Abstract: The invention relates to an on-site medical gas production plant (100) comprising a unit (50) for purifying gas, such as air, a first compartment (A) for storing purified gas, and a main gas line (10) fluidically connecting the gas purification unit (50) to the said first storage compartment (A). It furthermore comprises a three-way actuated valve (VA) arranged on the main gas line (10) upstream of the first storage compartment (A), and furthermore connected to the atmosphere (at 12) via a vent line (11), as well as an operating device (4) which controls at least the three-way actuated valve (VA), and at least a first gas analysis device (D1) of which a first measurement line (29) is fluidically connected (at 28) to the main line (10), upstream of the three-way actuated valve (VA), and which is electrically connected to the said operating device (4).

Abstract: The invention relates to a device for supplying gas to a patient, in particular a patient breathing spontaneously. The device includes a) a metering device (A) which is used to meter the gas to be inhaled by the patient (P) into the gas tank (B), b) a gas tank (B) which is used to store the gas to be inhaled by the patient (P), c) a demand valve (D) which regulates the volume flow of the gas inhaled by the patient (P), d) a reservoir (F) which is used to hold the gas exhaled by the patient (P), e) a carbon dioxide separating unit (G) which is used to separate carbon dioxide from the exhaled gas, f) a pump (H) which is used to return the exhaled gas purified of carbon dioxide into the gas tank (B), and g) an analysis/control unit (J) which analyzes the gas returned to the gas tank (B) and controls the metering device (A) according to the composition of said gas.

Abstract: An apparatus and methods for the administration of positive airway pressure therapies. The apparatus can include a housing, a blower and a mask. The housing is configured to be stably secured on the head of a patient. The blower is secured relative to the housing. A mask in fluid communication with the blower is configured to communicate pressurized air produced at least in part by the blower to the airways of a user.

Abstract: A sound machine having a pseudo random white noise generator provides white noise sound therapy of selectable tone/texture, bandwidth and/or peak frequency to those suffering from tinnitus or others seeking noise-masking or sleep or relaxation. The sound machine having a pseudo random white noise generator includes a user input interface having a tone/texture user input control, a band pass user input control and a peak select user input control. The tone/texture user input control selects the tone/texture of the white noise sound generated, the bandpass user input control the bandpass of the white noise sound generated and the peak select user input control provides the ability to select frequency peaks of the white noise sound generated.

Abstract: A method to induce an immediate psychosomatic change in a patient optimal for a particular medical procedure, is provided. The method uses a brain-computer interface integrating a loop of biofeedback and neurofeedback components, interactive, immersive, 3D virtual reality (VR) modules utilizing hypnotic or guided-response, learning, placebo and experience-ratification principles. The method will differentiate between low and high hypnotizable patients as well their specific abilities and limitations by their distinct brain patterns and will deliver VR output content appropriate for the current and targeted psychosomatic state of the patient, needs, and stage of a particular medical procedure thus being applicable to any medical patient regardless of abilities. The device will continuously measure the patient's physiological markers and will customize the intensity, order, timing, and content of the output “dose.

Abstract: Introduced are a bed device system and methods for: gathering human biological signals, such as heart rate, breathing rate, or temperature; analyzing the gathered human biological signals; and controlling the bed device system, e.g., a temperature of the bed device, based on the analysis.

Abstract: A compact packaged intermittent urinary catheter having a longitudinally elongated intermittent urinary catheter retained within a longitudinally compacted elastic package. A method of using the catheter wherein at least a portion of the package is used as a drainage tube for the catheter.

Abstract: A torque for controlling the advancement and rotation of a right heart catheter during a right heart catheterization procedure. The torque has a casing with a cavity for receiving a core, and a lumen for receiving the right heart catheter. A gripper is disposed within the core to tightly grip the right heart catheter. The core has a plurality of threads that engage teeth of a handle. The handle is attached to the casing at an axis and rotates about the axis during use. The core has an elongated spiraled recess which is engaged by a guide pin attached to the casing and extending within the cavity. When the handle is rotated, the teeth of the handle engage the threads to rotate the core, and the guide pin engages the elongated spiraled recess to move the core laterally, thereby advancing and rotating the right heart catheter.

