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I have a question that I have not been able to find the answers to on the internet, and I was hoping that someone knowledgeable on genetics could assist me with the answers.
I was wondering if RH negative blood can be found in any species other than humans.
(All I have been able to find out regarding this is that the RH factor is based on a group of blood cells only specific to humans...Yet it was first discovered on the Rhesus monkey...So I would be very interested to know if animals have anything similar to what is known as RH negative blood type in humans?).
(Maybe I need to ask someone who is an expert in veterinary science this question?).
Edited by Emily2025, 15 December 2010 - 12:53 PM.


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Savox Low Profile Digital Servo SAVSC1252MG
Savox SC-1252MG Low Profile Super Speed Metal Gear Digital Servo
In Stock
Warning: Last items in stock!
Availability date:
More information about Savox Low Profile Digital Servo SAVSC1252MG
Low profile dimensions make the SC-1252MG a perfect choice for any vehicle with tight spaces. Ideal for 1/10 scale touring/on-road, the SC-1252MG can also function in planes as a thin wing servo. At .07 (@6.0V sec/60), its superfast response is impressive for steering around the oval or the F1 track. Built tough with durable metal gears.
Super high 4096 resolution and metal gears.
Super light-weight.
Coreless Motor provides high speed, incredible efficiency, and low power consumption than comparable servos.
The aluminum case design not only looks good but also helps operation to remain cool and smooth.
Our servos are totally green – from materials to production, these servos are environmentally friendly.
Ideal as a steering servo for 1/10 surface applications and in gliders and airplanes that have thin wing profiles.
Specifications for Savox Low Profile Digital Servo SAVSC1252MG
Main Category
|Radio Systems
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Dimensions(mm): 40.8X20.2X25.4
Weight(g): 44.5
Speed(@4.8V sec/60): .09
Torque(@4.8V oz-in): 89
Speed(@6.0V sec/60): .07
Torque(@6.0V oz-in): 97.2
Gear: Metal
Bearing: 2BB
Case: Aluminum
25 Tooth Spline
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subset: commoncrawl


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Gymnastics is a great sport for children – it's exciting, challenging and fun. Parks and Recreation has a dynamic gymnastics program that is a favorite of many children. Through our program, your child will:
The Parks and Recreation Gymnastics program has a broad offering from parent/toddler classes for tots as young as 18 months to advanced classes for children up to 12 years old. We have classes Monday through Thursday and on Saturdays. Our professional and enthusiastic instructors make class fun and exciting – they are a key reason why more than 300 children take gymnastic classes with us each week!
Our classes create a great foundation of gymnastics skills and are a great value – our three month program often costs the same as other one month programs.
More information


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Cosmetic Plastic Surgeons in Laguna Hills
You can choose a cosmetic plastic surgeon in Laguna Hills from this list with confidence, knowing that he or she possesses exceptional training, outstanding credentials and experience with all areas of the face and body.
This list features only plastic surgeons in the city of Laguna Hills. To widen your search, choose a nearby city from the list to the left, or click here to search by ZIP code.
|Surgeons highlighted below have purchased an Enhanced Practice Profile
|Personal Website
Eugene D. Elliott, M.D., FACS9900 Talbert Avenue Suite 101 Fountain Valley, CA Tel: Click for phone number714-241-0646
|16.3 Miles
Steve T. Vu, M.D.17742 Beach Blvd. Suite 335 Huntington Beach, CA Tel: Click for phone number714-848-1133
|18.11 Miles
Andrew Smith, M.D. ,FACS341 Magnolia Ave., #206 Corona, CA Tel: Click for phone number951-734-2500
|19.16 Miles
Jed H. Horowitz, M.D.3991 MacArthur, Ste. 320 Newport Beach, CA Tel: Click for phone number949-720-3888
|19.47 Miles
Steve T. Vu, M.D.800 Magnolia Ave. Suite 105 Corona, CA Tel: Click for phone number951-279-7888
|19.82 Miles
Michael Jun Watanabe, M.D.24401 Calle de la Louisa Suite 102 Laguna Hills, CA Tel: Click for phone number949-859-8551
|0.78 Miles
Robert M. Kachenmeister, M.D.26732 Crown Valley PKWY Suite 585 Mission Viejo, CA Tel: Click for phone number949-645-3333
|3.16 Miles
Daniel B. Kim, M.D.26732 Crown Valley Parkway Suite 585 Mission Viejo, CA Tel: Click for phone number949-364-1010
|3.16 Miles
Daniel B. Kim, M.D.Suite 585 26732 Crown Valley Parkway Mission Viejo, CA Tel: Click for phone number949.645.3333
|3.21 Miles
Burr von Maur, M.D.Suite 351 27800 Medical Center Road Mission Viejo, CA Tel: Click for phone number949-364-9107
|3.41 Miles
The surgeons listed above are members of The American Society for Aesthetic Plastic Surgery, licensed by the state of California and certified by The American Board of Plastic Surgery (ABPS).
Choose Your Plastic Surgeon Carefully
Remember, any licensed physician is legally allowed to advertise as a "cosmetic" surgeon, even if he or she has no formal surgical training. Your body is nothing to take chances with, so avoid the risk. Selecting a board-certified plastic surgeon from this list is your assurance that your doctor has the highest quality training and advanced surgical skills.
ABPS Certification and ASAPS Membership Matters
The ABPS is recognized by the American Board of Medical Specialties to certify doctors in the specialty of plastic surgery. Following medical school, ABPS-certified plastic surgeons must have completed a minimum of 5 years of surgical training, including an accredited plastic surgery residency program. Members of ASAPS must be in at least their third year of active practice following ABPS certification.


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I have to submit a lesson plan with the objective of learning and practicing the vocabulary of hobbies and to revise adverbs of frequency. I made silly mistakes on my previous attempts and i only have one attempt left so I am a little hesitant to submit this new attempt. I was wondering if this lesson plan is good enough to submit.
Lesson plan: hobbies vocabulary
Level: elementary
Objective: to learn and practice the vocabulary of hobbies and to revise adverbs of frequency.
Target language: read/s books, paint/s pictures, swim/s, cook/s, dance/s, garden/s, sew/s, knit/s, play/s video games, ride/s horses, ride/s bike.
Assumed knowledge: they know basic sentence structure using adverbs of frequency. (Subject + adverb of frequency (often, sometimes, rarely, weekly, daily).
Preparation and aids:
-picture cards featuring images of actions the words they will learn.
-word search for homework.
Anticipated problem: students may want to use dancing but not dance.
Solution: lead them to use the correct sentence structure. 'Sally swims often'.
Lesson Plan
Warmer: hang man with the adverbs of frequency (often, sometimes, rarely, weekly, daily) on the board. (T-S)(5 minutes).
Concept check the students remember the meaning.
Ask the class what tasks they would do daily? e.g.: brush hair, brush teeth, get dressed, shower.
Ask the class what tasks they would do weekly? e.g: grocery shopping.
Ask the class what tasks they would often do? E.g: exercise, walk the dog, visit friends.
Ask the class what tasks they would rarely do: go to the doctor, go to the dentist.
Ask the class what tasks they would sometimes do: go to the park.
(These answers will be up to the students and what was covered in the lesson on adverbs of frequency)
Lead-in: draw a stick figure on board and name it with the class (eg: Sally). Discuss with the class about the stick figure. Tell the class that Sally likes to keep very busy, in her free time she likes to do many fun activities. She regularly does these activities.
'What are these activities called?'
'Sally has many ______'
Elicit the word 'hobbies'. Tell the class that hobbies are activities, or interest that people do in their spare time for fun and relaxation. Hobbies are done more than once, they can be done daily, weekly, often, sometimes or even rarely but need to be done every so often.
Concept checking questions:
'Do people do hobbies as a job?'
'If a person does an activity once and never again, is it a hobby?'
'Is a hobby a fun activity?'
'Is a hobby a stressful activity?'
Drill the words 'hobbies and hobby' and sentence, 'Sally has many hobbies', chorally.
Write the word 'hobby/ hobbies' on the board as a heading.
(T-S)(10 minutes)
Explain that there are many different hobbies and that the class will be learning a few that Sally is interested in today.
Present the new vocabulary using the flash cards. Eg: the card of a person reading. Using the flash cards elicit the new vocabulary from the students.
Feed the word to the students the words if they do not know the word.
In order to get the correct form of the word lead the students to the correct grammatical structure.
Lead the students with, "Sally ____"
With each new word discuss the hobby and ask concept checking questions.
Some lead questions to ask:
-"Does anyone have the same hobby?"
-"What do you need to do this activity?"
-"Can this activity be done inside or outside or both?"
-"How often can some do activity like this and why?"
Drill the word.
Write the word on the board.
(T-S ) (20 minutes)
Production: Break up the students in to pairs and tell them they need to come up this two sentences per pair (one each). Tell the class the can use details that they came up with from the previous stage and that they need to include an adverb of frequency. When they are done making their sentences they will tell the class out loud. And the teacher will write the sentences on the board.
Come up this an example sentence with the class and write it on the board.
Eg: Sally often rides horses in the park.
(T-S, PW, S-T) (10 minutes)
Homework: word search with the new vocabulary.


