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Biomedical subjects

P G Walker

Publications and source records attributed to P G Walker.

At least 19 recordsLinked to original sources

Activation and extinction models for platelet adhesion.

Adherent platelets are an important part of both thrombus formation and in certain stages of atherogenesis. Platelets can be activated by potent chemicals released from adherent platelets and adhere far more readily than unactivated ones. An analytical and numerical model is presented utilising high Peclet number for the activation and adhesion of platelets in shear flows. The model uses a similarity transformation, which characterises the relationship between convective, diffusive transport and the bulk platelet activating reaction mechanism. A first order surface reaction mechanism is used to model platelet adhesion at the wall (cell) surface. The reduced Damköhler number, M, characterises the importance of the bulk reaction and includes both convective and diffusive terms. For a high rate of blood flow (M-->0) the activation of platelets can effectively be terminated. In contrast, for (M-->infinity) an inner layer of activated platelets exists with an infinitesimally thin reaction sheet separating activated and non-activated platelets. This characterisation by the Damköhler number highlights results found clinically, in that thrombus forms in areas of low shear (high M) and in some cases an increased blood flow (low M) can inhibit the activation of platelets completely. The model shows the critical balance that exists between convection, diffusion and reaction.

Humans↗

Adhesion of leukocytes under oscillating stagnation point conditions: a numerical study.

Leukocyte recruitment from blood to the endothelium plays an important role in atherosclerotic plaque formation. Cells show a primary and secondary adhesive process with primary bonds responsible for capture and rolling and secondary bonds for arrest. Our objective was to investigate the role played by this process on the adhesion of leukocytes in complex flow. Cells were modelled as rigid spheres with spring like adhesion molecules which formed bonds with endothelial receptors. Models of bond kinetics and Newton's laws of motion were solved numerically to determine cell motion. Fluid force was obtained from the local shear rate obtained from a CFD simulation of the flow over a backward facing step.In stagnation point flow the shear rate near the stagnation point has a large gradient such that adherent cells in this region roll to a high shear region preventing permanent adhesion. This is enhanced if a small time dependent perturbation is imposed upon the stagnation point. For lower shear rates the cell rolling velocity may be such that secondary bonds have time to form. These bonds resist the lower fluid forces and consequently there is a relatively large permanent adhesion region.

Arteriosclerosis↗

Comparison of single-round polymerase chain reaction (PCR) and pepsin-trypsin digest (PTD) methods for detection of Myxobolus cerebralis.

Single-round polymerase chain reaction (PCR) and pepsin-trypsin digest (PTD) methods were compared for the detection of Myxobolus cerebralis. Parallel tests were conducted on a total of 1743 free-ranging and 400 hatchery-reared salmonids. Concurrent results were found in 84.6% of the free-ranging fish samples, and 83.5% of the hatchery samples. PCR identified M. cerebralis more frequently than did PTD, and did so in many geographic locations previously considered free of the parasite. Average myxospore count by PTD among both free-ranging and hatchery fish increased significantly (p < 0.001) with a subjective evaluation of amplicon staining intensity.

Animals↗

Platelet deposition in stagnation point flow: an analytical and computational simulation.

A mathematical and numerical model is developed for the adhesion of platelets in stagnation point flow. The model provides for a correct representation of the axi-symmetric flow and explicitly uses shear rate to characterise not only the convective transport but also the simple surface reaction mechanism used to model platelet adhesion at the wall surface. Excellent agreement exists between the analytical solution and that obtained by the numerical integration of the full Navier--Stokes equations and decoupled conservation of species equations. It has been shown that for a constant wall reaction rate modelling platelet adhesion the maximum platelet flux occurs at the stagnation point streamline. This is in direct contrast to that found in experiment where the maximum platelet deposition occurs at some distance downstream of the stagnation point. However, if the wall reaction rate is chosen to be dependent on the wall shear stress then the analysis shows that the maximum platelet flux occurs downstream of the stagnation point, providing a more realistic model of experimental evidence. The analytical formulation is applicable to a large number of two-dimensional and axi-symmetrical surface reaction flows where the wall shear stress is known a priori.

Arterial Occlusive Diseases↗

Evaluation of the precision of magnetic resonance phase velocity mapping for blood flow measurements.

