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Browsing the "Air Jordan IV Fear Pack" Tag
Air Jordan Retro 4 "Fear"
August 18, 2013 BY Patrick Johnson / 45 5 / 5
While Jordan Brand surprised everyone with this past weekend's release of the Air Jordan IV "Green Glow" with its glow in the dark flavoring, it hasn't stopped ...Read More
Russell Westbrook in Air Jordan IV "Fear"
August 8, 2013 BY Aaron Hope / 3 0 / 5
It was just yesterday that Sneaker News scooped you on the Air Jordan 'Fear Pack' release date coming up on August 24th. The day before that, we saw recent Jordan Brand e...Read More
Bun B Shows Off Fall 2013 Air Jordans
July 31, 2013 BY Brendan Dunne / 28 0 / 5
Want a quick look at just about every must-have Jordan Brand release for Fall 2013? Then look no further than Bun B's recent goodies, a set of seeded sneakers that should have yo...Read More
Air Jordan IV "Fear" Insoles
July 23, 2013 BY Brendan Dunne / 4 0 / 5
The theme surrounding the "Fear Pack" Jordans continues to come into clearer focus as their release draws near. Pictured here are in the insoles from the Air Jordan IV R...Read More
"Fear Pack" Air Jordan Retros
July 11, 2013 BY Brendan Dunne / 33 0 / 5
When word first hit that the Air Jordan IV "Fear" was part of a great group including the Air Jordan III and the Air Jordan V, it was assumed that those other models would ...Read More
Air Jordan "Fear Pack" (and "Green Glow" IV)
June 28, 2013 BY Brendan Dunne / 36 0 / 5
Thanks to Jordan Brand's product seeding tendencies, the full Air Jordan "Fear Pack" is now on display for your viewing pleasure. Keep in mind that each of the sneake...Read More
"Fear" Air Jordan 4
June 19, 2013 BY Brendan Dunne / 36 c 0 / 5
The Air Jordan IV will get all spooky on us later on in 2013 in the form of the Air Jordan IV "Fear" shown. The colorway is a chilling black and white with touches if a spo...Read More
Air Jordan IV "Fear"
June 1, 2013 BY Brendan Dunne / 48 0 / 5
Jordan Brand's got plans to whip up a "Fear Pack" of Jordans for 2013, with the (sold separately) sneakers in the set inspired by Mike's ability to put fear int...Read More
Air Jordan IV "Fear Pack"
May 29, 2013 BY Brendan Dunne / 38 0 / 5
The next group of themed Jordans to arrive looks to be the "Fear Pack", a set of black and white speckled retros. The details remain pretty slim at this point, but these ne...Read More


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Men And Women Working Together To Enlarge God's Kingdom
December's Newsletter – Men And Women Working Together To Enlarge God's Kingdom
For the Christian it must be clear what his or her duties are. After all being a Christian is not a sometime affair. The requirements of the Christian, goes on throughout the life span of the Christian- with no time off. For the competitor doesn't take any time off and neither can the Christian. The bible says in 1 Peter 5:8 "Be sober, be vigilant; because your adversary the devil, as a roaring lion, walketh about, seeking whom he may devour." With such formidable competition, it is to the Christian's advantage to add to the ranks to meet this challenge. You see when two or more come together to do God's work, two things happen- 1 (the most important) God is in the midst ready to fight your battle, Click Here To Finish
By Deacon Herbert Ruff

subset: commoncrawl


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Book this hotel and collect nights after your stay
The Hotel San Carlos - Downtown Convention Center is located in downtown Phoenix, Ariz. The Dodge Theatre, Chase Field, US Airways Arena, Arizona Science Center, Herberger Theater, Orpheum Theatre, and Phoenix Symphony hall are all within six blocks of the hotel.
Hotel Features.
The smoke-free Hotel San Carlos - Downtown Convention Center is the only historic boutique property in the Phoenix area. Lobby decor preserves the hotel's historic past with polished wood floors, chandeliers, and floor-to-ceiling mirrors. The hotel has two restaurants: Bistro 202, serving breakfast and lunch, and the Ghost Lounge, offering dinner and a bar. Street-front shopping directly outside the lobby includes a men's apparel shop, barber shop, gift shop, and shoeshine/repair shop. Hotel San Carlos includes a third-floor heated outdoor pool and sundeck surrounded by potted plants, globe streetlights, and cushioned lounge chairs. The hotel provides two meeting rooms and discounted use of a nearby 24-hour fitness center.
All 128 guest accommodations feature high ceilings, antique furnishings, tapestries, and crown moldings. Cable TVs, phones, and complimentary wireless Internet are provided. Coffeemakers are stocked with gourmet coffee. Bathrooms feature Rusk toiletries, shower/tub combinations, white tile floors, and pedestal sinks. Valet (surcharge) and self-parking (surcharge) is available.
Self parking costs USD 12 per day
Valet parking costs USD 20 per day
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Self parking costs USD 12 per day
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We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


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Jersey City Hindu temple celebrates Krishna's birthday
Sunday, August 17, 2014 10:59 PM
Inappropriate photo? Alert us.
Lord Krishna, the eighth incarnation of the Hindu god Vishnu, turned 5,126 this weekend and hundreds of people gathered for Jersey City's popular festival in Govinda Sanskar Kendra Center and temple Sunday night to mark the occasion. Aug. 17, 2014 (Mike D'Onofrio/The Jersey Journal)


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Geometrical significance
Abstract | References | Similar Articles | Additional Information Abstract: It is proven that the Löwner-Heinz inequality , valid for all positive invertible operators on the Hilbert space and , has equivalent forms related to the Finsler structure of the space of positive invertible elements of or, more generally, of a unital -algebra. In particular, the Löwner-Heinz inequality is equivalent to some type of ``nonpositive curvature" property of that space.
Retrieve articles in Proceedings of the American Mathematical Society with MSC (1991): 46L05, 58B20 Retrieve articles in all journals with MSC (1991): 46L05, 58B20
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Level 15 Melancholy
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2014-10-11 14:39:24 by Rational-Delirium
So I started working on this three days ago after taking a one year break from it, so four days total. Enjoy.
The F's are the inbetweens.
This is what it originally looked like with the keyframes.
Latest Movies
Christmas Collab 2013
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What can we do with a bunch of rubber band and snowmen?
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2 seconds intro. 5 seconds video. 1 second credits.
Comedy - Original
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Goldilocks & the Three...
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Little Goldilocks stumbles upon something BIG...
Comedy - Parody
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-Dominaliek- | Techno Song |
Scria | Classical Song |
Choric | Video Game Loop |
Favorite Movies
Arc Infinitum 1
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Sci fi detective
What? Voltorb is evolving
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A Voltorb Evolves
Comedy - Parody
Time Bros pt. 1/2
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Two friends on a journey through time.
Comedy - Original
Game Gramps
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Them confounded contraptions
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Favorite Games
Cydonia 2
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A fast-paced futuristic bullet hell shooter.
Action - Shooter - Multidirectional
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How fast can you go?
Skill - Avoid
no-one has to die.
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Choose who lives and who dies. Your decisions change everything.
Adventure - Other
Falling Chibi
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I want to throw some chibi away and cover them with bubble.
Skill - Other
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Ice Cap Zone (S3PC remake) | Video Game Song | |
AIM - Beyond Machine | Cinematic Loop | |
Simple and Clean Rmx Off V | Dubstep Song | |
Tranquil Universe 2014 | Ambient Song |
Recent Game Medals
Get A Clef!
5 Points
That's all you gotta do.
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Tricked You!
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Beat Maze.exe
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Amazing poo
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Get 150 points.
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Great poo
10 Points
Get 100 points.
Medal Stats.
Good poo
10 Points
Get 50 points.
Medal Stats.
10 Points
Unlock this medal to see it's details.
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5 Points
run 50m length
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25 Points
Find a coat
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Flash Light
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Total Medals Earned: 200 (From 73 different games.)
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Im going to be building a fermentation chamber and all i need right now is a love controller, not that smart with volts and what not but im figure for a 115 volt fridge i need to match it with a 115vac lover controller, please let me know so i can get what i need and not waste money...thanks
The TSS2 is what you want. It is a few more bucks than the single stage, but you'll thank me later. You use one stage for the cool side, then, depending on where you live, you can hook the other up to power a small ceramic "lizard lamp" for warming. This is great for those Feb/Mar/Nov/Dec brews here in the lower midwest, where it is 75 one day, 40 the next.
thats the one i was looking at, thanks
You'll need a 115v AC model for a fridge +2 on the dual stage. It's nice to have a unit that will heat and cool.
+3 on the dual stage. I've got a single on the shelf and really wish I would have gone with the dual for that heating option. Probably will be ordering a dual as funds become availiable.
For details on setting up the TSS2, check the side by side conversion thread in my sig.


text: On 4/13/06, Bruce Dubbs <bdubbs at swbell.net> wrote: > > Adding an errata page to the Website is not hard. If that is needed, I > don't have a problem doing it. I think it should be. There are probably various security issues and other bug fixes that could be mentioned there. -- Dan


