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Other Names for this Disease
- Mammary pseudoangiomatous stromal hyperplasia
- Pseudoangiomatous stromal hyperplasia of the breast
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.
Your Questions Answered
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My 20-year-old daughter just had a breast lump removed and the pathology report indicated she has pseudoangiomatous stromal hyperplasia. Although we understand it is a benign condition, we want to learn more about it and are having difficulty finding information. What are the chances that another lump will develop? Is there a link between this condition and the use of birth control pills? If so, does this mean she should not use oral contraceptives in the future? Click here for answer


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A century after its iconoclastic origin in Charles A. Beard's Economic Interpretation of the Constitution of the United States, progressive history is at loose ends. The Progressive narrative posited fundamental conflict between the people as a whole and property-minded businessmen. This was a durable theme as long as a concept of national unity existed as the political context in which the people and the interests did battle. Since the 1960s, however, the demography and economics of relentless modernization have disaggregated the people into a multitude of preference-seeking racial, gender, and cultural groups, defying even the most determined effort to "imagine" a coherent national community. At the same time a post-progressive generation of scholars defended the framers' constructive republican statesmanship. Even latter day Beardians were forced to take note: Edward Countryman's has described the popular celebration of the Constitution's ratification as expressing the understanding of American society presented in Federalist 10.
Unruly Americans, by University of Richmond historian Woody Holton, is a tendentious and unapologetic neo-populist fable that dismisses the favorable view of the founders advanced in recent scholarship. A historian with "attitude," Holton aims to write the good name of the people into the story of the Constitution to show they were not simply "'passive spectators' of the Miracle at Philadelphia." Denying that the Constitution was intended to correct the weaknesses of the Articles of Confederation, Holton asks: "What do we really know about the motives that set fifty-five of the nation's most prominent citizens...on the road to Philadelphia?" He does not find the answer in the writings of Anti-Federalist opponents of the Constitution on whom past Progressive historians relied. The Anti-Federalists, besides being elitist politicians at the state level, agreed with the Federalists that the national government needed to be strengthened and the public credit restored. Holton turns for political inspiration instead to uneducated farmers and ordinary Americans, a natural populist constituency whose instinctive radical democracy, he believes, is the key to understanding the founders' intent.
Holton's historical method, loosely conceived, is that of literary-social discursive analysis. In the revolutionary era an explosion of periodical literature occurred, producing "a cornucopia of documents" in which "freemen of all walks of life" were able to express their opinions. Conscious of their newly won equality as republican citizens, ordinary Americans flooded the state legislatures with petitions concerning a wide range of policy proposals. "After more than two centuries," Holton observes, "many of their ideas retain the power to stir the imagination."
Clearly Holton's historical imagination has been stirred. Articulating an ingenious populist version of original constitutional intent, he writes: "From the complex struggles of the 1780s, the Founding Fathers extracted a simple lesson: that the uneducated farmers who seized the ship of state during the American Revolution had damn near driven it aground." The Constitution's overriding purpose was to prevent this, and permanently to reduce the force and effect of radical democracy. Holton says contemporary Americans don't know this, however, because the traditional account that enshrines the Constitution and magnifies the framers has "become as powerful an institution as the Supreme Court or the Electoral College." It has given wealthy and well-educated Americans "a breezy sense of political entitlement," while having "the opposite effect on ordinary citizens, chipping away at their self-confidence."
* * *
From the standpoint of uneducated farmers, the political condition of the country in the 1780s was good because the Revolution made America a democracy. Economic conditions were bad, however, because of a decline in productivity, loss of overseas markets, heavy public and private indebtedness, scarcity of hard currency, and high taxes. Under the Articles of Confederation Congress had no real authority and states in effect made public policy for the nation. The condition of economic distress therefore suggested the need to create a national government with authority to adopt fiscal, tax, and commercial policies for the country as a whole. This was the view of the Madison-Hamilton educated framer faction that Holton says wrote the Constitution on the premise that "ordinary Americans lacked the capacity for self-government."
Taking the part of the farmer-ordinary American faction, Holton contends that the real problem was the failure of the state legislatures to listen to the voice of the people. States imposed oppressive taxes and demanded payment in specie. They redeemed at face value war bonds bought by speculators from original farmer-soldier recipients at a fraction of their face value. Rather than grant relief, state lawmakers cracked down on debtors, whose misery and distress Holton chronicles in exacting detail. Worse still, the few who benefited from this injustice did so "not by selling goods and services in an open marketplace but by obtaining favorable policies from the government." Himself an educated populist, Holton nevertheless understands the uneducated populist mind. Blaming deliberate government policies for their distress, farmers "naturally looked to the government for redress." They demanded tax and debt relief through established political procedures. When this didn't produce results the farmer-ordinary American faction "felt compelled to play the trump card of rebellion."
Holton describes a populist mindset that appeals to the democratic virtues of emotion, passion, and fellow feeling as the basis of political action, in contrast to elitist insistence on the faculty of reason which is not equally possessed by all citizens. "Americans who favored tax and debt relief," he explains, believed "the greatest threat to proper representation came not from uneducated or overly emotional representatives, but from those who could not sympathize with the plight of their constituents." Although no explanatory political anthropology is offered, it appears that powerful emotivist tendencies, rather than rational reflection, disposed unruly Americans to regard rebellion as a legitimate policy-making "mechanism."
Imagination stirred, Holton adopts a promiscuous conception of rebellion that includes any form of refusal, disobedience, protest, resistance, or demand for redress, whether individual or collective, actual or threatened, rhetorically aggressive or physically violent. Rebellion breaks out when angry farmers burn down the county jail, declare themselves victims of great injustices, form an association refusing to pay taxes, overpower the sheriff to rescue a fellow rebel, or force the repeal of an oppressive tax by the threat of an expanding insurrection. Although Shays's Rebellion is well known in the history books, Holton claims "there were actually multiple revolts up and down the seaboard" that had a decisive effect on the course of American politics. In the Virginia backcountry alone there were 155 recorded cases in which sheriffs and deputies attempting to seize property of delinquent debtors were "kept off by force of arms." In about half the states debtors and taxpayers assaulted the county court, the symbol of government power. Holton observes: "No one could say for sure who set fire to several Virginia courthouses in the 1780s—that was what made arson so attractive."
Not that as a historical empath he cares much about it, but Holton raises an important theoretical question. The right to revolution formed the basis of the American claim to national independence. How to recognize the right of revolution, reconciling it with limited constitutional government, was a central issue in republican political theory. The untroubled inference drawn in Holton's account is that populist rebellion was a legitimate form of political action for achieving the ends of republican government. The Revolution placed government in the hands of the people. The farmer revolts expressed the conviction that the Revolution had failed to bring about the fundamental changes the people desperately desired. Holton says the populist mind "believed that sometimes a rebellion could lead to a truly democratic election." Americans seeking tax and debt relief therefore "often found that threats of rebellion could be tremendously effective." As if attesting the "rationality" of populist disorder, Holton notes that "The most organized rebellions of the 1780s were attempts to threaten violence without actually using it."
* * *
In Holton's telling the wave of farmer-ordinary American uprisings struck fear into the minds of delegates to the Constitutional Convention, motivating them to contain radical democracy and render it politically innocuous. He claims modern Americans don't know this, however, because Convention delegates were in a "pattern of denial." They avoided express reference to agrarian rebellion and blamed the country's political troubles on the vices of the state governments. Influenced by "simple masculine pride" and reluctance to admit "they had simply replaced British imperial officials in the saddle," the framers reasoned that insurrections were nearly impossible to prevent, whereas it was "relatively easy to make government institutions less responsible to popular whimsy."
Distrust of democracy was expressed in structural devices such as the separation of powers, appointment of senators by state legislatures, and indirect election of the president. The most insidious restraints on popular influence were those "least visible in the Constitution itself." In Holton's view the principal barrier was extension of the sphere of republican government from the states to the country as a whole. By this means many of the states' most important functions were transferred to the national government. Holton asserts that by uniting Americans in a single polity, the framers divided the community into a multitude of interests and parties, making it practically impossible for "an angry populace" to control the government. In the words of a Connecticut populist, the design of the Constitution "was calculated to induce the freemen to imagine themselves at liberty, while they are destined to be allured or driven around as if impounded."
Although a majority according to historical estimates, ordinary Americans opposed to the Constitution were outmaneuvered in the ratification debate. At every step of the way Holton sees the framers combining subtlety, deception, and indirection with prudence, candor, and moderation to craft a winning strategy. Their desperate desire to curb the power of the people "forced them to drop or moderate some of their favorite restraints on grassroots influence." Shrewdly, the framers never approved an inflammatory proposal "if they could accomplish the same object using a mechanism that their fellow citizens would find easier to swallow." Almost accusatorily, Holton says the framers created a government "substantially immune to popular influence—and yet sufficiently democratic to be ratified."
Taking a broader view, however, Holton claims that the people made their mark on the Constitution. True, the "accusation of plebeian incompetence" was written "into the fabric of the nation's founding document." Nevertheless insurgent Americans' voice was heard. The "greatest compromise" in the making of the Constitution was between the framers and the American people. "In a real sense," he writes, "Americans who tilled the soil were present in the Pennsylvania state house that summer." Their opinions and just demands were expressed in the rebellions of the 1780s. Holton says that if the convention delegates "had not feared the nation's agrarian majority would reject it, they would have created a more considerably elitist document."
The framers, then, were neither cynical economic self-aggrandizers as Beard argued, nor enlightened statesmen seeking the common good as recent scholarship has depicted them. In Holton's view they were frightened aristocrats, attempting to reverse the course of democratic revolution, who "disguised their antidemocratic intentions." Holton concedes that the Constitution "offered something of value to nearly every free American" and brought economic prosperity to the nation. But it came at the enormous political cost of overthrowing rule by the people for rule by educated national elites.
Holton intends a story of hope and inspiration, not an elegiac reflection. The message of the book is that although they are no longer an uneducated majority, the people still have the right and the power, the wit and the wisdom, to govern themselves by their own devices—including rebellion and the threat of rebellion—as they see fit. By being true to their ungovernable inner self, Americans can reclaim the spirit of populist originalism so imaginatively presented in Unruly Americans. Woody Holton does not aspire to serious constitutional scholarship, but without intending it he provides an always timely reminder of the peril of popular sovereignty thinking.

subset: commoncrawl


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This is a gorgeous sweet and piquant salsa. Try it with slices of roast turkey around the holidays (especially great if you want to brighten up leftovers). You can roast the peppers in the oven or on the grill. You could also halve and pit the peaches and give them a quick spin on the grill, not to fully soften them, but just to give them some nice grill marks and get those juices going a bit more (especially if they are not perfectly ripe).
Katie Workman, author of The Mom 100 Cookbook
2 tablespoons rice vinegar | kosher salt and freshly ground pepper to taste | |
1 tablespoon fresh lemon juice | 1 red pepper, roasted and diced | |
2 tablespoons minced cilantro | 2 cups finely diced peeled ripe peaches | |
1 teaspoon honey | 1/4 cup chopped onion |
In a medium-sized bowl combine the vinegar, lemon juice, cilantro, honey, salt and pepper. Add the bell pepper, peaches and onion and gently toss together . Cover and chill salsa up to 2 hours.
Yummy recipes, DIY projects, home decor, fashion and more curated by iVillage staffers.
The very dirty truth about fashion internships... DUN DUN @srslytheshow http://t.co/wfewf
Behind-the-scenes pics from iVillage.


