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Garden Pics From Today
Hello everyone,
Got around the backyard with the camera today...This is Fair Maiden with St Paul...
Avocado on the left, Cathedral Windows on the right.
Chesapeake Bay
Wow, lotsa hosta! Thank you for posting, Don! It's great to put the garden with the name. Fried Bananas and Alligator Shoes are my favorites of the batch. And I do think I need to get Luna Moth...every time I see a pic here on the forum, I like it.
Don, you have a lot of really nice looking plants! My favorites are Prairie Sky and Dress Blues. BTW, I just received my new Dress Blues in the mail yesterday and I ordered that one based on your recommendation in an earlier post. I think I am going to love it!
Wow, Don! These pics are great, so great that I had to look again, and again! I actually remembered some names from your orders last year, lol. Alligator Shoes is looking so fine, your GA you say is leggy, but it is easier to see the detail of each leaf that way! A beautiful Angel of a hosta.
I saw a mama sized Deep Blue Sea today - impressive! Your Unforgettable
is just that...unforgettable! I could say something about each one, but I'm not the only kid on this block! Loved these pics, thanks!
Wow, Don! I've been hoping to get a glimpse of your Prairie Sky this season...what a knockout. I love Deep Blue Sea. I bought it from Green Mountain thanks to YOUR endorsement last season. Same with Fair Maiden...only in my garden due to your enabling. Very pretty, sweet-looking hosta!
Now I'm going back to ogle some more...!
Thanks, everyone...Wow Jadie, Green Mountain gave you a nice piece of Deep Blue Sea! And, once I got a Fair Maiden, I had to show everyone who would look!
Glad I can be of service to gardeners who enjoy being enabled : )
One hand enables the other...Or, something like that!
Don B.
Nice photos Don. Great selection of hostas. Your gardens remind me of mine in 2011. You'll be shaking your head in about three years wondering where you're going to put all those huge hostas! I can't wait for your before and after pictures.
What's the name of the one in the middle of your fragrant hosta bed? The smaller one behind Fried Bananas?
Hi Don,
That's a great shot of Silver Bay. I've never been able to capture that blue on camera. I'm not a good photographer... I just point and shoot on automatic.
My Guardian Angel is sparse in the center too in its third year. I wonder when it'll get fuller??? It was recommended to me instead of Earth Angel. I like it though.
I finally got Deep Blue Sea last year and am liking it. It looked a bit lop-sided in a spin out bag first thing in spring but has improve in habit since then. Yours and Jadie's are nicely proportioned.
Hoosier Dome wears battle scars, honestly come by. No disgrace in that. It keeps on going too.
Love all your pictures, Don. I agree, hosta give a lot of joy.
You do great with the pictures. I picked up my new phone today and go to a Saturday CLASS on how to use it. It has either a 14 or 16 MP camera, hope the color rendition is accurate. I hate cool yellow hosta when I know they are warm toned. Your Cerveza looks spot on to me, and of course it brings out the blue in your Fragrant Blue. If anyone can get a whiff of Fragrant Blue it will be Jo. Neither have I discerned a scent from it.

subset: commoncrawl


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Life on Earth
This brief text weaves environmental and health issues throughout the book and motivates students to find the answers to engaging questions. For one-semester courses in Introductory Biology for non-majors. A briefer version of the highly successful Biology: Life on Earth, 7e, Life on Earth 4e helps instructors and students manage a wealth of scientific information in a meaningful and relevant way. Life on Earth 4e provides briefer, more streamlined coverage of topics and has an abbreviated diversity unit as compared to Biology: Life on Earth, 7e.
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text: Building Estimation Jobs 1 was found based on your criteria Post a job. It's free! Proposed improvements Fixed-Price – Est. Budget: $80.00 Posted March 25 2015 Dear Having considered the nature of the building you will be in a position to discuss if it is a success overall when compared to its requirements. Further, you will display, through graphics and text, alternative detail design to counter the factors discussed in parts 1 and 2.This will involve option appraisal of alternative materials, methods and possibly some comment on spatial use. As with part 2, scale drawings details, written information and product research will be expected to ... architectural-design building-estimation civil-engineering construction creative-writing engineering-drawing information-architecture methods-engineering structural-engineering technical-writing


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Syfy Cancels 'Being Human'
UPDATED: The NBCUniversal-owned cabler is ending the show after its fourth season.
Syfy is canceling Being Human after its fourth season.
The NBCUniversal-owned cable network made the official announcement Tuesday, midway through the show's current 13-episode run.
"Showrunner Anna Fricke and the talented producers, writers, cast and crew have done an amazing job bringing this show to life over the past four seasons and we sincerely thank them and the series' production company Muse Entertainment for their hard work," Syfy said in a statement announcing the cancellation. "They've saved the best for last with the final six episodes that revisit the story's beginning, leading to a not-to-be-missed send-off for Aidan, Sally, Josh and Nora."
PHOTOS: 2014's New Broadcast and Cable TV Shows
Syfy promises that the final episodes will be "full of twists, turns and surprises that will culminate in a spectacular series finale" set to air April 7.
Being Human, a North American adaptation of the popular U.K. supernatural drama of the same name (which ended in 2013) centering on a werewolf, vampire and ghost who live together, debuted in January 2011 to nearly 2 million viewers.
The current season picked up four months after the events of the season-three finale. Never a ratings hit, Being Human hovered around 1 million viewers for its most recent run of episodes.
Executive producers are Fricke, Michael Prupas, Stefan Pleszczynski, Rob Pursey and Toby Whithouse. Irene Litinsky is producer.
The news of Being Human's cancellation comes at an interesting time for Syfy, which has gone through an executive reorganization. On Monday, Syfy reality chief Tim Krubsack departed the company, while Syfy Films senior vp Gregory Noveck and director of development Joshua Banta exited in November. Bill McGoldrick also replaced Mark Stern as exec vp original content for Syfy.
At the moment, the remaining scripted originals on Syfy's docket are Ron Moore's Helix, Haven (with a supersized fifth season), Bitten, Defiance, the final season of Warehouse 13 and the upcoming Dominion, as well as Canadian dramas Lost Girl and Continuum.
The stars of Being Human, Sam Huntington, Sam Witwer, Meaghan Rath and Kristen Hager, issued a thank-you to the fans via a two-minute video. Watch below.
Being Human airs its final episodes starting March 3 at 9 p.m.
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more slideshows
Studio-to-Street Style: The Best Tops To Hit the Gym and BeyondHit the gym and beyond in these versatile, must-have pieces.
10 Easter Nails You Can Wear to Work on MondayNo bunnies here!
10 Foods to Calm InflammationFrom edamame to tomato sauce, these foods will do your
Get the Perfect Haircolor
Do it at the salon Blonde hair shows the true tones of a hair dye—which are often green- or yellow-based—so a single dose of at-home color can leave hair looking fake. Have a professional layer colors until you achieve the ideal darker tone, then make follow-up trips at least every four weeks. Make your shade last Prevent color fade by using a UV-protectant mist. "Blonde hair is especially likely to bleach out in the sun, but using UV-blocking products prolongs the life of your color," Vo says.
KEYWORDS: Hair Care,Hair color


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07/09/10 By Sheila O'Malley
Mark Lair to perform at the 2010 Jade's Jazz Festival!
Local Les Schwab Tire Center sponsors Auto Mechanic at Fest
Les Schwab Tire of La Pine sponsors Mark Lair, an extraordinary jazz singer/saxophonist from Iowa at the 2010 Jade's Jazz Festival! Mark owns an auto body and mechanic shop in northwest Iowa and we are pleased to present him at this year's festival.
World class lineup of Jazz musicians and vocalists from around the country descend upon scenic La Pine, Oregon for this August 6-8 Festival. Jade's Jazz Festival August 6, 7, & 8th, is a benefit for La Pine Community Kitchen and La Pine Park & Recreation District. The event features live artists from around the country, as well as local musicians. Nestled against the Cascade Mountains, La Pine will be hosting Jazz greats such as David Patrone, from San Diego, California (www.davidpatrone.com), Detour:Jazz, from Bend, Oregon (www.detourjazz.com), Louis Landon, from New York (www.louislandon.com), Lino, now from Bend, Oregon (www.linomusic.com), Bella Via from Central Oregon, Mark Lair II, from Iowa, Bobby Gibson, now from Redmond, Oregon (www.bobbygibson.com), Hot Club du Jour, from the Oregon coast, Slick Side Down, from Portland/Bend (www.myspace.com/slicksidedown), JazzBros! from Bend, Oregon (www.bouheymusic.com), Nina Wachter, from Louisiana, and rachaelsong, from Terrebonne, Oregon (www.myspace.com/rachaelsongmusic). Recently back from London, performer/storyteller Guy J. Jackson will be Master of Ceremonies and will be featured throughout the festival. The event also features an appearance by "Kelly, the Crooning Mixologist". Kelly Edwards is a producer and director, and currently has a hit play "Lamppost Reunion" at McMenamins in Bend. For more information about festival dates and times, go to www.jadesjazz.net.
