text:
Deviant Art
Audubon, Great White HeronBachman's cat would appear to be merely restingAudubon, Great White Heron5 years ago in Free Verse More Like This
in the evening sun
if it weren't for the bill speared through its heart.
The Heron is tall as a woman, twice as cruel,
and at least as beautiful.
I brought the bird all the way from Florida
as a gift for my friend,
a pillar of living ivory
to walk among his Magnolias.
But already it's swallowed a dozen ducks,
bitten several children, and now
(the most dire offense) slain poor Francis.
It will be shot and stuffed within the week,
but beasts can't be blamed
for their wickedness.
When it flew along the banks of the Keys,
it snapped up fish with the grace of sharpened wind.
My deckhands would remove their hats
when a flock circled, dove,
and thinned out the flashing tide in an instant.
Even I once gasped at the display.
But a miracle on the marsh
is a crime in the garden.
Even though the animal will die
under trees that are strange to it,
I envy him.
Because my thin brother was hatched
possessing the virtues of a specter,
while I am left clin
SH. Hinata-murderer:Family CH3SH. Hinata-murderer:Family CH34 years ago in Introductions & Chapters More Like This
What's written in -...- means a person talking.
I should apologize that my stories has a lot of grammar and spelling mistakes, but that's just something I can't control So I APOLOGIZE about it
Please don't get angry about it..!
Hinata is a murderer: Family Ch3.
Destroy Konoha!? Hinata repeated in her head.
Konoha was a country for which Hinata fight all these years and now she had an opportunity to destroy it.
I I could join you, but - Hinata took a breath for a moment. But? Repeated Sasuke. But if you promise that I will not have to fight with Naruto or Hokage. Hinata quietly finished and Sasuke smirked.
As you wish I am going to fight Naruto. Sasuke added and Hinata looked away.
There is nothing that is holding me from destroying Konoha. Maybe that way Naruto will be able to bring Sasuke home Maybe I could
CeilingI throw myself back on the bed and look upCeiling7 years ago in Free Verse More Like This
To lose myself in an expanse of white
Crackling in my mind like a fresh sheet of drawing paper.
And in that crisp newness images spring forth:
Rolling waves, blooming trees, hills and fields,
The rays of a lemon-colored sun across a pink-and-orange sky,
And birds with plumage of a hundred deep and shining hues.
The images dance and roll and spill down the walls
Flowing like water and frolicking like dogs
A violent orchestra of color erupting from a blank;
I think of this, and wait for winter to turn into spring.
Forget Me.Why can't I be happy and not aloneForget Me.3 years ago in Traditional Fixed Forms More Like This
A shattered soul with no home
I search for that person who can complete me
But they all end up being cunts and I flee
I am a bird with a broken wing flying in circles
Going through life having to jump constant hurdles
My heart hurts and it bleeds
I have nobody to fulfill its needs
Is there any hope? probably not
My only fate is to lay down and rot
Somebody please help I can't go on like this
Sinking ever so slowly into an abyss
All I can do is bleed and cry
Slowly awaiting my time to die
I know I am not the only one who wishes for an end
Someone to enter their life and stop this trend
This is a search that seems as though it is a never ending endeavour
I am destined to be lonely, broken, sad, and alone forever
Fuck it I am almost done
I will most likely never fine the one
ApocalypseTrees grow, birds fly, and people die,Apocalypse3 years ago in Free Verse More Like This
It is part of the inevitability of life,
This world continues to rotate even as wars plague it,
But when the nukes fly who knows what will be the result,
Most likely worldwide panic and starving people,
The Earth barely holding the title of a cripple let alone a planet,
War is unnecessary, vile, and a waste of time,
We need to stand together and fix this bullshit world we live in,
Everything we hold dear will burn and fall apart,
Leaving all broken with an empty heart,
Stand and quit being a sheep,
Don't just listen you must question every peep,
99% of the words the government says are lies,
They wish for war even though it's the cause of our poor economic condition,
All they want is more fucking power and a bigger paycheck,
They don't give the slightest fuck about you and me,
Hearing them speak makes my ears bleed,
I want nothing more than peace in this world,
But with idiots at the wheel we are fucked,
This Earth is the developing child and they
SH. Hinata-murderer: Chase Ch6SH. Hinata-murderer: Chase Ch64 years ago in Introductions & Chapters More Like This
What's written in -...- means a person talking.
I should apologize that my stories has a lot of grammar and spelling mistakes, but that's just something I can't control So I APOLOGIZE about it
Please don't get angry about it..!
SasuHina. Hinata is a murderer: Chase. Ch6.
Hinata watched the sun slowly rising as she couldn't sleep. Hinata didn't slept the whole night, thinking about what will happen today. She didn't know a thing about today's mission.
She knew at least something from all the previous missions, but about this one she didn't know a thing.
Hinata felt blind, blind because Sasuke was the one who made her go blind that way. Blind, not knowing, not seeing, not hearing anything what was going on in their own world, where the only goal was to destroy Konoha.
No, it didn't bother Hinata anymore that they will try to destroy Konoha, there was Naruto, who wouldn't let innocent people die, there were Sakura and Ino, who would hea
Don't hate me-Minato x KushinaDon't hate me-Minato x Kushina4 years ago in Emotional More Like This
Don't Hate Me
[A MinaKushi fanstory]
[Minato X Kushina from Naruto]
By: Kaede Natsu Sakurano
"Minato! Quit joking with me!" Pink-haired Kushina pushed the 12-year old blonde boy away. Anger flashed in Kushina's grey eyes as she stared into Minato's blue ones.
Minato Namikaze shrugged, "I wasn't joking, I'm serious. I want you to go out with me." Kushina Uzumaki wasn't the type of girl that any boy would want to go out with. She concealed the nine-tailed fox beast within her body, so she was shunned by most of the village. Along with that, she was too serious. She knew that her genin classmate, Minato, was a joker and loved by everyone. They were two opposites and would never go well as a couple. Also, Minato could as well be lying.
Kushina shook her head, "I have to worry about the Chunin Exams, and you should too, because we are on the same squad. I don't want you to weigh us down."
Minato chuckled, "All right, Ms. Sassypants, I won't weigh us down. I'll be the one to make us pass. I
The Curiosity ShopThe shopkeeper stands behind a wooden counter, elegantly carved and pockmarked with age. He is neither young nor old; there are small transformations in his features and expression, from moment to moment, that make it impossible to guess his age. These changes are so remarkable that, all by themselves, they prevent his face from being forgettable.The Curiosity Shop7 years ago in General Fiction More Like This
The ceiling of his shop is nearly invisible through a mass of dangling kites from Japan and China. Antique umbrella stands and rapiers in leather scabbards line the floor and walls. The rows of towering shelves are packed with joke rubber vomit and red-hot candies, baskets of delicate seashells and specimens in jars of formaldehyde.
A bell over the door jingles to announce new arrivals, and most days the shopkeeper sees a stream of interested customers. University students breeze through the stacks, humming along with the music coming through their earbuds and flicking their eyes around curiously. Occasionally they stop moving completely and
CanadaXReaderCanadaXReader4 years ago in Short Stories More Like This
Thanksgiving. Your favorite holiday. Not only was this your favorite holiday because it meant food, and lots of it, it meant that you got to spend the whole weekend in the same large house as your neighbor, best friend, and longtime crush, Matthew. Every year your family and his would travel to your grandparent's lake house to have a huge thanks giving dinner, and of course the annual hockey game.
