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Welcome to the Majd Research Group in Department of Bioengineering at the Pennsylvania State University!
We are interested in molecular processes on cell membranes and the role of these molecular events in healthy and diseased cellular functions. Employing biomaterials and micro/nano fabrication techniques, we develop platforms to study these membrane-involved processes.
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- April, 2015- Congrats to Michael for receiving a CERI grant!
- April, 2015- You Jung and Soo gave two talks on their research at the Society for Biomaterials annual meeting in Charlotte.
- April, 2015- DoYoung receives an Erickson Discovery Grant, congrats!
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subset: commoncrawl


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the media is the biggest hypocrite there is, its a game they have talked like this for years, it all in the game
Originally written on Bob's Blitz | Last updated 2/11/13
Earlier this morning we noted that folks continue to drop the n-word way too easily and what does The Big Lead come up with? Kevin Garnett dropping the word on a local broadcast last... Full story at Bob's Blitz ~ http://www.bobsblitz.com
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text: 9780141384566 0141384565 Mystery fiction. England New York Chicken House Carnivals Mystery and detective stories. en 213480574 Mystery and detective stories Young adult fiction When two of sixteen-year-old Pete's childhood classmates disappear from a carnival the same night, he is a suspect, but his own investigation implicates other old friends he was with that evening--and a tough, knife-wielding enemy determined to keep him quiet. Unknown value: shs 2008 1st American ed. Black Rabbit summer Fiction 488 Young adult works Juvenile works 9780545057523 0545057523 Missing persons Brooks Kevin Brooks, Kevin. Homosexuality 2008 nyu England Drug abuse Friendship


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Why should the experience of an Apple keynote just be a few times a year? Joel's song conjures the wonder and trepidation of finding that the Apple Store is Down, while a randomly-generated Keynote presentation rolls along incoherently to its classic-rock beat. Reload the page to watch a new one! Click to play. (It might take a second to buffer; we didn't add a loading bar.) Lyrics and MP3 download after the jump. "Apple Store Is Down" Download [320kbps, MP3] Apple Store Is Down Best not make any plans today. The Apple store is down, new shit is on its way. A tablet Mac or new SDK. Doesn't matter,'cause it's Apple, As long as Steve goes slow in the keynote: "Had a great business year, our future success is clear. CHORUS But I have just one more thing to show before I disappear. And I think it's the most exciting thing that we are gonna launch this year. Boom it's here." Listen, Steve, my friends and I have decided that it's okay that you know (whoa) that we don't want for you to die. If it happened the stock would flatten. So if you go, go slow! I need a new boat. "My hair is gone. I'm grizzled gray. Retire you ask? Not today. CHORUS 'cause I have just one more thing to show before I disappear. It might be the most important product that we're gonna launch this year. Boom it's here." BRIDGE: My head is swimming; my mouth is dry. I hardly can believe that I am worthy to be in this distortion field. CHORUS 'cause I want just one more thing to own before I disappear. And my life needs one more thing to glow to add a little cheer. Oh thank god it's here. Special thanks to #boingboing's Chris_B for mixing assistance and Jonathan Coulton for a guitar.
Song: 'Apple Store Is Down'
• Discuss this post in our forums
12 Responses to "Song: 'Apple Store Is Down'"
Wait, who is actually singing this? Joel Johnson?!
No, Liberace!
Why aren't you making a lots of money singing, Joel? Girls should be throwing their bras at you. Also, sweet animation. I esp. like the gremlin atop the bulldog.
And Rob you Know how I love these things. Jesus guys this is "Table of Malcontents + Gadget Lab + Boing Boing" all in once.
Maybe a Dagon VS R'lye Comparison chart would have been the candy atop of the pie, but that's just the word of a dork, don't mind. Anyhow, I laughed the hell out of me.
Chords please?
Speaking as the O.G. Apple Fan Boy that was absolutely beautiful.
Thank you, Camillo! And everyone else. This was unbelievably fun.
Oh God. The Grape line graph with Juice/Drank was too much for me. I'm dying here.
That's awesome.
Fuckstravfuckganza indeed.
The chords:
A F#m D Dm C#m E4
A C# D Dm C#m Bm E4 Dm
A F#m D (E) Dm
A F#m D E4
F#m Bm F#m E4 Dm
To be heard around campfires all summer!
The song definitely feels like a JoCo song.
My day is now made of LAUGH.


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News Standalone Trailer for Sword Art Online Posted
posted on 2012-03-31 00:14 EDT
Three-minute video for anime adaptation of Reki Kawahara light novel series streamed
A standalone trailer for the upcoming anime adaptation of Reki Kawahara's light novel series Sword Art Online was posted on Saturday on the official website for the show. The two-cours (two-quarter or half-year) anime will premiere in Japan next July. Another trailer was also posted on Friday to promote both Sword Art Online as well as Accel World, another upcoming anime that adapts a Kawahara novel.
The story revolves around a boy named Kazuto "Kirito" Kirigaya who enters a virtual-reality, massively multi-player online (MMO) world called "Sword Art Online." There is no escape from this world unless the player clears the game, but "game over" means the death of the player.
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Book Room Red
No. 50
Book Room Red, the muddiest of our reds, is particularly suited to smaller rooms where the stronger Eating Room Red can be a little overwhelming. It takes its name from the reading rooms or small libraries favoured by the English aristocracy and creates an unapologetically clubby feel. Red & Warm Tones Undercoat.
