| 1. |
- Arora, Satish, et al.
(författare)
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Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Heart Transplant Recipients
- 2018
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Ingår i: Circulation. Heart failure. - 1941-3297. ; 11:9, s. 004050-004050
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation, and the effect of different immunosuppressive regimens on CAV is not fully understood. The randomized SCHEDULE trial (Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitors Avoidance) evaluated whether initiation of the proliferation signal inhibitor everolimus and early cyclosporine elimination can reduce CAV development. Methods and Results The SCHEDULE trial was a multicenter Scandinavian trial, where 115 de novo heart transplantation recipients were randomized to everolimus with complete cyclosporine withdrawal 7 to 11 weeks after heart transplantation or standard cyclosporine-based immunosuppression. Seventy-six (66%) patients had matched intravascular ultrasound examinations at baseline and 12 and 36 months. Intravascular ultrasound analysis evaluated maximal intimal thickness, percent atheroma volume, and total atheroma volume. Qualitative plaque analysis using virtual histology assessed fibrous, fibrofatty, and calcified tissue as well as necrotic core. Serum inflammatory markers were measured in parallel. The everolimus group (n=37) demonstrated significantly reduced CAV progression as compared with the cyclosporine group (n=39) at 36 months (Δ maximal intimal thickness, 0.09±0.05 versus 0.15±0.16 mm [ P=0.03]; Δ percent atheroma volume, 5.3±2.8% versus 7.6±5.9% [ P=0.03]; and Δ total atheroma volume, 33.9±71.2 versus 54.2±96.0 mm3 [ P=0.34], respectively]. At 36 months the number of everolimus patients with rejection graded ≥2R was 15 (41%) as compared with 5 (13%) in the cyclosporine group ( P=0.01). Everolimus did not affect CAV morphology or immune marker activity during the follow-up period. Conclusions The SCHEDULE trial demonstrates that everolimus initiation and early cyclosporine elimination significantly reduces CAV progression at 12 months, and this beneficial effect is clearly sustained at 36 months. Clinical trial registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01266148.
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| 2. |
- Gullestad, Lars, et al.
(författare)
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Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial
- 2016
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Ingår i: Transplant International. - : Wiley-Blackwell Publishing Inc.. - 0934-0874 .- 1432-2277. ; 29:7, s. 819-829
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Tidskriftsartikel (refereegranskat)abstract
- The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.
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| 3. |
- Gustafsson, Erik, et al.
(författare)
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Carbon cycling on the East Siberian Arctic Shelf – a change in air-sea CO2 flux induced by mineralization of terrestrial organic carbon
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189.
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Tidskriftsartikel (refereegranskat)abstract
- Measurements from the SWERUS-C3 and ISSS-08 Arctic expeditions were used to calibrate and validate a new physical-biogeochemical model developed to quantify key carbon cycling processes on the East Siberian Arctic Shelf (ESAS). The model was used in a series of experimental simulations with the specific aim to investigate the pathways of terrestrial dissolved and particulate organic carbon (DOCter and POCter) supplied to the shelf. Rivers supply on average 8.5 Tg C yr−1 dissolved inorganic carbon (DIC), and further 8.5 and 1.1 Tg C yr−1 DOCter and POCter respectively. Based on observed and simulated DOC concentrations and stable isotope values (δ13CDOC) in shelf waters, we estimate that only some 20 % of the riverine DOCter is labile. According to our model results, an additional supply of approximately 14 Tg C yr−1 eroded labile POCter is however required to describe the observed stable isotope values of DIC (δ13CDIC). Degradation of riverine DOCter and POCter results in a 1.8 Tg C yr−1 reduction in the uptake of atmospheric CO2, while degradation of eroded POCter results in an additional 10 Tg C yr−1 reduction. Our calculations indicate nevertheless that the ESAS is an overall small net sink for atmospheric CO2 (1.7 Tg C yr−1). The external carbon sources are largely compensated by a net export from the shelf to the Arctic Ocean (31 Tg C yr−1), and to a smaller degree by a permanent burial in the sediments (2.7 Tg C yr−1).
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| 4. |
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| 5. |
- Humborg, Christoph, et al.