This tradition had been going on for as long as you could remember, and every year you managed to embarrass yourself in front of Matthew. Your sister Daisy was dating Matthew's brother Alfred, and was always supporting you in your efforts to woo him; even though you always failed.
But this year was different. You had made a fool-proof plan to impress him and gain his affection.
"Hey ______, are you ready to play hockey?" Daisy asked you.
"You know it." You replied confidently. You had spent almost every day after school at the ice skating rink practicing your coordina
ComforterComforter5 years ago in Concrete Poetry More Like This
hundred nights
(the triple lunes that
extrasensory perceptionI will make a cameraextrasensory perception7 years ago in Free Verse More Like This
For smells and stillness
And capture wet grass fumes
Who synthesize a sweet drift in the
Ten oclock breeze;
Dark blue harmonies
On highway nine
Where thirsty Thursday greens
Mingle with warm winds
Across the river
And darken
The integrity of the water.
Theres something less
Concrete about this explanation,
That burrows through one breath,
And I cant quite let escape
The vastness of its depth.
Mass Effect 3 Alternate Endings. SPOILERSMass Effect 3 Alternate Endings. SPOILERS4 years ago in Flash Fiction & Vignettes More Like This
**EDIT** Holy crap this got way more attention than I was expecting. The comments and support have been amazing everyone!
A few points: Credit where credit is due; this ending, as much as everyone seems to love it, was only created because the amazing team at Bioware created a universe that was so rich and full of life and detail. As much as I know a lot of fans are hurt by what they did, we need to remember that Bioware still created an incredible trilogy, one of the best ever. So hats off to them all round.
Also, this was written really fast and so the ending (specifically the last part on how you actually win using TIM's signal) isn't very fleshed out. I know there are holes, and they can actually be fixed quite easily. This isn't perfect. Also, this doesn't deal with a 'happy' ending. If there were to be one, or you were to even CONSIDER taking the fourth option, you'd need to be damn ready. I'm talking ALL war assets e
October Two-Eight...October Two-Eight:October Two-Eight...7 years ago in Haiku & Eastern More Like This
Haikus to Describe the Day
(Thank You, FEF)
Thank you, FEF.
Due to last night, now I can't
get haikus out... ARGH!
Now due to you guys,
I shall document my day
(In haiku, of course!).
No zero block choir.
Froze outside, got online in
library. Hurrah!
Art class was a pain.
Thumb is sore due to carving
Taipei 101.
History was cool.
Turned in an essay way late
(due on the thirteenth).
Science was alright.
Calculations for lab shown:
helpful but boring.
Mandarin was hell
(Then again, it always is).
... Miracles exist!
Lunch was interesting.
Random conversations and
chicken pot pie... yum.
English, hard to say.
Ups and downs were abundant.
Last class, though, so yay.
Videogame Club
was non-existant because
of a fire drill.
Bus ride home was fun.
Reflection of the school day,
Zune pumping music.
Overall, the day
was fair, with Facebook chain, mouse
head, and... well, classes.
|Sta.sh Submit


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Product Information:
The Loop Side Table by Umbra is simple and pure in its form, giving the illusion of a balancing table top and its tubular structure below. The table top is constructed of 4 mm tempered glass while the base is powder coated steel. This table is great for small spaces such as condos, apartments or small homes.
Product Details
Weights & Dimensions
|Base Material: Metal
|Top Material: Glass
|Shape: Round
|Design: Table
|Distressed: No
|Hidden Storage Compartment: No
|Exterior Shelves: No
|Cabinets Included: No
|Country of Manufacture: China
About the ManufacturerUmbra is the worldwide leader in modern, original, casual, innovative, and affordable design for the home. They are a Toronto-based homeware design company born over 30 years ago when graphic designer, Paul Rowan, couldn't find a nice window shade to hang in his apartment window. So, he made one, and people liked it. He soon teamed up with childhood friend, Les Mandelbaum, and Umbra (in Latin, "shade") was born. Les and Paul began re-imagining everyday items into modern-ware.
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Overall Rating
Based on 44 reviews
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Love this little table! Carolyn from Reston, VA on 08/17/2015 – Verified Buyer
I was looking for a small, contemporary table that would take up a little visual and physical space as possible. I found it in this Loop Side Table. What a great little table! It came nicely packaged-no damage. The table is in three pieces that you just need to screw together--no tools required. I repeat: NO TOOLS REQUIRED! This table is exactly what I was looking for--it fits discretely between two club chairs and is the perfect height and size for a glass or two. The price is amazing. this table looks great. So happy. Pros: easy to assemble, lightweight, yet still substantial;great price
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Excellent easy to assemble end table. Victor from Paso Robles, CA on 03/31/2015 – Verified Buyer
This is a very contemporary end table. It came in three pieces and was extremely easy to assemble in under 5 minutes. It is exactly as described on the webpage. It is light,so really is not intended for heavy objects but is good for placing a couple of wine glasses or other drink glasses. I would recommend this end table which is also very reasonably priced. Pros: Great value and easy to assemble. Cons: A tad on the light side.
Was this helpful? Yes 1 No 0
Chic side table Joann from GA on 10/30/2014
This table has a very sophisticated look and fits well in a variety of settings: living room, bedroom, den or porch. I move it around as I need it. Clean lines, and looks like it cost much more. One caveat: if you have young children you may want to keep it out of reach. It's quite lightweight (a plus for me) and could easily be knocked over by a young child.
Was this helpful? Yes 1 No 0
Very nice! Sue from Mount Horeb, WI on 08/18/2015 – Verified Buyer
I love this table. As noted in other reviews, it is perfect for setting a beverage on but not stable enough to hold anything too heavy. The clean contemporary design is really nice and the price is fantastic. It looks like it would have a much more expensive price tag. Pros: Great design, Great price. Great size for small room Cons: None
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Perfection! Margaret from Spring Lake Heights, NJ on 08/23/2015 – Verified Buyer
I have been searching for a glass topped end table for a while. I found this table and it was available in a light aqua that matches my family room perfectly. I ordered it on a Wednesday and it arrived on Saturday. Wow, I was impressed. It took two minutes to put it together. No screws needed. It is better than I was wishing for as the color is spot on. Am extremely pleased. The price was very good as well. Pros: Great value, extremely eacy to assemble, great color. Cons: None
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Media releases
Release date:
Thu, 09/03/2015
Local 80 year old vegetarian supporter will be opening the show
Release date:
Thu, 07/30/2015
ANIMAL CHARITY VIVA! is asking whether Northern Ireland is in danger of becoming mega farm central after plans were announced for yet another giant pig farm (in Limavady).
Release date:
Mon, 06/15/2015
Release date:
Wed, 04/01/2015
Celebrity chef takes cruelty off the menu
ANIMAL CHARITY VIVA! has written to celebrity chef Heston Blumenthal to congratulate him on the ethical decision to remove foie-gras from all his menus – both in the UK and Australia.
Release date:
Thu, 10/16/2014


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News Stories
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- Physical Chemistry
"Dynamics and Vibrational Spectroscopy of Water, Alcohols, and Carbon Dioxide in Ionic Liquids" by Professor Steven Corcelli (University of Notre Dame).
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"Applying Ideas of Visual Cognition to Problem Solving in Physics" by Professor N. Sanjay Rebello (Dept. of Physics and Astronomy, Purdue University).