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28 Seahurst, WA Driveway and Paving Professionals
Your driveway is part of the first impression that guests get of your Seahurst, WA home. And if it's worn, cracked or stained ... well, that doesn't exactly start things off on the right foot. Hire a driveway and paving contractor to remedy the problem, to repair or even create new walkways, paths, patios and other hardscaping. More
Stanley Patrick Striping
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Gencon Pacific is a Commercial General Contractor of over 37 years in the Tacoma area. We have recently branched out with out residential and small projects division. Our small... Read More
Emerald Paving
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Emerald Paving's employees are highly skilled professionals who take pride in customer satisfaction. Since 1983 Emerald has constructed numerous paving projects from the Cascades... Read More
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We are an asphalt and concrete contractor serving the entire Puget Sound. We specialize in all phases of asphalt, seal coating, striping and concrete flat work. From minor repairs... Read More
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Newcastle United Football Club
- Nickname:Magpies
- Founded:1881
- Manager:Alan Pardew
- Ground:St James' Park
- Capacity:52193
- Last Game: 04-Mar-2015 19:45
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Angry Kinnear earns support
07 Dec 2008 - 11:30:02
Newcastle United first-team coach Chris Hughton believes Joe Kinnear had every right to feel aggrieved with the referee after being sent to the stands in the 2-2 draw with Stoke City.
The Magpies' interim manager now seems likely to be in trouble with the Football Association after being banished to the stands by referee Mike Riley.
Kinnear was sent from the dugout late in the game after furiously protesting about the free-kick from which the Potters scrambled their late equaliser.
He already has to answer a charge of improper conduct later this month after calling Martin Atkinson 'a Mickey Mouse referee' during the 2-1 defeat at Fulham last month.
Speaking about Kinnear's dismissal, Hughton said: "I think it was for perceived comments, but from where I was, I certainly didn't hear anything.
"Joe's okay, he is fine. He just felt that every now and again it is not a bad idea to have a little change of voice.
"One thing I can tell you is that it's a very, very emotional game, certainly at that stage of the game."
Meanwhile, Hughton blamed a poor second-half showing for the loss of two points as the Magpies surrendered a 2-0 half-time lead given to them by a Michael Owen brace.
"We're very disappointed, certainly after what we regarded as a very good first half," he continued.
"We felt we could have gone in more than two goals ahead. We had a couple of good chances. Michael Owen had a good chance, Jonas Gutierrez had a good chance so certainly at half time we were very happy.
"We expected them to come out firing, which is what they did do and what you've got to be able to do is defend.
"And we perhaps felt on the goals that we didn't defend them well enough."
Related Newcastle United News
Related Newcastle United News


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The graph has a very long time scale so it is hard to spot individual years. It is the lows that are the problem here - the late 1920s just before the crash and the great depression, and the late 1990s. The spikes occur at moments like 1932 and 1982 when valautions were low and it was indeed a good time to invest
THIS week's column looks at an exercise in projecting long-term returns by Standard Life, the insurance group. As the final paragraph tries to make clear, the returns from a diversified portfolio are likely to be quite low.
Antti Ilmanen, a quant from the AQR group (and author of the excellent book Expected Returns, which featured in a previous column), makes the point even more succinctly in the attached graph. What does the line show? Mr Ilmanen's definition is that
The "60/40 expected real return" is the forward-looking long-run real return of a 60/40 U.S. stock/bond portfolio. Stocks' forward-looking real return is proxied by an average of two measures: (i) smoothed earnings yield, or the inverse of the Shiller P/E and (II) the sum of dividend yield and 1.5% (a proxy for long-run growth rate in earnings per share). Bonds' real yield is the difference of the 10-year Treasury yield and a measure of expected inflation over the next decade. Inflation expectations are proxied by an average of several survey forecasts; before these became available in 1978, statistical estimates are used.
As you can see, the outlook for expected returns is as low as it has been in more than a century, with real US returns likely to be 2.3% a year. Overaggressive pension funds (and endowments) beware!
Two points are crucial. The first is the inverse relationship between starting valuations and likely future returns; when valuations are high, future returns are low and vice versa. The second is a point I have been emphasising for years. While equities can be cheap or dear relative to bonds, the level of bond yields is a useful signalling mechanism for investors. High nominal bond yields are a sign that investors expect the future level of short rates and nominal growth to be high; high real rates give the same message about real growth. Low rates imply low growth expectations. Yes, bond yields have been manipulated downwards by central banks but central banks have indulged in these operations because they fear the growth outlook is weak. That has an implication for profits growth.
Admittedly, there is a very weak relationship between GDP growth and equity returns. But that seems to be because growth expectations are priced into markets; equities in weak economies are underpriced. That brings us back to the starting valuation level, which is still too high in the US (see the Shiller p/e, or indeed the dividend yield.)


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A common skin problem of adolesence. Acne often disfigures and scar the skin to an extent that may cause depression and low self-confidience among people.
• Acne is almost always seen in the teenage years
• severity of disease differs per individuals
• Peak severity is in the late teenage years But acne may persist into the third decade and beyond, particularly in females.
Articles in: Minor
Home » Archive » MinorAcne- a disfiguring skin problem
April 25, 2014 # 7:53 pm # Dermatology # 4 CommentsSchizophrenic writings: Story of my Psychiatry postings
December 6, 2013 # 11:16 pm # Psychiatry # No CommentOnce a patient appeared in the Psychiatry OPD. She was childish though old enough and somewhat sweet for a psychiatric patient. She was humble and respected the doctor tremendously. "She is not much different from a baby" I said to my self.
"Look at the power of the mind, look what it can make out of people. I have seen people …
Mental Illness Among Healthcare Professionals
October 15, 2013 # 8:10 pm # Psychiatry # 2 CommentsThe healthcare field can be stressful, to say the least. From school and training to actual careers, healthcare students and professionals often suffer from anxiety, depression and other psychological ailments. Plus, there seems to be a stigma surrounding mental illness in healthcare professionals; it seems as though doctors, nurses and specialists are expected to treat mental illness, but never experience …


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Preheat the oven to 425 degrees F.
In a large glass baking dish, toss the asparagus with the olive oil and garlic. Season lightly with salt and pepper, and toss. Bake until the asparagus are tender and lightly browned, 15 to 20 minutes, depending upon the thickness of the stalks, stirring twice.
Remove from the oven and toss with the lemon juice. Admust the seasoning, to taste.
Serve warm or at room temperatuer.
Go to Full Version of
Garlic Roasted Asparagus Recipe


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WEATHER REPORT: Friday, May 9, 2014
Tyler, Texas (KETK) — TGIF!
Today, we'll see patchy fog early with a few showers and thunderstorms. Otherwise, we'll notice a mixture of clouds and sunshine all while becoming warmer. Then, we'll have another chance of a few scattered thunderstorms in the afternoon, mainly to the south of Tyler and Longview. The overall rain coverage will be about 30 percent. The high will top off around 84 degrees with winds out of the south, southwest at 10-15 miles per hour.
Tonight, we'll see hit and miss thunderstorms ending late with a low of 68 degrees.
Make it a great day, East Texas! And don't forget to honor your beautiful mothers this weekend.


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Today's business challenges present a new wave of HR, talent and organization priorities. Deloitte's Human Capital services leverage research, analytics, and industry insights to help design and execute critical programs from business driven HR to innovative talent, leadership, and change programs.
The 2014 Global Top Five Rewards Priorities Survey suggests that employers around the world face similar challenges despite different political and geographic climates.
Welcome to the open talent economy—a new era in talent management. This collaborative, transparent, technology-enabled, rapid-cycle way of doing business has changed the talent landscape. Take in the new vista in this new report.
Faced with tougher, more numerous challenges, today's organizations are demanding more from their change initiatives by pursuing strategies that are customized, precise, and sustainable.
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text: Nassau chamber: Shop downtown By: Claude Solnik December 8, 2009 Comments Off A group representing thousands of local merchants on Tuesday asked Long Islanders to be kind this holiday season by shopping locally. The Nassau Council of Chambers of Commerce, which represents 50 chambers of commerce and thousands of businesses, launched a holiday campaign encouraging shoppers to choose downtown stores over malls and shopping centers. The "It Starts Here… ... Subscribe Login Email Address: Password: Already a paid subscriber but not registered for online access yet? For instructions on how to get premium web access, click here.Forgot your password? Print, Digital & Mobile1 Year$129 Digital & Mobile Only1 Month Intro Rate$2.99----------1 Year$99 Digital & Mobile Only1 Month Intro Rate$2.99----------1 Year$99 Print, Digital & Mobile1 Year$129 Print, Digital & Mobile1 Year$129----------Digital & Mobile Only1 Month Intro Rate$2.99----------1 Year$99 Share this:EmailPrintFacebookTwitterGoogle +1 downtowns 3:45 pm Tue, December 8, 2009 Long Island Business News Claude Solnik


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District gathers to celebrate Australia Day
Australia Day ceremonies were held around Campaspe Shire.
January 28, 2013 6:06pmCampaspe Shire's small towns shone in this year's Australia Day awards, with residents scooping all of the shire-wide accolades.
Rushworth residents Harry Ashton and Jake Thompson won the Campaspe Shire Citizen of the Year and Young Citizen of the Year awards, while Tongala's Shaun Mackrell was named Arts Person of the Year.
The day was celebrated around the district, with ceremonies held, flags raised and barbecues enjoyed.
Batsman is recovering
On-field medical emergency at Vibert Reserve highlights need for each club to have a defibrillator.
Howe's first for Hawks
Local football talent Dan Howe played well in his first game for reigning AFL premiership club Hawthorn last Thursday night.
Merrigum keeps PO
A mighty cheer may soon be heard down Merrigum way; the town has officially saved its post office.
Walker back in town Saturday night
Benny Walker is armed with a notepad and pen at all times just in case he gets that flash of inspiration.
Point-of-sale proves popular
New point-of-sale technology has been installed at three post offices across the district which has seen sales as much as triple in some stores.
Ogden remains Bomber
Elusive small man re-signs with club
Greyhounds show true colours
Owners walk dogs through Seymour to counter some misconceptions abiout the breed after devastating Four Corners program.
Tocumwal's $2mil. health win
The NSW Government has made a significant funding announcement to expand the health service in Tocumwal.
Games thanks
Hot on the heels of the inaugural Heathcote Community Games, organisers have thanked the community for its effort in making the first games a success.
More services urged
Cobram bus users and the bus operator are pushing for more services, more often.
Temporary highway closure
A court case site visit has lead to the brief closure of the Cobb Highway at Mathoura.
New industry support for growers
Fruit Growers Victoria plans to give fruit growers in Victoria more on-farm support as a result of its organisational restructure.
Truck drivers targetted by Benalla Police and VicRoads
In a joint operatin between Police and VicRoads, truck drivers were stopped on the Hume Highway with 12 vehicles issued with defect notices.
Discover unbelievable local deals from local businesses every week in the Goulburn and Murray Valley area with Leapon.com.au!
Search properties for sale or rent across North Central Victoria and Southern NSW. Visit your local website for local homes....