Community Authors
Sheila O'Malley
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RED PIANO RECORDS To Release The Debut Recording From: Pianists/Composers FRANK CARLBERG & LEO GENOVESE SHADOWS and REFLECTIONS
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Kama Ruby: Rock Dreams in Jazz. Words From a Mentor.
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Motema Music Proudly Announces The Release of JOE LOCKE'S Most Personal & Emotive Work To Date, LOVE IS A PENDULUM
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The Top 10 In Action Sports
01Welcome to Qasr Al-Farid: The Rock With A Door That Will Rock Your World
0218 Things That Will Give Anyone Who Did Duke Of Edinburgh A Serious Flashback
0316 Things That Will Give 90s Skater Kids A Serious Flashback
04This 10 Year Old Kid Just Nailed A Dub Cork 1080... On His Second Attempt
05The 10 Most Spectacular Road Trips on Earth
06Water Slides, Plane Wings and Danny MacAskill: This is Road Cycling Like Never Before...
0724 Reasons Why Snowboarding Was Better In The Early Noughties
08Could Scientists Be About to Build a Terminator? They're Closer Than You Think…
09Win a Holiday for 2 in Chamonix with Three #holidayspam
1017 Holiday Beer Photos That Every Skier Takes to Make Their Friends Jealous
Chromag: All Mountain All Time
A Mountain Biking video by Chromag - 1,079 views
Cortland riding his Stylus... Everywhere Cortland Thibodeau rides out of Port Albernie B.C. Mountainous terrain combined with the lush coastal climate mean chunky trails...most of which you have to get to on your own power. Throw in a set of mid-trail or back-yard dirt jumps and this is just the terrain the Stylus was designed around.
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Omixon is a global biotechnology company that commercializes disruptive innovations specializing in targeted applications for Next Generation Sequencing (NGS). The Omixon Holotype HLA™ product combines a targeted HLA Assay and the Omixon HLA Twin™ software to deliver the most accurate high-resolution HLA genotyping available. Omixon maintains an active grant-funded research program and assists scientists and clinicians to analyze the most challenging genomic regions including HLA, KIR and ABO.
Omixon Blog
Join Us at EFI for Free NGS Workshops on Holotype HLA™
Contact us for more informations about our workshops Novele Allele Discovery with HLA Twin genotyping software, featuring the Traffic Light System (TLS) for efficient throughput With 99.8% accuracy in genotyping NGS data, the Omixon Holotype HLA combined assay and software …more0 comments
Next-Generation Sequencing Based HLA Typing of Saliva and Blood Samples from the Same Donors Produces Concordant Typing Results
Authors: Szilveszter Juhos, György Horváth, Attila Bérces, Curt Lind, Deborah Ferriola, Anh Huynh, Larissa Slavich, Dimitri Monos, Mike Tayeb, Rafal Iwasiow Aim: We are presenting the results of next-generation sequencing (NGS) based HLA typing, using blood and saliva sources from …more0 comments


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translated/localized stringfiles containing messages from Sails core and dependencies
Localized stringfile containing messages used in Sails command-line interface and runtime. This is one part of the effort towards making Sails more accessible to non-native English readers/speakers.
How This Module Works
These files are here for future use-- this project is an early-stage work in progress.
- Environment variables are used to determine a user's locale. (defaults to English)
// From Sails core, an adapter, a generator, a hook, or some other dependency: var STRINGFILE = require'sails-stringfile'; // Internally, this module runs node's native `util.format()` method, // so you can also template strings: var localizedMessage = STRINGFILE'cli.new.success' 'myApp' some:'stuff' 'more stuff' // Then, appropriate msg is brought in auf deutsch, espanol, traditional chinese, english, etc. console.loglocalizedMessage;
Current language support targets are:
- English
- French
- Spanish
- Traditional Chinese
- German
(please send a PR if you have a request and we'll add it to this list!)
How Can I Help?
The existing strings need to be pulled out of log messages and errors in:
- sails core
- anchor core
- waterline core
- sails-generate-*
- sails-hook-*
- sails-adapter-* (adapters)
Code comments and other support files (like README) in newly generated sails modules (or a new project) should be pulled out into the generator scope and brought in using the same mechanism. This is only relevant for generators:
- sails-generate-new
- sails-generate-frontend
- sails-generate-backend
- sails-generate-views
- sails-generate-gruntfile
- sails-generate-controller
- sails-generate-model
- sails-generate-generator
A stringfile needs to be created in the
localesin this repository for each language we want to support, mapping the string keys to a reasonable log message in the target language (the English stringfile is a good reference to see how a particular type of message should be worded, etc.).
MIT c. Mike McNeil 2014


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Glitterman Moves Up Big; Cee's Tizzy Still First
For the second consecutive week, the 10 top stallions held down the fort, although there were several minor switches in the ranks.
For the second consecutive week, the 10 top stallions held down the fort, although there were several minor switches in the ranks.
A high buy-back rate and only one break-out horse were the key points Monday during the first session of the two-day Fasig-Tipton Texas 2-year-olds in training sale at Lone Star Park.
A plan by Republicans in the New York Senate would pump an additional $7 million into the state's Thoroughbred breeding fund.
First-year stallions Fusaichi Pegasus and High Yield will join Coolmore's North America-Australia shuttle contingent this summer, as will Spinning World. Coolmore announced those additions to its Southern Hemisphere roster at Rosehill Gardens racetrack on Saturday, the same day as the running of the Coolmore Classic (Aust-I).
Gin Talking, Maryland Horse of the Year and champion 3-year-old filly of 2000, has been retired from racing because of ankle problems and is booked to Dixieland Band.
The Blood-Horse, Inc., is introducing a new sales supplement that offers more detailed information in an easy to read format.
Slady Castle, who was New Jersey's Stallion of the Year 11 consecutive years, was euthanized March 21 because of kidney failure.
Steve Haskin, the award-winning turf writer and senior correspondent for The Blood-Horse, analyzes the top pedigrees for this year's Kentucky Derby candidates. During his 29 years with the Daily Racing Form, Haskin became known for his insightful coverage of the Triple Crown races. Haskin won the Red Smith Award for Kentucky Derby writing in 1997, 1999, and 2000 and received the David Woods Award for best Preakness story in 1997.
Millionaire Seeking the Pearl, the first Japanese-trained runner to win a race in Europe, produced her first foal, a Storm Cat colt, on March 1 for Richard Santulli and George Prussian's Jayeff B Stables.
Eugene Melnyk announced the retirement of his stakes winner Queen's Park from racing.
Never Knock, dam of champion Pleasant Tap and classic winner Go for Gin, died three days after delivering an A.P. Indy filly on March 2 at William du Pont III's Pillar Stud near Lexington.
The 11 top stallions from last week's 2001 leading sires list continue to hold down the fort. Cee's Tizzy, with $1,324,440, and Maria's Mon, with $1,160,703, remain one-two, and Allen's Prospect continues to hold down the ninth spot. The other seven just switched positions.
Grade I winner Capote Belle produced her first foal, a Storm Cat filly, March 17 for owners Robert and Lawana Low at Mr. and Mrs. Craig Bandoroff's Denali Stud near Paris, Ky.
Robert and Janice McNair's Stonerside Stable privately purchased champion Ajina from the Allen Paulson Living Trust.
Ocala, Fl. - Victoria Racing Stable's Saint Damien and Bea Oxenberg & Olga Melin's Miss Annie Bea head their respective divisions of the $100,000 OBS Championship Stakes at the Day of Champions race card set for Monday, March 19 at the Ocala Breeders' Sales Company's racetrack. Post time for the first race is 1:30 p.m.
Australian quarantine officials reacted quickly to the confirmed case of Foot and Mouth disease in France by expanding its horse ban to the whole European Union. Australia's Quarantine and Inspection Service (AQIS) stated the import ban would also apply to any other country in which foot- and-mouth disease is endemic, or in which there is an outbreak. This means Argentina was an immediate and automatic inclusion to those 'temporarily suspended'.
Answer Lively, the 1998 Breeders' Cup Juvenile (gr. I) winner and that year's Eclipse Award-winning 2-year-old male, is experiencing fertility problems in his first year at Hill 'n' Dale Farms near Lexington. Dr. George D. Mundy, the farm's general manager and resident veterinarian, said on Friday only one of the first 12 mares bred to Answer Lively has been pronounced in foal.
Although three of the top broodmare offerings failed to sell, the Equine Spectrum online auction Thursday resulted in five fillies or mares selling for $1.4 million. Half of the 14 stallion nominations in the catalog were sold for an additional $300,000.
Grade I winner Dixie Union, who entered stud this year at Gerald Ford's Diamond A Farms near Versailles, Ky., as the property of a syndicate managed by William S. Farish's Lane's End Farm, has been relocated to Lane's End near Versailles.
Grade II winner Altibr Dead
Shadwell Stable's grade II winner Altibr was euthanized March 13 because of complications from laminitis.
Weekend Surprise, dam of classic winners Summer Squall and A.P. Indy, died after foaling a Belong to Me filly Tuesday. The foaling was without incident, but that evening Weekend Surprise hemorrhaged and died. The filly has been placed on a nurse mare and is doing fine.
