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New Hampshire's House is considering whether 17-year-olds accused of crimes should be treated as juveniles or adults.
Forty other states and the federal government treat the youths as juveniles. New Hampshire lowered its age from 18 to 17 in 1996, and attempts to raise it have failed over the years.
The House is voting Wednesday whether to reverse the 1996 law.
Supporters argue the teens are still of an age when they can be rehabilitated if sent to the state reformatory instead of prison.
But the state's police chiefs argue the teens should be held accountable.


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I greatly appreciate the accessibility of the Tribeca Film Festival's virtual programming, but there's one film in particular that I'd have preferred to see on a big screen rather than on my laptop: Into the Cold: A Journey of the Soul. Like other sport/nature/travelogue documentaries taking us into remote landscapes, such as Touching the Voidand Encounters at the End of the World, you just want to see those epic vistas as large as possible, hopefully to engulf your vision and let you pretend you're right there with the explorers and filmmakers, even if there's no way you could possibly comprehend how much warmer you are than the people on screen.
Sebastian Copeland, best known for his photography books on Antarctica, traveled to the North Pole last year for the centennial of Robert Peary's first-ever expedition to the top of the world. He was joined by one other person, adventurer Keith Heger, and the two took turns with a camera, documenting the treacherous journey for what resulted in this film. Copeland's goal, other than to achieve something few humans would dare, was to take more photos of icy expanses so that you and I might fall in love with the Arctic region. Because, as he says at the beginning of the film, "we will not save what we do not love."
Yes, Into the Cold is another doc about global warming. Multiple times in the film Copeland remarks that his trip is an anniversary occasion while also sadly noting that the Peary expedition may never see a bicentennial repeat because the ice covering the Arctic Ocean will likely no longer be there to walk on. Some cynics could argue that no one else would want to make the trek after watching Copeland's film. For one, the frost bite, hunger, and arduous terrain depicted is hardly a big sell. And anyway, thanks to Into the Cold, we get to see -- and in the best, most comfortable ways -- experience the majesty of the place without having to actually go there.
In a way, knowing that the ice is quickly melting, Copeland's mission was to take his beautiful pictures and shoot this extraordinary movie to preserve the images for posterity. He'll tell you in his narration, though, that his photographs represent only a small part of what he saw up there. Having myself experienced an iota of what he did -- I merely walked on a Patagonian glacier that he'd likely consider like a tropical beach in comparison -- I do know what it's like to see natural, ever-changing landscapes I'll never be able to properly represent through even snapshots or stories. It makes me think of a favorite line by Rutger Hauer's character in Blade Runner about the uniqueness and transience of memory. What undocumented sights Copeland captured solely with his eyes are like "tears in rain."
Could Into the Cold be even more convincing of the global warming argument than, say, An Inconvenient Truth or The 11th Hour(the film presented by Leonardo DiCaprio, who serves with Copeland on the board of Mikhail Gorbachev's environmental organization Global Green USA)? Perhaps not, but it's much more visually stimulating. Rather than those two docs, Into the Cold, despite being relatively void of characters, continually called to mind Encounters at the End of the World, in part because Copeland's speech pattern in his voice-over narration is oddly similar to that of Werner Herzog's. Ironically, Encounters puts things instead into the perspective that it's humanity that is like tears in rain.
Encounters ends with the paraphrasing of a saying by Alan Watts about how the universe perceives itself through our eyes and ears, and "we are the witness through which the universe becomes conscious of its glory, its magnificence." Into the Cold, meanwhile, concludes with more urgency to be more conscious and connected to the "land that hosts us" and that we must protect not our planet but ourselves from ourselves. No matter what I believe as far as the climate change debate, though, I like to think of Copeland's film and photographs as merely a witnessing of the glory and the magnificence so that both we and the universe may be conscious of and appreciate it, while either we or it still remains.
categories Features, Reviews, Tribeca Film Festival, Cinematical

subset: commoncrawl


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The Complete Book of Questions: 1001 Conversation Starters for Any Occasion - eBook
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As Willow Creek Community Church's key evangelism leader for over sixteen years, Garry Poole is the innovator of seeker small groups and a strategist of creative outreach initiatives. Passionate about reaching people for Christ, Garry and his team have trained thousands of leaders to launch seeker small groups in their own settings. His award-winning book, Seeker Small Groups, provides a detailed blueprint for facilitating small group discussions that assist spiritual seekers with investigating Christianity. He also wrote The Complete Book of Questions, a collection of 1001 conversation starters and numerous group study guides including The Three Habits of Highly Contagious Christians; The Tough Questions Series, and Experiencing the Passion of Jesus (with Lee Strobel) to accompany Mel Gibsons film, The Passion of the Christ. In 2005, it became the first discussion guide ever to receive the prestigious Charles Kip Jordon Christian Book of the Year award. Garry lives in suburban Chicago.
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vprso5 Stars Out Of 5love this bookJanuary 3, 2015vprsoQuality: 5Value: 5Meets Expectations: 5This review was written for Complete Book of Questions, The: 1001 Conversation Starters for Any Occasion.Our family loves to sit down and ask each other these questions. it is fun to hear the answers.
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jasonkpowersDenver, COAge: 25-34Gender: male5 Stars Out Of 5Great for every occasionNovember 16, 2010jasonkpowersDenver, COAge: 25-34Gender: maleQuality: 4Value: 5Meets Expectations: 5This review was written for Complete Book of Questions, The: 1001 Conversation Starters for Any Occasion.I love this book because there's questions for days when you just want to have a general conversation, not too deep, and there's questions to really bring you closer together.
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text:
Dreadful the horse came by his name honestly.
When Dreadful arrived four years ago at Rose Ridge Farm in Rives Township, the thoroughbred stallion had spent a couple of months at the Jackson County Animal Shelter in an animal-rescue situation.
Then nearly 11, he was underfed, untrained and ill-groomed.
"He was covered by what looked like dreadlocks," said Janet Hamilton of Rose Ridge Farm. "He was sick and weak from malnutrition. You could count every rib."
Dreadful. The name fit.
Although not in the business of collecting stray horses, Hamilton felt this one was special.
Hamilton is a Jackson attorney who keeps hunter horses — the kind that jump fences — and teaches riders to compete in horse shows.
Years ago, she helped bring about Dreadful's birth to Silent Signal, a mare owned by one of her students.
Hamilton contacted a thoroughbred breeding farm in Oakland County to arrange for Silent Signal to be bred with a stallion named Treasury Secretary. She was partly responsible for Dreadful's existence.
Given a stall at Rose Ridge Farm, Dreadful began to blossom after a few weeks of habitually voracious eating.
"Once I realized he was going to live, he got all fat and sleek and beautiful," Hamilton said.
Training Dreadful to be a show horse was a failure.
The horse ran beautifully and took fences elegantly, Hamilton said, but was too impulsive.
Dreadful once dragged Hamilton through a pasture. Another time he reared and broke her foot. Then he threw Hamilton while she taught him to canter.
"I went flying so far and so fast, I decided not to get back on him," Hamilton said.
Don't get the wrong idea. Dreadful is not mean.
"He has a sweet disposition," Hamilton said. "He just has a problem controlling his impulses. He cannot help himself. He wasn't raised right."
A year or two after he arrived at Rose Ridge Farm, Dreadful developed a breathing problem thought to be an allergy to something in the pasture.
Knowing it was best to sell the horse, Hamilton learned she could not get breeding papers.
The original owner never obtained papers, and Hamilton found the Oakland County breeding farm, which has since shifted operations to Lexington, Ky., either could not or would not provide documentation a dozen years later.
"He's kind of unmarketable," Hamilton said. "I cannot sell him as a trained horse. I can't sell him for breeding purposes because I can't get papers on him. And now he has this allergy."
Papers or no papers, The Jockey Club — the authority on thoroughbred bloodlines in North America — informed Hamilton its records show Silent Signal was indeed bred to Treasury Secretary in 1994.
Forgive me for using human terms to explain what that means.
Silent Signal is a great-granddaughter of Native Dancer, a legendary racehorse who won 21 of 22 starts. Her uncle was Alydar, who finished second three times in a classic 1978 Triple Crown duel with Affirmed. Her first cousins include Alysheba, winner of the 1987 Kentucky Derby.
Treasury Secretary is the son of arguably the greatest race horse in American history, Secretariat. Dreadful is Secretariat's 15-year-old grandson, and Hamilton said if she ever registers a name for the horse, she'd want it to be Triple Sec (named after the Triple Crown winner).
"It sounds preposterous, but it is 100 percent true," Hamilton said.
Secretariat's amazing story is told in a movie currently playing nationwide. If you see "Secretariat," now you know the horse that rose to the top of the thoroughbred world had a grandson once so down on his luck he stayed at the Jackson County Animal Shelter.
Dreadful has an amazing story, too.


