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End of racism comedy and lecture tour at The Woods
January 10th, 2011 | SMWC
Master storyteller Preacher Moss, described as one of the best comedy-lectures on the college circuit today, will have the audience thinking and laughing as he performs on January 18, 2011 at 8 p.m. in Sullivan Lounge at Saint Mary-of-the-Woods College.
As a former writer for Saturday Night Live, In Living Color, My Wife and Kids and The George Lopez Show, Moss's comedy is distinguished for being fashioned out of everyday of life and engaging audiences in contemporary issues facing society. He has also appeared on Comedy Central and Politically Incorrect.
The Association for the Promotions of Campus Activities voted his End of Racism Comedy and Lecture Tour as "Best Diversity Act" on college campuses in 2008 and 2009. Described as intelligent, thought provoking and "seriously funny," Moss performs to audiences all over the country, offering the perspective of being both black and Muslim in America.
The End of Racism is not just the name of the tour, but a commitment shared by many. Moss knows how to deliver the goods on how audiences see race through laughter.
"Comedy is a great way to bring out the irony of situations but also to give a meaningful contribution to the truth," said Moss. "What it is and what it could be."
Moss plays to the hearts and minds of college students, faculty and administrators all across the country. With his insight on racial understanding vs. racial interaction, he has quickly become one of the funniest social commentators on the college scene today.
The Saint Mary-of-the-Woods College Student Association Committee is sponsoring the event. For more information, contact Director Campus Life, Jeff Malloy at (812) 535-5219.
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HEALTH chiefs have launched an initiative to get kids moving this summer after figures revealed more than two thirds of borough youngsters do not get enough exercise.
Change4Life has teamed up with Disney to launch the new 10 Minute Shake Up campaign at primary schools to help improve the fitness levels of pupils who do not achieve the recommended 60 minutes of exercise per day.
Figures show only 32 per cent of children aged five to ten in Dudley are active for at least an hour on five or more days a week - meaning a staggering 68 per cent of borough primary pupils fail to meet recommended daily physical activity levels.
Not surprising perhaps then that in Dudley nearly a quarter (23.6 per cent) of reception aged children have been labelled overweight or obese - higher than the national average of 22.3 per cent - according to 2012/13 figures from the Health and Social Care Information Centre.
The figure rises to 37.1 per cent for year six children - compared to the national average of 33.3 per cent.
However - Joy Boyes, Dudley's behaviour change intervention officer, hopes to start to turn things around with the launch of the new campaign which aims to get children across the country moving for an extra 100 million minutes through short ten-minute-activity bursts.
To kick-start the campaign, a host of borough schools staged their own 10 Minute Shake Up on Tuesday July 15 at 3pm.
Councillor Rachel Harris, Dudley's cabinet member for health, said: "The 10 Minute Shake Up campaign is a great way to encourage children to do more exercise and, together with our local events, should set them on the way to their recommended 60 minutes exercise a day.
"The good news is there's lots going on in the borough to keep children active and entertained, from free local events to discounted sports club sessions."
Health experts say increased physical activity in school aged children leads to better academic achievement, behaviour and physical health, increased attention span, improved self-confidence and a reduced risk of developing chronic conditions in the future.
Parents can find out more about activities taking place in the borough by visiting www.lets-get.com/activezone or search for Change4Life on the internet to sign up for a free 10 Minute Shake Up pack which includes a stopwatch, wall chart, activity cards, reward stickers and Disney inspired ideas for fun short-burst activities.

subset: commoncrawl


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*We have experienced higher sales volume on these boots than we anticipated, and certain sizes are not available until early April. Please check back, or touch base with our Facebook page to find out when we'll have these boots back in stock! -Thanks, from the Schnee's Team
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And then there were two.
Doug Collins and Martha Zoller will be at each other's throats for another month after neither candidate had enough votes to nab the Republican nomination in Georgia's 9th District U.S. House race.
Craig Herrington will continue his tenure as the post 3 representative on Hall County's school board.
Hall County Commissioner Ashley Bell went down to defeat in Tuesday's Republican primary, losing his District 4 seat to challenger Jeff Stowe.
Polls are open until 7 p.m. today for a primary election that includes a host of hotly contested local races along with a vote on a regional transportation sales tax and for a representative in the newly drawn 9th District in the U.S. House.
This isn't your typical primary election.
Chances are, many voters don't know what a county probate judge does.
One calls herself a "firebrand." Another repeats that he's the only "consistent conservative." And the third rarely sits down without mentioning the U.S. Constitution.
One candidate's political accomplishment is another's example of excessive government.
The two men running for post 3 on the Hall County Schools Board of Education say the biggest issues for the board are overcoming a shrinking budget and a rising student body.
Southside Gainesville residents took to the pews of St. John Baptist Church on Tuesday night to hear a different kind of message.
Two candidates who see the economy as a top concern for Georgia are making their last pitches this week to potential constituents in what is the newly redrawn state House District 103 seat.
In the race to be the newest member of Georgia's congressional delegation from Northeast Georgia two candidates who see themselves as the other's chief rival might be their own worst enemies.
No or some experience. Loads of experience. Each resume is different, but each of the five candidates say they have what it takes to become Hall County's next sheriff.
The "Ethics Express" made a stop in Gainesville on Tuesday afternoon, hoping to unload its informational cargo on local voters.
Page 7 of 38
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A STAND up comedian has embarked on writing a trilogy of an epic adventure — trying to find the right man.
Mum-of-three Lindsey Davies is busy promoting her first published book, Mr Wrong, while juggling being a screenplay writer and part-time saleswoman.
The first of her trilogy sees Roxy Hart share her search for Mr Right in a comical tale of heartbreak, disastrous dates and disappointments.
Ms Davies, of Mersey Street, Leigh, said: "I started the book about five years ago after a break up and I realised a lot of my comedy was becoming about my relationship with men.
"I wrote a few chapters and my friends and family had told me it was funny and I should carry on.
"But then I got sidetracked because I went back to university so it ended up in a draw and at the back of my mind.
But then, a few months ago, she found the start of her novel and sent it off to a publisher — Whiteley Publishing.
Ms Davies said: "They loved it and gave me a deadline to finish it by.
If only I had done it five years ago, who knows where I would be now.
"It is a reflection of my own life and there is always one essential flaw that stops Roxy being with the men that she meets.
"Each chapter is named after the flaw that puts her off, so there is The Mummy's Boy, The Narcissist and so on."
The 36-year-old is a regular on the Manchester comedy scene and has already started work on her second book.
"I am writing the second instalment now but it is difficult to find the time with everything else that is going on but I am sure I will get it done," she added.
Mr Wrong is available from Amazon and Waterstones.


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The ACTU has accused Prime Minister Tony Abbott of outsourcing its policymaking to big business, in what it calls ''a grievous failure of leadership''.
Writing in Fairfax's Sunday newspapers, president Ged Kearney says the government has established some 40 reviews of government spending since coming to office, as a Trojan horse for its true privatisation agenda.
''The Coalition are not taking ownership of decision-making but instead outsourcing it to their big business friends,'' Ms Kearney said.
''It is a grievous failure of leadership to give big business a free-for-all with exclusive rights to advise the government to the exclusion of all other sections of the community.'' Ms Kearney said appointing Business Council of Australia president Tony Shepherd as head of the Commission of Audit, which will recommend wide-ranging cuts to government spending, predetermines the audit's outcome.
Treasurer Joe Hockey and Finance Minister Mathias Cormann have left it up to the audit commissioners, who include former senator Amanda Vanstone and former Finance and Treasury department heads Peter Boxall and Tony Cole, to rule on potential conflicts of interest. A Commission of Audit spokesman said the commissioners were ''too busy at the moment'' to respond to questions.


