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Book your room at Hakuna Matata Beach Lodge & Spa
Comfort BungalowMax Occupancy: 2 guests
Comfort Bungalow (plus)Max Occupancy: 3 guests (up to 2 children, 1 infant)
Standard BungalowMax Occupancy: 2 guests (up to 1 child, 1 infant)
Honeymoon SuiteMax Occupancy: 3 guests (up to 2 children, 1 infant)
Executive Bungalow (Suite)Max Occupancy: 3 guests (up to 2 children)
Get an overview of this hotelLodge with private beach, full-service spa
Located in Bububu, this beachfront lodge is in the historical district and within 9 mi (15 km) of Chapwani Island, Shangani Beach, and Prison Island. Forodhani Gardens and Livingstone's House are also within 9 mi (15 km).
Property Features
Catch some rays on Hakuna Matata Beach Lodge & Spa's private sand beach, pamper yourself at the full-service spa, or enjoy snorkeling.
Room Amenities
All 14 individually decorated rooms feature free WiFi and pillowtop beds. Guests will also find patios, sitting areas, and room service.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
Simply walk outside to feel the sun on your face at the sand beach. Pamper yourself with a treatment at the full-service spa and enjoy amenities at Hakuna Matata Beach Lodge & Spa like an outdoor pool and a spa tub.
Guests can enjoy a complimentary breakfast each morning. Dining options at the lodge include a restaurant and a coffee shop/café. Guests can unwind with a drink at one of the lodge's bars, which include a beach bar and a bar/lounge. A computer station is located on site and high-speed wireless Internet access is complimentary. This beach lodge also offers a garden and a terrace. Complimentary self parking is available on site.
Hakuna Matata Beach Lodge & Spa has designated areas for smoking.
- Airport transportation - pickup (surcharge)
- Arcade/game room
- Bar/lounge
- Beach bar
- Beach sun loungers
- Beach towels
- Pool umbrellas
- Billiards or pool table
- Coffee shop or café
- Coffee/tea in lobby
- Computer station
- Designated smoking areas
- Dry cleaning/laundry service
- Free breakfast
- Free self parking
- Free WiFi
- Full-service spa
- Garden
- Gift shops or newsstand
- Hair salon
- Library
- Luggage storage
- Multilingual staff
- Number of buildings/towers - 18
- On private beach
- Outdoor pool
- Pool sun loungers
- Restaurant
- Spa services on site
- Spa treatment room(s)
- Spa tub
- Terrace
- Total number of rooms - 14
- Tours/ticket assistance
- Wedding services
- Year Built 2005
Family Friendly Amenities
- Arcade/game room
- Cribs/infant beds (complimentary)
- Free Wi-Fi
- On private beach
- Outdoor pool
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Free self parking
Room Amenities
- Air conditioning
- Ceiling fan
- Free toiletries
- Free cribs/infant beds
- Daily housekeeping
- Day bed
- Free WiFi
- Hair dryer
- In-room safe (laptop compatible)
- Individually decorated
- Individually furnished
- Patio
- Phone
- Pillowtop mattress
- Premium bedding
- Private bathroom
- Room service
- Room service (limited hours)
- Separate sitting area
- Shower only
- Turndown service
Where to Eat
A complimentary cooked-to-order breakfast is served each morning between 7:30 AM and 10 AM.
Onsite venue - This beachfront restaurant specializes in international cuisine and serves lunch and dinner.
Room service (during limited hours) is available.
Nearby Things to Do
An outdoor pool and a spa tub are on site. Other recreational amenities include a private beach.
Children under 6 years old are not allowed in the swimming pool without adult supervision.
The recreational activities listed below are available either on site or nearby; fees may apply.
- Scuba diving nearby
- Boat tours on site
- Bicycle rentals on site
- Ecotours on site
- Fishing on site
- Snorkeling on site
Spa Services
Sultans Spa has 2 treatment rooms. Massages are available on the beach and in the spa; other services include deep-tissue massages, hot stone massages, and Swedish massages. A variety of treatment therapies are provided, including aromatherapy. The spa is equipped with a spa tub.
Children under 8 years old are not allowed in the spa without adult supervision.
- Facial treatments
- Massages
- Body scrubs
- Massages on beach
- Manicures and pedicures
- Hot stone massage
- Deep tissue massage
- Swedish massage
- Aromatherapy treatments
- Spa tub in spa
- Body wraps
- Number of treatment rooms 2
- Body treatments
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible bathroom
- Roll-in shower
Hotel Policies
Check-in time starts at 8 AM
Check-in time ends at 8 PM
Check-out time is 11 AM
Payment types
Children and extra beds
- Children are welcome.
- Kids stay free! Children stay free when using existing bedding. Children may not be eligible for complimentary breakfast.
- Free cribs (infant beds)!
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
Only service dogs are allowed
No rollaway/extra beds available
- New Year's Eve (31 December) Gala Dinner per adult: TZS 50.00
- Resort fee
Optional extras
- Airport shuttle fee: TZS 45000 per vehicle (one-way)
We should mention
Reservations are required for massage services and spa treatments. Reservations can be made by contacting the lodge prior to arrival, using the contact information on the booking confirmation. A resort fee is included in the total price displayed. Only registered guests are allowed in the guestrooms.


text:
Bugs, bruisers and buddies
Gary Guidice and Ed Weber are back at it, scouring Colorado, "the best trout state," for it best stream
Updated: July 10, 2010, 2:14 AM ETBy Gary Giudice | Special to ESPNOutdoors.com
Editor's note: Contributor Gary Giudice, who penned Wannabe Trout Bums and The Slam Haunts Me for ESPNOutdoors.com, is back with trout buddy Ed Weber as they scour Colorado which they deem the best trout state searching for its best trout stream.
Colorado may be the best trout state in America. Ed Weber and I think so. We're no experts by any means, but we have fished every state that claims a trout fishery.
So now we're in "The Rocky Mountain State" searching ...
Read full story
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subset: commoncrawl


text:
Love Blacktually
Family Guy, Series 7 Episode 1 of 16
Brian meets the girl of his dreams, Carolyn. However, Cleveland moves right in and sweeps Carolyn off her feet. Desperate to win her back, Brian must do anything he can, even if it means involving Cleveland's ex-wife, Loretta.
On TV
Next Monday 23:25
More episodes
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text:
|Good habits, which bring our lower passions and appetites under automatic control, leave our natures free to explore the larger experiences of life. Too many of us divide and dissipate our energies in debating actions which should be taken for granted.
– Ralph W. SockmanRate it:
|Good heart is the best religion; its light is the most powerful light.
– Mehmet Murat ildanRate it:
|Good humor is a paradox. The unexpected juxtaposition of the reasonable next to the unreasonable.
– HelitzerRate it:
|Good humor is one of the best articles of dress one can wear in society.
– William Makepeace ThackerayRate it:
|Good humor isn't a trait of character, it is an art which requires practice.
– David SeaburyRate it:
|Good ideas are not adopted automatically. They must be driven into practice with courageous patience.
– Hyman RickoverRate it:
|Good instincts usually tell you what to do long before your head has figured it out.
– Michael BurkeRate it:
|Good intention is even better than the best action, but both are one and the same in the life of a positive person.
