Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

Non-newtonian and flow pulsatility effects in simulation models of a stented intracranial aneurysm.

Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge '07, are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and wall shear stress (WSS) output are used as a means of comparing the CFD simulations. In addition, a WSS distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. It is concluded that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, to understand dynamic flow effects, and to discriminate more effectively between stent designs.

Modelling the interaction of haemodynamics and the artery wall: current status and future prospects.

Clinical research has historically focused on the two main strategies of in vivo and in vitro experimentation. The concept of applying scientific theory to direct clinical applications is relatively recent. In this paper we focus on the interaction of wall shear stress with the endothelium and discuss how 'state of the art' computer modelling techniques can provide valuable data to aid understanding. Such data may be used to inform experiment and further, may help identify the key features of this complex system. Current emphasis is on coupling haemodynamics with models of biological phenomena to test hypotheses or predict the likely outcome of a disease or an intervention. New technologies to enable the integration of models of different types, levels of complexity and scales, are being developed. As will be discussed, the ultimate goal is the translation of this technology to the clinical arena.

No cumulative effects for one or two previous concussions.

BACKGROUND: Sports medicine clinicians and the general public are interested in the possible cumulative effects of concussion. OBJECTIVE: To examine whether athletes with a history of one or two previous concussions differed in their preseason neuropsychological test performances or symptom reporting. METHOD: Participants were 867 male high school and university amateur athletes who completed preseason testing with ImPACT version 2.0. They were sorted into three groups on the basis of number of previous concussions. There were 664 athletes with no previous concussions, 149 with one previous concussion, and 54 with two previous concussions. Multivariate analysis of variance was conducted using the verbal memory, visual memory, reaction time, processing speed, and postconcussion symptom composite scores as dependent variables and group membership as the independent variable. RESULTS: There was no significant multivariate effect, nor were there any significant main effects for individual scores. There was no measurable effect of one or two previous concussions on athletes' preseason neuropsychological test performance or symptom reporting. CONCLUSION: If there is a cumulative effect of one or two previous concussions, it is very small and undetectable using this methodology.

Oat gum lowers glucose and insulin after an oral glucose load.

Foods containing soluble dietary fibers delay glucose absorption and lower postprandial plasma glucose. This effect of oat bran has been attributed to oat gum (80% beta-glucan). However, purified oat gum has previously not been available for human studies. In this study the glucose and insulin responses to consuming 14.5 g of specifically prepared oat gum with 50 g glucose were compared with the response to guar gum with glucose and to glucose alone in nine healthy, fasting subjects. Plasma glucose and insulin increases after the glucose drink were greater than after both gum meals between 20 and 60 min (P less than 0.01). The responses to the two gum meals were nearly identical. These results establish that the more palatable oat gum lowers postprandial plasma glucose and insulin concentrations in humans and may be comparable with or of greater benefit than guar gum.

The combination of magnetic resonance angiography and computational fluid dynamics: a critical review.

Computational Fluid Dynamics (CFD) has proven to be a valuable technique in the study of blood flow in arteries because of its capability of obtaining quantitatively velocities and wall shear stress. However, the "bottleneck" problem limiting the application of CFD is the difficulty of constructing anatomically realistic arterial geometries. In this survey, an overview is presented of the progress over the last decade in the development of magnetic resonance angiography (MRA) techniques, medical image processing and CFD, as well as the combination of these techniques in hemodynamics research. It is demonstrated that with modern angiographic techniques such as MRA, noninvasive measurement of human angiograms becomes possible and practical. Together with digital medical image processing and analysis techniques, computational models can be constructed for the "real" human arteries without making any geometric assumptions. When allied with state-of-the-art CFD codes, velocity and wall shear stress distributions, as well as particle trajectories, can be determined in the arteries.

Oat beta-glucan reduces blood cholesterol concentration in hypercholesterolemic subjects.