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THREE apprentices have been given the chance to get on the first rung of the employment ladder after starting work on a £1.7 million Twin Valley Homes development in Bastwell.
Nathan Selby, an apprentice bricklayer and Luke Kenyon, apprentice joiner have been placed with contractors Bardsley Construction through the Constructing the Future Lancashire Shared Apprenticeship scheme.
Kieron Tierney, 28, an apprentice groundworker, from Clitheroe, has already secured permanent employment with Mayo Civil Engineering, Bardsley's groundwork sub-contractor, after completing a work placement.
Kieron is in his second year and is working towards NVQ Level 2 in Groundworks, but has already been offered a full-time post.
The scheme on Gretna Road and Pearl Street consists of six bungalows and 14 properties and should be finished in summer.
Twin Valley managing director Ian Clark said: "We're continuously looking to develop, whether it's new homes, new careers or new ways of working. This new development will provide much-needed new affordable housing as well aswork opportunities for three young men.
"We pride ourselves on our apprenticeship scheme, and we have had many successes over the year, and we hope this trio can follow in their footsteps."
Paul Strutt, managing director of Bardsley Construction, said: "We firmly believe that our role isn't just to build new homes but to establish strong communities, which is why we endeavour to recruit trade apprentices and local supply chain partners at all our developments and the Gretna Road and Pearl Street project is no exception."


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Dan_ad_nauseam wrote:linguoboy wrote:falasha wrote:As it turns out (I have a googler too) the root of the word for "peas" - not just Chickpeas but ALL peas - is BIRD DROPPINGS. And it comes from the MOTHER of all peas; Chickpeas. If you are not familiar with chickpeas then you won't understand. Chickpeas fueled the connecting of the world through the Roman Army. It was a very important commodity - WAIT! It was the MOST important commondity, besides water, to ancient man.
It's a shame to waste such top-drawer material here. You should self-publish. Regardless whether this is ingenious trollery or completely wrongheaded sincerity, it deserves a larger audience.
I suspect that when Falasha finishes his book, he should contact Dr. Poonai's publisher.
After interpreting the symbols in your post, I have concluded;
1) you are the worst kind of sexist human, and
2) you have written a book and have either published it yourself or are trying to get it published.
You don't understand that other people don't have the same motivations as you or even that we are actual people. You see others as tools to be used to your benefit. When you insisted that I did not know the Knights that say NEE were a metaphor, I knew you were a little off.


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This article does not cite any references or sources. Please help improve this article by adding citations to sources.
Mordenkainen is one of the most powerful archmagi of the Flanaess. In the World of Greyhawk he has played diverse roles throughout many stories and adventures, but is most notable for being the shadow-leader of the Circle of Eight, a cabal of eight magi and a great force of neutrality.
Resources about Mordenkainen sometimes disagree with each other, since even the official publications for the World of Greyhawk sometimes contradict each other. It is clear, however, that he is one of the greater heroes (or antiheroes) of the Flanaess.
External linksEdit
There is an article about Mordenkainen at the Great Library of Greyhawk.


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Watching FGR gets better and better.
A powerful Luton side, playing before a noisy partisan crowd of more than 6,000 were matched by a swiftly maturing Forest Green team, showing character, courage and determination.
The worst was feared after Luton went ahead early in the game, but Rovers did not crumble. Instead they regrouped, fought back, found parity and at half-time could have gone in ahead.
Everyone had responded, there were heroes all over the field, and the expensively assembled Luton team knew they would be in a battle for the rest of the game.
A penalty had been given against Rovers, perhaps harshly, but that is what happens when you are playing away. It was missed in spectacular fashion.
Rover's goal was splendidly executed. An exquisitely delivered Klukowski free kick – a thumping Taylor header and Rovers were back on level terms. Some reports described the header as 'glancing'. It was not Matty met the cross firmly and with tremendous accuracy.
I enjoyed the duels Taylor had with Luton defender Steve McNulty, Built like Trevor Horsley, but with a shorter hair cut, McNulty impressed me. These fans were noisy and partisan, exactly as home supporters should be. They were a very effective twelfth man, inspiring and perhaps influencing the match officials.
The small band of away fans (just over 100) responded splendidly. During the second half they could be heard around the ground as they were outnumbered by 60-1. Proud and loud they supported Rovers augmented by an equally vocal group of injured squad members. The second half saw two red cards.
Referee Kinseley is a known prolific card wielder and when given the opportunity did so again. Experienced players like Lawless and Bangura should have known better. Neither were innocent, but in the melee that followed Bangura's red card I thought others guilty as well.
We also saw the first appearance of Dale Bennett in a Rovers shirt. He is a true warrior, both swift and determined. Despite narrow squeaks there were no more goals and the game quietly subsided. It had been another fine advertisement for the Blue Square Premier. It proved to me that Rovers are good enough for the play-offs and good enough for promotion – but so are Grimsby, Wrexham, Mansfield, Luton and Kidderminster.
Newport may be failing. It will be the teams that keep going to the end and have a good push at Easter that will go up. No game will be easy. There was a name for the future on the team sheet Saturday – Saul Williams was named as substitute. He will have gained much from being closely involved in such a game, and his confidence will be boosted by the faith the manager has shown in him Good Luck for the future Saul, and for our other youth players.
I close with two votes of thanks. First to Luton. Messrs Joyce, Healey and Light were escorted to the ticket office by Luton legend and England International Brian Stein. Then we were shown the press lounge and given a programme and at half-time there was tea, coffee and lashings of sandwiches, as well as a chance to warm up. Well done Luton and take note FGR!
The warmest vote however goes to the management, staff and players of Forest Green Rovers. At home against Wrexham and at intimidating Kenilworth Road they have played a full part in two thrilling matches. Ability and attitude cannot be questioned.
We are all on a stirring journey. It will be fun wherever it ends.


