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Age Suitability:
|EU Warning: Not suitable for children under the age of 3 years due to small parts which could cause a choking hazard
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Mix and match Num Noms to create sweet, scented recipes! Collect over 100 Num Noms in Series 2! Nums are adorable, scented, squishy characters with tons of personality. Noms are scented and motorized! Stack the Nums on top of the Noms to make over 5,000 sweet scented combinations. Build up your appetite with the Num Noms Diner Pack. Create wacky flavour recipes like Double Cheese Burger! Includes 3 Nums, 1 motorized Nom, 1 spatula, 1 food tray container and 1 collector's menu.


text:
The book tells the true story.
Technology was part of everyday life for her family.
They were using several electronic devices simultaneously most of the time.
It had changed the way they ate, slept, make friends, fought, planned and played.
No mobile phones, MP3 players, TV, DVDs or computers were allowed in the house.
She said it had changed the way they ate, slept, made friends, fought, planned and played.
When "the experiment" began, the children where very unhappy about it. However, they got used to their new way of life.
What will you find most difficult about the week?
What, if anything, will you enjoy about having no electronic devices?
What will you do in your free time, without a phone/ TV/MP3 player/ the Internet/DVDs/ computer/ video games?
How will you keep in contact with friends?

subset: commoncrawl


text:
Fluoro Yellow Multi-purpose Stickers, Circle 18 mm, 216/PackProduct Number: 932289
Make your life easier by identifying contents of drawers or containers. Mark your name on small household or office objects. Even decorate gifts and envelopes. The labels' small size makes them highly versatile for use in any number of situations. 18 mm fluoro yellow circles, and with resealable packs of 216 labels the convenience goes on and on.
Product Description:
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text:
Head Start administrators with ACTION Inc., took a crash course in administration procedures this week, another step in restoring the anti-poverty agency to the good graces of federal administrators.
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The course, taught Monday and Tuesday by consultants and staffers with the Georgia Community Action Agency, was geared toward helping ACTION correct a dozen "deficiencies" identified by the federal regulators in a July 27 letter to ACTION Board Chairman Walter Butler.
The prognosis looked good for ACTION, said Lorraine Daniels, executive director of the GCAA.
The state organization is providing the course and other help at no charge to Athens-based ACTION. GCAA is a statewide organization of "community action agencies" such as ACTION that provide services to poor people.
"We're getting the agency in the best shape it can be for the upcoming review. They're not too far off course," she said.
ACTION faces a deficit of about $1.4 million and is under scrutiny from federal and state agencies over how it has spent grant money, but after an influx of new members on its board of directors, ACTION officials say the agency is on the road to recovery.
The nonprofit corporation administers about $13 million a year in federal, state and local grant money.
More than half of that is for the Head Start program, which helps prepare low-income children for kindergarten in Clarke and nine other area counties. Other ACTION programs help pay winter utility bills for poor people, weatherize homes and collect and distribute food to the needy.
Federal administrators from an Atlanta regional office plan to visit ACTION's Athens offices Sept. 15-16 to see how well the agency is correcting the Head Start deficiencies, said John Scoggins, ACTION's interim president and CEO.
Scoggins said the federal criticisms, some of which date back more than a year, primarily are on issues such as monitoring, reporting and administration - not on the job teachers are doing in the classroom.
"It's all administrative. We don't have any problems in the classroom," he said.
"There's no doubt the agency is doing good work. The problem is, the system needs to be able to tell the story," agreed Daniels.
She said she thinks the agency can begin meeting federal standards, though neither she nor Scoggins would say when all the "deficiencies" can be corrected.
Some already have been fixed, such as making sure fire extinguishers had been inspected in Head Start Buildings.
But others take longer, such as building an effective "policy council" to ensure the parents of Head Start children have a say in making policy decisions for the program, Scoggins said.
"Some of them are not instant solutions," he said. "You can put all kinds of policies in place, but you have to go back and make sure the policies work."
The stakes are high for ACTION to find solutions. Failure to correct them within 30 days is "grounds for termination," meaning the administration of Head Start could be yanked from ACTION and given to another agency, according to the July 27 letter from federal Head Start regulators in Atlanta.
Faced with a $1.4 million deficit, the agency has reconstituted its nearly defunct board of directors and adopted a plan to eliminate the deficit.
ACTION's Head Start program serves 854 children enrolled in classes in 14 centers in Clarke, Madison, Oglethorpe and seven other area counties. An additional 76 children are enrolled in an Early Head Start program for younger children, said ACTION's interim Head Start director, Jo Ann Frey.
Directors of the Head Start centers participated in this week's training session, along with several other ACTION Head Start administrators.
Frey replaced longtime ACTION Head Start director Patricia Barker, one of two administrators replaced during ACTION's internal shake-up.
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text:
The Wales DNA Project was established in 2006 by Janet Lewis Crain as a volunteer effort to allow all persons with Welsh ancestry on their Y chromosome and/or mtDNA lines who have been DNA tested to enter this information into one database in order to further the genetic research of Wales' ancient populations.[1] A long term goal is to establish a modal haplotype for as many of the Welsh Princes[2] as possible. See List of rulers of Wales. At present there are results representing one Lewis DNA line back to Rhys Goch ca 1100 and purportedly back to 300 AD.[3] and a line representing the Lord Of Penllyn Rhirid VLAIDD (Abt 1175).
This projects differs from the Welsh Patronymic Project in several ways. For one, mtDNA will be represented by those who have mtDNA lines back to Wales. For another, the emphasis is on geographic location of an ancestor, i.e.; those who were there before 1800. If they were known to not be indigenous Welsh, this will be noted. It is hoped to collect the DNA results of descendants of the Marcher Lords; those rulers who controlled the Welsh Marches. Today those areas include Cheshire, Shropshire, Herefordshire (all English counties) and Monmouthshire (a Welsh county). The western half of Gloucestershire (England), as well as Flintshire and Wrexham (Wales) are also sometimes included.
Project background Edit
Due to the importance of determining the genetic profile of the indigenous populations of the British Isles, The Wales/Cymru DNA Project will attempt to collect the DNA haplotypes of as many persons as possible who can trace their Y chromosome and/or mtDNA lines to Wales. Many researchers believe that there was less replacement from invaders there than elsewhere, excepting small inaccessible islands and similar locales.[4]
Tradition holds that the Celts retreated as far West in Wales as possible to escape invading populations.[5]This DNA project seeks to determine the validity of this theory.
This project is open to descendents from all of Wales.
The surname list on the project site is by no means exhaustive. Many are pre-1066 names, considered to be Celtic or Roman, heavily influenced in some areas, such as Abergele. After 1066 there was Norman influence. From many of the surnames, several variations were derived.
Since David Beers Quinn stated in his book Roanoke Voyages that some of John White's colonists were from Wales, all persons of Welsh descent should check out the names of interest being sought by the Lost Colony DNA Project.
Every effort is being made to insure the integrity of this project and ensure its worth to researchers. It is an entirely volunteer project.
References Edit
- ^ http://www.genpage.com/walesdnaproject.html
- ^ Roger Turvey. The Welsh Princes: The Native Rulers of Wales, 1063-1283. London and New York: Longman Publishing, 2002.
- ^ [1]
- ^ Y Chromosome Evidence for Anglo-Saxon Mass Migration Michael E. Weale,*1 Deborah A. Weiss,†1 Rolf F. Jager,*‡ Neil Bradman,* and Mark G. Thomas*
- ^ Brian Sykes. Saxons, Vikings, and Celts; the Genetic Roots of Britain and Ireland W.W. Norton & Company New York ~ London
External links Edit
|This page uses content from the English language Wikipedia. The original content was at Wales DNA Project. The list of authors can be seen in the page history. As with this Familypedia wiki, the content of Wikipedia is available under the Creative Commons License.


text: Marking the end of National Tree Week, everyone should do their bit by planting a tree. Used for centuries by famous garden designers like Capability Brown to sculpt magnificent landscapes and induce a feeling of grandeur and status, today trees are sometimes overlooked as a key ingredient within your average back garden. Trees are incredibly rewarding to grow and can instantly add height and drama to any border or plot. Viewed as the bone structure of the garden, they can cleverly trick, frame and draw the eye. When choosing trees, their eventual mature height is the top consideration for many, however most overlook characteristics such as seasonality and additional interest.