– Anuj SomanyRate it:
|Good intentions will always be pleaded for every assumption of authority. It is hardly too strong to say that the Constitution was made to guard the people against the dangers of good intentions. There are men in all ages who mean to govern well, but they mean to govern. They promise to be good masters, but they mean to be masters.
– Daniel WebsterRate it:
|Good is good and enough is enough, but good enough is not…
– Chase LeBlancRate it:
|Good is not always good.
– Dejan StojanovicRate it:
|Good judgement comes from experience. Experience comes from bad judgement.
– UnknownRate it:
|Good judgement comes from valuable experience; and paradoxically, such "valuable experience" is the direct product of many bad judgements made in the past.
– Deodatta V. Shenai-KhatkhateRate it:
|Good judgement is the result of experience ... Experience is the result of bad judgement.
– Fred BrooksRate it:
|Good judgment comes from experience, and experience comes from bad judgment.
– Barry LePatnerRate it:
|Good judgment comes from experience, and often experience comes from bad judgment.
– Rita Mae BrownRate it:
|Good knowledge of an art or profession is essential to be successful in life. A man with insufficient knowledge will always cause harm to himself and others.
– Vikrant ParsaiRate it:
|Good laws have their origins in bad morals.
– Ambrosius MacrobiusRate it:
|Good leaders always understand that Leadership is neither a recognition award nor a license to execute power, but it's a great responsibility to bring out the best in others while meeting their organizational goals.
– Deodatta V. Shenai-KhatkhateRate it:
|Good Leaders are always in short supply. It's been an all time scarce commodity. The good thing is that there is also very little competition to become a Good Leader. So you should join that line, and be a Good Leader. Good Luck!
– Deodatta V. Shenai-KhatkhateRate it:
|Good leaders make people feel that they're at the very heart of things, not at the periphery. Everyone feels that he or she makes a difference to the success of the organization. When that happens people feel centered and that gives their work meaning.
– Warren BennisRate it:
|Good leaders must first become good servants.
– Robert GreenleafRate it:
|Good leadership consists in showing average people how to do the work of superior people.
– John D. RockefellerRate it:
|Good looking and good luck rarely walk the same road.
– Vikrant ParsaiRate it:
|Good lovers understand each other;Better lovers respect each other;Best lovers live to trust each other; Great lovers dwell in each other.
– Anuj SomanyRate it:


text: Getty Images [ Giants Have An Unlikely O-Line Leader In Year Two of Offense [AUDIO] By Armen Williams June 20, 2015 Giants center Weston Richburg was at left guard last year in his rookie season. Now in his natural position at center, not only does he need to play like a veteran but the team is looking at him as one, too. Read More|Comment Category: armen and levack, Audio, Geoff Schwartz, NFL, NY Giants, Sports, Videos Tags: Geoff Schwartz, Giants, Offensive Line, Weston Richburg Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


text:
Walk through a field and engage in battle in this Japanese gameplay from TGS.
Views: 7,684
| Posted: 09/21/2010
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This site is part of the Defy Media Gaming network. Copyright © 2014 Defy Media, LLC; all rights


text:
Venture capital heads of terms (term sheets)
A term sheet is a document that outlines the key financial and other terms of a proposed investment. Investors use a term sheet as a basis for drafting the investment documents. With the exception of certain clauses — commonly those dealing with confidentiality, exclusivity and sometimes costs — provisions of a term sheet are not usually intended to be legally binding. In addition to being subject to negotiation of the legal documentation, a term sheet will usually contain certain conditions that need to be met before the investment is completed and these are known as conditions precedent.
If a company seeks to raise venture capital in the UK, the principal documents needed for an investment round are generally a subscription agreement, a shareholders' or investors' rights agreement (frequently these are combined into a single subscription and shareholders' agreement) or an investment agreement and articles of association. The provisions of a term sheet will be included in these documents…
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Briefings from Taylor Wessing
Introduction of personalised tax protection 2014 in relation to pension savings
For the tax year from 6 April 2014, the standard lifetime allowance has reduced from £1.5m to £1.25m.
The regulator and FCA issue a guide on how workplace DC pensions are regulated to protect consumers
One of the areas highlighted last year by the Regulator was the regulation of workplace DC pension schemes.
Analysis from The Lawyer
Corporate crunch time: who will triumph at The Lawyer Awards 2014?
As the equity capital markets rocketed back into favour and global M&A saw at least a partial return to form, there have been some rich pickings for The Lawyer's Corporate Team of the Year award shortlisted firms in 2014.
Singapore: Cash course
The city-state is working hard to become a global wealth management hub, and law firms are gearing up for a prosperous new world


text:
If you are the type of person that likes to read blogs and websites like beautiful you then I think it's a fairly safe bet to say you're the type of person who likes to achieve things. Has goals. Is going places. Go you!
But even for highly motivated and juiced up people, sometimes we can all come across a stumbling block or even what feels like an outright brick wall that we need to overcome. It's when those blocks and bricks start flying or dumping at our feet that things can feel really tough and goals and achievements we might have had a strong eye on can begin to waver. Our head can get filled with notions that we have to completely flip things (or even our whole life) totally around, or make drastic changes that can feel oh so hard.
And I have no doubt there are times in our lives that call for that type of overhaul but if wanting to break through or change or achieve something, I'm a believer that often the outcome we want might not nearly be as far away as we think. Could it be just a matter of tweaking something? Mixing up a pattern of doing things? Creeping up on … Read the rest


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gemthejewel Photographer
Serena RauchModel Female Montreal, Quebec, Canada My MM URL: http://www.modelmayhem.com/Rina_111
Mayhem # 2888293
About MeHey everyone! It's been a while since I've done a shoot, but I'd love to get some more experience and do some fun, elegant, classy, sublime, and editorial type of shoots! I really do enjoy the creative process of a photo shoot and all the details that go into perfecting an image, an expression, and a style. I still have so much to learn in the way of expressions, but I've got a lot better at poses and I have a killer wardrobe to boot! I'd love to do a shoot outside with lace, and fur, and dramatic makeup. In general, I'd like to attempt to align myself more with outdoor elements and work with the photographer to get that amazing juxtaposition of light, shadow, and pose. To me modeling, is about expressing who you are and feeling comfortable in your own skin. I would actually like to pursue it as a profession, so I'm looking to join an agency! In the mean time, practice makes perfect and in the meantime don't hesitate to contact me and I'll make time even though I have a busy school schedule:) My spring break actually starts the 17th! P.S NO NUDES thanks very much and I am willing to travel for shoots if expenses are paid. On shoots, I would describe myself as punctual, open to direction, and just very enigmatic. I can't wait to meet you all!! xox
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JVLADIMIR Photographer
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Photographe Jean Goulet Photographer
W A L K E R Photographer
bicycledays Model
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Product Details
When these Silver Dollars were first released, they were meant to commemorate the recently deceased President Eisenhower and legislation to create them was signed into effect by President Richard Nixon.
There are no coins with the date of 1975 as coins from both that year and 1976 were made with a special bi-centennial double date of 1776-1976 in honor of American independence.
All of these coins will grade Brilliant Uncirculated and contain 40% U.S. Silver. Actual Silver weight in each Silver Dollar is 0.3161 oz.
Quantities of 20 are packaged in square tubes!
