text: Phone: (888)326-5043 Email: email@example.com Home | Destinations | Interests | Cruise Specials | Tour Specials | Vacations | All About Sandals | About Me Collette Europe Spotlight on Tuscany Spotlight on Tuscany Register ProfileSend me a quotePrinter-friendlyEmail this pageNo ratings yetAdd review The rolling hills of Tuscany are home to sprawling vineyards, charming medieval hill towns and enchanting cities steeped in history, culture and legend. Discover them for yourself on this relaxing sojourn into the Italian countryside. Visit Florence, Siena, Pisa and San Gimignano. Sample cheese at the farm where it is made. Partake in a Tuscan cooking class. Savor a seven-night stay in Montecatini Terme, the famous resort and spa town. Enjoy free time to explore the cultural treasures of Florence, including Michelangelo's 'David.' Discover the charming town of Lucca, Italy's best-kept secret. Learn about the heroic deeds of WWII at remains of the Gothic Line and visit the Museum of Liberation. Enjoy fabulous local wines and the region's famous cuisine. This is Tuscany as you always imagined it. Call (888) 326-5043 for more information or to book today! Mention code 13729974Tour OperatorColletteOfferOffer valid through 3/31/2018Duration8 DaysItineraryDayDestinationDescriptionDay 1Montecatini TermeOvernight Flight: Rolling landscapes, savory wines, delicious food and stunning architecture...this can only be Tuscany. Unpack once on this journey among Italy's most charming towns.Day 2Montecatini TermeMontecatini Terme, Italy - Tour Begins: Your tour opens in the famous spa resort town of Montecatini Terme, nestled in the heart of the rolling hills of Tuscany. This evening, get to know your fellow travelers during a welcome dinner where regional foods and Italian wines kick off your adventure.Day 3FlorenceFlorence: A cultural tour in the 'Cradle of the Italian Renaissance' showcases the beautiful city of Florence. Join a local Florentine guide who highlights many of the city's priceless treasures including a visit to the Academy Gallery* - housing Michelangelo's monumental statue of David. At the Piazza del Duomo, the center of religious life in medieval Florence, see the impressive Cathedral of Santa Maria del Fiore and the gilded bronze doors of the Baptistery dedicated to St. John. Take the remainder of your day to explore this unparalleled city as you choose.Day 4LuccaLucca - Borgo a Mozzano - Gothic Line: Set out on a guided visit to Lucca, Tuscany's best-kept secret. Renaissance walls, Romanesque churches, medieval streets flanked by towers, and delightful squares are just some of Lucca's charms. Visit the medieval Basilica di San Frediano. Its otherwise simple facade is adorned with a colorful 13th-century mosaic. Enjoy some time to explore at your own pace. Then set off for Borgo a Mozzano to see the remarkable Ponte del Diavolo (Devil's Bridge). Continue on to the Gothic Line. Built by the Germans, it was one of their last lines of defense during WWII. We will visit the Museum of Liberation and see the actual fortifications and bunkers.Day 5PisaPisa: Explore the many historic sites in the ancient maritime Republic of Pisa including the Piazza dei Miracoli, or 'Field of Miracles' (UNESCO). Keep your camera handy during our stop at the famous Leaning Tower of Pisa. You probably won't be able to resist taking a picture that makes it appear as if you are holding this iconic structure up. Visit the Baptistery, the largest in all of Italy. This impressive building of Romanesque and Gothic architecture is known for its perfect acoustics. This evening we travel to the quiet countryside to learn the secrets of traditional Tuscan cuisine. Partake in a cooking class featuring a bounty of local ingredients and culinary techniques that have been passed down for generations. Then sit down and enjoy the fruits of your labor during dinner.Day 6SienaSiena: Welcome to Siena. Discover this charming town with a local guide. Embark on a walking tour through its narrow Gothic streets. Take in stunning palaces, mansions and the historic Piazza del Campo along the way. Then, it's your choice! Explore Siena's beautiful Gothic Cathedral at your own pace or join your guide to get to know local life in a contrada (neighborhood). Next we make our way to a Tuscan winery and meet the people behind some of Chianti's finest wines. Learn from experts as you savor a selection of the local varieties. You'll also learn about the art of winemaking and the process of making olive oil.Day 7Montecatini TermeMontecatini Terme: The day is yours to relax and experience the local flavor. Take this opportunity to shop at the local boutiques and dine at one of the many fine local restaurants. Or, perhaps you will choose an optional excursion to Cinque Terre with its rugged coastline dotted with terraced vineyards. Explore its string of fishing villages nestled between the mountains and the Mediterranean.Day 8San GimignanoCheese Farm Visit - San Gimignano: Begin the day with breathtaking views of the Tuscan hills as we make our way to a cheese farm. Learn how the famous pecorino cheese is made before sampling it for yourself. Afterwards, travel to the hilltop village of San Gimignano, one of the most picturesque places in Tuscany. Explore this enchanting medieval town, from its famous 14 towers to its magnificent vistas overlooking the vineyards of Tuscany. Enjoy free time and perhaps indulge in some gelato. A delightful experience awaits this evening when you attend a Tuscan feast featuring traditional cuisine and savory wines in the magical Tuscan countryside.Day 9Montecatini TermeMontecatini Terme - Tour Ends: Your journey comes to a close today. Depart with many fond memories of Tuscany.Dates/PricingClick Quote or call (888) 326-5043 to get additional information on your chosen travel date. Special offers or competitive pricing may be available!DatePrice / DescriptionQuoteMay 11, 2018$1,799.00* (USD) / Land OnlyMay 18, 2018$1,799.00* (USD) / Land OnlyJune 08, 2018$1,799.00* (USD) / Land OnlyJuly 13, 2018$1,799.00* (USD) / Land OnlyAugust 17, 2018$1,799.00* (USD) / Land OnlySeptember 07, 2018$1,799.00* (USD) / Land OnlySeptember 14, 2018$1,799.00* (USD) / Land OnlySeptember 28, 2018$1,799.00* (USD) / Land OnlyOctober 05, 2018$1,799.00* (USD) / Land OnlyOctober 12, 2018$1,799.00* (USD) / Land OnlyOctober 19, 2018$1,799.00* (USD) / Land OnlyNovember 02, 2018$1,599.00* (USD) / Land OnlyNovember 04, 2018$1,599.00* (USD) / Land OnlyNovember 07, 2018$1,599.00* (USD) / Land OnlyNovember 09, 2018$1,599.00* (USD) / Land OnlyNovember 30, 2018$1,599.00* (USD) / Land OnlyJanuary 18, 2019$1,349.00* (USD) / Land OnlyFebruary 15, 2019$1,349.00* (USD) / Land OnlyMarch 01, 2019$1,599.00* (USD) / Land OnlyMarch 15, 2019$1,599.00* (USD) / Land OnlyMarch 22, 2019$1,599.00* (USD) / Land OnlyApril 05, 2019$1,699.00* (USD) / Land OnlyApril 24, 2019$1,699.00* (USD) / Land OnlyApril 26, 2019$1,699.00* (USD) / Land OnlyLodgingGrand Hotel Tettuccio Montecatini Terme, ItalyDisclaimer* NOTE:Tour prices are land only rates based on per person, double occupancy. Some dates may feature various changes in hotels, sightseeing and inclusions. Please confirm your specific itinerary at the time of booking. Government taxes and fees are additional. Land rates are guaranteed at time of deposit. Certain taxes and fees are to be paid upon exiting the country in local currencies. Airfare is additional and is available through Collette Vacations. Caribbean DestinationsHawaii DestinationsMexico DestinationsEurope DestinationsUSA DestinationsSandals Special OffersFree Destination Weddings!Sandals Resorts BrochureBeaches Vacations!Win a Free Honeymoon!!Honeymoon Registry!Pittsburgh WeddingsNo Problems in Jamaica!Top SuppliersAir Tahiti Nui


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Question about Pioneer 6 CD changer PD-M501 With One Wxtra Magazine
It powers up but when I press eject the cartridge won't come out
Posted by Anonymous on
SOURCE: I have freestanding Series 8 dishwasher. Lately during the filling cycle water hammer is occurring. How can this be resolved
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Posted on Jan 02, 2017
SOURCE: Ejecting magazine on Pioneer CDX-fm1257
I have very gently taken a pair of needle nose pliers and grasping the edge of the cartridge that holds the disk carefully work it back into the magazine.
