New Techniques in the Evaluation of Cerebrovascular Disease

Numerous reports in the literature indicate that various noninvasive vascular techniques can now be used to evaluate atherosclerosis at the carotid bifurcation. This article reviews noninvasive screening techniques currently available and being developed. Particular emphasis has been placed on the practicality of these techniques as well as their limitations. Our conclusions are that noninvasive techniques cannot be used as definitive screening tests for cerebrovascular disease. Although these tests are frequently useful when positive, the false negative rate of these tests would appear to be significant and variable in different hands. Nonstenotic ulcers are usually not detected and total occlusion often not differentiated from stenosis. These tests should be viewed as the beginning rather than the end result of a developing field. At present, contrast arteriography remains the definitive test to evaluate the presence and significance of extracranial cerebrovascular disease.     

Morphological age-dependent development of the human carotid bifurcation

The unique morphology of the adult human carotid bifurcation and its sinus has been investigated extensively, but its long-term, age-dependent development has not. It is important fundamentally and clinically to understand the hemodynamics and developmental forces that play a role in remodeling of the carotid bifurcation and maturation of the sinus in association with brain maturation. This understanding can lead to better prognostication and therapy of carotid disease. We analyzed the change of sinus morphology and the angle of the carotid bifurcation in four postnatal developmental stages (Group I: 0-2 years, Group II: 3-9 years, Group III: 10-19 years, and Group IV: 20-36 years, respectively) using multiprojection digital subtraction angiograms and image post-processing techniques. The most significant findings are the substantial growth of the internal carotid artery (ICA) with age and the development of a carotid sinus at the root of the ICA during late adolescence. The bifurcation angle remains virtually unchanged from infancy to adulthood. However, the angle split between the ICA and external carotid artery (ECA) relative to the common carotid artery (CCA) undergoes significant changes. Initially, the ICA appears to emanate as a side branch. Later in life, to reduce hydraulic resistance in response to increased flow demand by the brain, the bifurcation is remodeled to a construct in which both daughter vessels are a skewed continuation of the parent artery. This study provides a new analysis method to examine the development of the human carotid bifurcation over the developmental years, despite the small and sparse database. A larger database will enable in the future a more extensive analysis such as gender or racial differences.     

Pulsatile non-newtonian blood flow in three-dimensional carotid bifurcation models: a numerical study of flow phenomena under different bifurcation angles

Flow and stress patterns in human carotid artery bifurcation models, which differ in the bifurcation angle, are analysed numerically under physiologically relevant flow conditions. The governing Navier-Stokes equations describing pulsatile, three-dimensional flow of an incompressible non-Newtonian fluid are approximated using a pressure correction finite element method, which has been developed recently. The non-Newtonian behaviour of blood is modelled using Casson's relation, based on measured dynamic viscosity. The study concentrates on flow and stress characteristics in the carotid sinus. The results show that the complex flow in the sinus is affected by the angle variation. The magnitude of reversed flow, the extension of the recirculation zone in the outer sinus region and the duration of flow separation during the pulse cycle as well as the resulting wall shear stress are clearly different in the small angle and in the large angle bifurcation. The haemodynamic phenomena, which are important in atherogenesis, are more pronounced in the large angle bifurcation.     

Carotid endarterectomy for prevention of stroke.

Carotid endarterectomy, a frequently performed operation, has been used as a strategy for preventing stroke in patients with carotid bifurcation disease. The safety and efficacy of the operation were recently challenged by a number of sources. Three major responses to this challenge were to retrospectively review the natural history of carotid bifurcation disease compared with the immediate and long-term results of carotid endarterectomy, to initiate 6 prospective randomized trials to determine the efficacy of carotid endarterectomy for a variety of indications, and to develop appropriateness initiatives and guidelines for using this surgical procedure by organizations concerned with health care policy. I review the current status of these 3 areas of endeavor. In those areas where studies are complete, carotid endarterectomy has been shown to be highly effective in reducing stroke risk. Risk reduction has ranged from 66% to 80% compared with medical management. Based on these sources and findings, I present a list of indications for the operation for surgeons who are able to do the operation safely and within the guidelines established by the Stroke Council of the American Heart Association.     

