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Full profile →'">
The author is a Forbes contributor. The opinions expressed are those of the writer.
two-drug combo pill against hepatitis C is so effective, Wall Street analysts say, that it's possible that public health officials could begin thinking about eradicating the liver-damaging virus, which may afflict 3.2 million Americans and is spread mostly through sharing needles and needle stick injuries, according to the Centers for Disease Control & Prevention. In some of them, like the musician Lou Reed, it leads to liver failure and death. Gilead's pill could become one of the best-selling medicines in history.
But Gilead's super-effective drugs have already drawing controversy, because of their expense and because some doctors and patients think that the company had sharp elbows that have prevented another effective combination from reaching the market. (Click here to see the new data on Gilead's combo.)
Gilead, already the top maker of HIV drugs, received approval from the Food and Drug Administration for Sovaldi, one-half of the new combo pill, on Dec. 6 and priced it at $1,000 per pill, or $84,000 for a 12-week cost of therapy. Even by itself, Sovaldi gets rid of the virus in many patients who were failed by other treatments, and allows many of them to forego inteferon, an infused treatment that causes terrible flu-like symptoms. Surveys of fund managers conducted by International Strategy & Investment Group show they expect sales of Sovaldi to be $3 billion next year, which would make it the most successful drug launch ever. As a result of those expectations, Gilead currently sports a market capitalization of $112 billion, and these fund managers expect that within a year Gilead will be worth more than , quadruple its sales.
Already, though, that high price is leading to charges of profiteering. Médecins Sans Frontières has supported an effort to oppose the Indian patent on the drug, arguing that it should be produced as a generic so that it can be made available to parts of the world that could not afford its current high price.
But the high hopes for Gilead go beyond that single pill to a combination with a second drug, ledipasvir. Together, these two medicines cure 95% of patients with the genotype 1 version of hepatitis C (the virus is identified using its genetics), usually allowing patients to forego interferon but the other old mainstay, ribavirin, which causes anemia. Three-quarters of Americans with hepatitis C are infected with viruses classified as genotype 1. The combo might work in as little as 8 weeks, and Gilead will file for FDA approval early in 2014.
"[I]f 8 weeks of treatment with a single daily tablet containing two antivirals is sufficient to cure most patients with the disease, we expect discussions to turn toward HCV eradication, and not just disease control," wrote Geoffrey Porges an analyst at Sanford C. Bernstein, in a note to clients. "If indeed such discussions emerge, the market for these medicines could be much larger, and more sustainable, than our recently raised forecasts."
The eight-week cure rates look slightly worse than the 12 week ones, and may not get approved; for Gilead, a 12-week course may be better, meaning more revenue. But the company hasn't priced the new combo yet, and it could cost even more than Sovaldi alone. "[T]hink about today's data as data for an entirely new drug that has not yet been priced," ISI analyst Mark Schoenebaum wrote to his clients.
The big question for stock-watchers is how much room will be left for other drug companies. , the drug giant spun off from Abbott Labs last year, has its own all-oral hepatitis C combo, but it includes the anemia causing ribavirin and takes six different pills to Gilead's one. Roy Friedman, a director of a private foundation who posts under the name DewDiligence on Twitter, argues that AbbVie and its partner Enanta could still wind up with a 38% share of the hepatitis C market.
Hepatitis C patients will be thrilled to get this new treatment. But some will also be angry. Gilead acquired Sovaldi when it bought a tiny drug developer called Pharmasset for $11 billion in 2011. The deal, which has caused Gilead shares to quadruple in three years, looks like one of the smartest in biotech. But in order to make the economics make sense, Gilead dropped a combination between Pharmassett and Bristol-Myers Squibb and replaced Bristol's drug with its own. That's the data that were just released.
Some patients were enraged by the fact that Gilead mothballed an effective drug combination.A San Antonio woman named Margaret Dudley even started an online petition accusing the company of profiteering. "[T]his cure is literally being withheld from millions by pharmaceutical giant Gilead Sciences because they are more concerned about profits than human lives," she wrote.
For patients with the genotype 1 version of hepatitis C, Gilead's new combo looks to work every bit as well as the old one. But for those with another variant, called genotype 3, the data are less promising. Given the flood of profits expected from this combination, Gilead should look very hard about getting genotype 3 studies started with Bristol – and fast. Drug companies tend to do better in the long run when they can argue they have the ethical high ground, and Gilead lost some of that credibility with the deal that literally bought the company's future.


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Danny Graham began to repay his £3.5m transfer fee by scoring his first Premier League goal for Swansea City to seal a morale-boosting victory over Stoke City as footballing beauty beat the "Beast" yesterday.
The Swans' record signing from Watford in the summer had not found the back of the net in five attempts for the Welsh club in the top flight. But, after Scott Sinclair's ninth-minute penalty, Graham ended his long wait in the 85th minute after dispossessing former Middlesbrough team-mate Jonathan Woodgate before coolly beating Stoke goalkeeper Asmir Begovic to open his Swansea account.
The Swansea manager, Brendan Rodgers, said: "Danny has been outstanding since he arrived at the club, but when you have his quality then it was only a matter of time.
"It was a wonderful finish. He was under pressure one versus one and lots of strikers would lash at it and miss the chance. He showed great composure and technique in his finish. It's great for him to get off the mark because he knows strikers are judged on goals."
Rodgers believes his side can claim 10 home victories this season and Swansea were on their way to triumph No 2 after Sinclair's opener. A precise through-ball from the outstanding Joe Allen did not appear to threaten the Stoke backline until Ryan Shawcross clumsily upended Wayne Routledge, leaving referee Michael Jones with little option but to signal towards the spot.
The award of the spot-kick was, bizarrely, in almost identical fashion to the one Swansea gladly received against West Bromwich Albion two weeks previously. Rodgers' men had the same end result as Sinclair coolly stepped up on a humid afternoon to send Begovic the wrong way.
Stoke, fresh from their Europa League victory over Turkish side Besiktas on Thursday night, began slowly, but gradually imposed their renowned physicality on to this hard-fought battle and could have drawn level on 21 minutes.
Jonathan Walters outmuscled Mark Gower and the Republic of Ireland striker saw his excellent 25-yard effort tipped on to the crossbar by the Swansea keeper Michel Vorm.
Stoke should have gone down to 10 men following a reckless tackle from Andy Wilkinson on pint-sized winger Nathan Dyer, but Jones cautioned the Potters full-back as well as Peter Crouch for a late challenge on Gower.
Glenn Whelan hit the post with a second-half free-kick for Stoke then Sinclair forced Begovic into a superb flying save before Graham sealed the win.
Tony Pulis, the Stoke manager, said: "Ryan's challenge was poor and it gave Swansea the start everyone in the Premier League wants. It lifted them.
"We hit the post and woodwork and, from that point until the second goal, I thought we were the team who would get the equaliser," he added.
