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Gear Review
Stacy Newton
Jamie Mitchell 10x world champion Molokai-2-Oahu wearing Kaenon Polarized
10x WORLD CHAMPION MOLOKAI 2 OAHU
From Coffs Harbor, Australia, Jamie Mitchell is a professional paddler and one of the worlds ultimate watermen. As a 10x consecutive Molokai to Oahu Paddleboard Race Winner and a Battle of the Paddle champion, since 2002 Jamie has dominated nearly every competition he has entered.
Also known as a fearless big wave surfer, Jamie has received invitations to some of the worlds elite big wave riding events including the Tow-in World Cup and the Mavericks Paddle-in contest. In 2007 Jamie was nominated in Billabongs XXL Big Wave Awards, for a massive wave ridden at Todos Santos, Mexico.
Outside of competition, Jamie has earned membership into the notorious 30/20 Club, a brotherhood of elite watermen who have paddled 30 miles, or more, through open-ocean in addition to having ridden 20 foot waves in the traditional paddle-in method, unaided by a tow-in vehicle. He can be found traversing the globe in search of massive waves and can often be seen paddling across the deep blue, accompanied by some of nature's most intimidating creatures.
For Jamie, the ocean is more than the blue area on a map or a weekend destination. To him, it is a way of life and an arena to embrace, explore and experience some of the greatest moments of his life.
View More Details on Kaenon Gauge Sunglasses - Polarized


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Information on "Conflict" and "Eastern Africa"
1 2
June 2015
5 Jun 2015
The Soldier and the Street
Africa's armed forces have already learned one important lesson from the African Union Mission in Somalia (AMISOM), write Marie Besançon and Stephen Dalzell. You need effective civil-military operations (CMO) to complement the other components of your military mandate. More on «The Soldier and the Street»
May 2015
25 May 2015
What Now for Burundi? Five Key Risks
Burundi is teetering on the brink of renewed internal conflict. Today, Stephen Graham and Anthony Morland consider what a return to the dark days of the 1993-2005 civil war could mean for this fragile central African state and its equally volatile neighbors. More on «What Now for Burundi? Five Key Risks»
April 2015
9 Apr 2015
Global Threats in Africa
What steps should the international community take in order to mitigate the development and security threats coming out of Africa? Shannon Dick recommends adopting a broad brush approach that engages with non-traditional partners from the security, development, environmental, and health fields. More on «Global Threats in Africa»
July 2014
30 Jul 2014
Assessing Mombasa's Credentials as a Battleground in Kenya's War on Terror
What explains Mombasa's status as a critical battleground in Kenya's war against terrorism? The answer, according to Herman Butime, lies between the role the city plays in linking regional secessionist and religious tensions together, and the contradictions fueling Jihadist activity in East Africa and beyond. More on «Assessing Mombasa's Credentials as a Battleground in Kenya's War on Terror »
June 2014
11 Jun 2014
Shortages, Clan Rivalries Weaken Somalia's New Army
Even if it remains poorly-resourced, writes the IRIN, the Somali National Army (SNA) is expected to become the mainstay of the country's national security. Standing in its way, however, are the clan loyalties that subvert the sense of nationhood the SNA must ultimately have. More on «Shortages, Clan Rivalries Weaken Somalia's New Army»
January 2014
14 Jan 2014
Saving South Sudan
How can other governments and international organizations bring the world's youngest country back from the brink of state failure? Beyond offering material assistance to the war-torn country, writes J. Peter Pham, they might also want to look at the nature of the conflict more realistically. More on «Saving South Sudan»
September 2013
11 Sep 2013
Ethnic Tensions Simmer on Kenyan Coast
Despite the introduction of a curfew and a heightened police presence, ethnic tensions in Kenya's Tana Delta region remain high. Today, Joseph Akwiri reveals what the locals think – the government better intensify its security efforts if it wants to avoid more violence in the future. More on «Ethnic Tensions Simmer on Kenyan Coast»
April 2013
3 Apr 2013
Interview with Hilde Johnson, UN Special Representative for South Sudan
Improving South Sudan's state- and nation-building capacities remains a huge task, says UN Special Representative Hilde Johnson. In today's interview, she outlines the work being done by the UN mission in the world's newest state. More on «Interview with Hilde Johnson, UN Special Representative for South Sudan»
October 2012
22 Oct 2012
Factors Responsible for Al-Shabab's Losses in Somalia
The African Union Mission's advance across Somalia transformed al-Shabab from a powerful militant group to a weakened band of insurgents. Alexander Meleagrou-Hitchens and Hussein Solomon also attribute the decline of al-Shabab to clan rivalries and poor handling of the drought in 2011. More on «Factors Responsible for Al-Shabab's Losses in Somalia»
August 2012
3 Aug 2012
Ethiopia and Eritrea: Rising Tensions Amid New Opportunities for Engagement
Although tensions between Ethiopia and its former province remain tense, Eritrea's improving financial situation and the growing weakness of al-Shabaab in the region may provide opportunities for engagement between the two countries, or so argue Chatham House analysts. More on «Ethiopia and Eritrea: Rising Tensions Amid New Opportunities for Engagement»
1 2

subset: commoncrawl


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watch: "sunday (psychic conversation #9)" – crocodiles
Crocodiles, the fuzz-rock band out of San Diego, have a new video for their song "Sunday (Psychic Conversation #9), shot by Sam Macon. The song is off their upcoming album Endless Flowers, which will be out June 4th on French Kiss.
The fuzzed-out look of this video totally matches the fuzzed-out guitars, and the whole thing has a retro vibe courtesy of some nice camera filters. Basically, it's a video Instagram.
If you're more interested in the audio than the video – or if your cruel employer blocks YouTube, like mine does – you can stream the audio or snag the mp3 via Stereogum below.
Crocodiles – Sunday (Psychic Conversation #9) [mp3]
Fact to Impress Your Friends With: Frontman Brandon Welchez is married to Dee Dee Penny of Dum Dum Girls and he played in an early version of that band. The pair formed ZOO MUSIC, which has released records from Dirty Beaches, Reading Rainbow, and Woven Bones
[via You Ain't No Picasso]


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Posted 17 Feb 2012
Link to this post
Hi there,
Now i'm not sure if there's a solution for this particular problem.
Scenario; Client has a site(a) in which they want to embed sections from the site i'm developing, site(b).
To enable them to do so i'm providing them with some iframe markup to put into their CMS.
The problem being, that some of the pages they're embedding have radwindows in, and these RadWindows are wider than the size of the iframe the page is contained within.
Try try and resolve this i made the iframe larger than the actual content, and overlay some of their content on site(a), using a transparent background on the iframe. This allowed my RadWindow sufficient space.
However, what i had overlooked is if there's any content underneath the iframe, such as links etc, they're no longer accessible because the iframe is above them .
So i guess my question would be; is there a solution for this ? I guess what i need is the RadWindow to open independantly so its not restricted by the size of the iframe it's in. However, i also need it to be able to interact with the page at which it is called from (i use the closeandrebind event for radgrid/window).
Any suggestions welcome,
Posted 20 Feb 2012
Link to this post
Hi Alan,
This is a general layout issue that is not related to the RadControls in any way. How to organize the real estate of your page so that both the iframe and the controls around it are visible is a decision the developers and designers should take to match their needs.
In case the most common use of your page is to be loaded in this iframe you may redesign it so that it does not require this much space.
Overall, there is only one way to ensure that a RadWindow will not be locked in an iframe and this is to open it from the topmost frame of the site. This approach has some limitations, though - the most important one is that both pages must come from the same domain in order for JavaScript to allow the cross-frame function call. The second is that the parent page must be prepared to receive the command to open the certain RadWindow (easiest done by using radopen and a RadWindowManager). To utilize this approach you may find the following resources useful: here and here for checking if you are in an iframe or RadWindow and here for calling functions accross different iframes and RadWindows (get_contentFrame() returns a DOM reference to the iframe of the RadWindow so you can replace it with a getElementById("your iframe") ) to call a function from the context of the main page in your own page.
Kind regards,
the Telerik team
Posted 23 Feb 2012
Link to this post
thanks Marin.
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text:
I cowered into Jacob's side, my eyes scanning the forest for the other werewolves. When they appeared, striding out from between the trees, they weren't what I was expecting. I'd gotten the image of the wolves stuck in my head. These were just four really big half-naked boys.
Bella Swan, New Moon, Chapter 14, p.323


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World Book Day - What is your favourite book and how do we get more children into reading?
Posted: March 06, 2014|
READERS, writers, illustrators and publishers in Gloucestershire are joining people across the globe to celebrate the 17th annual World Book Day.
Events are taking place at schools and libraries across the county today in a bid to encourage young people to get into reading.
The county has a rich literary heritage and among Gloucestershire's most famous authors are Jilly Cooper, from Bisley, who has written and compiled 41 books, and Katie Fforde, from Rodborough, who has just published her 20th novel. Harry Potter writer JK Rowling also grew up in Tutshill in the Forest of Dean.
Author Katie said the whole issue regarding encouraging people to get into books was one of promoting wider access to reading and reading materials.
"What I would like World Book Day to do is to offer books to people who don't normally access them … to make books available in, for example, prisons and waiting rooms," she said.
At independent Stroud Bookshop, a spokeswoman said World Book Day was very much about introducing children to books.
Vouchers are given out in schools encouraging boys and girls to go to a nearby book store, perhaps for the first time, soak up the often unique atmosphere, and select something to read.
The scheme, welcomed by Stroud Bookshop, enabled pupils to swap their vouchers for a World Book Day title or put it towards a different selected reader, she said.
"We see it very much from the children's point of view," she said.
Meanwhile, readers said that there is still a thriving literary scene in the county, despite the challenge of competing with TV, film and social media.
Edward Granger, 32, from Gloucester, said there are many popular writing groups in the county.
"I write short stories as a hobby and there is a really good literary scene in Gloucestershire with lots of groups for support and advice or to just share ideas."
Keen reader Elizabeth Ryder from Churchdown, often buys her books from Waterstones, she said: "I usually go for the older type books such as Barbara Pym. I really like them, she wrote a series of books.
"They are very interesting and you can always go back to them without getting bored. I like thrillers too and I like Agatha Christie books too."
Grandmother Janet Lewis, added:"I do not read a lot of books myself but my granddaughter Katie does mostly on her Kindle.
"She enjoys reading JK Rowling books. I think it is important children read books."
Matthew Brookes is an author from The Reddings in Cheltenham who published his debut collection of short stories Beautiful Chaos in 2012. He said there is no comparison between novels and TV, adding: "You never know what is going to happen in a book whereas television is predictable."