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Product Spotlight
Featured Research
Quick Stats
You are here
Hooper Oil Finds Silver Lining
Convenience chain increases foodservice offering with Long John Silver.
Hooper Oil Co., operator of five Quick Stop convenience stores, opened its second co-branded unit is less than a year with a full-service Long John Silver's restaurant.
Chain President David Hooper Jr. previously converted a non-branded delicatessen food operation at a similar facility in Brownsville, Tenn. to the Long John Silver's menu, which then set a record within the Long John Silver system for a c-store food operations. He said the new unit would be even bigger.
"We will have seating for 24 persons inside the Long John Silver's Restaurant space, which is a 'bumpout' or 'bolt-on' restaurant concept, meaning the restaurant facility is adjacent to the petroleum and c-store space," Hooper said. "We have two pay-points to provide fast, efficient services for gas, c-store or restaurant customers."
The unit includes a Baskin Robbins kiosk for dessert. The entire facility is 5,000 square feet. Hooper Oil, which also serves as an ExxonMobil jobber, said it is exploring the possibility of adding branded fast food to its remaining c-stores.


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An interim legislative committee is planning to study Wyoming's beer and liquor tax this summer.
The Trail End Historic Site will be reopening for the season on April 1, with not only a new exhibit but in celebration of the Kendrick Mansion's 100th anniversary.
The Buffalo Kiwanis Club's 55th Annual Stars of Tomorrow contest was held Sunday afternoon at the Buffalo High School Auditorium.
At their last meeting the Johnson County Healthcare Center's Board of Trustees discussed Medicaid, the gap between their reimbursements and actual costs for the nursing home, and the point system for resident patients.
More discussions are expected at today's Johnson County Commissioner's meeting on last summer's Gilead Fire and costs involved with fighting the fire.
The Buffalo City Council will discuss the reconstruction project on Burritt Street at the old High School Hill at the meeting Tuesday afternoon.
Susan Thomas, wife of former Wyoming Senator, Craig Thomas, addressed the Sheridan County Republican Women at a luncheon today. She spoke about the foundations she created with her husband to help underprivileged students attend college and succeed.
The Sheridan Police Department arrested 24-year-old Sheridanite, Ben Morton, on suspicion that he broke into Lucinda's Artesian Gallery Friday night.
Last week, the Casper City Council voted to amend, rather than repeal, an ordinance that banned smoking in all public places.
Gas prices in Wyoming are the lowest in the country, and Sheridan's prices are below the statewide average.


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directing agent to use specific E1 on outgoing calls
we are using IPCC 7.1 with CVP 3.1, and CCM 4.2.3 and AS 5400 voice gatway, we need a way to restrict agent making ougoing calls trough ccm to use specific E1 when making thier calls, please how can we achieve this
Make new CCS for group 2, with new patterns:
1- Pattern Definition: define your own patterns by adding a prefix on them - to determine the E1.
Example: if you have 2410132 as a pattern put is as 90 (90 is the prefix- example) under âPrefix Digits (Outgoing Calls)â
Under the pattern definition put the âCalling Party Transform Maskâ = 918881111
Send the calls through your trunk to the AS400
Now if any agent call 2410132 the pattern will send to the gateway as 902410132
2- Assign this CCS to Group 2 phones.
3- Pots Definition: make the stripping on the pots as below:
dial-peer voice 10 pots
destination-pattern 90...T
port 7/2:D
forward-digits (number of right-justified dialed digits to be forwarded - put the number of digit you need to forward without 90)
If you dial 2410132 the pots will be as below, and the call will send through E7/2:
dial-peer voice 10 pots
destination-pattern 902410132
port 7/2:D
forward-digits 7
hope this help


text:
Vienna is the capital of Austria. Vienna has an important music tradition and Viennese music is world famous. The Vienna Philharmonic Orchestra is also world famous and criticism over reluctance to accept women and ethnic minorities is less extreme than before. The State Opera House in Vienna is also world famous as is the Vienna Boys Choir. When will they accept girls there?
Vienna is situated on the river Danube which is one of the major European rivers and for a landlocked country like Austria this waterway is important. Round Vienna are the Vienna Woods (Wienerwald).
Vienna is also a United Nations centre and many international conferences happen there. [1]


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All season the Texas Tech Red Raiders waited for an offensive game like the one they had against Baylor last week.
Tech won the game, 45-38. But it was the precise way the offense performed that caught the eye of coach Tommy Tuberville.
While passing for 462 yards and rushing for 173 yards, the Red Raiders finally looked like the offensive machine Tuberville envisioned when he became their coach last winter.
"I told the players (Monday) in our team meeting that one thing I noticed offensively was we looked a lot more consistent and a lot more physical," Tuberville said. "We were very good on third down, which I thought was the difference in the game.
"We were 10 out of 16 on third-down conversions, and that is huge, especially when you throw the ball as much as we do. We controlled the ball as we had (95) offensive snaps, and it was obvious."
Tuberville, though, admits there are things the Raiders (3-2, 1-2 Big 12) need to nip in the bud before they host 18th-ranked Oklahoma State (5-0, 1-0) Saturday.
For starters, Baylor ran a botched on-side kick by Danny Carona 38 yards for a touchdown. It was the second straight game that Carona had an on-side kick run back for a touchdown.
The Bears also perfectly executed a fake punt on fourth-and-7 that netted 34 yards and was the big play that highlighted Baylor's third touchdown.
In addition, the Bears ran up and down the field to the tune of 507 total yards. And they managed to finish the game without committing any turnovers.
"We played much better in the game in some areas and some areas we didn't," Tuberville said. "We did enough to get the win, it was an exciting game in Dallas and I think that everybody watching the game on television and in the stands had a fun game to watch.
"It's tough on coaches to go through games like that because of the ups and downs. (But) I saw our team grow mentally and physically throughout the game."
Oklahoma State also grew throughout its game last week against Louisiana-Lafayette. The Cowboys trailed in that contest 21-17 at halftime before scoring 24 points in the third quarter en route to claiming a 54-28 victory.
OSU's Big Three of quarterback Brandon Weeden, running back Kendall Hunter and wide receiver Justin Blackmon completely took over that game. Weeden was 29 of 47 for 351 yards and five touchdowns, Hunter rushed for 126 yards and a touchdown and Blackmon caught a career-high 13 passes for 190 yards and a pair of touchdowns.
"Going into the game against Oklahoma State, they have a high-powered offense and they have scored a lot of points," Tuberville said. "Again, our defense has to improve.
"If we are going to give ourselves a chance to win the game, we are going to have to play better defensively. Offensively, we are in a rhythm, but we have to continue to go out and do that. We can't take any weeks off. And the same thing with special teams."
— One of the bright spots early in the season, defensive end Scott Smith was suspended indefinitely last Friday for breaking team rules. And coach Tommy Tuberville said the suspension would last for the remainder of the season. "We aren't doing this to make an example out of anybody. But when we come in, we set rules and (the players) know the rules and what we go by."
— At age 30, Tech offensive coordinator Neal Brown is the third-youngest coordinator in the FBS.
— That botched on-side kick by Donnie Carona against Baylor has become a YouTube hit. On the play, Carona booted the kickoff just eight yards, and he and two other teammates stood and watched as Baylor's Terrance Ganaway picked it up and ran 38 yards for a TD. On Monday, the 22-second clip was viewed by 2.8 million folks.
— The Red Raiders will wear camouflage uniforms against Missouri on Nov. 6 to benefit the Wounded Warrior Project (WWP). The WWP is a non-profit company which provides a support group and services to injured members of the armed forces and their families.
SERIES HISTORY: Texas Tech leads Oklahoma State, 21-13-3 (last meeting, 2009, 24-17 Oklahoma State).
As they showed against Baylor, there's nothing wrong with the Red Raiders' offense that a few successful rushing plays can't fix. Tech had 18 passing plays and five rushing plays that went for 10 or more yards against Baylor. That balanced attack -- 462 yards passing, 173 yards rushing -- enabled the Raiders to put on their best offensive performance of the season. Meanwhile, the Cowboys have gotten more aggressive on defensive lately. They didn't have any interceptions in their first two games, but have eight in their last three games.
Tech can't miss assignments on defense like it did against Baylor and expect to go home with a win. Oklahoma State has a more proficient offense than the Bears, and Baylor was able to hang 38 points and 507 yards on the Raiders. Tech's defense will receive one of its stiffest challenges of the season this week. OSU quarterback Brandon Weeden is fourth in the nation in passing yards per game (322), running back Kendall Hunter is fifth in the country in rushing yards per game (140) and wide receiver Justin Blackmon is first in the country in receptions per game (9.4) and receiving yards per game (149.6).
QUOTE TO NOTE: "It is hard to improve on 45 points and 600 yards, but we can do that. We can eliminate mistakes and be better in certain situations." -- Texas Tech coach Tommy Tuberville
THIS WEEK'S GAME: Oklahoma State at Texas Tech, Oct. 16 -- Texas Tech finally exploded on offense last week against a solid team, as it ran up 635 yards in the win over Baylor. But the Red Raiders can ill-afford any special-teams blunders like the two crucial ones that cost them 14 points against the Bears. OSU has one of the best trios in America at the skilled positions in QB Brandon Weeden, RB Kendall Hunter and WR Justin Blackmon.
KEYS TO THE GAME: The Red Raiders finally located their running game last week against Baylor when they rushed for a season-high 173 yards on 36 carries. If Tech can match that performance -- and if quarterback Taylor Potts can continue throwing strikes -- the Red Raiders could conceivably go 6-1 down the stretch. Oklahoma State consistently gets off to slow starts, so Tech must take advantage of that. OSU trailed in the first halves of games against Troy, Texas A&M and Louisiana-Lafayette before rallying for victories.
QB Taylor Potts — He's first in the nation in passes completed per game (32.2), third in passing yards per game (329.8) and eighth in passing yards (1,649).
CB Jarvis Phillips — Leads the country in interceptions per game at .80. Phillips has returned four interceptions for 114 yards and a touchdown.
WR Lyle Leong — Did not score a touchdown for the first time this season last week against Baylor. But he has nine TDs on the year and is tied with OSU's Kendall Hunter for 11th in the nation in scoring at 10.8 points per game.
— DE Aundrey Barr will miss the rest of the season after injuring his knee and sitting out against Baylor. Barr had surgery to repair his torn meniscus.
— OT Chris Olson was used effectively on one running play at tight end against Baylor because of a shortage of burly players at that position. Olson also went out on a passing route during one play.
— CB Will Ford is still dealing with hamstring problems that first popped up in the preseason. Ford missed the Baylor game after pulling the hamstring last week in practice.
— DL Bobbie Agoucha did not dress for the game against Baylor because of a concussion, and probably won't play against Oklahoma State.
— LB Sam Fehoko only got in a few snaps against Baylor because of an injured knee, and he could be limited again this week.


