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Systemic therapies are typically combined with topical corticosteroids for the management of moderate-to-severe atopic dermatitis. Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2 that is being tested for atopic dermatitis. We aimed to assess the efficacy and safety of upadacitinib plus topical corticosteroids compared with placebo for the treatment of moderate-to-severe atopic dermatitis.In this randomised, double-blind, placebo-controlled, phase 3 trial (AD Up) adults (aged 18-75 years) and adolescents (aged 12-17 years) with chronic atopic dermatitis that was moderate to severe (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] score of ≥3, and weekly average Worst Pruritus Numerical Rating Scale score of ≥4 at baseline) were enrolled at 171 clinical centres across 22 countries in the Asia-Pacific region, Europe, the Middle East, North America, and Oceania. Patients were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily, all in combination with topical corticosteroids for 16 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity, geographical region, and age. Study investigators, study site personnel, and patients were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved at least a 75% reduction in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of improvement from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03568318, and is active, but not recruiting.Between Aug 9, 2018, and Dec 20, 2019, 901 patients were randomly assigned to receive upadacitinib 15 mg plus topical corticosteroids (n=300), upadacitinib 30 mg plus topical corticosteroids (n=297), or placebo plus topical corticosteroids (n=304). At week 16, the proportion of patients who had achieved EASI-75 was significantly higher in the upadacitinib 15 mg plus topical corticosteroid group (194 [65%] of 300 patients) and the upadacitinib 30 mg plus topical corticosteroids group (229 [77%] of 297 patients) than the placebo group (80 [26%] of 304 patients; adjusted difference in EASI-75 response rate vs placebo, 38·1% [95% CI 30·8-45·4] for the upadacitinib 15 mg group and 50·6% [43·8-57·4] for the upadacitinib 30 mg group; p0·0001 for both doses). The proportion of patients who had achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg plus topical corticosteroid group (119 [40%] patients) and upadacitinib 30 mg plus topical corticosteroid group (174 [59%] patients) than the placebo group (33 [11%] patients; adjusted difference in vIGA-AD response vs placebo, 28·5% [22·1-34·9] for the upadacitinib 15 mg group and 47·6% [41·1-54·0] for the upadacitinib 30 mg group; p0·0001 for both doses). During the double-blind period, upadacitinib 15 and 30 mg were well tolerated in combination with topical corticosteroids. The most frequently reported treatment-emergent adverse events (≥5% in any treatment group) were acne, nasopharyngitis, upper respiratory tract infection, oral herpes, elevation of blood creatine phosphokinase levels, headache, and atopic dermatitis. The incidence of acne was higher in the upadacitinib 15 mg (30 [10%] of 300 patients) and upadacitinib 30 mg (41 [14%] of 297 patients) groups than the placebo group (six [2%] of 304 patients). The incidence of adverse events leading to discontinuation of study drug (four [1%] patients in the upadacitinib 15 mg plus topical corticosteroids group, four [1%] patients in the upadacitinib 30 mg plus topical corticosteroids group, and seven [2%] patients in the placebo plus topical corticosteroids group) and serious adverse events (seven [2%] patients, four [1%] patients, and nine [3%] patients) were similar among treatment groups. No deaths were reported in any treatment group.Upadacitinib plus topical corticosteroids was well tolerated and superior to placebo plus topical corticosteroids. Upadacitinib as combination therapy had a positive benefit-risk profile in adults and adolescents with moderate-to-severe atopic dermatitis.AbbVie.

Contains fulltext : 225356.pdf (Publisher’s version ) (Closed access) BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD(TM)). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Wireless networks show several challenges not found in wired networks, due to the dynamics of data transmission. Besides, home wireless networks are managed by non-technical people, and providers do not implement full management services because of the difficulties of manually managing thousands of devices. Thus, automatic management mechanisms are desirable. However, such control mechanisms are hard to achieve in practice because we do not always have a model of the process to be controlled, or the behavior of the environment is dynamic. Thus, the control must adapt to changing conditions, and it is necessary to identify the quality of the control executed from the perspective of the user of the network service. This article proposes a control loop for transmission power and channel selection, based on Software Defined Networking and Reinforcement Learning (RL), and capable of improving Web Quality of Experience metrics, thus benefiting the user. We evaluate a prototype in which some Access Points are controlled by a single controller or by independent controllers. The control loop uses the predicted Mean Opinion Score (MOS) as a reward, thus the system needs to classify the web traffic. We proposed a semi-supervised learning method to classify the web sites into three classes (light, average and heavy) that groups pages by their complexity, i.e. number and size of page elements. These classes define the MOS predictor used by the control loop. The proposed web site classifier achieves an average score of 87 % ± 1 % , classifying 500 unlabeled examples with only fifteen known examples, with a sub-second runtime. Further, the RL control loop achieves higher Mean Opinion Score (up to 167% in our best result) than the baselines. The page load time of clients browsing heavy web sites is improved by up to 6.6x.

Wireless Networks have become ubiquitous to support the growing demand from mobile users, and other devices, like in the Internet of Things (IoT). This article proposes a Software-Defined Wireless Networking architecture specialized in 802.11 Wireless LANs, called Ethanol, which provides a more fine-grained control. Ethanol is the first wireless SDN architecture that extends the control to the user devices. Further, Ethanol allows intelligent white-box control with finer grain than the state of the art, since it is optimized for WiFi. The proposed architecture is evaluated on a prototype over three use cases. Ethanol can be deployed in any Access Point (AP) running embedded Linux, since it has a negligible overhead — up to 1% in memory and 0.1% in CPU usage. Our results show that Ethanol dynamically alter the throughput of an application up to 3x during a prioritization period, returning bandwidth to other applications outside this period. Only by controlling the best time to perform the handover, our results show about 45% improvement over the traditional signal-based handover process.

