text:
|8 mei 2003
|8 nov 2001
|8 nov 2001
|Ook gepubliceerd als
|Timothy Ringeisen
|Oorspronkelijke patenteigenaar
|Timothy Ringeisen
|Citatie exporteren
|BiBTeX, EndNote, RefMan
|Patentcitaties (5), Verwijzingen naar dit patent (18), Classificaties (53), Juridische gebeurtenissen (1)
|Externe links: USPTO, USPTO-toewijzing, Espacenet
[0001] 1. Field of the Invention
[0002] The present invention relates to an improved porous polymer useful for various applications in industry, including the medical industry, for example, as a biological prosthesis and particularly useful in vascular surgery. The porous polymer can be made by use of a new gel enhanced phase separation technique, which, among other advantages, permits enhanced shape-making capability.
[0003] 2. Statement of Related Art
[0004] The present invention encompassing polymer engineering and processing came about from efforts to improve existing properties of porous polymers, including medical devices and prostheses and, in particular, medical devices (e.g., vascular grafts). Accordingly, a review of the vascular graft art is appropriate.
[0005] The search for the ideal blood vessel substitute has to date focused on biological tissues and synthetics. Despite intensive efforts to improve the nature of blood vessel substitutes many problems remain, such as increasing failure rate with decreasing caliber of the blood vessel substitute, a high failure rate when infection occurs, and aneurysm formation. The major need for vascular grafts is for adequate supply of blood to organs and tissues whose blood vessels are inadequate either through defects, trauma or diseases. Vascular grafts are also needed to provide access to the bloodstream for individuals undergoing hemodialysis. The three major types of vascular grafts are peripheral, arterial-to-venous access, and endovascular.
[0006] Peripheral grafts are those used in the neck and extremities, with the most common being used in the leg. This results in supply problems being some intermediate and most small diameter arteries are replaced or bypassed using an autologous saphenous vein, the long vein extending down the inside of the leg, with a secondary source being the radial veins of the arms. In a given patient, suitable veins may be absent, diseased or too small to be used, and removal of the vein is an additional surgical procedure that carries attendant risk.
[0007] Additionally, arterial-to-venous access grafts are used to access the circulatory system during hemodialysis. Vascular grafts used in connection with hemodialysis are attached to an artery at one end and sewn to a vein at the other. Two large needles are inserted into the graft. One needle removes the blood where it flows through an artificial kidney machine and is then returned to the body via the second needle. Normal kidney function is destroyed by several acute and chronic diseases, including diabetes and hypertension. Patients suffering from kidney failure are maintained by dialysis three times a week for approximately four hours per session. Due to the constant punishment these grafts undergo, there is a high occurrence of thrombosis, bleeding, infections, and pseudoaneurysm.
[0008] Endovascular grafts are used to reline diseased or damaged arteries, particularly those in which aneurysms have formed, in a less invasive manner than standard vascular surgical procedures. Various surgical techniques and materials have been developed to replace and repair blood vessels. Ideally, the thickness of the prosthesis is minimized, so that it can be delivered to the implantation site using a percutaneous procedure, typically catheterization and kept in place utilizing stents. Problems associated with this type of implantation include thrombosis, infection and new aneurysm formation at the location of the stent.
[0009] Initially, autografts were used to restore continuity; however, limited supply and inadequate sizes forced the use of allografts from both donor and umbilical cord harvest such as that described in U.S. Pat. No. 3,974,526. Development of aneurysms and arteriosclerosis as well as the fear of disease transmission necessitated the search for a better substitute. Artificial vascular grafts are well known in the art. See for example U.S. Pat. No. 5,747,128; U.S. Pat. No. 5,716,395; U.S. Pat. No. 5,700,287; U.S. Pat. No. 5,609,624; U.S. Patent No. 5,246,452 and U.S. Pat. No. 4,955,899. Development of two different fibrous and pliable synthetic plastic cloths revolutionized vascular reconstructive surgeries. Whenever suitable autograft was not available woven grafts of polyethylene terephthalate (Dacron®) and drawn out polytetrafluoroethylene (Teflon®) fibrils as defined in U.S. Pat. Nos. 3,953,566; 4,187,390 and 4,482,516 were used. Even though these products were widely used they did have many drawbacks including infection, clot formation, occlusions and the inability to be used in grafts smaller than 6 mm inside diameter due to clotting. Additionally, the graft had to be porous enough so that tissue ingrowth could occur, yet have a tight enough weave to the fibers so that hemorrhage would not occur. This made it necessary to pre-clot these grafts prior to use. Recently, vascular prostheses have been coated with bioabsorbable substances such as collagen, albumin, or gelatin during manufacture instead of preclotting at surgery. For purposes of this patent disclosure, the term "bioabsorbable" will be considered to be substantially equivalent to "bioresorbable", "bioerodable", "absorbable" and "resorbable".
[0010] Compliance problems with woven polyethylene terephthalate and drawn out polytetrafluoroethylene prompted interest in thermoplastic elastomers for use as blood conduits. Medical grade polyurethane (PU) copolymers are an important member of the thermoplastic elastomer family. PU's are generally composed of short, alternating polydisperse blocks of soft and hard segment units. The soft segment is typically a polyester, polyether or a polyalkyldoil (e.g., polytetramethylene oxide). The hard segment is formed by polymerization of either an aliphatic or aromatic diisocyanate with chain extender (diamine or glycol). The resulting product containing the urethane or urea linkage is copolymerized with the soft segment to produce a variety of polyurethane formulations. PU's have been tested as blood conduits for over 30 years. Medical grade PU's, in general, have material properties that make it an excellent biomaterial for the manufacture of vascular grafts as compared to other commercial plastics. These properties include excellent tensile strength, flexibility, toughness, resistance to degradation and fatigue, as well as biocompatiblity. Unfortunately, despite these positive qualities, it became clear in the early 1980s that conventional ether-based polyurethane elastomers presented long-term biostabilty issues as well as some concern over potential carcinogenic degradation products. Further, in contrast to excellent performance in animal trials, clinically disappointing results with PU-based grafts diminished the attractiveness of the material for this application.
[0011] Recent developments in new generation polyurethanes, however, have made this biomaterial, once again, a promising choice for a successful long-term vascular prosthesis. Specifically, the new generation of polyurethanes solved the biostabality problems but still provide clinically disappointing results. Poor performance is largely due to limitations of current manufacturing techniques that create a random or non-optimal fibrous structure for cell attachment using crude precipitation and/or filament manufacturing techniques. (U.S. Pat. Nos. 4,173,689; 4,474,630; 5,132,066; 5,163,951; 5,756,035; 5,549,860; 5,863,627 & WO 00/30564)
[0012] Nonwoven or non-fibrous polyurethane vascular grafts have also been produced, and various techniques have been disclosed for swelling and/or gelling polyurethane polymers.
[0013] U.S. Pat. No. 4,171,390 to Hilterhaus et al. discloses a process for preparing a filter material that can be used, for example, for filtering air or other gases, for filtering gases from high viscosity solutions, or for preparing partially permeable packaging materials. A first solution containing an isocyanate adduct dissolved in a highly polar organic solvent is admixed into a second solution containing a highly polar organic solvent and a hydrazine hydrate or the like. The first solution is admixed into the second solution over an extended period of time, during which time the viscosity of the admixture increases as the hydrazine (or the like) component reacts with the isocyanate to produce a polyurethane. The first solution is added up to the point of instantaneous gelling. The final admixture is coated onto a textile reinforcing material, and the coated material is placed in a water bath to coagulate the polyurethane. The resulting structure features a thin, poreless skin that must be removed, for example, by abrasion, if the structure is to be useful as a filter.
[0014] U.S. Pat. No. 4,731,073 to Robinson discloses an arterial graft prosthesis comprises a first interior zone of a solid, segmented polyether-polyurethane material surrounded by a second zone of a porous, segmented polyether-polyurethane, and usually also a third zone surrounding the second zone and having a composition similar to the first zone. The zones are produced from the interior to the exterior zone by sequentially dipping a mandrel into the appropriate polymeric solution. The porous zone is prepared by adding particulates such as sodium chloride and/or sodium bicarbonate to the polymer resin to form a slurry. Once all of the zones have been formed on the mandrel, the coatings are dried, and then contacted to a water bath to remove the salt or bicarbonate particles.
[0015] U.S. Pat. No. 5,462,704 to Chen et al. discloses a method for making a porous polyurethane vascular graft prosthesis that comprises coating a solvent type polyurethane resin over the outer surface of a cylindrical mandrel, then within 30 seconds of coating, placing the coated mandrel in a static coagulant for 2-12 hours to form a porous polyurethane tubing, and then placing the mandrel and surrounding tubing in a swelling agent for 5-60 minutes. After removing the tubing from the mandrel, the tubing is rinsed in a solution containing at least 80 weight percent ethanol for 5-120 minutes, followed by drying. The coagulant consists of water, ethanol and optionally, an aprotic solvent. The swelling agent consists of at least 90 percent ethanol. The resulting vascular graft prosthesis features an area porosity of 15-50 percent and a pore size of 1-30 micrometers.
[0016] U.S. Pat. No. 5,977,223 to Ryan et al. discloses a technique for producing thin-walled elastomeric articles such as gloves and condoms. The method entails dipping a mandrel modeling the shape to be formed into a coagulant solution, then dipping the coagulant coated mandrel into an aqueous phase polyurethane dispersion, removing the mandrel from the dispersion, leaching out any residual coagulant or uncoagulated polymer, and finally curing the formed elastomeric article. When the polyurethane dispersion comprises by weight about 1 to 30 parts per hundred of a plasticizer based on the dry polyurethane weight, the dispersed polyurethane particles swell. Thus, if the dispersion featured polyurethane particles having a mean size between 0.5 and 1.0 micrometer in the unplasticized condition, they might be between 1.5 and 3.0 micrometers in the plasticized condition. The inventors discovered that such swollen polyurethane particles produce a superior product, whereas in an unplasticized condition, particles of such a size (1.5-3.0 micrometers) impede uniform drying because of the large interstitial space between particles. Preferred coagulants are ionic coagulants such as quaternary ammonium salts; preferred plasticizers are the phthalate plasticizers.
