| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 4. |
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| 5. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 6. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 7. |
- Ashizawa, T., et al.
(författare)
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Consensus-based care recommendations for adults with myotonic dystrophy type 1
- 2018
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Ingår i: Neurology-Clinical Practice. - : Ovid Technologies (Wolters Kluwer Health). - 2163-0402 .- 2163-0933. ; 8:6, s. 507-520
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.
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| 8. |
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| 9. |
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| 10. |
- Hellsten, Torbjörn, et al.
(författare)
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Fast wave current drive in JET ITB-plasma
- 2005
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. ; , s. 273-278
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Konferensbidrag (refereegranskat)abstract
- Fast wave current drive has been performed in JET plasmas with internal transport barriers, ITBs, and strongly reversed magnetic shear. Although the current drive efficiency of the power absorbed on the electrons is fairly high, only small effects are seen in the central current density. The main reasons are the parasitic absorption of RF power, the strongly inductive nature of the plasma and the interplay between the fast wave driven current and bootstrap current. The direct electron heating in the FWCD experiments is found to be strongly degraded compared to that with the dipole phasing.
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| 11. |
- Massey, M.K., et al.
(författare)
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Evolution of Electronic Circuits using Carbon Nanotube Composites
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6:32197
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Tidskriftsartikel (refereegranskat)abstract
- volution-in-materio concerns the computer controlled manipulation of material systems using external stimuli to train or evolve the material to perform a useful function. In this paper we demonstrate the evolution of a disordered composite material, using voltages as the external stimuli, into a form where a simple computational problem can be solved. The material consists of single-walled carbon nanotubes suspended in liquid crystal; the nanotubes act as a conductive network, with the liquid crystal providing a host medium to allow the conductive network to reorganise when voltages are applied. We show that the application of electric fields under computer control results in a significant change in the material morphology, favouring the solution to a classification task.
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| 12. |
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| 13. |
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| 14. |
- Mahajan, Anubha, et al.
(författare)
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Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
- 2018
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:11, s. 1505-
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Tidskriftsartikel (refereegranskat)abstract
- We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
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| 15. |
- Mordijck, S., et al.
(författare)
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Collisionality driven turbulent particle transport changes in DIII-D H-mode plasmas
- 2020
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 60:6
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Tidskriftsartikel (refereegranskat)abstract
- The results of the experimental dimensionless scan in this paper confirm that there is an increase in density peaking towards lower collisionality and that this can be partly linked to a shift in the turbulence regime from ITG towards TEM. However at the lowest collisionality, the changes in turbulence and transport are much more pronounced than expected from direct collisionality effect on the turbulence. In this paper, the collisionality, ν ∗ is varied by a factor 5, while keeping ρ ∗, q, β, M, fixed. Additionally, a 3 Hz gas puff modulation is applied to modulate the electron density profile and extract the perturbed transport coefficients using two diagnostics. The transport analysis shows that the increase in density peaking at low ν ∗ is linked to an increase in the inward particle pinch and not an increase in core fueling. These observations are not only in agreement with prior modeling scans of how turbulence changes as a function of collisionality and its impact upon the particle fluxes, but also with the multi-machine database (Fable E. et al 2010 Plasma Phys. Control. Fusion 52 015007) (Angioni C. et al 2003 Phys. Rev. Lett. 90 205003). The changes in turbulence across the collisionality scan were captured at large scale by the BES and at smaller scale by the DBS. A comparison with gradient-driven GENE simulations showed similar trends at both scales. Moreover, the changes observed in overall transport are in agreement with gradient-driven TGLF particle flux simulations. This indicates that TGLF/GENE when given the gradients as input, are able to reproduce the experimentally observed turbulence changes.
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| 16. |
- Penney, J. I., et al.