Abstract: The present invention is a catheter actuation handle for deflecting a distal end of a tubular catheter body, the handle including an auto-locking mechanism. The handle comprises upper and lower grip portions, an actuator, and an auto-locking mechanism. The auto-locking mechanism is adapted to hold a deflected distal end of the catheter in place without input from the operator. When the distal end of the catheter is deflected from its zero position, it typically will seek a return to its zero position, and as a result exerts a force on the actuator. The auto-locking mechanism acts by providing a second force that resists this force from the distal end and holds the distal end in place. As a result, the operator does not need to maintain contact with the buttons to maintain the distal end 18 in a set position once placed there by actuating the actuator.

Abstract: A catheter includes a shaft having at least one lumen. The lumen comprises a longitudinally-extending trough defined by a longitudinally-extending recess, within which a component is disposed, and a longitudinally extending open edge. The lumen further comprises a longitudinally-extending channel defined by a longitudinally-extending cavity and by the open edge of the trough. A planarity wire is disposed within the cavity and is configured to close the open edge of the trough to within a pre-defined tolerance that is less than the size of the component to retain the component in the recess.

Abstract: The catheter has a catheter body and a deflectable section with a flat deflection beam having a different deflection initiation location on each side of the beam to provide nonsymmetrical bi-directional deflection via a single continuous puller wire with two longer parallel segments connected by a U-bend segment anchored at a distal end of the beam. A spacer is provided on each side of the beam to guide and bind the respective puller wire segments and maintain a predetermined separation distance between the puller wire and the beam, including a neutral bending axis of the beam, for reducing the beam's bending moment. One or more heat shrinking tubes may surround the spacer and the beam to tightly constrain the puller wire to the beam.

Abstract: A coated medical device (10) including a structure (12) adapted for introduction into a passage or vessel of a patient. The structure is formed of preferably a non-porous base material (14) having a bioactive material layer (18) disposed thereon. The medical device is preferably an implantable stent or balloon (26) of which the bioactive material layer is deposited thereon. The stent can be positioned around the balloon and another layer of the bioactive material posited over the entire structure and extending beyond the ends of the positioned stent. The ends of the balloon extend beyond the ends of the stent and include the bioactive material thereon for delivering the bioactive material to the cells of a vessel wall coming in contact therewith. The balloon further includes a layer of hydrophilic material (58) positioned between the base and bioactive material layers of the balloon.

Abstract: Methods and devices quickly and accurately locate the sphenopalatine ganglion (SPG) while performing a sphenopalatine ganglion block procedure that introduces a medication to the SPG. The methods and devices also prevent the medication applied to the SPG from flowing down a patient's throat during the procedure.

Abstract: A single stage instrument is used to insert a chest drainage tube into the inter-pleural space to facilitate drainage. The instrument is scissor-like with cylinder-like channels to slidably enclose the distal section of the tube therein when closed. The tip of the instrument is curved to enter the skin incision and the offset pleural incision whereafter the instrument is rotated 180 degrees to align the curved tip with the pleural space. The curved tip facilitates sliding the chest drainage tube through the instrument to effect sufficient insertion length. Once the instrument is in place, the tube is slid along the instrument to ensure that all drainage holes in the chest drainage tube are within the pleural cavity. Thereafter, the instrument is withdrawn leaving the chest drainage tube in place. After withdrawal of the instrument, it is opened laterally for lateral disengagement with the chest drainage tube.

Abstract: A surgical method of implanting an implantable drainage apparatus. The method comprising the steps of cutting the skin of a patient, inserting the implantable drainage apparatus into the body of the patient, the implantable drainage apparatus comprising a drainage device, an energy source adapted to supply energy to the drainage device, a connecting tube connected to the drainage device, a bellows adapted to generate a suction and a motor connected to the bellows, being adapted to compress the bellows to move fluid out of the bellows and at the same time pre-tension the bellows, placing the drainage device at a placement area in the patient's body, placing the connecting tube at a treatment area in the patient's body.

Abstract: A method of draining cerebrospinal fluid from a human brain. The method includes providing a drainage catheter having a proximal end and a distal end. The drainage catheter has a plurality of openings formed therein. The plurality of openings includes a first opening, a second opening, and a most proximal opening. The second opening is disposed closer to the distal end than the first opening. A cross-sectional area of the first opening is less than a cross-sectional area of the second opening. The distal end of the drainage catheter is inserted into a human brain. Cerebrospinal fluid is drained from the human brain. The cerebrospinal fluid passes into the drainage catheter through the plurality of openings and out of the drainage catheter through the proximal end. A rate at which the cerebrospinal fluid passes through the drainage catheter is controlled to maintain intracranial pressure within a selected range.