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An MMT site bringing you dogma-free economics without the pleadings of self interest
Thursday, February 23, 2012
Ralph Musgrave's letter in The Financial Times
Read it at The Financial Times | Letters
Bigger deficits do not always mean more debt (part 2)
From Mr Ralph Musgrave
(h/t Ralph via email)
Posted by Tom Hickey at 1:25 PM
Labels: debt, deficit, MMT, Ralph Musgrave
3 comments:
- Mike Norman said...
That was Ron Paul's idea, too. Just have the Fed destroy the Treasuries it holds. It's got no need for them and they shouldn't be counted as part of the debt.
- February 23, 2012 at 1:45 PM
- Dan Kervick said...
Great point Ralph and Mike.
- February 23, 2012 at 3:26 PM
- Letsgetitdone said...
Who's going to have them do it? That would require Congressional action, which will not be forthcoming. Proof Platinum Coin Seigniorage is better, because Congress has already legislated that. It would only take our President to use it.
- February 25, 2012 at 3:13 PM
Subscribe to: Post Comments (Atom)


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Friday night obituary update
The following obituaries were provided by local funeral homes. Read our complete obituaries in The Herald-Dispatch Saturday and at www.herald-dispatch.com.
ALMA OPAL ADKINS, 101, of Hamlin, W.Va., widow of Winford Adkins, died June 6. She was a homemaker. Funeral service will be 1 p.m. Sunday, Koontz Funeral Home, Hamlin; burial will follow at Powell Cemetery, Hamlin. Visitation will be one hour prior to service.
DONNA ANDERSON, 51, of Kite, Ky., wife of Delmas Anderson, died June 5 in Greg and Noreen Wells Hospice Care Center. Funeral service will be 11 a.m. Monday, Rebecca Old Regular Baptist Church, Kite; burial in Felix King Cemetery, Kite. Visitation after 6 p.m. Saturday, Nelson Fraizer Funeral Home Chapel, Hindman, Ky. www.nelsonfrazierfuneralhome.com.
GLADYS CASKEY, 69, of Winchester, Ky., formerly of Ashland, wife of William Caskey, died June 6 in Clark Regional Hospital. Arrangements are pending at Steen Funeral Home, Central Avenue Chapel.
TIM CRAGER, 85 of Scott Depot, W.Va., formerly of South Point, Ohio, died June 4. Funeral service will be held at noon Tuesday, Chapman Funeral Home, Hurricane, W.Va.; burial follows in Highland Memorial Park, South Point, Ohio. Visitation will be from 6 to 8 p.m. Monday at the funeral home.
CPL. RICHARD ISBELL, 19, of Pike County, Kentucky, son of the late William and Roma Isbell will be buried at noon Saturday in Highland Memorial Park, Staffordsville, Ky. He was a member of the United States Army, missing in action since 1951 during the Korean Conflict. Local arrangements by Nelson Frazier Funeral Home, Martin, Ky. www.nelsonfrazierfuneralhome.com.
DONNA KING, 81, of Clothier, W.Va., died June 6 at home. Arrangements are incomplete at Evans Funeral Home and Cremation Services, Chapmanville, W.Va.
THELMA JEAN LANE, 74, of Huntington died June 5 in Emogene Dolin Jones Hospice House. Funeral services will be 11 a.m. Monday, Wallace Funeral Home and Chapel; burial will be in White Chapel Memorial Gardens. Visitation will be one hour prior to service. Donations are suggested to Emogene Dolin Jones Hospice House, 3100 Staunton Rd., Huntington, WV 25702. www.timeformemory.com/wallace.
WILLARD LEEDY, 96, of Gallipolis, Ohio, widower of Margaret Juanita Leedy, died June 5. He retired from the A&P Tea Company. Funeral service will be 2 p.m. Tuesday, First Baptist Church, Gallipolis. Visitation from 6 to 7:30 p.m. Monday, Willis Funeral Home, Gallipolis. Donations are suggested to Ohio Valley Christian School. www.willisfuneralhome.com.
AVA CAROLINE PRATER, 79, of Pikeville, Ky., widow of Earnest Prater, died June 3 in Pikeville Medical Center. She was a homemaker. Funeral service will be 1 p.m. Sunday, Aflex (Ky.) Baptist Church; burial in the family cemetery, Beechcreek, Ky. Visitation after 6 p.m. Saturday at the church. www.nelsonfrazierfuneralhome.com.
KEITH DEKKER RUSSELL, 60, of Lavalette, son of Flora Russell, died June 4 in Adena Hospital, Waverly, Ohio. He retired from the Wayne County Board of Education. Funeral services will be 2 p.m. Sunday, Morris Funeral Home Chapel, Wayne; burial will follow in Community Memorial Gardens, Wayne. Visitation one hour prior to service.
DALE EVERETT WORKMAN, 32 of Dingess, son of Flavel and Stella Workman of Dingess, died June 5. He was a former coal miner. Services will be 2 p.m. Wednesday, Calvary Baptist Church, Dingess; burial will follow in the family cemetery, Dingess. Visitation one hour before service. Arrangements by Evans Funeral Home and Cremation Services, Chapmanville, W.Va.


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Online Temporary Power Form
If you are building a new home or commercial facility and require temporary power for construction in the City of Anaheim, please fill out the following fields or apply in person at Anaheim Public Utilities (Electrical Division, 201 S Anaheim Blvd. Suite 701, Anaheim, CA 92805.) An Electrical Designer will contact you within 2 business days to discuss your installation. For more information, please click on the following link to view Anaheim Public Utility's Temporary Power checklist.
Please Describe what the temporary service will be used for:
So we may best serve you, please provide us the below information for us to contact you.


text:
Hang tight!
Recipe by sal
"Cool and tasty - best of all easy! A definite winner."
Hmm. None of these ingredients are on sale today.
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2 (46 fluid ounce) cans
pineapple juice
1 liter
lemon-lime flavored carbonated beverage
1 (4 ounce) package
sweetened raspberry-flavored drink mix powder
Very yummy. I think the 4 oz package must be a typo. I used a .4 packet of raspberry drink mix and it came out really nice. As the other reviewer said, 4 oz is an awful lot.
I tried this recipe and it had WAY too much raspberry powder in it. I used the 4 oz. it called for, but I would cut that down by a lot. The flavor itself was ok, but it was so strong and so sweet no one could drink it. I ended up pouring the whole bowl out! I even tried diluting it! I might try again, but would have to do some major tweeking.
9 Ratings
I doubled this for a dinner get together and it went over well. For the soda-pop, I used Fresca, and it gave it just enough sweetness to the drink. It was perfect. Will most definitely use this recipe again! Loved it.
I made this punch for a bridal shower (and spiked it with Bacardi Rum!) and it was a total hit! Everyone was asking for the recipe! P.S. It definitely should be 0.4 oz package of drink mix (I used Crystal Lite), NOT 4 oz!
Great Punch!
I made this for my kids and while I find it to be too expensive for such a sweet drink for them (I think something other than canned pineapple might work better with taste and price (maybe the frozen or boxed?) ) it turned out great. Everyone drank this one up. I may try it again for guest.
I made this for our office Christmas party and it was really good. I made half the recipe (one can of pineapple juice, about one little packet of the raspberry ice Crystal Light, and one liter bottle of soda). I used club soda instead of sugary soda. I thought the lemon-lime soda would make it too sweet. If you're making it for kids then go with the sweet soda. I'm making it again for Xmas Eve and will be spiking it with vodka or rum.
* Percent Daily Values are based on a 2,000 calorie diet.
Pineapple Punch Drink
Serving Size: 1/15 of a recipe
Servings Per Recipe: 15
Amount Per Serving
Calories: 147
Calories from Fat: 2
With our 2,700+ chicken breast recipes, you'll never serve the same old chicken again.
The firm, juicy texture of zucchini make them a perfect side to toss on the grill.
Delicious recipes, party ideas, and cooking tips! Get a year of Allrecipes magazine for $7.99!
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A refreshing, delicious fruit punch with ginger ale and orange sherbet.
See how to make a refreshing alcohol-free punch.


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3:25 pm
Wed July 2, 2014
Peoria Police ready for July 4th celebration
By Denise Molina
The city of Peoria plans to have up to 55 officers on hand to monitor the crowds and for traffic control. Steve Roegge is a Lieutenant with the Peoria Police Department's Special operations Unit.
"The one thing we ask is patience. You know, it's such a large event. It's a Friday. We expect large crowds. We just ask people to come down, enjoy it and understand that we're doing the best we can to get as many people out of here as we're able to."
Roegge says the city will shut down Water Street beginning at four Friday afternoon. The exit to Washington Street from I-74 eastbound will also be closed while the fireworks are displayed over the Illinois River. It will remain closed until around 10:30.


