Objectives To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.Methods Two phase 3,... Show moreObjectives To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.Methods Two phase 3, double-blind randomised controlled trials including patients with inadequate responses to methotrexate (contRAst 1) or conventional synthetic/biologic disease-modifying antirheumatic drugs (cs/bDMARDs; contRAst 2). Patients received background csDMARDs. Through a testing hierarchy, subcutaneous otilimab (90/150 mg once weekly) was compared with placebo for week 12 endpoints (after which, patients receiving placebo switched to active interventions) or oral tofacitinib (5 mg two times per day) for week 24 endpoints. Primary endpoint: proportion of patients achieving an American College of Rheumatology response ≥20% (ACR20) at week 12.Results The intention-to-treat populations comprised 1537 (contRAst 1) and 1625 (contRAst 2) patients. Primary endpoint: proportions of ACR20 responders were statistically significantly greater with otilimab 90 mg and 150 mg vs placebo in contRAst 1 (54.7% (p=0.0023) and 50.9% (p=0.0362) vs 41.7%) and contRAst 2 (54.9% (p<0.0001) and 54.5% (p<0.0001) vs 32.5%). Secondary endpoints: in both trials, compared with placebo, otilimab increased the proportion of Clinical Disease Activity Index (CDAI) low disease activity (LDA) responders (not significant for otilimab 150 mg in contRAst 1), and reduced Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Benefits with tofacitinib were consistently greater than with otilimab across multiple endpoints. Safety outcomes were similar across treatment groups.Conclusions Although otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib. Show less
BACKGROUND: Domiciliary measurements of airflow obstruction and inflammation may assist healthcare teams and patients in determining asthma control and facilitate self-management. OBJECTIVE: To... Show moreBACKGROUND: Domiciliary measurements of airflow obstruction and inflammation may assist healthcare teams and patients in determining asthma control and facilitate self-management. OBJECTIVE: To evaluate parameters derived from domiciliary spirometry and fractional exhaled nitric oxide (FENO) in monitoring asthma exacerbations and control.METHODS: Patients with asthma were provided with hand-held spirometry and FENO devices in addition to their usual asthma care. Patients were instructed to perform twice-daily measurements for 1 month. Daily symptoms and medication change were reported through a mobile health system. The Asthma Control Questionnaire was completed at the end of the monitoring period.RESULTS: One hundred patients had spirometry, of which 60 were given additional FENO devices. Compliance rates for twice-daily measurements were poor (median [interquartile range], 43% [25%-62%] for spirometry; 30% [3%-48%] for FENO); at least 15% of patients took little or no spirometry measurements and 40% rarely measured FENO. The coefficient of variation (CV) values in FEV1 and FENO were higher, and the mean % personal best FEV1 lower in those who had major exacerbations compared with those without (P < .05). FENO CV and FEV1 CV were associated with asthma exacerbation during the monitoring period (area under the receiver-operating characteristic curve, 0.79 and 0.74, respectively). Higher FENO CV also predicted poorer asthma control (area under the receiver-operating char-acteristic curve, 0.71) at the end of the monitoring period. Show less
The foundations of today’s societies are provided by manufactured capital accumulation driven by investment decisions through time. Reconceiving how the manufactured assets are harnessed in the... Show moreThe foundations of today’s societies are provided by manufactured capital accumulation driven by investment decisions through time. Reconceiving how the manufactured assets are harnessed in the production–consumption system is at the heart of the paradigm shifts necessary for long-term sustainability. Our research integrates 50 years of economic and environmental data to provide the global legacy environmental footprint (LEF) and unveil the historical material extractions, greenhouse gas emissions, and health impacts accrued in today’s manufactured capital. We show that between 1995 and 2019, global LEF growth outpaced GDP and population growth, and the current high level of national capital stocks has been heavily relying on global supply chains in metals. The LEF shows a larger or growing gap between developed economies (DEs) and less-developed economies (LDEs) while economic returns from global asset supply chains disproportionately flow to DEs, resulting in a double burden for LDEs. Our results show that ensuring best practice in asset production while prioritizing well-being outcomes is essential in addressing global inequalities and protecting the environment. Achieving this requires a paradigm shift in sustainability science and policy, as well as in green finance decision-making, to move beyond the focus on the resource use and emissions of daily operations of the assets and instead take into account the long-term environmental footprints of capital accumulation. Show less
Soil viral ecology is a growing research field; however, the state of knowledge still lags behind that of aquatic systems. Therefore, to facilitate progress, the first Soil Viral Workshop was held... Show moreSoil viral ecology is a growing research field; however, the state of knowledge still lags behind that of aquatic systems. Therefore, to facilitate progress, the first Soil Viral Workshop was held to encourage international scientific discussion and collaboration, suggest guidelines for future research, and establish soil viral research as a concrete research area. The workshop took place at Søminestationen, Denmark, between 15 and 17th of June 2022. The meeting was primarily held in person, but the sessions were also streamed online. The workshop was attended by 23 researchers from ten different countries and from a wide range of subfields and career stages. Eleven talks were presented, followed by discussions revolving around three major topics: viral genomics, virus-host interactions, and viruses in the soil food web. The main take-home messages and suggestions from the discussions are summarized in this report. Show less
Arithmetic geometry concerns the number-theoretic properties of geometric objects defined by polynomials. Mathematicians are interested in the rational solutions to these geometric objects. However... Show moreArithmetic geometry concerns the number-theoretic properties of geometric objects defined by polynomials. Mathematicians are interested in the rational solutions to these geometric objects. However, it is usually very difficult to answer questions like this.A. Beilinson and S. Bloch conjectured a very general height theory in 1980s, which was used by B. Gross and R. Schoen in their study of the Gross-Schoen cycles. The height of canonical Gross-Schoen cycles is conjectured to be non-negative. This was verified when the curve is an elliptic or hyperelliptic curve, while very few are known in the non-hyperelliptic case.During my PhD study, I study the Beilinson-Bloch height of canonical Gross-Schoen cycles on curves with an emphasis on the genus 3 case (almost all genus 3 curves are non-hyperelliptic). I studied its unboundedness and singular properties, and did explicit computation for the height of the canonical Gross-Schoen cycle of a specific plane quartic curve.The method used in my thesis should be helpful for verifications. Show less