Abstract: A method of treating a constricted sinus passageway of a patient includes traversing the canine fossa region of the patient so as to form a passageway in the sinus cavity. A cannula is positioned in the passageway. A visualization tool such as an endoscope is passed through a lumen or channel in the cannula to aid in visualization of the anatomical site of interest. A balloon dilation catheter is then deployed through or along the cannula so as to place the balloon within or across the constricted anatomical space (e.g., ostium). The balloon is then expanded so as to expand at least a portion of the constricted anatomical space. Alternative embodiments include the use of an optional guide wire and incorporating a endoscope lumen through the balloon dilation catheter.

Abstract: A gel assembly comprising a polymeric gel layer between metal layers. A gel assembly process comprising providing a colloidal polymer in solution, drying the solution to form a polymeric gel layer and forming metal layers on either side of the polymeric gel layer. A method of drug delivery comprising loading a polymeric gel layer with drug, forming metal layers on either side of the polymeric gel layer, wherein the polymeric gel layer comprises a material that is sensitive to a stimulus, and subjecting the polymeric gel layer to the stimulus to release the drug from between or through the metal layers.

Abstract: A method for planning an infusion into hepatic tissue into a patient includes: obtaining anatomical and/or physiological patient data of the patient's liver or a region of the liver; determining at least one patient parameter from the patient data; planning the infusion using the anatomical patient data, physiological patient data, and/or at least one patient parameter, wherein planning includes determining how an administered substance is distributed in the tissue and/or how the administered substance influences physiological properties of the tissue; and determining a distribution and/or effectiveness of a therapeutic agent administered with the substance or after the substance.

Abstract: A needleless connector has a body having an internal cavity with a sealing ridge, a port, an output flow channel, and a fluid flow path between the port and output flow channel. The connector also has a collapsible valve disposed within the cavity. The valve includes a cylindrical wall having a center axis, an internal surface, and a shoulder configured to sealingly contact the ridge of the body, thereby blocking the fluid flow path. The valve also includes a head fixedly attached to the wall. The head has a smiley cut at a first angular position about the center axis and a continuous top surface that is generally perpendicular to the axis. The valve also includes a first dimple formed in the internal surface of the cylindrical wall. The dimple extends around the internal surface over an angle in the range of 90-270°.

Abstract: Devices or methods such as for stimulating excitable tissue or sensing physiologic response or other signals that can use separate fixation mechanism is described. An implantable apparatus can include a modular electrostimulation electrode assembly that can include a first module and a second module that can be end user-attachable to each other and end user-detached from each other. The first module can include an electrostimulation electrode fixation support member that can be laid flat against or otherwise conform to a surface of a heart, and can define a centrally located open portal such as for permitting electrode access to the surface of the heart. The second module can include an electrostimulation electrode that can be inserted through the portal of the fixation support member such as to contact the surface of the heart such as to deliver chronic electrostimulation to the heart.

Abstract: A method of forming a medical device contact element includes annealing an elongated rod of Ti-15Mo alloy material to form an annealed rod having a Young's Modulus of less than 13.5 Mpsi and an elastic range or strain of at least 0.7%. Then forming a contact ring element from the annealed rod and assembling the contact ring element into a medical device. Contact rings and lead receptacles including the same are also described.

Abstract: A method of forming an electrode array is disclosed, the method comprising: forming an elongate comb structure comprising a plurality of longitudinally-spaced electrode contacts extending from and supported by a spine; electrically connecting each of a plurality of electrically conductive pathways to a respective one of the plurality of electrode contacts; placing the conductive pathways adjacent the contacts; placing silicone over the conductive pathways and contacts; curing the silicone so as to substantially retain the longitudinal spacing between neighboring contacts; and severing the spine from the plurality of electrode contacts.

Abstract: A medical electrical lead system that includes a catheter extending from a proximal catheter end to a distal catheter end; a lead, insertable within the catheter, including a lead body extending from a proximal lead end to a distal lead end and an active fixation member positioned at the distal lead end; and an advancement tool for advancing the distal lead end outward from the distal catheter end. The advancement tool is adapted to be positioned around the lead body and further adapted to be removably fixedly engaged with the proximal catheter end.

