text:
|Publication number
|Publication type
|Application number
|Publication date
|6 Jan 2005
|Filing date
|8 May 2004
|Priority date
|9 May 2002
|Also published as
|Publication number
|Birinder Boveja, Angely Widhany
|Original Assignee
|Boveja Birinder R., Angely Widhany
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (18), Referenced by (94), Classifications (22), Legal Events (8)
|External Links: USPTO, USPTO Assignment, Espacenet
This Application is a continuation of application Ser. No. 10/195,961 filed Jul. 17, 2002, which is a continuation of Ser. No. 10/142,298 filed on May 9, 2002, entitled "METHOD AND SYSTEM FOR MODULATING THE VAGUS NERVE (10th CRANIAL NERVE) USING MODULATED ELECTRICAL PULSES WITH AN INDUCTIVELY COUPLED STIMULATION SYSTEM".
The present invention relates to neuromodulation, more specifically neuromodulation of vagus nerve with pulsed electrical stimulation, to provide therapy for neurological and neuropsychiatric disorders.
The 10th cranial nerve or the vagus nerve plays a role in mediating afferent information from visceral organs to the brain. The vagus nerve arises directly from the brain, but unlike the other cranial nerves extends well beyond the head. At its farthest extension it reaches the lower parts of the intestines. The vagus nerve provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Observations on the profound effect of electrical stimulation of the vagus nerve on central nervous system (CNS) activity extends back to the 1930's.
The present invention is primarily directed to a method and system for selective electrical stimulation or neuromodulation of vagus nerve, for providing adjunct therapy for neurological and neuropsychiatric disorders such as epilepsy, depression, involuntary movement disorders including Parkinson's disease, anxiety disorders, neurogenic/psycogenic pain, obsessive compulsive disorders, migraines, obesity, dementia including Alzheimer's disease, and the like.
In the human body there are two vagal nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagus nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagus nerve does not cause substantial slowing of the heart rate or cause any other significant deleterious side effects.
One of the fundamental features of the nervous system is its ability to generate and conduct electrical impulses. Most nerves in the human body are composed of thousands of fibers of different sizes. This is shown schematically in
In a cross section of peripheral nerve it is seen that the diameter of individual fibers vary substantially, as is also shown schematically in
The diameters of group A and group B fibers include the thickness of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially in the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter.
Nerve cells have membranes that are composed of lipids and proteins (shown schematically in
The lipid component of the membrane is a double sheet of phospholipids, elongated molecules with polar groups at one end and the fatty acid chains at the other. The ions that carry the currents used for neuronal signaling are among these water-soluble substances, so the lipid bilayer is also an insulator, across which membrane potentials develop. In biophysical terms, the lipid bilayer is not permeable to ions. In electrical terms, it functions as a capacitor, able to store charges of opposite sign that are attracted to each other but unable to cross the membrane. Embedded in the lipid bilayer is a large assortment of proteins. These are proteins that regulate the passage of ions into or out of the cell. Certain membrane-spanning proteins allow selected ions to flow down electrical or concentration gradients or by pumping them across.
These membrane-spanning proteins consist of several subunits surrounding a central aqueous pore (shown in
A nerve cell can be excited by increasing the electrical charge within the neuron, thus increasing the membrane potential inside the nerve with respect to the surrounding extracellular fluid. As shown in
Typically in nerve cells, the resting membrane potential (RMP) is slightly less than 90 mV, with the outside being positive with respect to inside. To stimulate an excitable cell, it is only necessary to reduce the transmembrane potential by a critical amount. When the membrane potential is reduced by an amount ΔV, reaching the critical or threshold potential (TP); Which is shown in
For a stimulus to be effective in producing an excitation, it must have an abrupt onset, be intense enough, and last long enough. These facts can be drawn together by considering the delivery of a suddenly rising cathodal constant-current stimulus of duration d to the cell membrane as shown in
Cell membranes can be reasonably well represented by a capacitance C, shunted by a resistance R as shown by a simplified electrical model in diagram 5C, and shown in a more realistic electrical model in
When the stimulation pulse is strong enough, an action potential will be generated and propagated. As shown in
A single electrical impulse passing down an axon is shown schematically in
The information in the nervous system is coded by frequency of firing rather than the size of the action potential. This is shown schematically in
In terms of electrical conduction, myelinated fibers conduct faster, are typically larger, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation, compared to unmyelinated fibers. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (μs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 μs) and a higher amplitude for activation. Because of their very slow conduction, C fibers would not be highly responsive to rapid stimulation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.
As shown in
TABLE 1 Conduction Fiber Fiber Velocity Diameter Type (m/sec) (μm) Myelination A Fibers Alpha 70-120 12-20 Yes Beta 40-70 5-12 Yes Gamma 10-50 3-6 Yes Delta 6-30 2-5 Yes B Fibers 5-15 <3 Yes C Fibers 0.5-2.0 0.4-1.2 No
The modulation of nerve in the periphery, as done by the body, in response to different types of pain is illustrated schematically in
Vagus nerve stimulation, as performed by the system and method of the current patent application, is a means of directly affecting central function.
The vagus nerve is composed of somatic and visceral afferents and efferents. Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagus nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull.
In considering the anatomy, the vagus nerve spans from the brain stem all the way to the splenic flexure of the colon. Not only is the vagus the parasympathetic nerve to the thoracic and abdominal viscera, it also the largest visceral sensory (afferent) nerve. Sensory fibers outnumber parasympathetic fibers four to one. In the medulla, the vagal fibers are connected to the nucleus of the tractus solitarius (viceral sensory), and three other nuclei. The central projections terminate largely in the nucleus of the solitary tract, which sends fibers to various regions of the brain (e.g., the thalamus, hypothalamus and amygdala).
As shown in
In the neck, the vagus lies in a groove between the internal jugular vein and the internal carotid artery. It descends vertically within the carotid sheath, giving off branches to the pharynx, larynx, and constrictor muscles. From the root of the neck downward, the vagus nerve takes a different path on each side of the body to reach the cardiac, pulmonary, and esophageal plexus (consisting of both sympathetic and parasympathetic axons). From the esophageal plexus, right and left gastric nerves arise to supply the abdominal viscera as far caudal as the splenic flexure.
In the body, the vagus nerve regulates viscera, swallowing, speech, and taste. It has sensory, motor, and parasympathetic components. Table two below outlines the innervation and function of these components.
TABLE 2 Vagus Nerve Components Component fibers Structures innervated Functions SENSORY Pharynx. larynx, General sensation esophagus, external ear Aortic bodies, aortic arch Chemo- and baroreception Thoracic and abdominal viscera MOTOR Soft palate, pharynx, Speech, swallowing larynx, upper esophagus PARA- Thoracic and abdominal Control of cardiovascular SYMPATHETIC viscera system, respiratory and gastrointestinal tracts
On the Afferent side, visceral sensation is carried in the visceral sensory component of the vagus nerve. As shown in
The afferent fibers project primarily to the nucleus of the solitary tract (shown schematically in
U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like. Applicant's method of neuromodulation is significantly different than that disclosed in Zabara '254, '164' and '807 patents.
U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy needs to be continuously sustained over a prolonged period of time. The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application.
U.S. Pat. No. 5,299,569 (Wernicke et al.) is directed to the use of implantable pulse generator technology for treating and controlling neuropsychiatric disorders including schizophrenia, depression, and borderline personality disorder.
U.S. Pat. No. 6,205,359 B1 (Boveja) and U.S. Pat. No. 6,356,788 B2 (Boveja) are directed to adjunct therapy for neurological and neuropsychiatric disorders using an implanted lead-receiver and an external stimulator.
U.S. Pat. No. 5,807,397 (Barreras) is directed to an implantable stimulator with replenishable, high value capacitive power source.
U.S. Pat. No. 5,193,539 (Schulman, et al) is generally directed to an addressable, implantable microstimulator that is of size and shape which is capable of being implanted by expulsion through a hypodermic needle. In the Schulman patent, up to 256 microstimulators may be implanted within a muscle and they can be used to stimulate in any order as each one is addressable, thereby providing therapy for muscle paralysis.
U.S. Pat. No. 5,405,367 (Schulman, et al) is generally directed to the structure and method of manufacture of an implantable microstimulator.
U.S. Pat. No. 6,622,041 B2 (Terry, Jr. et al.) is directed to treatment of congestive heart failure and autonomic cardiovascular drive disorders using implantable neurostimulator.
The method and system of the current invention provides afferent neuromodulation therapy using pulsed electrical stimulation to a cranial nerve such as a vagus nerve(s). The selective stimulation is to provide therapy for at least one of epilepsy, depression, anxiety disorders, neurogenic pain, compulsive eating disorders, obesity, dementia including Alzheimer's disease, and migraines. The method and system comprises both implantable and external components. The power source may also be external or implanted in the body. The system to provide selective stimulation may be selected from a group consisting of:
In one aspect of the invention, the selective stimulation to a vagus nerve(s) may be anywhere along the length of the nerve, such as at the cervical level or at a level near the diaphram.
In another aspect of the invention, the stimulation may be unilateral or bilateral.
In another aspect of the invention, the external components such as the external stimulator or programmer comprise telemetry means adapted to be networked, for remote interrogation or remote programming of the device.
In another aspect of the invention, the pulse generator may be implanted in the body.
In another aspect of the invention, the implanted pulse generator is adapted to be re-chargable via an external power source.
In another aspect of the invention, the implanted lead body may be made of a material selected from the group consisting of polyurethane, silicone, and silicone with polytetrafluoroethylene.
