| 1. |
- Acharya, B. S., et al.
(författare)
-
Introducing the CTA concept
- 2013
-
Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Abazov, V. M., et al.
(författare)
-
The upgraded DO detector
- 2006
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
-
Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
|
|
| 3. |
|
|
| 4. |
- Actis, M., et al.
(författare)
-
Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
-
Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
-
Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Dahl-Jensen, D., et al.
(författare)
-
Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
-
Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
|
|
| 8. |
- Cirasuolo, M., et al.
(författare)
-
MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT
- 2014
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 1996-756X .- 0277-786X. ; 9147, s. 91470-91470
-
Konferensbidrag (refereegranskat)abstract
- MOONS (the Multi-Object Optical and Near-infrared Spectrograph) has been selected by ESO as a third-generation instrument for the Very Large Telescope (VLT). The light grasp of the large collecting area offered by the VLT (8.2m diameter), combined with the large multiplex and wavelength coverage (optical to near-IR: 0.8 -1.8 mu m) of MOONS will provide the European astronomical community with a powerful, unique instrument able to pioneer a wide range of Galactic, extragalactic and cosmological studies, and it will provide crucial follow-up for major facilities such as Gaia, VISTA, Euclid and LSST. MOONS has the observational power needed to unveil galaxy formation and evolution over the entire history of the Universe, from stars in our Milky Way, through the redshift desert, and up to the epoch of very first galaxies and reionization of the Universe at redshifts of z > 8-9, just a few million years after the Big Bang. From five years of observations MOONS will provide high-quality spectra for > 3M stars in our Galaxy and the Local Group, and for 1-2M galaxies at z > 1 (for an SDSS-like survey), promising to revolutionize our understanding of the Universe. The baseline design consists of similar to 1000 fibres, deployable over a field-of-view of similar to 500 arcmin(2), the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8 -1.8 mu m with two spectral resolving powers: in the medium-resolution mode (R similar to 4,000-6,000) the entire wavelength range is observed simultaneously, while the high-resolution mode will cover three selected sub-regions simultaneously: one region with R similar to 8,000 near the Ca II triplet to measure stellar radial velocities, and two regions at R similar to 20,000 (one in each of the J- and H-bands), for precision measurements of chemical abundances.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Schüpbach, S., et al.
(författare)
-
Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.
|
|
| 14. |
- Wolff, E. W., et al.
(författare)
-
Changes in environment over the last 800,000 years from chemical analysis of the EPICA Dome C ice core
- 2010
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:1-2, s. 285-295
-
Tidskriftsartikel (refereegranskat)abstract
- The EPICA ice core from Dome C extends 3259 m in depth, and encompasses 800 ka of datable and sequential ice. Numerous chemical species have been measured along the length of the cores. Here we concentrate on interpreting the main low-resolution patterns of major ions. We extend the published record for non-sea-salt calcium, sea-salt sodium and non-sea-salt sulfate flux to 800 ka. The non-sea-salt calcium record confirms that terrestrial dust originating from South America closely mirrored Antarctic climate, both at orbital and millennial timescales. A major cause of the main trends is most likely climate in southern South America, which could be sensitive to subtle changes in atmospheric circulation. Sea-salt sodium also follows temperature, but With a threshold at low temperature. We re-examine the use of sodium as a sea ice proxy, concluding that it is probably reflecting extent, with high salt concentrations reflecting larger ice extents. With this interpretation, the sodium flux record indicates low ice extent operating as an amplifier in warm interglacials. Non-sea-salt sulfate flux is almost constant along the core, confirming the lack of change in marine productivity (for sulfur-producing organisms) in the areas of the Southern Ocean contributing to the flux at Dome C. For the first time we also present long records of reversible species such as nitrate and chloride, and show that the pattern of post-depositional losses described for shallower ice is maintained in older ice. It appears possible to use these concentrations to constrain snow accumulation rates in interglacial ice at this site, and the results suggest a possible correction to accumulation rates in one early interglacial. Taken together the chemistry records offer a number of constraints on the way the Earth system combined to give the major climate fluctuations of the late Quaternary period.
|
|
| 15. |
|
|
| 16. |
- Banasik, Karina, et al.
(författare)
-
The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins.