text:
Soldiers, police and villagers battled to protect power plants in Serbia from rising flood waters on Sunday, as the death toll from the Balkan region's worst rainfall in more than a century, reached 37.
Twelve bodies were recovered from the worst-hit Serbian town of Obrenovac, 30 km (18 miles) southwest of the capital, Belgrade, but the number was likely to rise as waters receded.
"The situation is catastrophic," Prime Minister Aleksandar Vucic told reporters.
Hundreds of soldiers and residents scrambled to raise sandbag barriers around the perimeter of the Kostolac power plant east of Belgrade, where a Reuters cameraman said waters from the swollen River Mlava, a tributary to the much larger River Danube, had come to within a kilometer.
Workers at the plant joined the effort, digging up a road in a bid to divert waters that threatened to flood nearby coal mines. The Kostolac plant supplies 20 percent of Serbia's electricity needs.
Russian cargo planes carrying boats, generators and food joined rescue teams from around Europe and thousands of local volunteers in evacuating people and building flood defenses after the River Sava, swollen by days of torrential rain, burst its banks.
Rains eased and flood waters receded on Sunday in some of the worst-hit areas of Serbia and Bosnia, but the Sava was forecast to rise further. Thousands of people have since, been displaced.
Children shoes donated to evacuated people from the Serbian town of Obrenovac are seen in a shelter hall in Belgrade.
People sit in a boat after being evacuated from their flooded houses in the town of Obrenovac, southwest of Belgrade.
Serbian army soldiers evacuate people in an amphibious vehicle.
A woman cries after being evacuated from her flooded house.
An aerial view of the flooded city of Brcko.
Evacuees from the Serbian town of Obrenovac are seen lying on beds in a shelter hall.


text:
The International Legal Framework against Corruption
It is now unquestionable that corruption has become an issue of international concern. A complex set of substantive and procedural rules has emerged concerning the prevention and repression of corruption which represent the international legal framework against corruption. This study begins by tracing the emergence of this framework and engages in a systematic analysis of its content, highlighting weaknesses and innovative aspects. What does international law require States to do in relation to corruption? What happens if States do not meet their international obligations? The responses to these questions constitute the core of this book.
410 pages
Publication Date: 11/7/2012
Format: Paper


text:
Sausage, Egg and Biscuit Casserole
Makes 8 servings, total time:
1 lb bulk breakfast sausage
7 eggs
1 1/4 cups whole milk
3/4 cup heavy cream
1 tsp/ each table salt and black pepper
8 frozen buttermilk biscuits
1 1.2 cups shredded cheddar
Preheat oven to 375, coat a 7x11 inch baking dish with nonstick spray and place on a baking sheet. Brown sausage in a saute pan over medium heat, breaking into chunks. Transfer cooked sausage to a paper-towel-lined plate. Whisk together eggs, milk, cream, salt and black pepper in a large measuring cup; set aside. Layer biscuit bottoms in prepared dish. Sprinkle half of sausage over biscuits, and top with half the Cheddar. Repeat layering (except cheddar.) Pour egg mixture over top; transfer to oven and bake 30 minutes. Sprinkle remaining Cheddar over top of casserole and bake until eggs are set (center is no longer jiggly and instant-read thermometer registers 165), a toothpick inserted into biscuits come out clean, and tops are golden 10-15 minutes more. let casserole stand 10 minutes


text:
6-bedroom family home with 1 full and 2 half baths. Master bedroom on main level, has half bath. Major renovations in 2006, including installation of double-capacity commercial septic tank with leach filed, new windows, siding, oil furnace, electrical, plumbing, new floors in kitchen, living room and 2 baths. The floors in some of the bedrooms and the staircase were professionally hand refinished. The house has an oil-heated hot water tank for endless supply of hot water. There is also a computerized well system to prevent running dry from commercial over use. Located in picturesque Seal Cove, just a short walk from the sand beach, fisherman`s wharf and the historic herring smoke houses. 5 of the 6 bedrooms offer a terrific ocean view, as well as both decks and the back yard. This spacious house currently sleeps 13. The property is an established seasonal rental property with financial statements available. A fantastic rental opportunity.
Property Details
- Beds: 6
- Parking Type Description: None 0 cars
- Lot Size: 0.54 ACRES
- Elementary School: Gmcs
- Property ID: 100902136
- Baths: 3 (Full: 1 3/4: 0 1/2: 2 Other: 0)
- New Construction: No
- Estimated Annual Taxes: $2,705
- School District: Grand Manan (104)
- Style: 2-Storey
- Status: Sold on 6/20/2014
- Living Area: 1,891 Square Feet
- High School: Gmcs


text:
jee mains 2016 results
JEE Main 2016 Result – Scores
Result of JEE Main can be cloven into two: Part-1 will consist of scores, which will be disclosed on 27 April 2016. Whereas, Part-2 will allocated candidates their All India Rank (AIR) and will be disclosed on 7 July 2016.
The scores of the candidates will be calculate as per the marking scheme. Candidates will be able to predict the scores via answer key but the final scores will only be issued by CBSE. Once the scores are official disclosed, candidates will not be able to challenge or change it. Also, candidates will have to download the scores because no score/ rank card will be dispatched to the candidates.
JEE Main 2016 Normalization Procedure
The purpose of normalizing the marks is to provide fair chance to all the candidates. In it, class XII percentile is calculate. Mentioning to clarify, percentage is that which is calculate out of 100. Whereas, percentile is calculate to state how many candidates have scored below the candidate, in reference.
It state how many candidates have scored less than the best scorer. It is a benchmarks as
In Pen and Paper mode, Joint Entrance Examination (JEE) Main was conducted on 4 April, 2016. The Computer Based (online) exam, of it, is started, today, on 10 and 11 April, 2016. Almost 13.5 lac candidates have registered for the examination, out of which 10 lakh (approx) opted for the offline mode. CBSE, the conducting body, will upload the answer key and the OMR, on 18 April, 2016. Following which JEE Main 2016 result will be announced, on 27 April, 2016. The All India Rank, of the candidates, will be revealed on 7 July, 2016. Top 1.5 lakh rank holder of JEE Main will be declared eligible to apply for JEE Advanced 2016 . More information about the examination is given below, have a look.
Incoming searchs:
1.jee mains 2016 results
2.jee mains 2016 results data
3.jee mains 2016 updates
4.jee mains 2016 results manabadi


