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Foobot Indoor Air Quality Monitors
The Foobot Indoor Air Quality Monitor has been discontinued. As an alternative we recommend the Blueair Aware™ Air Quality Monitor.
Description of Foobot Indoor Air Quality Monitors
The Foobot is an amazing device that will quickly and simply provide you with information about your indoor air quality (IAQ). Perhaps you sense a problem in your home or business and think that its time to buy an air purifier; time to get a Foobot. Own an air purifier and interested in determining if it is actually improve your environment's air quality? We strongly recommend the Foobot as your solution for knowledge and educated decision making. Not only does the Foobot offer real time IAQ feedback with colored LED lights, it also maps your IAQ trends over time, accessible through a free downloadable App for Apple and Android operating systems. You will be able to see when your air quality is better or worse and can begin monitoring behaviors to determine the cause of your IAQ changes. The Foobot is so intelligent, it monitors all of the rooms in a single story home up to 1100 sq. ft. For larger homes we recommend one Foobot monitor per floor. Not only will you know the airborne particle and gas counts in your home, you will also be able to track the dangerous Carbon Dioxcide levels with Foobot. Additionally, you will receive important air quality warnings from the World Health Organization that apply to the area where you live. Revolutionary and ingenious, the Foobot will change the way you think about air.
Foobot Indoor Air Quality Monitors are ideal for someone who...
- Is interested in a healthier lifestyle.
- Suffer from respiratory issues including allergies, asthma or COPD
- Want to locate the sources of pollution in their home and remove them
- Would like to determine if their air purification system is reducing harmful contaminants.
- Wants free, helpful advise for improving their air quality.
- 24/7 single floor, multi-room air quality monitoring
- Monitors:
- Fine airborne particles count (0.03 pm to 2.5 pm)
- Total VOC level
- Carbon Monoxide level
- Carbon Dioxide level
- Temperature
- Humidity
- Colored LED lights provide hands-free on your indoor air quality
- Free downloadable app and cloud storage for your data
- Free IAQ notifications from the World Health Organization
- Receive predictive data about your habits which effect your indoor air quality
- Optional community interaction for the sharing of data, ideas and solutions
- Dynamically adaptive sensor readings and wifi updates ensure sensor accuracy
- 5 Volt USB power adapter
- Size 0.03 pm to 2.5 pm
- Range: 0 mg/ m3 to 1.4 mg/m3
- Precision: +/-12%
- Sensors: MOS sensor tech. auto motive industry grade; high reliability and stability; low latency detection
- Detects: Formaldehyde, Iso-Butane, Toluene, Methane, Benzene, Carbon Monoxide, Carbon Dioxide, Temperature, Humidity and more
Expert Review: Courtesy of AllergyBuyersClub.comTh Foobot is the first consumer friendly air quality monitor for people interested in not just monitoring their air quality but also learning how to improve the health of their home. The device is attractive, simple to install and simple to understand. There are some intelligent additional features such as tips, community and games that all lead to a single outcome; educating you about the air you are breathing.
If you are concerned about the quality of air inside your home, you will find the Foobot to be an indispensable addition to your life. This seemingly simple device monitors your air for Carbon Monoxide, Formaldehyde, Carbon Dioxide, Methane, Ammonia, Benzene, Iso-Butane, Toluene as well as other dangerous VOCs. If levels reach a level that is considered unsafe, the Foobot will alert you with its colored LED display system. You will use the free App to evaluate long term trends and interact with the Foobot community. Let the Foobot ensure safe air in your home while providing a unique educational tool for the family,
Foobot Air Quality Monitor
|Model Number
|Square Foot Coverage
|Monitors 1,100 sq. ft.
|Power Requirements
|Energy Consumption
|3.2"W x 2.6"D x 6.7"H
|1 lb
|Finish / Color


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Touch a value for a description
A Starter Site is a brand new website. As it has recently been launched, it's unlikely to have traffic, revenue, or page rank.
This is a duplicate website. The content and design are in use on at least one other website.
NO RESERVE Good looking basic SEO optimized health niche related content site ready to make money.
Please describe your business model:
Allofnursingcare.com is a relatively new website Allofnursingcare.com consists of highly useful and informative articles related to its niche i.e. nursing. The kind of content it provides is highly attractive to the readers. With these types of content, the monetization is easy. We all know the fact that search engines like Google always gives extra preference to sites that are rich in high quality content. Therefore since the site offer very interesting and informative content it will naturally attract high amount of traffic towards it.
This is the reason why the potential buyer will have ample opportunity to make a handsome amount of income by monetizing the website through different channels like Ad sense etc. A savvy buyer with good skills in site refreshing and ad placement can easily increase the current income with good layout and testing.
Have you done any Search Engine Optimization?
All the basic elements of SEO have been implemented in the website like sitemap.xml, robots.txt, and Google Analytics.
What is the traffic building potential of this site?
SEO optimization of the website can be made quite easily because all the basic SEO elements have already been implemented in the website. The website has every potential of brining huge amount of traffic with a little bit of effort in the SEO front.
What makes this website better than its competition?
The site has highly useful and informative content based on its niche i.e nursing (Articles=31). We all know the fact that search engines like Google always gives extra preference to sites that are rich in content. Therefore since the site offer high quality, useful and informative content it will naturally will have an edge over its competitors.
Which platform does the website use? Can anyone handle it?
The site is built on Wordpress format which is extremely easy to handle. Even a novice will be able to handle the backend of the website because of it's highly user friendly format. Moreover, we all know the fact that the wordpress format is extremely SEO friendly since it offers several easy to use plug-in like Yoast SEO that are very useful for SEO.
What is the USP of the website?
Besides its SEO friendly nature, the site is built on .com domain which generally gets a huge advantage over the other domain extensions like .info etc. Moreover, the domain name itself is very meaningful and keyword optimized which will give it extra benefit in SEO.
What is the advantage of having a meaningful domain name which is also keyword optimized?
Meaningful domain names which is also optimized with keywords offers extra SEO benefit. Search engines like Google always gives extra preference to domains that are meaningful and keyword optimized. Therefore this domain naturally has an extra edge over its competitors.
What is the search value of the keyword used in the domain name?
Nursing -100K-1M (Low competition)
What are the potential traffic sources of the site?
What is the earning potential of this website?
If the website is properly optimized with SEO and other traffic building efforts and once it starts receiving a substantial amount of traffic it will have an enormous potential to make a huge amount income through Ad-sense other similar sources.
Can the website's traffic be accurately tracked?
Yes, it can be tracked through Google Analytics which has already been incorporated in the website.
Why are you selling the business?
This is one of my line of business, I have several niche websites to sell on flippa are coming up shortly.
Where is your domain hosted?
|Site Established ?
|April 2017
|Built With ?
|Google Analytics Detected ?
|Domain Registered ?
|29 January 2017
|Registrar ?
|Content Unique ?
|Design Unique ?
|Pages In Google ?
|MajesticSEO Inbound Links ?
|SEOmoz mozRank ?
|Alexa Rank ?

subset: commoncrawl


text: Mens Polo Shirts & Mens T Shirts Shop by productShop by brand Sort by: Choose... Name Alphabetical Brand Alphabetical Price Low to High Price High to Low Refine Sort by Name Alphabetical Brand Alphabetical Price Low to High Price High to Low Levi's Slim Fit Crewneck Tees (2-pk) £30.00 Levi's Housemark Tee £25.00 Levi's Slim Fit Crewneck Tees (2-Pk) £32.00 Ted Baker Bates Mouliné Polo Shirt £69.00 Barbour Line Logo T Shirt £29.95 Barbour International Steve Mcqueen Close-Up T Shirt £34.95 Barbour International Steve Mcqueen Distance T Shirt £34.95 Barbour International Steve Mcqueen Varsity T Shirt £34.95 Barbour International Indicator T Shirt £29.95 Barbour Companion T-Shirt £29.95 Esprit Text Printed T Shirt £15.00 Esprit Short Sleeve Nep Striped T Shirt £15.00 Esprit Pocket T Shirt £19.00 Esprit San Francisco Print T Shirt £10.00 Superdry Vintage Logo 1st T-Shirt £24.99 Superdry Classic Cut Pique Polo Shirt £34.99 Superdry Classic Pique Logo Polo Shirt £34.99 Superdry Vintage Logo Emboss T-Shirt £24.99 Superdry Men's High Flyers Reworked T-Shirt £24.99 Superdry Men's Vintage Logo Raglan T-shirt £24.99 Superdry Vintage Embroidery T-shirt £16.99 Superdry Vintage Embroidered T-Shirt £16.99 Esprit 1968 Polo Shirt £29.00 Esprit Patterned Pocket T Shirt £25.00 Esprit Printed Cuba T Shirt £15.00 Esprit Retro-Style Surf Board T Shirt £12.00 Esprit 1968 Ink T Shirt £29.00 Esprit Dyed Berry T Shirt £15.00 Crew Clothing Oxford Pique Polo £39.00 Crew Clothing Classic Crew T Shirt £19.00 Crew Long Sleeved Navy Rugby Shirt £59.00 Crew Clothing Pique Polo Shirt SS17 £37.00 Joules Woody Classic Fit Polo Shirt £34.95 Joules Kielder Slim Fit Polo Shirt £39.95 Joules Filbert Classic Stripe Polo Shirt £39.95 Joules Parkside Long Sleeved Slub T Shirt £39.95 Joules Plaintee T-Shirt £22.95 Joules Onside Classic Rugby Shirt £59.95 Joules Marltee Supersoft T-Shirt £24.95 Gant Contrast Collar Polo Shirt AW17 £70.00 Tommy Hilfiger New York Logo Tee £35.00 Tommy Hilfiger Striped Slim Fit Polo £85.00 Results: 1 - 42 (of 133)|Show all><Goto page...1234 Next page Barbour Barbour International Calvin Klein Camel Active Crew Clothing Esprit Gant Joules Levi's Selected Homme Superdry Ted Baker Tommy Hilfiger White Stuff Our mens polo shirts and mens t shirts effortlessly add style and class to your wardrobe. The mens polo shirts that we provide are perfect for any informal occasion that requires a smart casual look, while our mens t shirts are perfect for the casual look. We provide a wide variety of mens polo shirts and mens t shirts from a range of prominent brands that include Ted Baker, Esprit, Crew Clothing, Gant, Tommy Hilfiger and many more. So with our mens polo or t shirts , you can have the right garment for the right occasion.


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Contentedly enjoying some chat along with a rather excellent Hungarian dessert wine at the BirdLife partner conference in Budapest, I idly checked the BirdGuides news page on my iPhone: it wouldn't load but I just put that down to a hotel wifi connection overloaded with BirdLife partners from 43 countries skyping home. It was a short while later that I stole a quick glance at my email, thereby sealing my fate for the next 30 or so hours. Not only was our web server down, but, chillingly, the duty engineer at our ISP claimed not to be able to find a bootable operating system on it. Website crises habitually fall into two categories: short-term panics that are usually quickly resolved by unflappable engineers, or unfolding disasters of epic proportions. A dreadful sinking feeling told me this was the latter, as I made my apologies and scurried back to my hotel room.