John Messara Wednesday called for the Australian Quarantine and Inspection Service (AQIS) to reconsider its total ban on the importation of horses from Britain and Ireland into Australia. The Arrowfield Stud CEO called the ban for 'an indefinite period' an 'over-reaction'.
The outbreak in Europe of foot and mouth disease and subsequent ban until further notice by Australian authorities of all imported horses from the United Kingdom isn't the only potential setback for the shuttle stallion business. On Tuesday, the value of the Australian dollar slipped to an all-time low versus American currency when it hit $.5028.
Six-year-old Innuendo, winner of the March 10 Orchid Handicap (gr. IIT) at Gulfstream Park, has been retired from racing and is booked to Seeking the Gold.
Leading sire Cee's Tizzy has company in the millionaire club by 2001 progeny earnings. Maria's Mon, whose son Monarchos earned $600,000 in winning the March 10 Florida Derby (gr. I) at Gulfstream Park, increased his yearly earnings to $1,060,461 and in the process zoomed from 39th to second on the sire's list. Champion 2-year-old male in 1995, Maria's Mon (Wavering Monarch -- Carlotta Maria, by Caro) stands at Josephine Abercrombie's Pin Oak Stud near Versailles, Ky.
Not that it wasn't already very serious, but the implications foot and mouth disease could have on the Thoroughbred industry became scary business Wednesday when the Australian government placed an indefinite ban on the importation of horses to that country from the European Union.
Appalling livestock losses in England caused by the foot-and-mouth (FMD) outbreaks are unlikely to affect the general movement of shuttle stallions from Britain. The situation could change, however, if the measures taken by English authorities fail to control the disease over the next six to eight weeks.
A lawsuit involving a Seattle Slew season sold to Skara Glen Stable by Script R Farm Partnership has been settled out of court.
In what came as no surprise, North America's Horse of the Year also is California's Horse of the Year.
Ashford Stud first-year stallion High Yield (Storm Cat -- Scoop the Gold, by Forty Niner) now has 13 mares in foal, according to a statement from the farm.
De La Rose, a champion turf filly and grade I stakes producer, was euthanized Tuesday, March 6, at Henryk de Kwiatkowski's Calumet Farm near Lexington because of the infirmities of old age. The 23-year-old mare had dropped weight and been weakened by the harsh winter, according to the farm.
First-year stallion Greenwood Lake has 10 of the first dozen mares he bred scanned in foal.
European champions Giant's Causeway and Montjeu have made fine starts as first-year stallions at Coolmore Stud in Ireland.
The Maryland Horse Breeders Association named Gin Talking the 2000 Maryland-bred Horse of the Year and champion 3-year-old filly. The daughter of Allen's Prospect finished the season with three consecutive stakes victories, including her second triumph in a Maryland Million event at Laurel.
Champion Anees and Belmont Stakes (gr. I) winner Commendable have made successful starts as stallions at Dr. and Mrs. John C. Chandler's Mill Ridge Farm near Lexington.
The breeding shed report on Seattle Slew continues to be "amazing," according to Three Chimneys Farm owner Robert N. Clay on Wednesday.
The Florida Thoroughbred Breeders' and Owners' Association announced its 2000 champions.
Seth Hancock, Alan Porter, John Veitch, and Ric Waldman are constantly asked for their opinions on Thoroughbreds and breeding. On March 6 they shared those opinions with the Kentucky Thoroughbred Farm Managers' Club in Lexington. About 280 members and their guests listened to the visitors and panel moderator Ed Bowen.
The first race for 2-year-olds was contested at Sunland Park March 4, and a colt by Devon Lane named Devon's Prospect took advantage of six others to win a maiden special weight event by 7 3/4 lengths.
Grade I stakes-placed Wondertross has been retired from racing, but owners George Steinbrenner and William Condren have not yet decided where to stand the 5-year-old son of Chief's Crown.
Fasig-Tipton will not conduct a sale of 2-year-olds in training this spring in Kentucky. The company decided to call off its early May auction at the Churchill Downs Sports Spectrum in Louisville, Ky., because "it never achieved the level of success that we had hoped for," said Boyd Browning, Fasig-Tipton's general manager and executive vice president.
The Grayson-Jockey Club Research Foundation has allocated more than $1 million for 12 projects this year. Much of the research involves two-year projects that will be funded along with five carryover initiatives from 2000.
Fusaichi Pegasus, last year's Kentucky Derby (gr. I) winner, has 13 mares in foal, according to Ashford Stud near Versailles, Ky., where he stands at stud.
Pensioned broodmare Quarrel, whose first five foals were either stakes winners or stakes-placed, succumbed March 6 to the effects of old age.
This time of year all it takes is a big win by a stallion's runner(s) to move him up considerably on the leading sire list. Take for example California stallion Cee's Tizzy, whose son Tiznow earned $600,000 in winning the March 3 Santa Anita Handicap (gr. I). Cee's Tizzy advanced from ninth to first, and now has 2001 progeny earnings of $1,234,158.
President Bush on Monday nominated Lane's End Farm owner William S. Farish to be ambassador to Britain. White House spokesman Ari Fleischer announced the nomination during his daily press briefing. Farish, 62, is chairman of the board of Churchill Downs and is a Bush family friend. The nomination, which had been rumored for weeks, is subject to Senate confirmation. Farish played host to former president George Bush at last year's Kentucky Derby and to candidate Bush during the presidential election.
British and Irish breeders are hoping mares that can't be shipped to stallions because of restrictions imposed by the foot-and-mouth outbreak will be able to do so later in the breeding season. Movement of horses in Great Britain, outside the immediate exclusion zones around the 70 confirmed British outbreaks of foot and mouth, is not controlled. Dispensation, with proper precautions, is possible even within such zones.
Another historic Marion-County, Fla. Farm has been added to the list of training facilities on the marketplace. A portion of Hooper Farms in Ocala was bought by a group of Ocala-based real estate agents. Greg and Carla Lord and Gary and Catherine Achtenhagen, who work for Glen Miller Realty, purchased 181-acres of the storied operation in January.


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Hi, my name is Max and I really enjoy travelling and continuing to explore the world with my wife. We love experiencing new places and tend to enjoy the food and cocktails of the world as much as the sights.
Our daughter Norah was born 14/7/14 and we are looking forward to taking her on many travels with us in the future.
I work in graphics for TV broadcast and my wife Louise is a primary school teacher; we live together in our little Victorian house just outside of London.


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Winnipeg Free Press - PRINT EDITION
Hanging out at the comments section
A story titled The sad state of Portage Place had readers happy to contribute their two-cents' worth.
Send a Letter to the Editor
The Free Press welcomes letters from readers
To send a letter for consideration on our Letters page: Fill out our online form at the link above, or Email firstname.lastname@example.com, or Fax (204) 697-7412, or Mail Letters to the Editor, 1355 Mountain Avenue, Winnipeg, Manitoba, R2X 3B6.
I remember when this mall was built to save downtown. I also remember the late '80s was the beginning of the rumbling that the Jets needed a new arena.
No one at the time had the foresight to put the money and land toward a new arena project. No new arena ultimately cost the city the Jets 1.0. The buzz around the MTS Centre seems to indicate that a downtown arena does much more for the area than a mall ever would. To me this is a failure of vision of the city leadership at the time.
Just spend one lunch at the food court and you'll know why people stay away from Portage Place.
-- LuckyBucky
Yes, I worked for 13 years in Portage Place. Every time we stepped into that food court we would hum the tune from the canteen scene in Star Wars.
-- fortboy
It's very creepy to stand and wait for a bus outside Portage Place or even when you have to "cut through" in order to get to our church it can get very sketchy. Within two minutes of coming in the front doors you are accosted by persons looking for money or trying to sell you something -- and it's not clothing.
-- musical one
Humbug, I work downtown and I go every weekday at noon to Portage Place to buy lunch. I also use transit to commute from home to work and back and take the bus at Portage Place.
Nobody bugs me, nobody hassles me, nobody asks for anything.
-- Ygdrassil
I still remember when there was a huge Club Monaco, a large Holt Renfew, and other high end retailers on the second floor. Now it's either an empty storefront, dollar stores, some sort of half-arsed put-together store (like the shoe repair or junk book store) or an office of some type.
I walk through there on my lunch almost every day and think that it should be so much more considering the heavy amount of foot traffic, but then upon closer look it only appears that one third of the traffic might actually have a job and disposable income. The other two-thirds are just hanging around killing time.
-- kmc
Portage Place can be saved. However, it means the left wing liberals have to put on blindfolds for a bit. The police will have to step on civil rights a little bit. Stop loitering. Period. Make it difficult for "non-shoppers" to hang around. Create a no pan handling area. No exceptions. Arrest people for public drunkenness every day. Park a van out back, and fill it up over, and over again for 60 days, and people will learn, and behaviours will change. If the city really wants to fix the problem it can. Just don't get caught up in the "working poor," "racism" garbage the plagues any discussion on solutions.
