Biomedical subjects

Y Takami

Publications and source records attributed to Y Takami.

At least 73 records · Page 4Linked to original sources

PubMed1997

Quantitative approach to control spinning stability of the impeller in the pivot bearing-supported centrifugal pump.

The Gyro C1E3 pump has been developed as a completely sealless centrifugal pump driven by a magnetic coupling system for long-term usage. The Gyro C1E3 pump is a pivot bearing-supported pump in which the impeller is supported with the top and bottom pivot bearings. In the Gyro C1E3 pump, the impeller spinning is affected by the force balance between the floating force (Ff[N]) of the hydrodynamic effect and the magnetic thrust force (Tf[N]). The authors quantitatively investigated the floating force of the impeller in vitro to determine the magnetic coupling distance (MCD[mm]) that would result in stable impeller spinning. In vitro tests were performed using a loop filled with 37% glycerin solution to obtain the relationship between the MCD and floating speed (Rf, rotational speed when the impeller starts floating [rpm]) and the relationship between the MCD and Tf. From the obtained relationships, we calculated Ff and determined the relationship between the Ff and the rotational speed (R). Furthermore, we determined the relationship between d (minimum required MCD [mm]) and R from the results of determining the relationship of the MCD and Tf and of the Ff and R. The following relationships were obtained: Rf = 6.24 x 10(4) x MCD-1.35; Tf = 5.27 x 10(3) x MCD-2.29; Ff = 4.71 x 10(-6) x RPM1.69; and d = 9.02 x RPM-0.85 where RPM is the rotational speed. It was demonstrated that the floating force of the impeller is a function only of the rotational speed in the pivot bearing-supported Gyro C1E3 pump. The floating force is estimated to be 10 N to 40 N at rotational speeds of 1,500 rpm to 3,000 rpm at which the Gyro pump may be used in most clinical situations. It would be possible to control the impeller position of the Gyro pump automatically at the stable spinning condition by controlling the adequate magnetic coupling distance based upon its relationship with the rotational speed which was obtained in this study.

Blood Viscosity↗

PubMed1997

The simple in vitro thrombogenic test: modified methods for same priming pumps.

The improvement of antithrombogenicity is one of the major objectives for the development of blood pumps. Previously we reported that an in vitro thrombogenic test was useful as a pilot study, especially to predict thrombogenic areas. In this study we modified the method for testing pumps with identical priming volumes by eliminating the blood reservoir. Identical compact mock loops (priming volume of 53 ml, without pump) were constructed and tested with the same priming volume of Nikkiso centrifugal pumps, noncoated verus heparin-coated. Two pumps were run simultaneously using the same source of fresh heparinized human blood (activated clotting time [ACT] 150-250 s) for 4 or 6 h. Results indicated that the heparin-coated pump had a longer thrombus free period than the noncoated one. The thrombi location and forms were consistently in the same places the in vivo study had identified. It is suggested that this modified in vitro thrombogenic test is a feasible pilot study, as well as the one previously reported. The minimal priming volume will allow evaluation of multiple pumps simultaneously with the same source blood.

Anticoagulants↗

PubMed1997

Hydraulic assessment of the floating impeller phenomena in a centrifugal pump.

A compact eccentric inlet port centrifugal blood pump (C1E3) has been perfected for a long-term centrifugal ventricular assist device as well as a cardiopulmonary bypass pump. The C1E3 pump incorporates a sealless design and a blood stagnation free structure. The pump's impeller is magnetically coupled to the driver magnet in a sealless manner. The latest hemolysis study reveals that hemolysis is affected by the magnetic coupling distance between the driver and impeller magnet. Furthermore, a floating phenomenon can be observed in a pivot bearing supported pump. Attention was focused on the relationship between the floating phenomenon's characteristics and the magnetic coupling design in the C1E3 pump. Studies were conducted to evaluate the hydromechanical performance in the floating phenomenon. In this study, the relationship between the magnetic coupling design and the floating phenomenon was verified with a smooth spinning condition. The optimized magnetic coupling distance for the floating mode was estimated to be 12 mm for left ventricular assist device and 9 mm for cardiopulmonary bypass pump. Obtaining an optimal spinning condition is required for regulating the magnetic coupling force. To develop a double pivot bearing pump, it is necessary to establish an optimal spinning and/or floating condition and to determine the proper magnetic coupling and magnetic force between the impeller and driver.