And so it was to be.
Initially our Master Boot Record appeared to be mashed: not a very nice thing to happen to anyone, but fixing it is a routine procedure and most patients go on to live a full and happy life. I suggested to the helpful engineer at our ISP that he might copy off a few vital files for me before patching the MBR "just in case anything went wrong". A short while later he called me back and cheerfully told me he couldn't read any files on the disk, but "not to worry", we'd get them off the most recent backup. Having a long and well-founded distrust of backups, I found it difficult to share his optimism. Hours pass; I can't sleep. Eventually I call to see what the story is: less cheery this time, he tells me that yes they have the backup, but the vital website configuration files are not present. You mean they're missing?!! Yes, but "not to worry", he has passed our case on to the escalation team. Meantime they have worked hard to reinstall the OS and "even upgraded it to the latest version". This a bit like the fire chief telling you that sorry your house has burned down and no, they couldn't save your filing cabinet with the house plans, but don't worry, we've cleared the site and, hey, we even upgraded your septic tank so you're good to go!
So with little sleep and and regretting the glass or two of wine I had so recently savoured, I'm faced with having to rebuild the BirdGuides website configuration more-or-less from scratch. Fortunately Hungarian coffee is just as potent as their dessert wine, and the BirdGuides "escalation team" swings into action. I hang a Do not Disturb sign on the hotel room door. A moment of inspired paranoia a while back prompted me to make a few backups of my own: I remember these, dig them out and get to work. But by lunch time I'm tired and starving and no longer fit to be left in charge of any server, let alone the BirdGuides server. I'm persuaded to take a break, so I wander down to the hotel restaurant and ask if they do a light lunch. The kind waitress tells me she has just the ticket - the Hungarian Business Lunch Special: four courses topped and tailed with an aperitif and coffee. Very, very tempting - but absolutely lethal in my condition, so I have to disappoint her and ask for a sandwich instead, and a very strong coffee. She brings me an aperitif anyhow - I must look like I need it.
Late afternoon, and birdguides.com is emerging from its near death experience. The bird news team is busily catching up with entering the day's news and we're almost ready to go live. Dave and Fiona are frantically testing and making sure all those obscure parts of the website are still functional, all the while blogging and tweeting to keep you all informed. Meantime I'm wrestling with a recalcitrant security certificate. At last the lock symbol appears, and you can confidently buy all those goodies from BirdGuides in the firm assurance that your security is protected by a company called GoDaddy.com. It's time to throw the switch.
Within seconds the traffic on birdguides.com kicks in, and grows, and grows, and grows. It's heartwarming and also rather scary to watch. Will the server cope? Have we forgotten anything? To imagine that so many people have been sitting (im)patiently at their browsers just waiting for this moment! It made my day. I wander down to the restaurant again, but sadly the Hungarian Business Lunch Special is off the menu.
So, as politicians promise after all good disasters, lessons will be learned. We clearly need to improve our resilience. But it is worth saying that our data - your data - was unaffected: it lives on a dedicated RAID array of hard drives and on a separate dedicated database server.
Thanks are due to Adrian at our ISP who toiled through the night to help us, and to my colleagues Fiona and Dave, without whose help and support the whole process would have taken so much longer.
I'm off to the Hortobágyi for a few days and this time I won't be checking my email...


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Usher's 'Chains' Reminds Everyone That Racial Injustice Still Exists in America | Usher | Music | BET
Listen to it exclusively on Tidal.
Listen to it exclusively on Tidal.
The family of Mohamed Bah is calling for the Department of Justice to investigate the killing of the 28-year-old at the hands of the NYPD in 2012.
In a recent New York Magazine interview, Sybrina Fulton, the mother of Trayvon Martin, spoke on how she's used her son's tragic death to help other families of victims of gun and police violence.
The Garner family demands reform of the justice system.
The family of Eric Garner and supporters will gather at Cadman Plaza in New York City on Saturday for a rally commemorating one year since the 43-year-old died after a police officer held him in a chokehold.
Community activists testified in front of the the New York City Council Monday at a hearing on proposed police reforms, amid an urgent push to improve interactions between civilians and authorities following outrage over police-involved killings.
BET.com celebrates phenomenal mothers who were inspired by their children to become leaders tackling issues in their communities.
Plus, Ramarley Graham's family settles for $3.9 million.
Nearly three years after a police officer shot and killed Ramarley Graham at his home in the Bronx, New York, the family has agreed to accept a $3.9 million settlement from the city in a wrongful death lawsuit.
Presented by


text: Home Gallery Video Old Spice Meet the Wolfdog Old Spice Has a Wolfish New Marketing Director You could stand to learn a lot from this hairy guy. Published on Mar 11, 2013 Editor's Pick Marketing directors, look no further -- you've got yourself a new mentor. Wolfdog is Old Spice's newest marketing lead, and he's pretty good at what he does, which includes keeping at hand a host of "cliche business-man decorations" and making a million dollars by doing essentially nothing. Although his wolfish tendencies do come out once in a while, including his urge to eat humans, he never fails to turn even that into the most important marketing lesson of all. Because sometimes, America, you have to devour people. The new film by Wieden & Kennedy Portland promotes Old Spice's new premium line of "guy scents," including Wolfthorn and Hawkridge, which the brand previously shilled in an Alaska-only Super Bowl spot. The video is part of a bigger multiplatform push that sees Mr. Wolfdog commandeering all of Old Spice's digital and social channels this week. Coming up will be more digital shorts in which Wolfdog will entertain surprise guests and engage with Old Spice fans. He'll also be updating via the brand's Twitter handle @oldspice and on his personal blog There's even a tutorial video that shows human and non-human types alike "How to Use Computers," business-person style. Rate this Ad You must be registered to rate the ad. Please Login or Register Now About CreditsDateMar 11, 2013Agency:Wieden + Kennedy PortlandClient:Old SpiceExecutive Creative Director:Susan HoffmanExecutive Creative Director:Joe StaplesCreative Director:Craig AllenCreative Director:Jason BagleyInteractive Creative Director:Matt O'RourkeCopywriter:Jarrod HigginsCopywriter:David NeevelArt Director:Ruth BellottiDirector of Interactive Production:Pierre WendlingSenior Interactive Producer:Mike DavidsonJunior Interactive Producer:Andrew AbrahamDigital Strategist:Jocelin ShalomUX Designer:Jake DoranTech Lead:Ryan BowersDirector:MinivegasLine Producer:Kyle HillExecutive Producer:Dominic BernacchiProducer:Lauren BeckerProducer:Brian BourkeAnimation Director:Maarten BoonTech Lead:Scott Kosman CategoryTVCWeb Film Latest Creativity News on Ad Age Why One Greek Agency Started Selling Its Own Sunglasses and Coffee Terence Neale Joins Park Pictures, Biscuit Adds Errol Morris McDonald's Delivers Long-Lost Sauce to Crazed 'Rick and Morty' Fans On Twitter Related work Old Spice: Simu-Date-Her Date Simulator Wieden & Kennedy Portland Old Spice: Answers Old Spice: Endless Quest Wieden + Kennedy Portland


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Coinciding with the tenth anniversary of Bushwick Open Studios, Making History Bushwick is a 400 page hardcover book written, edited and published by the core collective members of Arts in Bushwick, the facilitators of the annual arts event in Brooklyn, New York.
The glossy 9×9 inch hardcover is available on Amazon and features 400 pieces of art by 405 artists, submitted as part of an open call exhibition in Bushwick in spring of 2015.
The book launch party will be hosted September 30, 6-9pm, the opening night of Bushwick Open Studios 2016, at Arts in Bushwick's official group gallery show Seeking Space: Making the Future, at David&Schweitzer Contemporary, featuring Arts in Bushwick's seventh annual open call of work, this year including 305 local artists.
To introduce the art in the context of its geography, Making History Bushwick shares historical ephemera from a nascent and maturing arts organization, following its growth trajectory through ten years of volunteer artist-coordinators and community builders. The timeline turns to the historical record of Bushwick and moves into a deep archive of stories from ten years of Arts in Bushwick's existence and some of the problems posed by organizing arts events that create influence in a rapidly gentrifying community.
Making History Bushwick was made not just in celebration of our organizational anniversary, the amazing and creative talent that has associated with Arts in Bushwick and our neighborhood, but as a way to document, question and understand our history, experience, place and current events of our beloved space in context.
As a collective, Arts in Bushwick's principal asset is our ability to empower a socially responsible group of intersectional humans to create art and showcase it to our community and beyond through projects like . What becomes apparent in the front of the book is that our greatest vulnerability as an arts collective is when we ignore the role that artists, and our art plays, whether we like it or not, in how the neighborhood, and its economy, have changed over time. Furthermore, how this negatively impacts the lives of local community members and eventually also displaces the artists who created value for real estate development.
The conversation sheds light on the difference between being merely 'open' and actually 'inclusive' of existing communities and the role art plays in the geography and culture of a changing urban landscape and economy. While it is crucial to recognize the potential and inherent influence of artists, technology and creative manufacturing to our local economy, Arts in Bushwick challenges itself, and arts organizations everywhere, to be responsible for building accessible, equitable and sustainable new economies and begin to build alliances with all community stakeholders.
Arts in Bushwick strives to have this open, and often difficult, conversation because we believe art is political, it is revolutionary, and it can and should be used to integrate and intersect the lives of all members in the Bushwick community, past, present and future. We feel ours is a local example we can share through media that will ring true for many people around the world.
Making History Bushwick is a first-of-its-kind document, presenting a contemporaneous snapshot of a vital and growing arts community in the heart of New York City. With more than 400 artworks, essays by noted writers, critics, community activists and members of the thriving Bushwick scene, the book presents an alternative, inclusive, present-tense model for history making. The handsome full-color hardcover volume is the first publication from Arts in Bushwick, 488 pages with a limited edition of 2000 copies.
The art work in the book comes from a groundbreaking exhibition. In May 2015, Arts in Bushwick organized the largest exhibition in its decade long history, including 402 artworks from 405 artists, all drawn from an open call which collected high resolution submissions for the book on artsinbushwick.org. Artists had to self-identify as part of the Bushwick art community and donate their work. The exhibition culminated in a spectacular benefit gala, where the entire show was offered for sale in a raffle style and 260 of the 402 works were sold. The money raised at the gala, $32,000, was used to self-published AiB's first book.
The book was launched September 30, 2016 as part of the festivities for the tenth annual Bushwick Open Studios. Making History Bushwick starts with a collection of published articles that combined with testimonies from key past volunteers describing the history of our all-volunteer organization. Also included are a collection of texts and works on displacement and gentrification that illustrates the paradigms and conflicts that Arts in Bushwick grapples with. The book concludes with a complete catalogue by artworks from the 2015 Making History show.
Contributing writers include James Panero, Hrag Vartanian, Tom Angotti, Loren Munk, Robin Grearson, Aniela Coveleski, Nicole Brydson, Anthony Rosado and many more. A few of the 400+ artists included are Rico Gatson, William Powhida, Tamara Gozales, Meryl Meisler, Deborah Brown, Meg Hitchcock, Lori Ellison, Etty Yaniv, Don Pablo Pedro.