Years and mint marks will be of our choosing.
Silver -- why buy Silver from APMEX?Silver is one of the world's favorite bullion investments and is a popular way to diversify one's wealth. Call our Account Managers toll free at (800) 375-9006 or to chat live with our product expert. APMEX is where to buy Precious Metals! Also, you can come to us when it is time to sell Gold, Silver, Platinum, and Palladium.
|Product ID:
|Brilliant Unc
|Grade Service:
|Mint Mark:
|S - San Francisco
|Metal Content:
|0.3161 troy oz
|US Mint
|3.1 mm
|38.1 mm
|Inner Pack:
|Outer Pack:
Reviewed by 7 customers
Sort by
I ordered 10 of these Silver Ikes. They were delivered in a timely and secure manner. All but one are in better condition than I expected. The last one almost looks like some substance got onto the coin. All 10 received were Bicentennials! I love Bicentennial Coinage, how did they know? Just one with the Apollo Reverse would have been cool, but like I said... love Bicentennials.
- Attractive Design
- Common (higher mintage)
I had leftover aucation Bucks to spend so I used them to obtain 1 of these. I don't usually buy this coin from APEX b/c they charge way too high of a premium for a 40% Silver common coin. My local shops sell them right at Spot.
- Recognized Brand
- Easy to Sell
- Mint Condition
- Common (higher mintage)
- Priced Too High
I bought this coin because I needed a silver Eisenhower. The coin is great but it had a few old oxidized abrasions and a some gouges and deep scratches. Obviously this coin was meant to be in another low grade bin.
- Recognized Brand
- Value (low premium over spot)
- Collectible (lower mintage)
- Attractive Design
- Easy to Sell
- Mint Condition
- A Few Nicksgouges And Ab
The coins were exactly as advertised. I purchased 20 and they came neatly packaged in a square tube. Thanks APMEX!
- Recognized Brand
- Mint Condition
- Easy to Sell
- Attractive Design
Great coin for the value. Great piece of American history.
- Mint Condition
- Attractive Design
Nice coin for the price, good bargain purchase
- Recognized Brand
- Easy to Sell
This is a great buy because it is 40% silver and 60% copper both are moving up in price as. During WWII's Manhattan Project copper was impossible to find and caused the price to go through the roof and the government had to borrow several tons of silver to replace copper from the U.S. Treasury. Another great thing about this coin is that it has not been touched since the time it was struck and put in plastic so you really do get a well preserved piece of history.
We provide all of our customers with a refund, return and / or exchange on everything we sell including all bullion and certified coins. If for any reason, you have a problem, please feel free to call us. We will always do our best to accommodate you.


text:
So I was doing those random battlegrounds and some nerd was all, "MAN SITTING IN THE SPAWNING AREA IS POINTLESS U NOOB!" and I was all, "http://www.youtube.com/watch?v=ggB33d0BLcY'
Dear Fonzie...
Please report any Code of Conduct violations, including:
Threats of violence. We take these seriously and will alert the proper authorities.
Posts containing personal information about other players. This includes physical addresses, e-mail addresses, phone numbers, and inappropriate photos and/or videos.
Harassing or discriminatory language. This will not be tolerated.


text:
CleanPhoto... Photographer
AmiyaaModel Female Los Angeles, California, US My MM URL: http://www.modelmayhem.com/amiyaa
Mayhem # 3183164
About MeHello I'm Amiyaa, looking to expand my knowledge, talent, and skills in all aspects of entertainment. I'm here to network and hopefully meet and greet photographers, agents, talents, and talent scouts from all over the world. I'm 25 years old, and if it matters, I'm a pre-op transsexual. I am ambitious, intelligent, and content to do and be my very best in this industry. I'm excited and look forward to meeting and working with you.
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AdotLdot Model
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Veterans Affairs
Multiple agencies have combined forces to create an online venue addressing problems experienced by veterans trying to access military education benefits.
The online complaint system is a joint effort among the departments of Veterans Affairs, Defense, Education and Justice, along with the Consumer Financial Protection Bureau and the Federal Trade Commission. Troops and their families who run into problems getting access to education benefits under the Post-9/11 GI Bill and the DOD Military Tuition Assistance Program can submit complaints, and the agencies will work with the schools on the vets' behalf to find resolutions.
Whether the problems are related to funding, treatment or practices, the centralized system is designed for troops and their beneficiaries to report bad experiences.
"The online complaint system empowers veterans and their dependents and provides them a direct line to VA and our partner agencies," Allison Hickey, VA undersecretary for benefits, said in a Jan. 30 release. "The feedback we receive from veterans, service members and their families will help us strengthen enforcement of the 'Principles of Excellence' for institutions of higher learning serving veterans and their families to ensure students are receiving the education benefits they have earned and deserve."
The reporting system can be accessed via websites through the Defense Department and the VA's GI Bill.
About the Author
Amber Corrin is a former staff writer for FCW and Defense Systems.
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Meet 100 women and men who are doing great things in federal IT.
Click here for the full list
The outgoing speaker helped push forward data and transparency measures that have opened up the House of Representatives to the American people.
The Census Bureau announced plans to fold in new technology and third party data into its 2020 population count, but questions remain about the viability of the Bureau's enterprise IT.
A technology roadmap can help agencies reap the benefits FITARA has to offer. Here are the four stages of a successful effort.
In the newest Federal Employee Viewpoint Survey, feds show they're feeling better than they have over the past few years – but there's still room for improvement, especially in mission-critical IT.
The General Services Administration's Enterprise Infrastructure Solutions contract will anchor the agency's NS 2020 telecommunications strategy.
House and Senate both approve a measure to maintain funding at fiscal 2015 levels through Dec. 11.
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Agency heads, acquisition officers and even CIOs don't need to be hard-core techies. FCW's four-part look at the expertise that's really required to make federal IT run.
FCW recognizes 14 individuals having an outsized impact early in their careers.
To Date there is No Enforcement or Resources to assist Veterans with folow up of Complaints on the Principles of Excellence Complaint System Website. This is tantamount to a BIG JOKE at the expense of wounded Veterans
8609 Westwood Center Drive, Suite 500Vienna, VA 22182-2215 703-876-5100
© 1996-2013 1105 Media, Inc. All Rights Reserved. This copy is for your personal, non-commercial use only.To order presentation-ready copies for distribution to colleagues, clients or customers, visit: www.1105Reprints.com


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The Spoonflower Handbook is here!
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text:
Athlete Profile
Athlete: Stacie Tovar
- Region:
- North Central
- Team:
- CrossFit Omaha
- Affiliate:
- CrossFit Omaha
- Gender:
- Female
- Age:
- 30
- Height:
- 5'5"
- Weight:
- 145 lb
|Filthy 50
|Fight Gone Bad
|Sprint 400m
|Run 5k
|Clean & Jerk
|228 lb
|180 lb
|335 lb
|Back Squat
|305 lb
|Max Pull-ups
How I Eat
I eat strict Paleo
I eat quality foods but don't measure the amount
I eat 1-3 full cheat meals per week
How I Train
I workout mostly at a CrossFit Affiliate
I have a coach who determines my programming
I incorporate CrossFit.com workouts
I record my workouts
My Athletic Background
I played youth or high school level sports
I played college sports
I regularly play recreational sports
My Experience With CrossFit
I began CrossFit with a coach (e.g. at an affiliate)
I have completed the CrossFit Level 1 certificate course
I have attended one or more specialty courses
I have had a life changing experience due to CrossFit
I train other people
My Work/Rest Schedule
I do multiple workouts in a day 3+ times a week
I strictly schedule my rest days
How long have you been doing CrossFit?