Assisted Circulation↗

PubMed1997

Development and initial testing of a permanently implantable centrifugal pump.

To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI-601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 L/min against 150 mm Hg at 2,500 rpm. The normalized index of hemolysis (NIH) value of this pump was 0.0028 g/100 L at 5 L/min against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.

Animals↗

PubMed1997

The hemolysis test of the Gyro C1E3 pump in pulsatile mode.

While a centrifugal pump is generally used for nonpulsatile blood flow, it can also produce a pulsatile flow by alternating the impeller rotational speed (rpm) periodically. However, there is a concern that this centrifugal pump pulsatile mode may induce added hemolysis as a result of the repeated acceleration and deceleration of rpm. Thus, a hemolysis study of the pulsatile modes of the Gyro C1E3 centrifugal pump (Gyro-P) was conducted. The results were then compared with the nonpulsatile mode of the same pump (Gyro-N) and the nonpulsatile BioMedicus BP-80 (Bio-N) pump. Three different conditions were simulated: left ventricular assist device (LVAD), cardiopulmonary bypass (CPB), and percutaneous cardiopulmonary support (PCPS). The beating rate of the Gyro-P was set at 40 bpm, with repetition of two different impeller speed (the lower being 70% of the higher speed). The 2 impeller speeds were set to obtain the same average flow as that of the nonpulsatile mode. The hemolysis results of the Gyro-P were comparable to or better than those of Bio-N, and no excessive hemolysis was observed, compared to the Gyro-N. In conclusion, The Gyro-P had an excellent hemolytic characteristic and generated no excessive hemolysis in most clinical usage conditions. With the concern of hemolysis eliminated, this pulsatile mode may have various possible mode advantages.

Analysis of Variance↗

PubMed1997

Hemolytic effect of surface roughness of an impeller in a centrifugal blood pump.

The present study investigates how the surface roughness of an impeller affects hemolysis in the pivot bearing supported Gyro C1E3 pump. This study focuses on particular areas of the impeller surface in the impeller type centrifugal pump. Seven Gyro C1E3 pumps were prepared with smooth surface housings and different impeller parts with different surface roughnesses. The vanes, top side, and backside of the impeller were independently subjected to vapor polishing, fine sand blasting, or coarse sand blasting to produce three different grades of surface roughness. These surfaces were then examined by a surface profile instrument. Using these pumps with different impellers, in vitro hemolysis tests were performed simulating cardiopulmonary bypass (5 L/min, 350 mm Hg). The findings of this study conclusively proved that surface roughness of the back side of the impeller has the greatest effect on hemolysis, followed by the top side and then the vanes. The following are reasons for these findings. First, the shear rate may be greater on the back side than on the top side because of the smaller gap between the back and the housing and the greater relative speed against the impeller. Second, the fluid beneath the impeller may have a longer exposure time because there is little chance for the fluid to mix beneath the impeller. Third, the shear rate may be greater on the top side of the impeller than on the vanes because a vortex formation occurs behind the vanes.

Analysis of Variance↗

PubMed1997

Reconsideration of total erythrocyte destruction phenomenon.