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A 200-pound bear killed by an Upshur County girl is on display at the West Virginia Attorney General's office in Charleston.
Miranda Ware was only 17 when she shot the bear on Dec. 14, 2012, in Randolph County. It is one of 52 bears that were killed that day, officials said. Ware's bear was estimated to have been about 4 years old.
Loaned by the West Virginia Bear Hunters Association, the symbolic state bear is now on display in the east wing rotunda, just in front of the Attorney General's Office. It joins another black bear already on display.
Article Photos
This bear on display at the West Virginia Attorney General's Office in Charleston was harvested by Upshur County resident Miranda Ware.
"It is wonderful to have another bear representing our office and standing proud in the halls of our beautiful Capitol," Attorney General Patrick Morrisey said in a press release. "It is fitting that the state's animal is a black bear because they are strong, resourceful and noble.
"We are honored that Miranda Ware, her family and the West Virginia Bear Hunters Association would be willing to loan this bear to us, so that the entire state can marvel in her beauty."
Ware's bear will remain outside of Morrisey's office for the next year. The black bear that it will join is a permanent display.
Beth Ryan, the communications director for the West Virginia Attorney General's office, said that a new bear will join the other in display each year. The display of bears outside of the office has been a long-standing tradition, Ryan said.
"I know it's been going on for a number of years," Ryan said. "It's fitting because the bear is the state mammal. It's a nice way for people to be able to see up close and personal the state animal.
"A lot of people have never seen a bear in the wild," she said. "While these are no longer bears in the wild, it still is a bear that they can see. It's just a way for people to get to know what a black bear is like in the state."
Ware, who is now 18, is the daughter of Kevin and Mary Ware. She said the bear on display is only the second bear she has hunted. She said that next year, she will be hunting with a group of friends and wants to give them the opportunity to get their own bear.
"I just like the enjoyment of being out in the woods and being that close to such large animals," Ware said, adding that it was her dad's friend that introduced her to bear hunting. "Not many girls bear hunt. My dad has always hunted, and I've always hunted with him."
She said Eric Beck, president of the West Virginia Bear Hunters Association called her dad to ask if he knew of any bears that could be donated for display. She said her father asked her about donating her bear for display, and she was excited about it.
According to the press release, Beck said his group was eager to assist in getting a new bear for display.
"It's our state animal," Beck said. "It's part of our heritage to bear hunt, and we wanted to show people what a majestic and beautiful creature it is."


