The concept of isogeometric analysis is proposed. Basis functions generated from NURBS (Non-Uniform Rational B-Splines) are employed to construct an exact geometric model. For purposes of analysis, ...the basis is refined and/or its order elevated without changing the geometry or its parameterization. Analogues of finite element
h- and
p-refinement schemes are presented and a new, more efficient, higher-order concept,
k-refinement, is introduced. Refinements are easily implemented and exact geometry is maintained at all levels without the necessity of subsequent communication with a CAD (Computer Aided Design) description. In the context of structural mechanics, it is established that the basis functions are complete with respect to affine transformations, meaning that all rigid body motions and constant strain states are exactly represented. Standard patch tests are likewise satisfied. Numerical examples exhibit optimal rates of convergence for linear elasticity problems and convergence to thin elastic shell solutions. A
k-refinement strategy is shown to converge toward monotone solutions for advection–diffusion processes with sharp internal and boundary layers, a very surprising result. It is argued that isogeometric analysis is a viable alternative to standard, polynomial-based, finite element analysis and possesses several advantages.
We investigate the effects of smoothness of basis functions on solution accuracy within the isogeometric analysis framework. We consider two simple one-dimensional structural eigenvalue problems and ...two static shell boundary value problems modeled with trivariate NURBS solids. We also develop a local refinement strategy that we utilize in one of the shell analyses. We find that increased smoothness, that is, the “
k-method,” leads to a significant increase in accuracy for the problems of structural vibrations over the classical
C
0
-continuous “
p-method,” whereas a judicious insertion of
C
0
-continuous surfaces about singularities in a mesh otherwise generated by the
k-method, usually outperforms a mesh in which all basis functions attain their maximum level of smoothness. We conclude that the potential for the
k-method is high, but smoothness is an issue that is not well understood due to the historical dominance of
C
0
-continuous finite elements and therefore further studies are warranted.
We present an LES-type variational multiscale theory of turbulence. Our approach derives completely from the incompressible Navier–Stokes equations and does not employ any
ad hoc devices, such as ...eddy viscosities. We tested the formulation on forced homogeneous isotropic turbulence and turbulent channel flows. In the calculations, we employed linear, quadratic and cubic NURBS. A dispersion analysis of simple model problems revealed NURBS elements to be superior to classical finite elements in approximating advective and diffusive processes, which play a significant role in turbulence computations. The numerical results are very good and confirm the viability of the theoretical framework.
Isogeometric analysis of structural vibrations Cottrell, J.A.; Reali, A.; Bazilevs, Y. ...
Computer methods in applied mechanics and engineering,
08/2006, Letnik:
195, Številka:
41
Journal Article
Recenzirano
Odprti dostop
This paper begins with personal recollections of John H. Argyris. The geometrical spirit embodied in Argyris’s work is revived in the sequel in applying the newly developed concept of isogeometric ...analysis to structural vibration problems. After reviewing some fundamentals of isogeometric analysis, application is made to several structural models, including rods, thin beams, membranes, and thin plates. Rotationless beam and plate models are utilized as well as three-dimensional solid models. The concept of
k-refinement is explored and shown to produce more accurate and robust results than corresponding finite elements. Through the use of nonlinear parameterization, “optical” branches of frequency spectra are eliminated for
k-refined meshes. Optical branches have been identified as contributors to Gibbs phenomena in wave propagation problems and the cause of rapid degradation of higher modes in
p-method finite elements. A geometrically exact model of the NASA Aluminum Testbed Cylinder is constructed and frequencies and mode shapes are computed and shown to compare favorably with experimental results.
Metabolic regulation of NLRP3 Hughes, Mark M.; O'Neill, Luke A.J.
Immunological reviews,
January 2018, Letnik:
281, Številka:
1
Journal Article
Recenzirano
Summary
A shift in our understanding of macrophage biology has come about as a result of recent discoveries in the area of metabolic reprogramming of macrophages. The NLRP3 inflammasome drives the ...activation of caspase‐1, leading to the production of IL‐1β, IL‐18, and a type of cell death termed pyroptosis. The NLRP3 inflammasome has been shown to sense metabolites such as palmitate, uric acid, and cholesterol crystals and is inhibited by ketone bodies produced during metabolic flux. The NLRP3 inflammasome has also been shown to be regulated by mitochondrial reactive oxygen species and components of glycolysis, such as Hexokinase. Here, we review these findings and discuss their importance for inflammation and furthermore discuss potential therapeutic benefits of targeting NLRP3.
