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"I thought Medicare covered everything. I'm so glad I called."
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Our customers will tell you, that things like this don't happen to them. Our Medicare Supplemental Insurance Brokers on staff are also licensed "field underwriters.†we will not only aid you to find the least expensive for Medigap Insurance Costs, but we will make sure that you do be approved for the insurance policy we go forward with any paperwork. By answering a few quick questions about your health, you could easily qualified for Medicare Supplemental Plans which should approve you on the spot, without a bunch of stress or concerns of revoking coverage.
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A Medigap Insurance Plan is not an stand-in for traditional Medicare like a Medicare Advantage Policy, instead it works with traditional Medicare. Also, Medigap Insurance Plans differ from Medicare Advantage Plans because they have no co-pays, no deductibles, and no issues with being "in nework" as to where you can receive medical treatment..
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If you are on Medicare, you are possibly looking at tough final decisions on signing up for a great Medicare Insurance Policy and you are possibly having the wool pulled over your eyes by Medicare Advantage salespeople.
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We're not like others, because of the fact we work for you, not just one Medigap Plan Carrier. licensensed agents thoroughly check into each of the Medicare Supplemental Insurance Plan Providers that offer Medigap Policies and seek out the good ones that have a great reputation and also they can honor their contracts for many years to come. It's pretty simple,, our team excludes all the tiny Medicare Supplement Policy Providers and the unprofessional.
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Things like this don't happen on our watch.
All the licensed Medigap Plan Agents on our team also are Medigap Plan field underwriters.†So that means we will not only assist in buying the best Medigap Rates, but we will make certain that qualify for the policy before we ask you to apply. Simply by answering a couple uncomplicated questions about your medical history, you could easily be instantly approved for a Medicare Supplement Policy accepts your application you the first time, sans annoying frustrations or worry of of losing coverage.
We won't suggest a Medicare Supplement Insurance Plan for you unless we know that you qualify to be approved by the Medicare Supplement Insurance Plan provider. Additionally, our Best Premium Promise ensures that you never pay a dime for what we do and that you will always pay the best rate for the recommended plan you are qualified for.
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One of the best "Scandinavian" crime novels I have read, Burial Rites is the work of an Australian who visited Iceland on a cultural exchange. Based on a true 19th-century story, this powerful book has the stark and tragic trajectory of the sagas, where a veneer of Christianity cannot conceal a bleak and stoic belief in the workings of fate. Old superstitions are rife, convicted murderers face the barbaric penalty of death by beheading with an axe, yet the rites of Christianity are enforced.
Get this book at the discounted price of £11.69 from The Independent Bookshop or call 0843 0600 030
In 1829, three people in a remote farmstead are convicted of the murder of their employer, beaten and stabbed to death. One of the accused, a servant woman in her thirties, is sent to work for a local family while she waits for a court in faraway Copenhagen to decide her fate, which, if there is no mitigation, will be death.
Chained and half-starved, Agnes Magnusdottir is initially regarded as a monster, but gradually the mother of the family and the young priest who attends her, come to realise that the story was far more complex than the facts presented in court. The dead man was not a simple farmer but something with resonances in an ancient past and a highly manipulative personality. Confined with him in the isolation of a deep Nordic winter were two women and a lusty young man. As one character says, "It's hard to be alone in winter". The urges and paranoia that can overtake humans in such circumstances are unflinchingly presented.
Hannah Kent's prose is extraordinarily terse and precise as she tells the story from several different viewpoints: the older housewife whose health is failing, the priest who has to oppose fellow-clergy in his sympathy for the "murderess", and that of Agnes herself, whose struggle for survival amid the harshest of landscapes and the cruelty of human beings is described with vivid intensity.
Yet the beauty and fascination of this way of life is movingly portrayed, as is the spirit of its highly literate people. Kent's immersion in Icelandic lore seems total, though she came from the other side of the world. Great stories are universal.Reuse content

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Are you looking for Tafe near PERTH? Hotfrog helps you find the most popular businesses related to Tafe near PERTH WA! Find the best Tafe in PERTH.
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Tag - FE Technologies
Sony ceases FED development due to lack of funding
Sony officially abandoned plans to purchase a plant and equipment to develop its Field Emission Display (FED) technology in February because it couldn't locate funding for the equipment. Sony owned 37.8 percent of FE Technologies, a company that was devoted to developing and releasing a commercial 26-inch TV by the end of 2009. Sony has already began liquidating its remaining assets related to the technology.
Now AAPL Stock: 135.72 ( + 0.38 )
Cirrus creates Lightning-headphone dev kit
Apple supplier Cirrus Logic has introduced a MFi-compliant new development kit for companies interested in using Cirrus' chips to create Lightning-based headphones, which -- regardless of whether rumors about Apple dropping the analog headphone jack in its iPhone this fall -- can offer advantages to music-loving iOS device users. The kit mentions some of the advantages of an all-digital headset or headphone connector, including higher-bitrate support, a more customizable experience, and support for power and data transfer into headphone hardware. Several companies already make Lightning headphones, and Apple has supported the concept since June 2014. http://bit.ly/29giiZj
Apple Store app offers Procreate Pocket
The Apple Store app for iPhone, which periodically rewards users with free app gifts, is now offering the iPhone "Pocket" version of drawing app Procreate for those who have the free Apple Store app until July 28. Users who have redeemed the offer by navigating to the "Stores" tab of the app and swiping past the "iPhone Upgrade Program" banner to the "Procreate" banner have noted that only the limited Pocket (iPhone) version of the app is available free, even if the Apple Store app is installed and the offer redeemed on an iPad. The Pocket version currently sells for $3 on the iOS App Store. [32.4MB]
Porsche adds CarPlay to 2017 Panamera
Porsche has added a fifth model of vehicle to its CarPlay-supported lineup, announcing that the 2017 Panamera -- which will arrive in the US in January -- will include Apple's infotainment technology, and be seen on a giant 12.3-inch touchscreen as part of an all-new Porsche Communication Management system. The luxury sedan starts at $99,900 for the 4S model, and scales up to the Panamera Turbo, which sells for $146,900. Other vehicles that currently support CarPlay include the 2016 911 and the 2017 models of Macan, 718 Boxster, and 718 Cayman. The company did not mention support for Google's corresponding Android Auto in its announcement. http://bit.ly/295ZQ94
Apple employees testing wheelchair features
New features included in the forthcoming watchOS 3 are being tested by Apple retail store employees, including a new activity-tracking feature that has been designed with wheelchair users in mind. The move is slightly unusual in that, while retail employees have previously been used to test pre-release versions of OS X and iOS, this marks the first time they've been included in the otherwise developer-only watchOS betas. The company is said to have gone to great lengths to modify the activity tracker for wheelchair users, including changing the "time to stand" notification to "time to roll" and including two wheelchair-centric workout apps. http://bit.ly/2955JDa
SanDisk reveals two 256GB microSDXC cards
SanDisk has introduced two 256GB microSDXC cards. Arriving in August for $150, the Ultra microSDXC UHS-I Premium Edition card offers transfer speeds of up to 95MB/s for reading data. The Extreme microSDXC UHS-I card can read at a fast 100MB/s and write at up to 90MB/s, and will be shipping sometime in the fourth quarter for $200. http://bit.ly/294Q1If
Apple's third-quarter results due July 26
Apple has advised it will be issuing its third-quarter results on July 26, with a conference call to answer investor and analyst queries about the earnings set to take place later that day. The stream of the call will go live at 2pm PT (5pm ET) via Apple's investor site, with the results themselves expected to be released roughly 30 minutes before the call commences. Apple's guidance for the quarter put revenue at between $41 billion and $43 billion. http://apple.co/1oi1Pbm
Twitter stickers slowly roll out to users
Twitter has introduced "stickers," allowing users to add extra graphical elements to their photos before uploading them to the micro-blogging service. A library of hundreds of accessories, props, and emoji will be available to use as stickers, which can be resized, rotated, and placed anywhere on the photograph. Images with stickers will also become searchable with viewers able to select a sticker to see how others use the same graphic in their own posts. Twitter advises stickers will be rolling out to users over the next few weeks, and will work on both the mobile apps and through the browser. http://bit.ly/29bbwUE


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Costa Rica
Last updated in October 2016
Costa Rica and Germany enjoy a cordial relationship founded on mutual trust. Bilateral relations are untroubled and focus mainly on trade and economic exchange, long-standing development cooperation and cooperation on environmental issues and climate protection as well as cultural, scientific and academic relations.
