text:
|Publication number||US6190855 B1|
|Application number||US 08/742,572|
|Publication date||20 Feb 2001|
|Filing date||28 Oct 1996|
|Priority date||28 Oct 1996|
|Also published as||CA2239070A1, CA2239070C, CN1160453C, CN1211277A, DE69739503D1, EP0870013A1, EP0870013A4, EP0870013B1, US6855489, US7374870, US20050186553, WO1998018908A1|
|Publication number||08742572, 742572, US 6190855 B1, US 6190855B1, US-B1-6190855, US6190855 B1, US6190855B1|
|Inventors||Robert E. Herman, John Chapman, Chong-Son Sun, Jean M Mathias, Veronique Mayaudon, Serge de Gheldere, Daniel F. Bischof|
|Original Assignee||Baxter International Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (60), Referenced by (39), Classifications (13), Legal Events (8)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The invention generally relates to the eradication of contaminants using photodynamic therapy. The invention also generally relates to the processing of whole blood and its components for storage and transfusion. In a more specific sense, the invention relates to the extracorporeal treatment of collected whole blood and its components with photoactive materials to eradicate viruses and other pathogenic contaminants.
With the coming of blood component therapy, most whole blood collected today is separated into its clinically proven components for storage and administration. The clinically proven components of whole blood include red blood cells, used to treat chronic anemia; platelet-poor plasma, from which Clotting Factor VIII-rich cryoprecipitate can be obtained for the treatment of hemophilia; and concentrations of platelets, used to control thrombocytopenic bleeding.
It is well known that blood can carry infectious agents like hepatitis-B virus; the human immunodeficiency (AIDS) virus; the Herpes virus; and the influenza virus. To avoid the transmission of these infectious agents during blood transfusions, donors of blood are routinely screened and also undergo serologic testing to detect the presence of these agents. Still, it is difficult to always assure that these infectious agents are detected.
The use of photodynamic therapy has been suggested as a way to eradicate infectious agents from collected blood and its components. Still, there has been a general lack of success in economically adapting the benefits of photodynamic therapy to the demands of the blood banking industry. One reason for this is that not all biological contaminants are carried free within the blood where they can be readily coupled to photoactive agents. Some biological contaminants are entrained on or within white blood cells out of the reach of photoactive agents.
For this and other reasons, the promise of photodynamic therapy in treating the nation's banked blood supply has gone largely unfulfilled.
The invention provides improved systems and methods for treating blood constituents to adventitious viral agents.
One aspect of the invention provides systems and methods which remove viral agents from plasma. The systems and methods remove from the plasma targeted cellular matter that does or might entrain viral agents. In a preferred embodiment, the targeted cellular matter includes leukocytes. The system and methods add to the plasma a photoactive material, which binds to viral agents that are free of entrainment by the targeted cellular matter. Radiation emitted at a selected wavelength into the plasma activates the photoactive material and thereby eradicates the free viral agents.
In a preferred embodiment, a system for treating plasma comprises tubing adapted to be coupled a plasma source, and a filter in the tubing to separate cellular matter from the plasma conveyed from the source. The system includes a transfer container coupled to the tubing to receive cellular matter-reduced plasma from the filter, and a source of photoactive material to be mixed with the plasma. In this embodiment, the tubing includes a path to vent air from the transfer container in a path that bypasses the filter.
In a preferred embodiment, systems and methods remove viral agents entrained within the cellular matter by conveying plasma in a first path through a filter. The systems and methods convey the cellular matter-reduced plasma from the filter in a second path, which includes a connected transfer container. The systems and methods mix the cellular matter-reduced plasma with a photoactive material within the transfer container, forming a plasma mixture.
In this embodiment, the systems and methods convey a portion of the plasma mixture from the transfer container in a flush path, which includes the second path, to thereby expose residual contaminants in the second path to the photoactive material. The systems and methods then separate the transfer container from the filter by severing the second path. After severance from the filter, a remnant of the second path remains attached to the transfer container. However, due to the prior flushing step, all contaminants in the attached second path remnant have been exposed to the photoactive material. Subsequent radiation of the transfer container thereby eradicates contaminants, which are free of entrainment by cellular matter, both within the transfer container and the attached second path remnant.
In a preferred embodiment, the flush path by passes the filter and also provides a path to vent air from the transfer container.
Another aspect of the invention provides systems and methods for treating plasma using multi-stage filtration, which targets for removal different species of cellular matter. The systems and methods separate a first species of cellular matter by filtration through a first filter media, thereby removing contaminants entrained within the first species of cellular matter. The systems and methods separating a second species of cellular matter by filtration through a second filter media, thereby removing contaminants entrained within the second species of cellular matter. The systems and methods add to the plasma a photoactive material and emit radiation at a selected wavelength into the plasma to activate the photoactive material, thereby eradicating the contaminant that is free of entrainment by cellular matter. In a preferred embodiment, the first filtration media targets leukocytes for removal, while the second filtration media targets platelets for removal.
Another aspect of the invention provides a kit that envelopes photoactive material in an overwrap that includes a light filtering material. The light filtering material absorbs light that activates the photoactive material. The presence of the light filtering material in the overwrap protects the photoactive material from photo-degradation due to absorption of ambient light during handling and storage prior to use.
In a preferred embodiment, the photoactive material within the kit includes methylene blue. In this embodiment, the light filtering material includes a blue material having phthalocyanine pigments.
In a preferred embodiment, the photoactive material is contained in liquid form within the kit. In this embodiment, the overwrap also includes material that reduces liquid vapor loss from the kit.
Other features and advantages of the invention will be pointed out in, or will be apparent from, the drawings, specification and claims that follow.
FIG. 1 is a plane view of a blood processing and storage kit for reducing the presence of viral agents in plasma;
FIG. 2 is an exploded, perspective view of the laminated walls of the overwrap envelope shown in phantom lines in FIG. 1;
FIG. 3 is a side view of the laminated walls of the overwrap envelope shown in FIG. 2;
FIG. 4 is a top perspective view of the laminated walls of the overwrap envelope, after having been joined by a peripheral heat seal;
FIG. 5 is an exploded side view of the leukocyte reduction filter that forms a part of the kit shown in FIG. 1;
FIG. 6 is a top perspective view of the interior of the outlet housing part for the filter shown in FIG. 5;
FIG. 7 is a plane view the kit shown in FIG. 1 being used to convey plasma from a source container, through the leukocyte reduction filter, and into the processing and storage container;
FIG. 8A is a plane view the kit shown in FIG. 7 being used to vent air and residual plasma from the processing and storage container in a bypass path around the leukocyte reduction filter;
FIG. 8B is a plane view of the kit shown in FIG. 8A being used to flush the tubing section next to the container with photoactive material, to assure exposure of residual viruses occupying the tubing section with photoactive material;
FIG. 9 is a perspective view of the kit shown in FIGS. 8A and 8B, after separation of the processing and storage container and placement of the processing and storage container in an irradiation chamber;
FIG. 10 is a plane view of an alternative embodiment of a blood processing and storage kit for reducing the presence of viral agents in plasma, in which the photoactive material is stored within an auxiliary container whose walls include a light filtering material;
FIG. 11 is a plane view of an alternative embodiment of a blood processing and storage kit for reducing the presence of viral agents in plasma, which includes an integrally attached air reservoir;
FIG. 12A is a plane view of the kit shown in FIG. 11 being use to vent air and residual plasma from the processing and storage container into the air reservoir;
FIG. 12B is a plane view of the kit shown in FIG. 12A being used to flush the tubing section next to the container with photoactive material, to assure exposure of residual viruses occupying the tubing section with photoactive material; and
FIG. 13 is a plane view of another alternative embodiment of a blood processing and storage kit for reducing the presence of viral agents in plasma, which reduces the presence of viral agents in plasma by the removal by filtration of least two different cellular blood species which actually do or potentially can entrain viral agents.
The invention is not limited to the details of the construction and the arrangements of parts set forth in the following description or shown in the drawings. The invention can be practiced in other embodiments and in various other ways. The terminology and phrases are used for description and should not be regarded as limiting.
FIG. 1 shows a blood constituent processing and storage set or kit 300. The kit 300 is intended, during use, to assist in the removal of viral agents from plasma. The viral agents are either carried free within the plasma or are entrained on or within cellular matter (e.g., red blood cells, platelets, and leukocytes) that the plasma carries. The kit 300 shown in FIG. 1 will be described in the context of reducing the presence of viral agents in single donor units of plasma, because it is particularly well suited for this purpose.
The kit 300 includes a processing and storage container 302, which carries an integrally attached length of flexible transfer tubing 304. In the illustrated embodiment, the transfer tubing 304 is made from medical grade plasticized polyvinyl chloride plastic. However, other flexible medical grade plastic materials can be used.
The transfer tubing 304 includes an integrally attached in-line filter 306. The filter 306 includes a filter media 307 (see FIG. 5) that removes from plasma cellular matter that does actually or potentially entrain viral agents.
As FIG. 5 shows, the filter media 307 is encased within a two part housing 348A and 348B made, for example, from polycarbonate, although any engineering medical grade plastic with appropriate toxicology characteristics can be used. The housing 348A/348B is sealed about the filter media 307 by, for example, sonic welding.
The pore size of the filter media 307 can be tailored to remove by exclusion all or some species of cellular matter found in plasma, depending upon the extent to which viral agents sought to be eliminated are entrained by the different cellular species. In the illustrated embodiment, the principal cellular species targets of the filter 306 are leukocytes, for it is known that leukocytes entrain many viral agents. With this objective in mind, the filter media 307 comprises a non-fibrous membrane having a pore size smaller than the size of leukocytes, to thereby remove leukocytes by exclusion. In the illustrated embodiment, the media 307 also includes a prefilter material, which removes fibrin clots and other large size aggregates from the plasma.
The composition of the membrane for the media 307 can vary. For examples, hydrophilic membranes made from nylon, acrylic copolymers, polysulfone, polyvinylidene fluoride, mixed cellulose esters, and cellulose ester can be used to remove leukocytes by exclusion. Non-hydrophilic membranes can also be treated to serve as a membrane for the filter media 307. Likewise, the composition of the prefilter for the media 307 can vary. For example, the prefilter can comprise fibers of glass or polyester. Material selection takes into account customer preferences, performance objectives, and manufacturing requirements, including sterilization techniques.