4+ years
Athlete Coverage
Watch Michelle Kinney, Alessandra Pichelli, Stacie Tovar and Gretchen Kittelberger compete in the Handstand Push-Up/Hill Run Event in Big Sky, Montana.
Video, Posted Wed, 09.04.13
When you leave Montana, the world seems two-dimensional again. The rise of CrossFit worldwide still seems a surprise to many on the fringe, but the answer to all of it was on display in Big...
Article, Posted Wed, 08.21.13
It's tournament time at the CrossFit Games. March Madness might be long in the past, but CrossFit fans had their brackets in order for the ZigZag Sprint, a four-...
Article, Posted Fri, 07.26.13
"Trusting in my preparation, I do expect to perform at a very high level and compete with the top 50 women for a spot on the podium." Photos by: Tony Frescas Nothing is a given...
Article, Posted Sun, 07.14.13
Here are your 2013 Reebok CrossFit Games qualifiers. Here are your 2013 Reebok CrossFit Games qualifiers. Africa Man David Levey Woman Carla Nunes Da Costa Team...
Article, Posted Mon, 06.10.13
After three days and seven events at the 2013 North Central Regional, Elisabeth Akinwale, Deb Cordner Carson, and Stacie Tovar earned the three qualifying spots.
Video, Posted Sun, 06.02.13
With an incredibly deep and talented pool of competitors, Akinwale had to fight until the end. Last weekend, Jason Khalipa won five events and took second on the other two at the...
Article, Posted Sun, 06.02.13
"I wanted to drop it so bad, but the people in the crowd were waving at me and cheering so loud I had to keep going ..." ~Grace Dresher In the midst of gloomy...
Article, Posted Sun, 06.02.13
Deborah Cordner Carson, Stacie Tovar and Elisabeth Akinwale are seemingly untouchable in the North Central Regional and are looking to go back to the 2013 Reebok CrossFit Games.
Video, Posted Sun, 06.02.13
Join Sean Woodland, Pat Sherwood and Nicole Christensen on tonight's show, as they discuss the highs and lows from Day 2 of competition at the Asia, North Central, North West, and South West...
Video, Posted Sat, 06.01.13
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text:
Bambara Hotel Monaco
Trust Bambara Hotel Monaco for all your Bed and Breakfast needs. Look for us in Bountiful.
Marriott Ogden Hotel
No need to book a ticket for a foreign meal. We at Marriott Ogden Hotel will help you find the top-notch Hotel for all your dining and lodging needs.
Utah Olympic Park
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text: Online Videos Rise: Where are the Advertisers? Posted on Friday, February 25, 2011 by JD Rucker The trends are clear: more people are watching videos online and spending less time in front of the television. Perhaps more importantly, it's easier to skip television ads thanks to technology ... Read More


text:
The new Liveable Communities Grants program will provide $4 million dollars over four years for innovative projects that support a range of ideas for new initiatives or platforms focussed on helping older people increase their participation in the community and lead rewarding, active lives.
Minister for Ageing John Ajaka said that liveable communities enabled everyone, regardless of age or ability, to lead active, independent, healthy lives and access their community freely and safely.
The grants are open to non-government organisations, academics, entrepreneurs, small businesses and local councils.
Entries must address one of the following categories:
Successful entries will be assessed on innovation, understanding of community and the potential for creating sustainable long-term solutions.
Upgrades include new critical care services, new operating theatres, extra inpatient beds and a new emergency department. The redevelopment will also create more than 1000 construction jobs each year the project runs.
NSW Premier Mike Baird said the redevelopment will deliver world-class health services to Western Sydney's growing population and help create future job opportunities.
"We want to ensure we use all the skills of Western Sydney local industries so that funding for the project is invested back into the community and the local economy," Mr Baird said.
More than 12,000 people work and visit Westmead daily and consultation with local staff, clinicians and the community has been a key part of the design process.
Cr Garrard was first elected to represent the Woodville Ward in September 1974 and has been re-elected on ten consecutive occasions. This is his sixth term as Lord Mayor.
"It is a great honour to again have the opportunity to serve the people of Parramatta in the capacity of Lord Mayor. Parramatta is growing at a rapid rate and Council is playing a crucial role in facilitating that growth and ensuring resident's needs are met along the way," Cr Garrard said.
"For Parramatta to continue to grow and develop we need to be a 'Smart City' driven by intelligent planning and leading-edge innovative technologies that will improve the functionality and liveability of our City, while respecting our rich heritage.
"Having launched Council's Smart City committee, ParraConnect, five years ago I am committed to seeing that our City fosters innovative entrepreneurship and collaboration between governments, businesses and our local communities.
"I have always been a strong advocate of our neighbourhoods and this term I want to introduce a 'Neighbourhood focus' to Council so that we bring our residents with us into the future.
"By redefining our neighbourhoods, we have the opportunity to better focus on service delivery and efficiency, effectively bringing local government closer to the community.
"There are many positive changes taking place in Parramatta, with work set to start on a $300 million redevelopment of Pirtek stadium, plans for the Powerhouse Museum to come to the City and work still underway to determine the first route of the Western Sydney Light Rail.
"We have made great progress on the $2 billion Parramatta Square urban renewal project, which will see a new City heart created for residents, workers and visitors.
"We also stand at the crossroads of how Local Government will be administered for generations to come with the Independent Pricing and Regulatory Tribunal (IPART) soon to release its recommendations on the State Government's 'Fit for the Future' reform process. I support Council's proposal for the creation of a new Parramatta based Council with the scale and capacity to deliver growth and improved services.
"We will continue to work closely with State and Federal Governments to achieve large scale projects to enhance our City and secure Parramatta as Sydney's dual CBD.
"I would like to congratulate and thank the outgoing Lord Mayor Cr Scott Lloyd and Deputy Lord Mayor Cr Steven Issa who have done a commendable job keeping the City moving forward over the past year. I look forward to continuing the great work that the Council has been achieving."
A winding stream that changes shape and form, areas of green open space and public art installations are among the features of a concept design for Parramatta Square's public domain area which is now on public exhibition.
Parramatta City Council last night voted to endorse the Draft Concept Design for a four-week exhibition period to seek feedback from the community and stakeholders.
The $35 million investment by Council is central to the $2 billion Parramatta Square redevelopment that will include commercial, residential, educational and civic buildings.
Key to the concept design is a central fountain and watercourse that winds through the length of the 10,000sqm space. While the final design is still to be determined, the stream could take on a variety of forms including still water, running water, a shallow curtain, mist or spray.
"As a river city, Parramatta has a long and well-established connection with water and this design pays tribute to that, with a water feature that lends itself to a variety of different interpretations," Lord Mayor of Parramatta Cr Scott Lloyd said.
"This is a unique opportunity to define the future heart of our City, to create an engaging space that will be used by thousands of residents, visitors and workers every day. Council and the design team aim to create a world-class public square befitting Sydney's dual CBD that respects and pays homage to our unique heritage, while creating a versatile, modern and visually appealing space."