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"SciFinder Scholar: The Essential Chemistry Resource" by Professor David Zwicky (Chemical Information Specialist, Purdue University).
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Chemistry Department Advisory Committee Panel Discussion Chemistry Graduate Students are invited to participate in a roundtable discussion of how to prepare for a professional career in chemistry. The discussion will feature a panel of Chemistry Department Advisory Committee (CDAC) members – Purdue Chemistry alums with experience including industry leadership, university research and entrepreneurship.
10/08/2015 4:30 pm - 5:30 pm
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"The Life and Times of a Professor at a Primarily Undergraduate Institution" by Professor Chris Bradley (Mount St. Mary's University).
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Muse Watson and Matthew Cowles star. In this horrifying tale, five hunters become the prey in a deadly game. When Steve, a New York City fire fighter, and his military buddy Frank leave the city on a well-deserved bow-hunting trip, they have no idea the
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This horror film is a real "B" movie. But I HAD to buy it because it was filmed at a horse ranch/bed and breakfast in PA where I help out. Read morePublished on February 11, 2013 by S. DeVonish
A bunch of hunter are hunted by other hunters that want to eat their flesh. Gory scenes, that are ridiculously campy and none of the characters are likeable. Waste of time.Published on April 8, 2007 by Mr. Right
I maybe the only one who liked this movie. I thought the gore was there!!! A mountain gal with some help on the boobs and the dad was the coolist! Read morePublished on June 13, 2006 by whitewolf
looks like it was shot with my camcorder from 1996. unrealistic dialogue. not the least bit able to be engulfed in.Published on August 7, 2005 by Deanna Bieniasz


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Why would a brand see theological language as rich ground for advertising? Perhaps because theology and advertising share the same root.
James Lee had been commissioned to start an African-American congregation. After reading Acts, his group decided on a multicultural plant instead.
Fall books
We asked college and seminary professors to write about one of their favorites.
Few secrets are as devastating as those that make us rethink our identity. Heidi Neumark discovered one when her daughter Googled their name.
Today's Century articles and blog posts, news articles, CCblogs network highlights, daily lectionary readings, and witnesses from the cloud.
In his recent address before Congress, Pope Francis invoked the spiritual legacy of Thomas Merton and in particular his "capacity for dialogue and openness to all." This ostensibly fond recollection of Merton is emblematic of the kind of talk that has endeared many liberals, Catholics and others, to Pope Francis: papal language that instills hope for eventual doctrinal change in the
It was the summer of 1991. I was 27 and doing my best to get through an intense unit of Clinical Pastoral Education at a large Boston teaching hospital.
It's a humanitarian crisis that has riveted the international community: refugees from Syria, Afghanistan, Libya, and elsewhere seeking asylum from civil war and violence. Images of the small, drowned body of Aylan Kurdi ignited our consciences and challenged world leaders to begin addressing the needs of these refugees.
The surge of unaccompanied minors into countries like Sweden mirrors the marked increase of Central American children entering the United States in 2014, fleeing violence at home.
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Bryan's United Air Conditioning
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There's something very cool about the yin and yang blend of this Wood and Titanium Ring from hersteller on Etsy. There's a beautiful and very modern harmony between the exotic rosewood interior and the highly-polished titanium shell on the exterior. It's ebony and ivory for a new era. (BUY)
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Stylish Luxury Apartments in Raleigh, NCONLINE LEASING NOW AVAILABLE!Welcome to our unique luxury apartments in Raleigh NC - the ultimate retreat for you to call home! We offer chic one, two and three-bedroom homes outfitted with stylish extras. You'll absolutely enjoy our exclusive amenities where you'll have the opportunity to cool off in the resort-inspired pool, or build strength at our fully equipped fitness center. So navigate through our site, then give us a call so we can help you make your move!
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Close cropped Night View of the Flight Deck of Delta Connection (Endeavour Air) CRJ-440 N8971A Cn 7971 taken at Ottawa International Airport (CYOW) at 2318 hrs local time on 23Jul2014. Photo taken... (more)
Final Rwy 05
Delta / CRJ / Final Rwy 23 /
"Flagship 3958" (FLG3958) just touching the nose down on 30R after a flight from FNT.
21L final


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The Grunge American Novel
Published: March 24, 1996
(Page 3 of 4)
"Infinite Jest" is sardonic, jaded and steeped in references to all strata of popular culture, from high to low. It exhibits both a savvy grasp of the cyberfrontiers on the horizon and a deep, abiding distrust of them. It is mildly subversive, occasionally ribald and sporadically crude. Think David Letterman with a postgraduate degree and diction, and you get at least some idea of the sensibility. "This has become a very hip book to read," says Alice K. Turner, the fiction editor at Playboy, who encouraged Wallace early in his career. "We've had a lot of skimpy fare for a long time."
Indeed, executives at Little, Brown quickly realized that the sheer length of "Infinite Jest" could work in their favor, and although Wallace was asked to cut about 300 pages from his initial draft, he was still allowed to exceed 1,000 pages, which meant that the book would be priced at $30. "We decided to play it as importance -- that the size lent a certain weight to the book, that there was a certain undeniability about it," says Amy Rhodes, head of marketing for the company. Her strategy revolved around a kind of dare: are you reader enough for this book?
To create that elusive, ephemeral entity known as buzz, the company compiled a list of 4,000 booksellers, industry insiders and media types and sent out a staggered series of six postcards that cryptically heralded the release of an at-first-unspecified book that gives "infinite pleasure" with "infinite style." And when blurbs to that effect became available from other authors and critics, Little, Brown put them on postcards and dispatched another series of three. Says Paul Slovak, senior vice president of publicity for Viking Penguin, "The promotional campaign has been brilliant."
And Wallace -- wittingly or unwittingly -- has served it well, projecting the perfect measure of aloofness, particularly in his appearance, which flouts conventional vanity in a manner that doth protest perhaps a bit too much. He often wears a bandanna wrapped tightly around his head, as if to avoid combing his shoulder-length hair and to coddle his febrile mind. His wire-rimmed glasses, stubble of beard and hole-ridden sweaters lend him the aspect of a doctoral candidate so deep in thought that he cannot afford the time or energy for grooming. Yet he runs regularly to stay fit, and his bathroom contains special tooth polish to combat the effects of the tobacco he chews. There's also a special acne medication to keep his skin unblemished.
He hates that his publicity tour involves so many photography sessions. "Whenever the picture comes out, it's absolutely appalling to me," he says. "I just so wish that wasn't what I looked like. I've just figured it out: I'm not going to look at them anymore."
"DO YOU GUYS KNOW 'THE CHARLIE ROSE Show'?" Wallace asks two of his faculty friends at Illinois State, a married couple many years older than he, when he visits their house to say goodbye before his three-week tour. "Would you think it was whorish if somebody went on it?"
"No, no," says Charles Harris, a professor of English. "It's on late at night, and it goes into things at length. Are you going on it?"
"I did have a no-TV pledge," Wallace sighs.
"Until they asked?" jokes Harris's wife, Victoria.
After considerable introspection, Wallace nixes "Charlie Rose," just as he turned down the "Today" show before it. In the interviews he does grant, Wallace draws sharp boundaries about what he will discuss and begs assurances about how it will be presented. "If you quote that," he will qualify something he has just said, "I'd really like you to quote that I acknowledge it sounds banal and cliched."
