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|Course Name
|Book Online
|PMP Exam Prep Boot Camp
|4 days
|Book now Enquire
|PMP Exam Prep Boot Camp
|4 days
|Book now Enquire
|PMP Exam Prep Boot Camp
|4 days
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|PMP Exam Prep Boot Camp
|4 days
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|PMP Exam Prep Boot Camp
|4 days
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This course provides everything you need to know to pass the Project Management Professional (PMP)® exam and become a certified Project Management Professional (PMP)® . It consists of five days of instructor-led classroom training.
PMP® is a globally recognised qualification which indicates competence as a project manager and the ability to lead projects effectively.
Pre-Course Reading
We recommend you purchase a copy of the "A Guide to the Project Management Body of Knowledge (PMBOK® Guide)", Fifth Edition (ISBN 978-1935589679), which is what the PMP® exam is based on.
It is advised that you read pages 1 to 63 before class and bring the book with you each day.
To apply for the PMP® exam, you must have either of the following:
Continual Certification Requirements as stated by PMI (Project Management Institute)
To retain their certification, PMP® holders must earn a certain amount of PDUs (Professional Development Units) a year. The current requirements are:
Who Should Attend?
This training is intended for any Project Managers who are looking to gain PMP® certification and demonstrate skills and experience in project management.
Course Structure
Course Content
This course covers the following topics:
The five project management Process Groups:
The ten project management Knowledge Areas:
Any other material from the "A Guide to the Project Management Body of Knowledge (PMBOK® Guide)" likely to appear in the PMP® exam
Why choose The Knowledge Academy?
Click 'Book Now' or 'Enquire' next to the date of your choice and our expert advisors will be in touch.
What is PMP®?
PMP® (Project Management Professional) a globally recognised project management credential. PMP® demonstrates that project managers have the experience and competency to lead projects efficiently and effectively.
PMP is provided by the PMI (Project Management Institute), a global not-for-profit project management association for project, program and portfolio management professionals.
Case Study
Hong Kong and China used the methodologies a PMP® would use from the "A Guide to the Project Management Body of Knowledge (PMBOK® Guide)" to manage the construction of a pipeline to transport natural gas from China to Hong Kong.
In the late 2000s, Hong Kong's existing source for natural gas, the Yacheng 13-1 gas field in Hainan, China, was becoming depleted. The answer was for CLP/CAPCO (a joint venture between ExxonMobil Energy and CLP Power Hong Kong) to construct a new pipeline connecting Hong Kong to the longest natural gas pipeline in the world, the Second West-East Gas Pipeline (WEPII).
With a target of bringing WEPII's gas to Hong Kong by the end of 2012, the project had to be managed efficiently and effectively.
By using best practices from "A Guide to the Project Management Body of Knowledge (PMBOK® Guide)", the Hong Kong line was finished on time and within budget. Before the project's initiation, the team thoroughly planned and scheduled every part to ensure the pipeline would properly and was safe. In order to meet the tight deadlines required, the project was developed using the waterfall methodology, where each stage was completed before the next one was started. In addition to this, the scope was tightly controlled, with any changes going through a thorough management process.
The spaces remaining on all courses across the website reflect the availability of the maximum printed course materials and equipment available in stock for any given event. If the spaces remaining do not appear, then there is comfortably enough lead time to provision course materials and equipment upon booking.
Our R.E.P. Provider ID number is 3444.
All of our instructors are fully accredited and have over ten years of experience in PMI methodologies.
5 days of classroom training, 35 PMI required contact hours, guidance with the PMP® exam application process, support to maintain PDUs and extensive PMP® practice test questions with unique PMP® prep workbook.
No, you will have to apply directly to PMI to book and take your exam.
To apply for the PMP® exam, the PMI requires that you have either: a university degree and at least three years of project management experience, with 4,500 hours leading and directing projects and 35 hours of project management education; or a secondary diploma (high school or the global equivalent) with at least five years of project management experience, with 7,500 hours leading and directing projects and 35 hours of project management education.
Our exam pass guarantee gives you confidence that we will support your learning until you pass your PMP® exam. We guarantee that you will pass your PMP® exam after completing our PMP® class. All we require is for you to take the exam within 30 days of completing the class. Attend all class days and complete all class assignments, including your PMP® practice exams. If you do not pass the exam after the 1st attempt, we will allow you to attend the class again free of charge. Should you fail the exam on your 2nd attempt, you will be eligible to enrol in the class again, free of charge. PMP® examination results must be verified to confirm re-enrolment and is subject to availability.
Yes, a certificate is included.
Before the class, please read pages 1 to 63 of the Project Management Institute's Project Management Book of Knowledge (PMBOK), Fifth Edition (ISBN 978-1935589679).
The training hours are 9am to 5pm.
A minimum of 2 hours of homework will be set each day.
You can report your activities to PMI online, using their CCR system. Alternatively, you can complete and submit a PMP® Professional Development Activities Reporting Form to PMI. This can be obtained from http://www.pmi.org/Certification/~/media/PDF/Certifications/CCR%20Activity%20Reporting%20Form.ashx
You will receive confirmation details as soon as your place has been booked and confirmed.
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Special Seminar: "The impact of network structure on criticality in cortical circuits"
SpeakerJohn Beggs, Associate Professor of Biophysics, Indiana University at Bloomington
Date May 13, 2013
Time 12:00 pm
Location 144 Loomis
Sponsor Center for the Physics of Living Cells
Contact Stephanie Johansson
E-Mail firstname.lastname@example.com
Phone 217-300-4241
Event type Seminar/Symposium
Views 1845
Originating Calendar Physics - Physics of Living Cells Seminar
Cortical circuits have been hypothesized to operate near a critical point for optimality. Previous evidence supporting this came from bulk signals that did not show individual neuron activity. Using a 512 electrode array, we recorded up to seven hundred spiking neurons simultaneously and found two main things: (1) Avalanche shapes can be collapsed onto a universal scaling function, a key indicator of criticality; (2) The network structure of effective connections strongly influences dynamics. Cortical circuits not operating at the critical point may be associated with neuropathologies, so mechanisms maintaining critical network structure may be essential for neurological health.


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Customer Reviews
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01/08/2017Ellen H.
United States
VERY happy!
This item was everything I hoped it would be. My husband loved the wood the used and the size of the item as well. Keep in mind that it does take every bit of the 2 months to get as quoted on the website. I also was very pleased with how easy it was to communicate with Route One Apparel via email and the timliness of the responses that I received.


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Added: 17 Jan 2017 | Category: Toys |
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Kristina Williams, Managing Editor, is earning her MSLIS at the University of Illinois at Urbana-Champaign. She works at the Undergraduate Library, providing reference and instruction support. Before library school, Kristina dabbled in teaching, publishing, and radio production. An AmeriCorps alum, Kristina believes deeply in the strength of character built by service to one's community, and the enrichment made possible by civic engagement and getting to know your neighbors, both personally and professionally. Her non-library interests include running, listening to outlaw country, and expanding her repertoire of jokes.
Carissa Hansen, Community Manager, is a student in the University of Wisconsin-Madison's distance LIS program. She currently lives in Minneapolis, Minnesota and works full-time as the archives assistant in the Special Collections, Preservation and Digitization department of the Hennepin County Library system. She developed a love for digitization and archival work while working as an archives assistant at the University of Minnesota-Twin Cities, where she earned her BA studying English and Family Social Science. In the past, she's also worked in the Fargo Public Library system. Her professional interests include archival processing, archival metadata, public service, outreach and programming, digitization, information literacy, and the history of librarianship. You can reach out to Carissa online via LinkedIn or Twitter @libchans.
Nisha Mody, Consulting Editor, is getting her MLIS at the University of Illinois at Urbana-Champaign. Previously, she was working as a speech-language pathologist, and prior to that, she worked as an IT consultant and IT recruiter managing to dabble in voiceover work as well. Currently, she works at the Communications Library at University of Illinois. Nisha is interested in critical librarianship (#critlib woot!), specifically with information literacy in reference and instruction. She also volunteers as a librarian at the Champaign County Jail for Urbana Champaign Books to Prisoners. She is also a co-founder of the Human Library Champaign-Urbana. Her dream is to apply social justice initiatives in the academic library. Nisha loves avocados, eggs, and bunnies (in no particular order). You can find her on twitter @nishamody.


