| 1. |
- Bergh, Niklas, 1979, et al.
(författare)
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Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
- 2020
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:2, s. 567-576
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. Methods and results: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7–11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. Conclusions: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
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| 2. |
- Broch, Kaspar, et al.
(författare)
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Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients : Design of the randomized controlled EVOLVD trial
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. Methods: The Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4-8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2, renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. Conclusion: The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.
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| 3. |
- Gustafsson, Finn, et al.
(författare)
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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients : Long-term Follow-up From the Randomized SCHEDULE Study
- 2020
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1534-6080 .- 0041-1337. ; 104:1, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. METHODS: In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. RESULTS: Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. CONCLUSIONS: These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
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| 4. |
- Nelson, Lærke Marie, et al.
(författare)
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Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy
- 2020
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 33:5, s. 517-528
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45–61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL-3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL-3Y (r = −0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.
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| 5. |
- Ng, Nawi, 1974, et al.
(författare)
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Sustainable Behavior Change for Health Supported by Person-Tailored, Adaptive, Risk-Aware Digital Coaching in a Social Context: Study Protocol for the STAR-C Research Programme
- 2021
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Vasterbotten Intervention Programme (VIP) in the Region Vasterbotten Sweden is one of the very few cardiovascular disease (CVD) prevention programmes globally that is integrated into routine primary health care. The VIP has been shown as a cost-effective intervention to significantly reduce CVD mortality. However, little is known about the effectiveness of a digital solution to tailor risk communication strategies for supporting behavioral change. STAR-C aims to develop and evaluate a technical platform for personalized digital coaching that will support behavioral change aimed at preventing CVD. Methods: STAR-C employs a mixed-methods design in seven multidisciplinary projects, which runs in two phases during 2019-2024: (i) a formative intervention design and development phase, and (ii) an intervention implementation and evaluation phase. In the 1st phase, STAR-C will model the trajectories of health behaviors and their impact on CVDs (Project 1), evaluate the role of the social environment and social networks on behavioral change (Project 2) and assess whether and how social media facilitates the spread of health information beyond targeted individuals and stimulates public engagement in health promotion (Project 3). The findings will be utilized in carrying out the iterative, user-centered design, and development of a person-tailored digital coaching platform (Project 4). In the 2nd phase, STAR-C will evaluate the implementation of the coaching programme and its effectiveness for promoting behavioral change and the spreading of health information across social networks and via social media (Project 5). The cost-effectiveness (Project 6) and ethical issues (Project 7) related to the coaching programme intervention will be evaluated. Discussion: The STAR-C research programme will address the knowledge and practice research gaps in the use of information technologies in health promotion and non-communicable disease (NCD) prevention programmes in order to narrow the health inequality gaps. Ethics: STAR-C has received approval from the Swedish Ethical Review Authority (Dnr. 2019-02924;2020-02985). Dissemination: The collaboration between Umea University and Region Vasterbotten will ensure the feasibility of STAR-C in the service delivery context. Results will be communicated with decision-makers at different levels of society, stakeholders from other regions and healthcare professional organizations, and through NGOs, local and social media platforms.
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| 6. |
- Andersson Ersman, Peter, et al.
(författare)
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Monolithic integration of display driver circuits and displays manufactured by screen printing
- 2020
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Ingår i: Flexible and Printed Electronics. - : Institute of Physics Publishing. - 2058-8585. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report all-screen printed display driver circuits, based on organic electrochemical transistors (OECTs), and their monolithic integration with organic electrochromic displays (OECDs). Both OECTs and OECDs operate at low voltages and have similar device architectures, and, notably, they rely on the very same electroactive material as well as on the same electrochemical switching mechanism. This then allows us to manufacture OECT-OECD circuits in a concurrent manufacturing process entirely based on screen printing methods. By taking advantage of the high current throughput capability of OECTs, we further demonstrate their ability to control the light emission in traditional light-emitting diodes (LEDs), where the actual LED addressing is achieved by an OECT-based decoder circuit. The possibility to monolithically integrate all-screen printed OECTs and OECDs on flexible plastic foils paves the way for distributed smart sensor labels and similar Internet of Things applications.
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| 7. |
- Asayama, Shinichiro, et al.
(författare)
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Three institutional pathways to envision the future of the IPCC
- 2023
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Ingår i: Nature Climate Change. - : Nature Portfolio. - 1758-678X .- 1758-6798. ; 13:9, s. 877-880
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Tidskriftsartikel (refereegranskat)abstract
- The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.
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| 8. |
- Badam, Tejaswi, et al.
(författare)
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CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases
- 2022
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Ingår i: Epigenetics. - : Taylor & Francis Group. - 1559-2294 .- 1559-2308. ; 17:9, s. 1040-1055
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.
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| 9. |
- Blomqvist, Göran, 1963-, et al.
(författare)
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Microplastics in snow in urban traffic environments
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Microplastics from road traffic, mainly from tyre wear, are globally considered to be one of the largest sources of microplastic contamination in the environment. Plastics can either be deposited in the road vicinity, at the roadside and in ditches or spread via stormwater and air to the environment and receiving water bodies. In cold climates, microplastics, as well as other traffic-related pollutants, can be temporarily stored in snow and ice on and around roads and streets. The location and concentration of these pollutants is influenced by winter operations, where ploughing and skid control contribute to redistribution, and by melting and compaction of ice and snow. This creates reservoirs of microplastics and other pollutants, which are released into stormwater or surrounding soil during thaws, but also provides an opportunity to reduce the spread of microplastics by managing snow and ice appropriately. In the present report, a case study of microplastics in snow has been carried out in the municipality of Karlstad in Sweden, to get an idea of the potential variation, both in terms of concentration and total amounts in relation to traffic and the location of the sampling in the street environment. Microplastics have been analysed by pyrolysis GC/MS to identify tyre-specific polymers in combination with eight commonly occurring plastic types. In addition, six municipalities in different parts of the country responded to a questionnaire on microplastics in snow and urban snowmelt management. The results show that microplastics related to tyre wear (rubber polymers) tend to be present in higher concentrations on and near the carriageway. Other plastics show a less clear link to traffic. Along a salted bicycle lane, an elevated level of polypropylene, from which the brush of the sweep-salting machine is made, could be detected in the surface layer of the snow. In general, knowledge about microplastics in urban snow is low in the municipalities that responded to the survey.
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| 10. |
- Engquist, Isak, et al.
(författare)
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Highly conducting nanographite-filled paper fabricated via standard papermaking techniques
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society. - 1944-8244 .- 1944-8252. ; 12:43, s. 48828-48835
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Tidskriftsartikel (refereegranskat)abstract
- Eco-friendly and cost-effective materials and processes to manufacture functional substrates are crucial to further advance the area of printed electronics. One potential key component in the printed electronics platform is an electrically functionalized paper, produced by simply mixing common cellulosic pulp fibers with high-performance electroactive materials. Herein, an electronic paper including nanographite has been prepared using a standardized and scalable papermaking technique. No retention aid was needed to achieve a conducting nanographite loading as high as 50 wt %. The spontaneous retention that provides the integrity and stability of the nanographite paper, likely originates partially from an observed water-stable adhesion of nanographite flakes onto the fiber surfaces. The resulting paper exhibits excellent electrical characteristics, such as an in-plane conductivity of 107 S/cm and an areal capacitance of 9.2 mF/cm2, and was explored as the back-electrode in printed electrochromic displays.
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