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Dunlop SP31 P195/65R15 89S Features & Benefits:
M&S-rated, all-season tread design. Helps deliver all-season traction and wet handling. Circumferential tread grooves. Help pump water away from the footprint for excellent wet traction. Multi-Pitch Tread Design Technology?. Helps reduce noise for a quiet ride. Asymmetric tread. Helps maintain wet and dry traction. |


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By Ms. Donoghue, a petition (accompanied by bill, Senate, No. 1006) of Eileen M. Donoghue, Karen E. Spilka and James B. Eldridge for legislation relative to the notification breast abnormalties. Public Health.
Sponsors: | |
Status: | Referred to Joint Committee on Health Care Financing |
Petitioners: Eileen M. Donoghue, Karen E. Spilka, James B. Eldridge


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Marami ang nabibighani sa kagandahan ng Baguio at ng Banaue Rice Terraceshindi lamang mga Filipino kundi pati na rin mga ibang lahi na nakakita na ritoaktwál man o sa larawan lamang. Subalit gaano man kasikát ang dalawang lugar na yan, marami pa rin ang hindi nakaaalam kung saang probinsya mismo ng Pilipinas sila matatagpuan.
The Mountainous RegionSituated in Luzon, Cordillera Administrative Region consists of six provinces: Abra, Benguet, Ifugao, Kalinga, Mountain Province, and Apayao. The region covers most of the areas within the mountain range known as Cordillera Central.
One of the 17 regions comprising the Philippines, Cordillera Administrative Region is beloved by many Filipinos primarily because two of the most beautiful places in the country is found therethe City of Baguio and Banaue Rice Terraces.
The Summer Capital of the PhilippinesThe independent City of Baguio is usually the destination of many peoplelocals and touristscome summertime. Situated at an altitude of approximately 1,500 meters, it boasts of cool and foggy early mornings and evenings, not typically experienced in the lower parts of the country. Although not a part of the governance of the province of Benguet, Baguio is geographically located in the said province. Significant spots located in Baguio include Loakan Airport, Camp John Hay Leisure Resort, Philippine Military Academy, University of the Philippines Baguio, Mines View Park, Burnham Park, and a number of shopping malls including SM City Baguio. The summer capital is home also to the annual flower festival known as Panagbenga.
The Rice TerracesThe Banaue Rice Terraces are the main tourist attraction in the province of Ifugao. According to some historians, ancestors of the indigenous people of the region carved these 2,000-year-old terraces into the mountains largely by hand, with minimal use of equipment. They built the terraces to provide level steps on which they could plant rice. Majestic and impressive as they can be, the Banaue Rice Terraces were not built in a day or even in a month, so to speak. They were a result of a long process which took years. Many surmise that the terraces had not even been finished. In fact, the Banaue Rice Terraces are only a part of the Rice Terraces of the Cordilleras ancient human-made structures carved into various areas of the massive mountain range of Cordillera Central, dating back about 2,000 to 6,000 years. Rice terraces may be found also in the other Cordillera provinces, although the ones in the municipality of Banaue remain to be the most popular and well-tended. To this day, locals still tend rice and vegetables on the terraces; however, since that more and more Ifugao of the younger generation no longer find farming appealing and lucrative, the characteristic steps of the terraces have gradually eroded.
Sa Madaling Salita
Ang Lungsod ng Baguio ay nasa Benguet, samantalang ang Banaue Rice Terraces naman ay nasa Ifugao. Ang dalawang ito ay ilan lamang sa mga ipinagmamalaking lugar sa Pilipinas na pawang matatagpuan sa Cordillera Administrative Region.
Photos by Ron Cantiveros | Filipino JournalReference: http://en.wikipedia.org/wiki/Cordillera_Administrative_Region [06/20/08]
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The astonishing hidden world of the deep ocean
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track your influence!
Ocean explorer Robert Ballard takes us on a mindbending trip to hidden worlds underwater, where he and other researchers are finding unexpected life, resources, even new mountains. He makes a case for serious exploration and mapping. Google Ocean, anyone?
This talk was presented at an official TED Conference. TED's editors featured it among our daily selections on the home page.
- Interactive transcript (23 languages)
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text:
This is a three piece denim suit and I've been wearing it for three whole days.
justin timberlake
I may or may not have listened to "Suit and Tie" 10 times already and I may or may not be ready to hit play again.
home decor
Everyone knows Justin Timberlake is adorable and a great singer and a great actor. But did you know he has ridic home decor style, too? Here's how to get the look.
justin timberlake
Justin burst on to the stage singing "Like I Love You" with a guitar strapped around his body. This was the first time in my life I wished I was an instrument.


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Availability: Ambassador Hotel
Please enter your travel dates.
Single Room - Room Only
Double Room
Twin Room, 2 Single Beds
Quadruple Room
Hotel in Glasgow (North West Glasgow) near Botanic Gardens
This hotel is located in Glasgow (North West Glasgow), close to Botanic Gardens, Kelvingrove Art Gallery and Museum, and Museum of Transport. Also nearby are Scottish Exhibition and Conference Centre and Clyde Auditorium.
Hotel Features
In addition to complimentary wireless Internet access, Ambassador Hotel provides a computer station, free self parking, and free parking.
Room Amenities
Televisions come with digital channels. Guestrooms also feature complimentary wireless Internet access, refrigerators, and safes.
Information missing or incorrect? Tell us!Ambassador Hotel Amenities
- General
Ambassador Hotel features concierge services, express check-in, and express check-out. A computer station is located on site and high-speed wireless Internet access is complimentary. This Glasgow hotel also offers a safe deposit box at the front desk and a television in the lobby. Complimentary self parking is available on site.
Ambassador Hotel is a smoke-free property.
- Total number of rooms - 26
- Number of floors - 2
- Concierge services
- Express check-in
- Express check-out
- Free Wi-Fi
- Computer station
- Luggage storage
- Free parking
- Free self parking
- Free guest parking during stay
- Safe-deposit box at front desk
- Free on-street parking
- Smoke-free property (fines apply)
- Smoke-free property
- Number of buildings/towers - 1
- Television in lobby
- Internet
Available in all rooms: Free Wi-Fi
Available in some public areas: Free Wi-Fi
- Parking
Free parking, Free guest parking during stay, Free self parking, Free on-street parking
- Room Amenities
- Direct-dial phone
- Refrigerator
- Coffee/tea maker
- Wake-up calls
- Daily housekeeping
- Private bathroom
- Complimentary toiletries
- Makeup/shaving mirror
- Bathtub or shower
- Hair dryer
- In-room safe
- Clock radio
- Desk
- Window opens
- Trouser press
- Iron/ironing board (on request)
- Cribs/infant beds available
- Digital TV service
- Free Wi-Fi
- City view
Ambassador Hotel Policies & Fees
- Check-in
Check-in time starts at 1:30 PM
Check-in time ends at 10 PM
Minimum check-in age is 21
Special check-in instructions:
Guests planning to check in after 10 PM must advise the hotel in advance. Contact details are available on the reservation of confirmation email after booking.
- Check-out
Check-out time is 11 AM
- Payment types
Accepted at this hotel: American Express, MasterCard, Visa
- Pets
Pets not allowed
- General
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
No elevators
- Fees
- The following fees and deposits are charged by the property at time of service, check-in, or check-out.
- Early check-in fee: GBP 10.00
- Crib (infant bed) fee: GBP 10.00 per stay
The above list may not be comprehensive. Fees and deposits may not include tax and are subject to change.
- Additional Details
This property's policy is to refuse certain bookings for the purpose of group events or parties, including pre-wedding stag/bachelor and hen/bachelorette parties.


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Peter Cherewyk has worked in the financial field for over 10 years. He completed his Bachelor of Commerce from the University of Alberta, and is currently working towards a Chartered Financial Analyst designation. He enjoys hockey and hiking and the opportunity to teach others.
Financial Edge
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The Highest Priced Stocks In America
5 Types Of Workers Who Respond To Disaster
Protesting With Your Money: Does It Work?
5 Jobs That Cash In On Disasters
Your Worst Financial Mistakes And Why You Made Them
The Goldman Sachs Accusation Explained
The U.K.'s Most Dangerous Jobs
Look Smart: Financial Calculations You Can Do In Your Head
On This Day In Finance: July 7, 2003 - WorldCom Pays $750 Million
Calculating Covariance For Stocks
Advantages And Disadvantages Of ETFs
4 Types Of Money Market Yields
The Series 79 Exam: What It Is And When You Need It
Introduction To The Series 65 Exam
Valuing Firms Using Present Value Of Free Cash Flows
Valuing A Stock With Supernormal Dividend Growth Rates
How To Calculate Required Rate Of Return
Stock Analysis
Great Dividend Yield Payouts
In good times more risk can be taken. But for now, let's look at a couple of companies ... -
Grocery And Clothing Earnings Released
Consumer staples and grocery stocks will always be in demand, both in good and bad ... -
Don't Miss Friday's Earnings Releases
In case you missed earnings that were released this last week, go over them now. -
Buying Opportunity: Colleges In The Crosshairs
Student loans in default could increase regulations placing restrains on the education ... -
4 Bargain Credit Companies
Companies that provide credit services and loans for consumers are looking better ... -
Lithium Ion Battery Stocks
Instead of trying to pick the best cellular phone company, electric car or green ... -
Graphics Cards Investing
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Finding the right stock to reduce volatility is not as exciting, but it is essential ... -
5 Companies Looking To Repurchase
Buyback announcements could mean major blocks of shares will be removed from the ... -
Battery-Powered Car Stocks Gaining Momentum
With Tesla's new IPO the battery-powered car is gaining hype and momentum. Should ...


