text:
Meals: Breakfast, Lunch & Dinner
Arrive at Singapore, after clearing the immigration, you will be met by our local representative and transferred to Hotel. Check in at the hotel .
In the Evening take a tour of the world's only 'Night Safari', The world's first Night Safari set in 40 hectares of secondary jungle will unfold the mystery and drama of the tropical jungle after dusk with stunning effect. See a myriad of nocturnal animals, from fierce predators to timid forest dwellers, in their natural habitat under subtle moon glow lighting. Roam the jungle in the complete safety and comfort of your Tram which takes you through the East and West Loop passing by a large reservoir and weaving through selected habitats designed specifically to replicate the natural environment from the Himalayan Foothills to the Southeast Asian Rainforest and Indian Subcontinent. On completion of the tram ride, your tour guide will lead you on a walking trail where you will be able to view some animals at closer quarters.
Return back to hotel . Overnight in the hotel at Singapore.
Meals: Breakfast, Lunch & Dinner
After breakfast, proceed for the Singapore city tour explore the city by driving round the Civic District, passing by the Padang, Cricket Club, historic Parliament House, Supreme Court and City Hall. Next, stop at the MERLION PARK and enjoy the impressive views of Marina Bay. Do not miss out this picture-taking opportunity with The Merlin, a mythological creature that is part lion and part fish. Visit THIAN HOCK KENG TEMPLE, one of Singapore's oldest Buddhist-Taoist temples, before driving past Chinatown. Stop by a LOCAL HANDICRAFT CENTRE and observe craftsmen at work up-close. Proceed to the NATIONAL ORCHID GARDEN, located within Singapore Botanic Gardens, which boasts a sprawling display of 60,000 orchid plants. Our final stop at LITTLE INDIA will entrance you with the scent of joss sticks, jasmine and spices.
Return back to the hotel. Rest of the time free at leisure. Overnight in the hotel at Singapore.
Meals: Breakfast, Lunch & Dinner
After Breakfast check out from the hotel and get transfer to the airport to board the flight for Kuala Lumpur. In Afternoon you will arrive in Kuala Lumpur. Transfer and Check in to the hotel. Rest of the day free at leisure. Overnight at hotel in Kuala Lumpur.
Meals: Breakfast, Lunch & Dinner
After breakfast, proceed for half-day city tour covering Masjid Jamek (Jamek Mosque), which is the oldest mosque in Kuala Lumpur, Tugu Negara or War Memorial where we honor those who perished in the war which is inside Lake Garden, Chinatown located on Petaling Street is full of good bargains and deals, food of sorts and rich Chinese culture. See the Thien Hou Temple, Moorish-styled Federal Court, the Railway station which is a striking piece of Mohammedan architecture, the Tudor styled Cricket Club and the Kings Palace, Handicraft center where you can find fine and splendid Jewelry making demonstrations. Return back to the hotel and Rest of the day at leisure. Overnight will be in the hotel in Kuala Lumpur.
Meals: Breakfast, Lunch & Dinner
After breakfast, transfer to Genting Highlands, the most exciting hill resort, only 50 kms from Kuala Lumpur. Arrive at Genting hotel, then proceed for Genting indoor and outdoor theme park Tour "The World's Best City Of Entertainment" Amidst the freshness of cool, Crisp Mountain airs about 6,000 feet (above sea level lies Malaysia's only casino resort and is a World-Class City of Entertainment). Fringed by one of the oldest tropical jungles in the world, you can enjoy yourselves with the numerous indoor and outdoor amusement triads, casino, cinemas, restaurants and shopping malls Boating on the lake, fun rides on bumper cars and roller coasters are just a few of its attractions. Late night free to own enjoy the nightlife and international Dinner shows or try your luck at the world-class casino. Overnight in the hotel Genting Highlands.
Meals: Breakfast, Lunch & Dinner
After breakfast, rest of the day free at leisure till check out and then transfer to Kuala Lumpur airport to board the flight back to home.
Description : Singapore
Description : Kuala Lumpur
Description : Genting
Mr. P. Mariappan
No. 1/458, A/5 Main Road, Adayakarunkulam, Vickramasingapuram Ambasamudram, Tirunelveli, Tamil Nadu, India - 627425
+91-9500094193, 9080000101
3N/4D Manali Volvo Tour Package - 4 D / 3 N
Delhi - Manali
Andaman Honeymoon Ship Tour - 7 D / 6 N
Chennai - Port Blair - Havelock Island
Andaman Holiday Vacation Cruise Tour Package - 7 D / 6 N
Chennai - Port Blair
Andaman LTC Cruise Tour - 7 D / 6 N
Chennai - Port Blair
Lakshadweep Samudram Cruise Tour Package - 5 D / 4 N
Cochin - Lakshadweep
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Chennai - Port Blair
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Chennai - Port Blair
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Male City
Maldives Holiday Vacation Package - 4 D / 3 N
Maldives - Male
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Andaman - Port Blair - Havelock


text:
Format Maps
Results: 1-3 of 3 | Refined by: Original Format: Maps Remove Subject: United States Remove Location: United States Remove Language: Spanish Remove Contributor: Campo, Josef Del Remove
Descripcion hidografica, que comprehende la America septentrional, desde la Punta, y Rio de Sn. Juan, hasta Filadelfia, con sus yslas, bajos y sondas adjacentes:
Scale ca. 1:2,000,000. Manuscript; pen-and-ink and watercolor. Has watermark. Depths shown by soundings. Includes text and 3 profiles. Available also through the Library of Congress Web site as a raster image. Vault AACR2
- Contributor: Campo, Jošef Del
- Date: 1780
Plano de la Bahia de la Ware y entrada de Filadelfie ...
Scale ca. 1:200,000. Manuscript, pen-and-ink and watercolor. Soundings shown in fathoms. No. "41." LC Luso-Hispanic World, 848 Includes sailing directions and index. Available also through the Library of Congress Web site as a raster image. Vault AACR2
- Contributor: Campo, Josef Del
- Date: 1780
[Puerto del Boston.
Scale ca. 1:34,000. Title on attached label on verso: The city and harbour of Boston. Manuscript, pen-and-ink and watercolor. Relief shown pictorially. Soundings shown in fathoms. Shows settlements and fortifications. No. "43" in lower left margin. Includes index, sailing directions, and view of entrance to the bay. LC Maps of North America, 1750-1789, 957 LC Luso-Hispanic World, 961 Available also through the Library of ...
- Contributor: Campo, Josef Del
- Date: 1780

subset: commoncrawl


text:
Firefighters put out garage fire
CLARKSTOWN Volunteer firefighers rushed to 4855 Clarkstown Road for a reported fire in a garage attached to a home about 8:30 p.m. Wednesday.
Muncy Area Fire Chief Scott Delany, the first on the scene, confirmed the garage was on fire but said firefighters put out the bulk of the fire within minutes.
In addition to Muncy Area, firefighters from Hughesville, Pennsdale and Picture Rocks were dispatched to the fire but most of the equipment soon went available.
Shorly before 9 p.m., firefighters were called to the Alexander-Nissan dealership at 125 Lycoming Mall Road in Muncy Township for a report of flames and smoke through the building's roof.
It turned out to be only smoke and fire from the structure's chimney.


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Young Preschool Book of Transport
Preschool Book of is a series of fifteen colourful books:
The books are kid friendly. The design and layout of the books is so planned that they attract the kids automatically. As the kids turn over the pages, they find the book much more interesting, which makes them curious to learn more. This quest makes them learn quickly and more than required from their age group.