[0017] In each instance, there are severe shape-making limitations, e.g., the known non-fibrous methods appear to be limited to working with a relatively low viscosity liquid that can be coated onto a surface, or into which a shape-forming mandrel can be dipped. It would be desirable if the polymer could be rendered in the form of a gel because a gel, inter alia, can be molded. In other words, the gel can be plastically shaped and can retain its molded shape without reverting to its original shape. Usually the molded shape is preserved so that the shaped polymer retains the new shape and will return to the new shape if deformed, provided that the elastic limit is not exceeded. Further, most of the above-discussed non-fibrous art results in a product that features a non-porous layer at least at some location in the product. Thus, the prior art does not seem to appreciate the desirability of a prosthesis such as a vascular graft containing channels or porosity extending continuously from the exterior surface to the luminal surface of the graft.
[0018] One of the reasons for failure of vascular grafts is due to the formation of acute, spontaneous thrombosis, and chronic intimal hyperplasia. Thrombosis is initiated by platelets reacting with any non-endothelialized foreign substance, initiating a platelet agglomeration or plug. This plug continues to grow, resulting in occlusion of the graft. If the graft is not immediately occluded the plug functions as a cell matrix increasing the potential for rapid smooth muscle cell hyperplasia. Under normal circumstances, platelets circulate through the vascular system in a non-adherent state. The endothelial cells lining the vascular system accomplish this. These cells have several factors that contribute to their non-thrombogenic properties. These factors include, but are not limited to, negative surface charge, the heparin sulfate in their glycocalyx, the production and release of prostacylin, adenosine diphosphate, endothelium derived relaxing factor, and thrombomdulin. Thus, adherence of a thin layer of endothelial cells to the vascular prosthetic results in enhanced healing times and reduced failure rates of the graft.
[0019] Other reasons for artificial graft failure are neointima sloughing due to poor attachment and aneurysm formation resulting from compliance mismatch of the new graft material to the existing vascular system. It is important to know that materials with different mechanical properties, when joined together and placed in cyclic stress systems, exhibit different extensibilities. This mismatch may increase stress at the anastomotic site, as well as create flow disturbances and turbulence. Additionally, poor attachment geometry can lead to the problematic results above, due to flow disturbances and turbulence. For example, the harvesting of autograft veins typically causes a surgeon to use a graft of non-optimal diameter or length. A graft diameter mismatch, of perhaps 60% or more, causes a drastic reduction in flow diameter. Such flow disturbances may lead to para-anastomotic intimal hyperplasia, anastomotic aneurysms, and the acceleration of downstream atherosclerotic change.
[0020] Finally, artificial graft failures have been linked to leaking of blood through the device. Pre-clotting and the addition of short-lived bioabsorbable substances such as collagen, gelatin and albumin can prevent this as well as provide a matrix for host cell migration into the prosthesis. One problem with this approach is that the same open fibrous weave that permits blood leaking also allows the viscous bioabsorbable substances and clotted blood to accumulate on the luminal surface and easily detach resulting in complications (e.g., emboli) downstream from the device.
[0021] The present invention manufactured through a novel gel enhanced phase separation technique solves the above listed problems that occur in existing vascular prostheses, both fibrous and non-fibrous.
[0022] According to the method of the present invention, a porous polymer is prepared by dissolving the polymer in a solvent and then adding a "gelling solvent". The "gelling solvent" for the polymer is not to be confused with a "non-solvent", which is a substance that causes the polymer to precipitate out of solution. The non-solvent is sometimes referred to interchangeably as the "coagulant" or the "failed solvent". Unless indicated otherwise, for purposes of this invention, the solvent that dissolves the polymer is interchangeably referred to as the first solvent, and the gelling solvent is interchangeably referred to as the second solvent.
[0023] Significantly, when a "gelling solvent" is added to a polymer/solvent solution the polymer does not precipitate out as it would with a "non-solvent". Instead, the entire volume begins to thicken as the dissolved polymer absorbs the "gelling solvent". As more "gelling solvent" is added, the viscosity of the entire volume increases to the point where it becomes a gelatinous mass that can be picked up, e.g., a stable gel. This gel can then be spread out onto plates or transferred into molds. The plates or molds can then be immersed into a non-solvent that leaches the original solvent from the gel or placed under vacuum to pull the solvent from the gel, leaving an intercommunicating porous network. The unit is then cured for several hours in an oven to permanently set the architecture. Varying the concentration of polymer in the first solution and/or the concentration of the "gelling solvent" added will reproducibly alter the porosity. Polymers useful for the creation of the finished article (e.g., a tubular prosthesis) include but are not limited to the following groups: a) polyurethanes; b) polyureas; c) polyethylenes; d) polyesters; and e) fluoropolymers.
[0024] The articles created using this technique include, but are not limited to, a non-metallic, non-woven, highly porous graft material having an inner surface and an outer surface, and having a plurality of openings throughout its bulk providing a highly convoluted intercommunicating network of chambers between its two surfaces, the walls of the chambers providing a large surface area. In part, it is this highly porous, convoluted intercommunicating network of chambers that allows the present invention to overcome problems that have plagued previous vascular grafts.
[0025] The creation of a stable gel that can be injected into finely detailed molds without risk of clumping of the precipitate or salt, is a vast improvement over existing technologies. This gel will open up the possibility of mass production of complex prostheses, including heart valve, bladder, intestinal, esophagus, urethra, veins and arteries, via an automated system. Additionally, articles produced through the practice of this invention include larger components, with complicated geometries, and unique density-property-processing relationships; of which, these articles may be used in various industries (e.g., automotive, consumer goods, sporting goods, etc.).
[0026] FIGS. 1-10 are Scanning Electron Microscope (SEM) images of four different vascular grafts made from four different species of polymer using the gel enhanced phase separation technique;
[0027]FIG. 11 is an optical photograph showing a pattern of tissue invasion into the porosity of the graft;
[0028]FIG. 12 is a schematic illustration of the polymeric microstructure in the prior vascular grafts (right drawing) versus the polymeric microstructure in the vascular grafts of the present invention (left);
[0029]FIGS. 13a-13 c show a possible embodiment of the present invention allowing for improved suturing; and
[0030]FIGS. 14a-14 d show various embodiments of the present invention made possible by the gel enhanced phase separation technique.
[0031] While working with several different species of polymer, a new and unique method for controlled incorporation of intercommunicating pores within the polymers was discovered. In a preferred embodiment, the method for preparing the porous polymers involves dissolving the polymer in a solvent and then adding a "gelling solvent". The "gelling solvent" for the particular polymer is not to be confused with a "non-solvent" that causes the polymer to precipitate out of solution. Solid polymer particles placed in contact with a gelling solvent swell as they absorb the gelling solvent and take on fluid like properties but do not loose cohesiveness and remain as discrete, albeit swollen particles.
[0032] A common example of this phenomenon exists in the polymers used to make soft contact lenses. Hydroxyethylemethacrylate (HEMA) can achieve water contents ranging from 35% to 75% when immersed. The water is absorbed into this solid brittle polymer and transforms it into a swollen soft mass. Water functions as a "gelling solvent" for this polymer.
[0033] When a "gelling solvent" is added to a polymer/solvent solution, the polymer does not precipitate out as it would with a "non-solvent". Instead, the entire volume begins to thicken as the dissolved polymer absorbs the "gelling solvent". As more "gelling solvent" is added the whole mass turns into a gelatinous mass that can be picked up. If the beginning polymer/solvent volume was 20 ml, and 20 ml of "gelling solvent" were added, the result would be 40 ml of gel. This gel can then be shape-formed, e.g., molded, for example, by spreading or injecting the gel over a plate or a three-dimensional object, or by forcing a plate or three-dimensional object into the gel. The plates or molds can then be immersed into a non-solvent that leaches the original solvent from the gel. Alternatively, the plates or molds may be placed under vacuum to pull the solvent from the gel, leaving an intercommunicating porous network. The unit is then cured for several hours in an oven to permanently set the architecture. (In most cases the gelling agent is also removed in the leaching or vacuum process.) Varying the polymer concentration in the original solution and/or varying the concentration of the "gelling solvent" added will reproducibly alter the porosity. For example, the lower the concentration of polymer, the more porous is the final product. Polymers useful for the creation of the final article include but are not limited to the following groups: a) polyurethanes; b) polyureas; c) polyethylenes; d) polyesters; and e) fluoropolymers.
[0034] The articles created using the techniques of the current invention include a non-metallic, non-woven highly porous graft material having a plurality of openings throughout its substance providing a highly convoluted intercommunicating network of chambers between its two surfaces, the walls of the chambers providing a large surface area. In part, it is this highly porous, convoluted intercommunicating network of chambers that allows the present invention to overcome problems that have plagued previous vascular grafts, and further offers unique properties useful to the various aforementioned industries and product types.
[0035] Similar appearing technologies that utilize simple phase separation/precipitation in non-solvents or leaching of solid particles such as salt are difficult if not impossible to reproduce on a large scale due to their demand for constant skilled human interaction. Additionally they are limited in the final conformation of medical device formed. The creation of a stable gel, which can be injected into finely detailed molds without risk of clumping of the precipitate or salt, is a vast improvement over existing technologies. This gel will open up the possibility of mass production of complex articles such as, for example, prostheses, including heart valve, bladder, intestinal, esophagus, urethra, veins and arteries, via an automated system. A specially designed press can be used for injection of the gel into custom molds containing wings, flaps, ribs, waves, multiple conduits, appendages or other complex structures unavailable to prior art devices. The molds will then move to an immersion and/or vacuum chamber to remove the dissolving solvent and "gelling solvent", after which the devices are placed into a curing oven.