Substitutes: Swansea Moore 6 (Routledge, 66), Lita (Graham, 90). Stoke Huth 5 (Wilson, 33), Jerome 5 (Delap, 54), Shotton (Pennant, 80). Booked: Swansea Taylor, Routledge, Gower. Stoke Wilkinson, Whelan, Pennant, Shotton, Crouch.
Man of the match Allen. Match rating 6/10.
Possession: Swansea 55% Stoke 45%.
Attempts on target: Swansea 5 Stoke 6.
Referee M Jones (Cheshire).
Attendance 19,523.Reuse content

subset: commoncrawl


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Articles tagged dave matthews band
18 Jul 2016 // 1:00 AM
The third part of our examination of the 100 Greatest Alternative Singles of the '90s, including Sonic Youth, Primal Scream, Garbage, Pixies and more.READ more
11 Sep 2013 // 6:30 AM
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31 Oct 2012 // 10:20 PM
One of today's biggest musical trends owes a debt to one of music's oldest traditions – buddies gathered on a front porch jamming with guitars, banjos, and mandolins. Some of today's most popular groups sound like they belong in the Appalachian Mountains in the 1920s, not on alternative radio of the 2010s.READ more
8 Sep 2010 // 9:00 PM
Aside from the mountains, headliners Jimmy Cliff, Dave Matthews Band and Jack Johnson gave festival goers a truly memorable experience.READ more
24 Jul 2009 // 9:00 AM
Last August, just before the Democratic National Convention in Denver, Dave Matthews opened a rally for then-Sen. Barack Obama at Red Rocks Amphitheatre. The packedREAD more
21 Jul 2009 // 3:47 AM
What's the difference for the Dave Matthews Band between playing indoors and outdoors? "If you have an open-air place or just sort of aREAD more
11 Sep 2008 // 10:00 PM
DMB and Michaelson rock NYC, raising funds for Stand Up for a Cure, a cancer research group, as well as 9/11 first responders.READ more
26 Aug 2008 // 9:59 PM
Even though I shed my DMB obsession years ago, I can't help but feel this is the end of an era. With Moore's passing, the band has lost its saxophone pillar, an irreplaceable voice, and they will never be the same.READ more
25 Aug 2008 // 3:34 AM
Even if it had been a merely half-hearted performance—which it wasn't, not even close, though who'd have blamed 'em if it were?—READ more
9 Jun 2008 // 10:00 PM
Guitarist Tim Reynolds has recently joined Dave Matthews Band on the road and in the studio for the first time since 1998. Last week, Reynolds spoke with PopMatters' Robert Costa in an exclusive backstage interview to talk about DMB and his own band TR3.READ more
12 Dec 2006 // 8:00 PM
The perfect primer for the new fan, it also deserves to worm it's way into the collections of Dave's diehard fans.READ more
21 Jun 2004 // 10:00 PM
Occasionally I'll come across an album that instantly strikes an internal chord—one that speaks directly to me, often using smart, introspective lyrics. It'READ more
28 Oct 2002 // 10:00 PM
Seems the small Pennsylvania town of Hershey is not only famous for its chocolate. It's also got its fair share of Dave Matthews BandREAD more
19 Jun 2002 // 12:00 AM
Their high caliber of musicianship allows them to improvise live, something many bands neither have the ability nor the willingness to do.READ more
26 Feb 2001 // 2:00 PM
"Idid it / Do you think I've gone too far?" Dave Matthews asks on the chorus of "I Did It", the first single from theREAD more
Depeche Mode "Where's the Revolution" (Singles Going Steady) // Music
Beth Bombara "Sweet Time" (audio) (premiere) // Music
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'Fire Emblem Heroes' Is a Bad Crossover
// Moving Pixels
"Fire Emblem Heroes desperately and shamelessly wants to monetize our love for these characters, yet it has no idea why we came to love them in the first place.READ the article


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Why I'm Still in Minnesota
... dip, spiral-cut ham with mashed potatoes and bacon green beans, and my favorite: a homemade Bengali feast. Kichuri (rice & lentil dish), Bengali eggs, Kosha Murgir Mongsho (cinnamon-chile chicken curry), Bhuna Gorur Mongsho (cumin beef curry) might take several hours to prepare, but I feel like it's worth someone else cooking all day for the absolute, unqualified joy I feel when I eat this food. Shameless. Thank you, Normita and Jenn. Jerks.
The real UN assembly: Isanti-Cambridge-Mitchell
Move over Barrack and United Nations delegates. This is what diplomacy is all about: getting in there and sharing cultures and experiences.
Today has been a culture shock 101. Yes, Americans and Australians speak the same language (with a few discrepencies along the way - fyi soft drink is called pop here, Lara) and dress the same and act the same. But the real shock came when we got to really see what life is about here. School, family and culture; it's the ...
Minneapolis Day 2
... then the quick dash to gulp down a heap of water... Boy oh boy does ginger burn your throat!!! I enjoyed being in a whole foods store again- just love it in there! The air conditioning was a bonus as well! I bought a couple of boxes of my favorite protein and energy bars and then headed across the road to catch the bus over the Hennepin Bridge to walk back to my B&B! I got into my room and ate my carrot cupcake from whole foods... Oh it was so yummy! Shortly after I changed ...
Why was the engine dripping oil?
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Where did the time go?!
... to spread my wings. I am only 22- what else am I supposed to do other then travel the globe? A large number of people over the past few months have said to me, "Man, I wish I could do that". "That" meaning traveling to a completely foreign place on the other side of the world. My response, "You can." Then there is silence. I chose to travel while others choose ...


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Test screening - investors fill in feedback forms 3
Crew members filling in feedback forms straight after the dreadful test screening. Most of the feedback agreed that the futuristic drama element did not work. Having two teenagers in the future berating you about destroying the planet for 90 minutes does not make for an entertaining night at the movies. This was one of over forty test screenings to gather feedback.
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Mussel End Farm
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Set in the beautiful Gloucestershire Countryside, Mussel End Farm is a charming and delightful Bed and Breakfast run by Louise and Simon Middle with two spacious and comfortable rooms offering stunning views of the countryside. This traditional 17th Century farmhouse nestled in large well kept gardens sits on an award winning livestock and arable farm, which provides the produce for our truly home cooked breakfast. After a long day exploring Gloucestershire, where over half of the county is designated an Area of Outstanding Natural Beauty, or walking along the nearby magnificent River Severn; you can relax in our lovely gardens. You'll be assured of a warm welcome, peaceful surroundings and beautiful views whenever you visit.