text:
Harris 115
Office Hours, Summer 2017: 4pm-4:30pm M-R
Ph.D., Temple University, Fox School of Business
M.B.A., Temple University, Fox School of Business
B.S., University of Delaware, Lerner College of Business & Economics
Dark Tourism, Death Consumption, Consumer Behavior, Materialism
Recent articles published in Refereed Journals
Podoshen, Jeffrey S. (2017), "Trajectories in Holocaust Tourism," Journal of Heritage Tourism (in press).
Wallin, Jason, Jeffrey S. Podoshen, & Vivek Venkatesh (2017). "Second Wave True Norwegian Black Metal: An Ideologically Evil Music Scene?" Arts and the Market (in press).
Fang, Yiwei & Jeffrey S. Podoshen (2017). "New Insights into Materialism and Conspicuous Consumption in China," Journal of Consumer Ethics (in press).
Andrzejewski, Susan A. and Jeffrey S. Podoshen (2017), "The Influence of Cognitive Load on Nonverbal Accuracy of Caucasian and African-American Targets: Implications for Ad Processing," Journal of International Consumer Marketing, 29 (2), 83-90 .
Podoshen, Jeffrey S., Vivek Venkatesh, Jason Wallin, Susan Andrzejewski and Zheng Jin (2015), "Dystopian Dark Tourism: An Exploratory Examination," Tourism Management, 51 (December), 316-328.
Podoshen, Jeffrey S., Susan Andrzejewski, Vivek Venkatesh and Jason Wallin (2015), "New Approaches to Dark Tourism Inquiry: A Response to Isaac," Tourism Management, 51 (December), 331-334.
Podoshen, Jeffrey S., James M. Hunt and Susan Andrzejewski (2015), "Attribution Processes in Cross-Cultural Heritage Tourism," Journal of International Consumer Marketing, 27 (2), 123-136.
Venkatesh, Vivek, Jeffrey S. Podoshen, Kathryn Urbaniak and Jason Wallin (2015), "Eschewing Community: Black Metal," Journal of Community and Applied Social Psychology, 25 (1), 66-81.
Podoshen, Jeffrey S., Andrzejewksi, Susan and James Hunt (2014), "Materialism, Conspicuous Consumption and American Hip-Hop Subculture," Journal of International Consumer Marketing, 26 (4), 271-283.
Podoshen, Jeffrey S., Vivek Venkatesh and Zheng Jin (2014), "Theoretical Reflections on Dystopian Consumer Culture: Black Metal," Marketing Theory, 14 (2), 207-227.
Podoshen, Jeffrey S. (2013), "Dark Tourism Motivations: Simulation, Emotional
Contagion and Topographic Comparison," Tourism Management, 35 (April), 263-271.
Segal, Brenda W. and Jeffrey S. Podoshen (2013), "An Examination of Materialism, Conspicuous Consumption and Gender Differences," International Journal of Consumer Studies, 37 (2), 189-198.
Podoshen, Jeffrey S. and Susan A. Andrzejewski (2012), "An Investigation into the Relationships Between Materialism, Conspicuous Consumption, Brand Loyalty and Impulse Buying." Journal of Marketing Theory and Practice, 20 (3): 319-334.
Dobscha, Susan, Jenna Drenten, Kent Drummond, Terrance Gabel, Christopher Hackley, Sidney Levy, Jeffrey Podoshen, Dennis Rook, Katherine Sredl, Rungpaka Amy Tiwaskul and Ekant Veer (2012), "Death and All His Friends: The Role of Identity, Ritual, and Disposition in the Consumption of Death," Advances in Consumer Research, XL, Association for Consumer Resarch.
Podoshen, Jeffrey S. and James M. Hunt (2011), "Equity Restoration, The Holocaust and Tourism of Sacred Sites," Tourism Management, 32 (6): 1332-1342.
Podoshen, Jeffrey S., Lu Li and Junfeng Zhang (2010), "Materialism and Conspicuous Consumption in China: A Cross-Cultural Examination," International Journal of Consumer Studies, 35 (1): 17-25.
Podoshen, Jeffrey S. and James M. Hunt (2009), "Animosity, Collective Memory and Equity Restoration: Consumer Reactions to the Holocaust," Consumption, Markets and Culture, 12 (4): 301-327.
Podoshen, Jeffrey S. (2009), "Distressing Events and Future Purchase Decisions: Jewish Consumers and the Holocaust," Journal of Consumer Marketing, 26 (4): 263-276.
Makarem, Suzanne C., Susan M. Mudambi and Jeffrey S. Podoshen (2009), "Satisfaction in Technology-Enabled Service Encounters," Journal of Services Marketing, 23 (3): 134-144. Highly Commended Award Winner – voted as one of the top four papers published in the journal for 2009 by the Emerald Literati Network and the journal's editorial team.
Podoshen, Jeffrey S. (2008), "The African American Consumer Revisited: Brand Loyalty, Word of Mouth, and the Effects of the Black Experience," Journal of Consumer Marketing, 25 (4): 211-222.
Podoshen, Jeffrey S. (2008), "Why Take Tunes? An Exploratory Multinational Look at Student Downloading," Journal of Internet Commerce, 7 (2): 180-202.
Podoshen, Jeffrey S., Emanuela Verenca and Sonia Ketkar (2008), "Transition in Romania: Is Joining the EU a Win for All?" International Journal of Business in Emerging Markets, 1 (2), 107-123.
Podoshen, Jeffrey S. (2006), "Sins of the Fathers: The Holocaust and the Leisure Travel Decision Among American Jews," Tourism Analysis: An Interdisciplinary Journal, 11 (5): 331-336.
Podoshen, Jeffrey S. (2006), "Word of Mouth, Brand Loyalty and Acculturation: A New Look at the American Jewish Consumer," Journal of Consumer Marketing, 23 (5): 266-282.
Peer-reviewed Essays
Podoshen, Jeffrey S. (2014), "Reactionary Modernism: An Essay on the Post-postmodern Condition," Journal of Research for Consumers, 25.
Chapters in Edited Volumes
Venkatesh, V., Nelson, B.J., Thomas, T., Wallin, J.J., Podoshen, J.S., Thompson, C., Jezer-Morton, K., Rabah, J., Urbaniak, K. & St. Laurent, M. (Accepted). Exploring the language and spectacle of online hate speech in the black metal scene: Developing theoretical and methodological intersections between the social sciences and the humanities. In N. Varas-Díaz & N. Scott (eds.) Heavy Metal and the Communal Experience. Lanham, MD: Lexington Press.
Venkatesh, V., Wallin, J. J., Walschots, N., Netherton, J., & Podoshen, J. (in press). Transcending and Subjugating Death in Necrophilic Death Metal: Examining the Ethos of Abjection and Sex Pollution in A Niche Cultural Art Form. In A. Aggrawal, E. Hickey, & L. Mellor (eds.), Necrophilia: A Global Anthology. San Diego, CA: Cognella, Inc
Podoshen, J. (2016). Examining death and learning about life. In S. Dobscha (ed.) Death in a Consumer Culture (pp. 316-319). New York: Routledge.
Venkatesh, V., Podoshen, J., Perri, D., & Urbaniak, K. (2014). From pride to prejudice to shame: Multiple facets of the black metal scene within and without online environments. In V. Venkatesh, J. Wallin, J. Castro, & J. E. Lewis (eds.) Educational, behavioral and psychological considerations in niche online communities (pp. 364–388). Hershey, PA: IGI Worldwide.
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Free surface is below than expected..results are not good
Hello dears
Hope you will be having a good day. I am trying to simulate flow through reservoir of a dam. Boundary conditions were inlet, free surface (as given in bump tutorial) and outlet is spillways (which is at the top most of the dam). I did a steady state analysis but the level of the water (free surface)remained well below the spillways in the results; but physically some water should be going out of the spillways to conserve mass coming in from inlet. So physically the results are wrong. I think that problem is with in the expressions defining such as UpPres etc. I can not exactly figure out what DownH, UpH, DownPres and UpPres exactly mean in the tutorial. Height of free surface should be around 135m. I gave DownH=91.44m and UpH=51.86m. and free surface was somewhere around 55 m. Please suggest what I should do to bring it to the required level.
Dear, :)
What you should do?
You should try to be clear in the description of your problem.
DownH=91m, UpH=52m ????!!!! What's this???? And you expect a free surface at 135m????!!!!???
In the tutorial, DownH is the downstream free surface height (the free surface height at the outlet boundary); UpH is the upstream free surface height (the free surface height at the inlet boundary); DownPress and UpPress are the pressures on these boundaries (they are calculated using the hydrostatic law : rho*g*h).
oohhhh...okkkk... Thank you very much. You cleared my mind. In tutorial it was not written that what they meant. I will run a simulation by taking these values and am hoping for the best. Thanks again.
Thanks and further confusion
Hello thanks RUI. I ran various solutions and got good results. But my question to the forum is that if we are locating the free surface ourselves then what is the role of CFX into it?? Should it not calculate the height of the free surface itself? Our height is an initial guess but still it effects the solution so much. Whatever value should we give it should converge to the exact free surface height? Another question to clear my self is . In the bump free surface tutorial if water is falling out of a weir (in free atmosphere) then we should give 0pa of relative pressure instead of DownPrees. Is it correct?
I suspect you will need to move the downstream boundary further downstream.
for the first case, split the U/S plane horizontally and create an Inlet boundary opening at your U/S plane, lower than weir crest. use a mass flow boundary (equal to flow rate times density) and solve the model, this should give you the correct water level for corresponding Flow rate.
for the second case, again split the U/S plane horizontally and create a surface as high as your water level and make it an Opening boundary with Mass and Momentum option set to "Opening Pres. and Dirn".
for relative pressure, use a CEL function defining the hydrostatic pressure at the boundary.
hi guys,i have the seem problem of the surface tension!
i have to localise the surface between water and air during the flow,my question is:how can cfx do this?i have the boundarys like described in the tutorial but i still have unaccurate results!!
what i have to do ?
thanks a lot
Thanks for replying but; I have two questions then 1. why define as opening as it is an outlet and water can not come back from the weir after falling down? 2. why hydrostatic bc when it is going in the free atmosphere?
free surface problem