Included below are a few brief excerpts from the book and the introduction can be read on our blog.
From Chloë Bass, artist, co-lead organizer of Arts in Bushwick 2007-2011:
[It] Feels important to me in terms of artistic practice as well: A studio visit shouldn't be a sales pitch; it should be a direct and frank conversation about the way the artist has been working, the results of the work, and how the visitor feels about that process and those results. I hope that this sentiment of reachability, humanity and direct connection persists as Arts in Bushwick continues to grow and change. I value the flexibility of the organization's structure because it offers opportunities for the results the public sees to reflect the people who are doing the work at any given time. Simultaneously, I hold fast to the "good neighbor policy": it's great to bring visibility to Artists and an Arts Community (writ large). That can provide strength, in a certain way. But the most important work we do is not at the large scale, it's at the small: person-to-person and neighbor-to-neighbor.
From Five Things You Can Do About Gentrification in New York City by Tom Angotti, 2013:
TALK TO PEOPLE on your block and in your neighborhood. If you are a gentrifier, talk to the people getting gentrified. If gentrifiers are moving in and you're afraid you're going to be pushed out, talk to the gentrifiers. If we don't talk with each other we can't work together and if we don't work together gentrification will proceed unchecked. Talk, argue, become friends or enemies, but if we ignore each other it will only deepen the divide and make it harder to change anything. These connections are the best foundation for building alliances and creating community coalitions that can stop displacement and protect residents and businesses. Too many people get outraged at what's going on and never talk to anyone else about it, least of all the people who are "different." The people united will never be defeated!
From Making History Bushwick, by James Panero, 2016:
Just as with other historical arts neighborhoods, Bushwick will one day cease to be a place of artistic relevance, not necessarily as artists are pushed out, but as non-innovators push in, diluting the spillover of knowledge and diverting the flow of innovation to the next arts neighborhood. But as new spaces may give rise to new ideas, history is also lost in such transitions, which is why the artists of Bushwick rightly regard documentation as among their most important and lasting creations..
From History by Exclusion, Illuminating The Dark Matter of the Art World by Loren Munk, 2006.
Maybe now we may begin to question what is art, who gets to decide and what is the artist's place within society? As self-selected members of the art world, it is time we declared, "we are our own art history."
Each year, Arts in Bushwick organizes an exhibition and benefit raffle of locally produced art to raise funds for the all-volunteer organization. Previously a one-day benefit event, Making History was a three-week exhibition at the gallery Storefront Ten Eyck that began on April 19, 2016 and concluded with a raffle of the work on May 10, 2016.
Each work was submitted to the show through artsinbushwick.org and represented in an online gallery, which became the basis of Making History Bushwick. The pieces sold at the price of one $200 raffle ticket. Buyers chose the works they would take home when their number was called from a hat.
Fundraising at this event created the budget for the publication of Making History Bushwick, and the front of book text was contributed by Arts in Bushwick's volunteers or reprinted with permission from sources that have written the first draft of recent art history of Bushwick.
Bushwick, Brooklyn has grown to include a highly concentrated community of artists, in part due to the annual Bushwick Open Studios fair, facilitated by the volunteer collective Arts in Bushwick. Recognized by art historians, critics, buyers, gallerists, and other artists across the globe who visit over 1,000 art studios, 60 gallery and performance spaces, and myriad murals packed into two square miles, the creative energy of the neighborhood is currently unrivaled, collaboration sometimes unavoidable—within certain spheres—and the pace of change in the area utterly overwhelming.
Over 1,200 artists registered for, and many more participated in, Bushwick Open Studios 2015, the 9th year of operation. Arts in Bushwick has also facilitated dozens of exhibitions, community programs, educational events, panels, blog coverage of the neighborhood, and year-round opportunities beyond the visual arts.
After 2015, the collective took a step back from operations to examine whether it was meeting its original goals of being inclusive and self-sustaining, and began a series of difficult internal conversations about its purpose and mission.
The core re-emerged in 2016 announcing changes to the Bushwick Open Studios dates, moving from June back to October, and hosted a town hall discussion with members of the Bushwick community about the future of the organization. Core members discussed goals to continue to produce popular events, all year around, while also breaking down the silos that separate us by class and culture through creating equitable visibility in the local community. The core also voted to stop producing a printed catalog to reduce waste and focus more attention on creating digital visibility for artists in Bushwick.
This new digital media, run and supported by members of the community, created the foundation for receiving the large scale of art submissions featured in Making History Bushwick. With sustaining membership levels for individual artists, galleries, non-profits, and small businesses, the collective seeks to create equitable visibility on a community platform where members can contribute public information about events, blog posts, classified ads, real time connection, all year around, in addition to facilitating open call submissions and event listings for the annual open studios.


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Tag: awkword
Awkword New Single Angels ft Jasiri X, MK Asante and Voli
Our man Awkword returns to Hip-Hop Kings with his new single "Angels" in typical thought-provoking fashion. Awkword New Single Angels also features Jasiri X, MK Asante and Voli.
We wouldn't expect anything else from Awkword, as "Angels" touches on subjects such as homelessness, police brutality and other socially conscious topics. We rely on Awkword alongside a handful of other artists to brings these discussion points forward in music. With help from Jasiri X, MK Asante and Voli, Awkword New Single Angels adds to the rappers impressive discography. Awkword has made the single available as a free download to fans.
Awkword continues to work hard in his mission to spread Hip-Hop globally. We're excited to hear the forthcoming music which will inevitably reach us as we approach 2017. Make sure you follow Awkword on Twitter (@AWKWORDRap) and you can listen to Awkword New Single Angels ft Jasiri X, MK Asante and Voli on the audio player below.
Category: Music
Awkword Cruel Intentions Remix ft Skyzoo, Big Pooh and Frank Drake
Our man Awkword returns to Hip-Hop Kings with a remix of the excellent single "Cruel Intentions." The Awkword Cruel Intentions Remix has been re-worked by Frank Drake and features Skyzoo and Big Pooh.
The original Cruel Intentions track was shared by Hip-Hop Kings just under a year ago, and marked the one year death of a mutual friend (Praverb the Wyse). The track was taken from the #PTheWyseVol2 tribute album (presented by Kyle W.Knapp) and was a HipHopDX premiere at the time. One year later, the talented Frank Drake shares his production abilities for an official remix. Awkword Cruel Intentions is also available to stream from the audio player below.
Awkword has also released his "Best of Awkword" mixtape which the remix features on. The project is available to download from Bandcamp and boasts an impressive 26 tracks. I've posted the official track listing below.
1. Intro
2. Words [prod. by Trilian (Serbia)]
3. Faking the Funk [prod. by Anno Domini]
4. Untitled [prod. by Cletus (Italy)]
5. The Dating Game (Remix) [prod. by DJ BrainDeaD (Israel)]
6. Notes from a Different Kitchen [prod. by The White Shadow of Norway]
7. It's Not Possible [prod. by Recluse Crew (Finland)]
8. I ft. DJ Dyllemma [prod. by ATG]
9. Interlude
10. Black & White [prod. by Audible Doctor]
11. The People's Champ [prod. by J. Glaze]
12. That Shit (Remix) [prod. by MistaSweet (Netherlands)]
13. Back to BK [prod. by Tone Spliff]
14. Cheers
15. Whose Streets? [prod. by Delegation of Sound (Netherlands)]
16. Wild Wild East [prod. by The White Shadow of Norway]
17. Untitled ft. Block McCloud [prod. by Cletus (Italy)]
18. Got Class? [prod. by Fresh Nerd]
19. Bars & Hooks ft. Shakespeare [prod. by Harry Fraud]
20. The Black Book [prod. by Blended Babies]
21. Go! ft. Maya Azucena [prod. by Domingo]
22. Gas Land (Frack Off) [prod. by Numonics]
23. Wake Up ft. Nif Monroe (Rough Mix)
24. New York Minute (World View Remix) [prod. by Harry Fraud]
25. I Am ft. Modenine (Nigeria), Five Steez (Jamaica), Holstar (Zambia), L.atasha A.lcindor, Third Eye (Malawi), Wakazi (Tanzania), The Assembly (South Africa), Maka (Nigeria) & DJ J Hart (France) [prod. by Teck-Zilla (Canada)] video
26. Outro
You can listen to Awkword Cruel Intentions Remix below.
Category: Music
Awkword Freestyle (Exclusive)
This is the latest video we have from Awkword, who gives Hip-Hop Kings an exclusive freestyle. During the "Kings of New York" series, the Awkword Freestyle is the latest video to go live on the HHKMusic YouTube Channel.
The Awkword Freestyle is a Hip-Hop Kings exclusive, and was filmed at the same time as the Awkword Interview that we have shared previously. In the interview, Awkword talks about his concept albums (including World View) which was the project we were introduced to. Awkword also talks about his collaborations (Atmosphere, Joell Ortiz, Chaundon and many others) and his upcoming album and gofundme campaign as well. If you've not watched the Awkword interview, check the end of the YouTube video below and we have linked the interview after the freestyle has finished.
As Awkword works on continuing to give back to the community and also give shine to other artists from all other the world, he has setup a gofundme campaign, which will enable Awkword to film and release a music video for "Africa/the Diaspora". The plan is to have rappers from all over the world (including Africa) appear on video in a high quality project which requires support of Awkword's fans. Please check the gofundme campaign and donate what you can to the project.
Subscribe to the YouTube channel and check out the other interviews from our Kings of New York series which include interviews with the likes of Masta Ace, Skyzoo, Torae, Ruste Juxx and many more. You can also search Awkword on Hip-Hop Kings to view plenty of previous tracks we have blogged and shared. You can watch the Awkword Freestyle on the YouTube player below.
Category: Exclusive
Awkword – I Am (International Collaboration)
DOWNLOAD | Awkword – World View
We have an international collaboration from Awkword titled "I Am". Guest appearances on the record come from the likes of Modenine, Five Steez, Holstar, Latasha, Alcindor, Third Eye, Wakazi, The Assembly and Maka. In a continual effort to connect us all through Hip-Hop music, in the first time in history, artists from every continent on earth feature on the same album. The single has been uploaded to the official soundcloud page.
Awkword has connected with Nigerian-born Canadian producer Teck-Zilla, Nigerian songstress Maka and French DJ J Hart to recruit an All-Star cast of artists to join him on the "I Am" Global Posse Cut, including Latasha Alcindor (USA), Holstar (Zambia), Wakazi (Tanzania), Five Steez (Jamaica), Modenine (Nigeria), The Assembly (South Africa), and Third Eye (Malawi). Fans can download World View (special bonus disc) on the link listed above.
You can listen to "I Am" on the soundcloud player below.
Category: Music
Awkword – When the Soldiers Fall
PREVIOUS | Skyzoo, Rapper Big Pooh and Awkword – Cruel Intentions
I would like to share the new track from Awkword titled "When the Soldiers Fall". Despite me posting this a few days after Veteran's Day (the inspiration to this track), Awkword is regularly featured on Hip-Hop Kings and is becoming a fan favourite with his continual release of quality music. Awkword shares the new single "When the Soldiers Fall" by uploading to his official audiomack website. Awkword explains the track was recorded 10 years ago, and of course Veteran's Day was the perfect time to release it. Please search Awkword in the Hip-Hop Kings archives, and you can listen to Awkword – When the Soldiers Fall on the audiomack player below.