- 2011
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 119-124
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The minor G allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G allele. Research Design and Methods: rs2802292 was genotyped in a phenotypically well-characterized population of young and elderly twins (n = 190) and in the population-based Inter99 cohort (n = 5768). All participants underwent oral glucose tolerance tests, and the twin population was additionally examined with an iv glucose tolerance test and a hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. Results: In the twin sample, carriers of the minor G allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (β) = -13% (-24; -1) (95% confidence interval), P = 0.03] and lower incremental area under the curve 0-120 min for insulin after an oral glucose load [β = -14% (-23; -), P = 0.005]. The G allele was associated with increased peripheral insulin action [glucose disposal rate clamp, β = 0.85 mg·kgfat-free mass(-1) · min(-1) (0.049; 1.64), P = 0.04] and lower hepatic insulin resistance index [β = -13% (-25; -1), P = 0.03]. Furthermore, carriers of the G allele had increased basal FOXO3A mRNA expression in skeletal muscle compared with T-allele carriers [β = 16% (0; 33), P = 0.047]. In the Inter99 sample, we found an association with reduced incremental area under the curve 0-120 min for insulin after an oral glucose load [β = -3% (-5; -0.07), P = 0.04], but this association was not significant after adjustment for body mass index. Conclusion: Our data indicate that the minor G allele of FOXO3A rs2802292 is associated with enhanced peripheral and hepatic insulin sensitivity in our small twin cohort, which may be mediated through increased FOXO3A mRNA expression, although no major metabolic impact of rs2802292 was found in the large Inter99 cohort.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Eyerich, K, et al.
(författare)
-
IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:9, s. e049822-
-
Tidskriftsartikel (refereegranskat)abstract
- Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention.Methods and analysisHere we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit (‘super-responders’ (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe.Ethics and disseminationApproval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.Trial registration numberRegistered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.
|
|
| 20. |
|
|
| 21. |
- Ling, Charlotte, et al.
(författare)
-
Impact of the peroxisome proliferator activated receptor-gamma coactivator-1 beta (PGC-1 beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1 beta expression and fibre type composition in human skeletal muscle
- 2007
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:8, s. 1615-1620
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Peroxisome proliferator activated receptor-gamma coactivator-lp (PGC-1 beta, also known as PPARGCIB) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1 beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1 beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1 beta expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods The PGC-1 beta Ala203Pro polymerphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1 beta expression, in vivo metabolism and markers for fibre type composition. Results Insulin-stimulated non-oxidative glucose metabolism (NOGM; p=0.025) and glycolytic flux rate (GF; p=0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1 beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1 beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p <= 0.001), there was no significant age-related decline in PGC-1 beta expression in carriers of the 203Pro allele (p >= 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1 beta expression. Finally, PGC-1 beta expression correlated positively with markers for oxidative fibres in human muscle. Conclusions/interpretation This study suggests that young carriers of a PGC-1 beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1 beta expression in muscle.
|
|
| 22. |
- López-Puertas, M., et al.
(författare)
-
Non-local thermodynamic equilibrium limb radiances for the mipas instrument on Envisat-1
- 1998
-
Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - 0022-4073 .- 1879-1352. ; 59:3-5, s. 377-403
-
Tidskriftsartikel (refereegranskat)abstract
- An evaluation of the effects that the assumption of local thermodynamic equilibrium (LTE) has on the retrieval of pressure, temperature and the five primary target gases (O3, H2O, CH4, N2O, and HNO3) from spectra to be taken by Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on the Envisat-1 platform has been conducted. For doing so, non-LTE and LTE limb radiances in the spectral range of 680–2275 cm−1 (4.15–14.6 μm) with a resolution of 0.05 cm−1 at tangent heights from 10 to 70 km have been computed. These calculations included the most updated non-LTE populations of a large number of vibrational levels of the CO2, O3, H2O, CH4, N2O and HNO3 molecules which cause the most prominent atmospheric infrared emissions. A discussion of the most important non-LTE effects on the limb radiances as well as on the retrievals of pressure-temperature and volume mixing ratios of O3, H2O, CH4, N2O, and HNO3 is presented, together with the most important non-LTE issues that could be studied with the future coming of MIPAS data.
|
|
| 23. |
|
|
| 24. |
- Manuilova, R.O., et al.