Evaluating the in vivo accuracy of magnetic resonance phase velocity mapping (PVM) is not straightforward because of the absence of a validated clinical flow quantification technique. The aim of this study was to evaluate PVM by investigating its precision, both in vitro and in vivo, in a 1.5 Tesla scanner. In the former case, steady and pulsatile flow experiments were conducted using an aortic model under a variety of flow conditions (steady: 0.1-5.5 L/min; pulsatile: 10-75 mL/cycle). In the latter case, PVM measurements were taken in the ascending aorta of ten subjects, seven of which had aortic regurgitation. Each velocity measurement was taken twice, with the slice perpendicular to the long axis of the aorta. Comparison between the measured and true flow rates and volumes confirmed the high accuracy of PVM in measuring flow in vitro (p > 0.85). The in vitro precision of PVM was found to be very high(steady: y = 1.00x + 0.02, r = 0.999; pulsatile: y = 0.98x + 0.72, r = 0.997; x: measurement #1, y: measurement #2) and this was confirmed by Bland-Altman analysis. Of great clinical significance was the high level of the in vivo precision (y = 1.01x - 0.04, r = 0.993), confirmed statistically (p = 1.00). In conclusion, PVM provides repeatable blood flow measurements. The high in vitro accuracy and precision, combined with the high in vivo precision, are key factors for the establishment of PVM as the "gold-standard" to quantify blood flow.

Aorta, Thoracic↗

Distribution of hepatic venous blood in the total cavo pulmonary connection: an in vitro study into the effects of connection geometry.

The total cavo pulmonary connection, or TCPC, is a surgical correction to congenital heart defects. The geometry of this connection has been shown to determine the fluid power loss as well as the distribution of hepatic fluid that enters through the inferior vena cava. In vitro studies were performed to measure the power loss and hepatic fluid distribution in models of the TCPC with four different geometries. It was found that a zero offset straight geometry provided good hepatic fluid distribution but large power loss. A zero offset flared geometry provided low power loss but poor hepatic fluid distribution. The optimal geometry from those tested was found to be the zero offset cowl geometry whereby an enlargement was made on one side of the inferior and superior vena cava. So long as the cowl was directed toward the pulmonary artery of lowest flow rate, low power loss and relatively good distribution of hepatic flow could be obtained.

Blood Flow Velocity↗

Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow.

We examined the hypothesis that disturbance of laminar flow promotes the attachment of leukocytes to the vessel wall in regions where the wall shear stress is otherwise too high. Isolated neutrophils, lymphocytes, or monocytes were perfused through chambers with backward-facing steps so that vortices occurred with well-defined reattachment of flow. Wall shear stresses downstream in reestablished flow equaled 0.07 Pa (low shear) or 0.3 Pa (high shear). In chambers coated with P-selectin, adherent leukocytes rolled. By use of a P-selectin-Fc fragment chimera, adhesion was predominantly stationary, enabling definition of initial attachment sites. Neutrophils adhered in all regions of the low-shear chamber, with a local maximum around the reattachment point. However, in the high-shear chamber, adhesion was restricted to the recirculation zone and immediately downstream from the reattachment point. Rolling at high shear stress allowed a population of regions where initial attachment could not occur. At high shear, lymphocytes and monocytes also formed attachments restricted to the region of the reattachment point. The results imply that all types of leukocytes might bind to a capture receptor in high-shear vessels with discontinuities in the wall and might then spread to other regions.

Blood Vessels↗

The influence of ventricular input impedance on the hydrodynamic performance of bioprosthetic aortic roots in vitro.