Category: Music
DJ J Hart ft K.Sparks, Awkword and Shakespeare – Love is Better
DOWNLOAD | DJ J Hart – Passport E.P
Taken from DJ J Hart's "Passport E.P" this is track 15 titled "Love is Better". DJ J Hart teams up with K.Sparks, Awkword and Shakespeare for "Love is Better" which is available to listen on soundcloud. The Passport E.P also features guest appearances from Sean Price, Inspectah Deck, J57 and Audible Doctor, and can be downloaded from the link listed above. You can listen to DJ J Hart ft K.Sparks, Awkword and Shakespeare – Love is Better on the soundcloud player below.
Category: Free Downloads, Music
Skyzoo, Rapper Big Pooh and Awkword – Cruel Intentions
DOWNLOAD | Skyzoo, Rapper Big Pooh and Awkword – Cruel Intentions
EXCLUSIVE | HHKMag Tribute to Praverb The Wyse
As we have just passed the one year anniversary of the death of Praverb The Wyse, we have a single to share titled "Cruel Intentions". Taken from the #PTheWyseVol2 tribute album (presented by Kyle W.Knapp), Skyzoo, Rapper Big Pooh and Awkword team up for the Cruel Intentions track, which is the lead single from the project. Shouts to DJ Fonz Solo on the cuts and production by South Africa's Jakk Wonders. 100% of the proceeds from this song and album will be donated to the family of Praverb The Wyse. You can view the artwork, download link and listen to Skyzoo, Rapper Big Pooh and Awkword – Cruel Intentions here.
Category: Music
Awkword ft Joell Ortiz, Wordsworth, Aaron Cohen and K.Sparks – Go! (NYC Remix)
PREVIOUS | Awkword ft Joell Oritz, Atmosphere and Maya Azucena – Go! (Original)
In 2003 we were introduced to Awkword with his signature track "GO!" which immediately caught my attention. Two years later, thanks to Brown Bag AllStars producer Audible Doctor, Awkword has teamed up with Joell Ortiz, Wordsworth, Aaron Cohen and K.Sparks for the Go! NYC Remix. The 2DopeBoyz premiere has received excellent reviews and is definitely worth it's replay value. You can listen to Awkword ft Joell Ortiz, Wordsworth, Aaron Cohen and K.Sparks – Go! (NYC Remix) on the audio player below.
Category: Music
Awkword ft Whatzisface – Aint Yo
DOWNLOAD | Awkword – World View
Releasing music from the vaults, Awkword returns with a 2005 freestyle titled "Aint Yo". Featuring Whatzisface (who forms a duo with Awkword called "The Artasins") the pair present a 10-year old freestyle for fans who may not have heard the track. Please check out the multiple previous Awkword tracks posted on Hip-Hop Kings and support Awkword by downloading his album "World View" from his official website listed above. You can listen to Awkword ft Whatzisface – Aint Yo on the soundcloud player below.
Category: Free Downloads, Music
Awkword – The Ivory Tower
PREVIOUS | Awkword ft Chaundon – Gas Land (Frack Off)
True to his unique and captivating style, Awkword presents a brand new single titled "The Ivory Tower". After being challenged to 16 bars regarding college, Awkword decided to create a full track on the US education system with the help of producer Dominant1 (Malawi, Africa). Please check Awkword's previous singles including HHK favourite "Gas Land (Frack Off)" by searching for Awkword in the archives. You can listen to Awkword – The Ivory Tower on the audio player below.
Category: Music


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Dakin Dream Pets Fish And Chips Cat and Mimi the Octopus Reissued With Tags
Online Auction 68068187
|Online Auction Description
Both of these newer Dream Pets are reissues or reintroductions of the original vintage Fish and Chips Cat and Mimi the Octopus.
The cat is 7 inch tall and the octopus is 6.5 inches tall.
The both have their paper tags and tush tags intact.
Their tush tags read: Dream Pets © Dakin; © Applause; Made in China.
Their paper tags have some of the history of Dream Pets printed on them.
All items are stored in and shipped from a pet-free, but not a smoke-free home.
I only ship within the USA; sorry but no international sales allowed.
Item is considered to be in used condition.
|Item Attributes (provided by seller)
|Contact Seller
|Contact Seller
|Payment Methods Accepted by Seller:
|Shipping Terms
|Buyer pays for shipping expenses
|Seller ships to United States address only.
Please no International buyers.
|Ships From
|80539, Colorado, United States
|Contact Seller For Postage
|Insurance Fee
|Shipping & Payment Details
|I try to ship within 1-2 days after payment is made.
Items paid by personal check are held 10 business days until the check clears at my bank.
Items paid with a Paypal Echeck are held until the check clears in Paypal before being shipped.
|The seller , colorado_native , assumes all responsibility for the contents of this listing


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our EXTRAORDINARY special guests
It's our honor to introduce you to the very special people who will be adding extra inspiration to The Weaving Kind Makerie retreat. Each of these fabulous people have touched our heart and inspired our soul in a unique way and we can't wait for them to share their fabulous gifts with you too.
Meet them below!
A note from Maryanne:
"I will be opening the ceremony by talking you through a special design process that's based on connecting with your emotions and being truly mindful and present in your world. We will then draw on these feelings to create a plan for a weaving that comes not from the inspirational work of others, but from deep within you. Our intention is to make an emotional connection with ourselves as artists, and use that to communicate on a deep level with our audience. Why make something pretty when you can make something extraordinary?"
Maryanne Moodie is a fiber obsessed maker from Australia working between Melbourne and Brooklyn, NY. She divides her time between designing and creating woven wall hangings, developing weaving kits, and teaching sold out workshops across the world. Maryanne is best known for applying unexpected color combinations to her nostalgic designs. She is inspired by the intricacies of vintage textiles, traditional costuming, modern art, and the natural world. Maryanne's work has been featured in New York Magazine, Anthology, O Magazine, Grazia, Interwoven, and online on Design*Sponge and The Design Files; she was also a finalist in the Martha Stewart American Made Awards in both 2014 and 2015.
INTENTION-SETTING MEDITATION: Sarah neubert
Join us in the early morning as Sarah leads us through a guided meditation that builds on the idea of drawing from the well of your soul as a basis for your creative work. This meditation is designed to help you explore your inner world, release creative blocks, and use your own thoughts, emotions, and questions as touchstones for your weaving practice.
Sarah Neubert is the founder and facilitator of The Weaving Kind. Through her own weaving work she has experienced much healing and personal growth, and is passionate about helping other weavers tap into community and discover the medicine of fiber.
More inspirational guest announcements coming soon!


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Ethnic Style Jewellery: Create a Bold Print Applique Bangle
Fiona Szabo, Maker, Craftivist, Lover of Bricoleur
- 0.5x
- 1x (Normal)
- 1.25x
- 1.5x
- 2x
Fabric, Cut on the Bias2:50
Assembling Adornments1:44
Gluing the Fabric3:49
Using Bondaweb, Securing the Lining2:30
Finishing Touches2:54
About This Class
Welcome to DIY applique jewellery making.
This stylish bangle workshop will show you how to adorn printed fabric to create a beautiful, bold print, ethnic style bangle.
Using a simple formula, I will show you how to design and produce a wonderfully iconic piece of statement jewellery. The techniques you will use are all very accessible. This class is aimed at a general level, requiring just basic hand-sewing skills, simple knitting skills (optional) using materials such as brocade fabrics, felt,ribbon, beads and gilt details, which you will assemble to transform a bangle.
- The composition of the piece includes floral or geometric inspired applique.
Follow my Pinterest inspiration board help you find further inspiration and join me in this quick DIY fun project.
I look forward to unique and inspired jewellery making with you !
Class Projects 1 See All
4 of 4 students recommendSee All
I really enjoyed this class. Fiona is a good teacher and the steps she outlined were easy to follow and taught with panache.
Fiona Szabo is a textile based jewellery designer and craft tutor.
As a modern-day maker, Fiona utilises eclectically sourced materials, along with treasured items, turning them into into statement pieces. Fiona feels that there is a very creative model at the heart of creative reuse and re-making – it is a place that affords a genuine value to materials.
Fiona began her career in textiles and design upon entering a national competition to win a job with the celebrated British fashion icon, Zandra Rhodes, where she made it to the finals of the competition. Her designs were modelled in front of TV cameras at London's Camden Palace, filming was for the 1987 Fashion Show Series, The Clothes Show. From there she gained a place at the fashion and textiles degree course at Brighton University and went into community arts and teaching as a freelance maker. Her textile based jewellery work has been a recent evolution.
Fiona regularly shares her creative ground as a maker and project organiser at The Knitting Bug at the Hub, a neighbourly knitting group and her co-founded creative collective, Remade In Brighton.
Find out more about her work at www.fionaszabojewellery.wordpress.com and follow her remaking community news at www.remadeinbrighton.org.uk
#fionaszabo on Instagram


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A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension.
To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients.
A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls.
We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD.
The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83).
The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension.
Cystic fibrosis (CF) is a recessive monogenic disorder characterized by multi-organ involvement and clinical heterogeneity that is incompletely explained by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene.1 Patients with CF, including those homozygous for DF508, exhibit a range of lung disease severity, and genetic variability in non-CFTR genes contributes to risk for severity of pulmonary disease.2–7
Intrinsic abnormalities in the CF liver reflect loss of CFTR (Cl− channel) function on the apical membrane of cholangiocytes.8,9 This dysfunction is predicted to result in defective (sluggish) bile flow, and is associated with a cholangiocyte-induced inflammatory response with activation and proliferation of hepatic stellate cells, which results in cholangitis and fibrosis in focal portal tracts.10–13 However, only a small fraction (~3–5%) of CF patients develops severe liver disease characterized by cirrhosis with portal hypertension (CFLD)1; thus, non-CFTR genetic variability may contribute to risk for severe liver disease.14–17
To determine the association between non-CFTR genetic polymorphisms and severe liver disease in CF with portal hypertension (CFLD), we studied 9 functional variants in 5 genes previously studied in CF liver disease, including α1-antitrypsin (also known as α1-antiprotease, α1AP, SERPINA1)18, angiotensin-converting enzyme (ACE)19, glutathione S-transferase (GSTP1)20, mannose-binding lectin 2 (MBL2)21 and transforming growth factor β1 (TGFB1).19 Our initial study compared polymorphic genotypes in these candidate modifier genes in CF subjects with CFLD and "control" CF patients (without CFLD, who were at least 15 years of age). We tested our initial findings in a second study in different populations of CF patients with and without CFLD.