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Protect merchandise, lower utilities, and increase comfort with Huper Optik window films
Want unique and modern design elements? With our amazing line of decorative films the possibilities are endless
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Enhancing antibodies by engineering multi-specificity has emerged as a promising new wave in antibody therapeutics. Antibodies are empowered through binding to at least two molecular targets simultaneously, thereby delivering a highly potent therapeutic, particularly for cancer immunotherapy. This meeting will explore the challenges of engineering multi-specificity to ensure stability and efficacy, and will review the numerous forms of multi-specific antibodies in development.
Join with colleagues from around the world in this discussion of the exciting breakthroughs in engineering antibodies, and see how cancer and other applications are advancing into a true therapeutic revolution.
Day 1 | Day 2 | Download Brochure
1:00 pm Conference Registration
1:45 Chairperson's Remarks
Matthew Robinson, Ph.D., Assistant Professor, Medical Oncology, Fox Chase Cancer Center
1:50 Bispecific Antibody Therapeutics Made by Dock-and-Lock
David M. Goldenberg, M.D., President, Garden State Cancer Center; CSO & CMO, Immunomedics, Inc. - Biography
Our group has developed a new platform technology, the Dock-and-Lock (DNL) method, which has the potential for making an unlimited number of bioactive molecules with multivalency, multifunctionality, and defined composition, generating diverse bioactive molecules of increased complexity. DNL involves the application of conjugation chemistry and genetic engineering to harness the dimerization and docking domain (DDD) of cAMP-dependent protein kinase and the anchoring domain (AD) of A-kinase anchoring proteins into respective modules capable of self-assembly and forming stably-tethered structures of defined composition. Modules may be made synthetically or genetically from proteins as well as non-proteins. Notable advantages of DNL over existing technologies include ease of manufacture with quantitative yields, and in vivo stability.
2:20 Trifunctional Antibodies: Combining Passive and Active Immunization for Cancer Therapy
Horst Lindhofer, Ph.D., Founder & CEO, TRION Pharma GmbH - Biography
Trifunctional antibodies (Triomab) have the capacity to induce long-lasting immunity. They combine passive immunization (i.e. direct tumor cell killing) with active immunization which raises a broad immune response going beyond the tumor associated antigen originally targeted by the Triomab. This talk will focus on the trifunctional antibody, catumaxomb, which is the first approved multispecific antibody worldwide.
2:50 Transcytosis of the Blood Brain Barrier with Bispecific Antibody Therapeutics
J. Michael Elliott, Senior Research Associate, Genentech
Bispecific antibodies are a logical next step for immunoglobulin therapeutics. Their ability to engage two unique targets simultaneously and with exquisite specificity greatly enhances potential applications of existing antibodies. We present here bispecific IgG1s with two independent Fab arms that are otherwise nearly identical to monospecific antibodies. These bispecifics are able to both cross the blood brain barrier utilizing transferrin receptor mediated transcytosis, and potently reduce amyloid-β (Ab) production in murine Alzheimer models through inhibition of the enzyme β-secretase (BACE1).
3:20 Sponsored Presentation (Opportunity Available)
3:35 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
Breakthroughs with Bispecific Antibodies
4:30 TRIBODY: Building Trispecificity by Fab-scFv Fusions
Nico Mertens, Ph.D., Director, Antibody Engineering, Biotecnol SA - Biography
Tribodies are antibody derived reagents based on fusions of different binders or effectors to the Fab chains. Due to the specific and stable heterodimerization of the Fab chains easy engineering of multispecific or multifunctional proteins is achieved. We will discuss functionality of this type of molecule as well as developability of these recombinant fusion molecules.
5:00 Bispecific Digoxigenin-Binding Antibodies for Targeted Payload Delivery
Ulrich Brinkmann, Ph.D., Scientific Director, Biologics Engineering, Roche Pharma Research and Early Development - Biography
Bispecific antibodies that bind cell-surface targets as well as digoxigenin (Dig) were generated for targeted payload delivery. Targeting moieties are IgGs that bind the tumor antigens Her2, IGF1R, CD22, or LeY. A Dig-binding single-chain Fv was attached in disulfide-stabilized form to C termini of CH3 domains of targeting antibodies. Bispecific molecules were expressed in mammalian cells and purified in the same manner as unmodified IgGs. They are stable without aggregation propensity and retain binding specificity/affinity to cell-surface antigens and Dig. Digoxigeninylated payloads were generated that retain full functionality and can be complexed to bispecific antibodies in a defined 21 ratio. Payloads include small compounds (Dig-Cy5, Dig-Doxorubicin) and proteins (Dig-GFP). Complexed payloads are targeted by the bispecifics to cancer cells and because these complexes are stable in serum, they can be applied for targeted delivery. Because Dig bispecifics also effectively capture digoxigeninylated compounds under physiological conditions, separate administration of uncharged Dig bispecifics followed by application of Dig payload is sufficient to achieve antibody-mediated targeting in vitro and in vivo.
5:30 Systems Biology Approach to the Design of Bispecific Antibody Targeting Two Redundant Pro-Survival Signaling Pathways in Cancer
Rachel Rennard, Scientist, Protein Engineering, Merrimack Pharmaceuticals
Multispecific antibody-like molecules targeting growth factor receptor signaling pathways comprise a promising new class of anti-cancer agents. However, these multi-specific antibodies are complex, and present significant design and CMC challenges. We have developed an integrated approach where we use mechanistic models of relevant biological systems to identify optimal molecular properties such as format, avidities and affinities. Rational engineering approaches are then used to construct molecules with robust pharmaceutical properties. Application of this approach to a bispecific molecule targeting two receptor tyrosine kinases will be presented.
6:00 Close of Day
Day 1 | Day 2 | Download Brochure
Antibodies for the 21st Century
Recombinant Protein Therapeutics
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BuzZ Sessions are facilitated, small-group discussions. Interactive participation leads to problem-solving solutions and future collaborations around focused topics.
To submit a topic for consideration, please click here.


text:
Is it all about some, umm, "interesting" accounting techniques used before the purchase of Autonomy by HP? Or is it all about how HP has mismanged Autonomy since the purchase and thus destroyed much of what was of value within it?
Don't forget, it's entirely possible that neither, either or both could be true here (neither, admittedly, being unlikely as something has destroyed a lot of value).
All of which leaves us with only one question as we watch this play out before us. Do you prefer salt or sugar on your popcorn?


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such hostility, reminds me of working people who resent the unemployed. lose the helmet dude, it's fucking with your head.
@hh: That comparison makes zero sense.
70% of bicyclists killed in crashes are because of fatal head injuries. A helmet wouldn't work every time but it's better than nothing.
- Forum Posts: 16510
- Wiki Points: 5553
- Followed by: 163
- Reviews: 8 Lists: 10
I don't really bike but I answered yes as if I did I would wear a helmet. I don't need any more head trauma in my life.
- Forum Posts: 1787
- Wiki Points: 1
- Followed by: 119
- Reviews: 0 Lists: 0
No, but then again I am not in a crazy city like San Francisco where I can get mowed down at any second.
I wear one.
#1 - I prefer a helmet to greasy sunscreen on my face / hair part by a long shot, and that shit does burn if you're light skinned and cycling several times a week in the summer. It shades your eyes a bit too, if you don't have sunglasses handy.
#2 - Falling onto bare pavement already sucks a lot.It doesn't need to be potentially fatal. Even if you avoid every random rock, bolt, and tire retread out there, bike parts might fail on you at any time.
#3 - I'm more worried about bad drivers noticing and avoiding me than total strangers judging my appearance.
I definitely don't agree with laws requiring helmets, because it basically creates a law for some of the people. The reality that many low-income earners commute to their jobs on a bike and are not going to bother buying a fucking helmet in that situation. Cops aren't going to stop and fine them for that, nor should they.
But I do think parents would be crazy not to require their kid to wear one, and if you are over 25, I think it's probably time to realize that you don't look cool on a bike anyway.
Nah. But I don't bike on the road with any regularity. My bicycling is mostly confined to dirt trails in the nearby park/woods.
I do wear a helmet for skiing, though. Two reasons: 1. people are perpetually pulling down the chairlift safety bar too fast and whacking me in the back of the head with it. 2. I ski fast. When I fall, I slide a long ways before I stop.
- Forum Posts: 2032
- Wiki Points: 308
- Followed by: 23
- Reviews: 1 Lists: 3
When I biked more often, I would absolutely wear a helmet. Not all helmets look awful.
But now that my commute to my college classes is an hour each way (I live in a pretty rural area), I have to drive pretty much exclusively.
- Forum Posts: 1533
- Wiki Points: 2
- Followed by: 11
- Reviews: 0 Lists: 0
i do probably half the time. i've just been lucky- i've gotten stuck in streetcar tracks and been doored, both times without a helmet, and only suffered scrapes and bruises. i'm also an idiot. there really isn't a good excuse. you just need to wear one.
- Forum Posts: 2107
- Wiki Points: 44
- Followed by: 15
- Reviews: 0 Lists: 2
I bike to and from work every day and I never wear a helmet. If I die, I die.
- Forum Posts: 1088
- Wiki Points: 0
- Followed by: 5
- Reviews: 0 Lists: 2
I have a wife and a kid...I kinda owe them not dying or getting brain damage, so yeah, I always wear a helmet.
- Forum Posts: 1897
- Wiki Points: 1071
- Followed by: 36
- Reviews: 12 Lists: 1
I've heard far more horror stories of people wearing helmets and the helmets causing injuries than helmets saving someone from injury.
- TheUnsavedHero
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- Follow
- Forum Posts: 1275
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- Followed by: 13
- Reviews: 0 Lists: 2
Haven't rode a bike in forever. When I did though, I generally didn't wear one. I'm of the mind of the "Tuck & Roll" method.
- Forum Posts: 202
- Wiki Points: 159
- Followed by: 16
- Reviews: 0 Lists: 4
Don't wear one because I don't own one. Though I do wear a helmet riding my motorcycle.
- Forum Posts: 1238
- Wiki Points: 4001
- Followed by: 13
- Reviews: 2 Lists: 4
No, because I don't see my skull as the weak point. I think I my problem would be my long and thin neck snapping.
I was unaware so many people didn't think helmets were effective. This is from an pro-helmet site, but it addresses most of the complaints I've heard here.
And if your argument is "I've never used a helmet and I'm just fine", you should think about all the statements you aren't hearing from people who didn't wear helmets and had different results.
Yes, absolutely. I ride in NYC and a helmet is essential, bike path or not.
It just takes one accident to damage your brain and forever impact your life. I wouldn't ride in a car without a seat belt even if there was light to no traffic, and I wouldn't ride a bike without a helmet.
Bikers who point to traffic, bike lanes, or the "safety" of the roads they ride miss the point. The majority of the time the rider is at fault in an accident or can directly influence the amount of danger they put themselves in. Patrick's accident was an example, it wasn't traffic or pedestrians that got in his way, it was a pothole.
Arms, legs, and backs get stronger with riding and become less susceptible to injury, but your skull and brain don't get extra padding.
I know there's a lot of debate over the effectiveness of helmets although I would question the agenda of any pro- or anti-helmet study. But if I can do something as menial as wearing a helmet to protect my brain, I will do it.