[0036] Composite or multifaceted materials can be fabricated by placing the gel in contact with one or more other materials. Examples of such other materials include, but are not limited to, biologically active agents, and biodegradable or non-degradable sutures or fibers and reinforcement rings. The gel could be, for example, injected over a suture, or injected into a mass of fibers. Additionally, two different gels composed of different polymer concentrations or polymers can be layered on top of or mixed with each other to create laminates and composites previously unknown. At this point, at least the gel portion of the resulting mass is still shapeable (e.g., moldable), and accordingly can be shaped by known techniques to the desired geometry. The solvent is then removed as described previously, leaving the porous polymer material and the other material mechanically attached to one another. The resulting composite body could represent the entire article, or it could be merely a component of a larger article (e.g., an entire prosthesis or simply a component thereof).
[0037] As suggested by the above embodiment of injecting the gel into a mass of fibers, one or more reinforcement materials (e.g., particulate, fibers, whiskers, woven materials, etc.) may be incorporated or admixed with the present polymers by known techniques. A very typical reason for incorporating such a reinforcement (but by no means the sole reason) is to enhance certain physical properties such as strength, stiffness, etc.
[0038] In the prosthesis embodiment of the invention, it is the intent to allow uninterrupted tissue connection, e.g., contiguous tissue, to exist throughout the entire volume of the prosthesis. Thus when a neointima forms across the lumen of the prosthesis, it is not only attached to the surface of the graft material, but additionally anchored to the tissue growing through the prosthesis. Once fully integrated with tissue, the graft is hidden by the newly formed endothelial cell lining from the blood flowing through it and thus benefits from the endothelial cells' non-thrombogenic properties.
[0039] Additionally, the material produced by this preferred teaching of the present invention may occupy only a small fraction of the overall volume of the device. This allows the tissue within the device to dictate the mechanical properties of the device preventing a compliance mismatch of the graft material to the existing vascular system.
[0040] Finally, the unique arrangement of intercommunicating chambers 30 within the device 10 manufactured by the process of the current invention prevents leaking of blood through the device by slowing the movement of blood through the thickness of the unit many times over, allowing it to clot and self-seal. The fibrous structure 50 in state of the art grafts 20 provides rounded cylinders 40 throughout the mass of the device (see FIG. 12, left side). These cylinders provide a low surface area and thus relatively low resistance to flow. To compensate for this, the density of cylindrical fibers 40 must be increased, reducing the overall porosity of the unit. The present invention overcomes this by providing thin flat plates 60 of polymer material having a relatively large surface area to disrupt flow through the chambers 30 defined by the flat surfaces (FIG. 12, right). The large surface area of each individual chamber slows the movement of blood, creating small interconnecting clots. These clots are then trapped within the internal chambers of device and cannot be sloughed off into the blood stream.
[0041] In another aspect of the present invention, other bioabsorbable substances can be impregnated into the chambers of the device and be protected from the circulating blood. For example, it may be beneficial to incorporate the bioabsorbable substance into the chambers as a liquid and freeze-dry it to form a microstructure. This microstructure, particularly if it is soluble in tissue fluids, can then be cross-linked or in some other way stabilized so that it typically must be degraded to be removed from the prosthesis. Incorporation of the stabilized microstructure can then be used to fine-tune the properties of the graft to that of the host vessel. The purpose of the microstructure is at least four-fold: (i) provide a temporary pore seal to further increase resistance to flow through the thickness of the unit; (ii) increase the biocompatibilty of the overall prosthesis for cellular attraction and attachment; (iii) provide for control of mechanical properties other than via concentration of constituents of the gel-enhanced phase separation process; and (iv) provide a medium for the delivery of biologically active agents to, for example, mediate or moderate the host response to the implant graft.
[0042] Useful bioabsorbable substances include collagen, gelatin, succinylated collagen, chondroitin sulfate, succinylated gelatin, chitin, chitosan, cellulose, fibrin, albumin, alginic acid, heparin, heparan sulfate, dermatin sulfate, keratan sulfate, hyaluronic acid, termatan sulfate, polymerized alpha hydroxy acids, polymerized hydroxy aliphatic carboxylic acids, polymerized glycolic acids and derivatives of these members.
[0043] Representing yet another important aspect of the present invention, an additional benefit of the microstructure isolation within the intercommunicating chambers is the ability to carry and retain one or more biologically active agents within the article or prosthesis. The biologically active agents can promote healing and tissue invasion, and are protected from the flowing blood. These biologically active agents include physiologically acceptable drugs, surfactants, ceramics, hydroxyapatites, tricalciumphosphates, antithrombogenic agents, antibiotics, biologic modifiers, glycosaminoglycans, proteins, hormones, antigens, viruses, cells and cellular components. The biologically active agent can be added to the microstructure before or after cross-linking. Moreover, the biologically active agent can be added during the gel enhanced phase separation process for producing the porous polymeric material. For example, the biologically active agent can be mixed with the polymer and first solvent prior to addition of the gelling solvent; it can be mixed with the gelling solvent prior to addition of the gelling solvent to the polymer/first solvent solution; or it can be mixed with the gel prior to removal of the solvents. Still further, the biologically active agent can be incorporated within the pores of the polymeric material after removal of the solvents.
[0044] Among the non-limiting advantages of using the present non-woven architectured synthetic implant instead of autograft or allograft as vascular grafts are the following:
[0045] 1. sterile off-the-shelf implant;
[0046] 2. availability of multiple diameter and length implants;
[0047] 3. can be molded into unique shapes and designs to improve handling characteristics;
[0048] 4. lowered risk of aneurysm;
[0049] 5. no risk of disease transmission;
[0050] 6. allows for easy ingrowth of fibrous tissue, which stabilizes and anchors the implant.
[0051] 7. allows for vascular ingrowth (vasa vasorum) nourishing the graft and providing access to free floating stem cells.
[0052] 8. the graft is straight, flexible and can be twisted in any direction. (This is a major advantage over autografts and allografts that must be implanted in their original shape to avoid complications.)
[0053] 9. allows for incorporation of bioabsorbable substances to improve biocompatability.
[0054] 10. allows for incorporation of biologically active agents to aid in healing.
[0055] 11. can be fabricated to have varying physical, chemical and mechanical properties along its length.
[0056] Among the non-limiting advantages of using the present non-woven architectured synthetic implant instead of present state-of-the-art woven or fibrous implants are the following:
[0057] 1. interpenetrating pore structure allows for rapid but stable cellular ingrowth;
[0058] 2. can be molded into unique shapes and designs to improve handling characteristics;
[0059] 3. pore structure with large surface area reduces hemorrhage through the implant;
[0060] 4. use of stabilized microstructure allows use of device with larger pore structure without hemorrhage risk;
[0061] 5. creation of a living tissue barrier protects the material of the implant from coming in direct contact with blood flowing through the lumen;
[0062] 6. allows for easy ingrowth of fibrous tissue which stabilizes and anchors the implant;
[0063] 7. unbroken weave of tissue throughout device distributes stresses in an optimal manner, reducing occurrence of compliance mismatches.
[0064] 8. allows for vascular ingrowth (vasa vasorum) which nourishes the graft and provides access to free floating stem cells.
[0065] 9. pore structure allows the device to carry bioabsorbable materials without loss to circulatory system.
[0066] 10. pore structure allows the device to support biologically active agents without dilution or loss to circulatory system.
[0067] 11. use of flat plates provides a greater surface area using less material allowing for a higher overall porosity.
[0068] Among the medical application areas envisioned for articles produced in accordance with the various teachings of the present invention include, but are not limited to, prostheses for use in vascular reconstructive surgery of mammals, including humans and other primates. The prosthesis may be used to repair, replace or augment a diseased or defective vein or artery of the body. The prosthesis may also be used as a substitute for the ureter, bile duct, esophagus, trachea, bladder, intestine and other hollow tissues and organs of the body. Additionally, the prosthesis may function as a tissue conduit, or, in sheet form it may function as a patch or repair device for damaged or diseased tissues. (e.g., heart, heart valves, pericardium, veins, arteries, stomach, intestine, bladder, etc.) When functioning as a tissue conduit (e.g., nervous tissue) the lumen of the prosthesis may also carry substances that aid in tissue growth and healing.
[0069] In a preferred embodiment of the present prosthesis invention, namely that of a vascular graft, the graft consists of a polyurethane conduit composed of small chambers with each chamber being formed of multiple thin flat partitions. The thickness of each polymer partition is only a fraction of its length and height. This allows a small mass of polymer to create a large surface area providing high resistance to blood flow through the thickness of the prosthesis. One chief disadvantage of a highly porous vascular graft is its high permeability to blood during implantation leading to blood leakage through the graft wall. The unique arrangement of the intercommunicating chambers within the device of the present invention, however, prevents the leaking of blood by drastically slowing its movement through the thickness of the graft and allowing it to clot and self-seal.
[0070] Referring now to the figures, those of FIGS. 1-10 illustrate Scanning Electron Microscope (SEM) images of four different vascular grafts made from four different species of polymer using the gel-enhanced phase separation technique. In particular, FIGS. 1, 4 and 7 are SEM images, taken at 250×, 240× and 260× magnification, respectively, showing the external graft surface using a siloxane polyurethane polymer, a carbonate polyurethane polymer, and a resorbable lactic acid polymer. The external surfaces have a high overall porosity. In contrast, the luminal sides of the grafts have a smooth, low pore surface to minimize flow disturbances. See, for example, FIGS. 3, 6 and 9, which are SEM images at 250× magnification of the luminal surface of vascular grafts made from the siloxane polyurethane polymer, the carbonate polyurethane polymer, and the resorbable lactic acid polymer, respectively. FIGS. 2, 5 and 8 are the corresponding SEM images through the cross-section of the above-mentioned polyurethane and lactic acid polymer grafts, but taken at magnifications of 250×, 260× and 150×, respectively. FIG. 10 is a 250× magnification SEM image of a cross-section of a vascular graft made from a non-resorbable Teflon® polymer. This area of the prosthesis provides multiple chambers capable of carrying other substances and provides a high surface area for cellular attachment while resisting flow through the graft.
