2,059 research outputs found
Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUSTâAdalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial
BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. METHODS: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2âyears and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12âmonths. All participants will receive the standard weight-based dose of adalimumab or placebo: 20âmg biweekly (if <â30âkg) or 40âmg biweekly (if â„â30âkg). DISCUSSION: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12âmonths. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 201
Abnormal IgD and IgA1 O-glycosylation in hyperimmunoglobulinaemia D and periodic fever syndrome
In order to determine the glycosylation pattern for IgD, and to examine whether there are changes in the pattern of IgD and IgA1 O-glycosylation in patients with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) during acute febrile attacks and during periods of quiescence, serum was obtained from 20 patients with HIDS and 20 control subjects. In the HIDS group, serum was obtained either during an acute febrile episode (n = 9) or during a period of quiescence (n = 11). The O-glycosylation profiles of native and desialylated IgA1 and IgD were measured in an ELISA-type system using the lectins Helix aspersa and peanut agglutinin, which bind to alternative forms of O-glycan moieties. IgD is more heavily O-galactosylated and less O-sialylated than IgA1 in healthy subjects. HIDS is associated with more extensive O-galactosylation of IgD and a reduction in O-sialylation of both IgD and IgA1. These changes are present both during acute febrile attacks and periods of quiescence. The T cell IgD receptor is a lectin with binding affinity for the O-glycans of both IgD and IgA1. The observed changes in IgD and IgA1 O-glycosylation are likely to have a significant effect on IgD/IgA1âT cell IgD receptor interactions including basal immunoglobulin synthesis, and possibly myeloid IgD receptor-mediated cytokine release
Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems.
The use of human and veterinary pharmaceuticals is increasing. Over the past decade, there has been a proliferation of research into potential environmental impacts of pharmaceuticals in the environment. A Royal Society-supported seminar brought together experts from diverse scientific fields to discuss the risks posed by pharmaceuticals to wildlife. Recent analytical advances have revealed that pharmaceuticals are entering habitats via water, sewage, manure and animal carcases, and dispersing through food chains. Pharmaceuticals are designed to alter physiology at low doses and so can be particularly potent contaminants. The near extinction of Asian vultures following exposure to diclofenac is the key example where exposure to a pharmaceutical caused a population-level impact on non-target wildlife. However, more subtle changes to behaviour and physiology are rarely studied and poorly understood. Grand challenges for the future include developing more realistic exposure assessments for wildlife, assessing the impacts of mixtures of pharmaceuticals in combination with other environmental stressors and estimating the risks from pharmaceutical manufacturing and usage in developing countries. We concluded that an integration of diverse approaches is required to predict 'unexpected' risks; specifically, ecologically relevant, often long-term and non-lethal, consequences of pharmaceuticals in the environment for wildlife and ecosystems
Latest Results from the Heidelberg-Moscow Double Beta Decay Experiment
New results for the double beta decay of 76Ge are presented. They are
extracted from Data obtained with the HEIDELBERG-MOSCOW, which operates five
enriched 76Ge detectors in an extreme low-level environment in the GRAN SASSO.
The two neutrino accompanied double beta decay is evaluated for the first time
for all five detectors with a statistical significance of 47.7 kg y resulting
in a half life of (T_(1/2))^(2nu) = [1.55 +- 0.01 (stat) (+0.19) (-0.15)
(syst)] x 10^(21) years. The lower limit on the half-life of the 0nu beta-beta
decay obtained with pulse shape analysis is (T_(1/2))^(0_nu) > 1.9 x 10^(25)
[3.1 x 10^(25)] years with 90% C.L. (68% C.L.) (with 35.5 kg y). This results
in an upper limit of the effective Majorana neutrino mass of 0.35 eV (0.27 eV).
No evidence for a Majoron emitting decay mode or for the neutrinoless mode is
observed.Comment: 14 pages, revtex, 6 figures, Talk was presented at third
International Conference ' Dark Matter in Astro and Particle Physics' -
DARK2000, to be publ. in Proc. of DARK2000, Springer (2000). Please look into
our HEIDELBERG Non-Accelerator Particle Physics group home page:
http://www.mpi-hd.mpg.de/non_acc
Effect of multiple micronutrient-fortified bouillon on micronutrient status among women and children in the Northern Region of Ghana: Protocol for the Condiment Micronutrient Innovation Trial (CoMIT), a community-based randomized controlled trial
Exoplanets and SETI
The discovery of exoplanets has both focused and expanded the search for
extraterrestrial intelligence. The consideration of Earth as an exoplanet, the
knowledge of the orbital parameters of individual exoplanets, and our new
understanding of the prevalence of exoplanets throughout the galaxy have all
altered the search strategies of communication SETI efforts, by inspiring new
"Schelling points" (i.e. optimal search strategies for beacons). Future efforts
to characterize individual planets photometrically and spectroscopically, with
imaging and via transit, will also allow for searches for a variety of
technosignatures on their surfaces, in their atmospheres, and in orbit around
them. In the near-term, searches for new planetary systems might even turn up
free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor
additions and modification
Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world
[No abstract available
Flavourful Production at Hadron Colliders
We ask what new states may lie at or below the TeV scale, with sizable
flavour-dependent couplings to light quarks, putting them within reach of
hadron colliders via resonant production, or in association with Standard Model
states. In particular, we focus on the compatibility of such states with
stringent flavour-changing neutral current and electric-dipole moment
constraints. We argue that the broadest and most theoretically plausible
flavour structure of the new couplings is that they are hierarchical, as are
Standard Model Yukawa couplings, although the hierarchical pattern may well be
different. We point out that, without the need for any more elaborate or
restrictive structure, new scalars with "diquark" couplings to standard quarks
are particularly immune to existing constraints, and that such scalars may
arise within a variety of theoretical paradigms. In particular, there can be
substantial couplings to a pair of light quarks or to one light and one heavy
quark. For example, the latter possibility may provide a flavour-safe
interpretation of the asymmetry in top quark production observed at the
Tevatron. We thereby motivate searches for diquark scalars at the Tevatron and
LHC, and argue that their discovery represents one of our best chances for new
insight into the Flavour Puzzle of the Standard Model.Comment: 18 pp., 8 figures, references adde
Surface and Temporal Biosignatures
Recent discoveries of potentially habitable exoplanets have ignited the
prospect of spectroscopic investigations of exoplanet surfaces and atmospheres
for signs of life. This chapter provides an overview of potential surface and
temporal exoplanet biosignatures, reviewing Earth analogues and proposed
applications based on observations and models. The vegetation red-edge (VRE)
remains the most well-studied surface biosignature. Extensions of the VRE,
spectral "edges" produced in part by photosynthetic or nonphotosynthetic
pigments, may likewise present potential evidence of life. Polarization
signatures have the capacity to discriminate between biotic and abiotic "edge"
features in the face of false positives from band-gap generating material.
Temporal biosignatures -- modulations in measurable quantities such as gas
abundances (e.g., CO2), surface features, or emission of light (e.g.,
fluorescence, bioluminescence) that can be directly linked to the actions of a
biosphere -- are in general less well studied than surface or gaseous
biosignatures. However, remote observations of Earth's biosphere nonetheless
provide proofs of concept for these techniques and are reviewed here. Surface
and temporal biosignatures provide complementary information to gaseous
biosignatures, and while likely more challenging to observe, would contribute
information inaccessible from study of the time-averaged atmospheric
composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets.
Fixed figure conversion error
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