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NYC Parks Events Calendar
Get up, get out, and do something! Just about any day of the year, you can find something fun, informative, and healthy to enjoy at an area park. Feel free to browse the listings below, or use the search tools to find an event that matches your interests and location.
Viewing 3,011–3,020 out of 17,954 events
from September 9, 2013 (x) to April 25, 2026
Tuesday, August 26, 2014
Exhibition: Tomorrow's World: The New York World's Fairs and Flushing Meadows Corona Park
at Arsenal (in Central Park), Manhattan
9:00 a.m.–5:00 p.m.
In celebration of the 50th and 75th anniversaries of the World's Fairs, Tomorrow's World will include never before exhibited vintage images from the Parks Photo Archive and…
Category: Education, Art, History, Seniors
Bryant Park Yoga
at Upper Terrace (in Bryant Park), Manhattan
10:00 a.m.–11:00 a.m.
Perfect your downward dog under the trees with YogaWorks instructors.
Category: Fitness, Outdoor Fitness
Weird, Wild & Wonderful
at The New York Botanical Garden, Bronx
10:00 a.m.–11:00 a.m.
The New York Botanical Garden invited members of the American Society of Botanical Artists to participate in a study of the eccentric, creating works of art based on unusual plants.
Category: Nature, Art
Dunes, Drawing and Dendrology: Drawing 'Chalk and Talk'
at Conference House Park Visitor Center (in Conference House Park), Staten Island
10:00 a.m.–12:00 p.m.
This introductory workshop provides basic how-to instruction, along with the materials, for exploring and capturing the varied landscape of Conference House Park.
Category: Education, Nature, Kids, Tours, Talks, Seniors
Garden Crew
at Mosholu Avenue and Broadway (in Van Cortlandt Park), Bronx
10:00 a.m.–1:00 p.m.
Get dirty helping out at the Compost Garden.
Category: Volunteer
Summer on the Hudson: Game Days
at West Harlem Piers Park, Manhattan
10:00 a.m.–2:00 p.m.
Play giant tic tac toe, lawn bowling and more!
Category: Festivals, Games, Kids, Waterfront
Summer Sports Experience: Calvert Vaux Park/Dreier Offerman Park
at Calvert Vaux Park, Brooklyn
10:00 a.m.–4:00 p.m.
Bring your kids to the Summer Sports Experience! In the program, Parks staff teach kids through intensive sports clinics. On site registration IS REQUIRED for Brooklyn clinics.
Category: Kids, Sports, Summer Sports Experience
Dinosaur Safari: Mysteries Revealed
at Bronx Zoo (in Bronx Park), Bronx
10:00 a.m.–5:00 p.m.
See more than 30 animatronic dinosaurs, including a 40-foot long tyrannosaurus rex, on this ride through the two-acre safari.
Category: Education, Nature, Kids
City Park's Foundation Puppet Mobile 'Little Red's Hood'
at Conference House Park Visitor Center (in Conference House Park), Staten Island
10:30 a.m.–12:30 p.m.
Come see this classic children's fairy tale re-imagined as an old fashioned puppert show within the great outdoors.
Category: Kids, Theater, It's My Park
Summer Sports Experience: Detective Keith Williams Park
at Detective Keith L. Williams Field House (in Detective Keith L Williams Park), Queens
11:00 a.m.–3:00 p.m.
Bring your kids to the Summer Sports Experience! In the program, Parks staff teach kids through intensive sports clinics.
Category: Kids, Sports, Summer Sports Experience
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Related Information
- Get information on upcoming events directly in your inbox by signing up for our Email Newsletters.
- Know about an event that's not on the calendar? Send us a tip!
- Planning an event and considering hosting it in a park? Make sure to read our Planning an Event page.


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Authorities in Kosciusko and Whitley counties are asking for help locating three men wanted for home improvement fraud.
Felony warrants have been issued for 22 year-old Bobby Allison and his brother 26 year old Elvis Allison of Silver Lake.
The two are wanted for a variety of home improvement scams in Whitley and Kosciusko counties.
Police in Kosciusko County are also looking for a third relative., 29 year-old Tyson Allison in connection with scams in Silver Lake. He may be driving a white Dodge Ram crew-cab pickup truck with Montana license plates.
Anyone with information about these three men are asked to contact either the Kosciusko or Whitley County Sheriff's Departments.
Copyright 2013 Nexstar Broadcasting, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.


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Hypnotism is practiced by many professional hypnotherapists, and has been used to help millions of people to overcome fears, conquer difficult problems, and to relax and reduce stress. Multiple studies have shown that using hypnosis to quit smoking works in a high percentage of cases — as high as 66%. While hypnosis may not be for everybody, it can aid in reducing stress, which is one of the reasons many smokers report that they smoke in the first place.
Hypnosis for smoking provides two main benefits:
Posted In: hypnosis (15) , how to quit smoking (331) , faq (18)


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By Steven Donald SmithAmerican Forces Press Service
WASHINGTON, May 29, 2006 On a day that is meant to represent more than just the unofficial start of the summer season, thousands of people lined Constitution Avenue here to watch a Memorial Day parade commemorating U.S. troops who have died while serving their country.
"The parade is great. I love it," said Todd Stockstiol, of Memphis, Tenn. "We can't take all the wonderful blessings we have in this country for granted. American troops have sacrificed so much for us. I really appreciate it."
The annual National Memorial Day Parade honors all U.S. military personnel who have served their country in uniform from the American Revolution to Operation Iraqi Freedom, and seeks to educate Americans about the sacrifices made by those who protect the nation, event organizers said.
The one-mile parade included active-duty servicemembers representing the U.S. Army, Navy, Marines, Air Force and Coast Guard, marching bands from across the country and several parade floats. Hundreds of veterans of World War I, World War II, the Korean War, the Vietnam War, the battles in Grenada and Somalia, and the Gulf War also marched in the parade, along with representatives from countries such as the United Kingdom, France and Canada.
Emmy Award-winning actor and film director Gary Sinise served as the grand marshal of the parade. The actor has been an active participant in the Defense Department's "America Supports You" program, which showcases Americans' support for U.S. troops. He also has visited troops stationed overseas on numerous occasions and launched the nonprofit organization "Operation Iraqi Children," which collects school supplies for Iraq's children.
Sinise said it was an honor to be the grand marshal of the parade. "This is a great way to spend Memorial Day," he said. "I can't think of a better way."
The parade also included several honorary marshals, such as 106-year-old World War I veteran Lloyd Brown. Brown is one of fewer than 30 World War I veterans still alive.
This year's parade was organized by the National Memorial Day Parade Committee, a coalition of military, veteran and civic groups in association with the White House Commission on Remembrance, America Supports You and the World War II Veterans Committee of the American Veterans Center, parade officials said.
Memorial Day, initially called Decoration Day, was first observed in 1868 with the purpose of decorating the graves of Union soldiers killed during the American Civil War. After World War I, it expanded in scope to honor all U.S. troops who died during all wars. One of the longest standing Memorial Day traditions is the Indianapolis 500, which has been running in conjuntion with the holiday weekend since 1911.
Anna Delao-Legeros, an Army veteran, said she came to the nation's capital with some of her classmates from the New York City College of Technology to pay her respects to the men and women who gave their lives to defend the United States and its ideals.
"Freedom is not free," she said. "It's important to remember that somebody has to pay for it."