In the illustrated and preferred embodiment, (see FIG. 5), the filter media 307 includes three filter media layers 342, 344, and 346. The first filter media layer 342 comprises USP Grade VI glass fiber or the equivalent. The second and third filter media layers 344 and 346 comprise polyethersulfone (PES) membranes, which remove leukocytes by exclusion. The second and third filter media layers 344 and 346 possess pore sizes which are approximately 10 fold smaller than the size of leukocytes and which decrease in the direction of flow. The second filter media layer 344 has a pore size in the range of about 0.9 μm to about 2.0 μm, with an average pore size of about 1.2 μm. The third filter media layer 346 has a smaller pore size in the range of about 0.3 μm to about 1.5 μm, with an average pores size of about 0.8 μm. The second and third filter media layers 344 and 346 also incidently remove red blood cells by exclusion.
The filter media 307 should preferably be capable of filtering 310 ml of plasma, suspended at a head height of 3 feet, in 20 minutes.
The housing part 348A includes an inlet 350, which, in use, conveys plasma and leukocytes into contact with the prefilter layer 342. The axis 351 of the inlet 350 is generally parallel to the plane of the layer 342 to uniformly perfuse plasma across the entire prefilter layer 342.
The housing part 348B includes an outlet 352, which conveys leukocyte-reduced plasma from the second and third PES filter layers 344 and 346. As FIG. 6 shows, the interior surface of the housing part 348B is grooved, creating a fluid manifold 354 that uniformly distributes leukocyte-reduced plasma to the outlet 352.
Referring back to FIG. 1, a length of branch tubing 308 is integrally attached to the transfer tubing 304 by conventional Y-connectors 316. The branch tubing 308 forms a fluid path bypassing the filter 306. As will be described in greater detail later, the branch tubing 308 serves to vent air.
The far end of the transfer tubing 304 carries an air pillow 310. The air pillow 310 prevents collapse of the tubing 304 and 308 caused by pressure differentials during steam sterilization of the kit 300.
The transfer tubing 304 further includes a conventional in-line frangible cannula 312 between the filter outlet 352 and the processing and storage container 302. The cannula 312 normally closes fluid the transfer tubing 304 to fluid flow.
The cannula 312 can be constructed in various ways. U.S. Pat. Nos. 4,181,140 and 4,294,247 disclose representative constructions for the cannula 312, which are incorporated herein by reference.
Alternatively, an external roller clamp or C-clamp of conventional construction could be used for the same purpose.
The branch tubing 308 includes a conventional in-line one-way valve 314. The valve 314 prevents fluid flow through the branch tubing 308 in the direction of the processing and storage container 302, while permitting fluid flow in the opposite direction away from the processing and storage container 302. For redundancy, the branch tubing 308 also includes an external roller clamp or C-clamp 318. The C-clamp 318 normally closes the tubing 308 between the one-way valve 314 and the processing and storage container 302.
The processing and storage container 302 can be constructed in various ways. In the illustrated and preferred embodiment, the container 302 includes an interior chamber 320. The transfer tubing 304 communicates with the chamber 320 for conveying plasma into the chamber 320. In a preferred implementation, the chamber 320 is capable of holding between 235 to 310 mL of plasma. A normally sealed outlet port 360 also communicates with the chamber 320. The port 360 is opened when it is time to remove plasma from the chamber 320.
The chamber 320 holds a photoactive material 326. The photoactive material 326 mixes with the plasma introduced into the chamber 320. The photoactive material 320 binds to extracellular viruses that plasma introduced into the chamber 326 may carry. When exposed to light energy in a particular spectrum, the photoactive material 326 inactivates the nucleic acids of the bound viruses, rendering them nonviable.
In the illustrated and preferred embodiment, the photoactive material 326 comprises 10 mL of liquid solution containing 83 micrograms of methylene blue in water at pH 3.1, without buffers or other additives. Methylene blue, a thiazine dye, possesses the ability to bind to nucleic acids with high affinity, targeting the viruses for destruction upon exposure to a particular spectrum of light energy. Methylene blue absorbs light in the 660 nm region of the visible spectrum, which is the spectrum region where plasma is most transparent. Methylene blue inactivates a broad range of viruses, such as HIV, human hepatitis B (HBV), human hepatitis C (HCV), and Parvo virus B19, with minimal loss of therapeutic plasma proteins.
The mixture of plasma and photoactive material 326 is irradiation by light within the chamber 320 as part of a viral inactivation process. The container 302 is therefore made of a material that is substantially transparent to the applied light energy. The material for the container 302 is also adapted to withstand contemplated storage conditions for the plasma.
In the illustrated and preferred embodiment, the applied light energy is in the white light spectrum (400 to 700 nm). The container 302 is therefore made of a plastic, poly(ethylene vinyl acetate) material. This material is transparent to white light and is also resistant to the cold temperatures at which frozen plasma is stored. This material is commercially available and is made and sold, for example, by Baxter Healthcare Corporation under the trademark PL-732® Plastic.
The container 302 also includes a flap 322, which extends below the chamber 320. The flap 322 carries a printed label 324 having identifying indicia. The flap 322 keeps the label 324 away from the chamber 320, where it could block or impede the irradiating light.
The container 302 also serves after the viral inactivation process to store the viral inactivated plasma at temperatures below −30° C., following standard blood banking procedures.
Further details of container 302 are found in copending U.S. patent application, Ser. No. 08/121,820, filed Sep. 15, 1993, and entitled “Container for Irradiation of Blood Products.”
As FIG. 4 shows, the kit 300 is preferably enclosed for storage and handling before use in an overwrap envelope 328 (FIG. 1 diagrammatically shows the envelope 328 in phantom lines). The overwrap envelope 328 serves multiple functions.
To minimize evaporation of the liquid photoactive material 326 from the container 302 prior to use, the envelope 328 includes a material 332 possessing a relatively low water vapor transmission rate (WVTR). In the illustrated and preferred embodiment, the targeted WVTR is about 0.020 gh−1 at 25° C. and 60% relative humidity.
The particular composition of the water vapor barrier material 332 can vary. In the illustrated and preferred embodiment, the water vapor barrier material 332 comprises an oriented polypropylene material having a thickness of 25 μm.
To prevent degradation of the photoactive material 326 prior to use, the envelope also includes a light filtering material 330 possessing the ability to absorb ambient light energy in the spectrum that activates the photoactive material 326. It has been discovered that, during storage and handling prior to use, the photoactive material 326 absorbs from ambient visible light (400 nm to 700 nm) the spectrum that initiates photoactivation. The incidental absorption of ambient visible light by photoactive material 326 initiates a photoreduction process, creating byproducts that are either partially or completely ineffective for viral inactivation.
For example, exposure of methylene blue to visible ambient light (whose emission spectrum includes the 660 nm region) converts the methylene blue into colorless leucomethylene blue. The leucomethylene blue photoreduction byproduct is not effective in inactivating viruses.
The particular composition of the light filtering material 330 will vary according to the light sensitivity spectrum of the particular photoactive material 326 used. In the illustrated and preferred embodiment, the light filtering material 330 comprises a blue die of phthalocyanine pigments. The blue die material 326 transmits not more than 1% of light in the range of 600 nm to 700 nm, which is the spectrum in which methylene blue is activated.
As FIGS. 2 and 3 show, in the illustrated and preferred embodiment, the overwrap envelope 328 comprises sheets S1 and S2, each of which comprises a multiple layer laminate L1 and L2. The water vapor barrier material 332 constitutes one of the exterior layers of each laminated sheet S1 and S2. The blue die comprising the light filtering material 330 is printed on the interior face of the water vapor barrier material 332.
Each laminated sheet S1 and S2 also preferably includes as another exterior layer a material 334 that flows in response to heat. The presence of the material 334 makes it possible to heat seal the two sheets S1 and S2 together, forming the envelope 328.
The particular composition of the heat flowing material 334 can vary. In the illustrated and preferred embodiment, the material 334 comprises a cast polypropylene material having a thickness of about 25 μm. The heat flowing material 334 can be attached to the layer 332, for example, by a polyurethane-polyester resin-epoxy.
Laminated sheets S1 and S2 as described, with the layers 330, 332, and 334 and suited for use as the overwrap envelope 328, can be purchased from Hosokawa Yoko Co., LTD. (Japan). The sheet material from this company has a weight of 50 g/m2 and density 1.0 g/cm3.
The envelope 328 is created by laying the sheets S1 and S2 of the overwrap laminate together (as FIG. 3 shows) and applying pressure and heat H along the sheet edges in a heat sealing die. The pressure and heat H form a peripheral heat seal 336, which joins the sheets S1 and S2 together, forming the envelope 328 (as FIG. 4 shows).
Despite the presence of the light filtering material 330, the overwrap envelope 328 as above described nevertheless retains sufficient transparency to other visible light spectrums to allow visual inspection of the contents of the overwrap envelope 328, for quality control or customer inspection purposes.
The overwrap envelope 328, including an appropriate light filtering material 330 as just described, can be used in association with other containers or in other systems which hold liquids or other materials sensitive to ambient light degradation. For example, photoactive materials 326 activated in different spectrum regions will require accordingly different light filtering material 330. For example, 4′-(4-Amino-2-oxa)butyl-4,5′8-trimethylpsoralen (S-59) is a photoactive material usable in conjunction with platelet-containing blood suspensions. S-59 is activated by ultraviolet-A light and can undergo intramolecular reactions when exposed to ambient UV-A and short wavelength regions of visible light. To protect against such degradation of S-59 material, the light filtering material 330 can comprise a UV-A absorbent red die.
For another example, as FIG. 10 shows, instead of using a light filtering overwrap envelope 328, the kit 300 (or another system) can include an auxiliary container 362 to store the light activated material 326 before use. The walls of the container 362 include an appropriate light filtering material 330 to protect the light activated material 326 from ambient light degradation before use. In this arrangement, the photoactivated material 326 is transferred from the auxiliary container 362 to plasma before the light activation process, either before or during filtration, or after filtration when the plasma occupies the processing and storage container 302. Of course, a container (like the container 302), which is intended to ultimately serve as a light transparent chamber, must remain free or essentially free of a light filtering material. In this arrangement, it is still desirable to provide an overwrap envelope 364 (shown diagrammatically in FIG. 10) to decrease water vapor loss of the liquid photoactive material 326 during storage and handling prior to use.
The overwrap envelope 328 (or 364 in the FIG. 10 embodiment) is torn away when it is time to use the kit 300. As FIG. 7 shows, a container 338 holding the plasma P is connected in a sterile fashion to the transfer tubing 304 near the air pillow 310. The source container 338 can, for example, hold fresh plasma or plasma that has been frozen and thawed. The plasma is harvested by conventional blood banking procedures. These procedures, which are accomplished through centrifugation of whole blood, yield plasma that is essentially free of red blood cells.
Known sterile connection mechanisms (not shown) like that shown in Spencer U.S. Pat. No. 4,412,835 can be used for connecting the container 338 to the transfer tubing 304. These mechanisms form a molten seal between tubing ends, which, once cooled, forms a sterile weld 360. The air pillow 310 is discarded after sterile connection between the source container 338 and the transfer tubing 304 is made.
As FIG. 7 shows, once the sterile connection is made, the source container 338 is suspended above the processing and storage container 302. The operator checks to assure that the clamp 318 is closed on the bypass branch tubing 308. The operator breaks the cannula 312, and the plasma P flows by gravity head pressure through the filter 306. The leukocyte-reduced plasma exits the filter 306 and drains into the chamber 320 of the container 302.