A team of four internationally-acclaimed design firms, including Danish architect Jan Gehl, has worked with Council to celebrate the City's connection to its riverside location by putting water at the heart of the design.
As well as the iconic water feature and main fountain, the public domain will include digital way finding and public art, a northern lawn and southern plaza, play garden, a new Town Hall lobby, focal artwork and multiple crossing points across the stream.
The draft concept was created by 42 – a design team including award-winning firms James Mather Delaney Design (JMD), Taylor Cullity Lethlean (TCL), Tonkin Zulaikha Greer (TZG) and Gehl Architects, Denmark. The team have won acclaim for their individual and collaborative work both locally and overseas, including projects in New Zealand, the UK and New York's Time Square and Broadway.
"Water becomes a centrepiece to Parramatta Square and will animate it in many wonderful ways. It will celebrate the great diversity of Parramatta's community and connect to a range of beautiful civic spaces that allow visitors, residents and workers to promenade, play, meet or be entertained," 42 spokesman and TCL director Perry Lethlean said.
"The public realm will also include many inviting lawn spaces, display gardens and extensive tree planting to create a memorable setting and a unique Parramatta identity."
Professor Jan Gehl of Gehl Architects said a great heart of a city is a key condition for a thriving urban community.
"Parramatta Square will become the new urban heart of a diverse and changing face of Parramatta. It will provide many opportunities for people to enjoy urban life in a great city," Professor Gehl said.
The design team includes Melbourne artist Callum Morton, who will oversee the public art masterplan for the new public space. Callum is Professor of Fine Art at Monash Art, Design and Architecture (MADA) in Melbourne, and has exhibited his work internationally.
Council recently announced that Walker Corp will be developing and sourcing buyers and tenants for Stages 2 and Stages 5 & 6 of Parramatta Square.
The public domain will be completed in stages to ensure coordination with the construction projects in Parramatta Square including the Western Sydney University high-rise campus, new civic and library facilities and commercial high-end office buildings.
The project will see 20,000sqm of space transformed, including the 10,000sqm, 40 metre-wide and 250 metre-long central area.
More than 1000 comments have already been received from the public through a number of focus groups, three community open days and an online survey. Residents and ratepayers are now being asked to provide their feedback on the draft concept design and can attend a number of open days during the four week exhibition.
Feedback can also be provided:
For artist's impressions of the new draft concept design click on the link below:
Moore Stephens Spring Wealth Management update covers the following:
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This September saw not for profit disability service provider Northcott host several highly successful Walk with Me events around New South Wales with the biggest event in Parramatta attracting a crowd of close to a thousand people and leading to road closures in Market and Church Streets.
Walk with Me is an annual event hosted by Northcott which encourages communities to unite and walk alongside people of all abilities, while encouraging a better understanding of disability and promoting social inclusion.
The Parramatta Walk with Me event commenced at the Riverside Theatre and ended in Centenary Square where the exuberant crowd were then entertained by Australian Idol winners Wes Carr and Damien Leith.
Other Walk with Me events took place in Campbelltown, Wagga Wagga, Moree, Tamworth and Dubbo with several hundred people taking part. For more information see www.northcott.com.au/news.
Held at the Dockside Pavilion in Darling Harbour Sydney, the Awards for Excellence gala dinner welcomed 750 guests from all around the state who came together to try their luck across five major categories.
The ATC will now battle it out for the national title at the Brisbane Convention and Exhibition Centre on Monday 26th October.
Continuing our award-winning success, this win comes off the back of the Best NSW Function/Convention Centre Caterer in 2014.
To see a preview of what Royal Randwick has to offer, watch our videos from the John Eales Medal Awards Night and the Hyundai Tucson Launch.
For more information on Events at the ATC, please visit:
Alternatively, please email firstname.lastname@example.com or call us on (02) 9663 8478.
When it comes to planning for growth, most SMEs are disciplined in developing a plan however the day to day demands, both external and internal, can make it difficult to execute plans in the most effective manner.
KPMG has released the 'Growth Intentions Snapshot 2015' a survey which sought to understand how SMEs plan for and implement initiatives to grow their businesses.
The key findings are as follows:
Click on the link above to download the report.
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Lifeline Western Sydney is one of the largest centres accredited by Lifeline Australia to answer telephone crisis calls to 13 11 14, and is a service of UnitingCareMental Health.
We operate 24/7 and answer over 80,000 crisis calls per year from people of all ages who are in crisis due to a range of issues including:
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This service would not be possible without our friendly, caring team of dedicated volunteers. As the demand for the Lifeline telephone crisis service is continuing to grow, we are looking to expand the team.
We run courses throughout the year at our training centre at Parramatta. Thanks to grants, donations and our fundraising events, we offer this course at a greatly subsidised rate of only $890 (actual cost of the course is valued at approximately $3,500).
Because of our investment in students, we ask for a minimum 12 month commitment to doing fortnightly, 4 hour shifts at Lifeline Western Sydney (and we'd love it if you could stay longer!).
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Charlie Thompson. Playing pedal steel since 1973. My influences are from that era: Buddy Emmons, Sneaky Pete, Lloyd Green, John Call and the music of Gram Parsons, Burrito Brothers and Pure Prarie League. I am availabale for gigs and recording - firstname.lastname@example.com
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text: Dodgers Brawl by Hilton Hater at June 12, 2013 1:05 pm. Comments The Dodgers and Diamondbacks go at it in this brawl, which stars when Ian Kennedy plunks Zack Greinke. This video is no longer available. Please check below for related videos. Edit Delete Follow Sports? Facebook Disqus Tag: Sports Related Videos: Sports Videos Related Post: Dodgers Brawl with Diamondbacks: Watch Now! Uploaded by: Hilton Hater Uploaded: June 12, 2013 Duration: 172 seconds


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The QuotesPros.com company is a source providing insurer data direct to consumers without requesting any personal information through its Internet database. The insurer information that can be viewed includes the monthly and annual costs of a policy as well as the different declarations that are available for a term plan. The QuotesPros.com company issues life, renter, health, auto and business coverage quotations that are updated using its real time link with national companies.
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Christmas Season
How to light your home for Christmas when you live in your car.
Dec 21, 2011 @ 11:01am
Nothing can stop this driver from spreading a little highway Christmas cheer — not even the 17-car pile-up he caused a mile back by distracting that truck driver.
Sources: Tosh.0


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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk.
We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk.
Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45–0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41–7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13–7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect.
Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.
Stroke is a complex disorder resulting from the interplay of genetics and environment, and genes potentially having an impact on disease pathogenesis (e.g. genes involved in hemostasis), intermediate phenotypes (e.g. atherosclerosis) or clinical risk factors (e.g. blood pressure regulation) have been tested for association with stroke risk [1]. Mostly nuclear genes have been intensively investigated thus far, while the role of the mitochondrial genome has been neglected. Mitochondria are extranuclear organelles whose primary function is the production of ATP through the oxidative phosphorylation (OXPHOS) respiratory chain. They also play a decisive role in intracellular signaling, metabolic pathways such as Krebs' or tricarboxylic acid cycle and the metabolism of amino acids, lipids, cholesterol and steroids. Mitochondrial function is required for normal vascular cell growth and function, and its dysfunction can result in apoptosis, favoring atherosclerotic plaque rupture. mtDNA is maternally inherited, does not recombine and exhibits high mutation and fixation rates, therefore making it an important tool in phylogenetics. Human mtDNA is a haploid, circular molecule of approximately 16,600 nucleotides encoding for thirteen OXPHOS polypeptides, twenty-two transfer RNAs and two ribosomal RNAs (Figure (Figure1)1) [2]. Particular combinations of certain polymorphisms define mitochondrial haplogroups and subclades (Table (Table1),1), which tend to be associated to broad geographic areas and/or populations [3].