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About this Publication TitleFinal Statements, 1862-1899
The final statement was issued when a soldier died while in service and discharged by "reason of death." A copy was forwarded to the Adjutant General's Office. A document lists personal information, including cause, place and date of death; and often a physical description, birth place, and next of kin. Also included are often an inventory of possessions at time of death, heir's receipts for effects, paymaster's receipts for money owed, and forms for effects and pay when no heirs are stated.
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Missing Air Crew Reports, WWII
Civil War "Widows' Pensions"
Revolutionary War Service Records
War of 1812 Pension Files Free Updated
Brady Civil War Photos Free


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The Crap We Missed – Friday 1.25.13
Welcome to Friday's The Crap We Missed that just drunk buttsexed the end of your workweek right in the butt. Today's another one of those special days when someone gets two pics. And that someone is Peter Stormare. Why? As if that first pic wasn't enough to convice you, try this. Still not getting it? Go watch this. I think I've made my point. We've also got Carlos the Jackal and this Frankie Muniz pic that I'm asshole enough to include in this type of collection.
They have the Internet in Hell, right?
- Photo Boy
Click Here To Start The Gallery
Photo: Bauer-Griffin, Fame/Flynet, Getty, INFdaily, Pacific Coast News, Splash News, WENN


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While doing "field research" on barbecue a few years back, I ended up in Hillsdale, Kansas, a tiny town in the middle of nowhere. There I discovered The Bank, a place that serves beautifully smoked meats and perhaps the greatest barbecue sauce I've ever tasted. A conversation with the pit boss revealed that his 'cue method was to forgo the dry rub and use hickory at a very low temperature, giving the meat more time in the smoker. Everything about these ribs told me that these were good ideas, and as soon as I got back in my rental car, I called Town Hall and told the staff to change our preparation immediately.
After you make these ribs the first time, you'll realize the hardest thing about preparing a batch is the cooking time. By that I mean when the air starts smelling of smoke and the ribs begin taking on a gorgeous deep color, well, you're going to want them right away. But, as I said, these ribs are the low-and-slow variety and patience is necessary. I often cook these ribs for parties, and guests inevitably ask me for the recipe. "No need to write it down," I say. "It takes 4 to 4 1/2 hours. Just some salt and pepper, and after a half hour, baste them with some apple juice, and then again after 2 1/2 hours. That's how you get that paper-thin, candylike glaze." For your convenience, I've written the instructions below.
At the restaurant and in this recipe, we use St. Louis-style ribs, which are the spareribs trimmed of the tips. But you can use regular spareribs or even babyback ribs. Make sure to ask your butcher to remove the membrane from the rib racks to let more of the hickory smoke flavor in.–Mitchell Rosenthal
LC No Smoker? No Sweat. Note
How to make head-turning ribs with ease? Simple. Forgo the dry rub on 'em. Smoke 'em low and slow. And slather 'em with a boozy sauce. Although in keeping with our approach to honest entertaining, we gotta be straight with you, the must-have-ness of these ribs is due in large part to that second edict, the one about being smoked nice and sloooooowly at a looooooow temperature. No smoker? No sweat. It's a cinch to jury-rig an outdoor smoker. Take a gander at some of our recipe testers' tactics, which you'll find in the comments beneath the recipe.
Special Equipment: 3 to 4 handfuls hickory chips, soaked in water for at least 30 minutes
Ribs with Spicy Bourbon Barbecue Sauce Recipe
- Quick Glance
- Serves 6
- 3 racks (about 10 pounds total) St. Louis or spareribs or baby-back ribs
- Salt and freshly ground black pepper
- 1 cup apple juice
- Spicy Bourbon Barbecue Sauce
- 1. Prepare a barrel smoker or adapt your charcoal or gas grill for smoking. You want the temperature to be between 225° and 250°F (107°C and 121°C). Take the rib racks out of the refrigerator and allow them to sit at room temperature for about 30 minutes while you get the fire ready.
- 2. Season the ribs liberally with salt and pepper. Place the racks, bone side down, in the smoker and toss in a handful of the soaked hickory chips. Smoke the ribs for 30 minutes, then baste them generously with half of the apple juice. Smoke for 2 1/2 hours longer, rotating the ribs every hour by moving the racks closest to the heat source to the farthest point and vice versa. Be sure to also add charcoal every hour or so to maintain the temperature inside the smoker at about 225°F (107°C). Add more soaked wood chips after 2 hours to keep the smoke flowing. After the additional 2 1/2 hours has passed, baste the ribs a second time with the remaining apple juice. Repeat, continuing to rotate the ribs, add charcoal, and toss more wood chips into the smoker at the previously mentioned intervals, until the ribs are tender and the meat pulls away easily from the bone, 4 to 4 1/2 hours total.
- 3. Transfer the racks of ribs to a baking sheet, take them inside, and plonk them on a platter or cutting board. Cut the ribs apart, slather them with some of the Spicy Bourbon Barbecue Sauce, and then plonk the rest of the sauce on the table for dipping and dousing.
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Leanin' Tree Christmas Card Assortment 20 Pack
Boot Barn Item #: 2007601
size: Click a button below Size Chartsize
- Assorted Christmas card set
- 20 fine art Christmas cards
- 22 designed envelopes
- 10 different designs with 10 different Christmas greetings
- 2 of each design
Spread your Christmas joy with these western inspired Christmas cards! The assortment includes 10 western Christmas scenes with Christmas designed envelopes. There are 10 different Christmas messages with art work. Cards and envelopes are printed on recycled paper.
Style(s): CHRISTMAS-AST90259
Lifestyle: Western
Color: No Color


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President day quotes
President day quotes – President's Day is celebrated throughout the United States on 20th of February every year in the memory of the first President of America. This day is celebrated with enthusiasm and respect for the "Father of his own Country", George Washington. This Day is dedicated for remembering all the presidents of United States. The contribution and the activities of Washington are honoured by the citizens. The parades and different types of activities take place in the corners of the nation to pay the homage. This President's Day is celebrated in general every third Monday of February in the year. In different states of US, people also commemorate Washington's Birthday that falls on 22 nd of February. Somewhere this day is known as Washington's Birthday as well. People on this day exchange different clipart regarding the day and download the colourful poster and desktop wallpapers images to show their respect to George Washington, Abraham Lincoln and others. The messages, sayings, and the messages of these famous presidents are also available. President's Day wishes are also given on our site. Fetch the President's Day Images, Poster, colouring pages and desktop background of President's Day from us where you will get diversified collection.
President day quotes
"If freedom of speech is taken away, then dumb and silent we may be led, like sheep to the slaughter." – George Washington
"If your actions inspire others to dream more, learn more, do more and become more, you are a leader." — John Quincy Adams
"The test of our progress is not whether we add more to the abundance of those who have much; it is whether we provide enough for those who have little." — Franklin D. Roosevelt


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Teacup Lake Snowpark and Trailhead
Just about any place you find on TravelOregon.com can be added to your own Oregon Roadtrippers Account. Find out how.
Get on the road with Roadtrippers
We've partnered with Roadtrippers to provide a great way to plan a trip around Oregon. So start planning your next road trip to here, there or pretty much anywhere in Oregon.
Very popular winter sports recreation spot with excellent cross-country ski trails, skijoring and snow-shoeing also popular. The trails are often groomed and the scenery around the lake is breathtaking.
What's around here? Location & Nearby Things to See & Do
These maps and directions are for planning purposes only. You may find that construction projects, traffic, or other events may cause road conditions to differ from the map results. For travel options, weather and road conditions, visit tripcheck.com, call 511 (in Oregon only), 800.977.6368 or 503.588.2941.
Is any of the information on this page incorrect?
A related Trip Idea
Road Trip: Parkdale and Odell
Rumor has it that there's more to the east side of Mt. Hood than awesome downhill skiing. Upon investigation, we can now confirm that it's true. Here are some fun spots along Highway 35. Pow For an alternative to alpine skiing and boarding, take…