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Relevant offers
In the last gasping decades of the 20th century, at the acme of the gossip columnist Felicity Ferret's calumny, to be captioned "a visitor from Hawke's Bay" in Metro magazine's party pages was instant social death.
You were officially a nobody. Some random whose name the photographer hadn't even bothered to check.
You might have been having the time of your life, a right old knees-up, but nobody gave two hoots.
You were from the provinces, or you may as well have been. Half-pickled from the free piccolos of Deutz, you were caught for posterity with an overly-chilled salmon blintz halfway between platter and open gob.
Recently I have attended a flurry of social events at which I was not on the guest list, at least not in any capacity of my own. I have been someone's plus one.
And belatedly I have realised that there is no shame. In fact, there is much to be praised. There is none of the expectations incumbent upon either invitee or host.
Unaware of the minefields to steer clear of (that a. the host's husband is recovering from a serious addiction to online porn, or b. the woman with the unusual cleavage is in the middle of suing her Thai surgeon for medical misadventure), you may tread with gay abandon across a wide open sea of subject matter.
Unburdened by duty, you are free to be scintillating and mysterious, to endear and impress. The fresh company may even prove to be charmed by your tired old party trick; your signature dance move.
In order to fling back the curtains on the real life and times of a plus one, I kept a small diary of my many social triumphs.
Restaurant soft launch
The invitation comes by email, from a colleague and dear friend. It's for lunch. At a new restaurant. The chef is a celebrity. Would I like to accompany her? Yes, please. I plan an outfit to thrill, yet not overwhelm.
With an elastic waist to allow for all the on-the-house ricotta gnudi, duck fat potatoes and lemon panna cotta I plan to avail myself of.
On arrival I compliment the PR. The celebrity chef. (Love your parmigiano-reggiano.) The other guests. During lunch I take a sincere interest in the PR's offspring; the celebrity chef's; and the other guests'.
I am patting myself on the back for being an exemplary plus one when I realise that there is also a hard
launch later in the week - a proper party with proper famous people and proper champagne - to which I am not invited.
The invitation comes by email, from a former-colleague and dear friend. It's for a brunch. She is allowed to bring someone. Would I like to come? Yes, I say, yes please.
With its mid-morning time-slot there is something wholesome about brunch. Wholesome yet potentially libertine, with all the possibility of drunken antics spilling over into the rest of the day.
I decide to dress appropriately with plunging neckline. My decolletage may be at best advantage but it is
entirely lost on the all-women invitees.
Why are we here? I have no idea. Oh, it is to promote a particular varietal of wine. I love wine. I hate talking about it.
Charmingly I blank out the presentation. Endearingly I text during the speeches. I scoff the food and make off with my two complimentary bottles.
Oscars lunch
The invitation comes by text, from a colleague and dear friend. Have you been invited to the Oscars lunch? No.
I am mildly peeved. I have never been invited to the Oscars lunch. I'll see if I can wangle you an invitation,
she says. Got you one! '
I swallow my pride. Plan my outfit. I decide to dress appropriately with plunging neckline and elastic waistband. My decolletage is not lost on the photographer. I am gratified by his attention.
And mildly peeved when I realise he has no idea what my name is, even though we once worked together.
We critique the red carpet attire of the proper famous people on the big screens. I stare down a badly dressed woman who fails to comprehend the genius of Pharrell William's outfit.
We take our seats. The young man sitting opposite me tells me he's my fangirl. He hopes I don't mind. By all means, I say. Be my guest.
The invitation comes by phone, from my mother. Will you come with me, she asks, to a wedding down country?
By all means, I say. I'm on a roll. I plan my outfit. A scrap of fluorescent silk and a fur coat. Perfect, I think, for a country wedding. I look like a prostitute from Belarus. I know nobody. How liberating, I think.
My mother and I spend a while talking to a woman about fine art auctions on cruise ships. She makes her excuses and escapes.
What an interesting conversation, my mother says to me. I look at her. I think she thought we were quite mad, I say.
No one under 60 talks to me. They clearly think I am a prostitute from Belarus. I tell an older woman I have
been admiring her lovely long legs.
She looks at me like I am quite mad. Bonkers. Like a crazy prostitute from Belarus.
- Sunday Star Times
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Knebworth Oakgrain Mussel Kitchen Doors
Knebworth Oakgrain Mussel
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If clean lines and simplicity are considered necessary in your kitchen, this handleless design will establish the conservative appearance that is required. The recessed furrow which acts as a door pull on Knebworth kitchen doors from our Bella style door range can be utilised at both the top or the bottom of the door and will incorporate an uncluttered appearance to your kitchen. This sleek, flat door is highly modern and will function wonderfully with just about any of our colour ranges.
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This battery-powered electric fence provides flexibility for precise placement and configuration. There are three main types of chargers: AC-Powered, Battery-Operated and Solar-Powered. With an electric fence, current is supplied by a high-voltage charger, which provides regularly timed pulses 55 to 65 per minute followed by approximately one second with no current flow. Find out more about solar powered electric fences and their installation. Solar powered electric fences can be used for a variety of purposes, either to keep cattle or other livestock in your field, or to keep other animals such as deer out of your field or garden.
This is a Patriot pet and garden complete electric fence kit. Great for yards, flower and vegetable gardens, and other similar areas. The Garden & Backyard Protection Electric Fence Kit is an easy, affordable do-it-yourself electric fence that protects a 50′ x 50′ area with three adjustable wires. Shop Electric Fence at acehardware.com and get Free Store Pickup at your neighborhood Ace. While most commonly used to keep livestock in a designated area, many people also use electric fencing to keep small animals and pets out of their gardens.
Zareba KGPDC-Z DC Garden Protector Battery-Powered Electric Fence Kit. Parmak 901 6-Volt Gel Cell Battery For Solar Powered Electric Fences Garden &. Solar Powered Electric Fence Charger Farm Horses & Cattle Adjustable Control. NO CHARGE 60 DAY REPLACEMENT WARRANTY W/ SHIPPING PAID. 3 Miles Of Fence. Ideal For Pets, Gardens And Small Pastures. McGregor Fence Kits, 100 Feet of Fence, with AC, Battery, or Solar-powered Chargers/energizers.
Patriot Pet And Garden Electric Fence Kit
Shop our selection of Electric Fencing in the Lumber & Composites Department at The Home Depot. Zareba 10 Mile Low Impedance Solar Fencer. A properly installed electric fence can discourage both these infamous nibblers without harm. If an AC outlet is not available to power the fence charger, a deep-cycle marine battery recharged by solar panels or with a standard battery charger can be used to power the fence. Any gardener soon learns the importance of fencing after the garden they spent months cultivating is destroyed in one night by groundhogs or deer. Before getting into a detailed discussion about installing your own solar-powered electric fencing, perhaps a brief review of fencing basics will be helpful to those who are new to the subject. The primary focus of these strategies is using electric fencing, physical barriers and traps to prevent large and small mammals from damaging your garden. Talk to someone knowledgeable about solar powered fences before ordering panels, batteries and controllers separately to build your own system. Solar power has a place in farms and gardens, with devices designed to do everything from heating water to powering tractors. More recently, you'd also be more likely to see a small solar charger powering an electric fence than a PV array on a residential street. Did you plant a garden this year that started out magnificently, but before you could harvest it, the deer had all but wiped it out? Are you thinking about getting a goat or two, but wonder how you're going to contain those very adept escape artists? Maybe it's time to start thinking about an electric fence. Keep your livestock in or intruders out with an electric fence that isn't tied to the grid and uses renewable, readily available energy. Because you are dealing with solar power, the fence charger will need to be installed in a place with direct, unrestricted sunlight.
Electric Garden Fence
Fi-Shock offers durable solar-powered electric fence chargers, and low-cost solar electric fence chargers for farm and garden use. They're used to contain cattle or livestock in a field or to keep unwanted animals out of a garden.


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Tel: (860)945-0621
Grades: K-9 | 257 students
- St. Mary Magdalen School is a Catholic elementary school in the Archdiocese of Hartford.
- It presently consists of grades pre-kindergarten through eight.
- It is situated in a suburb of Waterbury in the Oakville section of Watertown.
- St. Mary Magdalen School shares in the aim and purpose of Catholic Education by concentrating on the total development of each student.
- At St. Mary Magdalen School, we value the human life that Jesus affirmed, thus our stress on Respect -- respect of self and others, and our stress on Self-discipline.
School Overview
|School Membership(s)School Assoc.
|National Catholic Educational Association (NCEA)
Other school association(s)
|Religious Affiliation
|Roman Catholic
|Grades Offered
|Grades Kindergarten-9
Student Body
|Total Students
|257 students
|Student Body Type
|% Students of Color
State avg.: 22%
|Students by Grade
Academics and Faculty
|Total Classroom Teachers
|10 teachers
|Student : Teacher Ratio
National avg.: 13:1
Related Schools
Show me:
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- School Location Miles Grades Students
WaterburyGrades: PK-8 | 323 students
3.5 miles
55 Cole St
Waterbury, CT 06706
School Reviews
Recent Articles
February 11, 2017
Let's think about the employment process from the point of view of your making me want to hire you. Here are some points to ponder.
February 10, 2017
It is easy to fall into the trap of not keeping your skill-set current. There's no time and no need anyway. We look at why you need to keep things current and offer some suggestions as to how to proceed.
February 10, 2017
The only way private schools can build their financial security is through gifts. Major gifts offer proof of how deeply many donors feel about their private schools. Their munificence is a wonderful example to others.