Particular variants of the mitochondrial genome have been linked to aging [4,5], the strongest risk factor for stroke, and to several neurological and vascular disorders. Among the best-known examples of a mitochondrial disorder is that of MELAS (MIM: 540000), a mitochondrial encephalopathy characterized by lactic acidosis and stroke-like episodes. This syndrome is caused by the m.3243A>G mutation, an A to G transition at mtDNA nucleotide position 3243 [6,7]. Leber's hereditary optic neuropathy (LHON, MIM: 535000), a vascular disease of the optic disc, is also caused by mtDNA mutations that lead to respiratory chain dysfunction [8]. Interestingly, the phylogenetic background of haplogroup J influences the clinical penetrance and expression of the m.11778G>A and m.14484T>C primary LHON mutations [9,10]. This exemplifies how, although defined on the basis of evolutionarily neutral polymorphisms, common mtDNA variation of phylogenetic relevance assumes a functional role on the expression of particular complex traits. mtDNA variation has been associated with non-Mendelian and non-maternally inherited complex disorders such as Parkinson's disease [11], Alzheimer's disease [12], myocardial infarction [13], obesity [14], occipital stroke in migraine [15,16], and mean intima-media thickness of bilateral carotid arteries [17]. Increased mitochondrial oxidative stress and dysfunction has been linked to many ischemic stroke risk factors, including hypertension [18], diabetes [19], inflammation [20], plaque rupture [20], tobacco smoke and alcohol exposure [21]. The goal of the present study was to determine whether mtDNA SNPs or haplogroups predispose to ischemic stroke in a large cohort of Portuguese patients and controls.
Five hundred thirty four unrelated patients with a clinical diagnosis of ischemic stroke, who were under the age of 65 at stroke onset, were recruited through Neurology and Internal Medicine Departments throughout Portugal. Stroke was defined by the presence of a new focal neurological deficit, with an acute onset and symptoms and signs persisting for more than 24 hours, and was confirmed by Computed Tomography Scan (97% of cases) and/or Magnetic Resonance Imaging (in 25% of patients) [22]. All patients were seen and all neuroradiology tests were reviewed by study neurologists. Trauma, tumors, infection and other causes of neurological deficit were excluded.
Data collection forms were developed for this study that included extensive clinical information such as stroke characteristics, general clinical observation, neurological symptoms and signs, complications and interventions during hospitalization and situation at discharge. Data was also collected on relevant lifestyle aspects and previous clinical risk factors.
Four hundred ninety nine unrelated healthy individuals were included in this study as a control sample population. Since stroke is a late-onset disease, the control group was selected from a group of healthy volunteers with a higher mean age than the case group, thus minimizing the chances for mis-classification as "stroke-free". Control individuals were verified to be free of stroke by direct interview before recruitment, but no brain imaging studies were performed. The interview also included questions on established clinical and life-style risk factors for stroke.
The principal demographic and clinical characteristics and frequency of risk factors of this study sample are shown in Table Table2.2. The research protocol was approved by the ethics committees of participating institutions, and participants were informed of the study and provided informed consent.
We studied nineteen mtDNA SNPs (Figure (Figure11 and Table Table1)1) of phylogenetic relevance for classifying the Portuguese mitochondrial haplogroup variation which includes the most prevalent West Eurasian haplogroups (H, H1, V, pre-HV/HV, J, J1b, T, U, U4, U5, K1, I, X2b, and W), as well as some African haplogroups (U6a and L) more frequent in Portugal and in the Iberian Peninsula than in other European countries [23,24]. Haplogroups and their subclades, which show different frequencies and distributions in human populations, are defined by the combination of multiple markers (Table (Table1),1), embracing the information from the whole set of branches of the mtDNA tree rather than the status at any single point mutation. The nomenclature of clades follows Torroni et al. [25], Richards et al. [26], and Macaulay et al. [27]. The "Other" haplogroup category in Table Table33 (19 controls and 20 patients) includes individuals whose haplogroups could not be assigned to the clades in Table Table11.
Genomic DNA was extracted from whole blood samples using the NucleoSpin Blood XL kit (Macherey-Nagel; Düren, Germany) or a salting out procedure. SNPs were genotyped using Sequenom's iPlex assay (primer extension of multiplex products with detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) following manufacturer's protocol and detected in a Sequenom MassArray K2 platform. The primer sequences are available upon request and were designed using Sequenom's (San Diego, USA) MassARRAY® Assay Design 3.0 software according to the Cambridge reference sequence [2]. Extensive quality control was performed using eight HapMap controls of diverse ethnic affiliation, sample duplication within and across plates, non-Mendelian maternal inheritance check in three large pedigrees, and a minimum of 90% call rate. Genotype determinations were performed blinded to affection status. 0.2% of all calls were heterozygous, most likely due to mtDNA heteroplasmy, and these were not included in the analyses.
An unpaired Student's t test and a χ2 test were used to compare quantitative and qualitative clinical and demographic data, respectively, between cases and controls. χ2 tests were performed to explore the association of each mtDNA SNP and haplogroup with stroke risk. For haplogroup analyses, we compared each haplogroup with all other haplogroups pooled together. To adjust the association analysis for confounding factors, age-at-examination, hypertension, diabetes and ever smoking were included as covariates in multivariate logistic regression with backward elimination of risk factors. The interaction i among covariates in regression models was not strong (-0.5 <i < 0.5). Logistic regressions were performed using the R freeware [28]. Odds ratios (ORs) and their associated 95% confidence intervals (CIs) were uncorrected for confounding variables in the χ2 tests and corrected for covariates in regression models. Results were considered significant below the conventional level of 0.05. Since some of the markers are in linkage disequilibrium and the haplogroup comparisons are not independent, we did not perform corrections for multiple testing and uncorrected p-values are reported.
Table Table22 shows the general characteristics of our dataset. Since stroke is a very common late-onset disorder, we chose to have the control group significantly older than the case group to minimize misclassification biases of control individuals. Male to female ratio, hypertension, diabetes, ever smoking, and ever drinking were significantly higher in ischemic stroke patients than in controls, and the effects of these potentially confounding variables were accounted for in the multivariate logistic regressions with backward elimination of risk factors. Our group of patients has a similar risk factor profile than previously described older groups of ischemic stroke cases with similar male to female ratios [29,30], and therefore can be considered representative of the general ischemic stroke population.