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4:20 Instant Win Word – August 2014
<KICKS VIPWhat is the 4:20 Instant Win Word? Select the correct word and you'll get points, plus you'll get another entry into drawings $100 worth of groceries. Our latest winners of free groceries are Lisa Bowers of Nacogdoches, Sonja Payne of Lufkin, Sabrina Anthony of Chireno, Ashley Stuckey of Diboll, and Laura Sessum of Lufkin.


text: Look this way! View full-size image < previous next > Is this photo a winner? "This group of boys have played on the same basketball team for the past 5 years and were coached by the two amazing men flanking this goofy group of boys. Their years together has resulted in them becoming an impressive basketball team and even more impressive is the deep friendships and the strength of character that they have all developed. These young men are truly "champs." Thank you to CustomInk - making these t-shirts was a breeze & it was so great to see them wear them proudly. " - 14 U Falcons (Mar 12, 2013) Share this photo on: Twitter Facebook Pinterest Similar Photos: Basketball End of Season Party | k-12 athletics | k12 athletics Feeling inspired? Visit the CustomInk Design Lab to start your own group order. Design Your Own


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Subscribe for ONLY $1 an Issue
That's $10 for an entire year!
There's a new guy on the Daily Show and we have to admit, we're shocked it took Jon Stewart this long to hire a "Senior Latino Correspondent"!
Mexican-American stand-up comedian Al Madrigal made his debut Tuesday night, immediately correcting the host, "It's actually pronounced 'Señior' Jon, but thank you, good to be here," he joked.
Quite a bit of controversy was stirred up yesterday when Venezuelan President Hugo Chavez took to Twitter to thank Shakira for giving him a signed red guitar. But according to a statement made by Shakira's press office, she had "signed 6 guitars at the request of concert organizers" while she was on tour in Caracas, Venezuela.
Pitbull recently performed and we have exclusive concert video to share with you! Check out Mr. 305 performing his new hit single, "Give Me Everything" below. We haven't been able to reschedule our live Facebook chat with the Miami-based music sensation yet, but he was kind enough to share this video just for you! Be sure to keep checking in and we'll let you know when it's going to happen:
We were very excited to hear that Marc Anthony would be continuing his role as police officer Nick Renata on the Jada Pinkett Smith show HawthoRNe (TNT, returning June 14th). Watch the clip below to see Marc do his sexy lawman thing. We can't wait to watch how this love triangle resolves itself…
Broadway's Wonderland musical played its final performance this Sunday, May 15 at the Marquis Theatre in front of a packed house. Wonderland opened on Sunday, April 17.
When Nick Cannon sat down recently to talk to Gayle King for her new OWN show and said that the whole birthing process with his wife Mariah Carey was a "production," we were like, "Duh! It's Mariah freaking Carey!" What was he expecting?!
This just brought us back to That '70s Show and reminded us how freaking funny Wilmer Valderrama can be! After a few serious turns in movies like The Dry Land alongside America Ferrera, the Venezuelan and Colombian actor has returned to his roots with this hysterical spoof music video. All we have to say is, Enrique Iglesias better watch out.
Catch Wilmer as alter-ego Eduardo Fresco in "The Way I Fiesta" below. ¡Que loco!
Less than a month after Jasmine Villegas released her new music video for 'Jealous,' the part-Mexican singer is already busy shooting a new video for a song called, 'Werk.' The 17-year-old singer — who is best known for playing Justin Bieber's love interest in the video for his hit single, 'Baby' — shot the video for 'Werk' yesterday with
Jennifer Lopez paid a little visit to Meredith Vieira and the crew over on the Today show this morning to talk about the impending release of her new album Love? tomorrow and to share the world premiere of her latest muusic video for her single "I'm Into You" featuring Lil' Wayne.
In this episode the Rivera clan is celebrating little Johny's birthday, but the baby of the familia is started to get a little too big for his pantalones so they decide to teach him a lesson. Of course, Jenni is throwing him a big birthday party and his siblings make the day super special for him, but not without letting him know that his behavior is not going to fly around this casa.
Check it out:


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"I see the School growing stronger in the future, with a growing number of supporters as they learn what the school is doing for those students who need a little encouragement at this time in their lives. It is wonderful to be able to give a leg up to a young person, to enrich their lives through music. With a higher sense of worth and a good outlook on life, our graduates will spread the good news here and now in their future communities. " Mary Cates, CMS Founder
Sponsor a Student
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text:
Oakland won 2-1
Game 1: Friday, April 25 | ||
Oakland | 4 | Final |
Seattle | 3 | |
Recap »Boxscore » |
Game 2: Saturday, April 26 | ||
Oakland | 3 | Final |
Seattle | 5 | |
Recap »Boxscore » |
Game 3: Sunday, April 27 | ||
Oakland | 4 | Final |
Seattle | 2 | |
Recap »Boxscore » |
4:10 PM ET, April 27, 2008
Safeco Field, Seattle, Washington
SEATTLE (AP) -- While Seattle's Felix Hernandez continued ringing up strikeouts with his fastball snapping in the high 90s, Oakland's Joe Blanton plodded along, quietly putting together solid innings without any flash.
Blanton's workman effort was rewarded in the end, and the Athletics now head south for a key series with the Los Angeles Angels, surprisingly on top of the AL West.Blanton pitched seven solid innings, long enough for Oakland's offense to score four times in the eighth inning off Hernandez, rallying for a 4-2 win over the Mariners on Sunday.Emil Brown finally got Oakland on the board with a broken-bat, two-run single, and Jack Cust and Ryan Sweeney added RBI singles later in the inning as the A's took two of three from the Mariners."It's so encouraging for the guys to keep fighting to the end and to come back and win that game," Oakland manager Bob Geren said. "That was huge for the team and the confidence of all the players."Hernandez, Seattle's young star, was cruising through seven innings, striking out a season-high 10 and allowing just four hits. It seemed only a formality that he would get through the eighth and likely turn the ninth over to closer J.J. Putz.Oakland had other intentions, which began right away with Jack Hannahan's walk to open the eighth. Mark Ellis then doubled into the left-field corner, setting the stage for a big inning.Daric Barton worked a nine-pitch walk off Hernandez and Brown, second in the American League now with 22 RBIs, dumped a single into left field, scoring Hannahan and Ellis, and bringing Hernandez's day to an abrupt end."I want to drive them in, that's the biggest thing," Brown said. "I wanted to drive those guys in and having the right mentality when I'm up there in those situations helps."Brandon Morrow entered for Seattle and continued the trend, walking Frank Thomas on a 3-2 pitch. Cust, who struggled in the field with a pair of deep fly balls and struck out twice, lined a single into right to score Barton, giving Oakland its first lead. Sweeney then capped the rally, lining a single into left past a diving Adrian Beltre to score Brown. Sean Green finally got Seattle out of the inning with a strikeout of Hannahan.Hernandez (2-1) ended up allowing four runs on six hits, but lost for the first time in his last seven decisions."Everything was working the whole game," Hernandez said. "Those guys made adjustments. Like I say, it was a tough loss."The rally made Blanton (2-4) a surprise winner, after trailing all day but managing to keep the A's close long enough for their offense to show up. Blanton went seven innings, giving up two runs on eight hits and striking out three.Blanton pitched at least seven innings for the fourth consecutive start, but won for the first time since April 11 at Cleveland. He's now 5-0 in his career at Safeco Field."If the runs aren't coming, I feel like if we stay in the game, and keep giving the team a chance, they'll come around eventually," Blanton said.Huston Street pitched the ninth for his eighth save in nine opportunities. He also got the save Friday night as Oakland took two of three from its AL West rival.Meanwhile, Seattle slipped further back in the AL West, dropping four of six on its homestand and now heads out on a difficult six-game road trip to Cleveland and New York."There are some positives, but we are still not running on all cylinders," Seattle manager John McLaren said. "Too many guys [are] not swinging the bat well, not driving in runs when they are out there."Beltre had a two-out, RBI single in the first for Seattle, scoring Jose Lopez, and Yuniesky Betancourt hit his first homer of the season, a line drive into the Oakland bullpen in the fourth.Otherwise, Seattle missed out on scoring opportunities in the second and sixth, when Brad Wilkerson doubled and Kenji Johjima singled with one out, putting runners on first and third. Betancourt grounded into a double play that ended the inning.Oakland threatened in the fourth, loading the bases on singles by Ellis, Brown and a 20-foot broken-bat infield single from Thomas, where the barrel of the bat ended up in shallow left.Hernandez got Cust swinging at a 1-2 fastball, then induced Crosby's slow chopper to third, where Beltre fielded the grounder on the bag to end the inning.Game notes
Rain suddenly started falling in the bottom of the seventh with the Safeco Field roof open. The roof didn't completely close until three batters into the top of the eighth. ... Johjima had to get a new catching helmet in the fifth when a chunk of his broke off after Ellis' follow through caught the brim of Johjima's helmet.
Copyright by STATS LLC and The Associated Press
Regular Season Series
Oakland leads 10-9 (as of Sun 4/27) | ||
Wed 4/16 | SEA 4, @OAK 2 | Recap |
Thu 4/17 | SEA 8, @OAK 1 | Recap |
Fri 4/25 | OAK 4, @SEA 3 | Recap |
Sat 4/26 | @SEA 5, OAK 3 | Recap |
» Sun 4/27 | OAK 4, @SEA 2 | Box Score |
Mon 7/7 | @OAK 4, SEA 3 | Recap |
Tue 7/8 | @OAK 2, SEA 0 | Recap |
Wed 7/9 | SEA 6, @OAK 4 | Recap |
Thu 7/10 | @OAK 3, SEA 2 | Recap |
Thu 8/21 | OAK 2, @SEA 0 | Recap |
Fri 8/22 | @SEA 7, OAK 5 | Recap |
Sat 8/23 | OAK 5, @SEA 1 | Recap |
Sun 8/24 | @SEA 8, OAK 4 | Recap |
Fri 9/19 | @OAK 2, SEA 0 | Recap |
Sat 9/20 | @OAK 8, SEA 7 | Recap |
Sun 9/21 | @OAK 5, SEA 3 | Recap |
Fri 9/26 | @SEA 10, OAK 8 | Recap |
Sat 9/27 | @SEA 7, OAK 3 | Recap |
Sun 9/28 | @SEA 4, OAK 3 | Recap |
Complete Schedule: Athletics | Mariners |
Scoring Summary
1st | A Beltre singled to deep left, J Lopez scored. | 0 | 1 | |
4th | Y Betancourt homered to left. | 0 | 2 | |
8th | E Brown singled to left, J Hannahan and M Ellis scored, D Barton to second. | 2 | 2 | |
8th | J Cust singled to right, D Barton scored, E Brown to third, F Thomas to second. | 3 | 2 | |
8th | R Sweeney singled to left, E Brown scored, C Denorfia to third, R Davis to second. | 4 | 2 | |
View complete Play-By-Play |
Game Information
Stadium | Safeco Field, Seattle, WA |
Attendance | 32,612 (68.5% full) - % is based on regular season capacity |
Game Time | 2:34 |
Weather | 65 degrees, cloudy |
Wind | 0 mph |
Umpires | Home Plate - Doug Eddings, First Base - Casey Moser, Second Base - Dana Demuth, Third Base - Lance Barksdale |


