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Approximately 20% early-stage (I/II) colorectal cancer (CRC) patients develop metastases despite curative surgery. We aim to develop a formalin-fixed and paraffin-embedded (FFPE)-based predictor of metastases in early-stage, clinically-defined low risk, microsatellite-stable (MSS) CRC patients. We considered genome-wide mRNA and miRNA expression and mutation status of 20 genes assayed in 150 fresh-frozen tumours with known metastasis status. We selected 193 genes for further analysis using NanoString nCounter arrays on corresponding FFPE tumours. Neither mutation status nor miRNA expression improved the estimated prediction. The final predictor, ColoMet19, based on the top 19 genes' mRNA levels trained by Random Forest machine-learning strategy, had an estimated positive-predictive-value (PPV) of 0.66. We tested ColoMet19 on an independent test-set of 131 tumours and obtained a population-adjusted PPV of 0.67 indicating that early-stage CRC patients who tested positive have a 67% risk of developing metastases, substantially higher than the metastasis risk of 40% for node-positive (Stage III) patients who are generally treated with chemotherapy. Predicted-positive patients also had poorer metastasis-free survival (hazard ratios [HR] = 1.92, design-set; HR = 2.05, test-set). Thus, early-stage CRC patients who test positive may be considered for adjuvant therapy after surgery.

Acute limb ischemia is both a limb-threatening and life-threatening disease process. Nontraumatic acute peripheral arterial occlusion is most commonly caused by a thrombosis or an embolism.There is limited evidence on the use of bedside ultrasound for the detection of acute limb ischemia, but duplex ultrasonography is standard in the diagnosis and operative planning in chronic limb ischemia. Emergency physicians may use bedside ultrasound in the evaluation of patients with symptoms and signs suggestive of this disease entity.A 64-year-old man with a past medical history of hypertension and an ischemic stroke presented to the Emergency Department with2 h of severe upper left leg pain that radiated down to his foot. A bedside ultrasound of the left lower extremity was emergently performed. On B-mode ultrasound evaluation, echogenic material was visualized in the left common femoral artery, the artery was noncompressible, and there was an absence of Doppler flow signal. He was then directly taken to the operating room for an emergent limb-saving procedure.A focused examination of the aorta, iliac vessels, and femoral artery bifurcation with bedside ultrasonography may help to localize peripheral arterial occlusions and can assist the emergency physician in seeking timely surgical consultation and management.

Pollutant emissions for vehicles are a function of the amount of energy it consumes and the feedstock for that energy. A model was built to capture the energy and pollutant damage costs associated with using electric vehicles (EVs), hybrid vehicles and internal combustion engine cars in Singapore based on vehicles currently available in the Singapore market. These damage costs were compared to vehicle purchase price and fuel costs. This is part of broader work to compare the costs and benefits of EVs with hybrid and ICE vehicles in Singapore.

Besides its application in media printing, drop-on-demand (DoD) printing is becoming an attractive alternative to traditional micro-fabrication to build 3D structures with wide applications. In DoD printing, each type of nozzle (ejector) has its uniqueness and limitation in the dispensing material properties, driving parameters, and the ejected droplet dimension. This paper presents a multi-nozzle DoD printing machine to satisfy the increasing demand for multi-material dispensing in industry. On the hardware aspect, a microcontroller-based synchronizer is designed to synchronize the printing process from multi-nozzles with respect to a movable positioning stage. This real-time control contributes to accurate micro-droplet deposition. On the software aspect, a three-layer framework is proposed, including user interface, system manager, and hardware interface layer. This proposed structure greatly improves the system flexibility with which the user can dynamically configure the desired dispensers for 3D structure printing. Integrating these techniques into the printing system, the developed DoD system can achieve a flexible and friendly user interface, while dispensing a wide range of functional materials using various types of dispensing nozzles.