The mtDNA haplogroup distribution in the control group (Table (Table3)3) was in agreement with previously published data on a similar Portuguese normal population [23,24], with 8.3–9.9% of the individuals having mtDNA haplogroups characteristic of African populations (L and U6). With the genotyped SNPs, a haplogroup could not be assigned to an almost equal percentage of individuals in the control and patient groups (3.8 and 3.7%, respectively, classified as "Others" in Table Table3),3), which again is in concordance with other studies using equivalent approaches [11,31]. These individuals have either an ambiguous SNP-profile or belong to rare Eurasian haplogroups (e.g. R, Z, M). The fact that L, U6, and "Others" haplogroup categories are present in equivalent proportions in cases (12.0%) and controls (10.8%) (Table (Table3)3) further suggests that our dataset was well matched for ethnicity and lacks significant substructure.
Results of crude and adjusted association analyses of mitochondrial haplogroups are shown in Figure Figure22 and Table Table3,3, and those of single-markers are presented in Figure Figure33 and Table Table4.4. Sub-haplogroup H1 was found to be significantly less frequent in ischemic stroke patients than in controls when comparing each clade against all others pooled together (χ2 test OR = 0.61, 95%CI = 0.45–0.83, p = 0.001); when significant risk factors were included in the model as covariates (age-at-examination, hypertension, diabetes and ever smoking), the association remained significant (logistic regression OR = 0.57, 95%CI = 0.38–0.85, p = 0.007). The sub-haplogroup H1 is thus protective for ischemic stroke in this dataset. SNPs m.3010G>A, m.7028C>T and m.11719G>A, which together define H1, were found to consistently influence the risk for ischemic stroke in both the uncorrected χ2 test and the logistic regression model, their allelic state in H1 corroborating its protective effect. Stratification by sex revealed that the crude association of haplogroup H1 is quite consistent among males (OR = 0.65, 95%CI = 0.43–0.98, p = 0.038) and females (OR = 0.58, 95%CI = 0.37–0.93, p = 0.021), even though it did not reach significance in females when adjusted for co-variates (Figure (Figure2),2), most likely due to the small sample size.
Conversely, the pre-HV/HV, also known as R0 [32] (χ2 test OR = 3.14, 95%CI = 1.41–7.01, p = 0.003; logistic regression OR = 4.68; 95%CI = 1.51–14.54, p = 0.008), and U (χ2 test OR = 2.87, 95%CI = 1.13–7.28, p = 0.021; logistic regression OR = 4.01, 95%CI = 1.08–14.90, p = 0.038) mtDNA lineages emerge as potential genetic factors conferring risk for stroke (Figure (Figure22 and Table Table3).3). The relatively rare U5 sub-clade and its defining polymorphism m.13617T>C showed a trend for association with stroke risk only with the logistic regression test (OR = 2.17, 95%CI = 1.01–4.67, p = 0.048, and OR = 2.18; 95%CI = 1.01–4.70, p = 0.047, respectively).
To the best of our knowledge, this is the first comprehensive association study of mtDNA variation with ischemic stroke risk in an European population. In a large population sample of ethnically-matched cases and controls, we found that haplogroup H1 is protective while haplogroups pre-HV/HV and U increase risk for ischemic stroke. Since these haplogroups are defined by the combination of several polymorphisms also present in other clades (e.g. allele A of m.3010G>A is a phylogenetic marker of subclades H1 and J1b), the observed haplogroup associations cannot be attributed to particular SNPs, but instead to their precise arrangement. To exclude the possibility that the observed associations are due to population stratification with study participants of African or non-West Eurasian ancestries, we performed the statistical analyses in the overall dataset excluding the individuals with haplogroups U6a, L, and "Others" (54 controls and 64 patients), and obtained the same associations (data not shown). Unlike H1, the pre-HV/HV, U and U5 haplogroups were found in a small number of individuals, and therefore their association with stroke risk is only suggestive. Low counts tend to inflate the qui-square values and lead to false-positive results. We did not study the association of mtDNA with stroke subtypes since a much larger sample size would be required to have a representative number of individuals in each subtype and haplogroup category. Stratification by sex was performed as there are clear differences between male and female ischemic patients [33], and some of the associations (e.g. adjusted association of H1 in females) most likely did not reach statistical significance due to the relatively small sample sizes.
Earlier studies have addressed the contribution of mtDNA variation to stroke susceptibility. The m.12308A>G polymorphism defining haplogroups U and K, previously associated with occipital stroke in migraine [15,16] and suggested to increase the risk of developing stroke in MELAS patients with the m.3243A>G mutation [34], was not associated with ischemic stroke in our dataset. However, an association of the U5 subcluster with migrainous stroke has been reported [16] and is consistent with our tentative association of the U5 haplogroup and its defining m.13617T>C polymorphism with ischemic stroke. m.5178C>A, associated with aging [4] and cerebrovascular disorders (cerebral hemorrhage or infarction) in a small Japanese case-control sample [35] and with intima-media thickness in carotid arteries of Japanese type 2 diabetic individuals [17], could not be investigated here as it is Asian-specific [36]. Haplogroup A, unlike its defining polymorphisms m.663A>G in the 12S rRNA gene and m.8794C>T in the ATPase 6 gene, was recently found associated with atherothrombotic cerebral infarction in 440 Japanese females after adjustement for significant co-variates [37]. None of the three SNPs we studied in the 12S rRNA and ATPase 6 genes (m.709G>A, m.8701A>G, and m.9055G>A) were associated with ischemic stroke, suggesting that haplogroup A, but not its defining SNPs individually or other SNPs in the same genes, may constitute a risk factor for stroke in Japanese. Finally, we did not try to replicate the reported association with lacunar cerebral infarction of the m.16189T>C variant in the mtDNA hypervariable region [38] as we only investigated SNPs in the coding region and this polymorphism is not restricted to any particular haplogroup [39,40]. These discrepancies among reports highlight: i) the difficulty of finding reproducible mitochondrial genome associations with disease due to the continent-specificity of some mtDNA SNPs and clades, and ii) the necessity of performing association studies in very large samples so that even uncommon haplogroups are represented by a sufficient number of individuals. A power analysis of mitochondrial haplogroup association studies such as the present one (investigating 17 haplotypes) reveals that a sample of size similar to ours (515 cases and 515 controls) only provides 50% power to detect a change in haplogroup frequency from 0.251 in controls to 0.17 in cases (as observed here for H1) at a significance level of 0.05 [41]. Even though we only had 50% power, we detected an association of H1 at a significance level of 0.001, and this association would survive a Bonferroni correction for the seventeen crude or adjusted association tests performed for haplogroups, suggesting that it is an important association. Much larger cohorts are required for less common clades or finer changes in haplogroup frequency, and therefore the present study provides preliminary evidence of association that requires further validation in independent cohorts.
Although the polymorphisms that characterize the phylogeny are thought to be evolutionarily neutral, they may cause subtle alterations in the encoded transcripts or proteins, which collectively and over time, influence the risk of a stroke event. Given that stroke is mostly a late-onset disorder, it does not affect the successful transmission of mtDNA alleles and their fixation in the population. Additionally, several reports have documented the tissue-specific accumulation of mitochondrial deletions with aging [42,43], and it is conceivable that mtDNA polymorphisms or haplogroups which are neutral under normal circumstances become advantageous in post-mitotic tissues in the presence of acquired mutations.