Friends say there are powerful currents of ambition and competitiveness in Wallace that can be traced back to his childhood in Urbana, Ill., and his career as a junior tennis player of some local prominence. Wallace's father, a philosophy professor at the University of Illinois in Urbana-Champaign, and his mother, an English teacher at a community college, ferried him to tournaments throughout the Middle West.
At Amherst College in Massachusetts, however, it was the life of the mind that he pursued, and with a similar vengeance. His major was philosophy. He recalls that during his sophomore year a professor told him he was a genius: "It was the happiest moment in my life. I felt like I would never have to go to the bathroom again -- that I'd transcended it."
Mark Costello, a classmate, says Wallace was pegged by professors there as someone who could become an important philosopher. So when Wallace turned his intellectual energies toward fiction writing, it was a decision fraught with ambivalence and fear. "He was a guy under tremendous internal pressure," Costello says. "I think it was important to him to get a little external confirmation that he hadn't made an absurd choice."
His senior thesis at Amherst became the first rough chunk of "The Broom of the System," his 467-page Pynchonesque debut novel; shortly after he graduated and went on to what he derisively calls a "master of flatulent arts" program in creative writing at the University of Arizona, he had a contract with Viking Penguin, which published "Broom" in 1987. That same year he won a prestigious $25,000 Whiting Writers' Award. Two years later Norton published "Girl With Curious Hair," a collection of short fiction.


text: More from SI Report: Dodgers release pitcher Freddy Garcia Report: Dodgers release pitcher Freddy Garcia Marshawn Lynch sports gold cleats for Super Bowl Marshawn Lynch sports gold cleats for Super Bowl Louisville vs. FIU: Game time, live stream, TV coverage Louisville vs. FIU: Game time, live stream, TV coverage Pittsburgh-area high school football player dies after... Pittsburgh-area high school football player dies after... Close Tweet0 Share0 Comment0 Share0 Share0 Stumble It0 Print0 More SI Wire Report: Appeal for Seahawks cornerback Richard Sherman to be held Friday by Scooby Axson Email Posted: Tue Dec. 18, 2012 Seahawks cornerback Richard Sherman will have his appeal heard on Friday. (Otto Greule Jr/Getty Images)The appeal for Seattle Seahawks cornerback Richard Sherman's four-game suspension for using performance-enhancing drugs will be held Friday, reports ESPN.com.Sherman is appealing a positive test for a banned substance that violated the league's policy on performance-enhancing drugs and resulted in the four-game suspension, which he appealed allowing him to continue to play.Sherman has maintained that he did nothing wrong saying that he drank from a bottle a teammate had that contained a crushed Adderall pill. Sherman has 56 tackles, six interceptions and three forced fumbles this season."It's gonna get solved and I think at the end of the day it'll get worked out fine," Sherman said last week to Yahoo! Sports. The Seahawks (9-5) play the San Francisco 49ers (10-3-1) on Sunday night in a big NFC West showdown. Promoted Stories Comments


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Who do you support for Governor in Ohio in 2010?
Posted in the Cleveland Forum
16,741 - 16,760 of 35,567 Comments Last updated Sep 6, 2015
#18387 Apr 7, 2013
I tell young people this all the time: The day that child is born, start a college fund at the bank for him or her. If for some reason they don't want to go to college, then they can use that money for a down payment on a house or something.
#18388 Apr 7, 2013
Don't care this one is over with for now.
#18389 Apr 7, 2013
Teachers & counselors 7 most principals appreciated my involvement with my sons & the fact that I was a single custodial parent/dad.
I got understanding, cooperation & good information in return. It does work.
1 son is a fine mechanic, 1 has been in the Navy for nearly 10 yrs now & 1 is going to college working towards a Phd.
It wasn't easy being out numbered by 3 rambunctious boys, there was no one to to teach me or classes to go to. I was a work in progress myself...still am really.
#18400 Apr 10, 2013
#18402 Apr 10, 2013
teachers are nasty...they put on their college work ware clothes and the females are wearing their crankie hankies and they cry about how your mom cut your hair
#18403 Apr 10, 2013
since the days of walking out of a 2 desk school with open enrollment .....VOUCHERS are a parent best friend
#18407 Apr 10, 2013
Just curious...how could anyone legitimately 'judge' this post as incendiary or racy as was just done? Just curious
#18409 Apr 11, 2013
Strange how a working man like yourself can be so gung-ho about taking away unions and worker's rights, yet not a peep about CEOs running companies into the ground while giving themselves fat bonuses. Just like with your disbelief in global warming, your keepers have trained you well. Now jump through the hoop for the millionaires, little tea bagger.
Hey neat. Just read an article where over a million people a year die from air pollution in China. It's because they are not really regulated. You know, like what Bush did. Wonder if lung related illness is on the rise here in the US?
#18410 Apr 11, 2013
Yes, I know, liberals are on this constant strive to make us all immortal. Nobody should die of anything, and if they do, then government must do something about it.
I'm surprised you don't like GW. After all, under him, they lowered sulfur in diesel fuel which made it much more expensive. So now when your household goods and food cost a little more, thank GW. Next time you go to the grocery store, see if you can buy a 100 watt incandescent light bulb. You can't? And why not? That's right, it was under GW that those bulbs were made illegal to sell today, and in the coming years, all wattage of incandescent bulbs will no longer be for sale in this country.
There is nothing strange about my stance on unions. I can't tell you how many customers we lost because of them. Unions would hold their ground for pay increases or benefits, and the companies had no choice but to move down south or out of the country entirely just to get away from them. The less manufacturing in this area, the less work for me. The more of our customers that close shop, the less work for me. Why would I have any good opinion about unions?
Of course, that's not the only reason I hate unions. After all, I pay property tax and a lot of it. Over half of the money I pay in property taxes goes to the schools. Several years ago, they built all new schools because Strickland made us an offer our city Democrats couldn't refuse: we come up with half of the money for all new schools and the state will put us in more debt by matching our half.
We built the new schools and my property tax had the largest increase since I've lived here. One of the reasons it was so expensive is because the unions sued our city because they wanted to hire the lowest bidders to build our schools. According to state law, if we use state money, we have to use union companies and labor or pay prevailing wage. That cost us a bundle, and I'm paying for it.
#18412 Apr 11, 2013
"...the companies had no choice but to move down south..."
Wonder how much the owner of that company was making when he "had no choice"? The bottom line is when one looks at the pay increase over the last 20 years of the common working man, compared to what the CEOs give themselves, it is abundantly clear that their greed is the reason these companies do anything. We have flatlined while buddies of yours like GW opened the gates on the middleclass in favor of corporations. Also, GW was the one who deregulated the energy industry causing massive damage to the gulf coast due to BPs lax regulations.
You seem like a trained seal to me, barking back whatever bossman tells you to. Thinking what they have taught you to think. Believing the crap they slapped onto the side of a conservative Christian message which you folks gulped down hook, line and sinker. You keep believing that you are on the side of the poor little corporate CEOs. You keep singing the woes of their lavish lifestyles while chumps like yourself smile when tossed a plate of sh!t and preach to hard working taxpayers like myself that we should feel lucky to have it.
#18413 Apr 11, 2013
CEO's are paid just like your entertainment friends. This is because they do a job very few of us can do. Also, CEO's (like actors and actresses) are paid on contract. Their contract pay is based on past performances. They have a reputation for turning companies around from great losses or producing more profit of successful companies. And if you don't want to pay them the millions they ask for, no problem, your competition will, and then that very same CEO will put your business under.