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I think you can bring anybody to your room you want. The key card lets you in BLT, you would just have to let escort your friends in--- as in call you on the cell or room phone when they get to BLT. Swimming is a whole other story; I have no idea.
We were recently given the very exciting news that our waiting list came through and we will be staying at Bay Lake Tower in early June(we are staying on points) We were then pleasantly surprised to learn that some friends of ours will be visiting WDW at the same time as us and staying at POR. Our question are:
1. How strict is the BLT staff concerning us bringing our friends into the building?
2. Can our friends swim with us at the BLT pool since we are staying there on points or will we have to go to POR to swim with them?
3. Will they allow our friends onto the viewing balcony with us one evening to watch Wishes or do they have Balcony Police that will kick us off?(figuratively not literally of course)
We understand that even DVC members are not permitted to use the BLT amenities unless we are staying there and we do not wish to overstep our boundaries...but since we are staying there are they going to ask to see all our I.Ds or just one to prove that our family is staying on site? Again, not trying to offend or insult anyone, that's why I'm asking now because we really have never been in this position before and don't want to get anyone upset at us for doing something we were unaware we couldn't do
Thanks for any input!
Day 1 WDW Radio
Keep to the code
I think you can bring anybody to your room you want. The key card lets you in BLT, you would just have to let escort your friends in--- as in call you on the cell or room phone when they get to BLT. Swimming is a whole other story; I have no idea.
"I just want it to look like nothing else in the world... and it should be surrounded by a train" -Walt Disney.90 CB, 92 DI, 94 CR, 97 FWC, 99 CS, 00 CS, 02 CS, 04 POR, 05 POR, 07 POR, 08 POFQ, 09 POR, 11 POR.
I know we can bring anyone to the room, just wasn't sure about the pool or viewing area. Has anyone brought friends to Stormalong bay over at Beach club? I'm sure the rules would be similar at both resorts.
Day 1 WDW Radio
Keep to the code
Only guests actually staying at YC&BC can use Stormalong Bay. You usually have to show your room key to get in, and get a bracelet. No "guests of guests" are permitted. Even DVC members, who are allowed to pool hop (when capacity allows), are not allowed to hop to SAB.
I don't know the rules about the BLT area yet...
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Thanks Doc, I think the BLT pool rule has to be pretty close to the same as Stormalong Bay.
Day 1 WDW Radio
Keep to the code
I did find that the Bay Cove pool is also not available for pool hopping to DVC members (nor is the AKL/AKV pools, which I knew about but forgot to mention). Whether you can invite friends I'm not 100% sure, but I think it is generally disallowed at ALL resorts for non-resort guests, even if they are staying at another Disney resort (other than the DVC exception).
I believe that only DVC members staying AT BLT on points can get to the viewing lounge.
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New: Magic Your Way Ticket Price Calculator
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As far as the fireworks viewing, it is for DVC members staying at BLT....AND their guests. After the fireworks, the lounge is not very crowded and is a very nice place to have a quiet drink with the friends. We were there for marathon weekend and loved it.
we're staying at BLT next week! And we are planning on having some friends come to visit, so I can let you know!
- Jeanne
Engaged at Sunset Point - July 17th, 2008
Married at Sunset Point - March 3, 2009
Disney World & Disneyland Honeymoon
Aulani - September 2011
Wishes can come true, if you believe in them with all your heart.And the best part is, you'll never run out of wishes.They're shining deep down inside of you.'Cause that my friends is where the magic lives
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text:
Yesterday a lion keeper at Wellington Zoo in New Zealand was attacked by two large lions. At first when I watched the footage on television I was horrified, as the reporter was saying that basically the were playing with him. Then I realised that if they had wanted to they could have killed him very quickly.
I have attached a web-link, there may be some footage of the event as it was filmed by a visitor at the zoo.


text:
Hay For Sale
Hay Wanted
S Boisselle RANDOLPH COUNTY Siler City, NC 27344, NC 27344 336-879-2892, cell 336-324-428 Comments: Wanted Local Hay from Siler City area. Will come and get it out of the field if square. Rounds also wanted (20)Please call if you have extra in your first or second cutting. Thank you! S Boisselle
Ad Submitted:4/17/2008


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The Marines of Company E, 4th Tank Battalion, 4th Marine Division often get the same question when seen on post, "There are Marines at Fort Knox?"
Yes, there are Marines on post and they've been here since the 1980s. They are one of the only remaining groups to use the tank training ranges that remain at Fort Knox.
The reserve unit has an inspector instructor staff of about 15 Marines who are active duty and 120 reservists who train at least one weekend a month and two weeks a year.
The unit is the only Fort Knox unit still conducting tank training on the installation, 1st Lt. Thomas Hodge said.
"Armor hasn't totally left Fort Knox, just the armor school," he said.
The Marines probably will stay a while because Fort Knox has retained several tank ranges and the area offers plenty of room for the tanks to maneuver, he said.
A Marine Reserve unit operates a bit differently than the Army, Hodge said. It is a cross between what he National Guard and Army Reserve do for the Army.
Marine reservists can fulfill combat arms roles, something Army reservists cannot do, Hodge said adding the Army Reserve is mostly combat service support.
Reservists fulfill every military occupation specialty and duty, just as their active duty counterparts. In the 4th Tank Battalion, they provide armor support for the division, Hodge said.
"Fort Knox, being the former home of armor for the Army, it's only natural to have a tank company here representing the Marine Corps," he said.
One of the big things to do is to provide tank support and be ready to go with 72-hour notice, he said. In 2003, the company was called up for support in the invasion of Iraq.
During deployment, the company typically attaches to an active duty unit.
The Marine reservists come from all walks of life. Some with college degrees, some currently in college and others are business professionals or in management roles.
Hodge is a teacher.
"When the time comes and we are called up, we drop whatever we are doing," he said.
In 2011 they supported Operation African Lion, working with Moroccan forces. It was a month-long training mission.
It was a good experience for the Marines and helped them get used to the deployment process, Hodge said.
The experience helped to make smoother transitions to their deployment to Afghanistan in 2012, he said.
Staff Sgt. Matthew Schickel has been with the unit since 2004 and deployed with it to Afghanistan in March.
The mission was a little different than what the Marines were used to because it wasn't armor support. They worked on the pivotal task of route clearance. The task was to go up and down the routes to clear them before the forces came through. The main task was to make sure there was freedom of movement on the route and look for improvised explosive devices.
The fact that this company was chosen for this task is a part of why Schickel is a part of it. It has a good history and a good name, he said.
Hodge estimated 90 percent of the company comes from Kentucky and Southern Indiana.
"Our company has a very good reputation amongst the battalion for having great Marines and getting the job done," he said. "I think that's why Marines like coming here."
There are great marines with strong work ethics and integrity in this area that bring the values from home with them, he said.
The Marine Corps is picky about what reserve units it deploys and this one deploys a lot, he said.
Because in this type of warfare the IEDs are a majority source of casualties, to trust them to do route clearance means the Marines place a lot of confidence in this company, he said.
They averaged finding more IEDs than being struck by themwhich translates into a good performance, Hodge said.
They had a great welcome home to Fort Knox when they returned in November and the Freedom Riders were there to escort them back from the airport, an effort appreciated by all the Marines involved, he said.
After returning some went on leaveand some finished their active duty orders. Once the cut-off date hits, they all will go back to their civilian jobs and to training as tankers. There are mechanics, communications specialists and other support Marines in the unit as well.
It takes a lot of really good Marines to keep this company going and there are a lot of good Marines here, Hodge said.
"In my opinion it's because we pull from a really good population right around here," he said. "There are a lot of hard-working guys who aren't afraid to get their hands dirty and that shows whenever we come to work here."
"I think that's one of our best assets," Hodge said. "The average guys here from this area are just good people who love their country and want to do their part. "
Becca Owsley can be reached at (270) 505-1741 or email@example.com.
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BP Comment Quick Links
June 28, 2013 Transaction AnalysisMarmol Gets a Free Pass
Placed C-R David Ross on the 60-day disabled list. [6/25] Optioned 3B-R Will Middlebrooks to Triple-A Pawtucket. [6/25] Purchased the contract of 4C-R Brandon Snyder from Triple-A Pawtucket. [6/25] With Ross on the 60-day disabled list it's worth noting how rare it is for a catcher to miss time with concussion. Ross is one of the 10 catchers with multiple concussions over his career, according to our database, which dates back about a decade. Does that pass the smell test? Of course not. Catchers are hit with projectiles on a nightly basis—some twice within the same at-bat. To believe all those strikes have added up to as few concussions as are reported borders on naivety. Given the concussion revolution in football, don't be surprised if the way that backstops are examined following blows to the head becomes a bigger story in time. Jose Iglesias takes jobs. He knocked Pedro Ciriaco off the roster a few weeks back, and now he's nudged Middlebrooks to the minors. In fairness it's not all Iglesias' doing, though he stands to benefit the most. Middlebrooks struggled with plate discipline throughout the season, and those issues drove the Red Sox to demote him with the hope that he can sharpen his eye under dimmer lights. Expect to see him return in due time. Meanwhile Snyder, the Orioles' first-round pick in 2005, has a golden opportunity to prove he belongs on a big-league bench. The causes for optimism stem from his ability to play each corner position, and to swing a league-average bat.
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manga (ori) Collaborations
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manga (original) ^ ^
line art & light+shadow by friend
messy sketch & coloring by me
Created Mar 08, 2013. Unless noted Copyright 2013
Sayano .
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awwwww dis is soooo kawaii wat a cuuute collab kyaaaa xD am in luv w/da cute style n da soft colors/shading--n omigosh dat green outfit :D favie :33
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Fri May 18, 2012
Sudents Suspended Over Post-It Note Prank
By editor
Originally published on Fri May 18, 2012 4:49 pm
Good morning. I'm David Greene. It's not clear what message high school students in Clayton, Indiana were sending with this year's senior prank. They attached 11,000 blank Post-it notes to various surfaces, doors, chairs, desks. Six students got suspended, which led to a student protest, which led to 50 more suspensions. Tensions are easing. An administrator lifted the suspensions, calling it a first step in the healing process. No word on whether she delivered that news on a Post-it note. It's MORNING EDITION. Transcript provided by NPR, Copyright NPR.


