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When we were visiting family in upstate New York a few weeks ago, my mother-in-law, Pat, took me for a "girls night out" to visit some of the gift shops in Sharon Springs, NY. One of the places we visited was the Beekman 1802 store. What a beautiful store with gardening, beauty, clothing, food, and other unique products.
Beekman 1802
If you are a fan of the show Amazing Race, you may already be familiar with The Fabulous Beekman Boys, but their fascinating story was new to me:
A couple from New York City, Brent Ridge and Josh Kilmer-Purcell, decide to leave the big city behind and buy a farm in upstate New York. That farm? The historic Beekman Farms in Sharon Springs, NY. Since then, they've raised goats, made goat cheese and soap, launched a reality show, won CBS's Amazing Race, launched a website, written a best-selling cookbook, and opened a retail location. I think we can all agree they've been pretty busy the past few years.
I had a chance to see the newly opened retail store in Sharon Springs, and it is gorgeous! The decor had a sleek retro country vibe, with a black and tan color palette, and tin ceiling and wall tiles.
Shoppers grab wire baskets with slate bottoms (so the glass bottles and jars don't slide) for their purchases. The Beekman 1802 store sells many of the more popular Beekman 1802 items, including: goat cheese, goats milk soaps, jams, honeys, housewares, and so many other things. The products are made from natural ingredients, without chemicals or preservatives, and even the baby products are gentle for the most delicate skin types.
Beekman 1802 also sells their famous cookbook Everywhere I turned, I found something I wanted to purchase! One of my favorite items was the black pear bud vase, but since I was flying, with limited carry-on space, I knew better than than to purchase it that day. Our shop assistant explained that I could have my items shipped, or I could order from their website. Since I had several things I wanted to order, I decided to wait to order on the site. I could not resist getting one of their cookbooks though–that fit nice and flat in my carry-on. The shop assistant was professional and very kind to keep the shop open a few extra minutes, so we could shop.
I did actually purchase some creamed honey, but remembered I cannot have more than 2 oz of liquid in my carry-on, so gave the honey to my mother-in-law, with plans to go nuts at the Beekman 1802 online store (with shipping all over the US, thank you very much.)
The Beekman 1802 retail location is located at 187 Main Street, Sharon Springs, NY (about an hour west of Albany, and three hours north west of New York City.) For more information about Beekman 1802 and the Beekman Boys, visit their website. You can also find them on Facebook and Twitter.


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Our Services are Professional and Affordable
8 week Mindfulness-Based Stillness Meditation course – $280 course fee per person
- Reduce stress and improve sleep quality
- Improve digestion, oxygenation, tissue/cell repair, serotonin and melatonin levels
- Decrease heart rate and blood pressure
- Decrease muscular aches, pains and tension
- Slow the cellular ageing process
- Improve blood flow to organs
- Learn to be present, open and aware
- Improve attention, vitality and creativity
- Experience nurturing and healing at a deep soul level
1.5 hours x 8 weeks, with weekly notes and meditations emailed to you.
Locations and dates to be advised – join our newsletter list to receive updates.
GST included in price.
Weekly Mindfulness-Based Stillness Meditation Sessions – $15 per session
- Feel supported as you embark on a mindfulness meditation journey
- Hone your skills for your home-practice
- Guided meditation session emailed to you
45 minute regular weekly sessions held at various locations.
GST included in price.
Community Events & Corporate Programs – prices to be advised based on needs
Our greatest passion is in educating everyone about healthy ageing.
We will be running community based seminars on various topics.
We also offer businesses, including corporates and care facilities, programs in mindfulness meditation as a tool to reduce stress and increase creativity.
Join our mailing list, or follow us on social media, to find out dates for all our programs and sessions.
Private Case Management and Care Coordination Solutions – $120 per hour
How can we help you to stay living in your own home?
We will come out and meet with you and your family and find out your needs and wants.
Our goal is to create an individualised care plan just for you and coordinate the services you require.
Care coordination can be done as a one-off in the initial set up phase, or we can provide this on an ongoing basis.
We will conduct a 4 week and a 6 month review to ensure your needs are being met.
We can work with you on a short-term or ongoing basis.
Travel charges may be included if you live beyond Bayside Melbourne or the Mornington Peninsula.
GST included in price.
Dementia Support Solutions – $120 per hour
Are you a family carer stressed to the max caring for a loved one who is living with dementia?
We are here to help and support you.
Our senior consultants are all experienced dementia professionals. We will provide you with strategies and a care plan to help you care for your spouse or parent living with dementia, in the home environment.
Travel charges may be included if you live beyond Bayside Melbourne or the Mornington Peninsula.
GST included in price.

subset: commoncrawl


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* * *
it's not until after watching him hosting the academy awards did i really admire him as a character actor who is not afraid of showing a goofy side. before this he's nothing but a hot bod greek god with an australian accent. mr. hugh jackman. phew, is it hot in here, mate?
hugh jackman is a man's man. he's not playing a man in tights, a drunk swashbuckling pirate or a superhero with his underwear on the outside. he's wolverine. (can i hear some screaming?), a mutant with the ability to project razor-sharp steel-claws from his fist, and is self-healing, thus indestructible. not only that, he passionately protects the ones he loves and has a cool and temper of a disturbed beehive. how cool is that?
the movie is A plus. there's never a dull moment, and the only complaint mr. khairul has for the movie is that it's too short! more actions, please! the 'wolf' brothers shared the screen with awesome teeth-clenching moments packed with action! i'd dare say 'wolverine' surpasses even the x-men series.
don't agree? bite me.
* * *
'some people respect the badge. everyone respects the gun.' woah.
powerhouse names grace this movie. robert deniro. al pacino. the mere mention of their names can send goosebumps. ooh. (say it like those hyenas in disney's lion king).
and now they both shared the silver screen for this psycho thriller of two partnering cops investigating a serial murder involving the killing of bad guys who somehow made it pass the justice system. a poem is always left at the scene alongside the body. who? why?
from the beginning robert de niro takes on the role of the more brooding, sexy (yeah, sexy no kidding!) no-nonsense cop, while al pacino is the peace-maker wise guy with a smart mouth. you'd think that they're such big names that they'd try hard to overshadow each other to the point of over-acting but these are professionals, academy award-winners at work - they both gel well and in fact, complemented each other to bring out powerful performances, like always.
the movie starts with de niro's cop character speaking at a tv screen, confessing to the murder of 14 people. too early in the movie? and continues to narrate occasionally as he expresses his fear of being found out, and the urge to take justice into his own hands on those baddies that got away.
personally i've always preferred de niro than al pacino - but this movie is a must-see for fans of both.
* * *
you're tensed. you have a bad day. just loose yourself in the 'land of the lost'. it is silly fun. period.
if only they take out the toilet humors like dunking himself with dino pee (eww.) and a few other unnecessarily icky scenes. other than that, i thoroughly enjoy this movie purely for its amusing skits. will ferrel is not as funny as jim carey or steve carell but he can still make you laugh out loud. i like him in ben stiller's 'zoolander', and he's quirkily charming in that movie where his life is actually a narration from a real book. i forgot the title.
will ferrel is a has-been palentology got sucked into a weird parallel dimension, filled with dinos and weird creatures. a world where time overlaps - from swimming at a half buried motel in the mid of a desert to being chased by a t-rex to befriending a neanderthal named chaka. sucked along with him is a lovely brit research assistant and a loud-mouth redneck, who's painfully annoying though his heart is in the right place.
..while dinosaurs are about to attack the paleontologist
redneck to paleantologist : i'd join any battle with you, man. anytime, anywhere! (dengan bersemangat)
paleontologist : can the time be now, my friend? (dengan penuh dramatik dan penuh harapan berbunga-bunga)
redneck : (hesitant) well, i didn't think you'd call up that favor this soon, man. so i have to say no to this time. but any other time, i'm there!
pehtu dia blah! chaotic!
if you like brendan fraser's 'journey to the center of the world', then you might like this one. expedition to a new world, adventures at every corner, creatures to meet and monsters to fight. except that it's wackier, sillier - with corny b-grade looking alien-like amphibians, and erm, lacked the handsomeness such as brendan fraser's. but equally charming!
just leave your brain at the door and you'll laugh your teeth out. really.
* * *
can't wait for tomorrow. ipoh, here i come!


