Abstract: This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I) wherein R2 is a fused bicyclic ring of the formula (II). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

Abstract: A method and apparatus for reducing a patient's heart rate or blood pressure. The apparatus provides stimulation to the patient's atrial and/or nodal tissue within the associated refractory period of the ventricle but outside of an associated refractory period of the stimulated atrial an/or nodal tissue, responsive to detecting an occurrence of a ventricular depolarization following a preceding atrial depolarization. The apparatus may define a time window following the ventricular depolarization, following the atrial depolarization or determined based upon the timing of both the atrial and ventricular depolarizations. The stimulus may be delivered during or on expiration of the defined time window. The duration of the time window may be pre-set or determined based upon measurements of the patient's refractory periods.

Abstract: The present invention relates to quinazoline derivatives of formula I: wherein X, Y, Z, R1, R2, R3, and R4 are as defined herein. The invention also relates to a method of preparing these compounds, and use of these compounds for inhibiting tumor growth.

Abstract: In some examples, an electromechanical disassociation state (EMD) of a heart of a patient can be treated by delivering electrical stimulation to a tissue site to at least one of modulate afferent nerve activity or inhibit efferent nerve activity upon determining that the heart is in an electromechanical dissociation state, where the tissue site comprises at least one of a nonmyocardial tissue site or a nonvascular cardiac tissue site. The delivery of electrical stimulation may effectively treat the EMD state of the heart, e.g., by enabling effective mechanical contraction of the heart. In another example, an electromechanical disassociation state of a heart of a patient can be treated by determining autonomic nervous system activity associated with a detected EMD state of the heart of a patient, and delivering electrical stimulation therapy to the patient based on the determined autonomic nervous system activity of the patient associated with the EMD state.

Abstract: Neurostimulation to mitigate lung wetness is delivered to a patient based on a sensed parameter indicative of lung wetness. The neurostimulation is configured to at least one of increase parasympathetic activity or decrease sympathetic activity within the patient. In some examples, a patient response to the neurostimulation therapy may be detected to modify the neurostimulation therapy. The patient response may include, for example, changes in the contractility of a heart of the patient, changes in the heart rate, heart rate variability or blood pressure of the patient, changes in a bladder size of the patient, changes in bladder functional activity of the patient, changes in urine flow, changes in lung function, changes in lung composition, or changes in the nerve activity of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Techniques for minimizing interference between the first and second medical devices or between the different therapy modules of a common medical device are described herein. In some examples, a medical device may include shunt-current mitigation circuitry and/or at least one clamping structure that helps minimize or even eliminate shunt-current that feeds into a first therapy module of the medical device via one or more electrodes electrically connected to the first therapy module. The shunt-current may be generated by the delivery of electrical stimulation by a second therapy module. The second therapy module may be enclosed in a common housing with the first therapy module or may be separate, e.g., a part of a separate medical device.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: A first implantable medical device (IMD) implanted within a patient may communicate with a second IMD implanted within the patient by encoding information in an electrical stimulation signal. The delivery of the electrical stimulation signal may provide therapeutic benefits to the patient. The second IMD may sense the electrical stimulation signal, which may be presented as an artifact in a sensed cardiac signal, and process the sensed signal to retrieve the encoded information. The second IMD may modify its operation based on the received therapy information. Crosstalk between the first and second IMDs may be reduced using various techniques described herein. For example, the first IMD may generate the electrical stimulation signal to include a spread spectrum energy distribution or a predetermined signal signature. The second IMD may effectively remove a least some of the signal artifact in a sensed cardiac signal based on the predetermined signal signature.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: A first implantable medical device (IMD) implanted within a patient may communicate with a second IMD implanted within the patient by encoding information in an electrical stimulation signal. The delivery of the electrical stimulation signal may provide therapeutic benefits to the patient. The second IMD may sense the electrical stimulation signal, which may be presented as an artifact in a sensed cardiac signal, and process the sensed signal to retrieve the encoded information. The second IMD may modify its operation based on the received therapy information. Crosstalk between the first and second IMDs may be reduced using various techniques described herein. For example, the first IMD may generate the electrical stimulation signal to include a spread spectrum energy distribution or a predetermined signal signature. The second IMD may effectively remove a least some of the signal artifact in a sensed cardiac signal based on the predetermined signal signature.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: An implantable medical device may deliver pacing, cardioversion, and/or defibrillation stimulation to a heart of a patient via extravascular electrodes and delivers electrical stimulation to a nonmyocardial tissue site to modulate the autonomic nervous system of the patient. The implantable medical device may include a cardiac therapy module that generates and delivers at least one of pacing, cardioversion, or defibrillation therapy to a patient via an extravascular electrode, and a neurostimulation therapy module that generates and delivers a neurostimulation signal to the patient via a neurostimulation electrode. The cardiac therapy module and neurostimulation therapy module may be disposed in a common housing of the medical device. In some examples, at least one common lead may electrically couple the neurostimulation electrode and the extravascular electrode to the neurostimulation and cardiac therapy modules, respectively.

Abstract: A device and method of detecting the severity of myocardial ischemia and heart attack risk is provided. The method includes obtaining an electrogram signal, determining T-wave measurements based on the electrogram signal, and determining ST segment measurements based on the electrogram signal. The method also includes identifying T-wave alternans based on the T-wave measurements and identifying ST segment changes based on the ST segment measurements. The method further includes correlating the T-wave alternans with the ST segment changes in order to detect a severity of ischemia.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.

Abstract: Electrical crosstalk between two implantable medical devices or two different therapy modules of a common implantable medical device may be evaluated, and, in some examples, mitigated. In some examples, one of the implantable medical devices or therapy modules delivers electrical stimulation to a nonmyocardial tissue site or a nonvascular cardiac tissue site, and the other implantable medical device or therapy module delivers cardiac rhythm management therapy to a heart of the patient.