Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.

BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N­terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques. OBJECTIVES: To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity. DESIGN: Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study. SETTING: Patients recruited at clinical research sites in the United States and Japan. PARTICIPANTS: 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer's disease and mild-to-moderate Alzheimer's disease dementia. INTERVENTION: Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15). MEASUREMENTS: Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse events, magnetic resonance imaging, electrocardiogram, vital signs, laboratory testing, neurological monitoring, and immunogenicity. RESULTS: Treatment with donanemab resulted in rapid reduction of amyloid, even after a single dose. By 24 weeks, amyloid positron emission tomography mean changes from baseline for single donanemab doses in Centiloids were: -16.5 (standard error 11.22) 10-mg/kg intravenous; 40.0 (standard error 11.23) 20 mg/kg intravenous; and -49.6 (standard error 15.10) 40-mg/kg intravenous. Mean reduction of amyloid plaque in multiple dose cohorts by 24 weeks in Centiloids were: 55.8 (standard error 9.51) 10-mg/kg every 2 weeks; -50.2 (standard error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose of donanemab. Repeated dosing resulted in continued florbetapir positron emission tomography reductions over time compared to single dosing with 6 out of 28 patients attaining complete amyloid clearance within 24 weeks. Within these, 5 out of 10 patients in the 20 mg/kg every 4 weeks cohort attained complete amyloid clearance within 36 weeks. When dosing with donanemab was stopped after 24 weeks of repeat dosing in the 10 mg every 2 weeks cohort, florbetapir positron emission tomography reductions were sustained up to 72 weeks. For the single dose cohorts on day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose cohorts. Donanemab clearance was comparable across the dose levels. Mean donanemab elimination-half-life following 20 mg/kg single dose was 9.3 days with range of 5.6 to 16.2 days. Greater than 90% of patients had positive treatment-emergent antidrug antibodies with donanemab. However, overall, the treatment-emergent antidrug antibodies did not have a significant impact on pharmacokinetics. Donanemab was generally well tolerated. Amongst the 46 participants treated with donanemab, the following amyloid-related imaging abnormalities, common to the drug class, were observed: 12 vasogenic cerebral edema events (12 [19.7%] patients), 10 cerebral microhemorrhage events (6 [13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). CONCLUSIONS: Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid plaque despite treatment-emergent antidrug antibodies detected in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent event.

Towards identification of important plant areas (IPA) for Peninsular Malaysia. Methodology and future directions.

Malaysia is a megadiverse country and listed as one of the world's biodiversity hotspots. Land use changes and deforestation have led to the threat of, and extinction of plant species. In order to mitigate loss in population numbers, and to prevent species extinction events, Important Plant Areas (IPA) for Malaysia shall be identified. The identification of IPA is important to ensure that key natural areas are adequately protected and managed to preserve the species and its habitats. Currently, there are 1771 IPA identified globally and only seven tropical countries are actively involved excluding Malaysia. Inventory and biodiversity research are actively conducted in Malaysia, however, the initiative to identify IPA is still in its infancy. The first attempt for IPA identification was in the state of Terengganu by using herbarium database through scoring technique. In this paper, we discussed methods and criteria used in IPA identification globally. We also deliberated current IPA development in Terengganu and challenges such as collections biases and the need for a robust scoring technique to reduce judgement uncertainty. We suggested GIS based multi-criteria decision making, analytical hierarchy process and species distribution for Malaysian IPA. These strategies were considered to be effective tools in providing decision support for spatial planning aimed at plant conservation in Malaysia.

Modeling washoff of total suspended solids in the tropics.

Washoff behavior in the tropics is expected to behave differently from temperate areas due to differences in rainfall characteristics. In this study, rainfall, runoff and total suspended solids (TSS) were monitored from 9 catchments distinguished by different types of land use, in Singapore. The catchments ranged in size from 5.7ha to 85.2ha. Over 120 rain events were studied and more than 1000 storm samples were collected and analyzed. Monte Carlo analysis was applied to obtain the best fit values of the washoff model parameters consisting the washoff coefficient c3, washoff exponent c4 and initial mass on surface Bini. The exponent c4 was found to be approximately unity for all the events monitored, in agreement with other studies. The values of c3 and Bini were found to vary between events. Among all the rainfall and runoff characteristics studied, rainfall depth of the current event (d) was found to be the single parameter that significantly influenced the values of c3 and Bini. Contrary to expectations, Bini did not correlate well with antecedent dry period or with rainfall depth of the prior storm event. The results show that the common modeling practice where Bini is assumed to vary with antecedent dry period and previous rainfall depth should be reassessed when applied to catchments in the tropics. ANCOVA analysis showed that land use was not significant, but rather the variation of c3 and Bini with d was found to correlate well with the catchment area.