Quantification of the non-planarity of the human carotid bifurcation

The carotid bifurcation has been a region of particular interest due to its predilection for clinically significant atherosclerosis. It has been shown that the vessel geometry is a major determinant of the local haemodynamic properties which are believed to be associated with the location of atherosclerotic lesions. Current knowledge of the geometry of the carotid bifurcation is insufficient and restricted to basic geometric parameters. To provide some means of quantifying the degree of complexity of the 3D shape of the bifurcation, we made an initial attempt by evaluating the non-planarity of an arterial bifurcation based upon the singular value decomposition theorem.In this paper we present our results obtained on the right carotid bifurcations of six normal subjects, each of whom was scanned twice using the 2D time-of-flight MR sequence. The acquired 2D cross sectional images were processed by using our in-house software which comprises 2D segmentation, 3D reconstruction and smoothing. The centroids of each transverse slices were determined and used as input data for the non-planarity analysis. Our results using the singular value decomposition method have demonstrated discernible differences in non-planarity among individuals. Comparisons with the planarity definition proposed by other investigators suggest that the singular value decomposition method offers more information about the linearity and planarity of the bifurcation. However, it is also realised that a single measure of non-planarity can never fully characterise a bifurcation owing to the great variety of geometries.     

Three-dimensional geometry of the human carotid artery

Accurate characterization of carotid artery geometry is vital to our understanding of the pathogenesis of atherosclerosis. Three-dimensional computer reconstructions based on medical imaging are now ubiquitous; however, mean carotid artery geometry has not yet been comprehensively characterized. The goal of this work was to build and study such geometry based on data from 16 male patients with severe carotid artery disease. Results of computerized tomography angiography were used to analyze the cross-sectional images implementing a semiautomated segmentation algorithm. Extracted data were used to reconstruct the mean three-dimensional geometry and to determine average values and variability of bifurcation and planarity angles, diameters and cross-sectional areas. Contrary to simplified carotid geometry typically depicted and used, our mean artery was tortuous exhibiting nonplanarity and complex curvature and torsion variations. The bifurcation angle was 36 deg?±?11 deg if measured using arterial centerlines and 15 deg?±?14 deg if measured between the walls of the carotid bifurcation branches. The average planarity angle was 11 deg?±?10 deg. Both bifurcation and planarity angles were substantially smaller than values reported in most studies. Cross sections were elliptical, with an average ratio of semimajor to semiminor axes of 1.2. The cross-sectional area increased twofold in the bulb compared to the proximal common, but then decreased 1.5-fold for the combined area of distal internal and external carotid artery. Inter-patient variability was substantial, especially in the bulb region; however, some common geometrical features were observed in most patients. Obtained quantitative data on the mean carotid artery geometry and its variability among patients with severe carotid artery disease can be used by biomedical engineers and biomechanics vascular modelers in their studies of carotid pathophysiology, and by endovascular device and materials manufacturers interested in the mean geometrical features of the artery to target the broad patient population.     

Assessing biodiversity 'sampling packages': how similar are arthropod assemblages in different tropical rainforests?

Arthropod sampling protocols have been applied to four areas of undisturbed rainforest in Australia and Borneo at sites located between 28° S and 4° N. Seven different trapping methods have been used in each case following a strictly comparable protocol applied during single wet-season surveys at each location. A number of large scale patterns across sites correlated with latitude, altitude and/or biogeographical history are evident at the ordinal level. The results are used to evaluate two key ideas in biodiversity survey. The first tests questions of the constancy of particular trap types in terms of the target animals. The second attempts to design an efficient multiple method sampling 'package' for rapid biodiversity assessment. Across all sites similar traps behaved in a similar manner in terms of the profile of arthropods that they caught although Malaise traps and pitfalls are particularly 'constant' in this regard. Subsets of both trapping methods and target taxa are identified which will maximise the opportunities for detecting between site differences.     

