Abstract: There is provided a new and improved synthetic route for the synthesis of the compound 1-{2-[(1R)-1-aminoethyl]-4-chlorobenzyl}-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one (Formula (I)) that is readily scalable for commercial production. Also provided are important intermediate compounds that are formed in the new and improved synthetic route for the synthesis of the compound of formula (I).

Abstract: The present disclosure concerns the large-scale manufacture of pharmaceutical compounds, and novel intermediates for use in the manufacture. International Patent Application WO2011154737 discloses morpholine pyrimidines useful for treating cancer, processes for their preparation and pharmaceutical compositions thereof. In particular, WO2011154737 discloses, as experimental Example 2.02 on page 60, the compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)—S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (hereafter referred to as the compound of Formula (I)). The structure of the compound of Formula (I) is shown below. A synthetic route to the compound of Formula (I) is described at pages 51 to 57, 66 and 67 of WO2011154737, and is summarised below in Scheme 1.

Abstract: The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

Abstract: The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

Abstract: The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

Abstract: A speaking valve assembly (2, 200) for fitting to the machine end (13) of a tracheostomy tube (1) has a one-way valve (23, 236) that allows inhalation but prevents exhalation. The assembly further includes a pressure relief arrangement that remains closed during normal respiration and vocalisation but opens when pressure in the assembly rises above a normal level. In one arrangement the pressure relief arrangement takes the form of a ball valve (30) with a ball (32) that is lifted away from an opening (31) by excess pressure but falls back to block the opening when pressure reduces. An alternative pressure arrangement has a slidable collar (226) that normally covers vent apertures (223) in a housing (220) of the assembly. When pressure in the assembly rises above a normal level the collar (226) is pushed out to expose the vent apertures (223) and allow air to escape.

Abstract: A tracheal tube has a high-volume/low-pressure sealing cuff (10, 201, 310, 510, 610, 710, 810) with an outer surface provided with surface formations (211, 311, 511, 611, 711, 811) adapted to reduce the flow of secretions past the cuff. The formations could be in the form of an array of dimples (211) or a pattern of linear ridges or channels (611 or 711). Alternatively, the surface formations, could be a pattern of intersecting linear projections (311, 312, 313) or grooves (511). Instead the surface formations could be provided by a rough texture (811) on the outer wall surface.

Abstract: The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

Abstract: An inner cannula (20) for a tracheostomy tube assembly includes a thin, inner sheath (22) supported externally by a structural frame (23) having a longitudinal portion (25) and a plurality of ribs (26) extending circumferentially and spaced along the cannula. The inner cannula (20) is inserted within and is removable from an outer tracheostomy tube (1). The inner cannula (20) is made by coating a plastic layer on a core to form the sheath and then placing the sheath on a curved core. The structural frame (23) is then moulded about the sheath (22) in a mould 80.

Abstract: An HME has exchange elements (4) at opposite ends of a tubular housing (1, 101) and a central port (2) for connection to a tracheal tube (3). An oxygen port (5, 105, 105?) is located centrally with the major part of it being contained within a recess (40, 140, 140?) on the exterior of the housing and extending at right angles to the length of the housing. The oxygen port (5, 105, 105?) opens into a wider passage (32, 32?) extending within the housing, which opens on the external face (30) of the two exchange elements (4). A large suction aperture (60) aligns with the port (2) opening to the tracheal tube (3) and is covered by a hinged flap (61) when not in use.

Abstract: A coupling (2) for a tracheostomy tube (1) has first component (21) with a short sleeve (23) at its patient end that it fitted on the patient end of the machine end coupling (17) on the tube so that the machine end of the coupling extends within a part-spherical formation (24) at the opposite end of the first component. The coupling (2) includes a second component (22) with a male tapered fitting (27) at its machine end and a part-spherical formation (28) at its patient end that is a close sliding fit inside the part-spherical formation (24) on the first component (21).

Abstract: A sensor is configured to experience resistance changes in response to an external interaction. The sensor comprises a first layer of a conductive material having a first electrode connected thereto; a second intermediate layer of a material having a resistance sensitive to said external interaction; and a third layer including a first set of fingers interdigitated with a second set of fingers. A second electrode is attached to the first set of fingers and a third electrode is attached to the second set of fingers. The second layer includes a quantum tunnelling composite and provides electrical conduction between the first layer and the third layer. In a preferred embodiment, the first electrode is connected to either one of said second electrode or said third electrode to complete a parallel connection. A method is described for constructing such a sensor.