hi,i have declared the surface tension as an equation in dependance of the temperatur at cfx-pre.all others boundary conditions are like the tutorial but with my values! and the solver is starting,it means cfx-pre is correct,right??!
the problem is: i have to get the surface tension-curve after running to know how my surface tension is changing with different temperaturs because i have 2 temperature on the bottom.how did cfx know how my cells are fulling(water /air)and did cfx using my equation of the surface tension?
thank u very much
hydrostatic BC is for inlet, at the Outlet use a 0 Pa pressure BC (just Air) if water falls out of the model.
if you want to see the surface tension curve in CFX-post, you should create a point on water surface (IsoSurface made out of water Volume Fraction of 0.5) and extract the related variavle on that point along the time.
Are you sure surface tension is significant? Modelling surface tension is difficult and reduces the stability of the simulation so only model it if it is required.
my tension equation is:sigma(t)=-0,949*t+15,858
i have declared it as an expression,is it wrong?!
how shoul i declaring this point on the surface to get tension curve at cfx-post?
thank you
and i have an constant surface tension coeffizient!! i don´t know if it true ! anb do i have heat transfer to?i think so wright?!
it´s my master thesis,yes i have to modelling the surface tension:confused:
You have put your posting on a thread discussing dam break flows and surface tension is definitely not important there. Maybe in future you can start a new thread when you start a new conversation.
From what I see in your expression you have made surface tension a function of time, and a strange one at that. Two things look strange - Your expression will end up with negative surface tension eventually and - at t=0 sigma=15.858. I don't know what unit system you are working in but this looks strange to me.
Alternately if t is temperature then your expression will always return a negative surface tension as t is in Kelvin by default.
Are you sure your surface tension equation is correct? What fluid are you modelling anyway?
hi,my expression is depending on temperatur in degre celsius not time!
i´m modelling first of all water but later i have to modelling ch3oh,and the endexpression should be :
sigma(temperatur,concentration)=a(T).exp(0,72*(x(m eoh)+b(T))-c(T)*x(meoh)).
the the values of the expression are experimentally prouved.
do u understand my problem now?
thank u lot
and sorry for my broken english:-)
What is the length scale of the simulation? Either a Re number, Weber number or some other appropriate scaling number.
Surface tension is not fully linearised in the solver so is in effect solved explicitly (to an extent anyway). CFX is an implicit solver so that means as soon as you turn on surface tension the time step required for stability will reduce enormously. Are you sure your time step is small enough.
For the ink jet printer simulations I am currently doing I start the simulation with timesteps of 1e-11s, and allow it to grow to 1e-9s as the simulation progresses. Goes to show I mean REALLY small timesteps.
And these instabilities are magnified because your surface tension is not constant (and not even linear).
Hallo,my timestep is automaticly setting,my length scale is 50 mm!
do i have a heat transfer to?well the problem is : i have to get the surfacetension-curve as funktion of the temperatur first and than of the concentration.!should i set the surfacetension coefficient as constant?and how did the solver know where my surface exactly is?
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Customer Life-Cycle Marketing Demands New Metrics
February 10, 2015
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To win, serve, and retain customers, Forrester believes that modern marketers must make the transition from the traditional marketing funnel to the customer life cycle. Marketers must understand at what stage in the cycle marketing programs are most relevant, focus on information flows at customer hand-over points, and adopt across-cycle metrics to foster organizationwide customer obsession. This report will explain how CMOs must spearhead adoption of new metrics for performance management and optimize the transition to customer life-cycle marketing. This is an update to a previously published report; Forrester reviewed it for continued relevance and accuracy.
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Table of Contents
- Increasing Complexity Demands Customer Obsession
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|Publication number
|Publication type
|Application number
|Publication date
|Nov 29, 2011
|Filing date
|Feb 29, 2008
|Priority date
|Jun 5, 2002
|Fee status
|Also published as
|Publication number
|Mark A. Mitchnick
|Original Assignee
|Mitchnick Mark A
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (20), Non-Patent Citations (13), Classifications (21), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
1. Field of the Invention
The present invention relates to the delivery of antimicrobial functions or agents from the surface of coatings, particularly the release of antimicrobial functions or agents from the surface of medical devices, especially medical devices that have been inserted or implanted into patients. The invention particularly relates to the controlled or controllable delivery of such functions or agents.
2. Background of the Art
It has become common to treat a variety of medical conditions by introducing or implanting a temporary or permanent medical device partly or completely into a patient. These devices may be inserted or implanted (the term "implanted" shall be used herein to reflect both short term insertion and long term implantation) into many different organs and glands such as the heart, brain, esophagus, stomach, trachea, colon, biliary tract, urinary tract, vascular system or other location within a human or veterinary patient. These implants may be in the form of a device such as a pump, delivery system, sensing system, stent, catheter, balloon, wire guide, cannula, electrical pulsing or pacing system or the like. However, when such a device is introduced into and manipulated through the vascular system or implanted at a selected site, the tissue or vascular walls can be disturbed or injured. Clot formation or thrombosis, bacterial collection and infection and other adverse events can occur at the injured site or implantation site, causing acute or chronic injury or infection at the sire. Moreover, if the medical device is left within the patient for an extended period of time, thrombus and infections may often form on the device itself, again causing serious potential for damage and illness. As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, stroke, site infection, sepsis, implant rejection, and the like. Thus, the use of such a medical device can entail the risk of causing problems as serious or worse than the problems that the device's use was intended to ameliorate.
Another way in which blood vessels undergo stenosis is through disease. Probably the must common disease causing stenosis of blood vessels is atherosclerosis. Atherosclerosis is a condition which commonly affects the coronary arteries, the aorta, the iliofemoral arteries and the carotid arteries. Atherosclerotic plaques of lipids, fibroblasts, and fibrin proliferate and cause obstruction of an artery or arteries. As the obstruction increases, a critical level of stenosis is reached, to the point where the flow of blood past the obstruction is insufficient to meet the metabolic needs of the tissue distal to (downstream of) the obstruction. The result is ischemia.
Many medical devices and therapeutic methods are known for the treatment of atherosclerotic disease. One particularly useful therapy for certain atherosclerotic lesions is percutaneous transluminal angioplasty (PTA). During PTA, a balloon-tipped catheter is inserted in a patient's artery, the balloon being deflated. The tip of the catheter is advanced to the site of the atherosclerotic plaque to be dilated. The balloon is placed within or across the stenotic segment of the artery, and then inflated. Inflation of the balloon "cracks" the atherosclerotic plaque and expands the vessel, thereby relieving the stenosis, at least in part.
While PTA presently enjoys wide use, it suffers from two major problems. First, the blood vessel may suffer acute occlusion immediately after or within the initial hours after the dilation procedure. Such occlusion is referred to as "abrupt closure." Abrupt closure occurs in perhaps five percent or so of the cases in which PTA is employed, and can result in myocardial infarction and death if blood flow is not restored promptly. The primary mechanisms of abrupt closures are believed to be elastic recoil, arterial dissection and/or thrombosis. It has been postulated that the delivery of an appropriate agent (such as an antithrombic) directly into the arterial wall at the time of angioplasty could reduce the incidence of thrombotic acute closure, but the results of attempts to do so have been mixed.
A second major problem encountered in PTA is the re-narrowing of an artery after an initially successful angioplasty. This re-narrowing is referred to as "restenosis" and typically occurs within the first six months after angioplasty. Restenosis is believed to arise through the proliferation and migration of cellular components from the arterial wall, as well as through geometric changes in the arterial wall referred to as "remodeling." It has similarly been postulated that the delivery of appropriate agents directly into the arterial wall could interrupt the cellular and/or remodeling events leading to restenosis. However, like the attempts to prevent thrombotic acute closure, the results of attempts to prevent restenosis in this manner have been mixed.
