Objective
Recent studies have uncovered diverse cell types and states in the rheumatoid arthritis (RA) synovium; however, limited data exist correlating these findings with patient‐level clinical ...information. Using the largest cohort to date with clinical and multicell data, we determined associations between RA clinical factors with cell types and states in the RA synovium.
Methods
The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited patients with active RA who were not receiving disease‐modifying antirheumatic drugs (DMARDs) or who had an inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint, and tissue were disaggregated and processed with a cellular indexing of transcriptomes and epitopes sequencing pipeline from which the following cell type percentages and cell type abundance phenotypes (CTAPs) were derived: endothelial, fibroblast, and myeloid (EFM); fibroblasts; myeloid; T and B cells; T cells and fibroblasts (TF); and T and myeloid cells. Correlations were measured between RA clinical factors, cell type percentage, and CTAPs.
Results
We studied 72 patients (mean age 57 years, 75% women, 83% seropositive, mean RA duration 6.6 years, mean Disease Activity Score‐28 C‐reactive Protein 3 DAS28‐CRP3 score 4.8). Higher DAS28‐CRP3 correlated with a higher T cell percentage (P < 0.01). Those receiving MTX and not a biologic DMARD (bDMARD) had a higher percentage of B cells versus those receiving no DMARDs (P < 0.01). Most of those receiving bDMARDs were categorized as EFM (57%), whereas none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, or DAS28‐CRP3.
Conclusion
In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This article summarizes the results of the 6–7 July Workshop on Human Language Technology and Knowledge Management held in Toulouse, France. It describes invited keynotes, presentations, and results ...of brainstorming sessions to create a technology road map for this important area. The group also articulated grand challenges in human language technology and solutions to these challenges that could benefit facilities for knowledge discovery, access, and exploitation.
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CEKLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Efficient, effective and intuitive access to multimedia information is essential for business, education, government and leisure. Unfortunately, interface design typically does not account for users ...with disabilities, estimated at 40 million in America alone. Given broad societal needs, our community has a social responsibility to provide universal designs that ensure efficient and effective access for all to heterogeneous and increasingly growing repositories of global information. This article describes information access functions, discusses associated grand challenges, and outlines potential benefits of technologies that promise to increase overall accessibility and success of interaction with multimedia. The article concludes by projecting the future of multimodal technology via a roadmap of multimodal resources, methods, and systems from 2003 through 2006. PUBLICATION ABSTRACT
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
...experiments with C-1 7s' flight formation (fig.\ng., space-operations control, data-processing centers, and infrastructure-process energy) a second priority. * Employ a systems approach that ...subjects solutions to a businesscase analysis prior to adoption and that considers interdependencies across the domains of air, space, cyberspace, and infrastructure, employing evaluation metrics to guide investments that comprehensively consider fully burdened costs and life-cycle costs. * Accelerate assessment and transition through the employment of test beds such as experimental RPAs, or select bases that can pilot operations as well as process energy solutions. * Create relevant energy education and training and develop a culture of energy understanding that motivates the desired behavior of communities to assure an energy advantage. Because of its pervasive nature, energy is a shared responsibility, and the realization of the Energy Horizons vision will demand a full team effort to realize the "assured energy advantage" in the joint and coalition fight. By carefully focusing on the near term, midterm, and far term as a deliberate leader, fast follower, or watcher, and by working in full partnership with other services and agencies, the Air Force can more rapidly and efficiently advance its Energy Horizons. ...Energy Horizons helps our service ensure not only energy robustness, resiliency, and readiness but also concomitant efficiency in peacetime operations, independence of action during humanitarian and disaster relief, and military superiority during conflict.
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summarization entails analysis of source material, selection of key information, condensation of this, and generation of a compact summary form. While there have been many investigations into the ...automatic summarization of text, relatively little attention has been given to the summarization of information from structured information sources such as data or knowledge bases, despite this being a desirable capability for a number of application areas including report generation from databases (e.g. weather, financial, medical) and simulations (e.g. military, manufacturing, economic). After a brief introduction indicating the main elements of summarization and referring to some illustrative approaches to it, this article considers specific issues in the generation of text summaries of event data. It describes a system, SumGen, which selects key information from an event database by reasoning about event frequencies, frequencies of relations between events, and domain specific importance measures. The article describes how SumGen then aggregates similar information and plans a summary presentation tailored to a stereotypical user. Finally, the article evaluates SumGen performance, and also that of a much more limited second summariser, by assessesing information extraction by 22 human subjects from both source and summary texts. This evaluation shows that the use of SumGen reduces average sentence length by approx. 15%, document length by 70%, and time to perform information extraction by 58%.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The demand for ultrasound guided injections for musculoskeletal presentations has increased in recent years as practitioners and patients seek verification of needle position. Musculoskeletal ...management pathways regularly include injection therapy for pain relief and are sometimes indicated as a single intervention but may need to be supported by rehabilitation. Workload in radiology departments has expanded in volume and complexity as radiologists perform new interventional procedures that require medical expertise. Innovative responses are required to meet the demand for ultrasound guided musculoskeletal injections; one option is offering appropriate education to musculoskeletal sonographers, enabling them to extend their current scope of practice. The role of the extended scope physiotherapist in the United Kingdom provides evidence that role diversification can produce excellent patient outcomes whilst preserving financial resources. The professional, legal and clinical requirements of extending service provision to include new clinical staff presents challenges that have to be met with strong leadership and the provision of high quality education in ultrasound guided interventions. There are many indicators that the patient experience is enhanced by guiding musculoskeletal injections, and access to this service has impact on patients' confidence in their treatment pathway.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A new approach to the synthesis of optically pure
trans-perhydroazulenes and
trans-hydrindanes using a homochiral sulfoxide auxiliary to control both chemical reactivity and enantioselectivity is ...described.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this article, we describe the presentation components of two systems created at The MITRE Corporation: An Intelligent Multimedia Interface (AIMI) and the Textual Explanation PLANner (TEXPLAN) ...system. We then describe and analyze these two systems using the Standard Reference Model (SRM) for Intelligent Multimedia Presentation Systems (IMMPS) M. Bordegoni, G. Faconti, S. Feiner, M. Maybury, T. Rist, S. Ruggieri, P. Trahanias, M. Wilson, A standard reference model for intelligent multimedia presentation systems, Computer Standards and Interfaces, 18 (6,7) 477–496.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Webster's defines entertainment as "something diverting or engaging" or "a performance". IT occurs in a broad range of domains including games and toys, the fine arts, movies and radio, sports, ...travel, and education. Some examples from the digital world includes virtual games, interactive arts such as audience guided movies, augmented sports, virtual and nonvirtual travel guides, and computer-based tutors. Advances in AI and human-computer interaction offer seemingly endless opportunity to enhance traditional forms of entertainment and support the creation of new ones. However, several fundamental scientific and technical impediments must be overcome to achieve these promises
A scalable route to histone deacetylase inhibitors containing an unusual 2-aryl-3-cyano-5-aminomethylpyridine core has been developed which has the flexibility to deliver a range of compounds on at ...least a multigram scale. The key step involves a novel Mannich reaction using 3-dimethylaminoacrolein, formaldehyde, and a secondary amine to yield a 2-(alkylaminomethyl)-3-dimethylaminoacrolein. Tuning of this reaction in process development was fundamental to the success of the approach in terms of flexibility and operability on scale-up. This new methodology will also enable access an underutilised family of 3,5-disubstituted pyrid-2-ones and 2,3,5-trisubstituted pyridines.
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IJS, KILJ, NUK, PNG, UL, UM
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