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Manolo: climbing and informed choices
Some thoughts by Maurizio 'Manolo' Zanolla about climbing and the need to be conscious of the choices you make.
Some thoughts by Maurizio 'Manolo' Zanolla about climbing and the need to be conscious of the choices you make.
The video Avalanche emergency produced by Ortovox Safety Academy Lab for the new internet site dedicated to mountain safety.
Video tutorial that explores some common belaying mistakes.
The video by Petzl that demonstrates proper ice screw placement technique, as well as how to set an anchor and a v-thread in waterfall ice.
Ortovox: Safety recommendations avalanche airbag Tour 32+7 ABS & Tour 30+7 W ABS
The Cancer Council Australia has received a £10,000 donation from the initiative Climbers against Cancer.
Alpinism, courses, safety and fun on stunning Mont Blanc. The simple recipe of the Arc'teryx Alpine Arc'ademy 2013 that took place from 14 - 16 June at Chamonix to find out more about climbing and alpinism.
The film of the avalanche of snow and rocks opposite the via Ferrata de Saint Christophe en Oisans in France.
The French company Petzl has issued the following press release concerning the mechanical prusik ZIGZAG for arborists.
Official press release from Climbing Technology concering their rope friction based Via Ferrata Sets.
We have received and published the press release of the UIAA concerning the second recall in the last six months of Rope-friction Via Ferrata sets. We hope that in the near future this official press release will be translated in the languages of other countries concerned. On their websites a selection of manufacturers have already published the steps that need to be followed for the recalled products.
A sample of carabiners and quickdraws have been tested and analised by Emanuele Pellizzari at the Italian Mountaineering Club Gear and Techniques laboratory at Taggì di Sopra, Villafranca Padovana, Padova, Italy.
To rule out any possible risk for the user, SALEWA has decided to recall some Civetta II full-body harnesses and Vertigo 400 Alpindonna harnesses as a precautionary measure.
The final three videos with Tom Randall and Pete Whittaker explaining the climbing techniques needed for getting up cracks: offwidth, gear and gear placements and taping.
The first three short videos to learn the art of climbing cracks, a useful tutorial which examines everything from finger cracks to how to tape up
Planetmountain.com goes online today with its Gallery, the zone dedicated to mountain photography, climbing, alpinism, trekking, and skiing, with currently more than 10,000 photos.
The American magazine Outside has chosen Planetmountain as one of world's best 10 climbing sites.
Salewa has emitted a recall and substition for the carabiner Salewa Hot G2 Bent colour 0999/ red Article Code: 1557 – limited to the serial numbers 02 11 and 03 11
The French company Petzl has issued a recall which concerns its GRIGRI 2's (D14 2O, D14 2G, D14 2B ) with the first five digits of the serial number between 10326 and 11136.
The British Mountaineering Council has issued important Campus Board advice aimed primarily at children and teenagers.


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Severe weather
Flooding response
Floods 2014: Hampshire response with full information and links Updated 11 March
Flood warnings
- Environment Agency
- See a list of roads affected by flooding in Hampshire
Traffic and travel
BBC Solent radio has traffic and public transport updates for all of Hampshire: 96.1FM, 999AM and DAB Digital Radio and online.
- BBC Hampshire roads and travel with traffic cameras and incident updates
- Traffic and travel information (Romanse website)
- Romanse page on Twitter
- Hampshire County Council page on Twitter
Winter roads
Road salting
Which roads we salt and when salting happens. -
Salt (grit) bins
Salt bins for community use in Hampshire. -
Winter driving advice (external site)
Advice on safe driving in winter conditions from the Royal Society for the Prevention of Accidents. -
Winter maintenance policy
The County Council formal winter maintenance policy (part of the Highways Policy) - Download leaflet about safe driving in winter 848kb
Roads and transport news
- County Council welcomes Government acknowledgement that more more is needed to help repair roads damaged by flooding
- Hampshire Highways in safe hands for the future
- New energy-efficient streetlighting for National Parks
Did you know?
- Hampshire County Council manages over 5,000 miles of roads
- 45 First Priority salting routes are directly managed by Hampshire County Council on the County road network
- The average length of each salt route is 35 miles
- Five tonnes of salt are carried by each lorry on a salting run


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Newegg.com - A great place to buy computers, computer parts, electronics, software, accessories, and DVDs online. With great prices, fast shipping, and top-rated customer service - once you know, you Newegg.
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AWESOME DEALPros: Great bang for your buck. Some would guffaw at how small the included SSD is at 16gb, but after comparing it to some other off the shel win 8 laptops at the office, it would seem that intels smart cache tech really makes the most of it and this thing is the fastest win 8 notebook I've used so far. Also has a fast 3rd gen i7 so it can eat up anything that's thrown at it as long as the chips are fed data by the HDD+SSD consistently. Cons: Bloatware had to be uninstalled. but what do you expect? Did you find this review helpful? |
Amazing for the value!Pros: Fast CPU. GPU good if not amazing. Handles every game I play at 1080p. Metallic feel makes it feel very sturdy. Gaming pc that you can hide at a regular laptop to help with either theft or simply hiding your nerd. Keyboard feels AMAZING. Trackpad works pretty well for what you need, usually use an external mouse obviously. Overall was impressed to find I could play many games I was unsure about. JBL speakers honestly blew me away. I am no audio freak, as I game on turtle beach x11's and px21's just because I used before for xbox/ps3 and they work, but the JBL speakers added a new sense of sound that I thoroughly enjoy, perhaps I need better headsets..., Overall simply amazing for the price. Couldn't find comarative laptops in this price range, all were 650m and lower, while 660m was $1200+, honestly impressed by Lenovo and first time with an Nvidia gpu! PS SSD cache really speeds up boot time! Feels like 10sec boots! Cons: GPU doesn't hold up to standards I got from my main build of 7970 ghz with i5 2500k, but really isn't the laptops fault and I didn't expect that. Does get, escpecially around left palm area, but never enough to cause alarm or be a real issue and only happens when gaming for a good half hour to an hour before you notice it. Cooling pad DEFINITELY recommended. Screen isn't going to win any major awards but doesn't really change my opinion too much, although I do find watching youtube videos or browsing the internet to cause my eyes to strain, perhaps I am just more used to matte screens, but again while game I don't notice it, raising saturation +15 seemed to help but still going to tweak with it more. The hole by camera isn't centered right so with the protector the edge of my camera would be all black. I removed the cover to use the camera and it works, but looks bad to see camera offset. Not sure I really NEED the camera, but even for aesthetics it doesn't look like a quality laptop. Other Thoughts: Opted for 750gb HDD+16GB SSD over BLU-ray and 1TB HDD. Did I choose right? Depends on need. Both are $999 right now just about everywhere so its your choice. I chose SSD simply because I hoped for faster boot times, which I got, and While the extra space and Blu-Ray probably was the better deal, I know I would never use the blu-ray drive. Did you find this review helpful? |
Pretty goodPros: Handles most games so far at medium/high graphics. Depends on what I set the resolution to. Cons: Short battery life but thats what power outlets are for. Other Thoughts: Fred and Jake's feedback are pretty much spot on and I agree with them. The laptop does get hot when you push it but I haven't experienced the leaf blower so far. Did you find this review helpful? |
Pretty Nice though..Pros: Good computer, good resolution, nice keyboard, pretty fast and just overall has a very solid foundation. All hardware is good and checks out for me. Cons: It's unfortante but it comes with the repugnant Windows 8, it's clearly not handling w8 well, it's resolution when it comes to certain things is just impossible, it clips and cuts off important sections, it's somewhat unresponsive to certain commands, espically exiting windows. It's having trouble with drivers, as well as programs as a whole. It is very stubborn, but I [assume] that's more windows 8, however, this is not option to opt out of using windows 8 with this computer, thus I have to buy a 150$ disc to fix an awful operating system. Other Thoughts: Windows 8 is in it's early stages of use and it is not a good idea to put it on a computer such as this one. At the very least there should be, like I said, an opt out option to let you choose the operating system. The amount of flaws with windows 8 is so bothersome it probably has driven me away from Windows 8 forever, unless they pull it together which probably will never happen. As for the laptop itself it's very nice and I recommend it and has a good price for the laptop itself. Just remember to spare 150$ to throw it down on a version of Windows 7, so keep that in mind. 4 out of 7 people found this review helpful. Did you? |
Dead slow LenovoPros: Great Specs. To bad I never got the good one! Cons: Purchased Lenovo Y 580. It takes almost a month to get here. Arrives with dead Keyboard and touchpad. On with support withing 2 hour arrival, returned to lenovo within 24 hours. It will take them over 1 business week to credit my account. People in IT told me their Lenovos arent working well either. Should have listened. Never again will I look at Lenovo as a quality product. Other Thoughts: Look at Lenovos Facebook page. It is full of posts of lenovo gone bad. Hp never gave me problems. Its back to them for me 0 out of 12 people found this review helpful. Did you? |
Best laptop I ever had!Pros: Fast, Clean and simple, quiet fan for power, slim keyboard that feels great, Back-lit keyboard looks fantastic. Cons: Nothing other than battery life. Other Thoughts: Took a little while to get used to windows 8 but that's not the laptop fault. 2 out of 3 people found this review helpful. Did you? |
Mostly excellent, with a few notable caveatsPros: Display and power: Brilliant screen, better than I've seen on any laptop under $1400. Speedy i7 processor that's marginally faster than the more common (at this date) 3610QM at the same price. The 660M graphics are great, and most of my games are fluid at 1080p with minor detail adjustments; everything runs maxed at 1366x768. The audio is also surprisingly good for a laptop - there's even a hint of bass! The battery life is actually pretty good for a laptop with these components; in Power Saver mode I can easily get 5 hours out of it. (Keep in mind this is not an ultrabook, so 5 hours is actually pretty decent!) Cons: The drives. The hard drive is 5400 rpm, which completely cancels out any benefit from the SSD caches; one would be much better off eliminating the cache and going up to a 7200 rpm hard drive or an SSD. Also, with the 1080p display (the lowest model is only 720p), it would have been nice to have a Blu-Ray drive... Other Thoughts: I love, love, love NewEgg's customer service and recommend buying from the if at all possible; I would have were it not out of stock when I needed a new laptop. 11 out of 12 people found this review helpful. Did you? |