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Obviously, a brand you can trust and performance are reasons why you bought your Ford. But you have to keep it running by using the best replacement Starter parts possible. If you find yourself in need of parts to fix your Ford, then we can help you. If you drive a Ford, you know it's responsible to keep it in good working order. All Ford drivers will agree that the best parts, especially replacement Starter, are the only parts that they will install on their vehicle.
The days of crank-starting your engine are long gone, and now all vehicles, even your Ford, turn the motor over with an electric starter. When you turn the key, your ignition switch closes a circuit that sends current from the battery right to it. Your starter is a heavy machine and will be located next to the flywheel or flex plate. After verifying adequate current in your starting circuit with a voltage meter, if your Ford engine still doesn't start this is likely what needs to be replaced.
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Mercedes-Benz for Sale
Selected Filters:Type of Ad: Vehicles for Sale Make: Mercedes-Benz
1966 Mercedes-Benz 230SL
Beverly Hills, CA
1966 Mercedes-Benz 230SL Pagoda '66 Mercedes-Benz 230SL Pagoda with 2 tops in beige with with tan interior. Comes equipped with an automatic transmission, power steering,... More
Advertiser since 2009
2005 Mercedes-Benz CL55 2-Door Coupe
Bellevue, WA
2005 Mercedes-Benz CL55 in Black with Anthracite AMG Leather Interior. 5.5L V8 Engine. Automatic Trans. As an AMG model, this CL55 showcases a large... More
Advertiser since 2005
1997 Mercedes-Benz SL500 Convertible
Bellevue, WA
1997 Mercedes-Benz SL500 '40th Anniversary Edition' Convertible (1 of only 500 made for worldwide with only 250 to USA) in the sophisticated combination of... More
Advertiser since 2005
1974 Mercedes-Benz 450SLC Sunroof Coupe
Brook Park, OH
Chassis# 10702412005612 Paint Code: 862G Pine Green Metallic A 1974 Mercedes Benz 450 SLC, sunroof coupe. Pine Green metallic with a tan interior. 103,000 miles. Just came... More
Advertiser since 2011
2011 Mercedes-Benz CL65 AMG
Oyster Bay, NY
Amazing 6k mile original car with zero to complain about. This is a very rare opportunity to take advantage of a roughly $200k car... More
Advertiser since 1983
2017 Mercedes-Benz G63 AMG SUV
Temple Hills, MD
NEW ARRIVAL! 2017 MERCEDES BENZ G63 AMG WITH 563 HORSEPOWER AND 561LB-FT TORQUE. SHE IS ABSOLUTELY THE EPITOME OF BEAUTY AND THE BEAST COMBINED.... More
1979 Mercedes-Benz 450SL
Beverly Hills, CA
1979 Mercedes-Benz 450SL '79 Mercedes-Benz 450SL with 2 tops and 54,403 on the odometer in its original color code#606G maple yellow with brown interior. Comes... More
Advertiser since 2009
2014 Mercedes-Benz SL550 Convertible
Las Vegas, NV
This 2014 Mercedes-Benz SL-Class 2dr 2dr Roadster SL550 features a 4.7L 8 CYLINDER 8cyl Gasoline engine. It is equipped with a 7 Speed Automatic... More
1955 Mercedes-Benz 300SL Gullwing
Miami, FL
*1955 Mercedes 300 SL Gullwing* This excepcional example has benefited from a comprehensive professional restoration by Marc Pastorelli. This job was made with a open... More
1968 Mercedes-Benz 250S
Reno, NV
For your consideration... 1968 Mercedes 250 S...3rd owner of this classic auto...original engine was replaced w/ a factory Mercedes 280 engine, improving power and performance.... More
2009 Mercedes-Benz SL65 AMG SL65 Black Series
Miami, FL
2009 Mercedes SL65 AMG Black Series 10,200 Original Miles Grey over Black Fully Documented, Books, Tools and Records. Almost Completely Carbon Fiber, V12 BiTurbo, 661hp, 738lb ft of... More
2013 Mercedes-Benz G63 AMG
MERCEDES G 63 AMG STILL UNDER CERTIFIED WARRANTY (UNLIMITED MILEAGE) TILL JULY 2018, ALL THE OPTIONS YOU CAN THINK, $4950 DESIGNO BLACK LEATHER. Unlimited... More
1979 Mercedes-Benz Gazelle Roadster Replica
Oklahoma City, OK
www.leakecar.com for more info. To be auctioned in OKC, February 24-26, 2017. - 1.6L 4 cylinder engine - 4-speed manual transmission - Manufactured... More
1961 Mercedes-Benz 190SL
Amelia Island, Florida
1961 Mercedes-Benz 190 SL To be OFFERED AT AUCTION at RM Sotheby's Amelia Island event, March 10-11, 2017.Estimate:$200,000 - $225,000 US120 bhp, 1,897... More
1963 Mercedes-Benz 220SE Cabriolet
Astoria, NY
This 1963 Mercedes-Benz 220SE Cabriolet is an excellent original California car and an absolutely beautiful driver. Cream with a brown top and interior. The car... More
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Download video: NEW BMW 740i M Sport Package / 20" M Wheels / Quick BMW Review
Channel: Scott BMW Smith
TIP: Right-click and select "Save link as.." to download video
Initializing link download.....
Next Generation 2016 BMW 740i with 20 inch M Wheels. M Sport Package. New Panoramic Sky Lounge LED Roof. Executive Package & Ambient Air Package. 0 to 60 in 5.4 seconds. Quick BMW Review. Car Review. BMW 7 Series. Rev Time with Trish! Trish's instagram is BMW_TRISHA


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Example word problem:Chris has had three surprise birthday parties over the course of his life.The first surprise party was for his 28th birthday.The next one was x years later.The third party was 3x years later for his 60th birthday.How old was Chris at his second surprise party?
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The Choko Nuki series is sending you to a new and exciting place... school!
When you pop a woodie you can't hide, the cat-eared seitoucho reaches right over
and starts jacking you off in the middle of the lesson.
Fap and enjoy in situations where it seems like they'll get caught any time:
in class, in the auditorium, in a meeting room, in the library, in the clinic and more!!
Choko Nuki makes it easy to navigate all the scenarios!
Pick your favorite scenes with no hassle!
You don't have to play in order to unlock anything: it's all instantly available!
* 1280x720 size big screen!
* No voice or music


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- Details
- Specs
- Reviews
DETAILSBuilt on Five Ten's Stonelands Last, the Lace-Up is a high-performance tool that's designed to take climbers from their local gym to Hueco Tanks to long routes in the Alps. The Stonelands Lace-Up is truly the shoe to wear when you're looking for trouble. Inside the Stonelands Lace-Up is a synthetic sock for all day comfort; underneath is a supportive midsole for edging precision and both lateral and medial control. The new last cradles the foot in a flat-toed position for power and comfort.
- Short Description
- C4 Rubber
- Synthetic
- Supportive midsole for edging precision and both lateral and medial control
- Flat-toed position for power and comfort
- ft-stonelandlace-p
- Brand Name
- Five Ten


text: Seller: shawnandcheryl (588) 100%, Location: Manchester, Ships to: GB, Item: 222331395473 Antique mahogany wardrobe in very good condition for its age come with the original mirror. Splits into 4 . Delivery available upto 25.miles for an extra charge. Anyone wishing to purchase this wardrobe further a field can arrange there own courier. Material: Mahogany, Original/Reproduction: Original


text:
Förskola common core
Utforska relaterade ämnen
Outdoor Sound Exploration Station - This kindergarten teacher led her students in an inquiry project that resulted in this awesome outdoor sound exploration station for the playground! Science, math, reading, writing, research, planning, and 21st century skills are all involved, and the final result is fun for years to come. LOVE this!
Ready, Set, Measure! Measurement Task Cards for the Second Grade Common Core - This measurement task card pack was designed to address second grade Common Core Standards 2.MD.A.1, 2.MD.A.2, 2.MD.A.3, 2.MD.A.4, and 2.MD.B.5. A total of ten sets of task cards are included. Many have multiple uses, and all include recording sheets and answer keys. They are perfect for scoot games and math centers! $
FREEBIE.. contains 6 riddles aligned to the Common Core Standard 2.G.1 where students have to recognize and draw shapes having specific attributes, such as a given number of angles or a given number of equal faces. They must identify triangles, quadrilaterals, pentagons, hexagons, and cubes. Two different copies of the riddles are included. One with a shape word box and a trickier version without a shape word box.
A Treasure Of A Unit For 2nd Grade: Abuelo And The Three Bears {Common Core Aligned} ~This Unit Is Aligned To The CCSS And EACH PAGE Has The Specific CCSS Listed~ This is a 94 page resource and activity packet. $
Kindergarten Common Core Number Strategy Posters: {Math Wo
Three sets of counting printable practice pages for numbers 1-20 plus center mats that use winter season clip art and are common core aligned and differentiated. Available in color and black and white.
When I started teaching common core math three years ago, I was a little overwhelmed to say the least! So many things were different, and th...
This pack contains Spring themed alphabet practice, rhyming, syllables, patterns, numbers 1-20, counting, adding, subtracting, shapes, and more! 52 ready to use, no prep printables in ink saving black and white. Answer keys included. *Aligned to Kindergarten Common Core Standards* $
Do you remember using dot paper as a kid? It was always one of my favorite things! My grandmother used to carefully draw the dots by h...
Musical Paint - a wonderful iOS app for learning Music and other subjects through lessons aligned w/ common core standards