Posted on Jan 09, 2008
SOURCE: My Pioneer DEH-P835R Cd Player will play my cd but wont eject
Check in the front and you should see a small hole thats about the same diameter as a paper clip. Open up a paperclip to a straight 2 inches and poke it through the hole. It should release the door so you can get it open or at least seat the cd if thats whats making it not open.
Posted on Apr 26, 2009
SOURCE: Pioneer PD-M501 6-CD Player manual and what magazine cartridge
The standard cartridge for the Pioneer PD-M501 is the Pioneer JD-M300 6-disc magazine, and you can find them at Amazon.com for $25 new. The JD-M300 fits a lot of different brands of CD players, not just this particular brand and model. And here's a link to a copy of the owner's manual: http://www.scribd.com/doc/22613342/Pioneer-PD-M601-M551-M501
Posted on Jul 10, 2010
SOURCE: Pioneer CDX-P670 Wiring / Power
hi according to the manual the two pin connector is for the power and the pin nearest the square control plug is ground, the other pin is +12, have tried this with mine and it works
Posted on Jul 25, 2010
SOURCE: Pioneer PD-M501 6-CD Player manual and what magazine cartridge
CDs go in the Upside Down position. Your PD M501 will accept PRW 1139, PRW 1141 and 163.
Lexus Models: CDX-M9071zt CDX-M8036, CDX-M9071, CDX-M9741, CDX-M9751
Philips CDC-875 Pioneer CDX-FM35 Pioneer CDX-FM45 Pioneer CDX-M30 Pioneer CDX-M40 Pioneer PD-DM802
* Pioneer PD-DM902 Pioneer PD-M403 Pioneer PD-M423 Pioneer PD-M426 Pioneer PD-M450 PD-M453 PD-M455
* Pioneer PD-M501 Pioneer PD-M502 PD-M503 Pioneer PD-M510 Pioneer PD-M530 Pioneer PD-M550 Pioneer PD-M552 Pioneer
* PD-M600 PD-M601 PD-M603 Pioneer PD-M610 Pioneer PD-M630 Pioneer PD-M650
* Pioneer PD-M701 Pioneer PD-M702 Pioneer PD-M703 Pioneer PD-M710 Pioneer PD-M730
* Pioneer PD-M801 Pioneer PD-TM1 Pioneer PD-TM2 Pioneer PD-TM3 Pioneer CCS-430
* DCM-444 and DCM 777
Posted on Feb 28, 2011
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Lunch Puzzle is a fascinating puzzle game. You must feed hungry but very kind monster. To do that you must collect three and more foods in row and in this case monster can eat it.
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Island Lodge Road in Ottawa, Ontario
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Illinois Ag News Headlines
Illinois Sportsmen Invited to Farm Bill Forums Jan. 16, 17
Illinois Ag Connection - 01/10/2018
The Theodore Roosevelt Conservation Partners (TRCP), in cooperation with the Illinois Conservation Foundation (ICF), has scheduled three public forums entitled "Illinois Sportsmen's Guide to the 2018 Farm Bill."
The purpose of the forums is to help sportsmen learn about federal Farm Bill conservation programs that are important to the future of fish and wildlife habitat, and to the future of hunting and fishing in Illinois.
According to an analysis by the TRCP, if Congress fails to re-authorize these important Farm Bill conservation provisions in 2018, Illinois stands to lose up to 900,000 acres of wildlife habitat enrolled in programs like the Conservation Reserve Program (CRP), and more than 16,000 acres of hunting and fishing access funded under the Farm Bill through the Illinois Recreational Access Program (IRAP). Farm Bill programs also affect downstream water quality in Illinois rivers, lakes and streams.
"The 2018 Farm Bill will have a big impact on Illinois," said Eric Schenck, executive director of the Illinois Conservation Foundation. "These forums are a chance for sportsmen to learn what is at stake and how to make their voices heard in Washington, D.C."
The following Sportsmen Farm Bill forums are open to the public:
- Jan. 16, 5:30 p.m. - 6:30 p.m., National Great Rivers Research and Education Center, Conference Room, One Confluence Way, East Alton, IL
- Jan. 17, 11:30 a.m. - 12:30 p.m., Illinois Department of Natural Resources (Headquarters), Lakeview Conference Room B-C, One Natural Resources Way, Springfield, IL
- Jan. 17, 5:30 p.m. - 6:30 p.m., Gateway Building, Conference Room, 200 NE Water Street, Peoria, IL
To register for a Farm Bill forum and to download a copy of the "Illinois Sportsmen's Guide to the 2018 Farm Bill", go to www.ILCF.org.
The Theodore Roosevelt Conservation Partnership, or TRCP, is a non-profit 501(c)(3) coalition of conservation organizations, grassroots partners and outdoor related businesses, the main goal of which is enhancing conservation and preserving access for hunters and fishermen.
The Illinois Conservation Foundation, or ICF, is a non-profit 501(c)(3) conservation organization dedicated to conserving Illinois parks, fish and wildlife areas, and natural habitats, and maintaining Illinois outdoor heritage traditions.
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Other Illinois Headlines
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DRIFTing to Fast, Precise Data
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Builta Named GROWMARK Vice President, Energy and Logistics
In Sweet Corn, Workhorses Win
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- Member since May 6, 2013
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jeffakalucas g30rg3ryan's video
Dec 29, 2017 at 16:19Dec 29, 2017
Mauricio rules! I was with a group checking out a new feature at Blue (a rock ramp, gap to bridge landing) that had the roughest runout ever. Anywho... we watched as some came and challenged it. Some did good, some did a little better. Some were fast and some were slow... enter Mauricio. He hit it faster than anyone by a long shot, almost cleared the wood landing. He went far right, just missing a tree but landing and then gapping into the runout, a line that no one else was close to. Everyone was scratching their heads going "HOLY SHIT..."
jeffakalucas mikelevy's article
Dec 3, 2017 at 17:19Dec 3, 2017
The Insolent DH Bike Uses a Fox 40 Stanchion Tube as a Shock
"There are no non-drive-side photos of the bike, but you can see what looks like a single-sided bolt hole and two air valves if you look closely at the renderings, with an air piston dividing the chamber into two sections."