OBJECTIVE: Several studies have indicated that consumption of oat bran lowers blood cholesterol and this effect has been attributed specifically to oat bran's soluble fiber (beta-glucan). This study was designed to test this hypothesis. DESIGN: The purified fibre (oat gum, 80% beta-glucan) was isolated, and agglomerated in the presence of maltodextrin to facilitate dispersion in a drink. Subjects consumed the oat gum (2.9 g beta-glucan), or maltodextrin placebo, twice daily for 4 weeks, in a randomized, cross-over design with a 3 week wash-out between phases. Consumption was equivalent to a daily dose of about 70 g of oat bran. SETTING: The study was with free-living individuals. SUBJECTS: Twenty hypercholesterolemic male and female adults entered, and 19 completed, the study. INTERVENTIONS: Blood lipids from fasting individuals were measured weekly throughout the study. Diet was monitored using 3 day food diaries. RESULTS: There were no significant changes (P > 0.05) in blood lipids during the placebo phase. Mean initial total cholesterol (6.76 +/- 0.13 mmol/l) and low density lipoprotein (LDL) cholesterol (4.59 +/- 0.14 mmol/l) levels fell throughout the oat gum phase, and at week 4 each was reduced 9% relative to initial values (P = 0.0004 and 0.005 respectively). When oat gum was discontinued, total and LDL cholesterol returned to initial levels. There were no significant changes in high density lipoprotein (HDL) cholesterol. Triglyceride levels also remained unchanged except for a singular decrease at week 4 of the oat gum phase relative to the initial value, but not compared to the placebo value. The lowered mean total and LDL cholesterol levels occurred in the absence of any dietary changes. CONCLUSIONS: The main component of the soluble fibre of oats, beta-glucan, significantly reduced the total and LDL cholesterol levels of hypercholesterolemic adults without changing HDL cholesterol.

Formation and travel of vortices in model ventricles: application to the design of skeletal muscle ventricles.

Vortex-ring production was studied in axisymmetric elastomeric ventricles designed to stimulate flow in a cardiovascular assist device. A flow visualization technique was used to investigate the effects of reducing the inlet diameter and predilating the ventricle on vortex travel in two ventricles of different shape and size. In most cases, vortex rings formed during the filling phase. They were bounded by the incoming jet of fluid and the ventricular wall. The velocity of their centres during the filling period was proportional to the inflow velocity. During filling, vortex velocity was substantially independent of the shape and diameter of the two ventricles studied. It was dependent mainly on orifice diameter: a narrower inlet led to greater inflow velocities and proportionately greater vortex velocities. At the end of the filling phase, each vortex increased in size to occupy the full radial extent of the ventricle. This process was associated with a decrease in the axial velocity and strength of the vortex. At low flow rates, these losses resulted in the arrest of the vortex at end filling. Vortex motion in ventricles is particularly important in the design of a cardiovascular device such as the skeletal muscle ventricle (SMV), where small ejection fractions may leave blood at the apex of the ventricle relatively undisturbed. It is suggested that inlet diameter could be selected to favour the formation and travel of vortices, with a resultant reduction in apical residence time and hence a reduced risk of thrombus formation.

Isolation and structure elucidation of a novel product of the acidic degradation of cefaclor.

The acidic aqueous degradation of cefaclor, an orally administered cephalosporin antibiotic, has been investigated. The most prominent peak in the high-performance liquid chromatography profile of a degraded solution of cefaclor was isolated by preparative high-performance liquid chromatography. Mechanistically, the formation of this degradent from cefaclor involves a condensation of two cefaclor degradation products in which both products have undergone contraction from a six-membered cephem ring to a five-membered thiazole ring, presumably via a common episulfonium ion intermediate.

Isolation and structure elucidation of the major degradation products of cefaclor formed under aqueous acidic conditions.

The aqueous acidic degradation of the oral cephalosporin cefaclor was investigated. A number of degradation products were isolated and characterized. The degradation products can be loosely classified into three categories: thiazole derivatives, pyrazine derivatives, and simple hydrolysis or rearrangement products. Degradation pathways are proposed that involve (1) hydrolysis of the beta-lactam carbonyl with subsequent rearrangement, (2) ring contraction of the six-membered cephem nucleus to five-membered thiazole derivatives through an episulfonium ion intermediate, and (3) attack of the primary amine of the phenylglycyl side chain on the "masked aldehyde" at carbon-6 to form fluorescent substituted pyrazines.