Abstract: An HME has exchange elements (4) at opposite ends of a tubular housing (1, 101) and a central port (2) for connection to a tracheal tube (3). An oxygen port (5, 105, 105) is located centrally with the major part of it being contained within a recess (40, 140, 140?) on the exterior of the housing and extending at right angles to the length of the housing. The oxygen port (5, 105, 105?) opens into a wider passage (32, 32?) extending within the housing, which opens on the external face (30) of the two exchange elements (4). A large suction aperture (60) aligns with the port (2) opening to the tracheal tube (3) and is covered by a hinged flap (61) when not in use.

Abstract: A sensor for, and a method of, generating electrical signals indicating a positional property and an extent property of a mechanical interaction within a sensing zone. The sensor comprises a plurality of conductive layers. At least one conductive layer is a pressure-sensitive conductive layer comprising a quantum tunnelling conductance (qtc) material. Contact between conductive layers is allowed during the absence of a mechanical interaction within said sensing zone. The sensor may be configured to provide a three-terminal sensing functionality or a four-terminal sensing functionality. The sensing zone may be substantially two-dimensional or substantially three-dimensional. The sensor may be substantially flexible or substantially rigid.

Abstract: A detector comprising control circuitry and a sensor in which the detector comprises three layers. The first layer includes a first set of mutually connected electrically conducting elements and a second set of mutually connected electrically conducting elements. The third layer comprises an electrically conducting plane, and the second layer extends between the first and third layers. The electrical conductivity of the second layer varies in accordance with variations in the intensity of the interactions. In a first mode, the control circuit applies voltage between the first and third layers to generate a first current through the second layer, and provides a measurement of the first current. In a second mode, the control circuit applies voltage between the first and second sets of electrically conducting elements to generate a second current through the second layer, and provides a measurement of the second current.

Abstract: A sensor for, and a method of, generating electrical signals indicating a positional property and an extent property of a mechanical interaction within a sensing zone. The sensor comprises a plurality of conductive layers. At least one conductive layer is a pressure-sensitive conductive layer comprising a quantum tunnelling conductance (qtc) material. Contact between conductive layers is allowed during the absence of a mechanical interaction within said sensing zone. The sensor may be configured to provide a three-terminal sensing functionality or a four-terminal sensing functionality. The sensing zone may be substantially two-dimensional or substantially three-dimensional. The sensor may be substantially flexible or substantially rigid.

Abstract: A detector comprising control circuitry and a sensor, responsive to interactions of varying intensities, comprising three layers. The first layer includes a first set of mutually connected electrically conducting elements and a second set of mutually connected electrically conducting elements. The third layer comprises an electrically conducting plane, and the second layer extends between the first and third layers. The electrical conductivity of the second layer varies in accordance with variations in the intensity of the interactions. In a first mode, the control circuit applies voltage between the first and third layers to generate a first current through the second layer, and provides a measurement of the first current. In a second mode, the control circuit applies voltage between the first and second sets of electrically conducting elements to generate a second current through the second layer, and provides a measurement of the second current.

Abstract: A sensor configured to experience resistance changes in response to an external interaction is disclosed. The sensor comprises a first layer of a conductive material having a first electrode connected thereto; a second intermediate layer of a material having a resistance sensitive to said external interaction; and a third layer consisting of a first set of fingers interdigitated with a second set of fingers. The first set of fingers has a second electrode attached thereto whilst the second set of fingers has a third electrode attached thereto. The second layer comprises a layer formed of a quantum tunnelling composite. In a preferred embodiment, the first electrode is connected to one of said second electrode or said third electrode to make a parallel connection. A method for constructing such a sensing device for sensing an external interaction is also disclosed.

Abstract: The invention concerns benzamide compounds of Formula (I), wherein R1a, R1b, R1c, R2, R3, R4, m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of histone deacetylase (HDAC).

Abstract: An HME has a generally T-shape housing (1) with a central, laterally-extending port (2) for connecting to the machine end of a patient breathing tube (3) or mask. The housing (1) extends to either side of the port (2) and is curved to follow the shape of the patient's neck. Hygroscopic HME paper elements (4) are retained at opposite ends of the housing (1) so that all gas flowing to or from the tube via the HME passes through one or other of these elements. The housing (1) has a suction aperture (60) located directly opposite the port (2).