Detection of disease-associated deletions in case–control studies using SNP genotypes with application to rheumatoid arthritis

Genomic deletions have long been known to play a causative role in microdeletion syndromes. Recent whole-genome genetic studies have shown that deletions can increase the risk for several psychiatric disorders, suggesting that genomic deletions play an important role in the genetic basis of complex traits. However, the association between genomic deletions and common, complex diseases has not yet been systematically investigated in gene mapping studies. Likelihood-based statistical methods for identifying disease-associated deletions have recently been developed for familial studies of parent-offspring trios. The purpose of this study is to develop statistical approaches for detecting genomic deletions associated with complex disease in case–control studies. Our methods are designed to be used with dense single nucleotide polymorphism (SNP) genotypes to detect deletions in large-scale or whole-genome genetic studies. As more and more SNP genotype data for genome-wide association studies become available, development of sophisticated statistical approaches will be needed that use these data. Our proposed statistical methods are designed to be used in SNP-by-SNP analyses and in cluster analyses based on combined evidence from multiple SNPs. We found that these methods are useful for detecting disease-associated deletions and are robust in the presence of linkage disequilibrium using simulated SNP data sets. Furthermore, we applied the proposed statistical methods to SNP genotype data of chromosome 6p for 868 rheumatoid arthritis patients and 1,197 controls from the North American Rheumatoid Arthritis Consortium. We detected disease-associated deletions within the region of human leukocyte antigen in which genomic deletions were previously discovered in rheumatoid arthritis patients.     

Numerical flow studies in human carotid artery bifurcations: basic discussion of the geometric factor in atherogenesis

In this study fluid dynamic variables are analysed numerically in different human carotid artery bifurcation models in order to clarify the geometric factor in carotid bifurcation atherogenesis. The geometric variations describe healthy human carotid bifurcation anatomy and concern the shape of the carotid sinus and the angle between the branches. The flow conditions remain unchanged. The governing Navier-Stokes equations describing incompressible, pulsatile, three-dimensional viscous flow are approximated using a pressure correction finite element procedure which has been developed for time-consuming, three-dimensional, time-dependent viscous flow problems. The study concentrates on flow velocity, on detailed analysis of flow separation and flow recirculation, and on wall shear stress distribution. The results show that the extension and the location of the recirculation zone in the sinus as well as the duration of separated flow during the pulse cycle are affected by the geometrical variations. In view of the significance of the reversed flow zones and of the accompanied low shear regions in atherogenesis the geometry-dependent flow separation characteristics in the sinus is of substantial interest.     

Carotid geometry effects on blood flow and on risk for vascular disease

It has been widely observed that atherosclerotic diseases occur at sites with complex hemodynamics, such as artery bifurcations, junctions, and regions of high curvature. These regions usually have very low or highly oscillatory wall shear stress (WSS). In the present work, 3D pulsatile blood flow through a model of the carotid artery bifurcation was simulated using a finite volume numerical method. The goal was to quantify the risk of atherogenesis associated with different carotid artery geometries. A risk scale based on the average WSS on the sinus wall of the internal carotid artery was proposed-a scale that can be used to quantify the effect of the carotid geometry on the relative risk for developing vascular disease. It was found that the bifurcation angle and the out-of-plane angle of the internal carotid artery affect the formation of low stress regions on the carotid walls. The main conclusions are: (a) larger internal carotid artery angles (theta(IC)) generally increase the frequency and the area of blood recirculation and lower the WSS on the sinus wall, hence increasing the risk of plaque build-up; (b) off-plane angles were found to lower the WSS on the sinus for geometries with theta(IC)25 degrees . Larger off-plane angles generally increase the danger of plague build-up; (c) for theta(IC) < 25 degrees , the off-plane angle does not have an obvious effect on the hemodynamic WSS; (d) symmetric bifurcations were found to increase the WSS on the sinus wall and ease the risk of vascular disease.     

Endothelial nitric oxide synthase and calcium production in arterial geometries: an integrated fluid mechanics/cell model