Isolation and structure elucidation of the major degradation products of cefaclor in the solid state.

Cefaclor is a beta-lactam antibiotic that degrades slowly under normal storage conditions to several minor products. To obtain samples large enough to permit structure elucidation, cefaclor was allowed to degrade at 40 degrees C (75% relative humidity) and at 85 degrees C. The profile of degradation products formed under these conditions is qualitatively similar to the profile of degradation products observed in samples of cefaclor aged for 14 years at room temperature, although some products found in the sample degraded at 85 degrees C are not formed at the lower temperatures. Using preparative reversed-phase high-performance liquid chromatography (rp-HPLC) and a combination of spectroscopic methods, we have isolated and characterized 17 of these degradation products. Some of these products were also isolated from studies of aqueous degradations. The major products appear to have arisen from five distinct pathways: (1) isomerization of the double bond in the dihydrothiazine ring; (2) decarboxylation; (3) ring contraction of the cephem nucleus to thiazole structures; (4) oxidative attack at carbon 4 of the dihydrothiazine ring; and (5) intramolecular attack of the primary amine of the side chain on either the beta-lactam carbonyl to form 3-phenyl-2,5-diketopiperazines or the "masked aldehyde" at carbon 6 to form 2-hydroxy-3-phenylpyrazine derivatives. The pathway involving oxidation at carbon 4 is particularly important at ambient temperatures and is unique to the solid-state degradation.

Aqueous acidic degradation of the carbacephalosporin loracarbef.

The aqueous degradation of the carbacephalosporin loracarbef under moderately acidic conditions (pH range, 2.7-4.3) is described. Structures of a total of 10 compounds isolated by preparative reversed-phase HPLC have been proposed. Five of these 10 degradation compounds arose from hydrolysis of the beta-lactam ring followed by structural changes in the six-membered heterocyclic ring. Four compounds form from intermolecular reactions of loracarbef to form dimeric structures with peptide linkages. The remaining compound resulted from oxidation of the primary amine to a hydroxylamine. Pathways for the formation of these compounds from the parent loracarbef are proposed.

Modelling nanoscale fluid dynamics and transport in physiological flows.

The concept of nanotechnology is discussed, and its connection with biomedical engineering is elucidated. For the specific field of nanoscale flow and transport problems of physiological relevance, some typical examples are presented, and their interaction is discussed for some classic biomechanical problems like the flow in arteries with blood-wall coupling. Then, existing computational models are presented and classified according to the length scale of interest, with emphasis on particle-fluid problems. Final remarks address the essential unity of biomedical and engineering behaviour and the possible relevance to small-scale industrial research.

Flow in carotid bifurcations: effect of the superior thyroid artery.

The superior thyroid artery was ignored in previous fluid dynamics studies of carotid bifurcations. However, it is not clear to what extent the flow patterns within the carotid might be influenced by the presence of this outflow tract in reality. In this study, quantitative effects of the superior thyroid artery upon the flow patterns and wall shear stress in the carotid bifurcation were investigated in detail by a numerical simulation method. Comparisons of the maximum reversed flow velocities, flow patterns and wall shear stress were made between models with and without the superior thyroid artery. Results demonstrate that this small artery has only a marginal effect on the overall flow characteristics within the carotid sinus. However, it does have significant effects on flow patterns in the common-external side branch. An alternative approach is proposed to compensate for the absence of this small artery in numerical calculations.

Effects of stents under asymmetric inflow conditions.

Patient-to-patient variations in artery geometry may determine their susceptibility to stenosis formation. These geometrical variations can be linked to variations in flow characteristics such as wall shear stress through stents, which increases the risk of restenosis. This paper considers computer models of stents in non-symmetric flows and their effects on flow characteristics at the wall. This is a fresh approach from the point of view of identifying a stent design whose performance is insensitive to asymmetric flow. Measures of dissipated energy and power are introduced in order to discriminate between competing designs of stents.