Equilibrium moisture sorptions of two dried aqueous herbal extracts and their mixtures with dextrans of various molecular weights were investigated as a function of relative humidity at ambient temperature, and the data were analyzed by both the Guggenheim-Anderson-deBoer (GAB) and Brunauer-Emmett-Teller (BET) equations. Glass transition temperatures (T(g)) of the samples were measured by differential scanning calorimetry, and their dependence on the moisture contents of the extracts was analyzed by the linear, Fox and expanded Gordon-Taylor mathematical models. All dextran-extract mixtures exhibited single T(g) values, indicating that they existed as single homogeneous phases. The BET equation was found adequate for description of the moisture sorption isotherms for all samples. The dextrans appeared to reduce the hygroscopicity of the herbal extracts solely by a dilution effect. The observed increase in T(g) and accompanying decrease in tackiness of the herbal extracts in the presence of dextrans may be explained by the ability of dextrans to restrict the molecular mobility of simple sugars and to counteract the plasticizing effect of water in the extracts. The expanded Gordon-Taylor equation has proved useful in predicting the T(g) of hygroscopic amorphous herbal mixtures.

The main battery type employed in standby applications is the valve-regulated lead-acid (VRLA) battery. Float charging is normally used to maintain the battery in its fully charged state, however, float charging has limitations that can damage the battery and shorten its life. New charge regimes have evolved in recent years to tackle the intrinsic problems of float charging. The intermittent charge (IC) regime and the interrupted charge control (ICC) regime have been developed to prolong the service life of the battery in standby applications. The battery is normally maintained in the standby mode for a long period of time and there are infrequent discharge tests to verify the efficacy of the battery. Hence, the service life of the battery is highly correlated to its charge regime. This paper reviews the charge regimes for VRLA batteries, and assesses their charging performance and their impact on the service life of the battery. Recognising that temperature plays a significant role in battery operation, temperature compensation schemes are described for different charge regimes.

Secure and pervasive 3D CAD model sharing among all collaborative participants is vital to successful Product Lifecycle Management (PLM) applications. However, existing product data management (PDM) solutions only provide rigid 3D data access control mechanism like 'all-or-nothing' scenario and thus prevents companies from sharing their 3D data effectively. 3D data sharing can be facilitated if proper technologies are available to break the previous two-grade (grant-or-deny) scheme into more levels and present to a user a 3D model with proper level of detail reduction. Therefore, a collaborator can work on his 3D data as full model while viewing other models in lighter visualisation as mesh or bounding boxes. This paper proposes role-based visualisation to realise the above concept and a prototype system is developed to validate the proposed approach in commercial CAD/PDM applications. Several key issues and future work are discussed.

A support structure is necessary for part fabrication in some layered manufacturing (LM) processes, but the utilization of support structures often causes low efficiency and poor quality of the finished parts. In this paper, a process planning approach based on a multi-orientational deposition (MOD) method is proposed to minimize the use of support structures, so as to improve the efficiency in LM process and surface quality of a part built. An algorithm to determine the successive layer area difference (SLAD) for layer deposition and its application to overhang feature extraction and reduction using the MOD method is also introduced.

Cu-based composites reinforced with in-situ TiB 2 particles were synthesized through the reaction among Cu, Ti and B 4 C using a 3-kW CO 2 laser. The in-situ reaction resulted in the formation of TiB 2 and non-stoichiometric TiC 1− x particles in a Cu matrix. Some porosity was observed in the Cu–Ti–B 4 C system. However, with addition of Ni in the Cu–Ti–B 4 C system, almost full densed parts could be obtained due to improvement of wetting.

This paper presents a study of the effect of titanium carbide (TiC) on the performance of sintered copper-based materials as electrical discharge machining (EDM) electrodes. The aim of this study was to provide a preliminary evaluation of EDM electrodes fabricated by laser-based sintering using rapid prototyping technology (RP). Six batches of titanium carbide with content from 5% to 45% were fabricated by mixing, ball milling, pressing, and liquid phase sintering with copper-tungsten (Cu–W) and copper (Cu), respectively. The performance of the newly formed material is compared with commercial electrodes. The densification of TiC/Cu–W system was improved by the addition of nickel (Ni), as Ni shows good solubility in both Cu and W. The distribution of particle size becomes narrow as the proportion of TiC is increased. A uniform dispersion of small TiC particles in the Cu–W system and a narrow particle size distribution provide the possibility of obtaining dense electrodes. With increasing TiC, the relative density first increased and then decreased, whereas the electrical resistivity first decreased and then increased. EDM electrodes, with the addition of TiC, show good performance in surface finishing. This is an important characteristic as RP-sintered EDM electrodes are expected to be used as finishing electrodes. The surface roughness of most specimens is less than those machined using commercial electrodes. Electrodes with 15% TiC show the highest relative density, lowest electrical resistivity, and good EDM performance, i.e. lowest tool wear ratio (TWR) and highest material removal rate (MRR) at low current, and the best surface finish not only at low current, but also at high current.