text:
Christmas comes early in Germantown
Parade, tree lighting and fun run all planned Sfor Saturday
Germantown - It will soon begin to look a lot like Christmas in Germantown as the annual parade and tree lighting are slated for Saturday.
The Germantown Chamber of Commerce is once again hosting a daylong Christmas celebration for the community, starting with the 5K Candy Cane Run/Walk at 10 a.m. The run/walk begins at the Germantown Library, W16957 Mequon Road, and winds through neighborhoods south of Mequon Road, according to Lynn Grgich, executive director of the Chamber.
People can register for the run the day of the event; however, preregistration will secure an event T-shirt. Register at gtownrec.com.
The afternoon events kick off with the Christmas parade at 2 p.m., with the center of the route being along Main Street. From 2:30 to 5 p.m., the Christmas tree lighting activities will be held at the Germantown Library before the village tree is officially lighted for the holiday season. The tree is located outside of the library, where Village Hall and the police department are also located.
It may seem early for the event, but the chamber wanted to ensure local hunters were able to enjoy it before heading out of town on the weekends. Deer hunting starts the following weekend. The weather also tends to be more agreeable earlier in the holiday season, adding to the turnout of the event.
"We did want to pull more residents out to gather together for the event that day especially," Grgich said. "We get more spectators for the parade and more people in the parade."
There are about 50 entrants in the parade, ranging from local Scout groups to the Germantown High School marching band. A few local businesses are also decorating floats and Bernie Brewer and the racing sausages will be in attendance. Music groups will also play during the parade route.
Showalter is marshal
Germantown High School boys basketball coach Steve Showalter was named grand marshal of the parade for his leadership in helping the team win the state tournament last year.
Grgich said each year the parade also honors different dignitaries. This year John Gehl from Gehl Foods will be honored.
"He's retiring from the company, so we thought it was a great way to show some appreciation for all that he has done for the community," she said.
The parade is sponsored by Columbia St. Mary's Germantown Clinic and the Deutschstadt Heritage Foundation. The run/walk is sponsored by financial adviser Sherry Plevak at Edward Jones.
During the tree lighting celebration at the library, there will be free hot chocolate and cookies, as well as free horse drawn carriage rides. Kiwanis will have food available for purchase.
The chamber's goal is to keep the event free for residents in the community each year, which they are able to do through sponsorships.
"It's more for the quality of life you think of for a community. A Christmas parade may not be the first thing that comes to mind, but it really is a community draw and pulls the community together," Grgich said. "We are always grateful for our sponsors so we can keep the cost at nothing for residents."
For questions on the event, contact the Germantown Chamber office at (262) 255-1812.
- Danielle Switalski
WHAT: 5K Candy Cane Run Walk; Christmas parade; tree lighting activities
WHEN: 10 a.m.; 2 p.m.; and 2:30 p.m.
WHERE: Germantown library, W16957 Mequon Road; Main Street; Germantown library
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text:
Open Houses 6-22-13
An open house bridal shower for Christina Bergerson, bride to be of Jason Leonard, will be held on Saturday, June 29, at the Assumption Catholic Church basement in Morris from 1:30 to 3:30 p.m. Jason is the son of Paul and Barb Leonard of Cyrus. Come and go as you please. s25
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text:
Ya In Thai Co., Ltd.
Categories: Company in Thailand > Consumer products > Personal Products & Pharmaceuticals
Address: 20/4 Moo 2, Thanurat Rd., Nong Phrao Ngai, Sai Noi, Nonthaburi 11150 Thailand See map
0 reply, 5,992 viewed
Ya In Thai Co.,Ltd is a company under handle by Yanhee Hospital, a reputation hospital in Thailand.Ya in thai is a manufacturer of medications, vitamin supplements, cosmetic products and other related medications, and herbal medicine.
- Open days
Monday, Tuesday, Wednesday, Thursday, Friday, Saturday
Service hours
08:00 to 17:00
- Address
20/4 Moo 2, Thanurat Rd., Nong Phrao Ngai, Sai Noi, Nonthaburi 11150 Thailand
- Phone number
+66 (0) 2927 2000
- Fax number
+66 (0) 2927 3193
- Email
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text:
While lighting is an integral piece of any interior environment, choosing it can be an intimidating task. It is our goal to help you streamline the selection process and educate along the way! Here is our quick guide on the two types of wiring in table lamp construction:
Most table lamps are constructed with the electrical cord running through the body of the lamp and exiting out the side of the base. Typically, the cord will be completely hidden inside the body of the lamp, however, it can be visible when the body is transparent. The Morton Table Lamp above has a clear glass body fitted with a brass post running through the center to stylishly conceal the cord.
The most common misconception about French wired fixtures is that they require a conversion, or have a different voltage. Before you call your electrician, note that French wiring simply means the electrical cord exits through the bulb socket rather than the base.
This construction originates from the practice of taking an antique found object and turning it into a lamp without compromising the integrity of the object's design. Lamps made of a solid stone, metal, quartz or crystal like the Classic Balustrade Lamp above are often French wired to showcase the beautiful material of the base. It's also popular to French wire designs too thin to conceal a cord. These are some of our most popular French wired designs:
Shop our entire collection of lighting online or in any of our showrooms.


