| 1. |
- Angelillo-Scherrer, Anne, et al.
(författare)
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Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
- 2001
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 7:2, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- The growth arrest-specific gene 6 product (Gas6) is a secreted protein related to the anticoagulant protein S but its role in hemostasis is unknown. Here we show that inactivation of the Gas6 gene prevented venous and arterial thrombosis in mice, and protected against fatal collagen/epinephrine-induced thrombo embolism. Gas6-/- mice did not, however, suffer spontaneous bleeding and had normal bleeding after tail clipping. In addition, we found that Gas6 antibodies inhibited platelet aggregation in vitro and protected mice against fatal thrombo embolism without causing bleeding in vivo. Gas6 amplified platelet aggregation and secretion in response to known agonists. Platelet dysfunction in Gas6-/- mice resembled that of patients with platelet signaling transduction defects. Thus, Gas6 is a platelet-response amplifier that plays a significant role in thrombosis. These findings warrant further evaluation of the possible therapeutic use of Gas6 inhibition for prevention of thrombosis.
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| 2. |
- Awada, Imad Alex, et al.
(författare)
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An end- user perspective on the CAMI Ambient and Assisted Living Project
- 2018
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Ingår i: INTED2018 Proceedings. - : IATED. - 9788469794807 ; , s. 6776-6785
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Konferensbidrag (refereegranskat)abstract
- In this paper, we present the outcomes and conclusions obtained by involving seniors from three countries (Denmark, Poland and Romania) in an innovative project funded under the European Ambient Assisted Living (ALL) program. CAMI stands for "Companion with Autonomously Mobile Interface" in "Artificially intelligent ecosystem for self-management and sustainable quality of life in AAL". The CAMI solution enables flexible, scalable and individualised services that support elderly to self-manage their daily life and prolong their involvement in the society (sharing knowledge, continue working, etc). This also allows their informal caregivers (family and friends) to continue working and participating in society while caring for their loved ones. The solution is designed as an innovative architecture that allows for individualized, intelligent self-management which can be tailored to an individual's preferences and needs. A user-centred approach has ranked health monitoring, computer supervised physical exercises and voice based interaction among the top favoured CAMI functionalities. Respondents from three countries (Poland, Romania and Denmark) participated in a multinational survey and a conjoint analysis study.
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| 3. |
- Carraminana, Albert, et al.
(författare)
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Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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| 4. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 5. |
- Florea, Cristina, et al.
(författare)
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A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells
- 2017
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Berlin/Heidelberg. - 1617-7959 .- 1617-7940. ; 16:1, s. 297-311
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Tidskriftsartikel (refereegranskat)abstract
- Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.
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| 6. |
- Florea, Cristina, et al.
(författare)
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Determination of mechanical properties of chondrocytes in articular cartilage using atomic force microscopy
- 2014
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Ingår i: Solid State Phenomena. - : Trans Tech Publications Inc.. - 1012-0394 .- 1662-9779. ; 216, s. 134-139
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Tidskriftsartikel (refereegranskat)abstract
- Atomic Force Microscopy (AFM) based nanoindentation is a widely used technique for measuring mechanical properties of living cells, providing information for understanding their mechanobiological behavior. However, very local properties of cell surfaces have not been characterized earlier. The goal of this study was to develop an AFM-based technique to determine local elastic properties of bovine articular chondrocytes. The Youngs modulus of chondrocytes was 19.3 ± 5.6 kPa for spread cells and 10 ± 4.1 kPa for the round cells. The results were compared to previous studies in which different techniques were used to obtain more global properties of chondrocytes. Our findings suggest that using nanosized AFM tips, the very local cell properties can be measured.
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| 7. |
- Korhonen, Rami K., et al.