Abstract: Embodiments include an implantable electronic device with at least one electromagnetic field detection unit and at least one antenna, wherein the at least one electromagnetic field detection unit is connected to the at least one antenna. The at least one electromagnetic field detection unit responds to electromagnetic fields that occur or are present in an environment surrounding a patient outside an environment of an MRI device and electromagnetic fields that are shielded in the environment of the MRI device. The at least one electromagnetic field detection unit indicates an absence of the electromagnetic fields that typically occur in the environment surrounding a patient outside an MRI device and that are shielded in the environment of an MRI device.

Abstract: A device for electrically controlled of ions, comprises a first electrolyte; a first electrode, which is arranged in direct or indirect contact with the first electrolyte, an encapsulation; and an ion conductor, which is arranged to receive and/or deliver ions from/to the first electrolyte. The encapsulation is arranged to effectively enclose the first electrolyte, and the ion conductor is arranged to transport ions from/to an outside of the encapsulation.

Abstract: A system and a method for optimizing the configuration of multisite transcranial current stimulation, including providing an electric field characteristic target map on the brain's cortex, the target map including multiple cortical targets, the multiple cortical targets are localized and/or continuously varying and spatially extended, providing a weight map on the cortical surface prioritizing the important of areas in the target map for the purposes of optimization; and calculating, based on the target and weight maps, optimal currents and optimal locations for a plurality of electrodes intended for providing transcranial current stimulation to globally stimulate at once the multiple cortical targets with excitatory, inhibitory or neutral stimulation.

Abstract: An exemplary system includes 1) a cochlear implant module configured to be implanted within a patient and comprising cochlear implant circuitry configured to apply electrical stimulation representative of one or more audio signals to the patient, 2) an implantable sound processor module configured to be implanted within the patient and comprising sound processor circuitry configured to optically transmit data and/or power to the cochlear implant circuitry, and 3) an optical connector assembly configured to facilitate removable coupling of the implantable sound processor module to the cochlear implant module by way of the optical connector assembly. The optical connector assembly comprises one or more optical fibers configured to facilitate the optical transmission of the data and/or the power from the sound processor circuitry to the cochlear implant circuitry while the implantable sound processor module is removably coupled to the cochlear implant module by way of the optical connector assembly.

Abstract: A method of testing subjects' perception of complex shapes created by patterned multi-electrode direct stimulation of a retinal prosthesis is described. The complex shapes can be geometric shapes or characters such as letters of the alphabet and numbers.

Abstract: Described herein are methods of treating various neurological disorders using electrical nerve conduction block (ENCB) without causing electrochemical damage. Examples of the various neurological disorders can include pain, muscle spasticity, hyperhidrosis, vertigo, sialorrhea, or the like. The methods can include placing an electrode contact in electrical communication with a nerve that transmits a signal related to the neurological disorder. The method also includes applying an ENCB to the nerve through the electrode contact. The electrode contact can include a high charge capacity material that prevents formation of damaging electrochemical reaction products at a charge delivered by the ENCB. The method also includes blocking transmission of the signal related to the neurological disorder through the nerve with the ENCB to treat the neurological disorder.

Abstract: An electrical stimulation system including: a mechanism generating at least one electrical signal to be applied to a biological tissue that is to stimulated and measuring a response of the biological tissue to each electrical signal; a calculation mechanism estimating, based on each electrical signal and on a corresponding response of the biological tissue, at least one parameter of an electrical model of the biological tissue and its interface with the electrical stimulation system and determining, using the model, at least one parameter of a stimulation pulse to be applied to the biological tissue by the electrical stimulation system; and a mechanism generating a stimulation pulse to be applied to the biological tissue.

Abstract: A neuromodulation system and method includes delivering first electrical modulation energy to a patient through a timing channel at a relatively high energy level (e.g., at a frequency in the range of 2 KHz-50 KHz) during a first time period in accordance with a stored modulation energy delivery schedule, delivering second electrical modulation energy to the patient through the same timing channel at a relatively low energy level (e.g., at a frequency in the range of 2 Hz to 1500 Hz) during a second time period in accordance with the stored modulation energy delivery schedule.

