurate data on prompt gamma-ray emission in nuclear fission a major part of investigations is directed towards the selection of suitable detector systems. Here we have studied a new type of crystal scintillation detectors made from cerium bromide (CeBr(3)). For the first time a full characterization of such a detector is presented in terms of energy resolution, pulse-height linearity, intrinsic activity and intrinsic timing resolution. In particular the latter one is very important for prompt fission gamma-ray studies, because the presence of fast neutrons, emitted in fission too, requires the time-of-flight method for their discrimination. The energy resolution has been found to be comparable to that of cerium-doped LaCl(3):Ce detectors at an efficiency comparable to the one of a LaBr(3):Ce detector of the same size. The intrinsic activity of the CeBr(3) crystal was observed to be much lower compared to lanthanum halide crystals. The intrinsic timing resolution of a coaxial 1 in. x 1 in. sized detector was measured relative to that of a previously characterized LaCl(3):Ce detector and found to be (326 +/- 7) Ps at (60)Co energies, which is in between those of a LaBr(3):Ce and a LaCl(3):Ce detector of same size.
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| 26. |
- Billnert, Robert, 1981, et al.
(författare)
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Novel Scintillation Detectors for Prompt Fission γ-Ray Measurements
- 2012
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Ingår i: Physics Procedia. - : Elsevier BV. - 1875-3884 .- 1875-3892. ; 31, s. 29-34
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Konferensbidrag (refereegranskat)abstract
- In this work we present first results from measurements of prompt fission γ-rays from the spontaneous fission in 252Cf. New and accurate data on corresponding γ-rays from the reactions 235U(nth,f) and 239Pu(nth,f) are highly demanded for the modeling of new Generation-IV nuclear reactor systems. For these experiments we employed scintillation detectors made out of new materials (LaBr3, LaCl3 and CeBr3), whose properties were necessary to know in order to obtain reliable results. Hence, we have characterized these detectors. In all the important properties these detectors outshine sodium-iodine detectors that where used in the 1970s, when the existing data had been acquired. Our finding is that the new generation of scintillation detectors is indeed promising, as far as an improved precision of the demanded data is concerned.
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| 27. |
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| 28. |
- Bouzid, Mehdi, et al.
(författare)
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Non-local rheology of dense granular flows
- 2017
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- The rheology of dense granular flows is studied numerically in a shear cell controlled at constant pressure and shear stress, confined between two granular shear flows. We show that a liquid state can be achieved even far below the yield stress, whose flow can be described with the same rheology as above the yield stress. A non-local constitutive relation is derived from dimensional analysis through a gradient expansion and calibrated using the spatial relaxation of velocity profiles observed under homogeneous stresses. Both for frictional and frictionless grains, the relaxation length is found to diverge as the inverse square root of the distance to the yield point, on both sides of that point. We also make use of a micro-rheometer to determine the influence of a distant shear band on the local rheological behaviour. Finally, we compare various approaches based on different non-local constitutive relations and choices for the fluidity parameter. We emphasise that, to discriminate between the different approaches proposed in the literature, one has to go beyond the predictions derived from linearisation around a uniform stress profile, such as that obtained in a simple shear cell. We argue that future tests can be based on the nature of the chosen fluidity parameter, and the related boundary conditions, as well as the hypothesis made to derive the models and the dynamical mechanisms underlying their dynamics.
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| 29. |
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| 30. |
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| 31. |
- De Caterina, R, et al.
(författare)
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General mechanisms of coagulation and targets of anticoagulants (Section I) : Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:4, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.
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| 32. |
- De Caterina, Raffaele, et al.
(författare)
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New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes : ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:16, s. 1413-1425
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Forskningsöversikt (refereegranskat)abstract
- Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.
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| 33. |
- De Caterina, Raffaele, et al.
(författare)
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Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2016
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 115:4, s. 685-711
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.
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| 34. |
- De Caterina, Raffaele, et al.
(författare)
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Parenteral anticoagulants in heart disease : Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 769-786
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Tidskriftsartikel (refereegranskat)abstract
- Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
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| 35. |
- De Caterina, Raffaele, et al.
(författare)
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Vitamin K antagonists in heart disease : Current status and perspectives (Section III)
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1087-1107
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Tidskriftsartikel (refereegranskat)abstract
- Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
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| 36. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 37. |
- Ferrannini, E, et al.