Book Room Red 7 7
Marks when wiped As a fun of F&B paints, must admit I have been very disappointed with the Book room Red. I have purchased the eggshell paint to add accent colour to the kids room, they are F&B funs too. I have primed and painted bedside table, let it dry for a week, just to be sure. Today I tried wipe the dust of it with slightly wet cloth and it marked! Left smears of the colour of wet paint! Not a look I was after. What is going on F&B? I have used stiffkey and purbeck stone eggshell before and never had the same issue, I love them. Painted kitchen chairs and radiators and they are now as fabulous as the day I painted them(1 yr ago), and I clean them regularly. I have also used modern emulsion in ammonite, skimming stone and purbeck, as well as India yellow in estate emulsion. Fabulous colours, great quality! I do not mind paying extra for F&B paints but I do have expectation! Have to say, Book room red is a lovely, warm, pinky terracotta colour, but what's the point, wasted time and money on something I can't really use. 19 June 2015
Easy to work with. Rich, sophisticated tone. Fabulous colour used on timber panelling in a fairly dark bedroom with Lime White on the ceiling. The paint looks almost like a salmon colour in the tin but when used dries to a deeper, richer hue. Great with the dark oak bedroom furniture and polished brassware. Highly recommended! 30 January 2015
Nice colour, blotchy finish Two coats of topcoat over two of recommended undercoat and the result was still disappointing, a blotchy finish that wasn't as good as it should have been, given the price of the product. 20 December 2014
This product has great depth of colour. As ever, a high quality product that has added warmth and quality to our home. 18 September 2014
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Great paint F&B paint is great as being water-based it does not set off migraines for me like horrid synthetic paints do. It is also lovely to work with and apply. The floor paint so far seems very hard-wearing and has a nice sheen to it. I am pleased with the colour which is very warm without being to intense. 27 July 2013
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NEW YORK (CBSNewYork) — Derrick Gordon is coming home — and just in the nick of time it seems.
Gordon, the first openly gay player in Division I… 532 more words
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Derrick Gordon, who began his playing career at Western Kentucky and then transferred to UMass, announced on Sunday that he's decided to spend that year at Seton Hall… 263 more words
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These are the most expensive cities in the Middle East
Can you guess who's number one?July 5, 2015 3:00
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A volcanic ash cloud is a pretty good excuse for not being at work. So let's hope UAE employers don't use it as a good excuse to dock the pay of employees left stranded abroad.
April 18, 2010 10:10 by kippreport
Workers in the UAE (not to mention other Gulf countries) often complain that the law is skewed in favor of employers.
This is partly down to how local employment law applies to expats. For example, UAE firms can report employees as 'absconding' – preventing them from leaving the country – or make life difficult when staff want to switch jobs. Despite being illegal, many companies withhold employees' passports, apparently for 'safekeeping', but often as a form of control. And while there have been various initiatives to ensure employees' wages get paid on time, such measures are not always effective.
Another law is highly relevant to UAE residents left stranded abroad, following the flight cancellations after the volcanic eruption in Iceland. According to legal firm DLA Piper Middle East, employers can dock the pay of any staff member not returning to work on time.
Admittedly, this is not particularly out of the ordinary, or even particularly unfair under normal circumstances. In many countries, an employee who does not turn up to work would have their pay docked.
But a volcanic ash cloud is a pretty good excuse for not being at work. So let's hope UAE employers – who already wield such power over their staff – don't use it as a good excuse to dock the pay of stranded employees.
As DLA Piper's Neil Crossley said in a statement issued to the press, "we would encourage employers to be flexible given the circumstances". Crossley suggested that staff should be allowed to work remotely, or use up remaining holiday if they are trapped abroad.
Good advice. Let's hope Crossley's sensible suggestion is followed by Middle East employers.
Have you been affected by the flight cancellations due to the Iceland volcano eruption? How did your company react if you missed work? Have your say by submitting a comment below, or email us at [email protected].
1 Comment
The UAE should certainly not ask the workers who happen to be stranded elsewhere in the world to pay a hefty price for their circumstances that have left them stranded on foreign shores. What in heavens name are they supposed to do when all the flights from those places have been cancelled? Ride a donkey train? Sometimes the attitude of the labour market in these countries resembles those of people in the dark ages, one of the reasons that the Middle East can never enjoy a transparent business environment that automatically fuels growth…in situations like this, a more humane approach is called for, and individual companies should del with their off-work employees on a case-by-case basis, rather than tarring them all with the sme brush and calling them "absconding"……losses are being incurred already worldover – by the workers, by the airlines and so many related industries.
Volcano ash grounds more Middle East-Europe flights
April 18 2010
News Review: 19 April 2010
April 19 2010


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From Milwaukee, Madison and beyond, a daily dose of political news and glimpses behind the scenes
Joint Finance OKs ethics reform bill
Rep. Kitty Rhoades (R-Hudson), co-chairwoman of the committee, said the bill would make Wisconsin a national leader in ethics reform. The bill would merge the Ethics and Elections boards into a non-partisan agency that has unlimited funding to investigate public officials.
But Sen. Luther Olsen (R-Ripon) raised an issue that could become a snag in the Senate. Olsen said lawmakers should make it clear that the new Government Accountability Board can investigate officials even when it has not received a formal complaint.
He did not offer an amendment that would make that change, however. He said after the 16-0 vote that it was clear the amendment would not have passed the committee but that it may be raised when the bill comes before the full Senate this afternoon.
"If nobody complains about anything, than what does this board really do?" Olsen asked.
Other committee members said the change was unwarranted and that it would lead to a flood of politically motivated anonymous tips on the eve of an election. Reform advocates said they believed the current version of the bill already gave the board the power to investigate matters without a formal complaint.
Rep. Mark Pocan (D-Madison) said requiring a complaint was a low threshold.
"The threshold really is me writing something down, putting it on paper so you have a name on it," he said.
Doyle and legislative leaders from both parties said in December they wanted to pass an ethics reform bill, but the bill stalled in recent weeks as Assembly and Senate leaders differed over key provisions of the bill. But on Monday, leaders announced a compromise bill, and the Joint Finance Committee this morning adopted that version of the bill.
The latest version takes out the bill's "non-severability" clause that said if a court found any part of it unconstitutional, the entire law would be struck down. The bill retains a controversial provision that lawmakers and other public officials will be tried in their home counties rather than the counties where offenses occur - unless the accused chooses otherwise.
The new version of the bill includes a finding that such a provision is constitutional in an attempt to fend off a court challenge. Critics say the provision is illegal because it affords a different standard of justice to public officials than regular citizens.