Non-atherosclerotic vascular stenosis may also be treated by PTA. For example, Takayasu arteritis or neurofibromatosis may cause stenosis by fibrotic thickening of the arterial wall. Restenosis of these lesions occurs at a high rate following angioplasty, however, due to the fibrotic nature of the diseases. Medical therapies to treat or obviate them have been similarly disappointing.
A device such as an intravascular stent can be a useful adjunct to PTA, particularly in the case of either acute or threatened closure after angioplasty. The stent is placed in the dilated segment of the artery to mechanically prevent abrupt closure and restenosis. Unfortunately, even when the implantation of the stent is accompanied by aggressive and precise antiplatelet and anticoagulation therapy (typically by systemic administration), the incidence of thrombotic vessel closure or other thrombotic complication remains significant, and the prevention of restenosis is not as successful as desired. Furthermore, an undesirable side effect of the systemic antiplatelet and anticoagulation therapy is an increased incidence of bleeding complications, most often at the percutaneous entry site.
Other conditions and diseases are treatable with stents, catheters, cannulae, pacemakers, defibrilators, pumps, eluent drug delivery systems and other devices inserted into organs such as the heart, the brain, the esophagus, the trachea, the colon, biliary tract, urinary tract and other locations in the body, or with orthopedic devices, implants, or replacements. It would be desirable to develop devices and methods for reliably delivering suitable agents, drugs or bioactive materials directly into a body portion during or following a medical procedure, so as to treat or prevent such conditions and diseases, for example, to prevent site infection, either from short term insertion or long term implantation of the device. As a particular example, it would be desirable to have devices and methods which can deliver an antibacterial agent or other medication to the region of implantation, where the release of the antibacterial agent can be externally controlled, rather than relying on predetermination of a release rate. Additionally, the release rate should not be dependent upon external reading of the device or regular sampling of the blood stream to determine when release rates of a medical pump should be modified to adjust to altering patient conditions. The antibacterial delivery system should also be minimally additive in size or volume to the device being implanted. It would also be desirable that such devices would controllably deliver their agents over both the short term (that is, the initial hours and days after treatment) and the long term (the weeks and months after treatment). It would also be desirable to provide relatively precise control over the delivery rate for the agents, drugs or bioactive materials, and to limit invasive control in effecting that delivery. This would be particularly advantageous in therapies involving the delivery of a chemotherapeutic agent to a particular organ or site without requiring reinsertion or additional insertion to the patient through an intravenous catheter (which itself has the advantage of reducing the amount of agent needed for successful treatment). This would reduce the trauma to the patient and reduce additional invasion of the patient. A wide variety of therapies can be similarly improved by the practice of this methodology. Of course, it would also be desirable to avoid degradation of the agent, drug or bioactive material during its incorporation on or into any such device.
Problems experienced with the use of pumps, structural implants, pacemakers, defibrillators, and catheters, particularly catheters designed for urinary tract infections or indwelling vascular catheters such as those used in patients receiving long term chemotherapy for malignancies or antimicrobials for persistent infections present a significant risk in patients with an indwelling catheter. Although many such infections are asymptomatic, they are sometimes serious and can result in prolonging the length of stay and increasing the cost of hospital care. Bacteria are believed to gain access to the catheterized bladder either by migration from the collection bag and/or catheter or by ascending the periurethral space outside the catheter. It has been found that by coating catheters with silver or silver oxide reduced the incidence of catheter associated bacteriuria. Silver is known to possess antibacterial properties and is used topically either as a metal or as silver salts. It is not absorbed to any great extent and the main problem associated with the metal is argyria, a general gray discoloration. Although silver is an effective topical antibacterial agent, it tends to act only on bacteria in direct contact with the surface and is subject to chemical reactions such as oxidation, which reduce its long term effectiveness.
Additionally, where release of the antibacterial agent from a coating is solely by mass transfer release by elution or migration out of a coating, drug is unnecessarily released during movement to the implantation site. At a minimum, this drug is wasted during implantation, or in the case of highly active agents, it is released to a region where that drug is not needed.
U.S. Pat. No 5,418,130 describes a method for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers and irradiated with, for example, WV, visible, gamma or X-ray radiation. In particular, quaternary ammonium or phosphonium substituted, halo-psoralen compounds are described as being useful. This system is for use on solutions or dispersions of cells or the like and is not described for application on medical devices.
A typical drug delivery system with a biodegradable release layer is shown by U.S. Pat. No. 6,342,250. U.S. Pat. No. 6,251,136 describes a method of forming a release catheter comprising a method for coating a stent, comprising the steps of: providing a stent; applying a base layer of sticky material to selected surfaces of said stent; applying pharmacological agent in micronized, dry form to selected surfaces coated by said base layer; and applying a membrane forming polymer coating through which said pharmacological agent is able to diffuse to all surfaces of said stent.
U.S. Pat. No. 4,723,950 by Lee relates to a microbicidal tube which may be incorporated into the outlet tube of a urine drainage bag. The microbicidal tube is manufactured from polymeric materials capable of absorbing and releasing anti-microbial substances in a controllable sustained time release mechanism, activated upon contact with droplets of urine, thereby preventing the retrograde migration of infectious organisms into the drainage bag. The microbicidal tube may be produced by one of three processes: (1) a porous material, such as polypropylene, is impregnated with at least one microbicidal agent, and then coated with a hydrophilic polymer which swells upon contact with urine, causing the leaching out of the microbicidal agent; (2) a porous material, such as high density polyethylene, is impregnated with a hydrophilic polymer and at least one microbicidal agent; and (3) a polymer, such as silicone, is compounded and coextruded with at least one microbicidal agent, and then coated with a hydrophilic polymer. A broad range of microbicidal agents are disclosed, including chlorhexidine and triclosan, and combinations thereof. The purpose of Lee's device is to allow the leaching out of microbicidal agents into urine contained in the drainage bag; similar leaching of microbicidal agents into the bloodstream of a patient may be undesirable.
U.S. Pat. No. 6,168,601 shows a system utilizing the eutectic forming ability of related drugs to control release. Biologically active materials are provided in a cylindrical carrier medium with better control over the rate of delivery and length of time of delivery by providing a carrier having dissolved or dispersed therein at least two compounds having a common biologically active nucleus, but with different solubility parameters. The combination of the two different variants of the same drug with different solubility parameters provides the material with control over the rate of release of the compounds (by varying the proportions of the variants) and most importantly, extending the useful life of the device by enabling release of effective levels of the compounds over a longer period of time. The cylindrical carrier medium, comprised of silicone, further includes a tail, a skirt, or a rate-limiting membrane.
U.S. Pat. No. 5,091,442 by Milner relates to tubular articles, such as condoms and catheters, which are rendered antimicrobially effective by the incorporation of a non-ionic sparingly soluble antimicrobial agent, such as triclosan, The tubular articles are made of materials which include natural rubber, polyvinyl chloride and polyurethane. Antimicrobial agent may be distributed throughout the article, or in a coating thereon. A condom prepared from natural rubber latex containing 1% by weight of triclosan, then dipped in an aqueous solution of chlorhexidine, is disclosed. U.S. Pat. Nos. 5,180,605 and 5,261,421, both by Milner, relate to similar technology applied to gloves.
U.S. Pat. No. 6,224,579 discloses a method of producing a non-infecting medical article by imbuing the device in a solution containing synergistic amounts of two antibiotics. That article comprises a medical article prepared by exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.3 and 1.5 percent of a silver salt and between about 0.1 and 20 percent triclosan, where the treatment solution and the medical article do not contain chlorhexidine or a chlorhexidine salt.
Improved coatings and control of drug delivery is desired for medical devices.