Magnetic resonance image processing and structured grid generation of a human abdominal bifurcation.

Magnetic resonance angiography (MRA) offers a non-invasive approach to the acquisition of anatomically accurate human arterial structure. Combining the latest computational fluid dynamics (CFD) techniques with clinical data from MRA, the detailed haemodynamics information in the human circulation system can be obtained. In this paper, a novel computer method is presented, which generates automatically a computational grid for a human abdominal bifurcation from a set of conventional MRA images. The method covers the complete sequence from MR image segmentation, 3-D model construction, grid generation, to grid quality evaluation. Results demonstrate that the computer program developed is capable of generating a good quality grid for human arterial bifurcations from MRA images with minimum user input. The resultant grid can be used directly for further computer simulation of the flow.

A review of the numerical analysis of blood flow in arterial bifurcations.

Arterial bifurcation flow has been of special interest for some years because of its important role in the formation of atherosclerotic plaques and thrombi. To investigate the flow phenomena analytically, four major factors need to be accommodated--the three-dimensionality of a general bifurcation, the pulsatile nature of the laminar flow, the distensibility of the arterial wall and the non-Newtonian character of the blood. In this review, both engineering and medical aspects of each factor are carefully surveyed. It is demonstrated that the latest generation of computational fluid dynamics codes can treat this problem area and that it is both feasible and desirable to investigate the effects of each independent factor.

The numerical analysis of fluid-solid interactions for blood flow in arterial structures. Part 1: A review of models for arterial wall behaviour.

The structural response of a large artery is characteristically complex and includes the highly non-linear, history-dependent response of a nonhomogeneous anisotropic structure undergoing finite deformations. The mechanics of the arterial wall has been studied for nearly two centuries. The goals of such research range from the desire to have a basic knowledge and understanding of the mechanics and physiology of this complex structure to the need for data and methods for the design of arterial prostheses. In this paper, the models for arterial wall behaviour are critically reviewed. Firstly, the structure and general characteristics of the arterial wall are discussed. This is followed by a comprehensive review of the constitutive laws. Finally, structural analyses of the arterial wall by mathematical and numerical methods are discussed. Predictions using the authors' preferred models give focus to important issues, and in Part 2 the review and predictions are extended to the fluid solid coupled situation.

The numerical analysis of fluid-solid interactions for blood flow in arterial structures. Part 2: Development of coupled fluid-solid algorithms.

In this paper, the authors extend their study of wall mechanics given in Part 1 to the overall problem of fluid-solid interactions in arterial flows. Fluid-solid coupling has become a specific topic in computational methods and applied mechanics. In this review, firstly, the effects of elasticity of blood vessels on wave propagation and local flow patterns in large arteries are discussed. Then, numerical techniques are reviewed together with the alternative coupled methods available in fluid--wall models. Finally, a novel numerical alogorithm combining two commercial codes for coupled solid/fluid problems is presented. As a consequence of the present studies, wall effects are now able to be included in predictions of haemodynamics in a clinical context.

Reconstruction of blood flow patterns in human arteries.

Local haemodynamic factors in large arteries are associated with the pathophysiology of cardiovascular diseases such as atherosclerosis and strokes. In search of these factors and their correlation with atheroma formation, quantitative haemodynamic data in realistic arterial geometry become crucial. At present no in vivo non-invasive technique is available that can provide accurate measurement of three-dimensional blood velocities and shear stresses in curved and branching sites of vessels where atherosclerotic plaques are found frequently. This paper presents a computer modelling technique which combines state-of-the-art computational fluid dynamics (CFD) with new noninvasive magnetic resonance imaging techniques to provide the complete haemodynamic data in 'real' arterial geometries. Using magnetic resonance angiographic and velocity images acquired from the aortic bifurcation of a healthy human subject, CFD simulations have been carried out and the predicted flow patterns demonstrate the non-planar-type flow characteristics found in experimental studies.