The Republican-controlled Assembly will take up the bill at 11 a.m. and the Democratically held Senate will consider it at 1 p.m. Doyle, a Democrat, gives his State of the State address at 7 p.m.
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Respond to Review of Source Community Wholefoods
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Review: Great co-op with fresh, organically grown veggies and a big range of bulk goods. Most products are vegan, and some speciality vegan items as well. Profit goes back into the co-op to grow the garden :)
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DGK Rasta Angle Backpack
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Stash Points: 1,297
What is this?This is the number of points you get in The Zumiez Stash for purchasing this item. Stash points are redeemable for exclusive rewards only available to Zumiez Stash members. To redeem your points check out the rewards catalog on thestash.zumiez.com.
Jump into the rasta craze with the super steezy DGK Rasta Angle backpack.
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At first, Julie & Laurent asked us to show one of our ready-to-mount interactive installations for le Qu4tre's open doors (lequ4tre.fr). With our friends from Los Patos, we visited the former industrial building in the Paris suburbs, and decided to collaborate on an in-situ interactive piece for the event.
Our idea was to turn a stairway - connecting to the parking, maybe the most unwelcoming place in the building! - into an interactive playground.
As a player, you would throw a ball in the stairs, each hit lights on a stair. Your goal is to draw the full rainbow. Beware! If you hit a stair a second time, the whole stairway will light off!
The kids and the elders had so much fun throwing balls, that we had to get the balls downstairs every 20 minutes! Our next step is to find a way to automatically bring back the balls. We're studying how Golf Practice works right now ;)
Once we find the best solution, we will install our interactive game in Montmartre ;)
Detailed look on bit.ly/interac-stairs
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$2.90For more than a hundred years, Glasgow has been right up there in the major league of big-city crime. From Madelaine Smith and Oscar Slater, by way of the Bridgeton Billy Boys and the Norman Conks, through to modern villains like Paul Ferris and Tam McGraw, Glasgow's streets have spawned a succession of fascinating tales of true crime. Even in the twenty-first century, as the new Glasgow polishes
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Who won the award for Comment of the Week?
Bankruptcy, Biglaw, Celebrities, Dewey & LeBoeuf, Federal Government, Federal Judges, Law Schools, Minority Issues, Morning Docket, Partner Issues, State Judges, Student Loans
Ed. note: Due to the Labor Day holiday, we'll be on a reduced publication schedule today. We'll be back to normal tomorrow. A restful and happy Labor Day to all!
* The lone ex-Dewey partner who was sued by Citibank for defaulting on his capital loan is fighting back, claiming that he was "fraudulently induced" into signing up for the plan even though the bank knew that the S.S. D&L was sinking. [Reuters]
* If you're trying to avoid additional questions being raised about your alleged bad behavior, a resignation amid scandal isn't the way to do it. Suzanne Barr, the ICE official accused of running a federal "frat house," has quit her job. [New York Daily News]
* A federal judge taught the members of the Louisiana Supreme court that the year 1994 did, in fact, occur before the year 1995. Justice Bernette Johnson will now ascend to the rank of chief justice. [Times-Picayune]
* Because we're all a little hopeless these days: given the bleak realities of our economic situation, perhaps it's finally time to change the standard for a discharge of student loan debt in bankruptcy. [New York Times]
* "The groups that attempt to rank schools are involved in a lot of hogwash." Even if that's the case, people are still going to care about the University of Illinois's rankings nosedive after the Paul Pless to-do. [News-Gazette]
* Don't be scared by the absurd tuition rates or the abysmal job prospects, because law school is still a great investment for African-Americans — and for law schools in search of diversity, too. [National Law Journal]
* "[T]hat a lawyer would take this kind of case is shocking." Sadly, it's not. Angelica Marie Cecora, the alleged escort who filed a $5M suit against Oscar de la Hoya, now has to pay all of his legal fees. [New York Post]
Bankruptcy, Federal Judges, Judicial Divas, Law Schools, Money, Student Loans
Bankruptcy Still Can't Save You From Law School Debt, But That Doesn't Mean Judges Have to Like It
A federal judge calls for systemic change in the law school student loan system…
Bankruptcy, Clerkships, Crime, Drugs, Election 2012, Federal Judges, Guns / Firearms, Job Searches, Law Schools, Layoffs, Money, Morning Docket, Politics, Pro Se Litigants, Romance and Dating, S.D.N.Y., Sam Sparks, State Judges, Student Loans, Texas, Unemployment
* In case you've been sleeping under a rock, Mitt Romney picked Rep. Paul Ryan as his Vice Presidential running mate. Putting politics aside, this is a great pick, if only because Ryan is so handsome. Seriously, he's a total stud. [Wall Street Journal]
* "How can I be the one guy with a good degree who is going to be chronically unemployed?" Sadly, many lawyers are still looking for jobs after (multiple) layoffs, but thanks to a lack of positions, employment is just "not in the cards" for them. [New York Times]
* Deadliest clerkship? The Washington, D.C. judge who presided over one of the most violent mass shooting cases in the nation's capital was reportedly held up at gunpoint last week, with her law clerk in tow. [Fox DC]
* Something is rotten in the state of Denmark Texas. Judge Sam Sparks "know[s] the smell of bad fish," and now wants to know why the USADA waited so long to bring charges against Lance Armstrong. [Bloomberg]
* After reversing a bankruptcy court's decision that loan repayment would be an "undue hardship" for a law-school debtor, a judge took the time to rip law schools a new one over escalating tuition. [Oregonian]
* Match.com class-action plaintiffs found no love in court after a federal judge ruled that the dating website hadn't breached its user agreement. Much like their love lives, their claims aren't getting any action. [Reuters]
* A man who is his own lawyer has a fool for a client: 23% of all cases filed in the federal court for the S.D.N.Y. are brought by pro-se litigants, and the vast majority of them seem to have lost their minds. [New York Post]
American Bar Association / ABA, Law Schools, Rank Stupidity, Student Loans, U.S. News
Law Schools Misreport Debt Figures to the ABA; To No One's Shock, the ABA Does Nothing
Which law schools have reported inaccurate figures for their graduates' average indebtedness?