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Congratulations, You Bastards
Categories: Rams
Well, the day has finally come. Ladies and Gentlemen, your 2008 NFC West Champions, the Arizona Cardinals.
And their leader, Klobberin' Kurt Warner. So congratulations to the Cardinals and congratulations to Kurt.
I think I just threw up in my mouth a little bit.
I was watching the Rams game yesterday, and I was filled with a swirl of emotions, very few of them good. I would imagine that just about any St. Louis sports fan probably felt much the same way, watching as our very own St. Kurt took our very own lost tribe of football to the promised land. Hell, to complete the metaphor, there was even a desert involved.
You know, I have to admit, I was never a big Kurt Warner fan. I know, I know, how can you possibly be a St. Louis Rams fan and not like Warner? The man was the quarterback during the most successful (okay, the only successful), era the Rams have enjoyed since moving here back in 1994. He's a former MVP. A Super Bowl MVP. How can you not like Kurt?
Well, for one thing, I'm not real big on hearing about God all the time. I'm really not. I try to just let it go, but I don't really appreciate having to constantly hear about how much you love Jesus, how much you owe to Jesus, and how you felt he was with you out on the field. Guess what? The other guys probably love Jesus too. So what did you do so special that he likes you more than them, hmm?
On a related note, I've probably always been much too hard on J.D. Drew for similar reasons. I mean, honestly, J.D.? Don't you think that if god really cares about you that much, he would have made it so your effing quadriceps could hold up to more than a light jog without bursting into flames?
But I digress. See, I'm trying to be gracious here, and it totally isn't working.
One more thing: I just couldn't stand his wife. I know that's not exactly a shocking statement for someone to make, but I'm just putting it out there. Shrill and unpleasant were the two nicest things you could say. I have a friend who refers to her as a "wire haired man-goblin."
Just bad times, man.
Just bad times, man.
Of course, Warner also just happens to be one of the most charitable, generous people you're ever going to meet. Which then makes me feel like a complete tool for not being a fan. Honestly, how do you not like a guy who gives so freely? Well, it ain't easy, but I make it work somehow.
So anyway, all I could do while watching the Rams get trounced once again on Sunday was marvel at how different the fortunes of the team and its former star quarterback have been since Kurt left the Lou. St. Kurt wandered into the desert, only to find redemption there. St. Louis was left with the Martz/Zygmunt fun time happy hour, complete with appalling draft picks, internal strife, and paranoid fantasies galore.
St. Kurt found a home with a franchise that finally appears to be getting its collective shit together. St. Louis is still stuck with absentee ownership, as well as absentee management, a front office that literally doesn't seem to have ever actually watched a football game before. It's really sad when a member of the Bidwill family elicits envy in the mind of a St. Louisan.
St. Kurt has two of the best young receivers in all of football, Larry Fitzgerald and Anquan Boldin, both of whom were drafted and developed by the Cardinals. St. Louis simply decided they didn't need one of their best young receivers, Kevin Curtis. Curtis is starring in Philadelphia; his replacement in St. Louis, Drew Bennett, has been -- how do I put this delicately -- less than awe-inspiring.
So while we St. Louis football fans are stuck with a lousy team, a lousy front office, and not much of a light at the end of the tunnel, our prodigal quarterback leads the team that Bill Bidwill basically just absconded in the night with into the playoffs. We've got one of the worst stadiums I've personally ever seen; the Cardinals have a brand new, state of the art facility to play in. In short, life as a fan of St. Louis football sucks ass.
Hey, we've won a title just not too long ago, right? So why does this feel so shitty right now?
So congratulations to Kurt and the Kardinals. Just don't expect a fruit basket.
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Melissa Foley
Eddy Perez
To nominate an outstanding LSU faculty member for the Flagship Faculty honor, please e-mail the LSU Today.
The deadline to submit news items for the LSU Today e-mail newsletter is noon on the day prior to publication. Please enter calendar items on the LSU Master Calendar.
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What was your previous position and where?LSU was my first full-time academic appointment. While a graduate student at Harvard University, I served initially as a research and teaching fellow, then was promoted to head-of-sections for several interdisciplinary, core curriculum courses. Im afraid that I began my career working the evening shift at a suburban Winchells Doughnut Shop.
What brought you to LSU?When I was recruited by LSU, our university was engaged in a robust drive to strengthen humanities research and instruction. Ambitious projects underway at the time included the development of the English Short Title Catalogue, which is now a renowned database managed by the British Library; the development of rare book collections; and the cultivation of early-modern studies initiatives with universities ranging from our sister campus in Shreveport to the University of Goettingen in Germany. The mixture of strong support for cultural education, international humanities outreach, fervor for the then-emerging field of computer applications in the liberal arts and the genial ferocity of then A&S Dean Henry Snyder made for an unbeatable combination and an irresistible attraction.
What are your research interests?I presently am pursuing two major research projects while managing several others. My lead project might be described as the excavation of the early cultural history of cataclysmic geology. For several years, I have been exploring the vast, multi-lingual body of 17th- and 18th-century writing on the mysteries of the world underground: on volcanoes, earthquakes, caves and even the surprisingly large number of hermits for whom extreme circumstances made subterranean dwellings the best option. My underground project covers a huge body of speculative literature — what we might now call science fiction — about a world that few may enter and where fewer may even survive. It investigates the way that science deals with the invisible: with phenomena beyond the reach of apparatus. My second project examines another dimension of the invisible world: that of laughter, as codified in the joke anthologies of the early modern period. Evoked by but never contained within texts, that which is funny belongs to an array of invisible phenomena in which the Enlightenment had a keen interest. I am attempting to explain the reasons for the prodigious expenditure of energy by the age of reason in the preparing and publishing of multitudinous joke collections. I am also preparing edited multi-author volumes of essays on the sea and on motion and locomotion as understood and represented by enlightenment writers and artists. And I edit my two journals, 1650-1850 and ECCB: The Eighteenth-Century Current Bibliography.
What do you hope to accomplish at LSU?Although an individual person constitutes less than one-tenth of 1 percent of an institution, that measure is similar to the level of active ingredients in some of the most powerful chemical agents known to humankind. My present goal is to serve as such an active ingredient at LSU. Owing to the economic difficulties and related frustrations of our times, many faculty members feared being rendered inert. I aim to set an example of engagement by intellectuals in decision- and policy-making processes. I especially hope to change the way that LSU interacts with other institutions around the state: to set an example of leadership rather than rivalry in the statewide educational project.
What do you enjoy most about LSU?What I enjoy most is service as LSU Faculty Senate president, which is the best job in the state, with the most opportunity to work constructively with the greatest number of people in the widest variety of contexts. A close second would be the opportunity that LSU provides to interact with the other nine campuses and myriad institutions of the LSU System as well as with faculty and administrative leaders from campuses from Lake Charles to Ruston, from New Orleans to Shreveport, and around the nation. I must also confess to an inordinate pleasure in the production of The Faculty Senate Monthly Newsletter.
What are your major accomplishments?On the academic and research side, my favorite accomplishment is surely being honored as a Distinguished Research Master here in Louisiana and having published an array of books that have revived more than a few precious but forgotten cultural and intellectual resources. The privilege of organizing conferences in venues from Singapore to Shreveport has been an unforgettable odyssey through the frontiers of academic life. On the administrative side, having served in a leadership role in the development of the highly productive Louisiana Transfer Degree, the fruit of service on the Statewide Articulation and Transfer Council, ranks almost as high as several years of service on budget committees, assignments that have allowed me to contribute to the sustaining of a great institution in difficult times while also revealing the wondrous intricacies of a university filled with highly talented people. I am also pleased with having created a statewide network of colleagues interested in faculty governance, a network that now maintains the Alexandria Summit Meeting series.
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Back to Newsletters
May 2012 HCV Advocate
Download printable version
In This Issue:
HCV-Related Deaths and Cost-Effectiveness of Testing and Treatment
Alan Franciscus, Editor-in-Chief
What You Don't Know, You Can Sell
Tracy Swan, TAG
HCV Snapshots
Lucinda K. Porter, RN
IN MEMORIAM: Michael Carden
—Alan Franciscus, Editor-in-Chief
HealthWise: May is Hepatitis Awareness Month
Lucinda K. Porter, RN
Boceprevir and Telaprevir Improve Cure Rates for HIV/HCV Coinfected People
Liz Highleyman
HCV Advocate Eblast
Stay informed on the latest news ..click here to register for email alerts
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HCV-Related Deaths and Cost-Effectiveness of Testing and Treatment
—Alan Franciscus, Editor-in-Chief
Three research papers were recently published in the Annals of Internal Medicine that summarize key findings of studies about hepatitis C: The cost-effectiveness of baby boomer testing and HCV treatment, and the number of HBV, HCV and HIV deaths between 1999 and 2007.
Article: The Increasing Burden of Mortality from Viral Hepatitis in the United States Between 1999 and 2007 – KN Lyn et al.
In this study the authors looked at the number of deaths caused by HBV, and HCV and compared them to the numbers of deaths caused by HIV. The authors reviewed the U.S. multiple-cause mortality data between 1999 and 2007 (total ~22 million deaths) from the National Center for Health Science that included all U.S. states and the District of Columbia. The causes of the deaths reported were listed as either a single underlying cause or the contributing cause. HBV accounted for 1815 deaths, and HCV accounted for 15,106 deaths compared to the 12,734 deaths that were attributed to HIV. The authors also observed that viral hepatitis deaths were probably under reported compared to deaths from HIV. They also noted that when the cause of death was listed as HCV or HBV it was frequently in people coinfected with HIV, HBV, and/or HCV. Approximately 75% of the deaths related to HCV occurred in a relatively young age group (46 to 64 year olds) and the authors concluded that this "portends a large and ever-increasing health care burden from what the current U.S. Assistant Secretary of Health has dubbed the 'silent epidemic.'"
Comments: Annual deaths from HCV are climbing and have outnumbered deaths from HIV or HBV although many of the people who died were also coinfected. This report will hopefully drive more dollars into identifying those with hepatitis C so that they may seek medical care, which will lower the costs that future HCV-related illness will cause.
Article: The Cost-effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings – DB Rein, et al.
The majority of people who are infected with hepatitis C—more commonly referred to as the "baby boomer" population—were born between 1945 and 1965. In the above study, the cost-effectiveness of the entire spectrum of testing, medical management and antiviral therapy was measured using quality adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) to estimate future costs and potential savings. Using these models it was estimated that an additional 808,580 people with HCV could be identified. The screening cost per patient identified would be $2,874. If the patients were to receive medical care and treatment with PEG/RBV, the screening QALYS would be increased by 348,000 and costs for treatment (estimated at $5.5 billion) would result in an ICER of $15,700 per QALY. If the patients identified were treated with direct acting antivirals (boceprevir or telaprevir PEG/RBV triple therapy) then the QALY would increase by 532,200 and the increased costs of $19.0 billion for the DAA treatment would result in an ICER of $35,700 per QALY saved.
Comments: We already have a risk-factor basis for testing of hepatitis C. While risk factor assessment should always be an important part of screening for hepatitis C, it hasn't worked to identify the vast majority of people who have HCV. Implementation of birth-cohort screening as an additional screening tool would increase the number of people who could be identified and it would include the two largest at-risk groups who are infected with hepatitis C—newly infected and those who acquired HCV in the past. The current study found that there would be a significant cost-savings for a one-time test of the baby boomers (1945-1965) in terms of dollars, productivity and human lives.
Title: New Protease Inhibitors for the Treatment of Chronic Hepatitis C – S Liu, et al.
This study looked the cost effectiveness of boceprevir/telaprevir protease inhibitor (PI) triple therapy and the IL28B testing that is used to predict treatment response. The first part of the study tackled the question of whether PI therapy is cost-effective in preventing HCV-related liver cancer and increasing life expectancy. The authors used the information from the Phase 3 studies of boceprevir and telaprevir to estimate effectiveness, but adjusted the cost-effectiveness for various factors (race, degree of fibrosis, etc.) and compared the outcomes to treatment with PEG/RBV therapy. It was found that PI therapy reduced the lifetime risk of liver cancer by 38% for patients with mild fibrosis, and 28% for patients with advanced fibrosis. PI therapy increased quality-adjusted life expectancy by 3% for those with mild fibrosis and 8% for those with advanced fibrosis.
The authors also looked at the cost-effectiveness of IL28B gene testing to predict treatment response and found it was also cost effective, but to a lesser degree.
Comments: This is an important study and finding since the new PI therapy is more expensive and has more side effects than PEG/RBV therapy. The take away message on this study is that treatment with PI triple therapy will reduce future cases of liver cancer and death and in most cases it is cost-effective.
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What You Don't Know, You Can Sell
—Tracy Swan, TAG
Merck's Cavalier Attitude towards the Welfare of HIV/HCV Coinfected Patients
In places where access to antiretroviral therapy is widespread, people living with HIV are now dying from a common and curable coinfection: hepatitis C virus (HCV). HIV increases the risk for, and accelerates the rate of, liver disease from hepatitis C. Pegylated interferon and ribavirin, medications used to treat HCV, are less effective in people with HIV than in their HCV-monoinfected counterparts.
In 2011, the first hepatitis C protease inhibitors, Merck's boceprevir and Vertex's telaprevir, were approved based on trials in people with hepatitis C monoinfection. Both drugs are being studied in coinfected people, thanks to pressure from the international HIV/HCV community and encouragement from regulatory agencies. (See www.clinicaltrials.gov for more information on HCV treatment trials for HIV/HCV-coinfected people.)
Despite outrage from activists, Merck refused to study drug-drug interactions (DDIs) between boceprevir (Victrelis), their HCV protease inhibitor, and drugs commonly used to treat HIV, putting coinfected study volunteers at risk for drug-drug interactions in their own clinical trial.
