Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

A dynamic wheel-rail impact analysis of railway track under wheel flat by Finite Element Analysis

Wheel–rail interaction is one of the most important research topics in railway engineering. It involves track impact response, track vibration and track safety. Track structure failures caused by wheel–rail impact forces can lead to significant economic loss for track owners through damage to rails and to the sleepers beneath. Wheel–rail impact forces occur because of imperfections in the wheels or rails such as wheel flats, irregular wheel profiles, rail corrugations and differences in the heights of rails connected at a welded joint. A wheel flat can cause a large dynamic impact force as well as a forced vibration with a high frequency, which can cause damage to the track structure. In the present work, a three-dimensional (3-D) finite element (FE) model for the impact analysis induced by the wheel flat is developed by use of the finite element analysis (FEA) software package ANSYS and validated by another validated simulation. The effect of wheel flats on impact forces is thoroughly investigated. It is found that the presence of a wheel flat will significantly increase the dynamic impact force on both rail and sleeper. The impact force will monotonically increase with the size of wheel flats. The relationships between the impact force and the wheel flat size are explored from this finite element analysis and they are important for track engineers to improve their understanding of the design and maintenance of the track system.

Analysis of heat transfer and fluid flow in a triangular enclosure in presence of an adiabatic fin

Natural convection thermal boundary layer adjacent to the heated inclined wall of a right angled triangle with an adiabatic fin attached to that surface is investigated by numerical simulations. The finite volume based unsteady numerical model is adopted for the simulation. It is revealed from the numerical results that the development of the boundary layer along the inclined surface is characterized by three distinct stages, i.e. a start-up stage, a transitional stage and a steady stage. These three stages can be clearly identified from the numerical simulations. Moreover, in presence of adiabatic fin, the thermal boundary layer adjacent to the inclined wall breaks initially. However, it is reattached with the downstream boundary layer next to the fin. More attention has been given to the boundary layer development near the fin area.

An analysis of the KEEP CLEAR pavement markings effects on queuing vehicles dynamic performance at urban signalised intersections

KEEP CLEAR pavement markings are widely used at urban signalised intersections to indicate to drivers to avoid entering blocked intersections. For example, ‘Box junctions’ are most widely used in the United Kingdom and other European countries. However, in Australia, KEEP CLEAR markings are mostly used to improve access from side roads onto a main road, especially when the side road is very close to a signalised intersection. This paper aims to reveal how the KEEP CLEAR markings affect the dynamic performance of the queuing vehicles on the main road, where the side road access is near a signalised intersection. Raw traffic field data was collected from an intersection at the Gold Coast, Australia, and the Kanade–Lucas–Tomasi (KLT) feature tracker approach was used to extract dynamic vehicle data from the raw video footage. The data analysis reveals that the KEEP CLEAR markings generate positive effects on the queuing vehicles in discharge on the main road. This finding refutes the traditional viewpoint that the KEEP CLEAR pavement markings will cause delay for the queuing vehicles’ departure due to the enlarged queue spacing. Further studies are suggested in this paper as well.

TUNEL analysis of DNA fragmentation in mouse unfertilized oocytes : the effect of microorganisms within human follicular fluid collected during IVF cycles

Recently we reported the presence of bacteria within follicular fluid. Previous studies have reported that DNA fragmentation in human spermatozoa after in vivo or in vitro incubation with bacteria results in early embryo demise and a reduced rate of ongoing pregnancy, but the effect of bacteria on oocytes is unknown. This study examined the DNA within mouse oocytes after 12 hours’ incubation within human follicular fluids (n = 5), which were collected from women undergoing in vitro fertilization (IVF) treatment. Each follicular fluid sample was cultured to detect the presence of bacteria. Terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) was used to label DNA fragmentation in ovulated, non-fertilized mouse oocytes following in vitro incubation in human follicular fluid. The bacteria Streptococcus anginosus and Peptoniphilus spp., Lactobacillus gasseri (low-dose), L. gasseri (high-dose), Enterococcus faecalis, or Propionibacterium acnes were detected within the follicular fluids. The most severe DNA fragmentation was observed in oocytes incubated in the follicular fluids containing P. acnes or L. gasseri (high-dose). No DNA fragmentation was observed in the mouse oocytes incubated in the follicular fluid containing low-dose L. gasseri or E. faecalis. Low human oocyte fertilization rates (<29%) were associated with extensive fragmentation in mouse oocytes (80–100%). Bacteria colonizing human follicular fluid in vivo may cause DNA fragmentation in mouse oocytes following 12 h of in vitro incubation. Follicular fluid bacteria may result in poor quality oocytes and/or embryos, leading to poor IVF outcomes.

Fluid-structure interaction analysis of full scale vehicle-barrier impact using coupled SPH-FEA

Portable water-filled barriers (PWFB) are roadside structures used to separate moving traffic from work-zones. Numerical PWFB modelling is preferred in the design stages prior to actual testing. This paper aims to study the fluid-structure interaction of PWFB under vehicular impact using several methods. The strategy to treat water as non-structural mass was proposed and the errors were investigated. It was found that water can be treated with the FEA-NSM model for velocities higher than 80kmh-1. However, full SPH/FEA model is still the best treatment for water and necessary for lower impact velocities. The findings in this paper can be used as guidelines for modelling and designing PWFB.