Commencement, Job Searches, Law Schools, Movies, Student Loans, Videos, YouTube
How The Other Half Graduates: A Cooley Commencement Speech Inspired By 'My Cousin Vinny'
The student speaker at Cooley Law's graduation offers an… interesting perspective…
Law Schools, Money, Romance and Dating, Student Loans
Is Law School Loan Debt Ruining Your Love Life?
You probably never thought that your student loans would be both financially and romantically ruinous, but as it turns out, young adults aren't keen on getting into bed with six-figures of debt every night.
Attorney Misconduct, Bankruptcy, Biglaw, Law Schools, Morning Docket, Murder, New York Times, Perverts, Prisons, SCOTUS, State Judges, Student Loans, Supreme Court
* Speaking on the condition of anonymity, one Supreme Court justice thinks that things will be back to normal at One First Street come the start of the next term, despite his colleagues' loose lips. [National Law Journal]
* Hourly billing rates for associate are on the rise nationwide, while partner and counsel billing rates only saw modest bumps. Is Biglaw back in business, or is this just another "retention strategy"? [New York Law Journal]
* This is a really hard to believe newspaper headline: "Law firm recognizes employees have life outside of work." Carlton Fields, what kind of gypsy voodoo magic spells are you casting? [South Florida Sun-Sentinel]
* Another day, another editorial about the "irretrievably broken" state of legal education in our country. But the ABA admins needn't worry their oblivious little heads, because people will keep applying. [New York Times]
* And in today's disturbing law school debtor news, Jason Bohn's charge was upgraded to first-degree murder after a DA announced via indictment that Bohn allegedly intended to torture his victim. [New York Post]
* "Quite frankly, these are the actions of a dirty old man." You can look, but never lick: it's not really a good thing when a judge uses a sentence like this to describe an attorney's alleged client relations skills. [CBS News]
* For it's one, two, three strikes you're out at the old ball fraud game. Lenny Dykstra pleaded guilty to bankruptcy fraud among a potpourri of other felony counts, and he'll now face up to 20 years in prison. [CNN]
Glenn Reynolds, Law Professors, Law Schools, Quote of the Day, Student Loans, Videos, YouTube
Quote of the Day: The Broken Economics of Legal Education
How can we fix the broken model of law school economics? Professor Brian Tamanaha has some ideas.


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February 6th 2012


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Bill Rancic Defends His Wife Giuliana After Fashion Police Controversy: 'I Tried to Get Them to Release the Footage' 41 years, 2,186 covers and 55,435 stories from PEOPLE magazine's history for you to enjoy
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- March 18, 2013
- Vol. 79
- No. 11
Casey Anthony: Out of Hiding
Testifying in Court for the First Time, Casey Anthony Claims to Be Bankrupt, Unemployed-and Unemployable
Despite the makeover, Anthony, 26, testified at a bankruptcy hearing on March 4 how the past 20 months have been marked by unemployment and financial troubles. Claiming assets of $1,084 and debts of $792,119.23 (mostly owed to her lawyer), she described how she has been relying on strangers-who send her cash and gift cards-and friends for help getting by. "I don't pay rent. I don't pay utilities," she said in a loud, direct voice. "I live for free off the kindness of those I'm living with."
Citing safety concerns, Anthony refused to name her benefactors, but a source close to her tells PEOPLE that she has reconciled with her entire family, including her father, George, whom she famously accused, during her murder trial, of molesting her. (He denied the allegations.) "They're still rebuilding their relationship," says the source. "But her parents have helped her out both emotionally and financially."
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WASHINGTON – We have different opinions, admitted the White House's faith-based advisers on Tuesday when they presented their recommendations. But we were able to find "meaningful common ground," they added.
After a year of work, the 25 members of the first Advisory Council on Faith-Based and Neighborhood Partnerships presented a report that included more than 60 recommendations for six issues - economic recovery and domestic poverty, fatherhood and healthy families, environment and climate change, inter-religious cooperation, global poverty and development, and reform of the Office of Faith-Based and Neighborhood Partnerships.
The proposals provide suggestions on how the government can better work with faith-based and community groups to tackle major social issues. more >>
Churches and aid organizations already have massive relief efforts going on in Haiti but that's not stopping them from looking more south where Chile is reeling from one of the strongest earthquakes on record.
"[W]ithout even stepping a foot into Central Chile, it is clear that the hundreds of thousands affected by this earthquake desperately need our prayers – and will also need our help as we learn more about the extent of the damage," said Randy Hurst, World Missions Communications director for the Assemblies of God.
International and local relief organizations are still assessing the needs and damage on the ground as initial deliveries of food and supplies are being made. more >>
A Scottish man who benefited from the Salvation Army's services to the elderly left the ministry with an unexpected $1.27 million in his will.
The Salvation Army in Angus, an eastern county in Scotland, revealed this past weekend that Robert Saddler, a retired architect, had given the second largest donation ever to the branch's community care service. The largest gift, $1.5 million, was given 13 years ago and used to set up the service.
Saddler, who reportedly has no immediate living family, had received help from the Salvation Army Angus since he was in his 80s. Ministry workers had shopped and collected medicines for him until his death at the age of 95. The particular Salvation Army service that Saddler used helps elderly people maintain an independent life. more >>
Spring break is officially in session at many schools in the United States. But this year, thousands of students will hit Florida's beach with something else on their mind other than soaking in the sun.
More than 2,500 Christian students from across America are expected to attend one of five week-long outreach events hosted by Campus Crusade for Christ as part of their annual "Big Break" conferences.
Between Feb. 28 and April 3, participating college students will join forces on Panama City Beach to not only help prepare and pack meals for 1 million Haitian earthquake victims, but also to share their faith and recruit other students on the beach to help. more >>
The massive 8.8-magnitude earthquake that struck Chile Saturday morning is not like the one that devastated Haiti in January, said a relief expert at World Vision.