The present invention relates to medical devices that are inserted or implanted into patients and that have antimicrobial coatings that controllably release free radicals into the vicinity of the device. These devices may have coatings that alter their rate of flow release or elution release of an antibacterial agent from a coating on the device upon immediate, local or external stimulation or external activation. By immediate is meant that the coating or element is itself heatable or responsive to radiation (e.g., Infrared responsive, RF responsive, etc.), local means that an adjacent element may generate the heat or accept radiation emission and convey the energy to the layer or element to stimulate the release of the free radical, and external activation includes a signal from a distal control to mechanically alter the size of an opening, or cause a stretching of elongation of the element to open pores or holes. The coating should therefore be responsive to immediate, local or external control such as by heating (e.g., by electrical resistance where an external wire is present on the device) or responsive to external RF [radio frequency] stimulus, sonic control [e.g., to disrupt a coating or to activate a battery driven circuit in the system], local radiation stimulation or activation and the like. By having control of the release rate, and in some structures without invasion of the patient by mechanical means in addition to the device itself, the release rate can be in response to need at the implant site. The class of compounds to be released are free radical compounds, compounds that release free radicals upon immersion or stimulation, the free radicals acting as the antibacterial agent. Semiconductor materials capable of emitting radiation (e.g., UV radiation that can be generated internally from the semiconductor to activate free radicals) may be used to control release of free radicals in a layer responsive to the emissions or temperatures that can be generated by the semiconductor.
Over the past few years, free radicals have been implicated in all sorts of diseases. Every health supplement and face cream seems to include some protection against them—but what are they and, more importantly, what do they do? We first need to go back to basic level chemistry to understand what a free radical is. The chemical bonds that hold atoms together to make molecules contain pairs of electrons. For example, there are two electrons in each of the bonds holding the hydrogens of water to the oxygen. The two electrons act to stabilize the bond between the atoms. However, some molecules, especially those containing oxygen, can easily gain an extra one of these bonding electrons. As this electron is not paired with any other electrons, it makes the molecule very reactive. In a sense this molecule or atom with the extra, available electron is a molecule with a free chemical bond. This is essentially what a free radical is—a molecule containing unpaired electrons. This molecule will steal electrons from other molecules in order to pair its lone electron. In stealing this electron the structure of the electron-donating molecule may be changed or even turned into a free radical itself. Free radicals are generated by all sorts of different processes in the body. Approximately 5% of the oxygen that our cells use to burn sugars to release energy is lost as oxygen free radicals. UV light, cigarette smoke, and various other agents generate free radicals. White blood cells deliberately produce free radicals to kill invading bacteria. Free radicals can destroy enzymes, make proteins brittle, make cells leaky, cause cholesterol to become stuck in arteries and mutate DNA. Much of the process of ageing appears to be due to a very slow but steady wearing out of the body by free radical damage.
The body deals with free radicals either by using antioxidant enzymes, which degrade the radicals back to harmless water and oxygen, or with chemicals called antioxidants, which react with and neutralize the radicals. Vitamin C and vitamin E are the two most important antioxidants within the body. Vitamin E neutralizes radicals in the fats and oils of our body while vitamin C protects the water-soluble biomolecules.
Free radicals are relatively free from controversy in the medical field with respect to their toxicity, effectiveness, and long term effects. Although free radicals in solution are recognized as fighting or killing bacteria or viruses, much literature addresses the presence of free radicals in the body as unhealthy, contributing to cell deterioration, especially skin and tissue aging. A great deal of commercial literature focuses on the increase of antioxidants in diets to reduce the amount of free radicals in human blood streams to reduce aging effects. There is still incontrovertible evidence that free radicals in solution have a direct and immediate effect on disabling or killing bacteria and viruses. However, except for ozonation, there appears to be little effort that has been made in the direction of finding any useful method for applying free radicals to human therapy, except for the natural free radical generations effected by the body as part of its immune response.
Free radicals are atoms or groups of atoms with an unpaired valence electron. Free radicals can be produced by photolysis or pyrolysis in which a bond is broken without forming ions (e.g., hemolytic fission). The presence of the unpaired electrons causes free radicals to be highly active. Free radical generating compounds, especially those that are responsive to light and/or heat to generate the free radicals are especially well known in the photocatalytic art. Among the many types of free radical generating initiators known in the polymer art are triazines, s-triazines, quaternary ammonium compounds and salts; halogen releasing compounds; diazonimum salts, iodonium salts (especially diary iodonium salts), phosphonium salts (especially triaryl phosphonium salts), sulfonium salts (especially triaryl sulfonium salts), biimidazoles, benzophenones, and the like. Some of these materials are quite stable in aqueous environments, generating the free radicals only upon thermal or photoinitiation. Other classes of free radical generating compounds more typically known in the medical environment as a treatment for in vitro liquid supplies are fibrates (e.g., fenofibrate); NSAIDS such as benoxaprofen, carprofen, ketoprofen, naproxen, suprofen, Tiaprofenic acid; Germicides such as Bithionol, buclosamide, fenticlor, hexachlorophene, tetrachlorosalicylanilide, and triclosane; tetracyclines such as demeclocycline, doxycycline and tetracycline; quinolones such as cyprofloxacin, fleroxacin, lomefloxacin, nalidixic acid, and ofloxacin; psoralens such as bergamot oil, 5hydroxypsoralen, isopsoralen, 5-methoxypsoralen, 8-methoxypsoralen, and trimethylpsoralen; diphenhydramine, thiazides, sulfonylureas; azines such as chlorpromazine, and promethiazine. The use of brominated or halogenated psoralens is particularly useful in activation in the practice of the invention, either as pure coatings or dissolved or dispersed in polymeric coatings. Other types of intercalators may be utilized besides the psoralens and substituted psoralens such as those listed below. These intercalators may be used to target viruses or other blood contaminants, or cancer cells. Thus, halogenated or metal atom-substituted derivatives of the following compounds may be utilized as sensitizers: dihematoporphyrin esters, hematoporphyrin derivatives, benzoporphyrin derivatives, hydrodibenzoporphyrin dimaleimade, hydrodibenzoporhyrin, dicyano disulfone, tetracarbethoxy hydrodibenzoporhyrin, tetracarbethoxy hydrodibenzoporhyrin dipropionamide; and the like. The above compounds in their non-halogenated or non-metal atom substituted forms are disclosed in U.S. Pat. Nos. 4,649,151, 4,866,168, 4,883,790, 5,053,423 and 5,059,619, incorporated by reference herein. When modified with halogen atoms or metal atoms, the above-identified classes of compounds may be sensitized with electromagnetic radiation, including visible light. Semiconductors such as titanium dioxide and zinc oxide also produce free radicals upon UV and visible light exposure, and are preferred sources of free radicals in compositions used in the present invention.
Polymeric compositions are often used as coatings on medical devices, such as catheters or stents, as shown in U.S. Pat. No. 5,964,705, either as the structural material for the device or as an insulating or protective coating. Such medical devices, where the polymer is formed by a free radical polymerization process, may have residual free radical polymerization catalyst present in the polymer coating. The concentration of such free radical catalysts in polymers is typically on the order of 1-3% by weight. Literature citing extreme ranges of free radical catalysts may indicate levels as high as 10% by weight, but these are truly unrealistic amounts added to provide broad ranges of protection for purposes of legal disclosure. Even at those levels, and particularly where the inclusion in the polymer does not provide them in an active state or enable them to be come active, such low levels of free radical polymerization catalysts would not be a sufficiently high concentration of materials to maximize antibacterial activity according to the practice of the invention, and such activity has never been reported in the literature.