BACKGROUND AND AIM OF THE STUDY: Hydrodynamic function testing using pulsatile flow simulators provides a valuable means of comparative assessment of heart valves in vitro. The majority of pulsatile flow simulators consist of modular rigid chambers and a positive displacement pump with an infinite input impedance, in which the inertia of the test fluid results in pressure oscillations when the valves under test are opening and closing. For mechanical and stented bioprosthetic valves these pressure oscillations decay quickly. However, due to the highly compliant nature of tissue roots, the resulting pressure and flow oscillations are extreme and extend throughout systole. With increasing interest in the use of free-sewn roots and valves it is most desirable to improve this hydrodynamic model. The aim of this study was to investigate the influence in changes in ventricular input impedance on the hydrodynamic characteristics of free-sewn aortic roots and stented valves. METHODS: The Leeds pulsatile flow simulator was modified to incorporate additional compliance chambers in the form of a viscoelastic impedance adaptor (VIA) at the pump/ventricular interface. Six 23 mm bioprosthetic aortic roots fixed with 0.5% buffered glutaraldehyde at zero pressure, and a size 23 mm stented porcine aortic bioprosthesis were tested in this modified simulator, at the conditions of maximum and minimum input compliance. RESULTS: The pressure and flow waveforms for the fixed aortic roots showed considerable differences at the conditions of maximum and minimum input compliance. Indeed, the extreme pressure oscillations observed at minimum compliance (infinite input impedance) were not present at maximum compliance, and the forward flow waveform was much smoother. In contrast, for the stented valve, the differences in the pressure and flow waveforms between maximum and minimum input compliance were minimal, but this was expected due to the lack of compliance in the stented valve itself. In addition, the flow and pressure waveforms at maximum compliance in the VIA were comparable for the fixed aortic roots and the stented bioprosthesis, thus allowing direct comparison of the characteristics of these two different devices. Using test conditions of maximum input compliance, effective orifice area for the roots was 1.69 cm2 compared with 1.47 cm2 for the stented valve. CONCLUSION: An appropriate physiological model for the hydrodynamic testing of compliant tissue roots has been established.

Aortic Valve↗

Dependence of adhesive behavior of neutrophils on local fluid dynamics in a region with recirculating flow.

We have recently described patterns of adhesion of different types of leukocytes downstream of a backward facing step. Here the predicted fluid dynamics in channels incorporating backward facing steps are described, and related to the measured velocities of flowing cells, patterns of attachment and characteristics of rolling adhesion for neutrophils perfused over P-selectin. Deeper (upstream depth 300 microm, downstream depth 600 microm, maximum wall shear stress approximately 0.1 Pa) and shallower (upstream depth 260 microm, downstream depth 450 microm, maximum wall shear stress approximately 0.3 Pa) channels were compared. Computational fluid dynamics (CFD) predicted the presence of vortices downstream of the steps, distances to reattachment of flow, local wall shear stresses and components of velocity parallel and perpendicular to the wall. Measurements of velocities of perfused neutrophils agreed well with predictions, and suggested that adhesion to P-selectin should be possible in the regions of recirculating flow, but not downstream in re-established flow in the high shear channel. When channels were coated with a P-selectin-Fc chimaera, neutrophils were captured from flow and immobilised. Capture showed local maxima around the reattachment points, but was absent elsewhere in the high shear chamber. In the low shear chamber there was depression of adhesion just beyond the reattachment point because of expansion of flow and depletion of neutrophils near the wall. Inside the recirculation zones, adhesion decreased approaching the step because of an increasing, vertically upward velocity component. When channels were coated with P-selectin, neutrophils rolled in all regions, but lifted off the surface as they rolled backwards into low shear regions near the step. Rolling velocity in the recirculation zone was independent of shear stress, possibly because of the effects of vertical lift. We conclude that while local wall shear stress influences adhesive behavior, delivery of cells to the wall and their behavior after capture also depend on components of flow perpendicular to the wall.

Blood Flow Velocity↗

Motion correction for the quantification of mitral regurgitation using the control volume method.

Quantifying mitral regurgitation is difficult because of the complexity of the flow, geometry and motion of the mitral valve. In this paper a MRI compatible phantom was built incorporating a left ventricle and mitral valve motion. Valve motion was obtained using a pneumatic piston. The mitral valve was made regurgitant and the regurgitant volume quantified using a modified control volume method. The modification to the method was the addition of mitral motion correction. This was attained by moving the control volume in unison with the mitral valve and by correcting for this motion in the integration of velocity. This correction was found to be simple, in that it represented the volume swept out by the moving control surface. The measured regurgitant volume was compared to a second MR measurement using a single slice technique, made possible by the tubular construction of the phantom's left atrium. Regression analysis between these two methods produced a regression line of y = 0 + 1.02 x; R = 0.97; standard error of the estimate = 3.47 ml.

Blood Flow Velocity↗

The effect of sizing on the hydrodynamic parameters of the Medtronic freestyle valve in vitro.

