Restitution Properties Research Articles

Carbon outclasses wood in racket paddles: Ratings of expert and intermediate tennis players

Wooden racket paddles were modified with rubber and carbon fibre laminates and their differences tested in terms of flexural, damping, and coefficient of restitution properties. Four rackets types were designed: a wood reference, wood with rubber, carbon fibre 0°, and carbon fibre 90°. Seven expert and eight intermediate tennis players tested the rackets. To determine which of the four rackets suited the players best, we asked the players to compare the rackets two by two. After each pair tested, participants had to fill out a 4-item questionnaire in which different aspects of the rackets' performance were judged. The most preferred racket was the 0° carbon fibre racket, followed by the 90° carbon fibre racket, the wood racket and, finally, the 1-mm rubber racket. Thus, rackets with the highest stiffness, least damping, and highest coefficient of restitution were the most preferred. Interestingly, although experts and intermediate players overall judged the rackets in very similar ways according to force, vibration, and control, they were sensitive to quite different physical characteristics of the rackets.

QT restitution properties of middle-aged women with different exercise capacities

Background Framingham Study data indicate an incremental risk of cardiovascular death in relation to low exercise capacity in women. The reason for death is still not clear. Methods QT restitution properties in 80 middle-aged women were investigated to confirm whether the cardiac restitution property was affected by the exercise capacity. Exercise tests were performed according to the Bruce protocol. Seventy cases were divided into the low–exercise capacity group (LEC group) and high–exercise capacity group (HEC group) by median exercise capacities. Sequential QT intervals and their preceding TQ intervals were measured, and the QT restitution curve (QTRC) was constructed. Two exponential equations were used to match the data and calculate the maximum slope (Smax) of QTRC, respectively. Results With elevation in the exercise level, the women in the LEC group had a higher change rate of QT intervals (41 ± 10 vs 29 ± 3 ms/Met, P = .001) and TQ intervals (46 ± 12 vs 41 ± 7 ms/Met, P = .046); and the ratio of QT interval alterations to TQ interval alterations increased (0.41 ± 0.09 vs 0.36 ± 0.07, P = .003). The Smax of the QTRC in the LEC group was higher than that in the HEC group (1.43 ± 0.44 vs 1.13 ± 0.34, P = .002). There was an inverse relationship between Smax and exercise capacity ( r = −0.43, P = .001). Conclusion Middle-aged women with low exercise capacity have steeper QTRCs than those with high exercise capacity, denoting a more unstable alternation of QT interval with elevation in exercise level.

Effects on electricalrestitution of given esmolol during cardiopulmonary resuscitation in a swine ventricularfibrillation model

：Objective To investigatethe effect on electrical restitution of β1-adrenergic receptor antagonist esmolol administered duringcardiopulmonary resuscitation in the porcine ventricular fibrillation model. MethodVentricular fibrillation untreated for four minutes was induced by dynamic steady statepacing protocol in 40 healthy male pigs, in which local unipolar electrograms wererecorded using one 10-electrode catheter that was sutured to the left ventrieularepicarditan. During CPR, animals were randomized into two groups to receive saline asplacebo or esmolol after two standards doses of epinephrine. At postresuscitation 2-hour,six pigs were randomly selected from each group and the second VF induction was performed.Local activation-recovery intervals (ARI) restitutions and the VF inducibility betweencontrol group and esmolol group were compared. Western blotting was performed to determinecardiac ryanodine receptor (RyR2) protein expression, and their phosphorylation status.Results No sig-nificant differences were observed at the restoration of spontaneouscirculation between two groups. Higher postre-suseitation 2-hour survival rate wasobserved in the esmolol group. Esmolol significantly flattened ARI restitution slope,lessened regional difference of ARI restitution, decreased the VF inducibility, andalleviated RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR significantlyimproved postresuscitation 2-hour survival rate. Its effects on modulating electricalrestitution property and intracellular calcium handling make up the most important reasonswhy β1-blockadesignificantly reduced the onset and maintenance of VF. Key words: Veutricularfibrillation; Action potentials; Restitution property; Cardiac ryanodinereceptor; Beta-adrenergic receptor

Abnormal restitution property of action potential duration and conduction delay in Brugada syndrome: both repolarization and depolarization abnormalities

