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Nicolas Anelka insists he is happy at West Brom and that he did
Anelka has been charged by the FA and could face a minimum five-match ban if found guilty
Anelka has been charged by the FA and could face a minimum five-match ban if found guilty
Shouting from the sidelines isn't the only way that sports fans can make their views known. Will Dean looks at a new exhibition that highlights the art of the well-written banner
He was a hero to West Ham fans, the working class of the East End
Other football clubs have moved into stadiums with tracks - with mixed fortunes
Spurs' match in Italy was overshadowed by racist behaviour
Tottenham Hotspur 3 West Ham United 1
Italy's capital has been rattled by increasing militancy by the extreme right since October, often with racist overtones.
Striker demands Spurs correct alarming dip in form
Lazio 0 Tottenham Hotspur 0
Paolo Gabriele could face jail but insists he released papers to make Pontiff aware of endemic 'evil and corruption' in Rome
Fears of a Mafia turf war in Rome and the surrounding areas have being re-ignited after a Neapolitan gangster was gunned down in busy square in front of dozens of people.
The Germany forward Miroslav Klose is days away from turning 34 but competition for places and a desire to play at the 2014 World Cup in Brazil keep him motivated despite the occasional twinge.
Djibril Cisse has "no doubt" QPR will stay in the Barclays Premier League this season.
Lazio have sacked coach Davide Ballardini and replaced him with former Napoli boss Edy Reja.
Lazio sporting director Igli Tare has brushed aside reports linking Mauro Zarate with a move to Arsenal.
Lazio beat Sampdoria 6-5 on penalties to lift the Italian Cup after Wednesday's final at the Stadio Olimpico finished 1-1 following extra-time.
Cantus Cölln's imagined reconstruction of a Vespers performance in St Peter's, Rome, captures the collision of 16th-century polyphony and 17th-century monody in psalms, hymns and canzonas by Virgilio Mazzocchi, Carissimi, Frescobaldi and Palestrina. The string playing is zestful, while Concerto Palatino's sackbutts and cornett add lustre. Sadly, the singing is often thin and unsupported, sounding more authentic to the early days of the early music movement than baroque devotional music.


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The final major Derby preps are in the books.
In the storied 139 year history of America's most famous horse race, many jockeys, trainers and owners have made the trip to the 'Ville with the prohibitive favorite and the most likely winner… on paper.
If you are like me, what you hope to see after all the prep races is some sort of separation.
You want clarity applied to a sport where the obvious is as rare as a Jeff Ruby ribeye.
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subset: commoncrawl


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PDFClerk Pro 3.4 adds watermark support
updated 05:05 pm EDT, Sun October 19, 2008
PDFClerk 3 4 update
Sintraworks has released the latest version of its PDF utility, PDFClerk Pro 3.4. The update features enhanced scriptability, improved automatic outline generation, inline editing of text annotations, support of watermarks and page labels, new shortcuts, and a redesigned user interface. The program can be used to create or edit PDF documents. Users can produce PDF files with text or graphics content, or merge the content of multiple documents with tools for appending or interleaving pages.
Pages can be exchanged between separate documents by dragging from one to another. The program supports vector objects, layered graphics or text boxes, overlay page labels, and automated page relabeling. Templates are provided, but users are also able to define their own. Files can be exported as an image file, with an option to apply a filter to reduce file sizes. PDFClerk Pro 3.4 is available from Sintraworks for �35 (~$50 USD).


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How to Make Popcorn Without Oil (+ Healthy Popcorn Toppings, Popcorn Recipes)
Making popcorn without oil is easy! I get a lot of questions about popcorn- it seems to be a really popular snack, but most people don't know how to make it healthy. Most popcorn is covered in oil, butter, or sugar for kettle corn. Popcorn can be a healthy, low-fat, snack that fits into our meal plans if you omit the oil and sugar and get creative in the kitchen with your own spices!
To make your own popcorn at home you need:
- 3 tbsp popcorn kernels (makes about 5 cups)
- paper bag
- Add popcorn kernels to a paper bag.
- Close bag. We found that we needed to staple the bag closed or we sometimes had a popcorn over flow, but you can also just fold the bag over and close it.
- Microwave the popcorn as usual for approximately two minutes. If you know your microwave runs a little stronger, I would decrease the time by :15 second increments.
- Open the bag carefully, there will be some steam coming from the bag!
Now here's the fun part...TOPPINGS! Try these or come up with your own:
- Nutritional Yeast
- Salt & Vinegar
- Italian Seasoning
- Cayenne, Salt, and a Squeeze of Lime Juice
- Old Bay
- Cinnamon or Pumpkin Pie Spice
- Paprika and Parsley (trust me!)
- Dill & Ground Black Pepper


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December 1, 2015
CHICAGO (AP) -- A spokesman for R. Kelly says the R&B singer is suffering complications from throat surgery and will miss promotional appearances for his new album and memoir.
Kelly's publicist said in a statement that the singer was on his way to New York on Wednesday morning when he became ill and returned to Chicago for medical treatment. Kelly had surgery last year to treat an abscess on his vocal cords.
Kelly's new album, "Write Me Back," came out Tuesday and his memoir, "Soulacoaster: The Diary of Me," releases Thursday.
The Grammy winner's publicist says Kelly will have to cancel appearances on "The Jimmy Fallon Show," NBC's "Today" and at a book party.
Kelly's spokesman says it's unclear how long the singer will be sidelined.
Click Here to access the online Public Inspection File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or firstname.lastname@example.com.


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Search Results: 'watercolor journal'
Eugene Delacroix: Drawings and Watercolors
eBook (ePub): $1.99
Download immediately.
Eugene Delacroix was the greatest French painter of the Romantic Movement. Delacroix's output was enormous. After his death his executors found more than 9,000 paintings, pastels, and drawings in his... More > studio and he prided himself on the speed at which he worked, declaring 'If you are not skilful enough to sketch a man falling out of a window during the time it takes him to get from the fifth storey to the ground, then you will never be able to produce monumental work.' Among great painters he was also one of the finest writers on art. He was a voluminous letter writer and kept a journal from 1822 to 1824 and again from 1847 until his death - a marvelously rich source of information and opinion on his life and times. His influence, particularly through his use of color, was prodigious, inspiring Renoir, Seurat, and van Gogh among others. Van Gogh wrote about him: 'Only Rembrandt and Delacroix could paint the face of Christ.'< Less
Travel in Time with the Watercolors of Jean Masetti
Paperback: $28.00
Ships in 3-5 business days.
I have published a children's story book and three books of my watercolor paintings. I decided to continue to record my art, so this will be my fifth offering. These books have become almost a series... More > of journals telling a story of my sights and experiences, so you too can travel in time with the watercolors of Jean.< Less
A Painter's Journal
Hardcover: $31.95
Ships in 6-8 business days.
My Costume Journal
Paperback: $25.00
Ships in 3-5 business days.
This 44 page booklet presents a treasure of full color watercolor paintings. They were inspired by a young group people who create and sew beautiful costumes reflecting different periods in time. It... More > will give you a sense of history in how we lived and dressed and an appreciation of fashion through the ages.< Less
Art Journal Alaska 2006
eBook (PDF): $13.50
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Art Journal Alaska 2006
Paperback: $20.60
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Driving from Alaska to Florida: a journal of paintings and photographs
Paperback: $14.95
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Experience a road trip from Alaska to Florida through the journal, photographs and paintings of an artist. What would YOU do if you were not afraid? Does it makes you smile to think of the... More > opportunities that a moment before you thought impossible? I gathered my paintings and put them together in a book to document this grand adventure. The trip began as a whimsical smile and turned into a warm memory. A memory that I share with you. Is this book a journal of paintings and photographs or is it license and encouragement to you to do those things you've stopped yourself from doing? You will have to answer that question for yourself.< Less
The Journal of Possibility: Quotes, Questions and Art to Keep You Inspired
Paperback: $17.00
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Original watercolor paintings and questions to keep you inspired, introspective and stretching out of your comfort zone. There is plenty of blank space for you to write, doodle, draw, color or... More > collage. There is no limit to your creativity or how you use this journal. Capture your dreams, goals, thoughts and gratitude's, memorable moments and vision for your future. The possibilities are endless.< Less
My Photo Book
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This is a collection of Stick and Ink sketches I have done along with watercolor. There are also sample pages from my Watercolor Sketchbook Journals.
Traveling Conversations
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When three friends, who are also professional artists, were separated by family moves they decided to keep in contact by exchanging small paintings. This book is a collection of watercolor paintings... More > they sent to each other in a sketchbook journal which follows them from 2005 to 2010.< Less
Top 10see more >
Dream Girl
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Yule Songs: A Chase Hill...
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My Life in Music
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Check out all 28 different things to dip in paint. Get your hands dirty with one of these tonight! 1. Wooden Candlesticks Almost Most Perfect 2. Succulent Pots DIY 3. Glass Milk Bottle Bondville 4. Macrame Guide 5. Pillows Nimi Design 6. Lampshade I Love To Create 7. Escort Cards Almost Makes Perfect 11. Clothespins Hello Bee 12. Tote Bag …Read More »
Tag Archives: things
Amazing Stuff You Can Make With Pipe!
We've compiled a wonderful list of 25 different things you can make with pipe. Take a peek, get inspired and get to work! 1. Shelving DIY Show Off 2. Lighting Hello Lidy 3. Towel Holder Squirrelly Minds 4. Drawer Pulls Upcycled Treasures 5. iPad Holder Bubbly Life 6. Stools Love Grows Wild 7. Garment Rack Beautiful Mess 8. Plate Rack …Read More »
Things I'd Do Differently If I Had A Parenting Do-Over
Get In On The Action Don't miss out on the fun, join in and play with your kids. My kids watched TV as soon as they could sit up and they're still sweet, sane, emotionally well-adjusted little human beings in spite of it. So, I would totally let a new baby watch TV, too. But this time around, I'd be …Read More »
DIY scarves – Easy ideas reusing old T-shirts, sweaters and scraps
The scarves are lovely fashion accessories. They can keep you warm during the cold winter days or just complement your outfit. If you love playing with scarves then you'll know that you can't have "too much" of them. It's time to recycle some old clothes and make a new fashionable accessory for your lovely neck. These DIY scarves ideas are …Read More »
Miley Cyrus and Patrick Schwarzenegger Heat Things Up Poolside in Miami
Miley Cyrus and Patrick Schwarzenegger have taken their love to the Miami heat! After their wild night clubbing on Wednesday, during which Miley donned a pasties and a silver wig, the new duo was seen poolside at a Miami hotel on Thursday afternoon. Miley and Patrick were accompanied by a group of friends that included pop artist Cody Simpson. Ever …Read More »
Things EVERY Woman Deserves To Experience
To come home from work, to something like this. She works hard, she loves harder. Make it your business to make her relax every once in a while.. A purely INTELLECTUAL date There's nothing sexier to an educated woman than a mentally stimulating conversation with her man… A first or even 50th date that goes like this. There was a …Read More »
40 Things We Learned From Beyonce's HBO Documentary
You get to watch Beyonce and Julez (Solange's son) play "Heart and Soul" on the piano and Beyonce sings to her not-yet-born daughter. She addresses rumors that she used a surrogate mother, saying: "A child, you don't play around with that." Beyonce's pretty spiritual. Immediately after she miscarried, Beyonce went to the studio to write "the saddest song she's ever …Read More »


