Abstract: The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4A, R4b, and R5, are as defined herein, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of CLL.

Abstract: Apparatus for securing a therapy delivery device relative to a burr hole and method for making same. In one embodiment, the apparatus includes a base for seating in or near the burr hole. The apparatus may further include a stabilizer that may be engaged with the therapy delivery device. The stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: Apparatus for securing a therapy delivery device relative to a burr hole and method for making same. In one embodiment, the apparatus includes a base for seating in or near the burr hole. The apparatus may further include a stabilizer that may be engaged with the therapy delivery device. The stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: Apparatus for securing a therapy delivery device relative to a burr hole and method for making same. In one embodiment, the apparatus includes a base for seating in or near the burr hole. The apparatus may further include a stabilizer that may be engaged with the therapy delivery device. The stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: This invention provides treatment compositions as well as systems and methods of determining and administering an effective amount of treatment for a neurological disorder. The treatment composition can contain a labeled interfering RNA (iRNA) agent capable of decreasing expression of a target RNA associated with the neurological disorder. The methods of the invention include determining an effective amount of a therapeutic composition by introducing a solution containing a tracer into the brain of a mammal. The tracing solution is monitored until a target volume of distribution at steady state distribution is substantially achieved, and the rate of delivery of the therapeutic composition is determined. The therapeutic composition can then be administered at the rate determined by use of the tracing solution.

Abstract: A system for performing an intraparenchymal drug infusion including a pump device, a delivery tube, a sensor, and a processor. The tube is fluidly coupled to the pump device, establishing an infusate pathway from the pump to an infusate exit port of the delivery tube. The sensor is positioned to sense a parameter indicative of pressure in the infusate pathway. Finally, the processor is programmed to generate information indicative of infusate delivery effectiveness of a drug infusion procedure based upon information from the sensor. In some embodiments, the processor generates a net infusion pressure profile, such as a pressure-time curve, and prompts display of the pressure profile to a neurosurgeon for subsequent evaluation of infusate delivery effectiveness.

Abstract: This invention provides treatment compositions as well as systems and methods of determining and administering an effective amount of treatment for a neurological disorder. The treatment composition can contain a labeled interfering RNA (iRNA) agent capable of decreasing expression of a target RNA associated with the neurological disorder. The methods of the invention include determining an effective amount of a therapeutic composition by introducing a solution containing a tracer into the brain of a mammal. The tracing solution is monitored until a target volume of distribution at steady state distribution is substantially achieved, and the rate of delivery of the therapeutic composition is determined. The therapeutic composition can then be administered at the rate determined by use of the tracing solution.

Abstract: A catheter for use with a medical infusion or other fluid system. The catheter may include a flexible elongate tubular core that is resistant to radial collapse, and a separate tubular tip member forming the catheter distal tip. The catheter may further include a flexible, e.g., elastomeric, jacket that surrounds at least a portion of the tubular core. The jacket may have a radial compliance that is greater than that of the tubular core. The jacket may further define an outer diameter that is about 4 to about 6 times greater than an outer diameter of the core.

Abstract: This invention provides treatment compositions as well as systems and methods of determining and administering an effective amount of treatment for a neurological disorder. The treatment composition can contain a labeled interfering RNA (iRNA) agent capable of decreasing expression of a target RNA associated with the neurological disorder. The methods of the invention include determining an effective amount of a therapeutic composition by introducing a solution containing a tracer into the brain of a mammal. The tracing solution is monitored until a target volume of distribution at steady state distribution is substantially achieved, and the rate of delivery of the therapeutic composition is determined. The therapeutic composition can then be administered at the rate determined by use of the tracing solution.

Abstract: A catheter for use with a medical infusion or other fluid system. The catheter may include a flexible elongate tubular core that is resistant to radial collapse, and a separate tubular tip member forming the catheter distal tip. The catheter may further include a flexible, e.g., elastomeric, jacket that surrounds at least a portion of the tubular core. The jacket may have a radial compliance that is greater than that of the tubular core. The jacket may further define an outer diameter that is about 4 to about 6 times greater than an outer diameter of the core.

Abstract: Embodiments of the present invention include anchor assemblies and methods for using the same to immobilize a device within a body portal. In one embodiment, the anchor assembly is utilized to immobilize a catheter relative to a covered (e.g., skin-covered) burr hole formed in a skull. Anchor assemblies in accordance with embodiments of the present invention may include anchors located subdermally that may be unlocked from outside the body to release the device without a surgical procedure.