-- NewVoiceofReason
Portage Place is the perfect location for a downtown supermarket. I'd like to see the Lucky Supermarket open up there, along with an area of market stalls to support startup businesses.
-- goldenbob
Used to go there but very little now. No reason except to park to go to a movie or MTS Centre. If the drug dealers and thugs are there... keep the place open for them so that these rats don't head to other parts of town. At least we know they are all together. A major crackdown will have them scrambling to other places.
-- brandonboy
Polo Park underwent a major renovation about a year before Portage Place was constructed. Cadillac Fairview was behind both projects, and plans appeared very similar at the time. Both were touted as major retail centres. Polo Park survived, and with some modifications to the original plans, seems to have thrived. Portage Place became dubious within a couple of years of opening. A lot of businesses and buildings were destroyed to create the sparkling new Portage Place. But it quickly returned to slum status.
-- Gordon Arnold
I was in high school when Portage Place opened-I loved going there- great stores, great restaurants to eat at. I started working downtown a few years ago and have only been there once- it was just so sad, how it's changed. There was nothing. I feel bad for the retailers.
-- zen
Maybe....we could trade it for some land on Kenaston???
-- Pegger7
Republished from the Winnipeg Free Press print edition January 13, 2013 A10
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Download Negative Attitude from our fatest mirrorA Negative Attitude Affects Every Aspect Of Your Life
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10th Grade 2 Negativity's Negative Affect On Relationships When you have a negative attitude it does not just affect
Date added: August 1, 2013 - Views: 2
Managing Negative Attitudes EMDA 2010 Steven Graham, Danielle Rogacki, ... Once you have assessed the negative attitude and behavior to determine that it's not you as
Date added: March 11, 2013 - Views: 11
How to Keep a Positive Attitude at Work Identify your negative thoughts. egative thoughts cause negative feelings. ay attention to
Date added: May 13, 2013 - Views: 7
Lesson 5: Negative attitudes Activity 3 (10mins): Challenging stereotypes (Slides 22-23) Now that students have an appreciation of how it feels to be stereotyped, they
Date added: July 1, 2014 - Views: 1
WRAP-UP: ATTITUDE A BAD ATTITUDE MAY COME FROM YOUR ENVIRONMENT. • Social factors like poverty, parents, hard classes, and negative friends can wear
Date added: October 25, 2011 - Views: 86
Therefore, if we have negative attitudes, these negative attitudes affect what ... negative attitude limits performance, saps motivation, and inhibits learning.
Date added: September 9, 2012 - Views: 3
Dealing with Negative Attitudes in the Workplace Employee Training Seminar by SkillPath Seminars On-Site at FSU Wednesday, November 13, 2013 • 9AM – 4PM • LUC ...
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negative attitude and whether it predicted discrimination (see Chapter 6 for a discussion specifically relating to prejudiced attitudes and discriminatory behavior ...
Date added: May 24, 2013 - Views: 4
TMME Monograph3, 159 studies aiming to change attitude actually end up in setting the objective of transforming a 'negative' attitude into a 'positive' one.
Date added: August 12, 2011 - Views: 29
Literature Review on Attitudes towards Disability 3 Executive Summary Improving attitudes to people with disabilities is a key priority of the National Disability
Date added: January 9, 2012 - Views: 9
Negative Attitudes in Small Business By Rori Chandler-Bailey Small businesses are faced with many dilemmas that must be dealt with on an ongoing basis.
Date added: January 27, 2013 - Views: 10
Mastering Soft Skills for Workplace Success 35 Enthusiasm and Attitude Having a positive attitude in the workplace can help with potential promotions.
Date added: April 6, 2012 - Views: 48
Building Positive Attitudes in the Workplace 2011 Constant Training 2 Attitude The What, Why, and How How do you define attitude? Are attitudes contagious?
Date added: December 23, 2011 - Views: 54
language attitude among female students is 2.7599 and standard deviation is 0.54763 while they are 2 ... Regarding the observed negative attitude towards English, ...
Date added: October 26, 2012 - Views: 5
Research of nursing students revealed that negative attitudes and ... nurse with a negative attitude, I try to manipulate the student patient care assignment in
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Positive Vs. Negative, Facilitator Note, Scenario Sheets and Worksheet Be creative when thinking about helping young carers to see that most negative
Date added: November 13, 2012 - Views: 14
Five Attitudes of Effective ... Discussion on the Five Effective Teacher Attitudes First Attitude: ... candidates there was also a negative response to ...
Date added: October 6, 2011 - Views: 55
Attitude As you take your journey towards Black Belt Excellence, you will learn the importance of having the right attitude, what the right attitude is, and how you
Date added: June 29, 2014 - Views: 1
Psych 301, 9/19/3 Attitudes and Behavior How do attitudes guide behavior? Experience and learning Attitude: Evaluation of objects and ideas to indicate like or dislike
Date added: February 18, 2012 - Views: 3
Character Education "Positive Attitude" Grades 5-8 DEFINITION: A positive attitude is the ability to have positive thoughts about one's self and one's environment ...
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Can We Reduce Students' Negative Attitude Towards Math? 58 Nowadays, it is not possible trying to resist to the new technology use on the knowledge transfer,
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Images, Anxieties and Attitudes toward Mathematics ... negative attitude, and low self esteem and positive attitude is obvious as they represent opposite
Date added: October 26, 2013 - Views: 1
worksheet. Explain how to change a negative attitude to a positive attitude. Explain that they will work on their focus attitudes for one week. 6.
Date added: December 26, 2011 - Views: 39
58% had negative attitude about nursing education practical exam.57% suggested some changes in criteria of examination. References: 1.
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Understand the three components of attitude. 3. Understand how attitudes can be changed. 4. ... the impact of negative attitudes on workers, management, and pa-
Date added: October 22, 2011 - Views: 30
Work Environment and Job Attitude among Employees in a Nigerian Work Organization ... negative attitude to work while the workers view of
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A negative attitude is often compared to the flu, because it is highly contagious and because it can get much worse if left untreated. A bad attitude, being
Date added: October 16, 2011 - Views: 18
1 Cover letter On the negative attitude towards left-handedness of pupils. Malkhaz Makashvili, Tamar Taliashvili. Ilia Chavchavadze University, Tbilisi, Republic Georgia.
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Employee Attitudes and Job Satisfaction • 397 Even though organizations cannot directly impact employee personality, the use of sound selection
Date added: October 22, 2012 - Views: 269
Exchanging a Negative Attitude for Worshipful Gratitude The goal of this challenge is to begin to remove negative thought processes, patterns, actions,
Date added: April 11, 2013 - Views: 19
If you have been exhibiting a negative attitude and expecting failure and difficulties, it is now the time to change the way you think. It is time to get rid of
Date added: July 4, 2012 - Views: 4
Your attitude, whether positive or negative, also affects the job search process. Many employers say attitude is more important than experience or education.
Date added: June 23, 2013 - Views: 20
Attitudes 5 Introduction Do general education teachers have a negative attitude towards students with special needs and the idea of inclusion?
Date added: March 4, 2014 - Views: 1
Negative? Personal Self-Improvement: Positive Attitude by Marlene Shiple, Ph.D. 2 of 4 Checklist for a Positive Attitude Check any of the following ...
Date added: March 13, 2014 - Views: 4
attitude towards environmental issues towards discipline in both government and ... environmental attitude, positive attitude, negative attitude, secondary ...
Date added: January 24, 2013 - Views: 8
A Poor Attitude: A Deterrent to Reading Improvement L. D. Briggs Abstract Today's teachers are confronted with children who display a poor attitude toward school in
Date added: January 17, 2014 - Views: 1
"Rising Professional" - Work Ethics: Attitude Work Ethics – Attitudes (Revised 10/20/07) 4 of 5 Have students look back at their negative aspects list.
Date added: February 18, 2012 - Views: 35
High School Students' Attitude towards Learning English Language ... Both negative and positive attitudes have a strong impact on the success of language learning.
Date added: September 25, 2013 - Views: 2
Is Attitude Toward Masturbation Related to Sexual Arousal? Laura Hansen ... These studies indicate that negative attitudes toward masturbation have theoretical
Date added: February 17, 2014 - Views: 1
negative attitude. We make those kinds of choices every day. How can we adjust our attitudes? How can we learn to be more positive? One way is to give "positive
Date added: July 3, 2013 - Views: 2
Factors related to observed attitude change toward ... negative attitude shifts share essentially similar views of instructor behaviour. They speak
Date added: January 16, 2012 - Views: 13
In studying attitude towards mathematics, many instruments have been developed based on various definitions of attitude and have generally moved from being ...
Date added: August 14, 2013 - Views: 7
362 Attitudes, Attributions and Social Cognition above may reveal negative attitudes towards immigrants in their behaviour, their self-reports may appear more ...
Date added: February 17, 2012 - Views: 23
Changing Negative Attitudes Towards Persons with ... line assessments of attitudes, attitude change was measured immediately following the intervention
Date added: December 15, 2011 - Views: 13
Attitude theorists postulate that attitudes are formed early in life and that, ... Research has shown that old people themselves have negative attitudes toward .