EDM has been used extensively in the tool and die industry. The materials normally used in EDM electrodes are various types of copper, graphite, tungsten, brass and silver. Copper–tungsten (Cu–W) electrodes have been used widely to machine die steel and tungsten carbide work-pieces owing to the high thermal conductivity of Cu, and the better spark erosion resistance, low thermal expansion coefficient and high melting temperature of W. TiC is an extremely hard refractory material with a high melting temperature, and high thermal shock and abrasion resistance. The effect of the titanium carbide (TiC) in sintered copper–tungsten (Cu–W) electrodes on their EDM performance was investigated. Six batches of specimens with TiC content varying from 5 to 40% were fabricated by mixing, ball milling, pressing, and liquid phase sintering. The densification was improved by the addition of Nickel (Ni) due to the good solubility of Ni with Cu and W. The distribution of particle size became narrower with increasing TiC. A uniform dispersion of fine TiC particles in the Cu–W system and a narrower particle size distribution provide the possibility for obtaining dense electrodes. The relative density first increased and then decreased with increasing TiC while the electrical resistivity correspondingly first decreased and then increased. The tool material with added TiC showed good performance. The surface roughness decreased with the increase of relative density and vice versa. The highest relative density, lowest electrical resistivity, and best EDM could be obtained by 15% TiC addition, i.e. the lowest TWR, highest MRR and best surface finish.

This paper studies the formation of composites using a CO 2 laser machine for rapid prototyping fabrication. In this process, Cu–Ti–C and Cu–Ni–Ti–C powder mixtures were milled before laser scanning. The ball-milled powder mixture was layered and scanned under the laser beam. Formation of in situ TiC was detected after laser scanning. With addition of Ni, both the microstructure structure and surface quality of the laser-fabricated parts can be improved because of the improved melting of Cu and wettability of Cu with in situ TiC.

Different types of structural and aerodynamic nonlinearities commonly encountered in aeronautical engineering are discussed. The equations of motion of a two-dimensional airfoil oscillating in pitch and plunge are derived for a structural nonlinearity using subsonic aerodynamics theory. Three classical nonlinearities, namely, cubic, freeplay and hysteresis are investigated in some detail. The governing equations are reduced to a set of ordinary differential equations suitable for numerical simulations and analytical investigation of the system stability. The onset of Hopf-bifurcation, and amplitudes and frequencies of limit cycle oscillations are investigated, with examples given for a cubic hardening spring. For various geometries of the freeplay, bifurcations and chaos are discussed via the phase plane, Poincare maps, and Lyapunov spectrum. The route to chaos is investigated from bifurcation diagrams, and for the freeplay nonlinearity it is shown that frequency doubling is the most commonly observed route. Examples of aerodynamic nonlinearities arising from transonic flow and dynamic stall are discussed, and special attention is paid to numerical simulation results for dynamic stall using a time-synthesized method for the unsteady aerodynamics. The assumption of uniform flow is usually not met in practice since perturbations in velocities are encountered in flight. Longitudinal atmospheric turbulence is introduced to show its effect on both the flutter boundary and the onset of Hopf-bifurcation for a cubic restoring force.