Even though both monstrous quakes have caused or is expected to result in the deaths of many people, the challenges facing relief workers in each country is different, said Steve Matthews of World Vision's global rapid response team.
"This (Chile) quake will not be like the one in Haiti," said Matthews on Saturday. more >>
The U.S. government needs to enhance the religious literacy of its foreign service officers and diplomats so that they can better address foreign policy challenges, a report advised.
Task force members of the report "Engaging Religious Communities Abroad: A New Imperative for U.S. Foreign Policy," sponsored by The Chicago Council on Global Affairs, said for too long the government has ignored the fact that religion plays a large role in the lives of the people its officers interact with overseas.
It is imperative that representatives of America engage with local religious communities and receive training on how to relate to these religious groups in order to fulfill its foreign interests, the task force said. more >>


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Publications (287)1982.42 Total impact
- AIDS (London, England) 07/2015; 29(11):1425-1427. DOI:10.1097/QAD.0000000000000744 · 6.56 Impact Factor
Article: Changing utilization of Stavudine (d4T) in HIV-positive people in 2006–2013 in the EuroSIDA study[Show abstract] [Hide abstract]
ABSTRACT: Objectives The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe.Methods Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T.ResultsA total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19–20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23–29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16–19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80–0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17–9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60–6.02) versus HIV RNA < 400 copies/mL.Conclusionsd4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.HIV Medicine 06/2015; DOI:10.1111/hiv.12254 · 3.45 Impact Factor
Article: Major differences in organization and availability of health care and medicines for HIV/TB coinfected patients across Europe: Health care for HIV/TB patients in Europe[Show abstract] [Hide abstract]
ABSTRACT: The aim of the study was to investigate the organization and delivery of HIV and tuberculosis (TB) health care and to analyse potential differences between treatment centres in Eastern (EE) and Western Europe (WE). Thirty-eight European HIV and TB treatment centres participating in the TB:HIV study within EuroCoord completed a survey on health care management for coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV centres). Descriptive statistics were obtained for regional comparisons. The reported data on health care strategies were compared with actual clinical practice at patient level via data derived from the TB:HIV study. Respondent centres in EE comprised: Belarus (n = 3), Estonia (1), Georgia (1), Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4) and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1), Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of HIV and TB in EE are less often located at the same site (47% in EE versus 100% in WE; P < 0.001) and less often provided by the same doctors (41% versus 90%, respectively; P = 0.002), whereas regular screening of HIV-infected patients for TB (80% versus 40%, respectively; P = 0.037) and directly observed treatment (88% versus 20%, respectively; P < 0.001) were more common in EE. The reported availability of rifabutin and second- and third-line anti-TB drugs was lower, and opioid substitution therapy (OST) was available at fewer centres in EE compared with WE (53% versus 100%, respectively; P < 0.001). Major differences exist between EE and WE in relation to the organization and delivery of health care for HIV/TB-coinfected patients and the availability of anti-TB drugs and OST. Significant discrepancies between reported and actual clinical practices were found in EE. © 2015 British HIV Association.HIV Medicine 05/2015; DOI:10.1111/hiv.12256 · 3.45 Impact Factor
Article: Hepatitis C seroconversions in HIV infection across Europe:Which regions and patient groups are affected?[Show abstract] [Hide abstract]
ABSTRACT: In the last decade, several outbreaks of sexually acquired acute hepatitis C (HCV) infection have been described in HIV-positive men who have sex with men (MSM). The aims of this study were to determine whether there has been an increase in the number of acute HCV infections in different parts of Europe. HCV seroconversion was defined as an HCV-antibody test change from negative to positive within the observation period in EuroSIDA. Binomial regression was performed to determine factors associated with being tested for HCV and HCV seroconversion. A total of 223 HCV seroconversions were observed from 16,188 tests [1.38% (95%CI 1.20-1.56)] among 5,736 patients between 2002 and 2013. Overall the odds of acquiring HCV infection increased by 4% per year (OR 1.04 [95%CI 0.99-1.09]; p=0.10). Overall 63.2% (141/223) of all seroconversions were seen among MSM. Similar patterns were observed across all European regions (p=0.69, test for interaction) and HIV transmission risks groups (p=0.69, test for interaction). In multivariate analysis, North, South and East Europe had higher odds of HCV seroconversion compared with Western Europe (OR 1.90 [1.28-2.81], 1.55 [0.99-2.45], and 1.86 [1.21-2.84]; p=0.0014, p=0.058, and p=0.0044, respectively). Within EuroSIDA a significant increase in HCV seroconversions can be observed after accounting for increased levels of testing for HCV in recent years. This highlights the need for increased HCV prevention efforts among HIV-positive persons in Europe. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 04/2015; DOI:10.1111/liv.12848 · 4.41 Impact Factor
Article: Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals[Show abstract] [Hide abstract]
ABSTRACT: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment. Three thousand nine hundred and forty-one HCV antibody-positive EuroSIDA patients with follow-up after 1 January 2000 were included, with causes of death classified using CoDe methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD. LRD accounted for 145/670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively). Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.AIDS (London, England) 04/2015; DOI:10.1097/QAD.0000000000000674 · 6.56 Impact Factor
Article: Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial[Show abstract] [Hide abstract]
ABSTRACT: HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts > 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD. Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white). We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts > 500 cells/μL. © 2015 British HIV Association.HIV Medicine 04/2015; 16 Suppl 1(S1):55-63. DOI:10.1111/hiv.12234 · 3.45 Impact Factor
Article: Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study.[Show abstract] [Hide abstract]
ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.PLoS Medicine 03/2015; 12(3):e1001809. DOI:10.1371/journal.pmed.1001809 · 14.00 Impact Factor
Article: Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults[Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. DESIGN: Observational European cohort collaboration study. METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). RESULTS: The study included 19 968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.AIDS 11/2014; 29(2). DOI:10.1097/QAD.0000000000000530 · 6.56 Impact Factor