During a particular long-term in vitro hemolysis test, the plasma free hemoglobin suddenly increased even though the hemolysis level had risen linearly for the previous several hours. This phenomenon was dubbed the total destruction of erythrocytes (TDE) phenomenon, and it was hypothesized that this was the result of the accumulation of sublethal damage to erythrocytes. It was suggested that the TDE might demonstrate the hemolytic characteristics of a pump more sensitively than a conventional hemolysis test. However, the previous report did not consider the effects of temperature or contamination. To study these effects, 3 long-term hemolysis tests were concluded under the following conditions. For Study 1 blood temperature was maintained at 27 degrees C (n = 2); for Study 2, at 37 degrees C (n = 4); and for Study 3, at 37 degrees C with gentamicin (n = 4). The BioMedicus and Nikkiso pumps were used as they were in our previous report. Gas sterilization of all circuits and pumps preceded experimentation. In Studies 1 and 3, hemolysis increased linearly for 29 h. However, in Study 2 a sudden increase of hemolysis occurred for both pumps. Possible causes of this were the dramatic changes in environmental factors such as severe acidosis, high O2 and glucose consumption, and CO2 accumulation. In contrast, neither Study 1 nor Study 3 showed a sudden increase in hemolysis. The plasma free hemoglobin increased linearly in both groups until 29 h of pumping. The environmental changes resulting from contamination were considered to be the cause of the sudden increase in hemolysis. In conclusion, the TDE did not reflect mechanical blood cell damage, but rather different environment situations. Hemolysis increased linearly up to 29 h in either 27 degrees C or germ-free conditions.

Animals↗

PubMed1997

In vitro thrombogenesis study in the Gyro C1E3 for vibration assessment.

To clarify the correlation between vibration and thrombus formation in a centrifugal blood pump, a preliminary simulated thrombus study was conducted for possible detection of thrombus formation inside a pump. Additional in vitro thrombogenesis studies were performed to confirm the results of the preliminary study. The primary data acquisition equipment included an accelerometer (Isotron PE accelerometer, Endevco, San Juan Capistrano, CA, U.S.A.), digitizing oscilloscope (TDS 420, Tektronic, Inc., MA, U.S.A.), and pivot bearing centrifugal pumps. The accelerometer was mounted to the top of the pump casing to sense radial and axial accelerations. For the preliminary study, a piece of Silastic was adhered to each of the 3 common areas of thrombus formation inside the pump. The results provided baseline information to speculate on the possibility of detecting thrombus formation by vibration signal changes. For the next studies, fresh bovine blood was harvested under sterile conditions and with strict avoidance of air contact, adding 1.0 U/ml of heparin. The sterilized test circuit consisted of 3/8 inch tubing (Tygon) and a soft reservoir. During the operating time, the activated clotting time (ACT) was maintained between 150 to 300 s using protamin. A restrictor on the outflow tube maintained the flow rates at about 4.5 L/min. The pumps ran continuously for 6 h. Possible blood clot formation inside the pump was monitored by observing the vibration signal from the device for 6 h. These studies revealed that it was possible to distinguish between an impeller that did not form thrombus and ones that formed fibrogenous thrombus using vibration signal assessment. Vibration assessment is worthwhile as a thrombus monitoring tool for a centrifugal blood pump.

Analysis of Variance↗

PubMed1997

Comparison of the Gyro C1E3 and BioMedicus centrifugal pump performances during cardiopulmonary bypass.

The compact eccentric inlet port (C1E3) centrifugal blood pump was developed as a cardiopulmonary bypass (CPB) pump. The C1E3 pump incorporated a sealless design with a blood stagnation free structure. The pump impeller was magnetically coupled to the driver magnet in a sealless manner. To develop an atraumatic and antithrombogenic centrifugal pump without a shaft seal junction, a double pivot bearing system was introduced. Recently, a mass production model of the C1E3 was fabricated and evaluated. The ratio of the normalized index of hemolysis (NIH) of the C1E3 was 0.007 g/ 100 L, in comparison to the NIH of the BP-80, 0.018 g/ 100 L, each in a CPB condition of 5 L/min against 325 mm Hg. Both pumps were compared in identical in vitro circuits. To further evaluate the pumps during cardiopulmonary bypass for reliability and function, 6 h of CPB was performed on each of 8 bovines using either the C1E3 or BP-80 centrifugal pump. The BP-80 and C1E3 provided pump flows of 50-60 ml/kg/min without incident. The hemodynamics were stable, and the hematology and biochemistry data were within normal ranges. There were no statistically significant differences between the 2 groups. Concerning the plasma free hemoglobin values, a mass production model of the C1E3 pump had the same hemolysis levels as the BP-80. Our preliminary studies reveal that the C1E3 pump is reliable. Also, the C1E3 will satisfy clinical requirements as a cardiopulmonary bypass pump.