It is well known that atherosclerosis occurs at very specific locations throughout the human vasculature, such as arterial bifurcations and bends, all of which are subjected to low wall shear stress. A key player in the pathology of atherosclerosis is the endothelium, controlling the passage of material to and from the artery wall. Endothelial dysfunction refers to the condition where the normal regulation of processes by the endothelium is diminished. In this paper, the blood flow and transport of the low diffusion coefficient species adenosine triphosphate (ATP) are investigated in a variety of arterial geometries: a bifurcation with varying inner angle, and an artery bend. A mathematical model of endothelial calcium and endothelial nitric oxide synthase cellular dynamics is used to investigate spatial variations in the physiology of the endothelium. This model allows assessment of regions of the artery wall deficient in nitric oxide (NO). The models here aim to determine whether 3D flow fields are important in determining ATP concentration and endothelial function. For ATP transport, the effects of a coronary and carotid wave form on mass transport is investigated for low Womersley number. For the carotid, the Womersley number is then increased to determine whether this is an important factor. The results show that regions of low wall shear stress correspond with regions of impaired endothetial nitric oxide synthase signaling, therefore reduced availability of NO. However, experimental work is required to determine if this level is significant. The results also suggest that bifurcation angle is an important factor and acute angle bifurcations are more susceptible to disease than large angle bifurcations. It has been evidenced that complex 3D flow fields play an important role in determining signaling within endothelial cells. Furthermore, the distribution of ATP in blood is highly dependent on secondary flow features. The models here use ATP concentration simulated under steady conditions. This has been evidenced to reproduce essential features of time-averaged ATP concentration over a cardiac cycle for small Womersley numbers. However, when the Womersley number is increased, some differences are observed. Transient variations are overall insignificant, suggesting that spatial variation is more important than temporal. It has been determined that acute angle bifurcations are potentially more susceptible to atherogenesis and steady-state ATP transport reproduces essential features of time-averaged pulsatile transport for small Womersley number. Larger Womersley numbers appear to be an important factor in time-dependent mass transfer.     

Imaging individual protein aggregates to follow aggregation and determine the role of aggregates in neurodegenerative disease

Protein aggregates play a key role in the initiation and spreading of neurodegenerative disease but have been difficult to study due to their low abundance and heterogeneity, in both size and structure. Fluorescence based methods capable of detecting and characterising single aggregates have recently been developed and can be used to measure many important aggregate properties, and can be combined with sensitive assays to measure aggregate toxicity. Here we review these methods and discuss recent examples of their application to determine the molecular mechanism of aggregation and the detection of aggregates in cells and cerebrospinal fluid. The further development of these methods and their application to the aggregates present in humans has the potential to solve a major problem in the field and allow the identification of the key toxic species that should be targeted in therapies.     

Carotid bifurcation position and branching angle in patients with atherosclerotic carotid disease

Carotid artery bifurcation (CB) is the preferred site for development of atherosclerosis (AS) in extracranial cerebral arteries; internal carotid artery stenosis is the most common cause of ischemic stroke. The frequent atherosclerotic disease of CB may best be explained by the hemodynamic influence of complex blood flow that results from the unique geometry of the bifurcation. Few papers analyze all possible geometric structural characteristics of this bifurcation. While performing many carotid endarterectomies, we noticed that a certain correlation between CB height in the neck and its angle existed, that a larger angle is accompanied with increased frequency of elongation and kinking and that CB shape influences distribution of atherosclerosis. The purpose of this paper is to quantify and evaluate these clinical observations. Radiogrametric analysis of 154 bi-plane orthogonal aortic arch arteriograms of patients with symptomatic atherosclerotic carotid artery disease was performed and a total of 289 CBs were analyzed. The CB height in relation to cervical spine segments was measured and real angles of each bifurcation were calculated. A positive linear correlation between CB height and angle exists: the CB angle increases /decreases 3.34 degrees for each third of the cervical vertebral body height or intervertebral space height. The CB is positioned a little higher on the left side. The proximal border of the atherosclerotic process is found at the level of intersection of the axes of the common carotid artery branches in 92.6% of examined CBs. In lower CBs (with smaller angles) the proximal border was located in the last segment of the common carotid artery, while in high bifurcations (wider angles) the proximal border of the AS process is more distally in the blood flow, in the beginning of the internal carotid artery, and the process was more extensive. High CBs are more suitable for eversion endarterectomy while normal and low CBs are more suitable for open (classic) carotid endarterectomy. The influence of the geometric risk factor demands further investigation.     

A Unified Method for Detecting Secondary Trait Associations with Rare Variants: Application to Sequence Data