[0071] The speed and extent of peripheral tissue ingrowth determines the long-term compliance of the graft. FIG. 11 is a 100× magnification optical photomicrograph showing fronds of tissue growing into the pores of a porous prosthesis and expanding to form an intercommunicating tissue network. The type, size and density of the pores of the vascular graft of the present invention not only affects the speed and extent of peripheral tissue ingrowth, but also influences the development and stability of an intimal endothelial layer. Upon implantation, the graft surface in contact with the host tissue bed typically is of a higher overall pore density so that tissue can quickly grow into the prosthesis and secure it (compare, for example, FIG. 7 with FIG. 8). In contrast, the luminal surface of the graft usually has a smooth, low pore density surface in contact with blood to minimize flow disturbances. Not entirely without intercommunication, the luminal surface of the conduit does present enough porosity so that the new cellular lining can be anchored to the tissue that has grown into the device (compare, for example, FIG. 9 with FIG. 8). The pore size ranges from about 20 to about 75 microns in diameter.
[0072] Present commercially available vascular prostheses fail to form a complete endothelial lining. At best they have an anastomotic pannus formation that rarely achieves 2 cm in length. To achieve long-term patancy, a prosthesis probably will require complete endothelialization, and such can only be supported if there is full micro-vessel invasion from the surrounding connective tissue into the interstices of the prosthetic device, nourishing the neointima. Accordingly, in the second aspect of the present invention, where a secondary bioresorbable "microstructure" material is incorporated into the interstices of the polyurethane graft "macrostructure", such investment of the secondary bioresorbable material can encourage the formation of the complete endothelial layer, e.g., by allowing for ingrowth of collateral circulation to nourish the cells within the prosthesis.
[0073] Materials such as collagen gels have been utilized for years to avoid pre-clotting of vascular grafts and to improve biocompatability of the implant. Due to the high solubility of these materials, their benefits are short lived. Within a matter of hours these gels are stripped out leaving the prosthesis nude. Several hours may provide sufficient time to avoid pre-clotting, but is not adequate to aid in tissue integration. In response to the foreign material the body forms a dense tissue capsule over the external surface of the graft. This capsule prevents infiltration of micro vessels through the prosthesis necessary to stabilize an endothelial layer on the luminal surface.
[0074] In contrast, and in a particularly preferred embodiment of the present invention, the pore structure of the present prosthesis accommodates and protects the collagen gel (refer again to FIG. 12). Additionally, once incorporated, the gel may be lyophilized and cross-linked. Preferably the cross-linking will be accomplished by a di-hydrothermal technique that does not require the use of toxic chemicals. The pore structure and cross-linking should allow the gel to remain within the pore structure of the graft for several days, instead of hours. This additional time should be sufficient to encourage cells to enter the device and attach to each polymer partition making up the graft, forming a living tissue barrier between the material of the graft and host cells and body fluids. Micro vessels are now free to grow from the external tissue bed, between the individually encapsulated polymer partitions, where they can stabilize a luminal endothelial layer. During that time between implantation and cellular invasion, the microstructure will provide increased resistance to fluid leakage and influence the biomechancial properties. In this way a more compliant macrostructure can be implanted which possesses characteristics that can be tailored to those of the host vessel by the physical properties of the microstructure. Specifically, the porous polymeric material is very compliant, and if the porous polymeric material ends up being more compliant than the tissue to which it is to be grafted, the secondary bioabsorbable material can reduce the overall compliance of the prosthesis to approximately that of the host tissue. Over time, host cells, which dictate the overall compliance of the graft, replace the microstructure.
[0075] Additionally, the di-hydrothermally cross-linked microstructure provides a larger window of time for utilization of biologically active agents than would exist for the gel alone. Growth factors can be retained within the boundaries of the prosthesis for an extended period of time where they can influence cells entering the device. The effective lifetime of anti-coagulants can be extended, providing additional protection until endothelialization occurs.
[0076] A different approach to promotion of capillary endothelialization through the walls of the vascular graft is disclosed in U.S. Pat. No. 5,744,515 to Clapper. Specifically, the graft is sufficiently porous to allow capillary endothelialization, and features near at least the exterior wall of the graft a coating of tenaciously bound adhesion molecules that promote the ingrowth of endothelial cells into the porosity of the graft material. The adhesion molecules are typically large proteins, carbohydrates or glycoproteins, and include laminin, fibronectin, collagen, vitronectin and tenascin. Clapper states that the adhesion molecules are supplied in a quantity or density of at most only about 1-10 monolayers on the surface of the graft, and specifically on the pore surface. Thus, unlike the present secondary bioabsorbable materials, the adhesion molecules of Clapper seemingly would have a negligible effect on, for example, tailoring the mechanical characteristics of the graft, e.g., mechanical compliance.
[0077] Again, one of the primary application areas envisioned for the present invention includes a prosthesis for use in vascular reconstructive surgery of mammals, including humans and other primates. The prosthesis may be used to repair, replace or augment a diseased or defective vein or artery of the body. FIG. 13, for example, shows non-limiting embodiments of the present invention allowing for improved suturing. Specifically, FIG. 13a shows how the host vessel 110, situated into the graft material 100, provides less resistance to flow through the lumen. (Like numbers refer to like items, and are therefor omitted for brevity.) FIGS. 13b and 13 c show how sutures can be placed so that they do not encroach upon the lumen, thus minimizing flow disturbances. A longitudinal suturing method 120 is shown, and compared to a transverse method 130. FIG. 14 shows a representative, but non-limiting selection of various physical or structural embodiments of the present invention made possible by use of the gel-enhanced phase separation technique. For example, FIG. 14a is an end-on view of a vascular graft showing that the present vascular graft may be provided with a pair of flaps 220, extending from the central axis 210 to prevent rolling of the graft 200 once implanted. The vascular graft 300 of FIG. 14b provides additional support when compared to FIG. 14a, namely, by providing two pairs of flaps 310. FIG. 14c illustrates a graft 400 with wings 410 to facilitate suturing. FIG. 14d is a view of a longitudinal section through a graft 500 showing reinforcement rings 510 around the circumference of the graft. FIG. 14e depicts a "Y" graft 600 used to split the blood flow from the central axis 210 into a plurality of graft bifurcations 610.
[0078] The "Y" graft, or branched geometry is particularly useful to the vascular graft embodiment, as well as others, and this and other synthetic grafts may be attached by a port, connector or anastomosis, to an artery, vein, or other tubular or hollow body organ to effect a shunt, bypass, or to create other access to same. Additionally, a graft or other device produced with this invention may comprise a plurality of branches, with each branch having a length or diameter that may vary independently from the other branches. As an example, the inlet or proximal branch may be large, and attached to the large section of aorta, while distal sections may be significantly smaller, and of different lengths, to facilitate attachment to smaller coronary arteries.
[0079] The large proximal section could allow adequate blood flow through a single attachment to the aorta, thereby decrease possibility of leakage at various proximal anastomoses, while decreasing the procedural time. Likewise, diametric and length matches, or closer matches, will allow faster and easier connections; since the surgeon can trim the graft section to the appropriate length, and the surgeon will not have to rework the graft material to allow the larger natural vein to connect with the smaller coronary artery, thereby further decreasing procedure time.
[0080] This process will allow the graft to be of decreasing diameter with increasing length, thereby approximating the anatomy of the coronary artery system. This allows the surgeon to trim the graft to any length, while maintaining a constant graft-vein diameter ratio, thereby allowing in situ customization of the graft length without incurring turbulent flow due to diameter mismatch.
[0081] In addition to facilitating the procedure, by reducing the duration of the surgical procedure and attachment complexity thereof, the diameter tailoring of this embodiment will allow the maintenance of a constant flow velocity, while the volume decreases (following the branches, each of which reduce the flow). This constant velocity is important to keeping blood-borne material in the mix; that is, plaque deposits may be deposited on the arterial wall or bifurcation junctions (e.g., the ostium) in the coronary system, in natural as well as in the synthetic graft.
[0082] The tailorable properties of material manufactured by the processes of this current invention allow for the manufacture of grafts and other vascular prostheses that may demonstrate flexibilities and expansion, under normal or elevated blood pressures, similar to that of natural arteries. This constraint-matching avoids problems associated with existing grafts, that is, these grafts and prostheses readily expand during the systolic pulsing. Grafts or harvested veins that do not expand can cause spikes in blood pressure, and may cause or exacerbate existing problems, including or due to high blood pressures.
[0083] The unique characteristics of the many polymer species available, both now as well as those anticipated in the future, make it impractical to provide a comprehensive list of gelling solvents. To address this problem, below is provided an example of a step-by-step process for the identification of useful dissolving solvents and gelling solvents for a single polymer species, as well as how the solvents may be removed to provide the porous, solid polymer material. This process example provides guidance in how to utilize the information provided in this disclosure; however it is recognized that alternate selection methods and/or criteria are known to those skilled in the art.
[0084] A siloxane-based macrodiol, aromatic polyurethane, supplied by Aortech Biomaterials, was selected for this example.
[0085] 1) The manufacturer identified dimethyl acetimide, n-methyl pyrrolidinone, and tetrahydrofuran as solvents for the polymer.
[0086] 2) A 0.25-gram sample of polymer was placed into the bottom of 20 small bottles. Five milliliters of 20 common laboratory solvents, including the three listed by the manufacturer, was added to the bottles. The bottles were left for 48 hours at room temperature after which they were used to identify those solvents that dissolved or resulted in swelling of the polymer. Twelve polymers were identified and are listed below along with freezing point ("F.P.", also known as melt point), boiling point ("B.P."), vapor pressure ("V.P."), and solvent group (S.G.). (Other properties that can aid in the selection of solvent and gelling solvent include, but are not limited to, density, molecular weight, refractive index, dielectric constant, polarity index, viscosity, surface tension, solubility in water, solubility in alcohol(s), residue, and purity.)