(författare)
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The environments of luminous radio-WISE selected infrared galaxiess
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 483:1, s. 514-528
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Tidskriftsartikel (refereegranskat)abstract
- We have observed the environments of a population of 33 heavily dust obscured, ultraluminous, high-redshift galaxies, selected using Wide-Field Infrared Survey Explorer (WISE) and NRAO 1.4 GHz VLA Sky Survey atz > 1.3 with the infrared array camera on the Spitzer Space Telescope over 5.12 arcmin x 5.12 arcmin fields. Colour selections are used to quantify any potential overdensities of companion galaxies in these fields. We find no significant excess of galaxies with the standard colour selection for IRAC colours of [3.6] - [4.5] > -0.1 consistent with galaxies atz > 1.3 across the whole fields with respect to wide-area Spitzer comparison fields, but there is a > 2 sigma statistical excess within 0.25 arcmin of the central radio-WISE galaxy. Using a colour selection of [3.6] - [4.5] > 0.4, 0.5 magnitudes redder than the standard method of selecting galaxies atz > 1.3, we find a significant overdensity, in which 76 per cent (33 per cent) of the 33 fields have a surface density greater than the 3 sigma (5 sigma) level. There is a statistical excess of these redder galaxies within 0.5 arcmin, rising to a central peak similar to 2-4 times the average density. This implies that these galaxies are statistically linked to the radio-WISE selected galaxy, indicating similar structures to those traced by red galaxies around radio-loud active galactic nuclei.
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| 17. |
- Petty, C. C., et al.
(författare)
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DIII-D research towards establishing the scientific basis for futurefusion reactors
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 59:11
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D research is addressing critical challenges in preparation for ITER and the next generation of fusion devices through focusing on plasma physics fundamentals that underpin key fusion goals, understanding the interaction of disparate core and boundary plasma physics, and developing integrated scenarios for achieving high performance fusion regimes. Fundamental investigations into fusion energy science find that anomalous dissipation of runaway electrons (RE) that arise following a disruption is likely due to interactions with RE-driven kinetic instabilities, some of which have been directly observed, opening a new avenue for RE energy dissipation using naturally excited waves. Dimensionless parameter scaling of intrinsic rotation and gyrokinetic simulations give a predicted ITER rotation profile with significant turbulence stabilization. Coherence imaging spectroscopy confirms near sonic flow throughout the divertor towards the target, which may account for the convection-dominated parallel heat flux. Core-boundary integration studies show that the small angle slot divertor achieves detachment at lower density and extends plasma cooling across the divertor target plate, which is essential for controlling heat flux and erosion. The Super H-mode regime has been extended to high plasma current (2.0 MA) and density to achieve very high pedestal pressures (similar to 30 kPa) and stored energy (3.2 MJ) with H-98y2 approximate to 1.6-2.4. In scenario work, the ITER baseline Q = 10 scenario with zero injected torque is found to have a fusion gain metric beta(TE) independent of current between q(95) = 2.8-3.7, and a lower limit of pedestal rotation for RMP ELM suppression has been found. In the wide pedestal QH-mode regime that exhibits improved performance and no ELMs, the start-up counter torque has been eliminated so that the entire discharge uses approximate to 0 injected torque and the operating space is more ITER-relevant. Finally, the high-beta(N) (<= 3.8) hybrid scenario has been extended to the high-density levels necessary for radiating divertor operation, achieving similar to 40% divertor heat flux reduction using either argon or neon with P-tot up to 15 MW.
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| 18. |
- Volpati, D., et al.
(författare)
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Exploring the alignment of carbon nanotubes dispersed in a liquid crystal matrix using coplanar electrodes
- 2015
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 117:12
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Tidskriftsartikel (refereegranskat)abstract
- We report on the use of a liquid crystalline host medium to align single-walled carbon nanotubes in an electric field using an in-plane electrode configuration. Electron microscopy reveals that the nanotubes orient in the field with a resulting increase in the DC conductivity in the field direction. Current versus voltage measurements on the composite show a nonlinear behavior, which was modelled by using single-carrier space-charge injection. The possibility of manipulating the conductivity pathways in the same sample by applying the electrical field in different (in-plane) directions has also been demonstrated. Raman spectroscopy indicates that there is an interaction between the nanotubes and the host liquid crystal molecules that goes beyond that of simple physical mixing.