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In the world of rock radio festivals, very little locally tops KROQ's two seasonal smorgasbords, Weenie Roast in late spring, Almost Acoustic Christmas near the start of winter. Save for a particularly packed Rock the Bells bill, the same goes for hip-hop and mainstay station Power 106 FM — their Powerhouse lineup helps bring summer to a close with giants of the genre … and their annual Cali Christmas, held once again Wednesday night at Gibson Amphitheatre, ushers in the holidays.
This year's event, capped by the first major SoCal appearance from 50 Cent since releasing his fourth album Before I Self Destruct, was bolstered by performances from mad-hatter Southern rhymer T-Pain, Brooklyn's own Fabolous, popular Latin rapper Pitbull, Houston star Chamillionaire and newcomers Jay Sean, the New Boyz and Jeremih.
Personal note: I had intended to review last night's bash … but suddenly found myself having to put down our family dog Roosevelt instead. Because of that and the need to burn up some personal days to get holiday shopping done, Soundcheck may be rather quiet until early next week, when I'll return with a review of Lady Gaga at Nokia Theatre and my annual Top 20 albums of the year. (Of course, should there be any major breaking news, I'll be back sooner than expected.)
In the meantime, click here to take a look at more of Kelly A. Swift's pictures from Power's big blowout.
Previous concert reviews:
[rssfeedme cat="soundcheck" feedpath="category/concert-reviews/" max="10″]


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Flexrake The Scoop - Poop Scoop & Spade with Aluminum Handle
|Flexrake's The Scoop features a pan and spade made of durable, non-rusting aluminum & alumiLite aluminum handles. Sturdy yet lightweight construction. Flexrake Scoops are made in America with superior materials to last a lifetime. Durable, non-rusting aluminum & alumiLite construction Sturdy yet lightweight 3' AlumiLite handle Aluminum handles are both lighter weight and more durable than old-fashioned wood handles. Perfect for quick, easy clean-ups!Made in the USA.
Flexrake Jumbo Jaws Scooper
|The Flexrake Jumbo Jaws Scooper picks up your pet's messes on all surfaces and is designed for easy pickup using just one hand. The extra large spring-action scoop is made with high density polypropylene and measures 32" inches. Heavy duty spring action makes the "jaws" easy to open and close. One-hand scooping operation Picks up on all surfaces Heavy duty polypropylene construction
Flexrake Jaws Scoop - Poop Scoop
|The Flexrake Jaws Scoop is designed for one handed pick-ups on all surfaces and is made of durable polypropylene plastic. Rugged, polypropylene construction stands up to the elements and rinses clean with the hose. One-handed pickups on all surfaces Made of durable polypropelyne plastic Powerful spring action jaws The Jaws Scoop makes cleaning up after your dog much faster and easier, the powerful spring action ensures the jaws stay closed until you're ready to empty it.The Flexrake Jaws Scoop has a long 22" handle to help eliminate unnecessary bending. The Jaws Scoop is 5.5" Wide and great for pick up on grass, cement, dirt, and other hard surfaces.
Flexrake Rake With Wood Handle
|Flexrake Rake With Wood Handle is sturdy with lightweight construction. Rakes are made of durable non-rusting aluminum. Made in America of superior materials to last a lifetime. Picks up where your dogs leave off! Sturdy yet lightweight construction Durable non-rusting aluminum head Made in the USA Note: Rake only.
Flexrake Spade Only with Aluminum Handle
|Flexrake Spade with Aluminum handle features a sturdy but lightweight construction. The durable, non-rusting aluminum makes cleaning up after your dog easy. This is sold separately from the dog scoop and is only the long spade. Aluminum spade only Durable, long-lasting pickup tool Will not rust
Flexrake Scoop/Rake with Wood Handle Large
|Flexrake Large metal scoop and painted rake with wood handles and vinyl-covered comfort grips. Perfect for grassy surfaces. Durable and dependable for years of backyard cleanup. Makes quick work of a messy job. Vinyl covered comfort handles Perfect scoop for grassy surfaces Metal scoop & painted rake
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|Flexrake's metal scoop and spade with wood handles and vinyl-covered comfort grips. Durable and dependable for years of backyard cleanup. Makes quick work of a messy job. Metal scoop & spade with wood handles Vinyl-covered comfort grips Cleans messes quickly Small - (6.5"W X 8"D X 39"H)Large - (11"W X 11"D X 39"H)
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|Flexrake Wood Dog Scoop and Steel Rake allows you to clean up pet messes without bending or stooping over. This scoop and spade set features molded non slip vinyl grips with a durable, sturdy construction. The cherry stained wood handles are long-lasting. Made in the USA. Made in the USA Durable wood dog scoop and steel rake Non-slip grip
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Hey there, time traveller!
This article was published 8/2/2013 (1654 days ago), so information in it may no longer be current.
IF you thought the Assiniboine River warming huts were only good for warming up skaters, wait until Louis Riel Day weekend.
Thanks to Manitoba Music, the innovative river trail shelters will rock with the diverse sounds of homegrown talent Feb. 17 from 1 p.m. to 4 p.m.
The musical lineup includes Red Moon Road (acoustic folk and roots), singer-songwriter JD Edwards, fiddle player Melissa St. Goddard, up-and-coming roots singer Haley Carr and jazz group The Lucas Sader Project.
The Forks will also be hosting an on-ice dance party at the Big City warming hut, featuring the turntable artistry of DJ Hunnicutt and DJ Co-op.


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Daily Dispatch: New Tennis Season Gets Underway Down Under
Happy New Year! The new tennis season is upon us as action gets going in Brisbane, Auckland, Doha, Chennai, and Shenzhen.
Before we get down to 2013, here's a great compilation by Lindsay Gibbs of the best tennis writing of 2012.
Steve Tignor wants to discard these five tennis phrases in 2013:
2. "David Ferrer doesn't get enough respect."
The Second Spaniard isn't on many, or maybe any, magazine covers, which is too bad. And he's rarely mentioned among the contenders for Grand Slam titles, which is slightly unfair considering that he's the fifth best player in the world. But the man known as the Little Beast does get his props these days. This pro's pro is universally lauded for making the most of what he has, and for not being a jerk about it. The trouble may come if and when Ferrer ever begins to beat the Top 3 on a regular basis—that's when the lack of respect, from their fans, might kick in.
Alarming stat of the day: The slumping John Isner has won just four tennis matches since Winston-Salem (August) last year.
Daft reporter question of the day:
Q to Serena Williams: "We saw Caroline Wozniacki do a great impression of you several weeks ago. Who can you do a great impression of?"
The players participating in Hopman Cup, including Novak Djokovic, Ana Ivanovic, Tommy Haas, Venus Williams, John Isner, Jo-Wilfried Tsonga, Fernando Verdasco, and more, got dressed up for a New Year's Eve ball in Perth.
Maria Sharapova spoke to the press about withdrawing from Brisbane with a collarbone injury:
Tweet of the day:
Happy New Year!!! twitter.com/ovi8/status/28…
— Alex Ovechkin (@ovi8) January 1, 2013
Comments are closed.