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The IT Services Web team possesses expertise with social media strategy, and a representative would be happy to meet with you to discuss how to leverage social media to better connect with your students, clients, or constituents. Prolific social media sites include Facebook, Twitter, Google+, and LinkedIn.
How do I request this service?:
Contact the ITS Solutions Centre.
What is the cost for this service?:
When is this service available?:
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How do I get help with this service?:
Contact the ITS Solutions Centre.
Who can use this service?:
Service Provider:
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Web Publishing and Hosting


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Lacrosse news straight to your inbox.
Tuesday August 6th, 2013 1:09am
Inside Lacrosse's Preseason All-Americans from the 2013 Face-Off Yearbook are out. It's constantly among the most debated content on InsideLacrosse.com.
It's well-debated among the staff before it even hits the press. Here, we debate what guys could have been included, or what honorable mention stars could move up by years end.
You can pick up a copy of the 2013 Face-Off Yearbook for more expansive coverage.
Lyle Thompson, Albany — I think his freshman season was overlooked in 2012. He put up 22 goals and 16 assists and finished with the second-most groundballs on the Danes' squad with 39. Whether he plays attack or midfield, Lyle's putting up some points in 2013. Simply put, he's got skills that even some of the guys on the first- and second-teams don't have, at least not yet. Lyle's one of the calmest guys I've seen on the field, and he is a tough guy to game-plan, even for top teams. If Albany can improve this season, I think Lyle could get a bit more recognition this time around. This is a guy who played against Paul Rabil and Casey Powell in the Bowhunter Cup in Sept. 2010 before his final high school season. To me, he's already on another level than a lot of the players in the NCAA landscape. I got to watch him up close at the Founders Cup just a couple months back, and he was so obviously the most dominant player on the floor. I think he's primed for big things this coming season.
Casey Carroll, Duke — I'll take the guy that hasn't played NCAA lacrosse since 2007: Duke's Casey Carroll. Yes, that makes him an old man, a full nine years older than possible freshman linemate Jamie Ikeda. But it's not like the guy's been sitting at a desk crunching numbers on Wall Street. He returns to Duke (the esteemed Fuqua School of Business, no less), after five years as an Army Ranger. He was a first-team All-American in '07, and while returning to that form as a 28-year-old might be a lot to ask, I could see him sneaking past his preseason honorable mention spot to maybe second-team honors. Either way, his leadership will be invaluable for the Devils.
Nicky Galasso, Syracuse — This is either easy pickins' or complete speculation depending on how you assess the situation, but I think a lot of us are kind of waiting on bated breath here to see what Nicky Galasso can do up in the Dome this spring. He was a third-team AA after his freshman season, so putting him as honorable mention after barely playing in 2012 is either giving him too much credit or not enough, and while I don't think he is getting "disrespected" in the least here, I would not be surprised if he puts together another All-America-caliber season and gets himself back onto one of the first three teams. So much of his success will be dictated by how he clicks in with the Orange. This is probably kind of hopeful, as I saw enough of Galasso in high school to know that it sure would be fun to watch him play well at 'Cuse.
And while we're talking AAs, lets not forget some of the other ranks of the NCAA. The entire midfield of our DIII All-America second-team has the potential to make the top spot by the end of the season. Tony Rossi started for Stevenson as a freshman, and after missing last year, I expect him to come back as a force. In reviewing coaching surveys, Colby's Ian Deveau frequently popped up as a POY for the NESCAC. And the greatest name in the SUNYAC, Jimmy van de Veerdonk, also got a lot of love from coaches, earning nods for AA, All-SUNYAC, SUNYAC POY, and even potentially Midfielder of the Year. All three could play middie for my team any day.
Jake Hayes, Robert Morris — I'm going off the radar a bit with Robert Morris senior Jake Hayes at attack. Hayes put up 42 goals last year. Robert Morris' transition-heavy and high-scoring offense will do the same this year, so it's not out of the question for him to put up similar production. The Colonials will have to elevate a little for him to get an All-America nod, but with 11 wins last year and an overtime loss in the NEC semis that could have gone the other way, they have what it takes this year to sneak around the Top 20 and get some recognition.
Also, I have to mention all the Virginia attackmen. It's already been discussed that UVa is potentially under-ranked at No. 9. If Matt White, Mark Cockerton, freshman James Pannell or Nick O'Reilly take contrl of the offense in the post-Stanwick era, expect them on the list.
Joey Sankey/Jimmy Bitter, North Carolina — Yes, I'm cheating and picking two players instead of one, but I believe both players are marked for tremendous potential to make the second and third-team All-American lists. For the first time in awhile, the Tar Heels enter a season with a consistent group at attack, with senior Marcus Holman leading these two talented sophs on the unit. The group, as they hinted at least year, will feed off each other and continue to develop into one of the top-ranked units in the country. If UNC can win groundballs and play a little more staunch defense, they should start making a push deep into Memorial Day. My story, sticking to it.
Pick up a copy of the 2013 Face-Off Yearbook for more expansive coverage of the coming season, as well as the rest of the NCAA landscape.


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**Cadillac User Experience (CUE)** Discussion, A new safety recall for the SRX in Item Specific Cadillac Discussion; I got a safety recall today concerning the manual shift mode on the SRX. The recall claims that the manual ...
- 04-15-13 11:55 PM #1Cadillac Owners Enthusiast
- Automobile(s): SRX
- Join Date
- Jul 2011
- Posts
- 697
A new safety recall for the SRX
I got a safety recall today concerning the manual shift mode on the SRX. The recall claims that the manual mode may unexpectedly shift back to auto and remove engine braking if you have selected the sport or manual mode to down shift on a hill or curve. The recall says it is reprogramming required and no hardware. I also had my instrument lights go out and on for several times today and that will be looked at also. Anyone else have that issue? I had it with my 2011 SRX also. It seems to be an issue right around sunset when the ambient light is affected by trees and buildings and the auto dimming goes from night to day settings back and forth until the light level stabilizes on one or the other. It is an unacceptable flaw and one that makes dusk driving a strain. It might turn out to be "Unfixable" like the Canuk's STS issue.
Re: A new safety recall for the SRX
I made a mistake when I said that my wife's car had an instrument light problem. She subsequently told me that the entire system, DIC, center console and all of the CUE functions went out including the big screen. The radio was on and stayed on. After about ten minutes everything came back on. This will be one of those hard to re-create for the dealer to investigate. If any of you have had a similar experience I would appreciate a description of it and how you resolved it so that I can relate this to my dealer.


text:
Welcome to E-Books Directory
This is a freely downloadable e-book.
SQL Performance Explained by Markus Winand
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SQL Performance Explained
by Markus Winand
Number of pages: 91
SQL performance problems are everywhere, everyday. SQL Performance Explained is a free SQL tuning e-book for developers. It avoids unnecessary details about database internals but highlights the one topic that is most often neglected: proper indexing.
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/// Sprint Board Walked Away From MetroPCS Takeover
February 25, 2012 | All Things Digital
Sprint Nextel Corp.'s board explored but rejected a multibillion-dollar deal to acquire smaller wireless rival MetroPCS Communications Inc., people familiar with the matter said. MetroPCS, which provides cellular service to 9.3 million customers, had a market value of about $4.3 billion as of Friday's closing price. Its shares gained 6.4% to $12.78 in after-hours trading on news of the talks. Read the rest of this story on the original site »
Read the rest here:
Sprint Board Walked Away From MetroPCS Takeover
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Get The Leftover Fireworks Out Of Your Garage
There will be no questions asked during Saturday's fireworks amnesty day in Omaha.
Police Sergeant Matt Manhart says unused fireworks won't be the only thing collected. "Individuals can pull right up," he said, "They can drop off any of their unwanted firearms, ammunition, fireworks or explosive devices. We'll thank them and send them on their way."
Items can be dropped off from 9am until 3pm Saturday at the Omaha fire station near 103rd and Fort, or at Seymour Smith Park at 72nd and Harrison.