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2005 Pontiac Grand Am • 20,000 miles
Drove to work everything ok, left work, turned the key saw a puff of smoke from under the hood opend the hood and smelled electrical smoke and car wouldnt start. Good alt., Good batt., Power n lights come on but wont turn. Dont know if its passlock or something else. Please help
May 12, 2013.
May 12, 2013.
Check out the related content below while we wait for the question to be answered by a professional mechanic.
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College can be a great experience for both you and your student. Getting involved can help you to stay connected with your student as well as Clemson. It can give you a unique opportunity to learn about Clemson while making friends with other families from all over the United States. Below is a list of current ways for families to be involved here at Clemson.
Host Clemson Events: Back to School Socials and New Student Receptions
Parents' Council hosts back to school socials and new student receptions. These are both events to share about Clemson and get others excited about considering going to school here. There are particularly common in out-of-state areas where there are numerous students who have been accepted to Clemson University or numerous people who have made plans to come to Clemson. These are great ways to meet other families from the same area.
Student Life
Volunteers assist Parents' Council Advisory Board members in reviewing student life issues on campus.
Open the original version of this page.
Usablenet Assistive is a Usablenet product. Usablenet Assistive Main Page.


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Ask Search Post
Birds for Sale in 76227(1 - 9 of 9)
Baby Blue & Gold Macaw with Papers jkjkjllMacaw · Colleyville, TXBaby Blue & Gold Macaw with Papers.The have been hand reared from very young age and so are very friendly and tame towards everyone inclu...Freddie G. · 1 week ago
$480 We have two parrots that we are giving them for a good home jkjPoicephalus · Richardson, TXWe have two parrots that we are giving them for a good home .They are well socialized, Well trained and tamed alongside other home pets a...Garry F. · 2 weeks ago
$380 Healthy talking pair of blue and gold macaw parrots availableMacaw · Mckinney, TX… . Text or call me at 419 x 871 x 0316 if interested. ThanksMarcelo I. · 15 hours ago
$480 Lovely Female and Male Macaw available ljkjkjlMacaw · Mckinney, TXLovely Female and Male Macaw available,Very socialized and well tame. Vet checked and micro chipped. Health and medical certificates from...Kinsley I. · 1 week ago
Blue and Gold Macaw parrots for Good HomeMacaw · Plano, TXGreat Blue and gold macaw pairs hand reared cuddly tame Hatch Certificate and Care Sheets for more info text via () - Images and contact ...Marketplace User ·Over 4 weeks ago on AdvertigoTools
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Green Cheek Conure and Peach Face LovebirdsConure · Carrollton, TXI have Green Cheek Conures weaned and ready for their forever home. They are yellow sided Pineapple split images do not do them justice. ...Marketplace User ·Over 4 weeks ago on AdvertigoTools
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$550 kjfdnok xzbluebabies Trained Congo African Grey ParrotsAfrican Grey Parrot · Bartonville, TX… @ for more info's via www.xzbluebabies.com or call 949 X 392 X 1541Sonia D. · 3 days ago
Free fhfdgtdfdffdTrained Pair of Talking African Grey ParrotsAfrican Grey Parrot · Highland Village, TX… .for more details and pics text us via (323) 400x37x69Mirella S. · 5 days ago
Taliking African Grey parrots for rehomingAfrican Grey Parrot · Denton, TXMy birds are well tamed and have been hand fed from hatch day till now DNA certified and have a cage and play toys Interested person can ...Marketplace User ·Over 4 weeks ago on AdvertigoTools
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More Listings on Oodle Marketplace Atlanta Pets | Columbia Pets | Hartford Pets | Lakeland Pets | Las Vegas Pets | Manchester Pets | New York Pets | Providence Pets | Raleigh Pets | Richmond Pets | San Diego Pets | San Jose Pets | San Francisco Pets | Saint Louis Pets | West Palm Beach Pets. Oodle Marketplace is a great place to find used cars, used motorcycles, used RVs, used boats, apartments for rent, homes for sale, job listings, and local businesses.
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I'm on it as soon as possible!
Here's where I officially drop off the stories, I'll probably send you a PM when I finish it but if your anything like an Obsess, just check here on this website:
3300 Update DUN.
Requesting Topic Lock, because I'm giving up on writing more stories.
3300 Update DUN.
A piece of salmon is not worth another mans life...
TheKaiserKnight wrote:
I am dissapoint. Seriously. Why? That's so boring to think about. As a writer it's so hard to think about giving it up. I know you might have reasons. But seriously. Don't let it be because of something silly.
School and Projects man, I get what you mean- I'm sick of not being able to do my thing.
This was a fun summer thing I planned to drag out until December, I can barely finish a segment of a paragraph and read an essay
in the same day.
I'm glad you drag this out of the ground tho' maybe I'll bring up another forum later in the summer.
Good day to you
3300 Update DUN.


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- Jessa Duggar shares a rare photo of her brother Josh Duggar's daughter Meredith - US Weekly
- Michael Lohan's estranged wife Kate Major is detained by cops at an airport - TMZ
- Is there something between Ben Affleck and Halle Berry? - Gossip Cop
- The Hunger Games author Suzanne Collins says goodbye to the popular series after the final movie is released - Just Jared Jr
- What happened backstage with Kylie Jenner at The Ellen Show? - Radar
- Bryan Cranston tears up over a Breaking Bad memory - Huffington Post
- Leonardo DiCaprio's Oscar race heats up - Lainey Gossip
- The Captain America: Civil War movie may be better than the comic book - The Hollywood Reporter
24 April 2014 at 6:27 PM
Jaime King Celebrates Birthday at Carolina Herrera Luncheon!
About this photo set: Jaime King celebrates her 35th birthday by attending an intimate lunch for the Carolina Herrera Archive Print Collection on Wednesday afternoon (April 23) in Beverly… Read More Here
Photo #: 3098416
Posted to Camilla Belle, Jaime King, Jared Eng, Liberty Ross, Liz Goldwyn, Lucy Punch, Lydia Hearst


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- Filed Under
A Lafayette teenager is accused of intentionally inflicting serious injuries that hospitalized her 11-month-old son last month.
The boy had a spiral fracture to his right femur, torn frenulums to his upper lip and tongue, and bruises on his head and thigh, court documents state.
The mother, 19-year-old Megan E. Schultz, was charged Wednesday in Tippecanoe Superior Court 1 with battery on a child resulting in serious bodily injury, and neglect of a dependent resulting in serious bodily injury.
Both counts are Class B felonies, each punishable by six to 20 years in prison.
A warrant has been issued for Schultz's arrest.
The boy is expected to recover from his injuries, said Detective Bragg McDole of the Lafayette Police Department.
The investigation began March 13, when detectives were called to St. Elizabeth East hospital. Someone took the 11-month-old to the hospital that morning, and a doctor informed detectives that a spiral fracture requires a "good amount force" to break the bone.
According to a probable cause affidavit, Schultz told police that the injury was likely caused March 12 by her 2-year-old daughter, who Schultz claimed was jumping in a Pack 'n Play while the boy was lying down.
She reportedly did not take her son to the hospital that evening, despite noticing his swollen leg, because he bruises all the time.
The boy was transferred to Riley Hospital for Children after his initial treatment at St. Elizabeth. Doctors there told detectives that the 11-month-old's spiral fracture could not have been caused by his sister jumping on his leg.
Rather, they said, most spiral fractures are caused by forceful twisting.
His torn frenulums also likely were not accidental, doctors said, and would have resulted in significant bleeding.
Schultz was the main caretaker for her children on March 12, when the injuries were likely inflicted, the affidavit states.
- Sophia Voravong/ email@example.com


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Overall, hotel was improved in appearance, breakfast offering, and internet service over last year. Room decor can stand some sprucing up.
Phone Number:
Location: United States > Arizona > Central Arizona > Tempe
Business Center with Internet Access Fitness Center with Gym / Workout Room Free Breakfast Free High Speed Internet ( WiFi ) Free Parking Kitchenette Pets Allowed ( Dog / Pet Friendly ) Suites Swimming Pool Wheelchair access
#1 Green Hotel in Tempe
Price Range (Based on Average Rates):
Hotel Class:3 star — Hawthorn Suites by Wyndham Tempe 3*
Number of rooms: 68
- Official Description (provided by the hotel):
- Hawthorn Suites by Wyndham Tempe/Mesa/Phoenix Located just off 101 Price Freeway near Route 60, Hawthorn Suites by Wyndham Tempe hotel, near Sky Harbor International Airport, combines southern hospitality with the comforts of home. Our Tempe, AZ, hotel provides easy access to all major highways, including Interstate 10 and Loops 101, 60 and 202, and is convenient to Mill Avenue District, Arizona State University and Sun Devil Stadium.Start each morning with a free hot breakfast buffet, then workout in our fitness and exercise center and unwind in our spa. Make a splash in our outdoor pool or enjoy a relaxing soak in our hot tub. All suites feature free high speed Wi-Fi Internet access, two 32" LCD TV's in each room, microwaves, refrigerators and in-room safes. Handicapped-accessible suites are available, and kids 17 and under stay free with an adult. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Travelocity, Expedia, Booking.com, Orbitz, Wyndham, Priceline, Cheap Tickets, Hotels.com, Low Cost Holidays, Odigeo and Otel so you can book your Hawthorn Suites by Wyndham Tempe reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Hawthorn Suites By Wyndham Tempe Hotel Tempe
- Hawthorn Suites Tempe
- Tempe Hawthorn Suites
- Hawthorn Suites Phoenix