(författare)
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Multiscale In Silico Modeling of Cartilage Injuries
- 2023
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Ingår i: Advances in Experimental Medicine and Biology. - 2214-8019 .- 0065-2598. ; 1402, s. 45-56
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Bokkapitel (refereegranskat)abstract
- Injurious loading of the joint can be accompanied by articular cartilage damage and trigger inflammation. However, it is not well-known which mechanism controls further cartilage degradation, ultimately leading to post-traumatic osteoarthritis. For personalized prognostics, there should also be a method that can predict tissue alterations following joint and cartilage injury. This chapter gives an overview of experimental and computational methods to characterize and predict cartilage degradation following joint injury. Two mechanisms for cartilage degradation are proposed. In (1) biomechanically driven cartilage degradation, it is assumed that excessive levels of strain or stress of the fibrillar or non-fibrillar matrix lead to proteoglycan loss or collagen damage and degradation. In (2) biochemically driven cartilage degradation, it is assumed that diffusion of inflammatory cytokines leads to degradation of the extracellular matrix. When implementing these two mechanisms in a computational in silico modeling workflow, supplemented by in vitro and in vivo experiments, it is shown that biomechanically driven cartilage degradation is concentrated on the damage environment, while inflammation via synovial fluid affects all free cartilage surfaces. It is also proposed how the presented in silico modeling methodology may be used in the future for personalized prognostics and treatment planning of patients with a joint injury.
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| 8. |
- Kunnappilly, Ashalatha, et al.
(författare)
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A Novel Integrated Architecture for Ambient Assisted Living Systems
- 2017
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Ingår i: The 41st IEEE Computer Society International Conference on Computers, Software & Applications COMPSAC 2017. ; , s. 465-472
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Konferensbidrag (refereegranskat)abstract
- The increase in life expectancy and the slumping birth rates across the world result in lengthening the average age of the society. This change in demography has many consequences, the major being the insufficient number of caregivers. Therefore, we are in need of techniques that will assist the elderly in their daily life, while preventing their social isolation. The recent developments in Ambient Intelligence (AmI) and Information and Communication Technologies (ICT) have facilitated a technological revolution in the field of Ambient Assisted Living (AAL). At present, there are many technologies on the market that support the independent life of older adults, requiring less assistance from family and caregivers, yet most of them offer isolated services, such as health monitoring, supervised exercises, reminders etc. There are only very few architectures that support the seamless integration of various functionalities and none of them incorporates user preferences or are formally analyzed for their functionality and quality-of-service attributes which is needed in order to ensure safe mitigations of potential critical scenarios. In this paper, we propose a novel architectural solution that seamlessly integrates necessary functions of an AAL system, based on user preferences. To enable a first level of the architecture's analysis, we model our system in Architecture Analysis and Design Language (AADL), and carry out its simulation for analyzing the end-to-end data-flow latency, resource budgets and system safety.
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| 9. |
- Sorici, Alexandru, et al.
(författare)
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CAMI - An Integrated Architecture Solution for Improving Quality of Life of the Elderly
- 2016
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Konferensbidrag (refereegranskat)abstract
- The increasing ageing population worldwide imposes some new challenges to the society like the provision of dependable support while facing a shortage in the numbers of caregivers, increased health costs and the emergence of new diseases. As such there is a great demand for technologies that support the independent and safe living of the elderly and ensuring that they are not socially isolated. Ambient Assisted Living (AAL) technologies have thus emerged to support the elderly people in their daily activities, while removing the need of caregivers being always physically present in order to look after the elderly. The current AAL systems are intelligent enough to take critical decisions in emergency situations like a fall, fire or a cardiac arrest, hence the elderly can live safely and independently. In this abstract, we describe our solution that aims at integrating all relevant functionalities of an AAL system, based on feedback collected from representative users. This work is carried out in the European Union project called CAMI (Artificially intelligent ecosystem for self-management and sustainable quality of life in AAL).
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| 10. |
- Tjwa, Marc, et al.
(författare)
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Gas6 promotes inflammation by enhancing interactions between endothelial cells, platelets, and leukocytes
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:8, s. 4096-4105
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Tidskriftsartikel (refereegranskat)abstract
- The role of Gas6 in enclothelial cell (EC) function remains incompletely characterized. Here we report that Gas6 amplifies EC activation in response to inflammatory stimuli in vitro. In vivo, Gas6 promotes and accelerates the sequestration of circulating platelets and leukocytes on activated endothelium as well as the formation and enclothelial sequestration of circulating platelet-leukocyte conjugates. In addition, Gas6 promotes leukocyte extravasation, inflammation, and thrombosis in mouse models of inflammation (endotoxinemia, vasculitis, heart transplantation). Thus, Gas6 amplifies EC activation, thereby playing a key role in enhancing the interactions between ECs, platelets, and leukocytes during inflammation.
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