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When Swindlers Worked the 'Big Con' on Stock InvestorsAmy Reading
April 16 (Bloomberg) -- In the 1900s and 1910s, hundreds of swindling teams worked the Big Con in U.S. cities.
The time was right because, by the beginning of the century, the sensational exploits of robber barons and the vast fortunes to be had from railroad, mining and other industrial enterprises had created an appetite for financial speculation that most Americans couldn't satisfy.
The stock markets were open only to the few who could afford the high share minimum and margin requirements. This moment in history -- after gambling ceased to be widely considered immoral and before securities became a standard part of retirement funds -- left middle-class businessmen quivering for opportunity.
Enter the confidence man, who calibrated his pitch just right: He wasn't offering something for nothing; he was looking for a wide-awake investor who knew how to read the winds.
The Big Con was a precisely constructed play in nine acts. Take the experiences of J. Frank Norfleet, a prosperous, self-made cattle rancher from the Texas Panhandle, who was visiting Dallas in November 1919 to sell land.
Finding Mark
Norfleet's swindling began when the members of the Furey gang "put the mark up," or identified him as a likely victim. They looked for out-of-towners, ideally, rich ones who weren't too familiar with the financial industry. Norfleet fit the bill.
In the ornate lobby of the St. George Hotel, with his pants tucked into his cowboy boots, Norfleet stuck out. One of the swindlers, Reno Hamlin, befriended him and expressed interest in a carload of mules Norfleet had for sale. Just then, W.B. Spencer strode into the lobby. Hamlin introduced Spencer as a buyer for the Green Immigration Land Company in Minneapolis who might be interested in Norfleet's land.
Hamlin and Spencer, the steerers of the gang, were "playing the con" for Norfleet, a crucial step that involved fostering intimacy. This took several days, as the ropers wined and dined their mark and earned his trust. Then they "roped the mark," or transferred his loyalties to the inside man.
Spencer and Hamlin met Norfleet in the lobby of another fine Dallas hotel, the Adolphus, where they intended to discuss their land deal. But as Norfleet sat down, he felt something pressing against his thigh. He discovered a wallet with cash, a cipher code card and other documents, all inscribed with the name J.B. Stetson. The men ascertained that Stetson was a guest of the hotel, and they knocked on his door to return the wallet.
Stetson was, in reality, Joe Furey, the gang's ringleader. In gratitude for the return of his wallet, he pressed a $100 bill on the rancher. Norfleet refused, as they knew he would. Furey then suggested that he repay Norfleet's kindness by investing $100 on the local stock exchange and allowing his benefactor to keep any profits.
Thus began Act 4, in which Furey "told the mark the tale." Furey alias Stetson said his job was to play the market using information in encrypted telegrams sent to him by United Brokers, a clandestine syndicate of Wall Street firms. United Brokers controlled large enough blocks of stock that it could swing the market. Since Furey always knew its manipulations in advance, he could place opportunistic orders.
Furey dashed to the brokerage. Twenty minutes later, he was counting $800 into Norfleet's hand. It is a truism of the Big Con that no mark has ever been able to resist "the convincer," the material proof that the mechanism behind the con actually works. Furey then confessed that he was in debt, and asked Norfleet for help. He wasn't permitted to place his own money on United Brokers' stock picks, Furey explained. Would Norfleet consent to use Furey's money but sign his own name on the stock orders, and split the profits? Furey would be happy to reinvest Norfleet's cut.
Signed Orders
Over the next few days, Norfleet sat in Furey's room in the Adolphus and filled out "buy" and "sell" orders as Furey deciphered his telegrams. Furey took the orders to the exchange and returned with his arms full of cash (actually, newsprint sandwiched between real bills). Norfleet's profits had reached $28,000, or about $350,000 in today's currency.
Suddenly, E.J. Ward, the secretary of the exchange, burst into the room. Norfleet had been speculating on the exchange illegally, Ward said, because he wasn't a registered member. Ward would have to seize Norfleet's profits.
Furey volunteered a solution. If Norfleet could retroactively back his speculation with the cash deposit required of members, could he keep his winnings? Ward said he could.
Next, Furey and Spencer began "giving the mark the breakdown," which involved gently sussing out how much money he could raise at a moment's notice. Norfleet said he could get $20,000 from his bankers.
The swindlers then "put the mark on the send," dispatching him to raise the cash. This was usually a fragile juncture, and so Spencer accompanied Norfleet. While Spencer ate Eliza Norfleet's corn pone and baked ham, Norfleet visited his banker.
Then came "taking off the touch," when the money under Norfleet's arm vanished before he realized it was gone. It wasn't until Furey failed to appear at the Cadillac Hotel in Dallas the next morning that Norfleet realized he had been swindled.
The last act of the Big Con called for "blowing off" or "cooling out the mark." The swindlers designed the endgame so that the mark returned to his regular life without complaint.
This part of the con didn't work as expected with Norfleet. He wasn't cooled out and didn't slink home in shame. As it turned out, he wasn't a typical mark. At the last minute, he decided to get even with the men who swindled him. But that's another story.
(Amy Reading is the author of "The Mark Inside: A Perfect Swindle, a Cunning Revenge and a Small History of the Big Con," recently published in paperback by Vintage. The opinions expressed are her own.)
To contact the writer of this article: Amy Reading at firstname.lastname@example.com
To contact the editor responsible for this post: Max Berley at firstname.lastname@example.com


text:
The Norwegian Ministry of Magic governs the Wizarding community in Norway. On display in the Ministry is a letter from Goodwin Kneen to his cousin Olaf that describes an early form of Kwidditch (Quidditch).
- Quidditch Through the Ages (First appearance)
This article or section is a stub. You can help by expanding it.