Dynamic load sharing in heavy vehicle suspensions - further analysis of the equalisation effects of larger air lines

This paper provides details on comparative testing of axle-to-chassis forces of two heavy vehicles (HVs) based on an experimental programme carried out in 2007. Dynamic forces at the air springs were measured against speed and roughness values for the test roads used. One goal of that programme was to determine whether dynamic axle-to-chassis forces could be reduced by using larger-than-standard diameter longitudinal air lines. This paper presents a portion of the methodology, analysis and results from that programme. Two analytical techniques and their results are presented. The first uses correlation coefficients of the forces between air springs and the second is a student’s t-test. These were used to determine the causality surrounding improved dynamic load sharing between heavy vehicle air springs with larger air lines installed longitudinally compared with the standard sized air lines installed on the majority of air-sprung heavy vehicles.

Biomechanical characteristics of peripheral diabetic neuropathy : a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

Background: Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Methods: Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Findings: Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes.; Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Time-domain hydroelastic analysis of a flexible marine structure using state-space models

This article deals with time-domain hydroelastic analysis of a marine structure. The convolution terms associated with fluid memory effects are replaced by an alternative state-space representation, the parameters of which are obtained by using realization theory. The mathematical model established is validated by comparison to experimental results of a very flexible barge. Two types of time-domain simulations are performed: dynamic response of the initially inert structure to incident regular waves and transient response of the structure after it is released from a displaced condition in still water. The accuracy and the efficiency of the simulations based on the state-space model representations are compared to those that integrate the convolutions.

Fluid-structure interaction analysis by coupled FE-SPH model based on a novel searching algorithm

Fluid–Structure Interaction (FSI) problem is significant in science and engineering, which leads to challenges for computational mechanics. The coupled model of Finite Element and Smoothed Particle Hydrodynamics (FE-SPH) is a robust technique for simulation of FSI problems. However, two important steps of neighbor searching and contact searching in the coupled FE-SPH model are extremely time-consuming. Point-In-Box (PIB) searching algorithm has been developed by Swegle to improve the efficiency of searching. However, it has a shortcoming that efficiency of searching can be significantly affected by the distribution of points (nodes in FEM and particles in SPH). In this paper, in order to improve the efficiency of searching, a novel Striped-PIB (S-PIB) searching algorithm is proposed to overcome the shortcoming of PIB algorithm that caused by points distribution, and the two time-consuming steps of neighbor searching and contact searching are integrated into one searching step. The accuracy and efficiency of the newly developed searching algorithm is studied on by efficiency test and FSI problems. It has been found that the newly developed model can significantly improve the computational efficiency and it is believed to be a powerful tool for the FSI analysis.

Heat transfer analysis of viscous incompressible fluid by combined natural convection and radiation in an open cavity

The effect of radiation on natural convection of Newtonian fluid contained in an open cavity is investigated in this study. The governing partial differential equations are solved numerically using the Alternate Direct Implicit method together with the Successive Over Relaxation method. The study is focused on studying the flow pattern and the convective and radiative heat transfer rates are studied for different values of radiation parameters namely, the optical thickness of the fluid, scattering albedo, and the Planck number. It was found that in the optically thin limit, an increase in the optical thickness of the fluid raises the temperature and radiation heat transfer of the fluid. However, a further increase in the optical thickness decreases the radiative heat transfer rate due to increase in the energy level of the fluid, which ultimately reduces the total heat transfer rate within the fluid.

Automated 3D mapping & shape analysis of the lateral ventricles via fluid registration of multiple surface-based atlases

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles, designed for monitoring degenerative disease effects in clinical neuroscience studies and drug trials. First we used a set of parameterized surfaces to represent the ventricles in a manually labeled set of 9 subjects' MRIs (atlases). We fluidly registered each of these atlases and mesh models to a set of MRIs from 12 Alzheimer's disease (AD) patients and 14 matched healthy elderly subjects, and we averaged the resulting meshes for each of these images. Validation experiments on expert segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease-related alterations monotonically improved as the number of atlases, N, was increased from 1 to 9. We then combined the segmentations with a radial mapping approach to localize ventricular shape differences in patients. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases, and we formulated a statistical stopping criterion to determine the optimal value of N. Anterior horn anomalies in Alzheimer's patients were only detected with the multi-atlas segmentation, which clearly outperformed the standard single-atlas approach.

Genome-Wide Gene Expression Analysis Reveals a Dynamic Interplay between Luteotropic and Luteolytic Factors in the Regulation of Corpus Luteum Function in the Bonnet Monkey (Macaca radiata)

Although LH is essential for survival and function of the corpus luteum (CL) in higher primates, luteolysis occurs during nonfertile cycles without a discernible decrease in circulating LH levels. Using genome-wide expression analysis, several experiments were performed to examine the processes of luteolysis and rescue of luteal function in monkeys. Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted in differential regulation of 3949 genes, whereas replacement with exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes (1563 down-regulation and 2871 up-regulation). A model system for prostaglandin (PG) F-2 alpha-induced luteolysis in the monkey was standardized and demonstrated that PGF(2 alpha) regulated expression of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome revealed that 120 genes were regulated in an antagonistic fashion by PGF(2 alpha). Based on the microarray data, 25 genes were selected for validation by real-time RT-PCR analysis, and expression of these genes was also examined in the CL throughout the luteal phase and from monkeys treated with human chorionic gonadotropin (hCG) to mimic early pregnancy. The results indicated changes in expression of genes favorable to PGF(2 alpha) action during the late to very late luteal phase, and expressions of many of these genes were regulated in an opposite manner by exogenous hCG treatment. Collectively, the findings suggest that curtailment of expression of downstream LH-target genes possibly through PGF(2 alpha) action on the CL is among the mechanisms underlying cross talk between the luteotropic and luteolytic signaling pathways that result in the cessation of luteal function, but hCG is likely to abrogate the PGF(2 alpha)-responsive gene expression changes resulting in luteal rescue crucial for the maintenance of early pregnancy. (Endocrinology 150: 1473-1484, 2009)