The invention encompasses various devices, including a medical device for insertion into a patient, the device having a surface with a coating thereon or containing within its outermost layer, an antimicrobial amount of at least one compound that provides microbe suppressing free radicals into an aqueous environment in contact with the device upon external stimulation of the coating, layer or compound. The device may provide the coating releases an amount of free radicals upon heating that increases in a rate of release from the coating to an aqueous environment by at least 20% when heated from 37� C. to 50� C. The device may have the coating release an amount of free radicals upon sonication that increases in a rate of release from the coating to an aqueous environment by at least 20%. The device may be designed with the coating comprising at least 0.0001% by weight of compounds that release free radicals when in contact with an aqueous environment. The device may have the coating comprise at least 0.005% by weight of compounds that release an antimicrobially active amount of free radicals when in contact with an aqueous environment. The device may alternatively have the coating comprise at least 0.1% by weight of compounds that release an antimicrobially active amount of free radicals when in contact with an aqueous environment. The device may have the compound generate free radicals upon stimulation by electromagnetic radiation. The device may have the coating comprises at least 1.0% or at least 1.5% by weight of the compounds. The free radical releasing compound may comprise a quaternary salt or a compound that releases halogen free radicals. The coating or outer layer may comprise at least 0.005% by weight of compounds that release an antimicrobially active amount of free radicals when stimulated by heat or electromagnetic radiation. There may be an electromagnetic receiver that initiates heat generation in the device to elevate the temperature of the coating. A battery may electrically attached to said device to power heat generation, or a transmitting wire is electrically attached to said device to power heat generation from an outside power source.
The invention may be alternatively described as medical device for insertion into a to patient, the device having a containing within its outermost layer an antibacterial amount of at least one compound that provides microbial-suppressing free radicals into an aqueous environment in contact with the device upon external stimulation. It ius referred that the compound comprises TiO2, ZnO, SiO, and other metal oxides either alone or in combination. The stimulation is preferably provided by infrared radiation, ultraviolet radiation or visible light. The antimicrobial agent may also be a photoactive compound.
In the practice of the present invention, coatings with free radical generating or free radical providing compositions should be present in the coatings on medical devices of the present invention as at least 0.0001% by weight of the coating because of the high activity of free radical materials. The coatings or compound contained within the coating on the device might make up only a fraction of the weight—possible as little as 0.0001%, at least 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, 2%, 5% by weight, at least 10% by weight, at least 12% by weight, at least 15% by weight, at least 20% by weight, at lest 25% by weight at least 30% by weight, up to solid coatings of 100% by weight of the free radical generator. Solid coatings are preferred but water immiscible oil-based coating may also be provided, although these can be rubbed off during insertion.
Coatings may be applied to the surfaces of the medical devices by any convenient method, including but not limited to dip coating, spray coating, iontopheresis, deposition coating, manual application, and the like. As the activity of the free radicals tends to be a surface phenomenon, or at least material is released from the surface, the coatings do not have to be thick to provide effective results. Coating of less than 0.5 microns can provide some significant activity, and layers thicker than 100 microns do not provide significantly additional effectiveness, although the thicker layers would provide a greater life and endurance. Therefore, the nominal thickness of 0.5 to 100 microns is merely a general range, and not exclusive of other thicknesses. Generally preferred ranges would be from 0.5 to 50 microns, 1.0 to 50 microns, 1 to 30 microns, 2 to 30 microns, or 2 to 25 microns.
The use of normal migration of free radical providing materials out of the coating is one method of providing local free radical antimicrobic activity. Providing thermally responsive or photoresponsive free radical generators requires some more substantive structure. For example,
Layer 35 is a structural support layer in the catheter 2, supporting layer 37 that contains coils 12, 16, 18 and 32. Those coils 12, 16, 18 and 32 are powered through wires 36 and 38. These types of coils are traditionally used as RF responsive microcoils for generating a field of view under MRI (magnetic resonance imaging), but here with appropriate thickness, they can also be used as resistive wires. When sufficient current is passed through the coils 12, 16, 18 and 32, those coils would generate heat that could trigger free radical release in layers 39 and/or 40, either or both of which may comprise the free radical generating composition. Tubes 24, 24a, 26, 26a, 28, 28a, 30 and 30a represent microcatheters, light pipes, material delivery tubes and the like as designed into the structure. The figure shows microcatheters 24 and 30 as material 25 delivery ports. These material delivery ports 24 and 30 may deliver drugs locally during primary catheter treatment procedures and then be used to deliver ingredients that would actively cause release of free radicals in layer 40. Microcatheters 26 and 28 could be light pipes to deliver radiation towards layers 39 and/or 40 to cause photoinitiated release of free radicals from those layers 39 and/or 40. The release could be from the surface of layer 40 or from an interior wall of layer 39 so that free radicals are released into delivery tube 4 to diffuse out of that tube or to be forced out of the delivery tube 4. Component 22 may be a preamplifier, battery, RF receiving system, sonar-receiving system, or the like to control liquid flow through delivery tubes 26 and/or 28, or to control electrical flow into wire 20 and into the coils 16, 18, 10 and 32. Individual coils 13, 15, and 17 are shown, as is the spacing B and 19 between sets of coils. The coils are shown as two (32) or three (34) windings.
Coatings of materials can be provided in many variants and forms that can be externally activated. By the term "externally activated" it is meant that direction must be given from an outside source to initiate increased rates of release of the free radicals, and that even if there is some level of free radical release from the implanted or inserted structure, that rate may be increased upon an initiating signal from outside the patient or even with a sensor signaling function in the patient and communicatively attached to the device. The free radical materials are provided as a coating on at least a portion of the implanted device. The coating may have an initial release capacity for the free radicals of the coating composition and/or may have an additional and alternative antibacterial or anticlotting or other medically active compound that is released spontaneously during dwell of the implanted or inserted device. The free radical material must be deliverable by a signal function, as explained above. The coating may therefore be associated with a heating element, such as a resist heating element, a light emitting heating element (e.g., infrared emitter, or other radiation emitter with an absorber/thermal converter thermally connected to the free radical releasing layer), mass conductive heating element, or the like. The free radical providing layer may also be solvent activatable, where the introduction of a particular class of solvents or solutions to the region will leech and/or activate free radical materials from the coating. Alternatively, radiation projection onto the coating may cause release of free radicals as is the case with TiO2, free radical photonitiators, and coatings whose solubility change to release more dissolved or dispersed material when photoinitiated. Such release functions are well known in the photoimaging, printing and lithographic arts.
Prophetic Examples
A stent comprising an array of Titano� bars and cross-bars providing flexibility and elastic memory that can undergo compression and expansion is dip coated into a solution comprising a bioinert polysiloxane polymeric binder and trial sulfonium tetrafluoroborate in a weight ratio of 10:90 in an organic solvent. The coating would be applied in an amount that upon drying would provide a 10 micron thick coating. A nickel/cadmium battery is electrically connected to the bars, with an intermediate RF receiver with switching capacity. The RF receiver is programmed to response to a preprogrammed signal so that upon receipt of the signal, a circuit is closed for a specified period of time (e.g., 1 minute) during which the battery heats the stent and the coating, the heat stimulating release of free radicals from the coating.
An alternative design places an ultraviolet radiation-emitting semiconductor underneath the coating and over the stent bars and cross-bars. The battery is electrically connected to the semiconductor so that upon being powered up, the semiconductor emits UV radiation, photoinitiating release of the free radicals.
A catheter is coated with TiO2 and a UV emitting fiber optic is placed into the catheter at the skin's surface and fed down the catheter. The light source is turned on causing a photoinduced release of free radicals from the TiO2. Alternatively, the catheter itself (with transparency through the structural material of the catheter (as in a radiation transparent window) can be used to transmit the light from an external source to the region of the free radical releasing composition.
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|U.S. Classification
|604/265, 427/2.28, 427/2.1, 424/423, 427/2.11, 604/266, 424/422, 427/2.24, 427/2.3, 427/2.12, 604/264
|International Classification
|Cooperative Classification
|European Classification
|Sep 26, 2014
|Maintenance fee reminder mailed
|Jan 20, 2015
|Surcharge for late payment
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|Jan 20, 2015
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