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Date: 1900 ca.
Description: Letterhead stationery of Wendell Anderson, the mayor of La Crosse, with an engraving of city hall.
Description: Letterhead stationery of David S. Rose, the mayor of Milwaukee, showing an engraving of Milwaukee City Hall.
Date: 1968
Description: Certificate of Merit presented to Father James E. Groppi of Milwaukee on January 7, 1968, for his work as Advisor of the Milwaukee NAACP Youth Council. The...
Date: 1944
Description: Cover of International Harvester Company's annual report, featuring a photograph of Marines using International Harvester equipment during the invasion of...
Date: 1910-07-13
Description: Blueprint of the west elevation of the Chicago residence of Nettie Fowler McCormick, widow of Cyrus Hall McCormick. The plan presents alterations and addit...
Date: 1918
Description: Neal Harrington was assigned to the American Expeditionary Forces in October 1918. He was sent to France with the 20th Engineering Corp as a 2nd lieutenant...
Date: 1919 ca.
Description: Third page of a four-page pamphlet advertising Alfred Lawson and, by extension, his line of airliners. Reproduces the second half of a letter from the Aeri...
Date: 1922-09-18
Description: Certificate naming the officers of the Green Bay Football Club: President, E.L. Lambeau (Earl "Curly" Lambeau); Vice President, Joseph M. Ordens; Treasurer...
Description: First page of a four-page pamphlet promoting Alfred Lawson and, by extension, his new line of airliners. Page includes an image of the "Winged America" tro...
Date: 1972
Description: Letterhead for the Commandos Project I organization.
Date: 1949
Description: Front cover of International Harvester Company's annual report, featuring a color photograph of a semi-truck driven along a road through rocky terrain.
Date: 1920-09-13
Description: Letter to Alfred Lawson from Otto Praeger, the second assistant Postmaster General, accepting Lawson's proposals for carrying air mail along three routes:...
Date: 1950-03-30
Description: Green Bay Packers letterhead dated March 30th. The content of the letter is detailing a future Green Bay Packers stock drive and is sent from Lee Joannes.
Date: 1965
Description: Letterhead of Tripod Chevrolet of Clintonville, Wisconsin, with three-quarter views of various Chevrolet models, including the Corvair, Corvette, and Cheve...
Date: 1976-09-07
Description: Letter on Frackelton & Co. letterhead regarding a business transaction between Frackelson & Co. and Lawson & Goodnow Manufacturing Co. of New York.
Description: Fourth page of a four-page pamphlet advertising Alfred Lawson and, by extension, his line of airliners. Includes eight photographs and drawings of Lawson A...
Date: 1935-12-28
Description: A letter to M.A. Wertheimer from John M. Hancock detailing a business plan for Lehman Brothers.
Date: 1911
Description: Front cover of International Harvester Company's annual report.
Date: 1925 ca.
Description: This page from a stock book from Ferdinand Hotz's Chicago based jewelry business shows his inventory of gemstones, his costs, and the clients who bought th...
Date: 1917-03-29
Description: Telegram to George W. Ellis of Green Bay, from Ernest La Rue Jones, president of the Aeronautics Manufacturers' Association. Text reads: Lawson familiar ae...
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text:
Phil Hayden
Queens Village, NY 11429
OS Related: IBM Z/OS, VSE/ESA, ICCF, IMS/MVS, SPUFI/QMF, TSO/ISPF, Windows NT – 2003 Server, JCL
Programming: CICS, BMS, COBOL, RPGII, Assembler, PL/1, CA-Top Secret
Crystal Reports XI, Power Builder, PL/SQL(Oracle SQL),Transact-SQL(SQL Server)
Database: DB2 v9, VSAM, Oracle, SQL Server , CA-Top Secret
Volt Workforce Solutions, Philadelphia, PA 08/10 to 12/11
IT Consultant/ Senior Software Developer
Developed Publications Software utilizing Cobol, PL/1,CICS and DB2 Stored Procedures in a fast paced environment to enrich the process of creating YELLOW PAGES advertisements. Responsible for the maintenance and support of the Sales Force system integration from an MS/SQL server to the Mainframe DB2 Tables , producing sales reports, invoices and payroll files. Created CICS modules to maintain phone book directory information which also defined geographical boundaries of each directory. Responsible for the creation of DB2 Loads and Unloads of directory tables to store data across multiple regions.
U.S Mortgage Company, Pine Brook, NJ 11/04 to 06/09
IT Consultant/ Senior Software Developer
Coded and created a user friendly online Cobol/CICS historic mortgage application system for HMDA and State / Banking Audits, dramatically reducing time spent archiving prior years analytical data reports.
Responsible for the maintenance and enhancement of the loan origination and servicing software. Duties included Database field mappings of required mortgage disclosures, Logic enhancement via Gupta code, data reporting via Crystal XI Reports Web Enterprise, and Data Extraction via MS SQL, Sybase SQL on a multi-tier Windows network environment.
Telcordia Technologies, Piscataway, NJ 11/00 to 03/04
Senior Software Developer
Areas of development and maintenance covered Customer Record and Number Administration processing for routing of 800 Toll Free numbers to Service Control Points across the Number Planning Area, utilizing PL1, COBOL, CICS, VSAM, under IMS/MVS. Position required a strong emphasis on quality control utilizing CMM (Capability Maturity Model) as well as ISO (International Standards Organization) 9000 compliance throughout the whole development cycle.
Prepared technical design, document, flow analysis, development, testing and integration testing of all code requirements developed.
Kanebo Information Systems Corp., NY, NY 11/94 to 10/00
Senior Software Developer
Responsible for various software development project of Japanese bank in US operations
which included installation and customize integrated global banking system on IBM mainframe utilizing PL1, CICS, VSAM. Designed, programmed and distributed ACH, Payroll, and Check processing Interfaces.
Created a loan transaction detail database interface utilizing PowerBuilder and Transact-Sql
Responsible for Disaster Recovery procedures that includes utilization of disaster recovery facility
from DASD restoration, system/application start up and remote connection interfaces over multiple facilities.
Development software covered wholesale banking to retail banking, such as commercial loans, international funding, foreign exchange and associated general accounting
LaGuardia Community College, LIC, New York
PSI Institute, New York, NY Certificate of Computer Programming
Grumman's Data Systems Institute, L.I, N.Y Certificate of Computer Operations
Information Systems Project
New York, NY - cics, db2, cis, create, information systems, sdlc,...
Project Customer
Jersey City, NJ - cics, cobol, jcl, db2, rider, tools, ims, client,...
Programmer Analyst Technical Support
Jersey City, NJ - cics, cobol, aix, db2, os, programmer analyst,...
Programmer Analyst Technical Support
Jersey City, NJ - cics, cobol, aix, os, db2, linux,...
Customer Service Sql Server
Leonia, NJ - cobol, cics, db2, command, programmer, ssis,...
Data Project
New York, NY - cics, db2, cobol, informatica, etl, jira, unix,...
Quality Assurance Testing
New York, NY - cics, db2, pl, broker, analyst, programmer, coding,...


text:
Join Chris Orwig for an in-depth discussion in this video Performing a better catalog backup, part of Lightroom 3 Advanced Techniques.