text:
Genotoxic Impurities In Pharmaceuticals
Sponsored Links
Decisions to approve, prescribe and consume medicines involve risk/benefit assessments by regulatory agencies, health care professionals and consumers. For serious or life threatening conditions, drugs with higher risks for adverse effects or for serious adverse effects are sometimes acceptable. For example, some life-saving cancer chemotherapies are known human carcinogens. However, if one is suffering from a life threatening tumor, a 5% risk of a secondary, treatment-related tumor is generally considered acceptable. Arguably, the same is not true for impurities found in drug substances and drug products; impurities convey only risk with no associated benefit. Drug impurities might be viewed as "pollutants" in the pharmaceutical world. Much like pollutants in the environment, few people believe that they can be entirely eliminated. The challenge for regulatory agencies is to promulgate standards that assure that unavoidable drug impurities impart no or acceptable levels of risk.
Residual impurities resulting from manufacturing and formulation, or from degradation of the active pharmaceutical ingredient (API) and excipients, may be present in pharmaceutical products. A subset of these impurities may present a potential for genotoxicity and therefore pose an additional safety concern to clinical subjects and patients. The pharmaceutical industry and those that regulate it recognize their respective obligation to limit genotoxic impurities. Therefore, substantial efforts are made during development to control all impurities at safe concentrations. However, the effort made to limit impurities must be commensurate with the risk assessed at each phase of clinical development, taking into account the extent of the hazard, the disease indication, the size and characteristics of the exposed population, and the duration of that exposure, as well as the likely delay in the availability of beneficial medicines if the burden of limiting or controlling impurity levels is disproportionate. A balance of these considerations can be described best as the ''as low as reasonably practicable'' (ALARP) principle. It follows that the presence of impurities with genotoxic (mutagenic) potential may be unavoidable in clinical trial and ultimately in approved and marketed materials. Control of impurities in the drug substance and degradants in drug product are addressed in ICH Quality Guidelines Q3A(R) and Q3B(R), respectively, and the Q3C guideline that deals with residual solvents. However, no specific guidance for determining acceptable levels for genotoxic impurities is provided in these documents other than to recognize the fact that unusually toxic impurities may require tighter limits of control.
Limiting Genotoxic Impurities:
A major change in impurity testing involves a new regulatory guidance designed to tightly limit substances possessing potential for genotoxicity. The European Agency for the Evaluation of Medicinal Products (EMEA) guidance on genotoxic impurities, which became effective on Jan. 1, 2007, now applies a 1.5 mg daily exposure limit for such substances in most pharmaceuticals based on a precedent application of the threshold of toxicological concern (TTC) concept to food additives and food contact materials. Before the EMEA draft guidance, genotoxic impurities had been addressed only as a footnote in ICH Q3A (R2) "Impurities in New Drug Substances".
In 2004, the Pharmaceutical Research and Manufacturers of America (PhRMA) formed a task force to discuss genotoxic impurity limits. Concerned the 1.5 mg/day limit would be applied to drugs synthesized in the United States, even while these drugs were still in clinical development, the PhRMA group proposed a staged TTC approach that ties permissible impurity levels to the stage of development. Because clinical studies are conducted with limited duration of dosing, the group reasoned that total exposure is very low, and thus higher intake levels should be allowable during early clinical studies without a net increase in risk. PhRMA's staged TTC approach applies to all clinical routes and to compounds at all stages of development, for identified and predicted impurities. The TTC limits would not apply to already marketed products.
US FDA has considered both the guidelines in setting limits on genotoxic impurities.
Emea Guideline On Limits Of Genotoxic Impurities
The European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) published a guideline on the limits of genotoxic impurities. This guideline recommends dichotomizing genotoxic impurities into those for which there is "sufficient (experimental) evidence for a threshold-related mechanism" and those "without sufficient (experimental) evidence for a threshold-related mechanism.
" Those genotoxic compounds with sufficient evidence would be regulated using methods outlined in ICH Q3C, for class 2 solvents. This approach calculates a "permitted daily exposure" (PDE) which is calculated using the NOEL or LOEL from the most relevant animal study plus incorporation of safety factors. Examples of genotoxins that may fall into this class include chemicals that induce aneuploidy by interfering with the mitotic spindle, chemicals interfering with activity of topoisomerase or chemicals that inhibit DNA synthesis.
For genotoxic compounds without sufficient evidence for a threshold-related mechanism, the guideline proposes a policy of controlling levels to "as low as reasonably practicable" (ALARP principal). This approach specifies that every effort should be made to prevent the formation of such compounds during drug substance synthesis and, if not possible, efforts should be made to reduce such impurities through technical efforts (e.g. purification steps). Compounds falling into this class are generally those that interact with DNA either directly or indirectly such as alkylating agents, intercalating agents or agents generating free radicals. Since all exposures to such agents theoretically convey some level of carcinogenic risk, regulatory agencies generally perform quantitative risk assessments to calculate the increased levels of adverse events, such as cancers, that result from particular exposures and set exposure levels which result in "acceptable" risks; often 1 in 105 or 1 in 106 additional cancers from lifetime exposures.
While the approach described above has sound scientific support, in most instances sufficient mechanistic data will be lacking with which to decide whether a threshold mechanism is applicable for genotoxic impurities. Furthermore, it is also unlikely that data will exist on which quantitative risk assessments can be performed. The guideline recognizes these limitations and therefore proposes the use of a "threshold of toxicological concern" (TTC) for genotoxic impurities. The TTC refers to a threshold exposure level to compounds that will not pose a significant risk of carcinogenicity or other toxic effects and was originally developed as a "threshold of regulation" for food contact materials by the FDA. The draft guideline proposes a TTC of 1.5 ug/day. This threshold corresponds to a 10-5 lifetime risk of cancer, a risk level that the EMEA considers justified due to the benefits derived from pharmaceuticals. Importantly, however, this draft guideline only addresses levels of genotoxic impurities in marketed products; the guideline is silent on what might constitute acceptable TTCs for drugs during development, especially for trials of short duration.
1- Genotoxic Compounds with Sufficient Evidence for a Threshold-Related Mechanism
Examples of mechanisms of genotoxicity that may be demonstrated to lead to non-linear or thresholded dose-response relationships include interaction with the spindle apparatus of cell division leading to aneuploidy, topoisomerase inhibition, inhibition of DNA synthesis, overloading of defence mechanisms, metabolic overload and physiological perturbations (e.g. induction of erythropoeisis, hyper- or hypothermia). For (classes of) compounds with clear evidence for a thresholded genotoxicity, exposure levels which are without appreciable risk of genotoxicity can be established according to the procedure as outlined for class 2 solvents in the Q3C Note for Guidance on Impurities: Residual Solvents. This approach calculates a "Permitted Daily Exposure" (PDE), which is derived from the NOEL, or the lowest observed effect level (LOEL) in the most relevant (animal) study using "uncertainty factors" (UF).
2- Genotoxic Compounds without Sufficient Evidence for a Threshold-Related Mechanism
The assessment of acceptability of genotoxic impurities for which no threshold mechanisms are identified should include both pharmaceutical and toxicological evaluations. In general, pharmaceutical measurements should be guided by a policy of controlling levels to "as low as reasonably practicable" (ALARP principle), where avoiding is not possible. Levels considered being consistent with the ALARP principle following pharmaceutical assessment should be assessed for acceptability from a toxicological point of view.
2.1 Pharmaceutical Assessment
A rationale of the proposed formulation/manufacturing strategy should be provided based on available formulation options and technologies. The applicant should highlight, within the chemical process and impurity profile of active substance, all chemical substances, used as reagents or present as intermediates, or side-products, known as genotoxic and/or carcinogenic (e.g. alkylating agents). More generally, reacting substances and substances which show "alerting structure" in terms of genotoxicity which are not shared with the active substance should be considered. Potential alternatives which do not lead to genotoxic residues in the final product should be used if available. A justification needs to be provided that no viable alternative exists, including alternative routes of synthesis or formulations, different starting materials. This might for instance include cases where the structure, which is responsible for the genotoxic and/or carcinogenic potential, is equivalent to that needed in chemical synthesis (e.g. alkylation reactions).
If a genotoxic impurity is considered to be unavoidable in a drug substance, technical efforts (e.g. purification steps) should be undertaken to reduce the content of the genotoxic residues in the final product in compliance with safety needs or to a level as low as reasonably practicable. Data on chemical stability of reactive intermediates, reactants, and other components should be included in this assessment. Detection and/or quantification of these residues should be done by state-of-the-art analytical techniques.
2.2 Toxicological Assessment
The impossibility of defining a safe exposure level (zero risk concept) for genotoxic carcinogens without a threshold and the realization that complete elimination of genotoxic impurities from drug substances is often unachievable, requires implementation of a concept of an acceptable risk level, i.e. an estimate of daily human exposure at and below which there is a negligible risk to human health. However, these approaches require availability of adequate data from long-term carcinogenicity studies. In most cases of toxicological assessment of genotoxic impurities only limited data from in vitro studies with the impurity (e.g. Ames test, chromosomal aberration test) are available and thus established approaches to determine acceptable intake levels cannot be applied. Calculation of "safety multiples" from in vitro data (e.g. Ames test) are considered inappropriate for justification of acceptable limits. Moreover, negative carcinogenicity and genotoxicity data with the drug substance containing the impurity at low ppm levels do not provide sufficient assurance for setting acceptable limits for the impurity due to the lack of sensitivity of this testing approach. Even potent mutagens and carcinogens are most likely to remain undetected when tested as part of the drug substance, i.e. at very low exposure levels. A pragmatic approach is therefore needed which recognizes that the presence of very low levels of genotoxic impurities is not associated with an unacceptable risk.
Benefits of the use of the TTC approach:
The establishment of more widely accepted TTC values would benefit consumers, industry and regulators. By avoiding unnecessary extensive toxicity testing and safety evaluations when human intakes are below the relevant TTC value, it will allow limited resources of time, animal use, cost and expertise to be devoted to the testing and evaluation of those substances with greater potential to pose risks to human health. In consequence, its application will contribute to a considerable reduction in the number of animals used for safety testing.
Considerations On Testing Of Impurities For Genotoxic Potential:
The general framework for genotoxicity testing of pharmaceuticals is given in two internationally agreed ICH safety guidelines (ICH S2A, ICH S2B). One of these guidelines (ICH S2B) describes the standard battery of tests for genotoxicity for drug substance, which consists of:
(i)A test for gene mutation in bacteria.
(ii)An in vitro test with cytogenetic evaluation of chromosomal damage in mammalian cells
(iii)An in vivo test for chromosomal damage in rodent hematopoietic cells.
The ICH safety guidelines (S2A and S2B) state: ''for compounds giving negative results, the completion of this 3-test battery, performed and evaluated in accordance with current recommendations, will usually provide a sufficient level of safety to demonstrate the absence of genotoxic activity.'' In this context, genotoxicity is a broad term encompassing effects from mutagenicity through DNA reactivity, DNA damage, and chromosomal damage, both structural chromosome breakage and aneuploidy. Any compound that produce a positive result in one or more assays in the standard battery has historically been regarded as genotoxic, which may require further testing for risk assessment. Thus, the standard battery of genotoxicity assays used for testing the API provides important information about a diversity of mechanisms of genotoxicity, both directly and indirectly associated with effects on DNA. Genotoxicants that do not act directly on DNA are typically associated with threshold-related mechanisms, while those that directly target DNA (typically detected in assays measuring the reverse or forward mutations in a specific gene with a selection agent) are considered by regulatory authorities not to have threshold- related mechanisms. Requirements for control of genotoxic impurities in pharmaceutical products are different depending upon whether or not there is evidence for a threshold-related mechanism. DNA-reactive genotoxic impurities for which there is no evidence of a threshold-related mechanism are regarded to be potentially trans-species and multi-organ carcinogens that may require control at relatively low levels. In contrast, it is accepted that impurities acting via threshold-related mechanisms do not require control at similarly low levels. Since the main concern that should drive control of impurities to relatively low levels is direct DNA reactivity, the primary endpoint of relevance for genotoxic impurities is mutagenicity. DNA-reactive carcinogens can be identified with a low incidence of false negative results by a procedure that combines the assessment of chemical structural features that infer DNA reactivity (such as electrophilicity) with a single biological hazard identification test such as a bacterial reverse mutation test, known as the ''Ames test''. A flexible use of this approach is sometimes advisable since genotoxicity assessment of impurities in mammalian cells may be needed for specific structural groups, such as carbamates, which are known carcinogens and that are known to be inefficiently detected in bacterial genotoxicity tests. A clearly negative result in an appropriate genotoxicity test (i.e., a bacterial reverse mutation test or mammalian cell assay) usually indicates a sufficient level of safety to conclude the absence of genotoxicity for the purpose of controlling impurities.
Impurity Classification With Respect To Genotoxic Potential:
It is proposed here that impurities be classified into one of five classes using data (either published in the literature or from genotoxicity testing) and comparative structural analysis to identify chemical functional moieties correlated with mutagenicity. The five classes are:
Class 1--Impurities known to be both genotoxic (mutagenic) and carcinogenic
This group includes known animal carcinogens with reliable data for a genotoxic mechanism and human carcinogens. Published data on the chemical structure exist demonstrating the genotoxic nature of the impurity.
Class 2--Impurities known to be genotoxic (mutagenic), but with unknown carcinogenic potential
This group includes impurities with demonstrated mutagenicity based on testing of the impurity in conventional genotoxicity tests, but with unknown carcinogenic potential.
Class 3-- Alerting structure, unrelated to the structure of the API and of unknown genotoxic (mutagenic) potential.
This group includes impurities with functional moieties that can be linked to genotoxicity based on structure, but which have not been tested as isolated compounds. They are identified based on chemistry and using knowledge based expert systems for structure-activity relationships. The alerting functional moiety is not present in the structure of the parent API. Some widely recognized alerts for DNA reactivity, i.e., mutagenic activity, are depicted in Fig. 9.1.