In another aspect of the invention, the implanted lead comprises at least one electrode selected from the group consisting of platinum, platinum/iridium alloy, platinum/iridium alloy coated with titanium nitride, and carbon.
In yet another aspect of the invention, the implanted lead comprises at least one electrode selected from the group consisting of spiral electrodes, cuff electrodes, steroid eluting electrodes, wrap-around electrodes, and hydrogel electrodes.
Various other features, objects and advantages of the invention will be made apparent from the following description taken together with the drawings.
For the purpose of illustrating the invention, there are shown in accompanying drawing forms which are presently preferred, it being understood that the invention is not intended to be limited to the precise arrangement and instrumentalities shown.
Co-pending patent application Ser. No. 10/195,961 and Ser. No. 10/142,298 are directed to method and system for modulating a vagus nerve (10th Cranial Nerve in the body) using modulated electrical pulses with an inductively coupled stimulation system. In the disclosure of this patent application, the electrical stimulation system comprises both implanted and external components.
In the method and system of this Application, selective pulsed electrical stimulation is applied to a vagus nerve(s) for afferent neuromodulation. An implantalbe lead is surgically implanted in the patient. The vagus nerve(s) is/are surgically exposed and isolated. The electrodes on the distal end of the lead are wrapped around the vagus nerve(s), and the lead is tunneled subcutaneously. A pulse generator means is connected to the proximal end of the lead. The power source may be external, implantable, or a combination device.
Also, in the method of this invention, a cheaper and simpler pulse generator may be used to test a patient's response to neuromodulation therapy. As one example only, an implanted stimulus-receiver in conjunction with an external stimulator may be used initially to test patient's response. At a later time, the pulse generator may be exchanged for a more elaborate implanted pulse generator (IPG) model, keeping the same lead. Some examples of stimulation and power sources that may be used for the practice of this invention, and disclosed in this Application, include:
For an external power source, a passive implanted stimulus-receiver may be used. Such a system is disclosed in the parent application Ser. No. 10/142,298 and mentioned here for convenience.
The selective stimulation of various nerve fibers of a cranial nerve such as the vagus nerve (or neuromodulation of the vagus nerve), as performed by one embodiment of the method and system of this invention is shown schematically in
The carrier frequency is optimized. One preferred embodiment utilizes electrical signals of around 1 Mega-Hertz, even though other frequencies can be used. Low frequencies are generally not suitable because of energy requirements for longer wavelengths, whereas higher frequencies are absorbed by the tissues and are converted to heat, which again results in power losses.
Shown in conjunction with
Shown in conjunction with
The circuitry contained in the proximal end of the implantable stimulus-receiver 34 is shown schematically in
The circuitry shown in
For therapy to commence, the primary (external) coil 46 is placed on the skin 60 on top of the surgically implanted (secondary) coil 48. An adhesive tape is then placed on the skin 60 and external coil 46 such that the external coil 46, is taped to the skin 60. For efficient energy transfer to occur, it is important that the primary (external) and secondary (internal) coils 46,48 be positioned along the same axis and be optimally positioned relative to each other. In this embodiment, the external coil 46 may be connected to proximity sensing circuitry 50. The correct positioning of the external coil 46 with respect to the internal coil 48 is indicated by turning "on" of a light emitting diode (LED) on the external stimulator 42.
Optimal placement of the external (primary) coil 46 is done with the aid of proximity sensing circuitry incorporated in the system, in this embodiment. Proximity sensing occurs utilizing a combination of external and implantable components. The implanted components contains a relatively small magnet composed of materials that exhibit Giant Magneto-Resistor (GMR) characteristics such as Samarium-cobalt, a coil, and passive circuitry. Shown in conjunction with
The proximity sensors (external) contained in the proximity sensor circuit 50 detect the presence of a GMR magnet 53, composed of Samarium Cobalt, that is rigidly attached to the implanted secondary coil 48. The proximity sensors, are mounted externally as a rigid assembly and sense the actual separation between the coils, also known as the proximity distance. In the event that the distance exceeds the system limit, the signal drops off and an alarm sounds to indicate failure of the production of adequate signal in the secondary implanted circuit 167, as applied in this embodiment of the device. This signal is provided to the location indicator LED 280.
The Siemens GMR B6 (Siemens Corp., Special Components Inc., New Jersey) is used for this function in one embodiment. The maximum value of the peak-to-peak signal is observed as the external magnetic field becomes strong enough, at which point the resistance increases, resulting in the increase of the field-angle between the soft magnetic and hard magnetic material. The bridge voltage also increases. In this application, the two sensors 648, 652 are oriented orthogonal to each other.
The distance between the magnet 53 and sensor 50 is not relevant as long as the magnetic field is between 5 and 15 KA/m, and provides a range of distances between the sensors 648, 652 and the magnetic material 53. The GMR sensor registers the direction of the external magnetic field. A typical magnet to induce permanent magnetic field is approximately 15 by 8 by 5 mm3, for this application and these components. The sensors 648, 652 are sensitive to temperature, such that the corresponding resistance drops as temperature increases. This effect is quite minimal until about 100� C. A full bridge circuit is used for temperature compensation, as shown in temperature compensation circuit 50 of
The signal from either proximity sensor 648, 652 is rectangular if the surface of the magnetic material is normal to the sensor and is radial to the axis of a circular GMR device. This indicates a shearing motion between the sensor and the magnetic device. When the sensor is parallel to the vertical axis of this device, there is a fall off of the relatively constant signal at about 25 mm. separation. The GMR sensor combination varies its resistance according to the direction of the external magnetic field, thereby providing an absolute angle sensor. The position of the GMR magnet can be registered at any angle from 0 to 360 degrees.
In the external stimulator 42 shown in
Also shown in
This method enables any portable computer with a serial interface to communicate and program the parameters for storing the various programs. The serial communication interface receives the serial data, buffers this data and converts it to a 16 bit parallel data. The programmable array logic 264 component of programmable array unit receives the parallel data bus and stores or modifies the data into a random access matrix. This array of data also contains special logic and instructions along with the actual data. These special instructions also provide an algorithm for storing, updating and retrieving the parameters from long-term memory. The programmable logic array unit 264, interfaces with long term memory to store the predetermined programs. All the previously modified programs can be stored here for access at any time, as well as, additional programs can be locked out for the patient. The programs consist of specific parameters and each unique program will be stored sequentially in long-term memory. A battery unit is present to provide power to all the components. The logic for the storage and decoding is stored in a random addressable storage matrix (RASM).
Conventional microprocessor and integrated circuits are used for the logic, control and timing circuits. Conventional bipolar transistors are used in radio-frequency oscillator, pulse amplitude ramp control and power amplifier. A standard voltage regulator is used in low-voltage detector. The hardware and software to deliver the pre-determined programs is well known to those skilled in the art.
The pulses delivered to the nerve tissue for stimulation therapy are shown graphically in
The selective stimulation to the vagus nerve can be performed in one of two ways. One method is to activate one of several "pre-determined" programs. A second method is to "custom" program the electrical parameters which can be selectively programmed, for specific therapy to the individual patient. The electrical parameters which can be individually programmed, include variables such as pulse amplitude, pulse width, frequency of stimulation, stimulation on-time, and stimulation off-time. Table two below defines the approximate range of parameters,
TABLE 2 Electrical parameter range delivered to the nerve PARAMER RANGE Pulse Amplitude 0.1 Volt-10 Volts Pulse width 20 μS-5 mSec. Frequency 5 Hz-200 Hz On-time 10 Secs-24 hours Off-time 10 Secs-24 hours
The parameters in Table 2 are the electrical signals delivered to the nerve via the two electrodes 61,62 (distal and proximal) around the nerve, as shown in
Referring now to
TABLE 3 Lead design variables Proximal Distal End End Conductor (connecting Lead body- proximal Lead Insulation and distal Electrode - Electrode - Terminal Materials Lead-Coating ends) Material Type Linear Polyurethane Antimicrobial Alloy of Pure Spiral bipolar coating Nickel- Platinum electrode Cobalt Bifurcated Silicone Anti- Platinum- Wrap-around Inflammatory Iridium electrode coating (Pt/Ir) Alloy Silicone with Lubricious Pt/Ir coated Steroid Polytetrafluoro- coating with Titanium eluting ethylene Nitride (PTFE) Carbon Hydrogel electrodes Cuff electrodes
Once the lead is fabricated, coating such as anti-microbial, anti-inflammatory, or lubricious coating may be applied to the body of the lead.
In one embodiment, the implanted stimulus-receiver may be a system which is RF coupled combined with a power source. In this embodiment, the implanted stimulus-receiver contains high value, small sized capacitor(s) for storing charge and delivering electric stimulation pulses for up to several hours by itself, once the capacitors are charged. The packaging is shown in
As shown in conjunction with
The refresh-recharge transmitter unit 460 includes a primary battery 426, an ON/Off switch 427, a transmitter electronic module 442, an RF inductor power coil 46A, a modulator/demodulator 420 and an antenna 422.
When the ON/OFF switch is on, the primary coil 46A is placed in close proximity to skin 60 and secondary coil 48A of the implanted stimulator 490. The inductor coil 46A emits RF waves establishing EMF wave fronts which are received by secondary inductor 48A. Further, transmitter electronic module 442 sends out command signals which are converted by modulator/demodulator decoder 420 and sent via antenna 422 to antenna 418 in the implanted stimulator 490. These received command signals are demodulated by decoder 416 and replied and responded to, based on a program in memory 414 (matched against a "command table" in the memory). Memory 414 then activates the proper controls and the inductor receiver coil 48A accepts the RF coupled power from inductor 46A.