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ABSTRACT: Objective: To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events. Design: Prospective cohort. Methods: EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events. Results: There were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5–19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8–12.5). Patients with thrombocytopenia (platelet count ≤100 × 109/l) had a slightly increased incidence of AIDS-defining events [adjusted incidence rate ratio (aIRR) 1.42, 95% CI 1.07–1.86], when compared to those with platelet counts 101–200 × 109/l, whereas the incidence of non-AIDS-defining events was more than two-fold higher (aIRR 2.66, 95% CI 2.17–3.26). Among non-AIDS-defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61–3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32–1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1 year prior to clinical events. Conclusion: Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease.AIDS 11/2014; 28(17):2565-2571. DOI:10.1097/QAD.0000000000000433 · 6.56 Impact Factor
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ABSTRACT: Introduction EuroSIDA has previously reported a poorer clinical prognosis for HIV-positive individuals in Eastern Europe (EE) as compared with patients from other parts of Europe, not solely explained by differences in patient characteristics. We explored regional variability in self-reported HIV management at individual EuroSIDA clinics, with a goal of identifying opportunities to reduce the apparent inequalities in health. Methods A survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA clinics. Responders in EE were compared with clinics in all other EuroSIDA regions combined (non-EE). Characteristics were compared between regions using Fishers exact test. Results A total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82 in non-EE). Participating clinics reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700–2399)]. The majority of clinics requested viral load and CD4 measurements at least every six months for patients on as well as off ART (EE 66.7%, non-EE 75%, p=0,72). Significantly fewer EE clinics performed resistance tests before ART as well as upon treatment failure (Figure 1). Half of the EE clinics indicated following WHO guidelines (EE 50%, non-EE 7.4%, p<0.0001), whereas most non-EE clinics followed EACS guidelines (non-EE 76.5%, EE 41.7%, p=0.017). The majority of EE clinics and ¼ non-EE clinics indicated deferral of ART initiation in asymptomatic individuals until CD4 ≤350 cells/mm3 (Figure 1). There were no significant regional differences in screening haematology, liver or renal function, which the majority of clinics reported to do routinely. However, EE clinics reported screening significantly less for cardiovascular disease (CVD), and only about half screened for tobacco use, alcohol consumption and drug use (Figure 1). Screening for cervical cancer and for anorectal cancer was low in both regions (Figure 1). Conclusions We found significant regional variability in self-reported HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of ART initiation for longer than non-EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both regions. Whether differences in HIV management are reflected in clinical outcomes deserves further investigation.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19504. DOI:10.7448/IAS.17.4.19504 · 4.21 Impact Factor
Article: The prevalence and predictive value of dipstick urine protein in HIV-positive persons in Europe[Show abstract] [Hide abstract]
ABSTRACT: Proteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m(2).Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19561. DOI:10.7448/IAS.17.4.19561 · 4.21 Impact Factor
Article: Major challenges in clinical management of TB/HIV co-infected patients in Eastern Europe compared with Western Europe and Latin America[Show abstract] [Hide abstract]
ABSTRACT: Introduction Rates of both TB/HIV co-infection and multi-drug-resistant (MDR) TB are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV co-infected patients are scarce. Our aim was to study the clinical characteristics of TB/HIV patients in Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR-TB and assess the activity of initial TB treatment regimens given the results of drug-susceptibility tests (DST). Material and Methods We enrolled 1413 TB/HIV patients from 62 clinics in 19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January 2011 to December 2013. Among patients who completed DST within the first month of TB therapy, we linked initial TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ≥4 active drugs in each region. Risk factors for MDR-TB were identified in logistic regression models. Results Significant differences were observed between EE (n=844), WE (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, p<0.0001) and MDR-TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03, (95% CI 1.00–4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88–6.22) and living in EE (aOR = 7.19, 95% CI 3.28–15.78) were associated with MDR-TB. For 569 patients with available DST, the initial TB treatment contained ≥3 active drugs in 64% of patients in EE compared with 90–94% of patients in other regions (Figure 1a). Had the patients received initial therapy with standard therapy [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would have been 64% vs. 86–97%, respectively (Figure 1b). Conclusions In EE, TB/HIV patients had poorer exposure to cART, less often a definitive TB diagnosis and more often MDR-TB compared to other parts of Europe and LA. Initial TB therapy in EE was sub-optimal, with less than two-thirds of patients receiving at least three active drugs, and improved compliance with standard RHZE treatment does not seem to be the solution. Improved management of TB/HIV patients requires routine use of DST, initial TB therapy according to prevailing resistance patterns and more widespread use of cART.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19505. DOI:10.7448/IAS.17.4.19505 · 4.21 Impact Factor
Article: Predictive value of prostate-specific antigen for prostate cancer: a nested case-control study in EuroSIDA[Show abstract] [Hide abstract]
ABSTRACT: Introduction Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV− men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV− men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men. Methods Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics. Results Sixty-one men were included with a median six (IQR 2–9) years follow-up. Time between last sample and PCa was seven (4–11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57) and CD4 of 437 (243–610) cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6) and 0.8 (0.5–1.2) µg/L] and fPSA [0.4 (0.2–0.8) and 0.3 (0.2–0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7–9.5) and 0.9 (0.6–1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4) and 0.2 (0.2–0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.7–12.9) and 5.4 (1.7–17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3–23.9) nmol/L at first sample) and SHBG [50.0 (34.0–66.0) nmol/L] levels were similar in cases and controls at first and last sample (all p>0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%). Conclusions PSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age-related cut-offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19510. DOI:10.7448/IAS.17.4.19510 · 4.21 Impact Factor
Article: Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression.[Show abstract] [Hide abstract]
