Rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis

Opportunities for asteroid retrieval missions

Asteroids and comets are of strategic importance for science in an effort to uncover the formation, evolution and composition of the Solar System. Near-Earth Objects (NEOs) are of particular interest because of their accessibility from Earth, but also because of their speculated wealth of material resources. The exploitation of these resources has long been discussed as a means to lower the cost of future space endeavours. In this chapter, we analyze the possibility of retrieving entire objects from accessible heliocentric orbits and moving them into the Earth’s neighbourhood. The asteroid retrieval transfers are sought from the continuum of low energy transfers enabled by the dynamics of invariant manifolds; specifically, the retrieval transfers target planar, vertical Lyapunov and halo orbit families associated with the collinear equilibrium points of the Sun-Earth Circular Restricted Three Body problem. The judicious use of these dynamical features provides the best opportunity to find extremely low energy transfers for asteroidal material. With the objective to minimise transfer costs, a global search of impulsive transfers connecting the unperturbed asteroid’s orbit with the stable manifold phase of the transfer is performed. A catalogue of asteroid retrieval opportunities of currently known NEOs is presented here. Despite the highly incomplete census of very small asteroids, the catalogue can already be populated with 12 different objects retrievable with less than 500 m/s of Δv. All, but one, of these objects have an expected size in the range that can be met by current propulsion technologies. Moreover, the methodology proposed represents a robust search for future retrieval candidates that can be automatically applied to a growing survey of NEOs

Near-Earth asteroid resource accessibility and future capture mission opportunities

In-Situ Resource Utilization (ISRU) has always been suggested for ambitious space endeavours; and asteroids and comets in particular are generally agreed to be ideal sources, both in terms of its accessibility and wealth. The future utilisation of asteroid resources is here revisited by, firstly, providing an estimate of the total amount of accessible resources in the Earth’s neighbourhood and, secondly, by envisaging a series of missions in order to retrieve resources from the most accessible objects known today. An analytical multi-impulsive transfer model is proposed in order to define the region in Keplerian space from which resources are accessible, and mapped subsequently into a near-Earth asteroid model, to understand the availability of material. This estimate shows a substantial amount of resources can be accessible at relatively low energy-cost; on the order of 1014 kg of material could potentially be accessed at an energy cost lower than that required to access the resources in the Moon. Most of this material is currently undiscovered, but the current surveyed population of near-Earth asteroid provides a good starting point for a search for future capture opportunities. The possibility of capturing, i.e., placing the asteroid into an orbit in permanent close proximity to Earth, a small-size NEO or a segment from a larger object would be of great scientific and technological interest in the coming decades. A systematic search of capture candidates among catalogued NEOs is presented, which targets the L2 region as the destination for the captured material. A robust methodology for systematic pruning of candidates and optimisation of capture trajectories through the stable manifold of planar Lyapunov orbits around L2 has been implemented and tested. Five possible candidates for affordable asteroid retrieval missions have been identified among known NEOs, and the transfers to the L2 region calculated. These transfers enable the capture of bodies with 2-8 meters diameter with modest propellant requirements. Because of the optimal departure dates, two of them have been identified as attractive targets for capture missions in the 2020-2030 time frame

Gravitational capture opportunites for asteroid retrieval missions

Asteroids and comets are of strategic importance for science in an effort to uncover the formation, evolution and composition of the Solar System. Near-Earth objects (NEOs) are of particular interest because of its accessibility from Earth, but also because of their speculated wealth of resources. The exploitation of these resources has long been discussed as a means to lower the cost of future space endeavours. In this paper, we analyze the possibility of retrieving entire objects from accessible heliocentric orbits and moving them into the Earth’s neighbourhood. The asteroid retrieval transfers are sought from the continuum of low energy transfers enabled by the dynamics of invariant manifolds; specifically, the retrieval transfers target planar, vertical Lyapunov and halo orbit families associated with the collinear equilibrium points of the Sun-Earth Circular Restricted Three Body problem. The judicious use of these dynamical features provides the best opportunity to find extremely low energy Earth transfers for asteroidal material. With the objective to minimise transfer costs, a global search of impulsive transfers connecting the unperturbed asteroid’s orbit with the stable manifold phase of the transfer is performed. A catalogue of asteroid retrieval opportunities of currently known NEOs is presented here. Despite the highly incomplete census of very small asteroids, the catalogue can already be populated with 12 different objects retrievable with less than 500 m/s of Δv. All, but one, of these objects have an expected size and transfer requirements that can be met by current propulsion technologies. Moreover, the methodology proposed represents a robust search for future retrieval candidates that can be automatically applied to a growing survey of NEOs