jeffakalucas Eastern-States-Cup's article
Jul 12, 2017 at 4:37Jul 12, 2017
Vittoria ESC - Plattekill DH Race Report and Video
They don't have any close/large/cheap lodging, they aren't near anything, you can't take the family (I mean, you can, my little family won't have any fun.) You have to be dedicated to spend a weekend at Platty vs. anywhere else. At Mountain creek we can stay, my family hits the water park and I go ride DH. I agree that I loved riding there but some trails have 12" of leaf coverage, man-made wood features that are rotted and may fail if you attempt to hit it, the trail signs are non-existent. It's a catch 22: They don't have money to put into the trails but people don't go cause they don't have money to put into the trails? Also, bike rentals at Platty are something like $2,000 refundable deposit. People don't have $2k that can go towards a shitty KHS rental. I get they want to protect themselves but...
jeffakalucas pinkbikeaudience's article
Jun 4, 2017 at 6:43Jun 4, 2017
Finals Result: Fort William DH World Cup 2017
@joose: She did some practice runs yesterday before qualitying and said her knee just didn't feel up to it and bailed
jeffakalucas Flo356's article
Jun 4, 2017 at 5:20Jun 4, 2017
DH World Cup Round 2, Fort William - Replay
Rachel Atherton out with a dislcoated shoulder....
jeffakalucas shimano's article
May 24, 2017 at 5:20May 24, 2017
Components of Adventure: Bryn Atkinson and Bas Van Steenbergen Ride Réunion Island
Music by Good Old War. Went to school with these guys. Crazy to pull up a MTB movie and hear them.
jeffakalucas mikekazimer's article
Apr 26, 2017 at 10:21Apr 26, 2017
SRAM's New Code Brakes - First Ride
@bobjerg: I also had no problem ordering and buying the bleeding edge adaptor. Caution, there are different avid/sram bleed kits. The basic bleed kits use a shitty syringe that has hoses that use a plastic thing to twist in. This will not work with the bleeding edge adaptor. You'll need the sram/avid PRO bleed kit that allows the threaded coupling to attach too. Ask me how I know!
jeffakalucas redbullbike's article
Apr 10, 2017 at 18:16Apr 10, 2017
Off-Season Antics with Aaron Gwin and Richie Rude - Video
@kwapik: that was awesome. Thanks for that!
jeffakalucas redbullbike's article
Apr 10, 2017 at 11:56Apr 10, 2017
Off-Season Antics with Aaron Gwin and Richie Rude - Video
I love seeing Gwin not being Gwin and taking my appreciation to another level. It's not often you see Gwin go for the huge huck, or the nose manual down the sewer wall. Both these guys are incredible on and off the bike and great representatives for mountain biking.
Posted in "Show your all mountain bike"
Mar 25, 2017 at 10:47Mar 25, 2017
Photo by jeffakalucas
7,182 views


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Lewmar Fiddle Blocks
Fiddle blocks from Lewmar are used in purchase systems to allow the trimmer to sheet in higher loads with ease. The Fiddle Blocks can be attatched onto the boom giving you a powerful purchase on your main block and tackle.
Lewmar HTX Fiddle Blocks
The HTX Lewmar Block range is the result of years of design and manufacturing experience, combined with collaboration with boat builders, designers, and sailors. Drawing upon the design of the racing range of sailboat blocks, the HTX blocks are constructed from a minimal number of alloy parts, providing enhanced reliability when sailing.
Lewmar Mid Range Fiddle Blocks
Racing Blocks from Lewmar are designed to achieve the best strength-toweight ratio within legal race limits. These sailboat blocks feature alloy cheeks and composite sheaves which run on dual Delrin ball races. They range in size from 60 mm to 80 mm.
Lewmar Synchro Fiddle Blocks
Synchro Lewmar sailboat blocks are engineered for speed, efficiency and superior handling. These blocks suit a range of purposes from performance cruising yachts to specific high-load low-movement applications on racing sailboats. Lewmar uses a combination of scientifically optimised block geometry, a Free-Spin bearing and self-aligning head to reduce friction and increase efficiency by up to 40% over budget blocks on mainsheet systems.
- Anchoring & Docking
- Backstay Adjusters
- Bailers
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- Davits & Hoists
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- Hydraulics
- Mainsail Handling
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- Spares Parts
- Spinnaker Poles
- Steering
- Traveler Cars & Tracks
- Winches
Copyright © 2018 Mauri Pro Sailing.


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Friends of Epsom Town plan following Portas review
A group aimed at engaging with people who use a town centre in Surrey is to be formed following a suggestion in a report by TV retail expert Mary Portas.
Liberal Democrat councillors are planning to launch Friends of Epsom Town, which will be a key consultee on all matters concerning the town centre.
The borough council was last month awarded a £100,000 government grant to reinvigorate the local economy.
It came from a £10m High Street fund set up after advice from Ms Portas.
There is also to be a new Business Forum to bring together key local traders, with the hope of encouraging members to match the government grant.
The Lib Dems also want to appoint a town centre manager.
'Lots of ideas'
Councillor Julie Morris said: "There are a number of Friends' groups already and we hope that many of those people will be interested in a new entity dealing entirely with our economic situation and restoring its vitality."
She said Friends of Epsom Town could become a key consultee when it comes to spending the grant money.
"Businesses have their say, but there's nothing for individual people who shop and visit," she said.
"They have lots of ideas and suggestions as to how we can encourage more people to use our shops and facilities.
A meeting to launch the group will be held on Monday 23 July at 19:30 BST at Epsom Methodist Church, and councillors hope it will be attended by as many residents as possible interested in "driving the organisation forward".


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Launching Ninety Day Loans At Everyday Loans Uk
When you fall into situations where you can't delay to take a decision in your financial career you need to take some external help as soon as straightforward. Fast loans are what you might be trying to find. But products and solutions do not need to repay the loan for long repayment tenure then fast short term loans are probably what are usually looking in order for.
Don't forget out-of-pocket charitable contributions. Many taxpayers come up tax credits on more considerable charitable gifts, by check or payroll deduction. However, you can also disregard out-of-pocket costs of increasing charity.
Because of this our next tip. What If I Can't Are entitled to A Bank Car College loan? If you're not "bankable" just yet, consuming.there are still lenders available that will offer you a loan, however, the rate won't be as pretty. I'd first ask the loan officer in the bank when having anyone they'd recommend to refer you to which to. You can also do they're certified on web pages that funnel for "bad credit auto short-term loans" and you'll get a slew of links to simply. Some of these sites will search multiple lenders for both you and could save some precious time.
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The report prepared and presented to the Government by crime analyst and commentator, Prof Ramesh Deosaran, on proposals to create a more effective Trinidad and Tobago Police Service (TTPS), has come up with the startling and likely ineffective suggestion that the top jobs in the service be decided by popular ballot.
Scrap the Police Service Commission (PSC), the probe team said it found out, having collected responses from what it described as "various sources".
As "an appointment alternative," the Deosaran team said its deliberations favoured a system in which the Police Commissioner and the Deputy Commissioners should be elected "by the direct vote of the eligible population, thus bringing the people's voice and representative government into action."
After having scrapped a previous arrangement in which the PSC made the choice as to who would be the country's top crime fighter, the Government of Trinidad and Tobago, through actions in the Parliament, settled upon a system which involved considerations for such positions by an international team. This was effected through a contract awarded to professionals at a university in the United States.
Embarrassingly, however, we have come to grief over this development, with the massive campaign of opposition and downright hostility from many quarters against nationals from Canada who were selected as commissioner and one of two deputy commissioners in that process.
Such was the stacking of the decks against them, from quarters high and low, that both gentlemen packed up their belongings one day and left together, midway during their assignment here.
And since 2012, we have laughably been in a merry-go-round, with a Trinidad and Tobago citizen as acting Commissioner, repeatedly having his tenure in office extended every six months.