This study sought to examine the action potential duration restitution (APDR) property and conduction delay in Brugada syndrome (BrS) patients. A steeply sloped APDR curve and conduction delay are known to be important determinants for the occurrence of ventricular fibrillation (VF). Endocardial monophasic action potential was obtained from 39 BrS patients and 9 control subjects using the contact electrode method. Maximum slopes of the APDR curve were obtained at both the right ventricular outflow tract (RVOT) and the right ventricular apex (RVA). The onset of activation delay (OAD) after premature stimulation was examined as a marker of conduction delay. Maximum slope of the APDR curve in BrS patients was significantly steeper than that in control subjects at both the RVOT and the RVA (0.77 +/- 0.21 vs. 058 +/- 0.14 at RVOT, P = 0.009; 0.98 +/- 0.23 vs. 0.62 +/- 0.16 at RVA, P = 0.001). The dispersion of maximum slope of the APDR curve between the RVOT and the RVA was also larger in BrS patients than in control subjects. The OAD was significantly longer in BrS patients than in control subjects from the RVOT to RVA and from the RVA to RVOT (from RVOT to RVA: 256 +/- 12 vs. 243 +/- 7 ms, P = 0.003; from RVA to RVOT: 252 +/- 11 vs. 241 +/- 9 ms, P = 0.01). Abnormal APDR properties and conduction delay were observed in BrS patients. Both repolarization and depolarization abnormalities are thought to be related to the development of VF in BrS patients.

Abnormal Action Potential Duration Restitution Property in the Right Ventricular Outflow Tract in Brugada Syndrome

Although patients with Brugada syndrome (BS) are at risk of ventricular fibrillation (VF) and ensuing death, the action potential duration (APD) restitution properties of the right ventricular outflow tract (RVOT) in patients with BS remain undetermined. Endocardial monophasic action potentials (MAPs) were obtained from 16 patients with BS and 17 control patients. MAPs were recorded from the RVOT in all patients. The MAP duration at 90% repolarization (MAPD(90)), effective refractory period (ERP), and maximum slope of the APD restitution curve were obtained. VF was induced with up to 3 extrastimuli from the RV apex or RVOT. There was no difference in MAPD(90) between the 2 groups, but the ERP was significantly shorter in patients with BS than in control patients (210.7+/-10.5 vs 223.8+/-13.4 ms, P=0.008). MAPD at the shortest diastolic interval was significantly shorter in patients with BS than in control patients (149.9+/-19.9 vs 179.8+/-13.7 ms, P<0.001). The maximum slope of the APD restitution curve was steeper in patients with BS than in control patients (2.90+/-1.29 vs 1.38+/-0.41, P<0.001). The shorter ERP, shorter MAPD at the shortest diastolic interval and steeply sloped APD restitution curve in the RVOT appear to be related to the inducibility of VF in patients with BS.

Impact of ionic current variability on human ventricular cellular electrophysiology

Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict arrhythmic risk preclinically challenging. Our goal is to investigate the role of ionic current properties and their variability in modulating cellular biomarkers of arrhythmic risk to improve risk stratification and identification in humans. A systematic investigation into the sensitivity of the main preclinical biomarkers of arrhythmic risk to changes in ionic current conductances and kinetics was performed using computer simulations. Four stimulation protocols were applied to the ten Tusscher and Panfilov human ventricular model to quantify the impact of +/-15 and +/-30% variations in key model parameters on action potential (AP) properties, Ca(2+) and Na(+) dynamics, and their rate dependence. Simulations show that, in humans, AP duration is moderately sensitive to changes in all repolarization current conductances and in L-type Ca(2+) current (I(CaL)) and slow component of the delayed rectifier current (I(Ks)) inactivation kinetics. AP triangulation, however, is strongly dependent only on inward rectifier K(+) current (I(K1)) and delayed rectifier current (I(Kr)) conductances. Furthermore, AP rate dependence (i.e., AP duration rate adaptation and restitution properties) and intracellular Ca(2+) and Na(+) levels are highly sensitive to both I(CaL) and Na(+)/K(+) pump current (I(NaK)) properties. This study provides quantitative insights into the sensitivity of preclinical biomarkers of arrhythmic risk to variations in ionic current properties in humans. The results show the importance of sensitivity analysis as a powerful method for the in-depth validation of mathematical models in cardiac electrophysiology.

Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a porcine ventricular fibrillation model

Objectives The aim of the study was to investigate the effect on calcium cycling protein and electrical restitution of β 1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Methods Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventricular epicardium. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standard doses of epinephrine. At post-resuscitation 2-h, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals (ARI) restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine expression of Ca 2+/calmodulin-dependent protein kinase IIδ(CaMKIIδ) and cardiac ryanodine receptor (RyR2) protein, and their phosphorylation status. Results Injection of esmolol combined with epinephrine during CPR significantly decreased recurrent rate of ventricular fibrillation during 2-h post-resuscitation, meanwhile it has no adverse affect on the restore of spontaneous circulation. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated CaMKIIδ hyper-activation and RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR has significant effects on modulating electrical restitution property and intracellular calcium handling, which contributes the most important reasons why β 1-blockade significantly reduced the onset and maintenance of VF.