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PRESQUE ISLE | With phase one of its $1.5 million renovation project now complete, officials with The Mark and Emily Turner Memorial Library announced on Monday that they will be kicking off phase two of their substantial makeover effort this spring. The final stretch of the renovation will outfit …
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Fundal Fibroid
Fibroid Uterus Tumors
Author: Dong Xiaolian
Do you know about your own body ? And how many do you know? Following me please, women friends. There are uterine fibriods whose growth are affected by the hormones and estrogen on our uterine walls. Most women suffer from them, but they are unware of that. Unfortunately, they are more common as thay age. Though they are benign tumors, they can trigger many discomfort.Stop Fibroid Method Click here
Pain and heavy menstruation is one of the apparent results. About 33% women are affected to blood loss as well as anemia. Freguent need to urinate is another symptom. Large fibriods which give a press on the bladder to reduce its capacity make you have a feeling to urinate more and more often. And with the utrine fibriods are bloating, they can make women looks pregnant. What a horrible thing for the women who want to be slim! If you have a fibroid near the cervix, you will suffer pain while having sex. Most severely, there are many difficulties for you to have children if you have the fibriods within the wall of the uterus. Certainly, there are many other discomfort such as bleeding in between periods, digestive complaints, pelvic pain and so on.
Of course, there are many corresponding ways to deal with the fibriods problem. If you want to none of your own children any more, you will choose the surgery to have a hysterectomy and the fibriods can't affect you for ever. Another surgery is to have a fibriod embolization and this kind of ways can also make you conceive difficultly. Well, you had better think about some natural cures. Most importantly, you should avoid taking birth control pills and choose a proper weight loss plan. Otherwise, there are many diet changes to help you to control the fibriods. Keep yourself from eating red meat , white bread, flour and so on. Keep yourself from agricultural fertilizers, pesticides, soft plastics and so on. If possible, you had better quit milk. And the organic or goat milk maybe the best choice for you. Besides above ways, a unique, 7 steps plan which are developed by an alternative practitioner is a useful tactic. It has been proved by many thousands of women worldwide and play an important role in the healing. Are you interested in having a try now? Stop Fibroid Secrets Click here
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8 Comments
April 29, 2011
How to get rid of uterine fibroid without surgery?
I want to kow if there is any natural method of getting rid of a fibroid. I have a very huge fundal fibroid outside my uterus, though it is not creating any discomfort, I am only 28 and this may cause complications in my pregnancy.
Can anyone suggest any natural methods for treating this
April 29, 2011
It is perfectly possible to learn how to get rid of uterine fibroids naturally but first and foremost you must understand that this is not a quick fix approach and will require a committed and systematic approach from yourself.
Your fibroids did not grow overnight and although common, not every woman will have fibroids. There are various causes of uterine fibroids and most of these are caused by lifestyle and dietary issues. Certain conditions need to exist for uterine fibroids to grow-there is never any single cause of this condition, but it happens due to the subtle interaction of various factors which cause an environment which triggers off growth.
By neutralising the conditions which caused fibroid growth in the first place, this will cause the fibroids to shrink naturally and once the conditions cease to exist, fibroids cannot grow any more. There is certainly a strong connection between the Western lifestyle fibroid growth. This does not just apply to our Western diet, but also factors such as stress, lack of exercise and poor sleep patterns all come into play.
To get rid of uterine fibroids naturally, you will need to use a tried and tested plan. Implementing ad-hoc treatments may help give symptomatic relief, but will not provide a proper solution.
The components of a successful plan will include:-
* A robust detox to help eliminate toxins
* Systems to rebalance hormone levels
* The correct diet for fibroid sufferers
* How to control stress levels
* The role of herbs
* The link between yeast and fibroids
Combining these elements makes for an extremely powerful method to rid you of your uterine fibroids.
April 29, 2011
what is the maximum size that a fundal fibroid can grow?
April 29, 2011
I am 12 wks pregnant and my dr. says I have a 9 cm fundal fibroid. Anyone had this and had a normal pregnancy?
The fundal fibroid apparently means that it's at the top of the uterus. So far, my dr says it is not pressing down on the uterus, so it's not affecting the baby, but I'm worried that it will get bigger as the pregnancy progresses, as it feeds off of estrogen and other pg hormones. Anyone had this and went on to have a successful pregnancy?? Thanks
Ann G
April 30, 2011
I have fibroids and two pregnancies. They found the fibroids when I was pregnant with my first.
Both my boys were born healthy (7.5 pounds) and I had normal pregnancies, labors and deliveries.
I now have a teenager and a pre-teen. I'd say I had successful pregnancies. Ask me in another ten years whether the parenting style ultimately worked out…
April 29, 2011
anyone tell me what a fundal fibroid is?
on medical report after having my hysterectomy
Nurse in Ohio
April 29, 2011
It is a tumor located at the top of the uterus.
April 30, 2011
uterine fibroid and treatment/conceiving?
I'm 27 years old and have just been diagnosed with fibroid; ultrasound report says enlarged uterus has a 3cm x 2cm and a 4cm x 2.4 post. Fibroid near fundus, a 2.4 x2.4 fundal fibroid and a 3cm x 3cm ant. Fibroid. The endometrum measures 1cm. The right ovary has a 3cm x 3cm simple appearing cyst.
I had an hysterscopy and endmetrial biopsy yesterday. I'm scheduled for laproscopy and a/d&c next. I'm wanting to conceive a baby but the dr seems doubtful of that happening 🙁 anyone who either has personal experience with this or is in the medical Field/I would really like some advice thank you!


text:
It's becoming very clear Lifetime's "Unauthorized Saved by the Bell Story" isn't a happy telling of the behind-the-scenes action of one of our favorite '90s Saturday morning classics.
A new clip from the TV movie shows Dustin Diamond (Sam Kindseth) as he arrives to the "Saved by the Bell" set for the first time and is shown around by Mark-Paul Gosselaar (Dylan Everett), who appears to have an overbearing stage mom. The boys are pretty impressed by the dressing rooms and star treatment. Someone who doesn't seem impressed, however, is castmate Lark Voorhies (Taylor Russell).
The film also stars Tiera Skobbye as Elizabeth Berkley, Alyssa Lynch as Tiffani Amber- Thiessen and Julian Works as Mario Lopez.
"The Unauthorized Saved by the Bell Story" premieres Monday, Sept. 1 at 9:00 p.m. ET/PT on Lifetime.


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2004 Volvo V70 Repair and Maintenance Costs
A guide to repairs, service, and maintenance costs for your 2004 Volvo V70
Never overpay. Check prices with our estimator
Verified by mechanics, reported by drivers like you
Ask a mechanic in our community
Our experts translate recalls into plain English
2004 Volvo V70 ProblemsAutomatic Transmission Shifts Very Hard and Erratic
There are several common complaints regarding Volvo V70 transmission shifting issues. Long shift times between gear shifts, hard shifting, hard downshifting and a loss of transmission operation to name a few.
If the issue is minor, a transmission software update may address this. If available, the software should be updated before any repairs are made. After a software update or repair, the shift adaptation needs to be reset. A good quality Volvo repair shop will know how to perform this task.
There are several technical service bulletins (TSB's) available from Volvo that address these shifting issues and they should be consulted by the repair shop during the automatic transmission diagnostic process.