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In this exercising, I'm going to introduce you to a new panel inside Bridge CS5 and it's this guy right there Export. And it's kind of weird the way it set up frankly. I don't really think much as the interface but it does a really great thing. It allows you to take a bunch of images and convert them to JPEG files. The reason that so incredibly useful is let's say you have a bunch of photographs that you captured to your digital camera's raw file format, and you want to hand off some of them to a client or a friend or a family member, well you don't want to get them a bunch of raw files, because they won't know what to do with them and they might mess them up, better to give them JPEG files which are universally usable.
There are all kinds of applications that support JPEG and they're compressed and smaller and you can shove a bunch of them on a CD and hand it off, that kind of thing. And also those of you who are creating intense layered Photoshop files, you want to show those to a client for approval better to give them a JPEG image. So that they're not overwhelmed, or they don't mess something up. So, here is how this works. I'm going to go ahead and switch over to my 03_open_org folder here inside the Bridge. I'm going to bring out my Metadata panel. It is brought up for me right now.
And I'll click on the flyout menu icon and I'll choose Create Metadata Template, and the reason I'm doing this is because you can assign the Metadata Template to your images as you convert them. So, I'm going to go up here to my right-pointing arrowhead and I'm going to choose Append Metadata and I'm going to choose Winter adventure which is a Metadata Template that I've created in advance. You're not going to be able to do this, because the files contained in the system level of my hard drive, but you'll be able to follow along just the same. I just want you to see that you can do this. Then here inside IPTC Core, notice the Creator is already set to me.
I'm going to go ahead and get rid of Description. We don't need that because the single description isn't going to be applicable to all of these files. I'm going to get rid of Date Created because that certainly isn't going to be applicable. Let's take this Copyright Notice here and update it to 2010 Type & Graphics Boulder, Colorado 80303. Copyright Status is Copyrighted. It could be Public Domain or Unknown as well. All right! Just one other thing I want to confirm, I'm going to go up all the way to IPTC legacy here and twirl it open and I see the Author and the Copyright, I want to make sure this Copyright Info URL is in there.
So, it's just deke.com, although you know what? I'm going to change it to lynda.com/ deke in honor of the fact that we're inside the lynda.com Online Training Library. And I'll go ahead and name this Template Generic Deke, because it would work for a lot of different files, and then I'll click on Save. So, I have now saved out a Metadata Template that I can use for my images. Now, I'll switch over to the Filter panel and notice these File Types here, this auto populated group of File Types. I'm going to click on DNG, and DNG is Adobe's open source Digital Negative format.
That's useful for all varieties of raw images captured by digital cameras from Olympus, and Nikon, and Canon, and so on and so on. But I want you to understand even though this is a great format that the Bridge supports all varieties of raw images out there, and you can apply what you're about to learn here to any kind of raw image as well. All right! So, now I'm going to press Control+A or Command+A on the Mac to select all of these Digital Negatives. Now, these guys would open in Camera Raw and they would require a fair amount of finesse.
So, I don't want to hand them off to an unsuspecting person, I want to give them JPEGs instead. So, we'll go over to Export and I'll go ahead and drag one of these thumbnails on to save for hard drive, which is weird in my opinion, because they are already saved to the hard drive. Why would I want to save them to the hard drive again? That doesn't make any sense, but that's what you do. That's where you start anyway. Then assuming you're good to go, click on this arrowhead right there, and that will bring up this dialog box. Now it's a two-panel dialog box.
It's a very important. So, I'm going to switch over to Image Options that's where you want to start. And it doesn't tell you that you're going to be saving JPEG images, but that's what you're going to be doing. Now, I recommend that you go ahead and save the images out to the highest quality format. Unless you're going to the web or something like that you're trying to post some web graphics, there is no point in using a lower image quality. So, let's go ahead and raise that to 12. And when I say there's no point, my point is that you might as well give your people the highest quality image as possible, and that quality is 12.
Don't just select it Maximize, because that will give you a quality of 10, 12 is your best setting. Now, you can go ahead and down sample your images if you want to, for example, if I choose Manual Size and Constrain to Fit then 1024 is going to be my maximum dimension in pixels. So, it's either going to be 1024 pixels wide or 1024 pixels tall, obviously I can adjust that. If I'm thinking people are going to be viewing these images on screen, then Bicubic Sharper is the way to go. If they're going to be printing the images, you can go with Bicubic (best for smooth gradients) instead.
And I explain my rationale there in Chapter 05. I'll tell you everything there is to know about down sampling and interpolation and all of this Bicubic stuff as well. All right! However, I do not want to resize my images. I'm going to say Don't Resize, turn that off. And we're going to drop-down here. I definitely want to include my Original Metadata and all my metadata as well, although you can select to just do the copyright or something along those lines. I want to apply a Metadata Template, so I'll go ahead and turn on that checkbox and I'll select this guy right there, Generic Deke, which I just saved a moment ago.
And I will append that metadata to the existing metadata inside the image, and then I could add additional keywords if I wanted to, don't need to and now, I'll go back to Destination. So, I just like to visit Image Options first and then come back to Destination. And I think we should publish this to a Specific Folder as opposed to cluttering up the original location here. So, I'll click on Browse and I'm going to create this folder inside the exercise_files folder, inside open_org and I'll go ahead and create a new folder like so, and we'll call this one JPEG files and that's it.
Go ahead and select it, click OK and that becomes the location to which my images will be saved. And this final option here is asking what to do if the Bridge encounters files with the exact same filenames. So, do you want to create a new file name? In other words, you're going to keep both files and the new file just have like a - 1 after it, or do you want to overwrite the existing files? Certainly, you want to copy over them, or do you want to skip? In other words you'll not create the new file, you'll preserve the old file instead. In our case, it doesn't matter because we don't have any files.
We just created that folder. I will go ahead and call this My JPEG settings so that I can use this preset over and over again. And now I'll click on Save. So there are My JPEG settings preserve for evermore, and I'll now click on Export as well in order to begin exporting my list of JPEG images. Notice it's going to start a little slow and then it's going to take off. Now the great thing is in the old days there was this command prior to CS5 here that allowed you to convert a bunch of images over to JPEG, but it was basically a script, and it had to open every single image inside of Photoshop inside Camera Raw.
So, you would see Camera Raw flash up on screen, and then file would get saved. And then Camera Raw will come up and screen again and then file would get saved. And it would happen over and over again and it wasn't especially fast. And even though this doesn't look like it's going all that fast, it's churning through these images much faster than the old image processor. All right! So, I'm going to twirl open this little hard drive here and we'll see the progress, and so you can see that many of the files, actually most of the files are done and it's just working on these last files right here. So, quite interesting.
Now, you can walk away from your computer if you like, and get a beverage, and then come back, do whatever you want, watch a commercial on TV. It should be done when you come back. Also notice down here inside the Export panel this blurry sort of the murky thing that we've got going, and in the background very blurrily, we see Exporting to Hard Drive, 96%. So that's encouraging. It's 96% done and now it is done. Awesome! Now all I have to do is close out, because I'm done with that operation. And I will click OK, because the updater was asking me if he could find updates whatever.
Anyway I'm going to switch over to JPEG files and here are my JPEG images, JPEG versions of every single one of those DNG files. These will open directly inside of Photoshop or your clients' favorite image handler. And notice that the Metadata is preserved, so the star ratings are still there, the labels are still there, this keywords are still going to be there so I click on this butterfly and go over to the Keywords panel, sure enough it's still a Butterfly. So that's totally awesome. So anyway, that's how you use the Export panel to convert a bunch of images over to JPEG files, the original images are still retained incidentally here inside Bridge CS5.
Download Deke's free dekeKeys and color settings from the Exercise Files tab.
- Assembling photorealistic compositions
- Understanding image size and resolution
- Correcting the brightness and color of images
- Creating accurate selection outlines
- Retouching and healing photos
- Mastering layers and effects
- Printing and exporting to the web