The RF coupled power, which is alternating or AC in nature, is converted by the rectifier 408 into a high DC voltage. Small value capacitor 406 operates to filter and level this high DC voltage at a certain level. Voltage regulator 402 converts the high DC voltage to a lower precise DC voltage while capacitive power source 400 refreshes and replenishes.
When the voltage in capacative source 400 reaches a predetermined level (that is VDD reaches a certain predetermined high level), the high threshold comparator 430 fires and stimulating electronic module 412 sends an appropriate command signal to modulator/decoder 416. Modulator/decoder 416 then sends an appropriate "fully charged" signal indicating that capacitive power source 400 is fully charged, is received by antenna 422 in the refresh-recharge transmitter unit 460.
In one mode of operation, the patient may start or stop stimulation by waving the magnet 442 once near the implant. The magnet emits a magnetic force Lm which pulls reed switch 410 closed. Upon closure of reed switch 410, stimulating electronic module 412 in conjunction with memory 414 begins the delivery (or cessation as the case may be) of controlled electronic stimulation pulses to the vagus nerve 54 via electrodes 61, 62. In another mode (AUTO), the stimulation is automatically delivered to the implanted lead based upon programmed ON/OFF times.
The programmer unit 450 includes keyboard 432, programming circuit 438, rechargeable battery 436, and display 434. The physician or medical technician programs programming unit 450 via keyboard 432. This program regarding the frequency, pulse width, modulation program, ON time etc. is stored in programming circuit 438. The programming unit 450 must be placed relatively close to the implanted stimulator 490 in order to transfer the commands and programming information from antenna 440 to antenna 418. Upon receipt of this programming data, modulator/demodulator and decoder 416 decodes and conditions these signals, and the digital programming information is captured by memory 414. This digital programming information is further processed by stimulating electronic module 412. In the DEMAND operating mode, after programming the implanted stimulator, the patient turns ON and OFF the implanted stimulator via hand held magnet 442 and the reed switch 410. In the automatic mode (AUTO), the implanted stimulator turns ON and OFF automatically according to the programmed values for the ON and OFF times.
Other simplified versions of such a system may also be used. For example, a system such as this, where a separate programmer is eliminated, and simplified programming is performed with a magnet and reed switch, can also be used.
In one embodiment, a programmer-less implantable pulse generator (IPG) may be used. In this embodiment, shown in conjunction with
In one embodiment, shown in conjunction with
Once the prepackaged/predetermined logic state is activated by the logic and control circuit 102, as shown in
In one embodiment, there are four stimulation states. A larger (or lower) number of states can be achieved using the same methodology, and such is considered within the scope of the invention. These four states are, LOW stimulation state, LOW-MED stimulation state, MED stimulation state, and HIGH stimulation state. Examples of stimulation parameters (delivered to the vagus nerve) for each state are as follows,
LOW stimulation state example is,
Current output: 0.75 milliAmps. Pulse width: 0.20 msec. Pulse frequency: 20 Hz Cycles: 20 sec. on-time and 2.0 min. off-time in repeating cycles.
LOW-MED stimulation state example is,
Current output: 1.5 milliAmps, Pulse width: 0.30 msec. Pulse frequency: 25 Hz Cycles: 1.5 min. on-time and 20.0 min. off-time in repeating cycles.
MED stimulation state example is,
Current output: 2.0 milliAmps. Pulse width: 0.30 msec. Pulse frequency: 30 Hz Cycles: 1.5 min. on-time and 20.0 min. off-time in repeating cycles.
HIGH stimulation state example is,
Current output: 3.0 milliAmps, Pulse width: 0.40 msec. Pulse frequency: 30 Hz Cycles: 2.0 min. on-time and 20.0 min. off-time in repeating cycles.
These prepackaged/predetermined programs are mearly examples, and the actual stimulation parameters will deviate from these depending on the treatment application.
It will be readily apparent to one skilled in the art, that other schemes can be used for the same purpose. For example, instead of placing the magnet 90 on the pulse generator 171 for a prolonged period of time, different stimulation states can be encoded by the sequence of magnet applications. Accordingly, in an alternative embodiment there can be three logic states, OFF, LOW stimulation (LS) state, and HIGH stimulation (HS) state. Each logic state again corresponds to a prepackaged/predetermined program such as presented above. In such an embodiment, the system could be configured such that one application of the magnet triggers the generator into LS State. If the generator is already in the LS state then one application triggers the device into OFF State. Two successive magnet applications triggers the generator into MED stimulation state, and three successive magnet applications triggers the pulse generator in the HIGH Stimulation State. Subsequently, one application of the magnet while the device is in any stimulation state, triggers the device OFF.
The advantage of this embodiment is that it is cheaper to manufacture than a fully programmable implantable pulse generator (IPG).
In one embodiment, a fully programmable implantable pulse generator (IPG) may be used. Shown in conjunction with
This embodiment may also comprise fixed pre-determined/pre-packaged programs. Examples of LOW, LOW-MED, MED, and HIGH stimulation states were given in the previous section, under "Programmer-less Implantable Pulse Generator (IPG)". These pre-packaged/pre-determined programs comprise unique combinations of pulse amplitude, pulse width, pulse frequency, ON-time and OFF-time.
In addition, each parameter may be individually programmed and stored in memory. The range of programmable electrical stimulation parameters are shown in table 4 below.
TABLE 4 Programmable electrical parameter range PARAMER RANGE Pulse Amplitude 0.1 Volt-10 Volts Pulse width 20 μS-5 mSec. Frequency 3 Hz-300 Hz On-time 5 Secs-24 hours Off-time 5 Secs-24 hours Ramp ON/OFF
Shown in conjunction with
Most of the digital functional circuitry 350 is on a single chip (IC). This monolithic chip along with other IC's and components such as capacitors and the input protection diodes are assembled together on a hybrid circuit. As well known in the art, hybrid technology is used to establish the connections between the circuit and the other passive components. The integrated circuit is hermetically encapsulated in a chip carrier. A coil 399 situated under the hybrid substrate is used for bidirectional telemetry. The hybrid and battery 397 are encased in a titanium can 65. This housing is a two-part titanium capsule that is hermetically sealed by laser welding. Alternatively, electron-beam welding can also be used. The header 79 is a cast epoxy-resin with hermetically sealed feed-through, and form the lead 40 connection block.
For further details,
The size of ROM 337 and RAM 339 units are selected based on the requirements of the algorithms and the parameters to be stored. The number of registers in the register file 321 are decided based upon the complexity of computation and the required number of intermediate values. Timers 340 of different precision are used to measure the elapsed intervals. Even though this embodiment does not have external sensors to control timing, future embodiments may have sensors 322 to effect the timing as shown in conjunction with
In this embodiment, the two main components of microprocessor are the datapath and control. The datapath performs the arithmetic operation and the control directs the datapath, memory, and I/O devices to execute the instruction of the program. The hardware components of the microprocessor are designed to execute a set of simple instructions. In general the complexity of the instruction set determines the complexity of datapth elements and controls of the microprocessor.
In this embodiment, the microprocessor is provided with a fixed operating routine. Future embodiments may be provided with the capability of actually introducing program changes in the implanted pulse generator. The instruction set of the microprocessor, the size of the register files, RAM and ROM are selected based on the performance needed and the type of the algorithms used. In this application of pulse generator, in which several algorithms can be loaded and modified, Reduced Instruction Set Computer (RISC) architecture is useful. RISC architecture offers advantages because it can be optimized to reduce the instruction cycle which in turn reduces the run time of the program and hence the current drain. The simple instruction set architecture of RISC and its simple hardware can be used to implement any algorithm without much difficulty. Since size is also a major consideration, an 8-bit microprocessor is used for the purpose. As most of the arithmetic calculation are based on a few parameters and are rather simple, an accumulator architecture is used to save bits from specifying registers. Each instruction is executed in multiple clock cycles, and the clock cycles are broadly classified into five stages: an instruction fetch, instruction decode, execution, memory reference, and write back stages. Depending on the type of the instruction, all or some of these stages are executed for proper completion.
Initially, an optimal instruction set architecture is selected based on the algorithm to be implemented and also taking into consideration the special needs of a microprocessor based implanted pulse generator (IPG). The instructions are broadly classified into Load/store instructions, Arithmetic and logic instructions (ALU), control instructions and special purpose instructions.
The instruction format is decided based upon the total number of instructions in the instruction set. The instructions fetched from memory are 8 bits long in this example. Each instruction has an opcode field (2 bits), a register specifier field (3-bits), and a 3-bit immediate field. The opcode field indicates the type of the instruction that was fetched. The register specifier indicates the address of the register in the register file on which the operations are performed. The immediate field is shifted and sign extended to obtain the address of the memory location in load/store instruction. Similarly, in branch and jump instruction, the offset field is used to calculate the address of the memory location the control needs to be transferred to.
Shown in conjunction with
Generally, two or more timers are required to implement the algorithm for the IPG. The timers are read and written into just as any other memory location. The timers are provided with read and write enable controls.
The arithmetic logic unit is an important component of the microprocessor. It performs the arithmetic operation such as addition, subtraction and logical operations such as AND and OR. The instruction format of ALU instructions consists of an opcode field (2 bits), a function field (2 bits) to indicate the function that needs to be performed, and a register specifier (3 bits) or an immediate field (4 bits) to provide an operand.
The hardware components discussed above constitute the important components of a datapath. Shown in conjunction with
In a multicycle implementation, each stage of instruction execution takes one clock cycle. Since the datapath takes multiple clock cycles per instruction, the control must specify the signals to be asserted in each stage and also the next step in the sequence. This can be easily implemented as a finite state machine.