Of the 158 CF patients evaluated for severe liver disease (CFLD; portal hypertension; enrolled 1/1999–12/2004), there were 128 patients who fulfilled criteria from 22 CF Centers in 10 countries (Australia, 8; Canada, 17; Czech Republic, 17; Germany, 3; Italy, 28; Netherlands, 1; Scotland, 2; Slovakia, 4; Turkey, 4; and U.S., 44). For patients without 2 defined mutations in CFTR, we tested further, using a panel of 70 mutations (Tm Bioscience/Luminex CFTR mutation detection assay). After genotyping was complete, >95% of CFLD patients with 2 defined mutations in CFTR had 2 pancreatic insufficient (PI) mutations (eTable 1). The 843 control patients (CF patients without CLFD) were enrolled from the U.S. (759 patients from 42 Centers) and Canada (84 patients from 32 Centers). The majority of the CF controls were ascertained from the GMS Lung Study population (DF508 homozygotes; 92.6%)5, Most of the other controls had biallelic PI mutations (see online supplement, Methods). These controls without CFLD were ≥ 15 years of age (1 SD above the mean age of diagnosis of CFLD), in order to exclude younger patients who might have occult liver disease.
Of the 191 CF patients evaluated for CFLD (portal hypertension; enrolled 1/2005–2/2007), there were 139 CF patients who fulfilled criteria from 35 CF Centers in 10 countries (Argentina, 5; Australia, 5; Canada, 24; Chile, 1; France, 9; Ireland, 8; Israel, 7; Italy, 14; United Kingdom, 4; and U.S., 62). The percentage of PI CFTR genotypes in CFLD subjects was similar to those in the initial study (eTable 1). The 1088 control patients (CF patients ≥ 15 years without CFLD) were ascertained from five countries (Canada, 391 patients from 32 Centers; Czech Republic, 30 patients; Ireland, 6 patients; Italy, 71 patients; and U.S., 590 patients from 54 Centers). The majority of the CF controls had 2 PI mutations (93.5%; mostly DF508/DF508 62.8%) (online supplement, Methods).
All patients had a diagnosis of CF, confirmed by sweat test and/or CFTR genotyping. CFLD was defined as cirrhosis in patients ≥ 2 years of age, confirmed by imaging (ultrasound, CT, MRI) showing hepatic parenchymal abnormalities of portal hypertension (esophageal varices, portal-systemic collaterals, splenomegaly) in the absence of another cause for liver disease. Data were independently reviewed by 2 hepatologists (P.R.D. and S.C.L.) with experience in CFLD to ensure inclusion and exclusion criteria were met, using case report forms, radiology and endoscopy reports, and clinical notes. When there was no consensus, the reviewers requested additional information to clarify the diagnosis of CFLD. No patient was excluded because of race or ethnic background, which were subject-defined.
We excluded 30 (19%) and 52 (27%) subjects originally submitted for the initial and replication studies, respectively, with a presumed diagnosis of CFLD, because they had milder liver disease without portal hypertension, or inadequate documentation. For the 47 patients with confirmed CFLD who had a liver transplant (26 in initial study; 21 in replication study), source documents were obtained from dates prior to transplant. Exclusion criteria for the CFLD group included portal vein thrombosis or other causes of liver disease (alcohol abuse, biliary atresia, clinically significant viral hepatitis, use of parenteral nutrition, and Wilson disease). The study was approved by the Institutional Review Boards of all participating institutions and written informed consent was obtained.
In common with previous reports, we found the mean age of diagnosis of CFLD (first documentation of portal hypertension) to be 10.6 (± 5.4) years (eFigure 1).15,22–25 The diagnosis of CFLD was first established after the age of 30 years in 7 subjects (ages of 32, 33, 35, 40, 43, 44, and 47 years), which is ≥ 4 SD above the mean of the normal distribution. Therefore, these patients were excluded from the genetic analyses (4 from the initial study, and 3 from the replication study).
Patients received a unique identifier code, and data was stored in a secure database in the UNC Bioinformatics Center. Clinical data on standard case report forms included self-reported race/ethnicity, pancreatic exocrine status, medical history, physical examination, laboratory blood work values, and abdominal radiology reports. In addition, we reviewed the following procedure reports if available: liver explant pathology (from liver transplant), liver biopsy, endoscopy and colonoscopy.
DNA was extracted from peripheral blood leukocytes using standard protocols.26 Genetic polymorphisms were determined by direct sequencing, by microsphere-based genotyping using Illumina BeadArray™ technology (San Diego, CA) and by site-directed mutagenesis (online supplement, Methods).
Immunohistochemistry with polyclonal rabbit anti-α-1 antitrypsin antibody and monoclonal mouse anti-CD68 (clone KP1) antibody (Dako Canada, Ontario, Canada), was performed on the Benchmark XT™ auto-immunostainer (Ventana Medical Systems, Tucson, AZ) at dilutions of 1:3000 and 1:5000, respectively. Immunodetection was performed using the Ventana, i-VIEW DAB, LSAB kit. Tissue sections were dewaxed, enzyme pretreated for α-1 antitrypsin, heat epitope retrieved for CD68, peroxidase, and endogenous biotin blocked using Ventana proprietary reagents. Sections were hematoxylin counterstained for nuclear detail (eFigure 2).
Genotype distributions were tested for consistency with expected Hardy-Weinberg equilibrium (HWE) proportions for cases and controls in the initial, replication and combined studies, using all subjects and then restricted to Caucasian subjects, using the PLINK software package (version 1.03; http://pngu.mgh.harvard.edu/~purcell/plink/).27
For the initial study, the association between polymorphisms and CFLD was assessed using Cochran-Armitage trend tests.28 All tests were 2-sided and unadjusted P values are reported, along with P values that were significant (P<0.05) after Bonferroni (adjusted for 9 tests) correction (appended to Tables). Analyses were performed using all samples, and only Caucasian samples.
For the replication study, the association between 2 polymorphisms from the initial study (SERPINA1 Z allele, and TGFB1 codon 10) and CFLD was assessed using Cochran-Armitage trend tests. Initial and replication samples were subsequently combined and analyzed for the SERPINA1 Z allele using Cochran-Armitage trend tests and logistic regression models (online supplement, Methods). Varying levels of covariate adjustment in the logistic regression models were made for ethnicity (as a 5-level categorical variable for all samples), gender, CFTR genotype and TGFB1 codon 10 genotype. Tests of interactions were performed to assess whether the odds of CFLD differed between males and females by SERPINA1 genotype. Odds ratios (and corresponding 95% confidence intervals) and uncorrected P values are reported. Bonferroni correction was applied to assess overall statistical significance in the replication and combined analyses (adjusting for 2 tests in the replication and 9 tests in the combined sample). Analyses were performed separately, using all samples and then using Caucasian subjects only.
Analysis of variance models were used to assess whether gender, SERPINA1 Z allele and CFTR genotype were associated with age of diagnosis of CFLD in the combined sample. Data were analyzed on all CFLD cases and Caucasian CFLD cases with a reported age at diagnosis with covariate adjustment for self-reported ancestry.
To estimate population attributable risk, we used a modified form of Levin's classic formula for population attributable fraction by replacing relative risk estimates with odd ratios, and using the proportion of control subjects carrying the Z allele as an estimate of the probability of exposure29–31 (online supplement, Methods). While this estimate is not exact, given our case–control sampling design (over-sampled older CF patients without CFLD), this estimate should provide a reasonable approximation, due to the modest frequency of CFLD in CF patients (~5%).
Characteristics of the initial group of 124 CF patients with severe liver disease and 843 CF patients without CFLD are shown in Table 1. The CFLD group was younger at enrollment, had more males, and slightly fewer Caucasians. The CFTR mutations in CFLD patients were representative of PI mutations in North American and European CF patients (Table 1, eTable 1)1. The prevalence of meconium ileus at birth in CFLD patients (18.2%) is comparable to the control (no CFLD) group, and typical for the general CF population with pancreatic insufficient CFTR mutations.1
Abnormalities in biochemical tests of the liver (AST, ALT and GGT) were not predictive of CFLD and showed no correlation with markers of hepatocellular synthetic dysfunction, such as international normalized ratio (INR) and serum albumin (Table 2). Preoperative assessment of data available from a subset of patients (n=22) who underwent liver transplant (n=43) showed a similar distribution of abnormal total bilirubin and, albumin values as the non-transplanted patients (Table 2, footnote "b" and "c").
In the analysis of previously studied gene modifiers of liver disease in CF (Table 3), association was seen only for the SERPINA1 Z allele (P=3.3×10−6; OR 4.72, CI 2.31–9.61) andTGFB1 codon 10 (P=2.8×10−3; OR 1.53, CI 1.16–2.03). The SERPINA1 Z allele displayed association for all CFLD patients, but was more prominent in females (eTable 2). Similar results were seen when the analysis was restricted to Caucasians (data not shown). It is noteworthy that small effects for the non-significant polymorphisms would not be detected with sufficient power by this study (see online supplement Methods – Power Analysis; eTable 3). The genotypes and minor allele frequencies for genetic variants in patients without CFLD were similar to those previously reported.5–7,18–21
Based on the associations for the SERPINA1 Z allele and TGFB1 codon 10 (Table 3), we enrolled additional CF patients with and without CFLD to test for replication (Table 4). The characteristics of the replication patients were similar to those in the initial study (Table 1), including the distribution of specific CFTR mutations (eTable 1), prevalence of meconium ileus (23.8%) and liver function abnormalities (Table 2, Table 4).
The association was replicated for the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59); Table 5), but the association was more prominent in males (eTable4), in contrast to the initial study (eTable 2). Similar results were seen when analyses were restricted to Caucasians (data not shown). The association of the TGFB1 codon 10 variant was not replicated for all patients (Table 5) or for males or females when analyzed separately (data not shown).
When the initial and replication populations were combined for analysis using Cochran-Armitage trend tests, the SERPINA1 Z allele displayed very robust association with CFLD (P=9.9×10−9; OR 4.17, CI 2.46–7.05 eTable 4); similar evidence for association was observed in analyses restricted to Caucasian subjects in the initial plus replication populations(data not shown ).
All polymorphisms had genotype distributions consistent with Hardy-Weinberg equilibrium (P > 0.01) in the initial, replication, and combined samples, irrespective of how samples were partitioned according to ethnicity and CFLD status.
We combined the initial and replication groups and performed logistic regression for the SERPINA1 Z allele to estimate the odds of CFLD, adjusting for the covariates of ethnicity, gender and CFTR genotype. Results remained consistent when using all subjects or Caucasian subjects only, with respect to both statistical significance estimates (P=1.5×10−8 or P=6.3×10−8, respectively) and odds ratio estimates (OR 5.04, CI 2.88–8.83 for all patients vs. OR 4.87, CI 2.75–8.64 for Caucasians only). In addition, we saw no evidence for interactions between gender and the SERPINA1 Z allele in all subjects or only Caucasians. Similar results were obtained by logistic regression adjusting only for ethnicity in the complete sample, and models that additionally adjusted for the TGFB1 codon 10 genotype (eTable 5).
We combined the initial and replication groups, and the population attributable risk for the Z allele was estimated to be 6.7% (Caucasians only, 6.6%) (see online supplement, Methods). A similar result was obtained using another method of estimating the probability of exposure, namely the average Z allele frequency of patients from North America, Europe and Australia (data not shown).