Vial S. # Contents F.P. B.P. V.P.(torr) G. Result 2 acetone −94.7 56.3 184.5 @ 20C 6 swell 5 chloroform −63.6 61.2 158.4 @ 20C 8 swell 7 p-dioxane 11.8 101.3 29.0 @ 20C 6 swell 11 methylene −95.1 39.8 436.0 @ 25C 5 swell chloride 12 n,n-dimethyl −20.0 166.1 1.3 @ 25C 3 dissolve acetimide 13 dimethyl 18.5 189.0 0.6 @ 25C 3 swell sulfoxide 14 1-methyl-2- −24.4 202.0 4.0 @ 60C 3 dissolve pyrrolidone 15 Tetrahydrofuran −108.5 66.0 142.0 @ 20C 3 dissolve 16 toluene −95.0 110.6 28.5 @ 20C 7 swell 17 m-xylene −47.7 139.3 6.0 @ 20C 7 swell 18 o-xylene −25.2 144.4 6.6 @ 25C 7 swell 20 methyl-ethyl- −86.7 79.6 90.6 @ 20C 6 swell ketone
[0087] 3) From the chart, Tetrahydrofuran (THF) was selected as the polymer dissolving solvent due to its low freeze point, low boiling point and high vapor pressure. The skilled artisan can see that, for this particular polymer, solvent group #3 is particularly preferred as the dissolving solvent, and that solvent group #6 and group #7 are particularly preferred as the gelling solvent. The chart also shows that certain solvents from solvent group #5 and group #8 also gave a positive result, e.g., swelling, but these solvents were in the minority; the majority of solvents from these groups neither dissolved nor swelled the polyurethane. Accordingly, this information can be used to prioritize a search for other suitable solvents.
[0088] 4) Five milliliters of a 12.5% solution of polymer and THF was placed into each of 9 small flasks with a magnetic stir bar at the bottom. Twenty milliliters of one of each of the 9 solvents identified as gelling agents was added to each flask with rapid stirring. After 2 minutes, stirring was stopped and the solutions were allowed to sit for 13 minutes. As expected, none of the additions resulted in precipitation of the polymer. As a control an additional flask was set up and 20 ml of ethanol (e.g., a failed solvent) was added with rapid stirring. A white precipitate immediately formed. After stirring was stopped the polymer precipitate drifted to the bottom of the flask.
[0089] 5) All 9 flasks showed signs of thickening even though the polymer to solvent concentration fell from 12.5% to 2.5%. (The control flask solvents (20 ml ethanol 5-ml THF/Polymer) became less viscous as the polymer fell out of solution.) Other parameters being kept equal, the viscosity of the resulting solution or mixture, upon adding the gelling solvent, increases with increasing concentration of polymer and increasing concentrations of gelling solvent. The viscosity also depends on the identity of the gelling solvent, and can range from a slight thickening to the formation of a gelatinous solid. At the concentrations listed, p-dioxane, dimethyl sulfoxide, and o-xylene produced the greatest thickening.
[0090] 6) Utilizing the information provided in the chart, the following methods were used to remove the solvent and gelling agent:
[0091] Sample A
[0092] Recognizing that p-dioxane has a freeze point, boiling point and vapor pressure suitable for freeze-drying; the Vial 7 gel was scooped onto a Teflon plate, spread out and frozen. The frozen gel (−15 C.) was then placed into a freeze-dryer for 12 hours. The THF, having such a low boiling point and high vapor pressure most likely does not freeze and thus is removed from the system first. Upon subsequently removing the p-dioxane, a white porous sheet was produced with a non-fibrous porosity greater than 90%.
[0093] Sample B
[0094] Recognizing that dimethyl sulfoxide has a boiling point and vapor pressure unsuitable for freeze-drying, the Vial 13 gel is instead poured onto a Teflon tray, frozen at −15 C. and then submerged into a non-solvent (ethanol) at −10 C. for 12 hours to leach out the solvent and gelling solvent. (Had the gel been thick enough to form a stable gelatinous mass, freezing and the use of chilled alcohol would not be required.) The sheet was then removed form the alcohol and soaked in distilled water 12 hours, after which it is dried and placed into a desiccator. The sheet formed was relatively stiff and had a non-fibrous porosity of greater that 75%.
[0095] Sample C
[0096] Comparing the boiling point and vapor pressure of o-xylene and THF the skilled artisan can see that it would be possible to heat the gel and selectively remove the THF solvent and leave the o-xylene gelling agent behind. Accordingly, the Vial 18 gel was poured into a Teflon dish and slowly heated from 21 C. to 66 C. over a 3-hour period. This increased the viscosity to that of a non-flowing gel without mechanical competence. The dish was then lowered into a 21 C.-ethanol bath for 12 hours to remove the o-xylene and any residual THF. A light tan sheet was produced with a non-fibrous porosity greater than 40%.
[0097] Instead of first dissolving the polyurethane in the THF, an attempt was made to dissolve the polyurethane in a solution of THF and gelling solvent provided in the same ratio as in the Example. The polyurethane did not dissolve.
[0098] Thus, the Example and Comparative Example show: (1) that in the polyurethane/THF system, ethanol is a failed solvent that causes polyurethane to precipitate; (2) that the polymer preferably is dissolved before being exposed to the gelling solvent; (3) that different gelling solvents affect the solution viscosity to a different degree; and (4) that there are different ways to precipitate the porous polymer from solution, and that the preferred technique may depend upon the properties of the dissolving solvent and gelling solvent.
[0099] Having taught the reasoning process that is used in choosing appropriate first and second solvents for a given polymer, and appropriate techniques for their removal once a desired shape has been fabricated, an artisan of ordinary skill can readily identify without undue experimentation other polymer/first solvent/second solvent systems that can be processed similarly to what has been described herein to produce porous polymeric bodies. Accordingly, the artisan of ordinary skill will readily appreciate that numerous modifications may be made to what has been described above without departing from the claimed invention, the scope of which is set forth in the claims to follow.
|Geciteerd patent
|4 mei 1936
|28 maart 1939
|American Box Board Co
|Titel niet beschikbaar
|Titel niet beschikbaar
|Titel niet beschikbaar
|Titel niet beschikbaar
|Citerend patent
|26 aug 2005
|22 juli 2008
|Vnus Medical Technologies, Inc.
|Apparatus, material compositions, and methods for permanent occlusion of a hollow anatomical structure
|25 jan 2006
|5 juli 2011
|Tyco Healthcare Group Lp
|Method and apparatus for impeding migration of an implanted occlusive structure
|19 dec 2008
|6 sept 2011
|Tyco Healthcare Group Lp
|Method for permanent occlusion of fallopian tube
|4 dec 2003
|13 maart 2012
|Kensey Nash Bvf Technology, Llc
|Compressed high density fibrous polymers suitable for implant
|25 jan 2006
|11 sept 2012
|Tyco Healthcare Group Lp
|Structures for permanent occlusion of a hollow anatomical structure
|1 juli 2011
|18 dec 2012
|Covidien Lp
|Method for permanent occlusion of fallopian tube
|18 okt 2010
|18 dec 2012
|Covidien Lp
|Method and apparatus for implanting an occlusive structure
|1 juli 2011
|3 maart 2015
|Covidien Lp
|Method and apparatus for impeding migration of an implanted occlusive structure
|25 jan 2006
|28 april 2015
|Covidien Lp
|Expandable occlusive structure
|20 april 2006
|28 april 2015
|Covidien Lp
|Occlusive implant and methods for hollow anatomical structure
|4 dec 2003
|9 juni 2005
|Ringeisen Timothy A.
|Compressed high density fibrous polymers suitable for implant
|8 jan 2003
|9 juni 2005
|Jean-Louis Duluco
|Gastric ring for treatment of obesity
|26 aug 2005
|9 maart 2006
|Mirizzi Michael S
|Apparatus and material composition for permanent occlusion of a hollow anatomical structure
|26 aug 2005
|9 maart 2006
|Mirizzi Michael S
|Apparatus, material compositions, and methods for permanent occlusion of a hollow anatomical structure
|25 jan 2006
|21 sept 2006
|Karabey Halil I
|Expandable occlusive structure
|25 jan 2006
|21 sept 2006
|Karabey Halil I
|Structures for permanent occlusion of a hollow anatomical structure
|20 april 2006
|14 dec 2006
|Taheri Syde A
|Temporary absorbable venous occlusive stent and superficial vein treatment method
|20 april 2006
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|Taheri Syde A
|Temporary absorbable venous occlusive stent and superficial vein treatment method
|Classificatie in de VS
|424/486, 428/36.8, 264/41, 521/82, 521/84.1, 428/36.9, 525/459, 525/453
|Internationale classificatie
|Coöperatieve classificatie
|Europese classificatie
|10 feb 2003
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text:
Credits & Info
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- Daily Feature September 22, 2012
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Author Comments
Rated 5 / 5 stars
Since that thing was a crying little troll i threw it off the edge after i returned to the mom ALL THE TIME
Rated 5 / 5 stars
bravo, so nice to see a re-imagination of that memorable mission.
Rated 5 / 5 stars
that was funny when mario made the snow get on the fake pegiun ha ha not falling for your tricks fake pegiun and i have mario 64 on nintendo ds i wish i could get super mario 64 on nintendo 64 from the wii shop channel but i need to get the gamecube controller for my wii
Rated 3.5 / 5 stars
This was good, but it seemed way too long, probably because I already knew what was going to happen.
Rated 5 / 5 stars
epic as hell make another one like this but a diffrent star level


text:
The Stillwater school district had the perfect site for its new Early Childhood Family Center — centrally located in the district and a bargain at $3.2 million, including a building worth $900,000 for free.
Just one problem: An environmental study found toxic contamination on the site. School district officials terminated the deal last month.
Just miles away in Baytown Township, St. Croix Preparatory Academy built a $21 million school in an area known to have water contaminated with trichloroethylene. The Minnesota Pollution Control Agency said the site meets all environmental safety guidelines, but critics have argued for more than two years that students and staff might not be safe down the road as more is known and environmental standards change.
