Abstract: A patient interface includes a plenum chamber pressurizable to a therapeutic pressure, a seal-forming structure configured to form a seal against the patient's face, and a positioning and stabilising structure configured to provide a force for maintaining the seal-forming structure in a therapeutically effective position. The patient interface also includes an RPT device connected directly to the plenum chamber. The PRT device includes an electric blower for providing airflow at the therapeutic pressure. The positioning and stabilising structure supports at least part of the weight of the RPT device. The patient interface may also include an electrical power source electrically connected to the RPT device.

Abstract: A mask apparatus for a respiratory treatment can permit delivery of breathable gas to a user. In one example, the mask may employ a frame and cushion to form a seal for both mouth and nose. The frame may be adapted for coupling with a respiratory treatment apparatus so as to permit communication of a pressurized gas from the respiratory treatment apparatus. The cushion, which may be foam, may have a substantially under the nose configuration or over the nose configuration. The mask may have a common plenum chamber for both nose and mouth. The cushion may further define a centrally open lip superior region. The cushion may be adapted to couple with the frame directly or to the frame in conjunction with a cushion support clip. Various features of the cushion may further promote sealing and comfort for the under the nose design.

Abstract: A mask apparatus for a respiratory treatment can permit delivery of breathable gas to a user. In one example, the mask may employ a frame and cushion to form a seal for both mouth and nose. The frame may be adapted for coupling with a respiratory treatment apparatus so as to permit communication of a pressurized gas from the respiratory treatment apparatus. The cushion, which may be foam, may have a substantially under the nose configuration or over the nose configuration. The mask may have a common plenum chamber for both nose and mouth. The cushion may further define a centrally open lip superior region. The cushion may be adapted to couple with the frame directly or to the frame in conjunction with a cushion support clip. Various features of the cushion may further promote sealing and comfort for the under the nose design.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using a patient response-based linear cutoff model. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. Real inflammation scores and tumor infiltration scores are determined based on a polar coordinate transformation of the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the real inflammation scores and tumor infiltration scores, a feature space is generated, and linear boundaries or linear cutoffs between a plurality of classifications in the feature space are identified based on the real inflammation scores, the tumor infiltration scores, and patient response data.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using artificial intelligence and machine learning. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. A machine learning algorithm is then trained using results of the image analysis and the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the training, a machine learning feature space comprising a plurality of classifications is generated, and boundaries between the plurality of classifications in the machine learning feature space are identified.

Abstract: The present disclosure provides methods of identifying a subject suitable for an anti-PD-?PD-L1 antagonist therapy comprising measuring assay CD8 localization and PD-L1 expression in a tumor sample obtained from the subject. In some aspects, method further comprises administering (i) an anti-PD-?PD-L1 antagonist therapy or (ii) an anti-PD-?PD-L1 antagonist and anti-CT-LA-4 antagonist combination therapy to a subject identified as having a tumor exhibiting an excluded CD8 localization phenotype, wherein the tumor is PD-L1 negative.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: The disclosure provides LAG-3 antagonists and methods comprising the same for treating a cancer in a subject based on a LAG-3 density score and/or a LAG-3 proportion score in a tumor sample from the subject. The disclosure also provides methods of identifying a subject responsive to a LAG-3 antagonist therapy.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-Ll positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.