Regular servicing of the transmission fluid can help with preventing transmission failure, but not in all cases. Follow the suggested fluid replacement interval recommended by Volvo. You will find this in your owners manual, or find it here>>
One or more door lock assembly may fail and cause door locking/unlocking problems.
The upper engine mount may wear prematurely. Symptoms may include a harsh feeling when the transmission is shifting and roughness when the engine is idling. Worn engine mounts should be replaced as necessary.
2004 Volvo V70 Questionswhat does it cost to replace timing belt (2 answers)
A shop scanned my car with a computer and it has twenty codes. How do I know what the codes mean ?
i get up too 60mphs on the highway and it jerks like there is not enough air getting to the engine or something. please tell me its not cat!!? car has 177,000 miles on.
2004 Volvo V70 RecallsVolvo Recalls Garmin 760 Portable GPS-Equipped Vehicles Due to Overheating Battery
Volvo is recalling all models equipped with Garmin 760 Portable Global Positioning System units because the battery may overheat, which could lead to a fire. Volvo advises owners to stop using the Garmin device immediately and consult the Garmin website to determine if they have a defective unit. The unit's battery will be replaced and a spacer inserted to prevent the problem from reoccurring. This will be performed free of charge.
When exposed to certain environmental conditions (hot climate and temperature cycling) over time and in combination with varying fuel quality, the fuel pump can develop cracks in the fuel pump flange. If cracks develop, a fuel smell and/or leak may be noted. Any fuel leak always increases the risk of a fire. Dealers will inspect and replace the fuel pump as necessary to correct this concern. The Volvo recall number is R220.
The fuel pressure sensor may at times transmit an incorrect signal to the engine control module. If the signal is outside of the pre-programmed allowable limits, the Check Engine Light can illuminate and a fault code will be stored. An engine misfire and/or engine stalling may occur. In certain traffic situations, this could cause an unsafe situation and possibly a crash. Dealers will replace the fuel pressure sensor to correct this concern. The Volvo recall number is R181.


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Volkswagen III for Sale
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1964 Volkswagen III Notchback S Model
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This car had recently been restored approximately 16 years ago. Less than 40,000 miles have been put on since the restoratin. Always parked in the... More
Offered By: Private Seller


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text: The Florida State Board of Education voted 4 to 3 Tuesday to reinstate a policy that prevents schools' letter grades from falling by more than one letter grade at a time. The change comes as the state prepares to implement a new evaluation system for schools. The move was praised by school leaders, who say the change will give them time to educate the community about the grading system.


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Phenylbutazone Usp Bp Ep Ip - Indiaprice: contact company for price
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With Instructables you can share what you make with the world, and tap into an ever-growing community of creative experts.
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Starvault's reponse to criticism related to having a handful of players as the official "test" team for a supposed MMO: "We've just have another 10ish folk kind enough to voulenteer added tot the test team" (SIC) This explains much about the state of the game :-)
My favourite hero is Rexxar.
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Garrosh Hellscream!
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I certainly hope Vol'Jin will be available one day as an avatar.


text:
Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice
- Li Bian1Email author,
- Elisabet Josefsson1,
- Ing-Marie Jonsson1,
- Margareta Verdrengh1,
- Claes Ohlsson2,
- Maria Bokarewa1,
- Andrej Tarkowski^ and
- Mattias Magnusson1
DOI: 10.1186/ar2799
© Bian et al.; licensee BioMed Central Ltd. 2009
Received: 28 April 2009
Accepted: 1 September 2009
Published: 1 September 2009
Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The pro-apoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis.
In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water.
Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P < 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell- or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group).
Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
The pyruvate dehydrogenase activator dichloroacetate (DCA) is a small molecule that has been used in humans for decades as a treatment for acquired and congenital forms of lactacidosis by shifting pyruvate metabolism from cytoplasmic lactate production to oxidative production of acetyl-CoA in the mitochondria [1]. Most recently, DCA was found to act as an efficient tumor growth inhibitor, both in vitro and in vivo, by shifting glucose metabolism from glycolysis to glucose oxidation in malignant cells. This shifting results in the release of pro-apoptotic mediators and decreases proliferation in malignant cells, thus eliminating active tumor cells while leaving the normal cells unaffected [1].
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation [2]. The prevalence of RA is 0.5% to 1% of the population worldwide. Females have a higher incidence (3:1) than males. Several lines of evidence show that the female hormone estrogen affects both the incidence and the progression of RA in humans [3, 4] and in animal models [5, 6]. RA is characterized by synovial cell proliferation and infiltration of inflammatory cells to the synovium. Cytokine production by these cells (for example, tumor necrosis factor-alpha [TNF-α] and interleukin [IL]-1, IL-6, and IL-17) plays a pivotal role in RA [7]. These cytokines, notably TNF [8] and IL-6 [9], may promote the development of osteoclasts [10], which increases bone erosion and systemic bone loss [11].
Because the cause of RA is complex and elusive, it continues to present therapeutic challenges, especially erosive arthritis. Murine collagen II (CII)-induced arthritis (CIA) is a widely used experimental model of RA and shares many histopathological features of the human counterpart [12]. It is usually used to investigate mechanisms relevant to RA as well as new anti-arthritic treatments [13]. As in the case of RA, CIA is primarily an autoimmune disease of the joints [14] with increased angiogenesis, inflammatory cell infiltration, synovial hyperplasia, and bone erosion. Because of the anti-proliferative and pro-apoptotic properties of DCA, we hypothesized that DCA may inhibit the development of arthritis in CIA. To this end, DCA was added to drinking water at the time of induction of CIA. Our results suggest that DCA significantly delays the onset and development of destructive arthritis in female DBA/1 mice. The protective effect of DCA was mediated in part via estrogen-dependent pathways.
Materials and methods
DBA/1 mice (Taconic Europe A/S, Ry, Denmark), 6 to 8 weeks old, were used for CIA experiments. For the delayed-type hypersensitivity (DTH) experiment, 6 to 8 week old mice were used. All of the mice were maintained in the animal facility of the Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden, in accordance with the local ethics board animal husbandry standards. Mice were housed up to 10 animals per cage under standard conditions of light and temperature and fed with standard laboratory chow ad libitum.
Collagen II-induced arthritis
Chicken CII (Sigma-Aldrich, St. Louis, MO, USA) was dissolved at a concentration of 2 mg/ml in 0.1 M acetic acid and then emulsified in an equal volume of complete Freund's adjuvant (Sigma-Aldrich). Arthritis was induced by intradermal injection of DBA/1 mice at the base of the tails with 100 μL of the emulsion. Booster immunization containing 100 μg of CII in incomplete Freund's adjuvant (Sigma-Aldrich) was administered 21 days after the priming. The experiments were terminated in 6 to 8 weeks.