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1967 Ford MustangClassified as a 1967 Ford Mustang 2-Door Coupe in great conditionRebuilt from Frame out with all work completed by professional specialistsBurgundy Metallic... More
1999 Ford Mustang GT 35th Anniversary Convertible. Dark Green Satin with Parchment leather interior. 5 - Speed 4.6L, V8. Excellent condition with 5,400 original miles.... More
1969 Ford Mustang Custom Fastback, Here is the long detailed description of what is basically a bad ass pro touring mustang. This car was... More
1967 Ford Mustang Coupe, 200, 6 Cylinder, Power Steering/Automatic. Fully Restored, Base/Clear Paint, New Tires/Shocks, New Disc Brakes. Excellent Condition In & Out. Looks,... More
1969 Mustang Mach 1. 9T02S197xxx. 390, 4 speed. Complete restoration. Body was chemical dipped. 95% original sheet metal. Restored using as few reproduction parts... More
1968 Ford MustangThis is a 1968 Ford Mustang with the original 289 cubic inch V8 engine2nd-Owner unit that has been well maintainedTwo tone Yellow... More
Like new 2012 Ford Mustang Boss 302 Laguna Seca edition with 379 original miles. Number #154 of 750 produced. Powered by a 444 horsepower... More
Freshly restored to factory standards with only 9 miles since the restoration was completed. This beautiful example has the rare factory ASC sunroof and... More
2013 Ford Mustang BOSS 302 Laguna Seca, New never registered BOSS 302 Laguna Seca. All original paperwork including paper carpet protector for feet.Car was... More
1966 Ford Mustang Convertible, mint condition, AOD trans, Leather interior, 3,016 miles on a Frame Off Restoration with engine rebuild, power rack and pinion... More
2007 Ford Mustang PARNELLI JONES, Great things can happen when the right combination of things comes together. The Saleen Parnelli Jones Limited Edition Mustang... More
2004 Ford Mustang Mach I - 40th Anniversary Limited Edition This car is a beautiful Ford Mustang 40th Anniversary Limited Edition Mach I with 4.6... More
1970 Ford Mustang Mach 1 428, This is a one of kind Mustang and the most fully loaded fastback to roll off the prodcutuin... More
1969 Ford Mustang Boss 429, This extremely rare RAVEN BLACK BOSS 429 is a two owner all original car. The car is in amazing... More
NEVADA CLASSIC CAR DEALER # 40339 , VIN # 2F03H196674 BAD ASS is all I can think of to say about this amazing 1972 Resto-Mod... More


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Black Bear Casino Resort Tickets and Event Dates
Venue Information
Venue Details
Black Bear Casino Resort is conveniently located at the intersection of I-35 and Hwy 210 in Carlton, MN just 20 minutes south of Duluth and approximatelytwo hours north of the Twin Cities.
1785 Highway 210
There is a 4-story free parking ramp. Valet parking is also available under the hotel canopy.Box Office Numbers
(218) 878-BEARAccessible Seating
Accessible seating is available.General Rules
Doors open 45 minutes prior to showtime.No smoking during the show.
Children Rules
Under the age of 18 must be accompanied by an adult.Miscellaneous
Restaurants onsite include:Seven Fires Steakhouse providing fine dining in an elegant atmosphere.
Sage Deli for a quick bite before or after the show.
Cobalt Cabaret offers live entertainment Thursday-Sunday with comedy every other Wednesday.
Buffet offers a wide variety of food.


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"I find it fascinating that most people plan their vacations with better care than they plan their lives. Perhaps that is because escape is easier than change." ~Jim Rohn Do you plan out your day? Your week? Your month? If so, how much do you plan? How far do you take it? I've known people who could easily have PhD's in planning… from Harvard!, and others who wouldn't know what a simple calendar looked like, much less how to use it, if it hit them up-side the head. So, where do I fit in? Post PhD — I'm the Continue reading >>
Jul 022012
July 2, 2012
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George Ayittey Discusses Why Africa is Poor on BBC radios Exchanges on the World Economy Recorded: Friday, October 25, 2013
Ghanaian economist and Research Fellow, George Ayittey argues that Africa is poor because it is not freedue to dictatorships. He spoke with host Justin Rowlatt and an audience at Paris Dauphine University in Paris.
Experts: George B. N. AyitteyType: RadioIssues: Culture/ Society, Diplomacy and Foreign Aid, Economic History and Development (International), Economic Policy, Economists, Free Market Economics, Trade
Anthony Gregory Discusses Habeas Corpus on the Ernie Brown Show Recorded: Thursday, May 2, 2013
Anthony Gregory, Research Fellow and author of The Power of Habeas Corpus in America: From the Kings Prerogative to the War on Terror, appeared on America's Radio News Network on Thursday, May 2 with host Ernie Brown. They talk about Anthony's new book, the history of the writ of Habeas Corpus, and how it is still relevant today.
Type: RadioIssues: Civil Liberties/ Human Rights, Criminal Justice/ Prisons, Law Enforcement, Terrorism and National Crises
Ben Powell on Globalism and Development 2012 Summer Seminar for High School Students Recorded: Tuesday, June 19, 2012
This presentation is from our 2012 Challenge of Liberty Summer Seminar for high school students, which was held from June 18 to 22, 2012, at the Independent Institute Conference Center, Oakland, California. View videos and more information about the Summer Seminars.
Experts: Benjamin W. PowellType: Independent Institute EventIssues: Economic History and Development (International), Economic History and Development (U.S.), Trade
Is U.S. Justice Broken? Recorded: Thursday, December 9, 2010
Part 1 | Part 2 | Part 3 | Part 4 | Part 5
From fingerprinting to criminal sentencing, from lawyer licensing to judicial selection, and from eminent domain to wealth transfers via class-action lawsuits, how do perverse incentives impact the law and what reforms would create a more just and efficient legal system?
Experts: David D. Friedman, Alex Kozinski, Edward J. López, David J. TherouxType: Independent Institute EventIssues: Crime, Criminal Justice/ Prisons, Law Enforcement
Part 1 | Part 2
Experts: David D. Friedman, Alex Kozinski, Edward J. López, David J. TherouxType: Independent Institute EventIssues: Criminal Justice/ Prisons
Edward López with David Theroux on the New Book, The Pursuit of Justice Recorded: Thursday, December 9, 2010
Independent Institute Research Fellow Edward Lopéz, Associate Professor of Law and Economics at San Jose State University and editor of the new Institute book The Pursuit of Justice, talks with Institute President David Theroux about the faulty incentives at the heart of government legal failures and whether market-based alternatives can provide viable solutions to the serious problems caused by the bureaucratization and politicization of the law.
Experts: Edward J. López, David J. TherouxType: RadioIssues: Criminal Justice/ Prisons, Law Enforcement, Privatization
The Supreme Court and the Battle for Second Amendment Rights Recorded: Thursday, July 22, 2010
In June 2008 the U.S. Supreme Court handed down a landmark ruling on the Second Amendment individual right to keep and bear arms with its Heller v. District of Columbia decision. Two years later, in June 2010, a second historic decision squeezed through the highest court in the land.
Experts: Stephen P. Halbrook, Donald E. J. Kilmer Jr.Type: Independent Institute EventIssues: Bureaucracy and Government, Civil Liberties/ Human Rights, Constitutional Law, Criminal Justice/ Prisons, Culture/ Society, Gun Control, History (U.S), Law Enforcement, Litigation, Political Ideology and Philosophy, Race Issues
David Theroux on the Arizona Immigration Law Recorded: Thursday, July 15, 2010
David Theroux discusses the Arizona immigration law on The Neil Asbury Show.
Experts: David J. TherouxType: RadioIssues: Crime, Criminal Justice/ Prisons, Immigration, Law Enforcement