Date added: March 22, 2013 - Views: 4
Negative attitude towards pressure ulcer prevention resulted to a ... Experienced using the Braden scale Working in Intensive Care Units or Medical Wards.
Date added: March 2, 2014 - Views: 1
negative attitude; maximum score 150 = very positive attitude; score of 90 = neutral attitude). The ATP – 30 has been used and validated with medical, pharmacy
Date added: January 24, 2013 - Views: 10
Mahanta 159 Many studies have reported that there are gender differences in attitude towards mathematics and girls have more negative attitudes than that of boys.
Date added: September 1, 2013 - Views: 1
found to produce a strong negative attitude to past condom use and to current intentions to use condoms among students in tertiary institutions (Edom and Harvey, 1995).
Date added: August 2, 2013 - Views: 1


text:
Lives in Portugal
Joined on Nov 4, 2005
I think I'll change my hobby to fishing....
jkjond: Excellent winner this year. It is encouraging to see this competition is maturing above the predictable winners of yesteryear.
you're kidding, right?
What a lottery competitions are. It depends whether judges awake to their left or right side or they just flip a coin? I feel so demotivated to enter in competitions because I can't understand what is going on their heads, honestly...
Why not at local zoo? What's the point?
LJohnK2: - No mask function
- No blemish removal
- No CCP
- No generic clarity slider
- No, No, No,
Hey Nikon com'on up here to Canada.... we have Community College Programs that have 2nd year Co-op students that can produce better than this.
What the hell is Nikon thinking !!!....seriously Nikon just open source your ADL algorithm so real programs like Lightroom can include it and be done with this.
Nik was bought years ago and CaptureNX was updated since, so why this sudden, idiot move??
LJohnK2: - No mask function
- No blemish removal
- No CCP
- No generic clarity slider
- No, No, No,
Hey Nikon com'on up here to Canada.... we have Community College Programs that have 2nd year Co-op students that can produce better than this.
What the hell is Nikon thinking !!!....seriously Nikon just open source your ADL algorithm so real programs like Lightroom can include it and be done with this.
Capture NX2:
- Mask function... check
- Blemish removal... check
- CCP... ? I know CCCP (former Soviet Union)
- Clarity Slider... check (with nik plugin)
- Yes, yes, yes... but those idiots at Nikon killed the software
While Canon enhances their RAW converter software, Nikon replaces CaptureNX with this short featured piece of crap. Did they bother to listen to their clients when this came as a Beta? I have some ideas where you can shove this, Nikon...
nycgazelle: Jesus Christ People! I can't believe all the stupid complainers about this. 9.99 is two cups of coffee a month. Life is expensive...THIS most certainly isn't. I like it because for the first time in years..I did buy photoshop at full pop once...I can have current versions and not pirate it. I feel great about giving Adobe 10 bucks a month because its an amount I don't even think about when it auto deducts. This prevents everyone who couldn't plop down X amount of dollars at once for the software to pay a modest fee and feel good about themselves and enjoy a tremendously awesome product.
I don't drink coffee...
flashkube: I just want to say that once you break away from Adobe products you will love it. I suffered for years learning their stuff with disorganized training videos all over the web. Adobe staff are certainly not friendly, either, if you manage to contact them through their convoluted and awful website.
If you have a Mac get Pixelmator for only $25. Much better to use AND the training videos are well organized on their website. After using it for a month I deleted Adobe Photoshop and good riddance, too.
For Windows or Mac try OnOne Software.com Creative Photo Suite. This gem makes me smile and dance when I edit photos. Photoshop always made me grind my teeth and curse under my breath nonstop.
That's because PS is becoming more and more a tool for just artists or bad photographers
Meanwhile, Nikon replaces Capture NX with a (not free) great piece of crap. Nice one Nikon!
How about a do-all-the-work-for-you feature? I could have a good night sleep while PS does it all for me.
Don Kiyoti: Too many DPReview people with their noses glued to their screens, staring at pixels, or fretting about what the other brand is doing, or worrying if their new camera might have "shutter shock" or some other trivial defect. When confronted with actual photography, they know not what to do and respond with fear and derision!
May be... But I still don't see "actual" photography here. Well, my son has done similar "works" when he was 4. I'll probably post them at next year competition.
Saffron_Blaze: Better stuff finds its way at the bottom of Flickr's Explore everyday. Much better.
so is a series of my pregnant cat having a crap with all that she is eating...
Really, I don't care. They are garbage. They don't tell me squat. I only see a group of amateur ugly pictures. I feel sorry for anyone with great skills being surpassed by "this"
Jeff Seltzer: It's really so unbelievable how many people don't get it. These images are not winners because they are beautiful, technically perfect photos. They are images from a series. The first image, for example, Sara Naomi Lewkowicz, is a well regarded photojournalist that as documenting domestic violence. Just look at many Pulitzer winning images - would you necessarily want them hanging on your wall because they are beautiful? If you want technically perfect images of sunsets, etc., then look elsewhere. The second image from Ludovic Maillard - he's a well regarded professional with a long CV including dozens of exhibitions. His images are not meant to be decor. Those criticizing these images as "ordinary" should AT LEAST do a little homework and research. Really, embarrassing for you.
Really, I don't care. They are garbage. They don't tell me squat. I only see a group of amateur ugly pictures. I feel sorry for anyone with great skills being surpassed by "this"
Lea5: Played around with some files of my D4 and D800E. It's not bad and the RAWs look very good. That's all I need, cause I do the rest in Photoshop. Never used the U-Points anyway.
Never used?? You really don't know what you've missed.
What a joke. I advise you all to leave a "nice" feedback to Nikon like I did. I'm considering to move to Canon just for spite.
madeinlisboa: Please, bring back last year judges. Very poor selection. I'm not even talking about the 12 finalists. Some of these are good, others technically poor or very common. I've seen the final selection and many were extremely Photoshopped and others very "contemporary". 2014 is a year to forget in the Sony Awards.
Before bashing my comment, I really liked last year finalists. This year they are way worse. I've seen much better in other photos from the competition. Anyone can win. It's not a matter of better or worse photo but the personal taste of the jury. Entering a photo competition is like playing the roulette.
Probably i'm a bit retro. Well contemporary "art" like an exhibition of anus portraits or bushed vaginas, or a series of a guy defecting in several positions is what makes me love contemporary...
To clarify some doubts, it works perfectly with older cameras. My files from a D700 look the same.
Brian OReilly: Pardon?
"Only Supports D7000 and later DSLR"
This is a really underhand way of saying that
According to the timeline on this page:
That means it does not support:
All D2 variants
This is really poor
So - to process Nikon NEF files with Nikon Capture NX2 I will need to keep 2 different versions of the SW on a machine
Same applies with Nikon Camera Control Pro2
But, I do not believe you can have 2 different versions of the SW on the same machine - so you need to have 2 different startup disks.
So much for using Nikon products and the longevity of the NEF format moving into the future
Do we need to keep legacy hardware and operating systems and Nikon SW so we can access our images?
Sorry for the rant - but this is really disappointing
Working perfectly with an "old" D700...


text:
The present invention relates to a new spongy material consisting essentially of hyaluronic acid or its derivatives. The characteristics of the new pharmaceutical preparations consist in assuring high concentrations of active principle for a long period of time, by exploiting the characteristics of slow release of the active principle.
The new pharmaceutical preparations can be utilized advantageously in all the numerous situations of microsurgical practice (in particular the ones relating to ear or in odontostomatology), in which it is necessary to use a substance that can be metabolized by the organism and is capable of making easier flap take, reepithelialization of mucous membranes, stabilization of grafts and filling of cavities.
The specific use of the new pharmaceutical preparations is particularly important and useful in the various ear pathologies and in the practice of otologic, otoneurosurgical and odontostomatological microsurgery, such as for instance repair of tympanic perforations.
1. A sterile slow release spongy material in a dose for a single topical application consisting essentially of a lyophilized non-crosslinked hyaluronic acid ester, said spongy material having an apparent volume ranging between 0.04 and 27 ml, an apparent density ranging between 0.00037 and 0.25 g/ml, an actual volume ranging between 0.01 and 2.5 ml, and an actual density ranging between 0.004 to 10 g/ml.
2. The sterile spongy material in a dose for a single topical application, according to claim 1, wherein said ester of hyaluronic acid is hyaluronic acid ethyl ester.
3. The spongy material, according to claim 1, in the shape of a microporous disk.
4. The spongy material, according to claim 3, wherein said microporous disk has a height of between 0.2 and 2 cm and has a diameter ranging between 0.5 and 4 cm.
5. The spongy material, according to claim 1, having a residual humidity ranging between 0.01 and 10%.
6. A method for treating wounds, which comprises applying to said wounds a sterile spongy material in a dose for a single topical application consisting essentially of lyophilized non-crosslinked hyaluronic acid or a derivative thereof.
7. A method of repairing tympanic wounds, which comprises applying to said tympanic wounds a sterile spongy material in a dose for a single topical application consisting essentially of non-crosslinked hyaluronic acid or a derivative thereof.