It has been observed that the triple layer membrane filter 306 described above provides plasma having a leukocyte level that is below the limit of flow cytometer detection (i.e., less than about one leukocyte per μL). The actual residual level of leukocytes in the plasma after filtration by the filter 306 is estimated not to exceed an average theoretical level of 0.004 leukocyte per μL. Based upon an initial leukocyte level of 0.79×108 per L, the leukocyte reduction percentage of the filter 306 is estimated to be about 99.99% (log reduction≧4.0).
The methylene blue photoactive material 326 is mixed with the leukocyte-reduced plasma within the container 302 by manual inversion.
As FIG. 8A shows, after mixing plasma P and photoactive material 326 within the container chamber 320, the clamp 318 is opened and the container 302 squeezed. Air A is vented from the container 302, through the bypass branch tubing 308 back into the source container 338. As FIG. 8A also shows, the venting of air A also displaces residual plasma P, out of the transfer tubing 304 between the filter 306 and the container 302 and into the bypass branch tubing 308. Viruses in the residual plasma P, having never entered the container chamber 320 have not been exposed to the photoactive material 326 and therefore should be removed before undertaking the desired photoactivation process.
As FIG. 8B shows, as air venting proceeds, an amount of the mixture M of photoactive material 326 and plasma P will enter the section 305 of the transfer tubing 304 between the filter 306 and the container 302. The mixture M is allowed to drain back into the container 302. The mixture M flushes this section of the transfer tubing 304 with the photoactive material 326 and plasma mixture. The flushing process assures that viruses still occupying this section of the tubing 304 after air venting will become mixed with the photoactive material 326. This assures that all viruses present in the container 302 and adjacent section 305 of tubing 304 are exposed to the material 326, to thereby assure the desired virucidal effect during subsequent exposure to light irradiation.
After air venting and flushing, as just described, the tubing 305 next to the container 302 is sealed closed using, for example, a dielectric tube sealer. As FIG. 9 shows, the remaining portion of the kit 300 containing the filter 306 is removed and discarded. A remnant of the tubing 305 remains connected to the container 302.
The container 302 holding the methylene blue and leukocyte-reduced plasma, and carrying a remnant of the tubing section 305, is placed into a white light chamber 356 (see FIG. 9). The chamber 356 comprises twelve fluorescent lamps 358, which supply output in the visible range (400 to 700 nm) to both sides of the container 302. The chamber 356 monitors the light intensity and adjusts exposure time to control total light dosage delivered to the container 306. The light activates the methylene blue to release singlet oxygen, which inactivates viruses in the plasma. The approximate time of illumination to deliver a targeted dose of 33 J per cm3 is 30 minutes. Further details of a light chamber can be found in Wolf et al. U.S. Pat. No. 5,290,221 and Bischof et al. U.S. Pat. No. 5,300,019.
After the illumination step, the leukocyte-reduced plasma is frozen within the container 302 at less than −30° C. for storage using conventional blood bank practices. The plasma within the container 302 is thawed when fractionation or transfusion is required.
In the illustrated embodiment (see FIG. 1), the kit 300 includes written instructions 374 for using the kit for its intended purpose. The instructions 374 direct the technician to handle the kit in a prescribed way to best accomplish the desired therapeutic objectives, as set forth in the preceding description and shown in FIGS. 7 to 9.
The instructions 374 may take various forms. Representative instructions 374 direct the technician, upon removal of the overwrap 328, to convey plasma through the tubing 304 from the source 338 through the filter 306 to separate leukocytes from the plasma. The representative instructions 374 also direct the technician to convey leukocyte-reduced plasma through the tubing 304 from the filter 306 to the transfer container 302. The representative instructions 374 also instruct the technician to mix the photoactivated material 326 with the plasma and to expose leukocyte-reduced plasma mixed with the photoactive material 326 to light that activates the photoactive material 326. The representative instructions 374 also direct the technician to store the plasma in the container 302 after the photoactivation process.
The instructions 374 can, of course, include further details based upon the particular configuration of the kit 300. For example, in the context of the kit 300 shown in FIG. 1, the instructions 374 can direct the technician to mix the photoactivated material with leukocyte-reduced plasma within in the container chamber 320. In this context, the instructions 374 can also direct the technician to expose the container chamber 320 to light that activates the photoactive material 326 mixed within the chamber 320 with the leukocyte-reduced plasma. The instructions 374 can also direct the technician to vent air from the container chamber 320 in a path that bypasses the filter 306, which in FIG. 1 comprises the branch tubing 308. The instructions 374 can also instruct the technician to flush the tubing 304 downstream of the filter 306 with plasma and photoactive material 326 from the chamber 320.
A study was conducted to demonstrate the ability of the kit 300 when used in accordance with the instructions 374 to inactivate viruses under intended use conditions. In the study, a maximum plasma volume of 310 mL was employed to provide the lowest concentration of methylene blue and the greatest fluid thickness to be illuminated. In addition, the nominal targeted light dose of 33 J/cm2 was reduced to 24 or 30 J/cm2 to further stress the study conditions.
Plasma was collected from CPD anticoagulated whole blood units following routine blood bank procedures, yielding plasma that is essentially free of red blood cells. The plasma was not frozen prior to treatment during the study.
A panel of viruses was selected to represent the most significant agents that can contaminate fresh frozen plasma and to represent a broad spectrum of physical/chemical forms of viruses (i.e., lipid enveloped and non-lipid enveloped RNA and DNA viruses, as well as intra-cellular viruses). The panel included the following viruses: BVDV (strain Singer); HIV Type 1 (HIV-1, strain IIIB); human herpes simplex virus Type 1 (HSV-1, strain MacIntyre); pseudorabies virus (PRV, strain Aujeszky); simian virus Type 40 (SV-40, strain Pa-57); duck hepatitis B DHBV; and cell associated HIV (H-9/HIV, HIV IIIB chronically infected H-9 cells).
These viruses were added to units of plasma before treatment in physiologically representative concentrations. A process control comprising an aliquot of virus-spiked plasma, was collected from each unit prior to processing in the kit 300. The process control served as the baseline value for the calculation of the virus load reduction, called the log reduction value (LRV). LRV represents either (i) the difference in log virus titers between the process control and the processed sample, or (ii) the difference in log virus titers between the process control and the validated sensitivity limit of the assay, if there was no recoverable virus (indicated by the use of the symbol “>” in the Table 1 below).
The virus panel and the log reduction values (LRV's) obtained by processing the plasma in the kit 300 in accordance with the instructions 374 are summarized in the following Table 1:
Results of Study on Viral
Inactivation Using the Kit 300
at 24 J/cm2
>5.93 ± 0.07
at 24 J/cm2
at 30 J/cm2
5.52 ± 0.38
at 30 J/cm2
>6.16 ± 0.06
at 24 J/cm2
4.27 ± 0.30
at 24 J/cm2
with 1 × 108
Table 1 demonstrates that use of the kit 300 is effective against small and large lipid enveloped viruses with either RNA or DNA genomes. Table 1 also demonstrates the capability of the kit 300 to inactivate certain non-enveloped viruses, which are not resistant to the virucidal action of methylene blue (for example, non-enveloped encephalomyocarditis virus (EMC) has demonstrated a resistance to the virucidal action of methylene blue).
The kit 300 provides more reliability and ease of use than the removal of leukocytes from plasma by lysing using conventional freeze-thaw processes. The kit 300 also provides greater removal of adventitious agents (i.e., viruses) than mere light inactivation (which does not remove intracellular agents) and/or bed-side filtering of plasma (which only removes fibrin clots, and not leukocytes).
FIG. 11 shows, as an alternative embodiment, a kit 300′ sharing many of the component parts of the kit 300 shown in FIG. 1. The common elements (which are assigned the same reference numbers as in FIG. 1) include the processing and storage container 302, the transfer tubing 304, the filter 306, the photoactive material 326, and the frangible cannula 312.
However, the kit 300′ shown in FIG. 11 does not include the branch tubing 308 and the air pillow 310.
Instead, the far end of the tubing 304 in the kit 300′ is closed by a plug 372. The kit 300′ also includes an air reservoir 370 integrally connected to the tubing 304 by the Y-connector 316 between the filter 306 and the container 302.
The air reservoir 370 takes the place of the air pillow 310. Like the pillow 310, the reservoir 370 contains a residual amount of air to prevent collapse of the tubing 304 during steam sterilization. The reservoir 370 also serves as a chamber to receive vented air and residual plasma from the container 302 at the end of the filtration process.
More particularly, using the kit 300′, plasma from the source container 338 is passed for leukocyte reduction through the filter 306 and mixed with the photoactive material 326 in the container 320 in the same manner previously described and shown in FIG. 7.
As FIG. 12A shows, after filtration and mixing, air A is vented from the container 302 into the reservoir 370. Residual plasma P is also displaced out of the tubing section 305 and into the reservoir 370. As FIG. 12B shows, as air venting proceeds, an amount of the mixture M of photoactive material 326 and plasma P will enter the section 305 of the transfer tubing 304 between the filter 306 and the container 302. The mixture M flushes this section of the transfer tubing 304 with the photoactive material 326 and plasma mixture.
In all other respects the process for handling the kit 300′ is the same as previously described with respect to the kit 300.
FIG. 13 shows, as another alternative embodiment, a kit 300″ sharing many of the component parts of the kit 300 shown in FIG. 1. The common elements (which are assigned the same reference numbers as in FIG. 1) include the processing and storage container 302, the transfer tubing 304, the branch tubing 308, the filter 306, the photoactive material 326, the air pillow 310, and the frangible cannula 312. The kit 300″ shown in FIG. 13 includes an additional in-line filter 376 in the transfer tubing 304 downstream of the filter 306. The filter 376 includes a filter media 378 that removes from plasma a second cellular species different than the species removed by the filter media 307, which second cellular species does actually or potentially entrain viral agents. In the illustrated and preferred embodiment, where the principal cellular species targeted by the filter media 307 are leukocytes, the second cellular species targeted by the second filter media 378 are platelets.
As described above in connection with the filter media 307, the pore size of the filter media 378 can be tailored to remove platelets from plasma by exclusion. It is believed that candidate materials for the media 307 formed with a pore size range of between 0.3 μm and 0.45 μm (which is smaller than the pore size range of the media 307) will serve to remove platelets from plasma by exclusion.
The presence of the second, downstream media 378, having a smaller pore size than the first, upstream media 307, also provides added assurance that the cellular species targeted for removal by the first media 307 (i.e., leukocytes) will, in fact, be depleted or essentially depleted from the plasma. In this respect, the smaller pore size media 378 serves both a redundant function of removing leukocytes and an added second step function of removing the smaller platelet species.
It should be appreciated that the second filter media 378 can, instead of being separately housed as the filter 378, be integrated as another layer with the already multi-layer filter media 307.
In all other respects the process for handling the kit 300″ is the same as previously described with respect to the kit 300.
Features and advantages of the invention are set forth in the following claims.
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|U.S. Classification||435/2, 422/44, 424/532, 424/530|
|International Classification||C12N5/06, A61J3/00, A61L2/00, A61K35/16, C12N7/00, A61M1/36|
|Cooperative Classification||Y10S435/975, A61L2/0011|
|23 Jun 1997||AS||Assignment|
Owner name: BAXTER INTERNATIONAL INC., ILLINOIS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HERMAN, ROBERT;CHAPMAN, JOHN;SUN, CHONG-SON;AND OTHERS;REEL/FRAME:008608/0179;SIGNING DATES FROM 19970422 TO 19970613
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domain: chemistry