text:
|Publication number
|Publication type
|Application number
|PCT number
|Publication date
|Feb 19, 2008
|Filing date
|May 5, 2003
|Priority date
|May 3, 2002
|Fee status
|Also published as
|Publication number
|Jennifer K. White
|Original Assignee
|The General Hospital Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (19), Non-Patent Citations (2), Referenced by (67), Classifications (9), Legal Events (9)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a national phase application of, and claims priority from, International Application No. PCT/US03/14160, filed May 5, 2003, under 35 U.S.C. 371, which claims the benefit of priority from U.S. Provisional Patent Application No. 60/377,721, filed on May 3, 2002. The entire contents of both applications are incorporated herein by reference.
The present invention relates to a prosthetic valve with an involuted structure. The present invention also relates to methods and apparatus for constructing an involution valve.
Since the implant of the first cardiac valvular prosthesis in the anatomic position in 1960, more than 50 different cardiac valves have been introduced over the last forty years. Unfortunately, after years of development of mechanical and tissue valves there remain significant problems associated with both types of valves.
Mechanical vs. Tissue Valves
Mechanical valves are durable in patients but require long-term anticoagulation therapy. Tissue valves offer freedom from anticoagulation therapy and the problems of bleeding, but tend to degenerate rapidly, particularly in younger patients. The most commonly implanted tissue valves are constructed from chemically-treated animal tissues (i.e., glutaraldehyde-fixed pericardial or porcine valves). The preservation, sterilization, and fixation processes currently used in tissue valve preparation are believed to contribute to the lack of longevity of tissue valves.
Ross Procedure
One alternative approach for aortic valve replacement has been to transpose the patient's own pulmonary valve into the aortic position in the same individual, as described by Ross in the late 1960's. Although a technically demanding procedure, the Ross procedure frees the patient from anticoagulation therapy and has substantial longevity compared to other types of tissue valves. A disadvantage of using the pulmonary valve to replace the aortic valve in the same patient is that the pulmonary valve must also be replaced. Most commonly, the replacement tissue for the excised pulmonary valve is a valve (aortic or pulmonic) derived from a cadaver ("homograft"). Problems arise from lack of donor availability and size mismatches between the donor homograft and the living recipient. Unfortunately, replacing the pulmonary valve with a homograft is associated with immunologically-mediated stenosis in some patients which limits their longevity.
Monocusp Procedure
Alternatively, a single flap of tissue from the pulmonary trunk has been used to create a pulmonary "mono-cusp" valve in pediatric patients undergoing the Ross procedure. Long-term function of the monocusp valve has yet to be documented. Historically, it is known that a single leaflet valve design has a less efficient closure than a tri-leaflet valve. The suboptimal function of a monocusp valve may adversely impact long-term results. It is a drawback that the mono-cusp procedure is restricted to replace a valve at the location where the tissue flap is created. The monocusp procedure does not provide a source for replacement of valves other than the pulmonary valve.
Trileaflet Valve Derived from Pulmonary Artery Tissue
Another previously described method to replace the aortic valve entails surgical reconstruction of a tube of tissue from the pulmonary artery of the same individual. In this procedure, a tube of tissue was harvested from the pulmonary trunk and reconfigured into a trileaflet valve. In order to create a valve, the base of the pulmonary tissue tube was sutured to the aortic annulus and to the aortic wall at three points. This procedure was attempted in three pediatric patients and abandoned due to immediate and severe aortic insufficiency in two patients. The failure of this valve replacement procedure resulted, in part, from the extreme technical challenge for the surgeon. In this procedure, the surgeon must simultaneously construct and implant the valve while attempting to surgically compensate for any size discrepancies between the donor tissue and the recipient valve site.
As described previously, promising attempts to create a tissue valve by reconfiguring an individual's own living tissues have been problematic. It would be advantageous to have a method to more efficiently, effectively, and reliably construct a functional and durable tissue valve. It would be desirable for the valve to be a non-immunogenic structure capable of cellular regeneration and repair.
U.S. Pat. No. 5,713,950, issued to Cox discloses a valve constructed from a tubular structure. This invention is a nesting of tubes dependent on multiple suture lines or points to join the tubes to create a valvular structure. It is a drawback that these sutures are positioned in areas of high stress during the function of the valve through the cardiac cycle. Although this valve is a simple design, it would be inefficient and difficult to use this method to reconfigure the patient's own tissues into a valvular structure.
U.S. Pat. No. 6,494,909, issued to Greenhalgh, discloses a device and means for a braided valve and minimally invasive deployment. The invention does not describe the area of attachment of the leaflets to the walls of the tubular structure to create a functional three-dimensional tri-leaflet valve. This invention does not describe a means for creating an autologous or living tissue valve. It is a further disadvantage that this invention describes that it is placed in a catheter for deployment. This is distinguished from other braided structures which are deployed by an internal mechanism with the potential for more maneuverable and narrower insertion profiles (such as that disclosed in Patent Cooperation Treaty application (designating the U.S.) No. PCT/US02/40349, filed Dec. 16, 2002, entitled "DYNAMIC CANNULA," and commonly assigned to the assignee of the present invention, the disclosure of which application is incorporated herein by reference in its entirety).
In one exemplary embodiment, the present invention provides for constructing a prosthetic valve by a technique referred to interchangeably as the "involuted cylinder" or "involution" method. The involution valve may be constructed of synthetic, semi-synthetic, organic or biological material or mixtures or combinations thereof. The valve is efficient to construct, may be derived from the patient's own tissues, and is particularly suitable for replacement of aortic or pulmonic valves.
In one exemplary embodiment, the present invention provides a valve constructed of a tubular structure involuted inside itself. The three-dimensional shape of the "involution valve" may be provided by folding, braiding, weaving, knitting, or combinations of these operations on the material. The material may be biological, synthetic, semi-synthetic, organic, or a combination of these materials. The patient's own tissue (e.g., pericardium, pulmonary artery, or aortic tissue) can be reconfigured into a functional valve using this method. Some examples of material sources include, but are not limited to, tissue derived from the same individual (e.g., pericardium, aortic, or pulmonary artery tissue) or a different individual of the same species (e.g., cadaver tissue) or a different species (e.g., decellularized porcine small intestinal submucosa).
The valve may be a scaffold, matrix, or other structure that undergoes a maturation process of living autologous cell deposition thereon. For the purposes of the present disclosure, the term scaffold will be referred to in an exemplary, but nonexclusive, manner. An example of a potentially suitable scaffold substance is decellularized porcine small intestinal submucosa. The scaffold could provide signaling to cells to organize as an autologous valve, provide a support structure for cell organization, or function as a non-immunogenic valve regardless of cell population. The scaffold can be a permanent, semi-permanent, or temporary structure capable of resorption or remodeling. In this manner, the valve would, when implanted and the patient adapted, have a lack of exposed immunogenic material.
The present invention provides a method of forming a valve or valve scaffold, comprising, in one exemplary embodiment: (1) providing a tube of material, (2) involuting the tube inside itself, (3) selectively attaching portions of the inside tube to the outer tube of material, (4) implanting the valve in a patient.
Accordingly, it is a feature of the present invention to provide a valve that has minimal immunogenic structure.
It is another feature of the present invention to provide a valve that is capable of cellular regeneration and repair and that is functional and durable.
Other features and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the appended claims.
The various features and advantages of the invention will be apparent from the attached drawings, in which like reference characters designate the same or similar parts throughout the figures, and in which:
The present invention generally provides a prosthetic valve formed by involuting a tubular structure inside itself The present invention also provides methods of forming an involution valve.
Primary Structure: Synthetic, Organic, and Biological Materials
In one exemplary embodiment of the present invention an involution valve is formed of synthetic or processed organic material. The material can be any of a number of different biologically inert materials. The following materials are set forth by way of illustration only and are not intended to be exclusive.
Synthetic Materials
Polyglycolic acids (PGA) can be used as non-woven mesh, having high porosity, good cell attachment, good growth and extracellular matrix formation, rapid bioabsorption, and biocompatibility. Examples of materials include, but are not limited to, polyhydroxyalkanotes (PHA or PHO); poly-4-hydroxybutyrates (P4HB) (PHA and P4HB have the properties of elasticity, mechanical strength, thermoplasticity, and have demonstrated increase in cell attachment during seeding with increased collagen development); PGA and P4HB hybrid in the form of thin PGA coated with P4HB to reduce stiffness but provide mechanical strength; absorbable and nonabsorbable suture materials, polylactic acid (PLLA); polycaprolactone; fibrin-gels (moldable); hydrogels (polyethylene glycol-based hydrophilic substances); dacrons; metals, or nitinols particularly biodegradable nitinols); mixtures and/or combinations thereof and the like.
Organic Materials
The valve may also be constructed of polymer-based substances; examples include, but are not limited to, polypropylene, polyester, silk, nylon, plastics, rubbers, silicones, papers or other suitable cellulose based product, polytetrafluoroethylenes (PTFE's), polyurethanes, mixtures and/or combinations thereof and the like.
Biological Materials
Pericardial tissue, arteries, veins, portions of the gastrointestinal tract, combinations of the forgoing and the like can be used. The material can be a chemically-treated tissue such as glutaraldehyde-fixed pericardium or other suitable tissue.
Tissue can be harvested, isolated (for example, a segment of tubular blood vessels such as the autologous pulmonary artery trunk, left or right pulmonary artery, and aorta), created (cell cultures) or tissue engineered (for example, cells populating a scaffold). The living material can continuously bathed in, for example, cell culture medium or Hank's solution so as to retain viability. Tissue sources include autologous (self) tissues, xenograft (e.g., decellularized animal tissues) or allografts (e.g., cadaver tissue). More specific examples of these include decellularized porcine small intestine submucosa ("SIS") and segments of a decellularized aorta, or vena cava tissue from cadaver donors. An example of a decellularization process is incubation of in trypsin/EDTA for 48 hrs to extract endothelial cells and myofibroblasts.
In one exemplary embodiment, the scaffold is decellularized porcine small intestinal submucosa which is reconfigured into a valvular structure, implanted into the individual, and allowed to mature by populating with autologous cells. Population of the scaffold with autologous cells can occur outside (e.g., in pulsatile cell culture "bioreactor") or inside the body (e.g., following implantation). Exposing the cell-populated scaffold to mechanical stresses has been shown to physically signal the cells to produce extracellular matrix material. The mechanical stresses may influence the mass, directionality, strength, and types of biomolecules (e.g., collagen) and cells integrating with the scaffold.
The materials described previously, as well as others, may be used to create a functional three-dimensional valve or scaffold using a method of the present invention. The valve is then implanted into the body, and depending upon the material and the configuration, allowed to mature by healing, endothelialization, autologous cell seeding, and extracellular matrix deposition
Secondary Structure: Homogeneous, Non-Homogenous, and Porosity, and Layering
The texture or surface structure of the valve material is significant and may be homogeneous or non-homogeneous. Human heart valves and the entire human endovascular system is lined with a smooth homogeneous layer of endothelial cells which serve a multitude of functions, including the prevention of thrombus formation. The material for the present invention may be living tissue such as blood vessels from the patient. In this case, the valve's surface is lined, in part, with a homogeneous layer of endothelial cells.
Other parts of the involution valve, such as an adventitial layer, which are exposed to the endovascular space, may pose a risk to form thrombus. In time following implantation, the non-endothelialized surfaces have the potential to be populated with a homogeneous layer of endothelial cells In most instances, it is preferable for the valve to be substantially completely lined with a smooth homogenous layer of endothelial cells on all surfaces that contact blood. Temporary systemic anticoagulation therapy in this patient during the endothelization period may reduce or eliminate the risk of thrombus formation. Alternatively, chemicals, drugs, growth factors and other agents that promote endothelization and retard thrombus formation may be bound to the valve material to provide local therapy.
In another case, the starting material for valve construction is pericardial tissue which has a smooth side (faces the heart's surface) and a rougher side of collagen and other constituents. Despite the homogenous nature of each side of these materials (e.g., human blood vessels or pericardium), the involution valve may be preferentially constructed such that the smooth side is the diastolic surface and the rough side faces the systolic side of the blood flow during the cardiac cycle. It appears to be advantageous to have the valve involuted such that the most homogeneous, smooth, endothelialized surface is facing the diastolic side of the circulation. This follows from the previous observations of others that tissue valve material undergoes degenerative changes and tends to form thrombus on the diastolic side versus the systolic side of the leaflets. The anatomical orientation in the circulation of the present invention as an aortic valve replacement is depicted in
The material of the involution valve may also be non-homogeneous. For example, the material can be provided as a laminate, mesh, knit, woven or nonwoven material, braids, strands, combinations thereof and the like. Meshes, braids (
These materials and fabrication methods may be exploited for their physical characteristics. For example, rib knit may be useful given its property of elasticity in its width direction. Jersey knit is known to have good wrinkle recovery and excellent drape. Double knits are known to be strong since production of the material is carried out on a circular-knitting machine with two sets of perpendicular needles. The physical characteristics of these materials and fabrication techniques may be exploited in light of the anatomy of the native human valve to construct a valve replacement with desirable elasticity, wrinkles, and strength properties.
Consider that the histology of the human native semilunar valves is referred to as highly anisotropic (i.e. not the same in all directions). It follows that the biomechanics of the "cusps" or "leaflets" are not the same in each direction. The leaflets are known to have gross wrinkles or "corrugations" of collagen fibers which expand perpendicular to the cuspal free margin (i.e. radial direction) and imparts a high compliance on the leaflet in this direction. The less compliant "crimp" or "pleat" in the collagen in circumferential direction is a predominate load bearing element, restricting leaflet during filling and cusp distention Strength is provided by groups of collagen cords radiate from the commissures (attachment points of leaflets to wall). These structural features enable the cusps to be pliable when the cusps are unloaded and the heart is contracted (systole), but inextensible when a load is applied during cardiac filling (diasole).
It may be advantageous to impart the physical properties of the human native valve to the present invention. For instance, one could purposefully choose a rib knit or jersey knit configuration of the material along the radial or circumferential direction of the valve construct in order to impart elasticity or draping characteristics to the leaflets. Imparting compliance to the valve leaflet has the potential to dissipate the force imposed by the cardiac cycle on the valve. This may increase strength and durability to the valve following implantation.
In prior studies of others, tissue engineered valve scaffolds have selectively populated with extracellular matrix material when stresses, such as imposed by the cardiac cycle, were mimicked in vitro. As exemplified, the selective use of the materials and fabrication techniques may be used to control the compliance and strength of the valve of the present invention. Controlling the physical properties of the materials and fabrication methods in this manner has the potential to more accurately signal the extracellular matrix materials and the cells that produce them to populate according to conditions that more precisely model the native system.
Strands or fibers of material may be elastic or nonelastic. The fiber diameter can vary in the same or in different fibers composing the material. One study using polyglycolic acid as a scaffold material in valve construction, advocated a fiber diameter of 12-15 μm. In certain cases, fiber diameter can be custom-extruded. The fiber may be rectangular, round, or twisted around itself in a clockwise or counterclockwise position. Each fiber could be a bundle of smaller diameter fibers.
Porosity of the scaffold material may be significant. The pores or spaces in the material may purposefully be sized to retard thrombus formation and promote endothelization and adhesion of circulating autologous cells. The scaffold materials themselves may be rough or smooth and the pores between them can form smooth shapes or shapes with sharp angles. Variables include pore shape, pore size, open or closed qualities, interpore connectivity, and pore wall morphology. Pores can be the spaces in a weave, braids, or knits. Pores can be introduced into the material by a variety of different techniques, including, but not limited to, cell opening agents and mechanical aperturing. The pores or spaces in the material may purposefully be sized to retard thrombus formation and promote endothelization and adhesion of circulating autologous cells.
In another instance, materials used to construct the valve could change their homogeneous properties and pore size. For example, if one constructed a weave of strands of decellularized porcine small intestal submucosa material, the hydrophilic nature of the material is such that it may form smaller pores and a more homogeneous structure after hydration or implantation in the body.
In certain substances, complex pore geometry (e.g., honeycomb shaped pores) can be created by dispersing paraffin spheres in the dissolved scaffold material (e.g., PLLA and PGA). The paraffin is subsequently dissolved to create pores in the scaffold material. Another technique is to use salt-leaching/sugar crystals/glass crystals to yield a porous matrix. The size of the pores can homogeneous (PGA) or heterogeneous (PLA). The scaffold pore sizes can range from approximately 100-500 microns, more preferably in the 100 to 240 micron range. Other investigators using PLA and PGA scaffolding have noted a decrease in compressive modulus for smaller pore sizes (100-200 microns) as compared to large pore sizes (250-350 or 420-500 microns).
The pores in the material or the orientation of spaces between the materials can be purposefully used to impart strength or elasticity to the valve. For example, a triaxial weave is a process of weaving three strands of material at 60 degree angles to one another (
The valve materials can be single or multi-layered. The layers can be orientated such that the directionality of the materials is parallel, perpendicular, or angled. For example, the material may be "biased", "radial", or a combination ("biased/belted") such as that used in automobile tire construction. In a bias construction the material is laid alternating at bias angles of 25 to 40 degrees to the surface layer direction. In a radial design a layer is 90 degrees to the surface material direction. Between these layers can be a series of alternating layers at low angles of 10 to 30 degrees to the surface direction. A combination of these may also be used. The directionality within each layer and orientation of the layers in respect to one another may be used to selectively impose strength and elasticity to the valve (
It is known from prior anatomical studies that the human semilunar valve leaflet consists of three histologically distinct layers; the ventricularis, the spongiosa, and the fibrosa. The ventricularis faces the inflow surface and consists of mostly collagen "corrugations" with radially aligned elastic fibers. The spongiosa is composed of loosely arranged collagen and glycoaminoglycans. The fibrosa opposes the outflow surface is mainly circumferentially arranged, "crimped," densely packed collagen fibers, mostly parallel to the free edge of the leaflet. With this in mind, the present invention could be constructed of layering material purposefully arranged. For example, the top layer (the future inflow surface of valve leaflet) may be compliant in the radial direction and the most bottom layer could have a directionality perpendicular to the top layer, imparting less compliance in the circumferential direction. A middle layer could be sandwiched in between which has an multi-directional, oblique, or loosely arranged material.
Investigators have expressed concern that the use of layering, and in particular, lamination of porcine small intestinal submucosa, may delaminate inappropriately following implantation. One way to overcome this would be to weave, knit, or braid the material to prevent delamination. A specific example is the use of a Leno weave in which the strands are arranged in pairs with one twisted around the other between other strands (
Tertiay Structure: Tubes, Sheets, and Sleeves
The scaffold can be formed according to the following exemplary method. A quantity of material is provided as a tube or as a sheet. If it is provided as a sheet, two opposing sides are joined together to form a tube by any of a number of techniques known to those skilled in the art and appropriate to the material being used, such as, but not limited to, weaving, interlacing, braiding, knitting, punching, tufting, laminating, suturing, stapling, gluing, welding, fusing, combinations thereof and the like (
One advantage of a tubular braid configuration is the possibility of creating a tubular valve that is collapsible (