text:
- Hedingham School and Sixth Form
Yeldham Road
Sible Hedingham
- Head: John Panayi Ba Cert Ed Npqh
- E firstname.lastname@example.com
- W www.hedingham.essex.sch.uk
- A mainstream state school for pupils aged from 11 to 18
- Boarding: No
- Local authority: Essex
- Pupils: 1095
- Religion: Does not apply
- Current Ofsted grade: Good on 3rd May 2013
- Previous Ofsted grade: Satisfactory on 20th January 2011
- Ofsted report: View the Ofsted report
What the parents say...
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Graphite Grey
Pearl Black
Pearl Red
Phoenix Red
Sand Beige
Silky Silver
Solid White
|Kerb Weight
|No of Doors
|4 doors
|Overall Height
|1670 mm
|Overall Length
|3600 mm
|Overall Width
|1475 mm
|Seating Capacity
|5 persons
|Alloy Wheels
|Steering Adjustment
|AM/FM Radio
|CD Player
|Central Locking
|Power Door Locks
|Steering Adjustment
88 replies 2015-06-16T09:02:16+05:00
40 replies 2015-06-08T18:25:27+05:00
38 replies 2015-11-23T07:49:34+05:00
33 replies 2015-10-23T09:26:59+05:00
29 replies 2015-05-03T05:08:09+05:00
Posted by Pakwheels User on Feb 20, 2017
It's Economi car. Car have same exterior but different prize on different versions. VR no power steering, AC,power window etc. VXl and VXR main difference is power windows. Company is taking ap...
Posted by Pakwheels User on Feb 08, 2017
Fuel economy is simply amazing. Steering control is way awesome than one can ever expect. Internal comfort is 10 on 10. One just can't get such an amazing ride in such reasonable amount. Shape is a...


text:
export xml from viretuemart category/product
This project received 13 bids from talented freelancers with an average bid price of $214 USD.Get free quotes for a project like this
Project BudgetN/A
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Project Description
I need a component for Joomla (I have the basis I have to develop some parts missing)
The component should display orderly manner in the list of store categories, such as:
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And from each category, list the products exactly like:
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Chester Higgins
Echo of the Spirit : A Photographer?s Journey
Книгу можно купить в интернет-магазинах:
· OZON.ru 2649р. [Проверить наличие]
ISBN: 0385509782Издательство: Doubleday
Год издания: 2004
Страниц: 208
Book Description In stunning photographs and an intimate, moving narrative, award-winning New York Times photographer, Chester Higgins, chronicles his forty-year quest to capture and celebrate the singular, defining qualities of people, places, and events. As a New York Times photographer, Higgins has taken glorious, one-of-a-kind pictures of people from all walks of life and covered grim disasters and history-making events. Throughout his career, Higgins has also pursued a more personal mission: in unforgettable photographs, he has documented the history and lives of people of African American and African descent. ECHO OF THE SPIRIT is Higgins's most personal work to date. In photographs rich in spirit and memory and a simple but elegant text, he focuses on the significant people and events of his own life, from his days as a boyhood preacher in New Brockton, Alabama, where he was reared by his mother and stepfather, to his first encounters with the...
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text:
Post Ur Setup \ My Setup: Tenor Keiwerth EX90 III Mpc : Super Tone master 6 * Lig : Orginal and FL Brass PlatedLast Post By: hfrank 02-24-2017, 04:47 PM
I have been searching the web for Leblanc Saxophones trying to put a serial number list together this is what I have found. Serial Number Type Year Source 542 Tenor Semi Rationale 1950's http://doctorsax.biz/LeBlanc_Rationale_Tenor.htm ...Last Post By: AMASAX Yesterday, 10:50 PM
Hello everyone, On another thread I've been trading free jazz clips with Jason Dumars and it occurred to me it would be cool to open a thread for members clips of only free jazz, free improvisation, new music, avant-garde, generally wacky ****! There are a number of players on SOTW that are...Last Post By: osloutah Yesterday, 07:25 PM
I learned how to do this 30 years ago from Ralph Loomis, principal clarinetist in the U.S. Coast Band for many years. I'm not sure if he came up with this himself, but I think he did. A few bucks worth of supplies will create a lifetime's worth of ligatures (I think I'm still using the wax paper...Last Post By: Rackety Sax Today, 04:21 AM
I know there are threads like this elsewhere - but what about one entirely devoted to Yamaha instruments? So, post your set-up!Last Post By: J.Max 02-24-2017, 04:11 AM
Yes.....I agree with all the above
And thank you very much
Don't want to get carried away
Did you end up selling the piece? If so, can I know how much did it go for? if you still have it and want to sell it, please let me know.. I might be interested..
There are plenty of these horns around, the Series IV and the repad is what makes this a bargain.
I love my TT, and it's just like this one- see my album . Set up right is the key. If what you get...
Pics here :87101
It's 10 in a box, thank you!
:) As a matter of fact, I do work VERY hard to get the last bit of toothpaste out of the tube, though I haven't yet injured myself.Rackety Sax Today, 04:21 AM
Here is the Rubber LR III 7 Alto: https://www.ebay.com/itm/201833754187LowWoodwindMan Today, 04:21 AM


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Reviewed By RJ S (Clinton Township, MI) Reviewed for a 2006 Chevy Colorado —10/28/2010 6:50 AM
Great product, does everything advertised and more. Only thing that bugs me is I think it could be made to switch from up to down a little easier.
Reviewed By Corey Y (New Blaine, AR) Reviewed for a 2015 Chevy Silverado —1/20/2016 5:19 PM
I bought this 4 months ago got it installed and it works great I pulled out a tractor buried up to its axles in mud sideways without strain it was a John Deere 5105 nothing too huge but you should have seen how it was buried had to chain the back end to a tree would have slid my whole truck towards it got the synthetic rope too I am very happy with it I've got installed on a 2015 Chevy Silverado four-wheel-drive highly recommend it, and I highly recommend buying it from auto anything.com


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Rating: 0.0/5 (Total votes: 0)
BPBible Portable is the BPBible Bible study tool packaged as a portable app, so you can take your Bibles with you on your iPod, USB flash drive, portable hard drive, etc. It has all the same great features as BPBible including support Bibles, commentaries, dictionaries, Gospel harmonies and more.
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Windows Software - Free Windows Downloads, Apps, Games, Freeware, Skype, Media Player, Antivirus, Gimp, Live, Starter for Windows XP, Vista, 7, 8, 10


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Hotel Ozkaymak Konya
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TravelPod Member ReviewsHotel Ozkaymak Konya
Room 115 - big room with two singles beds put together as I king and a double sofa bed.
Well here we go...
The air conditioner doesn't work properly, we have it on cold 5 deg and it is hot...
Hair dryer blew up after 2 minutes, literally 2 minutes...
Our room has a keyed safe... NO key!!!
Carpet ripped up.
Bathroom however is pretty good, not modern by any means but better than the last two days.
Dinner was a buffet with plenty of variety and very nice. The wait staff in lobby bar and lounge were very nice and happy to help us.
One of our fellow travellers a, Charles, had to strip his bed as it was musty, as in his words "smelt of underarm odour".
This review is the subjective opinion of a TravelPod member and not of TravelPod.com.
TripAdvisor Reviews Hotel Ozkaymak Konya
Travel Blogs from Konya
On the road to Konya And Happy Wedding anniversary
... at the Sultanhani Caravanserai built 1228 to sell goods and put up the camel trains traveling from China. Now heading to Konya the most conservative city we will be staying. We had a stop at the Melvana Museum where there is the burial place of the great Suri and his son. He was the founder of the Whirling Dervishes. Very opulent and heaving with locals. The most important artifact here (after the bodies) is a treasure box containing Siri's ...
Lots of driving and a Karavansay!
October 14 2015
This morning we left for a long day! I left my sunglasses behind but fortunately Perry has organized to get them sent on – they were under the bed! We first went to the Aspendos Theatre, which was absolutely brilliant – and is still being used nowadays. Long drive followed by a nice lunch again – I felt ...
Heading west from Cappadocia to Konya
... surprised by the litter all over the place. Sad. We arrive at a hotel for a night's stop just to the north of Konya. Again we find ourselves in the middle of another booming area full of new buildings and two new universities. We were going to go out and visit the ancient town of Lystra (Konya = the ancient Iconium which Paul visited on two of his journeys) but we decide that r&r in the nice spa-pool and fitness area is a better plan under the ...
A break in the heat
... hot here for the past week. The days start out hot and reach peak temperatures around 4pm, during our third shift. We wake up at 6am, work from 7-9:30am, eat second breakfast, work from 10am-1pm, eat lunch and rest for 2 hours and then have a final shift from 3-5:30pm. The last part of the day is the worst – as the heat increases the pace of work slows down and we seem to spend a lot more time on paperwork than ...
After a good night's sleep (Mert shooed away the drummers this morning, so it wasn't nearly as long or loud!) we packed up and hit the road! While traveling to Konya, we stopped in a town called Guzelyurt for a visit with a local Imam. The mosque was an old converted church built by St. Gregory. Gregorian chants originated in this area. Our Imam was young...early 30's.... Mert warned us he looks like George Clooney! We had the opportunity to ask questions about all sorts ...