It is to be noted here that Prof Deosaran himself had resigned from the PSC in frustration, over his conclusion that he was getting nothing done.
A reversion to the late, unlamented arrangement by which the CoP was first selected by the PSC, then to be subject to parliamentary approval, carrying with it the appearance of political involvement, Prof Deosaran and his team have discounted in their report, laid in parliament last week.
Coming therefore as a most novel approach to the appointment of some of the most critical positions in the country's crime-fighting apparatus, this latest proposal at least lends itself to conscientious consideration.
From all quarters in the society, from every angle, cutting across demographics and interests, public, private and non-governmental, we have been expressing views and opinions on this matter of the leadership of the TTPS, and its implications for effective management and suppression of the crime menace in our midst.
Perhaps this is what the Deosaran team picked up in its survey of opinions on the subject. And as a means of putting this sentiment up for further scrutiny and testing, the suggestion has come forward in the form of a recommendation to the government. In the end, however, this may turn out to be not as uncontentious as it appears at first blush.
Popular sentiment may render this task vulnerable to the inevitability of support along accepted political lines, and this will result in great disservice to the selection of a Commissioner of Police.
Given the importance attached to the task of those persons occupying the topmost positions in the Police Service, it could turn out to presenting the society with no real solution. The idea therefore, appears to be a non-starter.


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Weidmuller introduces the new WIL, an industrial LED lighting solution designed to improve visibility for maintenance work in a range of applications that include standard industrial control cabinets and field applications. The new Weidmuller Industry Light (WIL), with an IP67 aluminum housing, can withstand harsh environmental conditions while delivering a space-saving and effective lighting solution in the cabinet or on the machine.
The Weidmuller lighting solution features a unique LED arrangement in a robust and compact 8mm-deep housing. The 20-degree angle of the LEDs provide an ultra-wide light cone that can illuminate a broad area, eliminating the need to rotate the light for greater coverage. The LEDs have a light color of 6500K– similar to daylight– with a low power consumption of only 420mA and 24Vdc operating voltage.
The WIL LED lighting solution also offers streamlined installation and operation. Mounting holes are sized and spaced at 225mm apart to ensure easy installation in conventional control cabinets without the need for additional hardware. The WIL features an M12 plug with a prefabricated cable for an easy, weathertight connection to the 24Vdc power supply. It can also be powered using an I/O distributor block.
Weidmuller supports customers and partners around the world with products, solutions and services in the industrial environment of power, signal and data. The company develops innovative, sustainable and useful solutions that set standards in Industrial Connectivity today and continually work toward providing solutions for the technology challenges of tomorrow. The Weidmuller Group owns manufacturing plants, sales companies and representatives in more than 80 countries.
Toyota Canada today took an important step towards the future of sustainable mobility in Canada, announcing that the Toyota Mirai – powered by hydrogen fuel cell electric powertrain technology – is coming to
With its sustainable development strategy and diverse natural resources, Canada is today the 4th leading country in the world for clean energy adoption with two thirds of its electricity generated by renewable resources[1]. To help meet Canadian federal regulations requiring a 50% reduction in coal emissions by 2030 and Nova Scotia regulations requiring 40% renewable energy by 2020, Nexans has installed North America's longest submarine electricity cables as part of the Maritime Link Project conducted by NSP Maritime Link Inc. (NSPML), an indirect subsidiary of Emera Inc.
BJ TAKE Vice President of Sales, Doug Wilson, announces that they have partnered with A.M. Agency in Alberta and Next Inc., headquartered in the maritime provinces, to bring its LED lighting products to the Canadian market.
Doug explains "the significance of these partnerships is that prospective customers in Alberta and the maritime provinces can enjoy the energy-efficient lighting solutions offered by BJ Take while experiencing some of the best customer service in the industry". He continued, "Canadian manufactured LED lighting products are important to both our environment and our economy. By buying a Canadian made product you are bolstering our economy while having access to local manufacturing that is both flexible and offers short lead times".
Stella Cammalleri Céleste Tremblay
STANDARD PRODUCTS announces the addition of two new Account Managers to its Montreal Sales Team.
Stella Cammalleri joins STANDARD with more than 12 years experience in customer service, and a year in the lighting industry. "The addition of Stella will be a great addition to the Montreal Sales Team and will help the company maintain a high level of customer satisfaction," said STANDARD.
STANDARD also welcomes Céleste Tremblay to its Montréal Sales Team. With more than 15 years of experience in customer service, Céleste will be a great help in building and maintaining relationships with existing and future customers.
BJ TAKE recently announced that Upper Canada Industries will be taking over the Toronto territory. Vice President of Sales, Doug Wilson explained "the Toronto market represents a major portion of the Ontario marketplace and as such needed to have local customer service that specializes in distributor and specifier relations". In addition to Central Ontario, Upper Canada Industries will focus on capturing a larger marketshare of the energy-efficient lighting industry in Toronto.
Industry 4.0 scenarios such as Predictive Maintenance are based on the provision of data and networked communication. For this to happen, IoT-compatible devices equipped with the necessary communication options are required. With its new IoT interface, Rittal is now laying the foundation for the optimal integration of cooling units and chillers in Industry 4.0 applications. This makes continuous communication from the sensor to the cloud possible, as well as connection to superordinate monitoring or energy management systems.
Despite the rise in Voice over Internet Protocol (VoIP) telephone systems, many technicians and installers are not aware of how to troubleshoot network performance issues to ensure VoIP quality, says IDEAL Networks.
TE Connectivity (TE), a world leader in connectivity and sensors, introduces the LUMAWISE Endurance N Enhanced base, creating a platform for customers' rapid development and manufacture of NEMA/ANSI C136.41 compliant street and outdoor lighting control solutions.
"With this new development, we are helping designers reduce risk in project schedules and cut the cost of design changes by providing a complete base that enables complex control node solutions, so designers can focus their efforts on value-adding innovations," says Ben Nelson, TE business development manager.
Megger now offers a new insulation and continuity tester designed specifically for the telecommunications and cable testing markets. The MIT485/2TC-LG2 replaces Megger's original MIT480 range tester.
This handheld instrument features fixed test voltages of 50 V, 100 V, 250 V and 500 V, as well as variable test voltages from 10 V to 500 V. Insulation testing can be performed up to 100 GΩ at 500 V. A gated access feature to 500 V prevents accidental application of high voltage to sensitive equipment.
Less Cumbersome Testing
Keep up-to-date with the latest news affecting your industry, personnel appointments, career opportunities, upcoming events and new product launches by subscribing to EL Newswire.


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This virtual collection invites students into an engaging exploration of the Civil Rights Movement.
Explore the life and work of the Raisin in the Sun playwright and Civil Rights activist. Friday, January 19 at 10 pm
On Second Thought is a one-hour, daily news talk show that airs at 9 a.m. ET weekdays.
Season 2 of "Victoria" premiered on Sunday night to social media fanfare, and for your "Victoria" blogger, the double episode felt more like a movie than two episodes. There's a lot to unpack, so let's get into the recap.
Now nearly a week later those teams are preparing to compete again – only this time – it won't be at the Benz.
Make your secure online donation at GPB.org.
Thu., February 16, 2012 6:00pm
Senate Rules: The Road To Kill The Ethics Bill?
The Senate Ethics reform package which would place a $100 gift cap on lobbyist gifts to legislators is now in the hands the Senate Rules Committee. But ethics watchdog groups say that's a way to stall, if not kill, the bill altogether.