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Jane is brilliant, sarcastic, loyal, and failing school because she can't really be bothered to care about her standing. Why engage in class when it's all politics and drama, and you can do the advanced school work in your 15 minutes before the bus arrives? She does care for the sake of her friend Ally, though, and if Ally wants to participate in traditions like Big Little day, where Freshmen (Littles) choose Senior mentors (Bigs), she'll be damned if she's gonna see Ally go without a Little.
She's been best friends with Ally since forever. Which means she's in a prime position to notice when her BFF, (after a really tragic public vomiting incident,) starts acting- differently. To the point of sudden knowledge of Latin, entire wardrobe and style change, and new personality to go with the hair.
Jane's never really been one to take No for an answer, or acknowledge subtle hinting to back off, so it doesn't take many self-igniting text books and freak hail storms before she's figured out that Ally's actually sold her soul to the devil, via a new girl at school. And now this middleman for Hell is willing to strike a deal with Jane for Ally's freedom, just sign here please…
Maureen Johnson is a hilarious writer, and I really think this is the most fun I've had with any of her books I loled irl at least once a chapter, and was grinning like a maniac at the page for the rest of the time. Maybe I find demon possession hilarious. DON'T JUDGE ME OKAY?
But I both found it hilarious, and my religious sensibilities weren't (really) freaked out by the treatment of demons. There was no falling in love with fallen angels, for example. I always find that one a little bit hard to buy into, given the whole trust component in falling in love. Instead this time, the love interest was SO CUTE I just want to RUFFLE HIS HAIR and grin at him. *cough*
So yes, I loved the characters, including her whole family and the teachers, I loved the dialogue, the plot was satisfying, and I generally enjoyed it. I gave it four stars out of five.


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Agencies near Olney, TX
Olney, TX Home Health Care Agencies
Hamilton Hospital Home Health Agency901 West Hamilton Street, PO Box 158
Add Your Facility Adding your assisted living to the directory is completely free.
Other Senior Care Providers in Olney
- Adult Day Care Facilities in Texas
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Cities Near Olney, TX
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- Seymour, TX (4)
- Throckmorton, TX (2)
- Wichita Falls, TX (27)
Olney seniors that want to remain independent and live in their homes but need some assistance should consider an in-home care provider. Olney, TX home care agencies can provide seniors with assistance with daily activities and minor medical services in the comfort of the resident's home or apartment.
Seniors in Olney can stay in their homes and have home care workers visit to help with basic daily tasks and other services such as medication management. There are 1 home care companies that serve the Olney market.
Some page content retrieved from Google Places
Search Home Health Care Providers
Getting Started
- What is Home Care?
- Home Health Care vs. Non-Medical Home Care
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- How is Home Care Different from Other Care Options?
- When is Home Care Needed?
- Benefits of Home Care
- Talking to a Loved One
Choosing Home Care
- Selecting a Home Care Agency
- Medicare Quality Data
- Hospice Care
- Home Care Safety
- Considering Home Care Staff
Paying for Home Care
- Home Health Care Costs
- Ways to Pay for Home Care
- Medicare and Home Care
- Medicaid and Home Care
- Does Insurance Cover Home Care
- Using a Reverse Mortgage to Stay Home
For Caregivers
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Experts Weigh In


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With the hot weather in the summer often comes refreshing drinks like juices, smoothies and sweetened iced teas. These choices are high in sugar and although they may seem rejuvenating at the time, they are likely to cause a crash in your energy later in the day. Instead of going for these drinks opt for a healthier refreshing beverage by trying these tips.
1. Add homemade flavored ice cubes (http://www.rd.com/food/recipes-cooking/flavored-ice-cubes/) to your water for a colorful and tasty twist.
2. Add a squeeze of lemon or lime for some nice zest!
3. Add whole fruit (try strawberries, raspberries, oranges or even cucumbers) to your water for a flavorful taste.
4. Add herbs such as mint or basil for a nice twist. Add the leaves whole, dice them or muddle them for a stronger flavor.
5. Puree your favorite fruit (berries, peach, watermelon) and add to your water for a fresh, homemade healthier version of juice.
6. Try sparkling water! Sparkling water brands such as Polar and Poland Springs have fun flavors that are calorie free and naturally infused. Plus the carbonation will be an added twist in your water routine.
7. Add a few drops of rose water for a refreshing but different flavor.
8. Let your water soak overnight with some cut up fruit in it (try pineapple!).
**Try adding mint, lime juice and crushed raspberries to your water and soaking overnight to test out our favorite recipe!


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ST. LOUIS -A woman was found dead in a crashed car in north St. Louis early Sunday morning. Residents where the incident occurred want to know when the violence will end.
The homicide happened in the 4200 block of Evans in the Vandeventer neighborhood. Witnesses say someone fired multiple gun shots at the victim's burgundy Chrysler 300 that ultimately lead to a crash.
"Nobody wants to lose their love one to this violence. It's just unnecessary," said one resident
Police have not released the victim's name. The investigation is ongoing. Anyone with information in the case should call CrimeStoppers at 1-866-371-TIPS.
Two additional homicides Sunday are also being investigated in St. Louis. A man in his 20's was found shot to death at Marcus and Ashland at about 11:45 Sunday morning. Around 12:40pm, a woman was found shot to death at Taylor and St. Louis Avenue.


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Written by Cole Locascio
Born into a household with a recent high school graduate for a mother, I was lacking a father for the first four years of my life. Luckily for me though, my grandfather, "Big Daddy" (as pegged by my cousin), was the missing piece to the puzzle. Acting as the primary father figure in my tyke days, the bond we shared was immediately sparked. The key to the flame? Auburn football.
Ever since my first trip to the Plains at a mere age of three months, I was drawn in for life. The soaring of the eagle, the dense amounts of burnt orange spanning across Jordan-Hare, and the roarous cheers from the student section all shaped the early stages of my Auburn obsession… but I'm leaving out the most important part. Sitting way up in section 62, I had the closest thing to a father sitting by my side, each and every week. Shaking and shouting for our defense to wrap up and tackle, I could tell that this so called "game" was a way of life down here in the south — a religion.
A new season was lingering upon us – 2006. I was nine years old at the time when the nuke was dropped directly upon my heart. "Big Daddy's not going to be well for a while. He has cancer." My mother's words from that cool spring day still ring clearly through my ears. Confusion, ignorance, and slight bitterness jumbled to form the question, "So, what about the Auburn games?" My mother was floored by how "selfish" I was acting, and she immediately reprimanded me by my response. But what she didn't realize was that it was a complete misunderstanding.
My intentions were nowhere near selfish, as I knew in my heart and mind that the weekends my grandfather and I shared were the best parts of each other's weeks, and now my mom was telling me that they may never happen again. No more Auburn games, no more moments together in Jordan-Hare, no more Big Daddy. I remember having a pretty tough cry after the ride home, as I finally processed and made sense of the news. Even at the age of nine, I understood that the days with my college football buddy could very well be numbered.
- See more at: http://trackemtigers.com/more-than-a-game/#sthash.oJCJKuBF.dpuf


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Take care with liquid detergents
A recent case where a young child ended up injured after mistaking brightly coloured liquid detergent capsules or sweets has highlighted the need for safety precautions.
They burst easily when they are wet and if the liquid is swallowed it can cause local irritation, vomiting and respiratory distress, warns the National Poisons Centre in Beaumont Hospital Dublin.
These items present a serious risk of injury to children. They should be handled only by adults. Store them out of sight and reach of children. Always handle laundry capsules carefully and with dry hands. Never allow children to handle them.
Keep these products in their original containers. Close the container fully after taking out a capsule and put it back in the cupboard straight away
If your child swallows any of the liquid/contents of a tablet or capsule, rinse as much of the detergent as possible from the child's mouth with water.
Do not make your child vomit. If the contents come into contact with your child's hands, wash thoroughly. If they get into a child's eyes, rinse them carefully with water for 10-15 minutes.
Call a doctor or the Poison Information Centre (01-809 2166) or go to the A&E.
Health & Living


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Some web series pop out as fast as the creative diarrhea works its ways from inception inside the brain of anyone with a camera to the bowels of YouTube. Others, take time. Sometimes years. Crackle's new half-animated, half-live-action comedy web series Issues falls in the latter of those two camps.
The setup of Issues, which percolated during co-creator Matt Oates' college psych class, is rather simple—Dr. Ted (Josh Cooke) is a disgruntled psychologist sorting out "the bizarre neuroses and psychoses" of animated superheroes. Or, as our own Josh Cohen put it, "Issues is what happens when you take those Jerry Seinfeld and Superman AMEX commercials off the streets of New York City and into a pschyologists's office."
Voicing these original superheroes—like the flashing-exhibitionist Captain Magnificent or the blind K9 attack dog—are comedians Seth Green, Eric Stonestreet, Ron Livingston, Rob Riggle, Greg Grunberg, and Eddie Kaye Thomas. While it may be one of the last short form web series from Crackle, it certainly delivers with sharp, original biting comedy.
But hey now, let's show not tell you what the creators had to say about their series, from pitching the concept to Sony/Crackle, to early concept sketches and scoring voice talents of Grunberg, Green, Livingston and more. Oh, and the narrow dance with Sony's legal department between superhero parody and copyright cops.
We are expanding our own original video coverage more here at Tubefilter, so if you like what you're seeing, please let us know. And we wouldn't be complete if we didn't ask you guys to SUBSCRIBE to Tubefilter on YouTube and "Like" our videos. More are coming soon. Thank you guys, we heart you all.