8. The method according to claims 6 or 7, wherein said derivative of hyaluronic acid is an ester of hyaluronic acid.
9. The method according to claim 8, wherein said ester is hyaluronic acid ethyl ester.
10. The method according to claims 6 or 7, said sterile spongy material in a dose for a single topical application having an apparent volume ranging between 0.04 and 27 ml, an apparent density ranging between 0.00037 and 0.25 g/ml, an actual volume ranging between 0.01 and 2.5 ml, and an actual density ranging between 0.004 and 10 g/ml.
11. The method according to claims 6 or 7, wherein said sterile spongy material in a dose for a single topical application is in the shape of a microporous disk.
12. The method according to claim 11, wherein said microporous disk has a height of between 0.2 and 2 cm and has a diameter ranging between 0.5 and 4 cm.
13. The method according to claims 6 or 7, said sterile spongy material in a dose for a single topical application having a residual humidity ranging between 0.01 and 10%.
The present invention relates to a new spongy material consisting essentially of hyaluronic acid or its derivatives. For better evidence and simplicity the abbreviation lyophilized HA will be used in the following text to indicate the spongy material consisting of hyaluronic acid or its derivatives, whereas the abbreviation IAL solution will be used to indicate the 1% solution of hyaluronic acid sodium salt.
Hyaluronic acid
Hyaluronic acid is a natural heteropolysaccharide consisting of alternate residues of D-glucuronic acid and N-acetyl-D-glucosamine. It is a linear polymer having a molecular weight ranging between 50.000 and 13 millions, depending on the source it is obtained from, on the method of preparation and methods of determination; in the natural state it is present in the pericellular gels, in the basic substance of the connective tissues of the vertebrate organisms (of which it is one of the main components), in articular synovial liquid, in vitreous humour, in the tissue of human umbelical cord and in cock's combs.
Specific fractions of hyaluronic acid are known, having a definite molecular weight and which do not present any inflammatory activity and therefore can be used to make the cicatrization easier or to replace the endobulbar liquids or for the therapy of pathologies in the joints by means of interarticular injections, as disclosed in European patent n. 0138572 granted to the Applicant on Jul. 25, 1990.
Esters of hyaluronic acid, in which all the carboxylic groups of the acid or part of them are esteriliad, as well as the use of said esters in the pharmaceutical, cosmetic field and in the field of the biodegradable plastic materials, are also known, as disclosed in U.S. Pat Nos. 4,851,521 and 4,965,535 granted to the Applicant respectively on Jul. 25, 1989 and on Oct. 23, 1990.
It is known that hyaluronic acid plays an essential part in the processes of tissue repairs, mostly in the early steps of the process of granulation tissue formation, by stabilizing the clot matrix and by controlling its degradation, by promoting the call of inflammatory cells such as polymorphonucleates and monocytes, of mesenchymal cells, such as fibroblasts and endothelial cells and by orienting the subsequent migration of the ephitelial cells.
It is known that the administration of solutions of hyaluronic acid can accelerate the recovery of patients having bed-sores, wounds and scalds.
The role of hyaluronic acid in the several steps forming the process of tissue repair was disclosed, by construction of a theoretical model, by Weigel P. H. et al.: A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing" J. Theor. Biol., 119:219,1986.
Hyaluronic acid and its otologic application
Experimental research works are known on rats subjected to myringotomies (Stenfors L. E. et al.: Exogenous hyaluronic acid accelerates the healing of experimental myringotomies, Auris Nasus Larinx, 12 (suppl.1): 214,1985), which showed that the local application of solutions of hyaluronic acid at the border level of the tympanic perforation, produces a quicker and more complete healing of the lesion, showing the effectiveness of hyaluronic acid in repairing tympanic lesions.
Other studies showed that the application in middle ear of solutions of hyaluronic acid mixed with an absorbable gelatin sponge, reduces the formation of cicatricial adhesions, contrary to what was noted, only when absorbable gelatin sponges were used (Laurent C. et al.: Hyaluronic acid reduces connective tissue formation in middle ears filled with absorbable gelatin sponge: an experimental study. Am. J. Otolaryingol., 7: 181, 1986).
In these last years many experimental and clinical studies were carried out, in order to evaluate the effectiveness and tolerance of sodium hyaluronate solution (registered as pharmaceutical speciality in the assignee's name) in the treatment of tympanic perforations. In particular in a recent study on an experimemntal model concerning lesion of rat tympanic membrane, assignee's researchers, in co-operation with other researchers, carried out a morphological evaluation or tympanic membrane repair after application or IAL solution, in comparison with a spontaneous repair.
The results obtained in this study show that, tympanic membrane repair occurs on account or a true granulation tissue and that the administration of IAL solution produces in the animals an increase in the percentage of repaired tympanic membranes and a more regular development of the physiological repair steps (Govoni et al.: "An experimental approach to the biology of the healing process of tympanic membrane perforation: comparative morphological evaluation of spontaneous versus hyaluronic acid-modulated repair" 3rd Meeting on side effects of anti-inflammatory analgesic drugs and 13th European Workshop on inflammation. Verona, May 8-11, 1991).
In an experimental study on rats, a morphological and electrophysiological evaluation was carried out, in order to evaluate the potential ototoxicity of an IAL solution in comparison with methylcellulose, after direct administration of both compounds into rat middle ear. In accordance with the literature, the transitory auditire loss of transmissive type, which occurs after injection of IAL solution or methycellulose in rat middle ear was confirmed. The morphological analysis of middle ear shows a transitory call of inflammatory cells in both treatment groups and a diffuse degeneration of the epithelial cells only in the group treated with methylcellulose (Martini A. et al.: Hyaluronic acid as treatment of tympanic membrane perforation. A study of potential ototoxicity of hyaluronic acid in comparison with methylcellulose. Meeting lst-4th Sep. 1991 in York, Collegium oto-rhino-laryngologicum Amicitiae Sacrum).
Up today only pharmaceutical compositions have been described, containing hyaluronic acid and its esterified derivatives in the form of solutions, creams or capsules for the subcutaneous implantation.
A spongy material, consisting of hyaluronic acid or its derivatives, was never described.
The main problem, which, up today, was not solved, is that in all the numerous situations of microsurgical practice, in which the use is necessary of a substance which can be metabolized by the organism and is capable of making easier flap take, reepithelialization of mucous membranes, stabilization of grafts or filling of cavities (in particular in tympanic repairs), the administration of hyaluronic acid solutions needs an inert carrier, for instance little sponges of methylcellulose or gelatin or a conveyance in the form of cream.
The presence of a carrier such as methylcellulose can contribute to the development of local phlogistic reactions and of cicatricial and/or adhesional outcomes; moreover should methylcellulose be released by the carrier in the soluble form, by penetrating into middle ear, it could, as shown in the above-mentioned study, cause a temporary loss of hearing and a degeneration of the epythelial cells of middle ear.
The direct employment of hyaluronic acid solutions, besides causing the humidification of the area to be treated, and therefore its steeping, does not allow the controlled release of the active principle, which therefore has too short stay-times on the lesion and must be administered repeatedly.
Now we have found that, the new spongy material consisting of hyaluronic acid or its derivatives, according to the present invention, allows to avoid all the above-mentioned drawbacks. The pharmaceutical preparations, according to the present invention, can be used advantageously and represent a remarkable progress in the microsurgery field, in particular the microsurgery of middle ear and tympanic repair, and present many advantages in comparison with the pharmaceutical preparations and materials which have been used up today, besides in comparison with the use of hyaluronic acid solutions.
In fact, the spongy preparations of lyophilized HA, according to the present invention, allow to reduce the number of applications to be carried out and to avoid the self-dressing by the patient, by simplifying the application of said preparation and reducing the risk that the patient could produce, during the application, new traumas in the tympanic membrane or that he does not respect the optimum of the application conditions in asepsis.
Moreover they allow to avoid the humidification of the external auditory duct and of the eardrum, by reducing remarkably the possible phlogistic reactions, in particular of middle ear and of external ear and avoid the steeping, in particular of the skin covering the external auditory duct.
A further advantage of such preparation, according to the present invention, consists in allowing to avoid the use of some substances such as methylcellulose, which are supposed to be biologically inert, but can give rise to the formation of local phlogistic reactions and of cicatricial and/or adhesional outcomes, which are often caused by these substances, such as for instance gelatine sponges.
The pharmaceutical preparations, according to the present invention, consisting essentially of esters of hyaluronic acid, present the further advantage of releasing the active principle slowly and therefore of requiring only one administration, with evident huge advantages for patients, chiefly children, for the physician and for the health services.
For these reasons they are particularly useful in all the situations, in which it is necessary to protract the stay times of the pharmaceutical preparations in the tissues, in order to allow the anatomical structures to consolidate their own organization and their own connections with the adjacent structures.
The spongy material, consisting essentially of hyaluronic acid or its derivatives, which forms the object of the present invention, from a macroscopic point of view, appears as a higly microporous spongy little disk, being preferably between 0.2 and 2 cm high, having a diameter ranging preferably between 0.5 and 4 cm, having a residual humidity content ranging between 0.01% and 10%, being very hydrophilic and easily manageable, which spongy material, after having been compressed, can assume the shape of a discold , which is still sufficiently elastic so that it can be applied easily and brought into contact with the lesion to be treated.