Drug-drug interactions can have serious consequences for HIV/HCV-coinfected people, who risk forfeiting current and future treatment options for HIV and possibly HCV as well. DDIs can lower drug concentrations to an ineffective level, leading to drug resistance, or increase drug concentrations, worsening side effects and leading to treatment discontinuation; they can even be life-threatening, as was the case with ribavirin and didanosine (DDI; Videx).
The boceprevir coinfection study opened in mid-2009, before Merck had performed drug-drug interaction studies with HIV protease inhibitors in healthy volunteers, a common step in drug development. Nonetheless, coinfected study volunteers were allowed to use them; in fact, by default, HIV protease inhibitors— or Merck's own integrase inhibitor, raltegravir (Isentress)—were the only HIV treatment options for study volunteers, since non-nucleoside reverse transcriptase inhibitors were not allowed. Activists kept asking Merck to perform DDIs throughout boceprevir's development, but Merck's attitude remained cavalier; they did not launch key drug-drug interaction studies until two years later, months after boceprevir was approved.
The results of DDI studies with three ritonavir-boosted HIV protease inhibitors, atazanavir/r (Reyataz), darunavir/r (Prezista), and lopinavir/r (Kaletra) in healthy volunteers (rather than in the actual trial participants who were using boceprevir with HIV protease drugs for almost a year) were presented in March at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. The news was not good. Combining boceprevir with these HIV protease inhibitors lowered concentrations of each HIV protease inhibitor at both the highest and lowest (peak and trough) levels.
Boceprevir lowered the peak concentration of atazanavir/r by 25 percent, and the trough by 49 percent; darunavir/r peak decreased by 36 percent and trough by 59 percent; for lopinavir/r, coadministration with boceprevir dropped the peak concentration by 30 percent and trough by 43 percent. In turn, boceprevir levels dropped by 45 percent when co-administered with lopinavir/r and by 32 percent when administered with daruanvir/r; only atazanavir/r had no effect on the concentration of boceprevir.
Failure to characterize these drug-drug interactions put study participants—and coinfected patients—at an unacceptable level of risk, although the clinical implications—or the real-life impact on HIV and hepatitis C treatment outcomes—of these drug interactions are not clear. Nonetheless, the U.S. Food and Drug Administration warned that "drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together."
Regulators from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) went a step further, recommending that:
"[D]octors treating patients co-infected with hepatitis C and HIV should be aware of the findings of the drug interaction study. They should not co-administer Victrelis with ritonavir-boosted darunavir or lopinavir in HIV and hepatitis C co-infected patients. Co-administration of Victrelis with ritonavir-boosted atazanavir may be considered on a case-by-case basis if deemed necessary in patients with suppressed HIV viral loads and with an HIV strain without any suspected resistance to the HIV regimen. Increased clinical and laboratory monitoring is warranted."
"[D]octors treating patients co-infected with hepatitis C and HIV should be aware of the findings of the drug interaction study. They should not co-administer Victrelis with ritonavir-boosted darunavir or lopinavir in HIV and hepatitis C co-infected patients. Co-administration of Victrelis with ritonavir-boosted atazanavir may be considered on a case-by-case basis if deemed necessary in patients with suppressed HIV viral loads and with an HIV strain without any suspected resistance to the HIV regimen. Increased clinical and laboratory monitoring is warranted."
Vertex's rival protease inhibitor, telaprevir (Incivek) has outsold boceprevir: in the fourth quarter of 2011, telaprevir trounced boceprevir $456.8 million to $87 million. The opportunity to capture the coinfection market share may have motivated Merck's decision to delay drug-drug interaction studies. HCV is more likely to be diagnosed and treated in HIV-positive people than people with HCV alone, for several reasons. HIV treatment guidelines recommend HCV testing for all HIV-positive people; the infrastructure to deliver treatment is already in place; and hepatitis C is known to be more aggressive in people with HIV, so physicians and patients are more game to try for a cure.
After Vertex reported drug interactions between telaprevir and ritonavir boosted HIV protease inhibitors, boceprevir became a more attractive option for co-infected people. Merck's vice president of clinical research, Robin Issacs, alluded to off-label use in the company's February 8 press release. "Though VICTRELIS is not indicated for the treatment of chronic HCV in those who are also infected with HIV, we recognize that some physicians have prescribed or may be considering prescribing VICTRELIS for patients taking ritonavir-boosted HIV protease inhibitors. We felt it was important to share these data as part of our commitment to patient safety and transparency."
Where was Merck's commitment to safety during boceprevir's development? We can only hope that no patients have been harmed.
The boceprevir experience underscores the importance of timely DDI studies. There are other medications used by people with hepatitis C—whether or not they are coinfected with HIV—that warrant study, such as methadone, buprenorphine, and commonly prescribed psychiatric medications. Merck representatives have stated that the company will be more proactive with their promising second-generation hepatitis C protease inhibitor, MK-5172.
Activists have released a statement calling on regulatory agencies and pharmaceutical companies to study DDIs between experimental HCV drugs that are broken down by the body in a similar way with hormonal contraceptives, methadone, buprenorphine, lipid lowering agents, immunosuppressive drugs, herbal remedies, and commonly prescribed psychiatric medications in addition to HIV medications.
Reprinted with permission from tagline Spring 2012
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HCV Snapshots
—Lucinda K. Porter, RN
Article: Risk of Myocardial Infarction Associated with Chronic Hepatitis C Virus Infection: A Population-Based Cohort Study – Forde K A, Haynes K, Troxel A B, et al.
Source: Journal of Viral Hepatitis April 2012; Volume 19, Issue 4, pages 271–277
Chronic hepatitis C virus (HCV) infection is an inflammatory disease, leading scientists to wonder if those with HCV are at increased risk of heart attack, or acute myocardial infarction (MI). This retrospective study conducted in the United Kingdom analyzed data collected from 4809 subjects with HCV and 71,668 without HCV, from 1996 through 2008.
The Bottom Line: HCV was not associated with an increased risk of incident MI.
Editorial Comment: It is great to read some good news about HCV. However, heart disease is a huge problem in the U.S., so although there is no apparent increased risk for an MI, HCV patients still have the same risk as the general population. Remember, what is good for the heart is good for the liver, EXCEPT for red wine.
Article: Increasing Rates of Hepatitis C Past or Present Infection Reports Among Adolescents and Young Adults in Pennsylvania – Boktor S W, Waller K O, Ostroff SM
Source: International Conference on Emerging Infectious Diseases' Program and Abstracts Book, March 2012
Note: This HCV Snapshot comes from a conference abstract. Abstracts represent part of the story and unless and until these studies are published in a peer-reviewed journal, these data and conclusions are considered preliminary.
This study conducted in Pennsylvania examined chronic HCV case reports from 2003-2010. In seven years, the number of new cases of chronic HCV for people ages 15-34 years nearly doubled (1,384 in 2003 to 2,393 in 2010). However, overall rates for all age groups combined declined in the same period. Rural areas appear to have the greatest increases of chronic HCV among the 15-34 y/o population.
The Bottom Line: The number of reported cases of adolescents and young adults in Pennsylvania with chronic HCV has doubled, especially in rural areas.
Editorial Comment: This report begs for more research along with a comprehensive intervention strategy.
Article: Combination PEG-IFN a-2b/Ribavirin Therapy Following Treatment of Hepatitis C Virus-Associated Hepatocellular Carcinoma is Capable of Improving Hepatic Functional Reserve and Survival – Ishikawa T, Higuchi K, Kubota T, et al.
Source: Hepatogastroenterology March- April 2012; Pages 529-32
Liver cancer or hepatocellular carcinoma (HCC) in patients with HCV recurs frequently despite HCC treatment. In this study, investigators studied 54 subjects with HCV-associated Stage 1-2 HCC. One group of 29 subjects received combination peginterferon (PEG-IFN) and ribavirin following HCC treatment; the other 25 received nothing further after HCC treatment.
The Bottom Line: After three years, the PEG-IFN group had significantly better survival rates and liver function tests than the non-PEG-IFN group.
Editorial Comment: With liver cancer rates increasing, it is vital that we develop effective ways to treat patients with HCC. This research represents a potentially new approach to managing HCC by using combination peginterferon (PEG-IFN) and ribavirin off-label.
Article: AIDS Info: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
Source: U.S. Department of Health and Human Services http://aidsinfo.nih.gov/guidelines (Last updated: 3/28/2012; last reviewed:3/28/2012)
Note: This HCV Snapshot is based on the latest HIV/HCV co-infection treatment guidelines, rather than a summary of original research. The decision to include this was based upon its importance.
These guidelines take into consideration the newly approved HCV protease inhibitors (PIs) boceprevir and telaprevir and recommend the latest treatment guidelines for HIV/HCV co-infected patients. These recommendations include:
The Bottom Line: HCV treatment has increased challenges for patients with HIV/HCV co-infection when using peginterferon and ribavirin with or without telaprevir or boceprevir. These challenges include increased pill burden, toxicities, and potential drug interactions.
Editorial Comment: The information in this Snapshot is very simplistic. More details may be found on the provided link.
Article: Liver-Induced Inflammation Hurts the Brain – Garcia-Martinez R, Cordoba J
Source: Journal of Hepatology March 2012; Volume 56, Issue 3, Pages 515-517
Note: This HCV Snapshot summarizes an editorial rather than original research. The editorial underscores important concepts in HCV research.
Scientists are gathering more information on HCV's affect on the central nervous system (CNS), and the authors of this editorial review some of the pathways of this. A thumbnail sketch of this process is that HCV infection stimulates an immune response, first locally (in the liver) and then systemically (the entire body). This may lead to inflammation in the CNS.
The Bottom Line: Persistent CNS inflammation may have harmful effects on the brain. The authors recommend evaluation of therapies that may reduce or eliminate inflammation, peripherally, systemically, and/or neurologically.
Editorial Comment: It may be frightening to read about HCV's potential to harm the brain, an organ that is not as resilient as the liver. However, reading about the potential damage HCV may cause does not mean that we are helpless against it. And although there is no specific research to this claim, common sense suggests that good nutrition, daily exercise, stress reduction, adequate sleep, humor and a positive attitude may offset some of HCV's inflammatory reaction. What is good for the liver is also good for the brain.
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IN MEMORIAM: Michael Carden
—Alan Franciscus, Editor-in-Chief
It is with deep sadness that I announce that my friend and colleague, Michael Carden, died suddenly on Monday April 09, 2012. Michael was an incredible person—loved by family, friends, and colleagues.
I met Michael a couple of years ago at a conference. We shared a lot in common and soon became fast friends. Michael was real. He dedicated his life to helping underserved populations. The focus of his work was with injection drug users and he treated everyone with compassion and respect. His work in advocacy inspired me and many others through his many leadership roles in which he spoke for the populations he represented.
Michael always advocated for people first. He was one of the few who advocated for injection drug users and HCV on a local and national level. His work was admired, respected and made a difference. With the death of Michael we have lost a true champion for equal treatment for all people with hepatitis C. Personally, I have lost a kind, compassionate and loving friend. I miss you Michael.
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HEALTHWISE: May is Hepatitis Awareness Month
—Lucinda K. Porter, RN
As unscientific as this sounds, I don't know how else to say this—a lot of people have chronic hepatitis C virus infection (HCV). I wish I could say with certainty what that number is. The Centers for Disease Control and Prevention (CDC) estimate the number of people in the U.S. with chronic HCV at 3.2 million.1 Other research places the figure closer to 5 million or more.2,3 What these data have in common is that both represent a lot of people.
One thing that experts do agree on is this—the majority of those with HCV have yet to be diagnosed. Once again, they don't agree on the estimate, with the number of people who are unaware that they have HCV ranging from 50% to 75%. Regarding chronic viral hepatitis (hepatitis B and C), the U.S. Department of Health and Human Services states, "65%–75% of infected Americans remain unaware of their infection status and are not receiving care and treatment."4
No diagnosis means patients aren't aware that they risk infecting others. It may mean decreased quality of life. No diagnosis means no treatment. Diagnosis leads to choice, and choice leads to health. For instance, in the CDC's efforts to gather better data, they learned that the majority of those who are HCV antibody-positive admit to drinking an average of more than two drinks daily.
To which I would ask, if you had hepatitis C, wouldn't you want to know? Even if you didn't have insurance or the financial means to treat HCV, wouldn't you want the opportunity to make lifestyle changes to try to arrest further damage the virus was doing? Wouldn't you want to know if only to protect family members and others from possible infection? Perhaps you wouldn't want to give up drinking, but wouldn't you want to know that if you did, your health might improve?
I know I would. I am fortunate because I knew I had hepatitis C pretty soon after I contracted it. This knowledge motivated me to choose a healthy lifestyle, one free of alcohol and other liver-unfriendly substances. As the saying goes, knowledge is power.
Hepatitis C has been making the headlines quite a bit this year with news that more people in the U.S. die from HCV than from HIV. HCV-related deaths are increasing, an outcome that isn't necessarily inevitable since generally, HCV can be managed and treated. The CDC is trying to avert this crisis, with programs such as the first National Hepatitis Testing Day on May 19, 2012.
I am thrilled about the CDC's efforts, and I want to help them. How? By talking about HCV—a lot—to anyone and everyone who will listen. What if we acted like Paul Revere, shouting to the world, "Hep C is here, hep C is here." Granted, if we ran through the streets on horseback, we might be locked up. Still, what Paul Revere did was warn people, giving them the chance to save themselves.
I talk about HCV so much, that I am becoming a bore. I talk about it at church, at my Jazzercise class, at Toastmasters and in my writers' group. It comes up on planes, parties, and during bridge games. Granted, the subject pops up easily since I work in this field. It's not as if I am playing cards, and casually slip in the words "hepatitis C" after a "no trump" bid. I know many people whose lives changed because they followed-up with their doctors after talking to hepatitis C advocates.
I am not proposing that everyone with HCV get on a soapbox or declare a manifesto. There are huge personal and professional risks with self-disclosure. In fact, before you tell anyone you have HCV, be sure to read the Hepatitis C Support Project's A Guide to HCV
Disclosure. There is a time and place to mention this virus, as well as ways to bring it up.
If you are considering revealing your HCV status, perhaps you'll be inspired by Hank Johnson's story. Johnson is a U.S. Congressman from Georgia. While serving in the House of Representatives, he announced he had HCV, went through treatment, launched his reelection campaign while on treatment, and won. I figure if he could be so brave and honest, just about anyone can.