Dichloroacetate treatment
Distribution of mice in dichloroacetate treatment of collagen II-induced arthritis
Number of mice
Arthritis indexa
First experiment
3/4 (0.75)
30/4 (7.5)
35/6 (5.8)
22/5 (4.4)
Second experiment
6/10 (0.6)
34/10 (3.4)
31/10 (3.1)
39/10 (3.9)
Third experiment
7/8 (0.9)
38/8 (4.75)
OVX experiment 1
16/10 (1.6)
3/10 (0.3)
OVX experiment 2
63/21 (3.0)
23/19 (1.2)
Clinical evaluation of arthritis
All of the DBA/1 mice were inspected every second or third day after booster to assess the presence of arthritis. To evaluate the intensity of arthritis, a clinical scoring system of 0 to 3 points for each paw was used: 0, no sign of inflammation; 1, mild swelling or erythema or both; 2, moderate swelling and erythema; and 3, marked swelling and erythema. The arthritic index for each mouse was constructed by summing up the scores of all four limbs.
Delayed-type hypersensitivity reaction
To assess the impact of DCA on a T cell- and macrophage-dependent inflammatory response [15, 16], the DTH reaction was performed. Thirty female mice were divided into three groups (10 mice per group). Two groups were provided DCA in drinking water (0.3 and 3 mg/mouse per day, respectively). The control group was provided water only. After 2 days, all of the mice were immunized by epicutaneous application of 150 μL of a mixture of ethanol acetone (2:1) containing 3% (vol/vol) oxazolone (OXA) (Sigma-Aldrich) on the abdomen skin. One week after the priming, the right ears were challenged on both sides by topical application of 30 μL of 1% OXA, which was dissolved in olive oil. Thirty microliters of olive oil only was applied to the left ears as vehicles. The intensity of DTH reaction was examined as previously described [17].
Olive oil-induced inflammation
Olive oil-induced skin inflammation is granulocyte-mediated but T cell- and monocyte-independent [18]. A single intradermal injection of olive oil into mouse footpad induces massive infiltration of polymorphonuclear cells, which give rise to a localized footpad swelling. The thickness of footpad can be measured and relates to severity of the inflammatory process [19]. Thirty microliters of olive oil (Apoteksbolaget, Göteborg, Sweden) was injected intradermally in a hind foot dorsum of mice. Footpads were measured before and 24 hours after injection using an Oditest spring caliper (Kröplin, Schluchtern, FRG). The footpad swelling was expressed as footpad increased thickness (in millimeters) after injection and was scored as described previously [20].
Analyses of hormone, antibody, and cytokine levels
The level of serum hormones was analyzed by the following radioimmunoassays: insulin-like growth factor (IGF1) (Mediagnost, Reutlingen, Germany), testosterone (MP Biomedicals, Irvine, CA, USA), and cortisol (CIS Bio International, Marcoule, France). Uteri were weighed as an indirect indicator of estradiol level [21]. Anti-CII antibody analyses were performed as previously described [22]. IL-6 levels in sera were analyzed as described before [23].
Histological examination
All four paws from DBA/1 mice were excised, followed by routine fixation, decalcification, and paraffin embedding. Tissue sections were stained with hematoxylin/eosin. The sections were studied by a blinded examiner regarding synovitis and erosion of bone/cartilage. Synovial hypertrophy was defined as a membrane thickness of more than two cell layers [23]. A histological scoring system was used: 1, mild; 2, moderate; and 3, severe synovitis or bone erosion [24]. Knee joints, ankles, toes, elbows, wrists, and hands were examined. A mean score from all of the inspected paws for each animal was calculated [25].
Impact of dichloroacetate on bone mineral density
The left femurs from DBA/1 mice were fixed in 4% (vol/vol) buffered formaldehyde for 3 days and then replaced by 70% (vol/vol) alcohol until analyses of bone mineral density (BMD) were performed. A peripheral quantitative computed tomography (pQCT) scan with a Stratec pQCT XCT Research M (Norland, Fort Atkinson, WI, USA) was used as previously described [26]. Trabecular BMD was analyzed with a metaphyseal scan at a point located at a distance of 3% of the length of the femur from the distal growth plate. The inner 45% of the area was defined as the trabecular bone compartment. Cortical bone parameters were determined with a middiaphyseal scan, which contained only cortical bone.
Statistical analysis
Statistical analyses were performed by using the Mann-Whitney U test and the chi-square test. Values are reported as median ± 10% to 90% range. A P value of less than 0.05 was considered significant.
Effect of dichloroacetate on development of collagen II-induced arthritis
Effect of dichloroacetate on inflammatory immune responses
Impact of dichloroacetate on in vivo cell-mediated inflammatory responses
DTH is a T cell-mediated immune reaction. To test the effect of DCA on DTH, DCA-treated mice and water controls were epicutaneously immunized and challenged with OXA. DTH reactivity was registered by measuring the increase in ear thickness 24 hours after the challenge. We did not find any significant differences in regard to the severity of DTH between DCA-treated mice and their controls (data not shown). Likewise, DCA had no effect on the granulocyte-dependent olive oil-induced inflammation (data not shown).
Dichloroacetate treatment ameliorates the cortical bone loss induced by arthritis
Impact of ovariectomy on dichloroacetate treatment of arthritis
Although OVX mice and sham-operated mice had different arthritis responses following DCA treatment, we did not find any difference between the OVX group and the sham group in regard to level of IL-6 (OVX: median 76 pg/mL, range 20 to 1,032 pg/mL versus sham: median 111.2 pg/mL, range 30 to 348.2 pg/mL) and anti-CII antibodies (optical density: OVX: median 0.91, range 0.37 to 1.32 versus sham: median 0.84, range 0.30 to 1.69). As an indirect indicator of estrogen levels, the weight of uteri from DCA- and water-treated intact female mice was recorded. No difference was found between the DCA group and their controls (DCA: median 50 mg, range 26 to 111 mg, n = 8 versus water: median 49 mg, range 15 to 104 mg, n = 8). We also measured the level of testosterone. There was no significant difference between the DCA group and the control group (Data not shown).
DCA delays the onset of CIA and at the same time alleviates the progress of CIA. Interestingly, this outcome is observed in female mice only. Female DBA/1 mice treated with DCA had a significant slower onset and less severe arthritis compared with water-treated controls. Importantly, the destructive action of inflammation on bone was almost totally inhibited in mice provided with DCA. The results of this study reveal for the first time that destructive arthritis can be inhibited by DCA administration. Our results also suggest that estrogen plays an important role in the beneficial effect of DCA.
DCA is a well-established drug used for the treatment of lactic acidosis. It also exhibits efficient anti-tumor properties due to its pro-apoptotic and anti-proliferative effects without visibly affecting non-cancerous cells or eliciting systemic toxicity [1]. RA, like a malignant tumor, is also characterized by increased cell proliferation. We therefore wanted to evaluate whether DCA could prevent the development of arthritis in a model of RA. To this end, we treated CIA in DBA/1 mice with DCA. We found that DCA can ameliorate arthritis potently, but only in female mice.