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution. METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/µL) and oIR (CD4 T-cell count > 500 cells/µL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells. RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses. CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

Associations of chemical tracers and faecal indicator bacteria in a tropical urban catchment.

Surface water contamination by human faecal wastes is a widespread hazard for human health. Faecal indicator bacteria (FIB) are the most widely used indicators to assess surface water quality but are less-human-specific and have the potential to survive longer and/or occur naturally in tropical areas. In this study, 13 wastewater chemicals (chloride, boron, orthosphophate, detergents as methylene blue active substances, cholesterol, cholestanol, coprostanol, diethylhexyl phthalate, caffeine, acetaminophen, ibuprofen, sucralose and saccharin) were investigated in order to evaluate tracers for human faecal and sewage contamination in tropical urban catchments. Surface water samples were collected at an hourly interval from sampling locations with distinct major land uses: high-density residential, low-density residential, commercial and industrial. Measured concentrations were analysed to investigate the association among indicators and tracers for each land-use category. Better correlations were found between different indicators and tracers in each land-use dataset than in the dataset for all land uses, which shows that land use is an important determinant of drain water quality. Data were further segregated based on the hourly FIB concentrations. There were better correlations between FIB and chemical tracers when FIB concentrations were higher. Therefore, sampling programs must be designed carefully to take the time of sampling and land use into account in order to effectively assess human faecal and sewage contamination in urban catchments. FIB is recommended as the first tier in assessment of surface water quality impairment and chemical tracers as the second tier. Acetaminophen and coprostanol are recommended as chemical tracers for high-density residential areas, while chloride, coprostanol and caffeine are recommended for low-density residential areas.

Clinical and immunochemical profiles of food challenge proven or anaphylactic shrimp allergy in tropical Singapore.

BACKGROUND: Shellfish allergy in Singapore is highly prevalent, and shrimp allergy is the most common. OBJECTIVE: This study aims to evaluate the clinical characteristics and immunological phenotype of shellfish allergy in this population. METHODS: Patients with self-reported shellfish allergy were recruited from outpatient clinics of three large hospitals and from a population survey. Open oral food challenges (OFC) to glass prawn (Litopenaeus vannamei) and tiger prawn (Penaeus monodon) were carried out on all patients except for those who had a history of severe anaphylaxis. Skin prick tests (SPT) and specific IgE to crude and recombinant allergens were carried out to evaluate shrimp and dust mite sensitization. Immunoblots were used to assess IgE-binding proteins. RESULTS: The 104 patients recruited were categorized into shellfish allergic (SA) when OFC was positive or had a history of severe anaphylaxis (n = 39), shellfish tolerant (ST) when OFC was negative (n = 27), and house dust mite positive controls (HDM(+) ) who were ST (n = 38). Oral symptoms (87.1%) were the predominant clinical manifestation. Positive challenge doses ranged from 2 to 80 g of cooked shrimp, with 25/52 patients reacting to either one or both shrimps challenged. The presence of specific IgE to shrimp either by SPT and/or ImmunoCAP(®) assay provided diagnostic test sensitivity of 82% and specificity of 22.2%. The inclusion of specific IgE to shrimp tropomyosin and IgE immunoblots with shrimp extracts did not improve the diagnostic proficiency substantially. CONCLUSIONS AND CLINICAL RELEVANCE: This study highlights the predominance of oral symptoms in shrimp allergy in tropical Asia and that a high provocation dose may be necessary to reveal shrimp allergy. Furthermore, specific IgE diagnostic tests and immunoblots were of limited use in this population.

Temporal variation of faecal indicator bacteria in tropical urban storm drains.