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514 Studios Photo/Video Rental
Main Studio - Suite 101
Natural Light Studio - Suite 200
Beautiful natural light studio space! 1,100 SF with wall to wall south facing windows.
This space is available to rent as a photo studio, short term office space, or client meeting space. Contact for pricing.
CLICK HERE to see what other clients have created in this space.


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Government to host summit on broadband and mobile 'not-spots'
The government will host a long-awaited 'not-spot' summit this week, it has been revealed.
Matt Warman, MP for Boston and Skegness, said the summit on Wednesday will see digital minister Ed Vaizey host representatives from both large and small fixed and mobile broadband providers, as well as groups like the National Farmers' Union and the Countryside Alliance.
The summit, which will look at ways to address variations in fixed and mobile broadband coverage across the country, follows a parliamentary debate led by Mr Warman in October.
In the debate, MPs joined Mr Warman in calling on the government to look at ways to help those in areas without adequate broadband or mobile coverage.
The long-awaited summit will also hear from Broadband Delivery UK, as well as BT and EE, Mr Warman said.
The MP, who is also a former technology journalist, said: "I am pleased that the government is listening to concerns from MPs and other groups about the variations in broadband coverage in both urban and rural areas, and is hosting the 'not-spot' summit to look at ways to improve coverage for families and businesses across the country.
"I have no doubt that the range of internet providers and interested groups will provide for an interesting and productive discussion on what we can all do to ensure better coverage going forward."
During October's debate, Mr Warman warned that without serious investment to connect the "final 5%", the government was risking isolating entire communities and creating a digital divide between those who are connected and those who aren't.
Digital minister Ed Vaizey defended the government's work in rolling out superfast broadband, saying it would reach 95% of homes and businesses by the end of 2017 as well as addressing how to connect the final 5%.
In November, Prime Minister David Cameron announced plans to introduce a new Universal Service Obligation (USO) giving everyone the right to a broadband connection of 10Mbps.
He said: "Access to the internet shouldn't be a luxury; it should be a right – absolutely fundamental to life in 21st century Britain.
"Just as our forebears effectively brought gas, electricity and water to all, we're going to bring fast broadband to every home and business that wants it."
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Saturday, May 30, 2015
GDT card for the Sketchy Challenge
6 comments:
- Sue said...
Louise, this is a gorgeous card. Your colouring is beautiful and your card design is so lovely with all the pretty details you have added...such a perfect card...
- May 30, 2015 at 3:13 PM
- brenda said...
What a gorgeous creation Louise all so beautifully embellished.
Thanks so much for sharing your lovely work and joining in our Vintage theme at Allsorts challenge.
B x
- May 31, 2015 at 2:48 AM
- brenda said...
Hi again Louise,
Just popped back to thank you for also joning in at FlonzCraft Vintage Stamping challenges with your lovely creation.
B z
- May 31, 2015 at 3:54 AM
- Margaret said...
Wow! Stunning! This is absolutely gorgeous. Love the image and all your beautiful details. Thanks for joining us at Creative Knockouts. Good Luck! Maggie, DT
- June 3, 2015 at 10:03 PM
- Tracy said...
I love your choice of image, beautiful details and the design too, thanks for joining Penny Black & More @ Allsorts challenge good luck.
Happy crafting
Tracy x
- June 4, 2015 at 5:37 AM
- susiestacey said...
Such a beautiful card, lots of gorgeous details.
Thank you for sharing at Allsorts 'Vintage' challenge and good luck x Susan x
- June 4, 2015 at 3:20 PM
My DT card for our Mid-way reminder for our challenge at All About Magnolia Our theme is All About Doohickeys For my card I u...
Good day, We have a new challenge starting at Paradise of Stamps, our theme SNOW For the shape of my DT card, I used Sizzix Orna...
Good day everyone, I have a Halloween decor to share with you, my new venture in Mixed Media and I'm loving it. Lots and l...


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text:
Press Release from Fair Games UK
FAIR GAMES UK To Reveal New Super Slim Machines Plus New Furniture And Digital Signage At ACOS
Come to Stand 5 to see Fair Games UK's hugely successful Tic Tac Toe game presented in the Timeless, Casino, and Wallmount cabinets.
New this year are is an assortment of Super Slim, 2-reel machines with cabinet profiles designed to complement a variety of popular machines.
Also on show are Fair Games' ever-popular and reliable Timeless machines featuring games such as Bar 7 & Irish Tic Tac Toe
A new range of furniture, chairs, and digital signage will help your business stand out from the crowd. Fair Games also offers a bespoke furniture service - ask for more details.


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Orbell The Takahe has been designed to be our new school's character.
The Takahe is a conservation icon and survivor. This unique flightless bird has genuine relevance to the Te Anau area as they were re-discovered in the Murchison Mountains of Te Anau in 1948 by Dr Geoffrey Orbell (hence the name).
Orbell represents the five core learning dispositions we believe are important for a Te Anau School Learner
Te Anau School's Learning Dispositions are:
- Connected to our world
- Live the FIORDLAND Values
- Inquiring minds
- Can do attitude
- Effective Communicators
Orbell's Learning Dispositions
|The atlas represents our knowledge of our local environment, NZ and the world we live in. This shows our students' ability to adapt to new places, understand and appreciate various people and their cultures.
|This represents the pack which holds the values, knowledge and attitudes of a Te Anau learner. This is taken everywhere they go. It also shows the tools they need to achieve as well as their ability to change with the times.
|Cups and string represents our ability to communicate in various forms with others. By speaking, listening, using technology, working
collaboratively as well as independently.
Sharing new knowledge with others in also
an important aspect of this.
|This represents thinking. Being a creative, problem solving, whole brain thinker, curious and inquisitive. It's important for our students to be able to think independently, sift and sort through new information and apply it to their learning and to learn from their mistakes.
|By dreaming big and having a can-do attitude, our students will be able to conquer any mountain they aim to climb. Remaining positive, persevering and setting themselves goals is an important aspect of achievement.
Orbell is wearing:
- A greenstone necklace (pounamu) representing Fiordland/Milford Sound
- Te Anau School uniform to show our uniqueness and pride.
- Orbell has a friendly and welcoming smile just like a Te Anau learner.


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Italy: Florence
Florence is a city rich in countless artistic beauties. Just considering the historical centre alone, churches, museums, galleries and palaces, each one a fine example of a definite architectural style, can be admired. The following are some of the monuments to be seen in the historical heart of the city: the Cathedral, Santa Maria Novella, the Medici's Chapels, the Academy, Santa Croce, Palazzo Vecchio (the Old Town Hall), the Uffizi Museum, the Old Bridge, 'Pitti' Palace and the imposing Boboli Gardens, a classical example of 'Italian-style garden'.