(författare)
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Differential Proteomics of Cardiovascular Risk and Coronary Artery Disease in Humans
- 2022
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Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 8, s. 790289-
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms.AimWe aimed to prospectively screen the proteome of four types of individuals: with or without coronary artery disease (CAD), each with or without multiple risk factors. Associations with individual risk factors and circulating biomarkers were also tested to provide a functional context to the protein hits.Materials and MethodsThe CAPIRE study (ClinicalTrials.gov Identifier: NCT02157662) is a cross-sectional study aimed at identifying possible new mechanisms promoting or protecting against atherothrombosis. Quantification (by aptamer technology), ranking (using partial least squares), and correlations (by multivariate regression) of ~5000 plasma proteins were performed in consecutive individuals aged 45–75 years, without previous cardiovascular disease, undergoing computed tomography angiography for suspected CAD, showing either >5/16 atherosclerotic segments (CAD+) or completely clean arteries (CAD−) and either ≤ 1 risk factor (RF+) or ≥3 risk factors (RF−) (based on history, blood pressure, glycemia, lipids, and smoking).ResultsOf 544 individuals, 39% were atypical (93 CAD+/RF−; 120 CAD−/RF+) and 61% typical (102 CAD+/RF+; 229 CAD−/RF−). In the comparison with CAD+/RF− adjusted for sex and age, CAD−/RF+ was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUCROC's of 0.72–0.81 (overall p = 1.0e−38). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA1c, and smoking.ConclusionsIn a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA1c. These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.
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| 38. |
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| 39. |
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| 40. |
- Freguglia, Paolo, et al.
(författare)
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Modelling Ecological Systems from a Niche Theory to Lotka-Volterra Equations
- 2020
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Ingår i: SEMA SIMAI Springer Series. - Cham : Springer International Publishing. - 2199-305X .- 2199-3041. ; 21, s. 1-18
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This paper is an attempt to analyze the notion of ecological niche as a community of different species and of ecosystem as a set of niches in order to formulate a dynamical model for an ecosystem. Our assumption is that the concept of fitness landscape allows to model the phenotype dynamics of an ensemble of species as a stochastic process. To take into account the interaction structure of different communities in the niches and the environment we introduce an ecological fitness potential to formulate a Lotka-Volterra system which describes the evolution of a mutual ecosystem in presence of finite resources. To explicitly consider the effect of fluctuations in the numerousness of the species, we associate a master equation to the average Lotka-Volterra system and we study the conditions of existence of a detailed balance equilibrium (i.e. a thermodynamic equilibrium) for the ecosystem. The explicit solution for the equilibrium probability distribution is a multinomial negative distribution and we discuss the relation between the detailed balance condition and relative species abundance distribution in the framework of Hubbell’s neutral theory. Moreover the theoretical distribution implies the existence of a correlation among the relative species distribution associated to the different communities. We use numerical simulations to illustrate the results on simple models.
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| 41. |
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| 42. |
- Grinkevich, Vera V., et al.
(författare)
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Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule
- 2022
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.
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| 43. |
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| 44. |
- Jackson, Sarah S., et al.
(författare)
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Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:15, s. 3973-3982
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Tidskriftsartikel (refereegranskat)abstract
- Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m(2) increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. Significance: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.
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| 45. |
- Jackson, Sarah S., et al.
(författare)
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Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project
- 2020
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Ingår i: Journal of Hepatology. - : ELSEVIER. - 0168-8278 .- 1600-0641. ; 73, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR >= 5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
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| 46. |
- Jing, Xiao, et al.
(författare)
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Safety benefit of cooperative control for heterogeneous traffic on-ramp merging
- 2022
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Ingår i: Transportation Safety and Environment. - : Oxford University Press (OUP). - 2631-6765 .- 2631-4428. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- The safety of heterogeneous traffic is a vital topic in the oncoming era of autonomous vehicles (AVs). The cooperative vehicle infrastructure system (CVIS) is considered to improve heterogeneous traffic safety by connecting and controlling AVs cooperatively, and the connected AVs are so-called connected and automated vehicles (CAVs). However, the safety impact of cooperative control strategy on the heterogeneous traffic with CAVs and human-driving vehicles (HVs) has not been well investigated. In this paper, based on the traffic simulator SUMO, we designed a typical highway scenario of on-ramp merging and adopted a cooperative control method for CAVs. We then compared the safety performance for two different heterogeneous traffic systems, i.e. AV and HV, CAV and HV, respectively, to illustrate the safety benefits of the cooperative control strategy. We found that the safety performance of the CAV and HV traffic system does not always outperform that of AV and HV. With random departSpeed and higher arrival rate, the proposed cooperative control method would decrease the conflicts significantly whereas the penetration rate is over 80%. We further investigated the conflicts in terms of the leading and following vehicle types, and found that the risk of a AV/CAV followed by a HV is twice that of a HV followed by another HV. We also considered the safety effect of communication failure, and found that there is no significant impact until the packet loss probability is greater than 30%, while communication delay's impact on safety can be ignored according to our experiments.
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| 47. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 48. |
- King, Sontoria D., et al.
(författare)
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Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:9, s. 1265-1269
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.
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| 49. |
- Kitahara, Cari M., et al.
(författare)
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Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
- 2016
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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| 50. |
- Klein, Alison P., et al.
(författare)
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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
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