- Overview
- Transcript
- View Offline
In the previous movie we discussed how we could use a preference so that we can frequently create a backup of our Lightroom catalog, and that will save it to the same location wherever that catalog file is. It's in the subfolder called Backups, and there it is we have this backup file. It's a same exact file name, same exact file size as the original catalog. This is really helpful especially if this catalog file gets corrupt or if we accidentally delete it or if just something happens to it, we now have this backup. Well, let's see what happens if we go back to Lightroom and then go ahead and quit it out.
Is it going to create another backup for us? Well, here let's press the shortcut to quit Lightroom. It's Command+Q on a Mac. It brings up my backup catalog dialog, because again I chose the option to back it up each time I close. Here, I'll go ahead and click Backup. This will go through checking the integrity, optimizing the catalog, creating that backup, and now inside of my backup's folder we now have two distinct and different backups. So, if you take a look at this.
You'll notice that we have these different catalog files, and they all have the same file name, and they also are the same file size. They're just located in different folders. Now, when you have a lot of images in your Lightroom catalog, these catalogs files are actually going to be pretty big. So then the question surfaces, do I really need to save all of my backups? Like how many backups do I actually need? Well, typically it's a good idea to have one or two or three, but if you have older backups you can get rid of those. So what we can do in these situations.
Let's say this is the older backup. Actually, this one is the older backup. Sorry about that. Let me make sure I am choosing the right one. We can go ahead and delete that or move it to the trash, because we don't necessarily need that. Now, again typically I recommend you have perhaps in regards to your backup one, two or three versions back, but you don't need 15 or 20 versions back, because really that information becomes quite irrelevant. You want to think about how much of a safety net do you need if you're rock climbing. Of course, you have one rope.
You want another and another and then maybe a net as well. In most situations having one, two, or three is going to be pretty good. Well, what else do we need to consider here? Well, one of the things that we need to consider is that this backup right now is on our internal drive. Let's say, for example, that I flyout to go do a photo shoot, and I fly back, and I am working in Lightroom. I quit it. It creates a backup for me. But then when I get back to my studio I all of a sudden realize my hard drive has been fried.
I mean it's toast. It is gone. In that situation, it's unfortunate. I've lost my catalog, and I've lost my backup of my catalog, because I put all my eggs in one basket. I haven't had time to back up my system. So really I've lost all of this work that I've done in regards to Lightroom catalog. Well, what you typically want to do is rather than have all your eggs so to speak in one basket; you want to have an external drive. Here, I'll just open up an external drive and on this drive you want to have a location perhaps something like Lightroom backups and you want to grab your backups.
Again, I'm recommending that you grab perhaps the three most recent backups. Then drag those over, drag them to this external drive, and then what you'll have is a copy of those in another location. Now if you're a little bit more adept with backup systems and whatnot, you could also automate this so that you have this happen frequently, yet in the same time you can always simply click and drag these over to another drive just to make sure that you have all of your eggs in one basket, so that you're spreading things out a bit, so that your backup strategies are even more effective.
- Maximizing file compatibility
- Speeding up the workflow with automation
- Working with catalogs, collections, and folders
- Diagramming multiple catalogs and computers
- Performing and restoring backups
- Setting up tethered capture
- Advanced retouching techniques, such as eye enhancement and blemish reduction
- Working with color profiles
- Perfecting prints from Lightroom
- Creating custom watermarks
- Making a custom web gallery
- Exporting and publishing photos


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Thursday, October 25, 2012
The National Hurricane Center is expecting Hurricane Sandy to pass well east of the South Carolina coast Friday but it should be close enough to generate hazardous surf conditions.
There is also a chance some of the outer bands from the storm could reach the coastal counties, so a chance of showers has been placed in the forecast for Friday and Saturday.
Right now, damaging winds are not expected in South Carolina although it may be breezy late Friday through at least part of the day Saturday.
It will not be a good weekend to go into the ocean as heavy surf and potentially deadly rip currents are expected.
Looking ahead, almost winter-like temperatures are expected next week.
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realmagick.com The shrine of knowledge.
Etrading Impact
A selection of articles related to etrading impact.
Original articles from our library related to the Etrading Impact. See Table of Contents for further available material (downloadable resources) on Etrading Impact.
- Is Subliminal Influence Used in Advertising?
- If we use the term subliminal in the way that it is commonly used, to mean any sort of hidden message, then yes, advertisers do frequently hide their message. This might even be considered a standard advertising practice. Advertising agencies are paid to...
Parapsychology >> Subliminal Persuasion
- Manifesting World Enlightenment: Part 2
- When thoughts are replaced by silence in the mind, perception arises. It is a part of the modern condition wherein the mind of humanity is constantly overwhelmed, by a million considerations and thoughts. In acquiring silence, the mind is enabled to get out...
Mind >> World Mind
- Our Pagan Village: The Importance and Persuit of Honor
- Candlelight flickers over the Beltaine revels. Food is laid out in the circle for the feast. Only one rule – no one can feed themselves. Each is dependent on friends and loved ones for sustenance, joy and delight. After an hour of laughter and revels and way...
Paganism & Wicca >> Daily Life
- Group Mind Basics (GM1)
- Anyone who has ever spoken in front of a group of people, knows that there is a peculiar sensation associated with the experience. A tightness of the throat often appears, or the speaker "gets butterflies in their stomach". Just as in the case of person to...
Mind >> Telepathy and Group Mind
- Transforming World Mind Inertia (GM7)
- Our entire world society is ultimately governed by the components of consciousness, not governments, corporations or institutions. Regardless of the apparent creativity of the architectural sciences, engineering or the ideologies we create, the true...
Mind >> World Mind
- Raising the World Mind (GM10-11)
- Part 1 | Part 2 Part 1 The wise live in accord with natural laws. It is they who understand that the laws of nature are much higher than the laws of man, because breaking them implies penalties far greater than a fine or prison sentence. When a person...
Mind >> World Mind
- Isis
- Egyptian. Also widely known as Stella Maris (Star of the Sea). She is the very well known Egyptian Goddess associated with rebirth and motherhood, and her cult became very popular in many areas during Roman imperial times. That cult has had a powerful impact...
Deities & Heros >> Roman
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- In July, I made the case to be cautious with US equities and take action, but I did not offer great alternatives then. Since then, I've found bottom-up investing in small-cap value Japanese stocks to be a compelling alternative.
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Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
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Oscars Lowdown 2014: Best Original Song - U2 looks to upend Disney's 'Frozen'
In the lead-up to the 86th annual Academy Awards on March 2, HitFix will be bringing you the lowdown on all 24 Oscar categories with multiple entries each day. Take a few notes and bone up on the competition as we give you the edge in your office Oscar pool!
The Best Original Song category enjoyed a hell of a lot more attention this season than it likely ever has as "Alone Yet Not Alone"-gate was a blight and an embarrassment. Not entirely for the composer of the song, mind you, who waged a one-man email campaign to get fellow branch members to vote for the track, but also for the Academy, which decided that disqualified the song, making it the only instance of a nomination being revoked due to perceived campaign malpractice in the Oscars' 85-year history. Given what happens under the hood every single season, if the Academy wants to go down that road, they better not stop with "Alone Yet Not Alone" — but I'm on the record about this. In its wake, the four remaining nominees are a poppy bunch, mostly, and the whole thing has become more competitive than expected.