A finite state machine consists of a set of states and directions on how to change states. The directions are defined by a next-state function, which maps the current state and the inputs to a new state. Each stage also indicates the control signals that need to be asserted. Every state in the finite state machine takes one clock cycle. Since the instruction fetch and decode stages are common to all the instruction, the initial two states are common to all the instruction. After the execution of the last step, the finite state machine returns to the fetch state.
A finite state machine can be implemented with a register that holds the current stage and a block of combinational logic such as a PLA. It determines the datapath signals that need to be asserted as well as the next state. A PLA is described as an array of AND gates followed by an array of OR gates. Since any function can be computed in two levels of logic, the two-level logic of PLA is used for generating control signals.
The occurrence of a wakeup event initiates a stored operating routine corresponding to the event. In the time interval between a completed operating routine and a next wake up event, the internal logic components of the processor are deactivated and no energy is being expended in performing an operating routine.
A further reduction in the average operating current is obtained by providing a plurality of counting rates to minimize the number of state changes during counting cycles. Thus intervals which do not require great precision, may be timed using relatively low counting rates, and intervals requiring relatively high precision, such as stimulating pulse width, may be timed using relatively high counting rates.
The logic and control unit 398 of the IPG controls the output amplifiers. The pulses have predetermined energy (pulse amplitude and pulse width) and are delivered at a time determined by the therapy stimulus controller. The circuitry in the output amplifier, shown in conjunction with (
The constant-voltage output amplifier applies a voltage pulse to the distal electrode (cathode) 61 of the lead 40. A typical circuit diagram of a voltage output circuit is shown in
To re-establish equilibrium, the recharge switch 222 is closed, and a rapid recharge pulse is delivered. This is intended to remove any residual charge remaining on the coupling capacitor Cb 229, and the stimulus electrodes on the lead (polarization). Thus, the stimulus is delivered as the result of closing and opening of the stimulus delivery 220 switch and the closing and opening of the RCHG switch 222. At this point, the charge on the holding Ch 225 must be replenished by the stimulus amplitude generator 206 before another stimulus pulse can be delivered.
The pulse generating unit charges up a capacitor and the capacitor is discharged when the control (timing) circuitry requires the delivery of a pulse. This embodiment utilizes a constant voltage pulse generator, even though a constant current pulse generator can also be utilized. Pump-up capacitors are used to deliver pulses of larger magnitude than the potential of the batteries. The pump up capacitors are charged in parallel and discharged into the output capacitor in series. Shown in conjunction with
Since a key concept of this invention is to deliver afferent stimulation, in one aspect efferent stimulation of selected types of fibers may be substantially blocked, utilizing the "greenwave" effect. In such a case, as shown in conjunction with
In one aspect of the invention, the pulsed electrical stimulation to the vagus nerve(s) may be provided anywhere along the length of the vagus nerve(s). As was shown earlier in conjunction with
The programming of the implanted pulse generator (IPG) 391 is shown in conjunction with
The transmission of programming information involves manipulation of the carrier signal in a manner that is recognizable by the pulse generator 391 as a valid set of instructions. The process of modulation serves as a means of encoding the programming instruction in a language that is interpretable by the implanted pulse generator 391. Modulation of signal amplitude, pulse width, and time between pulses are all used in the programming system, as will be appreciated by those skilled in the art.
The reed switch 389 is a magnetically-sensitive mechanical switch, which consists of two thin strips of metal (the "reed") which are ferromagnetic. The reeds normally spring apart when no magnetic field is present. When a field is applied, the reeds come together to form a closed circuit because doing so creates a path of least reluctance. The programming head of the programmer contains a high-field-strength ceramic magnet.
When the switch closes, it activates the programming hardware, and initiates an interrupt of the IPG central processor. Closing the reed switch 389 also presents the logic used to encode and decode programming and telemetry signals. A nonmaskable interrupt (NMI) is sent to the IPG processor, which then executes special programming software. Since the NMI is an edge-triggered signal and the reed switch is vulnerable to mechanical bounce, a debouncing circuit is used to avoid multiple interrupts. The overall current consumption of the IPG increases during programming because of the debouncing circuit and other communication circuits.
A coil 399 is used as an antenna for both reception and transmission. Another set of coils 383 is placed in the programming head, a relatively small sized unit connected to the programmer 85. All coils are tuned to the same resonant frequency. The interface is half-duplex with one unit transmitting at a time.
Since the relative positions of the programming head 87 and IPG 391 determine the coupling of the coils, this embodiment utilizes a special circuit which has been devised to aid the positioning of the programming head, and is shown in
Actual programming is shown in conjunction with
A programming message is comprised of five parts
All of the bits are then encoded as a sequence of pulses of 0.35-ms duration
The serial pulse sequence is then amplitude modulated for transmission
Telemetry data may be either analog or digital. Digital signals are first converted into a serial bit stream using an encoding such as shown in
An advantage of this and other encodings is that they provide multiple forms of error detection. The coils and receiver circuitry are tuned to the modulation frequency, eliminating noise at other frequencies. Pulse-position coding can detect errors by accepting pulses only within narrowly-intervals. The access code acts as a security key to prevent programming by spurious noise or other equipment. Finally, the parity field and other checksums provides a final verification that the message is valid. At any time, if an error is detected, the entire message is discarded.
Another more sophisticated type of pulse position modulation may be used to increase the bit transmission rate. In this, the position of a pulse within a frame is encoded into one of a finite number of values, e.g. 16. A special synchronizing bit is transmitted to signal the start of the frame. Typically, the frame contains a code which specifies the type or data contained in the remainder of the frame.
This embodiment also comprises an optional battery status test circuit. Shown in conjunction with
In one embodiment, the implantable device may comprise both a stimulus-receiver and a programmable implantable pulse generator (IPG).
With reference to
Again with reference to
As shown in conjunction with
In one embodiment, the external stimulator 42 is networked using the internet, giving the attending physician full control for activating and de-activating selected programs. Using "trial and error" various programs for electrical pulse therapy can be custom adjusted for the physiology of the individual patent. Also, by using the external stimulator 42, the battery 188 of the implanted stimulator unit 75 can be greatly extended. Further, even after the battery 188 is depleted, the system can still be used for neuromodulation using the stimulus-receiver module 120, and the external stimulator 42.
In one embodiment, an implantable pulse generator with rechargeable power source can be used. In such an embodiment (shown in conjunction with
In summary, the method of the current invention for neuromodulation of cranial nerve such as the vagus nerve(s), to provide therapy for neurological and neuropsychiatric disorders, can be practiced with any of the several power sources disclosed including,
Neuromodulation of vagus nerve(s) with any of these systems is considered within the scope of this invention.
In one embodiment, the external stimulator and/or the programmer has a telecommunications module, as described in a co-pending application, and summarized here for reader convenience. The telecommunications module has two-way communications capabilities.
In one aspect of the invention, the telecommunications component can use Wireless Application Protocol (WAP). The Wireless Application Protocol (WAP), which is a set of communication protocols standardizing Internet access for wireless devices. While previously, manufacturers used different technologies to get Internet on hand-held devices, with WAP devices and services interoperate. WAP also promotes convergence of wireless data and the Internet. The WAP programming model is heavily based on the existing Internet programming model, and is shown schematically in
The key components of the WAP technology, as shown in
In this embodiment, two modes of communication are possible. In the first, the server initiates an upload of the actual parameters being applied to the patient, receives these from the stimulator, and stores these in its memory, accessible to the authorized user as a dedicated content driven web page. The physician or authorized user can make alterations to the actual parameters, as available on the server, and then initiate a communication session with the stimulator device to download these parameters.
Shown in conjunction with
The standard components of interface unit shown in block 292 are processor 305, storage 310, memory 308, transmitter/receiver 306, and a communication device such as network interface card or modem 312. In the preferred embodiment these components are embedded in the external stimulator 42 and can also be embedded in the programmer 85. These can be connected to the network 290 through appropriate security measures (Firewall) 293.
Another type of remote unit that may be accessed via central collaborative network 290 is remote computer 294. This remote computer 294 may be used by an appropriate attending physician to instruct or interact with interface unit 292, for example, instructing interface unit 292 to send instruction downloaded from central computer 286 to remote implanted unit.
Shown in conjunction with
The telemetry module 362 comprises an RF telemetry antenna 142 coupled to a telemetry transceiver and antenna driver circuit board which includes a telemetry transmitter and telemetry receiver. The telemetry transmitter and receiver are coupled to control circuitry and registers, operated under the control of microprocessor 364. Similarly, within stimulator a telemetry antenna 142 is coupled to a telemetry transceiver comprising RF telemetry transmitter and receiver circuit. This circuit is coupled to control circuitry and registers operated under the control of microcomputer circuit.
With reference to the telecommunications aspects of the invention, the communication and data exchange between Modified PDA/Phone 502 and external stimulator 42 operates on commercially available frequency bands. The 2.4-to-2.4853 GHz bands or 5.15 and 5.825 GHz, are the two unlicensed areas of the spectrum, and set aside for industrial, scientific, and medical (ISM) uses. Most of the technology today including this invention, use either the 2.4 or 5 GHz radio bands and spread-spectrum technology.
The telecommunications technology, especially the wireless internet technology, which this invention utilizes in one embodiment, is constantly improving and evolving at a rapid pace, due to advances in RF and chip technology as well as software development. Therefore, one of the intents of this invention is to utilize "state of the art" technology available for data communication between Modified PDA/Phone 502 and external stimulator 42. The intent of this invention is to use 3 G technology for wireless communication and data exchange, even though in some cases 2.5 G is being used currently.