Germany enjoys a very positive image in Costa Rica, thanks in part to the country's well-assimilated German community.
Germany is one of Costa Rica's principal trading partners in the European Union. In 2015, Costa Rica exported to Germany goods worth USD 444.8 million and imported from Germany goods worth USD 209.5 million. Costa Rica's principal exports to Germany are bananas, pineapples, coffee and ornamental plants. Its main imports from Germany are machinery, chemical products and cars including spare parts.
Costa Rica is a popular holiday destination. Nearly 70,000 German tourists visited the country in 2015.
A bilateral investment protection and promotion agreement has been in place since 1998. A bilateral double taxation agreement was signed in San José in February 2014. The agreement, which was given its second – and final – reading in Parliament on 8 January 2016, still has to be formally signed by the President and published in Costa Rica's law gazette before it can enter into force on 1 January 2017.
Negotiations between the EU and six Central American countries – including Costa Rica – on a bi-regional Association Agreement providing for gradual customs facilitation were concluded in May 2010. Costa Rica's government ratified the agreement in July 2013. The Association Agreement's trade-related articles have been provisionally applied vis-à-vis Costa Rica since 1 October 2013.
Development cooperation
With per capita GDP of USD 10,936 in 2015, Costa Rica now ranks among the world's middle-income countries. The country's liberal economic policy and the population's generally high level of education have led to continuing stable economic growth over a period of several years, with the exception of 2009. According to official figures, the poverty rate stands at over 20 per cent, including an extreme poverty rate of 6.7 per cent. The country's Gini coefficient is 0.508 (2014).
In November 2006, the last new commitments were made in San José as part of "traditional" Technical and Financial Cooperation, which was in the process of being phased out. Since then, climate protection has evolved into a new priority area of cooperation through Costa Rica's inclusion in the Federal Government's International Climate Initiative. This relativises the termination of bilateral development cooperation. As a pioneer of climate-neutral growth – the current government of President Solís is also continuing to pursue the goal of achieving carbon neutrality by 2021 – Costa Rica is an attractive partner for Germany in testing new forms and methods of international climate cooperation.
In addition, Costa Rica is increasingly becoming a key partner and location for regional development cooperation projects. Cooperation by the Federal Ministry for Economic Cooperation and Development (BMZ) with Costa Rica as part of the Central American Integration System (SICA) focuses on supporting the competitiveness of small and medium-sized companies, promoting employment and business start-ups among young people, energy efficiency and energy conservation, protecting biodiversity and reducing emissions from deforestation and degradation (REDD). Germany also supports a joint project with the Inter-American Court of Human Rights to strengthen access to justice.
Culture and education
Although Costa Rica's political and economic as well as cultural affinities are largely with the United States, the cultural sector is an important component of German-Costa Rican relations. Partly in response to the growing U.S. influence, particularly in the mass media, Costa Ricans continue to be interested in European culture.
An important part of Germany's cultural work is promoting the German Colegio Humboldt, an International School with a total of nearly 1,000 students and kindergarten children, ten seconded teachers and four federal programme teachers. Four partner schools in Costa Rica are members of the Schools: Partners for the Future initiative, which is also funded by the Federal Foreign Office.
The German Academic Exchange Service's (DAAD) Regional Office in San José runs an Information Centre that conducts bilateral and regional programmes to promote the exchange of lecturers and students (particularly postgraduate students) as well as university cooperation throughout Central America. There are special bilateral agreements on academic and student exchanges with various Costa Rican institutions, including the National Council of Rectors (CONARE) and the public Universidad de Costa Rica (UCR), as well as with the Confederation of Central American Universities (CSUCA). The DAAD has a network of contact persons and supports alumni associations in the region. A total of some 80 exchange measures are funded with and within the region every year. In March 2005, a Humboldt Chair was established at UCR, which is designed to help further intensify interdisciplinary academic exchange. In addition, in September 2012 the Wilhelm and Alexander von Humboldt Special Chair in Humanities and Social Sciences was set up at UCR, which is co-funded by UCR and the DAAD.
There is a Goethe Centre in Costa Rica, at two locations in San José. It offers German courses at all levels and awards German language certificates to successful participants. Every year, a total of around 1,800 people enrol in one of the Goethe Centre's language courses.


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Have you seen the recent advert of Heinz Beans and the brief appearance of Kidrobot number 2. I wonder if Sket One's condiment series from Dunny Series 2010 had any influence on the random display of vinyl art.
What's the most random place you have your art toys displayed?
The post The Coolest Thing In The Fridge appeared first on Kidrobot Blog.


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NRS Bow/Stern 2" D-Ring Carrying Handles
| Write a Review | Ask a Question | 3 Questions
Item: 37355.02 | Product Details »
- Pennel Orca® material is strong and abrasion resistant.
- A 6" handle provides a reliable hold.
- The stainless steel 2" D-ring adds a secure attachment point.
- Triangle patch is 12 1/2" across, and 9 1/2" high.
Product Reviews
More Information
How To: Install D-Rings and Footcups (4:12)
Extra D-rings provide more gear tie-down options, and footcups give you greater paddling control. NRS Repairs demonstrates the steps for gluing them so they stay permanently in place.
How To: Inflatable Repair Adhesives Guide (4:16)
When repairing your Hypalon, PVC or urethane inflatable, or your plastic or composite kayak, it's vital that you choose the right adhesive and solvent for the job. Using the wrong materials will result in a poor repair and wasted effort. In this video, Josh from NRS Repairs shares an inflatable repair adhesives guide to help you understand when to use such glues as Clifton Hypalon, Shore, Stabond, Clifton Urethane, Vynabond and G/flex Epoxy. Solvents for repair prep are important too; you'll also learn when you can use toluene, MEK, acetone and alcohol.
Do you have questions about this product?
Get answers from real customers and in-house experts with AnswerBox.
- NRS Bow/Stern 2" D-Ring Carrying Handles
Q:Can this be applied to a PVC boat? Do you have another product like this that is compatible with PVC.Asked on 8/27/2016 by Eric from Glenwood Springs, CO
1 answer
A:Eric, the Pennel Orca items can be applied to PVC using Stabond Adhesive - http://www.nrs.com/product/1903/stabond-adhesive
- NRS Bow/Stern 2" D-Ring Carrying Handles
Q:Regarding the NRS Bow/stern 2" D-Ring Carrying Handle . . .