text:
Keenie Lou Wylie’s Camp Fire Vest
Lubbock youth was an active member of Camp Fire Girls
Keenie Lou Wylie designed and wore this ceremonial vest as an active Camp Fire Girl in Lubbock in the 1950s. As part of the Ao wa ki ya group, Wylie participated in activities that taught her home, health, craft, nature, business, and citizenship skills. Keenie’s younger sister Linda was also a Camp Fire Girl in the early 1960s. Their mother, Mary Francis Wylie, had been a Camp Fire Girl in Dallas in the 1930s and she remained active as a board member for the Lubbock council while her daughters participated.
Camp Fire Girls was founded in 1910 in Maine as a group that would nurture the personal worth of girls so they could realize their greatest potential as women. Officially chartered in 1912, America’s first nonsectarian organization for girls quickly spread throughout the nation. As early as 1912, groups were organized in Corpus Christi, El Paso, and Houston with clubs soon forming in other towns. The Lubbock council to which the Wylie family belonged was founded in 1929.
When Camp Fire began in 1910, it borrowed heavily from Native American imagery, symbolism, and ritual for its ceremonies, uniforms, and programs. At the time, an overly romanticized and simplified view of American Indian cultures was prevalent. The use of imagery and ideals, while problematic by today’s standards, was intended to be complimentary and respectful. Girls were encouraged to create their own Camp Fire name and create a symbolgram that would represent them.
Keenie Wylie designed and planned her symbolgram in her memory notebook, then made it into a felt emblem that she attached to the back of her vest. Her patch included a red heart that rules over all, yellow wings for adventure, and green mountains for climbing higher.
Today, Camp Fire is a co-ed group committed to inclusivity. Its councils in Texas bring together boys, girls, and families of all backgrounds through one organization, where they learn to play together, work together, and appreciate their similarities and differences in positive ways.
Courtesy Camp Fire, Austin
Clothing and Accessories
Time Period: 1946 - 1970
This artifact is not on view.