Abstract: An electrical neuromodulation system and method of treating an ailment of a patient using a neuromodulation device. Electrical modulation energy is delivered at a first frequency from the neuromodulation device to a first set of electrodes having a first combined electrode impedance. A second set of electrodes having a second combined electrode impedance less than the first combined electrode impedance is automatically selected. The electrical modulation energy is delivered at a second frequency to the second set of electrodes, wherein the second frequency is greater than the first frequency.

Abstract: An implantable system, and methodology, for improving a heart's hemodynamic performance featuring (a) bimodal electrodes placeable on the diaphragm, out of contact with the heart, possessing one mode for sensing cardiac electrical activity, and another for applying cardiac-cycle-synchronized, asymptomatic electrical stimulation to the diaphragm to trigger biphasic, diaphragmatic motion, (b) an accelerometer adjacent the electrodes for sensing both heart sounds, and stimulation-induced diaphragmatic motion, and (c) circuit structure, connected both to the electrodes and the accelerometer, operable, in predetermined timed relationships to the presences of valid V-events noted in one of sensed electrical and sensed mechanical, cardiac activity, to deliver diaphragmatic stimulation.

Abstract: A method for adjusting a pacing rate in a dual-chamber, leadless pacemaker implanted in a heart may involve determining, with a leadless atrial pacemaker implanted in an atrium of the heart, that an intrinsic atrial contraction rate of the atrium is faster than a ventricular contraction rate, transmitting a first signal from the atrial pacemaker to a leadless ventricular pacemaker implanted in a ventricle of the heart to increase a ventricular pacing rate of the ventricular pacemaker, receiving the transmitted first signal with the ventricular pacemaker, and increasing the ventricular pacing rate, based on the received first signal.

Abstract: Aspects herein include an implantable medical device, such as an implantable cardiac rhythm management device. The implantable medical device can include a housing, control circuitry disposed within the housing, and telemetry circuitry in electrical communication with the control circuitry. The control circuitry can be configured to execute a post-procedural system check procedure after the expiration of a preselected first time period. The first time period can be greater than or equal to 0.5 hours and less than or equal to 48 hours. In various aspects, the post-procedural system check procedure can include measuring diagnostic properties for one or more electrodes of an electrical stimulation lead attached to the implantable medical device. The first time period can begin to elapse after detection of a triggering event or a command by a system operator.

Abstract: A system may include a processor configured to automatically obtain magnetic resonance imaging compatibility information relating to compatibility of an active implantable medical device implantable in a patient with an MRI modality from at least two information sources. The processor may also be configured to automatically determine compatibility of the active implantable medical device with the magnetic resonance imaging modality based on the magnetic resonance imaging compatibility information.

Abstract: Systems and methods for communicating between medical devices. In one example, a method for communicating between a plurality of medical devices in a medical device system comprises, with a first medical device, communicating a first message to a second medical device. The method further comprises, with the second medical device, receiving the first message, wherein the first message comprises a plurality of communication pulses. A first set of the plurality of communication pulses represent a synchronization portion of the first message. A second set of the plurality of communication pulses represent a relative device address portion of the first message. A third set of the plurality of communication pulses represent a command portion of the first message. A fourth set of the plurality of communication pulses represent a payload portion of the first message.

Abstract: An implantable device has a cylindrical base, at least one electrode on the cylindrical base, at least one electrically conducting lead on the cylindrical base connected to the electrode wherein the electrically conducting lead has a feature size of <10 micrometers. A protective coating on the cylindrical base covers the at least one electrically conducting lead.

Abstract: An implantable medical device includes circuitry for generating and delivering electrical stimulation therapy. A power source is included in the implantable medical device for storage of the energy for the stimulation therapy. Techniques and circuits are provided for minimizing energy losses associated with the storage of the stimulation therapy energy. The implantable medical device circuitry includes charging circuitry that is operated in at least a first mode and a second mode, such that the charging circuit is operable in one of the at least first and second modes based on whether an intrinsic cardiac event is detected. The charging circuit is operable to charge the output capacitor to a first threshold capacity that is less than a pacing capacity of the output capacitor until a given cardiac cycle elapses without a sensed intrinsic cardiac event during operation in the first mode.