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In the spirit of giving for this season, I thought with all the excitement that I would put out a pre-release of memcached 1.4.4 for Windows 64-bit. This is a release based of my first successful modifications to memcached as well as libevent to get it to compile on Windows 64-bit. This was compiled on Windows 2008 and is available from our labs website here.
We are working hard to continue improving this for the Windows platform and expect a lot of good things to come out of 2010!
Happy New Year!
未经允许不得转载:SuperMan's blog » memcached Windows 64位


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The Crap We Missed – Friday 10.25.13
Welcome to Friday's The Crap We Missed, which happens to be the smallest gallery of the week, born purely out of lack of content and not at all because of the allure of having whiskey for lunch. You're still getting some old favorites as well as some newbs, like Kobe Bryant, who I'm not sure if he's ever been in TCWM, but yesterday he was taunting a lion (even though, let's be honest, she was probably asking for it), so he's in. Then there's blonde Johnny Depp with Amber Heard and the albino assassin tasked with murdering anyone who touches his bracelets, and finally, Martin Scorsese remembering that time Leo and his boys dumped pig's blood all over Jonah Hill at the prom.
Damn, two days in a row with Jonah Hill slams? Here, redouche your memory. Now, let the hate flow through you,
- Photo Boy


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Yale School of Drama Presents CLOUD NINE, 1/22-26
YALE SCHOOL OF DRAMA (James Bundy, Dean; Victoria Nolan, Deputy Dean) presents CLOUD NINE by Caryl Churchill, directed by Margot Bordelon, January 22-26, 2013, at the Iseman Theater (1156 Chapel Street).
CLOUD NINE features original compositions by Palmer Hefferan, set design by Kate Noll, costume design by Elivia Bovenzi, lighting design by Masha Tsimring, sound design by Sam Ferguson, dramaturgy by Alex Ripp and Emily Reilly, and stage management by Sonja Thorson.
The cast includes Chris Bannow, Timothy Hassler, Gabe Levey, Brenda Meaney, Hannah Leigh Sorenson, and Mickey Theis.
CLOUD NINE will be performed at the University Theatre, 222 York Street in New Haven. The performance schedule is:
Tuesday, January 22 8PM (Opening)
Wednesday, January 23 8PM
Thursday, January 24 8PM
Friday, January 25 8PM
Saturday, January 26 2PM and 8PM
Tickets, $10-$25, are available online at drama.yale.edu, by phone at (203) 432-1234, and in person at the Box Office (1120 Chapel Street at York Street).


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A Wireless Event (also called Wireless Distribution Event or Wi-Fi event) is a special event which gives out either a Pokémon or an item that is special in some way. To receive the gift through special events, you must have a DS, the specified game, obtained the Pokédex in that game and no more than a certain number of Wonder Cards.
Known Events
Diamond and Pearl
Member Card - Unlocks an area to catch Darkrai. Was available in both DP and Pt.
Secret Key - Unlocks room to Rotom's room to get machines that can change Rotom's form.
HeartGold and SoulSilver
- Celebi - Receives a special event Celebi that unlocks various events in HGSS* and BW*.
- Crown Beasts - Allows the player to receive three shiny Legendary Beasts known as the Crown Beasts that unlock events in BW*.
Black and White
Victini - Receives Liberty Pass that allows the holder to visit Liberty Garden and capture a Victini.


text: Skill Name Fire Arrow Skill Type Enemy Skill Skill Effect Heavy hit causing 200% damage. Used by Enemies Report Errors Retrieved from "http://pad.wikia.com/wiki/Fire_Arrow_(foe)?oldid=34669" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Effect:Strike Enemy Skill Languages: 中文


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We all know how frustrating it can be, especially when traveling in a foreign country or away from your area and suddenly flights are cancelled or changed, airports are closed due to hurricanes, snow storms, etc, and for some reason you can't use your cell phone to make calls, hopefully you can at least use the Internet to do some quick checking and here are some very useful links for you to check your flight status.
Live Flight Tracking
List of Airlines for you to call- This option is the least recommended in times of trouble because most people will be calling causing a long await.
Please keep us in mind when looking for Washington DC Lodging
We are located about 5 miles from DCA – Washington Reagan National Airport. You can take a taxi, shuttle or metro. About 29 miles from AID – Dulles International Airport. From here you can take a taxi but it is costly, a shuttle, or bus/metro and about 30 miles from BWI – Baltimore Washington International Airport. From this airport you can also take a taxi but it will be costly, a shuttle, or bus/train/metro.
Safe Travels,
Lucia Rosan
American Guest House in Washington DC


text: Top 10 Baby Gifts from our Buyer | UncommonGoods July 20, 2012 Gaby D Gaby is the Community Outreach Coordinator. She knits, reads, collects vinyl, yogas, and is the lead singer of a Brooklyn-based rock band. She is half-part Martha Stewart and half-part Fran Drescher. If she's not sleeping, she's probably Tweeting. Her favorite uncommon good is anything made by Dana Brandwein Oates or Emilie Shapiro. No Comments Leave a Reply Cancel Reply Name * Email * Website


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Topic: Husbands CA19-9
My husbands been doing really well. He had a few side affects from the cisplatin, feet tingling and some hear loss. He has been off it for a little over a month now. Just taking gemzar. His CA19-9 even come down to 70 when it was tested 3 weeks ago. Now just last Friday they checked the tumor marker and it jumped to 98 but all the other liver tests were normal. I don't know if its a reason to be worried but I am. I'm afraid that if all liver levels were normal and the tumor marker is starting to go up does it mean that the cancer could be else where? The tumor marker had been on a steady decline so I'm not sure what to make of this. We weren't scheduled to see the doctor for another 3 weeks. I had just called on the results. You would think the doctor would call.


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Sharona Floral Knit Dress
I'm normally not a big fan of floral prints, but I LOVE this dress!
So cute ans a steal to wear over and over again.Tags: dresses, Halloween 2011, black swan costumeAdded 6 Years Ago from dELiAs
Blowfish|Boots|Heels & Wedges|View All Shoes
A star style staple for summer is the fedora hat. Ashlee Simpson barely leaves the house without one, while Fergie's been seen in them for evening.
Aww, poor T Rex!!
I just love tank tops, and there's 13 different colors and prints.
I have one, and it's a lifesaver! if I stayed up up and don't feel like planning an outfit the next morning, throw on a romper, cute shoes, cute jewelry... going to the beach, throw on a romper.
We're in 'knots' over this cool tank!
These bracelets bring me back to my childhood. You can get 2 and give one away to your besty! $12.00Tags: delias, friendship bracelets, rope braceletsAdded 7 Years Ago from dELiAs
Who doesn't love woodstock!Tags: green, tees, peanuts, St. Patrick's DayAdded 7 Years Ago from dELiAs
($26.50) Item #156730. Available in sizes XS to XL / * 25" long. "Young Love" graphic (100% cotton) t-shirt. I really adore this graphic tee designed by Keren Richter! It's just super adorable and simple. I actually saw ... ($26.50) Item #156730. Available in sizes XS to XL / * 25" long. "Young Love" graphic (100% cotton) t-shirt. I really adore this graphic tee designed by Keren Richter! It's just super adorable and simple. I actually saw something similar (with a v-neck, for $32) on Blood Is The New Black: http://www.bloodisthenewblackstore.com/store/store.php?crn=2653&rn=7770&action=show_detail There is the same shirt on KarmaLoop (for an outrageous $36): http://www.karmaloop.com/products.aspx?ProductID=59254&VendorCode=BLK As well as a cheaper version (for $24.95) at Zumiez: http://www.zumiez.com/catalog/product/view/id/42887/s/b-i-t-n-b-young-love-white-tee/category/67/ Although I prefer the Delia's middle price-range, round-neck tee. If you enjoy fab-oh graphic tees, this is a must! It's up to you though which price range and type of tee (v-neck or round-neck) you wish to purchase. x.Tags: notcot, glam, t-shirts, Cool Hunting, SheFinds, delias, graphic tees, Zumiez, style dashAdded 7 Years Ago from dELiAs
A glam shoe for you and a new pair for someone in need: that is what your purchase of these Toms shoes will buy you during this glorious season of giving. In gold or silver metallic.Tags: silver, gold, metallic, flats, womens shoes, Toms Shoes, delias, shoe donationAdded 7 Years Ago from dELiAs
great lime green and warm and on sale. perf.
sweet. Only 6 bucks. OMG :)
bright and cheap and great for winter... plus on clearance!!! so cutie! 40 bucks ya'll!!
perfect and super cheap winter coat that is in style, trendy and warm. I love it and am considering buying in all available colors! Awesome!
A fun, casual addition to your wardrobe during the summerTags: rompers, jumpers, summer casualAdded 7 Years Ago from dELiAs
It's always tough to find long-torso swimwear. As a result, I rarely wear one pieces. This one is adorable, though - enough to make me rethink my bikini-only policy.Tags: beach, swimwear, one-piece, swimming suitAdded 7 Years Ago from dELiAs
I love these, they could go with alot.
I love the simplicity, and the back of this dress.
I love the vibrant color and pattern... and the name of the dress.
I love the purple.
I really like the print and color.
I love Minnie!!
A cute nautical-inspired skirt with a lot of movement. Printed double-layered skirt with side zipper for better fit.
Brown and turquoise my favorite, new, antique, vintage feel, flowers yet will go with anything!
All things nautical are big this spring!
Indian summer.
Every shirt you buy donates a little to the World Wildlife Fund!
This makes me giggle. :)