Quaternary Structure: Involution, Attachment, Interleaflet Triangles, Sinuses, Leaflet Modifications, and Stents
Creating leaflets by involution allows the material at the site of the infolding (i.e., the base of the valve) to retain its compliant nature. This may improve valve durability by facilitating the transfer of stresses and strains on the leaflets to the wall of the implant site (e.g., aortic root). Since the valve is created prior to insertion, it can be tested prior to use and the valve function is not wholly dependent on surgical implantation techniques.
In one geometry of the involution valve shown in
In one exemplary embodiment, three longitudinal incisions about 120 degrees apart are made in the cylinder to create three flaps of tissue. Preferably, though not mandatorily, the length "L" of the incision is approximately one half the height of the tissue cylinder height "h" less about twice the tissue thickness "t"; i.e., L=�h−2t. The length "L" of the incision should preferably be less than half the height "h" of the cylinder in order to eliminate a potential hole in the base of the valve caused by the incisions.
As shown in
In particular, with tubes of tissue such pulmonary artery, the longitudinal incisions in the cylinder release the constraints on the material and allow the flaps to be easily involuted and secured to the inner wall of the cylinder. Although, the incisions are not necessary, they allow each flap to be secured to the wall independently and may help the leaflets move distinctly from one another during the cardiac cycle. In addition, the perpendicular attachment of each leaflet edge to the wall may facilitate proper tissue repair and growth at each commissure. The presence of incisions at the commissure sites may promote healing and collagen deposition at the commissures.
In another embodiment, no incisions are made and the tubular structure is simply involuted inside itself and selectively attached to the outermost wall (
In another embodiment, a braided tube is involuted inside itself and the inner tube forms a passively closed inner tube structure or one-way valve in part, due to the forces created by the involution of the braided tube (
In another embodiment, the involution valve may be formed by a double cylinder structure in which the innermost tube is folded inside the outermost tube (
One exemplary method of attachment of the inner wall (with or without flaps) to the outer wall is by using three or more "U" sutures (
Historically, tissue valves with leaflets secured by sutures failed due to the stress imposed at the sites of attachment. In the design of the present invention, the tissue has retained or imparted with healing capabilities that would theoretically offer reinforcement by enabling tissue growth and reinforcement at the suture sites.
A mathematical stress analysis of the involution valve constructed of human blood vessel, indicated that an area of high stress would occur in a discrete area at each commissure (attachment area of the inner leaflets to the outermost wall) (see
Interleaflet Triangles
Native human semilunar valves have structures referred to as interleaflet triangles. These structures represent a triangular region between leaflets created by the angled attachment of the each leaflet to the wall. In the present invention, an analogous structure can be imposed in the involution valve by creating a triangular area of attachment of the leaflets to wall of the valve construct. This can be created by interlocking or interlacing the material with weaving, braiding or knitting techniques (
In the native human semilunar valves the annulus (imaginary coronal circle representing the base of the valve) moves in opposition to the sinotubular junction (imaginary circle at the level of the leaflets most superior attachment to the wall or sinus) during the cardiac cycle. During diastole, the annulus increases diameter as the sinotubular junction decreases diameter. During systole, the reverse is true, namely, the annulus reduces diameter and the sinotubular junction increases diameter. This motion may be important for valve longevity and the sharing of stress between the leaflet and wall during the cycle. Inserting interleaflet triangles into the involution valve construct may help restore the opposing movement of the annulus with respect to the sinotubular junction. The alteration to the base of the valve construct to construct interleaflet triangles may permit independent movement of leaflets in relationship to one another.
In certain instances, the present invention is created from a tissue cylinder, in this case the interleaflet triangle can be re-approximated with a linear angle of sutures to relieve the point stress at the leaflet commissures. Angling of the base of each leaflet more closely approximates the normal anatomy and helps disperse the stress on the leaflet to a tapered row of sutures rather than a single point of attachment at each commissure.
In a human's native semilunar valve apparatus there exists a space between each leaflet and the vessel wall referred to as the Sinus of Valsalva. This space is known to increase the efficiency of valve function by providing an eddy current of circulating blood which functions, in part, to maintain the separation of the leaflet from the wall during the opening of the valve.
In the present invention, the outermost wall of the involuted cylinder valve construct can be purposefully enlarged at the base of the valve to recreate a potential space between the leaflet free edge and the outer wall. One exemplary method of creating the enlargement is to construct the valve such that the outermost wall is a larger diameter than the innermost wall cylinder. If the starting material is a tube, one way to achieve this is to use a conical shape of the material such that the smaller diameter of the cone will be involuted into the larger diameter of the cone.
In more complicated methods of forming an involution valve, such as weaving, the sinuses can be integrated into the final geometry by creating selective pockets or outpouchings in the outer wall (see
Leaflet Modifications
As described previously, the native human semilunar valve leaflet ventricularis layer has gross corrugations of collagen and elastin in the radial direction which impart significant compliance in this orientation. In the circumferential direction, the fibrosa layer has a crimping of collagen that provides a counterforce to overextension of the leaflet during the period of more extreme loading-bearing (diastole). In order to more closely model the physical properties of the native human valve, the involution valve of the present invention may be constructed with excess material in the leaflet in the radial direction or circumferential directions. (
Modifications of the leaflets' shape by sculpturing the free edge may maximize leaflet coaptation (i.e., the adaptation or adjustment of parts to each other). Such alternative shape of leaflets include scalloping or rounding off the edges (concave). Other potential leaflet shapes are convex or bi-convex with formation of a central nodule by purposefully imparting a node shape at the midpoint. In certain cases, these shapes may better mimic native valve anatomy and help valve function.
A sheet of woven, knitted, or braided material may be used in combination with a rigid or semi-rigid frame ("stent") to create a valve. The stent can function to hold the valve in the involuted position, which aids the surgeon in implantation. In another embodiment, a sheet of woven porcine (or other suitable source) decellularized small intestinal submucosa is suspended in a stent (
If the involuted cylinder valve formed by any of the aforementioned methods and materials is orientated such that following implantation, the most viable and anti-thrombogenic surface opposes the diastolic side (
As shown in
As shown in
One advantage of a tubular braid configuration is the possibility of creating a tubular valve that is collapsible (
Apparatus and methods for forming, inserting and using expandable and collapsible structures, e.g., cannulae, which may serve as an analogous technology useful for creating a scaffold capable of having a reduced diameter during implantation and expanding thereafter are disclosed in copending Patent Cooperation Treaty (designating the U.S.) application No. PCT/US02/40349, filed Dec. 16, 2002, entitled "DYNAMIC CANNULA".
Alternative Scaffolding Techniques
A mold of scaffold can be created by a tricuspid "ventricular" and "aortic" stamp (e.g., a silicone-coated aluminum mold). Thermoplastic scaffolding material is inserted between the two stamps to create the complex shape of the aortic root and valve.
Some scaffold materials (such as, but not limited to, P4HB) with thermoplastic properties can be welded instead of sutured at the commissures.
Computer-aided molecular deposition of scaffold material potentially be used in lithography to create the three-dimensional valve. The same process could generate a flat sheet, cylinder, or cylinder with three equidistant incisions (see the involuted cylinder method) which then undergo secondary folding to create a valve.
Special Processes
The present invention also contemplates the construction of a scaffold generally having the configuration made of a synthetic material, which is then used as a support on which to seed and grow cells. The basic concept of seeding is to transplant autologous cells onto a biocompatible and biodegradable scaffold that has been pre-formed in the three dimensional structure of a heart valve. The cells are attached to the scaffold while keeping tissues in vitro with physical signals to guide development of tissues. As the cells form extracellular matrix, the biodegradable polymer scaffold starts to degrade. The scaffold and the attached cells are implanted into the body where cells continue to produce matrix materials, providing increasing mechanical strength while the scaffold finishes its degradation (usually in about 6-8 weeks).
Possible culture additives include, but are not limited to, cytokines, growth factors, microencapsulated growth factors, heparin products, cell markers to track cells post-implantation, transfection vectors (e.g., green fluorescent protein), anti-microbial anti-fungal agents, mixtures thereof and the like.
Possible cells which can be used to seed the scaffold include, but are not limited to, fibroblasts, endothelial cells, myofibroblasts, smooth muscle cells, fetal-type smooth muscle cells, mixtures thereof and the like.
Cell sources include, but are not limited to, peripheral blood, human umbilical cord, blood, arteries (e.g., carotid), human foreskin, bone marrow, adipose tissue, mixtures thereof and the like.
The involution valve can be constructed from a wide range of materials. The use of scaffolding materials (e.g., porcine small intestinal mucosa) offer the advantage of a potentially autologous living valve capable of growth and repair following maturation of the implant in the circulation.
The involution valve can being constructed as a braid, a knit, or a weave of material. The ability to fabricate the valve using these techniques enables the potential to create a valve with physical properties analogous to the native human leaflet. These techniques increase the potential strength and durability of the valve the reinforcement provided by interlacing the material at the attachment areas of the leaflet to the wall. It is advantageous that the involution valve can be constructed as a continuous structure using these techniques.
In contrast to previous attempts to reconstruct autologous arteries into valvular structures, the method described in this present invention enables a tri-leaflet valve to be constructed independent from its site of implantation. The valve may be transplanted to any desirable anatomical implant site. This reduces the technical challenge and allows the potential for pre-operative or intra-operative dynamic function testing prior to implantation. In certain instances, it is advantageous that the involution valve can assume a narrow profile and be deployed into the endovascular space by a minimally invasive means.
The involution valve can also be constructed from the patient's own tissues in an economical manner, offering an alternative treatment for valvular disease. If the valve retains its growth potential, it may be particularly useful for pulmonic valve substitution in the Ross procedure or in pediatric patients with congenital abnormalities of the pulmonary valve such as tetralogy of Fallot with absent valve syndrome.
The invention may also have applicability to non-medical application. The advantage of this design and method is the potential to create a valve with the following properties; large effective orifice area, a low pressure gradient, efficient closure velocity, and low regurgitation volume. The valve is suitable in rigid or non-rigid systems and wet or dry environments. The valve leaflets can potentially form a seal around an inner rod or piston. The valve can be constructed from a wide range of materials. The valve is potentially efficient and economical to construct and insert into the stream of flow. The invention will be further described in connection with the following examples, which are set forth for purposes of illustration only. Parts and percentages appearing in such examples are by weight unless otherwise stipulated.
A tri-leaflet tissue valve can be constructed from the main pulmonary artery by the involution method and implanted into the aortic position in sheep (see experiment 1). This valve may also be suitable as a replacement for other valves (e.g., pulmonary valve).
An involuted cylinder valve constructed from pulmonary artery tissue and implanted in the aortic position in sheep.
Materials and Methods
From previously sacrificed donor swine (n=4, 50 kg+/−10 kg), the main pulmonary artery and its main left and right branches were harvested. The main pulmonary artery trunk was trimmed to create a tissue cylinder of height equal to the diameter of the recipient aortic annulus. A=h≈d, where A=recipient aortic annulus diameter (mm), h=tissue cylinder height (mm), and d=tissue cylinder diameter (mm). Excess fat was trimmed from the specimen and adventitial layer was carefully peeled off as a single sheet of tissue and discarded. The tissue cylinder was incised with tree longitudinal incisions 120 degrees apart. L=� h−2 t, where L=incision length (mm), and t=wall thickness (mm) (see
In two specimens, the edges of all three flaps of tissues were rounded-off along their free-edge, creating concave-shaped leaflets. In all constructs the flaps were involuted into the tissue cylinder and sutured to the cylinder wall at three equidistant points using "U" sutures (see
A median sternotomy was performed and cardiopulmonary bypass was instituted in recipient sheep. Cold high potassium crystalloid cardioplegia was given by direct ostial cannulation. The ascending aorta was transversely transected 1 cm above the right coronary artery and native leaflets excised. The preformed valve construct was secured into the subcoronary position by interrupted 3-0 Tevdek™ sutures on the lower edge and a running 4-0 prolene along the superior aspect. The aortotomy was closed and the animal weaned from cardiopulmonary bypass. In animals that recovered cardiac function, echocardiography was performed to assess valve function.
The two animals that received valve constructs without rounded-off leaflet free-edges displayed mild aortic regurgitation on two-dimensional echocardiography with continuous-wave Doppler using a hand-held epicardial probe. In the same group, the short-axis view exhibited coaptation of all three leaflets during valve closure. Symmetrical leaflet movement and good mobility was observed throughout the cardiac cycle in four-chamber apical view. A mean flow velocity of 2.49 m/sec was obtained in one animal with a 14 mm aortic annulus diameter. The two animals with rounded-off leaflet free edges had severe aortic insufficiency due to prolapse of two or all three leaflets and could not be weaned from bypass.
In this experiment, a segment of the main pulmonary artery was reconfigured into an aortic valve using a technique referred to as the "involuted cylinder" method and implanted into the subcoronary position in four sheep. In two constructs the leaflets were modified, creating concave leaflet free-edges. The modification was designed to eliminate deadspace at the base of the leaflets and reduce the risk of thrombosis formation. However, in these modified constructs the central region of the leaflets was not supported adequately which resulted in leaflet prolapse under diastolic load. The constructs without rounded leaflets assumed a more cup-like configuration and exhibited no prolapse, most likely due to the suspension of the leaflets at all points along the free-edge. It may also be significant that the longitudinal axis of the pulmonary artery wall becomes the radial axis of the valve leaflet. Increased extensibility of the leaflet in the radial direction may act to lessen the central orifice by providing more coaptation area
A scaffold is constructed of decellularized porcine small intestinal submucosa. The involution method described above is used to form a functional three-dimensional valve. The valve is implanted into the individual and allowed to mature under in vivo conditions.
A Pulmonic Valve Replacement in Sheep Using an Involution Valve Constructed of Porcine Small Intestinal Submucosa
Materials and Methods
A sheet of 4-ply porcine small intestinal submucosa "SIS" (Cook, Inc.) of dimensions 68.2 mm long�20 mm wide was prepared. Two equidistant 8 mm long incisions were created extending from the free edge of the length to centerline of the material. The flat sheet was folded in half along the length with the smoother surface on the inside. A cylinder was formed by suturing the two free ends together with a running 7-0 prolene. The leaflets were secured in a perpendicular manner to the inner wall of the cylinder by "U" sutures. Two additional sheets of SIS were sutured to either end of the valve, creating two cylindrical cuffs of tissues at either end of the valve construct.
A median sternotomy was performed and cardiopulmonary bypass was instituted in a recipient sheep. Cold high potassium crystalloid cardioplegia was given by ascending aortic cannulation. The pulmonary artery was clamped and transected one millimeter above the pulmonary valve. The native pulmonary valve was excised. The preformed valve construct was secured at the superior aspect to the distal pulmonary trunk using 5-0 prolene. The cuff at the base of the valve was sutured to the proximal remnant of the pulmonary trunk Protomine™ was given and the animal was weaned from cardiopulmonary bypass. The animal recovered cardiac function and echocardiography was performed to assess valve function.
The animal was successfully weaned from bypass. The pulmonary valve replacement displayed no pulmonic regurgitation on two-dimensional echocardiography with continuous-wave Doppler using a hand-held epicardial probe. The short-axis view exhibited coaptation of all three leaflets during valve closure. Symmetrical leaflet movement and good mobility was observed throughout the cardiac cycle in four-chamber apical view.
An involution valve constructed from decellularized porcine small intestinal submucosa functioned as a trileaflet pulmonary artery replacement in an acute sheep model. Chronic studies are necessary to determine the ability of the scaffold material to endothelialize and populate with autologous cells following endovascular implantation. Further investigation as to the function of the valve following implantation will help determine its usefulness in patients.
A sheet of the patient's pericardium is harvested and formed into a valve construct using the involution method as described hereinabove at the surgical backtable. The valve construct is tested, then reimplanted into the same patient as a living autologous valve replacement.
Formation of Scaffold
An unwoven polyglycolic acid ("PGA") mesh sheet 24 mm�75 mm and 1.5 mm thick is prepared and rolled into a cylinder. Three equidistant longitudinal 10 mm incisions are used to create three flaps which are involuted inside the cylinder and secured 120 degrees apart to form commissures. Scallop-shaped segments of the outermost wall of the cylinder are removed between the commissures to form the scaffold.
The scaffold of Example 4 created of a material that will support cellular growth, e.g., celluloid. Peripheral blood is harvested, samples are spun in column and cells are recovered (e.g., circulating endothelial cells) which are then serial plated on fibronectin culture plates and allowed to expand (e.g., static growth for 1 week). Cells are then seeded onto a celluloid construct in a rotating, pulsatile, or continuous flow bioreactor for a period of time (e.g., 4 weeks), then the valve is implanted in the patient to continue to mature, differentiate, and evolve in vivo.
A valve is created by any of the examples or methods discussed hereinabove and temporarily implanted in the body (endovascular or other site) to allow maturation. For instance, the valve can be deployed using a minimally invasive apparatus into the descending aorta, exposed to the blood stream and mechanical stresses of the cardiac cycle for a period of weeks, and then removed from the body and reimplanted as a permanent valve replacement.
A valve is created by any of the examples or methods discussed hereinabove and implanted in the endovascular space using a minimally invasive means.
It will be understood that the terms "a" and "an" as used herein are not intended to mean only "one," but may also mean a number greater than "one." All patents, applications and publications referred to herein are hereby incorporated by reference in their entirety. While the invention has been described in connection with certain embodiments, it is not intended to limit the scope of the invention to the particular forms set forth, but, on the contrary, it is intended to cover such alternatives, modifications, and equivalents as may be included within the true spirit and scope of the invention as defined by the appended claims.
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|Jan 24, 2017
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|Collapsible prosthetic heart valves
|Sep 30, 2014
|Jan 31, 2017
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|Sep 10, 2015
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|Apr 1, 2016
|May 2, 2017
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|Oct 22, 2004
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|Martin Dauner
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|Mar 31, 2004
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|Boston Scientific Scimed, Inc.
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|Sep 14, 2007
|Mar 20, 2008
|Boston Scientific Scimed, Inc.
|Bioerodible endoprosthesis with biostable inorganic layers
|Sep 13, 2007
|Mar 20, 2008
|Boston Scientific Scimed, Inc.
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|Boston Scientific Scimed, Inc.
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|Replacement heart valve, valve holder and methods of making and using same
|Aug 8, 2008
|Jan 29, 2009
|David Paniagua
|Percutaneously implantable replacement heart valve device and method of making same
|Mar 10, 2009
|Jul 2, 2009
|Von Segesser Ludwig K
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|Sep 26, 2008
|Jul 22, 2010
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|May 24, 2012
|Apr 9, 2014
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|U.S. Classification
|623/2.12, 264/632
|International Classification
|Cooperative Classification
|European Classification
|Oct 18, 2004
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text:
Watch: Kim and Kanye Ceremony Rehearsal and More!
Viewers got to see all the drama leading up to the Kim and Kanye wedding in the season finale of Keeping Up With The Kardashians.
When the clan got to Paris to prep for Kim's wedding, Kris Jenner and her daughters Kourtney, Khloe, Kendall and Kylie all prepared for the big day.
The episode included a ceremony rehearsal, Kim getting ready day of, Rob not getting on the plane to Italy and more!