For the system of the current invention, the use of any of the "3 G" technologies for communication for the Modified PDA/Phone 502, is considered within the scope of the invention. Further, it will be evident to one of ordinary skill in the art that as future 4G systems, which will include new technologies such as improved modulation and smart antennas, can be easily incorporated into the system and method of current invention, and are also considered within the scope of the invention.
|Cited Patent
|Filing date
|Publication date
|7 Jul 1971
|12 Mar 1974
|Hagfors N
|Apparatus for delivering electrical stimulation energy to body-implanted apparatus with signal-receiving means
|30 Dec 1985
|27 Oct 1987
|Jacob Zabara
|Neurocybernetic prosthesis
|26 Oct 1987
|19 Sep 1989
|Jacob Zabara
|Neurocybernetic prosthesis
|25 Jan 1989
|25 Jun 1991
|Jacob Zabara
|Neurocybernetic prosthesis
|18 Dec 1991
|16 Mar 1993
|Alfred E. Mann Foundation For Scientific Research
|Implantable microstimulator
|3 May 1991
|5 Apr 1994
|Cyberonics, Inc.
|Treatment of neuropsychiatric disorders by nerve stimulation
|18 Nov 1991
|19 Apr 1994
|Cyberonics, Inc.
|Activation techniques for implantable medical device
|3 Mar 1993
|11 Apr 1995
|Alfred E. Mann Foundation For Scientific Research
|Structure and method of manufacture of an implantable microstimulator
|7 Nov 1996
|12 May 1998
|Sulzer Intermedics Inc.
|Transcutaneous energy coupling using piezoelectric device
|1 Aug 1996
|15 Sep 1998
|Plexus, Inc.
|Implantable stimulator with replenishable, high value capacitive power source and method therefor
|2 May 1998
|27 Jul 1999
|Cyberonics, Inc.
|Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity
|26 Oct 1998
|20 Mar 2001
|Birinder Bob Boveja
|Apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator
|30 Nov 2000
|12 Mar 2002
|Birinder Bob Boveja
|Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator
|24 Sep 2001
|12 Nov 2002
|Neuropace, Inc.
|System and method for adaptive brain stimulation
|21 Aug 2001
|16 Sep 2003
|Cyberonics, Inc.
|Treatment of congestive heart failure and autonomic cardiovascular drive disorders
|19 Apr 2001
|9 Dec 2003
|Nac Technologies Inc.
|Method and system for neuromodulation therapy using external stimulator with wireless communication capabilites
|31 Aug 2001
|27 Jan 2004
|Biocontrol Medical, Ltd.
|Treatment of disorders by unidirectional nerve stimulation
|29 Aug 2001
|6 Jul 2004
|Birinder R. Boveja
|Apparatus and method for treatment of neurological and neuropsychiatric disorders using programmerless implantable pulse generator system
|Citing Patent
|Filing date
|Publication date
|29 Jul 2005
|3 Mar 2009
|Cyberonics, Inc.
|Selective nerve stimulation for the treatment of eating disorders
|29 Jul 2005
|12 May 2009
|Cyberonics, Inc.
|Selective neurostimulation for treating mood disorders
|28 Oct 2005
|30 Jun 2009
|Cyberonics, Inc.
|Selective neurostimulation for treating epilepsy
|26 Jan 2006
|2 Feb 2010
|Cyberonics, Inc.
|Treatment of reproductive endocrine disorders by vagus nerve stimulation
|9 Mar 2010
|Neurovista Corporation
|Minimally invasive system for selecting patient-specific therapy parameters
|12 Feb 2004
|27 Apr 2010
|Albert Einstein College Of Medicine Of Yeshiva University
|Regulation of food intake by modulation of long-chain fatty acyl-CoA levels in the hypothalamus
|28 Sep 2005
|29 Jun 2010
|Neurovista Corporation
|Systems and methods for monitoring a patient's neurological disease state
|28 Jul 2004
|6 Jul 2010
|Cyberonics, Inc.
|Power supply monitoring for an implantable device
|27 Jan 2006
|21 Sep 2010
|Cyberonics, Inc.
|Controlling neuromodulation using stimulus modalities
|29 Dec 2006
|14 Dec 2010
|Neurovista Corporation
|Monitoring efficacy of neural modulation therapy
|28 Jul 2005
|21 Dec 2010
|Cyberonics, Inc.
|Autonomic nerve stimulation to treat a gastrointestinal disorder
|27 Oct 2006
|11 Jan 2011
|Cyberonics, Inc.
|Implantable neurostimulator with refractory stimulation
|26 Apr 2007
|11 Jan 2011
|Cyberonics, Inc.
|Non-surgical device and methods for trans-esophageal vagus nerve stimulation
|28 Apr 2006
|11 Jan 2011
|Cyberonics, Inc
|Threshold optimization for tissue stimulation therapy
|26 Apr 2007
|8 Mar 2011
|Cyberonics, Inc.
|Trans-esophageal vagus nerve stimulation
|2 May 2007
|19 Apr 2011
|Neurovista Corporation
|Providing output indicative of subject's disease state
|27 Jul 2007
|14 Jun 2011
|Cyberonics, Inc.
|Non-surgical device and methods for trans-esophageal vagus nerve stimulation
|26 Jan 2006
|5 Jul 2011
|Cyberonics, Inc.
|Medical imaging feedback for an implantable medical device
|27 Apr 2007
|5 Jul 2011
|Cyberonics, Inc.
|Dosing limitation for an implantable medical device
|21 Mar 2008
|11 Oct 2011
|Neuro Vista Corporation
|Implantable systems and methods for identifying a contra-ictal condition in a subject
|23 Jan 2009
|10 Jan 2012
|Boston Scientific Neuromodulation Corporation
|Stimulation of the stomach in response to sensed parameters to treat obesity
|29 Mar 2007
|3 Apr 2012
|Catholic Healthcare West
|Vagus nerve stimulation method
|25 Apr 2008
|19 Jun 2012
|Cyberonics, Inc.
|Blocking exogenous action potentials by an implantable medical device
|29 Mar 2007
|10 Jul 2012
|Catholic Healthcare West
|Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
|24 Apr 2009
|7 Aug 2012
|Cyberonics, Inc.
|Use of cardiac parameters in methods and systems for treating a chronic medical condition
|10 Mar 2009
|2 Oct 2012
|Catholic Healthcare West
|Vagus nerve stimulation method
|14 Nov 2006
|23 Oct 2012
|Neurovista Corporation
|Systems and methods of reducing artifact in neurological stimulation systems
|23 May 2011
|6 Nov 2012
|Cyberonics, Inc.
|Dosing limitation for an implantable medical device
|1 Oct 2010
|25 Dec 2012
|Flint Hills Scientific, Llc
|Detecting, quantifying, and/or classifying seizures using multimodal data
|29 Apr 2011
|26 Feb 2013
|Flint Hills Scientific, Llc
|Detecting, quantifying, and/or classifying seizures using multimodal data
|24 Oct 2008
|9 Apr 2013
|Cyberonics, Inc.
|Dynamic cranial nerve stimulation based on brain state determination from cardiac data
|27 Oct 2005
|23 Apr 2013
|Cyberonics, Inc.
|Sequenced therapy protocols for an implantable medical device
|20 Sep 2010
|28 May 2013
|Flint Hills Scientific, Llc
|Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
|20 Oct 2008
|4 Jun 2013
|Cyberonics, Inc.
|Neurostimulation with signal duration determined by a cardiac cycle
|2 Sep 2011
|24 Sep 2013
|Cyberonics, Inc.
|Implantable systems and methods for identifying a contra-ictal condition in a subject
|29 Apr 2010
|22 Oct 2013
|Flint Hills Scientific, Llc
|Algorithm for detecting a seizure from cardiac data
|25 Jan 2008
|22 Oct 2013
|Cyberonics, Inc.
|Changeable electrode polarity stimulation by an implantable medical device
|16 Sep 2010
|29 Oct 2013
|Flint Hills Scientific, Llc
|Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
|11 Jan 2010
|19 Nov 2013
|Cyberonics, Inc.
|Medical lead termination sleeve for implantable medical devices
|29 Mar 2007
|24 Dec 2013
|Catholic Healthcare West
|Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
|30 Jul 2010
|4 Feb 2014
|Cyberonics, Inc.
|Seizure detection using coordinate data
|30 Apr 2010
|11 Feb 2014
|Cyberonics, Inc.
|Validity test adaptive constraint modification for cardiac data used for detection of state changes
|10 Mar 2009
|25 Feb 2014
|Catholic Healthcare West
|Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
|15 Jun 2010
|25 Mar 2014
|Flint Hills Scientific, Llc
|Systems approach to comorbidity assessment
|15 May 2012
|1 Apr 2014
|Flint Hills Scientific Llc
|Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
|28 Oct 2005
|8 Apr 2014
|Cyberonics, Inc.
|Variable output ramping for an implantable medical device
|25 Apr 2011
|13 May 2014
|Cyberonics, Inc.
|Identifying seizures using heart rate decrease
|28 Dec 2005
|13 May 2014
|Cyberonics, Inc.
|Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders
|10 Mar 2009
|27 May 2014
|Catholic Healthcare West
|Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
|10 May 2006
|17 Jun 2014
|Covidien Ag
|System and method for reducing leakage current in an electrosurgical generator
|22 Jun 2005
|24 Jun 2014
|Cyberonics, Inc.
|Closed-loop feedback-driven neuromodulation
|3 Mar 2013
|1 Jul 2014
|Cyberonics, Inc.
|Dynamic cranial nerve stimulation based on brain state determination from cardiac data
|5 May 2010
|15 Jul 2014
|Cyberonics, Inc.
|Systems for monitoring a patient's neurological disease state
|2 Jun 2010
|22 Jul 2014
|Cyberonics, Inc.