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Samsung tweets the clearest Samsung Galaxy S 4 picture yet
0. phoneArena 11 Mar 2013, 22:08 posted on
A tweet directly from Samsung gives us the clearest picture yet of the upcoming Samsung Galaxy S 4 and we can see the resemblance to the GT-I9502 which was leaked earlier on Monday; gone are the square corners seen in an earlier leak and on cases said to have been produced with the phone in mind and instead we have a similar design to the current model...
This is a discussion for a news. To read the whole news, click here
172. Diego! (Posts: 575; Member since: 15 Jun 2009)
Guys this is not the S G S IV! It's a render made by a fan! Check it out!
ngMobileUSA/app_50284338973464 3
There are several pictures/images that are almost identical one to another. This is definetely not the S IV :D
173. procopiojose (Posts: 132; Member since: 26 Oct 2012)
the image is an s3.. haha.. zoom it in and you can see the same bezel as s3.. samsung is dong a good job confusing people..
175. Eonnaydra (Posts: 217; Member since: 23 Oct 2012)
Sorry,but this is just a bigger S3 with improved specs.I was hoping for a brand new design with premium materials,not a cheap plastic.
This time,I'm gonna buy the HTC One which is awesome,maybe the perfect android phone.
Xperia Z is also awesome,but it has some display flaws and some lag.
Samsung is becoming the new Apple with no innovations !
185. Taters (banned) (Posts: 6474; Member since: 28 Jan 2013)
Lol wait until you start using it. Farthest thing from the perfect Android phone.
179. djoscar4u (Posts: 59; Member since: 10 Sep 2012)
same stupid boring design.. I knew it. lmao


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Man, 31, arrested in connection with May stabbing
Attack happened on Fulton Street
Published 11:08 PM EDT Jun 14, 2013
Lancaster police have arrested a man in connection with a stabbing that happened May 4.
Police have arrested Miguel Camacho, 31, of Lancaster.
Officers were called about 2:20 a.m. that Saturday to check on a stabbing victim who arrived at the hospital in a private vehicle, police said.
Investigators said the 23-year-old Lancaster resident was stabbed multiple times during the attack in the first block of East Fulton Street between the Village Night Club and the 100 block of North Duke Street.
Copyright 2013 by WGAL All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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John Sargent - Answers QuestionsPrincess_V Mar 12, 2010 5:25 PM
I'm not sure if anyone has read this:
Here are some excerpts:
"In the end, an e book will be priced to reflect the value consumers put on it. We believe at first release an e book is worth more and people will pay more for it. Over time it will become worth less as demand tapers. However, some digital books will retain their value over time just like print books. Some will increase their value over time (many physical books are now only available as trade paperbacks, after they have been out in the cheaper mass market formats). So our digital pricing will vary to reflect the value of the book at the time. But in general, our plan is to price books below ten dollars after there initial sales demand slows (usually within a year)."
"2) Will retailers have flexibility to price books at a discount? No, the sale price will be fixed by Macmillan. Retailers will promote and market books, but we will control the price for the book
3) How can we trust Macmillan to carry out its pricing pledge? An interesting question in that we have never made a pricing pledge. Historically, e book pricing has been driven by a number of factors, and it may well have appeared to be inconsistent. We never promised to price books in a certain way and have actually never controlled retail prices before now. And many of our decisions on list prices were driven more by our Amazon relationship than by our relationship with consumers. Looking forward, it will be a very fast moving world. I have told you our intent on e book pricing. I cannot guarantee or pledge what price we will be charging in the future. Personally I doubt that typical prices for general interest digital books will break out over $15.00. I also believe the majority of digital books will be priced below $10.00, as most Macmillan books are now and will be on day one of the agency model.
4) Will we be re-pricing e books that have a $14.00 digital list price while there is a mass market paperback edition available? Yes! To a customer price of $9.99 or below."
"In the end, an e book will be priced to reflect the value consumers put on it."
This is where I vote with my wallet!


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Education Plan of Action
Provide a forum to discuss the advancement of educational issues and for business and industry to actively support education in Watauga County, providing a conduit through which ideas and suggestions can flow between educational leaders and the business community.
- Promote linkages between educational institutions and employers that are designed to advance the caliber of education/training to meet 21st century needs of area business, industry and the community, through programs such as:
- Internships
- Graduation projects
- Cutting edge technology
- Imagination Library
- Participate in collaborative efforts between Watauga County Schools, the Watauga Campus of Caldwell Community College & Technical Institute and Appalachian State University.
- Support efforts on behalf of children and students which address:
- quality early childhood development options
- prevention of under-age substance use
- integration of life skills into the school curriculum
- exposure to the broad spectrum of the arts
- cross-cultural international exchange program opportunities
- initiatives to increase high school completion
- adequate funding for educational programming at all levels
- Promote the Watauga County Schools Spelling Bee and encourage student participation.
- Conduct the Spelling Bee for Grown Ups using the proceeds to fund community educational programs/organizations.


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To the QUICK is seeking essays, articles, and columns that perform thematic, theoretical, and cultural analyses of media arts like TV shows, films, music, or cultural movements or issues such as the recent rise of witchcraft, artificial intelligence, representations of racism, etc. These media forms have in the past been dismissed as unimportant cultural markers when measured against the mass of "literary" studies. To the QUICK continues the work of media literacy and cultural studies programs by drawing attention to the meaning existent in all discussions and arts. We also take the notion of "interdisciplinary" to heart, believing that each discipline is another way of reading the world and yet is part of a very similar critical attitude. To the QUICK therefore takes the stance that each discipline can--by writing in a carefully contextualized fashion--say informative and fascinating things even to readers outside of that field.
If not already implicit, you should make clear how your analysis is culturally relevant, what issues your reading is bringing up. The less the subject is popular or well-known, the greater the need to point out this cultural relevancy rather than relying on the weight of a theoretical framework.
It is not necessary that essays implement critical theory. However, theory is a way of reading the world and can be useful and exciting. Essays should still avoid one of the pitfalls of academic writing: the dropping of esoteric terms or phrases without context. Careful emphasis should be placed on the relevancy of allusions and terminology; the reader should not have to wallow through a dense litter of meaningless prose.
Three quick tips:
Essays and articles: 4500 words maximum
Columns: 250 - 1750 words
Book reviews: 500 - 1000 words
DEADLINE: Monday, March 6th 2000 (postmarked by)
Indicate a word count for all text, including endnotes. Style should be according to the latest edition of The Chicago Manual of Style. We are also interested in reprinting pieces published elsewhere. TTQ also needs pieces for our three columns: The Obligatory Old Book Review takes an "old" book, author, or theorist and presents an original argument as to how and why the author's ideas still apply to or are reflected in today's society; The Rewrite Department uses experimental non-fiction to comment on contemporary cultural issues; and Slipstream picks out an event of cultural significance from the contributor's life, describing and analyzing it in a memoir-like, creative style. For examples of these, peruse our journal magazine on-line at www.agoron.com/~matthewk/quick.
Our current Fall 1999 issue may be purchased by mailing a check (payable to "Joe Bisz," the Managing Editor) for $5.00 each plus shipping ($1.18 up to three copies, $1.58 four to six) to our address below. This issue features essays on Xena: Warrior Princess, Comedy Central's 'Cow and Chicken', IKEA furniture company, and the lyrics of Tupac Shakur, among others.
Feel free to query with essay, column, or artwork ideas. Queries recommended for book reviews. We occasionally publish "feature" articles that are a little longer; let us know if your piece has been truncated. Electronic submissions are preferred in RTF, Word, or WordPerfect format firstname.lastname@example.com but you may also mail manuscripts or correspondence to the QUICK at the address below.
Include a self-addressed stamped envelope for our reply, and enough postage if you would like your material returned. to the QUICK takes First North American print and electronic rights for all essays, articles, and columns published.