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Monoclonal antibody | |
Type | Whole antibody |
Source | Humanized (from mouse) |
Target | VEGF-A |
Clinical data | |
Trade names | Avastin |
AHFS/Drugs.com | monograph |
Licence data | EMA:Link, US FDA:link |
Pregnancy cat. | C (US) |
Legal status | ℞ Prescription only |
Routes | Intravenous |
Pharmacokinetic data | |
Bioavailability | 100% (IV only) |
Half-life | 20 days (range: 11–50 days) |
Identifiers | |
CAS number | 216974-75-3 |
ATC code | L01XC07 |
DrugBank | DB00112 |
ChEMBL | CHEMBL1201583 |
Chemical data | |
Formula | C6638H10160N1720O2108S44 |
Mol. mass | approx. 149 kDa |
(what is this?) (verify) |
Bevacizumab (pronounced bev-a-siz-you-mab) (trade name Avastin, Genentech/Roche) is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels. It is licensed to treat various cancers, including colorectal, lung, breast (outside the USA), glioblastoma (USA only), kidney and ovarian.
Bevacizumab is a humanized monoclonal antibody that produces angiogenesis inhibition by inhibiting vascular endothelial growth factor A (VEGF-A).[1] VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab was the first clinically available angiogenesis inhibitor in the United States.[citation needed]
Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for certain metastatic cancers. It received its first approval in 2004, for combination use with standard chemotherapy for metastatic colon cancer.[2] It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, breast cancers and glioblastoma multiforme of the brain.
The first indication approval for metastatic colorectal cancers saw huge uptake of this pioneer of anti-VEGF therapy which till today remains as a cancer type that responds well to Avastin. The overwhelming data of trials for usage of Avastin with a fluoropyrimidine demonstrates its efficacy and safety; which continually extends survival for this group of patients.
The reason for its overall success is attributed to the fact that its parent company, Roche, allows their scientists to have one fifth of their working time to spend on a research area of their own interest. This led one of their scientists, Napoleone Ferrara, to chance upon and develop this novel therapy that has since extended the lives of thousands of patients. 27 February 2004.[3]
At one point bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011.[4][5] The approval for breast cancer was revoked because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging. In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval.[6] In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.[4] The drug remains approved for breast cancer use in other countries including Australia.[7]
Clinical trials are underway for many other indications including ovarian cancer, pediatric osteosarcoma, and certain non-malignant eye diseases. In the curative setting (adjuvant therapy), clinical studies are underway in breast cancer and lung cancer.
Bevacizumab is a humanized monoclonal antibody, and was the first commercially available angiogenesis inhibitor. Its main action is the inhibition of the function of a natural protein called vascular endothelial growth factor (VEGF) that stimulates new blood vessel formation. Because most malignant tumors are highly dependant on angiogenesis it was expected that Bevacizumab can stop or delay growth of tumors. Bevacizumab binds directly to VEGF to form a protein complex which is incapable of further binding to VEGF receptor sites (which would initiate vessel growth) effectively reducing available VEGF. The Bevacizumab/VEGF complex is both metabolized and excreted directly.
Colorectal cancer[edit]
Bevacizumab was approved by the FDA in February 2004 for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment) and with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer. This recommendation was based on the E3200 trial — addition of bevacizumab to oxaliplatin/5-FU/leucovorin (FOLFOX4) therapy.
In adjuvant colon cancer, data from two large randomized studies have shown no significant benefit and a potential to cause harm in this setting.[8]
It was approved by the EMEA in January 2005 for use in colorectal cancer.[citation needed]
Lung cancer[edit]
In 2006, the FDA approved bevacizumab for use in first-line advanced nonsquamous non-small cell lung cancer in combination with carboplatin/paclitaxel chemotherapy. The approval was based on the pivotal study E4599 (conducted by the Eastern Cooperative Oncology Group), which demonstrated a 2-month improvement in overall survival in patients treated with bevacizumab (Sandler, et al. NEJM 2004). A preplanned analysis of histology in E4599 demonstrated a 4-month median survival benefit with bevacizumab for patients with adenocarcinoma (Sandler, et al. JTO 2010); adenocarcinoma represents approximately 85% of all non-squamous cell carcinomas of the lung. A subsequent European clinical trial, AVAiL, was first reported in 2009 and confirmed the significant improvement in progression-free survival shown in E4599 (Reck, et al. Ann. Oncol. 2010). An overall survival benefit was not demonstrated in patients treated with bevacizumab; however, this may be due to the more limited use of bevacizumab as maintenance treatment in AVAiL versus E4599 (this differential effect is also apparent in the European vs US trials of bevacizumab in colorectal cancer: Tyagi and Grothey, Clin Colorectal Cancer, 2006). As an anti-angiogenic agent, there is no mechanistic rationale for stopping bevacizumab before disease progression. Stated another way, the survival benefits achieved with bevacizumab can only be expected when used in accordance with the clinical evidence: continued until disease progression or treatment-limiting side effects. Another large European-based clinical trial with bevacizumab in lung cancer, AVAPERL, was reported in October 2011 (Barlesi, et al. ECCM 2011). First-line patients were treated with bevacizumab plus cisplatin/pemetrexed for four cycles, and then randomized to receive maintenance treatment with either bevacizumab/pemetrexed or bevacizumab alone until disease progression. Maintenance treatment with bevacizumab/pemetrexed demonstrated a 50% reduction in risk of progression vs bevacizumab alone (median PFS: 10.2 vs 6.6 months, HR 0.50, p<0.001). The National Comprehensive Cancer Network recommends bevacizumab as standard first-line treatment in combination with any platinum-based chemotherapy, followed by maintenance bevacizumab until disease progression. Bevacizumab is given as an intravenous infusion every three weeks at the dose of either 15 mg/kg or 7.5 mg/kg. The higher dose is usually given with carboplatin-based chemotherapy, whereas the lower dose is usually given with cisplatin-based chemotherapy.
Breast cancer[edit]
In December 2010, the FDA removed the breast cancer indication from bevacizumab, saying that it had not been shown to be safe and effective in breast cancer patients. The combined data from four different clinical trials showed that bevacizumab neither prolonged overall survival nor slowed disease progression sufficiently to outweigh the risk it presents to patients. This only prevented Genentech from marketing bevacizumab for breast cancer. Doctors are free to prescribe bevacizumab off label, although insurance companies are less likely to approve off-label treatments.[9][10] In June 2011, an FDA panel unanimously rejected an appeal by Roche. A panel of cancer experts ruled for a second time that Avastin, the best-selling cancer drug in the world, should no longer be used in breast cancer patients, clearing the way for the U.S. government to remove its endorsement from the drug. The June 2011 meeting of the FDA's oncologic drug advisory committee was the last step in an appeal by the drug's maker. The committee concluded that breast cancer clinical studies of patients taking Avastin have shown no advantage in survival rates, no improvement in quality of life, and significant side effects. Patient support groups were disappointed by the committee's decision.[11]
On October 11, 2011 the U.S. Food and Drug Administration (FDA) announced that the agency is revoking the agency's approval of the breast cancer indication for Avastin (bevacizumab) after concluding that the drug has not been shown to be safe and effective for that use.
Avastin will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme).[12]
History relating to breast cancer[edit]
In 2010, before the FDA announcement, The National Comprehensive Cancer Network (NCCN) updated the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines) for Breast Cancer to affirm the recommendation regarding the use of bevacizumab (Avastin, Genentech/Roche) in the treatment of metastatic breast cancer.[citation needed]
In 2008, the FDA approved Bevacizumab for use in breast cancer. A panel of outside advisers voted 5 to 4 against approval, but their recommendations were overruled. The panel expressed concern that data from the clinical trial did not show any increase in quality of life or prolonging of life for patients — two important benchmarks for late-stage cancer treatments. The clinical trial did show that bevacizumab reduced tumor volumes and showed an increase in progression free survival time. It was based on this data that the FDA chose to overrule the recommendation of the panel of advisers. This decision was lauded by patient advocacy groups and some oncologists. Other oncologists felt that granting approval for late-stage cancer therapies that did not prolong or increase the quality of life for patients would give license to pharmaceutical companies to ignore these important benchmarks when developing new late-stage cancer therapies.[6]
On March 28, 2007, the European Commission approved bevacizumab in combination with paclitaxel for the first-line treatment of metastatic breast cancer.[13]
Renal cancers[edit]
In certain renal (kidney) cancers, Bevacizumab improves the progression free survival time but not survival time. In 2009, the FDA approved bevacizumab for use in metastatic renal cell cancer (a form of kidney cancer).[14][15] following earlier reports of activity[16] EU approval was granted in 2007.[citation needed]
Brain cancers[edit]
The FDA granted accelerated approval of Avastin for the treatment of recurrent glioblastoma multiforme in May 2009.[17] Treatment for initial growth is still in phase III clinical trial.[18]
In the September 2009 issue of the Journal of Clinical Oncology, UCLA researchers reported that Avastin improves response and survival in patients with recurrent glioblastoma in comparison to historical controls.[19] That study also found that it may be useful in the treatment of radiation necrosis, since it reduces edema and mass effect and diminishes blood-brain-barrier leakage.
In a Phase I clinical trial conducted in 2009–2010, John A. Boockvar's team at Weill Cornell Medical College administered bevacizumab intra-arterially directly into the brain tumors of fourteen patients with recurrent glioblastoma multiforme. Results were sufficiently encouraging to propose a Phase II trial of the technique.[20] Preliminary data of a large multicenter trial reported at the ASCO meeting 2013 suggest that patients with newly diagnosed glioblastoma do not benefit from the addition of bevacizumab to chemoradiation therapy. [21]
First-line use of bevacizumab do not improve overall survival in patients with newly diagnosed glioblastoma, but progression-free survival is prolonged.[22]
Investigational uses[edit]
Bevacizumab did not meet its primary endpoint of extending overall survival (OS) in a recent phase III trial in unresectable gastric cancer (in combination with paclitaxel / Taxol), but it did demonstrate a positive result in treatment of ovarian cancer.[citation needed]
A study released in April 2009 found that bevacizumab is not effective at preventing recurrences of non-metastatic colon cancer following surgery.[23]
Bevacizumab has demonstrated activity in ovarian cancer,[24][25] and glioblastoma multiforme,[26] a type of brain tumour, when used as a single agent.
In 2010 two phase III trials showed a 27% and 54% increase in progression-free survival in ovarian cancer.[27]
Bevacizumab has been investigated as a possible treatment of pancreatic cancer, as an addition to chemotherapy, but studies have shown no improvement in survival.[28][29][30] It may also cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.
The drug is also undergoing initial trials as an addition to established chemotherapy protocols and surgery in the treatment of pediatric osteosarcoma[31] and other sarcomas, such as leiomyosarcoma.[32]
Uses in eye disease[edit]
Many diseases of the eye, such as age-related macular degeneration (AMD) and diabetic retinopathy, damage the retina and cause blindness when blood vessels around the retina grow abnormally and leak fluid, causing the layers of the retina to separate. This abnormal growth is caused by VEGF, so bevacizumab has been successfully used to inhibit VEGF and slow this growth.
Bevacizumab has recently been used by ophthalmologists in an off-label use as an intravitreal agent in the treatment of proliferative (neovascular) eye diseases, particularly for choroidal neovascular membrane (CNV) in AMD. Although not currently approved by the FDA for such use, the injection of 1.25-2.5 mg of bevacizumab into the vitreous cavity has been performed without significant intraocular toxicity.[33] Many retina specialists have noted impressive results in the setting of CNV, proliferative diabetic retinopathy, neovascular glaucoma, diabetic macular edema, retinopathy of prematurity[34] and macular edema secondary to retinal vein occlusions.
When bevacizumab is used in the treatment of macular degeneration, only tiny and relatively inexpensive doses (compared to amounts used in colon and other cancers) are required. Some investigators believe that bevacizumab at a cost of around $42 a dose is as effective as ranibizumab at a cost of over $1,593 a dose.[35][36]
The primary pharmacokinetic difference between intraocular Bevacizumab and Ranibizumab is the very large difference in systemic half-lives, i.e. 2 hours for Ranibizumab versus 20 days for Bevacizumab. Since Bevacizumab was designed as a cancer treatment, the long systemic half-life is considered to be a positive feature (allowing greater exposure time of the tumor to the drug), while the same long half-life is a negative feature in intraocular treatment, since it has no benefit outside of the eye and may in fact be detrimental. Although the systemic exposure with both drugs is very low, Ranibizumab has a much lower average systemic exposure (area under the curve), so it may be conjectured to have a commensurately lesser chance of systemic adverse events.
