Patent Description:
The invention described herein relates to devices for the treatment of chronic total occlusions. More particularly, the invention described herein relates to devices for crossing chronic total occlusions and establishing a pathway blood flow past the chronic total occlusions.

Due to age, high cholesterol and other contributing factors, a large percentage of the population has arterial atherosclerosis that totally occludes portions of the patient's vasculature and presents significant risks to patient health. For example, in the case of a total occlusion of a coronary artery, the result may be painful angina, loss of cardiac tissue or patient death. In another example, complete occlusion of the femoral and/or popliteal arteries in the leg may result in limb threatening ischemia and limb amputation.

Commonly known endovascular devices and techniques are either inefficient (time consuming procedure), have a high risk of perforating a vessel (poor safety) or fail to cross the occlusion (poor efficacy). Physicians currently have difficulty visualizing the native vessel lumen, can not accurately direct endovascular devices toward the visualized lumen, or fail to advance devices through the lesion. Bypass surgery is often the preferred treatment for patients with chronic total occlusions, but less invasive techniques would be preferred.

Described herein are devices and methods employed to exploit the vascular wall of a vascular lumen for the purpose of bypassing a total occlusion of an artery. Exploitation of a vascular wall may involve the passage of an endovascular device into and out of said wall which is commonly and interchangeable described as false lumen access, intramural access, submedial access or in the case of this disclosure, subintimal access.

<CIT> discloses a tube shaped rotational medical instrument insertable into a blood vessel of a patient to cross a total occlusion. The instrument comprises a shaft formed of a coil with a cutting tip and a rotational handle preventing application of excessive torque.

The device according to the invention is defined in claim <NUM>. The methods of operation disclosed are not claimed but are considered useful for understanding the invention.

In one aspect, the present disclosure is directed to a method of facilitating treatment via a vascular wall defining a vascular lumen containing an occlusion therein. The method may include providing an intravascular device having a distal portion and a longitudinal axis and inserting the intravascular device into the vascular lumen. The method may further include positioning the distal portion in the vascular wall, rotating the intravascular device about the longitudinal axis, and advancing the intravascular device within the vascular wall.

In another aspect, the present disclosure is direct to a device for facilitating treatment via a vascular wall defining a vascular lumen containing an occlusion therein. The device may include a shaft having a distal end and a proximal end. The shaft may include a coil having a plurality of filars wound in a helical shape, the coil extending from the distal end of the shaft to the proximal end of the shaft, and a sleeve, having a proximal end and a distal end, the sleeve extending from the distal end of the shaft and covering a portion of the coil. The device may further include a tip fixed to the distal end of the shaft, and a hub fixed to the proximal end of the shaft.

<FIG> is a cross-sectional view of an artery <NUM> having a wall <NUM>. In <FIG>, wall <NUM> of artery <NUM> is shown having three layers. The outermost layer of wall <NUM> is the adventitia <NUM> and the innermost layer of wall <NUM> is the intima <NUM>. The tissues extending between intima <NUM> and adventitia <NUM> may be collectively referred to as the media <NUM>. For purposes of illustration, intima <NUM>, media <NUM> and adventitia <NUM> are each shown as a single homogenous layer in <FIG>. In the human body, however, the intima and the media each comprise a number of sublayers. The transition between the external most portion of the intima and the internal most portion of the media is sometimes referred to as the subintimal space.

Intima <NUM> defines a true lumen <NUM> of artery <NUM>. In <FIG>, an occlusion <NUM> is shown blocking true lumen <NUM>. Occlusion <NUM> divides true lumen <NUM> into a proximal segment <NUM> and a distal segment <NUM>. A crossing device <NUM> is disposed in proximal segment <NUM> of true lumen <NUM>. Crossing device <NUM> may be used to establish a channel between proximal segment <NUM> and distal segment <NUM>. Crossing device <NUM> of <FIG> comprises a tip <NUM> that is fixed to a distal end of a shaft <NUM>.

<FIG> is an additional view of artery <NUM> shown in the previous figure. In the embodiment of <FIG>, the distal end of crossing device <NUM> has been advanced in a distal direction so that tip <NUM> is disposed in subintimal space <NUM>. With reference to <FIG>, it will be appreciated that tip <NUM> has passed through intima <NUM> and is disposed between intima <NUM> and adventitia <NUM> of artery <NUM>. The embodiment of <FIG> and other embodiments described herewithin show access to the subintimal space <NUM> by way of example, not limitation, as the crossing device <NUM> may alternatively pass through the occlusion <NUM> thus remaining disposed in the true lumen <NUM>.