(författare)
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Sea-air exchange patterns along the central and outer East Siberian Arctic Shelf as inferred from continuous CO2, stable isotope, and bulk chemistry measurements
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:7, s. 1173-1191
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Tidskriftsartikel (refereegranskat)abstract
- This large-scale quasi-synoptic study gives a comprehensive picture of sea-air CO 2 fluxes during the melt season in the central and outer Laptev Sea (LS) and East Siberian Sea (ESS). During a 7 week cruise we compiled a continuous record of both surface water and air CO 2 concentrations, in total 76,892 measurements. Overall, the central and outer parts of the ESAS constituted a sink for CO 2 , and we estimate a median uptake of 9.4 g C m -2 yr -1 or 6.6 Tg C yr -1 . Our results suggest that while the ESS and shelf break waters adjacent to the LS and ESS are net autotrophic systems, the LS is a net heterotrophic system. CO 2 sea-air fluxes for the LS were 4.7 g C m -2 yr -1 , and for the ESS we estimate an uptake of 7.2 g C m -2 yr -1 . Isotopic composition of dissolved inorganic carbon (δ 13 C DIC and δ 13 C CO2 ) in the water column indicates that the LS is depleted in δ 13 C DIC compared to the Arctic Ocean (ArcO) and ESS with an offset of 0.5‰ which can be explained by mixing of δ 13 C DIC -depleted riverine waters and 4.0 Tg yr -1 respiration of OC ter ; only a minor part (0.72 Tg yr -1 ) of this respired OC ter is exchanged with the atmosphere. Property-mixing diagrams of total organic carbon and isotope ratio (δ 13 C SPE-DOC ) versus dissolved organic carbon (DOC) concentration diagram indicate conservative and nonconservative mixing in the LS and ESS, respectively. We suggest land-derived particulate organic carbon from coastal erosion as an additional significant source for the depleted δ 13 C DIC .
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| 6. |
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| 7. |
- Nelson, Lærke M., et al.
(författare)
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Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation
- 2017
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Ingår i: Transplantation. - 0041-1337. ; 101:11, s. 2793-2800
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7–11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=−0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.
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| 8. |
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| 9. |
- Relbo Authen, Anne, et al.
(författare)
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Effect of everolimus vs calcineurin inhibitors on quality of life in heart transplant recipients during a 3-year follow-up : Results of a randomized controlled trial (SCHEDULE)
- 2017
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 31:9
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Tidskriftsartikel (refereegranskat)abstract
- The Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance (SCHEDULE) trial was a 12 month, randomized, open-label, parallel-group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. This study aimed to compare the effects of these treatments on quality of life (QoL). Within five post-operative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group). This study assessed quality of life (QoL), based on the Short Form-36, EuroQol-5D, and Beck Depression Inventory (BDI). Assessments were performed pre-HTx and 12 and 36 months post-HTx. At 12 and 36 months, the groups showed similar improvements in Short Form-36 measures (at pre-HTx, 12 and 36 months the values were as follows: Physical component summary: EVR: 31.5±110.9, 49.1±9.7, and 47.9±10.6; P<.01; CsA: 32.5±8.2, 48.4±8.5, and 46.5±11.5; P<.01; mental component summary: EVR: 46.0±12.0, 51.7±11.9, and 52.1±13.0; P<.01; CsA: 38.2±12.5, 53.4±7.1, and 54.3±13.0; P<.01); similar decrease in mean BDI (EVR: 10.9±10.2, 5.4±4.7, and 8.1±9.0; P<.01; CsA: 11.8±7.1, 6.3±5.4, and 6.2±6.5; P<.01); and similar Euro Qol-improvements. Thus, in this small-sized study, EVR-based and conventional CsA immunosuppressive strategies produced similar QoL improvements.
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| 10. |
- Abdollahi Sani, Negar, et al.
(författare)
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Flexible lamination-fabricated ultra-high frequency diodes based on self-supporting semiconducting composite film of silicon micro-particles and nano-fibrillated cellulose
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-ΌPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-ΌPs and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-ΌPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm2, a current rectification ratio up to 4 × 103 between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.
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