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ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; pConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients. ispartof: BIOMEDICINES vol:10 issue:10 ispartof: location:Switzerland status: published

Additional file 1: Detailed description of the monitoring process in RABBIT-SpA.

Additional file 1.

Additional file 1. Study design.

Additional file 2. MRI sequence parameters.

and S2 are presented in the Supplementary data file. (DOCX 25 kb)

Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human onoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed ignificant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.

Orientador: Fabiano Fruett Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação Resumo: A pandemia de Covid-19 trouxe novos desafios às instituições de ensino em todo o mundo, pois houve um súbito interesse por soluções de ensino a distância na oferta de disciplinas, incluindo as de ciência e tecnologia. O ensino a distância está impactando diretamente na formação dos profissionais que desenvolverão as soluções de IoT sob medida das quais residências, escritórios, empresas e cidades dependem cada vez mais. Independentemente disso, o treinamento em IoT precisa considerar as particularidades das comunicações sem fio, pois é essencial garantir a comunicação em qualquer solução de IoT. No entanto, esse treinamento é impactado pela dificuldade de realizar experimentos remotos que reproduzam o comportamento do canal sem fio. Além disso, o aprendizado dos principais conceitos teóricos da conectividade sem fio seria facilitado pela adoção de métodos práticos centrados no aluno, os chamados métodos de treinamento indutivos. Este trabalho apresenta um ambiente de emulação de redes remoto, de baixo custo e de código aberto, capaz de reproduzir o comportamento de links não guiados e de baixa potência sob diferentes configurações. O ambiente de emulação incorpora abordagens indutivas na experimentação com conectividade sem fio. O ambiente de emulação foi oferecido aos participantes de um curso de pós-graduação que ocorreu no primeiro semestre de 2020 e novamente no primeiro semestre de 2021. A análise dos resultados em relação a uma edição anterior do curso, quando o ambiente de emulação não foi utilizado, indica uma melhora substancial nas notas gerais. Uma pesquisa de final de curso com os alunos de 2020 e 2021 indicou que o ambiente de emulação contribuiu para a compreensão dos princípios que regem a conectividade sem fio. As evidências sugerem que este ambiente remoto é uma ferramenta útil para investigações acadêmicas das particularidades dos canais sem fio de baixa potência Abstract: Educational institutions around the world had to respond to the new challenges brought about by the Covid-19 pandemic. These included the need to adapt programs to the distance learning model, including those related to science and technology. Since then, distance or remote learning has had an impact on the training of the workforce that will develop the IoT solutions society will increasingly rely on. Training on IoT must consider the peculiarities of the wireless connectivity since, quite often, the development of IoT solutions stumbles upon it. Also, it can be difficult to run remote, controlled, repeatable experiments that reproduce a realistic behaviour of the signal. These are often done with the use of simulation software. Besides, several authors sustain that the adoption of learning methods centred on the student, also known as inductive training methods, could facilitate the absorption of theoretical concepts, here applied to wireless connectivity. This paper presents a remote, low-cost, open-source network emulation environment that incorporates inductive learning approaches, good for reproducing the behaviour of low power wireless links operating under different conditions and configurations. This emulation environment was offered at a postgraduate course that ran during the first semester of 2020 and again during the first semester of 2021. An analysis of the results against an earlier edition of the course, when the emulation environment was not used, indicated a substantial improvement in the overall grades. A survey carried out with the students at the end of the courses in 2020 and 2021 suggested that the emulation environment contributed to a better comprehension of the wireless connectivity principles. These findings implied that learners could use the emulation environment as a tool to investigate the particularities of low-power over-the-air channels Doutorado Telecomunicações e Telemática Doutor em Engenharia Elétrica CNPQ 161999/2018-2