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Hey there, time traveller!
This article was published 9/10/2010 (2510 days ago), so information in it may no longer be current.
Most of Winnipeg's Jewish community can trace its ancestry to Russia and to grandparents and great-grandparents who immigrated to Canada in the early part of the 20th century.
Since then, there have been two other major influxes of Russian-born Jewish immigrants into the city. The first occurred in the early 1970s when, during a period of détente with the Western world, the Soviet Union allowed a significant number of Jews to emigrate for the first time in decades. The second is occurring now, as dozens of Russian families are settling in Winnipeg, most of them after spending several years living in Israel.
In the last five years, about 2,000 Russian-Israeli immigrants have chosen Winnipeg as their new home. For many of them, their reason for leaving Israel is related to security. Many Russians in Israel live in outlying cities such as Sderot and Ashdod which, due to their proximity to Gaza, bear the brunt of rocket attacks from Hamas.
The majority of those who have come to Winnipeg have done so with the assistance of the organized Jewish community, under the auspices of the Jewish Federation of Winnipeg. In a program that is unique to North America, the federation works collaboratively with the provincial government, helping to pre-screen applicants for the Manitoba Nominee Strategic Recruitment Initiative. This co-operative effort benefits both the province and the Jewish community, which has been trying to grow its numbers for several years.
Through this program, potential Jewish immigrants are invited to send a query letter to the federation expressing their interest in moving to Canada and describing their family situation, post-secondary education and work experience. Assuming they meet the criteria outlined by the nominee program, they are then invited to come to the city on an exploratory visit.
During this visit, volunteers show them around the city, familiarize them with the community and its amenities and set up meetings for them with Manitoba Immigration, prospective employers and recent satisfied immigrants. Once the decision to move to Winnipeg is confirmed, community agencies provide assistance arranging documentation, housing and English-language classes.
Yosef Perlman is one of the volunteers who often meet with potential immigrants. Israeli born and raised, he moved to Canada four years ago and knows firsthand what kind of questions the prospective immigrants will have and what kinds of challenges they are likely to confront.
"I know how hard it is when you first come," says the 44-year-old airport security worker who jokes about coming from "plus 40 weather to minus 40 weather."
In addition to assisting during exploratory visits, Perlman is also active within the Israeli-Russian community on a day-to-day basis, helping those who settle in Winnipeg feel at home. About once every two months, he helps organize a Manitoba-style social for Russian and Israeli adults. He also makes sure all newcomers are aware of the community supports available to them and of the existence of two helpful Russian language websites, winnipeg.ru and russianmanitoba.ca.
Russian-born Elena Livni relies on these websites, as well as on the Russian newspaper Perspectiva, for keeping her informed about events in the Jewish and general communities and for keeping her connected to those from similar backgrounds. Like many of her fellow Israeli immigrants, the 39-year-old learned about Winnipeg's unique immigration initiative mainly from the Internet. Less than a year after her exploratory visit to the city in the fall of 2006, she moved to Winnipeg with her husband and two young children.
"I didn't know a lot about Canada," Livni says, "but a friend told me about the Jewish community support in Winnipeg and so I went on the Internet, wrote them a letter and the Jewish community invited me to come and visit."
An accountant by profession, Livni now works in real estate. Many of her clients are Russian-Israelis who, much more so than long-time Jewish community members, are dispersed in all areas of the city, including the North End, the former hub of Jewish life in Winnipeg.
For many of these newcomers, Canada represents a second immigration and a second opportunity. As a result, they are highly motivated to succeed and to truly make a place for themselves in Winnipeg and in Winnipeg's Jewish community.
"You have to make a decision about what you want and do it for yourself and for your kids," Livni says candidly. "If you really want something, you overcome the difficulties and go ahead. We did it already once, so we know that it can be done."


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text:
Indian villagers look on as the funeral pyre of Sarabjit Singh burns at Bhikhiwind village, 45kms from Amritsar. Singh, an Indian convicted 16 years ago in Pakistan for spying and deadly bombings, died on May 2 after being savagely beaten with a brick in Lahore prison, sparking a furious response from Indian politicians. Singh was cremated with state honours in his native village in northwest India where hundreds of angry demonstrators shouted "Down with Pakistan!" as they gathered to pay their tribute.
© The Financial Times Ltd 2016 FT and 'Financial Times' are trademarks of The Financial Times Ltd.


text:
An Otley man who plucked a "lifeless" five-year-old girl from the River Wharfe in Ilkley has been honoured for his bravery at a prestigious awards ceremony.
The ceremony recognising the courageous and innovative actions of local people and police officers to tackle crime and improve their communities was held in Wakefield.
Mark Gilmore, Chief Constable of West Yorkshire Police, hosted the evening alongside Police and Crime Commissioner Mark Burns-Williamson at the Calder Park site of the Regional Scientific Support facility.
Throughout the event tales of courage, heroism and people going above and beyond their civic and professional duty were heard.
Receiving an Assistant Chief Constable Award was Simon Wood, 27, of Otley, who on August 22 last year jumped into the River Wharfe in Ilkley to save the life of five-year-old Lily Waddington.
Lily had got into difficulties during a day out in the town with her grandparents. Life saver Simon managed to pull her from the water in the nick of time.
Also among the awards was a tale of bravery in which two members of the public helped two officers tackle a team of robbers armed with hammers during an incident at a post office in Burley-in-Wharfedale last year.
Local resident Marcus McLeod initially spotted suspicious activity at the post office and flagged down a police car containing PC Tim Brown and PCSO Darrin Thompson.
While PC Brown was parking the vehicle, PCSO Thompson entered the building and was immediately confronted by the two masked suspects. With no thought for his own safety he grappled with one of the men while the other repeatedly struck him with a sledge-hammer.
As the struggle continued outside, Mr McLeod saw the attack and rugby tackled the suspect armed with a sledgehammer. With the assistance of PC Brown, the suspect was detained with his accomplice making off towards a waiting getaway vehicle.
Another male member of the public, who has asked for his name not to be detailed, then gave chase and was struck by the vehicle as it attempted to leave the scene. Fortunately all those involved in the incident suffered only minor injuries.
The second suspect was later identified and arrested.