The two decisions highlight a growing debate: When is it appropriate to construct a school building on or near a contaminated site, and how do you handle the real or perceived threats?
Some say it's not worth the risk. Changing health and safety standards could mean that today's safe conditions will be deemed hazardous in 10 or 20 years.
"You should not build schools on contaminated sites unless other sites aren't available," said Lenny Siegel, executive director of the Center for Environmental Oversight in Mountain View, Calif.
Others argue that fear of these sites is sometimes overblown. The sites often offer dirt-cheap land to cash-strapped school districts. And the result can be that once-hazardous sites are cleaned up and become community assets.
"We know it becomes political and people lose perspective when kids are involved. And I can understand that," said Hans Neve, supervisor of the Minnesota Pollution Control Agency's Voluntary and Investigative Cleanup Program. "But it's a constant struggle for us to explain the realities versus perceptions."
St. Croix Prep opened its facility at the southwestern corner of Washington County roads 14 and 21 in fall 2009.
The site is in the Baytown Special Well Construction Area, which state officials designated in 1987 when they learned trichloroethylene had seeped into groundwater. Hundreds of wells in Baytown Township, West Lakeland Township, Bayport and Lake Elmo have been tested for the chemical solvent widely used for metal degreasing.
The maximum level of TCE allowed in drinking water is 5 parts per billion. A system installed in Bayport's city and private wells is designed to keep the TCE below that level. St. Croix Prep gets its water from the city.
But drinking the water isn't the only potential danger. TCE can be released into indoor air from vapor intrusion through underground walls and floors, as well as from volatilization from the water supply.
Some argue St. Croix Prep didn't consider vapor intrusion and isn't taking the necessary steps to protect students and staff from it.
"It's time to take responsibility and make sure that site is safe," said Bayport resident David Beck. "Monitor the site. Test the air quality."
But state and federal environmental officials say that, at current TCE levels, vapors are unlikely to seep through the soil into the building. They assess this by using a variety of factors, including the concentration of the chemical in the groundwater, geological makeup of the site and type of building.
Kurt Schroeder, staff hydrogeologist for the Minnesota Pollution Control Agency, said the groundwater contamination would have to be at the water table's surface to pose a threat. It's well below that, he said.
The area of concern for vapor intrusion stretches about a mile east of Hagberg's Market in Lake Elmo, the main source of TCE contamination, said Schroeder. That's about 3 1/2 miles from St. Croix Prep.
St. Croix Prep officials note there are about 600 homes in the TCE plume and two other schools abut the borders. At the school closest to the plume, Andersen Elementary in Bayport, no TCE contamination was found in 2008 tests.
St. Croix Prep had two studies performed on the site by American Engineering Testing Inc. — one before construction in March 2008 and a follow-up in June 2009 after new concerns were raised. The MPCA also issued an opinion in February 2009 that the site was safe after the agency received complaints from an elected official.
"We wanted to make sure we have good, solid information to give to the parents and community before things got out of control," said Mike McGinley, a parent of three students at the school and an environmental engineer.
TCE guidelines could change in the near future, though. The EPA is reviewing drinking standards and has determined that scientific advances allow for stricter regulations for several carcinogenic compounds, including TCE.
Tisha Petteway, press officer for the EPA, said the agency plans to revise TCE standards within the next year based on the findings from a human health assessment. Less than 10 years ago, the EPA lowered TCE standards from 30 parts per billion to 5.
The Center for Environmental Oversight's Siegel has worked with schools across the nation on vapor intrusion. He said many people don't understand the complexities of assessing TCE contamination.
TCE is a chemical that moves. Though a site is clear of TCE at one point doesn't mean that will be the case in the future, Siegel said.
But Siegel said there are protections. A vapor barrier to vent vapors away from the building can be put in during or after construction. And building owners should commit to ongoing tests of water and air quality throughout the life of the building.
"I'm not telling people that the site is unsafe," Siegel said. "The evidence so far looks like it is (safe). But you need to monitor as long as the contamination is there."
St. Croix Prep put in a barrier, but not a vapor barrier as described by Siegel. School officials said they would continue to monitor the scientific discussions around TCE to see if they should test for air quality.
When Stillwater school district leaders learned in August that the land for the district's Early Childhood Family Center was contaminated with PCE, they decided to search for a new site.
PCE, formally known as tetrachloroethene, is used in dry cleaning and metal-degreasing operations. It can cause neurological disorders and is classified as a possible human carcinogen.
The site could have been cleaned up. But district officials didn't want to delay the project or put anyone at risk, said Assistant Quperintendent Ray Queener.
"As hard as it was to walk away from this site, there's no level of risk I'm willing to take in building this facility," Queener said.
The South Washington County school district faced a similar situation nearly four years ago when building its third high school.
The district bypassed a 120-acre piece of land on Dale Road because it was about a half-mile from a former 3M Co. landfill. Instead, it built East Ridge High School on an 80-acre site near Bielenberg Sports Center that was more expensive and harder to develop.
Soil samples from the Dale Road site showed only traces of perflourochemicals — not enough to pose health concerns. But district leaders decided not to build near the site where 3M dumped industrial solvents and chemicals during the 1960s.
"The board and administrators had some concerns about what they could find there someday," said Tom Nelson, who was superintendent at the time. "The ultimate issue with parents is safety. We decided we can't spend that kind of money and constantly be worried."
Nelson said some of the district's top administrators disagreed with the decision. And two of the seven board members voted against it.
Board member Jim Gelbmann said he felt the Dale Road site was a better choice because of its central location near the Woodbury-Cottage Grove border — a move that would soften the north-south rift between the district's communities.
The Dale Road site also got a clean bill of health. Perflourochemicals found in soil samples were in trace amounts, typical for that part of Washington County, Gelbmann said. 3M burned waste from the landfill back in 1968 after the company found out about groundwater contamination, sending the chemicals into the air.
Anyone who has old carpeting in their house probably has higher level of contaminants than the Dale Road site, Gelbmann said.
"I felt like it was more of a perception issue, rather than a health and safety issue that would endanger students and staff at the district," he said.
Nelson agreed there's always an issue of perception.
"You can tell people that the site had some problems but it's been cleaned," Nelson said. "But people get unnerved when it comes to health and safety. And I think you have to be extra cautious."
The Mahtomedi school district, on the other hand, built athletic fields on top of a former Bellaire landfill in Grant. The district plans to build a new $17.7 million elementary school about 800 feet to the east of the old waste disposal area. The district bought the relatively inexpensive 70-acre site from Waste Management Inc. in 2004 after an outside environmental consultant took soil samples and conducted other tests.
The tests found construction debris and a small amount of petroleum contamination that needed to be removed, said Phil Belden, the school district's supervisor of buildings and grounds. Mahtomedi worked with the Pollution Control Agency to ensure the land was environmentally safe to use before finalizing the purchase.
As part of the agreement, Waste Management sealed off a well and removed a house, maintenance garage and debris, including 540 tons of soil. It also paid $400,000 to remove petroleum and metal contamination and added 2 feet of land cover.
Additional tests for soil, air and water contamination were performed this summer and the property met all MPCA requirements, Belden said.
"We're fully confident this is going to be a safe site, a great site for students and families for years to come," said Superintendent Mark Larson.
The district put in a vapor barrier and other protections.
"We feel the need to guarantee the public that this is safe," Larson said.
The school district probably would have spent two to three times as much for other land in the area, Belden said.
"I think people should give the district some credit for picking this site," he said.
Jim Markoe, board chairman at St. Croix Prep, is perplexed by the ongoing criticism and thinks people perceive there's a problem when there isn't.
"There are 500 families that have seen the information and studies and choose to send their kids here," said Markoe, who has three children at the school. "This is a school of choice. Why would we put our children at risk?"
Megan Boldt can be reached at 651-228-5495.
TCE (trichloroethylene): A chemical solvent widely used for degreasing metal parts. Some household products — such as correction fluid, paint removers, adhesives and spot removers — may also contain TCE. It is one of the more common man-made chemicals found in the environment. Risk: Long-term exposure to high levels of TCE in drinking water can damage the liver, kidney and immune and nervous systems. It can also harm developing fetuses. Some studies suggest that exposure to low levels of TCE over many years also may be linked to an increased risk of several types of cancer. Minnesota's standards: 5 micrograms per liter in drinking water, per EPA guidelines.
PCE (tetrachloroethene): A manufactured chemical widely used in dry-cleaning and metal-degreasing operations. Risks: It can cause neurological disorders, dizziness, headaches and nausea. It is also classified as a possible human carcinogen. Minnesota standards: 100 micrograms per cubic meter and 20 micrograms per cubic meter as the long-term exposure concentrations for noncancer and cancer health effects, respectively.
PFCs (perflourochemical): Perfluorochemicals have been used for decades to make products that resist heat, oil, stains, grease and water. Common uses include nonstick cookware, stain-resistant carpets and fabrics. Risks: High doses of the chemicals cause thyroid and liver problems, as well as birth defects in mice. But few studies have examined the health affects in people, leaving a lack of evidence that PFCs are harmful to people. Studies by 3M of workers exposed to PFCs during manufacturing show no apparent impact on health. Minnesota standards: Health risk limits have been set for PFOA and PFOS at 0.3 micrograms per liter. Because of limited toxicological research on the remaining perflourochemicals, there is little scientific information to develop health standards.


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- About
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The 50th Anniversary 1964.5 Mustang Tribute Car at SEMA - booth 24695
This Tribute Car will be local during SEMA (in booth 24695) and then will be travelling on a Nationwide Tour throughout 2014 and then ultimately auctioned in January 2015 with proceeds benefitting The National Down Syndrome Society.
The Drake Automotive Group is booth 24695 (Central Hall) and is "60's themed" with all the staff in costume yesterday today (including Scott Drake himself and his son Troy!) and has created quite a stir at SEMA so far!!!
The last 2 days (Thurs & Fri) will be regular "tradeshow style" clothing in the booth...