But like quarter backs who can't throw for a year or so, a star pitcher that has a terrible ERA the next year, or even the famous actor that acted in a flop movie, these people still get the money they were contracted for. CEO's no different.
You can't blame CEO's for the money you make either. It's the American consumer that's responsible. We won't support a floor sweeper making $22.00 per hour. We will sooner buy our products from Chinese or Indian companies. Every company would like to pay their employees more, but when they pay them more, they have to charge more for their product. When unions force them to pay employes more than their worth, the company faces more competition from overseas companies, and then has to relocate to stay alive. It's either that or join their former employees in the unemployment line.
You liberals don't understand business. You don't want to. Liberals only think of themselves and nobody else. They can never put the shoe on the other foot.
#18414 Apr 11, 2013
I need some xxx rated movies. Please give me your email if you want to sell, give or trade.
#18415 Apr 12, 2013
Every company would like to pay their employee more !!!
what planet are you on ?
It's the selfish greedy companies that have contributed to this financial mess we are in and to be honest known of the above candidates are fit to wipe my azz let alone be in charge of the the great state of Ohio. they are like all politicans money and power they don't give a monkeys about the man on the street. they are all crooks who are only interested in fame and feathering their own nest.
#18416 Apr 12, 2013
Me!! Lol
#18417 Apr 12, 2013
You are a company b1tch and I have no respect for you as a man.
#18418 Apr 12, 2013
Yes, yes, repeat what the bossman told you. What about companies that worked for years until some "superstar" CEO bought it out and ran it into the ground? Oh, and I'm sure the companies moved their jobs to China because they didn't want to pay a floor sweeper $22 and hour...yah, right. I'm sure it's not because they don't want to be regulated or pay a decent wage. That couldn't possibly be it...right? What color is the sky on your planet? Ours is blue.
You are a fool. A blind, meek little company fetch boy. Get your nose out of bossman's @ss once and awhile and perhaps you'd see what a sniveling tool you are.
#18419 Apr 12, 2013
Kasich is a liar. He helped Bill Clinton pass NAFTA and expand GATT. Those two acts are what killed our economy the past 15 years. Ohio was a large manufacturing state and we have lost most of it. People complain about CEO of companies. If the CEO is looking out for the best interest of his/her company they will take operations overseas. There are lower wages fewer regs, and lower corporate taxes just to name a few. I am against foreign crap. After Bill Clinton pushed NAFTA through with people like Kasich's help, we have un-safe Mexican trucks on our highways with drivers working for as little as $4 per hour. China and Japan bring their crap in here with little or no tariff on finished goods yet finished American manufactured products face up to 65% tariff going into Japan and China.
#18420 Apr 12, 2013
You class envy union goons crack me up. Having been a member of a couple of unions in my lifetime, I can speak from experience that in todays world, they are more useless then tits on a boar hog and Ive often believed that their greed has destroyed American Manufacturing.
It was Ross Perot who warned you union idiots about NAFTA but being the good little democrat puppets you are, you let Clinton begin the exporting of U.S. manufacturing jobs and it continues today.
Whine and moan about CEO's and republicans all you want. You only have your greedy union leaders to blame.
#18421 Apr 12, 2013
Sorry, I have no real "bossman" because I work for a small company with less than 15 employees. My employer could care less about what I think of CEO's or major corporations.
You are correct, businesses don't want to be regulated and yes, they do move when those regulations get too cumbersome. That's why DumBama created hundreds of new regulations on businesses and we are experiencing the result of that which is hovering around 8% unemployment for over four years.
No American business wants to move out of the US. They have to--and not for profit either. You haven't talked to any of these business people but I have. I spoke with owners and supervisors during their debate of whether to move down south or our of the country. Between taxes, regulations, workman's compensation insurance and yes, unions, it's impossible to produce sellable products.
It's the straw that broke the camels back in most cases. And let me tell you something Mr. Global Warming, you have plenty of straws on that camels back yourself, but you would never look in the mirror and partially blame yourself. Instead, blame some CEO whom you never met and who's job you don't understand.
#18425 Apr 12, 2013
To most of the last 5 posters (except Canton who wouldn't agree that the sun is bright & night is dark); Most 'greedy CEO's" answer to board members & stock holders. Who are some of those stock holders? Obama, Bush, Buffet, Soros, You & me if you have a 401K or a Roth or whatever. You & I don't vote directly but the Fund Management Companies vote for the collective clients whose funds that they do manage.
The financial problems have to be spread around. Unions helped greatly to ruin GM, Chrysler, Hostess & others.
Then do not forget AIG, Enron, numerous banks & too many others to remember that made financial screw ups & thefts rippled around the world & back.
Then there's the politicians around the world that promised too much & the citizens that expected too much.
Yep, ther's plenty of sources of blame.
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1001 E. 101st Terrace Suite 325
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The teacher population of 22 teachers has stayed relatively flat over five years.
|Total Enrollment
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|Diversity ScoreThe chance that two students selected at random would be members of a different ethnic group. Scored from 0 to 1, a diversity score closer to 1 indicates a more diverse student body.
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text:
|29. Apr. 1997
|6. Juni 1995
|12. Mai 1993
|Auch veröffentlicht unter
|Nirmala Ramanujam, Anita Mahadevan, Rebecca R. Richards-Kortum, Michele F. Mitchell, Sharon Thomsen
|Ursprünglich Bevollmächtigter
|Board Of Regents, The University Of Texas System
|Zitat exportieren
|BiBTeX, EndNote, RefMan
|Patentzitate (3), Referenziert von (57), Klassifizierungen (18), Juristische Ereignisse (7)
|Externe Links: USPTO, USPTO-Zuordnung, Espacenet
This is a continuation of application Ser. No. 08/060,432, filed May 12, 1993 now U.S. Pat. No. 5,421,339.
The invention relates to methods and apparatus to differentiate between histologically normal and histologically abnormal tissues, and to differentiate neoplastic tissue from histologically abnormal non-neoplastic tissue.
Screening for Cervical Intraepithelial Neoplasia (CIN)
Although there has been a significant decline in the incidence and mortality of invasive cervical carcinoma over the last 50 years, there has been an increase in both the reported and actual incidence of CIN. As a result, it has been estimated that the mortality of cervical carcinoma may rise by 20% in the years 2000-2004 unless screening techniques for CIN are improved.
Present screening for CIN and cervical cancer is relatively inexpensive but labor intensive because it initially relies on the results of a Pap smear; a false negative error rate of 20-30% is associated with insufficient cell sampling and/or inexpert reading of Pap smears. , Given an abnormal Pap smear, colposcopic examination of the cervix (with a magnifying lens) followed by colposcopically directed biopsy and histologic examination of the tissue sample can provide a diagnosis of CIN. Histologic confirmation of the diagnosis, while relatively time-consuming and expensive, is necessary because the accuracy of classification among abnormal tissues by colposcopy alone is limited, even in experienced hands.
Improving the predictive value of colposcopy in distinguishing CIN from other abnormal tissues (e.g., tissue infected with human papilloma virus (HPV) or inflammatory tissue) could reduce the required number of biopsies and thereby increase the speed and efficiency of the screening process. Diagnosis and treatment might be combined in a single office visit, with colposcopically directed treatments including loop electrosurgical procedures (LEEP), cryo and laser therapies, and chemopreventive agents. Further, explication of improved methods to classify tissue as normal or abnormal, while not leading directly to a diagnosis of CIN, would reduce costs by allowing performance of colposcopy by medical technicians less skilled than trained colposcopists (usually physicians).