text:
Best Joint: Uncle Dan's Rib House BBQ
Where: 1001 Lake Air Dirve – Waco, Texas
Online: www.uncledansribhouse.com
What: They serve some of the best BBQ in Texas from brisket to turkey
Why: Everything served has a great smoked flavor. The sauce they use has just the right spicy kick without all the sweetness of eastern BBQ. Uncle Dan has even catered a BBQ dinner in Sweden for the US ambassador.


text:
PCI-6011E Digital Input block
Simulink® Real-Time™ Library for National Instruments®
I/O Module Input
Block Output Data Type
TTL low = 0.0
Enter numbers between 1 and 8 to select the digital input lines used with this port. This driver allows the selection of individual digital input lines in arbitrary order. The number of elements defines the number of digital lines used.
For example, to use all of the digital inputs for one port, enter
Number the lines beginning with 1 even if this board manufacturer starts numbering the lines with 0.
Enter the base sample time or a multiple of the base sample
time (
-1 means sample time is inherited).
If only one board of this type is in the target computer, enter
-1 to
locate the board.
If two or more boards of this type are in the target computer,
enter the bus number and the PCI slot number of the board associated
with this driver block. Use the format
To determine the bus number and the PCI slot number, type:
tg = slrt; getPCIInfo(tg, 'installed')


text:
Pirate Bay film to be distributed for free
File-sharing website The Pirate Bay is at the forefront of the pro-piracy movement. It's only fitting then that new feature doc about them, TPB AFK: The Pirate Bay Away From Keyboard, is to be given away for free.
Restricted Content
Registration is required to read the entire article and to gain access to other restricted areas of the website


text: PORTLAND, Ore. ( TheStreet) -- This week, Miami Dolphins offensive lineman Richie Incognito was suspended indefinitely by the team for hazing fellow offensive lineman Jonathan Martin to the point that he had to leave the team.Yes, Miami fans, that is your business. According to ESPN's Adam Schefter, Incognito used racial epithets, references to Martin's sexual orientation and other taunts to prod Martin and continue a pattern that began -- and by all accounts should have ended -- after Martin's rookie season in 2012. Though Martin apparently didn't go to coach Joe Philbin to complain -- potentially because Incognito was on the Dolphins' six-player "leadership council" and may not have taken kindly to having Martin go over his head -- Philbin took responsibility for the environment in his locker room. The NFL players' union is now investigating Martin's case as harassment. So where do Miami fans come in? It isn't great to lose two members of your team's offensive line without anyone playing a down of football, but they're not the coach or the Dolphins' owners, right? They shouldn't have any say in personnel decisions or matters concerning team behavior or player safety, should they? As long as ownership and the league in general keeps using them as an ATM, of course they should. In fact, they already have. A combination of a terrible economy and a similarly awful on-field product has shrunk Dolphins season ticket sales from 61,000 in 2006 to little more than 40,000 last year. The team is 4-4 and has had exactly three winning seasons and one playoff appearance within the last decade. Current Dolphins owner Stephen Ross spent much of 2008 buying up the Dolphins' stadium and surrounding land and pocketed $37.5 million from Canadian life insurance firm Sun Life Financial in a naming rights deal. He has since floated several ideas for stadium upgrades, including a $200 million hotel tax to cover a partial roof, but has been unsuccessful in convincing local government and taxpayers that it's a good idea. Never mind that the Miami-Dade area has been a little skittish about spending since the housing crisis slammed both buyers and homeowners there. Both the City of Miami and Miami-Dade County have been openly hostile toward anyone who even suggests that public money go toward a sporting venue, especially after both the city and country were left on the hook for nearly $510 million on the $634 million initial costs of building Marlins Park for Major League Baseball's Miami Marlins. Paying off the bonds will cost the country nearly $2.4 billion over the next 40 years, while the Marlins keep almost all revenue from the stadium - even for events that aren't Marlins games. Voters weren't above voting against stadium-endorsing City Commissioner Joe Sanchez in his run for Miami's mayoral office while Miami-Dade voters flat-out recalled Miami-Dade Mayor Carlos Alvarez over his backing of the stadium. The Marlins, meanwhile, repaid the taxpayers' investment by jettisoning the overwhelming majority of the team's star players at the end of 2012. The Marlins finished with the worst record in the National League in 2013 and were only beaten for the worst record in Major League Baseball by the equally tight-fisted Houston Astros -- baseball's most profitable team of all time with nearly $100 million going right to the front office this season. Now Miami regularly listens to the Dolphins and Ross ask them to consider paying half of the $350 million in costs for the stadium renovations Ross is proposing. Miami, the county and just about everyone else Ross has hit up for public cash has told him where he can stick his request. But maybe that's not the best use of their outrage. Many of those taxpayers are still Dolphins fans, after all, and the sudden loss of that team in itself doesn't make their lives any better. Since they have what the Dolphins want, maybe it's time that a group of NFL fans used some of the same leverage that team ownership has been using against them for years.