domain: history


text:
Free essay: introduction in healthcare it is very important to have strong leaders, especially in the nursing profession a nurse leader typically uses. Effective leadership is critical in delivering what leadership styles should senior nurses online learning units on fundamental aspects of nursing care. Effective time management skills for nurses sandi thorson not only works as a registered nurse on 12 up to the plate to take care of household issues so i. Every nurse has leadership the making of a leader an integral part of effective leadership involves the ability to listen and hear what others have. The role of the registered nurse nursing leadership and healthcare administrators to recruit and retain qualified nurses to provide effective, quality care. Home best essay » free essays » nursing: nursing leadership innovation concerning their health care (meyers, nd) the leadership role of the cnls is also.
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domain: medical


text:
- Johnny Depp dresses up as Jack Sparrow to visit children's hospital - TMZ
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Amanda Seyfried & Justin Long: Weekend Outing with Finn!
About Photo #2941458: Amanda Seyfried and her new boyfriend Justin Long step out together to pick up some treats for her beloved dog Finn at Tailwaggers on Saturday afternoon (August… Read More Here

domain: celebrity


text:
When playing casino games online, you’ll want to choose a casino that adheres to high standards. Check that the software is fair and that it provides a mobile app. Also, be sure to look at the customer service. All of these factors will play a huge role in your decision to choose an online casino.
Benefits of playing at an online casino
One of the major benefits of playing at an online casino is that you can play from anywhere and anytime. You can even play from the comfort of your home or on your mobile device. Online casinos also offer a huge selection of games. They are constantly updated with new games so that you can enjoy a wide variety of gaming options.
Online casinos are also convenient and easy to use. All you need to do is sign up for an account and deposit money to play. The rules for the games are clear and easy to read. Many online casinos also have tutorials to help you understand the game rules. Some even allow you to play free games before you decide to put real money on the line.
Casino online sites often feature a variety of games. These can range from roulette to blackjack. Some even offer live dealers via TV to play alongside you. Other games are web-based and can even be played on mobile devices. Blackjack, baccarat, and roulette are the most popular games available. These games vary in complexity and can become quite addictive.
Casino online games often feature bonus items and prizes to encourage players to spend money. Bonuses can range from free spins to real money. Some bonuses are tied to a specific amount of spending, such as making a minimum deposit. Loyalty bonuses are another popular feature of online casinos. Players who play a particular site regularly can earn free merchandise, free tournament entry tickets, and more. These types of bonuses can be highly addictive, so it’s important to monitor your spending habits.
When playing casino games online, players can make deposits with a variety of methods. Most sites accept credit cards or prepaid cards, though there are also other options, including bank wire transfers. While credit cards are the most common way to deposit money in an online casino, they may take several days to process. Other deposit options include e-checks, PayPal, and cryptocurrency.
There are dozens of different credit and debit card options. The most common ones are Visa and MasterCard, though there are some casinos that accept American Express as well. Another option is e-wallets, also called digital wallets. These applications are easy to use and usually do not charge a transaction fee.
An online casino should have an excellent customer service department to assist players with any issues that may arise. The support staff should be available via email, phone, or live chat. A casino that offers live chat service has trained representatives who can answer common questions and provide advice on how to resolve issues. A casino that does not offer live chat will still have customer support available via email or social media. Regardless of the method of contact, online casinos with good customer support departments will keep players satisfied for years to come.
Great customer service is important for online casinos because it can help keep customers from abandoning their accounts or playing in a negative manner. A first-time visitor to an online casino may be uncertain of game rules and payment methods. A great customer service team will help new players navigate the site and explain how to use it, including how to handle their money. Such services will help new customers feel welcome and appreciated, and encourage them to come back to the casino.

domain: gamble


Add:No.27 Jinshitan Industrial Park Dalian China Zip
Oil skimmer has been extensively applied in disposal of light substances on skimming off the liquid surface. Oil skimmers currently in use have such drawbacks that the oil level height to be skimmed is difficult to be adjusted, skimming distance is short, skimming scope is constrained, efficiency is low and stoste is high.
YQ-FOS series floating oil skimmer thoroughly addresses such issues that it can’t skim off liquid scum in a large range, is less prone to control flow amount and skim off liquid level height. The oil skimmer can collect scrum on the surface of the liquid and control oil slimming liquid height by controlling output flow of oil simmer. It is stable in operation.
YQ-FOS series floating oil simmer adopts double-wier-plate independent and adjustable structure. The length of the wire plate is not subject to any restriction. It can reduce over 50% of stoste discharge when compared with that of traditional oil skimmer.
Floating oil skimmer device is installed with acceleration channel for surface liquid that separate the liquid surface into several speedy flowing channels, make scant emulsion of scrum collected and attain effective effects of skimming oil. The floating oil skimmer can be timely switched on and off along with flotation of liquid. It can attain online oil skimming.
YQ-FOS series floating oil simmer mainly consists of floatingwire plate, main body and oriented limit frame. The floating weir plate consists of several turning plates for inlet entrance and is supported by central float bowl. Its main body adopts stainless steel plate to be welded. The equipment is controlled of its freedom by oriented limitation shelf. Outer float bowl provides buoyancy that is floating along with liquid level.
1. Pump type
2. Single weir type
3. Double weir type
1. Stainless steel floating weir plate
2. Stainless steel main body
3. Stainless steel inner floating barrel
4. Stainless steel outer floating barrel
5. Stainless steel oriented limited shelf
Characteristics of the equipment
1. Thickness of oil containing can be automatically adjusted: thickness of oil containing can be automatically adjusted along with oil receiving throughput. Waste oil is low in water;
2. Scope of oil recovery rate is wide: oil receiving amount is 0.01-160 tons per hour;
3. Convenient for use: installation and debugging of oil receiver is convenient and simple with a wide range. The distance between crest of weir to the liquid face is adjusted by ±20～30 millimeters while the rest work is done automatically by the oil receiver.
4. Durable material: all the materials can ensure operation without hindrance and at a long duration in all temperatures.
5. Strong applicability: fluctuation of storm has small impacts on oil receiving. Think oil level with the thickness of a paper can be precisely and automatically adjusted and collected;
6. Ground pump and under-water pump can be configured. Automatic flow means can be in use.
Scope of application
1. metallurgical industry
2. Machinery factory
3. Oil field
5. Metal processing industry
6. Parts cleaning machine
7. Heat treatment system