In the embodiment of <FIG>, shaft <NUM> of crossing device <NUM> defines a lumen <NUM>. Lumen <NUM> may be used to deliver fluids into the body. For example, radiopaque fluid may be injected through lumen <NUM> and into subintimal space <NUM>. In some useful embodiments, lumen <NUM> is dimensioned to receive a guidewire.

<FIG> is an additional view of artery <NUM> shown in the previous figure. In the embodiment of <FIG>, the distal end of crossing device <NUM> has been advanced so that tip <NUM> has moved in an axial direction through subintimal space <NUM>. With reference to <FIG>, it will be appreciated that tip <NUM> has moved distally past occlusion <NUM>. In <FIG>, tip <NUM> is shown residing between intima <NUM> and adventitia <NUM> of artery <NUM>. Axial advancement of tip <NUM> may cause blunt dissection of the layers forming wall <NUM> of artery <NUM>. Alternatively, the tip may cause blunt dissection of the materials comprising the occlusion <NUM> (not shown).

In some useful methods in accordance with the present disclosure, crossing device <NUM> is rotated about it's longitudinal axis and moved in a direction parallel to it's longitudinal axis simultaneously. When this is the case, rotation of crossing device <NUM> may reduce resistance to the axial advancement of crossing device <NUM>. These methods take advantage of the fact that the kinetic coefficient of friction is usually less than the static coefficient of friction for a given frictional interface. Rotating crossing device <NUM> assures that the coefficient of friction at the interface between the crossing device and the surround tissue will be a kinetic coefficient of friction and not a static coefficient of friction.

<FIG> is an additional view of artery <NUM> shown in the previous figure. In the embodiment of <FIG>, crossing device <NUM> has been withdrawn from true lumen <NUM> of artery <NUM>. With reference to <FIG>, it will be appreciated that a guidewire <NUM> remains in the position formerly occupied by crossing device <NUM>.

The position of guidewire <NUM> shown in <FIG> may be achieved using crossing device <NUM>. Guidewire <NUM> may be positioned, for example, by first placing crossing device <NUM> in the position shown in the previous figure, then advancing guidewire <NUM> through lumen <NUM> defined by shaft <NUM> of crossing device <NUM>. Alternately, guidewire <NUM> may be disposed within lumen <NUM> while crossing device <NUM> is advanced through the vasculature of a patient. When this is the case, guidewire <NUM> may be used to aid in the process of steering crossing device <NUM> through the vasculature.

With guidewire <NUM> in the position shown in <FIG>, guidewire <NUM> may be used to direct other devices to subintimal space <NUM>. For example, a catheter may be advanced over guidewire <NUM> until the distal end of the catheter is disposed in subintimal space <NUM>. After reaching the subintimal space, the catheter may be used to dilate subintimal space <NUM>. Examples of catheters that may be used to dilate the subintimal space include balloon catheters and atherectomy catheters.

<FIG> is a cross sectional view of an artery <NUM> having a wall <NUM>. In <FIG>, a crossing device <NUM> is shown extending through subintimal space <NUM> and around an occlusion <NUM>. In <FIG>, occlusion <NUM> is shown blocking a true lumen <NUM> defined by an intima <NUM> of wall <NUM>. Occlusion <NUM> divides true lumen <NUM> into a proximal segment <NUM> and a distal segment <NUM>. When a crossing member in accordance with some embodiments of the present disclosure is advanced through the subintimal space of an artery, the distal end of the crossing device may penetrate the intima and enter the distal segment of the true lumen after advancing beyond an occlusion.

In the embodiment of <FIG>, a tip <NUM> of crossing device <NUM> is disposed in distal segment <NUM>. Accordingly, it will be appreciated that crossing device <NUM> has pierced intima <NUM> distally of occlusion <NUM> and entered distal segment <NUM> of artery <NUM>. In <FIG>, shaft <NUM> is shown extending through intima <NUM> and subintimal space <NUM>. Shaft <NUM> of crossing device <NUM> may define a lumen <NUM>.