Some generic rule-based alerts may be quite unspecific (e.g., the general alerts for aromatic amines; and further consideration must be given to chemical structural constraints, chemical environment, or experimental data in the assessment of potential genotoxicity. Due to the uncertain relevance of structural alerts, regulatory action should not be based solely on the presence of a particular functional group; rather the accuracy for predicted genotoxicity should be evaluated case-by-case based on the available scientific literature, additional unpublished (proprietary) data on the chemical class and further available (genotoxicity) test results on closely related structures.
Class 4--Alerting structure, related to the API
This group includes impurities that contain an alerting functional moiety that is shared with the parent structure. The genotoxicity of the isolated impurity is unknown, but the genotoxicity of the active principle has been characterized through conventional genotoxicity testing. Similar chemical constraints and chemical environment exist for the alerting substructure in the impurity and the API.
Alkyl, Aryl, or H
Halogen = F, Cl, Br, I
EWG = Electron withdrawing group (CN, C=O, ester, etc)
Fig. 9.1 some examples of structurally alerting functional groups that are known to be involved in reactions with DNA (this list is not exhaustive) (Muller et al., 2006).
Class 5--No alerting structure or sufficient evidence for absence of genotoxicity
This group would be adequately covered by existing ICH Q3A(R), Q3B(R), and Q3C guidelines. It has to be emphasized that this classification system would be used solely for the purpose to decide whether an impurity possesses a high level of risk and is therefore to be controlled at very low levels of daily intake. Hence, this classification is not a general classification of genotoxicity.
Phrma Genotoxic Impurity Task Force White Paper:
The Pharmaceutical Research and Manufacturing Association (PhRMA) established a Genotoxic Impurity Task Force which developed a White Paper (document outlining the proposal is currently in press) and presented their proposal at various public meetings. The document outlines a procedure for testing, classification, qualification and toxicological risk assessment of potentially genotoxic impurities in pharmaceutical products. The Task Force proposed that all identified or predicted impurities should be classified into one of five classes: those known to be genotoxic (mutagenic) and carcinogenic, those known to be genotoxic (mutagenic) but with unknown carcinogenic potential, those with a unique alerting structure and of unknown genotoxic (mutagenic) potential, those with an alerting structure related to the parent active pharmaceutical ingredient, and those with no structural alert.
The Task Force proposal for addressing genotoxic impurities for marketing applications is similar to that of the previously described EMEA draft guideline. However, the Task Force recognizes that the TTC established a limit for daily human exposure to genotoxic impurities for lifelong treatment while most medicines are given for limited time spans, especially in early clinical development. Therefore, the Task Force proposes a staged TTC approach with adjusted limits for shorter duration clinical trials. The adjusted limits are derived from a linear extrapolation of the TTC for a lifetime daily exposure to short term daily exposures. The proposed limits for short-term exposures (?12 months) are based on a 10-6 risk because of the common inclusion in clinical studies of normal volunteers, for whom there is assumed to be no pharmacological benefit. The proposed limit for exposures greater than 12 months in duration is based on a 10-5 risk, because individuals in longer-term clinical studies have the target indication and may benefit from treatment, an approach consistent with the EMEA guideline.
Us Fda Center For Drug Evaluation And Research Guidance On Genotoxic Impurities:
ICH guidances do not provide clear recommendations for handling these types of impurities. The Center for Drug Evaluation and Research (CDER) of the USFDA is developing guidance to address issues with genotoxic impurities in pharmaceutical products. The CDER is considering the proposals of the EMEA and PhRMA in developing its guidance. The presence of genotoxic impurities should be avoided if possible. However, it is recognized that complete removal is often not possible. In these cases, the amounts of genotoxic impurity present should be limited to a level that represents an insignificant increase in risk to clinical trial subjects or patients.
This level may be based on adequate compound-specific data to calculate an acceptable risk-specific dose or may be based on a toxicological threshold derived from a robust carcinogenicity database. A staged implementation of the threshold approach is considered acceptable for products that are under development. In applying qualification thresholds, consideration should be given to the product's stage of clinical development, the maximum duration of drug administration at that stage, and the proposed indication. In some cases, increases in the recommended thresholds may be supported in the presence of a potential pharmacological benefit to patients.
Analysis Of Genotoxic Impurities:
In general, impurities should be quantitated at levels ?0.03 or 0.05% by weight according to ICH guidelines. Genotoxic impurities or potential genotoxic impurities must be controlled at levels significantly lower than the 0.03-0.05% levels that are typically reported by an HPLC impurity assay. Typically, developing limit tests (e.g. <50 ppm) for highly toxic impurities is readily achievable, however it can be difficult to develop a test to control a particular genotoxic impurity at 1 ppm (0.0001% w/w).
"For genotoxic impurities we need very sensitive and selective methods. One needs higher selectivity to determine ppm - level impurities and selective methods to separate low levels of genotoxic impurities from base line noise and other organic impurities. The typical HPLC methods with a nonspecific detector (e.g. UV) that are used to measure organic impurities may not be appropriate to quantitate low ppm levels of genotoxic impurities.
The quantitation of low levels (in the range of ppms) of impurities is the challenging part, and using specific detectors such as MS or MS-MS with LC will significantly improve the method selectivity and the quantitation limit. The goal for scientists is to identify potential genotoxic impurities early in development, develop analytical methods to test for these impurities in the intermediates, and if possible, to demonstrate that the manufacturing process controls them before reaching the final drug substance. "If you eliminate them early enough, then your actual active drug substance is pure, free of genotoxic impurities".
Genotoxic Impurities In Food Products:
Compounds that are both carcinogenic and genotoxic frequently give rise to difficulties for regulators and food businesses when they are present at low levels in foods. Among regulatory and advisory bodies, such as JECFA, EFSA and FDA, there is no international consensus on how to evaluate the potential risk of genotoxic carcinogens in food. In Europe , the Scientific Committee on Food (SCF) has addressed the topic of chemicals that may be genotoxic carcinogens in a written opinion. The SCF has evaluated genotoxic carcinogens in the diet (such as contaminants and natural toxicants) on a case by-case basis using a ''weight of evidence'' approach, whereas in the USA (e.g. US EPA), as well as in some European countries (e.g. Norway ), a quantitative risk characterization is commonly performed by mathematical low dose extrapolation of animal data. It is recognized that current risk analysis approaches to compounds in food that are genotoxic and carcinogenic in experimental animals may sometimes incur disproportionate or even unnecessary measures on the part of regulators and industry.
The risk assessment of genotoxic carcinogens has been considered recently by the European Food Safety Authority (EFSA) and by the WHO/FAO Joint Expert Committee of Food Additives (JECFA). In 2003, EFSA established a Working Group to consider how to improve advice given on the health risks arising from the presence in food of compounds that are both genotoxic and carcinogenic.
DNA-reactive carcinogens have long been known to be present in the human diet. Most problems with DNA-reactive carcinogens in food arise from chemicals that are either natural food constituents (such as ethyl carbamate) or contaminants (such as acrylamide, heterocyclic amines, polycyclic aromatic hydrocarbons and heterocyclic amines such as PhIP (2- amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), which are formed during cooking processes or by fungal toxins (such as aflatoxins) because they cannot be completely eliminated from the human diet unless the food itself is banned. Compounds that are incorporated into food intentionally, either directly (e.g. additives) or indirectly (e.g. residues of processing aids, pesticides, veterinary drugs or migrants from food contact materials) are assessed for their genotoxic and carcinogenic potentials prior to marketing, and compounds that might be DNA-reactive carcinogens would not be permitted.
Risk characterization:
Risk characterization has been defined as ''the quantitative or semi-quantitative estimate, including attendant uncertainties, of the probability of occurrence and severity of adverse effect(s)/event(s) in a given population under defined conditions based on hazard identification, hazard characterization and exposure. At its best, a risk characterization ''synthesizes an overall conclusion about risk that is complete, informative and useful for decision makers''. The usual hazard characterization approach for compounds that cause cancer by non-DNA-reactive mechanisms is to calculate a health-based guidance value, such as a tolerable daily intake, using the no-observed adverse effect level and uncertainty factors. Such an approach is not used for compounds that cause cancer by DNA-reactive mechanisms. The decision-making environment also may dictate the nature and focus of the advice. Depending upon the circumstances, risk managers could be presented a risk characterization containing only a qualitative judgment of risk. Alternatively, the risk characterization may include one or more quantitative estimates of risk in addition to the qualitative judgment. Whichever method of risk characterization is adopted, the output is only as reliable as the quality of the data used. This applies to all data used, i.e. hazard identification, hazard characterization and dose-response analysis and exposure estimation.
The decision-making environment also may dictate the nature and focus of the advice. Depending upon the circumstances, risk managers could be presented a risk characterization containing only a qualitative judgment of risk. Alternatively, the risk characterization may include one or more quantitative estimates of risk in addition to the qualitative judgment. Whichever method of risk characterization is adopted, the output is only as reliable as the quality of the data used. This applies to all data used, i.e. hazard identification, hazard characterization and dose-response analysis and exposure estimation.
The only data essential for qualitative approaches, such as ALARA (as low as reasonably achievable), is identification of the compound as a genotoxic carcinogen. An important decision is that the genotoxicity arises via direct covalent binding to DNA, rather than via a mechanism that would show a threshold in the dose-response relationship. Often data are available from a variety of genotoxicity tests and the decision is based on a weight of evidence approach, which takes into account the quality of the available data. Although the ALARA principle is an easy to understand concept, it poses some major difficulties for the risk manager as it does not discriminate between very potent and very weak carcinogens and does not take human exposure into account. It does not give any guidance on the magnitude of any risk that might be associated with a given ''reasonably achievable'' low exposure level. Although these difficulties would point to the alternative approach of calculating the intake levels associated with ''acceptably small risks'', the mathematical models necessary may give widely divergent answers and do not provide a reliable basis for the formulation of realistic risk management advice.
Conclusion :
The control of impurities bearing a genotoxic potential in pharmaceutical products and food products has received more and more attention over the past years. The inherent difficulties of true or hypothesized linear dose effect relationships have led to diverse strategies and risk calculations to achieve a rational level of control. Hence, a unified approach for product development and marketing would be useful. The ultimate risk concern for genotoxicants is carcinogenicity but carcinogenicity data are not available in most cases. Hence, a risk assessment based on surrogate data such as structure-activity relationships and limited genotoxicity testing in bacterial reverse mutation tests, knowledge about the relationship between genotoxicity and carcinogenicity, and a generic determination of virtually safe exposure levels for the world of genotoxic carcinogens is proposed. The risk assessment is based on Threshold of Toxicological Concern (TTC) approach for the intake of genotoxic impurities over various periods of exposure. This staged TTC is based on knowledge about tumorigenic potency of a wide range of genotoxic carcinogens and can be used for genotoxic compounds, for which cancer data are limited or not available. The delineated acceptable daily intake values of between ~1.5 mg/day for ~ lifetime intake and ~120mg/day for < 1 month are virtually safe doses. Based on sound scientific reasoning, these virtually safe intake values do not pose an unacceptable risk to either human volunteers or patients at any stage of clinical development and marketing of a pharmaceutical product. The intake levels are estimated to give an excess cancer risk of 1 in 100,000 to 1 in a million over a lifetime, and are extremely conservative given the current lifetime cancer risk in the population of over 1 in 4. This approach, together with a proactive process analysis of the chemistry behind the synthesis of the pharmaceutical product and matching analytical capabilities, ensures patient and volunteer safety and may not hinder inappropriately the fastest possible development of new medicines to improve patient health.
Apart from pharmaceuticals various difficulties are presented due to presence of low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, thus a structured approach has been proposes for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritization based on potential risk or concern.
In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.
References :
- Jacobson-kram, D., Mcgovern, T., 2007. Toxicological overview of impurities in pharmaceutical products. Advanced drug delivery reviews 59, 38-42.
- Muller, L., Mauthe, R.J., 2006. A rationale for determining, testing and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regulatory Toxicology and Pharmacology 44, 198-211.
- Rios, M., 2007. The impact of impurity analysis on future regulations. Pharmaceutical technology.
- CPMP, 2006. Guidelines on the limits of genotoxic impurities.
- Kroes, R., Kleiner, J., 2005. The threshold of toxicological concen concept in risk assessment. Toxsci. Advance. Access.
- Brian, J.O., Renwick, A.G., 2006. Approaches to the risk assessment of genotoxic carcinogen in foods: a critical appraisal, food and chemical toxicology 44, 1613-1635.
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Default password
Where a device needs a username and/or password to log in, a default password is usually provided that allows the device to be accessed during its initial setup. Manufacturers of such equipment typically use a simple password, such as admin or password on all equipment they ship, in the expectation that users will change the password during configuration.
Generally, if the current password of a device is not available it may be necessary to reset the device to factory defaults to re-enable the default password it was provided with from the factory. This often resets the entire device to factory defaults and includes all configuration and data. The default username and password is usually located in the instruction manual or located on the device itself.
Leaving the default password on devices connected to an open network (such as the internet) is a huge security risk.[1]
See also[edit]
External links[edit]
Examples of default password databases:
- Default device and software passwords
- Default Passwords
- Default password list
- Alecto - Default password Database Project
- Default password Database
- Default Password List
- Default OEM password database
This cryptography-related article is a stub. You can help Wikipedia by expanding it. |