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Download Chess Games, Opening Databases, And Other Chess Goodies At Chess.Com!With Chess.com's Game and Opening Explorer, you can easily search your opponent's games or check out millions of master-level games to see what openings are being played. These are not just raw game scores. You get full win/draw/loss statistics for every single line and move, giving you a good idea of what's hot and what's not over the board!Saving your favorite openings and positions from Chess.com's Game and Opening Explorer makes it easy and breezy to review and study important positions in your openings. No wonder it's the choice of beginners and GMs alike.Sign Up For Chess.com For Free And Download Chess Games Now!
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SPREP, SPC and US Government Join Forces to Advance Climate Adaptation
8 September 2011: The Secretariat of the Pacific Regional Environment Programme (SPREP) has announced that it, along with the Secretariat of the Pacific Community (SPC) and the US Government, have initiated a partnership to advance climate change adaptation.
According to SPREP, the partnership forms part of a larger US$21 million "fast start" finance commitment made by the US for a Pacific Small Island Developing States (PSIDS) to address climate change. SPREP says the partnership will be focused on strengthening the capacity of the countries and communities in the Pacific Islands to improve food security and water security, and to protect critical ecosystems. In addition, the partnership will assist countries in accessing information about climate impacts, enabling them to make more effective and sustainable decisions in the face of climate change.
According to SPREP, the US also announced it will manage the US$21 million "fast start" program through a US Agency for International Development project office based in Port Moresby, Papua New Guinea. [SPREP Press release] [SPC Press release]


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Dell P2714T 27" Class 10-point Touch Monitor - 1080p, 60Hz, 16:9, VGA / HDMI - 210-ABMCItem#: DEI-102033126 | Model#: 210-ABMC
Currently Out Of Stock!
You May Consider This Alternative
Dell P2714T 27" Class 10-point Touch Monitor Product Details
Dell P2714T 27" Class 10-point Touch Monitor
The Dell P2714T 27" Class 10-point Touch Monitor is an ideal display unit for both office and home. The 27" LED Display has a dynamic contrast of 8000000:1 for crystal clear visuals. It has a Full HD resolution with 16:9 Aspect Ratio and 10-point multi-touch display. There are USB and HDMI ports along with the traditional VGA port for connectivity. It is a PC compatible monitor and easily connects to your CPU. Order the Dell P2714T 27" Class 10-point Touch Monitor today!
What It Is And Why You Need It:
- 27" LED Display; view brilliant picture quality on a large touchscreen
- Windows 8 compatible; connects easily to any Windows 8 PC to explore the touch feature
- USB & HDMI Ports; provides connectivity to High definition and media devices
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Who Gets Kicked Out? Moving Trucks Spotted at Brangelina's House After Split Announcement
- 04:27 PM, Sep 22
On Set of David Cronenberg's Film Maps to the Stars
Photo credit: / WENN
To fit your screen, we scale this picture smaller than its actual size. The original picture size is 1000x881 pixels and this photo has been viewed 2602 times since August 18, 2013


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Fill this black box with candy and treats!
The Black Mini Favor Box is a small box that has a fold over top to keep all your little treats inside. The Black Mini Favor Box is made of card stock and is a 2 inch square. The Black Mini Favor Box is an excellent way to hand out your small event favors like personalized candy jars, key tags and much more.
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2 bedroom apartment WIEJSKA
Maksimum Konuk Sayısı6
Yatak odası2
Floor No.
|Wiejska, 00-502 Warszawa, Polonya
|Mülkiyet türü
|Referans kodu
|Acceptance rate
|Response time
|A few hours
|Calendar updated
There are big bed-settee, TV and a coffee table in the spacious living room. The dining room is combined with the kitchen. There are table and four chairs; since the kitchen is fully equipped – there are fridge, dishwasher, electric kettle, microwave oven - you will be able to prepare meals there. There are also pots, plates and cutlery. In one of the bedrooms there are wardrobe and one double-bed, in the second one there are two single beds. In the hall there is a closet. The bathroom is of modern design and there are shower, bathtub, basin and wc.
Kitchen: fridge, dishwasher, washing machine, electric kettle, microwave oven, pots, plates and cutlery.
Living room: TV, chest of drawers, sofa.
Dining room: table and 4 chairs.
Closet: vacuum cleaner, ironing desk, iron.
Bedroom 1: bedside tables, two single beds.
Bedroom 2: chest of drawers, double bed, bedside tables, wardrobe.
Our office is open until 8PM. If you wish to arrive after that time please contact us before. Arrival after 9PM is an additional fee of 30€.
|Haftalık fiyat
|Aylık fiyat
|Check-in Saati (Sonrası)
|Check-in before
|Check-out Saati (Öncesi)
|İptal Koşulları
Everything was perfect! The appartment is comfortable and clean and it has a great view. The owners are really kind. I recommend it for your stay in Warsaw
The host cancelled the booking, this review is automated.
The host cancelled the booking, this review is automated.
The location of the apartment is ok, it is within 30 min walks to the important places and it feels safe. Supermarket is close by. In the evening it is a bit noisy. The kitchen has no ventilation and very hot in the Summer.
The apartment has no ac and in the Summer ac is a must for this apartment.
What we missed beside the ac was a place to put the kitchen towel in the kitchen and a holder for the toiletpaper
Perfect location, city center (for us) in walking distance. Well connected by public transport. Clean and very efficient appartement, bedroom looks at quiet court yard. Absolutely to recommend for younger couples / families (staircases up to second floor).
Great flat.
Beautiful flat In the very heart of Warsaw, it's difficult to find parking places around this place and if you find one during the week its necessary to pay for it (Parking-meter 08:00 -18:00), Saturday and Sunday for free.
Also beware of a 100Euro (400PLN) CASH caution that is not mentioned on Wimdu.
-Center of the city.
-Old Building.
-If neighbors have party you will hear them.
-No lift nor access to wheel chairs.
Nice clean apartment, friendly helpful staff – warmly recommended!
We had wonderful days in this beautiful apartment in Podwale Street in the heart of Warsaw!
The apartment is cozy, very comfortable and is in a beautiful backyard. We can only recommend it!
The host cancelled the booking, this review is automated.
- Kalite güvenceli konaklama
- Her ev sahibi telefonla doğrulanmıştır
- SSL şifrelemesi ile güvenli ödeme