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The Village of Agrustos
The village of Agrustos belongs to the municipality of Budoni, in the province of Olbia-Tempio, region Sardegna.
The village of Agrustos is 2,32 kilometers far from the same town of Budoni to whom it belongs.
To the municipality of Budoni also belong the localities of Baia Sant'Anna (4,43 km), Berruiles (5,71 km), Birgalavo' (3,52 km), Limpiddu (1,30 km), Lotturai (-- km), Luddui (4,09 km), Luttuni (-- km), Lutturai (5,65 km), Maiorca (4,56 km), Malamori' (3,34 km), Matta e Peru (6,05 km), Muriscuvo' (2,31 km), Nuditta (6,29 km), Ottiolu (4,15 km), Pedra e Cupa (-- km), Ponte (2,24 km), S'Iscala (2,46 km), San Gavino (2,91 km), San Lorenzo (3,66 km), San Pietro (5,72 km), San Silvestro (4,25 km), Sant'Iscala (0,71 km), Solita' (2,50 km), Strugas (7,38 km), Su Linalvu (-- km), Tamarispa (5,18 km), Tanaunella (2,66 km).
The number in parentheses following each village name indicate the distance between the same village and the municipality of Budoni.
The locality of Agrustos rises 53 meters abobe sea level.
The population of Agrustos counts 206 inhabitants.
Please find in what follows:
- A set of photos about Agrustos (when available)
- Weather and weather forecast for the municipality of Budoni, to whom Agrustos belongs.
- Map and road map of Agrustos
- A selection of videos about Agrustos
- The latest news about Agrustos, the municipality of Budoni, the province of Olbia-Tempio and the Sardegna region.
Where to stay in Agrustos and its neighborhoods
Hotels, Resorts, B&B in Agrustos and its neighborhoods.
You can arrange the results by number of stars, by popularity, by distance or even by the guest review score choosing among young couples, mature couples, families with young children, families with older children, people withfriends, or solo travellers.
Free ads in Agrustos
Most recent free ads in Agrustos, municipality of Budoni, province of Olbia-Tempio, Sardegna region, updated at 06:08:28, 26 November 2015. Place your free ad on Agrustos: no registration needed. Place your free ad.
Up to now there is no free ad placed in Agrustos
|Most recent free ads in the province of Olbia-Tempio
|nonno de rosas giovanni
|Bilocale grazioso
|vendo multiproprieta
|Most recent free ads in the region Sardegna
|nonno de rosas giovanni
|Due fratelli
|affitto annuale
Photos of Agrustos
Photos provided by Panoramio. Photos are under the copyright of their owners.
Asinello Di Orune
Map and road map of Agrustos
Look at the interactive map of Agrustos and get the road maps, the satellite maps and the mixed ones too. Interactive maps of Agrustos also allow an immediate view of: bar,restaurants,pubs,pizzerias,dancing,night clubs,banks,jewellers,beauty centers,hair stylists,supermarkets,pharmacies.
Just fill in the free text search box placed on top of the map with any of previous categories and then press enter.
Please feel free to use the same free text search box placed on top of the map to find any kind of business activities you're interested into.


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Last Activity: 11-21-2011 10:45 PM
About Me
- About barrelracingstar121
- Biography
- Hi! im Garrett! I have had horses all my life. Im very knowledgable so dont be afraid to ask!
- Location
- Wisconsin
- Interests
- horse back riding, Photography
- Occupation
- stable hand at Sunborn Stables, Inc
- Gender
- Male
- Current Status
- ~A true horseman does not look at the horse with his eyes, he looks at his horse with his heart~
Contact Info
- Home Page
- http://garrettk.blog.com
- This Page
- /members/19788/
Trader Reviews
|iTrader Profile
|Recent Ratings


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Mango Moments - Week 6
Vote for your favourite Mango Moments clip of the week from Friends Provident t20 and win some great prizes
0:30 mins |
You are :
Domestic cricket 2014 - key changes The ECB has listened to the fans and made some key scheduling changes to domestic cricket
Hussey toasts Lord's victory Star batsman gets in the spirit after Notts Outlaws win Yorkshire Bank 40
Taylor lavishes praise on Read and Patel Pair were 'exceptional' says Notts batsman after Yorkshire Bank 40 win at Lord's
Glamorgan v Notts Outlaws: YB40, Final - Glamorgan Innings Watch the highlights of Glamorgan v Notts Outlaws from the YB40 Final at Lord's.
Glamorgan v Notts Outlaws: YB40, Final - Notts Outlaws Innings Watch the highlights of Glamorgan v Notts Outlaws from the YB40 Final at Lord's.
Read wants to emulate class of 1989 Notts captain excited about county's first Lord's final appearance in 24 years
Notts Outlaws v Somerset - YB40 semi-final Watch the highlights as Notts Outlaws booked a place in the YB40 Final at Lord's
Hampshire v Glamorgan - semi-final highlights Yorkshire Bank 40 semi-final highlights from The Ageas Bowl
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SYNOPSIS Lady Madison Sanford dreams of a blissful life being married to a gentleman with a title, and settling down to a contented life, taking her place as a lady in the ton, providing her husband with many heirs. She accepts an offer from, Lord Rankin, the Earl of Swain, but enter Mr. Chadwick Rochester who does not have a title, but plenty of masculine good looks, brooding eyes, and an arrogance that just does not bode well with the superior Lady Madison. So why is it when she contemplates her blissful life, it is the face of Mr. Chadwick Rochester that her mind conjures as her betrothed...?
daddsi_gensan 9 months ago
ohhhh my... do you know what i dreaded most? when i've read all your stories and all others on wattpad could not even be compared on how great your stories are. ooopppsss! redundancy. hehehe! your great! more books please!!!!!
ReaflorLauzonPadual 2 years ago
I've read almost all of your books and honestly, if i could be more honest, theyr really really good. Im so excited to read this one and to say that im expecting that this will be a good piece too is an understatement. Because your pieces are way better than good. Godbless:)
ihatetobeinlove 3 years ago
I never eally into reading historical fiction but I wanted to try. I think the story is amazing and the author is really a good person.
ddeezy21 3 years ago
Great story great job on all the details n did know Wat to think of this story till I have read it I love the how everything played out in the story great job again
ivhiejoy16 3 years ago
hi! i really fell in love with this story. can't think of new adjectives to describe how amazing you are. thanks a lot! (eye bags again, shoot!) i've got your stores already downloaded on my phone. and im so excited to read them all. >_<
book_worm_ 3 years ago
Soooooo why arent you slipping this story into the Watty awards for historical-fiction again? I think you should. It was a great story it got me into reading historical fictions. I actually used to think nothing of them until i read this one and now im hooked on the genre ^_^ ADD ADD ADD!


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Pyongyang's suspected missile test defies international warnings
SEOUL, South Korea
North Korea appeared to successfully fire a long-range rocket today, defying international warnings as the regime of Kim Jong Un pushes forward with its quest to develop the technology needed to deliver a nuclear warhead.
Pyongyang's state media quickly claimed that the country had succeed in its mission of putting a peaceful satellite into orbit with its long-range Unha-3 rocket. Officials at the North American Aerospace Defense Command, or NORAD, said North Korea appeared to have put an object into space.
But South Korea and Japan said they couldn't immediately confirm that. The launch was something of a surprise, as North Korea had indicated technical problems with the rocket and recently extended its launch window to Dec. 29.
The United Nations, Washington, Seoul and others see the launch as a cover for a test of technology for missiles that could be used to strike the United States. The White House called the launch a "highly provocative act that threatens regional security."
South Korean Defense Ministry spokesman Kim Min-seok told a nationally televised news conference that a South Korean Aegis-equipped destroyer detected the launch at 9:51 a.m., local time, and the first stage fell into the Yellow Sea about a minute later; the rocket then flew over a South Korean island near the border with North Korea a minute after that. The rocket was seen flying west of Okinawa at 9:58 a.m., and then disappeared from South Korean radars, Kim said.
Japan protested the launch and said one part of the rocket landed west of the Korean Peninsula, and the Philippines said another part landed 186 miles east of the Philippines. South Korean President Lee Myung-bak planned an emergency national security council meeting later today, and South Korean Foreign Minister Kim Sung-hwan warned that North Korea will face grave consequences.
Japan's Foreign Ministry said Tokyo immediately requested consultations on the launch within the U.N. Security Council.
Rocket tests are seen as crucial to advancing North Korea's nuclear weapons ambitions. North Korea is thought to have only a handful of rudimentary nuclear bombs. But Pyongyang is not yet believed capable of building warheads small enough to mount on a missile that could threaten the United States.