Next-generation sequencing has made possible the detection of rare variant (RV) associations with quantitative traits (QT). Due to high sequencing cost, many studies can only sequence a modest number of selected samples with extreme QT. Therefore association testing in individual studies can be underpowered. Besides the primary trait, many clinically important secondary traits are often measured. It is highly beneficial if multiple studies can be jointly analyzed for detecting associations with commonly measured traits. However, analyzing secondary traits in selected samples can be biased if sample ascertainment is not properly modeled. Some methods exist for analyzing secondary traits in selected samples, where some burden tests can be implemented. However p-values can only be evaluated analytically via asymptotic approximations, which may not be accurate. Additionally, potentially more powerful sequence kernel association tests, variable selection-based methods, and burden tests that require permutations cannot be incorporated. To overcome these limitations, we developed a unified method for analyzing secondary trait associations with RVs (STAR) in selected samples, incorporating all RV tests. Statistical significance can be evaluated either through permutations or analytically. STAR makes it possible to apply more powerful RV tests to analyze secondary trait associations. It also enables jointly analyzing multiple cohorts ascertained under different study designs, which greatly boosts power. The performance of STAR and commonly used RV association tests were comprehensively evaluated using simulation studies. STAR was also implemented to analyze a dataset from the SardiNIA project where samples with extreme low-density lipoprotein levels were sequenced. A significant association between LDLR and systolic blood pressure was identified, which is supported by pharmacogenetic studies. In summary, for sequencing studies, STAR is an important tool for detecting secondary-trait RV associations.     

To Control False Positives in Gene-Gene Interaction Analysis: Two Novel Conditional Entropy-Based Approaches

Genome-wide analysis of gene-gene interactions has been recognized as a powerful avenue to identify the missing genetic components that can not be detected by using current single-point association analysis. Recently, several model-free methods (e.g. the commonly used information based metrics and several logistic regression-based metrics) were developed for detecting non-linear dependence between genetic loci, but they are potentially at the risk of inflated false positive error, in particular when the main effects at one or both loci are salient. In this study, we proposed two conditional entropy-based metrics to challenge this limitation. Extensive simulations demonstrated that the two proposed metrics, provided the disease is rare, could maintain consistently correct false positive rate. In the scenarios for a common disease, our proposed metrics achieved better or comparable control of false positive error, compared to four previously proposed model-free metrics. In terms of power, our methods outperformed several competing metrics in a range of common disease models. Furthermore, in real data analyses, both metrics succeeded in detecting interactions and were competitive with the originally reported results or the logistic regression approaches. In conclusion, the proposed conditional entropy-based metrics are promising as alternatives to current model-based approaches for detecting genuine epistatic effects.     

Effect of common carotid artery inlet length on normal carotid bifurcation hemodynamics

Controversy exists regarding the suitability of fully developed versus measured inlet velocity profiles for image-based computational fluid dynamics (CFD) studies of carotid bifurcation hemodynamics. Here, we attempt to resolve this by investigating the impact of the reconstructed common carotid artery (CCA) inlet length on computed metrics of "disturbed" flow. Twelve normal carotid bifurcation geometries were reconstructed from contrast-enhanced angiograms acquired as part of the Vascular Aging--The Link That Bridges Age to Atherosclerosis study (VALIDATE). The right carotid artery lumen geometry was reconstructed from its brachiocephalic origin to well above the bifurcation, and the CCA was truncated objectively at locations one, three, five, and seven diameters proximal to where it flares into the bifurcation. Relative to the simulations carried out using the full CCA, models truncated at one CCA diameter strongly overestimated the amount of disturbed flow. Substantial improvement was offered by using three CCA diameters, with only minor further improvement using five CCA diameters. With seven CCA diameters, the amounts of disturbed flow agreed unambiguously with those predicted by the corresponding full-length models. Based on these findings, we recommend that image-based CFD models of the carotid bifurcation should incorporate at least three diameters of CCA length if fully developed velocity profiles are to be imposed at the inlet. The need for imposing measured inlet velocity profiles would seem to be relevant only for those cases where the CCA is severely truncated.     

Symptomatic carotid ischaemic events: safest and most cost effective way of selecting patients for angiography,before carotid endarterectomy.