Full Story
Tue., June 14, 2011 10:37am
Top Officials Leave Ethics Agency
The top two people in charge at the state's ethics agency are on their way out. The board of the state ethics commission says it's restructuring to save money. Critics say it's the latest move to dis-empower the commission.
Fri., May 13, 2011 8:57am
Utilities Can Give To Politicians
Utilities will be allowed to contribute to political campaigns under a new law the governor signed yesterday. Watchdog groups are concerned the law poses a conflict of interest.
Thu., April 14, 2011 12:24pm
Lawmakers Use Campaign Finance Bill to Close Lobbyist Loophole
State lawmakers Thursday gave their final approval to a bill aimed at closing a loophole in the state's ethics law.
Fri., April 8, 2011 9:43am
Loophole Omits Some Lobbyist Spending
Right now lobbyists don't have to report what they spend on state employees or the family members of elected officials.
Wed., October 27, 2010 12:58pm
Secret Money Part Of Georgia Races
Advocacy groups not affiliated with a political party have pumped money into some Georgia races this year. The fact that their donors are hidden bothers advocacy groups. Georgia's hotly contested 2nd and 8th Congressional districts are the recipients of most of the non party affiliated money.
Mon., January 25, 2010 12:48pm
Lawmakers Consider Ethics Reforms
State lawmakers are considering over a dozen bills meant to reform ethics l
Thu., January 14, 2010 10:35am
Ethics Reform Hot Topic At State Capitol
Ethics reform at the state capitol is getting another boost with a proposal


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1/24/2018IALLT Webinar: The (Ir)relevance of Language Resource Centers in Today's Technological ...
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1/26/2018CFP: Teaching and Learning L2 Pragmatics
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COERLL is pleased to offer a workshop on "Products and Practices of Open L2 Literacy: Materials and Methods from the Foreign Languages & the Literary in the Everyday (FLLITE) Project."
Are you a foreign language...
...Program Director who wants some new ideas for a teaching methods course?
...Curriculum Developer who wants to bridge "the language/literature divide"?
...Instructor who wants to create more innovative activities for the classroom?
...Graduate Student who wants to develop your teaching portfolio?
This workshop will demonstrate how collegiate foreign language programs can create up-to-date L2 literacy materials by adopting "open design" principles and practices. Workshop participants will learn how to design and produce Open Educational Resources (OER) that employ open technologies and open content. In brief, OER are educational materials made available through an open license that allows users to use, remix, improve and redistribute original content.
Participants will also learn the pedagogical principles of "The Literary in the Everyday," a concept that integrates the goals of lower division courses focused on language with the goals of upper division courses focused on literary and cultural analysis.
Finally, the workshop will introduce participants to the FLLITE project website where users will be able to publish their own OER. Foreign language program directors are encouraged to attend with their colleagues and graduate students.
The workshop will be held at the Glickman Conference Center, CLA 1.302B, The University of Texas at Austin. If you are traveling from out of town to attend, see the University's Visitor Resources page for travel information.
Lunch is included in this all-day workshop. A nominal tiered fee is charged to cover materials, refreshments, and lunch.
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Apple has acquired Vrvana, a Canadian startup, to reportedly get some help for shipping an augmented reality (AR) headset by 2022 as it ramps up work.
Magic Leap has uncovered the main form of its augmented reality framework to be made open. The Magic Leap One Creator Edition is intended to extend li
Smartphone, despite its increasing penetration, is still considered an expensive buy in developing countries and so is data. With an aim to reach out
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Exciting launches in autonomous vehicle technology in recent years seem to up the ante in the consumer automotive market, with some prominent technolo


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I stayed at the Meriton Old Town Hotel for 4 nights with a friend for our first visit in Tallinn. We were very satisfied with the hotel as everything we wanted to see was within walking distance. We also enjoyed the free aqua spa available at the other Meriton hotel only a 15 minute walk away (but be aware of towel rent: 3 EUR). Furthermore, the hotel itself is very charming.
The only thing that we did not like was the beds. They were small and the top mattress kept sliding off the bed (and me with it!).
Yes, the rooms are small and the breakfast is not that good. But the perfect location, friendly and helpful staff and the good price makes up for it.
- Official Description (provided by the hotel):
- The Rixwell Old Town Hotel in Tallinn is the only hotel in town, which is built into the original medieval city wall. The hotel's comfy 41 rooms offer an authentic taste of the Old Town at a reasonable price. This hotel is conveniently located in the heart of Tallinn Old Town's restaurant, museum and shopping district. Tallinn's famous Oleviste Church is located on the doorsteps of the hotel and the Town Hall Square is just a short walk away. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Hotels.com, HotelsClick, Ebookers, HotelQuickly and 5viajes2012 S.L. so you can book your Rixwell Old Town Hotel reservations with confidence. We help millions of travellers each month to find the perfect hotel for both holiday and business trips, always with the best discounts and special offers.
- Also Known As:
- Meriton Old Town Tallinn
- Hotel Meriton Old Town


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The Response Evaluation Criteria in Solid Tumors, or RECIST criteria (one-dimensional [1D] measurement), are widely used to measure response in tumors, but there are few studies evaluating these criteria in brain tumors. We compared linear and volumetric measurements in adult high-grade supratentorial enhancing gliomas to determine the agreement between measurements, in defining responses and in their subsequent relation to survival. We hypothesized that the 1D RECIST criteria maybe suitable for response assessment in adult high-grade gliomas. Tumor size on MRI scans in 104 patients with high-grade enhancing gliomas treated on clinical trial protocols was measured by using 1D (greatest length), 2D (two-dimensional: product of the two longest perpendicular diameters), 3D (three dimensional: product of the longest perpendicular diameters in one plane and the longest orthogonal diameter to that plane), enhancing volume (EV), and total volume (TV). A total of 388 T1 postgadolinium MRI scans (104 baseline and 284 follow-up scans) were evaluated. Volumetric analysis (EV and TV) was performed with commercially available software. Intraobserver and interobserver correlations (ρ) were high for all modalities (ρ > 0.92 and ρ > 0.71, respectively). Correlation was excellent (ρ > 0.9) among all modalities except for 3D (ρ < 0.6). Patient response rates ranged from 12% to 26%. Median progression-free survival (mPFS) and six-month progression-free survival (6mPFS) were not significantly different among the methods (range, 5.3 months to 5.9 months and 42% to 48%, respectively). Landmark analyses of response at two months using linear methods predicted overall survival with hazard ratios of 0.19 to 0.29 (P < 0.005). These results suggest high concordance among 1D, 2D, TV, and EV, but not 3D, methods in assessing enhancing tumor progression and in estimating mPFS and 6mPFS in adult brain tumor patients. The tumor response at two months assessed by linear methods correlated better with overall survival. Thus, linear methods are comparable to volumetric methods, but simpler to implement for routine clinical use and for designing clinical trials of brain tumors.
The past few decades have witnessed the emergence and implementation of various radiographic criteria in assessing tumor response and in guiding therapy. The WHO criteria, first introduced in 1979 (Miller et al., 1981; WHO, 1979), represented an early attempt to define objective response to an anticancer agent based on the change in the size of the lesion as measured by determining the product of the largest diameter and its perpendicular length for each measurable lesion (two-dimensional, 2D) and summing the products. Responses were characterized as follows (Table 1): complete response (CR), complete disappearance of tumor; partial response (PR), at least 50% decrease in the products of the two largest perpendicular diameters; progressive disease (PD), at least 25% increase in the products of the two largest perpendicular diameters; and stable disease (SD), neither PR nor PD. In 1990, Macdonald et al. (1990) suggested that the 2D WHO criteria be applied to brain tumors. They proposed specifically that these criteria would be more useful in patients who were not on steroids and also did not experience clinical deterioration other than that attributable to progressive tumor burden (e.g., systemic or metabolic disturbances). These Macdonald criteria have become the standard for many brain tumor trials.