The nominees are…
"Happy" from "Despicable Me 2" (Pharrell Williams)
Honestly? My opinion? "Happy" is the best of the nominees. I hear the groans. But it's a catchy piece of music from an artist who knows exactly how to wiggle his way into your ears. I never tire of this track — which also, by the way, comes in the context of the narrative in "Despicable Me 2," which is helpful — and that's saying something for a tune that could have been incredibly annoying. Anyway, it's probably on the outside looking in at the big musical number, but don't sleep on it: the song was released to radio again and shot up the Billboard chart recently. It's in commercials. It's everywhere. I could see more than a few voters ticking off this box because they're besieged by the track as of late. (Check out our interview with Williams here.)
"Let it Go" from "Frozen" (Kristen Anderson-Lopez and Robert Lopez)
But this one is sure to go to the big Disney anthem, despite some doozy lyrics like "the past is in the past." I kid. I may not have taken to "Frozen" this year but it has a rabid fan base that crosses generational lines, and "Let it Go" is going to be a hit from here to eternity. It's a call back to the kinds of songs that dominated this category years ago, whether "Under the Sea" or "A Whole New World" or what have you. It's iconic where the other nominees, admittedly, aren't (though I might prefer Mr. Freeze's version). That should go a long way toward securing it a win, but this is a pretty tight field this year, at least a three-way race.


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Category Archives: New Hampshire Slanguage
New Hampshire Slanguage: Fagged Out
I remember my grandparents and parents using the term, "fagged out," to mean exhausted or weary. Although I cannot prove that the term originated in New Hampshire, an ancient newspaper from this state seems to contain the earliest usage … Continue reading
New Hampshire Slanguage: Cunnin
Recently the word cunnin(g) was brought up in a FaceBook discussion group, as to whether or not it was New England slang. To be honest, I am not certain. But it was in a New Hampshire household where I heard … Continue reading
Posted in New Hampshire Slanguage Tagged baby, child, colloquialism, cunnin, cunning, cute, England, Hampshire, new, New Hampshire, slang, slanguage, sweet 3 Comments
New Hampshire Slanguage: Piazza
The word, piazza, was well known in New Hampshire in the early 18th century. Several references are made in newspapers of that time to piazzas found in warmer climates and seemingly indicative of outside living space covered with a roof. … Continue reading
Posted in History, New Hampshire Slanguage Tagged architecture, piazza, porch, slanguage 2 Comments
New Hampshire Slanguage: Hoodsie
To New Hampshirites, and other New Englangers, a "hoodsie" is a cup of ice cream.
This word, that originated … Continue reading
Posted in New Hampshire Slanguage Tagged cup, H.P. Hood & Sons, hoodsie, ice cream, New Hampshire 3 Comments
You say Catsup, I say Ketchup
Although today we think of a red tomato-based concoction, catsup in colonial days was quite different. Wild and dried meat … Continue reading
Posted in Current Events, History, New Hampshire Glossary, New Hampshire Slanguage Tagged catsup, ketchup, tomato Leave a comment


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'Closer' a take on disconnected couples
If you're scrupulously honest with your beloved, are you laying the groundwork for a great relationship? Or are you greasing the skids for a spectacular smash?
That's among the questions being vetted in Off the Wall Theatre's production of Patrick Marber's "Closer," which features Jeremy C. Welter's best work to date as a director. More on that in a minute. First, the setup. »Read Full Article
Tame Impala anything but at Turner Hall show
Kevin Parker's perfectionist tendencies went into overdrive on last year's "Lonerism," psychedelic band Tame Impala's sophomore full-length album. Besides insisting on playing nearly all the instruments in the studio, Parker mixed the album two times, flying from his native Australia to New York on both occasions, to get the details just to his liking.
Tame Impala didn't have the luxury of do-overs and fine tuning in its sold-out, 85-minute Turner Hall Ballroom set Sunday. And if Parker attempted to bring that obsessive craftsmanship to a live setting, he would run the risk of sabotaging the set's potential for spontaneity. »Read Full Article(1)
'Rep Lab' cooks up mixed batch of one-acts
In her curtain speech before Saturday night's sold-out performance of "Rep Lab," Sandy Ernst - who oversees the Milwaukee Repertory Theater's justly acclaimed intern program - made clear that the Rep simply couldn't stage its shows without each year's crop of two dozen interns.
But even as we routinely note these interns' presence - in smaller roles, as extras and in program credits, where they are listed as understudies and assistants - we rarely get to really see what they can do. Now in its third year, "Rep Lab" - short plays showcasing intern actors, directors, choreographers and designers - lets us appreciate how good they can be. »Read Full Article
Report: Fallon to replace Leno
Reports have surfaced that late-night host Jimmy Fallon will replace Jay Leno as host of "The Tonight Show" show next year.
NBC, which just finished fifth behind Univision in the February ratings, has denied the report. »Read Full Blog Post(6)


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Rig tuning/ rounding up
View Single Post
19th September 2008, 08:39 AM
Dream Team - School Guru
Join Date: Aug 2006
Posts: 2,177
Hi Marek,
Well, putting the mast foot all the way forward on a Carve 111 is about the same as dropping the anchor.
No wonder you can't get the C111 going.
For a 7.5 m2 rig, I'd suggest starting with the mast foot about 3/4 of the way back and maybe you will end up with it even a little further back than that.
I hope you aren't putting the mast foot all the way forward on your F-Type, as that would effectively kill alot of your performance on that board as well.
What led you to put the mast foot all the way forward...?
The only boards that need to be trimmed all the way forward are older formula boards with 10.0-12.5 rigs.
Virtually all other boards sail much more freely with the mast foot further back (sailor weight and sail size can have a small impact here).
Sounds like you've been trying to get the Carve 111 going, but left the emergency brake on.
15 knots....85 Kg. sailor weight....Carve 111.... you should be off on a plane with a couple of pumps.
Try and find a 42 cm vertical fin. This will help alot with early planing on the C-111.
If your back foot is dragging when you go for the footstrap, you don't have enough speed yet.
I think you still have a tendency to move back too soon and go for the rear footstrap way to early.
Let to board get up onto a plane before you even think about putting your back foot in.
Perhaps your board is "tail dragging" to some degree and this just makes getting on plane even harder.
It seems that you have a bit more to learn about fore and aft trim.
You do need to progressively move back, but only enough to get the nose up slightly to get the planing surfaces at the optimum angle to promote early planing.
Then you head off slightly, pump a bit and the board begins to light up.
At this point you can have your front foot in the front strap, but your back foot will be
in the center of the board and in front of the rear footstraps (how far in front I cannot tell you, but it will be somewhere between midway between the front and back straps, and the front of the back straps.
Once you find the "secret spot" the board will plane off easily and then you can gain some more speed and get it fully planing.
Then think about getting into the back strap.
If you move back too soon or too much, you just about eliminate any chance that your board will plane.
Combine this with pushing the nose down and making the board "plow" due to the mast foot being too far forward and you have the perfect recipe for making a easy to plane board into a very difficult to plane board.
Hope this helps,
View Public Profile
Find More Posts by Roger


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The Worthington Renaissance Fort Worth Hotel - Fort Worth
This hotel has 3 restaurants. Relax in the indoor pool during your stay. Guests can also enjoy drinks as there is a bar/lounge.
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The Worthington Renaissance Fort Worth Hotel - Fort Worth
Hotel Info: 1-877-214-4288from $179
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DiningBarWired - Onsite coffee shop.
Vidalias - This restaurant serves breakfast, lunch, and dinner.
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We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


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the dividend. Management should do it to atrack more investors, thus the stock will appreciate its value at a double digit. Go IGR. My target is 14$ at this year ended.
sold my IGR holdings today. trend has recently weakened significantly and is no longer compelling according to my work. has had a very nice run since December. good luck to all.probably will sit in BSV for a while. risky markets now.not a recommendation.