The World Almanac lists Fort Peck Dam as the largest embankment dam in the United States with the fifth-largest man-made reservoir. It is also the second-largest volume embankment dam and the largest “hydraulic fill” dam in the world.
Hydraulic fill dams are comprised of sediment pumped from the river bottom. The slurry was pumped through miles of huge pipelines to the centerline of the dam. The “core pool,” as it was called, ran the length of the dam, with water slowly draining back to the river while impervious material settled and formed the center of the dam.
Railroad cars then hauled rock and fill material via bridges, dumping their cargo on top of the layered embankment of the dam.
The Fort Peck Dam served as a model of design for the vast majority of major earth-fill dams built after it.
The embankment stretches four miles across the Missouri River Valley and contains 126 million cubic yards of earth fill.
Fort Peck Lake is 134 miles long at a normal operating level, with 1,600 miles of shoreline. Ninety-nine percent of the water released from Fort Peck Dam - or about 6.5 billion gallons per day - passes through the power plant. That translates into 2.8 million kilowatt-hours of pollution-free energy produced each day, on average.
Reprinted from Corps of Engineers brochure.


text:
Look no further – you’ve found the perfect set of artist quality watercolors!
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- Sealed for ultimate freshness
- Presented to perfection
Viridian, Sap Green, Emerald Green, Crimson Red, Scarlet, Vermilion, Orange, Yellow Ochre, Medium Yellow, Misty Rose, Lemon Yellow, Chinese White, Hooker’s Green, Cerulean Blue, Cobalt Blue, Ultramarine Blue, Violet, Prussian Blue, Burnt Sienna, Rose, Raw Umber, Burnt Umber, Paynes Grey and Ivory Black.
Check! Check! Check!
But before we could give these paints the official Castle Art Supplies “seal of approval” we checked two more boxes:
- Great value (hurry as our introductory price won’t be around for long)
- Peace of mind with our Money Back Guarantee+ which means that if you are not entirely happy with your paints we will refund you and you keep the paints.

domain: painting


text:
*** This giveaway has closed. Congratulations to Entry #141 Dezi A.! ***
Surprise! It’s another giveaway! Today I have an awesome product to share with you that I was so excited to have the chance to review. It’s called the Picture Keeper, and I get to give one away to a lucky reader!
So I’m guessing most of you have pictures saved on your computer, right? Maybe it’s photos of your kids or grandkids, snapshots from your travels, or maybe you have photos for your job. How many of you have all those precious photos backed up somewhere other than your computer? Don’t worry, I didn’t either!
As a blogger, I take hundreds of photos a day, trying to get the perfect shot of nachos dripping with cheese or the latest project I’m working on. Of course, I don’t keep every single one, but all those photos add up over time! Not to mention the ridiculous amount of adorable baby photos I have of my children…
I couldn’t imagine what I would do if one day I turned on my computer to find everything was gone. Probably like many of you, backing up all our photos was on a very long to-do that I never seemed to get to, and I wasn’t even sure the best way to do it anyway. So when Picture Keeper contacted me to review their product, I was thrilled. And after using it, I am even more thrilled to show you how cool it is!
Picture Keeper is the easiest way to make a backup copy of your pictures. The device fits in the palm of your hand and has embedded software that does all of the work for you. No software to install, no wires to connect, no monthly fees, and no passwords to remember. Awesome!
With Picture Keeper you can store thousands of pictures (up to 250,000 with the PK Pro), safely and securely. Just plug it in, click start and Picture Keeper automatically finds and saves your pictures, skipping any duplicates. I love that feature! Use it in a digital picture frame, LCD TV, photo kiosks or just store it away. Picture Keeper is both PC and Mac compatible, and once one Picture Keeper is full, the second will pick up right where the first left off. Amazing!
I honestly couldn’t believe how easy this handy, little device was to use. And I feel so much better knowing my pictures are now safe and sound! I stored my Picture Keeper in our fire-proof safe, just in case, and I’m so glad to cross this “project” off my to-do list!
Picture Keeper has 4 different models to choose from:
They range from $29.99 – $189.99 and store anywhere from 4,000 – 250,000 photos, depending on which model you choose.
And today I get to give away a PK 4 to one of you! This little guy holds 4,000 photos (at 1 MB per photo) and is so easy to use!
Of course, if you want to get started backing up your photos right away, you can use the coupon code: lovegrowswild314 to get a 15% discount PLUS free shipping through 3/31/14! Click HERE to shop!
Enter the giveaway below:
This post has been sponsored by Simplified IT Products, LLC – Picture Keeper, and I was sent product to review. All thoughts and opinions are 100% my own.

domain: photo


Six Easy Ways to Enhance Yard Privacy And Deter Mosquitos!
With the arrival of warm weather, more opportunities arise to spend relaxing leisure time outdoors. The beauty of nature inspires most people. Yet the presence of mosquitoes makes even idyllic natural settings uncomfortable and unhealthy. These flying pests pose a significant problem in Ontario.
Consider using six simple strategies to help increase your household’s outdoor privacy, while also deterring unwelcome flying insects. These steps won’t require much effort to implement. We’ve divided them into two broad categories. Have fun enjoying a lovely backyard this summer by using some of these ideas:
Three Helpful Tips to Increase Backyard Privacy
At first glance, it might seem challenging to create a peaceful outdoor retreat in the backyard if your home stands in a busy urban Toronto neighbourhood. Yet, take heart! Today many tools permit property owners to develop verdant green recreational zones even within densely populated city settings:
1. Select Trees And Shrubs With Care
First, consider using some elegant shade trees and shrubs in your landscaping. Both deciduous and evergreen varieties grow well in this region. By carefully selecting the best locations for your plants, you’ll eventually create refreshing, well-shaded grounds.
2. Use Outdoor Roller Shades to Augment Privacy
3. Install Portable Partitions
Privacy Roller Shutters Installation and Repair
Three Tips For Preventing Mosquito Infestations
To prevent swarms of mosquitoes from ruining a lovely garden retreat, you’ll want to rely on some common sense measures. Implementing these steps won’t remove every mosquito from the grounds, of course. However, you’ll discover you encounter fewer problems when you adopt these precautions:
1. Deter Mosquitoes Using Common Sense Tactics
2. Employ Retractable Mosquito Screens
3. Remain Indoors During Peak Mosquito Activity Hours
Finally, don’t rely on a backyard privacy screen alone to protect your household from painful mosquito stings. Limit everyone’s outdoor activities during peak mosquito hours at dawn and dusk. Remaining indoors behind roller screens at these times of the day holds value. You might consider providing breakfasts or casual dinners in screened porches or sunrooms, for example.
Create a Park-Like Backyard Oasis
Combining effective landscaping with the intelligent use of outdoor roller shades and portable partitions permits property owners to engineer lovely garden retreats! Don’t forget to include smart mosquito deterrents in your planning. By removing sources of standing water and insisting upon the use of insect repellents, you’ll avoid exposure to stings. Consider adding retractable screens to porches and sun rooms. By restricting your outdoor activities during dawn and dusk (the hours when most mosquitoes appear), you’ll also reduce your chance of sustaining harmful insect bites. Use all these common-sense measures to enhance your enjoyment of your yard this year.