ABSTRACT: Background: Use of unboosted atazanavir (ATV400) is approved in the US but not in Europe (1). Due to pharmacokinetic interactions it should not be used with tenofovir but can be used with abacavir/lamivudine (ABC/3TC) (1, 2) (3). Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant. Methods: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV-1 RNA >50 c/mL. Results: We included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co-infection 36%, median baseline CD4 at switch 540 cells (360, 700), time with VL≤ 50 c/mL 45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010). The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25 (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis virus co-infection, CD4 count at time of switching or third drug used in the previous regimen. Conclusions: A switch to ATV400+ABC/3TC in selected subjects with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long-term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19810. DOI:10.7448/IAS.17.4.19810 · 4.21 Impact Factor
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ABSTRACT: Introduction Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen. Materials and Methods A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m2 after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1–4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts. Results A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7–6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6–1.0), 5.6 (95% CI 4.5–6.7) and 37.4 (95% CI 34.0–40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90–0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1–6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5–5.1). External validation showed consistent CKD rates across risk groups (Figure 2). Interpretation Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19514. DOI:10.7448/IAS.17.4.19514 · 4.21 Impact Factor
Article: Gender differences in HIV-positive persons in use of cardiovascular disease-related interventions: D:A:D study[Show abstract] [Hide abstract]
ABSTRACT: Introduction There is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV-positive individuals. We investigated whether such differences exist in the D:A:D study. Materials and Methods Follow-up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10-year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors. Results At enrolment, women (n=13,039; median (interquartile range) 34 (29–40) years) were younger than men (n=36,664, 39 (33–46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high-risk group, initiation rates of most interventions (with the exception of anti-hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1). Conclusion Use of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19516. DOI:10.7448/IAS.17.4.19516 · 4.21 Impact Factor
Article: Lack of association between use of efavirenz and death from suicide: evidence from the D:A:D study[Show abstract] [Hide abstract]
ABSTRACT: Introduction A recent meta-analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide. Materials and Methods All D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression. Results A total of 4420 deaths occurred in 49,717 people over 371,333 person-years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART-experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months. Conclusions The finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19512. DOI:10.7448/IAS.17.4.19512 · 4.21 Impact Factor
Dataset: HepHIV2014 JL 120
Conference Paper: Elevation in Liver Transaminase (ALT-flares) in Transplant (TX) Recipients: Risk factors and Consequences[Show abstract] [Hide abstract]
ABSTRACT: Background: ALT-flares are frequently observed in TX recipients, but the underlying reason is only known for a fraction. At our hospital, performing a large number of solid organ (SOT) and human stem cell TX's (HSCT), we initiated a program aimed at improving our understanding of the clinical implication from liver injury during post-TX follow-up (FU). Here we report on the incidence and risk factors for ALT flares, and the short- and long-term association with mortality. Methods: Analysis included 1002 SOT (kidney (n=328), liver (170), lung (120), and heart (47)) and HSCT (337) recipients at our hospital, consecutive transplanted between Sept/09-July/13, and with prospective FU ≤ Oct/13. ALT-flares (>1.25xULN) were classified according to grade (NIH) and recognized cause (patient notes review). Poisson regression was used to determine incidence rate ratios (IRRs) of flares and death; generalized estimated equations allowed for repeated flares within individuals. Number and type of flare was included in models as time-updated variables. Results: 501 of 1002 (50%) patients experienced a total of 1197 ALT-flares (46% had 1, 23% 2, and 31% >2 flares) during 1937 person years of FU (incidence 0.62 (95% CI 0.58-0.65)/PYFU). The reasons for the ALT flare was often unknown (50%), due to infections (12%), drug-induced (DILI-11%) or other reasons, and most were grade 2-3 (16% grade 4). Incidence of flares was elevated for all types of TX compared with kidney TX, was high in first 4-12 weeks postTX and plateaued thereafter for all except liver SOT (fig). During FU, 152 recipients died, and the adjusted IRR of death associated with experiencing 1, 2, or >2 (versus 0) ALT-flares were 1.1 (0.6-2.0), 2.1 (1.1-3.7), and 5.1 (3.2-8.1); the excess risk with >2 ALT flares persisted when lagging time between ALT flare and death by up to 6 months, for all types of ALT flares (p<0.05)(except DILI-associated), accounting for competing risk or excluding liver TX patients. Conclusion: ALT flares occur frequently in the first 3 months after all types of TX, often remains unexplained, but if occurring several times is associated with excess risk of death 6 months thereafter. A better understanding of currently unrecognized factor contributing to ALT flares in this setting (e.g. HEV) is warranted.IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
Conference Paper: Regional differences in hepatitis testing, vaccination and treatment in the EuroSIDA studyHepHIV2014, Barcelona; 10/2014
Top Journals
- AIDS (London, England) (24)
- Journal of the International AIDS Society (24)
- The Journal of Infectious Diseases (15)
- HIV Medicine (13)
McGill University Health CentreMontréal, Quebec, Canada
University College London
Londinium, England, United Kingdom
- • Department of Infection and Population Health
- • Division of Medicine
- • Department of Primary Care and Population Health (PCPH)
Royal Free Academy of PMCLondinium, England, United Kingdom
UCL Eastman Dental InstituteLondinium, England, United Kingdom
University of ZurichZürich, Zurich, Switzerland
Universität Bern
Bern, BE, Switzerland
- Institute of Social and Preventive Medicine
University of New South WalesKensington, New South Wales, Australia
King's College LondonLondinium, England, United Kingdom
Hospital Carlos III - MadridMadrid, Madrid, Spain
WWF United KingdomLondinium, England, United Kingdom
University of Bristol
Bristol, England, United Kingdom
- School of Social and Community Medicine
Medical University of Silesia in KatowiceCatowice, Silesian Voivodeship, Poland
University Hospital of LausanneLausanne, Vaud, Switzerland
University of Rome Tor VergataRoma, Latium, Italy
Hospital de Santa MariaLisboa, Lisbon, Portugal
IT University of CopenhagenKøbenhavn, Capital Region, Denmark
Copenhagen University Hospital Hvidovre
Hvidovre, Capital Region, Denmark
- Department of Infectious Diseases
Royal Free London NHS Foundation Trust
Londinium, England, United Kingdom
- Department of Haematology
University of MilanMilano, Lombardy, Italy
University of HamburgHamburg, Hamburg, Germany
Brunel University
London, ENG, United Kingdom
- Health Economics Research Group
Odense University HospitalOdense, South Denmark, Denmark
Karolinska University HospitalTukholma, Stockholm, Sweden
Goethe-Universität Frankfurt am MainFrankfurt, Hesse, Germany
Istituto Superiore di SanitàRoma, Latium, Italy


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RELATED: Workforce Development: Who will run transit tomorrow?