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NEW YORK (CBS.MW) -- Stocks recovered from the sting of an IBM earnings warning Monday, with the Dow finishing only modestly lower while the Nasdaq swelled amid gains in the Internet and software sectors.
The broad S&P 500 also battled back after losing ground early on amid escalating worries that rising oil prices would stump the nascent economic recovery.
Big Blue's bad news hurt the hardware sector but all other tech groups gained decent traction. Software stocks interrupted a four-day losing stretch following good news from Computer Associates and buying interest spread to the chip and Internet sectors as well.
In the broad market, buyers flocked to oil, oil service, retail, natural gas, bank and defense issues while sellers remained in control in the airline and gold sectors. Check market stats and latest sector performance.
The Dow Jones Industrial Average DJIA, +1.20% gave back 22.56 points, or 0.2 percent, to 10,249.08 after declining as much as 151 points. Aside from IBM, losses were incurred by Merck, SBC Communications, Philip Morris and General Electric. Upside action was seen in Microsoft, United Technologies, Home Depot, Exxon Mobil, Boeing and Coca-Cola.
The Nasdaq Composite $COMPQ added 15.84 points, or 0.9 percent, to 1,785.87 after falling as much as 37 points and the Nasdaq 100 Index $NDX advanced 16.24 points, or 1.2 percent, to 1,392.96.
Most strategists expect the top averages to cling to well-traveled ranges before first-quarter results begin to hit the tape in earnest next week. Others don't expect earnings to knock stocks out of their doldrums on belief that companies will continue to offer cloudy outlooks.
One strategist feels investors' concerns are overdone.
"[Last year's] fear has given way to suspicion that the scale of the earnings recovery will disappoint, even if the economy recovers. A lot of [investors'] concerns strike us as overdone. The central banks are likely to favor moderation and operating margins are likely to stabilize. We believe corporate recovery is now the contrarian call of choice that favors industrials, information technology and banks," commented Subodh Kumar, CIBC World Market's chief investment strategist.
The Standard & Poor's 500 Index SPX, +1.44% gained 0.2 percent while the Russell 2000 Index RUT, +2.19% of small-capitalization stocks jumped 1.1 percent.
Barrington Research's Alexander Paris said the near-term risk is that the Middle East crisis overshadows economic recovery expectations.
But he views the ensuing downside as a buying opportunity on belief the economic recovery will be sustainable and soon filter into companies' bottom lines.
"While the market may look very confusing in the near term, the key points to remember are that we are still in the first inning of what will be a sustainable economic recovery. The cyclical upturn in corporate profits is not underway yet, but will be very shortly," Paris said in a note to clients.
Merrill Lynch's chief economist Bruce Steinberg surmises that the first-quarter reporting season will carry more upside surprises as profit margins continue to widen. He projects first-quarter gross domestic product to grow at a 6 percent rate, which would imply productivity growth of around 7 percent.
"There is no doubt that rising oil prices are the biggest risk to what is otherwise shaping up as a robust recovery," Steinberg told clients. "But it's clear that the latest price run-up reflects political risk, not the fundamentals of the supply-demand balance."
Volume totaled 1.09 billion on the NYSE and 1.67 billion on the Nasdaq Stock Market. Market breadth ended on a positive note, with winners outnumbering losers by 18 to 13 on the NYSE and by 19 to 17 on the Nasdaq.
On the fund flow front, U.S. equity funds lost an estimated $1.1 billion in the five business days ended April 4 -- the first outflow in eight weeks according to Trim Tabs. The technology funds tracked by the firm had outflows equal to 0.6 percent of assets over the past three days while gold funds remained a "hot area," with inflows equal to 1.2 percent of assets over the past three days.
The fund flow tracker said it remained bearish as corporate liquidity stayed negative. The trading float of shares, in fact, continued to grow due to an absence of corporate buying and new stock buyback announcements in March were the least since March 1997, Trim Tabs noted. On the plus side, new cash takeovers picked up in the previous month.
Read After Hours for trading after the closing bell.
IBM sacks indexes; oil issues spike
IBM IBM, +1.39% Shares slid 10.1 percent after the computer behemoth lowered its first-quarter earnings-per-share and revenue targets. Big Blue said the business environment remained "very tough" and that there was a continued slowdown in customer buying decisions. See the story.
Merrill Lynch sliced its 2002 earnings target for Big Blue and told clients that it was "not clear" whether IBM's business was getting that much worse or whether the negative announcement reflected the inclinations of its new chief executive, Sam Palmisano. SG Cowen said the magnitude of IBM's revenue shortfall suggests the problem is economy related and not company specific.
Among other hardware stocks, Electronic Data Systems fumbled 3.3 percent and storage colossus EMC slid 2.9 percent. And server behemoth Sun Micro SUNW, -2.33% lost 2.4 percent after announcing a cut in U.S. list prices for high-end servers.
Among the PC stocks, Dell Computer, Compaq and Hewlett-Packard watched early losses vanish and closed in the plus column.
IBM's bad news initially dealt chips SOX, +2.78% a loss but the group rebounded from its lows as Applied Materials and Advanced Micro Devices gained 1.2 percent and 1.9 percent, respectively. Leader Intel shed 0.4 percent.
The oil $OIX and oil service OSX, +3.95% areas remained bright spots in the broad market as crude futures for May delivery ascended 33 cents to $26.54 following news that Iraq had suspended exports for 30 days and would lift the halt on condition Israel withdraw from Palestinian areas. Read Futures Movers.
Among the movers in the energy patch: Schlumberger added 0.5 percent, Halliburton 4.1 percent, ChevronTexaco 1.4 percent and Dow stock Exxon Mobil 1.4 percent.
UBS Warburg chief U.S. economist Maury Harris said higher oil prices always present a "quandary" for the Fed as their immediate effect is to add to inflation while subtracting from growth.
"The relative importance of the growth and inflation implications typically depends on the backdrop at the time. In the current environment -- with the economy having ample slack and the trend in inflation already down to around 1 percent -- we believe higher oil prices reduce rather than increase the likelihood of near-term tightening," Harris told clients in a research note.
CA's good news boosts software group
Computer Associates CA, -13.13% climbed 4.2 percent after announcing that its fiscal fourth-quarter operating loss-per-share would be narrower than previous expectations while sales would be in line. The positive pre-announcement from Computer Associates came following a smorgasbord of warnings last week, including a brutal one from PeopleSoft.
And accounting software maker Intuit INTU, +0.94% sprinted 7.4 percent after raising financial targets for its fiscal third quarter. See the full story.
The Goldman Sachs Software Index $GSO gained 2.6 percent after losing 12.4 percent of its value over the past four trading days. Among stocks in the group, Microsoft rose 2.4 percent, Oracle added 1.7 percent and Siebel Systems 3.6 percent while BMC Software lost 1.4 percent.
The Internet group was boosted by sharp gains in EBay and Yahoo, which rose 3.8 percent and 3.7 percent, respectively. But AOL Time Warner AOL, +0.00% didn't join in the festivities and closed down 2.1 percent after Morgan Stanley sliced its price target price on the stock to $30 from $36. See the story.
In analyst actions, fiber-optic concern Sycamore Networks SCMR surged 17.6 percent after being upped by Lehman Brothers to a "strong buy" from a "market perform" on a "compelling" risk vs. reward ratio. The brokerage added that valuations on many wireline stocks are "overly pessimistic." Shares of Sycamore peer Ciena dipped 0.9 percent while Corning jumped 3.4 percent. See The Ratings Game.
Enterasys Networks ETS jumped 7.5 percent after announcing it would slice its work force by 30 percent as part of a previously announced restructuring.
Bank stocks gained some modest ground, with Bank of America BAC, +2.97% up 0.8 percent following a Bear Stearns upgrade to an "attractive" from a "neutral." The firm upped its 2003 earnings targets for Bank One ONE, -4.07% as well, sending shares 1.8 percent higher.
Online broker Ameritrade AMTD, +1.90%, meanwhile, added 1.9 percent after announcing Sunday that it has snagged privately-held Datek Online in a $1.3 billion stock deal. See the full story. Late Friday, Ameritrade lowered its second-quarter profit and revenue outlook given online trading activity levels. Check the story.
In the brokerage group, Merrill Lynch MER, -1.02% closed down 0.8 percent after the New York attorney general moved to reform the company's stock-rating procedures. Check the story.
Drug issues $DRG wobbled, though Johnson & Johnson JNJ, +0.63% bucked the trend and moved 0.5 percent higher despite a downgrade from A.G. Edwards on valuation. Fellow Dow component Merck traded down 2 percent.
Shares of PolyMedica PLMD soared 53 percent after the medical products firm disclosed the termination of a Securities and Exchange Commission investigation. See Screamers.
Read Movers & Shakers for the latest individual stock action.
Treasurys extend losses
Treasury issues closed sharply lower following a morning of extremely whippy action. Concerns about the inflationary repercussions of swelling oil prices weighed on sentiment in the long end of the yield curve and a rebound in stocks added to the negative tone.
The 10-year Treasury note eased 13/32 to yield $TNX 5.255 percent and the 30-year government bond lost 20/32 to yield $TYX 5.715 percent. See Bond Report.
Monday saw the secondary release of February wholesale inventories, which fell 0.7 percent in the ninth straight month of declines. Check economic calendar and forecasts.
No indicators are set for release Tuesday. Data watchers will have to wait until the end of the week to get their fix. Friday, in fact, will see three key reports hit the tape: March retail sales, the March producer price index and the April Michigan consumer sentiment index.
In the currency sector, the dollar eased 0.1 percent to 131.54 yen while the euro shaved 0.5 percent to 87.45 cents.