A Systems Engineering Tool for Small Satellite Design

The growing popularity of small satellites for applications of all kinds has lead to a marked increase in the number of requests from customers of The Aerospace Corporation for studies involving small satellites. The existing design tools used by the Corporation for concept evaluation of large spacecraft have, in many cases, proven inadequate for these small spacecraft studies. As a result, Aerospace is developing a systems engineering tool to support the conceptual design of small satellites. The Aerospace Corporation’s small satellite systems engineering tool utilizes a spreadsheet-based approach to efficiently track information regarding the mass, power, and volume of the satellite subsystems. This subsystem information is derived through a variety of means, including analytical relationships, iterative solvers, and databases of components appropriate for small satellites. Physics based models for such factors as solar illumination and external torques have been incorporated into the tool to aid in the analysis of the design. In addition to data tracking, the spreadsheet approach used makes it easier for a concurrent engineering methodology to be applied to the design process. This means the effects of a change in one subsystem are immediately propagated to the other subsystems, and system-level effects are more easily identified. The end result is a tool that facilitates rapid systems-level concept evaluation and trade-space exploration in support of the small satellite design process. This paper describes The Aerospace Corporation’s small satellite systems engineering tool. The approach underlying the tool, as well as an overview of the implementation, relationships between the subsystems, and the flow of information are presented

Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups

Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis

Caffeine and sprint cycling performance: effects of torque factor and sprint duration

Purpose: The aim of this study was to investigate the influence of torque factor and sprint duration on the effects of caffeine on sprint cycling performance. Methods: Using a counterbalanced, randomized, double-blind, placebo-controlled design, 13 men completed nine trials. In Trial 1, participants completed a series of 6 s sprints at increasing torque factors, to determine the torque factor, for each individual, which elicited the highest (TOPTIMAL) peak power output (PPO). The remaining trials involved all combinations of torque factor (0.8 N∙m∙kg-1 versus TOPTIMAL), sprint duration (10 s versus 30 s), and supplementation (caffeine [5mg∙kg-1] versus placebo). Results: There was a significant effect of torque factor on PPO, with higher values at TOPTIMAL (mean difference: 168 W; 95% likely range: 142 – 195 W). There was also a significant effect of sprint duration on PPO, with higher values in 10 s sprints (mean difference: 52 W; 95% likely range: 18 – 86 W). However, there was no effect of supplementation on PPO (p = 0.056). Nevertheless, there was a significant torque factor × sprint duration × supplement interaction (p = 0.036), with post hoc tests revealing that caffeine produced a higher PPO (mean difference: 76 W; 95% likely range: 19 – 133 W) when the sprint duration was 10 s and the torque factor was TOPTIMAL. Conclusions: The results of this study show that when torque factor and sprint duration are optimized, to allow participants to express their highest PPO, there is a clear effect of caffeine on sprinting performance

Potential effects of optical solar sail degredation on trajectory design

The optical properties of the thin metalized polymer films that are projected for solar sails are assumed to be affected by the erosive effects of the space environment. Their degradation behavior in the real space environment, however, is to a considerable degree indefinite, because initial ground test results are controversial and relevant inspace tests have not been made so far. The standard optical solar sail models that are currently used for trajectory design do not take optical degradation into account, hence its potential effects on trajectory design have not been investigated so far. Nevertheless, optical degradation is important for high-fidelity solar sail mission design, because it decreases both the magnitude of the solar radiation pressure force acting on the sail and also the sail control authority. Therefore, we propose a simple parametric optical solar sail degradation model that describes the variation of the sail film's optical coefficients with time, depending on the sail film's environmental history, i.e., the radiation dose. The primary intention of our model is not to describe the exact behavior of specific film-coating combinations in the real space environment, but to provide a more general parametric framework for describing the general optical degradation behavior of solar sails. Using our model, the effects of different optical degradation behaviors on trajectory design are investigated for various exemplary missions

Encouraging Patient Portal Use in the Patient-Centered Medical Home: Three Stakeholder Perspectives

BACKGROUND: Health care organizations are increasingly offering patients access to their electronic medical record and the ability to communicate with their providers through Web-based patient portals, thus playing a prominent role within the patient-centered medical home (PCMH). However, despite enthusiasm, adoption remains low. OBJECTIVE: We examined factors in the PCMH context that may affect efforts to improve enrollment in a patient portal. METHODS: Using a sociotechnical approach, we conducted qualitative, semistructured interviews with patients and providers from 3 primary care clinics and with national leaders from across a large integrated health care system. RESULTS: We gathered perspectives and analyzed data from 4 patient focus groups and one-on-one interviews with 1 provider from each of 3 primary care clinics and 10 program leaders. We found that leaders were focused on marketing in primary care, whereas patients and providers were often already aware of the portal. In contrast, both patients and providers cited administrative and logistical barriers impeding enrollment. Further, although leadership saw the PCMH as the logical place to focus enrollment efforts, providers and patients were more circumspect and expressed concern about how the patient portal would affect their practice and experience of care. Further, some providers expressed ambivalence about patients using the portal. Despite absence of consensus on how and where to encourage portal adoption, there was wide agreement that promoting enrollment was a worthwhile goal. CONCLUSIONS: Patients, clinicians, and national leaders agreed that efforts were needed to increase enrollment in the patient portal. Opinions diverged regarding the suitability of the PCMH and, specifically, the primary care clinic for promoting patient portal enrollment. Policymakers should consider diverse stakeholder perspectives in advance of interventions to increase technology adoption