MIAMI, Aug. 1 (UPI) -- A "disorganized" Tropical Storm Bertha, the second named storm of the Atlantic hurricane season, was headed into the Caribbean on Friday.
Tropical storm warnings were posted for Puerto Rico, the Virgin Islands, St. Lucia, Dominica, Martinique, Culebra and Vieques, meaning that the storm could hit within 24 hours. The National Hurricane Center in Miami said parts of Puerto Rico could be doused with up to 10 inches of rain.
In the Dominican Republic, the government posted a tropical storm watch for the eastern part of the country.
At 11 a.m. AST, Bertha's center was about 150 miles east-southeast of Martinique and 70 miles northeast of Barbados. The storm was moving north-northwest at a speedy 21 mph.
A U.S. Air Force hurricane hunter plane reported Bertha to be "slightly stronger but disorganized." The storm's maximum sustained winds were about 50 mph, with tropical storm winds extending as much as 115 miles from the center.
Forecasters said Bertha was expected to continue on its current course for the next couple of days without getting any stronger.


|Features||Blue Sky Bio||NobelActive®|
|Implants surgically and prosthetically compatible with NobelActive® and NobelReplace CC*||Yes||Yes|
|Compatible with Blue Sky Bio drills||Yes||Yes|
|ActivFluor®** surface treatment for enhanced osseointegration||Yes||No|
|Strong primary stability in all bone types||Yes||No|
|Only one body design needed||Yes||No|
|Platform switched conical connection||Yes||Yes|
|Abutment with integrated impression transfer, eliminating the need for additional implant level impression components||Yes||No|
|Orthopedic Grade 23 – Titanium 6AL-4V ELI (especially important for thin implants)||Yes||No|
*Not compatible with Gold Adapt Non-engaging UCLA abutments.
**ActivFluor is a fluoride modified surface. Various fluoride modified surfaces have been shown in multiple studies to generate a higher bone-to-implant contact (BIC) and higher torque out force significantly earlier than surfaces which are only blasted and not fluoride treated. The enhanced apposition of osteoblasts is primarily achieved by a modified nano topography of the implant surface and not by additional chemical activity. Click here for SEM images.


text:
Article ID: MF201307
Au65Cu18Si17 bulk metallic glass (BMG) exhibits an extraordinary low glass transition temperature (<100°C) and a wide supercooled liquid region. In order to elucidate the structural features of the extraordinary low glass transition temperature and high glass forming ability of the Au65Cu18Si17 BMG, high-energy X-ray diffraction (HEXRD) and Extended X-ray Absorption Fine Structure (EXAFS) measurements were carried out using synchrotron radiation. A sharp first peak and oscillation of the structure factor S(Q) up to the high wave number Q can be attributed to the dominant weighting factor of the Au–Au correlation over others. A reverse Monte Carlo (RMC) simulation was applied simultaneously to the HEXRD and EXAFS data. The obtained RMC model shows a quite highly dense packed structure with large amount of icosahedral type clusters around Au atoms while small ones around Si atoms. The partial Cu–Cu pair distribution function gCu,Cu(r) shows a sharp peak at a short interatomic distance, i.e., 2.38 Å. The Cu–Cu pairs with short interatomic distances and the large thermal fluctuation around Cu atoms are considered to be one of the structural characteristics of the low glass transition temperature of the Au65Cu18Si17 BMG.

domain: physics


ASTON MARTIN V8 VANTAGE
If I had to describe the Aston Martin Vantage in one word, I'd say Awesome!
The Vantage is... drop dead gorgeous!
The Aston Martin Vantage is like no other car we've tested to date. The thing that stood out most with this test drive was the V8 motor. At idle you can only hear the muffled sound of the motor purring, as you accelerate, you hear the motor picking up revs, but when the tacho-needle sweeps past the four grand mark, the mighty 4.3 liter V8 lets you know that "Hey... it's now time to go". With a kick in the seat, the exhaust valves open and the motor is allowed to roar to it's full potential, accelerating away from anything and everything else on the road (with four wheels). You can feel the Aston Martin racing heritage in this car, besides having manigi power, it also hugs the road though corners and stops the 4382mm long, 1866mm wide, 1570kg beaut safely and efficiently. It's great at everything; going, stopping around corners and around town., and the bonus is, it also looks absolutely fantastic. Usually with sports cars, there are some sacrifices that are made, but the Aston Martin has it all. All the modern safety features; like ABS, Traction Control...
the Aston Martin is the MOST EXCITING car I have ever driven... so far
I'm still having wet dreams about the VANTAGE
ASTON MARTIN V8 VANTAGE
The V8 Vantage is a hand-crafted sports car that offers electrifying performance and outstanding agility. The most affordable of all Aston Martins, it fuses traditional Aston Martin style and everyday usability. The result is the world’s most desirable sports car, certainly ours.
EXHILARATING PERFORMANCE, AGILITY, LIGHT WEIGHT AND OUTSTANDING HANDLING
At the heart of every great sports car is a great engine; and in the case of the V8 Vantage, this has never been more true.
The Vantage has a powerful 4.3 liter 283 kW (380 bhp) V8 engine, unique to Aston Martin. This is an engine designed by Aston Martin for Aston Martin. Developed for flexibility as well as outright performance, the front mid-mounted Eight also delivers an outstanding aural experience, as one would expect of an Aston Martin with a potential maximum speed of 280 kph (and we almost got there).
Extraordinary engine power is not the only reason for the superb performance of the Vantage. Just as important is its lightweight, all-alloy structure, which offers class-leading strength and rigidity.
The front mid-engined layout – the dry sump lubrication system allows the engine to sit low – and rear-mid transmission help provide optimum front to rear weight distribution as well as a low centre of gravity. The result is exceptional agility and inspired balance and handling.
DYNAMICS V8 VANTAGE POWERFUL, MUSICAL V8 ENGINE
THE HEART OF A GREAT SPORTS CAR
The Vantage is very fast. With 0-100 km/h in 5.0 seconds (0-60 mph in 4.9 seconds) and a potential maximum speed of 280 km/h (175 mph) its performance figures are as heady as you would expect of an Aston Martin.
V8 VANTAGE SPECIFICATIONS:
Two seat, two door body with rear tailgate. Bonded aluminium structure, Aluminium alloy, steel, composite, and magnesium alloy body. Extruded aluminium side impact bars. Halogen projector headlamps, LED rear lamps.
All alloy quad overhead camshaft 32 valve, 4.3 litre V8, Variable inlet camshaft timing, Dry sump lubrication system, Fully catalysed stainless steel exhaust system with active bypass valves. Front mid-mounted engine Rear wheel drive
Maximum power: 283 kW (380bhp) @ 7300 rpm
Maximum torque: 410 Nm (302 lb.ft) @ 5000 rpm
Maximum speed: 280 km/h (175mph) (we almost got there)
Acceleration: 0-100 km/h (62 mph) in 5.0 seconds, 0-60 mph in 4.9 seconds
Rear mid-mounted six speed manual gearbox, Alloy torque tube with carbon fibre propeller shaft, Limited slip differential
Final drive ratio 3.909:1
Rack and pinion power assisted steering, Column reach and tilt adjust
WHEELS & TYRES
10 spoke lightweight aluminium alloy wheels (standard) Front 8.5J x 18” Rear 9.5J x 18” Bridgestone Potenza tyres Front 235/45 ZR18 Rear 275/40 ZR18, 7 spoke lightweight aluminium alloy wheels, (optional) Front 8.5J x 19” Rear 9.5J x19” Bridgestone Potenza tyres Front 235/40 ZR19 Rear 275/35 ZR19
Independent double aluminium wishbones, Coil over aluminium monotube dampers, Front and rear anti-roll bars
Radial-mounted four piston monobloc calipers. Dynamic Stability Control (DSC). Traction Control. Anti-lock Braking System (ABS). Electronic Brakeforce Distribution (EBD) Emergency Brake Assist (EBA). Positive Torque Control. Ventilated and grooved steel discs (355mm front, 330mm rear)
Technical grain leather and Quantum fabric interior Alcantara and Quantum fabric headlining, Alloy facia, Anthracite interior fittings, 10 way electrically adjustable seats, Automatic temperature control, Heated rear screen, Radio tuner and 6 CD autochanger, Battery Disconnect Switch (BDS), Trip computer, Dual stage driver and passenger airbags, Side airbags, Alarm and immobiliser
Full natural grain leather with full Alcantara headlining, Alternative facia trims (walnut, mahogany, bamboo, piano black), High Intensity Discharge (HID) headlamps (dipped beam) with powerwash, Bright finish grille, Alternative brake caliper finish (black, red, silver), Platinum silver interior fittings, Heated seats, Heated front screen, Cruise control, Reversing sensors, Battery conditioner, Powerfold mirrors, Integrated GSM telephone*, Colour satellite navigation system with optional Traffic Messaging Channel (TMC)*, Tracker Horizon (UK only) Alarm upgrade - tilt and volumetric sensor, Tyre pressure monitoring, Smoker’s pack, Personalised sill plaques, Fire extinguisher, First aid kit
Length 4382 mm (172.5 inches)
Width 1866 mm (73.5 inches) (excluding mirrors) 2022 mm (79.6 inches) (including mirrors) (the mirrors are only there to see the other traffic disappearing in the Aston Martin's dust)
Height 1255 mm (49.4 inches)
Wheelbase 2600 mm (102.4 inches)
Front track 1568 mm (61.7 inches)
Rear track 1562 mm (61.5 inches)
Turning circle (kerb to kerb) 11.1 m (36 feet 5 inches)
Boot capacity 300 litres (10.6 cu.ft) (Like we care how big the boot is).
Fuel capacity 77 litres (16.8 UK gal / 20.2 US gal) Cd 0.34
Weight 1570 kg (3461 lb)
*Not available in all markets, please consult your dealer for details. Dealers will be in Sandton (Nick Naylor Tel: 011 509 5100), Cape Town, and Durban.
Aston Martin Lagonda Limited, Banbury Road, Gaydon, Warwickshire, CV35 0DB England.
it should be called the Aston Martin Ad-vantage
the Aston Martin was better than sex... I think
sleek and very, very fast
now I know how 'James' would feel
This thing is fast, very fast and very, VERY lekker
Now how would you sum a car like this up, in one word?
Thanks to Clifford Joffe (Marketing Director for Aston Martin),
and Aston Martin Sandton for the drive in their dynamic V8 Vantage.
I just couldn't resist putting this picture in... one day when I win the lotto I'll have one.
Made me feel like two million Dollars - Photo by Dylan Slater