OBJECTIVE: To determine the safest, least costly, and most effective way to select patients with symptomatic carotid ischaemic events for carotid angiography before carotid endarterectomy. DESIGN: Prospective cohort study. SETTING: University departments of clinical neurosciences and clinical neurology. PATIENTS: 485 Patients with carotid territory transient ischaemic attacks of the brain (n = 224) or eye (n = 162) or retinal infarction (n = 99) were referred to a single neurologist between 1976 and 1986. INTERVENTIONS: Clinical examination by auscultation over the precordium, supraclavicular fossae, and neck vessels (all patients). Cerebral angiography of patients suitable for carotid endarterectomy. MAIN OUTCOME MEASURES: Financial cost and number of disabling strokes after angiography. RESULTS: 296 Patients were investigated by cerebral angiography. Ischaemic symptoms had occurred in the distribution of 298 internal carotid arteries (symptomatic) that were imaged, two patients having bilateral symptoms. The presence or absence of a carotid bruit and the maximum percentage diameter stenosis of the origin of the symptomatic internal carotid artery were correlated. The prevalence of mild disease (diameter stenosis greater than or equal to 25%) of the symptomatic internal carotid artery was 57%, and if an ipsilateral carotid bruit was heard the probability of mild stenosis rose to 92%. The prevalence of moderate disease of the symptomatic internal carotid artery (stenosis greater than or equal to 50%) was 39%, and if a bruit was heard the probability doubled to 78%. The prevalence of severe internal carotid disease (stenosis greater than or equal to 75%) was 22%, and if a bruit was heard the probability was more than double, at 49%. The direct cost to both the NHS and the private health sector of investigating patients with symptomatic carotid ischaemia was estimated for several strategies of carotid artery imaging and expressed in terms of financial cost and number of strokes after angiography incurred in detecting all patients with diameter stenosis of the symptomatic internal carotid artery of greater than or equal to 25%, 50%, or 75%. To detect diameter stenosis of the internal carotid artery of greater than or equal to 25% it is most cost effective to proceed directly to cerebral angiography in patients with a carotid bruit over the symptomatic carotid bifurcation and to screen patients without a carotid bruit by duplex carotid ultrasonography; patients in whom duplex ultrasonography discloses stenosis of greater than or equal to 25% are then referred for cerebral angiography. To detect only more severe internal carotid disease (stenosis of greater than or equal to 50%) the same policy applies, unless the local duplex ultrasonographic service is particularly efficient and reliable, when it is probably most cost effective and safer to screen all patients by this method irrespective of the findings on cervical auscultation. To detect stenosis of 75% or greater it is most cost effective to screen all patients with duplex ultrasonography, whether a carotid bruit is present or not, because this approach reduces the number of angiograms required, is the least expensive, and results in the least number of strokes after angiography. CONCLUSIONS: Patients selection for cerebral angiography before carotid endarterectomy needs to be appropriate and cost effective. Sound clinical evaluation and duplex carotid ultrasound are required. The findings of this study should not be applied to other medical centres without first considering possible differences in the prevalence of carotid artery disease, the efficiency and reliability of duplex ultrasonography, the local complication rates of cerebral angiography, and the local costs of the imaging procedures.     

Non-invasive, ultra-sensitive, high-throughput assays to quantify rare biomarkers in the blood

Many diseases are easier to treat and control when detected at an early stage of disease progression. Often, disease-related antigens or biomarkers are shed from the primary site and present in the blood. Unfortunately, there are very few tests capable of detecting these rare biomarkers in the blood. A blood test would be very useful to diagnose the disease earlier, monitor effectiveness of treatments, predict recurrence, and monitor recurrence. There is certainly a need to develop assays that are ultra-sensitive, non-invasive, and high-throughput. Here we describe several highly sensitive immunological assays we have developed to detect rare serum antigens. Initially we created an assay named immuno-detection amplified by T7 RNA polymerase (IDAT). To enhance the effectiveness and streamline the procedure, this assay was amended to the facile amplification system termed fluorescent amplification catalyzed by T7 polymerase technique (FACTT). These assays have been used to analyze the tumor antigen HER2 and the prion protein PrPSc. They can also be applied to other tumor markers or antigens from a variety of diseases such as cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and hepatitis. These tests are not limited to testing only serum, but may also be applicable to detecting biomarkers in tissue, saliva, urine, cerebrospinal fluid, etc. Clearly, the FACTT-based technology represents an important step in the detection of rare molecules in fluids or tissues for a variety of diseases.     

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.     

Hold everything! Holding policies for protecting plasma supplies

In spite of advances in testing technologies for detecting infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), occasionally blood or plasma is collected that is potentially infectious, but is not detected as such by existing screening tests. We consider the effect of a holding policy for further reducing the number of potentially infectious units that are released for fractionation. The policy dictates a holding period during which all donated units are stored. If a donor tests positive for the infection in question at a subsequent donation, then all of that donor's units currently in storage are discarded. Otherwise, donated units are released at the end of the holding period. In the case of a single disease, we determine optimal holding periods as well as policies that are as effective as the best screening tests currently available.