How does DCA abolish the development of chronic destructive inflammation in CIA? B cells are important in the pathogenesis of RA by producing auto-antibodies and in T-cell activation [27]. Antibodies to CII have been detected in serum and synovial fluid of patients with RA [28, 29]. As in RA, anti-CII antibody production contributes to the development of CIA [30, 31]. The beneficial effect of DCA on arthritis is likely due to the down-regulation of B cells producing anti-CII antibodies because DCA-treated mice displayed significantly lower levels of anti-CII antibodies (Figure 3a). This may be a direct effect of DCA or mediated via reduction of pro-inflammatory cytokines. IL-6 is a pro-arthritogenic cytokine that affects B cells by promoting plasma cell differentiation, antibody production, and class switch [32–34]. A tendency toward lower serum levels of IL-6 was observed in DCA-treated female mice compared with water-treated mice (Figure 3b), which thus reflects a possible role of IL-6 in DCA-mediated inhibition of anti-CII antibody production. We could not show any effect of DCA on T cell-mediated inflammation (DTH) or granulocyte-mediated inflammation (olive oil-induced), suggesting that the observed beneficial effect is through humoral immunity, as indicated by the effect on anti-CII antibody production.
Because only female DBA/1 mice displayed amelioration of arthritis in response to DCA treatment, female hormones such as estrogen may play a role. A role of estrogens in RA is suggested by the therapeutic effect of estradiol in menopausal women with RA, a group of patients characterized by low levels of estrogens and high incidence of RA [3, 5, 35, 36]. In addition, estradiol has both prophylactic and therapeutic effects on arthritis development in CIA [37]. To test the hypothesis, endogenous estrogens were removed by OVX. The OVX group treated with DCA had an earlier onset of disease, more frequent and more severe arthritis, and more synovitis and bone destruction compared with the sham-operated group treated with DCA, which had intact estrogen production. A confounding factor is the fact that the OVX treatment in itself may worsen CIA [36], which could possibly mask anti-inflammatory effects of DCA. But the net effect of DCA on sham versus OVX mice is of several magnitudes greater than the effect of OVX on arthritis. DCA ameliorates arthritis by decreasing the frequency of arthritis by at least 40% in sham versus OVX mice (Figure 5a, day 38) and the severity by at least 65% (Figure 5b, days 37 and 38), whereas the earlier reported aggravating effect of OVX on arthritis severity is 20% and the effect on arthritis frequency is minimal or non-existent [36]. This suggests that the observed difference between mice unable to produce estrogens and water controls is indeed due to the DCA treatment. An ameliorating effect of estrogens on arthritis has been demonstrated in both mice and humans [3, 5, 35, 36]. However, the effect of DCA is probably not via increased production of estrogens as DCA treatment did not cause increased uterus weight. Rather, DCA elicits its effect by affecting estrogen signaling.
The beneficial effect of DCA on CIA may not be entirely dependent on estrogens. This is supported by the fact that DCA-treated mice unable to produce estrogen (OVX mice) had a lower frequency of arthritis (61.3%) than water-treated mice (86.4%) (Figures 5a and 1a, respectively). As only female mice benefited from DCA treatment, this observation indicates that DCA has some estrogen-independent but gender-dependent effects on inflammation. Also, the difference in response to DCA could be due to the fact that male hormones may inhibit the DCA effect.
Previous studies of DCA in inflammation have not focused on the effect on bone density. Our results clearly indicate that DCA can prevent cortical bone mineral loss in female mice in CIA (Figure 4a) as a result of increased cortical thickness (Figure 4b). This is in line with a recent study showing that down-regulation of arthritis severity will lead to not only absence of local erosion (that is, in cartilage and subchondral bone) but also systemic effects on BMD [36]. We believe that the beneficial effect of DCA on bone is mediated by a combination of estrogen-dependent effects and the decrease of the inflammatory response manifested by a reduced level of anti-CII antibodies. First, estrogen is important for bone maintenance and may provide protection from bone destruction in arthritis [3, 5, 35, 36]. The role of estrogen in the DCA-mediated effect was demonstrated by the fact that female mice, but not male or OVX-treated female mice, benefited from DCA treatment. Second, the lower levels of anti-CII antibodies found in DCA-treated animals may also prevent bone destruction as anti-CII antibodies induce bone erosions in the CIA model [38]. Such bone erosions may be mediated via anti-CII antibody-dependent C3 recruitment to the cartilage surface, which will initiate an immunological attack, eventually leading to bone destruction [39]. The DCA-mediated reduction of the pro-inflammatory cytokine IL-6 may also contribute to bone protection as IL-6 has potent effects on cartilage and bone destruction [40].
The effect of DCA on cortical bone may also be indirect. As animals have less arthritis, they are more prone to physical activity, which may account for the difference in cortical BMD [41] between treated and non-treated animals (Figure 4). This notion is furthermore in line with the observation that the effect of DCA on bone was mainly on cortical bone, and not on trabecular bone, which is less affected by physical training [42].
Here, we show for the first time that DCA, a potent drug against lactacidosis, also can protect against the development of arthritis in female mice. DCA ameliorates the development of destructive arthritis in part via estrogen and in part via direct down-modulation of inflammation. This warrants future studies of the therapeutical effect of DCA on already established arthritis. The recent long-term clinical trial of oral DCA in children showed that DCA is well tolerated and safe [43], suggesting that DCA can be a potential tool for treating female patients with RA.
bone mineral density
collagen II
collagen II-induced arthritis
delayed-type hypersensitivity
- pQCT:
peripheral quantitative computed tomography
rheumatoid arthritis
tumor necrosis factor.
We thank Berit Ericsson, Anette Hansevi, and Maud Petersson for excellent technical assistance and Hans Carlstén for critical reading of the manuscript. This work was supported by the Göteborg Medical Society, the Swedish Association Against Rheumatism, King Gustav V's Foundation, the University of Göteborg, the A.-G. Crafoord Foundation, the Börje Dahlin Foundation, European Union grants, the Inflammation Network, the A. M. E. Wolff Foundation, CMR, and the Göteborg Association Against Rheumatism.
Authors' Affiliations
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What Sank the Mary Rose? - All 4
A team of experts try to discover why Henry VIII's flagship capsized and sank
Mary Rose: Story of the ship
The Mary Rose - Henry VIII's warship. This page contains information and images covering the Story of the ship.
Your Visit - The Mary Rose
Visit The Mary Rose - Henry VIII's warship. Visitor information, Portsmouth Tourist information, travel information.
The Mary Rose - Portsmouth Museum
The Mary Rose - Henry VIII's warship, lost in 1545, recovered in 1982 and now on display in Portsmouth Historic Dockyard.
Sulfur in the Timbers of Henry VIII's Warship Mary Rose:...