Does one just clip it on to the bow or stern loop of the boat, with a carabiniere? Or what?
You need a picture.
Thanks, Kent DixonAsked on 9/19/2015 by Kent from Springfield, Ohio
2 answers
A:No, it gets glued on with special adhesive - not a clip on.
Sent from my iPhoneAnswered on 9/19/2015 by Anonymous
A:Kent, this patch, with both handle and D-ring, has to be glued to the inflatable. Use the combination of Clifton Hypalon Adhesive, Item # 38701.01, and Clifton Hypalon Accelerator, # 38702.01. Instructions and video are linked on the product pages.Answered on 9/19/2015 by Clyde from NRS
- NRS Bow/Stern 2" D-Ring Carrying Handles
Q:will this work on an older achilles hypalon raft?Asked on 10/12/2014 by Hollis from Albuquerque
1 answer
A:Yes, Hollis, you can adhere this to your boat. We recommend the combination of Clifton Hypalon Adhesive, Item # 38701.01 and Clifton Hypalon Accelerator, # 38702.01. See the videos there on the product pages for instructions.Answered on 10/12/2014 by Clyde from NRS
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How would Grifter's H2H stack to other comic book martial artist?
How good is Grifter H2H
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Frontiers of Legal Theory
By (author) Richard A. Posner
Format: Paperback
Normal Price: $67.00
Your Price: $60.30 AUD, inc. GST
Shipping: $7.95 per order
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Plus...earn $3.02 in Boomerang Bucks
Availability: Available to Backorder, No Due Date for Supply
Frontiers of Legal Theory by Richard A. Posner
Book DescriptionThe most exciting development in legal thinking since World War II has been the growth of interdisciplinary legal studies - the application of the social sciences and the humanities to law in the hope of making law less formalistic, more practical, better grounded empirically, better tailored to social goals. Judge Richard A. Posner has been a leader in this movement, and his new book explores its rapidly expanding frontier.
Buy Frontiers of Legal Theory book by Richard A. Posner from Australia's Online Bookstore, Boomerang Books.
Book DetailsISBN: 9780674013605
(235mm x 155mm x 25mm)
Pages: 464
Imprint: Harvard University Press
Publisher: Harvard University Press
Publish Date: 2-Apr-2004
Country of Publication: United States
Other Editions...
Books By Author Richard A. Posner
Divergent Paths, Hardback (January 2016)
Judges and legal scholars talk past one another, if they have any conversation at all. Academics criticize judicial decisions in theoretical terms, which leads many judges to dismiss academic discourse as divorced from reality. Richard Posner reflects on the causes and consequences of this widening gap and what can be done to close it.
Reflections on Judging, Hardback (October 2013)
Presents the main obstacles to coping with the dizzying pace of technological advance. The author calls for legal realism - gathering facts, considering context, and reaching a sensible conclusion that inflicts little collateral damage on other areas of the law.
Behavior of Federal Judges, Hardback (January 2013)
Federal judges are not just robots or politicians in robes, yet their behavior is not well understood, even among themselves. Using statistical methods, a political scientist, an economist, and a judge construct a unified theory of judicial decision-making to dispel the mystery of how decisions from district courts to the Supreme Court are made.
Henry Friendly, Greatest Judge of His Era, Hardback (March 2012)» View all books by Richard A. Posner
Henry Friendly is frequently grouped with Oliver Wendell Holmes, Louis Brandeis, Benjamin Cardozo, and Learned Hand as the best American jurists of the twentieth century. In this first, comprehensive biography of Friendly, Dorsen opens a unique window onto how a judge of this caliber thinks and decides cases, and how Friendly lived his life.
» Have you read this book? We'd like to know what you think about it - write a review about Frontiers of Legal Theory book by Richard A. Posner and you'll earn 50c in Boomerang Bucks loyalty dollars (you must be a member - it's free to sign up!)
Author Biography - Richard A. Posner
Richard A. Posner is Circuit Judge, the United States Court of Appeals for the Seventh Circuit, and a senior lecturer at the University of Chicago Law School.
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website design with payment facility
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- Total Bids 89
Project Description
i want to get a website built using either drupal or joomla.
site will be basic, it needs a home page with a bit of information on the process the website offers. with about 3 other pages (how it works, terms and conditions)
there must be two buttons the the home page. One which leads to a page which requires users to input information regarding a residential property
eg. bedrooms, bathrooms, address, size. the second will lead to a similar page where users will input information regarding a commercial property.
the payment system will either be generating invoices which will be e-mailed to the user and paid later or a credit card online payment system.
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ACT UP greets Obama and Nutter
President Obama was in Philly on June 30th to raise some bucks. ACT UP was there to greet him, and our mayor, who have both broken commitments to end AIDS by providing housing and treatment to those dying without it.
5 photos · 960 views


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- Horoscopes
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Montville — Tyler Quidgeon completed 10 of 11 passes for 230 yards and three touchdowns and ran six times for 53 yards and a touchdown as Montville High School beat Fitch on Friday night, 65-26.
Montville led by as much as 42-7 in the second quarter.
Buddy Dewaine had five catches for 186 yards and two touchdowns for Montville (3-2) and Jeremiah Crowley ran 14 times for 81 yards and two touchdowns.
Patrick Bogan (1-yard run), Chance Collier (9-yard catch), Xavier Santiago (65-yard fumble return) and Sean Peterson (51 yard run) also scored for Montville. Nick Veillette added a 26-yard field goal and six extra points.
Robert Duncan threw touchdown passes for 69 and 54 yards to Jonathon Johnston for the Falcons (1-4). Duncan also ran for a 1-yard touchdown.
In other games:
• Orrin Parke ran 21 times for 135 yards and a touchdown and Nico Ramos scored on both a run and interception return to pace New London to its 34-14 win over Windham.
New London shutout the Whippets in the second half, 15-0.
Ramos ran for a 34-yard touchdown for the Whalers (2-2) and returned an interception 40 yards for another score. Jose Garcia ran for a 12 yard touchdown, too.
Ashi Harkness returned a fumble 50 yards for a touchdown for New London and Dante Alston and Chase Cook combined on a safety.
Joseph Santiago ran 16 times for 87 yards and a touchdown for the Whippets (3-2). Jack Risley completed 6 of 16 passes for 119 yards and ran seven times for 43 yards.
• Zach Poirier ran 17 times for 134 yards and two second-half touchdowns while the Stonington defense sacked Griswold's Adam Davis 10 times in a 20-6 win.
Poirier ran for 114 of his 134 yards in the second half for the Bears (2-2). Divante White also threw a 5-yard touchdown to Matt Mitchell.
Adam Davis completed 17 of 28 passes for 164 yards and a touchdown for the Wolverines (3-2).
• Jake Mangual threw two touchdowns and ran for another to pace Waterford past the St. Bernard/Norwich Tech co-op, 40-0.
Mangual threw touchdown passes of 25 and 35 yards to Donny Craig for the Lancers (2-3). He also scored on a 1-yard run.
Josef Gustafson (1 yard), Isaiah Jones (5 yards) and Bishmee Sheppard (6 yards) also ran for touchdowns.
The Saints are 1-4.
• Evan Smith scored three touchdowns as the unbeaten Valley Regional/Old Lyme co-op trounced Enfield, 50-7, in a Pequot Football Conference interdivision game.
Smith scored on a 32-yard run, a 27-yard catch, and a 24-yard interception return for the Warriors (4-0).