NTPC Ltd, India’s largest integrated power producer, in its endeavour towards 100% utilisation of fly ash, has invited expression of interest (EOI) for the sale of fly ash from the designated ports of the Middle East and other regions.
The tender application commenced on 1 July 2021, will conclude on 25 July 2021.
Sustainable ash utilisation is one of the key concern areas at NTPC, and the company is ensuring sustainable solutions for complete utilisation for it. Fly ash is a by-product of power generation with coal, and the fly ash generated at NTPC stations is ideal for use in the manufacture of cement, concrete, concrete products, cellular concrete products and for bricks/blocks/tiles.
NTPC Ltd has collaborated with cement manufacturers around the country to supply fly ash. The power producer is leveraging Indian Railways’ sprawling network to transport fly ash in an economical and environment-friendly manner.
To promote the use of fly ash bricks in building construction, NTPC has set up fly ash brick manufacturing plants at its coal-based thermal power plants. These bricks are being utilised in plants, as well as township construction activities exclusively. On average, 60 million fly ash bricks are being manufactured annually by NTPCs own fly ash brick plants.
As per the MoEF&CC directives, NTPC stations are keeping at least 20% of total fly ash produced in reserve for the issue to fly ash brick/blocks/tiles manufacturers and issuing fly ash free of cost to them. Approximately 9% of the total fly ash produced in NTPCs stations is being utilised by fly ash bricks/blocks and tiles manufacturing units annually.
Further, during 2020 – 2021, almost 15 NTPC station supplied fly ash to various road projects and ash utilisation crossed by nearly 20 million t. Over the last 5 years, fly ash utilisation has grown up by 80% in the country.
Read the article online at: https://www.worldcoal.com/coal/05072021/ntpc-invites-eoi-for-sale-of-fly-ash/
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Martin Engineering has restructured its Italian business and relocated to a new purpose-built facility to boost customer service and accelerate growth.


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It is with a heavy heart that brings me to announce the passing of one of my own. Sometimes our lives take strange, winding roads. Sometimes, we find ourselves in places we never imagined in our wildest of dreams. Sometimes, life takes our breath away for wonderful reasons and sometimes for horrible reasons. Sometimes, we feel as though life is cruising in the sunshine and sometimes it feels as though the torrent is unrelenting. Sometimes, we turn a corner to find unexpected horror and sometimes unexpected beauty.
The most recent turn in our family’s road has brought us to our knees…yet again. Kaden was passed from my care to his father’s Saturday evening, when he took his own life. His father, who passed 3 1/2 years ago, was waiting with open arms to gather in his little boy. He is taking over the privilege of raising him, it is his turn now. It breaks my mother heart to relinquish the time I had with Kaden after only 16 1/2 years, not nearly not nearly not nearly long enough.
Once upon a time, a local community, a church family, a circle of the truest friends, and a mortal family came to our aid in a mobilization of love and support so swift, so effective and so completely, it would rival the best of the world’s militaries. Yet again, and sure enough, a different local community, a different church family, those same true friends, and that same mortal family answered the call once again in the same miraculous fashion. I shake my head in wonder at the ability and sheer power of a force of people united in love and purpose. That power is enough to fight back the darkness that threatens to overwhelm in times such as these. To watch my fellow man, some known to me and some not, step onto a battlefield to stand between my family and the impending darkness and sorrow at such a time, swords of service and love and action drawn…words cannot express the humility and gratitude I feel. To the depths of my very soul…I thank you. My children thank you. Spencer thanks you. Kaden thanks you. From my little family, some here, some on the other side…we thank you.
I have seen much sorrow in life, but it has also afforded me unprecedented access to peek behind the curtain and bear witness to the real mettle of my fellow man…to truly see what people are made of. And my friends, make no mistake…people are made of the stuff of angels.
Although God and I have had our differences over the years as I’ve struggled to understand the plan for my life, I have never doubted that there is a God, that He loves us to pieces, and that He has a grand plan in play for our lives. Jesus Christ is real, my friends. His love is real, His healing power is real, His ability to succor us perfectly and uniquely is real, the fact that He is my Brother is real. I’m not going to pretend that knowledge makes the pain any less right now, but it allows me to grieve in the light instead of the dark.
Lastly, suicide is real. It haunts our children who struggle and brings fear to the parents who battle it out in the trenches to save their children. I am no expert but I’ve lived through enough to know this…when we hold our anger, our fear, our grief, our sorrow…when we hold our stories inside, they make our hearts sick. Those feelings left unsaid for too long or too many times, they will poison our heart and eventually our minds to the point it proves fatal...ending in suicide. Feelings of that nature are not meant to stay in the dark. Satan does his best work in the dark, he is most effective in the dark. Every time we choose to give a sincere and truthful voice to our hurt and release the pain by telling our story to a parent or counselor or teacher or leader or trusted healthy friend, it’s a dose of antibiotics for the heart. It wards off sickness. Don’t keep secrets about the way you feel. Sometimes all that is needed is for us to be able to share our story and have someone look into our eyes and say, “I see you. I hear you. I feel what you are saying. Now I have a little bit of your story and I will hold it for you so it isn’t so heavy and you aren’t carrying it alone anymore.” Few things in the human experience are more beautiful than two of God’s children connecting in a moment of realness and validating each other’s experience. We must be brave and open our mouths to release our story. We must be brave and prepare ourselves to be a safe place for their words. To the parents of hurting children: Don't assume that because they aren't talking they don't have anything to say. Petition them, lovingly prod, coax their story from the dark to the light. My friends that are hurting: Say it. Speak it. Release it. Give it a voice. Bring those feelings out of the dark and into the light. It could save your very life #justsayit
I know many of you want to share your love and offer your condolences. We will bury Kaden as a family and grieve more privately this time. However, we want anyone and everyone, whether you know him or not…to come celebrate him with us at an open house Saturday night, April 27, 2019 from 6:00 -8:00 pm at the church located at 1250 East 200 South, Pleasant Grove, Utah. Casual dress .
Hope Squad, Your Tribe Clothing and JDawgs will be there.
Please come and grieve IN THE LIGHT.
Please feel free to share
To send flowers to the family or plant a tree in memory of Kaden Spencer Tressler, please visit our floral store.

domain: philosophy


text:
Welcome to trubee's Member Page
We live in Los Angeles in a beautiful canyon area and we’re in the process of building a home in Kayenta - a magical red rock area in sw Utah. As an avid cook and entertainer, I haunt the kitchen forums - especially as I am planning our dream kitchen in Utah
I live in: United States
My favorite forum 1 is Building a Home.
My favorite forum 2 is Kitchens.
First registered on February 15, 2006 .

domain: geography