Abstract: An implantable medical device (IMD) having a rechargeable and primary battery is disclosed, as are algorithms for automatically selecting use of these batteries at particular times. In one IMD embodiment, the primary battery acts as the main battery, and an algorithm allows the IMD to draw power from the primary battery until its voltage reaches a threshold, after which the algorithm allows the IMD to draw power from the rechargeable battery when it is sufficiently charged. In another IMD embodiment, the rechargeable battery acts as the main battery, and an algorithm allows the IMD to draw power from the rechargeable battery if it is sufficiently charged; otherwise, the algorithm allows the IMD to draw power from the primary battery. Further disclosed are techniques for telemetering data relevant to both batteries to an external device, and for allowing a patient to choose use of a particular one of the batteries.

Abstract: The present invention relates to a device for treating biological cells in an object, the device comprising: —a single winding coil element; —an electrical generator connected to the single winding coil element, the single winding being configured to be positioned essentially around the object; wherein the electrical generator is configured to discharge into the single winding coil element so that the single winding coil element generates a short duration pulsed electromagnetic field by magnetic induction in the single winding coil element, the electromagnetic field having a field strength that is sufficiently high to affect, preferably increase the permeability of cell membranes and/or intracellular membranes of the biological cells contained in the object when in operation the object is placed inside the single winding coil element.

Abstract: Systems and methods for increasing skin rejuvenation of a region of a patient's skin. The system includes: a pulsed electromagnetic field (PEMF) frequency generator that emits electromagnetic pulses to the region of the patient's skin; and a deep tissue diathermy device that applies heat to the region of the patient's skin up to temperature T. The system simultaneously applies the heat and the PEMF to the region of a patient's skin.

Abstract: A system for treating neurological conditions by low-frequency time varying electrical stimulation includes an electrical device for applying such low-frequency energy, in a range below approximately 10 Hz, to the patient's brain tissue. An implantable embodiment applies direct electrical stimulation to electrodes implanted in or on the patient's brain, while a non-invasive embodiment causes a magnetic field to induce electrical currents in the patient's brain.

Abstract: An apparatus and method are utilized to transiently implement diamagnetic behavior in both permanently and transiently magnetized particles.

Abstract: An apparatus is provided for stimulating brain neural networks of a subject comprising: at least one transmitter configured to generate an electromagnetic field through the brain neural networks of a subject, at least one brain wave measuring device for detecting subject brain wave frequency, a CPU for processing data concerned with detection of brain wave frequency of a subject, having a database for storing and analyzing natural and affected brain scans, and at least one computer readable medium containing a predetermined protocol for transmission of the electromagnetic wave frequency profiles. The apparatus further provides a resonance effect thereby inducing newly generated brain cells to migrate toward a brain tissue area having the pathology or lesion of interest, and initiating new brain pathways at the brain region of interest.

Abstract: Methods and arrangements for distinguishing between target areas and non-target areas during a laser surgical procedure involve coating or otherwise providing the non-target areas with a phosphorescent material that emits radiation, upon stimulation when a predetermined condition occurs, that is distinguishable from the treatment radiation.

Abstract: A fluid dispenser including a body (6) receiving a dispenser member (3) connected to a reservoir (1) and to a fluid dispenser orifice (73), an actuator member (4) for actuating the dispenser member (3) and a module (5) comprising at least one source of radiation (51), such as a LED, the body (6) having a module housing (65) wherein the module (5) is received. The dispenser also includes a dispenser and diffuser head (7) mounted on the body (6) and forming an application wall (74) into which the fluid dispenser orifice (73) opens out for applying the fluid coming from the dispenser orifice (73) onto the skin. The module (5) is integral with the dispenser and diffuser head (7), thus forming together an integral unit (U) which is received on and within the body (6).

Abstract: A method and apparatus for treatment of fungal infections and/or other foot skin disorders, comprises a shoe-type housing having a substantially hollow interior forming a treatment chamber, a supporting platform disposed within the hollow chamber; so that a foot of a patient positioned within the treatment chamber is supported by the platform, so that nails are disposed at the lower level of the front part of the chamber, whereas the heel of the foot is being elevated a rear part thereof. A delivery and control assembly for the aqueous solution is provided. At least one light delivery arrangement is disposed within or in the vicinity of the treatment chamber.

Abstract: A method of radio-ablation in conjunction with embolic implants used for pre-embolization of branch arteries in radio-ablation of the liver or other diseased tissue.