I think your extremely misguided if you think a dividend increase is in order...I only bought IGR a few months ago to diversify my real estate holdings in portfolio. I actually got the shareholder notice today which has a nice table about the dividend. 28% of my 4.5 cents is return of capital. Don't expect a dividend increase until the earnings support the current dividend. Funds with heavy return of capitals are bad news.Might not sell if but probably am not going to reinvest the dividend like I do with other reits until the dividend is less return of capital.
What other real estate investments do you have ?


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Stocks struggled to remain above water Tuesday, caught in the crosswinds of a strong dollar and Hurricane Gustav.
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Morgan Stanley cut its 2008 EPS estimate for the S&P 500. Abhijit Chakrabortti, Morgan Stanley chief global equities strategist, explained his outlook to CNBC.
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OSHA News Release - (Archived) Table of Contents
OSHA News Release – Region 3
U.S. Department of Labor
Region 3 News Release: III-02-03-20-022-PA
Date: Wed., March 20, 2002
Contact: Leni Uddyback-Fortson
Phone: (215) 861-5102
McCLURE, Pa. -- The U.S. Department of Labor Occupational Safety and Health Administration will officially induct Lozier Corporation, McClure, Pa. into its Voluntary Protection Program as a STAR site at a special flag ceremony on Thurs., March 21, 2002 at 11:30 a.m.
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The STAR program, designed for worksites with comprehensive, successful safety and health programs, is open to any industry, and to companies with injury rates below the national average for their industry.
U.S. Labor Department news releases are accessible on the Internet at http://www.dol.gov. The information in this release will be made available in alternative format upon request (large print, Braille, audio tape or disc) from the COAST office. Please specify which news release when placing your request. Call 202-693-7773 or TTY 202-693-7755.
|OSHA News Release - (Archived) Table of Contents


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Important Dates
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realmagick.com The shrine of knowledge.
Coca Cola Criticisms
A selection of articles related to coca cola criticisms.
Original articles from our library related to the Coca Cola Criticisms. See Table of Contents for further available material (downloadable resources) on Coca Cola Criticisms.
- Why are some experts skeptical about subliminal influence?
- There was once a legitimate scientific controversy over whether subliminal perception really occurs or not. The question was whether someone can perceive something unconsciously. All kinds of experiments were performed to try to prove that we were...
Parapsychology >> Subliminal Persuasion
- How Odin Became Santa Claus: Symbolism and Pagan Origins of a Gift-Giving Saint
- The story begins in the northern regions of Europe where the supreme god Odin, also known as Wodan among the German tribes, reigned. (He still lives among us in Wednesday, which is Wodan's day). Odin/Wodan was the god of wisdom, magick and occult knowledge,...
Deities & Heros >> Nordic & Germanic
- The Seven Shaman Principles
- The World is What You Think It Is Positive thoughts attract positive people and events, and negative thoughts attract negative people and events. Corollary: Everything is a dream Dreams are real and reality is a dream. The only test we use for a reality check...
Religions >> Native American, Shamanism
- Survivalists' Guide for the New Millennium: Chapter 6
- AS THE WORM TURNS Health and well being are part of the natural birthright of the human being. With all of its organs intact, the right diet, exercise and mental focus, a human body can overcome any disease. Even so, the effects of living in this...
Philosophy >> Survivalists Guide for the New Millennium
- The Old Ones Live in New Things Too
- Imagine living in a time where all things were sacred, in a place where everything you touched was part of a Goddess or God. Since all things were divine, each had a patron Deity. From doorways to ovens, from the farm, to the hunt, to the birth of anything...
Paganism & Wicca >> Daily Life
Coca Cola Criticisms is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Coca Cola Criticisms books and related discussion.
Suggested News Resources
- Georgia Gov. Deal blasts religious freedom bill, says opposing same-sex
- Gathering under the "Georgia Prospers" moniker, companies include Home Depot, Coca-Cola, Delta Air Lines, and UPS, with some threatening to take their business elsewhere. Immediately after its passage in the Senate, Deal urged lawmakers to amend the ...
- Ditch The Risk, Reap Rewards With This ETF
- As an investment factor, low volatility, like other factors, has its critics.
- Coca-Cola Amatil: Soft drink giant says one can a week not unhealthy, as
- I can understand that reasoning, that it's better to have one coke [a week] than a coke every day. "But the more you have, the more you crave. Ideally, people should be drinking water.
- Brennan: With soda tax, everything old is new again
- One of Nutter's chief critics on the soda tax - besides the American Beverage Association, its lobbyists, and local retailers - was former Mayor John F. Street.
- Coca-Cola Sues Armenian Anti-Trust Body
- YEREVAN (RFE/RL) — A franchised bottler of the Coca-Cola Company working in Armenia has taken the country's anti-trust body to court, considering its latest decision to impose a fine on it groundless.
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Li'l Abner by Al Capp
- December 30, 2013
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That looks an awful lot like Phineas of the Fabulous Furry Break Brothers on the far right. Just needs the glasses.
That's a take-off on the old English song—-Drink To Me Only With Thine Eyes.
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This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige®) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged ≥50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual–analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC™]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3–5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3–5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC™ total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely regarded as the agents of choice when treating the chronic pain of osteoarthritis (OA) [1-3]. This class of drugs prevents prostaglandin synthesis by nonselectively inhibiting both isoforms of cyclo-oxygenase (COX) [4,5]; this profile also accounts for their common side effects, including gastric irritation, renal impairment and inhibition of platelet aggregation [6-9]. NSAID use is associated with an increased risk for gastrointestinal ulcers and associated ulcer complications such as bleeds and perforations [7]. COX-2 selective inhibitors have demonstrated analgesic and anti-inflammatory efficacies comparable with those of traditional NSAIDs in patients with arthritis, combined with an improved safety profile [10-13].
Lumiracoxib (Prexige®, Novartis Pharma AG, Basel, Switzerland) is a novel COX-2 selective inhibitor in development for the treatment of OA and acute pain. Selectivity for COX-2 over COX-1 has been demonstrated for lumiracoxib both in vitro and in vivo [14]. In addition, lumiracoxib is distinct from other COX-2 selective inhibitors in that it lacks a sulphur-containing moiety but rather possesses a carboxylic acid group, which confers weakly acidic properties (pKa 4.7) [15]. The unique molecular structure translates into a distinct pharmacokinetic profile, such that lumiracoxib has a rapid plasma uptake (Tmax 2 hours) and a short mean plasma half-life of approximately 4 hours [16]. The pharmacokinetics of lumiracoxib are characterized by good oral bioavailability [17], dose proportionality with no accumulation, and no significant influence of age, sex, or body weight on apparent plasma clearance [18]. In addition, lumiracoxib has demonstrated sustained higher synovial fluid concentrations compared with plasma concentrations in patients with rheumatoid arthritis [19].
A four-week phase II study evaluated the efficacy of four doses of lumiracoxib (50 mg twice daily, 100 mg twice daily, 200 mg twice daily and 400 mg once daily) in patients with knee or hip OA [20]. All doses reduced OA joint pain intensity, with significance over placebo observed after the first week of treatment.