Alanine Transaminase↗

PubMed1997

Preclinical evaluation of the Kyocera Gyro centrifugal blood pump for cardiopulmonary bypass.

The Kyocera Gyro pump has been developed as a completely seal-less centrifugal pump to overcome the problems of the conventional centrifugal pumps. The Gyro pump is a double pivot bearing-supported centrifugal pump with several specific design features, including its eccentric inlet port. We investigated the feasibility of the Gyro pump for cardiopulmonary bypass (CPB) in a bovine model, comparing it with the BioMedicus pump (BP-80). Ten healthy calves (5: Gyro pump, 5: BP-80) underwent 6 h of mildly hypothermic CPB at approximately 33 degrees C. Both pumps provided more than 50 ml/kg/min without any incidents. The haemodynamics of both groups remained stable within the normal range. All haematology and biochemistry data demonstrated no significant differences between the two groups. However, values of plasma-free haemoglobin and lactate dehydrogenase were less throughout the experiments of the Gyro pump than those of the BP-80. To obtain flow equivalent to that of the BP-80, the Gyro pump needed less rotational speeds than the BP-80 (2749.7 +/- 233.3 versus 3170.6 +/- 300.8 rpm. p < 0.05). Less rotational speed in addition to the difference in operating principle may contribute to less blood damage during the CPB OF the Gyro pump. After pumping for CPB, no leakage or thrombus formation was observed in either pump. The present study indicated that the Kyocera Gyro pump can be applied as a centrifugal pump for CPB with the same performance as the BP-80 and with relatively less haemolysis than the BP-80.

Analysis of Variance↗

PubMed1997

In vitro thrombogenic evaluation of centrifugal pumps.

One of the major considerations in the development of a circulatory assist device is its antithrombogenecity. Although the precise evaluation should be accomplished by in vivo tests, these tests are costly and require a relatively long period. In this study, we established a simple in vitro test and assessed feasibility using 2 clinically available centrifugal pumps, the BioMedicus and Nikkiso pumps. Two identical mock loops were fabricated, and fresh heparinized human blood (activated clotting time of 150-250 s) was circulated at 5 L/min against a total pressure head of 100 mm Hg. After 3 h of pumping, only the BioMedicus pumps had thrombi while the Nikkiso pumps were thrombus free. Following 6 h of pumping, thrombi were observed in both pumps. Clotting patterns and locations were reproducible in each pump and similar to the results of clinical or ex vivo studies. This simple in vitro test was considered to be feasible as a pilot study, particularly to predict thrombogenic sites.

Centrifugation↗

PubMed1997

Hemolytic effects of surface roughness of a pump housing in a centrifugal blood pump.

The surface roughness of artificial blood contacting devices is an important surface property that is closely related to blood cell trauma. The present study investigated the effect of the surface roughness of a pump housing on hemolysis in an impeller-type centrifugal blood pump, a pivot bearing supported Gyro C1E3 pump. The purpose of the study was to determine which part of a housing has the greatest surface roughness effect on hemolysis in a centrifugal pump. Seven Gyro C1E3 pumps were prepared, each with a smooth surface impeller and a housing with differing areas of altered surface roughness. Both top and bottom housings were divided into half subregions, each with the same area. Seven test pumps were produced by subjecting various subregions of the housings to vapor polishing and sandblasting. The treated surfaces were then examined by a surface profile instrument. Using these 7 pumps with different areas of altered housing roughness, in vitro hemolysis tests were performed simulating cardiopulmonary bypass (5 L/min, 350 mm Hg). The results of this study are as follows. First, the surface roughness of the top housing had a greater effect on hemolysis than that of the bottom housing. Second, on the surface of the top housing, the surface roughness of the outer half area had a greater effect on hemolysis than that of the inner half area. Third, on the surface of the bottom housing, the surface roughness of the inner half area had a greater effect on hemolysis than that of the outer half area. These findings concur with previous studies of flow patterns in pumps. Thus, it is expected that the method in this study, comparative in vitro hemolysis tests of the pumps with surfaces of the same roughness but different locations, can be used to detect the high shear area inside a pump.