In this paper, the effect of a cubic structural restoring force on the flutter characteristics of a two-dimensional airfoil placed in an incompressible flow is investigated. The aeroelastic equations of motion are written as a system of eight first-order ordinary differential equations. Given the initial values of plunge and pitch displacements and their velocities, the system of equations is integrated numerically using a fourth order Runge-Kutta scheme. Results for soft and hard springs are presented for a pitch degree-of-freedom nonlinearity. The study shows the dependence of the divergence flutter boundary on initial conditions for a soft spring. For a hard spring, the nonlinear flutter boundary is independent of initial conditions for the spring constants considered. The flutter speed is identical to that for a linear spring. Divergent flutter is not encountered, but instead limit-cycle oscillation occurs for velocities greater than the flutter speed. The behaviour of the airfoil is also analysed using analytical techniques developed for nonlinear dynamical systems. The Hopf bifurcation point is determined analytically and the amplitude of the limit-cycle oscillation in post-Hopf bifurcation for a hard spring is predicted using an asymptotic theory. The frequency of the limit-cycle oscillation is estimated from an approximate method. Comparisons with numerical simulations are carried out and the accuracy of the approximate method is discussed. The analysis can readily be extended to study limit-cycle oscillation of airfoils with nonlinear polynomial spring forces in both plunge and pitch degrees of freedom.

This paper presents a study of the near-mirror-finish phenomenon in electrical discharge machining (EDM) when fine powder is introduced into the dielectric fluid as a suspension at the tool–workpiece or inter-electrode gap during machining. For this study, the dielectric flushing system of a conventional die-sinking EDM machine was specially modified to inject and distribute the powder into the dielectric fluid, especially at the gap between the tool and the workpiece. Machining was performed on various types of steel with different types of powder suspensions at a peak current of around 1 A. Particular combinations of powder-mixed dielectric and workpiece have been found to produce mirror-finish or glossy machined surfaces. Close scrutiny of the mirror-finish surfaces reveals shallow overlapping re-solidified discs with smooth rims, unlike typical EDMed surfaces, which are typically covered with deep craters, pock marks and globules. The various factors affecting the generation of the mirror-like surfaces are discussed. The appropriate settings of electrode polarity and pulse parameters and the correct combination of workpiece material and powder characteristics have a significant influences on the mirror-finish condition. The use of negative electrode polarity (i.e. with the tool as the negative electrode, which is a condition normally used for finishing EDM) is necessary to achieve the mirror-finish condition. Other features of the powder-mixed dielectric EDM are shorter machining time, more uniform dispersion of the electrical discharges, and stable machining. Based on the results of the experimental investigation, the types of material composition, powder properties and machine setting in bringing about near-mirror conditions are discussed.

This paper is concerned with the application of the technique of genetic algorithms to solve the problem of optimal facilities' layout in manufacturing systems design. A mathematical model is developed to examine the machines' layout and the pattern of material flow for the typical job shop and flow shop manufacturing environments. The analysis also considers various practical aspects, such as the constraints of restricted areas and reserved machinery locations, and also the irregularity of the shapes of manufacturing plants, etc. A genetic approach is developed to provide the optimal solution to the facilities' layout problem. The effectiveness of the proposed approach is evaluated with numerical examples. Indeed, the results indicate that the proposed approach provides an effective means to solve problems in facilities' layout.

This paper investigates the dynamic response of a coupled two-degree-of-freedom system with a cubic stiffness nonlinearity in both degrees of freedom. The mathematical model is based on a coupled system of Duffing's equations. The governing equations are derived for a two-dimensional airfoil oscillating in pitch and in plunge, but they can be applied to nonaeronautical problems, such as mechanical systems, by discarding the aerodynamics terms and setting the appropriate parameters to correspond to those for the particular dynamic system under consideration. Only the harmonic solution is considered and we use the method of slowly varying amplitude to investigate the dynamic response of the system to an external excitation. The equilibrium points are computed and a linear analysis is carried out to determine the stability of the equilibrium points. Examples are given for a dynamic system without aerodynamic forces to illustrate the complex structure of the jump phenomenon where the solution jumps from one branch of the amplitude-frequency curve to the other. An example in aeroelasticity is given which shows the behaviour of the airfoil motion as the velocity approaches the linear flutter speed. Numerical simulations are also carried out to verify the analytical results.