Human faecal contamination poses a widespread hazard for human health. In urban areas, sewer leakage may be an important cause of faecal pollution to surface water. Faecal indicator bacteria (FIB) are the most widely used indicators to monitor surface water quality. However, assessing whether a water body is meeting water quality criteria is made difficult by the high variability of FIB concentrations over time. In this study, the variation of FIB concentration in surface water from tropical urban catchments is investigated. Eleven urban sub-catchments were sampled hourly over 24-hr and samples analysed for FIB. It was found that FIB show a diurnal pattern that is characterised by daytime FIB concentrations that are significantly higher than nighttime FIB concentrations. This observed diurnal variation of FIB closely follows that of sewer flows and contrasts with observations in rural streams where FIB concentrations are known to be low in the daytime and high during the night. Field tracer tests provide qualitative evidence of sewage exfiltration and transport to drains via preferential flow paths. The diurnal FIB variation and field tracer tests indicate the likelihood of surface water contamination due to leaking sewers. The results further suggest that contamination of surface-water drains is likely a widespread problem in tropical urban areas due to extensive drainage networks and the persistence of FIB under tropical conditions. Because of FIB variation over time, the time at which samples are collected is important in being able to capture the daily maximum and minimum FIB concentrations. The Kruskal-Wallis test shows that hourly sampling from 04:00 to 07:00 and from 12:00 to 15:00 results in significantly different FIB concentration (minimum and maximum, respectively). Furthermore, the Wilcoxon-Mann-Whitney test shows that sampling at 12:00 and 14:00 results in significantly higher FIB concentrations, while sampling at 05:00 and 04:00 or 05:00 and 06:00 results in significantly lower FIB concentrations, than sampling at other hours of the day.

Distribution and abundance of human-specific Bacteroides and relation to traditional indicators in an urban tropical catchment.

AIMS: The study goals were to determine the relationship between faecal indicator bacteria (FIB), the HF183 marker and land use, and the phylogenetic diversity of HF183 marker sequences in a tropical urban watershed. METHODS AND RESULTS: Total coliforms, Escherichia coli, and HF183 were quantified in 81 samples categorized as undeveloped, residential and horticultural from the Kranji Reservoir and Catchment in Singapore. Quantitative-PCR for HF183 followed by analysis of variance indicated that horticultural areas had significantly higher geometric means for marker levels (4·3 × 10(4) HF183-GE 100 ml(-1)) than nonhorticultural areas (3·07 × 10(3) HF183-GE 100 ml(-1)). E. coli and HF183 were moderately correlated in horticultural areas (R = 0·59, P = 0·0077), but not elsewhere in the catchment. Initial upstream surveys of candidate sources revealed elevated HF183 in a wastewater treatment effluent but not in aquaculture ponds. The HF183 marker was cloned, sequenced and determined by phylogenetic analysis to match the original marker description. CONCLUSION: We show that quantification of the HF183 marker is a useful tool for mapping the spatial distribution and potential sources of human sewage contamination in tropical environments such as Singapore. SIGNIFICANCE AND IMPACT: A major challenge for assessment of water quality in tropical environments is the natural occurrence and nonconservative behaviour of FIB. The HF183 marker has been employed in temperate environments as an alternative indicator for human sewage contamination. Our study supports the use of the HF183 marker as an indicator for human sewage in Singapore and motivates further work to determine HF183 marker levels that correspond to public health risk in tropical environments.

Explicit nonlinear finite element geometric analysis of parabolic leaf springs under various loads.

This study describes the effects of bounce, brake, and roll behavior of a bus toward its leaf spring suspension systems. Parabolic leaf springs are designed based on vertical deflection and stress; however, loads are practically derived from various modes especially under harsh road drives or emergency braking. Parabolic leaf springs must sustain these loads without failing to ensure bus and passenger safety. In this study, the explicit nonlinear dynamic finite element (FE) method is implemented because of the complexity of experimental testing A series of load cases; namely, vertical push, wind-up, and suspension roll are introduced for the simulations. The vertical stiffness of the parabolic leaf springs is related to the vehicle load-carrying capability, whereas the wind-up stiffness is associated with vehicle braking. The roll stiffness of the parabolic leaf springs is correlated with the vehicle roll stability. To obtain a better bus performance, two new parabolic leaf spring designs are proposed and simulated. The stress level during the loadings is observed and compared with its design limit. Results indicate that the newly designed high vertical stiffness parabolic spring provides the bus a greater roll stability and a lower stress value compared with the original design. Bus safety and stability is promoted, as well as the load carrying capability.

Langerhans cell histiocytosis with hypogonadotrophic hypogonadism.

Langerhans cell histiocytosis (LCH) is a rare disease characterised by monoclonal proliferation and infiltration of organs by large mononuclear cells. Organs commonly involved include the lungs and pituitary gland. However, the disease association with hypogonadotrophic hypogonadism has not been reported in the literature, to our knowledge. We report a 26-year-old Chinese man with LCH, recurrent pneumothoraces, diabetes insipidus and hypogonadotrophic hypogonadism. The clinical features and management of the disease are reviewed.