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or 2 Easy Pays of $14.50
+ S&H and tax Good until February 21, 2017 4:59 a.m. ET
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A Note About Pad Tackiness
The tackiness of this pad will diminish with repositioning. We recommend that you don't move your pad once it's in place, as the pad will lose its adhesiveness.
Information supplied by Royal Palace® Rugs.


text:
Israel News
Business & Innovation
Middle East
American Politics
Ban Ki-moon at UN Human Rights Council 370.
(photo credit:REUTERS/Denis Balibouse)
UNITED NATIONS -UN Secretary-General Ban Ki-Moon said on Tuesday that the use of chemical weapons "under any circumstances" in Syria— whether it be an attack perpetrated by the regime of Bashar Assad or by his opposition— would constitute an "outrageous crime."But Ban's office told the Post that it has no definitive confirmation that such weapons were used this week, amid allegations from both parties in the Syrian conflict that the other had used deadly chemicals in an attack that killed up to 31 people.
By AMOTZ ASA-EL
By ADAM RASGON
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Home Retirement Resource Center Retirement Policy Issues
- Strength of Retirement System
- Retirement Plans: Workers' Access
& Support
- Understanding Tax-Deferred Benefits
- Fees in Retirement Plans
- Retirement Policy Issues
- Participant Education
- More ICI Retirement Resources
Retirement Policy Issues
Policymakers can and should take a range of steps to create a better retirement future for America. These include:
- Putting Social Security on a sound financial footing
- Helping workers gain a deeper understanding of retirement savings
- Fostering more innovations, such as automatic savings escalation and new ways to manage retirement income, and
- Facing up to fiscal challenges without undermining retirement savings.
- Focus on Funds: Investor Protections Missing from New Retirement Plan
Fri Oct 14 00:00:00 EDT 2016
- Focus on Funds: New California Retirement Plan Brings Many Risks
Fri Oct 07 00:00:00 EDT 2016
- ICI Submits Comment Letter on DOL Proposed Rule for Auto-IRAs Established by Municipalities for Private-Sector Workers (pdf)
Thu Sep 29 00:00:00 EDT 2016
- ICI Applauds Committee Passage of Open MEP Provision to Help Small Employers Offer Retirement Plans
Thu Sep 22 00:00:00 EDT 2016
- ICI Responds to DOL's Final Rule on State-Run Retirement Programs
Thu Aug 25 00:00:00 EDT 2016
- Secure Choice Is Risky for Workers and for the StateAug 17, 2016
- Three Reasons Why You Should Consider an IRAMar 8, 2016
- Better Retirements? Build on the System's Current Successes
Thu Sep 18 00:00:00 EDT 2014
- ICI Statement for Senate Hearing on "Retirement Savings 2.0: Updating Savings Policy for the Modern Economy" (pdf)
Tue Sep 16 00:00:00 EDT 2014
- 2014 ICI Retirement SummitApr 4, 2014
- The Future of Retirement
Thu Sep 27 00:00:00 EDT 2012
Copyright © 2017 by the Investment Company Institute


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Greetings Guest!!Dismiss Notice
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Meet Elesil Daelwon in the throne room of Brit. Castle next Sunday the 02.10 at 20:30
Discussion in 'UO Drachenfels' started by Drachenfels EM Feed, Sep 26, 2011.


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I wouldn't.
I wouldn't.
I wouldn't.
I have 3 children those exact ages.
Heck no would i be leaving them alone in the house.
We very occasionally let the 9yr old stay at the house while we go check the animals (we live on a farm) but id not expect her to be in charge or responsible for her siblings so they come with
No way
No and no
Not something I'd feel comfortable with. Too many what ifs. And I think they're actually more defenseless if they're sleeping in a way (eg if there was an intruder or fire).
I wouldn't do it. Too risky. They're asleep but they can easily wake up. My kids wake up occasionally (5 and 3) and wonder around the house. My 3yr old woke us up last week screaming in pain as he had wondered out of bed, tripped on a tiled step and cut his nose on the edge, blood everywhere, lots of trauma. It was 2.30 in the morning. So no, I wouldn't leave them to go for a walk. When he used to sleep in a cot I have on very very rare occasions driven 1 minute up the road to the petrol station for emergency supplies. But I was out of the house for less time than it takes to go to the loo.
No - not at all. I cant help but panic about everything - burglary, fire, you name it. And no to the other 2 questions too.
No, I don't think it's okay.
9 is very young to be home alone in charge of two younger siblings.
Too many 'what ifs'.
And yes, the eldest child having ASD may potentially make the situation less safe than if a neurotypical 9 year old was left home without parental supervision (I have an ASD child myself).
I have a very responsible nearly 9 year old, 6 year old who is also very well behaved and 3 year old and no way I'd leave them home alone for any length of time.
Pregnant for the first-time?
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text: In previous versions of Windows, there was no mechanism for creating multiple local Group Policy Objects. The only way you could filter Local Group Policy was by applying NTFS deny access permissions on the Group Policy. Windows Vista allows you to create multiple local GPOs. You can create them for any user, by name, for all the members of the local Administrators group, and for all users who are NOT members of the local Administrators group. You may wish to disable this ability in your domain: http://www.jsifaq.com/SF/Tips/Tip.aspx?id=11129