Interaction of Activation–Repolarization Coupling and Restitution Properties in Humans

Dynamic modulation of repolarization is important in arrhythmogenesis. An inverse relation exists in myocardium between activation time (AT) and action potential duration (APD). We hypothesized that resulting gradients of APD and diastolic interval (DI) interact with restitution properties and modulate the timing of repolarization. Activation-recovery intervals (ARI) were acquired from reconstructed noncontact unipolar electrograms from the left ventricular endocardium in 9 patients (7 male) with normal ventricles. At a basic paced cycle length (median, 450 ms), ARIs shortened along the path of activation, with a mandatory reciprocal increase of DIs. In the median patient, this range of DIs started at 230 ms at the site of earliest activation and increased to 279 ms at the site of latest activation at a basic cycle length of 450 ms. Four consecutive standard S1 to S2 restitution curves were performed. At sites with a longer ARI (and therefore shorter DI) close to the site of stimulation, premature stimulation produced more shortening of ARIs; therefore, the time course of restitution was steeper than at more distal sites. At normal heart rate, the decrease in ARIs along the conduction pathway compensated for later activation. Thus, dispersion in repolarization time (RT) is smaller than dispersion in ARI in a heart with a steep negative AT-ARI relationship. This protective effect is lost in hearts without such a relationship. In the patients with a steep AT-ARI relationship at basic cycle length, this relation is lost after premature stimulation and is a function of prematurity. Thus, dispersion in RT is larger after shortly coupled extra stimuli in patients with a steep AT-ARI relationship. A complex interplay exists between activation-repolarization coupling and restitution properties, largely driven by ARI and DI gradients. This plays a significant role in the dynamics of repolarization in humans.

A Novel Computational Model of the Human Ventricular Action Potential and Ca transient

We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our objective was to implement a model that: 1) accurately reflects Ca-dependent Ca release; 2) uses repolarizing K currents with realistic amplitude; 3) comes to steady state; 4) simulates basic excitation-contraction coupling phenomena; and 5) runs on a normal desktop computer. The model relies on the framework of the rabbit myocyte model developed by Shannon et al. in our laboratory, and includes a subsarcolemmal compartment (in addition to the other two commonly formulated cytosolic compartments, junctional and bulk) where the ion channels sense ion concentrations that differ from the bulk. Ion channels and transporters have been modeled on the basis of the most recent experimental data obtained in our group and from the literature. In particular, novel formulations of the rapidly and slowly inactivating components of Ito have been implemented and utilized to differentiate between endocardial and epicardial myocytes. The model has been validated against a wide set of experimental data including action potential adaptation and restitution properties, frequency dependent inotropy and intracellular sodium staircase. It also correctly predicts the effect of pharmacological intervention on K currents (e.g. chromanol 293 B and dofetilide administration) on ventricular repolarization. We conclude that this model is more robust than previously existing models and provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single cell level. To overcome the substantial limitations to experimental studies involving human cardiac tissue, due to its low computational cost this model is suitable to be integrated into multi-scale models of tissue and/or heart.

Optical Mapping Of VF In Isolated Swine Hearts With Scars

Ventricular fibrillation (VF) is the main cause of sudden cardiac death. We hypothesized that VF induced by large scars in an isolated porcine heart model could aid the understanding of VF in human hearts associated with structural disease. The explanted hearts were perfused with blood and Tyrode solution at 37C, and optically imaged with a voltage-sensitive fluorescence dye (di4-ANEPPS excited at 530nm with 150W halogen lamp). The emitted signal was filtered (610nm) and recorded with high speed cameras (MiCAM02, BrainVison, Jp) at 0.7mm spatial resolution. No optical signals could be recorded from the core of chronic infarcts or RF lesions. A total of 10 hearts were used: 4 controls, 3 with lesions generated via RF ablation and 3 with chronic infarcts. We observed the propagation of the depolarization waves and analyzed the VF waveforms at the border zone (BZ) and normal myocardium. We analyzed the VF waves in the frequency domain by calculating the dominant frequency (DF) on select regions of interest using Matlab (Mathworks, Ca). Our results showed that DF is smaller at the BZ compared to healthy tissue. Referenced to the average DF in the control hearts (10.07+/-0.54 Hz), the DF was slightly smaller in healthy myocardium of infarct hearts (i.e., 8.9+/-0.71Hz) and significantly smaller at the border zone (i.e., 6.03 +/- 0.86Hz). In ablated hearts, mean DF in normal myocardium was 9.16+/-0.7Hz and 7.24+/-0.66Hz at BZ, respectively. We suggest that these differences are related to the heterogeneous restitution properties as well as the changes in tissue structure at the BZ. The BZ of chronic scars is comprised of a mixture of viable and necrotic fibers; whereas in the acute settings of RF lesions, inflammation and edema are present at the BZ without alteration of fiber directions.