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Joakim Soria to have elbow checked
Kansas City Royals closer Joakim Soria will have his sore right elbow checked by Dr. Lewis Yokum in Los Angeles on Tuesday.
Schoenfield: Holland Has The Pitches
Right-hander Greg Holland has the weapons to step in for Joakim Soria as the Royals' closer, writes David Schoenfield. SweetSpot
Soria left Sunday's game after retiring only one of five batters he faced and said after the outing that his elbow felt "really bad."
Royals spokesman Mike Swanson said Monday the team believes Soria has some damage in the area of his ulnar collateral ligament.
Soria had Tommy John surgery on his elbow in 2003. He has been one of the best relievers in the American League since his rookie season of 2007, but his performance fell off last year. His ERA jumped to 4.03 and he had 28 saves, but lost the closer's job at times.
Copyright 2012 by The Associated Press
- Crasnick: Forming a formidable duo
- Caple: Ichiro returns to Japan with M's
- Caple: 49 things to know about Moyer
- Crasnick: Angels' Trout will have his day
- Stark: Lawrie bound for greatness
- Crasnick: One last season for Chipper
- Caple: A new beginning for Manny
- Stark: Educational experience for Harper
- Stark: Ramirez happy, healthy for Marlins
- Caple: Lane making comeback as reliever
- Crasnick: Keeping Lincecum and Cain
- Crasnick: Call it a South Side style change
- Stark: Phillies' infield beset by injuries
- Stark: Dotel the king of changing places
- Caple: Diamondbacks' Bauer quite unique
- Arangure: Long road for Grandal, Alonso
- Crasnick: D-backs' Drew taking small steps
- Crasnick: Darvish shines in spring debut
- Stark: McCutchen deal a positive for Bucs
- Crasnick: Youngsters give K.C. high hopes
- Stark: Whole lot to watch at Tigers camp
- Stark: Jays primed for postseason return
- Crasnick: Cubs' LaHair gets his big chance
- Crasnick: Cuddyer up to his old tricks
- Crasnick: Nicasio working on a miracle
- Stark: Chipper can see the end of the line
- Crasnick: Rangers seeking that true ace
- Stark: Rays' rotation all about quality
- Crasnick: Reds getting a read on Latos
- Stark: Braves avoid making changes
- Crasnick: Pujols' intro as an Angel
- Crasnick: Posey readying himself for 2012
- Stark: Cards move on with new faces
- Stark: Papelbon can't escape Boston past
- Blengino: Stephen Strasburg's contact issue
- Olney: MLB's difficult decision on Hamilton
- Szymborski: How bad teams can still compete
- Karabell (fantasy): Bounce-back candidates
- Karabell (fantasy): Top 200 rankings
- Law: Updated Top 100 prospects