text:
Pitman Training Preston
microsoft, computer training, Business Skills
If you have a little familiarity with Microsoft Office and want a total command of this software then the Microsoft Office Plus Diploma will give you the essential skills ensuring you become a valuable asset to any employer. This programme could increase your earnings potential and enhance your career prospects in today's competitive job market. The use of technology is paramount to the efficiency and effectiveness of a business and having the right staff with the right skills ensures that the business is able to meet its objectives. Therefore, a total command of Microsoft's universally accepted software is crucial; yet only a few take the time to learn it thoroughly and benefit from its full functionality. This Diploma will give you both increased satisfaction and job prospects. Whether you have a little familiarity with some of the programs already, or are coming to them completely new, the values of learning how to use and control Microsoft applications properly is a skill that will last and with expertise in these packages, you will soon become a valuable asset to any employer. What's more, it could increase your earnings potential and enhance your career prospects in today's competitive job market. Learning Microsoft Office skills is easy with Pitman Training. Our tried and trusted methods are the best available. You will work at your own pace in our comfortable premises, helped by experienced tutors as required. You choose your own hours and keep the reference materials when the course is over. On completion, you will receive a Pitman Training Diploma that is recognised nationally and internationally by employers. Successful completion of this Diploma will enable students to continue their studies to become Microsoft certified.
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Original Chex® Party Mix
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Got yourself a room full of fans dressed in orange? Serve them up a bowl of this tasty, cheddar-ific Chex Mix, and they'll go wild.
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Blogger Brooke McLay from Cheeky Kitchen shares a favorite recipe.
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|Home | About | Journals | Submit | Contact Us | Français
Radiolabeled arginine-glycine-aspartate (RGD) peptides are increasingly used in preclinical and clinical studies to assess the expression and function of the αvβ3 integrin, a cellular adhesion molecule involved in angiogenesis and tumor metastasis formation. To better understand the PET signal obtained with radiolabeled RGD peptides, we have constructed a compartmental model that can describe the time–activity curves in tumors after an intravenous injection.
We analyzed 60-min dynamic PET scans obtained with 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N′′-tetraacetic acid (DOTA)-RGD in 20 tumor-bearing severe combined immunodeficient (SCID) mice after a bolus dose (18,500 kBq [500 μCi]), using variations of the standard 2-compartment (4k) tissue model augmented with a compartment for irreversible tracer internalization. αvβ3 binding sites were blocked in 5 studies with a coinjection of cold peptide. In addition, 20 h after injection, static PET was performed on 9 of 20 mice. We fitted 2k (k3 = k4 = 0), 3k (k4 = 0), 4k, and 4kc (k4 = constant) models to the PET data and used several criteria to determine the best model structure for describing 64Cu-DOTA-RGD kinetics in mice. Akaike information criteria (AIC), calculated from model fits and the ability of each model to predict tumor concentration 20 h after tracer injection, were considered.
The 4kc model has the best profile in terms of AIC values and predictive ability, and a constant k4 is further supported by Logan–Patlak analysis and results from iterative Bayesian parameter estimation. The internalization compartment allows quantification of the putative tracer internalization rate for each study, which is estimated here to be approximately an order of magnitude less than k3 and thus does not confound the apparent specific binding of the tracer to the tumor integrin during the first 60 min of the scan. Analysis of specific (S) and nonspecific or nondisplaceable (ND) binding using fitted parameter values showed that the 4kc model provided expected results when comparing αvβ3 blocked and nonblocked studies. That is, specific volume of distribution, [VS = (K1k3)/(k2k4)], is much higher than is nondisplaceable volume of distribution, [VND = (K1/k2)], in nonblocking studies (2.2 ± 0.6 vs. 0.85 ± 0.14); VS and VND are about the same in the blocking studies (0.46 ± 1.6 vs. 0.56 ± 0.09). Also, the ratio of static tumor and plasma measurements at 60 and 10 min [CT(60)/CP(10)] is highly correlated (RS = 0.92) to tumor VS.
We have developed and tested a compartmental model for use with the 64Cu-DOTA-RGD PET tracer and demonstrated its potential as a tool for analysis and design of preclinical and clinical imaging studies.
The cell surface glycoprotein αvβ3 is a member of the integrin family whose primary role is mediating interaction between αvβ3-expressing cells and the extracellular matrix, pathogens, or other cells (1,2). αvβ3 is expressed on certain tumor and endothelial cells and plays an important role in tumor migration and angiogenesis (1,3); αvβ3 antagonists have been shown to induce cell death (1), making this integrin an attractive target for novel cancer therapeutics that inhibit angiogenesis and tumor growth. αvβ3 binds to the arginine-glycine-aspartate (RGD) peptide motif within its in vivo protein ligands (e.g., fibrinogen) (2). Small-molecule RGD peptide antagonists with a high affinity for αvβ3 have been developed with the intention of blocking αvβ3 function. Haubner et al. (4) developed the first αvβ3-specific PET tracer, 18F-galacto-RGD, and subsequently used it to image patients with cancer (5) in whom a strong association between tracer uptake and αvβ3 expression was observed (6). In squamous cell carcinomas of the head and neck region, uptake of radiolabeled RGD has been suggested to be a potential surrogate parameter of tumor angiogenesis (7). Generally, small-molecule αvβ3 PET tracers are being developed as a means to assess tumor aggressiveness and monitor αvβ3 expression before and after treatment with αvβ3 antagonists.
To accurately assess the magnitude of specific binding of a PET tracer to αvβ3, one must be able to separate the PET signal into perfusion and nonspecific and specific binding components. Recently, pharmacokinetic analysis of the 18F-galacto-RGD PET tracer was performed by Beer et al. (8) using 1- and 2-compartment tissue models fitted to biodistribution data from patients with cancer. Here we applied a similar compartmental modeling approach to the kinetic analysis of the 64Cu-c(RGDfK(1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid [DOTA])) (64Cu-DOTA-RGD) PET tracer in mouse models bearing tumors grown from cell lines that express low (A431 epidermal carcinoma), intermediate (U373 glioblastoma-astrocytoma), and high (U87 glioblastoma-astrocytoma) levels of αvβ3. Additionally, αvβ3 binding sites are blocked with a coinjection of cold peptide in selected studies, and 20-h postinjection static PET scans are acquired for selected blocked and nonblocked studies. Four different 2-compartment tissue models are fitted to tumor time–activity curves, and the best model was chosen using the Akaike information criterion (AIC) (9) calculated for each model fitted to both the dynamic scans at 60 min and dynamic data at 20 h after injection. Model-fitting results using a Bayesian or population kinetics approach (10) are also considered. We demonstrated that magnitude of specific binding, as calculated on the basis of fitted model parameters, strongly correlates to the level of αvβ3 expression. The 20-h postinjection scans facilitate estimation of the αvβ3-mediated tracer internalization rate (11,12) and allow us to determine whether this process confounds measurement of specific binding during the initial 60-min dynamic scan. We also explored the possibility of estimating the capacity of tumor to sequester tracer via specific binding to αvβ3 by deriving a macroparameter equal to the ratio of static tumor and blood-tracer concentration measurements.
The peptide c(RGDfK(DOTA)) was constructed as described previously (13). 64CuCl2 (specific activity, 185 GBq [5 Ci/mg]) (MDS Norion) was labeled by incubating 1.25 µg of c(RGDfK(DOTA)) with 64CuCl2 (37 MBq [1 mCi]) for 1 h at 50°C in a total volume of 200 µL of 0.1 M ammonium acetate (pH 7.1). The radiolabeled peptide was purified using a 1-mL strata-X 33-µm polymeric reversed-phase column (Phenomenex, Inc.). After a water wash, the labeled peptide was eluted in 100% ethanol, dried over argon gas at 60°C, and resuspended in 0.9% saline. In vivo metabolic stability of a similar compound, 64Cu-DOTA-cRGDfk peptide tetramer, was demonstrated by Wu et al. (14), suggesting our monomer has comparable stability.
Severe combined immunodeficient (SCID) mice were purchased from The Jackson Laboratory. All animal manipulations were performed with sterile techniques according to the guidelines of the UCLA Animal Research Committee. U87MG, U373, and A431 cells (2 × 106 cells/mouse) were resuspended in phosphate-buffered saline and Matrigel (BD Biosciences) and injected subcutaneously into the right front or right rear leg of 7-wk-old male mice. Imaging was performed after tumors had grown to an approximate size of 100 mm3 as measured using calipers.
Animals were imaged with a microPET FOCUS 220 scanner (Siemens) and a micro-CAT II scanner (Siemens) (15). 64Cu-DOTA-RGD (18,500 kBq [500 μCi]) was injected via tail vein cannulation. At the time of injection, 60-min dynamic small-animal PET scans with corresponding 7-min micro-CT scans were obtained, followed by 10-min static small-animal PET and micro-CT scans approximately 20 h after injection as previously described (16). For blocked studies, c(RGDfK) (Peptides International) was resuspended in 0.9% saline and mixed with the radiolabeled probe at 10 mg of peptide per kilogram of mouse; scans were acquired as described above. Late-time small-animal PET and micro-CT scans were obtained at approximately 20 h after injection. PET images were reconstructed with filtered backprojection and CT-based attenuation correction. Frame durations were 20 × 0.5 s, 5 × 10 s, 10 × 60 s, 9 × 5 min, and 1 × 4 min for 60-min scans. The 90-min scans used a framing scheme of 6 × 10 s, 10 × 60 s, 10 × 5 min, 2 × 10 min, and 1 × 9 min. A total of 20 mice were used, 4 with both U87 and A431 tumors, for a total of 24 tumor time–activity curves. Here, we primarily considered the results of the 5 blocked and 12 nonblocked studies (17 tumor time–activity curves); 7 additional datasets, collected under slightly different conditions, were used for the population-modeling portion of this study.
Using Amide (17), we determined the tracer concentration in tumors by drawing spheric (diameter, 1.5 mm) regions of interest (ROIs) in the area of the reconstructed PET image within the tumor that exhibited the highest radioactivity, as determined by visual inspection. Whole-blood concentration was estimated by drawing an ROI in the region of the image corresponding to the left ventricle of the heart. Activity concentrations are expressed as percentage injected dose per gram of tissue.