The associated m.3010G>A non-coding polymorphism, located in the conserved 3' end of the 16S rRNA gene, lies near non-coding point mutations known to confer resistance to chloramphenicol, a prokaryotic and mitochondrial protein synthesis inhibitor [44]. The synonymous m.7028C>T transition is located in the cytochrome c oxidase (COX) subunit I gene (COI) of complex IV. This protein complex is the terminal enzyme of the respiratory chain, which collects electrons from reduced cytochrome c and catalyzes the reduction of oxygen to water, and consists of 13 polypeptide subunits, 3 of which are mtDNA-encoded. m.11719G>A is a synonymous SNP in the ND4 gene. ND4 gene product is a subunit of the respiratory complex I which accepts electrons from NADH, transfers them to ubiquinone and uses the energy released to pump protons across the mitochondrial inner membrane. A mutation in ND4 (m.11778G>A) causing an arginine to histidine change at amino acid 340 [MIM 516003.0001] accounts for over 50% and 90% of all LHON cases among Caucasians and Asians, respectively. Interestingly, the penetrance of this mutation is higher within a J haplogroup background, but its effect is most prominent on the J2 subclade [8,9]. The physical proximity of the associated polymorphism in ND4 to known mutations suggests that it lies in or close to important functional domains and has the potential to alter the protein's function.
It is interesting to notice that the majority of polymorphisms associated with stroke risk in the present report are localized in complexes I and IV, whose deficiencies are the most frequently observed abnormalities of the OXPHOS system. It would be of great interest to assess if stroke patients display complex I and IV deficits relative to matched controls, prior to their first stroke, and to identify phenotypic differences among haplogroups using transmitochondrial hybrid cell (cybrid) technology [45]. In rats, a reduction in the aerobic capacity is concomitant with a decrease in the amount of proteins required for mitochondrial biogenesis and oxidative function in skeletal muscle, and with an increase in cardiovascular risk factors [46].
The ethiopathogenic complexity of stroke is paralleled by that of mitochondrial disorders, probably in part due to their dual genetic control (mitochondrial and nuclear) and interplay with the environment. A small minority of complex I to IV subunits are mtDNA-encoded and produced, while the majority of subunits are nuclear-encoded and transported into the organelle. It is likely that mtDNA polymorphisms and haplogroups act synergistically with nuclear genetic factors and environmental components, and therefore mtDNA-encoded gene/nuclear-encoded gene and mtDNA-encoded gene/environment epistatic interactions may explain a larger fraction of the ischemic stroke heritability.
We found suggestive evidence for association of the mitochondrial haplogroup H1 with ischemic stroke. For a deeper insight of the role of mtDNA variants in ischemic stroke, the full-sequencing of the molecule and the replication of the same polymorphisms in a large, well-matched, independent dataset are mandatory. If replicated in other populations, these influences on ischemic stroke risk are a relevant matter of public health given that haplogroups H1, pre-HV/HV, U, and U5 represent about 20% of the European population.
The authors declare that they have no competing interests.
MC, JMF, AMV, and SAO participated in study design. BVF, IA, GG, LG, MC, MVB, RMS, ANP, RT, CF, JRF, MRS, JPG, IM, GL, and JMF contributed to sample collection. AR, BVF, TK, HM, IA and GG generated genotyping data. AR, TK, HM, AMV and SAO assisted in statistical analysis. AR, TK, HM, JMF, AMV and SAO interpreted the results. All authors intervened in manuscript preparation and/or critical revision, read and approved the final manuscript.
The pre-publication history for this paper can be accessed here:
We are deeply grateful to all study participants and to the genotyping unit at the Instituto Gulbenkian de Ciência. This work was supported in part by the Marie Curie International Reintegration Grant 513760 (SAO), the Marie Curie Intra-European Fellowship 024563 (SAO), the grant PTDC/SAU-GMG/64426/2006 from the Portuguese Fundação para a Ciência e a Tecnologia (FCT), FCT fellowships (AR, TK, HM), and fellowships from the Portuguese Instituto do Emprego e Formação Profissional (BVF, TK).
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's Canada Institute for Scientific and Technical Information in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Ethan's Law 40th Birthday Party
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Sounds Like: C.L.U.X., Shinedown, Black Stone Cherry, Slash, Lynyrd Skynyrd
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Ethan's Law was in December 2007,
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Having been influenced largely by Southern Rock, they decided to pay tribute to a band they both admire and re...See Full Bio
"hey guys. We've all heard actually. We loved it. ... Thank you guys for paying such a great tribute to us. ..... Good luck with peace is free. It's fairly simple. . The trick is being able to feel the emotion in your voice. . . . . I'm sure y'all will do it great."


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She asked if we had rented our shoes for the trip.
That just shows the lady was the one way behind current times, as you put it. I'd much rather play the role of the squatter in the Arkansas Traveler story, the wiseacre hillbilly. It applies to any upland Southerner, and flummoxes the Starkville out of outsiders.the South has risen again, just not in the way most expected.
When I was a kid, my parents and I were traveling in New England. My mother asked some prick for directions to Con-cord. He laughed, and said "You mean conquered"? He gave us directions and walked off singing "Mammy". I thought it was pretty funny, being as how he sounded all British and aMm.I don't mind arky. Just so long as those mommafrickers who call us that don't move here.
My buddy took a yankee professor hunting one time. They were riding mules. Buddy comes to a fallen tree, and his mule jumps the log. Yankee professor approaches the log hollering, "Whoooo Ay, whoo ay!" Mule stops and he falls over the front. Buddy asks, "what were you hollering?" Yankee says, "just what I've read in books about making a horse stop, Whooo ay." Whoa.True story.
To me, the term Arky, when used by someone not from Arkansas, is belittling. I get images of backwoods people way behind current times. In the show Beverly Hillbillies, the characters never say where they're from, but make most of their references to this area and SW Missouri. This is what most of America thought of when they thought of Arkansas, and the term Arky has been around for a long time to collect and carry that stigma. When I was 15, I was on vacation with the family in Michigan. A lady was making small talk and found out that we were from Arkansas. She asked if we had rented our shoes for the trip. She was surprised that we owned shoes in Arkansas, and that's just 22 years ago.
Women who say "down there" when referring to their nunu.Just call it "my pussy".
I've always liked it when women use cutsie little words for it, like wizard sleeve.
Anything and everything Kardashian!
Did you tell her to fuck herself?
I was a kinder gentler Satch in the day. Corruption happened in college. It probably didn't even occur to say that as a kid. Stop using the left turn lane as a merge into traffic. Especially when the inside lane is clear for a mile, and all you'd have to do is hit the fucking accelerator.Stop using the drive thru window to learn about every menu item. If you find that you need to ask more than 2 questions as you order, walk your ass inside and get some personal service. Or drive away hungry, either way, people in the drive thru are in a hurry.Sentence fragments.Stop assuming the SEC is cheating because they are dominating in football. Don't like it? Win more.
If I ever get terminal where I know I am going to die in a couple of weeks anyway I am going to some busy interstate with road construction, get in the merge line when I am supposed to, and start shooting every son of a bitch who rolls by (right by the big MERGE NOW sign) who apparently thinks their time is so much more valuable than everyone else's.If I can't drive far I might just walk over to the merge to continue on 635 past 35E and start popping people from the bushes.
Just go to Dealy Plaza. There's a good spot behind a fence underneath a tree from what I hear. (too soon?)
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