The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility.
We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib ...treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety JADE REGIMEN: National Clinical Trial 03627767).
Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy).
Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events.
The definition of protocol-defined flare was not established, limiting the generalizability of findings.
Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response.
The ubiquity, large bandwidth, and spatial diversity of the fifth generation (5G) cellular signal render it a promising candidate for accurate positioning in indoor environments where the global ...navigation satellite system (GNSS) signal is absent. In this paper, a joint angle and delay estimation (JADE) scheme is designed for 5G picocell base stations (gNBs) which addresses two crucial issues to make it both effective and efficient in realistic indoor environments. Firstly, the direction-dependence of the array modeling error for picocell gNB as well as its impact on JADE is revealed. This error is mitigated by fitting the array response measurements to a vector-valued function and pre-calibrating the ideal steering-vector with the fitted function. Secondly, based on the deployment reality that 5G picocell gNBs only have a small-scale antenna array but have a large signal bandwidth, the proposed scheme decouples the estimation of time-of-arrival (TOA) and direction-of-arrival (DOA) to reduce the huge complexity induced by two-dimensional joint processing. It employs the iterative-adaptive-approach to resolve multipath signals in the TOA domain, followed by a conventional beamformer to retrieve the desired line-of-sight DOA. By further exploiting a dimension-reducing pre-processing module and accelerating spectrum computing by fast Fourier transforms, an efficient implementation is achieved for real-time JADE. Numerical simulations demonstrate the superiority of the proposed method in terms of DOA estimation accuracy. Field tests show that a triangulation positioning error of 0.44 m is achieved for 90% cases using only DOAs estimated at two separated receiving points.
Objective
To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse.
Methods
We induced SE by administering homocysteine 16‐18 hours after cobalt (Co) implantation. SE was ...monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro‐Jade C staining.
Results
Cobalt triggered seizures in a dose‐dependent manner (median effective dose, ED50 = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spike‐wave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic‐clonic movements, which were accompanied by generalized rhythmic spike‐wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro‐Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus.
Significance
We have developed a mouse model of severe, refractory cortical‐onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.
This paper describes, from motivations and main objectives to actual implementation, a novel agent-oriented programming language called JADEL. JADEL is designed to support the effective ...implementation of JADE agents and multi-agent systems in the scope of real-world model-driven development because it concretely helps developers by natively supporting agent-oriented abstractions, and because it is based on mature industrial-strength technologies. The four core abstractions that JADEL supports, namely agents, behaviours, communication ontologies, and interaction protocols, are presented by gradually introducing the specific syntaxes that the language provides for them. In the last part of the paper, a complete example of a simple JADEL multi-agent system is presented and discussed. Such an example is a well-known example from the official distribution of JADE and many programmers learned the basics of JADE from it. The choice of this example allows comparing JADEL source code with reference Java source code using JADE, and it clearly emphasizes the practical advantages of agent-oriented programming.
Section 1 introduces and motivates the presented work. Section 2 surveys major AOP languages and, even if it cannot be considered exhaustive, it highlights the specific features of selected languages that have been relevant for the design of JADEL. Section 3 provides an overview of the features of JADE that are supported by JADEL. Section 4 presents the language in details by discussing main supported abstractions, and by specifying its formal syntax. Section 5 presents the most interesting parts of a complete example of the use of JADEL to develop a simple multi-agent system. Finally, Section 6 concludes the paper with a discussion of the current state of the presented work, and a preliminary assessment of the proposed language.
Identifying the origin of jadeite jades has become increasingly important from both mineral resource and metamorphic geology perspectives. In this study, we differentiate Myanmar gem-quality ...blue-water jadeite jades from their Guatemala counterparts via integrating various non-destructive spectrographic techniques, including X-ray fluorescence (XRF), Ultraviolet-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. Our results show that the Myanmar blue-water jadeite jades are structurally homogenous with very few impurities, while their Guatemala counterparts commonly have a yellowish margin with scattered white albite and disseminated greenish inclusions of omphacite and (minor) aegirine-augite. Geochemically, the UV absorption spectral data indicate that the Guatemala samples have higher total Fe and Fe2+ contents, but lower Fe3+ content than the Myanmar samples. The Guatemala samples also have higher omphacite content (lower molar Na/(Na+Ca) ratio, as reflected by the lower IR absorption peak wavenumber) and higher heterogeneity (as reflected by the ~680 cm−1 Raman peak shift difference) than that from Myanmar. Major differences are also discovered in the blue series (Myanmar: 0–0.7 cm−1; Guatemala: 1.7–3.2 cm−1) and blue-green series (Myanmar: 6.9 cm−1; Guatemala 13.7 cm−1) of the Raman peak shift difference, which altogether can provide a novel, nondestructive method for distinguishing blue-water jadeite jades from different origins.
