Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was ...undertaken to develop new classification criteria for gout.
An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
Objective
Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was ...undertaken to develop new classification criteria for gout.
Methods
An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
Results
The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU‐negative synovial fluid aspirate), and imaging (double‐contour sign on ultrasound or urate on dual‐energy computed tomography, radiographic gout‐related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
Conclusion
The new classification criteria, developed using a data‐driven and decision analytic approach, have excellent performance characteristics and incorporate current state‐of‐the‐art evidence regarding gout.
We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new ...physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca^{+} data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve the relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.
High-harmonic generation is a universal response of matter to strong femtosecond laser fields, coherently upconverting light to much shorter wavelengths. Optimizing the conversion of laser light into ...soft x-rays typically demands a trade-off between two competing factors. Because of reduced quantum diffusion of the radiating electron wave function, the emission from each species is highest when a short-wavelength ultraviolet driving laser is used. However, phase matching–the constructive addition of x-ray waves from a large number of atoms–favors longer-wavelength mid-infrared lasers. We identified a regime of high-harmonic generation driven by 40-cycle ultraviolet lasers in waveguides that can generate bright beams in the soft x-ray region of the spectrum, up to photon energies of 280 electron volts. Surprisingly, the high ultraviolet refractive indices of both neutral atoms and ions enabled effective phase matching, even in a multiply ionized plasma. We observed harmonics with very narrow linewidths, while calculations show that the x-rays emerge as nearly time-bandwidth-limited pulse trains of ~100 attoseconds.
The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by ...phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds.
This Review Article provides a multi-stakeholder view on the current status of neoadjuvant therapy in lung cancer. Given the success of oncogene-targeted therapy and immunotherapy for patients with ...advanced lung cancer, there is a renewed interest in studying these agents in earlier disease settings with the opportunity to have an even greater impact on patient outcomes. There are unique opportunities and challenges with the neoadjuvant approach to drug development. To achieve more rapid knowledge turns, study designs, endpoints, and definitions of pathologic response should be standardized and harmonized. Continued dialogue with all stakeholders will be critical to design and test novel induction strategies, which could expedite drug development for patients with early lung cancer who are at high risk for metastatic recurrence.
Uncertainties in nuclear models have a major impact on simulations that aim at understanding the origin of heavy elements in the universe through the rapid neutron capture process ( r process) of ...nucleosynthesis. Within the framework of the nuclear density functional theory, we use results of Bayesian statistical analysis to propagate uncertainties in the parameters of energy density functionals to the predicted r -process abundance pattern, by way not only of the nuclear masses but also through the influence of the masses on β -decay and neutron capture rates. We point out the importance of the nonequilibrium end stage of the r process in determining the width of the resulting abundance pattern uncertainty bands. We additionally make the first identifications of specific parameters of Skyrme-like energy density functionals which show tentative correlations with particular aspects of the r -process abundance pattern. While previous studies have explored the reduction in the abundance pattern uncertainties due to anticipated new measurements of neutron-rich nuclei, here we point out that an even larger reduction will occur when these new measurements are used to reduce the uncertainty of model predictions of masses, which are then propagated through to the abundance pattern. We make a quantitative prediction for how large this reduction will be.
The administration of cells as therapeutic agents has emerged as a novel approach to complement the use of small molecule drugs and other biologics for the treatment of numerous conditions. Although ...the use of cells for structural and/or functional tissue repair and regeneration provides new avenues to address increasingly complex disease processes, it also faces numerous challenges related to efficacy, safety, and translational potential. Recent advances in nanotechnology-driven cell therapies have the potential to overcome many of these issues through precise modulation of cellular behavior. Here, we describe several approaches that illustrate the use of different nanotechnologies for the optimization of cell therapies and discuss some of the obstacles that need to be overcome to allow for the widespread implementation of nanotechnology-based cell therapies in regenerative medicine.
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