Repair of defects and containment in revision total knee replacement: a comparative biomechanical analysis.

The treatment of bony defects of the tibia at the time of revision total knee replacement is controversial. The place of compacted morsellised bone graft is becoming established, particularly in contained defects. It has previously been shown that the initial stability of impaction-grafted trays in the contained defects is equivalent to that of an uncemented primary knee replacement. However, there is little biomechanical evidence on which to base a decision in the treatment of uncontained defects. We undertook a laboratory-based biomechanical study comparing three methods of graft containment in segmental medial tibial defects and compared them with the use of a modular metal augment to bypass the defect. Using resin models of the proximal tibia with medial defects representing either 46% or 65% of the medial cortical rim, repair of the defect was accomplished using mesh, cement or a novel bag technique, after which impaction bone grafting was used to fill the contained defects and a tibial component was cemented in place. As a control, a cemented tibial component with modular metal augments was used in identical defects. All specimens were submitted to cyclical mechanical loading, during which cyclical and permanent tray displacement were determined. The results showed satisfactory stability with all the techniques except the bone bag method. Using metal augments gave the highest initial stability, but obviously lacked any potential for bone restoration.

Particle image velocimetry measurements of three proximal anastomosis models under a pulsatile flow condition.

This study was designed to examine the effects of the anastomotic angle on the flow and haemodynamic parameter distribution patterns of the proximal anastomoses, with emphasis on identifying site-specific haemodynamic features that could reasonably be expected to trigger the initiation and further development of anastomotic intimal hyperplasia. Particle image velocimetry measurements were carried out with three simplified glass proximal models under a physiological flow condition. The results revealed that the disturbed flow and the induced shear stress patterns including low recirculation flow, stagnation point, high wall shear stress, high temporal wall shear stress gradient, low time-averaged wall shear stress (TAWSS), and high oscillating shear index (OSI) occurred around the anastomotic joints and the flow field at proximal anastomosis was strongly affected by the anastomotic angle. Among the three models investigated, the 45 degrees backward anastomosis is found to have a smaller low-recirculation-flow region along the graft inner wall, non-stationary stagnation, and separation points, a higher TAWSS and smaller high-OSI low-TAWSS and low-OSI high-TAWSS regions.

Haloperidol versus chlorpromazine for schizophrenia.

BACKGROUND: Chlorpromazine and haloperidol are benchmark antipsychotic drugs. Both are said to be equally effective when used at equivalent doses, but have different side-effect profiles. OBJECTIVES: To compare the effects of haloperidol and chlorpromazine for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (August 2006). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of relevant trials. SELECTION CRITERIA: We included all randomised controlled trials that compared haloperidol with chlorpromazine for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by at least two reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. For dichotomous data we calculated the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis using a random-effects model. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately. AUTHORS' CONCLUSIONS: Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required.

Flow studies in three-dimensional aorto-right coronary bypass graft system.

This paper presents the fluid dynamics of blood flow in a coronary bypass model of the aorto-right coronary bypass system. Three-dimensional computational fluid dynamic simulations are developed of the blood flow in coronary artery-bypass systems, using the computational fluid dynamics software (FLUENT 6.0.1). These blood flow simulations are performed within small intervals of the cardiac cycle, using input data consisting of physiological measurements of flow rates in the aorta, obtained from earlier studies. We have calculated the flow-field distributions of the velocity and the wall shear stress at four typical instants of the cardiac cycle, two during systole and two during the diastole phase. Plots of velocity vector and the wall shear stress are displayed in the aorto-graft-coronary arterial flow-field domain, providing an insight into the link between fluid dynamics and arterial diseases. The prime regions of disturbed flow patterns are at the entrance into the graft from the aorta and at the exit from the graft into the right coronary artery. Our objective is to obtain an understanding of how the coronary artery is perfused by the graft, and thereby into the factors affecting graft patency.

Wavelet multiresolution analysis of the three vorticity components in a turbulent far wake.

The main objective of the present study is to examine the characteristics of the vortical structures in a turbulent far wake using the wavelet multiresolution technique by decomposing the vorticity into a number of orthogonal wavelet components based on different central frequencies. The three vorticity components were measured simultaneously using an eight-wire probe at three Reynolds numbers, namely 2000, 4000, and 6000. It is found that the dominant contributions to the vorticity variances are from the intermediate and relatively small-scale structures. The contributions from the large and intermediate-scale structures to the vorticity variances decrease with the increase of Reynolds number. The contributions from the small-scale structures to all three vorticity variances jump significantly when Reynolds number is changed from 2000 to 4000, which is connected to previous observations in the near wake that there is a significant increase in the generation of small-scale structures once the Reynolds number reaches about 5000. This result reinforces the conception that turbulence "remembers" its origin.