The Response Evaluation Criteria in Solid Tumors (RECIST) were introduced in 2000 (Therasse et al., 2000) in an attempt to simplify and standardize the objective response criteria to cancer therapy in solid tumors. These criteria used a unidimensional (1D) measurement (the sums of the longest diameters of tumors) instead of two-dimensional measurements (2D, the sum of products of perpendicular diameters) to determine response. With the RECIST criteria (Table 1), responses were redefined: CR was defined as complete disappearance of the lesion, PR as at least 30% decrease in the sums of the longest diameter of tumors, PD as at least 20% increase in the sums of the longest diameter of tumors, and SD as neither PR nor PD. There is excellent concordance between the RECIST criteria and the WHO criteria in determining response in extracranial tumors (Shi et al., 1998; Therasse et al., 2000), but there have been few studies validating these criteria in brain tumors. Furthermore, a fifth category, minor response (MR), is commonly used to capture smaller responses and is defined as a decrease between 12% and 25% in 1D, between 25% and 50% in 2D, and between 40% and 65% in three-dimensional (3D) and volume methods.
Advances in MRI technology have led to the ability to measure tumor volumes by automatic and/or manual outlining of tumor boundaries (Aoyama et al., 2001; Joe et al., 1999; Mazzara et al., 2004; Moonis et al., 2002; Shi et al., 1998; Sorensen et al., 2001; Weltens et al., 2001). Warren et al. (2001) evaluated 130 MRI scans in 32 children with brain tumors and found good concordance between the 1D, 2D, and enhancing volume (EV) methods in determining PR. However, there was fairly marked variation between the different methods in determining time to disease progression. Galanis et al. (2003) evaluated 614 MRI scans from 73 newly diagnosed adult brain tumor patients and found no difference in survival among patients characterized as responders or nonresponders on the basis of 1D versus 2D measurements. To the best of our knowledge, there have been no other studies evaluating the 1D criteria in adults with up-front and recurrent brain tumors, the setting of the majority of clinical trials in brain tumors.
Currently, the method most commonly selected by neuro-oncologists to measure objective response is use of the 2D Macdonald criteria (Prados et al., 2004) with 3D or volumetric methods (Batchelor et al., 2004). Additionally, there are variations in the criteria (Table 1) among groups that limit direct comparisons of response rates in clinical trials. Thus, there exists a need to simplify and standardize the methodology of these measurements. In this study, we evaluated contrast-enhanced MRI scans of 104 adults with high-grade supratentorial enhancing gliomas and compared the 1D, 2D, 3D, computer-assessed total tumor volume (TV), and EV measurements with one another and with clinical neurological status in determining tumor response and progression. We hypothesized that, as for other solid tumors, the 1D (RECIST) criteria are equivalent to other linear and volumetric criteria in assessing response and are thus applicable for response assessment in adult high-grade gliomas.
Adult patients with supratentorial high-grade gliomas on treatment protocols between the years 2001 and 2004 at the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Massachusetts General Hospital in Boston, Massachusetts, were eligible for this study. Only patients with measurable enhancing tumor by the methods discussed below, two or more available sequential MRI scans, and clear documentation of status of clinical progression were selected. In all cases, the baseline MRI was the same as the baseline MRI used for the given protocol. MRI scans were generally spaced apart by eight weeks according to protocol requirements, and in cases where MRIs were performed for nonprotocol reasons, no two scans used in this study were less than two weeks apart. The 2D Macdonald criteria were used to identify PD (>25% increase) and thus to remove patients from protocols. All the scans used for this study were performed while patients were on protocol, although some patients underwent more than one protocol.
Of note, all patients had undergone standard external beam radiation treatment, but none had stereotactic radiosurgery; therefore, most, though not all, of the observed tumor progression could be interpreted as authentic progression and not radiation-related necrosis (see discussion). Furthermore, all patients were on stable doses of steroids for at least five days prior to each MRI scan. The Institutional Review Board overseeing all of these institutions approved this study (Dana-Farber Cancer Institute protocol 03–260).
MRIs of the brain were performed on a 1.5-tesla scanner with a standard quadrature head coil. Patients received Magnevist (Berlex Biosciences, Richmond, Calif.) according to weight (0.1 cm3/lb) given as a bolus injection through a peripheral vein infusion. The brain was scanned immediately after injection, and all scans were completed within 30 min. Among others, axial and coronal T1 pre-gadolinium and postgadolinium images were obtained and used for this study. The digitized images were transferred to an Impax Diagnostic Workspace system (Agfa-Gevaert Group, Mortsel, Belgium), where they were available for review by the authors. For volumetric analysis, volume-calculating software (VITREA 2, 3.3.2, 1997–2002 [Vital Images, Inc., Minnetonka, Minn.]) was used to obtain the measurements.
Two investigators (G.D.S. and S.K.) performed all 1D, 2D, and 3D analyses of 388 MRI scans using digital calipers on an Impax workstation, while volumetric analyses and calculations were performed on a VITREA 2 workstation. On a subset of 50 randomly chosen scans, measurements were repeated by both of the aforementioned investigators to determine intraobserver and interobserver variability. Most patients (72%) had only one measurable lesion. The 1D measurement was the sum of the longest diameters in any plane (axial, sagittal, or coronal) of all visible contrast-enhancing lesions on the postgadolinium T1-weighted images. The 2D measurements were the sum of the products of the largest diameters and their maximum perpendicular diameters in the same plane. The 3D measurements were the sum of the products of the 2D measurements and the longest vertical diameters on the view perpendicular to the 1D and 2D planes (i.e., usually the coronal plane unless it contained the longest 1D diameters of any plane, in which case the axial plane was used for third measurement). In cases where there was a gradient of enhancement, a point was selected to begin the measurement at which there was a clearly visible transition from nonenhancement to enhancement. In cases where a nonenhancing cystic cavity was present within a surrounding area of enhancement, we maintained the same rigid criteria of measurement—the longest diameters of enhancing tumor, regardless of where the cystic cavity was located.
For volumetric analysis, the tumor was outlined in all axial planes with a computer-assisted, free-outline technique on postgadolinium T1 images, and EV or TV was calculated by using the VITREA 2 workstation. These raw measurements were compared to the baseline or best overall response scan for each patient, defined as the scan with the smallest size of tumor, which could have been either at the start of the study or on subsequent scans if the tumor responded to treatment. Tumor response was codified as CR, PR, MR, SD, and PD when compared to best overall response scan for each criteria as defined in Table 1. Clinical progression was defined as the appearance of a new neurological deficit or the permanent progression of an existing neurological deficit, that is, deficits that do not resolve with an increase in steroids. Median progression-free survival (mPFS) and six-month progression-free survival (6mPFS) were calculated separately for each measurement method and were defined from the date of protocol registration to the date of progression according to each measurement method. Overall survival was defined as time from registration to death.