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| 19. |
- Afanaciev, K.G., et al.
(författare)
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Investigation of the radiation hardness of GaAs sensors in an electron beam
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- A compact and finely grained sandwich calorimeter is designed to instrument the very forward region of a detector at a future e+e- collider. The calorimeter will be exposed to low energy e+e - pairs originating from beamstrahlung, resulting in absorbed doses of about one MGy per year. GaAs pad sensors interleaved with tungsten absorber plates are considered as an option for this calorimeter. Several Cr-doped GaAs sensor prototypes were produced and irradiated with 8.5-10 MeV electrons up to a dose of 1.5 MGy. The sensor performance was measured as a function of the absorbed dose.
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| 20. |
- Allardice, Jesse R., et al.
(författare)
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Engineering Molecular Ligand Shells on Quantum Dots for Quantitative Harvesting of Triplet Excitons Generated by Singlet Fission
- 2019
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Ingår i: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 141:32, s. 12907-12915
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Tidskriftsartikel (refereegranskat)abstract
- Singlet fission is an exciton multiplication process in organic molecules in which a photogenerated spin-singlet exciton is rapidly and efficiently converted to two spin-triplet excitons. This process offers a mechanism to break the Shockley-Queisser limit by overcoming the thermalization losses inherent to all single-junction photovoltaics. One of the most promising methods to harness the singlet fission process is via the efficient extraction of the dark triplet excitons into quantum dots (QDs) where they can recombine radiatively, thereby converting high-energy photons to pairs of low-energy photons, which can then be captured in traditional inorganic PVs such as Si. Such a singlet fission photon multiplication (SF-PM) process could increase the efficiency of the best Si cells from 26.7% to 32.5%, breaking the Shockley-Queisser limit. However, there has been no demonstration of such a singlet fission photon multiplication (SF-PM) process in a bulk system to date. Here, we demonstrate a solution-based bulk SF-PM system based on the singlet fission material TIPS-Tc combined with PbS QDs. Using a range of steady-state and time-resolved measurements combined with analytical modeling we study the dynamics and mechanism of the triplet harvesting process. We show that the system absorbs >95% of incident photons within the singlet fission material to form singlet excitons, which then undergo efficient singlet fission in the solution phase (135 +/- 5%) before quantitative harvesting of the triplet excitons (95 +/- 5%) via a low concentration of QD acceptors, followed by the emission of IR photons. We find that in order to achieve efficient triplet harvesting it is critical to engineer the surface of the QD with a triplet transfer ligand and that bimolecular decay of triplets is potentially a major loss pathway which can be controlled via tuning the concentration of QD acceptors. We demonstrate that the photon multiplication efficiency is maintained up to solar fluence. Our results establish the solution-based SF-PM system as a simple and highly tunable platform to understand the dynamics of a triplet energy transfer process between organic semiconductors and QDs, one that can provide clear design rules for new materials.
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| 21. |
- Gray, Victor, Dr, 1988-, et al.