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When the Israelites were preparing to cross the Jordan River into the Promised Land, they received this instruction:
When you see the ark of the covenant of the Lord your God with the Levitical priests carrying it, then you shall set out from your place and go after it. However, there shall be between you and it a distance of about 2,000 cubits by measure. Do not come near it, that you may know the way by which you shall go, for you have not passed this way before (Joshua 3:3-4).
How many times in your life have you felt unsure of where you were headed, not to mention how you were going to get there? Going off to college, managing finances, getting married, taking care of children, working through heartache and loss--all of these experiences can leave us wondering what we have gotten ourselves into and how we are supposed to handle it.
Having a guide in front of us or at least beside us is helpful when we are getting from Point A to Point B for the first time. Even Google Maps will do. But when we are navigating the complexities of life, it's not always that simple. Our situations are unique, and there may not be just one way or even one best way to get where we are going.
I find comfort in the fact that Jesus has gone this way before, all the way to death and beyond.
Therefore, since we have a great high priest who has passed through the heavens, Jesus the Son of God, let us hold fast our confession. For we do not have a high priest who cannot sympathize with our weaknesses, but One who has been tempted in all things as we are, yet without sin. Therefore let us draw near with confidence to the throne of grace, so that we may receive mercy and find grace to help in time of need (Hebrews 4:14-16).
Even though Jesus does not always make our path easy, he makes it easier by providing light--even if just a glimmer--in the darkness and by inviting us to come close to him. We do not have to follow the ark at a distance anymore. We can approach the throne of grace with confidence.
As we walk day by day and step by step in our journey, we should be willing to extend the same grace we have received to those around us. Every other person we encounter is still on his or her first attempt to survive this crazy world.
It's easy for me to be quick to judge, quick to condemn. Instead I should "put on a heart of compassion, kindness, humility, gentleness and patience; bearing with one another, and forgiving each other, whoever has a complaint against anyone" (Colossians 3:12-13). None of us has passed this way before.


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Top secret Clinton emails include talk on drone op
The two emails on Hillary Rodham Clinton's private server that an auditor deemed "top secret" include a discussion of a news article detailing a US drone operation and a separate conversation that could point back to highly classified material in an improper manner or merely reflect information collected independently, US officials who have reviewed the correspondence told The Associated Press.world Updated: Aug 15, 2015 01:19 IST
The two emails on Hillary Rodham Clinton's private server that an auditor deemed "top secret" include a discussion of a news article detailing a US drone operation and a separate conversation that could point back to highly classified material in an improper manner or merely reflect information collected independently, US officials who have reviewed the correspondence told The Associated Press.
The sourcing of the information could have significant political implications as the 2016 presidential campaign heats up. Clinton, the front-runner for the Democratic nomination, agreed this week to turn over to the FBI the private server she used as secretary of state, and Republicans in Congress have seized on the involvement of federal law enforcement as a sign that she was either negligent with the nation's secrets or worse.
On Monday, the inspector general for the 17 spy agencies that make up what is known as the intelligence community told Congress that two of 40 emails in a random sample of the 30,000 emails Clinton gave to the State Department for review contained information deemed "Top Secret/Sensitive Compartmented Information", one of the government's highest levels of classification.
The two emails were marked classified after consultations with the CIA, which is where the material originated, officials said.
The officials who spoke to the AP on condition of anonymity work in intelligence and other agencies. They would not detail the contents of the emails because of ongoing questions about classification level. Clinton did not transmit the sensitive information herself, they said, and nothing in the emails she received makes clear reference to communications intercepts, confidential intelligence methods or any other form of sensitive sourcing.
The drone exchange, the officials said, begins with a copy of a news article that discusses the CIA drone programme that targets terrorists in Pakistan and elsewhere. While a secret programme, it is well-known and often reported on. The copy makes reference to classified information, and a Clinton advisor follows up by dancing around a top secret in a way that could possibly be inferred as confirmation, they said. Several officials, however, described this claim as tenuous.
But a second email reviewed by Charles McCullough, the intelligence community inspector general, appears more suspect. Nothing in the message is "lifted" from classified documents, the officials said, though they differed on where the information was sourced from. Some said it improperly points back to highly classified material, while others countered that it was a classic case of what the government calls "parallel reporting" -- different people knowing the same thing through different means.
The emails came to light on Tuesday after Senator Chuck Grassley reported that McCullough found four "highly classified" emails on the unusual homebrew server that Clinton used while she was secretary of state. Two were sent back to the State Department for review, but Grassley said the other two were, in fact, classified at the closely guarded "Top Secret/SCI level".
Clinton spokesperson Jennifer Palmieri has stressed that Clinton was permitted to use her own email account as a government employee and that the same process concerning classification reviews would still be taking place had she used the standard 'state.gov' email account used by most department employees. The State Department, meanwhile, stressed that it wasn not clear if the material at issue ought to be considered classified at all.
Clinton says she exchanged about 60,000 emails in her four years as secretary of state. She turned over all but what she said were personal emails late last year. The department has been making those public as they are reviewed and scrubbed of any sensitive data.
The State Department advised employees not to use personal email accounts for work, but it was not prohibited.
First Published: Aug 14, 2015 20:04 IST


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Tired of talking/reading about Heaven? Didn't think so. Frankly, I could talk about Heaven all day every day. However, the month is sadly coming to a close, and thus we are nearly finished with the topic of Heaven (for now). So maybe you just read one article. Maybe two. Maybe all of them! Either way, when you finish an article, particularly one about Heaven, you may ask yourself questions such as: "What now? Where do we go from here? How does this legitimately affect me?" Let's reflect on the month real quick and see what we've covered and use that material to answer these questions.
We shouldn't be running away from Hell, but rather toward Heaven- "I believe it's time we shift our motivation from running from Hell to running towards Christ." (Travis Farr, in "Not Running from, but Running to") This may have been your initial motivation for salvation, and I'm in no way slamming you if it is. However, we need to now change that motivation. God's love is super-fantastically-amazingly-awesome, and if we turn toward that and pursue it with all of our strength, we will find that we are no longer running wildly away from Hell. This gives us a purpose of pursuing.
Heaven isn't about us; it's about God-
- Heaven is going to be a blast.
- Heaven is for worshipping and abiding with God.
- Heaven is not for vacationing.
– (Scott Paris, in "Modern Misconceptions about Heaven")
We need to be living Heavenly-minded lives- I'm not sure if this article struck home or not; only you can know that. However, if there is one thing that I want to repeat and get it as stuck in your mind as possible it is this: "You can't turn your thoughts toward the future if they're stuck in the past." This can have a variety of reasons for a variety of people, and while I don't have time to elaborate too much on the phrase, I think that you know what it means for YOU personally.
Hell isn't for partying. It's for punishment- If you dilute the severity of Hell, you consequently dilute the awesomeness of Heaven. We have to view Hell as it is: a painful, sad, terrifying place full of torment. There will not be a party in Hell. Nothing happy will happen in Hell. There is no deliverance out of Hell. And worst of all, the inhabitants of Hell are separated eternally from our Lord and Savior. There it is. Hell isn't to be messed around with.
Being involved in furthering God's kingdom brings the most lasting joy- No one will argue that temporal pleasure gives joy. However, as the name implies, it is not a lasting joy. It is temporal. God's Kingdom doesn't start after we die. It starts now.
Okay, so back where we started in this article. Where does this leave us? Honestly, I don't know. For me, it leaves me entirely awestruck. I'm just utterly amazed that I have a God who loves me so much that He not only rescued me from the torment in Hell but also is preparing an amazing, perfect place for me. Doesn't that make you excited? In awe? Ready to thank God? I realize that I'm not masterfully tying all of these components together in a conclusive way. However, I think that this topic does the talking for itself (at least it seems that way to me). Okay, let's see about this… Wrapping up the entire month's topic in one statement:
Seek first the Kingdom of God; that which is above, and press toward the goal of the high calling of Christ, not looking back, but keeping our eyes fixed fully on Christ.
That may or may not have been a run-on sentence, but you get the picture. So there it is. Don't pass up this chance to change the way you view… everything. Be in continuous remembrance of Heaven. When you close out of this tab or turn off your phone, there is about a 99% chance that you won't think back on this article again. Don't let that happen. FOCUS ON HEAVEN!!! It's all in your mind. Your actions follow your mind; ergo if we work on the battlefield of the mind, we will fare better on the battlefield of the actions. Here's something practical to do: set up reminders, sticky notes, phone alarms, anything that can get you to remember Heaven. Try it for the rest of today. Then go to a full day. Then two days. You get the picture. Pray that God will help you in this ongoing struggle. Remember, the kingdom of God starts now, not after we die. Heaven is about God, not us, not fear of Hell, not the pleasures of Heaven. May God be with as you strive to do this in your daily life.