Response rates and progression-free survival (PFS) were determined by each of the measurement methods described above. PFS curves were plotted by using the Kaplan–Meier method. Intraobserver and interobserver correlations were calculated with raw measurement data by using Pearson correlation coefficients. Analyses of correlation between different methods were performed comparing the percent change from baseline or best response scan with 95% CIs. MR and SD were combined to compare the concordance between the different methods in classifying response. Scan response rate was calculated by adding all the scans labeled as CR and PR and dividing by the total number of follow-up scans (284) in each method. Patient response rate was calculated by adding the number of responders (CR and PR) and dividing by the total number of patients (104) for each method. All analyses were performed with SAS statistical software version 8.0 (SAS Institute, Inc., Cary, N.C.). Median and six-month PFS rates were estimated by the Kaplan–Meier method. Landmark analysis was performed at two-month and six-month time points to determine whether response predicted overall survival. The landmark analysis at a fixed time point looks at all patients who are alive and not censored by that time and compares the subsequent overall survival between the two categories: those who have progressed by that time and those who have not (Anderson et al., 1983).
A total of 388 MRI scans were analyzed from 104 adult patients with measurable, enhancing high-grade gliomas. Ages ranged from 28 to 80 years, with a median age of 54 years (Table 2). There were 54 men and 50 women. Of these 104 patients, nine had anaplastic astrocytomas (AAs), seven had anaplastic oligodendrogliomas (AOs), four had mixed oligoastrocytomas, and 84 had glioblastoma multiforme (GBM). The median age was 55.5 years for GBM, 39 years for AA, 48 years for AO, and 39 years for mixed oligoastrocytomas. A total of 104 baseline scans and 284 follow-up scans were used for this analysis. The median number of scans per patient was three (two scans, 29%; three scans, 22%; four scans, 17%; five scans, 13%; and six or more scans, 18%). For 74 of the 104 patients, the tumors being evaluated were recurrent, whereas for the other 30 patients, the tumors were either up-front or postradiation treatment. Mean follow-up from initial scan was 7.4 months (median, 6.2 months), and 63% of the patients were alive at the time of analysis. Median tumor measurements were as follows: 1D, 5.06 cm; 2D, 15.61 cm2; 3D, 56.6 cm3; total volumes, 21.6 cm3; and enhancing volumes, 16.0 cm3.
To determine variability in measurements, intraobserver and interobserver correlations were calculated for a randomly selected sample of 50 MRI scans taken from the full set of 388 (Table 3). Intraobserver Pearson correlation coefficient rho (ρ) values using the raw measurements were all greater than 0.92 with narrow 95% CIs. Interobserver ρ values were all greater than 0.71 with wider 95% CIs.
Pearson correlation coefficients of percent changes were calculated for all pairwise methods (1D vs. 2D, 1D vs. 3D, etc.) measurements to determine the concordance between each pair of the measured modalities. A high concordance would demonstrate a high agreement in percent change for each scan as measured by a pair of modalities (e.g., 1D vs. 2D, etc). The 1D, 2D, TV, and EV measurements all correlated extremely well with one another, with ρ values greater than 0.91 and with narrow CIs (Table 4). The 3D measurements correlated poorly with the other methods.
We determined the degree of fit among all the methods in categorizing treatment response (Tables 5 and and6).6). All of the follow-up scans were classified into each response category according to the percentage change from baseline or best overall response as defined by the various measurement methods (Table 5). The CR rate was 1% in all methods, with more variance for the other responses due to differing criteria for response: PR, 5% to 17%; SD, 36% to 46%; and PD, 37% to 47%. The linear methods tended to be in closer agreement than the volume methods, with 1D and 2D being in closest agreement, and EV^ and TV being in least agreement. There was excellent scanwise agreement among all methods for detecting CRs (100%), PDs (93%), and SDs (88%) and less agreement for PRs (65%) when using 1D as the reference. EV^ and 3D^ methods, in which response was defined as a 50% reduction (rather than >65% reduction) in tumor volume, were associated with a higher overall response rate as compared to the other methods (13%–18% vs. 7%–12%, respectively). We also categorized each patient's best overall response as measured by each modality and calculated frequency of agreement between each modality with regard to response categories (Table 6). This shows that patient best overall response concordance rate is less than scan concordance rate (Table 5), with linear and volumetric methods agreeing better internally (e.g., 1D vs. 2D) than with each other (e.g., 1D vs. EV).
At the time of this analysis, 65 (63%) patients were still alive. We compared the mPFS and 6mPFS as measured by these methods as well as by clinical status (Table 7). The mPFS and 6mPFS for each of the modalities were comparable, with mPFS ranging from 5.3 to 5.9 months (Fig. 1) and 6mPFS ranging from 42% to 48%. The volume methods, in general, had a higher PFS than did the linear methods. A subset analysis of the 74 patients with recurrent tumors reveals a shorter mPFS (range, 4.3–5.5 months) and lower 6mPFS (30%–40%) compared to mPFS and 6mPFS for all patients; however, again the mPFS and 6mPFS were comparable across modalities. A subset analysis of GBMs showed an mPFS of 5.5 to 6.1 months, which was little different from that of the total population (5.3–5.9 months) because of the predominance of GBMs (84 of the 104 cases) in this study and low numbers of other tumor types. Median PFS based on clinical criteria was similar across the tumor subtypes (log-rank test P = 0.7) as was median overall survival (log-rank test P = 0.6). The lack of difference in overall survival among the tumor subtypes was attributed to the fact that the majority of the anaplastic gliomas were multiply recurrent. A subset analysis of the 75 patients (72% total) with only one measurable lesion revealed no significant difference from the overall patient population in mPFS (5.2–5.7 months) or in 6mPFS (42%–48%).
To correlate overall survival with PFS as defined by each of the modalities, we used landmark analysis. There was a significant correlation (P < 0.05, hazard ratios < 0.3) between nonprogression at two months (n = 99 patients alive at 2 months) and overall survival by the linear measurement methods (1D, 2D, 3D, 2D^, and 3D^) and one volumetric method (EV), but not by the other two volumetric methods (TV and EV^) (P > 0.05) (Table 8). However, there was no significant correlation between nonprogression at six months (53 patients alive at six months) and overall survival, with the exception of that observed by the 3D^ method. Although 65 patients were still alive at time of this analysis, only 53 patients reached the six-month follow-up to be included in the six-month PFS landmark analysis. There were only 17 subsequent deaths in this group. Among these patients, the maximum follow-up time was 26.8 months from entry to study, and the estimated median follow-up time (after adjusting for censoring by deaths) was 11.1 months from study entry. Clinical progression was better than all of the imaging modalities at both two months and six months in predicting overall survival. Landmark analysis of only the patients with recurrent disease (71 patients for two-month and 34 patients for six-month analyses) showed a similar trend but with lower significance levels.
A particularly problematic issue in measuring gliomas is that they grow in three dimensions and infiltrate extensively and asymmetrically in several directions. Furthermore, tumor size may be confounded by the presence of cystic areas that may or may not contain actual tumor. Consequently, we found that it was sometimes difficult to determine exactly where to begin and end a measurement, especially when a cystic cavity was present or when a gradient of enhancement was difficult to differentiate from normal brain tissue. However, this ambiguity is an inherent and accepted limitation of current radiographic criteria for measurement of brain tumors that is most effectively addressed by employing the same rigorous methodology described above in each measurement. Because we dealt with patients who had measurable enhancing tumor, this factor was less of a concern than dealing with patients in routine neuro-oncologic practice, where patients may be more likely to have non-enhancing or nonmeasurable lesions.