21 Oct 2005 ... The Mary Rose was for 35 years a principal warship in Henry VIII's navy before she suddenly capsized and sank in 1545, maneuvering for ...
Sulfurous shipwreck
A conservationist works on Henry VIII's warship, the Mary Rose. The ship wreaked havoc on the French navy for 34 years until she was wrecked in 1545. ...
Mary Rose Museum - New Home For A Henry VIII's Flagship
After 30-years of preservation, the Mary Rose, the pride of Henry VIII's navy, is unveiled. Find out how to visit the world's oldest existing ship.
Plan a Visit to the Mary Rose
At the Mary Rose Museum, see Henry VIII's flagship recovered from the Solent after more than 500 years underwater. A remarkable day out in Portsmouth.
Henry VIII's Mary Rose ship's crew were riddled with rickets, laser...
The tibia bones of sailors (pictured) who sailed on Henry VIII's Mary Rose ship were analysed at the Royal National Orthopaedic Hospital ...
Sulphur And Iron Commonly Found In Old Shipwrecks
16.05.2012 [RedOrbit] - Similar problems have previously been reported for the Dutch vessel Batavia in Australia, which was lost in 1629, and for Henry VIII's flagship Mary Rose in the UK, which sank off Portsmouth in 1545. "Our work on the Vasa and the Mary Rose has given us
Treasures from the sea
11.05.2012 [Deccan Herald] - Almost four centuries earlier, on July 19, 1545, another 'unsinkable' ship sank off the coast of England: Mary Rose was Henry VIII's (he of the six wives) favourite, state-of-the-art, fully armed and loaded warship – a veteran of 33 years of fierce sea
Guardian: The Cutty Sark: hoist the main sail!
23.04.2012 [The Guardian] - Meanwhile, the Mary Rose Museum is due to open in Portsmouth next year; this is dedicated to Henry VIII's flagship, raised from the Solent in 1982, having sunk nearly half a millennium earlier. The Cutty Sark's prolonged overhaul took on a different
Museum gives close-up view of Henry VIII's Mary Rose warship - CNN.com
30.05.2013 · New museum gives close-up view of Henry VIII's Mary Rose warship
Google Groups: relics from henry VIII's warship, the mary rose
12.10.2009: "nowhere else in the world is a single moment in tudor life captured as it is with the mary rose. "with the help of the new crew of the mary rose we are ...
Google Groups: relics from henry VIII's warship, the mary rose
12.10.2009: ... humanities lit authors shakespeare ```````````````````````````` (
Google Groups: Mary Rose Survives
24.08.2007: gmail.com> wrote: On July 19th, 1545, Henry VIII's flagship Mary
answers.com: Answers - The Most Trusted Place for Answering Life's Questions
Mary Rose [Si] A Tudor warship, flagship of Henry VIII's fleet which sank in the Solent off Portsmouth on its maiden voyage on the warm sunny afternoon
Mary Rose Museum Portsmouth Dockyard | Henry VIII's Warship
The Mary Rose Museum at Portsmouth's Historic Dockyard, is housed in a spectcular £37 million building.
Divers return to wrecksite of the Mary Rose - Past Horizons
For almost three decades since being raised from the Solent in 1982, the hull of the Mary Rose – Henry VIII's 500-year-old flagship which sank ...
Mary Rose - Promethean Planet
Step aboard King Henry VIII's finest warship, The Mary Rose.
The Mary Rose - Limited edition prints of the Tudor warship.
Limited edition prints on paper and on canvas taken from Geoff Hunt's magnificent new painting of The Mary Rose, Henry VIII's flagship.
The Mary Rose - The Anne Boleyn Files
The Mary Rose was a famous Tudor warship built in Portsmouth for Henry VIII's navy between 1509 and 1511. Henry VIII ordered the building of the Mary Rose, ...
10 things you might not know about the Mary Rose | Current Archaeology
Launched in 1511, the Mary Rose was intended to be the flagship of King Henry VIII's fleet. She was a new breed of warship with purpose-built gun-ports that
MARY ROSE - 1000075 | Historic England
The remains of the Mary Rose, Henry VIII's flagship built in 1509, which sank off Southsea Castle on July 19, 1545 with enormous loss of life as the King watched ...
Mary Rose and the Battle of the Solent 1545
Henry VIII's flagship Mary Rose sank on 19th July 1545 during the Battle of the Solent while leading the attack…
The Mary Rose
The Mary Rose was King Henry VIII's favourite warship and he named the ship after his sister. The ship was built in 1509, the year Henry VIII came to the throne.
The raising of the Mary Rose
The Mary Rose was built between 1509 and 1511 and served in Henry VIII's navy for 34 years until she sank off the south coast of England on July 19th, 1545.
Mary Rose Museum – Portsmouth, England | Atlas Obscura
Discover Mary Rose Museum in Portsmouth, England: Hauled from the water's depths, Henry VIII's flagship is preserved in this modernist capsule.
Henry VIII's Mary Rose Warship Goes On Display 30 Years After Salvage
Thirty years after it was plucked from the sea, Henry VIII's prized warship, Mary Rose, will go on display at Portsmouth Historic Dockyard.
Mary Rose
The Mary Rose was the flagship of King Henry VIII's Navy Royal. Begun in 1510 and launched in 1511 at the royal shipyard in Portsmouth…
The Mary Rose
The Mary Rose was King Henry VIII's favourite warship and he named the ship after his sister. The ship was built in 1509, the year Henry VIII came to the throne. ...
FLAGSHIP of Henry VIII's navy - The Mary Rose - The Tudors Wiki
The Mary Rose - Flagship of King Henry VIII 's Navy Click EasyEdit to add to this page! (Don't see the EasyEdit button...
h2g2 - Isle Of Wight Shipwrecks: The Mary Rose - A853643
Work on building the Mary Rose began in 1509, and she was launched in 1511. Named after Henry VIII's sister, she was a large ship, over 100 feet long and 36 feet wide.
The Mary Rose: What's in a Name? | History Today
The April issue of History Today carries an article on Henry VIII's favourite sister, Mary, a rather neglected Tudor in this most examined of dynasties.
Mary Rose
question is what is the story about the Mary Rose. > The "Mary Rose" was Henry VIII's flagship. It sunk off Southsea, Hampshire on ...
A Rose By Any Other Name is Probably the Ship… « the TUDOR ...
24.07.2012 Its title is Mary Rose: Tudor Princess, Queen of France, The Extraordinary Life of Henry VIII's Sister. Amazon calls it "the first biography of Princess Mary Rose for 50 years" but I suppose that is the line given them from the ...
Mary Rose by David Loades | On the Tudor Trail
30.06.2012 'Mary Rose: Tudor Princes, Queen of France, the extraordinary life of Henry VIII's sister' by David Loades.