|Processing for multi-channel signals
|27 Apr 2010
|9 Sep 2014
|Cyberonics, Inc.
|Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters
|30 Apr 2010
|9 Sep 2014
|Cyberonics, Inc.
|Method, apparatus and system for validating and quantifying cardiac beat data quality
|29 Dec 2009
|30 Sep 2014
|Cyberonics, Inc.
|Processing for multi-channel signals
|3 Mar 2013
|30 Sep 2014
|Cyberonics, Inc.
|Dynamic cranial nerve stimulation based on brain state determination from cardiac data
|25 Feb 2013
|7 Oct 2014
|Flint Hills Scientific, Llc
|Detecting, quantifying, and/or classifying seizures using multimodal data
|23 Oct 2012
|7 Oct 2014
|Cyberonics, Inc.
|Systems and methods of reducing artifact in neurological stimulation systems
|28 Dec 2005
|21 Oct 2014
|Cyberonics, Inc.
|Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders
|23 Apr 2013
|28 Oct 2014
|Cyberonics, Inc.
|Neurostimulation with signal duration determined by a cardiac cycle
|3 Dec 2012
|18 Nov 2014
|Flint Hills Scientific, Llc
|Detecting, quantifying, and/or classifying seizures using multimodal data
|16 Nov 2011
|23 Dec 2014
|The Board Of Trustees Of The Leland Stanford Junior University
|Systems and methods for treatment of dry eye
|24 Feb 2014
|3 Feb 2015
|Flunt Hills Scientific, LLC
|Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
|21 May 2013
|3 Feb 2015
|Flint Hills Scientific, Llc
|Detecting and validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
|18 Apr 2014
|31 Mar 2015
|Oculeve, Inc.
|Nasal stimulation devices and methods
|30 Sep 2013
|28 Apr 2015
|Flint Hills Scientific, Llc
|Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
|17 Nov 2005
|26 May 2015
|Cyberonics, Inc.
|Closed-loop vagus nerve stimulation
|12 May 2014
|2 Jun 2015
|Cyberonics, Inc.
|Methods and systems for managing epilepsy and other neurological disorders
|24 Nov 2004
|9 Jun 2015
|Flint Hills Scientific, Llc
|Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
|4 Dec 2014
|4 Aug 2015
|The Board Of Trustees Of The Leland Stanford Junior University
|Systems and methods for treatment of dry eye
|25 Nov 2013
|18 Aug 2015
|Dignity Health
|Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
|29 Dec 2006
|25 Aug 2015
|Cyberonics, Inc.
|Methods and systems for continuous EEG monitoring
|20 Nov 2003
|27 Jan 2005
|Dilorenzo Daniel John
|Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease
|5 Apr 2004
|27 Jan 2005
|Dilorenzo Daniel John
|Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease
|13 Jan 2005
|30 Jun 2005
|Boveja Birinder R.
|Method and system for providing electrical pulses for neuromodulation of vagus nerve(s), using rechargeable implanted pulse generator
|29 Mar 2005
|25 Aug 2005
|Boveja Birinder R.
|Method and system for providing therapy for autism by providing electrical pulses to the vagus nerve(s)
|5 May 2005
|8 Sep 2005
|Boveja Birinder R.
|Method and system for providing therapy for Alzheimer's disease and dementia by providing electrical pulses to vagus nerve(s)
|11 May 2005
|22 Sep 2005
|Boveja Birinder R
|Method and system for providing adjunct (add-on) therapy for depression, anxiety and obsessive-compulsive disorders by providing electrical pulses to vagus nerve(s)
|9 Sep 2005
|5 Jan 2006
|Boveja Birinder R
|Methods and systems to provide therapy or alleviate symptoms of chronic headache, transformed migraine, and occipital neuralgia by providing rectangular and/or complex electrical pulses to occipital nerves
|28 Jul 2004
|2 Feb 2006
|Armstrong Randolph K
|Power supply monitoring for an implantable device
|14 Oct 2005
|13 Apr 2006
|Boveja Birinder R
|Method and system for altering regional cerebral blood flow (rCBF) by providing complex and/or rectangular electrical pulses to vagus nerve(s), to provide therapy for depression and other medical disorders
|6 Oct 2005
|8 Jun 2006
|Signum Pharmaceuticals, Inc.
|Agents and methods for administration to the central nervous system
|3 Feb 2006
|15 Jun 2006
|Boveja Birinder R
|Method and system for cortical stimulation with rectangular and/or complex electrical pulses to provide therapy for stroke and other neurological disorders
|21 Dec 2005
|20 Jul 2006
|Jaax Kristen N
|Methods and systems for treating obesity
|2 Jun 2006
|28 Sep 2006
|Boveja Birinder R
|Method and system for cortical stimulation to provide adjunct (ADD-ON) therapy for stroke, tinnitus and other medical disorders using implantable and external components
|6 May 2005
|9 Nov 2006
|Alex Dussaussoy
|Lotion applicator
|22 Jun 2005
|28 Dec 2006
|Dilorenzo Daniel J
|Closed-loop feedback-driven neuromodulation
|21 Sep 2010
|12 May 2011
|Joshua Haarer
|Fiber reinforced silicone for cardiac and neurostimulation leads
|12 Oct 2009
|27 Jul 2011
|Milux Holding SA
|An accessory for an implant
|16 Oct 2006
|10 May 2007
|Cyberonics Inc
|Variable output ramping for an implantable medical device
|16 Nov 2007
|22 May 2008
|Lancaster Ron
|Enhancement of and continuous biasing of afferent nerves for treatment of obesity
|16 Nov 2011
|24 May 2012
|The Board Of Trustees Of The Leland Stanford Junior University
|Systems and methods for treatment of dry eye
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|27 Mar 2006
Owner name: NEURO AND CARDIAC TECHNOLOGIES, LLC, WISCONSIN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BOVEJA, BIRINDER R.;WIDHANY, ANGELY;REEL/FRAME:017379/0626
Effective date: 20060115
Owner name: NEURO AND CARDIAC TECHNOLOGIES, LLC, WISCONSIN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BOVEJA, BIRINDER R.;REEL/FRAME:017379/0682
Effective date: 20060115
|30 Nov 2009
|Fee payment
Year of fee payment: 4
|21 Feb 2014
|Maintenance fee reminder mailed
|11 Jul 2014
|Reinstatement after maintenance fee payment confirmed
|11 Jul 2014
|Lapse for failure to pay maintenance fees
|2 Sep 2014
|Expired due to failure to pay maintenance fee
Effective date: 20140711
|13 Oct 2014
|Patent reinstated due to the acceptance of a late maintenance fee
Effective date: 20141016
|16 Oct 2014
|Fee payment
Year of fee payment: 8


text:
Take a snapshot of anything on your computer screen.Windows Version 12.4.1. ... Added: 08/25/15Total Downloads4,624,677Last Week1,796
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subset: commoncrawl


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Apr 13, 2007
Commentary by Stephen Downes
I have seen both 3D scanning and 3D printing for myself in the National Research Council labs - this was almost five years ago so they must be getting at least a little closer to commercial application. It's a bit of a leap from that to desktop manufacturing, though, as this would require either that we stock every element in our printer (in addition to smelting capacities) or acquire some sort of transmutation capacity, which would be much bigger news than desktop manufacturing. Most of the 3D we'll be looking at for anything like the short term will be virtual - good for the Wii, less good for Transmutation Industries Inc.