(författare)
-
Modelling of non-LTE limb spectra of i.r. ozone bands for the MIPAS space experiment
- 1998
-
Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - 0022-4073 .- 1879-1352. ; 59:3-5, s. 405-422
-
Tidskriftsartikel (refereegranskat)abstract
- A new model for calculating the populations of the ozone vibrational states under non-LTE (Local Thermodynamic Equilibrium) conditions is presented. In the model, 23 vibrational levels of the O3 molecule, as well as three vibrational levels of the O2 molecule and two vibrational levels of the N2 molecule, are considered. The radiative transfer at the break-down of LTE was treated explicitly for 150 000 ro-vibrational transitions. The populations obtained were used to calculate limb radiances in various spectral regions of the 4.8 and 9.6 μm bands. Test retrievals of O3 vertical volume mixing ratio (VMR) profiles with a radiance model disregarding non-LTE were performed in order to assess the potential impact of non-LTE effects on the retrieval of the O3 abundances from MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) measurements.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Pilgaard, K., et al.
(författare)
-
The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men
- 2009
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:7, s. 1298-1307
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene. We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action. Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function. Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.
|
|
| 28. |
|
|
| 29. |
- Sanders, Kevin J., et al.
(författare)
-
Broadband MAS NMR spectroscopy in the low-power limit
- 2018
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 697, s. 29-37
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the performance of broadband adiabatic inversion pulses in the high-power (short high-powered adiabatic pulse, SHAP) and low-power (single-sideband-selective adiabatic pulse, S(3)AP) RF regimes on a spin system subjected to large anisotropic interactions. We show by combined experimental results and spin dynamics simulations that when the magic-angle spinning rate exceeds 100 kHz S(3)APs begin outperforming SHAPs. This is especially true for low-gamma nuclei, such as Li-6 in paramagnetic Li-ion battery materials. Finally, we show how S3APs can be improved by combining multiple waveforms sweeping over multiple sidebands simultaneously, in order to produce inverted sideband profiles free from intensity biasing.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Tillett, W, et al.
(författare)
-
DYNAMICS OF NAIL PSORIASIS WITH GUSELKUMAB TREATMENT AND WITHDRAWAL IN ASSOCIATION WITH SKIN RESPONSE AND PATIENT-REPORTED OUTCOMES: A POST HOC ANALYSIS OF THE VOYAGE 2 PHASE 3 TRIAL
- 2022
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 830-830
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Nail psoriasis can be difficult to treat, affects ~50% of patients with psoriasis and can involve the nail matrix (pitting, leukonychia) and/or nail bed (onycholysis, splinter haemorrhages). Evidence suggests nail psoriasis may be associated with risk of developing psoriatic arthritis, in particular distal interphalangeal joint erosion.1–3 Data to Week (Wk) 24 from VOYAGE 1 and 2, two Phase 3 clinical trials, indicate that the anti-interleukin-23 monoclonal antibody guselkumab (GUS) is more effective than placebo and as effective as adalimumab in treating nail psoriasis.4 Furthermore, GUS is also associated with maintained Psoriasis Area and Severity Index (PASI) following treatment withdrawal in VOYAGE 2; however, nail response is not as well understood in this context.5ObjectivesThis VOYAGE 2 post hoc analysis evaluated nail response and its association with skin response and patient-reported outcomes (PROs) in two groups, one experiencing GUS withdrawal and the other receiving continuous GUS.MethodsPatients had moderate-to-severe plaque psoriasis and nail psoriasis, were initially randomised to GUS, and achieved PASI 90 at Wk 28. Patients were then re-randomised to placebo (GUS withdrawal) or GUS every 8 wks (GUS continuation). Nail Psoriasis Severity Index (NAPSI; grading the most affected nail), fingernail Physician’s Global Assessment (f-PGA), PASI and Dermatology Life Quality Index (DLQI) are reported as observed at Wk 0, 16, 24 and 48.ResultsAmong 209 patients, NAPSI, f-PGA, PASI