The objective of the present work is to develop efficient, higher-order space- and time-accurate, methods for structural dynamics. To this end, we present a family of explicit isogeometric ...collocation methods for structural dynamics that are obtained from predictor–multicorrector schemes. These methods are very similar in structure to explicit finite-difference time-domain methods, and in particular, they exhibit similar levels of computational cost, ease of implementation, and ease of parallelization. However, unlike finite difference methods, they are easily extended to non-trivial geometries of engineering interest. To examine the spectral properties of the explicit isogeometric collocation methods, we first provide a semi-discrete interpretation of the classical predictor–multicorrector method. This allows us to characterize the spatial and modal accuracy of the isogeometric collocation predictor–multicorrector method, irrespective of the considered time-integration scheme, as well as the critical time step size for a particular explicit time-integration scheme. For pure Dirichlet problems, we demonstrate that it is possible to obtain a second-order-in-space scheme with one corrector pass, a fourth-order-in-space scheme with two corrector passes, and a fifth-order-in-space scheme with three corrector passes. For pure Neumann and mixed Dirichlet–Neumann problems, we demonstrate that it is possible to obtain a second-order-in-space scheme with one corrector pass and a third-order-in-space scheme with two corrector passes, and we observe that fourth-order-in-space accuracy may be obtained pre-asymptotically with three corrector passes. We then present second-order-in-time, fourth-order-in-time, and fifth-order-in-time fully discrete predictor–multicorrector algorithms that result from the application of explicit Runge–Kutta methods to the semi-discrete isogeometric collocation predictor–multicorrector method. We confirm the accuracy of the family of explicit isogeometric collocation methods using a suite of numerical examples.
•Explicit predictor–multicorrector isogeometric collocation methods are presented.•A semi-discrete predictor–multicorrector reinterpretation enables spectral analysis.•High-order accuracy in space is observed using a small number of corrector passes.•Higher-order accuracy in time is achieved using explicit Runge–Kutta methods.•Numerical examples confirm the accuracy of the family of methods.
Purpose
Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of ...administering combined cognitive and physical therapy early during a critical illness.
Methods
We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%).
Results
Early cognitive therapy was a delivered to 41/43 (95 %) of cognitive plus physical therapy patients on 100 % (92–100 %) of study days beginning 1.0 (1.0–1.0) day following enrollment. Physical therapy was received by 17/22 (77 %) of usual care patients, by 21/22 (95 %) of physical therapy only patients, and 42/43 (98 %) of cognitive plus physical therapy patients on 17 % (10–26 %), 67 % (46–87 %), and 75 % (59–88 %) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up.
Conclusions
This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.
This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly ...fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all.
► We couple isogeometric boundary element methods and unstructured T-spline surfaces. ► We extend the definition of analysis-suitable T-splines to encompass unstructured control grids. ► Our ...collocation procedure correctly accounts for sharp edges and corners, extraordinary points, and T-junctions. ► The approach is applied to several three-dimensional problems, including a real-world T-spline model of a propeller.
We couple collocated isogeometric boundary element methods and unstructured analysis-suitable T-spline surfaces for linear elastostatic problems. We extend the definition of analysis-suitable T-splines to encompass unstructured control grids (unstructured meshes) and develop basis functions which are smooth (rational) polynomials defined in terms of the Bézier extraction framework and which pass standard patch tests. We then develop a collocation procedure which correctly accounts for sharp edges and corners, extraordinary points, and T-junctions. This approach is applied to several three-dimensional problems, including a real-world T-spline model of a propeller. We believe this work clearly illustrates the power of combining new analysis-suitable computer aided design technologies with established analysis methodologies, in this case, the boundary element method.
Does Nitisinone prevent the clinical progression of the Alkaptonuria?
In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the ...progression of AKU over a three-year period.
Nitisinone is a beneficial therapy in Alkaptonuria.
Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU).
Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group.
Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases.
The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ± 0.19) and three (0.15 ± 0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ± 0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ± 0.08) and three (0.19 ± 0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ± 0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05).
This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.
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