Billy Buscetto caught a 17-yard touchdown from Phil Cohen (11 of 17 for 77 yards, two touchdowns) for VR/OL. Also, Tyler James scored on a 2-yard run and Jean-Luc Poulard ran for a 22-yard touchdown.
Driver dies after his car rolls over in Groton early Monday morning
Waterford man charged with aggressively driving 'look-alike cruiser'
Attorney fields questions at packed immigration forum for New London parents
Hartford to pay $885K to family whose dog was killed by cops
For a guy who does words ... these emails left me speechless
New London woman charged in crash that seriously injured man riding bike
Malloy's right, Connecticut not obligated to back Trump deportation policy
New London woman charged in crash that seriously injured man riding bike


text:
|By Business Wire
Article Rating:
|February 1, 2013 09:30 AM EST
AT&T Inc. (NYSE:T) will webcast a presentation by Randall Stephenson, Chairman and Chief Executive Officer, AT&T Inc. at the Silicon Flatirons Center "The Digital Broadband Migration: The Future of Internet-Enabled Innovation" Conference at the University of Colorado on Sunday, February 10 at 3 p.m. MT/4 p.m. CT. The webcast will be available live and for replay at AT&T Investor Relations.
About AT&T
AT&T Inc. (NYSE:T) is a premier communications holding company and one of the most honored companies in the world. Its subsidiaries and affiliates – AT&T operating companies – are the providers of AT&T services in the United States and internationally. With a powerful array of network resources that includes the nation's largest 4G network, AT&T is a leading provider of wireless, Wi-Fi, high speed Internet, voice and cloud-based services. A leader in mobile Internet, AT&T also offers the best wireless coverage worldwide of any U.S. carrier, offering the most wireless phones that work in the most countries. It also offers advanced TV services under the AT&T U-verse® and AT&T │DIRECTV brands. The company's suite of IP-based business communications services is one of the most advanced in the world.
Additional information about AT&T Inc. and the products and services provided by AT&T subsidiaries and affiliates is available at http://www.att.com. This AT&T news release and other announcements are available at http://www.att.com/newsroom and as part of an RSS feed at www.att.com/rss. Or follow our news on Twitter at @ATT.
© 2013 AT&T Intellectual Property. All rights reserved. 4G not available everywhere. AT&T, the AT&T logo and all other marks contained herein are trademarks of AT&T Intellectual Property and/or AT&T affiliated companies. All other marks contained herein are the property of their respective owners.
In his session at @ThingsExpo, Steve Wilkes, CTO and founder of Striim, will delve into four enterprise-scale, business-critical case studies where streaming analytics serves as the key to enabling real-time data integration and right-time insights in hybrid cloud, IoT, and fog computing environments. As part of this discussion, he will also present a demo based on its partnership with Fujitsu, highlighting their technologies in a healthcare IoT use-case. The demo showcases the tracking of patie...
Feb. 24, 2017 01:15 PM EST Reads: 631
20th Cloud Expo, taking place June 6-8, 2017, at the Javits Center in New York City, NY, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy.
Feb. 24, 2017 01:00 PM EST Reads: 1,823
In his general session at 18th Cloud Expo, Lee Atchison, Principal Cloud Architect and Advocate at New Relic, discussed cloud as a 'better data center' and how it adds new capacity (faster) and improves application availability (redundancy). The cloud is a 'Dynamic Tool for Dynamic Apps' and resource allocation is an integral part of your application architecture, so use only the resources you need and allocate /de-allocate resources on the fly.
Feb. 24, 2017 01:00 PM EST Reads: 1,326
Some people worry that OpenStack is more flash then substance; however, for many customers this could not be farther from the truth. No other technology equalizes the playing field between vendors while giving your internal teams better access than ever to infrastructure when they need it. In his session at 20th Cloud Expo, Chris Brown, a Solutions Marketing Manager at Nutanix, will talk through some real-world OpenStack deployments and look into the ways this can benefit customers of all sizes....
Feb. 24, 2017 12:45 PM EST Reads: 976
With major technology companies and startups seriously embracing Cloud strategies, now is the perfect time to attend @CloudExpo | @ThingsExpo, June 6-8, 2017, at the Javits Center in New York City, NY and October 31 - November 2, 2017, Santa Clara Convention Center, CA. Learn what is going on, contribute to the discussions, and ensure that your enterprise is on the right path to Digital Transformation.
Feb. 24, 2017 12:30 PM EST Reads: 2,502
In his keynote at 19th Cloud Expo, Sheng Liang, co-founder and CEO of Rancher Labs, discussed the technological advances and new business opportunities created by the rapid adoption of containers. With the success of Amazon Web Services (AWS) and various open source technologies used to build private clouds, cloud computing has become an essential component of IT strategy. However, users continue to face challenges in implementing clouds, as older technologies evolve and newer ones like Docker c...
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Have you ever noticed how some IT people seem to lead successful, rewarding, and satisfying lives and careers, while others struggle? IT author and speaker Don Crawley uncovered the five principles that successful IT people use to build satisfying lives and careers and he shares them in this fast-paced, thought-provoking webinar. You'll learn the importance of striking a balance with technical skills and people skills, challenge your pre-existing ideas about IT customer service, and gain new in...
Feb. 24, 2017 12:30 PM EST Reads: 2,483
@DevOpsSummit at Cloud taking place June 6-8, 2017, at Javits Center, New York City, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long developm...
Feb. 24, 2017 12:00 PM EST Reads: 1,494
Bert Loomis was a visionary. This general session will highlight how Bert Loomis and people like him inspire us to build great things with small inventions. In their general session at 19th Cloud Expo, Harold Hannon, Architect at IBM Bluemix, and Michael O'Neill, Strategic Business Development at Nvidia, discussed the accelerating pace of AI development and how IBM Cloud and NVIDIA are partnering to bring AI capabilities to "every day," on-demand. They also reviewed two "free infrastructure" pr...
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Cloud Expo, Inc. has announced today that Aruna Ravichandran, vice president of DevOps Product and Solutions Marketing at CA Technologies, has been named co-conference chair of DevOps at Cloud Expo 2017. The @DevOpsSummit at Cloud Expo New York will take place on June 6-8, 2017, at the Javits Center in New York City, New York, and @DevOpsSummit at Cloud Expo Silicon Valley will take place Oct. 31-Nov. 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
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In recent years, containers have taken the world by storm. Companies of all sizes and industries have realized the massive benefits of containers, such as unprecedented mobility, higher hardware utilization, and increased flexibility and agility; however, many containers today are non-persistent. Containers without persistence miss out on many benefits, and in many cases simply pass the responsibility of persistence onto other infrastructure, adding additional complexity.
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Official site: http://www.any-video-converter.com/products/for_video_free/
1. Multi-language;
2. Import audio CD disc and multi-video;
3. Convert video between any formats freely;
4. Convert video to a wide range of devices;
5. Able to download online videos;
6. Burn video to DVD or AVCHD DVD;
7. Full-featured media player;
8. Rip and extract audio from CDs and videos;
9. Make video editing easy;
10. Create HTML5 video with embedding Code;
11. Make animated GIF from video.
The output format & device options are too complicated and technical for average users.
Official site: http://www.videoconverterfactory.com/free-hd-video-converter/
1. Completely free. No hidden fees;
2. It renders a blue clear interface;
3. Read and output all video formats; Keep regular upgrades(e.g. Adding new devices)
4. 6X faster converting speed than other video converters;
5. It supports converting SD video to HD video;
6. Download videos from YouTube and more video sites with best quality;
7. Customize your favorite video with the powerful editing function: Split video, Join video, Merge audio
8. Special smart-fit settings for video and audio;
9. 3-simple-step converting process;
10. Convert video to 200+ formats and devices.
The software only supports English language.
