303 research outputs found
Risk assessment-led characterisation of the SiteChar UK North Sea site for the geological storage of CO2
Risk assessment-led characterisation of a site for the geological storage of CO2 in the UK northern North Sea was performed for the EU SiteChar research project as one of a portfolio of sites. Implementation and testing of the SiteChar project site characterisation workflow has produced a ‘dry-run’ storage permit application that is compliant with regulatory requirements. A site suitable for commercial-scale storage was characterised, compatible with current and future industrial carbon dioxide (CO2) sources in the northern UK. Pre-characterisation of the site, based on existing information acquired during hydrocarbon exploration and production, has been achieved from publicly available data. The project concept is to store captured CO2 at a rate of 5 Mt per year for 20 years in the Blake Oil Field and surrounding Captain Sandstone saline aquifer. This commercial-scale storage of 100 Mt CO2 can be achieved through a storage scenario combining injection of CO2 into the oil field and concurrent water production down-dip of the field. There would be no encroachment of supercritical phase CO2 for more than two kilometres beyond the field boundary and no adverse influence on operating hydrocarbon fields provided there is pressure management.
Components of a storage permit application for the site are presented, developed as far as possible within a research project. Characterisation and technical investigations were guided by an initial assessment of perceived risks to the prospective site and a need to provide the information required for the storage permit application. The emphasis throughout was to reduce risks and uncertainty on the subsurface containment of stored CO2, particularly with respect to site technical performance, monitoring and regulatory issues, and effects on other resources. The results of selected risk assessment-led site characterisation investigations and the subsequent risk reassessments are described together with their implications for the understanding of the site. Additional investigations are identified that could further reduce risks and uncertainties, and enable progress toward a full storage permit application. Permit performance conditions are presented as SiteChar-recommended useful tools for discussion between the competent authority and operator
Universities’ social responsibility through the lens of strategic planning: A content analysis
This paper examines the degree of social responsibility integration in Italian public universities’ medium and long-term planning documents. We adopted a qualitative approach, applying the content analysis technique to a selected sample of 20 strategic plans issued by Italian large and mega universities. The coding instrument was developed considering the 17 Sustainable Development Goals (SDGs) contained in the United Nations 2030 Agenda. Therefore, we identified 17 categories and 103 key symbols. The analysis undertaken showed that to date, Italian public universities still pay little attention in their planning documents to objectives regarding the multiple dimensions of Social Responsibility, mainly in relation to environmental issues, a failure detrimental to University Social Responsibility implementation and achievement. However, there is a greater sensitivity to Social Responsibility issues in some universities’ planning documents, therefore also more mature practices can be identified, showing universities that have institutionalized the concept of sustainability in their planning documents
Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N6-Formyllysine That Is Refractory to Histone Deacetylases
Aberrant protein modifications play an important role in the pathophysiology of many human diseases, in terms of both dysfunction of physiological modifications and the formation of pathological modifications by reaction of proteins with endogenous electrophiles. Recent studies have identified a chemical homolog of lysine acetylation, N[superscript 6]-formyllysine, as an abundant modification of histone and chromatin proteins, one possible source of which is the reaction of lysine with 3′-formylphosphate residues from DNA oxidation. Using a new liquid chromatography-coupled to tandem mass spectrometry method to quantify all N[superscript 6]-methyl-, -acetyl- and -formyl-lysine modifications, we now report that endogenous formaldehyde is a major source of N[superscript 6]-formyllysine and that this adduct is widespread among cellular proteins in all compartments. N[superscript 6]-formyllysine was evenly distributed among different classes of histone proteins from human TK6 cells at 1–4 modifications per 10[superscript 4] lysines, which contrasted strongly with lysine acetylation and mono-, di-, and tri-methylation levels of 1.5-380, 5-870, 0-1400, and 0-390 per 10[superscript 4] lysines, respectively. While isotope labeling studies revealed that lysine demethylation is not a source of N[superscript 6]-formyllysine in histones, formaldehyde exposure was observed to cause a dose-dependent increase in N[superscript 6]-formyllysine, with use of [[superscript 13]C,[superscript 2]H[subscript 2]]-formaldehyde revealing unchanged levels of adducts derived from endogenous sources. Inhibitors of class I and class II histone deacetylases did not affect the levels of N[superscript 6]-formyllysine in TK6 cells, and the class III histone deacetylase, SIRT1, had minimal activity (<10%) with a peptide substrate containing the formyl adduct. These data suggest that N[superscript 6]-formyllysine is refractory to removal by histone deacetylases, which supports the idea that this abundant protein modification could interfere with normal regulation of gene expression if it arises at conserved sites of physiological protein secondary modification
Nonlinear Quantum Photonics with a Tin-Vacancy Center Coupled to a One-Dimensional Diamond Waveguide
Color-centers integrated with nanophotonic devices have emerged as a
compelling platform for quantum science and technology. Here we integrate
tin-vacancy centers in a diamond waveguide and investigate the interaction with
light at the single-photon level. We observe single-emitter induced extinction
of the transmitted light up to 25% and measure the nonlinear effect on the
photon statistics. Furthermore, we demonstrate fully tunable interference
between the reflected single-photon field and laser light back-scattered at the
fiber end and show the corresponding controlled change between bunched and
anti-bunched photon statistics in the reflected field
Incidence of major adverse cardiovascular events in patients with rheumatoid arthritis treated with JAK-inhibitors compared to bDMARDs: data from an international collaboration of registries (the "JAK-pot'' study)
Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.
BackgroundEmerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST).Methods and findingsThe primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD (3,366 (95% UI: [1,465, 5,742] p ConclusionsCompared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels
Data From an International Collaboration of Registries
Funding Information: Supported by AbbVie, Galapagos, Pfizer, and Eli Lilly. Publisher Copyright: © 2025 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: Our objective was to assess the incidence of major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA) treated with JAK inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), or biologic disease-modifying antirheumatic drugs with other modes of action (bDMARD-OMA) in a multicountry, real-world population. Methods: Patients with RA from 15 registries in the JAK-pot collaboration were included. MACE incidence was analyzed using two approaches: a within-registry analysis aggregating country-specific estimates from registers with >25 incident MACEs through meta-analysis and an individual-level data combined analysis. We used adjusted linear mixed Poisson regression to obtain incidence rate ratios (IRRs) of MACEs between treatment groups, accounting for multiple treatment courses. Results: The study included 73,008 treatment courses (16,417 JAKi, 35,373 TNFi, and 21,218 bDMARD-OMA) and 828 incident MACEs among 51,233 patients. Median follow-up time was 1.3 years, with most of the follow-up concentrated in the first two years of treatment. Incidence rates were 7.0, 7.6, and 11.8 per 1,000 person-years for JAKi, TNFi, and bDMARD-OMA, respectively. Compared to TNFi, JAKi (within-registry adjusted IRR 0.89, 95% confidence interval [CI] 0.63–1.25) had similar incidence rates of MACEs and bDMARD-OMA had higher rates (within-registry adjusted IRR 1.35, 95% CI 1.10–1.66). Combined analysis showed similar results. Conclusion: Observational data from the JAK-pot collaboration show no evidence of an increase in cardiovascular events during the first two years of use with JAKi compared to TNFi in the general RA population.publishersversioninpres
Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration
Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe
Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe
This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021–April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations
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