The National Eye Institute (NEI) of the National Institutes of Health (NIH) announced in October 2006 that it would fund a comparative study trial of ranibizumab (Lucentis) and bevacizumab (Avastin) to assess the relative safety and effectiveness in treating AMD.[37] This study, called the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT Study), enrolled about 1,200 patients with newly diagnosed wet AMD, randomly assigning the patients to one of four treatment groups.[38] The CATT Study was conducted at 47 clinical sites throughout the United States, following the patients for 2 years.[39] Initial results of the study showing essentially similar outcomes using either drug at one year were formally published after peer review in the New England Journal of Medicine on May 19, 2011.[40] Similar results in this cohort were maintained at two years, with bevacizumab showing non-inferiority to ranibizumab, although a statistically non-significant trend to improved visual outcomes from injections given monthly rather than as required was noted with both drugs.[41]
Drug administration[edit]
Bevacizumab is usually given intravenously every 14 days. In colon cancer, it is given in combination with the chemotherapy drug 5-FU (5-fluorouracil), leucovorin, and oxaliplatin or irinotecan.[citation needed] Clinical trials are underway to test an intra-arterial technique for delivering the drug directly to brain tumors, bypassing the blood–brain barrier.[20][42] For treatment of eye diseases it is injected intravitreously.
Adverse effects[edit]
Bevacizumab inhibits the growth of blood vessels, which is part of the body's normal healing and maintenance. The body grows new blood vessels in wound healing, and as collateral circulation around blocked or atherosclerotic blood vessels. One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease.[43]
The main side effects are hypertension and heightened risk of bleeding. Bowel perforation has been reported.[44] In advanced lung cancer, less than half of patients qualify for treatment.[45][46] Nasal septum perforation and renal thrombotic microangiopathy have been reported.[47] In December 2010, the FDA warned of the risk of developing perforations in the body, including in the nose, stomach, and intestines.
In 2013, Hoffmann-La Roche announced that the drug was associated with 52 cases of necrotizing fasciitis from 1997 to 2012, of which 17 patients died.[48] About 2/3 of cases involved patients with colorectal cancer, or patients with gastrointestinal perforations or fistulas.
These effects are largely avoided in ophthalmological use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.[citation needed]
In countries with national health care systems (such as the UK and Canada), many of those national health services have restricted bevacizumab on the basis of cost-benefit calculations; in the U.K., for example, the National Institute for Health and Clinical Excellence has taken the position that bevacizumab should not be funded by the NHS because it costs nearly £21,000 per patient but only minimal benefit in many cancers.[49] In 2006 the Scottish Medicines Consortium recommended against the NHS funding Avastin for first-line treatment of metastatic carcinoma of the colon or rectum, due to estimated costs of £24,000 to £93,000 per quality-adjusted life year (QALY).[50]
The addition of bevacizumab to standard treatment can prolong the lives of breast and lung cancer patients by several months, at a cost of $100,000 a year in the United States.[51] For colorectal cancer, Robert J. Mayer wrote in the New England Journal of Medicine that bevacizumab extended life by 4.7 months (20.3 months vs. 15.6 months) in the initial study, at a cost of $42,800 to $55,000.[52] Costs in other countries vary; in Canada it is reported to cost $40,000 CAD per year.[53]
On Tuesday, February 14, 2012 Roche and its U.S. biotech unit Genentech announced that counterfeit Avastin had been distributed in the United States.[54] The investigation is ongoing, and differences in the outer packaging make identification of the bogus drugs simple for medical providers. Roche analyzed three bogus vials of Avastin and found they contained salt, starch, citrate, isopropanol, propanediol, t-butanol, benzoic acid, di-fluorinated benzene ring, acetone and phthalate moiety, but no active ingredients of the cancer drug. According to Roche, the levels of the chemicals were not consistent therefore whether the chemicals were at harmful concentrations could not be determined. The counterfeit Avastin has been traced back to Egypt and it entered the legitimate supply chains via Europe to United States.[55][56]
See also[edit]
- colorectal cancer
- glioblastoma multiforme
- metastatic breast cancer
- renal cell carcinoma
- Vascular endothelial growth factor (VEGF)
- ^ Los, M.; Roodhart, J. M. L.; Voest, E. E. (2007). "Target Practice: Lessons from Phase III Trials with Bevacizumab and Vatalanib in the Treatment of Advanced Colorectal Cancer". The Oncologist 12 (4): 443–50. doi:10.1634/theoncologist.12-4-443. PMID 17470687.
- ^ http://www.gene.com/gene/products/information/pdf/avastin-prescribing.pdf
- ^ Denise Gellene (27 Feb 2004). "FDA Approves Genentech's Avastin Colon Cancer Medicine". L.A. Times.
- ^ a b Pollack, Andrew (18 November 2011). "F.D.A. Revokes Approval of Avastin for Breast Cancer". New York Times.
- ^ "Cancer drug Avastin loses US approval". BBC. November 18, 2011.
- ^ a b "F.D.A. Approves Drug's Use for Breast Cancer". The New York Times. February 22, 2008.
- ^ "Breast cancer drug 'still safe' for Aussie women". July 22, 2010. Unknown parameter
ignored (help) - ^ "Lessons From the Adjuvant Bevacizumab Trial on Colon Cancer: What Next?". Jco.ascopubs.org. Retrieved 2012-08-05.
- ^ "FDA begins process to remove breast cancer indication from Avastin label" (Press release). FDA. 2010-12-16. Retrieved 2010-12-17.
- ^ Andrew Pollack (December 16, 2010). "F.D.A. Rejects Use of Drug in Cases of Breast Cancer". NY Times. Retrieved 2010-12-16.
- ^ Jennifer Couzin-Frankel and Yasmin Ogale (8 July 2011). "Once on 'Fast Track', Avastin Now Deralied". Science 333 (6039): 143–4. doi:10.1126/science.333.6039.143. PMID 21737712.
- ^ "FDA Commissioner announces Avastin decision Drug not to be safe and effective in breast cancer patients" (Press release). November 18, 2011.
- ^ Jasek, W, ed. (2007). Austria-Codex (in German) (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 978-3-85200-181-4.[page needed]
- ^ "FDA clears Genentech drug for kidney cancer". San Francisco Chronicle. August 2, 2009.[dead link]
- ^ "FDA Gives Roche's Avastin the Go-Ahead for Metastatic Renal Carcinoma". GENNewsHighlights. Genetic Engineering & Biotechnology News. August 3, 2009. Retrieved 2012-08-13.
- ^ Rini, B. I. (2007). "Vascular Endothelial Growth Factor-Targeted Therapy in Renal Cell Carcinoma: Current Status and Future Directions". Clinical Cancer Research 13 (4): 1098–106. doi:10.1158/1078-0432.CCR-06-1989. PMID 17317817.
- ^ Richard Pazdur, M.D. (May 2009). "FDA Approval for Bevacizumab". National Cancer Institute. Retrieved 2010-05-11.
- ^ "FDA Grants Accelerated Approval of Avastin for Brain Cancer (Glioblastoma) That Has Progressed Following Prior Therapy". Market Watch. 5 May 2009. Retrieved 2012-08-13.
- ^ OncoGenetics.Org (September 2009). "Avastin dramatically improves response, survival in deadly recurrrent glioblastomas". OncoGenetics.Org. Retrieved 2009-09-02.[dead link]
- ^ a b Burkhardt JK, Riina H, Shin BJ, et al. (January 2012). "Intra-arterial delivery of bevacizumab after blood–brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival". World Neurosurg 77 (1): 130–4. doi:10.1016/j.wneu.2011.05.056. PMID 22405392.
- ^ > http://www.medpagetoday.com/MeetingCoverage/ASCO/39566. Missing or empty
(help) - ^ PMID 24552317 (PubMed)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ^ Reed, Katie (22 April 2009). "Roche drug Avastin fails cancer study, shares fall". Reuters. Retrieved 22 April 2009.
- ^ Konner JA et al. Proc ASCO 2007 (May 2008). A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel (Tax), IP cisplatin (Cis), and IV bevacizumab (Bev) as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer. http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=31096.
- ^ Burger RA et al. J Clin Oncol 28:7s, 2010 (June 2010). Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=52788.
- ^ Cloughesy, T. F.; Prados, M. D.; Wen, P. Y.; Mikkelsen, T.; Abrey, L. E.; Schiff, D.; Yung, W. K.; Maoxia, Z. et al. (2008). "A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM)". Journal of Clinical Oncology 26 (15S): 2010b.
- ^ "Roche Claims Phase III Data Supports Use of Avastin in Ovarian Cancer". 12 Oct 2010.
- ^ Saif MW (2008). "New developments in the treatment of pancreatic cancer. Highlights from the "44th ASCO Annual Meeting". Chicago, IL, USA. May 30–June 3, 2008". JOP 9 (4): 391–7. PMID 18648128.
- ^ Rocha-Lima, Caio M. (2008). "New directions in the management of advanced pancreatic cancer: a review". Anti-Cancer Drugs 19 (5): 435–46. doi:10.1097/CAD.0b013e3282fc9d11. PMID 18418211.
- ^ Riess, Hanno (2008). "Antiangiogenic Strategies in Pancreatic Cancer". Pancreatic Cancer. Recent Results in Cancer Research 177. pp. 123–9. doi:10.1007/978-3-540-71279-4_14. ISBN 978-3-540-71266-4.
- ^ "Md. Girl,11, First To Try New Cancer Treatment".
- ^ "A Phase II Study of Neoadjuvant Bevacizumab and Radiation Therapy for Resectable Soft Tissue Sarcomas".
- ^ Arevalo, JF et al. (2008). "Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degenation: results of the Pan-American Collaborative Retina Study Group at 12 months follow up". Retina 10 (10): 1387–94. doi:10.1097/IAE.0b013e3181884ff4. PMID 18827735.
- ^ Azad, Rajvardhan; Chandra, Parijat (2007). "Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity". Indian Journal of Ophthalmology 55 (4): 319. doi:10.4103/0301-4738.33057. PMID 17595491.
- ^ Mundy, Alicia (June 17, 2010). "Medicare Eye Study Finds Untapped Savings". Wall Street Journal.
- ^ Tufail, A.; Patel, P. J.; Egan, C.; Hykin, P.; Da Cruz, L.; Gregor, Z.; Dowler, J.; Majid, M. A. et al. (2010). "Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study". BMJ 340: c2459. doi:10.1136/bmj.c2459.
- ^ http://clinicalstudies.info.nih.gov/cgi/wais/bold032001.pl?A_08-EI-0061.html
- ^ http://irvaronsjournal.blogspot.com/2007/09/catt-study-update-3-avastin-vs-lucentis.html[unreliable medical source?]
- ^ ClinicalTrials.gov NCT00593450 Comparison of Age-Related Macular Degeneration Treatments Trials: Lucentis-Avastin Trial
- ^ Martin, DF; Maguire, MG; Ying, GS; Grunwald, JE; Fine, SL; Jaffe, GJ (2011). "Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration". New England Journal of Medicine 364 (20): 1897–1908. doi:10.1056/NEJMoa1102673. PMC 3157322. PMID 21526923. Retrieved September 25, 2012.
- ^ Martin, D. F.; Martin, M. G.; Maguire, S. L.; Fine, G. S.; Ying, G. J.; Jaffe, J. E.; Grunwald, C.; Toth, M.; Redford, F. L.; Ferris Fl, 3. (2012). "Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration". Ophthalmology 119 (7): 1388–1398. doi:10.1016/j.ophtha.2012.03.053. PMC 3389193. PMID 22555112.
- ^ "World's first delivery of intra-arterial Avastin directly into brain tumor". SAWF News. November 17, 2009.
- ^ Semenza GL (May 2008). "A new weapon for attacking tumor blood vessels". N. Engl. J. Med. 358 (19): 2066–7. doi:10.1056/NEJMcibr0800272. PMID 18463385.
- ^ Sliesoriaitis, S; Tawfik, B (July 2011). "Bevacizumab-induced bowel perforation.". The Journal of the American Osteopathic Association 111 (7): 437–44. PMID 21803880.
- ^ Velcheti, Vamsidhar; Viswanathan, Avinash; Govindan, Ramaswamy (2006). "The Proportion of Patients with Metastatic Non-small Cell Lung Cancer Potentially Eligible for Treatment with Bevacizumab: A Single Institutional Survey". Journal of Thoracic Oncology 1 (5): 501. doi:10.1097/01243894-200606000-00023. PMID 17409907.
- ^ Vaughn, Christopher; Zhang, Louann; Schiff, David (2008). "Reversible posterior leukoencephalopathy syndrome in cancer". Current Oncology Reports 10 (1): 86–91. doi:10.1007/s11912-008-0013-z. PMID 18366965.
- ^ Eremina, Vera; Jefferson, J. Ashley; Kowalewska, Jolanta; Hochster, Howard; Haas, Mark; Weisstuch, Joseph; Richardson, Catherine; Kopp, Jeffrey B. et al. (2008). "VEGF Inhibition and Renal Thrombotic Microangiopathy". N. Engl. J. Med. 358 (11): 1129–36. doi:10.1056/NEJMoa0707330. PMC 3030578. PMID 18337603.
- ^ "Cancer drug Avastin tied to 2 cases of flesh-eating disease in Canada". CBC News. 2 May 2013. Retrieved 2013-05-02.
- ^ Briggs, Helen (BBC News Health Reporter) (August 24, 2010). "Critics condemn bowel cancer drug rejection". Retrieved 2010-08-24.
- ^ "Bevacizumab". Scottish Medicines. Retrieved 18 July 2012.
- ^ Berenson, Alex (February 15, 2006). "A Cancer Drug Shows Promise, at a Price That Many Can't Pay". New York Times.
- ^ Mayer, Robert J. (2004). "Two Steps Forward in the Treatment of Colorectal Cancer". N. Engl. J. Med. 350 (23): 2406–8. doi:10.1056/NEJMe048098. PMID 15175443.
- ^ "P.E.I. sole holdout on cancer drug". CBC News. November 26, 2009.[dead link]
- ^ "Counterfeits of cancer drug Avastin found in U.S". Reuters. February 15, 2012.
- ^ Berkrot, Bill (February 27, 2012). "Fake Avastin had salt, starch, chemicals:Roche". Reuters. Retrieved February 28, 2012.
- ^ Staton, Tracy (February 28, 2012). "Phony Avastin vials contained chemicals, but no drugs". FiercePharma.com. Retrieved February 28, 2012.
External links[edit]
- Avastin.com
- Off Label Uses of Avastin for AMD
- Avastin-info.com Information for healthcare professionals outside of the US
- Avastin News provided by insciences organisation
- Berenson, Alex (February 15, 2006). "A Cancer Drug Shows Promise, at a Price That Many Can't Pay". New York Times.
- NCI Drug Information Summary on Bevacizumab for Patients
- NCI Drug Dictionary Definition for Bevacizumab
- ClinicalTrials.gov NCT00222469 Phase II Clinical Trial of Bevacizumab for Adenocarcinoma of the Pancreas
- CATT Study Update 3: Avastin vs. Lucentis — To Get Underway by Year's End!
- ClinicalTrials.gov NCT00593450 Comparison of Age-Related Macular Degeneration Treatments Trials: Lucentis-Avastin Trial
- Sachdev JC, Jahanzeb M (October 2008). "Evolution of bevacizumab-based therapy in the management of breast cancer". Clin. Breast Cancer 8 (5): 402–10. doi:10.3816/CBC.2008.n.048. PMID 18952553.
- U.S. National Library of Medicine: Drug Information Portal — Bevacizumab
- NCCN Guidelines For Breast Cancer Updated; Bevacizumab Recommendation Affirmed
- Avastin Adverse Events Reported to the FDA Adverse Event Reporting System (AERS)