(författare)
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Direct vs Delayed Triplet Energy Transfer from Organic Semiconductors to Quantum Dots and Implications for Luminescent Harvesting of Triplet Excitons
- 2020
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Ingår i: ACS Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 14:4, s. 4224-4234
-
Tidskriftsartikel (refereegranskat)abstract
- Hybrid inorganic-organic materials such as quantum dots (QDs) coupled with organic semiconductors have a wide range of optoelectronic applications, taking advantage of the respective materials' strengths. A key area of investigation in such systems is the transfer of triplet exciton states to and from QDs, which has potential applications in the luminescent harvesting of triplet excitons generated by singlet fission, in photocatalysis and photochemical upconversion. While the transfer of energy from QDs to the triplet state of organic semiconductors has been intensely studied in recent years, the mechanism and materials parameters controlling the reverse process, triplet transfer to QDs, have not been well investigated. Here, through a combination of steady-state and time-resolved optical spectroscopy we study the mechanism and energetic dependence of triplet energy transfer from an organic ligand (TIPS-tetracene carboxylic acid) to PbS QDs. Over an energetic range spanning from exothermic (-0.3 eV) to endothermic (+0.1 eV) triplet energy transfer we find that the triplet energy transfer to the QD occurs through a single step process with a clear energy dependence that is consistent with an electron exchange mechanism as described by Marcus-Hush theory. In contrast, the reverse process, energy transfer from the QD to the triplet state of the ligand, does not show any energy dependence in the studied energy range; interestingly, a delayed formation of the triplet state occurs relative to the quantum dots' decay. Based on the energetic dependence of triplet energy transfer we also suggest design criteria for future materials systems where triplet excitons from organic semiconductors are harvested via QDs, for instance in light emitting structures or the harvesting of triplet excitons generated via singlet fission.
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| 22. |
- Koliopoulou, S, et al.
(författare)
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Metal nano-floating gate memory devices fabricated at low temperature
- 2006
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 83:4-9, s. 1563-1566
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Tidskriftsartikel (refereegranskat)abstract
- In this communication, we report on the realization of low-temperature processed Electrically Erasable Programmable Read-Only Memory (EEPROM) like device with embedded gold nanoparticles. The realization is based on the fabrication of a V-groove SiGe Metal Oxide Semiconductor Field Effect Transistor (MOSFET), the functionalization of a gate oxide followed by self-assembly of gold nanoparticles and finally, the deposition of an organic insulator by Langmuir-Blodgett (LB) technique. Such structures were processed at a temperature lower than 400 degrees C. The electrical characteristics of the final hybrid Metal Insulator Semiconductor FET (MISFET) memory cells were evaluated in terms of memory window and program/erase voltage pulses. A model describing the memory characteristics, based on the electronic properties of the gate stack materials, is presented.
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| 23. |
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| 24. |
- Notz, Dirk, et al.
(författare)
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Arctic Sea Ice in CMIP6
- 2020
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:10
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Tidskriftsartikel (refereegranskat)abstract
- We examine CMIP6 simulations of Arctic sea‐ice area and volume. We find that CMIP6 models produce a wide spread of mean Arctic sea‐ice area, capturing the observational estimate within the multimodel ensemble spread. The CMIP6 multimodel ensemble mean provides a more realistic estimate of the sensitivity of September Arctic sea‐ice area to a given amount of anthropogenic CO2 emissions and to a given amount of global warming, compared with earlier CMIP experiments. Still, most CMIP6 models fail to simulate at the same time a plausible evolution of sea‐ice area and of global mean surface temperature. In the vast majority of the available CMIP6 simulations, the Arctic Ocean becomes practically sea‐ice free (sea‐ice area <1 × 106 km2) in September for the first time before the Year 2050 in each of the four emission scenarios SSP1‐1.9, SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5 examined here.
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| 25. |
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| 26. |
- Petty, Aaron M., et al.
(författare)
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Applying Historical Ecology to Natural Resource Management Institutions: Lessons from Two Case Studies of Landscape Fire Management
- 2015
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 31, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the linkages between social and ecological systems is key to developing sustainable natural resource management (NRM) institutions. Frequently, however, insufficient attention is paid to the historical development of NRM institutions. Instead, discussion largely focuses on models of economic efficiency at the expense of the cultural, historical, and ecological contexts within which institutions develop. Here we use the research program of historical ecology to explore the development, maintenance, and change of two contemporary fire management institutions in northern Australia and Colorado, USA, to demonstrate how social institutions and ecological systems change and resist change over time and how institutions interact across scales to negotiate contrasting goals and motivations. We argue that these NRM institutions are not strictly speaking evolutionary or adaptive, and that historical context is critical when evaluating how and why particular institutions and institutional relationships develop. As with ecosystems, the present characteristics of the NRM institutions are dependent on what has happened before and their efficacy can only be evaluated retrospectively. Therefore, an understanding of history is essential to questions of the desirability and feasibility of institutional change where such shifts are required from an ecological, social, or economic perspective. We further propose that institutional conflict arises from the differing goals and motives of resource management institutions at different scales. Our cases reveal that larger-scale institutions can be successful at achieving narrowly defined goals but often fall short of achieving socially desirable sustainable outcomes. Our findings support the use of narratives of community history, place, and being in considering the resilience and sustainability of social-ecological systems. We offer that historical ecology is complementary with institutional and economic approaches to the analysis of NRM institutions, and possesses a particular strength in linking ecology to the values and norms of small social groups.