<FIG> is an additional view of artery <NUM> shown in the previous figure. In the embodiment of <FIG>, crossing device <NUM> has been withdrawn leaving a guidewire <NUM> in the position shown in <FIG>.

The position of guidewire <NUM> shown in <FIG> may be achieved using crossing device <NUM>. Guidewire <NUM> may be positioned, for example, by first placing crossing device <NUM> in the position shown in the previous figure, then advancing guidewire <NUM> through lumen <NUM> defined by shaft <NUM> of crossing device <NUM>. Alternately, guidewire <NUM> may be disposed within lumen <NUM> while crossing device <NUM> is advanced through the vasculature of a patient. When this is the case, guidewire <NUM> may be used to aid in the process of steering crossing device <NUM> through the vasculature of a patient.

Devices such as balloon angioplasty catheters and atherectomy catheters may be advanced over guidewire <NUM> and into subintimal space <NUM>. In this way, these devices may be used in conjunction with guidewire <NUM> to establish a blood flow path between proximal segment <NUM> of true lumen <NUM> and distal segment <NUM> of true lumen <NUM>. This path allows blood to flow through subintimal space <NUM> and around occlusion <NUM>.

<FIG> is a partial cross-sectional view of an exemplary crossing device <NUM>. Crossing device <NUM> of <FIG> comprises a tip <NUM> that is fixed to a distal end of a shaft <NUM>. In the exemplary embodiment of <FIG>, shaft <NUM> comprises a coil <NUM>, a sleeve <NUM>, a tubular body <NUM>, and a sheath <NUM>.

Tip <NUM> is fixed to a distal portion of coil <NUM>. Coil <NUM> comprises a plurality of filars <NUM> that are wound in a generally helical shape. In some useful embodiments of crossing device <NUM>, coil <NUM> comprises eight, nine or ten filars wound into the shape illustrated in <FIG>. Crossing device <NUM> includes a sleeve <NUM> that is disposed about a portion of coil <NUM>. Sleeve <NUM> may comprise, for example, PET shrink tubing, i.e. polyethylene terephthalate.

Sleeve <NUM> and coil <NUM> both extend into a lumen defined by a tubular body <NUM>. Tubular body <NUM> may comprise, for example hypodermic tubing formed of Nitinol, i.e. nickel titanium. With reference to <FIG>, it will be appreciated that a proximal portion of sleeve <NUM> is disposed between tubular body <NUM> and coil <NUM>. In some embodiments of crossing device <NUM>, a distal portion of tubular body <NUM> defines a helical cut. This helical cut may be formed, for example, using a laser cutting process. The helical cut may be shaped and dimensioned to provide an advantageous transition in lateral stiffness proximate the distal end of tubular body <NUM>.

A proximal portion of coil <NUM> extends proximally beyond the distal end of tubular body <NUM>. A hub <NUM> is fixed to a proximal portion of coil <NUM> and a proximal portion of tubular body <NUM>. Hub <NUM> may comprise, for example, a luer fitting. Sheath <NUM> is disposed about a portion of tubular body <NUM> and a portion of sleeve <NUM>. In some embodiments of crossing device <NUM>, sheath <NUM> comprises HYTREL, a thermoplastic elastomer.

With reference to <FIG>, it will be appreciated that tubular body <NUM>, coil <NUM>, sleeve <NUM>, and sheath <NUM> each have a proximal end and a distal end. The proximal end of sheath <NUM> is disposed between the proximal end of tubular body <NUM> and the proximal end of sleeve <NUM>. The distal end of sleeve <NUM> is positioned proximate tip <NUM> that is fixed to the distal end of coil <NUM>. The distal end of sheath <NUM> is located between the distal end of tubular body <NUM> and the distal end of sleeve <NUM>. With reference to <FIG>, it will be appreciated that sheath <NUM> overlays the distal end of tubular body <NUM>.

With reference to <FIG>, it will be appreciate that tip <NUM> has a generally rounded shape. The generally rounded shape of tip <NUM> may reduce the likelihood that crossing device <NUM> will penetrate the adventitia of an artery. Tip <NUM> may be formed from a suitable metallic material including but not limited to stainless steel, silver solder, and braze. Tip <NUM> may also be formed from suitable polymeric materials or adhesives including but not limited to polycarbonate, polyethylene and epoxy. In some embodiments of crossing device <NUM>, outer surface <NUM> of tip <NUM> comprises a generally non-abrasive surface. For example, outer surface <NUM> may have a surface roughness of <NUM> micrometers or less. A tip member having a relatively smooth outer surface may reduce the likelihood that the tip member will abrade the adventitia of an artery.