Spectroscopic Methods in Colposcopy
Spectroscopic methods for differentiating cervical neoplasia from normal cervical tissue in vivo have been described. The methods rely generally on observations that the fluorescence of abnormal tissue is significantly weaker than that of normal tissue at several excitation wavelengths, e.g., 330, 350 and 450 nm. This property has been used for spectroscopic identification of histologically abnormal tissue. For example, in vitro fluorescence intensity comparisons at an excitation wavelength of 330 nm yielded positive predictive value, sensitivity and specificity of 86%, 88% and 75% respectively on colposcopically normal and abnormal biopsies from the same patient. Differences between neoplastic (CIN) and non-neoplastic abnormal tissues (intimation and HPV infection) yielded the largest spectroscopic differences at an excitation wavelength of 330 nm.
Additionally, fluorescence spectra have been measured in vivo to detect neoplastic tissues in different organ systems. A variety of methods for making such determinations have been proposed. For example, ratios of autofluorescence intensity at two different emission wavelengths have been used by many groups, and scores based on multi-variate linear or non-linear regressions and fits to extract concentrations of various chromophores have been proposed by many others for inclusion in decision criteria.
In one application, 337 nm wavelength excitation was applied to colonic tissue. Multi-variate linear regression analysis was used to correctly distinguish adenomatous polyps from normal colon and hyperplastic polyps with positive predictive value, sensitivity and specificity of 86%, 86% and 80% respectively.
Tissue Classification Methods
Previous attempts to reliably distinguish CIN from intimation or HPV infection in vivo using colposcopy alone have been unsuccessful. Fluorescence intensity may be useful in this regard, but is not sufficient in itself because analogous fluorescence intensity measurements of the same tissue type may vary by more than a factor of two from patient to patient, and by about 15% within the same patient. Methods relating fluorescence intensities from abnormal and normal tissues of the same patient, however, tend to be more predictable and therefore more diagnostically useful.
Thus, in general, each patient must serve as her own control. Considering cervical tissues in a given patient excited with 337 nm wavelength electromagnetic excitation, tissues with HPV infection are less fluorescent with than tissues with chronic inflammation, and tissues with dysplastic changes exhibit even lower fluorescence than those with HPV infection. The lowest level of fluorescence (relative to analogous fluorescence measurements on other tissue types in the same patient) is exhibited by tissues with the most abnormal form of CIN. Analogous relationships among tissue fluorescence intensity measurements in a patient may exist if excitation wavelengths other than 337 nm are used because the shape and intensity of cervical tissue spectra do not change substantially when the excitation wavelength is increased or decreased by less than 10 nm.
Additional information useful for tissue classification may be found in the peak emission wavelength of tissues with CIN, which is positively correlated with the peak. emission wavelengths of normal tissue spectra from the same patient. This relationship, however, is not observed for tissue samples with inflammation or HPV infection.
Thus, a reliable method to spectroscopically classify tissue as normal or abnormal, and in the latter case to distinguish inflammation or HPV infection from CIN, is needed. Such a method could rely on one or more of the relationships described above, augmented with additional information indicative of the particular separation or classification desired.
The present invention includes in vivo spectroscopic methods and apparatus for differentiating normal tissue from abnormal tissue and for diagnosing CIN in diagnostic cervical tissue samples. Diagnostic cervical tissue samples are the tissue samples to be evaluated by the non-invasive methods of the present invention. The methods include analysis of tissue fluorescence intensity spectra or portions thereof from both histologically normal tissue and histologically abnormal tissue in a patient desiring diagnosis.
Reference in this application to histologically normal cervical tissue samples in a patient subject to the diagnostic methods of the present invention refers to tissue which is presumptively histologically normal. Normal tissue samples in such subjects are selected in vivo and tested non-invasively as described herein to ensure a substantial likelihood that they actually represent tissue which, if histologically evaluated, would be classified normal.
In certain preferred embodiments, the spectra are represented on two-dimensional plots with fluorescence intensity being represented on the vertical axis and wavelength on the horizontal axis. For calculations involving slope measurements at predetermined wavelengths within spectra having different (unnormalized) peak values, each spectrum is normalized to. its own maximum intensity value. For calculations involving the ratio of the peak intensity of a spectrum from unknown tissue (i.e., from a diagnostic cervical tissue sample) to the peak intensity of a spectrum from (presumptively) normal tissue in the same patient, normalization is not performed.
Detecting Tissue Abnormality
According to the present invention, an in vivo method of detecting tissue abnormality in a diagnostic cervical tissue sample in a patient having known normal cervical tissue comprises illuminating the diagnostic tissue sample and normal cervical tissue with electromagnetic radiation (preferably about 337 nm wavelength). A plurality of normal fluorescence intensity spectra are detected from the known normal cervical tissue, the spectra being obtained serially or simultaneously, preferably through fiber optics which may be placed at a fixed distance from the cervical tissue. In some embodiments, spectra may be detected through analysis of a cervical image which includes the tissue areas to be sampled.
A peak normal fluorescence intensity value is measured in each said normal fluorescence intensity spectrum, and an average peak normal fluorescence intensity calculated from said peak normal fluorescence intensity values. A fluorescence intensity spectrum is also detected from the diagnostic tissue sample, and a peak fluorescence intensity value measured from said fluorescence intensity spectrum.
A predetermined portion of the fluorescence intensity spectrum (preferably in the region corresponding to wavelengths between about 410 nm and about 430 nm) from the diagnostic tissue sample furnishes slope information for calculation of a slope parameter which is indicative of tissue abnormality. The predetermined portion is empirically identified in prior clinical trials as facilitating accurate classification of tissue, and the slope parameter is preferably a function of average slope in the predetermined portion. Each spectrum is preferably normalized to its own maximum value prior to calculation of the slope parameter.
Relative peak fluorescence intensity (preferably relative to average peak normal fluorescence intensity) is calculated as a function of said peak fluorescence intensity value, and tissue abnormality is detected as a function of the calculated slope parameter and relative peak fluorescence intensity. The latter function is preferably a predetermined empirical discriminant function obtained from prior clinical trials. The discriminant function may be either linear or nonlinear.
Detecting CIN
According to the present invention, an in vivo method of detecting CIN in a diagnostic cervical tissue sample in a patient having known normal cervical tissue comprises classifying the diagnostic cervical tissue sample as abnormal by a method described herein, followed by illumination of the diagnostic tissue sample and known normal cervical tissue with electromagnetic radiation, preferably of about 337 nm wavelength.
A first fluorescence intensity spectrum from the diagnostic tissue sample is detected, as is a second fluorescence intensity spectrum from the known normal cervical tissue. A first slope parameter which is indicative of CIN in the diagnostic cervical tissue sample is calculated from a predetermined portion of said first fluorescence intensity spectrum (corresponding to wavelengths between about 440 nm and about 460 nm). A second slope parameter which characterizes normal cervical tissue in the patient is calculated from a predetermined portion of said second fluorescence intensity spectrum (corresponding to wavelengths between about 410 nm and about 430 nm). Both first and second slope parameters are preferably calculated after normalization of the respective fluorescence intensity spectra to peak fluorescence intensity values of 1. Additionally, both first and second slope parameters are preferably functions of average slopes in said normalized first and second fluorescence intensity spectra respectively in regions lying substantially between wavelengths corresponding to the respective predetermined portions.