Accurate assessment of tumor response is also difficult in clinical trials of brain tumors because different methods are used among clinical trial consortia. Thus, there is not a clear consensus that enables comparison among different trials. In this study, we show that linear measurements (except 3D) of enhancing lesions correlated well with volumetric measurements and in determining mPFS, but that response assessment by linear methods differed from that by volume methods. However, response categorization at two months with linear methods was superior at predicting overall survival.
One concern of using objective, quantitative radiologic criteria to determine changes in tumor size is that of reproducibility across observers (interobserver correlation) and across different sessions for the same observer (intraobserver correlation) (Chisholm et al., 1989; Erasmus et al., 2003; James et al., 1999; Lavin and Flowerdew, 1980; Sorensen et al., 2001; Vos et al., 2003). We demonstrate that the same observer is likely to interpret a lesion quite closely over the course of two sessions. Our two observers interpreted the same lesions in close but less conforming ways. This is an unavoidable limitation of all the methods. The interobserver variations were least for the linear methods and higher for the volumetric methods (Table 3).
As shown in Table 5, there was good concordance among the linear methods in classifying response. CRs were seen by all radiologic criteria in three total follow-up scans representing three patients. The 1D method has the potential to underestimate progression as compared to the other methods. The reason for this is that progression is defined in the 1D method as a 20% increase in the diameter of the lesion. A 20% increase in the diameter of a sphere is equivalent to a 44% increase in area and a 73% increase in volume (Gehan and Tefft, 2000; James et al., 1999; Warren et al., 2001). However, the 2D criteria uses a 25% increase in area, whereas 3D and volumetric criteria use either a 65% or 50% increase in volume to define progression.
In this study, the number of scans determined by the 1D, 2D, and 3D linear methods to show stable disease was higher than that by volumetric methods EV and TV. Not unexpectedly, the EV method using a 50% decrease in tumor volume as a measure of response (EV^) produced a higher number of partial responders, although the mPFS and 6mPFS results were not significantly different from those determined by the other methods (Table 7). In general, volumetric methods gave higher PRs and lower PDs, or, conversely, linear methods gave higher PDs and lower PRs. The selection of a particular method involves balancing a potential discarding of active treatments with acceptance of slightly less effective treatments. However, since there is good correlation between all methods in determining mPFS and 6mPFS, which are increasingly the end points for clinical trials in malignant gliomas, these small differences in response rates are probably not significant.
By landmark analysis, the tumor response at two months assessed by the linear methods correlated better with overall survival than that by volume methods (Table 8). However, tumor response assessed by both linear and volumetric methods at six months did not correlate with overall survival, in part reflecting the short duration of response of current therapies and in part because of our limited data set, since of the 53 patients included in the analysis only 17 had subsequently died at the time of analysis. Thus, the analysis may not be adequately powered. It is important to emphasize that a primary end point of phase 2 trials conducted in the North American Brain Tumor Consortium is 6mPFS; this study raises the important question of whether this end point is useful. Recurrent malignant gliomas tend to progress and the patients die relatively quickly, which provides a partial explanation for why a six-month assessment would not be helpful at predicting overall survival, since the disease of most patients will have progressed by six months. Furthermore, since the number of patients alive at that time is small, it may not have been adequately powered to detect a difference. Certainly, a larger prospective study will help to resolve this issue.
For predicting overall survival, the strongest criterion at two months, and the only criterion with significant correlation at six months, was clinical progression. Thus, it may be that despite continuing attempts to define and refine radiographic criteria in an attempt to help guide therapy, the best method to do so might still be the clinician's professional assessment based on history and examination.
An important concern when generalizing these results to the total brain tumor population is that the patients we studied were mostly recurrent glioma cases with enhancing tumors. Extrapolation to newly diagnosed tumors or nonenhancing tumor may or may not be appropriate. Galanis et al. (2003) have attempted to address this issue in a study of 614 MRI scans in 73 patients with both high-grade and low-grade, newly diagnosed gliomas. They found that 1D measurements (RECIST criteria) or 2D measurements in gadolinium-enhanced images were both associated with survival improvement, and there was no evidence that either method was superior. However, 1D and 2D T2-based tumor measurements correlated less well with survival. For nonenhancing tumors, volumetric measurement may potentially be more useful. A second issue is that none of our patients had undergone stereotactic radiosurgery or placement of carmustine wafers. For patients who receive these treatments, radiation necrosis and tumor progression might easily be confused (Guerin et al., 2004; Kleinberg et al., 2004; Shinoda et al., 2002; St. Clair and Given, 2003). As a result, the various measurements of enhancement alone will not capture the true tumor burden and may not be of prognostic significance. It is possible that a small minority of patients in this study who received only standard radiotherapy may have developed radiation necrosis. Whenever radiation necrosis is suspected, additional imaging with positron emission tomography, magnetic resonance spectroscopy, single photon emission computerized tomography, or surgical biopsy is performed. Nonetheless, we cannot exclude the possibility that radiation necrosis was mistaken for tumor progression in a small minority of patients in this study.
Most of the patients in this study (about 80%) received steroids at some point during their treatment. Steroids are known to affect the enhancement and edema of the tumor (Ostergaard et al., 1999) and must be taken into account when assessing response. To control for this issue, all patients had to be on a stable dose of steroids for at least five days prior to the imaging studies. The exceptions were a small number of patients with significant clinical deterioration who had to be treated immediately with high doses of steroids. Despite the increased steroid doses, these patients all had PD on their imaging studies.
It is well known that gadolinium enhancement can be affected by a variety of factors, including the rate and amount of gadolinium injected and the timing of image acquisition. In our study, patients received standard doses of gadolinium and within 30 min of scan, which should have reduced the variability due to technique. We do not feel that this contributed significantly to the measurement errors across scans for each patient.
To summarize, our results show that 1D measurements were comparable to higher dimensional modalities in assessment of tumor growth and in correlation with disease progression and survival. We propose simplifying measurements in brain tumor trials so that there is more comparability across consortia. Thus, as prior studies have done for solid tumors (James et al., 1999; Park et al., 2003), this article validates the RECIST criteria as objective measures of tumor response in glioma patients. As treatment responses improve, one of these measurement methods may turn out to be superior in assessing response. Computerized measurement of enhancing tumor volume potentially provides the most accurate measure of tumor burden and merits further study, as this may ultimately be superior in assessing true response. Other methods under study to assess tumor response are likely to be of utility in the near future, including functional MRI, methionine-PET scans, single photon emission computerized tomography, magnetic resonance spectroscopy, and biomarkers (Fountas and Karampelas, 2004; Mazzara et al., 2004).
Given that response assessment differed among the methods, standard criteria should be established for all brain tumor trials to enable comparability across treatments in different consortia. We have shown that the RECIST criteria are useful in determining objective response of enhancing brain tumors to therapy; these criteria can easily be used in all centers. These findings are likely to be of importance in the design of future clinical trials of brain tumors.
1We gratefully acknowledge the support of the Martin and Pauline Elkin, Neil Harrington, and Cynthia Martin Brain Tumor Clinical Research Funds.
4Abbreviations used are as follows: 1D, one-dimensional; 2D, two-dimensional; 3D, three-dimensional; 6mPFS, six-month progression-free survival; AA, anaplastic astrocytoma; AO, anaplastic oligodendroglioma; CR, complete response; EV, enhancing volume; GBM, glioblastoma multiforme; mPFS, median progression-free survival; MR, minor response; PD, progressive disease; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; TV, total tumor volume.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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I need an example of how to write an annotated bibliography for the book No Country For Old Men. everytime I redo the assignment my teacher says I am just writing a summary not really an annotated bibliography
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