A linear compartmental model (Fig. 1) was used in this study, where u(t) represents plasma concentration of the tracer calculated by correcting PET-measured blood concentration for partial-volume effects and absence of uptake by blood cells. A recovery coefficient of 0.7 (18) and hematocrit of 50% (19) are assumed, resulting in a PET-measured whole-blood (WBPET)–to–actual plasma (Pa) tracer concentration ratio of
for the 60-min dynamic scans, and
for the 20-h postinjection scans, where partial-volume effects are not an issue because of low plasma concentration of tracer and comparable activity in myocardium. Spillover from the myocardium may slightly increase apparent tracer concentration at 20 h after injection; here we assumed spillover error is negligible. Compartments q1(t) and q2(t) represent the amount of free or nonspecifically bound and specifically bound tracer within tumor extravascular space, respectively. Several model structures could be used to describe the 20-h postinjection data point; here we assumed internalization is a linear process mediated by binding of ligand to receptor, thus, compartment q3(t) was added to represent tracer that has been irreversibly internalized by tumor cells (20). Model equations are written as
where, putatively, K1 represents the tracer extravasation rate (min−1), k2 represents the rate of tissue efflux of free or nonspecifically bound tracer (min−1), and k3 represents the rate of specific binding (min−1) of 64Cu-DOTA-RGD to the extracellular portion of the αvβ3 integrin. k4 and kint represent rates of dissociation (min−1) and internalization (min−1) of specifically bound tracer, respectively. Note that kint is assumed to represent internalization; however, all slow uptake mechanisms are lumped into this parameter. The measurement model is written as
where VB is the fractional blood volume of the tumor (unitless) and c(t) is the tumor time–activity curve. Here we considered 4 structural perturbations of the model shown in Figure 1: a 2k model(k3 = k4 = 0) assumes PET data can be accurately described without explicitly accounting for the specific binding of 64Cu-DOTA-RGD to the αvβ3 integrin; a 3k model (k4 = 0) explicitly accounts for the specific binding of the tracer to integrin, which is assumed to be irreversible; a 4k model assumes reversible binding of tracer to integrin; and a 4kc (k4 = constant; k4 > 0) model assumes that k4 has approximately the same value across all datasets. Each of the 4 model variants is augmented with a compartment representing irreversible internalization of tracer by tumor cells (Eq. 5).
The SAAM II/PopKinetics tracer kinetic modeling program (21,22) was used to implement the model shown in Figure 1 and estimate unknown parameters (K1, k2, k3, k4, and kint). Each measured PET data point, i, was assigned a weight (wi) equal to the reciprocal of the data variance, calculated as follows:
where σi is the SD, di is frame duration, and μi is mean ROI value. Standard 2-stage (STS) and iterative 2-stage (ITS) parameter-estimation algorithms (10) were implemented using PopKinetics. The STS method sequentially fits a particular model (e.g., 4kc) individually to n PET-derived datasets using the SAAM II computational engine and calculates the mean and SD of each parameter across all datasets. The ITS method repeats this process using mean and SD values calculated using the STS method as Bayesian constraints (18,23) on the parameter space, resulting in a new set of parameter means and SDs to be used as Bayesian constraints for the next round of fits. This iterative process continues until all parameters reach a preset convergence value. Given a large enough population size, n, the ITS method can detect fixed effects in the model structure, which occur when the SD of a parameter across all n datasets approaches zero. All models were fitted to 60-min dynamic scans and then extrapolated to the 20-h postinjection data by extending the simulation time for each fitted model; the input function was extrapolated to 20 h by fitting a single exponential term (Ae−λt) to the 60-min and 20-h data points. Additionally, each model was fitted to the 60-min dynamic data plus the 20-h data.
The AIC was used to determine which of the 4 proposed model structures was most appropriate for use with 64Cu-DOTA-RGD. The AIC (9) considers goodness of fit and structural parsimony with the purpose of selecting a single model, from a group of candidate models, that best describes the data of interest while not being overly complex. The AIC is written here as
where J(p) is the objective function used to assess goodness of fit, nP is the number of adjustable model parameters, nD is the number of data points to which the model is fitted, p is the parameter vector that minimizes the objective function, and s(,ti) is the model simulation at time ti and parameter vector (22). On the basis of this criterion, the model with the lowest calculated AIC value is considered to have achieved the optimal balance between goodness of fit and structural parsimony. Additionally, we considered the ability of each model to predict the 20-h postinjection data by extrapolating models fitted to the initial dynamic PET scan.
Specific (S) and nondisplaceable (ND), that is, nonspecific, volumes of distribution (V) were calculated for blocked (n = 5) and nonblocked (n = 12) tracer studies using the following equations (24):
where K1, k2, k3, and k4 were calculated by setting kint to zero and fitting the model to data from the 60-min dynamic PET scans. Total volume of distribution (Vd) is defined as
Equations 10 and 12 are used only when k4 is nonzero; Patlak uptake [Ki = (K1k3)/(k2 + k3)] (25) could be calculated in the case where k4 is zero.
All statistical analysis (standard and paired t test, Spearman correlation, linear regression) was performed using GraphPad Prism (version 4.03 for Windows; GraphPad Software) (available at: http://www.graphpad.com).
Figure 2 shows 2k, 3k, 4k, and 4kc models fitted to tumor time–activity curves from 4 selected 60-min dynamic scans; kint(Eq. 5) is fixed at zero. Qualitatively, the first 10 min of some fits are slightly off, possibly because of lower weights assigned to these data points. The mean and SD of the 5 estimated model parameters calculated using STS and ITS estimation methods are VB = 0.049 ± 0.024 (unitless) (STS) and 0.074 ± 0.044 (ITS); K1 = 0.046 ± 0.017 min−1 and 0.031 ± 0.011 min−1; k2 = 0.18 ± 0.20 min−1 and 0.13 ± 0.12 min−1; k3 = 0.041 ± 0.035 min−1 and 0.063 ± 0.029 min−1; and k4 = 0.013 ± 0.006 min−1and 0.0094 ± 0.0 min−1. These were calculated by applying STS and ITS parameter-estimation methods to the 4k model, which was fitted to all 24 tumor time–activity curves. The ITS method converges to the 4kc model (k4 = 0.00938 min−1 for all studies) after 23 iterations, using a convergence criterion of 0.05; this value of k4 was used for the aforementioned 4kc model fits (Fig. 2) and all subsequent 4kc fits.
Figure 3A plots AIC values for the blocked αvβ3 studies, in which the 2k model has the lowest value for 4 of 5 fits; Figure 3B shows that the 2k model also has the lowest AIC for 2 of 3 nonblocked A431 studies. 3k and 4kc models have the lowest values (<1% difference between AIC3k and AIC4kc for each study) for 2 of 2 U373 studies and 5 of 7 U87 studies (Fig. 3B). The 4k model has the highest AIC value for all blocked and A431 studies, and the 2k model has the highest AIC value for 7 of 9 U373 and U87 nonblocked studies. A lower AIC value indicates a more appropriate model structure.
Figure 4A depicts a representative extrapolation to the 20-h postinjection data using the aforementioned fits to the 60-min dynamic scans. 2k, 4k, and 4kc models provide similar extrapolations, with 4kc giving a slightly better qualitative prediction; the 3k model predicts a constant accumulation of tracer in tumor, resulting in a much higher predicted concentration than that measured by the 20-h postinjection scan.
Because the 2k and 4k models performed poorly and the 3k and 4kc models performed equally well with respect to AIC analysis (Fig. 3), 3k and 4kc models were fitted to data from each 60-min dynamic scan plus the 20-h postinjection datum, with kint (Eq. 5) set as an adjustable parameter. AICs calculated for each fit (not shown) show that 4kc has the lower value across the 13 tumor models when fitted to dynamic plus 20-h postinjection scans and, thus, the better structure. Figure 4B depicts a representative fit (black curve) of the 4kc model to dynamic PET data plus the 20-h postinjection data with the first hour of data and fit shown in the inset. kint was then set to zero (gray curve) for the fitted model depicted in Figure 4B; qualitatively, little change is seen during the first hour of the simulation (Fig. 4B, inset), whereas a dramatic decrease in tumor concentration is seen over the remaining 17 h of the simulation (Fig. 4B). Figure 5A compares estimated values of VB, K1, k2, and k3 based on the 4kc model fitted to 60-min dynamic data only and 60-min dynamic data plus the 20-h postinjection data (nonblocked and blocked studies). Estimated values of VB, K1, k2, and k3 based on the 4kc model fitted to each of these 3 datasets are all similar (P > 0.2, paired t test), with the exception of k3 based on blocked studies with 20-h data (solid black circle, P < 0.05, paired t test), which is lower than the other 2 estimated k3 values (open circles). We compared mean values across all 13 tumors with 20-h scans and determined that kint is approximately an order of magnitude lower than k3 (Fig. 5A); also, the mean estimated value of kint based on blocked studies is higher than kint based on nonblocked studies. Table 1 lists estimated parameter values for the 4kc model fitted to data from αvβ3 blocked and nonblocked dynamic scans and the 20-h postinjection scan where available; models are fitted to dynamic scan data only, with kint fixed at zero, for the 4 studies without a delayed static scan.
Specific (VS) and nondisplaceable (VND) volumes of distribution (Eqs. 10 and 11) were calculated for all blocked and nonblocked studies using parameter values based on model fits to the 60-min dynamic scans (Table 1). Figure 5B plots mean ± SD of both VS and VND for all blocked and nonblocked studies, with nonblocked organized by tumor type, location, and scan duration. No statistically significant difference between VS and VND is detected for the blocked studies, and a significant increase in VS is observed for the nonblocked studies (P<0.001, n = 12), using a standard t test. Qualitatively, A431 tumors located in the thigh show a small increase in VS, whereas all remaining tumor types exhibit a much larger increase. This analysis was repeated using ROIs drawn on regions of the reconstructed PET image corresponding to muscle and liver (not shown). Blocking of αvβ3 via coinjection of cold peptide appeared to have no effect on the relationship between VS and VND in these tissues, suggesting that tracer uptake in muscle and liver is independent of αvβ3.
Additionally, VS and VND were calculated using values of K1, k2, k3, and k4 estimated by Beer et al. (8) on the basis of dynamic PET scans of 19 patients with cancer; the mean value (shown without SD) across all patients is plotted in Figure 5B. We compared means and found that both VS and VND calculated from patient PET scans were qualitatively similar to volumes of distribution calculated from our mouse studies ([0.635 (n = 19) vs. 0.754 (n = 17)] for VS and [0.271 (n = 19) vs. 0.261 (n = 17)] for VND). To obtain parameter values comparable to those listed here, we multiplied each K1 listed in Beer et al. by 0.45 (patient hematocrit ≈ 45%) (26) because tracer concentration in whole blood was used as an input function in the patient study.