CIN is detected in the diagnostic cervical tissue sample as a function of said first and second slope parameters, the function preferably comprising a predetermined empirical discriminant function which, in some preferred embodiments is linear.
FIG. 1 is a schematic representation of apparatus to classify cervical tissue according to the present invention.
FIG. 2 is a schematic representation of apparatus for multi-pixel spatial-spectral imaging of the cervix.
FIG. 3 is a schematic representation of apparatus to acquire and process spectroscopic images of the cervix.
FIG. 4 represents a population of induced fluorescence intensity spectra representing colposcopically normal and histologically abnormal tissue, with a discriminant function for detecting tissue abnormality.
FIG. 5 represents a population of induced fluorescence intensity spectra representing histologically abnormal tissue (i.e., CIN, inflammation, HPV), with a discriminant function for detecting CIN.
FIGS. 6A-6F illustrate a flow chart to practice preferred embodiments of the methods of the present invention.
CIN--cervical intraepithelial neoplasia
HPV--human papilloma virus
Normal/abnormal tissue classification requires induced fluorescence intensity spectra from tissue areas known to be normal with a sufficiently high probability of accurate classification. Normal and abnormal cervical tissues are primarily identified in vivo by colposcopists In any given patient, it is preferable to collect a plurality of fluorescence intensity spectra from tissue areas identified as normal by a colposcopist. An expected error rate of about 10-20% has been observed, which primarily represents samples which are colposcopically normal but in fact comprise inflammatory tissue. As explained below, provision is made for removal of erroneously-identified normal samples, with the result that those remaining are presumptively normal.
As a patient is examined, peak normal fluorescence intensity values are measured on each spectrum from normal tissue. The intensity values are averaged and a standard deviation of normal peak values calculated. Depending on the degree of confidence required in the screening results and the skill of the operators, a portion of all spectra initially identified as colposcopically normal are discarded (i.e., the spectra are not included in calculation of the average peak normal fluorescence intensity, but may be assigned to the group of spectra to be classified subsequently as normal or abnormal). Criteria for discarding colposcopically normal samples may preferably require discarding all spectra associated with peak values which fall more than one standard deviation below the average peak normal fluorescence intensity.
The peak fluorescence intensity of any test fluorescence spectrum (associated with cervical tissue to be evaluated for normality/abnormality) is divided by the corresponding average normal fluorescence intensity for that patient to yield a relative peak fluorescence intensity for that spectrum. Because normal tissue tends to have relatively high and uniform peak fluorescence intensities in any given patient, the above division will generally result in relative peak fluorescent intensities clustered around a value of approximately 1 for normal tissues. On the other hand, because abnormal tissue (whether characterized as inflammation, HPV infection, or CIN) tends to have lower-than-normal peak fluorescence intensities, the above division will generally result in relative peak fluorescent intensities clustered around a value substantially less than 1 for abnormal tissues. This condition furnishes a partial basis for classifying spectra as representing either normal or abnormal tissue.
A more complete basis for identification of spectra as representing either normal or abnormal tissue is provided by examination of a slope parameter associated with each spectrum, the parameter preferably being derived from slopes measured in the range 400-440 nm, preferably 410-430 nm, and in some preferred embodiments 415-425 nm, as measured on a spectrum normalized to its own peak fluorescence value. The measured slope value is largely governed by two factors, i.e., the peak emission wavelength of fluorophores contributing to the spectrum, and the reabsorption effect of oxy-hemoglobin with an absorption peak at 420 nm. As more hemoglobin contributes, the peak shifts to longer wavelengths and the slope increases. Similarly, as more NADH fluorescence contributes, the peak shifts to longer wavelengths and the slope increases. These effects are observed in diseased tissue, and probably account in part for the capacity of methods of the present invention to differentiate types of diseased tissue on the basis of their induced fluorescence spectra.
The parameter may be an average or tangential slope or other representative value of the range of actual slope values which will in general be found within the specified range (predetermined portion) in any normalized spectrum. Wavelengths defining the extent and location of the predetermined portion of a normalized spectrum which is indicative of tissue abnormality are determined from clinical trials involving fluorescence spectra obtained from tissue with histologically proven diagnoses. That is, the definition of the predetermined portion is empirically derived by comparing slopes over the entire wavelength range to find the portion of that range yielding the best discrimination using the methods described above.
To evaluate a diagnostic cervical tissue sample, a relative peak fluorescence intensity and a slope parameter are calculated as explained above from its induced fluorescence intensity spectrum. The calculated values may then be plotted as a point on the graph of FIG. 4. The line 72 represents a predetermined empirical discriminant function which substantially separates points characterizing colposcopically normal and histologically abnormal tissue. If the point falls below line 72, the tissue sample is diagnosed as normal, whereas if the point falls above line 72, the tissue sample is diagnosed as abnormal. These decision criteria may be implemented mathematically as well as graphically by considering the equation of the line which can be derived from FIG. 4. Note that the position of line 72 (slope and intercept) are subject to change with the addition of more data points from clinical trials to those already present on FIG. 4. Note also, that the position of line 72 may also be expected to change when populations having a substantially different incidence of abnormal cervical tissue from that illustrated in FIG. 4 are considered.
Although normal/abnormal tissue classification on the basis of induced fluorescence spectra is useful for preliminary screening, patients identified as having abnormal cervical tissue must be further evaluated. In particular, CIN should be differentiated from inflammation or HPV infection because of the potential for CIN to progress to invasive cancer.
As an aid to classification, a correlation has been observed between the wavelengths associated with peak intensity in corresponding fluorescence intensity spectra obtained from normal and neoplastic tissue in the same patient. Whereas three sample peak intensity wavelengths of normal spectra in a single patient were observed to be 398, 426 or 442 nm, the corresponding peak intensity wavelengths from CIN spectra in the same patient were observed to be 442, 450 or 460, respectively. Thus, the peak intensity of a fluorescence intensity spectrum tends to occur at longer wavelengths in fluorescence intensity spectra from tissue with CIN, compared to corresponding spectra from normal tissue in the same patient. This wavelength shift is relatively uncommon in abnormal tissues representing HPV infection or inflammation.
A two-dimensional scatter plot was developed to map out the relationship in a population of patients between the peak emission wavelength of the abnormal spectrum and average normal spectra from the same patient. This is shown in FIG. 5, where the abscissa corresponds to the slope of the abnormal spectrum over the wavelength range 440 to 460 nm, and the ordinate represents the average slope of the normal spectra from the same patient over the wavelength range 410-430 nm. All spectra were normalized to a peak intensity of 1 prior to slope calculation. Note that the slope of the spectra from samples with HPV infection or inflammation does not appear to correlate to the average slope of the corresponding normal spectra (linear correlation coefficient=0.072). However, the slope of the spectra from samples with CIN displays a positive correlation (linear correlation coefficient=0.442) to the average slope of the corresponding normal spectra. This enables differentiation of abnormal samples with CIN from those with HPV infection or inflammation. A predetermined empirical discriminant function which allows one to carry out the differentiation for each new patient is represented by the line 82 in FIG. 5, which minimizes the number of misclassified samples.