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ABA Military Pro Bono Project Outstanding Services Awards
The Project's success depends on its volunteers! Attorneys from law firms, corporate law departments, and other legal organizations throughout the nation accept pro bono cases from the Project. Thank you to all of the attorneys and pro bono coordinators who have registered with the Project and have accepted pro bono cases on behalf of our servicemembers!
Special thanks to the recipients of the ABA Military Pro Bono Project Outstanding Services Award, from the ABA Standing Committee on Legal Assistance for Military Personnel (LAMP), for their extraordinary pro bono services through the Project.
The ABA Military Pro Bono Project Outstanding Services Award recipients for 2014 services are as follows:
Law Firms and Organizations
Holland & Knight LLP
Troutman Sanders LLP
James Michalski and Richard Bixter (of Holland & Knight LLP)
Dean Waldt (of Ballard Spahr, LLP – Phoenix, AZ)
Robert K. Holmes (of Holmes & Holmes – Glendale, CA)
Koji Fukumura and Dane Voris (of Cooley LLP – San Diego, CA)
Charles L. Coleman III (of Holland & Knight LLP – San Francisco, CA)
Mark Stockwell (of Brownstein Hyatt Farber Schreck, LLP – Denver, CO)
Brian Hole (of Holland & Knight LLP – Fort Lauderdale, FL)
Michael Abel (of Holland & Knight LLP – Jacksonville, FL)
Fred Lotterhos III and Michael Gropper (of Holland & Knight LLP – Jacksonville, FL)
Sarah Sullivan (of Florida Coastal School of Law – Jacksonville, FL)
Thomas S. Cargill (of Foley & Lardner LLP – Orlando, FL)
Henry "Bucky" Fox (of Berger Singerman LLP – Tallahassee, FL)
Steven Chung (of Steven Chung and Associates – Honolulu, HI)
Letisha Luecking Orlet (Attorney at Law – Nashville, IL)
Polina Arsentyeva (of Rathje & Woodward, LLC – Wheaton, IL)
Jake Cohen (Attorney at Law – Roxbury, MA)
Robert Allen Fairbairn (of Fairbairn Law Offices – Salem, MA)
Paula Nightingale (of Paula J. Peters, P.A. – Annapolis, MD)
Scott Swafford (of Swafford Law, LLC – Annapolis, MD)
Michael Wilson (The Law Offices Michael D. Wilson, PLLC – Biloxi, MS)
Ronald Campione, Angela Scafuri, and Polina Dostalik (of Bressler, Amery & Ross, P.C. – Florham Park, NJ)
Marshal Willick and Trevor Creel (of Willick Law Group – Las Vegas, NV)
Steve Cohen (of Kramer Dillof Livingston & Moore – New York, NY)
Sean Sheely, John Toriello and Sean Barry (of Holland & Knight LLP – New York, NY)
Phillip J. Tucker (of The Tucker Law Firm – Edmond, OK)
Robert Lenard (of Law Office of Roland Robert Lenard – Clarksville, TN)
Eli Burriss (of DLA Piper LLP – Dallas, TX)
Ronald Tigner and Karl Schulz (of Cozen O'Connor – Houston, TX)
Carole Cross (of the Law Office of Carole Cross – Hurst, TX)
Joseph Lacome (Attorney at Law – Kyle, TX)
Kelvin Green (of The Law Office of Kelvin Green – South Jordan, UT)
Evan Inslee (Attorney at Law – Lake Tapps, WA)
Morgan Gabse (Attorney at Law – Seattle, WA)
Who receives the ABA Military Pro Bono Project Outstanding Services Award?
Is there language and a logo that I can link on my firm's website to show that I am a Project volunteer?
Donate! See how you can become an ABA Military Pro Bono Project Star Ranking Supporter!


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- 2012-04-02 23:20:25
this cake was inspired by way better cakes on CC. but almost broke me. =/ it was a last minute idea and didn't have enough time or energy to get it better. my mmf was not cooperating and so that's why it wasn't as smooth and clean as would have liked.
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Nov. 20 - Mid-Term Reports
Educate students for success by providing a superior, relevant education.
Our students will be productive, successful contributors to society.
|Durham Bus Tracker Parents and guardians can locate their child's bus
with a free and easy to use Smart Phone application (or they
can do it from their laptop/desktop/ipad). How?
Download the "Durham Bus Tracker" application on your smart phone or go to https://m.durhambustracker.com/secure/
1. Create an account
2. Enter your full name
3. Enter your email address
4. Create a unique password
5. Save
To add a student whose bus you'd like to track you'll need the student's last name and their student ID #. If you're unable to locate your child's bus please call the transportation department's routing section at 850-983-5102 and ask for Dangela Bryant.