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Richest Celebrities
Brian Williams Net Worth
Brian Williams Net Worth is
$40 Million
Brian Williams's salary
$13 Million
Brian Williams Bio/Wiki 2018
Brian Douglas Williams, or only Brian Williams is a leading American journalist, best-known as the controlling editor and anchor of NBC Nightly Information. It Is an everyday television information program, rated No. 1 in Usa. It's aired live from the NBC studio at Rockefeller Center. Brian did on a handful of stations, before assuming his present place in 2004. He began his professional career in the early eighties, showing on KOAM TV and afterwards transferred to act as a correspondent on WTTG TV. From the conclusion of decennary he was promoted to the job of the headlines anchor on WCBS TV. For 2013, Brian Williams internet worth is approximated at $30 million bucks and his yearly wages sums to $13 million.
Brian Williams Net Worth $30 Million
Williams was born in 1959, within an Irish Catholic family. For several years his daddy Gordon L. Williams has served as a vice-president of NRMA (Nationwide Retail Retailers Association). Gordon was regarded as a rich and powerful guy, although his fortune never arrived close to Brian Williams internet worth. As a teen Brian volunteered in the Middletown Township Fire Department and attended Mater Dei High-School. Although his household was well to do, as a way to feel more impartial Williams was employed as a busboy. After graduation from high-school Brian attended three distinct learning associations (Brookdale Neighborhood College, Catholic University of America and The George Washington College), but didn't figure out how to get a diploma. The millionaire notes that leaving university was clearly one of his biggest errors, even though Brian's specialist vocation was not hampered by having less teaching.
Brian Williams internet worth increase gained impetus in the late eighties, when he he began anchoring weekend nighttime and weekday midday newscasts on WCBS TV. In 1993 he left this place to start out employed as a White House correspondent for NBS Information. 36 months after Williams was offered a chance to host his own information program, The Information with 0Brian Williams, which shortly became the main trademark show on both CNBC and MSNBC. In 2004, when a long-time Nightly News anchor and leader newsman Tom Brakaw left the present, Brian was agreed to suppose his place. Since his first day in the system Brian has held the Nightly Information near the top of the evaluation tables, pulling 10 million spectators normally. Williams' closest rival is Gibson along with his plan The Globe News with Charles Gibson.
How about his private life? Since 1986 Brian has been joyfully married to Jane Gillan Williams. The few got two children: Brandon Williams and Alison. Brian's daughter, now in her mid-twenties, is an aspiring performer, recording artist and comedienne, famous for her part in tv series Women. Despite her expert success, several years must pass before Alison's fortune comes near to Brian Williams internet worth.
|Net Worth
|$40 Million
|$13 Million
|Date Of Birth
|May 5, 1959
|Place Of Birth
|Elmira, New York
|6 ft (1.85 m)
|Journalist, Firefighter, Actor, Editor, Voice Actor
|Brookdale Community College, The George Washington University
|Jane Stoddard Williams (m. 1986)
|Allison Williams, Douglas Williams
|Gordon L. Williams
|Brian Douglas Williams, Williams Brian
|TV Shows
|,"NBC Nightly News" (2004-), "Dateline NBC", "Rock Center with Brian Williams","The Daily Show", "Saturday Night Live", "30 Rock", "The Soup" (2004)
|The Sins of Pluto Patterson
|Co-Worker #2
|One Angry Dwarf
|Cheese Bread Man
|The Sins of Pluto Patterson
|Short production assistant
|One Angry Dwarf
|Short audition assistant


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Dr. Kanani, a rarely regarded cosmetic dentist can renovate your smile. Los Angeles, California (PRWEB) Sep 28, 2013 Top dentist in Woodland Hills, Dr. Kanani, is courteously charity nominal recommendation onArticle source: http://www.prweb.com/releases/dental-implants-cost/dentist/prweb11159584.htm
Dr. Kanani, Renown Dentist in Woodland Hills, Unveils New Prices on Dental Implants
September 28, 2013
Dr. Kanani Gives Advise on a Benefits of Dental Implants and He Reveals New Prices for Dental Implants
September 25, 2013
Dental Implant Los Angeles Los Angeles, California (PRWEB) Sep 24, 2013 Dr. Kanani is a really renouned dentist in Woodland Hills and he is now charity advise on what dental implants are, how it might be a good choice for those who humour from tooth detriment and how muchArticle source: http://www.prweb.com/releases/dental-implants/dentist/prweb11159524.htm
Dr. Kanani, Woodland Hills Dentist: Tooth Loss and Job Prospects
June 21, 2013
Dr. Kanani Introduces Perio Protect to Fight Gum Disease Los Angeles, California (PRWEB) Jun 21, 2013 In America, a need for a good grin is overpowering, generally for those looking for work. A Jun 12, 2013 essay by CNBC, "Bad Teeth, Broken Dreams: Lack of Dental Care Keeps Many Out of Jobs" (cnbc.com/id/100810944) reported estimationsArticle […]
Dr. Kanani, Woodland Hills Dentist: Dangers of Tooth Damage and Obstructive Sleep Disorder
May 19, 2013
Dr. Kanani, a rarely regarded cosmetic dentist can renovate your smile. Los Angeles, California (PRWEB) May 19, 2013 Grinding your teeth during night can do most some-more repairs than only losing sleep, or irritating your spouse. AtArticle source: http://www.prweb.com/releases/dental-implants-cost/dentist/prweb10744398.htm
Woodland Hills Dentist Dr. Kanani, Explains The Process Of His One Of A Kind Dental Implant Procedure, Which He …
March 20, 2013
Mar 15,2013 outlines a 6 month duration given Dr. Kanani has started his Flap-less/Drill-less dental make procedures. He announces 100% success rate to date given he started behaving this procedurs that also lowers a cost of dental implants. Los Angeles, CA (PRWEB) Mar 18, 2013 Dental implants are customarily dear though mostly effective tooth replacements. […]