Congressman Johnson was born in the years where there is the greatest prevalence of HCV—1945 through 1965. These Baby Boomers are becoming Senior Boomers, and some of them will be very sick. This generation, known for social activism and speaking out against injustice, will face yet another cause. This time, we will be fighting for our lives.
If you want to help, here are a few suggestions.
Check out the Helpful Links at www.hcvadvocate.org/library
Take care of your health. This is the top priority and the foundation that all activism rests on.
Be informed. Learn whatever you can about HCV. Look at reliable sources of information. For information and links to other good sources, check out www.hcvadvocate.org. Click on the "Advocacy" link for information on the latest issues, as well as sample letters you may use.
Come out of the closet. If you are comfortable with disclosure, tell others. You may be surprised to see how many people have or know of someone who has HCV. If you are the first person they have encountered with this, you may be the voice of hope.
Express your opinion to elected officials. Ask them to support and fund hepatitis C programs. To prepare for this, see the amazing link below to the Caring Ambassadors Program's Hepatitis C by the Numbers Advocacy Map. The map provides hepatitis B and C population information for congressional districts, along with links to information to contact elected officials.
Write a letter for the opinion pages of your local newspaper.
Record a public service announcement (PSA) for your local radio.
Add a PSA to the signature line of your email. Feel free to use mine, which says, "Hepatitis C causes more deaths in the U.S. than HIV does. The majority of people with hepatitis C do not know they have it; most were born from 1945 through 1965. Don't get scared—get tested."
Use social media to spread the word. Post information on Facebook and Twitter. Follow other hepatitis activists and retweet their posts. The CDC's Twitter handle is @cdchep
Get involved. There are many fine organizations devoted to education, advocacy, and other vital needs surrounding hepatitis C and other types of viral hepatitis. A few noteworthy organizations are listed under Additional Resources at the end of this article.
Finally, encourage people born between 1945-1965 to be tested for viral hepatitis. I do not see the point of waiting for the medical establishment to recommend universal testing. We screen for colon cancer, a test that involves massive preparation, sedation, time, and so on. We screen for breast cancer, a test that is also costly. A simple blood test for HCV is inexpensive and so much less trouble than bowel preparation and getting your breasts squashed.
Please join me and other activists who are working to increase the public's awareness about viral hepatitis. Together we can change the world.
Lucinda K. Porter, RN is the author of
Free from Hepatitis C
Additional Resources
Centers for Disease Control and Prevention
Know More Hepatitis Campaign
Hepatitis C Support Project
HCV Advocacy: Advocates and Activists Needed!
National Alliance of States and Territorial AIDS Directors (NASTAD)
Be sure to check out the Viral Hepatitis Advocacy Toolkit
National Viral Hepatitis Roundtable
Preparing for Hepatitis Day
Project Inform
U.S. Department of Health and Human Services
Combating the Silent Epidemic of Viral Hepatitis
World Hepatitis Alliance
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Boceprevir and Telaprevir Improve Cure Rates for HIV/HCV Coinfected People
—Liz Highleyman
Adding the HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivek) to pegylated interferon/ribavirin (PEG/RBV) significantly increases the likelihood of sustained response for HIV/HCV coinfected patients, according to findings presented at the recent 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.
An estimated one-third of people with HIV also have chronic hepatitis C. HIV/HCV coinfected individuals experience more rapid liver disease progression compared with HCV monoinfected people and they do not respond as well to interferon-based therapy.
Last year's approval of the first direct-acting antiviral agents for HCV ushered in a new era of treatment. Not only do they increase the chances of a cure for people with difficult-to-treat HCV genotype 1, they also allow many to receive shorter therapy.
HIV-positive people have eagerly awaited data showing whether this also holds true for the coinfected population. Boceprevir and telaprevir were approved only for people with HCV monoinfection. Clinicians can prescribe approved drugs to anyone, but most are hesitant to do so without safety data.
Interim results from clinical trials of boceprevir and telaprevir were reported in 2011, but the data presented at CROI are the first to show that the protease inhibitors improve cure rates for coinfected people. While these 12-week sustained virological response (SVR-12) data fall short of the "gold standard" 24-week SVR cut-off, the U.S. Food and Drug Administration now recognizes undetectable HCV RNA at 12 weeks after completion of treatment as a good indicator of a cure.
Mark Sulkowski from Johns Hopkins presented findings from a Phase 2 trial of boceprevir triple therapy in HIV/HCV coinfected patients (abstract 47). In this study 100 previously untreated participants with HCV genotype 1 were randomly assigned to receive 800 mg oral boceprevir three times daily or placebo, plus weekly pegylated interferon alfa-2b (PegIntron) and weight-adjusted ribavirin.
Everyone started with a four-week PEG/RBV lead-in, followed by triple therapy with boceprevir for 44 more weeks. While HIV-negative patients who achieve early HCV suppression can stop treatment sooner, prior studies suggest that people with HIV respond more slowly to interferon, and everyone in this trial was treated for 48 weeks.
All participants were taking antiretroviral therapy (ART). Based on prior pharmacokinetic datawhich later turned out to be inadequate, as discussed below,people were limited to regimens containing a ritonavir-boosted HIV protease inhibitor plus two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).
Most participants (about 70%) were men and the median age was 44 years; 65% had HCV genotype 1a. Most had high HCV RNA and about 5% had cirrhosis at baseline. The median CD4 T-cell count was nearly 600, indicating good immune function, and almost all had undetectable HIV viral load.
At 12 weeks after completion of treatment, 61% of participants in the boceprevir triple therapy arm achieved SVR compared with just 27% in the placebo arm (toward the lower end of sustained response rates in prior dual therapy coinfection studies).
Two people in the boceprevir arm and one in the placebo group experienced HCV relapse after completing treatment. Three patients taking boceprevir and four taking placebo experienced HIV viral load rebound. Absolute CD4 T-cell counts fell in both groups–a known side effect of interferon–but CD4 cell percentages remained stable.
People on boceprevir experienced more side effects
overall. Seven people (21%) taking boceprevir and 11 (17%) taking placebo had serious adverse events. However, the researchers concluded, the safety of boceprevir in coinfected patients is "consistent with that observed in [HCV] monoinfected patients."
Douglas Dieterich from Mount Sinai School of Medicine presented findings from a Phase 2 trial that tested telaprevir plus PEG/RBV in 60 previously untreated coinfected patients with HCV genotype 1 (abstract 46).
Part A included 13 coinfected participants with CD4 counts of at least 500 who were not yet on HIV treatment. Part B included 47 people on ART. Based on findings from drug-drug interaction studies, 24 patients took the NNRTI efavirenz (Sustiva) plus tenofovir (Viread) and emtricitabine (Emtriva), while 23 took the ritonavir-boosted HIV protease inhibitor atazanavir (Reyataz) plus NRTIs.
Here too, most participants were men, the average age was about 45 years, and about two-thirds had genotype 1a. Most had high baseline HCV viral load and about 10% had advanced liver fibrosis or cirrhosis. Median CD4 cell counts were high and patients on ART had suppressed HIV viral load.
Participants were randomly assigned to receive oral telaprevir or placebo plus weekly pegylated interferon alfa-2a (Pegasys) and ribavirin. People taking atazanavir received the standard 750 mg three-times-daily telaprevir dose, while those taking efavirenz increased their dose to 1125 mg to compensate for a known drug-drug interaction. Triple therapy lasted 12 weeks, followed by PEG/RBV alone through week 48. Again, all participants were assigned to the full course regardless of early response.
Overall, 74% of coinfected patients taking telaprevir triple therapy achieved SVR-12, compared with 45% of those taking PEG/RBV alone (near the high end of rates seen in dual therapy coinfection studies).
Among participants in Part A not taking ART, SVR-12 rates were 71% with telaprevir and 33% with PEG/RBV alone. By ART regimen, 69% of those using efavirenz and 80% of those using boosted atazanavir achieved SVR-12 with telaprevir, compared with 50% of those taking placebo.
Three people taking telaprevir experienced HCV RNA breakthrough while on treatment, and one telaprevir recipient and two placebo recipients experienced HCV relapse after completing therapy. No one showed evidence of HIV rebound. Again, absolute CD4 cell counts fell across the board but percentages remained stable.
As with boceprevir, telaprevir triple therapy recipients experienced more side effects. Three people on telaprevir, but none in the placebo group, discontinued due to adverse events; however, no one experienced severe rash, and anemia was equally common at 18%.
Drug-Drug Interactions
One factor that has hampered development of new HCV therapies for the coinfected population is concern about drug-drug interactions. Because of the way they are processed by enzymes in the liver, some drugs can raise or lower concentrations of other agents. This can lead to elevated drug levels that worsen side effects or reduced drug levels that allow viral breakthrough.
Interactions should be evaluated in laboratory studies and healthy uninfected volunteers before new drugs are tested in HIV/HCV coinfected patients. But despite demands of advocates and encouragement from regulatory agencies, this does not always happen.
The risks of inadequate interaction studies recently came to light regarding boceprevir. While telaprevir was tested with HIV antiretrovirals in humans prior to coinfection trials, decisions about which HIV drugs to use in the boceprevir coinfection trial were based on educated guesses from laboratory data.
Studies in uninfected volunteers later revealed that coadministration of boceprevir with three widely used ritonavir-boosted HIV protease inhibitors–atazanavir, darunavir (Prezista), and lopinavir/ritonavir (Kaletra) reduced concentrations of the HIV drugs by up to 59%. Conversely, coadministration with lopinavir/ritonavir or darunavir/ritonavir decreased boceprevir total concentrations by 32% to 45%.
Before these findings were reported at CROI (abstract 771LB), Merck issued a "Dear Health Care Professional letter" in February describing the data and stating that the company "does not recommend" coadministration of boceprevir with ritonavir-boosted HIV protease inhibitors.
However, as Sulkowski reported, boceprevir triple therapy appeared safe and effective for coinfected people taking boosted HIV protease inhibitors in the Phase 2 trial. A small number of participants experienced HIV viral breakthrough, but this was actually less common in the boceprevir arm (three of 64 patients) than in the placebo arm (four of 34 patients).
Researchers also presented data at CROI from drug-drug interaction studies looking at novel HCV agents in the development pipeline.
Researchers from Janssen tested interactions between antiretrovirals and the next-generation HCV protease inhibitor TMC435 (abstract 49). In studies of 48 healthy volunteers, 150 mg once-daily TMC435 did not significantly affect levels of rilpivirine (Edurant), raltegravir (Isentress), tenofovir, or efavirenz. TMC435 levels did not change when combined with the first three drugs, but coadministration with efavirenz reduced total TMC435 concentration by about 70%.
The integrase inhibitor raltegravir–among the most well-tolerated and least prone to interactions of HIV drugs–has also shown minimal interference with either boceprevir or telaprevir.
Bristol-Myers Squibb researchers reported on interactions with the promising experimental HCV NS5A inhibitor daclatasvir (formerly BMS-790052) (abstract 618). In studies of 49 healthy volunteers, 60 mg once-daily daclatasvir did not significantly change concentrations of atazanavir/ritonavir or efavirenz, and both daclatasvir and tenofovir remained within expected ranges when used together. Daclatasvir levels rose modestly with atazanavir/ritonavir but declined with efavirenz; the researchers calculated that daclatasvir dose adjustments should compensate for these interactions.
Changing Guidelines
Taken together, these findings indicate that HIV/HCV coinfected people can nearly double their likelihood of sustained response to hepatitis C treatment by adding boceprevir or telaprevir to PEG/RBV. In fact, sustained response rates approach those for HIV-negative people, showing that HCV direct-acting antivirals can help overcome factors that predict poor interferon response.
Reassuringly, HIV/HCV coinfected patients did not experience worse side effects with boceprevir or telaprevir than people with hepatitis C alone, alleviating one of the key concerns about treating this population.
"I don't think we expected results for either drug to be so good," Dieterich said at CROI. Cure rates were "shockingly comparable" in HIV/HCV coinfected and hepatitis C monoinfected people and adverse event rates were "virtually the same."
Drug-drug interactions with telaprevir and especially boceprevir remain an important issue, and conflicting findings make it difficult to establish firm guidelines.
As described in the March 2012 HCV Advocate, a group of HIV and HCV experts developed guidance on hepatitis C treatment of coinfected patients for the state of Maryland, published in the December 14, 2011, advance online edition of Clinical Infectious Diseases. But after the boceprevir interaction findings were revealed, the guidance was withdrawn before going to press.
The latest update to the U.S. Department of Health and Human Services adult antiretroviral treatment guidelines, published March 27, for the first time includes recommendations for using HCV protease inhibitors in HIV-positive people. (See "HCV Snapshots" in this issue.) For coinfected patients not on ART or taking raltegravir, the panel recommends either boceprevir or telaprevir. Due to uncertainty about boceprevir interactions, the panel advises people on ART to use telaprevir with either atazanavir or efavirenz.
However, Dieterich suggested in a post-CROI interview that "it's perfectly appropriate to use either boceprevir or telaprevir" for coinfected people on ART, "as long as you're cognizant of drug-drug interactions" and frequently monitor both HIV and HCV viral load.
Fortunately, new HCV agents in the pipeline will be better tolerated, more convenient, and less likely to interact with medications for HIV or other conditions common among people with chronic hepatitis C. But if coinfected people need treatment due to progressive liver disease, they should not wait. Most experts don't expect interferon-free oral regimens to be approved for at least three years, with another couple of years added for a coinfection indication.
While there's a lot of promise in the pipeline, we're already entering an era of effective therapies, according to Kenneth Sherman from the University of Cincinnati. "They are not always easy to take, but they are very effective...We don't want patients to give up that opportunity in the hopes that a great thing will come along."
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Director Emil Kahr teamed up with DP Yusuke Sato to create this dark yet beautiful universe.
Director: Emil Kahr
Producer: Thomas Guindon
DP: Yusuke Sato
Sound: Mark Sayfritz
Editor: Brenden Mendez
Art Director: Jon Goldtsche
Dancer: Emilie Livingston
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Segunda Edición, 30 de enero
News 12 New Jersey En Español, las noticias más locales de Nueva Jersey.
Newsday.com now uses Facebook for our comment boards. Please read our guidelines and connect your Facebook account to comment.
Two swimmers rescued from rip currents in Long Beach Northport PlayStation event lets public play unreleased games Hot Halloween tradition continues in Lido Beach 'It's crazy that I survived' Suspect scratches 30 vehicles on Massapequa street One camper's beginning and another's end Splish Splash thrills visitors on Long Island Turtles released back into the wild in Hampton Bays Osprey untangled from fishing line Lemurs can paint! Car lurches into service garage, knocks another car off lift Famous Montauk eatery sold