and DLQI showed similar trends in both groups until Wk 24. All endpoints improved from baseline; and at Wk 24, patients in the GUS withdrawal and GUS continuation groups achieved a mean NAPSI of 1.7 and 1.8 (nail matrix 1.0 and 1.0; nail bed 0.7 and 0.8); f-PGA 0.9 and 0.9; PASI 0.6 and 0.6; and DLQI 2.2 and 2.3, respectively (Table 1). Nail changes continued to follow skin trends through Wk 48 (Figure 1); with GUS withdrawal, worsening of PASI and DLQI was proportionally greater than that of NAPSI and f-PGA; with GUS continuation, PASI and DLQI remained fairly stable, and NAPSI and f-PGA continued to improve. Nails were numerically slower to respond to GUS initiation and withdrawal than skin, with a more pronounced delay for nail matrix vs nail bed. In patients who sustained a PASI 90 response at Wk 48, despite GUS withdrawal, a high level of nail response was also maintained.Table 1.NAPSI, f-PGA, PASI and DLQI through Wk 48 in GUS withdrawal and GUS continuation groupsWk 0Wk 16Wk 24Wk 28Wk 48GUS withdrawal*GUSRPlacebon97969696NAPSI5.0 (2.1)2.5 (1.9)1.7 (1.9)1.9 (2.1)Nail matrix2.7 (1.3)1.5 (1.3)1.0 (1.2)0.9 (1.3)Nail bed2.2 (1.2)0.9 (1.0)0.7 (1.0)1.0 (1.1)n98979797f-PGA2.5 (0.8)1.3 (0.9)0.9 (0.8)1.1 (1.0)n101101100100PASI23.1 (9.0)1.3 (2.7)0.6 (1.4)5.2 (6.1)n101101100100DLQI14.5 (6.1)2.8 (4.1)2.2 (3.6)7.0 (7.4)GUS continuationGUSRGUSn108106107105NAPSI4.4 (1.8)2.4 (2.2)1.8 (2.0)1.2 (1.6)Nail matrix2.5 (1.2)†1.4 (1.3)1.0 (1.2)0.7 (1.0)Nail bed1.9 (1.2)1.0 (1.1)0.8 (1.0)0.5 (0.8)n108106107105f-PGA2.4 (0.9)1.1 (0.9)0.9 (0.9)0.7 (0.8)n108108108106PASI22.6 (8.8)1.2 (2.1)0.6 (1.1)1.3 (3.5)n107108108104DLQI14.3 (6.4)2.9 (4.2)2.3 (4.0)1.8 (3.4)Data are mean (standard deviation). *n=10 reinitiated GUS upon loss of 50% of Wk 28 PASI 90(at n=1 Wk 36, n=2 Wk 40, n=7 Wk 44); †n=107; R, re-randomisation of PASI 90 responders.ConclusionGUS treatment through Wk 48 improved nail psoriasis, skin psoriasis and PROs. When GUS was withdrawn, loss of response was slower in nails vs skin. These findings support that nail outcomes follow skin outcome trends with GUS treatment and that nail outcomes should contribute to evaluation of treatment efficacy and disease progression.2,3,6References[1]Robert B. Dermatology 2010; 221 Suppl 1: 1–5;[2]Antony A et al. J Rheumatol 2019; 46: 1097–102.[3]Wilson F et al. Arthritis Rheum 2009; 61: 233–39;[4]Foley P et al. JAMA Dermatol 2018; 154: 676–83;[5]Conrad C et al. AAD 2021. P26573.[6]Conrad C et al. Dermatol Ther 2022; 12: 233–41.AcknowledgementsThis analysis was funded by Janssen and medical writing support was provided by OPEN Health Medical Communications.Disclosure of InterestsWilliam Tillett Speakers bureau: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Alexander Egeberg Speakers bureau: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and JanssenPharmaceuticals, Consultant of: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and JanssenPharmaceuticals, Grant/research support from: Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, Enikö Sonkoly Speakers bureau: AbbVie, Eli Lilly, UCB, Janssen, Novartis, Sanofi and LEO Pharma, Grant/research support from: Pfizer, Patricia Gorecki Employee of: Janssen, Anna Tjärnlund Employee of: Janssen, Jozefien Buyze Employee of: Janssen, Sven Wegner Employee of: Janssen, Dennis McGonagle Speakers bureau: Abbvie, BMS, Celgene, Janssen, Novartis, Lilly, UCB, Grant/research support from: Abbvie, BMS, Celgene, Janssen, Novartis, Lilly, UCB
|
|
| 34. |
|
|
| 35. |
- Warnke, Clemens, et al.
(författare)
-
Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
- 2014
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 76:6, s. 792-801
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AI(JCV)) in the diagnosis of natalizumab-associated PML.Methods: AI(JCV) was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AI(JCV) was calculated as published.Results:Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AI(JCV) > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AI(JCV) > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI(JCV) > 1.5.Interpretation: Determination of the AI(JCV) could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. Ann Neurol 2014;76:792-801
|
|
| 36. |
|
|
| 37. |
- Yusuf, D, et al.
(författare)
-
The transcription factor encyclopedia
- 2012
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
-
Tidskriftsartikel (refereegranskat)
|
|