The mean and median age of recognition (diagnosis) of portal hypertension in all CFLD patients was ~10–11 years (eFigure 1) and 90% of patients had CFLD diagnosed before 20 years of age. Males had an earlier age of diagnosis of CFLD than females for all subjects (males=8.5 yrs, females=10.5 years; P=0.007), and for self-reported Caucasians (males=9.7 years, females=11.5 years; P=0.027). Age at diagnosis of CFLD was not associated with the presence of the SERPINA1 Z allele, CFTR genotype or self-reported ancestry.
A CFLD subject carrying a single copy of the SERPINA1 Z allele accumulated SERPINA1 protein within hepatocytes adjoining the fibrosed portal tracts, but SERPINA1 protein is not seen in hepatocytes of a CFLD patient without the Z allele (eFigure 2).
Previous studies have suggested that genetic polymorphisms may act as modifiers of liver disease in cystic fibrosis, but these studies were small and phenotyping did not address the development of severe (biliary) cirrhosis associated with portal hypertension.18–21 To increase the likelihood of identifying genetic modifiers that are relevant to the development of severe liver disease in CF, i.e., cirrhosis with portal hypertension, we performed 2 sequential studies in different groups of patients. The initial study involved 5 candidate genes that had previously been studied as modifiers of CF liver disease18–21, and the replication study tested for confirmation of SERPINA1 Z allele and TGFB1 codon 10 variant as modifiers of severe liver disease in CF.
This study had 3 key design features. First, we used rigorous criteria to identify CF patients with portal hypertension ("cases"), reflecting hepato-biliary cirrhosis, and key source documents were reviewed independently by 2 experts to confirm the CFLD phenotype. Second, for CF patients without CFLD ("controls"), we studied only patients who were ≥ 15 years of age, in order to exclude younger patients with predisposition to develop CFLD. Third, we enrolled a large number of CF patients with and without CFLD in order to improve statistical power. For the initial study, ~50% of the CFLD patients were from outside North America and 93% were self-described as Caucasian, and all control CF patients were from North America. For the replication (second) study, a slightly greater percentage of CFLD patients were from North America (63% versus 50%), and there were some control CF patients (10%) from outside North America.
Genetic analyses of the initial cohort showed that a single copy of the SERPINA1 Z allele and each additional copy of the TGFB1 codon 10 C allele were associated with significantly increased odds of CFLD. In the replication study, the SERPINA1 Z allele was confirmed as a modifier of liver disease in CF, whereas the TGFB1 codon 10 variant was not confirmed. It is noteworthy that small effects of the non-significant polymorphisms in other genes would not be detected with sufficient power by this study. The association of the SERPINA1 Z allele with CFLD contrasts to a previous "negative" study, which used less stringent phenotypic markers of CF liver disease, such as liver function tests, which do not correlate with severity of CFLD (portal hypertension).18
When the initial and replication study populations were combined for joint analysis by multivariable logistic regression, the magnitude of the effect of the SERPINA1 Z allele was large compared to most genetic association studies (odds ratio ~5) when gender, ethnicity and CFTR genotype were included as covariates. The strength of the association of the SERPINA1 Z allele with CFLD varied by gender for the initial versus the replication studies, but the overall odds were not statistically different for females and males when all subjects were analyzed. Population stratification is unlikely to account for the results for the SERPINA1 Z allele; the prevalence of the Z allele (1.14%) in our CF patients without CFLD (controls) is similar to that reported for > 85,000 individuals genotyped in pertinent regions of the world (1.20%).32,33 (eFigure 3 and eTable 4).
The mechanism of the SERPINA1 Z allele as an adverse modifier of liver disease in CF patients likely reflects the dual stimulation of hepatic stellate cells by inflammatory mediators from both CFTR-deficient cholangiocytes and hepatocytes containing the misfolded SERPINA1 protein, i.e., these inflammatory stimuli induce hepatic stellate cells to migrate and proliferate in the bile duct regions in a pro-fibrogenic manner.10–13,16,34–38 Bile duct ligation with resultant cholestasis induces more activated stellate cells and fibrosis in the liver of homozygous transgenic PiZ versus wild-type mice, which is compatible with this proposed mechanism of the Z allele as an adverse modifier in CF.39 Further studies are necessary to better define the pathogenesis of the Z allele in CFLD.
The Z allele variant causes misfolding of the SERPINA1 protein, which results in an accumulation of protein in hepatocytes. The most prevalent CFTR mutation, DF508, is also a misfolding mutation, expressed predominantly in cholangiocytes in the liver.8–13,34–38 However, it is unlikely that folding mutations in CFTR and SERPINA1 induce an amplified, adverse effect on the proteosomal degradation pathway, because these 2 genes are predominantly expressed in 2 different cell types in the liver.8,9,34–38 Furthermore, heterozygosity for the Z allele is associated with the risk and progression of a variety of liver diseases, including cryptogenic cirrhosis, biliary atresia, viral hepatitis, alcoholic cirrhosis and non-alcoholic fatty liver disease.37,38,40
By studying a large number of CF patients with well-defined severe liver disease and portal hypertension, we confirmed and refuted some previous observations and discovered new information about the clinical features of these patients. We confirmed that 1) CFLD is more common, and diagnosed earlier, in males; 2) specific CFTR mutations do not correlate with CFLD, but CFTR mutations with residual function (pancreatic sufficient mutations) are uncommon in subjects with CFLD; 3) hepatic synthetic function is preserved for long durations in most CFLD patients; 4) thrombocytopenia due to hypersplenism is common in subjects with portal hypertension due to CFLD; 5) liver biochemical tests are poorly predictive of severe liver disease and portal hypertension in CF and 6) severe liver disease (portal hypertension) develops in pediatric patients by age 10–12 years.14–17,22–25 In addition, we made a striking observation about the age distribution of diagnosis of severe liver disease, whereby the prevalence of severe liver disease does not increase in CF adults, despite progressive increase in longevity; more than 90% of our CFLD patients were diagnosed by age 20, with a mean (and median) age of diagnosis of 10–11 years. We were not able to confirm any association of meconium ileus with CFLD, as previously reported in some, but not all, studies;15–17,22–25,41 the prevalence of meconium ileus in our patients with CFLD (~20%) was similar to that reported for pancreatic exocrine insufficient patients.1
In summary, we studied 2 large populations of CF patients with and without liver disease and portal hypertension in order to test genes previously studied as modifiers of liver disease. Of these candidate genes, only the SERPINA1 Z allele was significantly associated with CFLD and portal hypertension. This polymorphism is relatively uncommon in CF (~2.2% of CF patients are carriers), but the odds ratio for association with severe liver disease is relatively high (~5) for the contribution of a genetic modifier to a Mendelian disorder. Moreover, the estimated population attributable risk among CF patients is 6.7%. From a clinical perspective, a rare variant with large penetrance (such as the Z allele) may be more useful than a common variant with low penetrance, to screen for genetic polymorphisms. The availability of this first marker, SERPINA1 Z allele, for the development of severe liver disease in CF illustrates the possibility of identifying risk factors in CF patients early in life, conceptually as a secondary component of neonatal screening after the diagnosis of CF is confirmed.
This study was supported by grants from the Cystic Fibrosis Foundation (SILVER0Z00, KNOWLE00A0, DRUMM04P0, DRUMM0A00); the National Institutes of Health (NIH R01GM074175, DK066368, GCRC RR00046, CTSA UL1RR025747); the Prince Charles Hospital Foundation; the OWHC/CIHR Fellowship; VZFNM00064203 and NS9488/3 from the Czech Ministry of Health; MIUR, Rome, Italy and Regione Campania, Italy; a Fellowship in Rare Diseases from The Health Research Board Grant (RFRD - 05–07); Genome Canada through the Ontario Genomics Institute (2004-OGI-3–05); the Lloyd Carr-Harris Foundation; and Canadian Cystic Fibrosis Foundation.
Role of the Sponsor: The funding organizations had no role in the design and conduct of the study; in the collection, management, analysis, and the interpretation of the data; or in the preparation, review or approval of the manuscript.
United States of America
Alabama: University of Alabama at Birmingham, Birmingham -- J.P. Clancy; Pulmonary Associates, Mobile -- L.J. Sindel.
Alaska: Providence Alaska Medical Center, Anchorage -- D.M. Roberts and V. Roberts.
Arizona: Phoenix Children's Hospital, Phoenix -- P.J. Radford and N. Argel; University of Arizona, Tucson -- W.J. Morgan and J.L. Douthit.
Arkansas: University of Arkansas Medical Sciences, Little Rock -- D.E. Schellhase, P. Anderson and A. Taggart.
California: University of California, Davis School of Medicine, Davis -- B. Morrissey; Children's Hospital of LA, Los Angeles -- A.C.G. Platzker, M.S. Woo, L. Fukushima and E. Hsu; Northern California Kaiser Permanente Medical Care Program, Oakland -- G.F. Shay; Bay Area Pediatric Pulmonary, Oakland -- K.A. Hardy; Lucile Packard Children's Hospital, Stanford University Medical Center, Palo Alto -- R.B. Moss and C.E. Dunn; University of California-San Diego, Children's Hospital, San Diego -- M.S. Pian; Naval Medical Center, San Diego -- H.A. Wojtczak and L. Burns; California Pacific Medical Center, San Francisco -- N.R. Henig; University of California San Francisco, San Francisco -- D.W. Nielson; Ventura County Medical Center, Ventura -- C. Landon and A. Thompson.
Colorado: Denver Children's Hospital, Denver -- F.J. Accurso; University of Colorado Adult Cystic Fibrosis Program, Denver -- J.A. Nick and M. Jones.
Connecticut: Connecticut Children's Medical Center, Hartford -- C. Lapin and V.M. Drapeau; Cystic Fibrosis Care Center, Yale University, New Haven -- M.E. Egan.
Delaware: Nemours/Alfred I. Dupont Hospital for Children, Wilmington -- R. Padman.
Washington, D.C.
Children's National Medical Center, Washington -- G.B. Winnie and C. George.
Florida: University of Florida, Gainesville -- E.L. Olson; Batchelor Children's Institute, University of Miami, Miami -- M.J. Light; Nemours Children's Clinic - Orlando, Orlando -- D.E. Geller; All Children's Hospital, St. Petersburg -- M. Gondor and J. Flanary.
Georgia: Emory University CF Center, Atlanta -- A.A. Stecenko; Medical College of Georgia, Augusta -- M.F. Guill.
Illinois: Northwestern University Feinberg School of Medicine, Chicago -- S.A. McColley; Children's Memorial Hospital, Chicago -- S.A. McColley and E.M. Potter; Loyola University Medical Center, Maywood -- Y. Chung and M. Garvey.
Indiana: Riley Hospital for Children, Indianapolis -- M.S. Howenstine; Indiana University School of Medicine - Adult Cystic Fibrosis Center, Indianapolis -- A. Sannuti and J. Yeley.
Iowa: Blank Children's Hospital, Des Moines -- D.G. Sloven; University of Iowa, Iowa City -- R.C. Ahrens and M. Teresi.