Analysis of Variance↗

PubMed1997

A pivot bearing-supported centrifugal pump for a long-term assist heart.

A pivot bearing-supported centrifugal blood pump has been developed. It is a compact, cost effective, and anti-thrombogenic pump with anatomical compatibility. A preliminary evaluation of five paracorporeal left ventricular assist studies were performed on pre-conditioned bovine (70-100 kg), without cardiopulmonary bypass and aortic cross-clamping. The inflow cannula was inserted into the left ventricle (LV) through the apex and the outflow cannula affixed with a Dacron vascular graft was anastomosed to the descending aorta. All pumps demonstrated trouble free performance over a two-week screening period. Among these five studies, three implantations were subjected for one month system validation studies. All the devices were trouble free for longer than 1 month. (35, 34, and 31 days). After achieving one month studies, all experiments were terminated. There was no evidence of device induced thrombus formation inside the pump. The plasma free hemoglobin levels were within normal ranges throughout all experiments. As a consequence of these studies, a mass production model C1E3 of this pump was fabricated as a short-term assist pump. This pump has a Normalized Index of Hemolysis of 0.0007 mg/100L and the estimated wear life of the impeller bearings is longer than 8 years. The C1E3 will meet the clinical requirements as a cardiopulmonary bypass pump. For the next step, a miniaturized pivot bearing centrifugal blood pump P1-601 has been developed for use as a permanently implantable device after design optimization. The evolution from C1E3 to the PI-601 converts this pivot bearing centrifugal pump as a totally implantable centrifugal pump. A pivot bearing centrifugal pump will become an ideal assist pump for the patients with failing heart.

Animals↗

PubMed1996

Organization of the chicken histone genes in a major gene cluster and generation of an almost complete set of the core histone protein sequences.

We present a detailed picture of the disposition of the histone genes in the chicken genome and an almost complete set of the core histone protein sequences. Thirty-nine histone genes, six H1, nine H2A, eight H2B, eight H3 and eight H4, were located within a histone gene cluster of 110 kb, which was covered by five cosmid clones and two lambda clones. Results of our sequence analyses, together with those reported previously, generated a set of the core histone amino acid sequences as follows: three H2A variants, four H2B variants, two H3 variants and an H4 protein.

Amino Acid Sequence↗

PubMed1996

Dispase/detergent treated dermal matrix as a dermal substitute.

A method for preparing acellular allogeneic dermal matrix (ADM) and its effectiveness as a dermal substitute are described. Treatment of rat skin with Dispase followed by Triton X-100 completely removed cellular components from the dermis. Subcutaneously implanted ADM evoked no immunological reaction and 20 weeks after implantation, the size of the implanted ADM was reduced to about 60 per cent of its original area. ADM became completely vascularized within 2 weeks after implantation into full thickness skin defects in the rat and inhibited extensive wound contracture. A second layer of ADM placed onto the implanted ADM served as an excellent dressing, providing mechanical protection and permitting vascularization of the underlying implant. Onlay skin autografts placed onto vascularized allogeneic ADM showed good survival when the skin was grafted more than 1 week after ADM implantation. Dispase/detergent treated ADM derived from animal or human skin may be useful in full thickness skin defects providing a vascularized bed for subsequent epidermal coverage.

Animals↗

PubMed1996

Effect of surface roughness on hemolysis in a pivot bearing supported Gyro centrifugal pump (C1E3).

The blood contacting surface quality is an important pump parameter for blood compatibility and cell damage. This study investigates the surface roughness and the effect it has on hemolysis in a centrifugal blood pump. In vitro hemolysis tests were performed with a pivot bearing supported Gyro centrifugal pump (C1E3) simulating cardiopulmonary bypass (CPB; 5 L/min, 350 mm Hg) and left ventricular assist device (LVAD; 5 L/min, 100 mm Hg) conditions. To produce 4 different grades of surface roughness, the impellers and housings were subjected to vapor polishing, sand papering, fine sand blasting, or coarse sand blasting. Seven pumps were assembled with different impeller and housing surfaces. These surfaces were then examined by a surface profile instrument and a scanning electron microscope. The results of this study are as follows. First, the effect of surface roughness on hemolysis was significantly greater in the CPB condition than in the LVAD condition. Second, surface roughness, regardless of whether it is the impeller or pump housing, had little effect on hemolysis in the LVAD condition. Third, in the CPB condition, the surface roughness of the pump housing has a greater effect on hemolysis than does that of the impeller. From a hemolytic point of view, an extremely smooth pump housing is required for use of an impeller type centrifugal pump as a CPB device. In contrast, it is conceivable that a smooth surface is not always essential for an impeller type centrifugal pump that is used as an LVAD.