Increased uptake of divalent metals lead and cadmium into the brain after kainite-induced neuronal injury.

An increase in iron level, number of iron positive cells and ferritin expression has been observed in the rat hippocampus after neuronal injury induced by the excitotoxin, kainate. This is accompanied by an increased expression of divalent metal transporter-1 (DMT1) in the lesioned hippocampus, suggesting that the transporter may be partially responsible for the iron accumulation. DMT1 has a broad substrate range that includes other divalent metals such as lead (Pb) and cadmium (Cd), and the present study was carried out to elucidate the uptake of these metals in the kainate-injected brain. The technique of atomic absorption spectroscopy was used for analyses. Significantly higher lead and cadmium levels were detected in the hippocampus and other brain areas of intracerebroventricular kainate-injected rats treated with lead and cadmium in the drinking water, compared to intracerebroventricular saline-injected rats treated with lead and cadmium in the drinking water. Since very low levels of lead and cadmium are present in the normal animal, these results indicate increased uptake of lead and cadmium into brain areas as a result of the kainate injections. Increased iron levels were also detected in the hippocampus of the kainate-injected rats. The above results show increased uptake of divalent metals into brain areas undergoing neurodegeneration.

Comparisons between different approximations to energy dissipation rate in a self-preserving far wake.

By using a four-hot-wire probe and an eight-hot-wire probe, different approximations to energy dissipation rate have been made in the far field of a cylinder wake. The appropriateness of the various approximations is evaluated by examining their mean values, spectra, conditional analysis, and scaling range exponents. It is found that there are significant differences between the instantaneous values of E(iso), the isotropic dissipation rate, and other approximations. The present measurements also allow the examination of the spatial correlation between the energy dissipation rate and the enstrophy Omega. While the correlation between E(iso) and Omega is low, there is a strong correlation between the other approximations to energy dissipation rate and the enstrophy Omega. The scaling range exponents show that the substitutes to the energy dissipation rate and enstrophy based on isotropy are more intermittent than their corresponding true values. The present results suggest that using E(iso) as a substitute of should be re-examined, especially for the instantaneous values.

Numerical study on the pulsatile flow characteristics of proximal anastomotic models.

Haemodynamics was widely believed to correlate with anastomosis restenosis. Utilizing the haemodynamic parameters as indicator functions, distal anastomosis was redesigned by some researchers so as to improve the long-term graft patency rate. However, there were few studies upon the proximal anastomosis. Therefore, in this study, flow characteristics and distributions of the haemodynamic parameters in proximal anastomosis under physiological flow condition have been investigated numerically for three different grafting angles: namely, 45 degrees forward facing, 45 degrees backward facing, and 90 degrees anastomotic joints. The simulation results showed a flow separation region along the graft inner wall immediately after the heel at peak flow phase and it decreased in size with the grafting angle shifting from 45 degrees forward facing to 45 degrees backward facing. At the same time, a pair of vortex was found in the cross-sectional planes of the 45 degrees backward facing and 90 degrees grafts. In addition, stagnation point was found along the graft outer wall with small shifting during the physiological cycle. High spatial and temporal wall shear stresses gradients (WSSG) were observed around the anastomotic joint. Low time-averaged wall shear stress (WSS) with elevated oscillation shear index (OSI) was found near the middle of anastomosis at the aorta wall and along the graft inner wall respectively, while high time-averaged WSS with low OSI was found at the heel, the toe, and the region downstream of the toe. These regions correlated to early lesion growth. Elevated time-averaged WSSG was found at the same region, where the elevated low-density lipoprotein (LDL) permeability was observed as reported in the literature. The existence of nearly fixed stagnating location, flow separation, vortex, high time-averaged WSS with low OSI, low time-averaged WSS with elevated OSI, and high time-averaged WSSG may lead to graft stenosis. Moreover, the simulation results obtained were consistent with those of experimental measurements. Based on the validated simulation results, the 45 degrees backward-facing graft was found to have the lowest variation range of time-averaged WSS and the lowest segmental average of WSSG among the three models investigated. The 45 degrees backward-facing graft is thus recommended for the bypass operation with expected higher patency rate.