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Number: 0828
Aetna considers the use of irreversible electroporation (IRE) including use of the NanoKnife for tissue ablation experimental and investigational for all indications (including the following; not an all-inclusive list) due to insufficient evidence in the peer-reviewed literature:
The field of irreversible electroporation (IRE) in medicine has been growing in recent years as a tool in tissue ablation (Rubinsky, 2007). The process of IRE occurs as a consequence of certain electrical fields being applied across a cell permeabilizing the cell membrane and leading to cell death, primarily when the electrical fields cause permanent permeabilization and consequent loss of cell homeostasis. In comparison with current physical ablation technologies, IRE does not result in any thermal effect (Breton and Mir, 2011).
The Nanoknife is a low-energy direct current (LEDC) thermal ablation system, which received Food and Drug Administration (FDA) 510K clearance on October 24, 2011 (FDA, 2011). The NanoKnife System has received FDA clearance for the surgical ablation of soft tissue. It has not received clearance for the therapy or treatment of any specific disease or condition (AngioDynamics, 2011). The NanoKnife System transmits LEDC energy from the generator to electrode probes placed in a target area for the surgical ablation of soft tissue.
Ball et al (2010) conducted a clinical trial of IRE for tumor ablation therapy. A pulsating direct current of 20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors of the liver, kidney, or lung via needle electrodes inserted under computed tomography (CT) or ultrasound guidance with use of a relaxant general anesthetic. Twenty-one patients were included. The results showed that electrical discharge produced generalized upper body muscular contractions requiring neuromuscular blockade. Two patients developed positional neuropraxia because of the extended arm position requested for CT scanning. Some patients developed self-limiting ventricular tachycardias that are now minimized by using an electrocardiogram (ECG) synchronizer. Three patients developed pneumothoraces as a result of the needle electrode insertion. The authors concluded that relaxant general anesthesia is required for IRE of the liver, lung, and kidney and that an ECG synchronizer should be used to minimize the risk of arrhythmias. The authors further noted that attention to the position of the arms is required to maximize CT scan quality but minimize brachial plexus strain and that simple post-operative analgesia is all that is required in most patients.
Pech et al (2011) studied 6 patients scheduled for curative resection of renal cell carcinoma (RCC) to assess the feasibility and safety of ablating RCC tissue by IRE. Irreversible electroporation was performed during anesthesia immediately before the resection with ECG synchronization. Analysis of hematological, serum biochemical, and ECG variables, including ST waveforms and axis deviations, showed no relevant changes during the study period. No changes in cardiac function after IRE therapy were found, but 1 case of supraventricular extrasystole was encountered. Initial histopathologic examination did not identify any immediate adverse effects of IRE. The authors concluded that "IRE seems to offer a feasible and safe technique by which to treat patients with kidney tumours and could offer some potential advantages over current thermal ablative techniques."
Thomson et al (2011) conducted a single-center prospective non-randomized cohort study to investigate the safety of IRE for tumor ablation in humans. Thirty-eight study subjects received IRE treatment under general anesthesia. The study population included patients with advanced malignancy of the liver, kidney, or lung (69 separate tumors) which were unresponsive to alternative treatment. Clinical examination, biochemistry, and CT scans of the treated organ were performed before, immediately after, and at 1 month and 3 post-procedure. The authors reported no mortalities occurring by 30 days post-procedure and that transient ventricular arrhythmia occurred in 4 patients and that ECG synchronized delivery was used subsequently in the remaining 30 patients, with 2 further arrhythmias (supraventricular tachycardia and atrial fibrillation). One patient developed obstruction of the upper ureter after IRE. One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension. There was no other evidence of adjacent organ damage related to the electroporation. Two patients developed temporary neurapraxia as a result of arm extension during a prolonged period of anesthesia and biopsy in 3 patients showed coagulative necrosis in the regions treated by IRE. The authors further noted that complete target tumor ablation verified by CT was achieved in 46 of the 69 tumors treated with IRE (66 %), while most treatment failures occurred in renal and lung tumors. The authors concluded that IRE appears safe for human clinical use if ECG-synchronized delivery is utilized. They recommended comparative evaluation with alternative ablative technologies.
Charpentier (2012) explored IRE as a novel, non-thermal form of tissue ablation using high-voltage electrical current to induce pores in the lipid bilayer of cells, resulting in cell death. PubMed searches were performed using the keywords electroporation, IRE, and ablation. The abstracts for the 2012 meetings of both the American Hepato-Pancreato-Biliary Association and the Society for Interventional Radiology were also searched. All articles and abstracts with any reference to electroporation were identified and reviewed. All studies and abstracts pertaining to electroporation were reviewed. All data pertaining to the safety and effectiveness of IRE were extracted from pre-clinical and clinical studies. Pre-clinical data detailing the theory and design of IRE systems were also extracted. Pre-clinical studies have suggested that IRE may have advantages over conventional forms of thermal tumor ablation including no heat sink effect and preservation of the acellular elements of tissue, resulting in less unwanted collateral damage. The early clinical experience with IRE demonstrated safety for the ablation of human liver tumors. Short-term data regarding oncologic outcome is now emerging and appears encouraging. The author concluded that IRE is likely to fill a niche void for the ablation of small liver tumors abutting a major vascular structure and for ablation of tumors abutting a major portal pedicle where heat sink and collateral damage must be avoided for maximum efficacy and safety. Moreover, they stated that studies are still needed to define the short-term and long-term oncologic effectiveness of IRE.
Olweny and Cadeddu (2012) provided an overview of the current research on renal tissue ablation, high-lighting novel ablation techniques and technologies. Although nephron-sparing surgery is the gold standard treatment for small renal masses confirmed malignant, ablative therapies are an option in elderly patients, who may be poor surgical candidates. Radio-frequency ablation (RFA) and cryoablation have each been used for renal tissue ablation for over a decade, but their effectiveness in ablation of central lesions or lesions more than 3 cm in size is limited. Increasing ablation size and improving effectiveness of thermal energy delivery are the goals of research in RFA and cryoablation. The authors stated that novel ablation technologies including IRE, microwave ablation, and high-intensity focused ultrasound among others have undergone preliminary pre-clinical and clinical evaluation in select series, but require further development and assessment of outcomes prior to routine clinical use for renal tumor ablation.
Kingham et al (2012) evaluated the safety and short-term outcomes of IRE to ablate peri-vascular malignant liver tumors. A retrospective review of patients treated with IRE between January 1, 2011 and November 2, 2011 was performed. Patients were selected for IRE when resection or thermal ablation was not indicated due to tumor location. Treatment outcomes were classified by local, regional, and systemic recurrence and complications. Local failure was defined as abnormal enhancement at the periphery of an ablation defect on post-procedure contrast imaging. A total of 28 patients had 65 tumors treated; 22 patients (79 %) were treated via an open approach and 6 (21 %) were treated percutaneously. Median tumor size was 1 cm (range of 0.5 to 5 cm). Twenty-five tumors were less than 1 cm from a major hepatic vein; 16 were less than 1 cm from a major portal pedicle. Complications included 1 intra-operative arrhythmia and 1 post-operative portal vein thrombosis. Overall morbidity was 3 %. There were no treatment-associated mortalities. At median follow-up of 6 months, there was 1 tumor with persistent disease (1.9 %) and 3 tumors recurred locally (5.7 %). The authors concluded that this early analysis of IRE treatment of peri-vascular malignant hepatic tumors demonstrated safety for treating liver malignancies. They stated that larger studies and longer follow-up are needed to determine long-term effectiveness.
Narayanan et al (2012) evaluated the safety of percutaneous IRE in patients with pancreatic adenocarcinoma. Irreversible electroporation was performed in patients with pancreatic cancer whose tumors remained unresectable after, or who were intolerant of, standard therapy. The procedures were all performed percutaneously under general anesthesia. Patients were then followed for adverse events, tumor response, and survival. A total of 15IRE procedures were performed in 14 patients (1 was treated twice). Three patients had metastatic disease and 11 had locally advanced pancreatic cancer (LAPC). All patients had received chemotherapy previously, and 11 had received radiation. The median tumor size was 3.3 cm (range of 2.5 to 7 cm). Immediate and 24-hour post-procedural scans demonstrated patent vasculature in the treatment zone in all patients. Two patients underwent surgery 4 and 5 months after IRE, respectively. Both had margin-negative resections, and 1 had a pathologic complete response; both remain disease-free after 11 and 14 months, respectively. Complications included spontaneous pneumothorax during anesthesia (n = 1) and pancreatitis (n = 1), and both patients recovered completely. There were no deaths directly related to the procedure. All 3 patients with metastatic disease at IRE died from progression of their disease. The authors concluded that percutaneous IRE for pancreatic adenocarcinoma is feasible and safe; and they stated that a prospective trial is being planned.
Martin et al (2013) evaluated the overall survival (OS) in patients with LAPC treated with IRE. A prospective, multi-institutional evaluation of 54 patients who underwent IRE for unresectable pancreatic cancer from December 2009 to October 2010 was evaluated for OS and propensity matched to 85 matched stage III patients treated with standard therapy defined as chemotherapy and radiation therapy alone. A total of 54 LAPC patients have undergone IRE successfully, with 21 women, 23 men (median age of 61 (range of 45 to 80) years). Thirty-five patients had pancreatic head primary and 19 had body tumors; 19 patients underwent margin accentuation with IRE and 35 underwent in situ IRE. Forty-nine (90 %) patients had pre-IRE chemotherapy alone or chemo-radiation therapy for a median duration 5 months. Forty (73 %) patients underwent post-IRE chemotherapy or chemo-radiation. The 90-day mortality in the IRE patients was 1 (2 %). In a comparison of IRE patients to standard therapy, these researchers have seen an improvement in local progression-free survival ([PFS]; 14 versus 6 months, p = 0.01), distant PFS (15 versus 9 months, p = 0.02), and OS (20 versus 13 months, p = 0.03). The authors concluded that IRE ablation of locally advanced pancreatic tumors remains safe and in the appropriate patient who has undergone standard induction therapy for a minimum of 4 months can achieve greater local palliation and potential improved OS compared with standard chemo-radiation-chemotherapy treatments. Moreover, they stated that validation of these early results will need to be validated in the current multi-institutional phase 2 IDE study.
Cannon et al (2013) evaluated the safety and effectiveness of IRE for hepatic tumors in the clinical setting. An IRB approved prospective registry of patients undergoing IRE for hepatic tumors over a 2-year period. Factors analyzed included patient and tumor characteristics, treatment related complications, and local recurrence free survival (LRFS) for ablated lesions -- LRFS was calculated according to Kaplan-Meier, with secondary analyses stratified by procedural approach (laparotomy, laparoscopy, and percutaneous) and tumor histology. There were 44 patients undergoing 48 total IRE procedures, 20 colorectal metastases, 14 hepatocellular, and 10 other metastases. Initial success was achieved in 46 (100 %) treatments. Five patients had 9 adverse events, with all complications resolving within 30 days. Local recurrence free survival at 3, 6, and 12 months was 97.4 %, 94.6 %, and 59.5 %, respectively. There was a trend toward higher recurrence rates for tumors over 4 cm (HR 3.236, 95 % confidence interval [CI]: 0.585 to 17.891; p = 0.178). The authors concluded that IRE appears to be a safe treatment for hepatic tumors in proximity to vital structures. Moreover, they stated that further prospective evaluation is needed to determine the optimal effectiveness of IRE in relation to size and technique for IRE of the liver.