MUSTANG 50th ANNIVERSARY CELEBRATIONS
Scott Drake (Drake Automotive Group - Henderson, NV) and The Mustang Club of America created a special partnership to restore and highlight this car as the "Tribute Car" for the Mustang 50th Anniversary Celebrations.
This special event will be held April 16th -20th 2014 at both The Las Vegas Motor Speedway, Las Vegas, Nevada and The Charlotte Motor Speedway, Concord, North Carolina and featured in one of the Scott Drake booths.
1964 ½ Ford Mustang Convertible
A tribute to the 50th Anniversary of the Mustang.
Purchased the car and supplied all parts for the restoration.
Mustangs of East Texas, a Mustang Club of America Regional Group in Tyler, Texas volunteered to restore the car. All the members deserve special recognition for spending so much of their free time working on and creating this beautiful Mustang.
Thank you so much! Without them this project would not have been possible. This club is a wonderful example of everything good about the automotive world.
Great people, working together, helping each other, mentoring new members and sharing automotive enthusiasm!
This Tribute Car will be attending many celebration events in 2014 celebrating the Mustangs 50th Anniversary. (see calendar)
You could be the lucky owner of this convertible Mustang, that is if you're the highest bidder. In January 2015 the auction will be held in Scottsdale AZ by one of the premiere auction companies.
Drake Automotive Group has given the title to The National Down Syndrome Society in which they will receive 100% of the funds when the Tribute Car is auctioned.
Nov 5- 8 2013 SEMA Show- Las Vegas , NV
Displayed @ Drake Automotive Booth # 24695
Feb 7-9 World of Wheels Autorama, New Orleans, LA
Feb 14-16 World of Wheels Autorama, Dallas, TX
April 16-20 Mustang Club of American and Ford Motor Co
50th Anniversary Celebrations
Las Vegas, NV OR Charlotte, NC
Displayed @ Scott Drake booth with model
Great photo opportunity for all who attend!
April 27 Fabulous Fords, Knott's Berry Farm - Buena Park, CA
May 23-25 Mustang Club of America National Show - Springfield, IL
July 2014 Mustang Round Up - Bellevue, WA
August 2014 North Texas Mustang Club - Fort Worth, TX
Aug 7 - 10 2014 Mustang Club of America National Show - Lincoln, NE
Aug 16, 2014 Woodward Dream Cruise - MI
Sept 2014 Mustangs at the Queen Mary - Ford Car Show - Long Beach, CA
Oct 10 - 12 2014 Mustang Club of America National Show - Savannah, GA
Jan 2015 Car to be auctioned at one of the premiere auction companies in Scottsdale, AZ.
* There is also a letter from the National Down Syndrome Society - signed by Mr. Jon Colman (President) and Mr. Charles H Gerhardt, III (Chairperson) acknowledging and accepting being selected as the charity partner that can be provided upon request.
Thank you,
Mel Carroll
(Marketing Manager @ Drake Automotive Group)


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Have some courage, Mr Cameron
Posted: March 14, 2013|
WITH reference to the article Clasp honour for World War II Bomber Boys.
For the record I served for 28 years in the Royal Navy – mostly as a submariner and during my service we fought and won the Cold War.
That service gives me a little insight into the suffering of men who fought and died on the Arctic convoys.
Those brave men richly deserve their medal which should have been awarded at the time.
Also for the record, my late father WO CH Lees served as an air gunner on Lancasters. He served in 57 Squadron and 617 Squadron completing 36 raids between August 1944 and April 1945.
The Bomber Command Clasp would be a fine and fitting award for all the ground crew who served in Bomber Command.
But the air crew should have had their own medal at the time and should have their own medal now, ie the Bomber Command Star.
I do not believe that Churchill snubbed my father, I believe that he betrayed my father and all his comrades and that betrayal has gone on to this day having been perpetuated and endorsed by al Prime Ministers to date.
Now is the time to put this betrayal right while there are still a few of these gallant old gentleman alive.
Have some courage Mr Cameron, award these men their Star now.
It is a fact that politicians start wars not service personnel.
The service personnel have the job of sorting out the mess once the war has started.
War is a brutal thing, people get killed, innocent people get killed.
Bomber Command did not start the war, but they did fight it under the command and direction of the politicians (we live in a democracy where the service personnel do what the politicians tell them).
But let us not forget that even though Bomber Command did not start the war, they did help to finish it as soon as possible, thus saving millions of lives.


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On The London Semester you will study abroad in London at highly ranked University of Roehampton. Roehampton is unique among London universities in having its housing, support services, classrooms, shops, and Student Union all within a 15-minute walk of each other. The picturesque campus is the ideal environment for study, and on its doorstep is one of the world's most exciting cities. You will experience:
Classes across departments – No need to limit yourself to one field! Study anything from politics to dance to health care with remarkable British professors.
Affordability – Check out one of the best cities in the world on the most affordable London study abroad option. Don't forget that many of London's best museums are free, and many pubs and restaurants offer inexpensive lunches. We have tons of tips for you on how to save money and still enjoy all that this incredible city has to offer.
Top-notch academics – Roehampton professors are highly regarded throughout England and the world and include famed novelists, criminologists, business moguls, and psychologists. Cutting-edge research is the stuff of everyday life here.
Best of both worlds - A campus setting with peaceful grounds, yet the bustling city center is just a short tube ride away.
Fun dorm life – Each residence hall is its own social and cultural hub, with entertaining events where you can get to know your British and international hallmates and make lifelong friends when you study abroad in London.
If you've ever wanted to study abroad in London, then check out The London Semester program. Here are just a few of the key highlights that make this program unique.
Your semester in London comes with excursions built into the cost at no additional fee. Heidi, our site director in London, puts together fun and interesting trips geared towards getting a true English experience. In the past, these excursions have included:
Heidi will send out weekly updates to our students to let them know about free or inexpensive activities in the area. She will also create the itineraries so that students may still be able to participate in additional excursions that our partner school in London may put on. Some of these may include trips to:
Oxford There's more to this classic English city than the ancient university that gives the city its fame. Throughout the town you can observe buildings of every architectural period since the Saxons as well as a wealth of attractions including shopping, museums, theatres, botanical gardens, parks and a cathedral.
Stonehenge This pre-historic site is certainly one of the most famous spots in England. Located in Wiltshire and dating back to approximately 2500 B.C., Stonehenge is an ancient ring of monolithic stones constructed by a lost civilization for a purpose that remains unknown. Now owned by the National Trust and listed as a prestigious UNESCO World Heritage site, Stonehenge is a great archaeological mystery with a distinctly ethereal feel.
Liverpool Liverpool, the great city of the north, is the very definition of a trendy cosmopolitan city and is certainly giving London a run for its money! With an outstanding musical, sport and maritime history, in this metropolis it would be easy to focus on the past. But with dazzling new museums and art galleries as well as an extensive amount of modern restaurants, wine bars and shops, while in Liverpool you're going to have to make some decisions – and that's not going to be easy!
Windsor Castle As a Royal home and fortress for more than 900 years, Windsor Castle and the surrounding town demonstrate the epitome of British life. The castle itself is the Queen's official residence and is often used for formal duties and state visits. Windsor is also home to St. George's Chapel, the chapel used for hundreds of Royal christenings, weddings and funerals. Across the tranquil River Thames lies Eton, home to the famously prestigious Eton College.
As a student on The London Semester at University of Roehampton, you will be living in one of the residence halls on campus. You will live in a single room, with bed linen, blankets, and pillows provided. The hall is self-catered, meaning that you will be able to prepare your own meals, but you have the option of purchasing a kitchen pack with basic cooking and eating utensils from the University of Roehampton (if you prefer, you can get your own supplies once you arrive in London). Groceries can be purchased in the village, which is a short 10-minute walk from the main campus, or can be purchased at Asda (a large supermarket), only a short bus trip from the campus.
Living in the residence halls provides you with the opportunity to meet and become friends with students from different cultures and backgrounds. There are also cafeterias, shops, and coffee and snack bars located on campus, as well as Student's Union facilities, where you can relax and spend time with your new friends!
Roehampton is front and center with some of the best academics around. The Higher Education Quality Council recently commended Roehampton for its outstanding academic standards and quality assurance systems.
Students can choose courses in the following fields: biological sciences, business, creative writing, cultural studies, education, health, media studies, psychology, and sports, exercise, and leisure.
For a complete list of course offerings, please click here.
3-4 courses (15 US credits)
Spring 2014*:
Start Date: January 7
End Date: June 6
Fall 2014*:
Start Date: September 11
End Date: December 14-31 (Students may depart as early as the 14th, but dorms will remain open through the 31st.)
*Cost subject to change at any time due to the current exchange rate.
*This is NOT an extra fee, but is a non-refundable deposit applied towards your total program fee. You will be directed to pay this after completing the online application.
"Studying in the UK has brought me in contact with nationalities from around the world and exposed me to a variety of different view- points on everything from politics to music to cuisine and behavior. I have a more open-minded view of the world and have been exposed to so many ideas and languages, customs
and traditions."
Emily B.


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Should your preferred language not be available, contents will be displayed in English.
Towering 60 stories over the Strip Wynn Las Vegas is one of the tallest buildings in Las Vegas. Opened on April 28, 2005, it is constructed so that visitors must enter the building to view the free attractions. The main attraction is a large, curtain waterfall behind a mountain that faces the strip. The waterfall falls into a 3 acre (12,000 m²) lake. The visual element of Lake of Dreams is driven exclusively by Barco projectors which integrate seamlessly with the overall presentation: two ELM-R18 projection systems and five XLM-H25 systems. As many as 3000 guests experience this astonishing display every day. When the show is inactive, the waterfall creates an animated color sequence on the screen, which is very attractive at night.
The ELM-R18 offers an ideal combination of durability and performance. Its unique design simplifies handling and control, ensuring efficiency. A rugged steel frame keeps the projector safe, while its innovative modular construction takes functionality to a new level. Combining exceptional source compatibility with Barco's TCR image processing, the ELM-R18 puts out 17,500 lumens of pristine light.