Official site: http://koyote-free-video-converter.en.softonic.com/
1. Multi-language;
2. Fully compatible with Windows XP;
3. Support many different formats;
4. Format profiles can be tweaked;
5. Convert your video for mobile devices;
6. You can choose to convert only some parts of your videos;
7. You can choose to only extract the sound of your video into MP3, WMA, MP2, AAC...
8. Very easy to use.
No video preview (only while converting).
Official site: http://www.freemake.com/free_video_converter/
1. 300+ input formats;
2. Convert online videos to MP3;
3. Cut, join, rotate, limit file size;
4. Additional functions: rip & burn DVD.
1. It only supports rip unprotected DVD movies;
2. Limited output formats and portable devices.
Official site: https://handbrake.fr/
1. Free and open source;
2. Convert video from nearly any format;
3. Multi-Platform (Windows, Mac and Linux).
1. Limited output formats and devices;
2. Not stress the focal points;
3. Sound - tracks out of sync / not in sync with the picture;
4. Program crash.
You can directly free download it here. The user interface is easy to understand and intuitive to use, so that you can begin using the software within minutes of installing it on your PC.
Step One: Click "Add Files" or simply drag and drop the wanted videos to the program.
Step Two: Select a video output format or your portable gadget. It supports almost any video and audio file formats. If you don't have much knowledge on video parameters, also you can select a device which means that the program has already set optimized parameters in advance. But indeed, it allows custom settings.
Step Three (Optional) : If you have editing requirement, it also meets your needs (Add subtitle, Rename video, Trim/Clip video, Cut, Crop, Merge videos…)
Step Four: Click "Run" to start converting.
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but the speed of that connection is only 9600baud so you might not be able to send info fast enough for your project.
What makes you think that serial is limited to 9600 baud? Heck even a Uno uploads sketches at 115200 baud.Lefty
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It was numbers of years ago. I was selling enterprise manufacturing application software and was quite inexperienced at it, as you'll soon see.
I was competing for a deal with a paint manufacturing company in Florida. (I was based in New York at the time.) I had made numbers of trips down there, presenting, answering questions, performing demonstrations, and building relationships with key managers. We were getting closer to the point where the customer was going to make a decision.
My main competition was a smaller company who regularly and dramatically discounted in order to win. It was our company's policy to determine a point below which we would not sell—even if it meant losing the deal. I knew that number. I knew it well.
But having gone through so much effort and expense up to this point, I couldn't let the competitor undercut me. I made the deliberate decision that I just couldn't let that happen again. So, in Florida once again, I closed the deal with the CEO of the customer's company for a few thousand less than the competitor's final, discounted offer.
I flew back to New York, proud to have brought in this business—until I handed the contract over to our CEO for signature. He refused to sign it. He told me to call the customer and tell her that we wouldn't be able to do business with them at that price and that we were therefore withdrawing our offer.
Of course the customer was livid. She railed on and on about how unethical we were and how I wasted her time. She was right about all that.
There was a lot that I didn't understand about business and sales before this happened. Needless to say I learned quite a bit since then and moved on, however much embarrassment and pain this unfortunate event caused me.
Many of you know me as someone who very rarely even uses the word "discount." I'll look for all sorts of ways to avoid discounting, as my clients will tell you. Well, now you know. It all started with an embarrassing mistake in Florida.
(Thanks to Codrut Turcanu for the idea…)
Image: picturequotes.com


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- The Nike Flex Experience 4 Print (TD) Toddler Boys' Shoe features a hook-and-loop closure for easy on and off. It delivers a perfect balance of comfort and natural movement through its minimal upper design, resilient midsole and locked-down feel.
- Articulated foam midsole provides a natural stride.
- Minimal upper design enhances flexibility.
- Seamless interior enhances comfort.
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Josh Groban guest starred on tonight's episode of FOX's "Glee," which wasn't quite as strong as the season opener, but still has me plenty optimistic about the jokes and songs to come. The theme of tonight's after school special, boys and girls, is Confidence. Well…confidence, and Josh Groban.
Acafellas: Will, stung by criticism of his choreography, forms an acapella group with some of the other improbably gifted at harmonizing male teachers (and, later, Finn and Puck). And I gotta say, it was pretty hysterical watching Ken Tanaka getting down with the boy band dance moves. Will's confidence blooms when the Acafellas (yes, the obligatory musical pun name) get a great reception, and he attributes Terri's increased interest in him (once a week!) to said newfound confidence. Sadly, it looks like she's just in it to get knocked up for reals.
Sandy is initially out of the group due to general creepiness, but claws his way back in by promising to deliver penpal Josh Groban at their next gig: the concertiest PTA meeting ever. They sing "I Wanna Sex You Up" (ha!), and while it turns out Josh Groban is just there to give Sandy a restraining order, he did love the show. Plus, he sketchily picked up Will's drunk mom, so that's something. And teaching Finn and Puck to dance like the Backstreet Boys reminds Will of how great he is at it (teaching, not dancing like the Backstreet Boys…though he's not too shabby at that, either), so he decides to turn his focus back to imparting wisdom and away from adult boy bands. Good call, Will. Good call.
Sowing the seeds of destruction: Quinn and her cheerleading minions convince Rachel that Will's choreography is terrible, and that they need Dakota Stanley, famed show choir choreographer and "Beauty and the Beast" understudy candelabra (and hateful dictator), to get them to regionals. With Will's confidence shaken and attention elsewhere, everyone but Finn decides to bring Dakota on. He immediately kicks Artie out for not trying hard enough…at walking. In fact, he slams everyone but the cheerleaders, causing a mass walkout until Rachel fires him. And wouldja look at that? They have the confidence to embrace the things that make them different after all!
Going after the gleeks individually, the Cheerios convince lovelorn Mercedes to try and date poor, flaming Kurt. With Rachel and Tina's "Gayvention" unsuccessful, Mercedes mistakes Kurt's friendship for a relationship and breaks his windshield when he tells her he's in love with someone else (Finn). Mercedes' loss is our gain, as she treats us to a suitably angry "Bust Your Windows." And dang, she's not just a great singer – Amber Riley's got moves, too. Kurt finally comes out to Mercedes, tearfully telling her that she's the first person he's told. Awww.
Since the glee club is back with a vengeance, Sue revokes the failed Cheerios' tanning privileges for the rest of the semester. One of them breaks down in tears, but Quinn simply thanks Sue for teaching her that when you really believe in yourself, you don't have to bring other people down. What the-? Intriguing development…
Odds and Ends:
- Victor Garber (noted spy daddy and Broadway actor) is playing Will's dad! And yet, somehow, they had him on for an entire episode without singing. I assume this will be remedied very soon. Also, how adorable was he with the bow tie and the newfound confidence to go to law school? Love him.
- Henri's "Two thumbs up!" cake cracked me up way more than it should have. Maybe it was the fact that he couldn't even eat it without any thumbs. Delicious, awkward, cakey irony.
- On the one hand, I respect Rachel for calling Finn out on his feelings for her. On the other hand, he totally offered to talk about what happened in the gym, and he has a girlfriend. So…I'd say I'm on Finn's side for now.
- Looks like Terri is noticing Emma noticing Will. Team Emma!