Space-frame nodes are joints connecting linear members in complex space frames. Each spherical node has a particular hole configuration that defines the orientation of the bolt holes used to connect the space-frame members. The hole configurations are determined by CAD software for space-frame design. Nodes with the same hole configuration vary in number depending on the design of the space frame. A computer-automated machining cell has been implemented to batch manufacture the spherical nodes. The machining cell consists of a three-axis vertical machining center interfaced with a two-axis CNC rotary table. To reduce changeover time between the machining of batches, produce consistent and reliable NC programs, and minimize manpower required to run the cell, a PC-based computer-automated process planning system has been developed to directly translate geometric data from the CAD software to NC programs, without intervention by the operator. An important consideration in the process plan for the machining of the space-frame node is the transformation of the CAD-defined bolt hole configuration to a mounting-hole-referenced configuration that minimizes setup and mounting hole requirements. Based on the optimal mounting-hole-referenced configuration, NC toolpaths are derived and corresponding NC programs are generated. This paper presents the approach to determine the optimal mounting-hole-referenced configuration and the operation of the automated process planning system that is suitable for the machining of spherical parts.

A man was kicked on the neck, 10 days after which he noted right-sided numbness. Clinically, he had diminished deep tendon reflexes over the left upper limb, absent left superficial abdominal reflexes, a left extensor plantar response, mild left hemiparesis, diminished pinprick, temperature and vibratory sensation up to the right T(4-5) dermatome and diminished proprioceptive sensation in the right upper and lower limbs. Cervicothoracic magnetic resonance imaging (MRI) revealed a left C(6-7) posterolateral disc prolapse with indentation and oedema of the cord at the same level. He was given intravenous dexamethasone, with mild resolution of his motor but not his sensory symptoms. Transcranial magnetic stimulation and evoked potentials performed 3 days later were unremarkable. He was discharged soon after, preferring to seek traditional therapy in his country. We attempt to explain the anatomical basis for his clinical signs, review the literature for similar cases, and examine the usefulness of available treatment and investigations.

Cracks on EDMed surfaces are of major concern. This paper discusses the nature of cracks found in the recast layer. The microstructure of the recast for a number of commonly used tools are then presented. Results are provided to illustrate the significance of the thermal conductivity of the work material on the recast layer thickness and crack density. Finally, some findings on iron, carbon steels and copper-aluminium alloys are included to help verify the findings for the tool steels.

Cracking of workpieces after electro-discharge machining remains a fundamental concern. This paper examines the microstructure and cracks arising in pure iron, 0.15C and 0.5C steels when subjected to the same machining conditions. Pure iron is found to have predominantly two-sub-layer recasts whereas 0.15C and 0.5C steels would typically have a third intermediate sub-layer of eutectic-like structure: the latter is expected to lead to a greater propensity to cracking. Two other factors that have been found to have an important influence on crack susceptibility are the thermal conductivity of the work material and the hardness of the recast layer.

Correlations of the His to ventricular (H-V) conduction time were made with the surface electrocardiogram during normal intraventricular conduction, unifascicular block (right bundle branch block), bifascicular block (left bundle branch block) and trifascicular block (right and left bundle branch block) in a patient with rate-dependent left bundle branch block who had transient right bundle branch block during recording of the His bundle electrogram. The results provide a functional confirmation of the theory that a prolonged H-V time is a manifestation of trifascicular disease.

Pulsus alternans of the pulmonary artery without systemic pulsus alternans is uncommon and is associated with multiple diseases. Two cases of pulmonary hypertension with pulmonary arterial pulsus alternans and right-sided heart failure are described. Primary pulmonary hypertension was demonstrated at autopsy in both cases. These two case reports constitute another previously unreported cause for pulsus alternans in the pulmonary circuit.

The effect of left bundle branch block on left ventricular performance was studied in a patient with rate-dependent left bundle branch block and an otherwise normal heart. The timing of left heart events, hemodynamic pressures and indexes of left ventricular contractility were determined during normal intraventricular conduction and during left bundle branch block. The results indicate that in the normal heart left bundle branch block has no significant effect on left ventricular performance.