"Barco's XLM-H25 units help transform our 45-ft high by 90-ft wide waterfall into a one of a kind visual display," said Danny Murphy, Director of Front Feature at Wynn Las Vegas. "Two additional projection surfaces, a 25-ft high mask of a human head and a 27-ft wide disc are also brought to life by our Barco projectors. All three surfaces function in the environment concurrently." The XLM-H25, featuring a light output of 27,000 center lumen is the ultimate standard for high-brightness projection. It is the first DLP projector with both a native wide-screen aspect ratio and 2048x1080 resolution. With its sturdy DMD engine and adjustable convergence system, the XLM-H25 is designed for around-the-clock presentations of truly magnificent proportions like those featured prominently in Lake of Dreams.
Today, Lake of Dreams is among the most popular and successful features located along the Las Vegas Strip. The thousands of guests who visit the attraction each week leave with a similar sentiment: as Murphy observed, "They always seem to appreciate the mere fact that a waterfall of this magnitude can be immediately transformed into a dynamic visual display."
06 October 2015
ITS Congress 2015: How Barco helps pave the way for smart transportation
Barco in 'Wonderland': come meet us at EAS 2015
05 October 2015
See Barco collaboration solutions at Almo E4 New York
27 September 2015
United States
New Century Hotels& Resorts
25 September 2015
04 August 2015
United States
Anheuser-Busch Oculto Campaign
20 July 2015
United States
University of California, Riverside - Student Recreation Center
14 July 2015
United States
Singapore Heritage Fest 2015
08 July 2015
3059 Premiere ParkwayDuluth, GA 30097United States
3078 Prospect Park DriveRancho Cordova, CA 95670United States
06 Oct 2015
06 Oct 2015 - 08 Oct 2015Mässans Gata/Korsvägen - SWEDEN


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No, once an account is closed all access to the account and its associated records is terminated. To preserve the records from an E-Verify account, a complete user audit report should be created and retained. E-Verify case information and documentation must be retained for your employees for the same length of time as their Forms I-9.
Under certain circumstances, an E-Verify account may be closed prior to the end of the 30-day period required by the E-Verify MOU. Those circumstances include:
- The company no longer exists
- Closing the account is necessary to protect the account from unauthorized access
- A company has duplicate or unnecessary accounts
- A company needs to reregister in order to change its E-Verify access method or
- E-Verify determines that closing an account before 30 days is necessary based on the requirements of law or policy
To request that your E-Verify account be closed prior to 30 days from your notice of termination based on one of these circumstances, you must make a written request for termination by fax or e-mail which includes the following:
- Request that your E-Verify account be closed prior to 30 days from your notice of termination, as required by the E-Verify MOU
- Explain why your account should be closed prior to 30 days from your notice of termination, referencing and explaining in detail one or more of the circumstances above and
- Specify the date you would like your E-Verify account closed
Closing E-Verify accounts prior to the end of the 30-day period, required by the E-Verify MOU, is at the discretion of E-Verify.
Any E-Verify account may be closed voluntarily. To close an account, a program administrator, corporate administrator, the signatory of the E-Verify memorandum of understanding (MOU), or an authorized company representative must submit written notice to E-Verify 30 days in advance of the date that the employer would like to close the account. Employers must request termination electronically through E-Verify, or submit a written termination notice to email@example.com or fax to 202-443-0215.
A corporate administrator may request termination electronically through E-Verify as follows:
- Log into E-Verify with your assigned login and password.
- From 'My Company Locations' click 'Close Company Accounts.'
- Enter the reason for requesting to close the account.
- Click 'Request Termination.'
You must continue to use E-Verify in accordance with the MOU during this 30-day period or until you have received an e-mail confirming that the account is closed, whichever is sooner. All open E-Verify cases must be closed, even if you request to close your E-Verify account.
A corporate administrator may terminate the company's corporate administrator account.
- Log into E-Verify with your assigned user name and password.
- From 'My Corporate Account' click 'Close Corporate Account.'
- Enter the reason for requesting to close the corporate administrator account.
- Click 'Request Termination.'
NOTE: The steps described above will only close the corporate administrator account. The company's verification locations (employer accounts) must be closed individually either by a corporate administrator or a program administrator for the verification location.
To change your security questions in E-Verify:
- Log in to E-Verify with your assigned user ID and password.
- From 'My Profile,' select 'Change Security Questions.'
- Select three questions and record an answer for each.
- Click 'Submit' to save your changes.
To reset your password in E-Verify:
- From the E-Verify login page, click 'Forgot Your Password.'
- Enter your User ID and click 'Submit.'
- Answer your password challenge questions and click 'Submit.'
- After successfully answering the challenge questions, create a new password.
If you did not create your password challenge questions, contact another corporate administrator to reset your password. If another corporate administrator is not available contact E-Verify Customer Support at 888-464-4218.
E-Verify Customer Support does not accept password reset requests through e-mail.
To retrieve your user ID in E-Verify:
- From the E-Verify login page, click 'Forgot Your User ID.'
- Enter the e-mail address associated with your E-Verify user ID and click 'Submit.' If the e-mail address that you entered is on file, your User ID will be e-mailed to you.
- Check your e-mail. Your user ID reminder should be in your inbox. Check your spam folder if the e-mail is not in your inbox.
Once you have completed all lessons in the E-Verify tutorial, the "Knowledge Test" link will be available from the main tutorial screen. If you have completed all lessons and are still unable to access the knowledge test, make sure you have green check marks next to each lesson on the Tutorial Home page and that you disable the pop-up blocker on your computer. If the problem persists, contact the technical support helpdesk at 1-800-741-5023.
As a corporate administrator you can manage important information about your company from the left navigation menu 'My Corporate Account.'
- From 'My Corporate Account,' select 'Edit Corporate Profile.'
- To modify any section of the Company Information page, click 'View/Edit' in the section you want to modify.
For more information on updating your company's profile, review the E-Verify User Manual for Corporate Administrators.
The E-Verify company ID number, which consists of four to six numerical characters, is located on the first page of the memorandum of understanding for the company location.
Corporate administrators may also obtain the company ID number for a company location as follows:
- Log in to E-Verify with your assigned user ID and password.
- From 'My Company Locations,' select 'View Existing Locations.'
- Enter the search criteria for the company location and click 'Display Company Summary List.'
- Click 'Edit' next to the company location for which you need the company ID number.
- The Company Information page will display the company ID number for that company location.


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George Marshall
America's Most Elusive Military Hero Finally Gets His Due
October 20, 2014
Even his heroism was private.
Devils in America
February 16, 2004
Reds: McCarthyism in Twentieth-Century America By Ted Morgan (Random House, 685 pp., $35) NEARLY FIFTY YEARS AGO the United States Senate voted to censure Senator Joseph McCarthy. Within three years of his disgrace, McCarthy was dead, his health destroyed by heavy drinking. His time in the limelight had been brief.
A Man of Good Intentions
July 29, 1996
Profound disappointment creased the usually impassive face of Warren Christopher the night of May 29. The secretary of state and his staff on the seventh floor of the State Department were hearing about the election returns from Israel. Benjamin Netanyahu, a committed foe of trading the Golan Heights for peace with Hafez al-Assad's Syria, had defeated Shimon Peres, Israeli architect of the land-for-peace enterprise. Christopher had invested more than three years of effort, as well as presidential, national and personal prestige in trying to broker such a deal.
Will the Pact Save Peace?
February 21, 1949
The North Atlantic pact, which involves one of the most fateful decisions in American history, is being discussed in a series of articles in the New Republic. Last week Captain B. H. Liddell Hart, noted British military expert, analyzed the defensibility of Western Europe, and in an editorial we gave our reasons for believing that the North Atlantic pact deserves support. The article below, by Blair Bolles, offering an argument against the plan, is published for its intrinsic interest.


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Pick me UP Limousine Service understand the demands of the corporate world and pride ourselves in providing highly efficient, always on time Corporate limo services.
Pick me Up Limousine Service is a class beyond excellence. We provide professional limousine services, for the entire bay area. We provide town car for airport transportation or a limo for your wedding day. We offer unparallelled service and competitive prices!!
Pick me Up Mobile version gives you easy way to make reservation in the palm of you hand. Specifically developed for mobile devices, incluiding Iphone, Android and Blackberry®


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Events Calendar
Scribes & Sketchers (CBMPL)
September 13, 2013 –
Scribes & Sketchers was so popular this summer that the Mounce Library is extending the program into the fall, meeting every second Friday of the month. Don't worry if you didn't get a chance to participate this summer; you can get started now. So if you are a writer or an artist and looking for a like-minded group to help get you to the next level, this is the place to be. Stick with it through next summer, and you could have your work published! Snacks will be provided. Bring your work and a good attitude with you.This event will be held from 4:30 to 6:30 p.m. on Friday, September 13 in Clara B. Mounce Public Library's first floor conference room. If you have any questions, contact Sam at (979) 209-5600.
Click here for more information


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Research projects at the CLE aim to bridge disciplinary boundaries and develop innovative interdisciplinary approaches to the study of languages, literary texts and cultures. The CLE fosters this by bringing together and promoting exchanges and collaborations with teachers and scholars with backgrounds in various domains (text linguistics, philology and discourse analysis among others) and disciplines (French, English, Italian, Spanish, Russian). Texts are examined in their historical, social and cultural context of production and in the original language, which makes the study of translation and reception a prominent aspect of our teaching and research.
The main areas of research developed by members of the CLE and doctoral students can be grouped in the following teaching and research areas:
1) Epistemology and methodology of differential comparison from an interdisciplinary perspective
2) Comparative analysis of literary and non-literary genres
3) Comparative analysis of Greek myths and their rewritings
5) Comparative analysis of fairy tales from the sources in Antiquity to the present day
6) Comparative poetics and translation studies
7) Comparative approach to children's literature
8) Comparative narratologies