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| 27. |
- Ruperto, N., et al.
(författare)
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A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis
- 2007
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Ingår i: Arthritis Rheum. - : Wiley. - 0004-3591. ; 56:9, s. 3096-3106
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. RESULTS: Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. CONCLUSION: While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.
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| 28. |
- Toolan, Daniel T. W., et al.
(författare)
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Insights into the Structure and Self-Assembly of Organic-Semiconductor/Quantum-Dot Blends
- 2022
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Ingår i: Advanced Functional Materials. - : John Wiley & Sons. - 1616-301X .- 1616-3028. ; 32:13
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Tidskriftsartikel (refereegranskat)abstract
- Controlling the dispersibility of crystalline inorganic quantum dots (QD) within organic-QD nanocomposite films is critical for a wide range of optoelectronic devices. A promising way to control nanoscale structure in these nanocomposites is via the use of appropriate organic ligands on the QD, which help to compatibilize them with the organic host, both electronically and structurally. Here, using combined small-angle X-ray and neutron scattering, the authors demonstrate and quantify the incorporation of such a compatibilizing, electronically active, organic semiconductor ligand species into the native oleic acid ligand envelope of lead sulphide, QDs, and how this ligand loading may be easily controlled. Further more, in situ grazing incidence wide/small angle X-ray scattering demonstrate how QD ligand surface chemistry has a pronounced effect on the self-assembly of the nanocomposite film in terms of both small-molecule crystallization and QD dispersion versus ordering/aggregation. The approach demonstrated here shows the important role which the degree of incorporation of an active ligand, closely related in chemical structure to the host small-molecule organic matrix, plays in both the self-assembly of the QD and small-molecule components and in determining the final optoelectronic properties of the system.
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| 29. |
- Toolan, Daniel T. W., et al.
(författare)
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Linking microscale morphologies to localised performance in singlet fission quantum dot photon multiplier thin films
- 2022
-
Ingår i: Journal of Materials Chemistry C. - : Royal Society of Chemistry. - 2050-7526 .- 2050-7534. ; 10:31, s. 11192-11198
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid small-molecule/quantum dot films have the potential to reduce thermalization losses in single-junction photovoltaics as photon multiplication devices. Here grazing incidence X-ray scattering, optical microscopy and IR fluorescence microscopy (probing materials at two distinct wavelengths), provide new insight into highly complex morphologies across nm and mu m lengthscales to provide direct links between morphologies and photon multiplication performance. Results show that within the small molecule crystallites three different QD morphologies may be identified; (i) large quantum dot aggregates at the crystallite nucleus, (ii) relatively well-dispersed quantum dots and (iii) as aggregated quantum dots "swept" from the growing crystallite and that regions containing aggregate quantum dot features lead to relatively poor photon multiplication performance. These results establish how combinations of scattering and microscopy may be employed to reveal new insights into the structure and function of small molecule:quantum dot blends.
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| 30. |
- Visvanathan, Sudha, et al.
(författare)
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The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial.
- 2010
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Ingår i: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA). METHODS: In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP). RESULTS: At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders. CONCLUSION: Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders. TRIAL REGISTRATION: NCT00036374.
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