- If this episode is any indication, they're working on fleshing out the supporting characters, which is one of the reasons I'm feeling optimistic about "Glee".
- There were less full-length song performances this week, no? And none by the glee club, in fact. It's probably pretty expensive to put them together, I suppose, but I kind of wanted to see "This is How We Do It" in its entirety. You know…just because. The lip-synching wasn't so glaring to me this week, though, so I'm glad for that.
Favorite Quotes:
- "They say it takes certainty more than talent to make a star. I mean, look at John Stamos." – Emma
- "Josh Groban loves a blousy alcoholic." -Josh Groban
- Something involving carpentry that I'm probably not allowed to quote in its entirety. But trust, it was hilarious.
- "This is How We Do It" -Montell Jordan, performed by the Acafellas during rehearsal
- "(That Girl is) Poison" -Bell Biv DeVoe, performed by the Acafellas at a sports bar
- "Mercy" -Duffy, performed by Vocal Adrenaline (though it really made me think of a great SYTYCD routine)
- "Bust Your Windows" -Jazmine Sullivan, performed by Mercedes at the car wash fundraiser
- "I Wanna Sex You Up" -Color Me Badd, performed by the Acafellas at the PTA meeting/big-budget rock concert
How did you feel about this week compared to last week? Are you hooked, or still testing the waters? What's going on with Quinn?


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Hong Bo Hotel
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... of the reflection on the window behind her so I snapped her picture as well. Kai was in love with the women's outfit and had me take a picture as she stood to get off the subway. She is contemplating having some clothes made and so she was using the people watching and picture posing as a shopping showcase. What struck me as funny was after the pictures were taken the lady then posted them to her friend on WeChat and soon after her phone started ringing and she ...
Day 15 - Hong Kong
... gauge what they are so we know what to compare to when we go out to the markets. Afterwards, we went to dinner with my family. It was great to get some vegetables and variety of food. I was getting a little tired of fried rice and pad thai. Although, the pad thai was still amazing. At dinner, my aunt and uncle sort of helped us plan our next few days here. You'll just have to wait and find ...
Hong Kong
... up as convenience stores. We then had another fab night out with Julia eating great Thai food.
The next day we headed over to Lamma Island for a little break from the city, where we trekked from one side to the other and (hopefully) helped Julia with some flat hunting along the way!
After two nights out we decided to have a quiet night and bought cheese and wine and sat on a roof top garden taking in the riverside city views. The evening ...
Kuala Lumpur to Hong Kong
... were getting on and off the train at a stop called Admiralty so we decided that this would be a good place to start. We came out of the station and straight into a large shopping mall filled with only top end designer stores. We spent some time window shopping before realising that we were well out of our flashpackers price range so decided to go exploring. It seemed like all the shops in this part of town were just Prada, Gucci and the like. We managed ...
The Trouble of Substance Abuse
... like MnM's (and had the same effect) while knocking back a couple of cans one after the other. That managed to give me a couple of hours respite. But unfortunately I was still a couple hours out of Heathrow. Fortunately I saw this girl in Hong Kong and got talking to her. Like me she was traveling and had sorted a job in Italy for a couple of months. We ...


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Erected in 1890, the Walnut Street Bridge was the first to connect Chattanooga's downtown with the North Shore. Structural modifications have been made to turn the bridge into what is now a pedestrian walkway. The 1/2-mile span is one of the longest pedestrian bridges in the world and very popular among local residents. Providing spectacular views of Coolidge Park, the Tennessee Aquarium and the Riverfront, the bridge is available for weddings and special events.
Tennessee Vacation eGuide
The 2016 eGuide gives you instant access to Tennessee's irresistible attractions and destinations. Peruse venues online, then put in your order to get a free guide delivered to your doorstep.


text:
Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study
DOI: 10.1186/cc4952
© Rommers et al.; licensee BioMed Central Ltd. 2006
Received: 22 March 2006
Accepted: 18 May 2006
Published: 21 June 2006
Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.
This non-randomized open parallel group follow-up pilot study was conducted in two mixed medical-surgical intensive care units at two teaching hospitals. Seven ICU patients with subcutaneous oedema (index group) and seven ICU patients without subcutaneous oedema (reference group) were studied. Anti-Xa activity was determined at 0, 3, 4, 6, 8, 12 and 24 hours after subcutaneous administration of 2,500 IU dalteparin. Plasma concentrations of factor anti-Xa activity were measured using a chromogenic factor Xa inhibition assay.
The characteristics of the index group were: age, 58 years; male/female ratio, 5/2; body mass index at admission, 23.4 kg/m2 (at study day, 30.6 kg/m2). The characteristics of the reference group were: age, 49 years; male/female ratio, 6/1; body mass index at admission, 24.8 kg/m2 (at study day, 25.0 kg/m2). In the index group, creatinine clearance was lower compared to the reference group (71 versus 131 ml/minute, p = 0.003). Sequential organ failure assessment score did not differ between index and reference groups (4 versus 5). Mean arterial pressure was comparable between index and reference groups (91 versus 95 mmHg) and within the normal range. The mean Cmax value was not different between ICU patients with and without subcutaneous oedema (0.15 ± 0.02 versus 0.14 ± 0.02 IU/ml, p = 0.34). In the index group, the mean AUC(0–24 h) value was slightly higher compared with the reference group (1.50 ± 0.31 versus 1.15 ± 0.25 h·IU/ml, p = 0.31). This difference was not significant.
In this pilot study, there was no clinically relevant difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for venous thromboembolism prophylaxis between ICU patients with and without subcutaneous oedema. Critically ill patients seem to have lower anti-Xa activity levels than healthy volunteers.
Venous thromboembolism (VTE) is a frequent (10% to 80%) complication in critically ill patients admitted to intensive care units (ICUs) [1, 2]. Critically ill patients have a higher risk of VTE due to several risk factors such as increased age, recent surgery, venous stasis as a result of prolonged immobilization, acute infectious disease, hypercoagulability resulting from acute phase responses, and vascular injury caused by central venous catheters or other invasive interventions [1–3]. Most ICU patients therefore receive thromboprophylaxis with mechanical methods, unfractionated heparin or subcutaneous low molecular weight heparins (LMWHs) [2, 4, 5]. Several randomized clinical trials and meta-analyses have demonstrated that subcutaneous LMWHs are efficient and safe in the prevention of VTE in surgical and medical patients [6–10]. Trials in ICU patients have, however, rarely been conducted.
Patients in the ICU with shock symptoms often require large volumes of fluid to maintain perfusion and thereby tissue oxygenation and to prevent multi-organ dysfunction syndrome. Due to the administration of large volumes of fluid as well as the underlying pathophysiological condition, ICU patients often suffer from substantial subcutaneous oedema.
A number of factors might interfere with the effectiveness of subcutaneous administrated LMWHs in critically ill patients, such as low cardiac output, decreased peripheral blood flow, use of vasopressors or subcutaneous oedema [11–14]. Subcutaneous oedema may impair the absorption of medication given by subcutaneous injection [15]. We postulate that the absorption of subcutaneous dalteparin, a LMWH used for thromboprophylaxis in our ICU, is impaired in patients with subcutaneous oedema. This possible impairment may be due to either a delayed absorption or to a reduced absorption.
Because it is difficult to measure LMWH concentrations directly, pharmacokinetic studies generally use surrogate biological effect markers such as anti-Xa activity [16–22], which has been shown to be correlated with the administrated dose as well as, although more controversial, the clinical effect [23–25].