All web results to the name "Mary Rose"
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I've told my wife "absolutely not, I forbid it" and then when whatever she
was doing is done I usually say "hmmm, nice job glad I had the idea!"
David Franzman
A Touch of the Tropics
----- Original Message -----
From: "Bonnie & Bill Morgan" <email@example.com>
To: <email@example.com>
Sent: Wednesday, June 02, 2004 8:53 PM
Subject: RE: [CHAT] clay pots/Dillon Seed Co
> I'm pretty lucky. Bill may shake his head at some of my ideas, but he's
> to really say "absolutely not." Over time, he has come to trust my
> on those sorts of things. Many times, I can even get him to work with me
> such projects. We really do have a partnership going after 34+ years
> together.
> Blessings,
> Bonnie (SW OH -zone 5)
> -----Original Message-----
> From: email@example.com [mailto:firstname.lastname@example.com] On
> Of email@example.com
> Sent: Wednesday, June 02, 2004 10:00 PM
> To: email@example.com
> Subject: Re: [CHAT] clay pots/Dillon Seed Co
> In a message dated 6/2/2004 8:30:10 PM Eastern Standard Time,
> email@example.com writes:
> Hmmmmmmmm......
> Who is it here that does all the miniature stuff? Auralie?
> How about a miniature garden with a doll's house claw tub planted with
> something like woolly thyme?
> Sounds good to me. I think the miniature climbing rose would be too big to
> shade it, but you might use one of the thymes or a tiny Veronica around
> I'll have to think about suitable plants.
> I've been wondering how some of these husbands would respond to the
> "classic" southern planter of a tire cut into points and turned
> You
> could make a real miniature scene in one of those. They're cheap,
> and
> can be whitewashed or painted to fit the theme.
> Auralie - who's in the throes of setting up a new computer and trying
> make and old DOS program necessary for my job work with the new WindowsXP
> which
> doesn't have DOS.
> ---------------------------------------------------------------------
> Support hort.net -- join the hort.net fund drive!
> http://www.hort.net/funds/
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> Support hort.net -- join the hort.net fund drive!
> http://www.hort.net/funds/
Support hort.net -- join the hort.net fund drive!


text:
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On September 4, 2013, the New Jersey Appellate Division in Lippman v. Ethicon, Inc., Docket No. L–9025–06, 2013 WL 4726834 (App. Div. September 04, 2013), reversed a ruling by the Superior Court, Law Division granting summary judgment to the defendant employers and dismissing plaintiff's claim under New Jersey's Conscientious Employee Protection Act (CEPA) on the grounds that the plaintiff had "failed to show that he performed a whistle-blowing activity" where plaintiff's job responsibilities included alerting his employer to potential safety issues related to the defendants' drugs and products. In the Appellate Division's view, an employee's job title or job responsibilities should not be considered "outcome determinative" when deciding whether a plaintiff has made out a cognizable claim under New Jersey's Conscientious Employee Protection Act (CEPA), N.J.S.A. 34:19–1 to –8.
Plaintiff Joel S. Lippman, M.D., brought a claim under CEPA, against his former employer, Ethicon, Inc., a subsidiary of defendant Johnson & Johnson, Inc. ("J & J") alleging he was terminated after repeatedly raising concerns about the safety or efficacy of several different pharmaceutical drugs and medical products. Plaintiff joined Ethicon in July 2000 as the Vice President of Medical Affairs. In that position Plaintiff was responsible for "safety, ensuring that safe medical practices occurred in clinical trials of [Ethicon's] products;… medical reviews, information from a medical standpoint; [and] medical writing." Defendants contended that when plaintiff expressed opinions regarding the safety of certain products; he was performing his "core job functions" and was not engaged in "whistle-blowing under CEPA." The defendants also argued that plaintiff's termination was unrelated to his work on the various safety review boards, but was in fact due to evidence that plaintiff had engaged in a "inappropriate sexual relationship with a subordinate."
In granting summary judgment to the defendants, the trial court relied on Massarano v. New Jersey Transit, 400 N.J.Super. 474, 477-79 (App.Div.2008), an earlier Appellate Division opinion which found the plaintiff was not engaged in whistle-blowing activities when she reported seeing important documents discarded in her employer's dumpster on the grounds that plaintiff was just "doing her job as the security operations manager by reporting her findings and her opinion to." The trial court held that since Lippman's core job responsibilities required him to monitor and report any concerns he may have had regarding the safety of defendants' drugs or medical products, plaintiff "failed to show that he performed a whistle-blowing activity."
Appellate Division Decision
The Appellate Division, however, reversed the trial court's grant of summary judgment in defendants' favor as inconsistent with "CEPA's broad remedial purpose" and on the grounds that "'Watchdog' employees, like plaintiff, are the most vulnerable to retaliation because they are uniquely positioned to know where the problem areas are and to speak out when corporate profits are put ahead of consumer safety." In support of its ruling, the court explained that the defendants had set up various quality boards to function as open forums where employees could freely express their opinions regarding the safety of certain drugs and medical devices.
The Appellate Division went on to explain that "watchdog" employees would refer to employees who "by virtue of his or her duties and responsibilities, is in the best position to: (1) know the relevant standard of care; and (2) know when an employer's proposed plan or course of action would violate or materially deviate from that standard of care." Just because an individual's job description includes the responsibility "to protect the public from exposure to dangerous defective medical products, CEPA does not permit the employer to retaliate against that individual because of his or her performance of duties in good faith, and consistent with the job description." Ultimately, the court reversed the trial court's grant of summary judgment and remanded the case for further proceedings.
The Lippman decision is a troubling one for many reasons. Regulators constantly exhort employers to instill a "culture of compliance" which requires hiring and encouraging "watch dog" employees to perform their job duties with both honesty and zeal. Lippman undermines an employer's incentives in this regard because it makes any such employee a potential plaintiff whistleblower within the meaning of CEPA. In the absence of a more favorable ruling by the New Jersey Supreme Court, New Jersey employers — particularly those in regulated industries — should tread carefully when dealing with employees who meet the Lippman definition of "watchdogs".
See more »
DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.
© Proskauer - Whistleblowing & Retaliation
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|"Hamilton Verissimo de Oliveira (Engenharia - SPO)" <hamilton.olive...@agenciaclick.com.br>
|Re: [RT] On building on stone
|Wed, 24 Mar 2004 20:43:44 GMT
-----Mensagem original----- De: Bertrand Delacretaz [mailto:firstname.lastname@example.com] > IMHO the current perception that Cocoon is a "big thing" is largely due > to the complexity imposed by Avalon, Sorry. Can't agree with that. Avalon was born from Cocoon codebase. What was imposed to Cocoon? Its should be the opposite. > and this will go away with a > simpler container framework. We'll just have to adjust our user's > perceptions once this is realized ;-) Hey, wait a minute. You're about to create a container that will support _hot deployable dynamic polimorphism_ and this will be simpler than ECM? I'd like to see that. -- hammett
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