BACKGROUND: An in vitro model has been established to investigate the effect of sizing on the hydrodynamic characteristics and leaflet motion of the Medtronic Freestyle valve. METHODS: The valves were tested in fresh porcine aortic roots. Two or three different sizes of valves were implanted in the same aortic root one after the other. The compliance of the fresh aortic and the composite roots was measured in the pressure range of 0 to 120 mm Hg, and the composite roots were then tested in a pulsatile flow simulator. The transvalvular gradient and degree of regurgitation were measured and the effective orifice area and performance index were calculated. Leaflet motion was recorded on video. RESULTS: The fresh aortic roots dilated by average 39.4% as the hydrostatic pressure rose from 0 to 120 mm Hg. Implantation of the Medtronic Freestyle valve did not change the distensibility of the aortic root significantly. The sizing protocol did not affect significantly the hydrodynamic performance. However, a significantly lower open leaflet bending deformation was found in the undersized valves. Regurgitation was found only at 2-mm undersized valves. CONCLUSIONS: Leaflet motion of the Medtronic Freestyle valve in vitro was best if 1 mm undersized, and this may be beneficial to long-term durability.

Aorta↗

Distribution of hepatic venous blood in the total cavo-pulmonary connection: an in vitro study.

OBJECTIVES: The objective of this project was to quantify the effects of geometry on the distribution of hepatic blood to the lungs in patients with a total cavo-pulmonary connection. The basis for this work is the supposition that hepatic blood is necessary for proper lung function. METHODS: Plastic models of these connections were made with varying degrees of offset between the inferior and superior vena cava and attached to an in vitro flow loop. Dye was injected into the inferior vena cava and its concentration quantified in each pulmonary artery. These data were converted to percentage concentration and distribution of hepatic blood to each lung. RESULTS: With no offset between the vena cava, hepatic blood distribution and concentration to each lung was similar to normal. For an offset of one or more diameters, hepatic blood tended to flow preferentially towards the nearest pulmonary artery with the opposite pulmonary artery exhibiting a deficit (<10% of normal). CONCLUSIONS: Distribution of hepatic blood to each lung was found to be a function of vena cava offset and pulmonary artery flow split. Under normal conditions, 60% of blood towards the right pulmonary artery, the hepatic blood distribution to both lungs could be maintained above 50% of normal if the inferior vena cava was offset towards the left pulmonary artery. Offsetting the inferior vena cava towards the right pulmonary artery jeopardized the delivery of hepatic blood to one lung.

Blood Flow Velocity↗

The in vitro hydrodynamic characteristics of the porcine pulmonary valve and root with regard to the ross procedure.

OBJECTIVE: The hydrodynamic parameters and leaflet motion of the porcine pulmonary root and valve and the performance of the pulmonary autograft implanted in subcoronary position or as a free-standing root were investigated at systemic and pulmonary pressures in vitro. METHODS: Ten fresh pulmonary and aortic roots (anulus diameter, 20-25 mm) were tested in a pulsatile flow simulator. Five free-sewn pulmonary valves were implanted in aortic roots in the subcoronary position, and 5 pulmonary roots were implanted as free-standing roots. The external diameter of the roots was measured at the sinotubular junction in a pressure range of 0 to 120 mm Hg. The transvalvular gradient and regurgitation were measured, and the effective orifice area was calculated. The leaflet motion was recorded on video tape. RESULTS: The fresh pulmonary roots were more compliant than their aortic counterparts (33% +/- 3. 0% vs 7% +/- 1.5% with dilatation at 0-30 mm Hg and 46% +/- 8.4% vs 35% +/- 7.8% with dilatation at 0-120 mm Hg). The pulmonary roots had a lower pressure drop at systemic than at pulmonary pressures. The pressure drops of the pulmonary roots were also lower than those of the aortic roots in the systemic pressure range. The leaflet opening of the pulmonary valve was triangular, with low bending deformation at all pressures. Implanting the free-sewn pulmonary valve in the subcoronary position or the pulmonary root as a free-standing root did not affect the hydrodynamic parameters and leaflet motion adversely. CONCLUSION: The pulmonary valve and root could easily withstand aortic pressures in vitro. A biphasic dilatation curve ensures that higher pressures did not overdilate the pulmonary root. Moreover, valve performance was better at systemic pressures.

Animals↗

The effect of sizing on the in vitro hydrodynamic characteristics and leaflet motion of the Toronto SPV stentless valve.