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The Taxanes: Dosing and Scheduling Considerations
The Taxanes: Dosing and Scheduling Considerations
The determination of optimal dosing and scheduling has been an important
objective during the development of the taxanes. This issue pertains to
both paclitaxel (Taxol) and docetaxel (Taxotere). The clinical development
of docetaxel has largely involved a single administration schedule (1-hour
infusion) and a narrow dosing range (60 to 100 mg/m², with most studies
using 100 mg/m² over 1 hour every 3 weeks). The range of paclitaxel
doses and schedules, on the other hand, has been broad (ranging from 135
to 250 mg/m² over 1 to 96 hours every 3 weeks).
Impressive antitumor activity has been reported recently for paclitaxel
on disparate administration schedules, which leads to the question of whether
an optimal dosing schedule truly exists for the taxanes. Fortunately, the
results of several prospective randomized studies, in addition to retrospective
analyses, may shed light on these questions. This review summarizes pertinent
preclinical, pharmacologic, and antitumor results pertaining to optimal
taxane dosing and scheduling in clinical practice.
In Vitro Cytotoxicity Studies
The results of in vitro studies designed to evaluate taxane dose-response
relationships and optimal taxane scheduling have been reviewed previously.[1,2]
Many relevant biologic effects in vitro, such as cytotoxicity, formation
of microtubule bundles and mitotic asters, increase in tubulin polymer
mass, stabilization of microtubules against depolymerization, apoptosis,
radiosensitization, antiangiogenesis, and inhibition of chemotaxis and
motility, appear to be directly related to the concentration of the taxanes.[3-14]
The taxanes may induce different intracellular effects, depending on
the drug concentration. They inhibit proliferation of cells by inducing
a sustained mitotic block at the metaphase/anaphase boundary at concentrations
much lower than those required to increase microtubule mass and microtubule
bundle formation.[15] Half-maximal inhibition of HeLa cell proliferation
and 50% blockade of mitotic metaphase occur at 8 nM of paclitaxel, whereas
microtubule mass increases half-maximally at 80 nM of paclitaxel, with
maximal effect at 300 nM.[15] At high concentrations, the unique effects
of paclitaxel in increasing microtubule mass and microtubule bundles have
been associated with growth inhibition.[12,15]
Because these effects have not been noted at the lowest effective concentrations,
they could not have accounted for the antiproliferative effects observed
at low concentrations. Instead, growth inhibition has been associated with
the formation of an incomplete metaphase plate of chromosomes and an arrangement
of spindle microtubules resembling the abnormal organization that occurs
at low concentrations of the Vinca alkaloids.[16]
Plateau and Threshold Concentrations
As paclitaxel concentrations progressively increase, a plateauing of
dose-response effects has been observed in various cell lines.[12,17-22]
In other words, a situation of diminishing returns occurs as paclitaxel
and docetaxel concentrations are increased above specific plateau concentrations,
the magnitude of which appears to vary between cell lines. The broad clinical
implication of these results is that there may be a critical plateau concentration,
ie, a dose above which toxicity, but not efficacy, increases.
The cumulative results of in vitro studies suggest that the precise
concentrations at which plateauing occurs depends on the specific treatment
schedule and varies according to tumor type. In addition, there appear
to be precise threshold concentrations below which drug effects do not
usually occur. Like plateau concentrations, the precise level at which
threshold effects take place also varies among cell lines. Threshold concentrations
typically are inversely related to the duration of treatment. In essence,
these preclinical observations resemble clinical observations to date.
Treatment Duration
For both paclitaxel and docetaxel, treatment duration appears to be
the most critical determinant of in vitro effect. Prolonging the duration
of exposure in vitro generally produces much greater cytotoxicity than
increasing drug concentration.[1,2,9,12,14,17,18, 20,23-25] For example,
an 11-fold increase in the duration of paclitaxel exposure was more effective
in increasing the cytotoxic effect of paclitaxel in an LC8A lymphoma cell
line than was a 100-fold increase in paclitaxel concentration.[12] Interestingly,
this effect appears to be much more pronounced in taxane-resistant cell
lines.[24,26-29] The taxane concentrations at which cell survival curves
plateau tend to decrease as the treatment durations are prolonged.
For paclitaxel, and probably docetaxel, the effects of increasing microtubule
mass are maximal at drug concentrations that are equimolar with tubulin
or when the stoichiometry approaches 1 M of paclitaxel per 1 M of polymerized
tubulin dimer.[4,30-33] The binding of paclitaxel to polymerized tubulin
is reversible with a binding constant of approximately 0.9 µM. Docetaxel,
which most likely shares the same tubulin binding site as paclitaxel, has
a 1.9-fold higher effective affinity for the site.[4] The assembly of guanosine
diphosphate- or guanosine triphosphate-tubulin induced by docetaxel also
proceeds with a critical protein concentration that is 2.1-fold lower than
that of paclitaxel.[4] In addition, comparative in vitro cellular pharmacologic
studies have demonstrated that higher intracellular levels of docetaxel
in P388 murine leukemia cells may also be attributed, in part, to its threefold
slower efflux rate.[4]
These differences may explain the varying cytotoxic potencies of the
taxanes, with median inhibitory concentrations generally much lower for
docetaxel.[4,21,22,33-36] The relative potencies may not necessarily translate
into a greater therapeutic index for docetaxel, since greater potency may
also result in more severe toxicity at identical drug concentrations in
vitro. In addition, the taxanes may
not be completely cross-resistant, although differences in potency may
confound the interpretation of both preclinical and clinical studies regarding
These schedule-dependent effects have also been documented in studies
designed to determine the
in vitro interactions of the taxanes with ionizing radiation.[9] In most
studies, the radiopotentiating effects of the taxanes have been directly
related to the duration of taxane exposure prior to radiation.[9] In one
series of studies involving lung cancer cells, a radiosensitizing effect
could not be demonstrated for treatment durations of less than 6 hours
at any concentration of paclitaxel.[37]
Preclinical Studies
In early studies performed by the National Cancer Institute, paclitaxel
was administered as a suspension and antitumor evaluations were limited
to studies using intraperitoneally (IP) implanted tumors treated with IP
drug administration or human tumor xenografts implanted in the subrenal
capsule and treated subcutaneously.[38] In mice-bearing IP-implanted P388
leukemia, paclitaxel administered every 3 hours for three doses (pharmacologically
simulating a 24-hour infusion schedule) was more effective than other schedules,
including those with multiple-drug treatments on days 1, 5, and 9, or daily
treatment for 9 consecutive days.[38] However, these studies were constrained
due to the limited solubility of paclitaxel in the formulation vehicles
used at that time, thereby precluding the design of proper comparative
studies of prolonged schedules and single-dosing schedules.
Lung Cancer Model
When studies designed to evaluate different schedules were later performed
by Bristol-Myers Squibb in the M109 lung cancer model using polyoxyethylated
castor oil (Cremophor EL) or polysorbate 80 formulations, no schedule-dependent
differences were observed.[39] However, neither the optimal schedule demonstrated
in the P388 leukemia studies (every 3 hours × 8 doses) nor prolonged
(eg, 3 24-hour) infusion schedules were evaluated.
The schedule-finding studies in the M109 model indicated that both daily
× 5 and daily × 7 schedules were superior to multiple daily
dosing for longer intervals (2 or 3 days between injections). Significantly,
maximal antitumor activity was achieved at doses that were substantially
lower than the maximum tolerated dose (MTD). This was particularly true
for the daily × 7-day schedule, in which dosing at the MTD did not
result in any therapeutic advantage over an equally effective, but less
toxic, lower dose.[40] These results are consistent with the plateau effects
noted in the dose-response curves from a variety of cell lines.
Other Models
Nevertheless, dose-response effects have been observed in many other
preclinical in vitro models. Progressive reductions in vertebral metastases
were noted in combined immunodeficient mice inoculated with PC-3 ML prostate
cancer cells that were previously incubated with increasing paclitaxel
concentrations from 0.1 to 1.0 µM [41] and in mice bearing bladder
Dose-toxicity relationships have been especially profound. Substantially
greater toxicity in both rapidly proliferating (lymphoid, myeloid, gastrointestinal)
and nonproliferating (peripheral nerve) tissues has been observed on almost
all schedules in mice, rats, and dogs.[43-45] The schedule's effects are
more profound in that lower total doses are typically required to induce
equivalent toxic effects in animals treated with more intermittent dosing
schedules or treatment over more prolonged durations.[38,43]
It is difficult to compare paclitaxel and docetaxel with respect to
dose and schedule dependency in preclinical studies in animals due to differences
in tumor models, dosing schedules, and the proximity of treatment doses
to the MTD. Nevertheless, results of limited studies with docetaxel have
indicated clear dose-response relationships, particularly with short- and
single-dosing schedules. Although one may conclude that the type of administration
schedule appears to have minimal impact on docetaxel's antitumor activity,
it should be noted that only limited studies with prolonged schedules have
been performed.[5,46,47]