<FIG> is a plan view showing an assembly <NUM> including crossing device <NUM> shown in the previous figure. In the embodiment of <FIG>, a handle assembly <NUM> is coupled to crossing device <NUM>. In <FIG>, handle assembly <NUM> is shown disposed about a proximal portion of shaft <NUM> of crossing device <NUM>. Handle assembly <NUM> comprises a handle body <NUM> and a handle cap <NUM>.

In some useful embodiments in accordance with the present disclosure, handle assembly <NUM> is long enough to receive the thumb and for fingers of a physician's right and left hands. When this is the case, a physician can use two hands to rotate handle assembly <NUM>. In the embodiment of <FIG>, grooves <NUM> are formed in handle body <NUM> and handle cap <NUM>. Grooves <NUM> may improve the physician's ability to grip handle assembly <NUM>.

<FIG> is an additional plan view showing assembly <NUM> shown in the previous figure. In <FIG>, a proximal portion of handle assembly <NUM> is positioned between the thumb and forefinger of a left hand <NUM>. A distal portion of handle assembly <NUM> is disposed between the thumb and forefinger of a right hand <NUM>.

In some useful methods, crossing device <NUM> is rotated and axially advanced simultaneously. Rotation of crossing device <NUM> can be achieved by rolling handle assembly <NUM> between the thumb and forefinger one hand. Two hands can also be used as shown in <FIG>. Rotating crossing device <NUM> assures that the coefficient of friction at the interface between the crossing device and the surround tissue will be a kinetic coefficient of friction and not a static coefficient of friction.

In some useful methods in accordance with the present disclosure, crossing device <NUM> is rotated at a rotational speed of <NUM> to <NUM> revolutions per minute. In some particularly useful methods in accordance with the present disclosure, crossing device <NUM> is rotated at a rotational speed of <NUM> and <NUM> revolutions per minute. Crossing device <NUM> may be rotated by hand as depicted in <FIG>. It is also contemplated that a mechanical device (e.g., an electric motor) may be used to rotate crossing device <NUM>.

<FIG> is a cross-sectional view of assembly <NUM> shown in the previous figure. With reference to <FIG> it will be appreciated that handle assembly <NUM> is disposed about sheath <NUM>, tubular body <NUM>, sleeve <NUM> and coil <NUM>.

<FIG> is a cross sectional view of handle assembly <NUM> shown in the previous figure. With reference to <FIG>, it will be appreciated that handle assembly <NUM> includes a plurality of grip sleeves <NUM> and a plurality of spacers <NUM>. In the embodiment of <FIG>, handle cap <NUM> includes male threads <NUM> that engage female threads <NUM> in handle body <NUM>.

When handle cap <NUM> is rotated relative to handle body <NUM>, the threads produce relative longitudinal motion between handle cap <NUM> and handle body <NUM>. In other words, handle cap <NUM> can be screwed into handle body <NUM>. As handle cap <NUM> is advanced into handle body <NUM>, the inner end of handle cap <NUM> applies a compressive force to grip sleeves <NUM>. Grip sleeves <NUM> are made from an elastomeric material. The compression forces applied to grip sleeves <NUM> by handle body <NUM> and handle cap <NUM> cause grip sleeves <NUM> to bulge. The bulging of grip sleeves <NUM> causes grip sleeves <NUM> to grip shaft <NUM> of crossing device <NUM>.

The force that each grip sleeve <NUM> applies to the shaft is generally equally distributed about the circumference of the shaft. When this is the case, the likelihood that the shaft will be crushed by the grip sleeves is reduced. At the same time, the grip sleeves provide an interface that allows significant torque to be applied to the shaft when the handle is rotated.