216 同質・同径2球の繰返し反発特性

216 同質・同径2球の繰返し反発特性

The Transfer Functions of Cardiac Tissue during Stochastic Pacing

The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K +]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction.

Calsequestrin-Mediated Mechanism for Cellular Calcium Transient Alternans

Intracellular calcium transient alternans (CTA) has a recognized role in arrhythmogenesis, but its origin is not yet fully understood. Recent models of CTA are based on a steep relationship between calcium release from the sarcoplasmic reticulum (SR) and its calcium load before release. This mechanism alone, however, does not explain recent observations of CTA without diastolic SR calcium content alternations. In addition, nanoscopic imaging of calcium dynamics has revealed that the elementary calcium release units of the SR can become refractory independently of their local calcium content. Here we show using a new physiologically detailed mathematical model of calcium cycling that luminal gating of the calcium release channels (RyRs) mediated by the luminal buffer calsequestrin (CSQN) can cause CTA independently of the steepness of the release-load relationship. In this complementary mechanism, CTA is caused by a beat-to-beat alternation in the number of refractory RyR channels and can occur with or without diastolic SR calcium content alternans depending on pacing conditions and uptake dynamics. The model has unique features, in that it treats a realistic number of spatially distributed and diffusively coupled dyads, each one with a realistic number of RyR channels, and that luminal CSQN buffering and gating is incorporated based on experimental data that characterizes the effect of the conformational state of CSQN on its buffering properties. In addition to reproducing observed features of CTA, this multiscale model is able to describe recent experiments in which CSQN expression levels were genetically altered as well as to reproduce nanoscopic measurements of spark restitution properties. The ability to link microscopic properties of the calcium release units to whole cell behavior makes this model a powerful tool to investigate the arrhythmogenic role of abnormal calcium handling in many pathological settings.

Effects of Procainamide and Sotalol on Restitution Properties, Dispersion of Refractoriness, and Ventricular Fibrillation Activation Patterns in Pigs

Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents. We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone. Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.5 mg/kg). Another six pigs received sotalol first and procainamide second. Before drugs and after each drug, 20-second episodes of electrically induced VF were recorded from a 21 x 24 unipolar electrode plaque (2 mm spacing) sutured on the lateral posterior left ventricular epicardium. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals during pacing. The combination of the two drugs reduced the maximum slope of the restitution curve and during VF reduced the number of wavefronts, the activation rate, the percentage of wavefront families exhibiting reentry, and the conduction velocity more than either drug alone. In addition, in the group that received sotalol first, both drugs together reduced the SD and the coefficient of variation of the spatial dispersion of refractoriness compared with baseline. Procainamide and sotalol combined have greater beneficial effects on restitution properties, dispersion of refractoriness, and the complexity of VF than either drug alone compared with baseline.

Tumor necrosis factor-α: a new mechanism of ischemic ventricular fibrillation?

Tumor necrosis factor-α: a new mechanism of ischemic ventricular fibrillation?

Ventricular Repolarization Restitution Properties in Patients Exhibiting Type 1 Brugada Electrocardiogram With and Without Inducible Ventricular Fibrillation

This study aimed to elucidate the contribution of the repolarization restitution property to the sustained ventricular fibrillation (VF) in Brugada syndrome. Although phase 2 re-entry develops as the trigger of VF, the other precipitating factors have remained unclear. Twenty-one patients with a type 1 Brugada electrocardiogram underwent programmed electrical stimulation. Before the VF induction, single extrastimuli were delivered at 3 basic drive cycle lengths (BCLs) (400 ms, 600 ms, and 750 ms) from the right ventricular apex (RVA) and outflow tract (RVOT), and the activation recovery interval (ARI) was measured at 5-mm vicinity of the pacing site. The maximum ARI restitution slope was determined using the overlapping least-squares linear segments. We found that VF was inducible in 10 patients. A repeated-measure analysis of variance revealed that the slope in the RVA was steeper in patients with inducible VF than in those without but that in the RVOT was similar. The slope was steeper at longer BCLs and also steeper in the RVA than RVOT at BCLs of 600 and 750 ms. In patients with inducible VF, the percentage of patients exhibiting a slope >1 was 0%, 20%, and 75% in the RVA and 0%, 0%, and 14% in the RVOT at BCLs of 400 ms, 600 ms, and 750 ms, respectively. No patients without inducible VF had a slope >1. These results suggest the repolarization restitution property is a contributing factor to the propensity for VF in Brugada syndrome and, regarding this property, the RVA plays more important role than the RVOT.