Rapid onset of analgesia is necessary if patients are to accept traditional NSAIDs or COX-2 selective inhibitor treatment, because these patients often use their medication intermittently on a pro re nata (when required) basis [21]. The present study was conducted to evaluate the analgesic efficacy and tolerability of lumiracoxib 400 mg once daily (four times the recommended chronic dose in OA) and to compare them with those of placebo and celecoxib 200 mg twice daily (recommended dose in OA is 200 mg/day, administered as a single dose or as 100 mg twice daily) [22] in patients with OA of the knee over a 7-day period, with particular focus on the onset of analgesia following the first dose.
This was a randomized, double-blind, placebo and active comparator controlled, parallel group study conducted in 32 centres in Germany. All patients provided written informed consent before study-related procedures were conducted, and the study was performed in accordance with the principles of good clinical practice and the Declaration of Helsinki (1964 and subsequent revisions). The study consisted of two phases: a single-dose pain assessment phase and a multiple-dose pain assessment phase.
Male or female patients aged 50 years or older with moderate-to-severe symptomatic OA of the knee, according to the American College of Rheumatology criteria [23], were eligible for inclusion. At screening, patients were required to be receiving NSAIDs/simple analgesics for their OA and to have pain intensity in the affected target joint of ≥40 mm on a 100 mm visual–analogue scale (VAS) after activity (walking 20 paces on a flat surface).
Exclusion criteria included secondary OA, concomitant significant medical problems, a history of gastrointestinal bleeding, peptic ulceration or open knee surgery within one year of study entry, and hypersensitivity to analgesics, antipyretics, NSAIDs, or sulfonamides. Patients who had undergone observational arthroscopy, arthroscopic surgery, or lavage within the preceding 180 days were not eligible for enrolment. Female patients who were pregnant, lactating, or of childbearing age and not using adequate means of contraception were excluded.
Concomitant treatment with H2 receptor blockers, proton pump inhibitors, misoprostol, methotrexate, warfarin, analgesics (other than rescue medication) and systemic corticosteroids was not permitted during the study; neither was physiotherapy for the target joint. Patients who had received intra-articular corticosteroids in the study joint during the three months before the study were excluded. Patients receiving chondroitin and/or glucosamine were excluded. Patients were permitted to use rescue medication (acetaminophen ≤3 g/day) during the study, although use of rescue medication was prohibited from midnight before the baseline clinic visit.
After an initial screening visit patients entered a 2- to 7-day washout period, during which any treatment with NSAIDs/analgesics was discontinued (if applicable). Patients were required to have VAS actual pain intensity at baseline of ≥50 mm for the most severely affected (target) knee joint after activity. (The pain requirement at baseline following washout [≥50 mm] was greater than at screening [≥40 mm]; thus, an increase in pain from screening to baseline was required for study entry.) Patients were subsequently randomly assigned (in the ratio 2:2:1) to oral treatment with lumiracoxib 400 mg once daily, celecoxib 200 mg twice daily, or placebo. Blinding was maintained by the double-dummy technique. Following 7 days of study medication, patients had a final clinic visit, during which final pain assessments were made, pain records from the patient diary were reviewed, and repeat functional status and safety assessments were made. Each patient was contacted by telephone for follow up approximately 14 days after study completion.
Compliance was evaluated by quantifying the returned study medication. Patients taking at least 80% of prescribed daily medication were deemed compliant.
In the single-dose pain assessment phase of the study, the analgesic efficacy of a single dose of study medication was evaluated. On the first day of treatment each patient rated actual pain intensity (100 mm VAS, after activity) for the target joint immediately before and at 3 and 5 hours after the first dose of study medication. The primary efficacy variable was pain intensity difference (PID) between the baseline pain assessment and the mean of the 3-hour and 5-hour pain assessments on the first day of treatment.
Secondary variables included evaluation of treatment over 7 days during the multiple-dose pain assessment phase. Patients rated actual pain intensity, average pain intensity and worst pain intensity using a 100 mm VAS after activity in the morning and evening immediately before taking the next dose of study medication. Actual pain intensity difference (APID), average pain intensity difference (AVPID) and worst pain intensity difference (WPID) from baseline were calculated. Pain relief was recorded each evening (between 18:00 hours and 22:00 hours) and morning (30–60 minutes after getting up) after taking the study medication using a 5-point categorical scale (0 = none, 1 = little, 2 = moderate, 3 = a lot, 4 = complete).
In order to evaluate the effect of study medication on usage of rescue medication, all patients were requested to record the date and time of rescue acetaminophen use after randomization.
Functional status was assessed at baseline and study completion using the total and all three subscales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) LK3.1 questionnaire (Likert scale) [24]: pain; stiffness; and difficulty in performing daily activities (DPDA).
At study end (or premature discontinuation), all patients completed a global evaluation of treatment effect, which was recorded on a 4-point categorical scale (1 = poor, 2 = fair, 3 = good, 4 = excellent).
All adverse events reported by the patient or discovered by the investigator during the study period were recorded and evaluated in terms of seriousness, severity and potential relationship to study medication. Safety assessments consisted of routine laboratory tests (haematology, biochemistry and urinalysis), measurement of vital signs and 12-lead electrocardiogram recordings, which were completed at screening/baseline and study end.
The primary efficacy variable was the APID between the baseline pain assessment and the mean of the 3-hour and 5-hour actual pain assessments after the first dose of study medication.
To maintain an overall 5% significance level, a closed-test procedure with a predefined sort order of the three hypothesis tests (each at the 5% two-sided level) of the primary variable was used [25]: superiority of lumiracoxib 400 mg once daily versus placebo; noninferiority of lumiracoxib 400 mg once daily versus celecoxib 200 mg twice daily; and superiority of lumiracoxib 400 mg once daily versus celecoxib 200 mg twice daily. In addition, in a prespecified, exploratory manner, celecoxib was assessed versus placebo to examine the sensitivity of the trial.
Use of sample sizes of 132 (lumiracoxib 400 mg once daily), 132 (celecoxib 200 mg twice daily) and 66 (placebo group) resulted in powers of 94%, 98% and 80%, respectively, to reject the three hypotheses in turn. The noninferiority margin of lumiracoxib 400 mg once daily to celecoxib 200 mg twice daily was predefined as 5 mm. An overall dropout rate of 10% and a common standard deviation of 30 mm were assumed.
Analysis of efficacy was performed for all randomized patients who had been exposed to study medication (intent-to-treat population). All randomized patients were included in the safety analysis.
PID was analysed using analysis of covariance (ANCOVA). The statistical fixed-effects model considered treatment and centre as main effects, whereas baseline actual pain was used as a covariate. Data from small centres were pooled using a predefined algorithm.
APID, AVPID and WPID were analyzed at each time point relative to baseline, using ANCOVA (as described above), and pair-wise comparisons of treatment groups were calculated. Pain relief was analyzed using a multiple logistic regression model with treatment as an explanatory variable. The WOMAC™ Total and subscale scores were analyzed using an ANCOVA model, fitting scores at baseline, pooled centre and treatment group. Finally, pair-wise comparisons of treatment groups for the patient's global evaluation of treatment effect were performed using a Cochran–Mantel–Haenszel test, adjusting for pooled centre. All secondary variables were analyzed on the intent-to-treat population and all tests were two sided, using a 5% level of significance.
After screening 418 patients, a total of 364 were enrolled into the study and received at least one dose of study medication (lumiracoxib 400 mg once daily [n = 144], celecoxib 200 mg twice daily [n = 145] and placebo [n = 75]). Five patients (1.4%) withdrew from the study, four from the lumiracoxib group (three due to adverse events and one for unsatisfactory therapeutic effect) and one from the celecoxib group (due to protocol violation).