The preparation of the finished product in the form of a spongy material is carried out by a lyophilisation process, starting from dilute solutions of active principle.
In order to show the characteristics of the spongy material, according to the present invention, as well as its pharmaceutical effectiveness, we will report two studies carried out by us in comparison with IAL solution.
A--Clinical effectiveness and local and general tolerance of the topical application of lyophilized HA, in comparison with 1% IAL solution, in subjects having a tympanic perforation.
The study, as described hereinafter, evaluates the effectiveness of lyophilized IAL, in comparison with 1% IAL solution (whose active principles are disclosed in European Patent EP n. 0138572, granted in the name of the Applicant on Jul. 27, 1990), in making the process of tympanic repair easier.
The following parameters have been considered as the main evaluation parameters:
1) number of complete tympanic repairs;
2) repair time.
FIG. 1 is a scanning election photograph of a spongy material obtained from HA, wherein the white bar represents 1 mm.
FIG. 2 is a scanning election photograph of a spongy material obtained from HYAFF, wherein the white bar represents 1 mm.
Experimental procedure
The study is multicentric, open, controlled lyophilized HA vs IAL solution, with random assignment of the patients to one of the two treatment groups.
Within the limits of such study 56 patients were engaged (24 men and 37 females, whose age ranged between 13 and 75 years; 30 of them were random assigned to the treatment group with lyophilized HA and 26 to the treatment group with IAL solution. Patients of both sexes were admitted to the study; they were more than 12 years old and had a monolateral consolidate tympanic perforation of traumatic or inflammatory etiology, present for a period of time equal to two months or over, and having a lesion size which was not above 40% of pars tense. From the study, patients were excluded presenting one or more of the following exclusion criteria: a) paramarginal tympanic lesions having a size above 2 mm2; b) pathologies in progress concerning middle and/or external ear (or serious pathologies in progress which could interfere with the repair process); c) use of cicatrizing drugs different from the drugs which had been foreseen for the study or drugs which could interfere with the process of tissue repair (for instance cortisone); outcomes of previous myringo-tympanoplastic surgical operations.
The patients were assigned, according to the random list, to one of two treatment groups (either to the group treated with lyophilized HA or to the group treated with IAL solution).
Case enumeration
The main characteristics of the patients under examination, subdivided in the two tratment groups, are summarized in Tables 1-7.
TABLE 1______________________________________Demographic characteristics HA lyophilized IAL solution______________________________________Patients 30 26sex:men 14 10females 16 16Age (years)X � S.D. 35,0 � 16,1 38,8 � 18,8range 15 to 62 13 to 75______________________________________
TABLE 2______________________________________Stay time of the tympanic wound HA lyophilized IAL solution______________________________________2 < months ≦ 6 6 46 < months ≦ 12 3 3months > 12 20 19______________________________________
TABLE 3______________________________________Starting size of the wound HA lyophilized IAL solution______________________________________mm2 (X � S.D.) 8.84 � 8.5 9.0 � 6.3______________________________________ (φgreater � φ smaller)
TABLE 4______________________________________Quadrants, wound location HA Lyophilized IAL solution______________________________________Fore-upper -- 4Fore-lower 6 4Hinder-upper 8 2Hinder-lower 5 5Multiple locations 11 11______________________________________
TABLE 5______________________________________Wound location HA lyophilized IAL solution______________________________________Central 14 13Marginal 4 --Paramarginal 12 13______________________________________
TABLE 6______________________________________Wound shape HA lyophilized IAL solution______________________________________Linear -- 1Reniform 8 7Roundish 22 18______________________________________
TABLE 7______________________________________Wound cause HA lyophilized IAL solution______________________________________Traumatic 8 8Phlogistic 22 18______________________________________
Treatment conditions
The patients, after dysepithelization operation of the tympanic wound edge, under local anaesthesia conditions, were subjected to the following procedures:
* Group A: IAL solution
At the end of the operation, the physician started the application to the external auditive duct, and well in contact waith the tympanic membrane, of a methylcellulous little tampon (Merocel�) medicated with IAL solution.
The patient provided for daily self-dressings, for the subsequent six days, by placing 0.5 ml of IAL solution in the external auditive duct by means of an insulin syringe without needle.
The little tampon was removed on the 7th day by the experimenter, who provided for the otoscopic tests of the wound.
In the case or complete healing of the wound, the patient was invited to come back on the 14th day for a further and final clinical examination, during which a tympanogram was carried out as well.
If, on the 7th day, the otoscopic test did not show a complete repair of the tympanic perforation, the experimenter applied a new medicated tampon to the patient external auditive duct, under the same conditions, as described hereinbefore.
Then the patient provided for the self-dressing for the subsequent six days (8th -13th day) coming back to be checked on the 14th day.
* Group B: lyophilized HA
The experimenter, after the operation, provided to apply lyophilized HA in contact with the tympanic membrane, then repeating the dressing on the 4th day. The wound otoscopic test was carried out on the 7th day.
In the case of complete wound healing, the patient was invited to come back on the 14th day for a further and final clinical examination, during which a tympanogram was carried out as well.
If, on the 7th day, the otoscopic test did not show a complete repair of the tympanic perforation, the experimenter provided for a further dressing cycle on the 7th and 10th day.
On the 14th day an otoscopic test was carried out, verifying the therapy results.
For both groups (A and B) the study foresaw four obligatory controls and finished on the 28th day with a last clinical examination, to which the patient was subjected.
Evaluation criteria
Before starting the treatment, a series of surveys concerning private data, anamnesies and routine laboratory tests, was carried out.
In particular one observed: otorhinolaryngology objectivity, presence expressed in days and months of the tympanic wound, etiology of the tympanic wound, otoscopic test specifying the laterality, quadrant, location and shape of the tympanic wound to be treated, wound size expressed in mm, which was calculated by measuring at otomicroscopy the two greatest diameters of the tympanic perforation, tonal audiometric test.
The examinations were carried out on the 7th, 14th, 21st and 28th day from the start of the treatment.
The following surveys were carried out:
1--otoscopic test;
2--survey of the complete wound repair which might have taken place;
3--size of the residual wound, in the case of incomplete repair;
4--tonal audiometric test;
5--tympanogram (in the case of perforation repair);
6--clinic judgement relating to the treatment effectiveness expressed as follows:
very good: complete wound repair, standard tympanogram;
good: complete wound repair, altered tympanogram;
fair: partial reduction and above 50% of the starting size of the wound;
insufficient: partial reduction and below 50% of the starting size of the wound;
no: no change in the size of the wound;
a negative: presence of inflammatory and/or contagious processes.
As to tympanogram, the different types of tympanogram were classified, according to Jerger's classification, as follows:
type A corresponding to a normal type, with bell-shaped curve and peak of maximum compliance at 0 mm H2 O;
type A1 with bell-shaped curve, peak of maximum compliance at 0 mm H2 O and reduced compliance;
type B with flat curve, very reduced compliance and absence of peak of maximum compliance;
type C with normal compliance and peak of maximum compliance shifted to pressure negative values;
type D with "W" morphology and "W" interpeak distance below 100 mm H2 O;
type E with camel's hump morphology and interpeak distance above 100 mm H2 O;
The therapeutic activity of the tested preparations was evaluated, according to the number of complete tympanic repairs and to repair time.
1) Number of complete tympanic repairs
In table 8 the data are set forth concerning the number of tympanic perforations, which, in the two treatment groups, proved to be completely repaired, partly repaired or unchanged.
TABLE 8______________________________________Otoscopic objectivity HA lyophilized IAL solution______________________________________Treated cases 30 26Complete repairs (no. and %) 17 (56.6) 13 (50.0)Partial repairs (no. and %) 11 (36.6) 9 (34.6)Unchanged perforations 2 (6.6) 4 (15.3)(no. and %)______________________________________
The data show that:
a--in the group treated with lyophilized HA, 17 patients out of 30 tested patients, achieved a complete repair of the tympanic wound, with a success percentage of 56.6% ; 11 achieved a partial repair, with a percentage of 36.6% and 2 patients presented an unchanged perforation (6.6%).
b--in the group treated with IAL solution, 13 out of 26 tested patients achieved a complete repair of the tympanic wound (50.0%), 9 achieved a partial repair (36.6%), and 4 patients presented unchanged perforation (15.3%).
2) Time of tympanic repair
In Table 9 the data are set forth, relating to the time of tympanic repair in the group treated with lyophilized HA and in the group treated with IAL solution.