ROSI is a mobile robot designed to inspect belt conveyor machinery in the mining industry. The proposed system is a wheeled and tracked mobile platform equipped with a robotic manipulator and several sensors to allow execution of the scheduled tasks.

Introduction Les traitements systemiques sont generalement associes aux dermocorticoides (DC) afin d’obtenir un controle de la dermatite atopique (DA) moderee a severe. Nous avons evalue l’effet d’epargne en dermocorticoides d’upadacitinib, un inhibiteur de Janus kinase (JAK) oral presentant une inhibition plus importante de JAK 1 que de JAK 2, JAK 3 ou de la tyrosine kinase 2, sur la base des donnees issues de l’essai AD Up. Materiel et methodes Des adultes et adolescents (12 Resultats Au cours de la periode controlee versus placebo, de 16 semaines, le delai median jusqu’a l’arret des DC a ete de 44 jours, 37 jours et mediane non atteinte chez les patients recevant l’upadacitinib 15 mg, l’upadacitinib 30 mg, ou le placebo, respectivement, avec un nombre de jours moyen sans DC de 51,7 ; 60,7 ; et 30,6 jours (aucune utilisation de DC), respectivement. A la semaine 16, la moyenne hebdomadaire des evaluations quotidiennes a revele que 56,6 % (162/286), 67,7 % (194/287), et 37,9 % (106/280) des patients traites par upadacitinib 15 mg, upadacitinib 30 mg, ou placebo, respectivement, n’utilisaient plus de DC ; De plus, 39,3 % (112/286), 57,6 % (165/287), et 13,7 % (38/280) des patients recevant l’upadacitinib 15 mg, l’upadacitinib 30 mg, ou le placebo, respectivement, n’utilisaient pas de DC et avaient egalement obtenu une reponse EASI 75. Discussion Dans l’ensemble, le traitement par upadacitinib a entraine un arret rapide et prolonge des DC avec des taux eleves de blanchiment cutane de facon dose–dependante chez des adultes et adolescents atteints de DA moderee a severe.

In this Statement, the authors take a position on the waiver of intellectual property (IP) protection currently being considered by the members of the World Trade Organisation. The waiver was initiated by India and South Africa as a measure to enable rapid access to affordable medical products that are necessary to combat Covid-19. The initiative gained momentum after the US decided to support it. The authors do not consider this path to be expedient. The Statement presents factual and legal arguments why a comprehensive waiver of IP protection is unlikely to be a necessary and suitable measure towards the pursued objective. Overall, it argues that IP rights may so far have played an enabling and facilitating rather than hindering role in overcoming Covid-19. The global community might not be better off if IP rights are waived, neither during nor after the pandemic. There are more efficient and direct ways to supply developing countries with vaccines quickly – if the industrialised countries are willing to do their share. The Statement can be supported by filling in the form: https://forms.gle/c4kc8m9JE44AwjoJ7.

Background: Systemic therapies are typically combined with topical corticosteroids (TCS) in the management of moderate-to-severe atopic dermatitis (AD). Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2 being developed for AD. AD Up was designed to assess the efficacy and safety of UPA+TCS versus placebo (PBO)+TCS in adolescents and adults with moderate-to-severe AD. Methods: AD Up (ClinicalTrials.gov, NCT03568318) is an ongoing pivotal, phase 3, randomised, double-blinded, placebo-controlled, multicentre study that enrolled patients from 171 clinical centres across the Asia-Pacific region, Europe, Middle East, North America, and Oceania. Adolescents (aged 12–17 years) and adults (aged 18–75 years) with chronic AD (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, validated Investigator’s Global Assessment for AD [vIGA-AD™] ≥3, and Worst Pruritus Numerical Rating Scale [NRS] score ≥4) were eligible to participate. Patients were randomised (1:1:1) to receive UPA 15 mg, UPA 30 mg, or PBO once daily, all in combination with TCS (medium-potency TCS [or lowpotency TCS or topical calcineurin inhibitor for sensitive skin areas] until skin was clear or almost clear or for up to 3 consecutive weeks, followed by low-potency TCS for 7 days; if lesions returned or persisted, step-down approach was repeated), stratified by baseline disease severity, geographic region, and age using interactive response technology. Study investigators, study site personnel, and patients remained blinded throughout the study. Efficacy was analysed in the intention-to-treat population, defined as all patients who were randomised in the main study. The coprimary endpoints were proportion of patients achieving ≥75% reduction from baseline in EASI (EASI 75) at week 16 and proportion of patients achieving vIGA-AD of clear or almost clear with ≥2 grades of improvement (vIGA-AD 0/1) at week 16. Selected key secondary endpoints included proportions of patients achieving EASI 90 at weeks 4 and 16, EASI 75 at weeks 2 and 4, and percent Worst Pruritus NRS improvement ≥4 at weeks 1, 4, and 16. Safety was assessed via adverse event (AE) monitoring. Missing responses were handled based on nonresponder imputation incorporating multiple imputation to handle missing data due to coronavirus disease 2019 (COVID-19; NRI-C). Safety was analysed in all patients in the main study who received ≥1 dose of study drug. Findings: Between Aug 30, 2018, and Dec 20, 2019, 901 patients were randomised. At week 16, significantly greater proportions of patients treated with UPA 15 mg+TCS or UPA 30 mg+TCS than PBO+TCS achieved the coprimary endpoints—EASI 75 (64·6% [194 of 300 patients] and 77·1% [229 of 297] vs 26·4% [80 of 304]; adjusted difference vs PBO+TCS: 38·1% [95% CI 30·8–45·4] and 50·6% [43·8–57·4]; p