Overall, the treatment groups were balanced for baseline demographics and clinical characteristics (Table (Table1).1). Between group differences in the distribution of female patients and patients aged ≥75 years were not statistically significant (sex, P = 0.3105; age, P = 0.8416) and were not considered to have influenced the outcome of the study.
More than 90% of patients in each treatment group achieved satisfactory compliance with prescribed medication during the course of the study.
The three main hypotheses of the primary efficacy variable (APID between the baseline pain assessment and the mean of the 3-hour and 5-hour actual pain assessments after the first dose of study medication) were tested in sequence. First, lumiracoxib exhibited a statistically superior analgesic effect to that of placebo, with an estimated treatment–placebo difference (least square mean) of 5.8 mm (95% confidence interval [CI] 1.89–9.75 mm; P = 0.004; Table Table2).2). Second, lumiracoxib was confirmed to be noninferior to celecoxib in this analysis, because the lower limit of the 95% CI for the difference between lumiracoxib and celecoxib (lumiracoxib–celecoxib difference) was less than -5 mm. In the third hypothesis test, lumiracoxib was not significantly superior to celecoxib in terms of the analgesic efficacy of the first dose (estimated least square mean difference in favour of lumiracoxib: 2.2 mm, 95% CI -1.06 to +5.45 mm; P = 0.185). Furthermore, celecoxib did not have a statistically superior analgesic effect compared with placebo (estimated treatment–placebo difference [least square mean]: 3.6 mm, 95% CI -0.29 to +7.54 mm; P = 0.069; Table Table22).
As early as 3 hours after the dose on the first day, lumiracoxib exhibited superior analgesic efficacy to that of placebo (estimated treatment–placebo difference: 4.5 mm, 95% CI 0.44–8.63 mm; P = 0.03). At the same time point, the percentages of patients who assessed their pain relief as either 'a lot' or 'complete' relative to baseline were 12.5%, 5.5% and 9.3% in the lumiracoxib, celecoxib and placebo groups, respectively. Corresponding values 5 hours after the dose were 11.1%, 10.3% and 8.0%, respectively.
For the second assessment phase (multiple dosing over 7 days), lumiracoxib was statistically superior to placebo at all time points and celecoxib was superior to placebo at most time points (Figure (Figure1).1). Lumiracoxib was numerically superior to celecoxib throughout the study, but this achieved statistical significance only in the evening assessment of the first day of treatment (P = 0.022). Although not tested statistically, celecoxib-treated patients appeared to have somewhat less pain relief at the evening assessments compared with morning assessments. At study end, the estimated differences for APID relative to placebo were statistically significant for both lumiracoxib (10.7 mm, 95% CI 4.70–16.7 mm; P = 0.001) and celecoxib (8.7 mm, 95% CI 2.68–14.66 mm; P = 0.005). However, no significant difference was apparent between the active treatment groups at study end (estimated difference for lumiracoxib versus celecoxib in APID: 2.0 mm, 95% CI -2.94 to +7.01 mm; P = 0.421).
At study end, 13.9% of patients receiving lumiracoxib experienced 'complete' pain relief at study end compared with 5.5% of patients receiving celecoxib and 5.3% of patients receiving placebo. Furthermore, the percentages of patients who assessed their pain relief as 'a lot' were 34.7%, 30.3% and 22.7% in the lumiracoxib, celecoxib and placebo groups, respectively. With respect to pain relief, lumiracoxib was significantly superior to placebo (P = 0.001) whereas celecoxib just failed to achieve significance (P = 0.051). There was no significant difference between the active treatment groups at study end (P = 0.076).
The majority of patients (87% of lumiracoxib-treated patients, 82% of celecoxib-treated patients and 84% of placebo-treated patients) did not require rescue acetaminophen during the study.
Overall, both active treatment groups were characterized by significantly improved WOMAC™ total scores compared with placebo at study end (Table (Table3).3). In addition, lumiracoxib was significantly superior to celecoxib (P = 0.026) with regard to the WOMAC™ total score. Lumiracoxib was superior to both celecoxib (P = 0.015) and placebo (P < 0.001) with regard to the DPDA subscale score, with the difference between the celecoxib and placebo groups just failing to achieve significance (P = 0.056). Mean changes from baseline in WOMAC™ total and subscale scores are also shown in Table Table33.
In terms of patient's global evaluation of treatment effect, substantially more patients in the lumiracoxib group (58.1%) assessed treatment effect as either 'excellent' or 'good' at study end compared with 48.6% of celecoxib-treated patients and 25.3% of placebo-treated patients (Figure (Figure2).2). For both active treatments, a highly significant difference relative to placebo was apparent (lumiracoxib, P < 0.001; celecoxib, P = 0.001); however, there was no difference between active treatment groups (P = 0.100).
Only one serious adverse event was reported (silent myocardial infarction in a celecoxib-treated patient). This event was suspected to be related to the study drug but it did not lead to premature discontinuation because it was detected on electrocardiogram recordings on the final study day. Three patients (2.1%) in the lumiracoxib group were prematurely withdrawn from the study because of adverse events, which included moderate bronchitis and mild nasopharyngitis in one patient each (both were considered to be unrelated to study drug). A further patient was withdrawn because of severe upper abdominal pain that was considered by the investigator to be related to study drug. Of note, this patient had previously (six months before study entry) experienced an episode of abdominal pain during short-term therapy with celecoxib.
Overall, a comparable and low proportion of patients in each treatment group reported at least one adverse event during the study: 14.6% in the lumiracoxib group, 11.0% in the celecoxib group, and 13.3% in the placebo group. Gastrointestinal disorders were the most frequent adverse events, occurring with greater frequency in both active treatment groups than with placebo. The majority of adverse events in each treatment group were of mild severity. Moderate adverse events were infrequent and were not associated with a specific body system.
Adverse events assessed by the investigator as being possibly study drug related occurred in 6.3%, 6.2% and 8.0% of patients in the lumiracoxib, celecoxib and placebo groups, respectively. Overall, adverse events affecting the gastrointestinal system were most frequently reported as being possibly study drug related (4.2%, 4.8% and 2.7% of patients in the lumiracoxib, celecoxib and placebo groups, respectively). There were no relevant changes in vital signs or electrocardiographic variables between baseline and study end in any of the treatment groups.
This short-term study established that lumiracoxib, a novel COX-2 selective inhibitor, provides rapid and effective analgesia in patients with OA of the knee. The primary efficacy variable (mean PID 3–5 hours after dose) was similar to those used in other single-dose studies of COX-2 selective inhibitors in acute pain [26] or in patients with OA flare [27]. Celecoxib was chosen as the active comparator because of its established analgesic efficacy in patients with OA of the knee [28,29].
Previous studies have shown that lumiracoxib provides significant pain relief over 13 weeks of treatment in patients with OA compared with placebo [30,31]. In the present study we found that the first dose of lumiracoxib 400 mg decreased OA pain intensity (100 mm VAS) 3–5 hours after dose by 19.8 mm (P = 0.004, versus placebo) compared with a mean decrease of 16.8 mm (P = 0.069, versus placebo) with celecoxib 200 mg and 13.4 mm with placebo. Lumiracoxib was noninferior but not significantly superior to celecoxib in this analysis 3–5 hours after dose. These findings are consistent with earlier pharmacodynamic studies with lumiracoxib, which found the difference from baseline in mean VAS scores at 4 hours after dosing to be >20 mm with lumiracoxib 400 mg compared with <5 mm in placebo-treated patients [32]. The results reported here are similar to findings with other COX-2 selective inhibitors, where the speed of onset of analgesia was studied in an OA population meeting OA flare criteria [27]. At 3 hours after the dose, the mean decrease in OA pain intensity (100 mm VAS) was 21.7 mm with valdecoxib 10 mg and 19.8 mm with rofecoxib 25 mg, as compared with 15.5 mm with placebo (P < 0.01). In addition, it has been reported that a 30–33% decrease in VAS pain scores represents a clinically meaningful change in either acute or chronic pain [33,34]. For lumiracoxib 400 mg, a 30% decrease from actual pain at baseline was observed at the 3–5 hour post-dose assessment, suggesting that this change in pain intensity was clinically relevant.