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Dmitry Chumack wrote:
> a technics of using single makefile and who knows in practice about
> advantages and disadvantages of this two methods. What method is more
> reliable and easier maintainable applied to real world projects.
The recursive makes, as the article says and you mention, can build too
little. If it can not build something that must be build, then is not
The basis of the article is that make is very good in doing his work when it
has all information available. Recursive invocations of make are separate
processes, and any of them has not all information about the whole task, so
it can't do a work as good as it can the other way. Then the Makefile
writers must use several ways to try to ensure that the build process is
complete, losing the main advantage of using make and adding risk because
make is very well tested for that job after many years of usage, and a hand
made hack for each project rarely is.
> And what about autotools and problems of recursive make? Does automake
> solve this problems?
No. The problem is solved just by not using recursive make invocations,
using autotools or not. The automake manual says a few words about this
topic, but not much, just about organizing directories and variables that
can be useful.


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THE PAROTID, like other salivary glands, is the site of origin of a variety of tumors. Such lesions, though of various types, benign and malignant, are for the most part rare, with the exception of mixed tumors and carcinomas. The latter are the subject of this discussion.
Since the first description of mixed tumors of the parotid by Virchow1 in 1863 the origin and classification of salivary gland tumors, both benign and malignant, has been disputed by pathologists throughout the world. Because of the presence of cartilage in some tumors, Virchow spoke of them as "diffuse enchondromas" and thought them to be of mesoblastic origin. With the finding of epithelial elements, however, the composite nature of the tumors became evident to him, and he first used the term "Zusammengesetze Geschwülste" or mixed tumors. In 1877, Cohnheim2 suggested that in an early stage of embryonic development more cells are produced than are required and a number of unappropriated
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Voting Math Doesn't Always Add Up
In my print column this week, I use the occasion of the upcoming Academy Awards to delve into the math of elections. A slew of alternate systems have been proposed to replace the plurality system in American elections, in which the recipient of the most first-place votes who clears a threshold, often below 50%, wins. Yet voting reformers can't all agree on a single best system.
The Oscars involve two stages of voting, for nominees and for winners. Since 1936, the nomination stage has worked like this: The Academy's accountants at PricewaterhouseCoopers sort paper ballots by first-place votes. For a category with five nominees, such as best picture, any film with first-place votes numbering more than one-sixth plus one of the total ballots earn nomination status. Then, if five films don't meet that criteria, the contenders with the fewest first-place votes are eliminated, and their ballots reassigned to the remaining contender listed highest, and the process is repeated until five piles are big enough to qualify for nominations. (Ballots listing five films without enough support to contend are eliminated from the vote total.)
The second stage is the simpler plurality system: The nominee with the most votes wins.
Voting reformers would love to see alternate systems used in selecting awards such as the Oscars, because change in political elections is usually preceded by proofs of concept in venues with lower stakes, such as student governments or professional associations. Even such scenarios don't always provide much information — the American Statistical Association has adopted a system called approval voting, in which voters indicate which candidates they'd be comfortable with, but in practice, there have almost always been just two candidates, and therefore a straightforward majority vote, said Ron Wasserstein, executive director of the group.
Failing a change in voting systems, scholars would like access to the Oscars ballots to seek clues as to voter behavior in real-world situations, rather than simulations.
But the Academy doesn't release any details about the balloting. Before the live telecast, the goal is to sustain suspense — with a leak of the results, "There's not much air in our balloon on Oscar night," said Bruce Davis, executive director of the Academy of Motion Picture Arts and Sciences. Afterwards, the rationale for secrecy is less clear, though fifth-place nominees wouldn't be pleased.
The Grammys and Golden Globes, which also have two-stage voting systems but don't include rankings in the first stage, also don't disseminate voting details. Bill Freimuth, the Recording Academy's vice president of awards, cites the "closed curtain of the voting booth," even when asked about anonymizing the ballots and then releasing them.
Voting scholars have criticized the Oscars voting system for some time, to little avail. "It affords the individual voter the greatest possibility that his or her vote will count toward at least one nominee," says Rick Rosas, one of two Pricewaterhouse partners who oversee the system. "It determines five works that have the broadest, deepest support amongst the voters."
The same system is used in some political elections, where it's called instant runoff in cases with one winner, or proportional voting in cases where there are multiple winners. Instant runoff, backed by the voting reform group FairVote, is set to take effect in the city of Minneapolis after being implemented in other municipalities, including Burlington, Vt.
However, the Minnesota Voters Alliance is fighting the instant runoff system in court, planning an appeal after losing in county court. Executive director Andy Cilek criticizes the system precisely because of Rosas's point that voters are given the greatest chance of having their vote count towards a winner. In his view, the reassignment of votes for unpopular candidates is a way of giving a voter more than one vote, and is therefore undemocratic. He'd rather see a plurality system. "A voter can't know for certain if a vote is going to help his candidate," Cilek said.
"I believe there is a misunderstanding about what instant runoff is," Jeanne Massey, executive director of FairVote Minnesota, responded. "It is merely a compression of two elections into one."
Other critics of instant runoff support a system that would allow voters to assign numerical scores to candidates. In one such system, the highest median score wins; in another, the highest mean score wins.
The leading advocate of mean scoring, known as range voting,
Temple University mathematician* Warren D. Smith, co-founder of the Center for Range Voting, concedes that instant runoff has an early start out of the gate compared to other voting systems. He blames it on "historical accident": "The instant-runoff-voting-pushers got organized sooner and range voting at that time was not yet appreciated."
Other scholars criticize range voting. "I don't like the idea of inviting people to carefully weight candidates and giving sophisticated people the ability to give greater power to their votes," says Nicolaus Tideman, a Virginia Tech economist. Such criticism was leveled on a test of such a system for Oscar voting that some blamed for the failure of "Hoop Dreams" to win a nomination for best documentary.
One seemingly logical solution is electing the Condorcet winner, the candidate that beats all others head to head on a majority of ballots. But there isn't always such a candidate. Also, "you get weird outcomes if you don't include all of the information" on ballots, said University of California, Irvine, mathematician Donald Saari.
Further reading: Smith's site on range voting contains a wealth of information on other voting systems, albeit in favor of his preferred system. He's also written about Oscar voting. Steven Brams, professor of politics at New York University, spoke to me last year about the math of elections. You can see a sample instant-runoff ballot here.
*This blog post originally and incorrectly said Warren Smith is a Temple University mathematician, an outdated reference. He is the co-founder of the Center for Range Voting.