Orientadores: José Antenor Pomilio, Saulo Finco Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação Resumo: Sistemas autônomos como dispositivos implantáveis, redes de sensores sem fio e sistemas embarcados requerem uma fonte de energia usualmente na forma de bateria ou supercapacitor. A miniaturização e a redução do consumo de potência em dispositivos eletrônicos modernos permite o uso de fontes alternativas como forma de estender a vida útil destes sistemas. A energia pode ser fornecida pelo ambiente, na forma de luz solar, vibração, calor ou ondas eletromagnéticas. O processo de captação e adequação desta energia é chamado de extração ou coleta de energia. O desenvolvimento de sistemas de extração de energia envolve desafios. Algumas fontes fornecem apenas dezenas de milivolts ou nanoamperes. Uma abordagem para extrair energia de fontes de baixa tensão é o projeto de osciladores que possam operar nestas condições. Esta área do conhecimento vem sendo objeto de intensa pesquisa. Várias estratégias são utilizadas, e sistemas operando com até 3,5 mV são descritos. Há, contudo um compromisso entre mínima tensão de operação, capacidade de potência e volume/complexidade. O comportamento de osciladores em tensão ultrabaixa é altamente não-linear e dependente dos parâmetros dos dispositivos e condições de operação. Técnicas convencionais são inadequadas para a análise destes circuitos em situação tão extrema. A impossibilidade de prever com precisão aceitável parâmetros como excursão de tensão e frequência de oscilação e a falta de compreensão mais profunda do mecanismo de funcionamento tornam difícil a especificação dos blocos seguintes ao oscilador no sistema de extração de energia. Este trabalho propõe a aplicação do oscilador com acoplamento nas portas como um módulo de extração de energia de tensão ultrabaixa. O comportamento do circuito é tipicamente como multivibrador astável e uma modelagem utilizando a teoria de oscilações não lineares é apresentada, tanto para circuitos com transistores MOS (MOSFETs) como com transistores bipolares (BJTs). A validade do modelo é verificada através de experimentos com protótipos discretos e uma boa concordância é obtida entre a teoria e a prática. A topologia necessita de uma tensão nas bases dos BJTs ou portas de MOSFETs convencionais de forma que a oscilação possa se iniciar. Um novo módulo, chamado de bloco de partida, é proposto que deriva esta tensão de polarização da fonte de alimentação, tornando o circuito independente de uma tensão preexistente. Um modelo linear para este bloco é apresentado e verificado através da caracterização de um protótipo. Experimentos com circuitos discretos utilizando o bloco de partida mostram que os osciladores podem iniciar sua operação com uma tensão única tão baixa quanto 50 mV. Os protótipos com BJTs e MOSFETs foram capazes de fornecer 173 µW e 560 µW para uma alimentação de 100 mV, respectivamente, demonstrando que a topologia pode ser uma alternativa competitiva em termos de desempenho, tensão de operação e complexidade quando comparada a outras já apresentadas na literatura Abstract: Autonomous systems, such as implanted devices, wireless sensor networks, and embedded systems, require an energy source which is usually in the form of a battery or a supercapacitor. The miniaturization and reduction of power consumption in modern electronic devices enables the use of alternative energy sources as a way of extending the life-span of these systems. The energy can be supplied by the environment, such as sunlight, vibration, heat, or RF waves. The process of extracting and fitting this energy is usually called energy harvesting. The development of energy harvesting systems presents challenges. Some sources can only supply dozens of millivolts or nanoamperes. One approach to harvest the energy of low-voltage sources is by designing oscillators that can operate in these conditions. This knowledge area is subject of intensive research. Many approaches are proposed, and systems operating with voltages as low as 3.5 mV are described. However, there is a tradeoff between minimum operating voltage, power capacity and volume/complexity. The behavior of oscillators at ultralow voltage is very nonlinear and dependent of the device parameters and operational conditions. Conventional techniques are not able to give reasonable results in the analysis of circuits in such extreme levels. The lack of a prediction of parameters like voltage excursion and oscillation frequency with acceptable precision and a deeper understanding of the working mechanism turn difficult the specification of the blocks that follow the oscillator in the energy harvesting system. This work proposes the application of the oscillator with coupling at the gates as an ultralow voltage energy harvesting module. The behavior of the circuit is typically as astable multivibrator and a modeling using the theory of nonlinear oscillations is presented, when applying MOS transistors (MOSFETs) or bipolar junction transistors (BJTs). The validity of the models is verified through experiments with discrete prototypes and good agreement is found between theory and practice. The topology needs a voltage biasing at the bases of the BJTs or gates of the conventional MOSFETs in order it starts oscillating. A new module, called starting block, is proposed that derives this biasing voltage from the voltage source, turning the circuit independent of a preexistent voltage. A linear model for this block is presented and checked by the characterization of a prototype. Experiments with discrete prototypes with the starting block show that the oscillators can start operating with a unique source as low as 50 mV. Prototypes with BJTs and MOSFETs were able to provide 173 µW and 560 µW from a supply of 100 mV, respectively, demonstrating that the proposed topology can be a competitive option regarding performance, operating voltage and complexity when compared with those previously presented Doutorado Eletrônica, Microeletrônica e Optoeletrônica Doutor em Engenharia Elétrica