Cooley (UK) LLP

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), <img class="EMIRef" id="144c60a3-d848-4d3a-9cda-26502c2374b5-ia01" /> that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD) , to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

This invention provides methods for treating or preventing kidney diseases and fibrosis, such as chronic kidney disease (CKD), kidney fibrosis, heart fibrosis, uterine fibrosis, and cystic fibrosis, with compounds of Formulae (I), (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (II), (III), (IIIA), and (IIIB); pharmaceutically acceptable salts and solvates thereof; and compositions thereof.

Provided herein are recombinant AAV vectors, AAV viral vectors, and capsid proteins for improved gene therapy, and methods for their manufacture and use in a multipartite (e.g., bipartite) delivery system. The vectors provide portions of transgene and direct their recombination in a cell to provide complete transgenes.

Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, and methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.

Described herein are methods for monitoring the radiation delivery during a radiotherapy delivery session and providing a graphical representation of radiation delivery to an operator (e.g., a clinician, a medical physicist, a radiation therapy technologist). The graphics are updated in real-time, as radiation data is collected by the radiotherapy system, and in some variations, can be updated every 15 minutes or less. A variety of graphical representations ("graphics") can be used to indicate the status of radiation delivery relative to the planned radiation delivery. Methods optionally include calculating a range of acceptable metric values, generating graphics that represent the range of acceptable metrics values, and generating a graphic that depicts the real-time values of those metrics overlaid with the range of acceptable metrics values.

Disclosed herein are systems and methods for guiding the delivery of therapeutic radiation using incomplete or partial images acquired during a treatment session. A partial image does not have enough information to determine the location of a target region due to, for example, poor or low contrast and/or low SNR. The radiation fluence calculation methods described herein do not require knowledge or calculation of the target location, and yet may help to provide real-time image guided radiation therapy using arbitrarily low SNR images.

In some embodiments, an apparatus includes a catheter having a catheter body, a light emitter disposed at a distal end of the catheter body, and a fluid conduit coupleable to a source of fluid. The fluid conduit configured to discharge fluid from the source via the conduit and out a distal end of the catheter body. A spacing member is disposed at the distal end of the catheter body and can be moved between a collapsed configuration and an expanded configuration. In the expanded configuration, the spacing member is disposed about the light emitter. The spacing member is at least partially transmissive and/or transflective of light emitted from the light emitter. The apparatus configured to be inserted at least partially into a body lumen, to discharge fluid into the body lumen, and to emit light from the light emitter to illuminate an interior wall of the body lumen.

The present disclosure provides Wnt pathway agonists and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of diseases.

Disclosed herein are methods for patient setup and patient target region localization for the irradiation of multiple patient target regions in a single treatment session. Virtual localization is a method that can be used to register a patient target region without requiring that the patient is physically moved using the patient platform. Instead, the planned fluence is updated to reflect the current location of the patient target region by selecting a localization reference in the localization image, calculating a localization function based on the localization reference point, and calculating the delivery fluence by convolving the localization function with a shift-invariant firing filter. Mosaic multi-target localization partitions a planned fluence map for multiple patient target regions into sub -regions that can be individually localized. De-coupled multi -target localization involves generating a separate planned fluence map for each target but constraining a cumulative fluence map to ensure dosimetric goals are met.

A non-transitory, processor-readable medium stores instructions that, when executed by a processor, cause the processor to receive multimodal data associated with a plurality of signals. The multimodal data is provided as input to a first machine learning model to produce signal data that represents the plurality of signals, and code associated with the multimodal data is executed to detect an anomaly in the multimodal data. The anomaly is located within the multimodal data by providing the multimodal data and the signal data as input to a second machine learning model. As a result, a plurality of propagation paths defined by the multimodal data is determined, and the plurality of propagation paths is traced to locate the anomaly within the multimodal data. The multimodal data is then provided as input to a third machine learning model to produce modified multimodal data that excludes the anomaly.