OBJECTIVES: We established an in vitro model to investigate the effects of valve sizing on the hemodynamic characteristics and leaflet motion of the Toronto SPV valve (St Jude Medical, Inc, St Paul, Minn). METHODS: Nine valves were first implanted in fresh porcine aortic roots and then retested in glutaraldehyde-treated porcine aortic roots. Three valves were 1- to 2-mm oversized, 3 were 1- to 2-mm undersized, and there were 3 size-for-size implantations. The elasticities of the aortic roots and the composite roots were measured in the pressure range between 0 and 120 mm Hg, and the composite roots were then tested in a pulsatile flow simulator. The transvalvular gradient and regurgitation were measured and the effective orifice area and performance index were calculated for each root. Leaflet motion was recorded on videotape. RESULTS: The external diameter of the fresh root increased by 35% as the hydrostatic pressure rose from 0 to 120 mm Hg, as compared with 11% for the glutaraldehyde-treated root. Valve implantation in the fresh root reduced the distensibility to 22% but did not change distensibility in the glutaraldehyde-treated root. The effective orifice area was dependent on the valve size, with the transvalvular gradient decreasing as the valve size increased. For the same size of valve the hydrodynamic parameters were slightly better if the valve was undersized by 1 mm. A significant difference in favor of the undersized valves was found in open-leaflet bending deformation. CONCLUSION: Leaflet motion of the stentless porcine aortic valve in vitro is improved if the valve is slightly undersized, and this may be beneficial to the long-term durability of the prosthesis.

Animals↗

The influence of size mismatch on the hemodynamic performance of the pulmonary autograft in vitro.

OBJECTIVES: We established an in vitro model to investigate the effect of size mismatch between the aortic and pulmonary root on the hydrodynamic performance and leaflet motion of the pulmonary autograft. METHODS: Ten fresh porcine pulmonary roots (annulus diameter: 19-25 mm) were tested in a pulsatile flow simulator. The autografts then were implanted in fresh porcine aortic roots (annulus diameter: 19-30 mm) and retested in the flow simulator. Three roots were oversized by 21-39%, three were undersized by 32-45% and there were four size for size implantations. The external diameter of the roots and autografts was measured at the sinotubular junction at hydrostatic pressures of 0 - 120 mmHg. The transvalvular gradient and regurgitation were also measured and the effective orifice area was calculated. The leaflet motion was recorded on video. RESULTS: The fresh pulmonary roots were more compliant than the fresh aortic roots (46 +/- 8.4% vs. 35 +/- 7.8% dilatation from 0 to 120 mmHg). The group of matching size autografts dilated by 43 +/- 4.9% in the same pressure range. The external diameter of the undersized autografts was 10 +/- 2.1% bigger than before implantation at 0 pressure and then the dilatation was 40 +/- 5.3% at 120 mmHg. The oversized implantation made the autografts 11 +/- 9.4% smaller in their relaxed state, but then they dilated by 65 +/- 11% as the pressure increased to 120 mmHg, resulting in a net dilatation of 54% over the original undilated state. The under or oversizing had little effect on the pressure gradient measured across the valves (5.6 +/- 2.57 mmHg before, 6.3 +/- 3.27 mmHg after implantation). Only the oversized valves showed significantly higher gradients than the native pulmonary valves. The effective orifice area of the undersized autografts was slightly bigger and the oversized autografts was slightly smaller after implantation, although the differences were not significant. The size mismatch did not cause regurgitation on the valves. The video images showed very low-open leaflet-bending deformation, both on the fresh pulmonary and the autograft valves. CONCLUSION: Under or oversizing the pulmonary autograft up to 40% of the annulus diameter did not affect the hydrodynamic parameters significantly. The compliance of the autograft root was able to compensate for the size mismatch without adversely influencing the valve performance.

Animals↗

Comparison of hypertonic saline-dextran solution and lactated Ringer's solution for resuscitating severely dehydrated calves with diarrhea.