Figure 5C depicts the strong correlation (RS = 0.92) that was observed between VS and the ratio of tracer concentration in tumor at 60 min after injection [CT(60)] to tracer concentration in plasma at 10 min after injection [CP(10)].
The results of our study suggest that the 4kc model, derived using the ITS parameter-estimation method, is most appropriate for describing 64Cu-DOTA-RGD PET data. Figure 6 summarizes the model discrimination process that was applied to the 2k, 3k, 4k, and 4kc structures. We were able to rule out the 2k and 4k structures by AIC analysis (Fig. 3) of each model fitted to the initial dynamic PET scans (Fig. 2). The 2k model structure yielded the lowest AICs for tumor time–activity curves in which concentration of free αvβ3 was low(blocked and A431 studies), suggesting that only a single compartment is required to describe 64Cu-DOTA-RGD kinetics in αvβ3-negative tissues. Likewise, the 3k and 4kc models yielded the lowest AICs for tumor time–activity curves in which density of free αvβ3 was high (U373 and U87 studies), suggesting that 2 compartments are needed to describe 64Cu-DOTA-RGD kinetics in αvβ3-positive tissues. Implementation of a fixed value of k4 is supported by the ITS parameter-estimation process, in which k4 converges to 0.00938 min−1 for all studies under consideration (Fig. 3), and by graphical analysis, in which Patlak uptake (Ki) and Logan volume of distribution (Vd) are highly correlated (RS ≈ 0.90, not shown) across all studies, suggesting little variability in tracer dissociation rate (k4), because Ki = f(K1, k2, k3) and Vd = f(K1, k2, k3, k4) when calculated from fitted model parameters. The 3k model structure is ruled out by fitting 3k and 4kc models to 60-min dynamic scans plus the 20-h postinjection scan, where the 4kc structure yields lower AICs (not shown); the 3k model also provides a less accurate prediction of the 20-h postinjection data, compared with 2k, 4k and 4kc structures (Fig. 4A). Although the PET-derived input function, u(t), is corrected for partial-volume effects, errors due to spillover, delay, and dispersion are assumed to be negligible and are not accounted for in the present study. The impact of spillover, in particular, is expected to be small, because uptake of αvβ3-binding RGD peptides by the myocardium is minimal (4).
By using the 20-h postinjection scans, we were able to estimate kint, the rate of irreversible tracer internalization. The black curve in Figure 4B depicts a model fit to selected 20-h data, with the inset showing the first 60 min of data and fit; the gray curve illustrates the effect of setting kint to zero, in which a negligible shift from the original fitted black curve is observed (Fig. 4B, inset). The effect of setting kint to zero suggests that although the internalization rate is high enough to produce significant retention of the tracer over a 20-h period, the rate does not confound apparent tracer retention because of specific binding to αvβ3 (k3) during the first 60–90 min after tracer injection. Even when fitting the model to data collected over a 20-h period, only a slight decrease in estimated value of k3 is observed with kint included in the model structure, compared with k3 estimated via a model fit to the 60-min dynamic scan with kint set to zero (Fig. 5A). Because tracer metabolite analysis has not yet been performed at 20 h after injection, it is possible that we overestimated 64Cu-DOTA-RGD plasma concentration at the late static scan. This overestimation would affect the accuracy of the input function past 60 min and thus the confidence level of the estimated value of kint. To assess the effect a lower actual tracer plasma concentration 20 h after injection might have on conclusions drawn from the fitted model, we lowered 20-h plasma values calculated from the reconstructed PET image by 2 orders of magnitude and then reestimated the input function as described in the "Parameter Estimation" section. As expected, the resulting kint values are higher than those listed in Table 1; however, the fitted model suggests that tracer internalization does not confound the apparent specific binding capacity of the tumor during the first 60 min after tracer injection, even when plasma concentration of tracer at 20 h after injection is assumed to be close to zero. That is, the result is similar to that shown in Figure 4B.
Figure 5A and Table 1 show that the average estimated value of kint is much higher in the blocked studies than in the nonblocked studies, suggesting that a greater fraction of αvβ3-bound peptide may be internalized per unit of time when the 10 mg/kg dose of cold peptide is coinjected with 64Cu-DOTA-RGD. The αvβ3 integrin is activated by the binding of substrate, which stimulates recycling of the integrin from the cell surface to the intracellular compartment. This process occurs when the integrin binds RGD sequences on molecules such as fibronectin or fibrinogen—analogous to the interaction between the integrin and 64Cu-DOTA-RGD described by our model—and may explain why internalization rates are higher in tumors exposed to a large bolus of integrin substrate in the form of coinjected cold peptide, compared with tumors exposed to tracer alone. The effect of kint on apparent tracer kinetics in blocked studies is similar to the effect seen in nonblocked studies (Fig. 4B).
Estimated values of specific volume of distribution (Table 1) appear to be strongly correlated with concentration of available αvβ3 binding sites within the tumor (Fig. 5B); with the exception of a single A431 study, VS increases in parallel with αvβ3 expression from baseline (blocked studies) to low (A431), intermediate (U373), and high (U87) expression. Estimated values of nondisplaceable (nonspecific) tumor uptake are approximately constant, regardless of αvβ3 status (Table 1; Fig. 5B). Along with the AIC analysis presented in Figure 3, which suggests a 1-compartment tissue model is most optimal for describing tracer kinetics in low αvβ3-expressing tissue, these data support the putative physiologic significance of the 2-compartment tissue model and associated parameters for 64Cu-DOTA-RGD, in which compartment q1(t) represents accumulation of tracer in the tumor resulting from nonspecific transport mechanisms such as extravasation (K1), tissue efflux (k2), and nonspecific binding (K1/k2). Compartment q2(t) represents accumulation in tumor due to specific binding (k3) and dissociation (k4) of tracer from αvβ3. Additionally, the internalization term kint was introduced and is required to fit the model to tracer kinetics measured over a 20-h period (not shown).
Interestingly, VS and VND calculated from a previous patient study involving 18F-galacto-RGD (8) closely match our results. Although variability across patients is not represented here, mean patient VND is virtually identical to VND calculated from our mouse studies and patient VS is similar to values calculated for the U373 tumor, which expresses αvβ3 at an intermediate level. This similarity suggests that the methods and model developed here for kinetic analysis of 64Cu-DOTA-RGD may be readily applied to patient data.
A high correlation (RS = 0.92) between the ratio of tracer concentration in the tumor at 60 min after injection to tracer concentration in plasma at 10 min [CT(60)]/[CP(10)] and specific volume of distribution (VS) (Fig. 5C) was gleaned from an extensive analysis of correlations between model microparameters (VB, K1, k2, k3, k4), macroparameters (VS, VND, Ki, Vd), and tracer uptake at discrete time points (10, 30, and 60 min). This correlation, along with the aforementioned discussion of patient VS and VND values (Fig. 5B), suggests that magnitude of αvβ3 expression could be estimated in a clinical setting on the basis of a blood sample taken at 10 min after injection and a single static PET scan at 60 min.
We conducted a thorough pharmacokinetic analysis of 64Cu-DOTA-RGD and observed the following. First, we demonstrated that the 4kc model, compared with the 2k, 3k, and 4k models, is the most appropriate structure for use with this tracer (and presumably other small molecule tracers that target αvβ3) and examined the putative physiologic significance of the 2-compartment tissue model commonly used in PET tracer kinetic analysis by demonstrating that VS, calculated on the basis of fitted model parameters, strongly correlates with the concentration of free αvβ3. Next, we showed that 20-h postinjection scans facilitated quantification of nonspecific internalization of tracer by tumor cells (kint), which is shown to occur at a slow rate relative to specific binding (k3) and dissociation (k4) and, thus, kint can be neglected for 1- to 2-h dynamic scans. Third, this model has potential for clinical applications, as demonstrated by the comparison of our results with a previous pharmacokinetic study in patients with cancer, in which the model-based values of VND and VS are similar, and the observation that VS can be approximated using a single blood sample and static PET scan.
We thank Dr. David Stout, Dr. Arion Chatziioannou, Waldemar Ladno, and Judy Edwards at the Crump Institute for Molecular Imaging for technical assistance in small-animal imaging; David Truong, David Vu, and Weber Shao (Crump) for computer support; and Stephan Schwarz at the Department of Nuclear Medicine, Medical University of Innsbruck, for excellent technical assistance in producing c(RGDfK(DOTA)). Funding was provided by NCI cancer education grant R25-CA098010 and NIBIB R01-EB001943.
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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Season 16 Episode #1612
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This half hour special will explore the most extreme ways to enjoy the great outdoors.
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Balsamic Chicken and Vegetables
We know how easy it is to resort to take-out on a busy weekday evening, but why bother? This tasty and simple low-carb meal can be ready in no time.Ingredients
1.25 lbs chicken tenders
2 TBSP olive oil
1/3 cup light Italian dressing
3 TBSP balsamic vinegar
2 TBSP honey
Generous pinch of red pepper flakes
Pepper to taste
1 bundle asparagus, trimmed and cut into 2-inch pieces
1 1/2 cups shredded carrots
1 cup of halved grape tomatoes
Whisk dressing, vinegar, honey, and seasonings together.
Heat olive oil over medium-high heat. Cook chicken for 8 minutes, flipping halfway through. Add half the dressing mixtures, and toss to coat chicken. Remove chicken onto a platter.
Add asparagus and carrots and sauté for 5 minutes. Remove and add to the platter with the chicken and top with the halved tomatoes.
Add remaining dressing and cook 1 minute or until thickened. Pour over chicken and vegetables and serve.
Nutritional Facts
- Servings
- 6
- For 1/6 the recipe
- Calories 344
- Saturated Fat 4 g
- Sodium 514 mg
- Carbohydrates 11 g
- Dietary Fiber 2 g
- Protein 27 g
2 replies
I don't know who thought added sugars worth 7 of the 11 carbs in this recipe was important and worth it. This simply is NOT my idea of a worthwhile diabetic friendly recipe with 7 grams per serving of ADDED sugars but that's just me. There's also more heart disease causing fructose in the honey and that probably help is to explain why there's a 60% positive correlation between diabetes and heart disease especially when they prepare high heart disease causing fructose recipes like this one. This is basically disgusting. If you leave out the sugars of balsamic vinegar and honey, the carbs are 4 grams.


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