Transportation YOU, a program of WTS International — the association for the advancement of women in transportation — capped off its year-long programs occurring around the U.S. at its flagship DC Youth Summit created for 21 standout young women and their mentors, women who themselves are rising leaders in the industry.
RELATED: Advancing women in transportation: closing the gap (blog)
"The future of the nation's infrastructure isn't just in the budget, it's in the talent and skills of the industry's future leaders. It's imperative to show young girls that sticking with their STEM talents can lead to a challenging and highly rewarding career in transportation. Partnering with WTS on the Transportation YOU program is a forward-thinking strategy will poise the USDOT for upward progress over the next 30 – 40 years," said Bryna Helfer, DOT's Senior Director of Public Engagement.
Other activities included hearing from Victor Mendez, National Deputy Secretary of Transportation; one-on-one meetings with some of DOT's female executives so that the students could ask questions about professional advancement in the industry; a trip to the FAA Command Center for more behind-the-scenes tours and an opportunity to hear from Vaughn Turner, VP of Technical Operations for the FAA's Air Traffic Organization and special panel session with women in management at FAA.
A significant component of the five-day program was a special academic challenge project on the topic of transportation and communities. This year's project, coordinated by a special team from Rutgers and Portland State Universities, introduced the Summit attendees to the impacts of transportation policies and infrastructure on the success of a community. They were split into teams to focus on various considerations for the Anacostia region of Washington, D.C. After group work and hands-on field study in the area the teams presented their findings in formal presentations.
"Each and every part of the Transportation YOU DC Summit is critical to illustrating to our attendees the depth and breadth of opportunities there are in this industry. The hands-on academic elements, behind-the-scenes tours, and networking events with women in various stages of their careers in disciplines across the board have a direct impact on how the industry is perceived as a viable career choice. Several of our Summit attendees have already reported they plan to change their intended study focus as they enter college next year," said Marcia Ferranto, WTS President/CEO.
The Transportation YOU initiative that takes place at the local level across WTS International's 50 chapters was spearheaded by USDOT in partnership with WTS in 2010 with the signing of a memorandum of understanding. The program is a source of scholarship, internship, and networking opportunities. It links young women with professionals in the field and inspires them to pursue STEM-related coursework and exposes them to career possibilities in the transportation industry not typically pursued by women.
The DOT has been unwaveringly determined to support President Obama's call to action to get more students, particularly young women, on track to take the helm of the country's infrastructure needs so that the U.S. can "Win the future" with a robust economy, thriving communities, and success of individuals. WTS was a natural fit for getting the program off the ground.
For more information about WTS International and Transportation YOU, contact Marcia Ferranto at 202-955-5085 or visit www.wtsinternational.org.
The Flatiron Flyer buses, which were supplied by MCI and can carry 57 passengers each, are specially branded with a unique blue-and-sunrise-orange paint scheme designed by RTD and a U.S. 36 corridor stakeholder group.
The Hadley mirror business will remain in Elkhart, Ind., but will relocate from the Hadley site to its own production facility over the next few months. The management, engineering, customer service, administrative and production personnel of the Hadley mirror business will remain with the business and transition to Safe Fleet.
Each year, more and more people look forward to BusCon as a chance to network, learn about new trends and technology, and gain the tools that are necessary to revitalize the way they tackle their own operations.
The countdown clocks were developed in part to address concerns about the overall accessibility of MTA's Bus Time system, which sends wait-time information to riders via text message, a QR code scan, or over a web site.
The report argues that the city should be pushing for the "gold standard" of BRT. That would include a control station that monitors buses and ensures they come at well-spaced intervals and enclosed stops that shelter customers.
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text: On Thu, Oct 25, 2012 at 4:44 PM, helix84 <helix84@...> wrote: > On Thu, Oct 25, 2012 at 11:38 PM, Francis Kayiwa > <francis.kayiwa@...> wrote: >> and I attempted the second one with the same results. So yes I have >> done both and you read that correctly. > > OK. Just pick one. Done. > >> tail /var/log/tomcat6/catalina.out > > The output is too short. It indicates that you just stopped Tomcat. So > delete the file, start Tomcat, wait until it's fully started (you can > watch it using "tail -f /var/log/tomcat6/catalina.out"), then attach > the whole file. Indeed it is too short. A URI to the logs can be found here. https://gist.github.com/3958191 Cheers, ./fxk -- "Beer busts, beer blasts, keggers, stein hoists, A.A. meetings, beer nights..." --Homer Simpson


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Scott Tong is a correspondent for Marketplace's sustainability desk, with a focus on energy, environment, resources, climate, supply chain and the global economy. He services the complete portfolio of Marketplace programming and has reported on several special series including long-term U.S. job creation, U.N. climate talks in Cancun, Mexico, the Japan earthquake and tsunami, the BP oil spill one-year anniversary, and famine in the Horn of Africa. He has reported from more than a dozen countries. Tong joined Marketplace in 2004, serving most recently as the China bureau chief in Shanghai from January 2007 to July 2010. While there, he reported on a special series on the economics of one-child and the 30th anniversary of the one-child policy in China, the Beijing Olympics, the food safety scares in 2007, labor strikes, slave labor, child lead poisoning and baby-selling in China's international adoption program. Prior to joining Marketplace, Tong worked as a producer and off-air reporter at PBS Newshour with Jim Lehrer for seven years, where he produced a special series from Iraq in 2003. Tong received his bachelor's degree in government from Georgetown University. A native of Poughkeepsie N.Y., Tong now lives in Arlington, Va. with his wife and three children. He's an acknowledged soccer dad, and enjoys cooking, cycling (he bikes to work on a regular basis), and running slowly.
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