Retrograde catheterization of the left atrium utilizing the Shirey technique was successfully performed in four patients with idiopathic hypertrophic subaortic stenosis. By traversing the inflow tract of the left ventricle on pullback from the left atrium to the aorta, this method served to separate definitively true hypertrophic subaortic stenosis from cavity obliteration. It was accomplished with relative ease and no complications. In patients with suspected idiopathic hypertrophic subaortic stenosis who are to have retrograde left heart catheterization, this approach to the left atrium is recommended as an alternative to the transseptal technique.

Among 68 patients with mitral insufficiency who had right and left cardiac catheterization and left ventriculography, 6 had retrograde transmission of the left atrial V wave into the main pulmonary artery. All of these patients had mitral insufficiency of acute onset. The remaining 62 patients had chronic mitral insufficiency that was considered severe in 17. Pulmonary vascular resistance was lower in the group with acute insufficiency (mean 139 dynes sec cm-5) than in the group with chronic severe insufficiency (mean 631 dynes cm-5) (P less than 0.005). Nondistensibility of the left atrium and low pulmonary vascular resistance were the two factors favoring retrograde transmission of V waves. Because both factors are present in acute mitral regurgitation, this finding is helpful in differentiating patients with acute mitral insufficiency.

An investigation of various multiple regression model-building techniques has been carried out on machinability data in order to study the suitability of the empirical equations employed. A comparative analysis of the full-form first-order regression mode and quadratic regression model has been performed also, to aim for a parsimonious and easily interpretable model to be used for the computation of various aspiration levels, which latter include the minimum unit production cost and the maximum unit production rate. In order to address the problem of the update of machinability data found in current systems, the raw data of the machining responses and machining variables are retained for future update, thus enhancing the models, which relate closely to the actual production process. This module can thus be incorporated into an expert system that has been discussed elsewhere, achieving progress towards an integrated machining system.

An analogue wattmeter has been developed for direct measurement of electrical power dissipation at the discharge gap during electrical discharge machining (EDM). A microcomputer samples power and corresponding gap voltage at regular intervals. Digitally encoded waveforms, which represent blocks of continuous power and voltage pulse trains, are stored on floppy disks for subsequent display and analysis. The advantage of using this microcomputer-based integrated measurement system is the ability to capture both typical and random events or phenomena in EDM and also to extract and process information from the digitized waveforms which represent characteristics of these events. In this investigation, samples of power and voltage pulse characteristics during four EDM tests have been recorded, analysed for unit and time-averaged variations and meticulously studied with the aid of the microcomputer-based system. Power and voltage waveforms have been reconstructed from the digital data and are suitably displayed. Random and systematic or cyclic variations as shown by the analysed data, together with the corresponding reconstructed waveforms, are presented. Reasons for the variations are discussed in the light of similar observations verified by other researchers. This paper reports part of a continuing programme involving the use of microcomputer-based measurement systems for both on-line monitoring and off-line analysis of the EDM process.

This paper makes an updated assessment of the technical and economic feasibility of transferring satellites from low Earth orbit to geostationary orbit using low thrust propulsion. In particular, the concept of a solar electric tug is discussed whereby the main propulsion unit is returned from geostationary orbit to low Earth orbit for re-use.

Idioventricular tachycardia (IVT) occurred in a patient with angina pectoris on three separate occasions associated with stress induced angina. It occurred immediately after a Master's test, a treadmill exercise test, and following an episode of paroxysmal atrial tachycardia which was precipitated by endocardial pacing. His bundle electrograms demonstrated that the rhythm was ventricular in origin. Cardiac catheterization documented the presence of severe coronary artery disease. Idioventricular tachycardia is often seen with acute myocardial infarction. It is rarely seen with angina or with exercise testing. To our knowledge this is the first reported case of IVT which could be repeatedly produced by stress induced angina.

The echocardiographic features of an aneurysm of the left sinus of Valsalva are described and correlated with angiographic findings. The echocardiogram showed the presence of a thin line of echoes occurring proximal to the anterior leaflet of the mitral valve and moving in and out of apposition with the posterior aortic wall. During systole, this line of echoes moved away from the aorta into the left atrium, and during diastole, the line moved into the aorta. Recognition of these features provides a potential noninvasive way to diagnose aneurysms of the left sinus of Valsalva prior to rupture.