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The difficult times / rocky road is over over over - now growth and positive events to look forward to plus trump cards.
Would not sell if you paid me = $.80 cents down and $3-4 up this year.
RG3039 we should be seeing confirmation of results once reviewed as per Conference call. You would hardly notice this from website , profile. Things chance so fast. All it is now Ligands,growth factors,Opus things are looking good.


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|Welcome to the MANGA Forum.
|You will have to register before you can post: log in or sign up at the top of the page to proceed. To start viewing messages, select the forum that you want to visit from the selection below.
wt happen 2 d episode 71?!
if u wanna watch anime try justdubs.net or animefreak.tv u might be able to find the episode ur looking for. I will devour their hearts and crap out their souls. They will all taste oblivion....which tastes just like red bull...which is disgusting. -O'malley (RvB)


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The Orlando Speed World Dragway held its last "Night of Fire" over the weekend, and u local member Hellobozos uploaded pictures and video from the event.
The event, which ran for 25 years, features jet trucks, jet funny cars, jet dragster, jet locomotives and more.
See more information on the Orlando Speed World Dragway website.


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A New Sales Model: Employees
The young woman chatting about the $100 Seychelles platform sandals in the Zappos.com video wears little makeup, her hair in a ponytail as her fingers caress the shoe's soul and straps.
She's cute, but she's no supermodel.
What she is: A Zappos employee chosen for her pep and "real people" look to wear and talk about shoes for sale on the company's website.
The online retail company owned by Amazon.com AMZN 1.55 % churned out about 58,000 short videos of mostly staff—not professional models—showing off shoes, bags and clothing in 2010. Zappos found that when a product includes a video explanation, purchases rise and returns decrease.
Marketing researchers and psychologists say that using "regular" people to model products can be especially effective in certain cases.
"If you just have a regular person who matches the target segment the consumer is likely to trust that communication more," says Steve Posavac, a professor of marketing at Vanderbilt University Owen Graduate School of Management.
When a product is very high end, however, a more aspirational marketing approach typically resonates with potential buyers, he adds.
Zappos first posted a handful of the videos on its website in early 2009. Now 11 employees speedily shoot and perform about 400 videos a day out of five padded shooting booths in the company's inventory warehouses in Shepherdsville, Ky.
"It's crazy to say the least," says Jason Lee Menard, video production manager for Zappos Development Inc.
And so far it's effective.
In the fall of 2010, the company did a test. It showed its products two ways—with the video and without the video—to track shoppers' behavior. It found purchases increased about 10% when a product included a video description, says Laurie Williams, video and photo products manager at Zappos. The company is still testing to figure out what components affect sales the most, she says.
Cutting down on the number of items customers return is perhaps most the significant benefit, she says.
"If you get the item and it's not what you wanted you become disenchanted," and the customer can have negative psychological association with buying, says Williams.
A handful of other retailers have recently started using staff who don't look like professional models to showcase their products.
J. Crew Group Inc. used staff as models for the first time last year to showcase its men's denim. After noticing that men around the office got their jeans to have a particularly desirable worn look by not washing them for months at a time, the company decided to use five staffers to explain this technique to customers, said Jenna Lyons, president and executive creative director at J. Crew.
J. Crew added a similar campaign last month with nine female staffers in khaki capri pants anchoring outfits styled "their own way." "Our hope is that it gives people a point of connection to J.Crew as a brand and also the people in it," said Ms. Lyons, in an email.
While J.Crew's staff looks intentionally well-styled and trendy in the brand's clothing, some of the shoes in the Zappos' videos actually look unflattering on the staff.
"We probably have the most negative reaction," when the shoe looks bad on the wearer, says Ms. Williams of Zappos. Sometimes the sample shoe isn't the right size for the person in the video, something the company is working on solving, she says.
Still, when one pair isn't presented in a flattering manner, "that is not going to stop you from moving on to the next shoe," says Baba Shiv, professor of marketing at Stanford Graduate School of Business. "You are more likely to buy a shoe."
Why? A video—even an unflattering one—produces what marketers call "the stimulation process," says Mr. Shiv. When a company shows people an item in action, "your brain is sort of naturally imagining, 'how is this product going to feel on me, how is it going to look on me,' " he says.
Not all videos on Zappos' website feature staff. Clothing videos on the website feature professional models for practical reasons. The models are already wearing the clothes for photo shoots for the website and tend to be a standard size, Ms. Williams says.
Videos with professional models also increased sales in Zappos' internal test, but the test wasn't conclusive and the company gets better customer feedback from videos that feature staff, says Ms. Williams. "If we could, we would shoot [the clothing] on regular people."
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Author Affiliations: Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas (Drs Rodrigue, Kennedy, Devous, and Park and Ms Rieck), and Departments of Radiology (Dr Devous) and Psychiatry (Dr Park), University of Texas Southwestern Medical Center, Dallas; and Center for Neuroscience and Regenerative Medicine, Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (Dr Diaz-Arrastia).
Importance Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection.
Objective To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ϵ4 allele), would show greater amyloid burden than those without such risk.
Design Cross-sectional study.
Setting General community.
Participants One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study.
Intervention Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18–labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ϵ4+ or ϵ4−.
Main Outcome Measure Amyloid burden.
Results Participants in the hypertension group with at least 1 ϵ4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ϵ4 allele.
Conclusions and Relevance Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging.
One of the major research foci in the aging field today is centered on the neural and cognitive decline that occurs with Alzheimer disease (AD). Understanding disease etiology and progression and developing effective disease-modifying treatments of AD are among the key scientific goals of the 21st century. Recent attention to the lack of efficacious treatments, coupled with the knowledge that neurobiological changes precede behavioral expression and clinical diagnosis of AD by a decade or more, highlights the importance of studying fibrillar amyloid deposition in healthy life-span samples to identify those individuals most at risk for future neuropathological decline.1