Thus, CIN tissue spectra are distinguishable from HPV or inflammation tissue spectra on a two-dimensional plot. The horizontal axis of the plot represents the value of a slope parameter obtained from an abnormal spectrum in the wavelength range of about 440 to 460 nm, while the vertical axis represents the value of a slope parameter obtained from a normal spectrum in the same patient in the wavelength range of about 410 to 430 nm.
A predetermined empirical function in two-dimensional space substantially separates points corresponding to CIN tissue fluorescence spectra from points corresponding to HPV or inflammation tissue spectra. In certain preferred embodiments, this function may be linear and acceptably minimize the number of misclassified points. In other preferred embodiments, the function may describe a nonlinear decision surface. Determination of the preferred decision surface for any population depends on the degree to which the population is characterized by clinical data used to estimate the decision surface.
FIG. 1 is a schematic representation of apparatus to classify cervical tissue according to the present invention. To obtain tissue fluorescence spectra, electromagnetic radiation (e.g., light, in certain embodiments) in the form of laser light from nitrogen laser 36 is applied through coupling lens 34 and single fiber optic excitation fiber 32 to probe 38. Also within probe 38 are collection fiber optic fibers 30 and quartz shield 40, the shield 40 acting to keep fibers 30 and 32 properly spaced from any surface to which probe 40 is applied, application to a cervix preferably being under colposcopic observation. Resulting tissue fluorescence is transmitted by fibers 30 through coupling lenses 28 to polychromator 27, and thence to intensified diode array 26. Array 26, controlled by controller 22 through gate pulser 24, detects fluorescence intensity spectra which are relayed through controller 22 to computer 20. Computer 20 is programmed to classify tissue in accordance with methods described herein.
Note that laser light is not necessary for practice of the present invention. Laser 36 may be replaced in some embodiments by an incandescent or other type lamp with an associated filter to produce quasi-monochromatic light. Additionally, fibers 32 and 30 may be replaced in some embodiments with fibers serving both the function of illumination (excitation) and transmission of tissue fluorescence. Intensified diode array 26 and polychromator 27 may be replaced by a subassembly comprising radiation filters and photomultiplier tubes to reduce costs in certain embodiments.
FIG. 2 schematically illustrates apparatus used in certain embodiments of the present invention to simultaneously collect fluorescence spectra from multiple areas of the cervix. A source 50 of electromagnetic radiation (delivered through fiber or non-fiber optics) is used to illuminate the desired areas of the cervix (sample 51), including both some normal and some abnormal areas. A geometric array 53 of fibers 52 collects tissue fluorescence originating from known normal and unknown regions of the cervix, the latter to be diagnosed. The ends of fibers 52 proximate to imaging polychromator 54 are arranged in a linear array 55 at the entrance slit to polychromator 54. Polychromator 54 is coupled to a charge coupled device camera 56. Polychromator 54 disperses wavelength across one axis of the array, and position on the cervix varies across the other dimension. Thus this system provides a spatial-spectral image on computer-display 58 of fluorescence spectroscopic information in the cervix.
The operator identifies one or more fibers which view normal cervix. The fluorescence intensity spectrum from each fiber viewing an unknown area of the cervix is then processed by the methods described herein to determine whether the tissue is histologically abnormal and whether CIN is present. This information can be presented as a spatial image of tissue histologic condition on computer-display 58.
FIG. 3 is a schematic illustration of apparatus for certain embodiments of the present invention. As in FIG. 2, illumination of sample 51 with electromagnetic radiation from source 50 results in fluorescence intensity spectra which are sensed by charge coupled device 56 after passing through variable band pass filter 62 and colposcope imaging optics 60. Computer/display unit 68 accepts spectra from charge coupled device 56 for processing and display.
This system provides a two-dimensional image of variation in fluorescence intensity as a function of position on the cervix at a specific wavelength band governed by the transmission characteristics (optical properties) of imaging optics 60 and filter 62, which can be rapidly changed. Images are acquired at bands centered near 398, 410, 426, 442, 450 and 460 nm sequentially. The maximum intensity IMAX is identified for each pixel. A composite image indicating the peak intensity as a function of position is then formed from these images. Images indicating the slopes of the fluorescence spectra from the tissue in each pixel over the ranges 410-430 nm and 440-460 nm are calculated according to I(426)-I(410) [(426-410)IMAX ] and I(460)-I(442)/[(460-442)IMAX ]. The operator identifies one or more pixels corresponding to normal regions of the cervix. A relative intensity image is constructed by dividing the peak intensity image by the average normal intensity. Thus, for each pixel the relative intensity and slopes at 410-430 nm and 440-460 nm are available. These data are used to classify the state of the tissue in each pixel according to the methods presented herein. This information can be presented on computer-display unit 68 as a spatial image of tissue histologic condition.
Data points in FIG. 4 represent induced fluorescence intensity spectra obtained from cervical tissue in a population of patients, each patient having both colposcopically normal tissue and histologically abnormal tissue. The latter tissue includes CIN, inflammatory tissue, and tissue having HPV infection. Note that fluorescence intensities plotted along the abscissa of FIG. 4 are relative to (divided by) average peak normal fluorescence intensity obtained from the population of spectra considered. Spectra from the two tissue groups are processed in accordance with methods described herein to classify the respective tissues as normal or abnormal. Decision surface 72 (a line in 2-space) is empirically established to minimize overlap of substantially normal 76 and substantially abnormal 74 groups. The equation of surface 72 as determined from FIG. 4 constitutes a predetermined discriminant function useful in detecting tissue abnormality in any diagnostic cervical tissue sample when fluorescence intensity spectra are induced in the tissue sample and processed according to methods described herein.
Data points in FIG. 5 represent induced fluorescence intensity spectra obtained from cervical tissue in a population containing histologically abnormal tissue, the latter tissue including CIN, inflammatory tissue, and tissue having HPV infection. Spectra from the three tissue groups are processed in accordance with methods described herein to classify the respective tissues as characteristic of CIN or not characteristic of CIN. Decision surface 82 (a line in 2-space) is empirically established to minimize overlap of substantially CIN 86 and substantially not-CIN 84 groups. The equation of surface 82 as determined from FIG. 5 constitutes a predetermined discriminant function useful in detecting CIN in any histologically abnormal diagnostic cervical tissue sample when fluorescence intensity spectra are induced in the tissue sample and processed according to methods described herein.
FIGS. 6A-6F illustrate a flow chart to practice preferred embodiments of the methods of the present invention. Note that steps in the flow chart continue from FIG. 6A to FIG. 6B, from FIG. 6B to FIG. 6C, and from FIG. 6C to FIG. 6D. FIGS. 6E and 6F represent subroutines to apply the particular decision rules applicable to either separation of tissue into normal and abnormal classifications (FIG. 6E), or identification of CIN in samples of abnormal tissue (which may include CIN, inflammation or HPV infection) (FIG. 6F). The subroutines (subcharts) illustrated in FIGS. 6E and 6F are called for within the steps illustrated in FIG. 6D. It is assumed in applying the steps called for in FIGS. 6A-6F that sufficient spectra are made available to ensure that normal cervical tissue in the patient is identified and characterized by fluorescence spectra with a sufficiently high likelihood of accurate classification, as indicated in the methods described herein.
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Owner name: IMPERIAL BANK, CALIFORNIA
Free format text: SECURITY INTEREST;ASSIGNOR:LIFESPEX, INC.;REEL/FRAME:008628/0590
Effective date: 19970716
|24. März 1998
|Certificate of correction
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Year of fee payment: 4
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