text:
- Photography
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Covering all things related to Canon and its lenses, The Canon Lens Experience is an immersive hub containing interviews, technical information, interactive tools, educational articles, and glossaries that take in the breadth of Canon's network of optics. This multi-faceted project began with a desire to uncover the wide range of options dedicated to Canon photographers and includes in-depth details about what makes Canon lenses so special and how these technologies can be employed for successful imaging results.
Beginning with Experiences, 15 photographers were chosen to best represent exactly how a Canon lens can function in real-world use. B&H surveyed a range of some of the most enticing genres of photography and spoke with leaders in each category to find out more about his or her practices, tools, and perspectives. The diverse group of photographers we selected comprise an impressive list of talent: architectural photographer Donna Dotan; portrait photographer Gregory Heisler; fashion photographer Jeremy Cowart; aerial photographer Jim Wark; wedding photographer Joe Buissink; product photographer John Kuczala; photojournalist John Tlumacki; music photographer Mike Lerner; air-to-air photographer Paul Bowen; sport photographer Peter Read Miller; landscape photographer Peter Tellone; wildlife photographer Ralph Lee Hopkins; travel photographer Randy Kerr; food photographer Sasha Gitin; and underwater photographer Stephen Frink. Each shares his or her stories on working in their respective fields and sheds some light on how and why they make the images they do.
The second stop, Virtual, serves as an interactive educational tool for gaining a better grasp of specific optical terms and controls, including different focal length lenses, depth of field, tilt-shift controls, image stabilization, and macro.
The final stop in The Canon Lens Experience, Lenses, is an all-encompassing overview of Canon's lens lineup, with a look at each lens from wide-angle to telephoto, and including more specialized options such as macro and tilt-shift lenses. Complementing this overview is an equally thorough A to Z guide of all the unique technologies Canon employs when designing its lenses. Including topics such as "what is an L lens?", "things to consider when purchasing a lens," and detailed looks at certain components that make up the versatile lineup from Canon. This section is offset by a more formal glossary of terms relating to lenses and photography, in general.