The primary objective of the study was to examine the single-dose onset of analgesia with lumiracoxib. As such, a dose of lumiracoxib appropriate for acute use (400 mg) was used. Previous studies with this dose of lumiracoxib in acute pain have shown that it provides rapid and effective analgesia [35-37]. The recommended chronic dose of lumiracoxib is 100 mg daily. In order for the active comparison to be relevant, a dose of celecoxib considered to be appropriate for acute pain was chosen (200 mg twice daily) [22]. (The recommended dose of celecoxib in OA is 200 mg daily, administered as a single dose or as 100 mg twice daily [22].)
Both lumiracoxib and celecoxib had statistically significant efficacy compared with placebo in terms of secondary efficacy variables assessed during the multiple-dose assessment period, including APID, AVPID, WPID and extent of pain relief. The significant treatment–placebo differences in actual pain intensity (100 mm VAS) at study end (10.7 mm for lumiracoxib 400 mg once daily, P = 0.001; 8.7 mm for celecoxib 200 mg twice daily, P = 0.005) were comparable with those previously reported after 13 weeks of treatment (8.8 mm for lumiracoxib 400 mg once daily; 6.3 mm for celecoxib 200 mg once daily) [31]. At study end, no significant differences were observed between active treatments in terms of APID. Substantially more patients in the lumiracoxib group assessed treatment effect as 'excellent' or 'good' at study end compared with those who received celecoxib (58% and 49%, respectively). Interestingly, only around 25% of placebo recipients rated treatment as 'poor' at the end of the study, despite a progressive increase in APID during treatment. This 'placebo effect' is not unique to the treatment of patients with joint disorders [38] and is perhaps attributable to psychological mechanisms such as an awareness of being closely observed and active compliance with the presumed wishes of researchers. It is notable, however, that against this background lumiracoxib maintained significant superiority in terms of analgesic efficacy.
Patients received celecoxib 200 mg in the morning and evening, whereas lumiracoxib was given in the morning only, with a lumiracoxib-matched placebo administered in the evening. The multiple-dose actual PID scores for lumiracoxib over the 7-day treatment period show that the analgesic effect of lumiracoxib is maintained over a 24-hour period and therefore supports once-daily administration.
Evaluation of WOMAC™ subscales in the study allowed assessment of the effect of treatment on aspects of patients' daily lives relating to their condition, including pain, stiffness and the ability to perform daily activities. Overall, both lumiracoxib and celecoxib were associated with significantly lower pain and stiffness WOMAC™ subscale scores than placebo at study end. This is of particular significance for patients with knee OA, whose mobility and quality of life can be severely impaired [39]. Treatment–placebo differences in the WOMAC™ total score at 7 days (8.9 for lumiracoxib 400 mg once daily; 4.8 for celecoxib 200 mg twice daily) were comparable with those seen in longer 13-week studies with lumiracoxib and celecoxib (7.5 for lumiracoxib 400 mg once daily; 6.0 for celecoxib 200 mg once daily) [31]. It has been suggested that the minimal difference perceived (MDP) clinically from baseline in WOMAC™ DPDA score should be the minimal difference that is perceived by 75% of patients (MDP75), and a recent study of 1354 patients reported the MDP75 for the WOMAC™ DPDA subscale to be 5.2 [40]. In this study, the change from baseline in the DPDA subscale score was 15.4 for lumiracoxib 400 mg once daily compared with 12.3 for celecoxib 200 mg twice daily. This suggests that lumiracoxib provided clinically meaningful improvements in the ability of patients to perform daily activities during this 7-day study.
Lumiracoxib was well tolerated in this short study. The incidence of adverse events was comparable between all three groups. Previous studies of lumiracoxib tolerability over 13 weeks of treatment have found that lumiracoxib 200 mg or 400 mg daily has gastrointestinal tolerability that is superior to that of traditional NSAIDs including diclofenac, ibuprofen and naproxen [41].
Lumiracoxib 400 mg (four times the recommended chronic dose in OA) had a rapid onset of action in patients with OA of the knee, with an analgesic effect significantly superior to that of placebo that was demonstrated as early as three hours following the first dose. In addition, analgesia was maintained throughout the dosing interval; lumiracoxib was superior to placebo for overall pain relief at both morning and evening assessments throughout the study. The rapid onset of analgesia represents a useful attribute in the management of patients with OA, who are likely to require intermittent pro re nata medication.
ANCOVA = analysis of covariance; APID = actual pain intensity difference; AVPID = average pain intensity difference; CI = confidence interval; COX = cyclo-oxygenase; DPDA = difficulty in performing daily activities; ITT = intent to treat; MDP = minimal difference perceived; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; PID = pain intensity difference; SD = standard deviation; VAS = visual–analogue scale; WOMAC™ = Western Ontario and McMaster Osteoarthritis Index; WPID = worst pain intensity difference.
Taiwo OA Fashola, Helen J Thurston, Klaus J Burger and Ulrich Trechsel were employees of Novartis when the study was conducted. All other authors have declared that they have no competing interests.
RHW, ES, GK, RM, HR and PS were investigators in the study, TOAF was the clinical trial leader (participating in study design and coordination), HJT performed the statistical analysis, KJB was Medical Advisor for Germany (participating in study design and coordination) and UT was the pain clinical programme leader (participating in study design and coordination). All authors were involved in data interpretation and participated in drafting the manuscript, and read and approved the final version.
The authors would like to thank Dr Alberto Gimona for his contribution to the design and conduct of this study.
This study was funded by Novartis Pharma AG. Preparation of the manuscript was supported by an educational grant from Novartis Pharma AG. Editorial support in preparing the manuscript was provided by Thomson ACUMED.
Investigators involved in the study from the various participating centres in Germany are as follows: Dr R Alten, Bochum; Dr W Daut, Kallstadt; Dr H-G Germann, Neunkirchen; Prof. J Grifka, Bad Abbach; Prof. HF Grobecker, Regensburg; Prof. FW Hagena, Bad Oeynhausen; Dr G Hein, Jena; Prof. HR Henche, Rheinfelden; Prof. E Hille, Hamburg; Dr T Jung, Deggingen; Dr G Krehan, Graben-Neudorf; Dr R Maeumbaed, Höchstadt; Dr W Mross, Bogen; Dr I Naudts, Rodgau-Dudenhofen; Dr D Popa, Veitsbronn; Dr H Runge, Erlangen; Dr Klinger, Offenbach; Dr E Schell, Nürnberg; Dr P Schlüter, Hemsbach; Dr G Scholz, Offenbach; Prof. J Sieper, Berlin; Dr Talke, Berlin; Dr H Thabe, Bad Kreuznach; Prof. G Weseloh, Erlangen; Prof. RH Wittenberg, Herten; Dr J Zacher, Berlin.
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