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text: Ludwig Revolution is an idiosyncratic take on classic fairy tales, told as only Creator/KaoriYuki can. The central story is about the flamboyant, narcissistic Prince Ludwig as he travels across the land in search of a suitable wife. Accompanied by his trusty manservant Wilhelm, Ludwig encounters a diverse cast of fair maidens from various fairy tales. ''Snow White'', ''Cinderella'' and many more are completely retold, and the resulting stories are sometimes unexpectedly hilarious, while at other times cruelly twisted. ----!!This manga contains examples of the following tropes:* AbusiveParents: Check.* AmbiguouslyGay: Oh, boy. Just take a look at Ludwig's wardrobe. It gets to the point where Cinderella borrows ''his'' slippers to attend the ball. Occasionally can be handwaved with the setting (some men's fashions from the past have not aged well).* AnachronismStew: Its delicious combined flavors will melt in your mouth, not in your hand!* AntiHero: Where to start...* AsLongAsItSoundsForeign: Subverted as many of the names Kaori Yuki picks actually exist in reality.* AuthorAppeal: In a side-column during the ''Sleeping Beauty'' story, Kaori Yuki admits that Ludwig's obsession and preference for big breasts actually is one of her own.* AxCrazy: How Lisette became a SelfMadeOrphan. She's by ''no'' means the only character who's Cuckoo for Cocoa Puffs.* AwesomeButImpractical: The prince goes everywhere in full visual kei regalia. Lisette works as a mercenary in a plastic/leather dress and high heels.* BadassGrandma: Her name is Babette and she is awesome. * BeautyEqualsGoodness: Subverted with Snow White. The eponymous princess here is a cruel slut who seduced her father since age 7, and is much more evil than the queen, mocking the queen that she can never be as beautiful as her. ** In the Goose girl, the story keeps hinting that the beautiful, kind, sweet and humble maid Albertina (with golden hair) is the true princess, as opposed to mean and selfish dark haired "princess Albertina". Later, the blond Albertina confesses that she was forced to switch places with her jealous maid, "princess Albertina" is executed and the blond Albertina marries the prince.[[spoiler: However, it was all a lie, there was no switch at all. The black haired Albertina was the TRUE princess who had earlier forced her maid to write letters and poems to Prince Cristo. The maid Albertina later uses these poems to convince Cristo that she's the real princess, mainly to get revenge on the real Albertina's family for executing her mother. And to live a life of luxury, of course.]] * {{Bifauxnen}}: [[spoiler: Queen Almaberga, who is identical to her son Ludwig. You can argue an inversion and say that Ludwig looks feminine]].* {{Bishonen}}: Ludwig himself, Wilhelm, Julius [[spoiler: sort of]].* BloodKnight: [[spoiler: Queen Almaberga, baby]].* BreakTheCutie: Lisette, who was tricked into slaughtering her family, as well as Hansel and Gretel, who had a poor abused childhood made much worse by an extremely deranged and savage experience, which turned them into cruel killers.** [[spoiler: Lisette probably loved killing her parents, as they forced her into prostitution as a child]].* {{Bowdlerization}}: Believe it or not, some of the stories are comedic and actually less morbid than the original. Cinderella's sisters don't mutilate themselves, Rapunzel's prince does not get blinded, and Literature/TheLittleMermaid [[spoiler: gets to marry her prince.]]* CrapsackWorld: What do you expect with ''Kaori Yuki'' taking already dark fairy tales and making them ''worse''???** Most notably Hansel and Gretel though. She actually mentions in a sidebar that she finds the original story so horrifying that she couldn't bring herself to make it the slightest bit funny. * DeadAllAlong [[spoiler:Maid Maleen]].* {{Dojikko}}: Cinderella.* DudeLooksLikeALady: [[spoiler: One of the side-effects of Ludwig and his mom looking exactly the same]].* DudeShesLikeInAComa: What did you expect when the story features a retelling of ''Snow White'' ?* EarnYourHappyEnding: Among all the cruelty inherent in Kaori Yuki's work, some lucky characters actually get one of these.* ElegantGothicLolita: Dorothea's clothes tend to go in that direction, with some of the princesses donning similar attire.* EmbarrassingNickname: Cinderella hated her previous nickname [[spoiler: Miss Bigfoot, because of her large feet]].* EverythingsBetterWithPrincesses: Ludwig is on a quest to search for a princess to be his bride, and meets plenty. Probably subverted as not all of them have it easy or are pure, however.* FairytaleMotifs: Uh, ''duh''.* AFateWorseThanDeath: [[spoiler:Dorothea has to go all over the world collecting gold for her master. Most of the time, she ends up making herself hated by everyone and every time she dies, she is revived in another body and has to do it all over again]].* FracturedFairyTale: Even more of a no-brainer than the above.* GodSaveUsFromTheQueen: Everyone is absolutely terrified of Ludwig's mother Queen Almaberga, [[spoiler:who is still quite alive]]. Also, Petronella's plans are for the sake of becoming the new queen.* GoldDigger: the Cinderella chapter is full to the brim with them.* {{Grimmification}}: See also CrapsackWorld.* HandsomeLech: Ludwig is the most overt example of this ever for a Kaori Yuki protagonist, picking and dumping women based solely on the size of their breasts.* HeelFaceTurn (Dorothea, [[spoiler:Lisette, Hansel and Gretel, Julius]])* HeirClubForMen: The indirect reason Ludwig needs to find a bride.* HelloNurse: Dorothea again.* HeroicSacrifice: [[spoiler:Dorothea sacrifices herself to revive Ludwig. However, she's revealed to be in a cycle of reincarnation, and thus not truly dead]].* KarmicDeath Some people do actually get it.* ILoveTheDead: Ludwig, in the first chapter. Until he get bored.* ImpossiblyCoolClothes: Prince Ludwig has ''quite'' the fashion sense.* InformedAbility: Cinderella's feet don't look the size they are said to be....** Although that can be explained as it is said that feet that are 27cms long ''are'' seen as rather large.. in Japan.* IdenticalGrandson: [[spoiler: Ludwig and his mom are IDENTICAL, to the point where Julius tries to kill Ludwig repeatedly for his mother's genocidal crazy]].* ItsPersonal: [[spoiler: The reason that Julius hates Ludwig so deeply is because he caused the death of his older sister with a great war. Only... it was [[IdenticalGrandson Lui's mom]]]].* JerkWithAHeartOfGold: Ludwig acts incredibly obnoxious towards people, but he puts himself in danger to save his friends.* MummiesAtTheDinnerTable: [[spoiler: Julius has no problems with talking to Ludwig's (supposedly) dead body or with making out with it]]. Also Ludwig's "hobby" at the beginning of the story...* {{Meido}}: Dorothea dons a sexy maid outfit, also true maids like Inga.* NoblewomansLaugh: Petronella, the poor maids outside her window got scarred for life because of that.** They thought it was her - it was actually Julius.* OffingTheOffspring: More than once with [[spoiler: Snow White, Hansel and Gretel]].* OneSteveLimit: We got two girls named Albertina, actually a plot point.* OneWingedAngel: [[spoiler: Petronella]]* {{Otaku}}: A prince, no less! His name is Christo.* ParentalIncest: Between Princess Blanche and her father. * ReallySevenHundredYearsOld: Dorothea* {{Reincarnation}}: Dorothea, in an unusual fashion. And of the "duty that survives death" kind.* ScaledUp: [[spoiler: Petronella's OneWingedAngel act. Unsurprisingly, it doesn't help]].* ScrewTheRulesIHaveMoney: I'm not just some disgusting "otaku", I am an otaku celebrity with money and power!* SheIsAllGrownup: Gender Flipped, Prince Silvio is all grown up at the end of his story.* ShoutOut: Ludwig and Wilhelm are the names of the original Grimm brothers, Dorothea was the name of their mother.* SpellMyNameWithAnS: As you can see, there's some confusion as to whether Ludwig's mother is named Amalberga or Almaberga. Amalberga's a real name, at least, so it's probably this one.* ThemeNaming: The names of Dorothea's pets are "Damian", "Jason" and "Carrie".* TrueLoveIsExceptional: It is very heavily hinted that the princess most suited for Ludwig is Idike, who doesn't have large breasts...* TrueLovesKiss: Subverted. [[spoiler: It wasn't the kiss what revived Idike, in fact it didn't revive her at all]]* {{Tsundere}}: Lisette, Rapunzel, Idike.** Ludwig too, toward [[HoYay Wilhelm]]. Especially strong during the Little Red Riding Hood story. * UglyGuyHotWife: One does wonder what Amalberga sees in her husband...* VainSorceress: Subverted by Dorothea, as the reason she looks youthful [[spoiler: is her curse]].* WholesomeCrossdresser: [[spoiler: Julius]].[[spoiler: Or maybe not. He was a feminine boy raised as a girl, "crossdressing" as a boy. He may also be transexual but that's unclear. [[ItsaLongStory It's complicated]]]]* WickedStepmother: Petronella, by marrying the King. [[spoiler: Shame the marriage is void because his last wife is still alive]].* WhoWantsToLiveForever: [[spoiler:Dorothea]] thanks Ludwig after he breaks her out of her [[{{Reincarnation}} reincarnation cycle]].* WomanScorned: Petronella.* {{Yandere}}: Julius.----


text:
Tomato-Basil Crostini
Juicy summer tomatoes and fresh basil top this easy crostini appetizer.
Total Time:
Level: Easy
Yield: Enough topping for 30 crostini
Advertisement - Continue Reading Below
- Simple Crostini
- 1 pt. chopped grape or cherry tomatoes
- ½ c. fresh basil leaves
- 1 tbsp. olive oil
- 1 tsp. red-wine vinegar
- Coarse salt
- ground pepper
- In a bowl, combine tomatoes, basil leaves, olive oil, and red-wine vinegar; season with salt and pepper. Top crostini with topping.
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It's been forever since I put anything on the calendar for this group, and I feel horrible about it. Y'know what makes me feel better? Python! And beer. Let's put these two primal forces of nerdery together and enjoy an evening of hacking in Python, meeting other Python hackers, and imbibing our favorite frosty beverages (even if that beverage is non-alchoholic). Nothing sloppy, just a friendly happy hour over Python.
Is this still going off even if it's only the 6 of us who RSVP'd?
0 · November 20, 2013
Libraries offer small to medium size rooms for community events.
0 · November 19, 2013
Hello all,
My name is Sabrina from Sonobi, one of Orlando's fastest growing startups. We are innovating real solutions in the programmatic/real-time bidding space and it's all powered by Python. From our proprietary ad code web server to our real time bidding platform, data aggregation and reporting, Sonobi runs on Python! We like solving difficult problems and Python allows us to do that efficiently and elegantly.
We are organizing a meetup sometime this week for everyone interested in the Python language. Along with food and drinks (alcoholic beverages included), we will have several Python coding challenges for you to dive into. You can bring your own laptop and hop on our network, or use one of our workstations here at the office.
Please email me at [masked] if you would like to join in on the fun!
0 · November 18, 2013
We just grab a coffee and speak French. Some people have been coming every week for months... it creates a kind of warmth to the group.
— Rafaël, started French Conversation Group
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Clothes swapping event and style workshop
by OutInCanberra 12 September 2012
If you love fashion and want to freshen up your wardrobe, the unique clothes swapping event at Westfield Belconnen is a must-do!
The clothes swapping event and style workshop is with Westfield Stylist, Ella Wallace. It will be held on Saturday 15th September at 11am. The event will raise money for Westfield Belconnen's local community partner, Cerebal Palsy Alliance ACT.
Participants can swap up to five items of clothing with their peers and can also enjoy champagne, canapés, a $20 Westfield Gift Voucher and a Spring/Summer fashion style workshop with Ella Wallace, who will provide style guidance to suit your personality, shape and budget.