text:
You really need to learn to read, I am not opposed to it. I have no argument against it.<quoted text>
So now your argument is shifting to the "Frankie's heroes in Utah" straw man?
They are not my heroes. I'm not going to bite.
They deserve the same civil rights as you do. Even the .005% of them that are criminals. Which is by the way the about same percentage for you, a heterosexual male.
Do you ban marriage because some men abuse their wives? Do you ban marriage because some men marry underage girls?
But I find it hilarious that you are invoking Utah as the people that are championing marriage equality, the same people that are the primary funding for Prop 8
Sort of a contradiction isnt it?


text:
AR-15 Combo Wrench
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AR-15 Combo Wrench is rated out of 5 by 249.Rated 5 out of 5 by GarandMan from Great wrench A real honest to goodness rugged wrench. Made of heavy powder coated steel.Date published: 2015-04-02Rated 5 out of 5 by NHcoyotehunter from Excellent quality, great price! Excellent quality, great price! What else can I say - it works!Date published: 2015-03-16Rated 5 out of 5 by Redd from AR-15 Combo Wrench Works for everything I,m going to need on my AR. Price $$ was just great. strength is very good for any job on AR-15's.. RedDate published: 2014-12-02Rated 5 out of 5 by Sheriffdude from Really good tool Excellent wrench, well made not cheap metal like others. Will be a good addition to my AR tool kit.Date published: 2014-11-28Rated 5 out of 5 by ARTHUR from Nice heavy duty wrench.Date published: 2014-08-06Rated 5 out of 5 by EUGENE from Good construction and fits nicely in my hand. Several function possibilities in one tool!!!!!!!!!Date published: 2014-05-19Rated 5 out of 5 by LARRY from Good quality. Good value.Date published: 2014-05-19Rated 5 out of 5 by JOHN from This a perfect tool for my AR build.Date published: 2014-05-17

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Date published: 2015-01-20

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Date published: 2015-01-16

2015-07-31T13:20CST

bvseo_cps, prod_bvqa, vn_cps_3.1.5

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