Abstract: A catheter for use with a medical infusion or other fluid system. The catheter may include a flexible elongate tubular core that is resistant to radial collapse, and a separate tubular tip member forming the catheter distal tip. The catheter may further include a flexible, e.g., elastomeric, jacket that surrounds at least a portion of the tubular core. The jacket may have a radial compliance that is greater than that of the tubular core. The jacket may further define an outer diameter that is about 4 to about 6 times greater than an outer diameter of the core.

Abstract: Apparatus for securing a therapy delivery device relative to a burr hole and method for making same. In one embodiment, the apparatus includes a base for seating in or near the burr hole. The apparatus may further include a stabilizer that may be engaged with the therapy delivery device. The stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: A system for performing an intraparenchymal drug infusion including a pump device, a delivery tube, a sensor, and a processor. The tube is fluidly coupled to the pump device, establishing an infusate pathway from the pump to an infusate exit port of the delivery tube. The sensor is positioned to sense a parameter indicative of pressure in the infusate pathway. Finally, the processor is programmed to generate information indicative of infusate delivery effectiveness of a drug infusion procedure based upon information from the sensor. In some embodiments, the processor generates a net infusion pressure profile, such as a pressure-time curve, and prompts display of the pressure profile to a neurosurgeon for subsequent evaluation of infusate delivery effectiveness.

Abstract: A system for performing an intraparenchymal drug infusion including a pump device, a delivery tube, a sensor, and a processor. The tube is fluidly coupled to the pump device, establishing an infusate pathway from the pump to an infusate exit port of the delivery tube. The sensor is positioned to sense a parameter indicative of pressure in the infusate pathway. Finally, the processor is programmed to generate information indicative of infusate delivery effectiveness of a drug infusion procedure based upon information from the sensor. In some embodiments, the processor generates a net infusion pressure profile, such as a pressure-time curve, and prompts display of the pressure profile to a neurosurgeon for subsequent evaluation of infusate delivery effectiveness.

Abstract: A breakaway connector for use with a medical (e.g., catheter) or other fluid system. The connector may include two couplers that engage one another via a substantially frictionless retention device. In one embodiment, the retention device includes a biased cylindrical roller attached to one coupler that contacts an outer surface of the other coupler. The outer surface may include a grooved surface to receive the roller when the couplers are fully attached.

Abstract: Apparatus and methods for securing a therapy delivery device relative to a burr hole. In one embodiment, the apparatus includes a base that is securable to bone, without the use of fasteners, either before or after insertion of the therapy delivery device into the burr hole. The apparatus may further include a stabilizer that may be engaged with both the base and the therapy delivery device while the delivery device is held with positioning apparatus. The base and/or stabilizer may frictionally engage the delivery device, e.g., receive it with interference, to secure the device in two or more non-parallel directions. In some embodiments, at least the stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: Apparatus and methods for securing a therapy delivery device relative to a burr hole. In one embodiment, the apparatus includes a base that is securable to bone, without the use of fasteners, either before or after insertion of the therapy delivery device into the burr hole. The apparatus may further include a stabilizer that may be engaged with both the base and the therapy delivery device while the delivery device is held with positioning apparatus. The base and/or stabilizer may frictionally engage the delivery device, e.g., receive it with interference, to secure the device in two or more non-parallel directions. In some embodiments, at least the stabilizer may include a surface coating or treatment operable to enhance frictional engagement with the therapy delivery device.

Abstract: Embodiments of the present invention include anchor assemblies and methods for using the same to immobilize a device within a body portal. In one embodiment, the anchor assembly is utilized to immobilize a catheter relative to a covered (e.g., skin-covered) burr hole formed in a skull. Anchor assemblies in accordance with embodiments of the present invention may include anchors located subdermally that may be unlocked from outside the body to release the device without a surgical procedure.

Abstract: A catheter for use with a medical infusion or other fluid system. The catheter may include a flexible elongate tubular core that is resistant to radial collapse. The catheter may further include a flexible, e.g., elastomeric, jacket that surrounds at least a portion of the tubular core. The jacket may have a radial compliance that is greater than that of the tubular core. The jacket may further define an outer diameter that is about 4 to about 6 times greater than an outer diameter of the core.