TABLE 9______________________________________Time of tympanic repair - complete repairs Total 7th 14th 21st 28th______________________________________Lyophilized HA 17 10 (58.8) 6 (35.3) 1 (5.9) --IAL solution 13 3 (23.1) 8 (61.5) 2 (15.4) --______________________________________ The percent value is indicated between brackets
The data show that:
a--in the group treated with lyophilized HA, out of 17 patients with complete repair of the tympanic perforation, 10 patients showed that the repair had occurred on the 7th day (I control), 6 patients on the l4th day (II control) and 1 patient on the 21st day (III control);
b--in the group treated with IAL solution, out of 13 patients with complete repair of the tympanic perforation, 3 patients showed that the repair had occurred on the 7th day (I control), 8 patients on the 14th day (II control) and 2 patients on the 21st day (III control) . . . pa
Tympanometric evaluations
In Table 10 the data are set forth, relating to the type of tympanogram noted in the patients who, in the two treatment groups, have achieved complete repair of the tympanic membrane.
TABLE 10______________________________________Tympanogram Lyophilized HA IAL solution______________________________________Complete repair 17 13Normal type A 11 (64.7) 10 (76.9)Altered type A1 -D 5 (29.4) 2 (15.9)Altered type B -- 1 (7.7)Not carried out 1 (5.9) --______________________________________ The percent value is indicated between brackets
The data show that:
a--in the group treated with lyophilized HA, 11 patients, out of 16 subjected to tympanometry, presented a tympanogram of type A (normal), according to Jerger; in the other 5 patients a tympanogram of type A1 -D was noted;
b--in the group treated with IAL solution, 10 patients, out of 13 patients subjected to tympanometry, presented a tympanogram of type A (normal), according to Jerger, 2 patients presented a tympanogram of type A1 -D and in one patient a tympanogram of B type, according to Jerger, was noted.
The general tolerance proved to be very good in both treatment groups; in no patient, in fact, adverse reactions of systemic type were noted; the two treatments proved to be well tolerated locally as well.
B--Effectiveness of a lyophilized pharmaceutical preparation or an estereal derivative or hyaluronic acid in the repair process or rat tympanic membrane.
The study, as described hereinafter, evaluates the effectiveness of a lyophilized pharmaceutical preparation of an estereal derivative of hyaluronic acid and precisely of the ethyl ester of hyaluronic acid (identified by abbreviation HYAFF7 and disclosed in European patent application EPA 216 453 filed on Apr. 1, 1987), in making easier the repair process or tympanic membrane in the experimental model or diabetic rat.
The diabetic rat was selected, as it represented a better experimental model, compared with a sound rat: in fact, in a diabetic rat the healing times are sufficiently longer, so that they assure a better observation or the tympanic repair process.
The merit of the application of estereal derivatives of hyaluronic acid has to be attributed to the characteristic of slow release of the active principle (hyaluronic acid), in times which are directly proportional to the esterefication degree thereby assuring longer stay times of the material in the tissues.
Model description
8 mature Sprague Dawley rats, being 5 months old, having a weight ranging between 350 and 400 g, made diabetic by streptozocin (STZ) treatment 60 mg/kg .p. for 30 days, have been subjected to bilateral tympanic perforation.
Use was made of the experimental method described by Martini et al.: Experimental tympanic membrane perforation, natural history of healing process in rat; Acta otorhinol, ital.; 10,559-577,1990.
Summing up, every animal was anaesthesized by intra-peritonaeal injection of sodium pentabarbital (Nembutal�), 45 mg/kg and then subjected to bilateral perforation of the hinder-upper quadrant of the pars tensa of the tympanic membrane, carried out at the operating microscopy with lanceolate bistoury.
Treatment conditions
the tympanic membrane of the left ear was dressed with a little spongy tampon consisting of lyophilized HYAFF7, having cylindrical form and being imbued with a drop of a physiological solution. In order to assure the permanence of the little tampon, a scarification was carried out of the walls of the external auditive duct, thereby causing a bleeding sufficient for the formation of a clot;
the tympanic membrane of the right ear was used as control. The tympanic membranes of the animals were examined at the operating microscopy on the 1st, 4th, 6th, 8th, 11th and 13th day.
The results obtained by examining the tympanic membranes at an operating microscopy show that:
1--all the tympanic membranes treated with HYAFF proved to be repaired 8 days after the treatment, whereas only 50% of the tympanic membranes, which had not been treated, showed the same results (the repair completion of the right tympanic membranes, which had not been treated, occurred after 11-13 days);
2--the tympanic membranes treated with HYAFF proved to be (at the last otoscopic test, i.e. on the 13th day) of better quality: shining, not opaque, without chromatic variations or dimorfirms.
Concluding, from the above cited data, the application of the spongy material consisting of esters of lyophilized HA proved to be valuable, as it favours, in a diabetic rat, a tympanic repair of better quality and in shorter times, when compared with a spontaneous repair.
The above disclosed clinic and experimental results, show that both pharmaceutical preparations of spongy material consisting of lyophilized HA and lyophilized HYAFF are active and effective in tympanic perforation therapy and more generally in otologic microsurgery.
The new slow release spongy material consisting of hyaluronic acid or its derivatives is obtained by the following process, forming a further object of the present invention.
Preparation process
1. Dissolution of the active principle
In a suitable apparatus, equipped with a heating system, suitable stirring and vacuum/nitrogen pressure/sterile filtrate system, hyaluronic acid, or one of its estereal derivatives, is dissolved in water for injectable preparations, so as to reach a concentration ranging between 1 mg/ml and 40 mg/ml.
2. Solution filtration
The solution containing hyaluronic sodium salt is filtered suitably through a sterilizing membrane, having a porosity of 0.2 micrometers, afterwards it is collected in a sterile environment.
3. Solution distribution
The filtered solution is parcelled out in a sterile environment, into suitable sterile containers, such as tiny bottles, blisters and the like, by dosing the solution so as to achieve 10 mg of active principle in each container.
4. Lyophilization
The containers, after having been filled up, are put into a lyophilization apparatus and the product is frozen to a temperature ranging between 0� C. and -90� C.; the temperature decrease for achieving the freezing is captied out at rates ranging between 1� C. every 20 seconds and 1� C. every 3 hours.
Drying step by high vacuum (residual vacuum in the chamber ranging between 1000 and 1Hg mm) and heating step with plate temperature ranging between -90� C. and +60� C., follow.
Both the cooling step and the heating step are handled by means of a computer, programmed as follows:
temperature decrease for freezing, value ranging between 1� C. every 20 seconds and 1� C. every 3 hours.
temperature increase for sublimation, value ranging between 1� C. every 20 seconds and 1� C. every 8 hours.
At the end of the lyophilization the tiny bottles are stoppered in a sterile way.
The tiny bottles of lyophilized product are drawn out from the sterile container at the time of use.
The thus obtained spongy material consists of hyaluronic acid or its derivatives and appears from a macroscopic point of view, as a higly microporous spongy little disk, being preferably between 0.2 and 2 cm high and having a diameter ranging poreferably between 0.5 and 4 cm, having a residual humidity content ranging between 0.01% and 10%, being very hydrophilie and easily manageable, which spongy material, after having been compressed, can assume the shape of a discoid still sufficiently elastic, so that it can be applied easily and brought into contact with the lesion to be treated.
Moreover the new spongy material, according to the invention, both the one coming from HA and the one coming from an ester of it, has the following characteristics:
apparent volume: ranging between 0.04 and 27 ml;
apparent density: ranging between 0.00037 and 0.25 g/ml;
actual volume: ranging between 0.001 and 2.5 ml;
actual density: ranging between 0.004 and 10 g/ml.
In particular a "little sponge" obtained from HA or a little sponge obtained from HYAFF, according to the process as described hereinbefore, were tested at a scanning electronic microscope (SEM Philips 505). As it results from the enclosed figures, of which FIG. 1 relates to the material obtained from HA and FIG. 2 relates to the material obtained from HYAFF, in both cases the materials appear as sponges having a lamelar structure, whose porosimetry can be drawn directly from the image, since the reference at the foot of each photograph as a white bar corresponds to 1 mm in length.
Though the two materials present a very similar structure, they differ from each other owing to the filling compactness, which is 6-10 times thicker in the sample of lyophilized HA (FIG. 1), compared with the one of HYAFF (FIG. 2). A microstructural characteristic of the lyophilized HA sample consists in the constant presence, in the lamellae forming the spongy filling, of micropores, which, on the contrary, do not appear in the HYAFF lamellae.
We can suppose that the slacker filling and the more uniform structure of the HYAFF lamellae contribute to give the improved characteristics of mechanical resistance and resilience, which can be observed on the HYAFF dry material.
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Strata trying again for utility solar in N.C.
- Staff Portland Business Journal
Strata Solar continues to push for construction of larger-scale solar projects, seeking authorization from North Carolina regulators for two additional 5-megawatt solar farms, including one in Rockingham County.
This week, Strata has filed applications with the N.C. Utilities Commission for projects in Warren and Rockingham counties and Strata spokesman Blair Schooff says the company plans to file applications for several additional projects soon.
"We are pretty bullish on the future of solar," he says. "We are not slowing down, and we see nothing that should slow us down."
However, Chapel Hill-based Strata has decided to drop plans for one solar farm it previously proposed. Schooff says the company has run into some development issues in the early planning for the 5-megawatt H Creek Farm planned for Lincoln County and does not plan to move forward with that venture.
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