text:
Press release
From the U.S. Forest ServiceThe U.S. Forest Service today announced that day-use fees at Whiteside Mountain and Whitewater Falls in the Nantahala National Forest will be waived on Veterans Day weekend, Nov. 10-12.
The fee waivers are offered in cooperation with other federal agencies under the Federal Lands Recreation Enhancement Act. Day-use fees will be waived at all standard amenity fee sites operated by the Forest Service.
"This is our way of saying thanks to the brave men and women - past and present - who put their lives on the line every day to keep us safe at home," said U.S. Forest Service Chief Tom Tidwell. "We encourage veterans, their families and all visitors to take time out over the holiday weekend to enjoy the benefits that nature provides at forests and grasslands throughout the country."
For more information, visit:
http://www.fs.fed.us/news/2012/releases/10/veterens-day.shtmlRead the full article
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text:
Drama Graduate Application Process
General Information about Admission
THE John Wells Directing Program
Applicants for The John Wells Directing Program should have at least 3 years of experience as a director as well as a strong sense of the kind of theatre they would like to explore. The ability to critically analyze and discuss a script is a necessary prerequisite. Interest in the use of media and exploring a variety of directing techniques is an advantage.
Design (Scenic, Costume, Costume Production, Sound, VIDEO & MEDIA)
Applicants for the Design Option should have experience in theatre and some background in art and design. A proficiency in drawing and painting is an advantage. Demonstrated ability to analyze and discuss a script is important and will be explored at the interview.
Dramatic Writing
Applicants for the Dramatic Writing Option should have prior writing and theatre experience, and an appreciation of Dramatic Literature. The ability to analyze and discuss a script is also a necessary prerequisite.
Production and Technology Management (PTM) (Technical Direction, Stage Management, Production Management)
Applicants for the Production Technology and Management Option should have practical experience in the theatre, as well as some background in mathematics and physics, organization and management, or both. Applicants must demonstrate basic proficiency in project planning and execution by submitting a portfolio of work.
To Apply
All graduate applicants must submit the following materials by January 1st.
- A graduate application form
- A personal statement of your educational and professional aspiration which addresses why you are pursuing this line of study, what you hope to gain from graduate school, and your artistic influences, interests and professional goals.
- Three letters of recommendation from people who are familiar with your work
- Transcripts from previously attended educational institution(s)
- $90 application fee (payable to Carnegie Mellon University)
- For Dramatic Writing: one finished play or screenplay
All of the above application materials can be submitted in a single package or under separate cover.
Please do not submit any visual materials in advance. No unsolicited material will be returned.
Final applicants in The John Wells Directing Program will be invited to the School of Drama to meet the directing faculty and conduct a short scene rehearsal with actors. At that time directors will also be asked to provide more visual material and discuss specific productions at length.
Application materials
All application materials should be mailed together or separately to:
Dick Block, Associate Head, School of Drama Graduate Admissions Coordinator Purnell Center for the Arts Carnegie Mellon University Pittsburgh, PA 15213-3890
Phone: (412) 268-7219 Fax: (412) 621-0281 Email: email@example.com
International students
In accordance with university policy, foreign students must present evidence of their ability to meet the expenses of tuition, room, board and other material needs when applying. Non-native English-speaking applicants are required to take the TOEFL examination. The University may also require applicants to take additional English proficiency tests to ensure that all students have sufficient language skills to pursue graduate level studies. Depending on the results of these tests, the School of Drama may require applicants to complete further classes in English prior to enrolling. For more information about international admission and immigration, please contact the CMU Office of International Education.
To Schedule an Interview
All graduate applicants in Design, Production Technology and Management and The John Wells Directing Program are required to attend an interview. Interviews will be scheduled after applications have been received. Click here to download the dates and locations for interviews. To schedule an interview, please email or call Dick Block, Associate Head of the School and Graduate Admissions Coordinator (email: firstname.lastname@example.com phone: 412.268.7219).
Please include your preferred city and date in your request as well as your field of study: Costume Design, Costume Production, Sound Design, Set Design, Lighting Design, Video & Media Design, Technical Direction, Stage Management, Production Management or The John Wells Directing Program.
Interviews will be schedules only after the formal application is received. Application materials can be submitted in a single package or under separate cover.
Graduate interviews are typically 30 minutes long, during whick time the faculty will review your artistic portfolio.
Offers to attend the School of Drama are made after all of the interviews are completed, usually around the end of March. Offers to students for admissions will be sent by mail (with the exception of international students who will recieve an email).
International students applying for Design or Production Technology and Management who are unable to visit the United States for an interview may schedule a Skype interview.
Read About Preparing for Your Interview/Portfolio Review
For further information about the Design Option please contact the Option Coordinators, Joe Pino at email@example.com or Narelle Sissons at firstname.lastname@example.com. If you have specific questions related to our MFA in Video & Media Design, please contact Larry Shea at firstname.lastname@example.com
For further information about The John Wells Directing Program contact the Option Coordinator, Marianne Weems at firstname.lastname@example.com.
For further information about the Dramatic Writing Option please contact the Option Coordinator, Rob Handel at email@example.com.
For further information about the Production Technology and Management Option, please contact Option Coordinator, David Boevers at firstname.lastname@example.com.