Kansas: PriVia, The Research Centers of Via-Christi, Wichita -- C.M. Riva.
Louisiana: Tulane University School of Medicine, New Orleans -- S. Davis, B. Quiniones-Ellis and C. Gabor.
Maine: Eastern Maine Medical Center, Bangor -- T.F. Lever and R. Welch; Maine Pediatric Specialty Group, Portland -- A. Cairns and M. Corrigan.
Maryland: Johns Hopkins University School of Medicine, Baltimore -- P.L. Zeitlin and L. Brass.
Massachusetts: Massachusetts General Hospital, Boston -- H. Dorkin; Children's Hospital, Boston -- H. Levy and I. Huntington; University of Massachusetts Memorial Health Care, Worcester -- B.P. O'Sullivan.
Michigan: University of Michigan Health System, Ann Arbor -- R.H. Simon, S.Z. Nasr, C.N. Lumeng and M.E. Ball; Children's Hospital of Michigan – Wayne State, Detroit -- D.S. Toder; Michigan State University CF Center, East Lansing -- R.E. Honicky; Spectrum Health Hospitals, Grand Rapids -- S. Fitch and L. Contreras.
Minnesota: University of Minnesota, Minneapolis -- W.E. Regelmann, J.R. Phillips; Children's Hospitals and Clinics of Minnesota, Minneapolis -- J. McNamara and M. Johnson.
Mississippi: University of Mississippi Medical Center, Jackson -- F.E. Ruiz and K.G. Adcock.
Missouri: University of Missouri, Columbia -- P. Konig; Children's Mercy Hospital, Kansas City -- P. Black and J.D. Weigel; Saint Louis University, St. Louis -- B.E. Noyes and V.L. Kociela; Washington University School of Medicine, St. Louis -- T. Ferkol, Jr. and M. Boyle.
Nebraska: University of Nebraska Medical Center, Omaha -- J.L. Colombo.
Nevada: University of Nevada, Cystic Fibrosis Center, Las Vegas -- T. Brascia.
New Hampshire: Dartmouth Hitchcock Medical Center, Lebanon -- H.W. Parker.
New Jersey: Monmouth Medical Center, Long Branch -- R.L. Zanni; Atlantic Health/Morristown Memorial Hospital, Morristown -- S.B. Fiel and P. Lomas.
New Mexico: University of New Mexico, Albuquerque -- J. Taylor-Cousar.
New York: The Women and Children's Hospital of Buffalo, Buffalo -- D. Borowitz; Schneider Children's Hospital, New Hyde Park -- J.K. DeCelie-Germana; Long Island Jewish Medical Center, New Hyde Park -- R. Cohen and M. Gannon; Columbia University, New York -- E.A. DiMango; Columbia University Medical Center, New York -- A.A. Mencin, S.J. Lobritto and M. Benitez; St. Vincent's Hospital, New York -- P.A. Walker, M.N. Berdella and E. Langfelder-Schwind; University of Rochester, Rochester -- C.L. Ren and A.K. Rovitelli; Upstate Medical University, SUNY, Syracuse -- R.D. Anbar and D.M. Lindner; Samaritan Medical Center, Watertown -- R.G. Perciaccante; Maria Fareri Children's Hospital at Westchester Medical Center, Westchester -- A.J. Dozor.
North Carolina: University of North Carolina at Chapel Hill, Chapel Hill -- M.R. Knowles and M.W. Leigh; Duke University, Durham -- J. Taylor-Cousar, J.A. Voynow and K.J. Auten; Wake Forest University Baptist Medical Center, Winston-Salem -- M.S. Schechter.
Ohio: Akron Children's Hospital, Akron -- G.J. Omlor and D.A. Ouellette; Cincinnati Children's Hospital, Cincinnati -- C.L. Karp; University of Cincinnati Medical Center, Cincinnati -- P.M. Joseph; Rainbow Babies and Children's Hospital, CWRU, Cleveland -- M.W. Konstan; Nationwide Children's Hospital, Columbus -- K.S. McCoy; Children's Medical Center, Dayton -- F. Royce and S. Bartosik; Toledo Children's Hospital, Toledo -- P.A. Vauthy and M.L. Vauthy.
Oklahoma: Tulsa Cystic Fibrosis Center, Tulsa -- J.C. Kramer and S. Hensel.
Pennsylvania: Geisinger Health System, Danville -- C.R. Perez; Penn State Children's Hospital and Penn State University College of Medicine, Hershey -- N.J. Thomas and J.C. Hess; Penn Presbyterian Medical Center, Philadelphia -- D.S. Holsclaw; Children's Hospital of Philadelphia-University of Pennsylvania, Philadelphia -- T.F. Scanlin, R. Rubenstein, C. Murray and M. Skotleski; Drexel University College of Medicine, Philadelphia -- S.B. Fiel, W.P. Sexauer, A. Ko and J. Hillman; University of Pittsburgh, Pittsburgh -- D.M. Orenstein.
Rhode Island: Rhode Island Hospital, Providence -- M.S. Schechter.
South Carolina: Medical University of South Carolina, Charleston -- P.A. Flume; University of South Carolina School of Medicine, Columbia -- D. Brown.
Tennessee: University of Tennessee Health Science Center, Memphis -- R. Schoumacher and B. Culbreath; Vanderbilt University Medical Center, Nashville -- P.E. Moore and B. Slovis.
Texas: Cook Children's Health Care System, Fort Worth -- N. Dambro and J. Garbarz; Texas Children's Hospital - Baylor, Houston -- P.W. Hiatt; Wilford Hall Medical Center, San Antonio -- K.N. Olivier; University of Texas Health Science Center, Tyler -- R. Amaro and L. Macleod.
Utah: University of Utah Pulmonary Division, Salt Lake City -- T.G. Liou.
Virginia: University of Virginia Medical Center, Charlottesville -- D.K. Froh; Children's Hospital of The King's Daughters, Norfolk -- C.E. Epstein; Virginia Commonwealth University, Richmond -- J. Schmidt, G. Elliot, R. Williams, M. Anderson and J. Gadd.
Washington: Seattle Children's Hospital/University of Washington, Seattle -- R.L. Gibson, S. McNamara and K. Worrell; University of Washington School of Medicine, Seattle -- S.M. Moskowitz; Deaconess Medical Center, Spokane -- M. McCarthy, C. Llewellyn and S. Wicks.
West Virginia: West Virginia University, Morgantown -- K.S. Moffett and L.S. Baer.
Wisconsin: University of Wisconsin, Adult CF Center, Madison -- G.A. do Pico and L.M. Makholm; University of Wisconsin, CF-Pediatric Pulmonary Center, Madison -- M.J. Rock and S.R. Osmond; Medical College of Wisconsin, Milwaukee -- J. Biller; Children's Hospital of Wisconsin, Milwaukee -- T. Miller.
Cystic Fibrosis Center, La Plata -- A. Fernandez and F. Renteria.
Prince Charles Hospital, Chermside, QLD -- S.C. Bell; Herston Royal Children's Hospital, Brisbane, QLD -- C. Wainwright and P. Lewindon; The Children's Hospital - Westmead, Sydney, NSW -- H. Selvadurai and K. Gaskin.
Universitair Ziekenhuis Gent, Gent -- S. Van Biervliet.
Alberta Children's Hospital, Calgary, Alberta -- M. Montgomery; Adult Cystic Fibrosis Clinic, University of Calgary Medical Clinic of the Foothills Medical Center, Calgary, Alberta -- H.R. Rabin and J. Leong; University of Alberta Hospitals - Paediatric, Edmonton, Alberta -- P. Zuberbuhler; University of Alberta Hospitals - Adult Clinic, Edmonton, Alberta -- N.E. Brown, Adult & Pediatric Clinics -- J. Tabak; BC Children's Hospital, Vancouver, British Columbia -- A.G.F. Davidson; St. Paul's Adult CF Clinic, Vancouver, British Columbia -- E.M. Nakielna; Victoria General Hospital, Victoria, British Columbia -- B. Habbick; Royal Jubilee Hospital - Adult, Victoria, British Columbia -- I. Waters and S. Wiltse; Health Sciences Centre, Winnipeg, Manitoba -- W. Kepron; Children's Hospital of Winnipeg - Paediatric, Winnipeg, Manitoba -- H. Pasterkamp; Saint John Regional Hospital, Clinic 2, St. John, New Brunswick -- D.N. Garey and G. Bishop; Janeway Child Health and Rehabilitation Centre, St. John's and Health Science Centre, St. John's, Newfoundland -- M. Noseworthy; Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia -- R.T. Michael, A.M. Dale and F.A. Gosse; IWK Health Centre, Halifax, Nova Scotia -- W. Robinson; Hospital for Sick Children, Toronto -- P.R. Durie and M. Corey; Hamilton Health Science Corp. - Adults, Hamilton, Ontario -- A. Freitag; Hamilton Health Science Corp. - Paediatric, Hamilton, Ontario -- L. Pedder; Hôtel Dieu Hospital - Paediatric, Kingston, Ontario -- R. Van Wylick; Hotel Dieu Hospital - Adult, Kingston, Ontario -- M.D. Lougheed and L. Kodiattu; Kitchener-Waterloo Health Center of Grand River Hospital - Adult, Kitchener, Ontario -- M. Jackson; Kitchener-Waterloo Health Center of Grand River Hospital - Paediatric, Kitchener, Ontario -- K. Malhotra; London Health Sciences - Children's Hospital of Western Ontario, London, Ontario -- B. Lyttle; London Health Sciences - Adult, London, Ontario -- N.A.M. Paterson; Ottawa General Hospital, Ottawa, Ontario -- S. Aaron; Children's Hospital of Eastern Ontario, Ottawa, Ontario -- M. Boland, T. Kovesi and A. Smith; Sudbury Regional Hospital, Laurentian Site, Sudbury, Ontario -- V.J. Kumar and S. Zinger; St. Michael's Hospital, Toronto, Ontario -- E. Tullis; Complexe Hospitalier de la Sagamie Hôpital de Chicoutimi, Chicoutimi, Quebec -- F. Simard; Sherbrooke - Centre Universitaire de Sante de L'Estrie, Fleurimont, Quebec -- L. Rivard and A. Cantin; Centre Hospitalier Regional de L'Outaouais, Hull, Quebec -- G. Cote; Montreal Children's Hospital of McGill University, Montreal, Quebec -- L.C. Lands; Hôpital Sainte-Justine, Montreal, Quebec -- J.E. Marcotte; Montreal Chest Institute, McGill University Health Centre, Montreal, Quebec -- E. Matouk; Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, Montreal, Quebec -- Y. Berthiaume, A. Jeanneret and M. Van Spall; Centre Hospitalier de l'Universite Laval, Québec, Quebec -- G. Rivard; Centre Hospitalier Regional de Rimouski, Rimouski, Quebec -- J. Boucher; Centre Hospitalier Rouyn-Noranda, Rouyn-Noranda, Quebec -- N. Petit; Regina General Hospital, Regina, Saskatchewan -- B. Holmes; Royal University Hospital, Saskatoon, Saskatchewan -- D. Cotton and K. Ramlall.