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VANCOUVER,British Columbia and SHANGHAI July 3,2018-ELIX Wireless, the pioneering developer of wireless charging technology, today announced that it has won the 2018 Red Herring Top 100 North America Award that recognizes the continent's most exciting and innovative private technology companies.
How safe is the ELIX E8K for electronics?
ELIX Wireless gets 2018 Red Herring Award
2018 Red Herring Top 100 North America Winners
Electric Vehicle Outlook 2018 - Bloomberg New Energy Finance
Electric Vehicle Charging Stations Market - Global Forecast to 2023
Wireless Car-Charging Testing Comes to GoMentum Station
Self-driving cars for country roads
China's Electric Car Makers Shine at Beijing Auto Show
Taking on the World: Women in Tech
Automakers and state governments cooperate on ad campaign for EVs
China just made it easier for self-driving tests to take place on any road in the country
Norway's EV Association Conducts Biggest Winter Electric Car Test Ever
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Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.
Citation: Bidinotto LT, Scapulatempo-Neto C, Mackay A, de Almeida GC, Scheithauer BW, Berardinelli GN, et al. (2015) Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord. PLoS ONE 10(9): e0137690. https://doi.org/10.1371/journal.pone.0137690
Editor: Marta M. Alonso, University Hospital of Navarra, SPAIN
Received: April 30, 2015; Accepted: August 19, 2015; Published: September 15, 2015
Copyright: © 2015 Bidinotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: aCGH data of the array can be accessed using the Gene Expression Omnibus number GSE64891. Aligned sequence data are available at the European Genome-phenome Archive (EGA) under accession number EGAS00001001432.
Funding: This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico [475358/2011-2] to RMR (www.cnpq.br); Fundação de Amparo a Pesquisa do Estado de São Paulo [2012/19590-0] to RMR and [2011/08523-7 and 2012/08287-4] to LTB (www.fapesp.br); the Foundation for Science and Technology (FCT) [PTDC/SAU-ONC/115513/2009] to RMR; and the National Cancer Institute [P30CA046934] to MGV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a very recent entity, recognized in the latest, 2007 edition, of the WHO classification of Central Nervous System Tumors [1]. RGNT is composed by two distinct features: a predominant glial component, whose morphology resembles pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular pseudorosettes. This rare tumor affects predominantly adult females (61%), with mean age around 32 years, typically originating in the fourth ventricle and/or aqueduct [1, 2]. Due to its usual indolent course, it is considered a WHO grade I tumor [1].
Hitherto, less than 100 cases are reported in the literature [3], most of them as case reports of MRI, histopathological and immunohistochemical findings [4–9]. There are few molecular studies, with the only recurrent genetic alterations identified being PIK3CA [10, 11] or FGFR1 mutations [12].
Herein, we describe a 33-year-old man with RGNT arising in a peculiar location, namely the spinal cord. We further performed immunohistochemistry and molecular analysis, using array-CGH, whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology.
Material and Methods
A 33-year-old male was operated on Barretos Cancer Hospital, to resect a tumor located in the spinal cord. Following gross-total resection, part of the lesion was formalin-fixed and paraffin embedded for standard H&E and immunohistochemistry staining, and the remaining tissue was snap frozen for further molecular analysis. Additionally, peripheral blood was collected. The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish these case details. The local Ethical Committee of Barretos Cancer Hospital has approved this study under the processes number 262/2009 and 408/2010.
Immunohistochemical analyses (streptoavidin-biotin peroxidase method) were performed for specific markers, according to the S1 Table. The reactions were performed using the Ventana System (Ventana Systems Inc.), following suppliers' recommendations.
Microsatellite instability analysis in tumor and blood DNA was performed according to Viana-Pereira et al [13]. For aCGH, two-color Comparative Genomic Hybridization microarray was performed using default Agilent enzymatic labeling protocol. Four hundred nanograms of both tumor and blood (used as reference) DNA were digested by AluI and RsaI restriction enzymes, and incubated with random primers. Blood DNA was labeled with cyanine-3, whereas tumor DNA was labeled with cyanine-5. Labeled DNAs were hybridized into Agilent Human Genome CGH 8x60K microarray slide, and washed according to supplier's protocol. The slide was scanned and decoded by the software Feature Extraction v.10.7 (Agilent Technologies). The signal intensities were log2 transformed, and the spots mapped to hg19. Data were Lowess normalized, smoothing corrected, and CBS segmented. aCGH data can be accessed using the Gene Expression Omnibus number GSE64891.
For known cancer-related hotspot mutational screening, Ion Torrent platform (Life Technologies) was used. The library was built according to the default protocol described by the supplier. Ten nanograms of tumor DNA was amplified using Ion AmpliSeq Library kit 2.0 (Life Technologies) and Ion AmpliSeq Cancer Primer Pool. After sample tracking preparation using Ion AmpliSeq Sample ID Panel, the positive Ion Spheres were enriched by Ion PGM Template One Touch 200 kit and further sequenced in an Ion 316 chip, using Ion PGM Sequencing 200 kit v2. The analysis was performed based on coverage and reads quality, and frequency of reference/variant bases in each position, using the software Ion Torrent Variant Caller v.3.6.2.
Exome sequencing was performed on tumor and peripheral blood DNA. Briefly, exome capture was carried out using the 50Mb Agilent SureSelect platform (Agilent Technologies), and paired-end-sequenced on an Illumina HiSeq2000 (Illumina Inc.) with a 100bp read length. Reads were mapped to the hg19 build of the human genome using bwa, and PCR duplicates removed with PicardTools 1.5. Somatic single nucleotide variants were called using the Genome Analysis Tool Kit v.2.4–9. Variants were annotated using the Ensembl Variant Effect Predictor v.71 incorporating SIFT and PolyPhenpredictions, COSMIC v64 and dbSNP build 137 annotations.
In order to validate the mutations identified through Exome NGS, primers for all somatic variants were designed and PCR [14] followed by direct sequencing was performed (S2 Table). Additionally, the most relevant hotspots regions of PIK3CA were assessed using the oligonucleotide primers (S2 Table). The PCR reactions of PIK3CA were performed in a final volume of 15 μL, under the conditions: 7.2 μL HotStar Master Mix (QIAGEN), 5.6 μL H2O2 (QIAGEN), 0.3 μL each primer and 0.6 μL MgCl2 5 mM. PCR amplification was performed in a Veriti 96 Well Thermal Cycler (Applied Biosystems) with an initial denaturation step at 96°C for 15', then amplified for 40 cycles of denaturation at 96°C for 45s, annealing at 55.5°C for 45s, extension at 72°C for 45s and final extension at 72°C for 10'.
After amplification, the PCR products were firstly purified with EXO-SAP (GE Techonology), and then submitted to a sequencing reaction using 1 μL of BigDye Terminator v3.1 (Applied Biosystems), 1.5 μL of sequencing buffer and 1 μL of each primer. The sequencing reaction was followed by post sequencing purification with BigDyeXTerminator Purification Kit following the manufacturer's instructions. Direct sequencing was performed in 3500xL Genetic Analyzer (Applied Biosystems).
For mRNA analysis, first-strand cDNA was synthetized from five hundred nanograms of tumor RNA using SuperScript III First-Strand Synthesis SuperMix (Invitrogen), according to the protocol provided by the supplier, using random hexamers. The nested PCR was performed using 2 pairs of primers specially designed for detecting the fusion KIAA1549:BRAF, according to Forshew et al. (2009) [15] (S2 Table). Finally, the PCR product was purified and sequenced.
KIAA1549:BRAF gene fusion was also evaluated by FISH, as previously described [16]. Briefly, FFPE sections were incubated at 56°C for 2 h, dewaxed in CitriSolv (Fisher), air dried, and dehydrated. Pre-hybridization procedure was performed with reagents from the SPOT-Light Tissue Pretreatment Kit (Invitrogen). Specimen were boiled in heat pretreatment solution for 50', washed in PBS, digested with the enzyme reagent for 55' at 37°C, washed in PBS, dehydrated and air dried. The KIAA1549/BRAF probe mix (200ng of BRAF SR DNA–BAC clone RP4-726N20—and 200ng of KIAA1549 SG DNA–BAC clone RP11-148L5) was applied to the selected hybridization area, which was covered with a coverslip and sealed with rubber cement. DNA co-denaturation was performed in the HYBrite (Vysis) at 85°C for 5' and hybridization was allowed to occur at 38°C for 40 h. Post-hybridization washes were performed by incubating in 2×SSC/0.3% NP-40 at 74°C for 3' then in 2×SSC at room temperature for 2', followed by dehydration. Finally, DAPI/anti-fade (0.3ug/ml in Vectashield mounting medium) was applied and the area covered with a coverslip.
Analysis was performed on epifluorescence microscope using single interference filter sets for green (FITC), red (Texas red) and blue (DAPI) as well as dual (red/green) and triple (blue, red and green) band pass filters. Fifty nuclei per specimen were analyzed for tandem duplication of KIAA1549 and BRAF, which was identified as presence of overlapping red and green fluorescent signals.
The patient presented with progressive gait disturbance, thoracic spine pain and bladder dysfunction. Physical examination revealed weakness of the upper and lower extremities and spasticity with clonus and exaggerated muscle stretching reflexes. A spinal MRI scan with gadolinium revealed a contrast enhancing, expansive lesion centrally located in the cervical-thoracic spinal cord (C6 to T3), and measuring 9.5x1.9x1.5cm, with extended seringomielin and hemosiderin (Fig 1).
(A and B) Magnetic resonance images showing an expansive lesion between C6 and T3.
A C6-T4 laminectomy and gross-total resection was undertaken. The patient was discharged after 18 days, and clinical examinations and MRI were performed every 6 months. In the last follow up (January 23rd 2014, 52 months after the surgery), besides the latent paraplegia, with sensitive level up to T4, and urinary bladder dysfunction, the patient was alive with no abnormalities.
Histopathological and immunohistochemical characterization