OBJECTIVE: To determine effectiveness of rapid i.v. administration of hypertonic saline-dextran (HSD) solution combined with oral administration of isotonic electrolyte solution for resuscitating severely dehydrated calves and to compare the resuscitative response with that of a conventional treatment of lactated Ringer's solution (LRS) i.v. and orally administered isotonic electrolyte solution. DESIGN: Prospective study. ANIMALS: 15 male dairy calves 3 to 10 days old. PROCEDURE: Baseline data were obtained. Osmotic diarrhea and severe dehydration were induced for 48 hours. Calves were then allocated to 3 treatment groups. The control group (group C) did not receive fluids, a second group (group H) received hypertonic saline (7.2% NaCl) solution with 6% dextran 70 and isotonic electrolyte solution, and a third group (group L) received LRS and isotonic electrolyte solution. Physical examinations were performed every 8 hours. RESULTS: Calves developed diarrhea, lethargy, severe dehydration (mean, 14% of body weight), azotemia, hyperkalemia, and mild acidemia. Group-C calves remained lethargic and severely dehydrated during the 24-hour treatment phase. Calves treated with HSD and LRS were effectively resuscitated; however, response for most variables was more rapid and sustained for the HSD-treated group. Cardiac output was greater in LRS- than HSD-treated calves 1, 2, and 8 hours after initiation of treatment because of continued i.v. administration of fluids. CLINICAL IMPLICATIONS: A combination of HSD and isotonic electrolyte solution was a rapid and effective method for resuscitation of severely dehydrated calves. It was similar in effectiveness to conventional treatment in which LRS and isotonic electrolyte solution were used for resuscitating calves with severe dehydration.

Administration, Oral↗

Clinical and laboratory assessment of hydration status of neonatal calves with diarrhea.

OBJECTIVE: To develop accurate, objective guidelines for assessing hydration status of neonatal calves with diarrhea. DESIGN: Prospective study. ANIMALS: 15 male dairy calves 3 to 10 days old. PROCEDURE: Dehydration and diarrhea were induced by administration of diuretic agents (i.e., furosemide, spironolactone, hydrochlorothiazide) and sucrose solution. Linear regression was used to examine the relationship between potentially useful factors for evaluating hydration status (extent of enophthalmos; skin-tent duration on neck, thorax, and upper and lower eyelids; heart rate; mean central venous pressure; peripheral [extremity] and core [rectal] temperatures; core-peripheral [rectal-extremity] temperature difference; PCV; and hemoglobin and plasma protein concentrations) and degree of dehydration, as determined by change in body weight. RESULTS: Best predictors of degree of dehydration were extent of enophthalmos, skin elasticity on neck and thorax, and plasma protein concentration. CLINICAL IMPLICATIONS: These experimentally determined guidelines provide practitioners with a simple, inexpensive, and practical method for evaluating hydration status of neonatal calves with diarrhea.

Animals↗

Quantification of the aortic regurgitant volume with magnetic resonance phase velocity mapping: a clinical investigation of the importance of imaging slice location.

BACKGROUND AND AIMS OF THE STUDY: Current techniques for assessment of aortic regurgitation (AR) are mainly qualitative. Magnetic resonance phase velocity mapping (PVM) provides accurate measurements of arterial blood blow. In AR, the aortic regurgitant volume (ARV) can be quantified with a single imaging slice measurement in the ascending aorta. The aim was to use PVM to: (i) quantify the regurgitant volume in patients with AR using an in vitro validated technique; and (ii) confirm in vivo our previous in vitro findings of the importance of measurement location. METHODS: Four healthy volunteers and 19 patients with AR, varying from mild to severe, were examined in a 1.5 Tesla MRI scanner. In 13 patients, the slice was placed: (i) between the aortic valve and the coronary ostia; (ii) at the sinotubular junction (SJ); and (iii) 2 cm above the SJ. In six patients, one measurement was taken as close as technically possible to the aortic valve. PVM measurements of the ARV were compared with angiographic/echocardiographic AR grading. RESULTS: No ARV was measured in healthy subjects. In patients, PVM results correlated well with angiographic/echocardiographic data. Repeatability of the PVM results was excellent and interobserver variability very small. The measured ARV decreased as the slice distance from the aortic valve increased, due to aortic compliance, in agreement to previous in vitro results. Close to the valve, acceleration did not affect the accuracy of velocity measurements. CONCLUSIONS: PVM has great potential to measure AR in a purely quantitative manner. Measurement location is important and results suggest that the closer the measurement to the valve the more accurate the ARV quantification.

Aortic Valve Insufficiency↗