Cerebral Palsy is the most common physical disability in childhood. Participants can register at the Westfield Belconnen Concierge for $25 per person. Five dollars from every registration will be donated to Cerebral Palsy Alliance ACT.
The event will be held at Westfield Belconnen, Centre Court, Level 1. For more information visit http://www.westfield.com.au/belconnen
Where? Westfield Belconnen, Centre Court, Level 1
When? Saturday 15th September 2012, 11am
How? For more information visit www.westfield.com.au/be
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Google releases Chrome browser for iPhone, iPad
The Chrome application released Thursday is the latest volley in the escalating rivalry between Google and Apple, the maker of the popular mobile devices.
Google's attempt to supplant Apple Inc.'s own Safari browser comes a day after it unveiled its plans to sell a low-priced tablet computer to compete against the iPad and Amazon.com Inc.'s Kindle Fire.
The arrival of Chrome on Apple's mobile operating system comes a month after Yahoo Inc. released a browser called Axis for the iPhone and iPad.
Chrome, though, is already dueling with Microsoft Corp.'s Internet Explorer for the bragging rights as the world's most popular browser.
Google Inc. revealed Thursday that Chrome now has 310 million active users.
Hotel industry supplier Electric Mirror to expand in Everett Facebook ready to test giant drone for Internet service Economy up 2.3%; 1st quarter revised higher Our finance industry has grown too large Procter & Gamble sales dip on softer volume Briefs: Port of Everett awards $15,000 to support tourism
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I am trying to use
easy_thumbnails in a
Django (1.5) project on my laptop (OSX Lion) using the local django development server (
runserver) or a python shell. I have the
PIL library installed with jpeg support and I am working in a virtual environment. I am testing the
easy_thumbnail app in a django shell with the following command:
th = get_thumbnailer(mymodel.image)
These commands work fine on the server, the thumbnail is created successfully. However, in my local django shell and when using runserver the same command leads to the following error:
File "/.../site-packages/easy_thumbnails/files.py", line 397, in get_thumbnail
thumbnail = self.generate_thumbnail(thumbnail_options)
File "/.../site-packages/easy_thumbnails/files.py", line 293, in generate_thumbnail
"The source file does not appear to be an image")
InvalidImageFormatError: The source file does not appear to be an image
The Python Imaging library works well on my computer. In a normal (non-django) python shell, I can read, verify and write jpeg images.
I have tried many different ways of working around this problem, as I am aware that this could potentially be a problem of library pahts, as suggested in this question. I am out of ideas what I could try to solve this problem, any hints would be greatly appreciated.


text:
Financial advice usually doesn't generate buzz on social media as much as, say, a grumpy cat photo or a Harlem Shake video.
But early this week, I came across a few financial words of wisdom on an index card that … Read more
Financial advice usually doesn't generate buzz on social media as much as, say, a grumpy cat photo or a Harlem Shake video.
But early this week, I came across a few financial words of wisdom on an index card that … Read more
A few months ago, my husband and I experienced debit card fraud. Reviewing our bank account online, I noticed a series of strange ATM withdrawals that we didn't make. The withdrawals were substantial, adding up to a few thousand dollars. … Read more
I just finished watching a new documentary on 401(k) plans. It was intended to be an exposé of sorts. The program combined criticisms of the U.S. retirement system and financial services industry with sinister music for added drama. After I … Read more
In sixth grade, I'd take my allowance to Phil's Pizza, exchange the bills for quarters, and feed a week's worth of funds into the Pac-Man machine. Within 15 minutes, I was broke. To behavioral economists, I was a case study … Read more
One of the most intriguing retirement studies issued in 2012 was by economists James Poterba of MIT, Steven Venti of Dartmouth, and David Wise of Harvard.* Their study looked at wealth holdings among Americans in their late 60s. And one … Read more
If you first learned how to think about saving and investing as I did, from a passbook savings account, bond funds can seem like a world turned upside down. I was reminded of this a few days ago when an … Read more
Here at Vanguard, we're in our busy season. As clients set New Year's resolutions to save more and prep for submitting their taxes, we receive more phone calls and emails. There's a tradition at Vanguard where employees from around the … Read more
Visit vanguard.com or contact your broker to obtain a Vanguard ETF or fund prospectus which contains investment objectives, risks, charges, expenses, and other information; read and consider carefully before investing.
Vanguard ETF Shares are not redeemable with the issuing Fund other than in Creation Unit aggregations. Instead, investors must buy or sell Vanguard ETF Shares in the secondary market with the assistance of a stockbroker. In doing so, the investor may incur brokerage commissions and may pay more than net asset value when buying and receive less than net asset value when selling.
Investments in bond funds are subject to interest rate, credit, and inflation risk.
Diversification does not ensure a profit or protect against a loss in a declining market.
Foreign investing involves additional risks including currency fluctuations and political uncertainty.
Stocks of companies in emerging markets are generally more risky than stocks of companies in developed countries.
An investment in a money market fund is not insured or guaranteed by the Federal Deposit Insurance Corporation or any other government agency. Although a money market fund seeks to preserve the value of your investment at $1 per share, it is possible to lose money by investing in such a fund.
All investing is subject to risk, including possible loss of principal.
Vanguard Marketing Corporation, Distributor


text:
Think piece
Chris Anderson would be the first to tell you that he does not understand how government works. As editor-in-chief of Wired magazine, which is published by Condé Nast, Anderson spends his days talking with people who live on the frontiers of technology as they search for the next Twitter or Facebook. Like most people, Anderson doesn't really care how government works. What matters to him is that it does work, especially on the Web.
Anderson will deliver a keynote address March 10 at the FOSE conference, presented by 1105 Government Information Group, Federal Computer Week's parent company. He recently shared his thoughts on what federal agencies could learn from entrepreneurs in Silicon Valley. Here are excerpts of that conversation.
22-year-olds changing the world
We've trained a generation to expect certain things of online services. To what extent can government services satisfy that? I live in as different a world as you can imagine from the government world. We do things on weekends with credit cards. We do things with 21-year-olds who have no limits. We don't have policies and procedures; we just do [it].
So that's obviously a really exciting way to start new companies and create new technology that doesn't necessary scale to large organizations. I know that because I work for a large organization. But there is a lot to be learned from 22-year-olds using open-source software on weekends to change the world. And the question is: To what extent can government do more with less? To what extent can government use these increasingly good, free and open tools out there to deliver services to a generation that expects them that way?
You look around and you see just a generation gap, total discontinuity between best practice in the private sector and best practice in the public sector in terms of the Web.
It feels like the lessons of Web 2.0 do not seem to fully propagate it within government. By that, I don't necessarily mean federal; it also applies to state. I was trying to pay a ticket online last night. The payment site has been down for four, five days. There isn't a start-up run by teenagers that could be down for more than 10 minutes without outrage. And an entire city's payment process is down for five days, and no one [cares].
I don't really understand why government can't look like any other good service. Why can't government look like Amazon, you know?
I'm sure there are real answers involving things like laws and regulations and restrictions and all of that kind of stuff, but none of that seems to explain why sites are down for five days. None of that seems to explain why things that should take 10 seconds take six weeks. None of that explains the sort of failure to innovate. I don't think regulation and legal restrictions are the answer. I think that basically there's kind of a general disregard for the consumer experience.
Not living up to expectations
We have been trained to basically expect things to work well and quickly. The Googles and the Amazons of the world have pretty much set the expectations for an online experience, and anybody who doesn't live up to that expectation is going to suffer.
I say that as part of a big company that also, in many ways, failed to live up to that expectation. And, you know, the fact that we're doing better than we used to is not good enough; we have to be living up to the standards that this generation expects. If our search doesn't work, it doesn't really matter why it doesn't work — it just should work.
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The General Services Administration's Enterprise Infrastructure Solutions contract will anchor the agency's NS 2020 telecommunications strategy.
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As Steve Kelman returns from a summer of aggressive medical treatment, he considers the all-too-common aversion to short-term sacrifices.
Massive open online courses can offer specialized IT instruction on a flexible schedule and on the cheap. That may not always mesh with government's preference for structure and certification, however.
The federal government craves more cybersecurity professionals. These six schools are helping meet that demand.
Former ACT president will take a job with Gartner, follow his spouse to Vienna, Austria.
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CFA vs MBA
CFA 2013: T-Minus 24 Hours 'Til Those Three Little Letters Will Be Within Reach
As those of you who've spent the last 4-5 months in a hermetically sealed bubble […]
CFA Police: "The Candidate Was Moving His Hat And Hands Around Using What Appeared To Be Signals"
Yesterday, at approximately 10:30AM, scores of financial services employees breathed a collective sigh of relief. Relief that months of studying had paid off in the form of a passing score on the Level II and II CFA exams. Relief that, even though months of studying had been a total waste of time with nothing to show for it, they could get on with their lives and stop wondering. One guy was less lucky. He's in a CFA holding cell right now pending an investigation, thanks to some supposedly suspect fidgeting and a couple proctors with itchy trigger fingers, possibly hoping to impress their superiors.
According to the suspect, "No one has ever accused me of having a nervous tic or cheating before…I don't understand how you could honestly mistake my, admittedly strange, gestures as signaling to an unknown accomplice."
High-Frequency Monitoring: A Short-Sighted Behavior
The more frequently you monitor your portfolio, the more likely you are to observe a loss.
This is likely to cause short-sighted decisions and could hurt your investment performance.
If you are checking your portfolio more than once per quarter, you're doing it too much.
Click to read more.
Dan Egan, Betterment Director of Behavioral Finance and Investing
We, elderly Second-Year Sages, like to offer recruiting advice as if we know how it's […]