To investigate whether indeed the absorption of dalteparin is impaired in ICU patients with subcutaneous oedema, we compared anti-Xa activity after subcutaneous injection of dalteparin in ICU patients with subcutaneous oedema with anti-Xa activity in ICU patients without subcutaneous oedema.
Materials and methods
This non-randomized open parallel group follow-up pilot study was performed in the ICUs of the St Elisabeth Hospital and the TweeSteden hospital in Tilburg, the Netherlands, from January 2003 until July 2005. Both ICUs served medical as well as surgical patients. The medical ethics committee of the St Elisabeth Hospital approved the study protocol for both hospitals.
Inclusion criteria were ICU patients with age >18 years and subcutaneous administration of dalteparin 2,500 IU once daily for VTE prophylaxis. Exclusion criteria were concurrent use of vitamin K antagonists, use of therapeutic doses of unfractionated heparin or LMWHs, severe liver failure (bilirubin >40 μmol/l), renal insufficiency (creatinine clearance <30 ml/minute), signs of disseminated intravascular coagulation (platelets <100 × 109/l, prolonged prothrombin time, and activated partial thromboplastin time), use of vasopressors and/or inotropics. All patients or their legal representatives gave informed consent before actual inclusion. After inclusion, the measurements took place on a day the patient had used dalteparin in the ICU unit for at least three days.
Two groups of patients were studied: ICU patients with subcutaneous oedema (index group) and ICU patients without subcutaneous oedema (reference group). Subcutaneous oedema was defined as a weight gain of at least 10% compared to the weight of the patient at admission and an appearance of substantial generalized subcutaneous oedema. This definition was chosen because we needed a measurement that was easy to use in common practice and, to our knowledge, there is no validated definition or measurement method for oedema in ICU patients. Patients were weighed by means of a 'weighing-bed'.
All patients received a subcutaneous injection of dalteparin (Fragmin®, Pharmacia BV, Woerden, the Netherlands) that was administrated by the nursing staff of the ICU using prefilled single-dose syringes (0.2 ml = 2,500 IU). The same technique and injection site, the abdomen or upper thigh, was used in every patient.
Primary endpoint was the difference in anti-Xa activity between index and reference group. On the study day, blood samples were obtained immediately before and 3, 4, 6, 8, 12 and 24 hours after administration of dalteparin. Blood was drawn by venipuncture. Each time 5 ml blood was collected in sodium citrate (0.109 M, 3.2%) tubes and sent to the laboratory as soon as possible. There, plasma was separated from cells by centrifugation (3,000 rpm for 10 minutes) and plasma was stored at -20°C for a maximum period of one month. Plasma concentrations of factor anti-Xa activity were measured with an ACL3000 instrument (Instrumentation Laboratory BV, Breda, The Netherlands) using a chromogenic factor Xa inhibition assay (Spectrolyse®Heparin Xa, Trinity Biotech, Ireland). The anti-Xa assay standard calibration curve of dalteparin ranged from 0.0 IU/ml to 0.8 IU/ml. The within assay and among assay precision (coefficient of variation) was, for 0.1 IU/ml heparin, 8.0% and 8.9%, respectively, and, for 0.5 IU/ml heparin, 3.7% and 6.6%, respectively.
A concentration-time curve of anti-Xa activity was determined for all patients. For each patient, the Cmax, the maximum observed activity, was estimated from the anti-Xa concentration curve and the AUC(0–24 h), the area under the concentration curve at 0 to 24 hours, was calculated by the trapezoidal rule. Of these measurements, we calculated the mean plasma concentrations of anti-Xa activity and mean Cmax and AUC0–24 h for both groups.
In addition, the following data were collected from the medical history of the patient: age, sex, weight (at admission and at study day), length, sequential organ failure assessment (SOFA) score at study day, and mean arterial pressure (MAP) at study day and diagnosis. On the study day, urine output over a 24 hour period was collected for determination of the creatinine clearance.
We calculated that seven evaluable patients were needed in each group to prove a difference of 50% in anti-Xa activity. We considered a difference of 50% in anti-Xa activity, in either AUC0–24 h or Cmax, to be clinically relevant. This was based on the assumption of a Cmax in healthy volunteers of 0.22 (standard deviation (SD) 0.07) IU/ml and an AUC0–24 h of 1.26 (SD 0.40) h·IU/ml [17] and a desired power of 80% and α of 5%.
Comparison of continuous variables was done by Students t test. The anti-Xa activity (Cmax and AUC(0–24 h)) was compared by the non-parametric Mann-Whitney test (mean ± SD). A p value of 0.05 is taken as cut-off for statistical significance.
Demographic and clinical characteristics of the patients
Index group with oedema (n = 7)
Reference group without oedema (n = 7)
P value
Age (years)
58 (32–85)
49 (21–71)
5 (71%)
6 (86%)
Length (cm)
171 (165–185)
176 (165–185)
Weight at admission (kg)
68 (47–80)
77 (65–90)
Weight at study day (kg)
89 (65–107)
77 (65–85)
Weight gain (kg)
21 (31%)
1 (1%)
BMI at admission (kg/m2)
23.4 (16.3–27.6)
24.8 (21.0–30.4)
BMI at study day (kg/m2)
30.6 (22.5–37.9)
25.0 (21.5–30.4)
SOFA score
4 (3–5)
5 (3–6)
Creatinine clearance (ml/minute)
71 (36–109)
131 (85–168)
Mean arterial pressure (mmHg)
91 (80–115)
95 (79–122)
Diagnosis (number)
Exacerbation COPD
Perforated appendicitis
Cerebral bleeding
Anti-Xa activity before (0 h) and 3, 4, 6, 8, 12 and 24 h after subcutaneous administration of 2,500 IU dalteparin
Anti-Xa activity (IU/ml)
0 h
3 h
4 h
6 h
8 h
12 h
24 h
AUC(0–24 h)
Index: with oedema
Mean (SD)
0.03 (0.02)
0.15 (0.05)
0.12 (0.05)
0.08 (0.04)
0.06 (0.03)
0.04 (0.04)
0.05 (0.06)
1.50 (0.81)
Reference: without oedema
Mean (SD)
0.02 (0.02)
0.14 (0.06)
0.11 (0.04)
0.08 (0.03)
0.05 (0.03)
0.02 (0.01)
0.02 (0.02)
1.15 (0.65)
Mean Cmax and AUC(0–24 h) anti-Xa activity
Index group with oedema (n = 7)
Reference group without oedema (n = 7)
P value
Cmax (IU/ml)
0.15 ± 0.02
0.14 ± 0.02
AUC(0–24 h) (h·IU/ml)
1.50 ± 0.31
1.15 ± 0.25
For non-intravenous, parenteral routes of drug administration, such as subcutaneous injection, decreased peripheral (cutaneous) blood flow, changes in local pH, oedema and scar tissue may alter the extent of absorption [14]. In one study the absorption of subcutaneous administrated insulin was significantly lower and delayed in patients with generalized subcutaneous oedema [15]. Therefore, we considered it possible that the absorption of dalteparin, administrated by subcutaneous injection for prophylaxis of VTE, might be influenced by subcutaneous oedema, very often seen in ICU patients with shock symptoms. In this study, we cannot confirm this hypothesis. Mean plasma concentrations of anti-Xa activity are comparable in ICU patients with and without subcutaneous oedema.