Differential evolution (DE) is a population-based metaheuristic search algorithm that optimizes a problem by iteratively improving a candidate solution based on an evolutionary process. Such ...algorithms make few or no assumptions about the underlying optimization problem and can quickly explore very large design spaces. DE is arguably one of the most versatile and stable population-based search algorithms that exhibits robustness to multi-modal problems. In the field of structural engineering, most practical optimization problems are associated with one or several behavioral constraints. Constrained optimization problems are quite challenging to solve due to their complexity and high nonlinearity. In this work we examine the performance of several DE variants, namely the standard DE, the composite DE (CODE), the adaptive DE with optional external archive (JADE) and the self-adaptive DE (JDE and SADE), for handling constrained structural optimization problems associated with truss structures. The performance of each DE variant is evaluated by using five well-known benchmark structures in 2D and 3D. The evaluation is done on the basis of final optimum result and the rate of convergence. Valuable conclusions are obtained from the statistical analysis which can help a structural engineer in practice to choose the suitable algorithm for such kind of problems.
A prompt and efficient DNA damage response (DDR) eliminates the detrimental effects of DNA lesions in eukaryotic cells. Basic and preclinical studies suggest that the DDR is one of the primary ...anti‐cancer barriers during tumorigenesis. The DDR involves a complex network of processes that detect and repair DNA damage, in which long non‐coding RNAs (lncRNAs), a new class of regulatory RNAs, may play an important role. In the current study, we identified a novel lncRNA, lncRNA‐JADE, that is induced after DNA damage in an ataxia‐telangiectasia mutated (ATM)‐dependent manner. LncRNA‐JADE transcriptionally activates Jade1, a key component in the HBO1 (human acetylase binding to ORC1) histone acetylation complex. Consequently, lncRNA‐JADE induces histone H4 acetylation in the DDR. Markedly higher levels of lncRNA‐JADE were observed in human breast tumours in comparison with normal breast tissues. Knockdown of lncRNA‐JADE significantly inhibited breast tumour growth in vivo. On the basis of these results, we propose that lncRNA‐JADE is a key functional link that connects the DDR to histone H4 acetylation, and that dysregulation of lncRNA‐JADE may contribute to breast tumorigenesis.
ATM activation upon DNA damage induces the long non‐coding RNA lncRNA‐JADE, which associates with BRCA1 to stimulate expression of JADE1 and hence histone H4 acetylation. LncRNA‐JADE is highly expressed in breast cancer and required for tumour growth in vivo.
We tested 288 pieces of the polished cabochon jadeite-jade with high quality green and smooth surfaces using the colorimeter Color i5 based on the CIE 1976 L＊a＊b＊ uniform color space. The color ...changes after alternating three CIE standard light sources D65, A and CWF were compared, and the degree of metamerism was evaluated. The results show that the CIE standard light sources D65, A and CWF increase the chroma of green and turn bluish green into vivid green, which are similar or to nearly colorless and transparent glass-like samples with fine textures. When the three light sources were individually alternated, the lightness of the jadeite-jades showed little change, but the tone changed significantly. Metamerism occurred only in 3 pairs among the 16 samples that were selected by cluster analysis for quality, and the metamerism colors were highly consistent of L＊D65∈（43.47, 46.75）, C＊D65∈（65.20, 68.80） and ho＊D65∈（138.10, 140.23）. We can conclude that the jadeite-jade green gradually turns to blue when the color temperature of the light source increases. But when considering both the light sources and the samples, D65 is more suitable to be the light source of jadeite-jade green when compared with the light sources CWF and A. Compared with the CIE standard green and high chroma green, high-quality jadeite-jade green has a slight yellow tone, low lightness and high chroma. The special metamerism index decreased to 1 when the light source alternated among D65, A and CWF. Therefore, the color of jadeite-jade green might be slightly influenced by alternating of the light sources.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with high prevalence and a complex pathophysiology. This relapsing and remitting skin disorder has many negative consequences on the ...patient's quality of life and that of his family. Until now, moderate-to-severe AD treatment was a symptomatic one, using skin emollients, topical corticosteroids, phototherapy, antihistamines and systemic drugs - immune suppressants and other systemic treatments (dupilumab). Starting from 2021, abrocitinib, a Janus kinase-1 inhibitor, was approved for the treatment of moderate-to-severe cases of AD in Europe, in adults. Multiple phase three studies (JADE MONO-1 NCT03349060; JADE MONO-2 NCT03575871; JADE TEEN NCT03796676; JADE COMPARE; GOODERHAM; JADE EXTEND) have yielded positive results in adults and adolescents suffering from this disease, with efficacy, a good tolerance, safe profile, and with generally mild side effects. The positive results were obtained even starting from the first stages of the oral drug administration. The low frequency of side effects and the advantage of having an orally administered medication makes abrocitinib an important additional tool for the treatment of moderate-to-severe forms of AD.
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