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text: TOP 10 Top 10 Better Man iPhone 5S Back to Top ▲ iPhone 5S 3 Camera Share on Facebook Share on Twitter 0 Shares Arguably the single most important piece of hardware in a smartphone these days is the camera, and Apple appears to have made significant strides in this department. The iPhone 5S sports an 8MP camera and has a new feature in the form of a dual-LED flash system that should help in low-light photography scenarios. Next Page TOP 5 4 3 2 1 Comments Show Comments More Like This Promoted Around the Web Special Features


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We have received another great Police Trade-In firearm guaranteed to go down in the history of Budsgunshop.com as one our ultimate super buys.
Smith and Wesson Model 10 38special Square Butt Grip.
Blue 4" Barrel 38 special caliber.
These guns are in 70%-80% with some holster wear, light scratches, and possibly some very light surface rust.
6 shot capacity.
Very tight lockup and smooth Smith and Wesson trigger.
As always Budsgunshop.com guarantees function on these revolvers.
This gun is not legal in Calif.
Seems that if law enforcement could trust it, it must be dandy for home defense. Still a little stumped on why a < 10rd gun isn't legal in CA. (maybe it's just a CA thing)


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Your game plan for sensible celebrating
Drinks before dinner, Aunt Sarah's famous pies, the family favorite sausage dressing, and all those other wonderfully delicious, traditional holiday foods just waiting to be gobbled up: What a quagmire for a dieter!
Should you forget about your eating plan for a day, and eat to your heart's content? Or should you try to stay on course as you navigate this minefield of temptations and family prodding?
My advice: Do both.
Throughout the holiday season, temptations are everywhere -- a busy social schedule, office and school parties, family functions, and neighborly gestures of sweets and treats. You need a strategy for dealing with the abundance of calories that are part and parcel of the holiday season.
Just Try to Maintain
Most people gain 2-5 pounds each year during the feasting season that starts at Thanksgiving and ends New Year's Day -- unless you live in New Orleans, where it continues through Mardi Gras. So how do you buck this trend and keep from adding back those hard-lost pounds?
The plan: Aim to hold steady at your current weight and focus on not gaining any additional pounds by Jan. 1. Adhere strictly to your plan until Thanksgiving, then cut yourself some slack but not too much.
Just knowing that you don't have face the pressure of losing weight during the holiday season -- and that you won't feel deprived as others celebrate -- will make it easier to balance your calories for maintenance.
If you prefer to keep losing, on the other hand, by all means stick with your eating plan through the holidays. Just be mindful that a dieter's most difficult time of year is upon us.
The Sensible Splurge
It is so hard to resist temptation, but it gets easier if you're equipped with a plan. Follow these tips to help you survive family gatherings without sabotaging your diet.
- Review your eating plan and see if you can reserve a few food items during the week to save up for the holiday feast. Be careful not to take away too much food, which could leave you hungry during the week. Getting hungry between meals can lead to bingeing, and we sure don't want that to happen!
- Portion control is critical to prevent weight gain. Enjoy small portions of foods high in fat and calories, share a dessert, limit alcohol, and fill up on simply prepared, nutritious selections like turkey breast and vegetables.
- Enjoy a small but filling meal before the gathering to prevent overeating. Include a lean or low-fat source of protein, as well as fiber from fruits, vegetables, beans, nuts, or whole grains for lasting fullness. A salad, a bowl of vegetable soup, or a sandwich on whole-grain bread are all good examples of mini-meals.
- Don't stand near the buffet or appetizers at a holiday gathering. Instead, survey the offerings, choose the best nutritional bets, put them on a plate, then go sit down and enjoy the meal. It's hard to know when you've had enough food when you stand around nibbling!


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Missing Teenage Girl Returns Home
Wednesday, August 6, 2014
(Honolulu, HI) -- A teenage girl who had been missing for two-and-a-half weeks is now safe and sound. Honolulu Police say 15-year-old Tiana Omayas-Kalili returned home on Sunday. She had been reported missing after not showing up to her ROTC program at Waianae High School on July 17th. Police have not released the circumstances surrounding her disappearance.


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People who use personal audio players should consider limiting their use to one hour a day and turn down the volume to prevent permanent hearing loss, the World Health Organization said Friday.
They're considered one of mankind's greatest medical achievements, yet people have balked at vaccines almost since the time of the first vaccination - in 1796, when an English country doctor named Edward Jenner inoculated an 8-year-old boy against smallpox.
At age 3, Angelica Lopez is helping to break a sound barrier for deaf children.
A new partnership with Oregon Health and Science University is bringing a high tech boost to cancer treatment at Bay Area Hospital.
At age 3, Angelica Lopez is helping to break a sound barrier for deaf children.
DNA barcoding has exposed some infamous cases of food fraud, like cheap catfish sold as pricey grouper and expensive "sheep's milk" cheese that was really made from cow's milk.
The Washington health exchange is 81,000 short of its goal for signing people up for insurance this year.
The World Health Organization says the two leading Ebola vaccines appear safe and will soon be tested in healthy volunteers in West Africa.
The flu is rampant in most of the country, and health officials say the season could peak soon.
Health officials are celebrating some important victories in 2014, and Time magazine even named Ebola fighters the persons of the year. Nevertheless, this was a black-eye year for public health.
Hershey is looking at replacing the high-fructose corn syrup in some of its products with sugar.
Reading about Harry Potter's adventures learning to fly his broomstick activates some of the same regions in the brain we use to perceive real people's actions and intentions.
Negotiations have bogged down between Mercy Medical Center in Roseburg and Regence Blue Cross Blue Shield of Oregon.
A major study lifts a cloud around Zetia and Vytorin, blockbuster drugs for lowering cholesterol.
As a crucial second sign-up season gears up, the Obama administration said Sunday that HealthCare.gov is stable and working well, a far cry from last year's frozen computer screens and frustrated customers.
They come in nearly every color scheme imaginable, from camouflage to bright pink. Most skiers and snowboarders on the slopes are wearing them, and if you're not, well, you are not just reckless, you are . GASP! . unfashionable.
Use of electronic cigarettes by high school students tripled over three years, according to a new government report released Thursday.
Dr. Robert Fuller didn't hesitate to go to Indonesia to treat survivors of the 2004 tsunami, to Haiti to help after the 2010 earthquake or to the Philippines after a devastating typhoon last year. But he's given up on going to West Africa to care for Ebola patients this winter.
Top medical experts studying the spread of Ebola say the public should expect more cases to emerge in the United States by year's end as infected people arrive here from West Africa, including American doctors and nurses returning from the hot zone and people fleeing from the deadly disease.
A Dallas nurse who recovered from Ebola has been reunited with her dog named Bentley, who has been quarantined since she fell ill.
Starting Monday, millions of people who have avoided colon cancer screening can get a new home test that's noninvasive and doesn't require the icky preparation most other methods do.
Because communities in Douglas County are in more rural areas, Dr. Bob Dannenhoffer says we are in a safe place. He says it's congested places near big airports where we have to be on guard.
Defense Secretary Chuck Hagel has ordered the military to prepare and train a 30-member medical support team that could provide short-term help to civilian health professionals if there are more Ebola cases in the United States.
Comparisons between the two deadly diseases surfaced in the last few months as the Ebola outbreak escalated. Both emerged from Africa and erupted into an international health crisis. And both have been a shocking reminder that mankind's battle against infectious diseases can take a sudden, terrible turn for the worse.
The largest U.S. gay-rights organization Saturday endorsed efforts to promote the use of a once-a-day pill to prevent HIV infection and called on insurers to provide more generous coverage of the drug.
Top government health officials said Sunday that they are opposed to placing a ban on travelers from Ebola-infected countries, warning that shutting down borders could impede efforts by aid workers to stop the spread of the deadly virus.
Ebola has arrived in the United States and people are scared. The nation's top infectious diseases expert said it's perfectly normal to feel anxious about a disease that kills so fast and is ravaging parts of West Africa.
A virus that has been causing severe respiratory illness across the country is responsible for the death of a 4-year-old boy, a state medical examiner determined.


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One of the earliest structured uses of dances may have been in the performance and in the telling of myths. It was also sometimes used to show feelings for one of the opposite gender. It is also linked to the origin of "love making." Before the production of written languages, dance was one of the methods of passing these stories down from generation to generation. Cultural dances are so precious to many civilizations, as they often contain pieces of their history and livelihood that would otherwise be lost. Many have looked to dance in the past as a way to convey joy, mourning, and even times of battle and war. The same is true at the roots of many people groups, as dance is a common language that unites us all on some level.
James born in 1946 in the then small town of Irvine in north Ayrshire Scotland. learned the basics of how to paint from my father using oils. Did not paint for many years until found a method of hand painting using an oil painting medium combined with a tablet. It has taken me some time to reach where I am today painting without limitations as to my choice of subjects from still life and landscapes to portraits, figurative and horse and dance movement. The style of my artwork is modern yet very traditional inspired by impressionist paintings and influenced by realistic styling to convey character and / or movement of my subjects hopefully allowing the viewer to enjoy a glimpse of the mood. My intention is to give a fresh perspective...
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This sort of thing is absolutely, definitely not to be encouraged. And yet the BBC's political editor Nick Robinson's election update last night was ever so slightly enlivened, not only by the mystery chap suddenly appearing behind him, but the Keystone Kops way in which he appeared to be chased off. By a BBC producer perhaps? As Robinson was saying at exactly the time he was interrupted, "it's all about personal credibility".
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