text:
Rating: 3.2/5 (Total votes: 5)
Huarong Trail Lite - If you like puzzle games such as Sudoku, definitely try out Huarong Trail! You may find a different way to have fun.
If you are looking for something different, you found it!
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FreewareAndroid - Free Downloads Android Market Apps, Applications, Games, APK, WiFi, Sync, GPS for Google Android OS


text:
How to Buy
Solutions Overview
This script is Copyright (C) 2011-2014 Tenable Network Security, Inc.
Synopsis :
The remote HP-UX host is missing a security-related patch.
Description :
s700_800 11.23 CDE Applications Patch :
A potential security vulnerability has been identified with HP-UX
running CDE Calendar Manager. The vulnerability could be exploited
remotely to execute arbitrary code. References: CVE-2010-4435,
See also :
Solution :
Install patch PHSS_41174 or subsequent.
Risk factor :
Critical / CVSS Base Score : 10.0
CVSS Temporal Score : 8.7
Public Exploit Available : true
Family: HP-UX Local Security Checks
Nessus Plugin ID: 52039 ()
Bugtraq ID: 46261
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text:
Free Aspen-to-Snowmass bus service here to stay
June 7, 2014
Public officials made the decision Thursday to fund the no-fare bus service between Aspen and Snowmass Village in the long term.
Additionally, the town of Snowmass Village will no longer be solely responsible for paying for the service in the summertime. The Elected Officials Transportation Committee, made up of the elected leaders from Snowmass, Aspen and Pitkin County, will cover the cost with their joint budget, which is funded by a half-cent sales tax applicable in each jurisdiction.
The politicians had other spending problems to address, though. They also voted to restore money pulled from capital funds to help pay for the Aspen Business Center pedestrian underpass and to make savings accounts created for two big projects — the entrance to Aspen and a transit center in Snowmass Village — more flexible.
Most of the elected officials agreed that what is meant by the "entrance to Aspen" doesn't have to apply only to an envisioned reconstruction of the stretch of Highway 82 from the airport to Main Street.
Rather, it could be any "tool to solve some kind of traffic problem," as Aspen Councilman Adam Frisch said. "If all of a sudden there's less cars on the road, then we don't have an entrance-to-Aspen problem.
"The entrance to Aspen … is just a bunch of ways to figure out how to solve a traffic problem. I think it does broaden what we can use."
Similarly, Snowmass Village Mayor Bill Boineau said he might be willing to allocate funds from the Snowmass Village transit center savings account to, for example, an enhancement of the Brush Creek intercept lot.
"It could be a more regional thing could help us all out," Boineau said. "It makes more sense to use these dollars collectively."
A point that was repeated consistently was that any project would have to be approved by the three governments on the committee anyway.
Another issue that the officials will address in the future is how to fund the redevelopment of the Rubey Park Transit Center, which is 60 percent to design, according to a memo from county Treasurer Tom Oken and consultant Bob Schultz to the committee. The committee will be asked to contribute from $1.5 million to $2 million for that in 2015.
Tough Mudder to use Brush Creek lot
The committee also voted to allow Tough Mudder, an obstacle-course mud run that is staging an event in Snowmass Village in September, to use the Brush Creek intercept lot for participant parking.
Representatives from Tough Mudder said they modeled their proposed parking and traffic-flow system after the Winter X Games, which has used the lot similarly for a number of years.
The event on Sept. 6 and 7 is expected to draw about 10,000 participants and spectators on its first day and 3,000 on the second, said Courtney Jordan, Tough Mudder senior operations manager. Snowmass hotels are already 60 percent full for the weekend, which she said means most people traveling in will be able to park their vehicles at their lodges.
Pitkin County Commissioner Michael Owsley said he would like for part of the lot to be reserved for commuting valley residents. Aspen City Councilwoman Ann Mullins also pointed out that Tough Mudder's plan did not allow for commuters to exit left, or upvalley, from the lot.
Blake Fitz, of the city of Aspen Parking Department, said the Jazz Aspen Snowmass Labor Day event and Winter X Games use a similar system and that "it's been proven." However, he said it has never included only a downvalley exit.
Roaring Fork Transportation Authority CEO Dan Blankenship commented that the number of commuters using the lot on an offseason weekend is likely to be low.
Owsley also said he didn't want Tough Mudder using the lot for equipment trailers.
"If it's just Tough Mudder vehicle parking, I have no problem with it," Owsley said. "As long as it's safe … and doesn't interfere with RFTA."
The three jurisdictions voted unanimously in favor of allowing Tough Mudder to use the lot as long as their plan addresses the concerns the officials raised.