Mandel et al (2013) noted that uveal melanoma (UM) is the most common primary intra-ocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of IRE for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, these researchers evaluated the use of IRE for uveal tumor ablation in human ex-vivo eye model. Enucleated eyes of patients with UM were treated with short electric pulses (50 to 100 µs, 1,000 to 2,000 V/cm) using a customized electrode design. Tumor bio-impedance was measured before and after treatment and was followed by histopathological evaluation. These investigators found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. The authors concluded that future studies should further evaluate the potential of IRE as an alternative method of UM treatment.
Yeung et al (2014) examined the safety and effectiveness of IRE for ablation of liver tumor. The PubMed and MEDLINE databases were systematically searched. Clinical research published in English in the last 10 years until October 2013 that address clinical issues related to IRE of human liver tumors were selected. "Liver tumor", "local ablative therapy", and "irreversible electroporation" were used as the search terms. The data extracted for this review was analyzed by the authors, with a focus on the safety and effectiveness of IRE. The complete response (CR) rates look promising, ranging from 72 % to 100 %, except in 1 study in a subgroup of liver tumors in which the CR rate was only 50 % that was likely due to the inclusion of larger-size tumors. In 1 study, the local recurrence rate at 12 months was approximately 40 %. As for the safety of IRE, there were only a few reported complications (cardiac arrhythmia, pneumothorax, and electrolyte disturbance) that were mostly transient and not serious. There was no reported mortality related to the use of IRE. The authors concluded that IRE is a potentially effective liver tumor ablative therapy that gives rise to only mild and transient side-effects. They stated that further studies with better patient selection criteria and longer follow-up are needed to clarify its role as a first-line liver tumor treatment modality.
Scheffer et al (2014a) provided an overview of current clinical results of IRE, a novel, non-thermal tumor ablation technique that uses electric pulses to induce cell death, while preserving structural integrity of bile ducts and vessels. All in-human literature on IRE reporting safety or efficacy or both was included. All adverse events were recorded. Tumor response on follow-up imaging from 3 months onward was evaluated. In 16 studies, 221 patients had 325 tumors treated in liver (n = 129), pancreas (n = 69), kidney (n = 14), lung (n = 6), lesser pelvis (n = 1), and lymph node (n = 2). No major adverse events during IRE were reported. Irreversible electroporation caused only minor complications in the liver; however, 3 major complications were reported in the pancreas (bile leak [n = 2], portal vein thrombosis [n = 1]). Complete response at 3 months was 67 % to 100 % for hepatic tumors (93 % to 100 % for tumors o 3 cm). Pancreatic IRE combined with surgery led to prolonged survival compared with control patients (20 months versus 13 months) and significant pain reduction. The authors concluded that in cases where other techniques are unsuitable, IRE is a promising modality for the ablation of tumors near bile ducts and blood vessels. They gave an extensive overview of the available evidence, which is limited in terms of quality and quantity. With the limitations of the evidence in mind, IRE of central liver tumors seems relatively safe without major complications, whereas complications after pancreatic IRE appear more severe. The available limited results for tumor control are generally good. These researchers stated that the future of IRE for difficult-to-reach tumors appears promising.
Silk et al (2014) evaluated biliary complications after IRE ablation of hepatic tumors located less than 1 cm from major bile ducts. A retrospective review was conducted of all percutaneous IRE ablations of hepatic tumors within 1 cm of the common, left, or right hepatic ducts at a single institution from January 2011 to September 2012. Computed tomography imaging performed before and after treatment was examined for evidence of bile duct dilatation, stricture, or leakage. Serum bilirubin and alkaline phosphatase levels were analyzed for evidence of biliary injury. There were 22 hepatic metastases in 11 patients with at least 1 tumor within 1 cm of the common, left, or right hepatic duct that were treated with IRE ablations in 15 sessions. Median tumor size treated was 3.0 cm (mean of 2.8 cm ± 1.2, range of 1.0 to 4.7 cm). Laboratory values obtained after IRE were considered abnormal after 4 treatment sessions in 3 patients (bilirubin, 2.6 to 17.6 mg/dL; alkaline phosphatase, 130 to 1,035 U/L); these abnormal values were transient in 2 sessions. Two patients had prolonged elevation of values, and 1 required stent placement; both of these conditions appeared to be secondary to tumor progression rather than bile duct injury. The authors concluded that this clinical experience suggested that IRE may be a treatment option for centrally located liver tumors with margins adjacent to major bile ducts where thermal ablation techniques are contraindicated. They stated that further studies with extended follow-up periods are needed to establish the safety profile of IRE in this setting.
Valerio et al (2014) stated that IRE has been proposed to be tissue selective and so might have favorable characteristics compared to the currently used prostate ablative technologies. The authors described the design of a trial to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localized prostate cancer. This is a single-center, prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. A total of 20 men who have MRI-visible disease localized in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include prostate-specific antigen (PSA) of less than or equal to 15ng/ml, Gleason score less than or equal to 4+3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimization of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. The authors concluded that the NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. This protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.
Valerio et al (2014b) evaluated the safety and clinical feasibility of focal IRE of the prostate. These investigators assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localized prostate cancer in 2 centers. Eligibility was assessed by mpMRI and targeted and/or template biopsy. Irreversible electroporation was delivered under trans-rectal ultrasound guidance with 2 to 6 electrodes positioned trans-perineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. Overall, 34 patients with a mean age of 65 years (S.D. = ±6) and a median PSA of 6.1 ng/ml (interquartile range (IQR)= 4.3 to 7.7) were included. Nine (26 %), 24 (71 %) and 1 (3 %) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range of 1 to 24), 12 grade-1 and 10 grade-2 complications occurred. No patient had grade greater than or equal to 3 complication. From a functional point of view, 100 % (24/24) patients were continent and potency was preserved in 95 % (19/20) men potent before treatment. The volume of ablation was a median of 12 ml (IQR = 5.6 to 14.5 ml) with the median PSA after 6 months of 3.4 ng/ml (IQR = 1.9 to 4.8 ng/ml). Multi-parametric MRI showed suspicious residual disease in 6 patients, of whom 4 (17 %) underwent another form of local treatment. The authors concluded that focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Moreover, they stated that further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.
Fornage and Hwang (2014) described the various techniques used for percutaneous ablation of breast cancer, their preliminary results, and their limitations. The techniques include thermotherapy (radiofrequency ablation, laser irradiation, microwave irradiation, and insonation with high-intensity focused ultrasound waves), cryotherapy, and IRE. The authors concluded that the techniques used for percutaneous ablation of breast cancer raise many questions and issues that must be addressed before percutaneous ablation can be adopted for the treatment of early breast cancer.
Wagstaff et al (2014) provided an overview of recent developments in the field of thermal ablation for renal cell carcinoma and focused on current standard techniques, new technologies, imaging for ablation guidance and evaluation, and future perspectives. Emerging long-term data on cryoablation and radiofrequency ablation (RFA) showed marginally lower oncologic outcomes compared to surgical treatment, balanced by better functional and peri-operative outcomes. Reports on residual disease vary widely, influenced by different definitions and strategies in determining ablation failure. Stratifying disease-free survival (DFS) after RFA according to tumor size suggested 3 cm to be a reasonable cut-off for RFA tumor selection. Microwave ablation and high-intensity focal ultrasound are modalities with the potential of creating localized high temperatures. However, difficulties in renal implementation are impairing sufficient ablation results. These researchers noted that IRE, although not strictly thermal, is a new technology showing promising results in animal and early human research. The authors concluded that although high-level randomized controlled trials (RCTs) comparing thermal ablation techniques are lacking, evidence showed that thermal ablation for small renal masses is a safe procedure for both long-term oncologic and functional outcomes. They stated that thermal ablation continues to be associated with a low risk of residual disease, for which candidates should be properly informed; cryotherapy and RFA remain the standard techniques whereas alternative techniques require further studies.
Scheffer (2014b) evaluated the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. A total of 10 patients with resectable CRLM were included in this study. During laparotomy, the metastases were treated with IRE and resected 60 mins later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 mins later (range of 51 to 153 mins). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypo-echoic ablation zone around the tumor. Triphenyl tetrazolium chloride showed avitality of all lesions, covering the complete tumor in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumors, it confirmed irreversible cell damage in the tumor-free margin of all specimens. The authors concluded that this ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Moreover, they stated that further characterization of tissue- and tumor-specific electrical properties is needed to improve ablation protocols for maximized tissue ablation.
Gomez et al (2014) reviewed the existing evidence on the techniques and results of ablation for pediatric solid malignant or aggressive benign tumors. These investigators searched MEDLINE for papers published between 1995 and 2012 that reported outcomes of radiofrequency, microwave and cryoablation, interstitial laser therapy, IRE and percutaneous ethanol injection for patients younger than 18 years old. Data collection included factors related to the patient, tumor biology, ablation technique and cancer-specific end-points. Additional series of predominantly adults including data on patients younger than 18 years old were also identified. These researchers identified 28 patients treated by ablation in 29 regions: 5 patients undergoing ablation for liver lesions, 9 patients for lung metastases, 11 patients for bone and/or soft tissue and 4 patients for kidney or pancreas. The ablation was performed to treat primary tumors, local recurrences and metastases. The histology of the tumors was osteosarcoma in 6 patients, Wilms tumor in 3, rhabdomyosarcoma in 3, hepatoblastoma in 3, desmoid tumor in 3, adrenocortical carcinoma in 2 and a single case each of leiomyosarcoma, Ewing sarcoma, paraganglioma, solid-pseudopapillary neoplasm, sacrococcygeal teratoma, hepatic adenoma, juxtaglomerular cell tumor and plantar fibromatosis. Eighteen of the patients (64 %) experienced a complication, but only 6 (21 %) of these needed treatment other than supportive care. The authors concluded that although ablative techniques are feasible and promising treatments for certain pediatric tumors, large multi-center prospective trials will be needed to establish efficacy.
|CPT Codes / HCPCS Codes / ICD-10 Codes
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":
|ICD-10 codes will become effective as of October 1, 2015:
|Irreversible Electroporation (NanoKnife) :
|No specific code
|ICD-10 codes not covered if selection criteria are met (not all-inclusive):
|Malignant neoplasm of colon and rectum
|Intrahepatic bile duct carcinoma [peri-biliary]
|Malignant neoplasm of liver, primary, unspecified as to type
|Malignant neoplasm of pancreas
|Malignant neoplasm of lung [pediatric]
|Malignant neoplasm of bone [pediatric]
|Malignant neoplasm of connective and other soft tissue [pediatric]
|Malignant neoplasm of breast
|Malignant neoplasm of prostate
|Malignant neoplasm of kidney, except renal pelvis
|Malignant neoplasm of ciliary body
|Secondary malignant neoplasm of lung
|Secondary malignant neoplasm of large intestine and rectum
|Secondary malignant neoplasm of liver and intrahepatic bile duct
|Secondary malignant neoplasm of other digestive organs [peri-biliary and pancreas]
|Secondary malignant neoplasm of kidney
|Secondary neoplasms of other parts of nervous system [uveal melanoma]
|Secondary malignant neoplasm of bone and bone marrow
|Secondary malignant neoplasm of breast
|Secondary malignant neoplasm of genital organs [prostate]
|Secondary neoplasm of other specified sites [connective and other soft tissue, pediatric]