Facultad de Medicina, Clinica Alemana-Universidad del Desarrollo, Santiago -- G. Repetto.
Czech Republic
CF Center, Charles University, Prague -- M. Macek, Jr., V. Vavrova, J. Bartosova and L. Fila.
Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre Cedex -- D. Debray; Hopital Necker-Enfants Malades, Paris -- F. Lacaille; CF Center, University Hospital Robert Debré, Paris -- A. Munck.
Medizinische Hochschule Hannover, Hannover -- B. Tümmler.
Our Lady's Children's Hospital Crumlin, Dublin -- M. Rowland and B. Bourke; Our Lady's Children's Hospital, Crumlin, Dublin -- G. Canny; St. Vincent's University Hospital, Elm Park, Dublin -- C. Gallagher.
Carmel Hospital, Haifa -- J. Rivlin; Shaare Zedek Medical Center, Jerusalem -- E. Picard; Schneider Children's Hospital, Petach Tikvah -- H. Blau; Hadassah University Organization, Jerusalem -- M. Wilschanski, C. Springer and E. Kerem; Safra Children's Hospital, Tel Hashomer -- Y. Yahav and Y. Bujanover.
Cystic Fibrosis Center, Pediatric Clinics University of Genova, G. Gaslini Children Hospital, Genoa -- R. Casciaro; Pediatrics, University of Milan, Milan -- C. Colombo; University of Naples Federico II, Naples -- G. Castaldo, F. Salvatore and V. Raia; Centro Fibrosi Cistica, Verona -- M. Cipolli and C. Castellani.
Erasmus University Rotterdam, Rotterdam -- M. Sinaasappel and D. Dooijes.
Royal Hospital for Sick Children, Glasgow -- S.C. Ling.
Institute of Molecular Physiology & Genetics, Bratislava -- H. Kayserova.
Pediatric Pulmonology, Hacettepe University, Ankara -- U. Ozcelik, N. Kiper and D. Dogru.
United Kingdom
University of Sheffield, Sheffield -- C.J. Taylor and J. McGaw.
Author Contributions: Dr Knowles had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study concept and design: Bartlett, Friedman, Ling, Pace, Zou, Silverman, Wright, Lange, Durie, Knowles.
Acquisition of data: Bartlett, Friedman, Ling, Pace, Bell, Bourke, Castaldo, Castellani, Cipolli, C. Colombo, J. Colombo, Debray, Fernandez, Lacaille, Macek, Rowland, Salvatore, Taylor, Wainwright, Wilschanski, Zemkova, Hannah, Phillips, Corey, Zielenski, Dorfman, Silverman, Drumm, Durie, Knowles.
Analysis and interpretation of data: Bartlett, Friedman, Ling, Pace, Corey, Zielenski, Wang, Zou, Silverman, Wright, Lange, Durie, Knowles.
Drafting of the manuscript: Bartlett, Friedman, Wright, Lange, Durie, Knowles.
Critical revision of the manuscript for important intellectual content: Bartlett, Friedman, Ling, Pace, Bell, Bourke, Castaldo, Cipolli, C. Colombo, Debray, Lacaille, Macek, Rowland, Salvatore, Wainwright, Wilschanski, Corey, Zielenski, Dorfman, Drumm, Wright, Lange, Durie, Knowles.
Statistical Analysis: Wang, Zou, Wright, Lange.
Obtained funding: Bartlett, Friedman, Bell, Bourke, Castaldo, Castellani, Cipolli, C. Colombo, Macek, Rowland, Salvatore, Taylor, Wainwright, Corey, Zielenski, Dorfman, Zou, Silverman, Drumm, Wright, Lange, Durie, Knowles.
Administrative, technical, or material support: Bartlett, Friedman, Pace, Hannah, Phillips, Silverman.
Study supervision: Bartlett, Friedman, Ling, Pace, Hannah, Durie, Knowles.
Financial Disclosures: No financial conflicts were disclosed.
Additional Contributions: We are indebted to the research coordinators from the University of North Carolina at Chapel Hill (Allison Handler*, RN, BSN, MS, CCRC; Lori Jee*, MSN, RN, FNP-C; Sally Wood*, BS; Sonya Adams*, BS; Leia Charnin*, BA; and Sarah Norris*, BS), the Hospital for Sick Children in Toronto (Mary Christofi*, BSc; Jennifer Breaton*, RN, BN, MHSc (C); and Nicole Anderson*, HonsBSc, CCRP), Case Western Reserve University (Colette Bucur*, CNP), and Hadassah University Hospital (Netta Malka*, RN, BSN and Limor Cohen*, RN, BSN); to the University of North Carolina Center for Bioinformatics (Airong Xu*, MD, MSIS; David Fargo*, PhD; and Hemant Kelkar, PhD, director) and Department of Pathology and Laboratory Medicine (Zhaoqing Zhou*, PhD, FACMG) for genotyping support; and Wanda O'Neal, PhD, director of the Molecular Biology Core Laboratory for the Cystic Fibrosis/Pulmonary Research and Treatment Center at the University of North Carolina at Chapel Hill for useful discussion. We are extremely grateful to Beth Godwin*, BA for administrative support and to Sarah Norris*, BS for editorial assistance. In conclusion, we express our gratitude to all the patients and their families for making this study possible.*(Received salary compensation for their contributions)
Additional Information: eTables 1 through 5, eFigures 1 through 3, and supplemental information are available at http://www.jama.com.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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My brother and I are both in college but my parents could only afford to send one of us out of state. My brother does basketball and because big name colleges are starting to look at him, he got to go. I'm happy for my brother but that just makes me wonder, "what about me?" Even though my parents pay for everything my brother buys, he has way more freedom than me. I live at home with my parents. I work a minimum wage job that has no benefits and my coworkers are assholes. Plus my boss only lets me work a couple hours a week. I'm not even sure if this job is worth the drive every day. My community college is incredibly small and I haven't made any friends. I go to work, go to school and come home. I occasionally go to the library. All my friends from high school are off doing there own thing and I'm stuck at home. What can I do to feel less lonely and how can I save up money to move out within a year?
Most Helpful Guy
Some people live good lifes, others are failures. Your brother lives a good life, and you are a failure. Even your parents think so. But you're not alone. I'm a failure too. So is everyone on gag.31|20|0
Most Helpful Girl
I don't know anything about you or your brother, but let's be honest. This is super screwed up. From reading it sounds like they favor him because of his athleticism, especially since you included they pay for everything for him. But let's be objective for a minute. Is there a reason why they wouldn't let you go away? Are you responsible? Do they have reason to worry about your grades? There's likely a reason you're not aware of or that you're not telling us.21|10|0
I am responsible my brother is actually a lot less responsible. I have to watch my younger brother because he is disabled. I know he is my brother but I never signed up to be a parent. Even if I have the money, I can't move out of the house because of him.
That's messed up. But if I were you, I'd try to make the most of it. Find a better job. Excel in your classes. Take great care of your younger brother. Be kind to your parents. While this situation totally sucks, you have the opportunity to grow in character while your brother (if I understand correctly) is learning to be increasingly co-dependant. In four years, you could be surprised how well your life has become.


text:
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The limited first edition comes in a digipak including bonus instrumental CD.
The wait is finally over! Nightwish present a new studio album. "Endless forms most beautiful" is the first Nightwish studio album featuring Dutch songstress Floor Jansen. Due to health problems, longtime drummer Jukka Nevalainen couldn't participate in the recordings, Kai Lahto (Wintersun) will fill in. The renowned evolutionary biologist and atheistic writer / leader Richard Dawkins will be a guest on Nightwish's eighth album.
Tracklist - Endless forms most beautiful
- 1.Shudder Before The Beautiful (Album Version)
- 2.Weak Fantasy (Album Version)
- 3.Élan (Album Version)
- 4.Yours Is An Empty Hope (Album Version)
- 5.Our Decades In The Sun (Album Version)
- 6.My Walden (Album Version)
- 7.Endless Forms Most Beautiful (Album Version)
- 8.Edema Ruh (Album Version)
- 9.Alpenglow (Album Version)
- 10.The Eyes Of Sharbat Gula (Album Version)
- 11.The Greatest Show On Earth (Album Version)
- 1.Shudder Before The Beautiful (Instrumental Version)
- 2.Weak Fantasy (Instrumental Version)
- 3.Élan (Instrumental Version)
- 4.Yours Is An Empty Hope (Instrumental Version)
- 5.Our Decades In The Sun (Instrumental Version)
- 6.My Walden (Instrumental Version)
- 7.Endless Forms Most Beautiful (Instrumental Version)
- 8.Edema Ruh (Instrumental Version)
- 9.Alpenglow (Instrumental Version)
- 10.The Eyes Of Sharbat Gula (Orchestral) (Instrumental Version)
- 11.The Greatest Show On Earth (Instrumental Version)
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It's literal, Nightwish comes back triumphant with this epic and diverse album, with some surprises here and there, like the religiously relevant"Weak Fantasy" or the hunting atmospheric sensation of "The Eyes of Sharbat Gula"; if you're a Symphonic Metal fan, this will certainly please your entire body. However, the one who takes the cake is definitly "The Greatest Show On Earth", just a few other songs on the scene can even get close to this 'opus perfectum' created by master Holopainen. 24 minutes of pure epicness and splendour. At first it's dark and melancolic, then comes a powerful metal riff and later the explotion that makes every Nightwish fan scream at the top of their lungs "WE WERE HERE"; and that's what Nightwish leaves as clear as can be... Indeed, they were here
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text:
POLICE were alerted when a man armed with a hammer shouted threats and demanded a man came out of his home.
Darren Paul Byrne, 38, said to have a drink problem, also started striking the front door with the hammer.
Police arrested him and Byrne claimed the man inside the flat had stolen his phone.
Prosecutor Justin Espie told Flintshire Magistrates Court at Mold yesterday that Byrne was drunk and intended to attack the other man – and therefore the prosecution put the case forward as having a weapon in dangerous circumstances.
Byrne, of Sealand Avenue in Garden City, admitted damage and possessing the hammer following the incident on April 11 and was sent to the crown court for sentence.
He was bailed in the meantime.
The court was told the victim initially rang 999 and said there was a man trying to break his door in.
Byrne shouted at him: "You have got my phone – pass it through the letter box or I will smash your head in with the hammer."
A neighbour also dialled 999 and said there was a man banging on the door with a hammer causing damage and shouting threats.
Police arrived and arrested Byrne, the hammer was seized and he said he had it for his own protection. He claimed the victim had stolen his mobile phone the day before.
Damian Sabino, defending, said his client had a drink problem.
It was his case that the victim had been to his home and had a drink and Byrne believed he had taken his mobile phone.
Instead of reporting the matter to police, his client, in drink, had gone around to try and get his phone back.
The other man had a reputation and Byrne had taken the hammer with him for protection.
"He lost the plot. In his own mind he thought if he did not get the phone back, he would cause damage to the value of the phone.
"This is not a violent vigilante but someone who was betrayed by a man he invited to his home for a drink.
"He realises how foolish he has been."
Mr Sabino stressed there had been no confrontation and he was never in a position where injuries could have been caused.
See full story in the Leader