<FIG> is a partial cross-sectional view showing a guidewire <NUM> that is disposed in a lumen <NUM> defined by a shaft <NUM> of a crossing device <NUM>. <FIG> is an additional view showing guidewire <NUM> and crossing device <NUM> shown in <FIG>. In some embodiments of crossing device <NUM>, shaft <NUM> defines a lumen <NUM>. When this is the case, a guidewire may be inserted into the lumen. The guidewire may be used to steer the crossing device. The guidewire may remain inside the lumen until it is needed for steering. When steering is needed, the guidewire may be advanced so that a portion of the guidewire extends beyond the distal end of the crossing device. A distal portion of the guidewire may then be advanced in the direction that the physician wishes to advance crossing device <NUM>.

In the embodiment of <FIG>, guidewire <NUM> has been distally advanced (relative to the position shown in <FIG>). With reference to <FIG>, it will be appreciated that a distal portion <NUM> of guidewire <NUM> is extending beyond the distal end of crossing device <NUM>. In the embodiment of <FIG>, distal portion <NUM> of guidewire <NUM> is biased to assume a generally curved shape when it is unrestrained by crossing device <NUM>.

In the embodiment of <FIG>, there are at least two degrees of freedom between guidewire <NUM> and crossing device <NUM>. First, guidewire <NUM> and crossing device <NUM> are free to rotate relative to one another. Second, guidewire <NUM> and crossing device <NUM> are free to move in a longitudinal direction relative to one another. It is sometimes desirable to use guidewire <NUM> as an aid in directing crossing device <NUM> through the vasculature of a patient. When this is the case, distal portion <NUM> of guidewire <NUM> may be advanced beyond the distal end of crossing device <NUM>. Guidewire <NUM> may then be rotated until distal portion <NUM> of guidewire <NUM> assumes a desired orientation.

<FIG> shows a heart <NUM> including a coronary artery <NUM>. An occlusion <NUM> is disposed in coronary artery <NUM>. Occlusion <NUM> divides a lumen of coronary artery <NUM> into a proximal segment <NUM> and a distal segment <NUM>. The proximal segment <NUM> may be easily accessed using endovascular devices and has adequate blood flow to supply the cardiac muscle. The distal segment <NUM> is not easily accessed with interventional devices and has significantly reduced blood flow as compared to proximal segment <NUM>.

<FIG> is an enlarged view showing a portion of heart <NUM> shown in the previous figure. In <FIG>, a crossing device <NUM> is disposed in proximal segment <NUM> of coronary artery <NUM>. <FIG> is an enlarged plan view of crossing device <NUM> shown in <FIG>. Crossing device <NUM> comprises a tip <NUM> and a shaft <NUM>.

<FIG> is an additional view showing crossing device <NUM> disposed in heart <NUM>. <FIG> is an enlarged plan view of crossing device <NUM> shown in <FIG>. In <FIG> crossing device <NUM> has been rotated approximately ninety degrees relative to the position shown in <FIG>.

Some useful methods in accordance with the present disclosure include the step of rotating crossing device <NUM>. When the proximal portion of a crossing device is rotated, it may be desirable to confirm that the distal end of the crossing device is also rotating.

Many physicians have experience using guidewires. These physicians are aware that twisting the proximal end of a guidewire when the distal end of the guidewire is fixed may cause the guidewire to break due to twisting. Accordingly, many physicians may be hesitant to rotate an intravascular device more than a few revolutions unless they are certain that the distal end of the device is free to rotate.

One method for determining whether the tip of a crossing member is rotating may be described with reference to <FIG>, <FIG>. As shown in the figures, crossing member <NUM> comprises a tip <NUM> fixed to the distal end of a shaft <NUM>. Tip <NUM> comprises a radiopaque marker <NUM>. Radiopaque marker <NUM> has a face <NUM> and an edge <NUM>. Face <NUM> has a width W and a length L. Edge <NUM> has a length L and a thickness T. In some useful embodiments of crossing device <NUM>, thickness T of radiopaque marker <NUM> is smaller then both length L and width W. When this is the case, radiopaque marker <NUM> may be used to provide a physician with visual feedback indicating that tip <NUM> of crossing device <NUM> is rotating.

During rotation of crossing device <NUM>, the shape of radiopaque marker provides visual feedback assuring the physician that the tip of the crossing member is rotating as the physician rotates the proximal portion of the crossing member. Radiopaque marker <NUM> provides two different appearances while it is being rotated and observed using fluoroscopic methods. When edge <NUM> of radiopaque marker is viewed on a fluoroscopic display a first appearance is achieved. When face <NUM> of radiopaque marker <NUM> is viewed, it provides a second appearance on the fluoroscopic display. With reference to the figures, it will be appreciate that the first appearance has a smaller footprint than the second appearance. When the appearance of radiopaque marker <NUM> is alternating between the first appearance and the second appearance, the physician can infer that tip <NUM> is rotating. This visual feedback allows the physician to confirm that the distal end of crossing member is rotating.