118 Al-SUJ2同径二球の衝突

Authors have been examining the restitution property of metal balls of same diameter and same materials to understand the impact phenomenon of the object. In this research the impact experiments on same diameter and different material spheres were conducted for aluminum (A5052) sphere and steel (SUJ2) spheres, and the restitution property was examined. The coefficient of restitution of aluminum and SUJ2 steel, decreased exponentially with the impact velocity. Finite element analyses were done by using the stress-strain relations obtained from the static compression test and dynamic compression test. The analytical results correspond well with the experiment results.

Master Curve for the Discrete-Element Method

The discrete-element method (DEM) is a numerical model consisting of the fundamental laws of motion and a suitable force-displacement model, such as the linear spring-and-dashpot model, as closure. The damping coefficient found in the latter is related to the phenomenological concept of coefficient of restitution of solid particles. However, the relationship between these two coefficients is strongly dependent on various material properties of the solid particles to be simulated, and so its determination often involves a numerical trial-and-error procedure. This paper addresses this problem by presenting a master calibration curve and equation that can be used to calculate the value of the damping coefficient directly from values of the coefficient of restitution and other material properties. The Buckingham Pi theorem was applied to derive a functional relationship between the two coefficients and other material properties, which allowed a large number of calibration curves to be collapsed onto a single master calibration curve.

Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles

The onset of ventricular fibrillation (VF) has been associated with steep action potential duration restitution in both clinical and computational studies. Recently, detailed clinical restitution properties in cardiac patients were reported showing a substantial degree of heterogeneity in restitution slopes at the epicardium of the ventricles. The aim of the present study was to investigate the effect of heterogeneous restitution properties in a three-dimensional model of the ventricles using these clinically measured restitution data. We used a realistic model of the human ventricles, including detailed descriptions of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy. We extended this model by mapping the clinically observed epicardial restitution data to our anatomic representation using a diffusion-based algorithm. Restitution properties were then fitted by regionally varying parameters of the electrophysiological model. We studied the effects of restitution heterogeneity on the organization of VF by analyzing filaments and the distributions of excitation periods. We found that the number of filaments and the excitation periods were both dependent on the extent of heterogeneity. An increased level of heterogeneity leads to a greater number of filaments and a broader distribution of excitation periods, thereby increasing the complexity and dynamics of VF. Restitution heterogeneity may play an important role in providing a substrate for cardiac arrhythmias.

Vulnerability to re-entry in simulated two-dimensional cardiac tissue: Effects of electrical restitution and stimulation sequence

Ventricular fibrillation is a lethal arrhythmia characterized by multiple wavelets usually starting from a single or figure-of-eight re-entrant circuit. Understanding the factors regulating vulnerability to the re-entry is essential for developing effective therapeutic strategies to prevent ventricular fibrillation. In this study, we investigated how pre-existing tissue heterogeneities and electrical restitution properties affect the initiation of re-entry by premature extrastimuli in two-dimensional cardiac tissue models. We studied two pacing protocols for inducing re-entry following the "sinus" rhythm (S1) beat: (1) a single premature (S2) extrastimulus in heterogeneous tissue; (2) two premature extrastimuli (S2 and S3) in homogeneous tissue. In the first case, the vulnerable window of re-entry is determined by the spatial dimension and extent of the heterogeneity, and is also affected by electrical restitution properties and the location of the premature stimulus. The vulnerable window first increases as the action potential duration (APD) difference between the inside and outside of the heterogeneous region increases, but then decreases as this difference increases further. Steeper APD restitution reduces the vulnerable window of re-entry. In the second case, electrical restitution plays an essential role. When APD restitution is flat, no re-entry can be induced. When APD restitution is steep, re-entry can be induced by an S3 over a range of S1S2 intervals, which is also affected by conduction velocity restitution. When APD restitution is even steeper, the vulnerable window is reduced due to collision of the spiral tips.