The histology revealed a WHO grade I RGNT typically found in the fourth-ventricle. This tumor featured the usual biphasic neurocytic (Fig 2A) and glial (Fig 2A and 2B) architecture. The neurocytic component consisted of a uniform population of neurocytes forming neurocytic rosettes, characterized by a ring of neurocytic cells with small and monomorphic nuclei with an eosinophilic and acellular neuropil core. Vascular pseudorosettes were also present (Fig 2A inset). The glial component was dominant, and resembled pilocytic astrocytoma composed of spindle to stellate in shape with elongate to oval nuclei and moderately dense chromatin. Some cells superficially resembled oligodendroglia cells with occasional perinuclear halos. Rosenthal fibers, hemosiderin deposits associated with thick-walled, and occasionally hyalinized vessels were observed. Immunoreactivity for synaptophysin (Fig 2C), neurofilament and MAP2 (Fig 2D) proteins were depicted in the neurocytic component, whereas the glial component exhibited positivity for GFAP (Fig 2E) and S-100. Neurocytic component was found negative for GFAP (Fig 2E). Mitoses were not observed and the proliferation index labeled by Ki-67 expression was observed in approximately 3% of cells (Fig 2F). There was no necrosis, anaplasia or microvascular proliferation. Due to the rarity of this lesion, and its atypical location, the case was further sent to an expert in neuropathology (B.W.S.), for a second opinion, who confirmed the initial diagnosis of RGNT.
(A) HE showing the neurocytic and glial area (H&E 200x). Inset detailing the neurocytic rosette with a neuropil core (H&E 1000x). (B) Glial component (H&E 200x). (C) Neurocytic component positive for synaptophysin (400x). (D) Neurocytic component stained by MAP2 expression (200x) that highlights the neuropil of the neurocytic rosette in detail (400x). (E) Neurocytic area negative for GFAP and glial area positive for GFAP (400x). (F) Ki67 showing low proliferation index in neurocytic area (200x).
Molecular profile
In order to better characterize the genetic alterations of this rare case, we performed an extensive analysis of genetic instability, either at the chromosomal (aCGH) and the nucleotide level (microsatellite instability), screened for the presence of mutations in 46 major cancer related genes, and extended the analysis to whole exome sequencing.
Array-CGH showed loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16 (Fig 3A). Moreover, we observed focal gains/losses in the chromosomes 1, 2, 3, 6, 7, 11, 14, 17, 22 and X, and local amplifications in 9q34.2 and 19p13.3 (S3 Table). A higher level of gain was observed at chromosome 7q34, encompassing the genes KIAA1549 through BRAF, with breakpoints in those genes (Fig 3A–dashed arrow). RT-PCR was performed to confirm that this genomic gain reflected the fusion of the genes KIAA1549:BRAF. The RT-PCR showed a band of the expected size (approximately 800bp) (Fig 3B). To further verify the presence of KIAA1549:BRAF gene fusion, the RT-PCR product was sequenced and the fusion between exon 16 of KIAA1549 and exon 9 of BRAF gene was detected (Fig 3C). Finally, we performed FISH to confirm the presence of the fusion (Fig 3D). As observed, the overlapping signals of KIAA1549 (green) and BRAF (red) generated by the tandem duplication, observed as red-green doublets or yellow spots, denotes the presence of KIAA1549:BRAF gene fusion (Fig 3D). Of note, the positive pattern for KIAA1549:BRAF fusion was found only in the neurocytic component, whereas the cells in the areas consistent with the glial component were negative.
(A) Plot representing the whole genome, highlighting the KIAA1549:BRAF fusion (dashed arrow), (B) Agarose gel representing: M. 100 bp ladder; 1. RT-PCR result using the pair of primers for detecting KIAA1549:BRAF fusion; 2. the housekeeping gene GAPDH; 3. negative control. C) Direct sequencing of the band of the Fig 3A.1, showing the fusion point of KIAA1549 (exon 16) and BRAF (exon 9). D) FISH results of the glioneuronal portion of the tumor showing yellow signals, representing the overlapping of KIAA1549 (green) and BRAF (red) signals (arrows). E) IGV visualization of exome NGS results (left) and direct sequencing validation (right) of MLL2 gene.
The tumor exhibited a microsatellite stable (MSS) phenotype (data not shown). Previously reported recurrent PI3KCA and FGFR1 hotspot mutations were not detected by direct sequencing and Ampliseq Cancer. Somatic mutations were identified in the genes MLL2 (Fig 3E), CNNM3, PCDHGC4 and SCN1A (Table 1) by whole exome sequencing and validated by direct sequencing.
This study describes for the first time a comprehensive genetic characterization of a case of RGNT of the fourth ventricle arising in the spinal cord. This is not the usual presentation, yet it has been previously reported [17, 18]. The MRI images showed a relatively well-demarcated lesion, with low and high intensities in T1 and T2, respectively, which corroborate findings of other studies [8, 17, 18].
The presentation of this case could resemble other tumor types described in the literature, such as glioneuronal tumor with neuropil islands (GNTNI), a WHO grade II/III that affects the spinal cord in in 23% of cases [3]. GNTNI is an infiltrative astrocytoma with scarce micronodules (islands of neuropil) or bigger and atypical islands delimitated by oligodendrocyte-like cells that stains for synaptophisin or Neu-N. The glial component of GNTNI is composed predominantly by a astroglial fibrillary or gemistocytic component, and not by a pilocytic component as find in RGNT, and this glial component can be atypical with increased mitotic activity, microvascular proliferation and necrosis. In the present case, the morphological diagnosis of RGNT at H&E-stained slides was further confirmed by immunohistochemistry. The neurocytic component was positive for synaptophisin, neuron specific enolase and MAP2, and the glial component was positive for GFAP and S-100 protein. Furthermore, no mitotic activity was observed. These morphological and immunohistochemistry differences were recognized and utilized to rule out the diagnosis of GNTNI, and confirm the diagnosis of RGNT.
In order to interrogate the genetic abnormalities of this rare case, we analyzed the presence of chromosomal and microsatellite instability. We found loss in 1p, gain in 1q, 7, 9 and 16. There are two studies that evaluated the co-deletion 1p/19q, and no alterations were found [19, 20]. Interestingly, we observed loss of the entire short arm of chromosome 1. Of particular interest was the observed gain of chromosomes 9 and 16, events not frequently described in SNC tumors [21]. Additionally, we found focal amplification at 19p13.3, where the SBNO2 gene is located. This gene codifies a protein that exhibits a RNA helicase activity [22], and is involved in anti-inflammatory responses, regulated by IL-10 in a STAT3-dependent way [23]. To date, there are no reports relating directly this specific gene to cancer development. Further studies are needed to understand whether SBNO2 gene amplification leads to protein overexpression, and gain of activity in RGNTs.
Importantly, we observed a gain in the chromosome 7 encompassing the genes KIAA1549 and BRAF, with intragenic breakpoints in both genes. We performed RT-PCR to validate the presence of a fusion, which was further confirmed by Sanger sequencing and FISH, which highlighted a fusion between the exon 16 of KIAA1549 and the exon 9 of BRAF. The presence of KIAA1549:BRAF fusion is found in 60% of pilocytic astrocytomas [16] and was not previously detected in RGNT in the literature [24–26]. Morphologically, the glial component of both tumors are identical, and could explain the finding of KIAA1549:BRAF fusion, that is frequently found in pilocytic astrocytomas. Interestingly, we observed the presence of the KIAA1549:BRAF gene fusion only in the neurocytic component.
We further performed extensive mutation profiling, corroborating recent studies that reported the absence of mutations in the BRAF, IDH1 and IDH2 genes [24, 27], and further failed to identify the presence of PI3KCA gene mutations as suggested by Ellezan and collaborators [10], nor FGFR1 gene mutations as suggested by Gessi and collaborators [12]. Importantly, whole exome sequencing identified somatic mutation in four genes—MLL2, CNNM3, PCDHGC4 and SCN1A. Among these genes, we found MLL2 to be of particular interest. MLL2, mapped on chr19q13.12, is described to be required for the maintenance of basal transcription machinery stabilization [28]. Loss-of-function mutations of this gene have been present in the genetic landscape of meduloblastoma [29, 30], since it is able to change the gene expression pattern by impairing H3K4me1/2 on genes enhancers [31].
In conclusion, our comprehensive molecular profiling of a RGNT case suggests the existence of a unique genetic pathway for the development of these tumors: KIAA1549:BRAF fusion is a possible driver by constitutively activating MAPK pathway, [32] and MLL2 mutation may lead to profound changes in the transcriptome [33]. Whole genome sequencing studies of low-grade gliomas suggest that few genetic alterations are required for oncogenesis, and there are some recurrent chromosomal abnormalities, depending on the histopathological subtype [33]. Taken together, these mechanisms may increase survival and/or tumorigenic capacity of cells, leading to the development of this rare entity.
Supporting Information
S1 Table. Primary antibodies and experimental details used for immunohistochemistry analysis.
S2 Table. Primers used in direct sequencing validation and KIAA1549:BRAF fusion.
S3 Table. Regions presenting point copy number gains and losses.
Author Contributions
Conceived and designed the experiments: LTB CSN CJ RMR. Performed the experiments: LTB AM GNB RT CAC LTF MVP MVG. Analyzed the data: LTB CSN AM GCA BWS GNB RT LTF MVP MVG CJ RMR. Contributed reagents/materials/analysis tools: LTB CSN AM CAC LTF MVG CJ RMR. Wrote the paper: LTB CSN CJ RMR.
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LONDON (REUTERS) - Athletics' world governing body voted overwhelmingly on Friday to provisionally suspend the Russian federation and the country's athletes from the sport following revelations of widespread, state-sponsored doping earlier this week.
The International Association of Athletics Federations' (IAAF) council voted 22-1 in favour of the sanction.
The decision came after the IAAF held a teleconference, hosted by president Sebastian Coe, to discuss the report released on Monday by the independent commission of the World Anti-Doping Agency (Wada), which recommended the punishment.
The report alleged "systemic" collusion between Russian athletes and the country's federation and anti-doping authorities and a "deeply-rooted culture of cheating" that enabled athletes to take performance-enhancing drugs without fear of being tested.
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