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Between all the attack ads, outrageous claims and steady flow of parodies of both candidates, election fever is reaching an all-time high. But guess what? There's still almost 100 days left until the big day in November, so why don't we all just calm down.
We've been watching Will Ferrell and Zach Galifianakis promote "The Campaign" for a while now, and it got us thinking about all the fictional candidates that are more entertaining than our current ones. Sure, Obama can sing a pretty good "Call Me Maybe," and Romney is all right at describing things, but we'd be having even more fun with the election if some of the candidates below were running.
From Will and Zach's "Campaign" posters to the multiple "Simpsons" characters that have sought office, we rounded up over a dozen of our favorite fictional campaign signs below (we even threw Colbert in there for good measure). Click through and vote for your favorites, and tell us who we missed in the comments.
Two dogs are always better than one.
Now THAT says "America."
Who wouldn't vote for a president with great "handshakefulness"?
We don't not love this sign.
You can't argue with that campaign strategy.
In 2009, Monty Burns actually "ran" for mayor in New York City and got a few write-in votes.
We imagine he'd be seeking the endorsement of the GOP.
You have to vote for him if he's been a good boy, right?
We'd have to change a few laws for them both to be president, but it would probably be worth it.
He didn't really think this one through.
"P.S. Sorry for all the deaths"
One thing all politicians need is reciprocity.
Um, Voldemort hates muggles so we're not really sure what this poster is trying to say **pushes glasses up from over nose**.
We know Colbert is a real person, but it was the character Stephen Colbert who ran for President of South Carolina and ended up with a fifth place finish. We love them both.


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Posts filed under "Inflation"
Category: Federal Reserve, Fixed Income/Interest Rates, Inflation
Category: Employment, Federal Reserve, Inflation, Investing, Markets, Psychology
This is the article that the Greenspan quote came from that popped the market today; I don't know how accurate it is (holographic image?) but
Gold price riding high on fear of terrorism, says Greenspan
Leo Lewis, Tokyo
February 09, 2006
"ALAN Greenspan, who stepped
down last week as chairman of the US Federal Reserve after 18 1/2 years, has
blamed the threat of terrorism for the high gold price, in his first private
sector speech since being let off the leash of officialdom.
According to
members of his audience of international investors – watching a holographic
image in Tokyo as he spoke in New York – Greenspan said the high cost of gold
did not reflect inflation or the strength of commodities, but rather a fear
among investors of a major geopolitical conflict. There were people who believed
that a nuclear weapon could be detonated within five years, the former American
central bank supremo said.
The low probability of such an event occurring would not necessarily avert a
spike in the gold price, he added.
Greenspan went on to discuss a range of topics, including the problems
created by a lack of investment in refining capacity by the oil industry. He
said this failure by the oil majors meant that the era of cheap energy was
almost surely over.
The former Fed chairman is also said to have indulged in a moment of
self-criticism over the central bank's failure to prevent the market bubble in
the late 1990s.
That may explain Gold's $20 whackage yesterday, but what about all the rest of the metals and commodities?
Also, if you missed this, you MUST read it:
Former Fed Chief's Inscrutable Statements Baffle Wife
Its a hoot!
and on the chance the article disappears, I'll archive it after the jump . . .
Category: Federal Reserve, Inflation, Investing
Category: Inflation


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I have been wanting to try clipless pedals for a long time. I finally ordered shimano a520's and a set of nashbar mountain bike shoes.
I guess they will take a little time to get used to. The shoes are a little too long but I think the cleat is where it needs to be. It feels like I'm pedaling with my tip toes. I guess they just feel different. I rode 9 miles on them today practicing getting in and out. I'm sure they will start feeling normal soon. I am going to try and go by the lbs this weekend and see about getting a general fit I also changed to a thomson set back seat post so I could put my brooks saddle back on. So now all mÝ measurements are out of wack.