<FIG> and <FIG> each show a crossing device <NUM> comprising a tip <NUM> fixed to a shaft <NUM>. Tip <NUM> comprises a radiopaque marker <NUM>. Tip <NUM> of crossing device <NUM> has been advanced through a proximal segment <NUM> of a coronary artery <NUM>. With reference to <FIG> and <FIG>, it will be appreciated that tip <NUM> is near wall <NUM> of coronary artery <NUM> and an occlusion <NUM> that is located in the true lumen of coronary artery <NUM>. When a surgical procedure is viewed on a fluoroscope, it may be difficult for the physician to determine whether or not tip <NUM> is disposed in the subintimal space of coronary artery <NUM>. Methods for determining whether the tip is disposed in the subintimal space may be described with reference to <FIG> and <FIG>.

For example, one method in accordance with the present disclosure may include the steps of positioning the distal end of a crossing device in a position that may or may not be in the subintimal space of an artery and injecting radiopaque fluid into the body from the distal end of crossing device <NUM>. If the radiopaque fluid remains in a localized area (e.g., in the subintimal space) then a physician viewing the radiopaque fluid on a fluoroscopic display can infer that the distal end of the crossing device is disposed in the subintimal space. If the radiopaque fluid rapidly enters the bloodstream and is carried through the vasculature, then the physician can infer that the distal end of the crossing device is disposed in the true lumen of the artery.

<FIG> is a representation of a fluoroscopic display <NUM> produced when radiopaque fluid has been injected into the body from the distal end of crossing device <NUM> while tip <NUM> is disposed in the true lumen of coronary artery <NUM>. In <FIG>, the radiopaque fluid <NUM> has rapidly entered the bloodstream and has cause the vasculature in fluid communication with proximal segment <NUM> to become illuminated on fluoroscopic display <NUM>. Radiopaque marker <NUM> is also visible in fluoroscopic display <NUM>.

<FIG> is a representation of a fluoroscopic display <NUM> produced when radiopaque fluid has been injected into the body from the distal end of crossing device <NUM> while tip <NUM> is disposed in the subintimal space of coronary artery <NUM>. In <FIG>, the radiopaque fluid <NUM> is disposed in a localized area (i.e., in the subintimal space). Radiopaque marker <NUM> is also visible in fluoroscopic display <NUM>.

Claim 1:
A device for facilitating treatment via a vascular wall defining a vascular lumen containing an occlusion therein, the device comprising:
a crossing device (<NUM>) comprising a tip (<NUM>) fixed to a distal end of a shaft (<NUM>) and a hub (<NUM>) fixed to a proximal end of the shaft (<NUM>), the shaft including:
a coil (<NUM>) having a plurality of filars wound in a helical shape, the coil(<NUM>) extending from the distal end of the shaft (<NUM>) to the proximal end of the shaft (<NUM>);
a sleeve (<NUM>) extending from the distal end of the shaft (<NUM>) and disposed about a portion of the coil (<NUM>); and
a tubular body (<NUM>) having a proximal end and a distal end, and covering a portion of the coil (<NUM>) and a portion of the sleeve (<NUM>), the distal end of the tubular body (<NUM>) extending beyond the proximal end of the sleeve (<NUM>), and the proximal end of the tubular body (<NUM>) is fixed to the hub (<NUM>);
and
a handle assembly (<NUM>) positioned about the crossing device (<NUM>) and configured to be coupled to the crossing device (<NUM>) such that torque is applied to the shaft (<NUM>) when the handle assembly (<NUM>) is rotated, wherein the handle assembly (<NUM>) comprises a handle body (<NUM>) threadedly connected to a handle cap (<NUM>), the handle cap (<NUM>) being configured to rotate relative to the handle body (<NUM>); and wherein the handle assembly (<NUM>) comprises at least one grip sleeve (<NUM>) configured to grip the shaft (<NUM>) in response to a rotation of the handle cap (<NUM>) relative to the handle body (<NUM>).