The pharmacokinetics of dalteparin is linear and dose-independent for anti-Xa activity. Absorption is rate-limiting after subcutaneous administration and peak plasma concentrations are attained after 2.8 to 4 hours. Bioavailability after subcutaneous injection is close to 90%. The apparent volume of distribution is close to the plasma volume. Elimination appears to occur mainly via the renal route, with a plasma elimination half-life of 2.4 to 4 hours [17, 18]. The mean Cmax values of 0.15 IU/ml and 0.14 IU/ml found in the index and the reference groups, respectively, are lower than the assumed Cmax value in healthy volunteers of 0.22 IU/ml. The mean AUC(0–24 h) value of 1.15 h·IU/ml in ICU patients without subcutaneous oedema is also lower than the demonstrated AUC(0–24 h) value in healthy volunteers (1.26 h·IU/ml) [17]. This can be an indication of lower anti-Xa activity levels in critically ill patients. Others find this as well [11, 12, 26, 27]. Dörffler-Melly [11] and colleagues demonstrated lower anti-Xa activity in ICU patients on vasopressors. The use of vasopressors, they explain, leads to adrenergic vasoconstriction of the peripheral blood vessels and thus impaired perfusion of the subcutaneous tissue. This was the reason to exclude patients on vasopressors and/or inotropics from our study. Priglinger and colleagues [12] showed lower anti-Xa levels in critically ill patients compared with medical patients in the normal ward. They did not find a correlation between the dose of norepinephrine and the anti-Xa activity. Priglinger and colleagues [12] and Freedman [13] mention altered cardiac output, pre-existing conditions and also use of vasopressors and decreased peripheral blood flow as possible reasons for lower anti-Xa activity in ICU patients. Mayr and colleagues [26] demonstrated very low anti-Xa levels in intensive care patients, especially in patients with high multi-organ dysfunction syndrome score and high body weight. And a recent study by Rutherford and colleagues [27] showed subtherapeutic trough levels of anti-Xa activity in critically ill trauma and surgical patients after once daily 40 mg enoxaparin by subcutaneous injection for deep venous thrombosis prophylaxis.
Critical illness may alter absorption, volume of distribution and clearance of drugs used in ICU patients and these alterations may have additive or opposing effects on drug exposure, elimination and half-life [14]. In contrast to unfractionated heparin, only a minor portion of LMWH binds to acute phase proteins and endothelial cells. Whether the bioavailability of LMWHs decreases during an acute phase response, as it can be found in critically ill patients, is unknown [12, 26]. These and other combinations of complex pathophysiological characteristics of the ICU patient may account for the lower anti-Xa concentration in our ICU patients.
In our study, the two groups are well matched in terms of age, sex, length, weight and body mass index at admission. As there was no difference in MAP between the two groups, tissue hypoperfusion was not a confounding variable. The SOFA score (0 to 24) is useful to assess organ dysfunction or failure and to evaluate morbidity. It can be used to characterize groups of patients for comparison in trials [28, 29]. The SOFA scores were equal in the index and reference groups, indicating comparability in morbidity between both groups. The two groups do not match in terms of creatinine clearance. The creatinine clearance in the index group is lower compared to the reference group (71 ml/minute versus 131 ml/minute). LMWHs can accumulate in patients with renal failure. It is known from the literature that renal insufficiency does not have any influence on Cmax and apparent volume of distribution of LMWHs, but significantly prolongs clearance and increased half-life [16, 19, 30, 31]. It looks like the elimination half-life was shorter in the reference group compared to the index group (Figure 1). This may have contributed to the slightly higher AUC(0–24 h) in the index group. However, no patients had a creatinine clearance of less than 30 ml/minute. The difference in AUC(0–24 h) is more likely due to the large inter-patient variability in anti-Xa concentrations after subcutaneous administration of 2,500 IU dalteparin (Table 2). The measurements of anti-Xa activity are in the lower part of the calibration curve; some of the data are below the detection limit (0.10 IU/ml). The reliability of the assay might be less in this part of the curve and may have contributed to the large inter-patient variability in the data and so to the higher AUC(0–24 h) in the index group. The AUC(0–12 h) and AUC(0–8 h), in which the lower concentrations play a less important role, were more comparable between the index and the reference group (0.90 and 0.71 IU/ml for the index group and 0.75 and 0.63 IU/ml for the reference group, respectively). High variability among patients in anti-Xa activity, however, has been reported by others [31]. The complex pathophysiological characteristics of the ICU patient may have played a roll in this as well.
When interpreting the results of this study, some other points must be taken into consideration. This is a pilot study with only a small number of patients. A relatively long inclusion period was needed to meet enrollment of the required number of patients not on vasopressors and/or inotropics. With our sample size calculation we considered a difference of 50% in anti-Xa activity to be clinically relevant. To prove that difference, we only needed a small number of patients, seven in each group. With a larger number of patients we might have been able to prove a less than 50% difference in anti-Xa activity between the two groups.
Although commonly used to monitor anticoagulant effectiveness of LMWHs, lower anti-Xa levels do not necessarily mean that critically ill patients are insufficiently protected against VTE using the subcutaneous route of administration [23–25]. To adequately answer that question would take a much larger efficacy study with a different endpoint, such as the presence of VTE instead of anti-Xa levels. Besides this, there are other mechanisms by which LMWHs influence haemostasis. These other mechanisms include inhibition of thrombin activity, inhibition of platelet function and, possibly, enhancement of fibrinolytic activity. Thus, anti-Xa activity may be a marker of LMWHs, which may or may not be causally related to the clinical outcomes [13, 23, 25]. It will be interesting to investigate, as Freedman also mentioned, the intravenous route of administration of LMWHs for thromboprophylaxis in critically ill patients and determine anti-Xa activity and efficacy [13].
Besides these limitations, this study is, to our knowledge, the first to investigate the influence of subcutaneous oedema on the absorption of LMWHs in the critically ill patient. Subcutaneous oedema is a common problem in the ICU patient. Notwithstanding the difficult patient population, we have managed to include comparable ICU patients in both groups. ICU patients have a complex pathophysiology that can influence the pharmacology of different drugs. It is important to investigate parts of this potential problem so we can optimize the use of drugs in critically ill patients.
In this pilot study there was no clinically relevant difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for VTE prophylaxis between ICU patients with and without subcutaneous oedema. Critically ill patients, however, seem to have lower anti-Xa activity levels than healthy volunteers. Whether these lower anti-Xa activities also translate into higher prevalence of thromboembolic events is still unclear. Further studies are necessary to identify the proper dose and route of application of LMWHs for VTE prophylaxis in the critically ill patient.
Key messages
ICU patients often suffer from subcutaneous oedema and it is unknown whether this oedema impairs the absorption of LMWHs given by subcutaneous injection.
We found no difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for VTE prophylaxis between ICU patients with and without oedema.
Critically ill patients seem to have lower anti-Xa activity levels than healthy volunteers.
= area under the concentration curve
- Cmax:
= maximal observed activity
= intensive care unit
= low molecular weight heparin
= mean arterial pressure
= standard deviation
= sequential organ failure assessment
= venous thromboembolism.
The authors thank all patients who have participated in this study and the intensivists and nurses at the ICUs and the clinical chemical and pharmaceutical laboratories of the St Elisabeth Hospital and the TweeSteden hospital in Tilburg and Catherijne A Knibbe for her effort and time spent in analyzing the data. Funding was received from a local research fund from the TweeSteden Hospital for the measurement of anti-Xa activity.
Authors' Affiliations
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