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Are you Louis Danoux?Claim your profile
Publications (20)40.21 Total impact
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ABSTRACT: Background: Protein glycation refers to the spontaneous reaction of reducing sugars with proteins and the subsequent formation of stable advanced glycation end products (AGEs). Glycation is linked with oxidative stress, and this association is called "glycoxidation". Glycoxidation alters the protein structure and function and causes tissue aging, as seen in human skin. Therefore, research on substances inhibiting glycoxidation appears to be crucial in the prevention of skin aging. With this aim, several plant extracts have been screened for antiglycation activity, and the results of the best candidates are presented in this article. Methods: Glycation was studied on human skin proteins (collagen, elastin, and albumin) and on a model of reconstructed skin. Oxidative stress has been addressed by testing the copper-induced low-density lipoprotein oxidation, ultraviolet irradiation of glycated dermis, and carbonyl activation of human dermal fibroblasts. A clinical test evaluated the extent of oxidative stress induced by ultraviolet A irradiation. Results: Among the tested products, several plant extracts have decreased the glycation effects on skin proteins collagen, elastin, and albumin. In addition, a plant extract has significantly inhibited the different forms of oxidative stress associated with protein glycation. Conclusions: We have demonstrated that plant extracts can relieve the deleterious effects of glycation on human skin. Moreover, a plant extract rich in antioxidant molecules has also significantly preserved the human skin from glycoxidation attacks.Clinical Chemistry and Laboratory Medicine 04/2013; 52(1):1-8. DOI:10.1515/cclm-2012-0828 · 2.71 Impact Factor
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ABSTRACT: The skin is a densely innervated organ. After a traumatic injury, such as an amputation, burn or skin graft, nerve growth and the recovery of sensitivity take a long time and are often incomplete. The roles played by growth factors and the process of neuronal growth are crucial. We developed an in vitro model of human skin explants co-cultured with a rat pheochromocytoma cell line differentiated in neuron in presence of nerve growth factor (NGF). This model allowed the study of the influence of skin explants on nerve cells and nerve fibre growth, probably through mediators produced by the explant, in a simplified manner. The neurite length of differentiated PC12 cells co-cultured with skin explants increased after 6 days. These observations demonstrated the influence of trophic factors produced by skin explants on PC12 cells.Experimental Dermatology 03/2013; 22(3):224-225. DOI:10.1111/exd.12095 · 3.76 Impact Factor
Article: Activation de neurones sensoriels par l'application topique de capsaïcine dans un modèle in vitro de ré-innervation cutanéeAnnales de Dermatologie et de Vénéréologie 12/2012; 139(12):B278. DOI:10.1016/j.annder.2012.10.509 · 0.92 Impact Factor
Article: Characterization of neurons from adult human skin-derived precursors in serum-free medium : A PCR array and immunocytological analysis[Show abstract] [Hide abstract]
ABSTRACT: Adult stem cells could be small sources of neurons or other cellular types for regenerative medicine and tissue engineering. Recently, pluripotent stem cells have been extracted from skin tissue, which opened a new accessible source for research. To routinely obtain a high yield of functional neurons from adult human skin stem cells with defined serum-free medium, stem cells from abdominal skin were cultured in serum-free medium. To differentiate them, we used a defined medium containing growth factors. Differentiated cells were identified using the following methods: (i) Oil-red-O staining for adipocytes, immunocytochemistry with antibodies recognising (ii) neurofilaments and PGP9.5 for neural differentiation, (iii) glial fibrillary acidic protein (GFAP) for glial differentiation, (iv) Ki-67 for proliferative cells, (v) FM1-43 staining to analyse vesicle trafficking in neuronal cells and (vi) a PCR array was used. Stem cells were floating in spheres and were maintained in culture for 4 months or more. They expressed nestin and Oct 4 and were proliferative. We induced specific differentiation into adipocytes, glial and neuronal cells. The yields of differentiated neurons were high and reproducible. They were maintained for long time (1 month) in the culture medium. Furthermore, these neurons incorporated FM1-43 dye, which indicates a potent acquisition of synaptic features in neurons. Stem cells from adult human skin could be valuable and reproducible tools/source to obtain high numbers of functional specific cellular types, such as neurons, for tissue engineering. In this work, the possibility to obtain a high yield of differentiated neurons, with the ability of endocytosis and vesicle cell trafficking, was shown.Experimental Dermatology 03/2012; 21(3):195-200. DOI:10.1111/j.1600-0625.2011.01422.x · 3.76 Impact Factor
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ABSTRACT: The nervous system takes part in skin homeostasis and interacts with skin cells. In in vitro organotypic skin models, these interactions are lost owing to the absence of nerve endings. We have developed an in vitro organotypic skin model based on a re-innervated human skin explant using primary sensory neurons from the dorsal root ganglia of rats. After 10 days of co-culture between skin explant and neurons, a dense network of nerve fibres was observed. The epidermis and dermis presented nerve fibres associated with cellular body from sensory neurons introduced in the co-culture. Epidermal thickness, cell density and quality of re-innervated skin explant were all higher when skin explants were re-innervated by sensory neurons at 10 days of culture. Proliferation of epidermal cell was not modified, but the apoptosis was significantly diminished. Hence, this innovative model of co-cultured skin explants and neurons allows better epidermal integrity and could be useful for studies concerning interactions between the skin and its peripheral nervous system.Experimental Dermatology 02/2012; 21(2):156-8. DOI:10.1111/j.1600-0625.2011.01421.x · 3.76 Impact Factor
Article: Ultraviolet-B irradiation induces epidermal up-regulation of heparanase expression and activity[Show abstract] [Hide abstract]
ABSTRACT: Heparan sulfate (HS) glycosaminoglycans are abundant components of basement membranes and cell surfaces where they are present associated with specific core-proteins to form proteoglycans, mainly perlecan, glypicans and syndecans. They play many roles such as modulation of cell proliferation and differentiation, cell-matrix adhesion and assembly. It was previously shown that HS content decreases during skin aging. This decrease could be explained either by a decrease of HS synthesis or by an increased activity of its degrading enzyme, heparanase (Hpse-1). Since UV-B irradiation is one of the most important factor for skin photo-damage, we decided to study the effects of UV-B irradiation on heparanase expression and activity in human epidermal keratinocytes. Normal human keratinocytes and reconstructed epidermis were submitted to increasing doses of UV-B. HPSE1 mRNA levels were measured using real time PCR and heparanase enzymatic activity was quantified in human keratinocyte cultures using a microtiter-based assay. Expression and distribution of Hpse-1 were also studied in reconstructed epidermis by immunofluorescence. Both HPSE1 mRNA level and heparanase enzymatic activity were increased after UV-B irradiation of keratinocyte cultures in a time and dose-dependent manner. Protein expression of Hpse-1 was also up-regulated with increasing doses of UV-B in reconstructed epidermis. Increase of Hpse-1 expression and activity in the epidermis after UV-B irradiation could contribute to skin photo-aging.Journal of photochemistry and photobiology. B, Biology 10/2011; 106(1):107-12. DOI:10.1016/j.jphotobiol.2011.10.013 · 2.96 Impact Factor
Article: Ultraviolet-B Irradiation Induces Differential Regulations of Hyaluronidase Expression and Activity in Normal Human Keratinocytes[Show abstract] [Hide abstract]
ABSTRACT: Skin aging is a complex process determined by genetic factors (intrinsic aging) and environmental factors (extrinsic aging). One of the most influential environmental factor is UV-B irradiation. Hyaluronic acid (HA) is an abundant component of skin extracellular matrix where it plays many roles such as hydration and architectural support. Downregulation of HA during photoaging was reported previously. Changes in expression and function of its degrading enzymes, the hyaluronidases (Hyals) might be involved in this decrease. In the present study, normal human keratinocytes were submitted to increasing doses of UV-B. The mRNA expression of HYAL1, HYAL2 and HYAL3 and the hyaluronidase enzymatic activity were quantified using real-time PCR and a microtiter-based assay, respectively. After UV-B irradiation, HYAL1 mRNA expression was upregulated whereas HYAL2 and HYAL3 mRNAs were downregulated and hyaluronidase enzymatic activity was increased in both cell layer and culture medium. In parallel, immunohistochemical studies performed on UV-B irradiated reconstructed epidermis confirmed that Hyal-1, Hyal-2 and Hyal-3 protein expression were differently regulated by UV-B. Taken together, our results demonstrate that UV-B irradiation induces differential regulations of hyaluronidase expression and enzymatic activity in human keratinocytes. These differential modulations of hyaluronidase expression and activity by UV-B could contribute to cutaneous photoaging.Photochemistry and Photobiology 06/2011; 87(5):1105-12. DOI:10.1111/j.1751-1097.2011.00959.x · 2.27 Impact Factor
Article: The evolution and use of skin explants: Potential and limitations for dermatological research[Show abstract] [Hide abstract]
ABSTRACT: Different models have been developed to understand the biology of skin or to test pharmaceutical/cosmetic products. These models can be in vitro models that possess advantages such as mono and co-culture models in 2D, which are very reproducible, or organotypic models (skin explant and reconstructed skin) that present a 3D organisation. Animal or human in vivo models allow studies that are closer to reality. In virtuo models developed on computers control all known parameters and do not require animals. The major limitations of these models are the lack of 3D structure for in vitro culture, the variability of results from organotypic models, ethical problems inherent to human and animal tests and the presence of numerous unknown parameters in in virtuo systems. Despite their limitations, skin explants seem to be an interesting model for studies. Skin explants may be kept from a few hours to 10-14 days on supports or directly in culture medium. These explants are generally cultivated at 37 °C, 5% CO(2), preferentially in serum-free conditions. Three basic techniques are used to characterise these models: histological stains, proliferation, apoptosis and cytotoxicity tests. Skin explants could be a very convenient model to study wound-healing, inflammation processes, autoimmune diseases, malignant transformation, stress, ageing, and to serve as screening tests.European journal of dermatology: EJD 11/2010; 20(6):671-84. DOI:10.1684/ejd.2010.1054 · 1.99 Impact Factor
Article: New peptidic active ingredient to reduce discomfort and painful sensations in sensitive skin[Show abstract] [Hide abstract]
ABSTRACT: IFSCC Magazines, 12 (2009) (1) 25–30 Approximately 40% of the population (all skin categories and phototypes) complain of sensitive skin. Sensitive skin is healthy but overresponsive, meaning it reacts faster and more intensely to several parameters including environmental factors such as temperature changes and the sun, use of cosmetic products, and certain medicines. It experiences discomfort, tingling, burning and intolerance to certain types of products, a condition referred to as neurosensitivity characterized by a lower threshold of tolerance. Currently, all of the causes are not known but an increase in the permeability of the stratum corneum and an exaggeration of the nerve response are considered to be involved in the phenomenon of sensitive skin. Lifestyle factors including tobacco, alcohol, stress, fatigue and emotions also have an effect. A new synthetic tetrapeptide, N-acetyl-L-tyrosyl-L-prolyl-L-phenylalanyl-L-phenylalaninamide (Ac-YPFF-NH2), mimicking a natural opioid peptide was developed with the aim to decrease skin nerve ending stimulation. This tetrapeptide was demonstrated in vitro to reduce cutaneous overreactivity by decreasing release of calcitonin gene-related peptide from sensory neurons via an agonist effect on the μ opioid receptors and in vivo to improve the comfort of sensitive skin by decreasing unpleasant sensations and pain induced by heat and capsaicin. This tetrapeptide targeting an exaggerated nerve response helps to relieve sensitive skin by normalizing the tolerance threshold for environmental factors or certain topically applied uncomfortable products or skincare treatments. Keywords: Calcitonin gene-related peptide, μ opioid receptor, nerve endings, peptide, sensitive skinInternational Journal of Cosmetic Science 12/2009; 31(6):480-480. DOI:10.1111/j.1468-2494.2009.00532_4.x · 1.38 Impact Factor
Article: Ulmann L, Rodeau JL, Danoux L et al.Dehydroepiandrosterone and neurotrophins favor axonal growth in a sensory neuron-keratinocyte coculture model. Neuroscience 159:514-525[Show abstract] [Hide abstract]
ABSTRACT: We have previously shown that axonal growth from a subset of sensory neurons was promoted by keratinocytes when the two cell types were co-cultured in a low calcium medium. This phenomenon involves the production of one or several diffusible factors. Here we show that the neuritogenic effect of keratinocytes was significantly reduced in the case of rat primary sensory dorsal root ganglion (DRG) neurons, or completely suppressed in the case of the sensory neuron cell line ND7-23, when the activity of neurotrophin receptors (Trk receptors) was blocked with K252a. This trophic effect apparently involved the activation of tyrosine kinase receptors A and B (TrkA and TrkB) expressed by subpopulations of small- to medium-sized DRG neurons, or only of TrkA receptors in the case of ND7-23 neurons. A residual neurite growth promoting effect of keratinocytes persisted in a fraction of DRG neurons after Trk receptor blockade. This effect was mimicked by the steroid dehydroepiandrosterone (DHEA) but not by other steroids such as pregnenolone, progesterone or 17beta-estradiol. The use of pharmacological agents which inhibit different steps of steroidogenesis indicated that DHEA was probably synthesized from cholesterol in keratinocytes. Our results strongly suggest that DHEA might act as a neurotrophic signal derived from keratinocytes to promote axonal outgrowth from a subpopulation of sensory neurons.Neuroscience 04/2009; 159(2):514-25. DOI:10.1016/j.neuroscience.2009.01.018 · 3.36 Impact Factor
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ABSTRACT: IFSCC Magazine, 11 (2008) (1) 21–29 Proteoglycans take an important part in tissue homeostasis. In the skin, Proteoglycans are present in the extracellular matrix of dermis, particularly with lumican which plays an important role in dermal homeostasis. In the epidermis, several small proteoglycans such as the syndecans are synthesized and play an important role in keratinocyte activation. There is much data on the alteration during skin aging of the synthesis and structure of glycosaminoglycans and some proteoglycans but little information on small proteoglycans, in particular lumican and syndecan-1. We recently observed a decrease in the synthesis of these two small proteoglycans with aging. We confirm in this work the decrease in lumican in dermis and syndecan-1 in epidermis with aging. These proteoglycans represent original important targets for cosmetology in the fight against skin aging. In different in vitro models, two synthetic acetyl tetrapeptides, AcTP1 and AcTP2, stimulate the synthesis of lumican and syndecan-1, respectively. The beneficial action of AcTP1 on skin thickness and firmness and of AcTP2 on epidermal cohesion has been confirmed in vivo.International Journal of Cosmetic Science 04/2009; 31(2):154-154. DOI:10.1111/j.1468-2494.2008.00451_3.x · 1.38 Impact Factor
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ABSTRACT: Le tissu adipeux est un organe jouant un rôle majeur dans le maintien de l'homéostasie métabolique. De plus, la masse grasse a acquis le statut d'organe endocrine. Enfin, récemment, la présence de cellules du système immunitaire a été mise en évidence dans le tissu adipeux et suggérée comme étant responsable du développement de l'inflammation chronique de bas niveau associée à l'obésité. Ces échanges de métabolites, d'hormones et de cellules entre compartiment adipeux et sanguin démontrent le rôle prépondérant de l'endothélium dans la masse grasse. Or, chez l'homme aucune étude n'a décrit l'endothélium du tissu adipeux. Cette étude a été menée afin de caractériser le système capillaire du tissu adipeux humain sous-cutané abdominal et d'évaluer l'influence du degré d'adiposité des patients sur l'état d'activation des cellules endothéliales du tissu adipeux humain. Nous avons déterminé, par observation in situ en immunofluorescence que le tissu adipeux humain possédait un réseau capillaire très développé caractérisé par la double expression des marqueurs de surface CD31 et CD34. L'analyse en cytométrie en flux du nombre de cellules CD31+/CD34+ du tissu adipeux de patientes normopondérées (indice de masse corporelle (IMC) compris entre 20 et 25) et obèses (IMC supérieur à 30) a montré que le nombre de cellules CD31+/CD34+ est maintenu constant, démontrant que la croissance excessive du tissu adipeux s'accompagne d'une extension de son réseau capillaire. La caractérisation par PCR quantitative en temps réel de transcrits exprimés dans les cellules endothéliales capillaires CD31+/CD34+ du tissu adipeux humain isolées par une technique d'immunosélection/déplétion a mis en évidence un état d'activation inflammatoire et angiogénique de ces cellules chez les sujets obèses. De plus, nous avons développé une technique de culture primaire de ces cellules permettant le maintien de l'expression des marqueurs endothéliaux. En conclusion, cette étude a permis de mettre au point des techniques d'immunohistochimie en fluorescence des réseaux capillaires du tissu adipeux humain et de culture primaire des cellules endothéliales. De plus, nos résultats montrent que le développement de la masse grasse chez l'homme module le phénotype des cellules endothéliales (activation inflammatoire et angiogénique).Archives of Cardiovascular Diseases 03/2009; 102. DOI:10.1016/S1875-2136(09)72174-6 · 1.84 Impact Factor
Article: Ulmann L, Rodeau JL, Danoux L et al.Trophic effects of keratinocytes on the axonal development of sensory neurons in a coculture model. Eur J Neurosci 26:113-125[Show abstract] [Hide abstract]
ABSTRACT: The epidermis, the outermost structure of the skin, fulfils important roles as a physical barrier between the organism and its environment and as a neuroendocrine, immune and sensory organ. It is innervated by unmyelinated sensory fibres conveying nociceptive and thermoceptive information. Little is known concerning the functional interactions between these sensory fibres and the keratinocytes, which constitute 95% of the epidermal cells. We have developed a coculture model of primary rat sensory neurons and keratinocytes, as well as of equivalent cell-lines: ND7-23 neurons and A431 keratinocytes. We show that primary dorsal root ganglion neurons survive well in a standard keratinocyte reference medium containing a low concentration of calcium, but fail to extend axons. However, when neurons are cocultured with keratinocytes, axonal outgrowth is strongly stimulated. The use of a Transwell culture system indicated that the stimulation of axonal growth depends on a soluble factor secreted by keratinocytes. Axon outgrowth was also induced by nerve growth factor or brain-derived neurotrophic factor, but not by neurotrophin 3 or glial cell-derived neurotrophic factor. Neurons cocultured with keratinocytes did not change their responses to ATP, capsaicin or high potassium solution, as measured by calcium imaging. The trophic effect of keratinocytes concerned essentially a population of medium-sized (17-25 microm) neurons, some of which expressed substance P-like immunoreactivity and responded to capsaicin. Our preparation, in which cells are maintained at low external calcium concentration, could represent a useful in vitro model for characterizing the effect of skin-derived guidance and trophic factors.European Journal of Neuroscience 08/2007; 26(1):113-25. DOI:10.1111/j.1460-9568.2007.05649.x · 3.18 Impact Factor
Article: Influence of aging on glycosaminoglycans and small leucine-rich proteoglycans production by skin fibroblasts[Show abstract] [Hide abstract]
ABSTRACT: Skin aging is characterised by a progressive deterioration of its functional properties, linked to alterations of dermal connective tissue. Whereas many studies have been devoted to collagen alterations during aging, the situation is less clear concerning glycosaminoglycans and proteoglycans. Particularly, the alterations of the expression of small leucine-rich proteoglycans (SLRPs), a family of proteoglycans strongly implicated in cell regulation, have never been studied. In the present study we measured glycosaminoglycans and small leucine-rich proteoglycans synthesis by skin fibroblasts from donors of 1 month to 83 years old. [3H]-glucosamine and [35S]-sulfate incorporation did not show significant differences of sulfated GAG synthesis during aging. On the other hand, a significant positive correlation was found between hyaluronan secretion and donor's age. Northern blot analysis of SLRPs mRNAs showed a significant negative correlation of lumican mRNA with donor's age, whereas decorin and biglycan mRNAs were not significantly altered. Immunohistochemical study and quantitative image analysis confirmed a decreased lumican accumulation in aged human skin. Taken together, our results suggest that impairment of glycosaminoglycans and SLRPs synthesis might be involved in the functional alterations of aged skin.Molecular and Cellular Biochemistry 10/2005; 277(1-2):63-72. DOI:10.1007/s11010-005-5073-x · 2.39 Impact Factor
Article: How Ecological Farming, Fair Trade and Sustainability Can Drive the Reasearch for New Cosmetic Active Ingredients
Article: Jeanmaire C, Danoux L & Pauly G. Glycation during human dermal intrinsic and actinic ageing: An in vivo and in vitro model study. Br J Dermatol145: 10-18[Show abstract] [Hide abstract]
ABSTRACT: Non-enzymatic glycation occurring in normal human skin plays an important part in ageing. OBJECTIVES To visualize and quantify, in human subjects, the extent of glycation during human dermal intrinsic and actinic ageing, and to develop a reliable reproducible in vitro model for evaluating the efficacy of potential inhibitors of glycation. By immunohistochemistry using a monoclonal antibody recognizing carboxymethyl lysine, an advanced glycation end-product (AGE) (first objective), and by incubating dead de-epidermized dermis (DED) with glucose to simulate ageing-induced glycation in a human dermal equivalent model (second objective). We found that glycation of the dermis generally arises after 35 years, then increases rapidly with intrinsic ageing. We also noticed an enhancement of glycation by solar irradiation that occurred via glycation of the elastic fibre network or solar elastosis tissue. In the model, production of AGEs appeared in a time-dependent way, mimicking glycation observed in vivo during chronological ageing. Irradiation of DED before incubation with glucose strongly enhanced induction of AGEs, corresponding to the effect of solar irradiation on AGEs observed in vivo. These results confirm a marked increase of AGEs during intrinsic ageing in normal human skin and also suggest that glycation is enhanced in photoaged skin.British Journal of Dermatology 08/2001; 145(1):10-8. DOI:10.1046/j.1365-2133.2001.04275.x · 4.28 Impact Factor
Article: Advanced histological technology and three-dimensional imaging: a fruitful partnership to visualize the human skin micro-anatomy and changes in cutaneous structures.Journal of cosmetic science 55(2):224-5. · 0.28 Impact Factor
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ABSTRACT: Learning from Nature: Biomimicry
Article: magazine The Global Publication of the International Federation of Societies of Cosmetic Chemists