Animals↗

PubMed1996

The effect of the impeller-driver magnetic coupling distance on hemolysis in a compact centrifugal pump.

Blood trauma is one of the important performance parameters of centrifugal pumps. To investigate the blood trauma induced by these pumps, in vitro hemolysis tests have become an important procedure and are increasingly used for pump development and comparisons. The Baylor compact eccentric inlet port (CIE) centrifugal blood pump was developed as a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump (CPB). The Baylor CIE pump incorporates a seal-less design with a blood stagnation-free structure. This pump can provide flows of 5 L/min against 350 mm Hg of total pressure head at 2,600 revolutions per minute. The pump impeller is magnetically coupled to the driver magnet in a seal-less manner. The latest hemolysis study revealed that hemolysis may be affected by the gap distance between the driver and the impeller magnet. The purpose of this study was to verify the effect of the magnetic coupling distance on the normalized index of hemolysis (NIH) with the CIE model and to obtain an optimal gap distance. The NIH value was clearly decreased by alteration of the magnetic coupling distance from 7.7 to 9.7 mm in CPB and left ventricular assist device (LVAD) conditions. The NIH, when using the pump as an LVAD condition, was reduced to a level of 0.0056 from 0.095 when the magnetic coupling distance was extended. The same results were also obtained when the pumps were used in a CPB condition. The magnetic coupling distance is an important factor for the CIE model in terms of hemolysis. Different coupling forces effect the bearings and impeller stability. These results suggest that an optimal driving condition with a proper magnetic coupling and an optimal force between the impeller and driver is necessary to develop an atraumatic centrifugal pump.

Blood Flow Velocity↗

PubMed1996

Modification of a pivot bearing system on a compact centrifugal pump.

The pivot bearing centrifugal blood pump was developed as a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. This pivot bearing supported centrifugal pump with an eccentric port (CIE) incorporates a seal-less design with a blood stagnation-free structure. This pump can provide flows of 12 L/min against 650 mm Hg total pressure head at 3,600 rpm, and in a CPB condition 5 L/min against 350 mm Hg total pressure head at 2,600 rpm. Very recently, the pivot bearing system was modified to obtain a stable and smooth spinning movement. The material of the female pivot was changed from ceramic to polyethylene. Three kinds of bearings were tested simultaneously with bovine blood in two types of in vitro circuits to determine the blood damage from the bearings. Pressure differences across the pump (total head pressure, delta P) of 140 mm Hg (n = 12) and 330 mm Hg (n = 12) were examined. The normalized index of hemolysis (NIH) was slightly higher in a ball bearing (BB) pump than in a polyethylene bearing (PB) pump and statistically higher than the BioMedicus Pump (BP-80) on delta P of 140 mm Hg. When the delta P was at 330 mm Hg, a comparison between the three types of pumps revealed no difference in NIH. In addition, the primary vane of the impeller was redesigned to obtain an atraumatic structure. In the second study (n = 14), there was no difference in the NIH between BP-80 and the current model when the delta P was 300 mm Hg (0.019 +/- 0.002 vs. 0.027 +/- 0.006, p = 0.3) and/or when the delta P was 100 mm Hg (0.0008 +/- 0.0001 vs. 0.0014 +/- 0.0002, p = 0.07). The modified pivot bearing had an improved spinning condition and no change in hemolysis. A proper selection of pivot bearing materials is important to develop an atraumatic centrifugal pump. The modification of the bearing system and redesign of the vane enabled a compact centrifugal pump to become a reality.

Animals↗