text:
This story is a scary take on a classic fairytale that...
- by Ultimate Whovian
- Rating:
- Published: 25 Sep 2014
- Updated: 20 Oct 2014
- Status: In Progress
This is a story about a boy named Jimmy who is convinced that he saw someone in the woods running away, someone that he'd never seen before. However, no matter how hard he tried to convince people, no one will believe him and his theories, stories and tales. So when his close friend Freya suddenly starts to listen to his he becomes even more determined then ever to figure out if his impossible girl in white is real. Filled with mystery, this story sets out to solve more then one case as he discovers a book filled with magical secrets of the past hidden away. Could this be something to do with... 'HER' ?
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text: GERMANTOWN, Md., Feb. 23 /PRNewswire-FirstCall/ -- Optelecom-NKF, Inc. (Nasdaq: OPTC) announces the following Webcast: What: Optelecom-NKF, Inc. Fourth Quarter 2009 Earnings Conference Call & Webcast When: Wednesday, March 10, 2010 @ 10:00 AM Eastern How: Live over the Internet -- http://www.videonewswire.com/event.asp?id=66480 Participant Dial In (U.S. Toll Free): 1-800-860-2442 Participant International Dial In: +1-412-858-4600 Parties should ask for: Optelecom-NKF Conference Call Playback Dial In (U.S. Toll Free): 1-877-344-7529 Playback International Dial In: +1-412-317-0088. Playback code: 438229 If you are unable to participate during the live webcast, the event will be archived at http://www.videonewswire.com/event.asp?id=66480 Optelecom-NKF, Inc., manufacturer of Siqura® advanced video surveillance solutions, provides a full range of network products based on an open technology platform that simplifies integration and installation. Our Siqura solutions offer a perfect blend of ease of use and processing power, enabling end users to optimize the effectiveness of their surveillance systems while reducing the total cost of ownership. All products and solutions are developed and tested for professional and missioncritical applications, such as at highway departments, airports, seaports, casinos, public transport authorities, hospitals, city centers, shopping centers, military bases, and corporate and government campuses. Founded in 1972, Optelecom-NKF is committed to providing its customers with expert technical advice and support. SOURCE Optelecom-NKF, Inc.


text:
Engine Mechanical problem
2004 Ford Explorer 6 cyl Front Wheel Drive Automatic
Can you email me a copy of the diagram for the spark plug/ wire firing order?
My son changed out my plugs/wires and he believes he put in same order but my engine turns off it also has a smell to it. I just want to make sure they are in the correct order.
have the same problem?
Tuesday, September 14th, 2010 AT 1:59 PM