The primary neuropathological features of AD include the deposition of amyloid plaques and tau-driven neurofibrillary tangles.2 Previous research from autopsy and in vivo imaging has estimated at least 20% of normal older adults carry elevated levels of β-amyloid3- 5 (Aβ). Current theories have proposed that amyloid deposition is one of the earliest detectable changes in the neuropathology of AD.6 Thus, identifying the most salient risk factors for Aβ deposition, especially modifiable environmental factors such as vascular health, can inform our understanding of individual differences in susceptibility to pathology as well as help direct medical efforts focused on prevention and early detection.
Although multiple genetic variants have been identified as risk factors for AD,7 the apolipoprotein E ϵ4 genotype (APOE ϵ4) is perhaps the best verified genetic polymorphism associated with a significantly increased risk of cognitive decline and dementia.8- 10 Individuals with 2 copies of an ϵ4 allele carry a 10- to 12-fold risk for AD in comparison with ϵ3 homozygotes.11 The APOE lipoprotein is involved in both cholesterol and Aβ transport12 and the ϵ4 polymorphism is additionally a risk factor for vascular disease.13,14
One major environmental risk factor for dementia is cardiovascular and neurovascular health. Multiple epidemiological studies have shown that risk factors for vascular disease, such as diabetes mellitus and hypertension, are also risk factors for cognitive decline.15- 18 Midlife elevations in blood pressure have been shown to predict diagnosis of dementia later in the life span, and hypertension in even healthy adults has been associated with poorer cognitive performance,19 increased rate of brain shrinkage,20 degraded white matter connectivity,21 and greater regional brain iron concentration22 compared with adults with normal blood pressure.23 Additionally, older adults with an APOE ϵ4 allele and cardiovascular disease may be at greater risk for cognitive decline than those without such factors,24,25 although high levels of atherosclerosis have been linked with increased cognitive decline independent of APOE genotype.26 Thus, genetic and vascular risk factors may work in synergy to bring about the neuropathological changes that lead to cognitive decline.
The goal of the current study was to examine the individual and combined impact of genetic (APOE ϵ4) and vascular (hypertension) risk factors on in vivo amyloid deposition in a healthy aging sample of middle-aged and older adults. We hypothesized that individuals with hypertension would show greater levels of Aβ deposition compared with their peers with normal blood pressure and that individuals with both genetic and vascular risk factors would show the greatest elevation in Aβ burden. We additionally tested the hypothesis that increased pulse pressure (PP) would be associated with higher levels of amyloid deposition, particularly in those participants with at least 1 APOE ϵ4 allele.
We recruited 147 participants (aged 30-89 years) who underwent cognitive testing, magnetic resonance imaging, and fluorine 18 (18F)–labeled florbetapir positron emission tomography (PET) imaging as part of the Dallas Lifespan Brain study27 (N = 350; ages 20-89 years). Participants were well educated (mean, 16.23 years) (Table 1), native English speakers, and screened for neurological and psychiatric disorders, loss of consciousness more than 10 minutes from a traumatic insult to the head, drug/alcohol abuse, stroke and major heart surgery or chemotherapy within 5 years, and Mini-Mental State Examination28 score less than 26.
All participants completed four 2-hour visits: 2 for cognitive and neuropsychological testing, followed by 1 for magnetic resonance imaging scanning, and 1 for amyloid PET imaging. The institutional review board approved study procedures and all participants provided written informed consent prior to enrollment and were debriefed in accord with university human investigations committee guidelines.
Venous blood was collected into EDTA anticoagulated tubes and genomic DNA was isolated by standard protocols.27 We typically isolated 50 to 70 μg of DNA from 2 mL of whole blood. APOE genotypes were determined by real-time polymerase chain reaction using TaqMan probes (Applied Biosystems Inc) unique for each APOE single-nucleotide polymorphism, rs429358 (assay ID C3084793 20) and rs7412 (assay ID C 904973 10), according to established protocols.29APOE data were available for all but 3 of the participants, for a total sample of 144 with complete data.
Blood pressure was measured twice at each cognitive and PET imaging visit and once at the magnetic resonance imaging visit, for a total of 7 blood pressure measurement points for each participant. Blood pressure was measured using an automatic sphygmomanometer (HEM-780; Omron) placed around the left arm while participants were seated for the cognitive and magnetic resonance imaging visits and supine for the PET imaging visit. All participants had blood pressure readings from at least 3 measurement points; however, 13 participants were missing 1 to 4 measurements. Systolic and diastolic pressure were averaged across all available occasions for each subject, and this mean blood pressure was used in part to determine vascular risk group membership (for categorical variable analyses). For continuous variable analyses of blood pressure effects, we computed PP (systolic minus diastolic) because it is a known correlate of arterial stiffness30 and may be a better predictor of coronary heart disease than either systolic or diastolic elevations in pressure.31
Participants were classified as having vascular risk if they reported a current physician diagnosis of hypertension or if their measured mean blood pressure over the 7 measurement occasions exceeded stage 1 criteria for diagnosis (ie, average systolic blood pressure greater than 140 mm Hg or average diastolic pressure greater than 90 mm Hg). A total of 75 participants from the sample of 144 were classified as having normal blood pressure, with a mean age of 54.3 years (range, 30-88 years). Because the groups differed in age considerably, we restricted the normotensive sample to adults 47 years and older (n = 118; mean age, 62.4 years), which was the age of the youngest person in the vascular risk group. In this reduced sample, 69 participants were classified as having hypertension and had a mean age of 74.0 years (range, 47-89 years). Fifty-four of those participants reported physician diagnosis and medication for hypertension and 15 reported no current diagnosis or history of hypertension but showed measured blood pressure elevations exceeding stage 1 criteria. Participants were classified as having genetic risk if they carried at least 1 ϵ4 allele. Among this age-restricted sample of 118, 22.8% were classified as having genetic risk (18.6% ϵ4 heterozygotes and 4.2% ϵ4 homozygotes). There was no significant effect of hypertension status (F1,114 < 1; P = .52; F1,114 < 1; P = .99) or genetic status (F1,114 < 1; P = .63; F1,114 = 2.81; P = .10) on education or Mini-Mental State Examination score, respectively (Table 1). However, both vascular risk groups (ie, hypertensive and either ϵ4− or ϵ4+) were significantly older (P range <.05-.001) than both normotensive groups (Table 1). Age was entered into all statistical models to account for this difference.
Because our participants were prospectively selected for a study of healthy aging, we had insufficient information and variance to create a risk factor score (such as the Framingham index). Less than 3% of the sample reported regular smoking, less than 0.5% were diagnosed with type 1 diabetes, and approximately 4% of the sample reported a history of type 2 diabetes (all non–insulin dependent). Mean (SD) body mass index in the sample was 26.18 (3.48) (calculated as weight in kilograms divided by height in meters squared) and was not correlated with amyloid burden (r = 0.03; P = .76).
Fifty-four of the participants in the vascular risk group reported taking antihypertensive medications: β-blockers (n = 9), ace inhibitors (n = 9), angiotensin receptor blockers (n = 4), calcium channel blockers (n = 4), potassium-sparing diuretics (n = 3), α-blockers (n = 1), or a combination of at least 2 of these medications (n = 24). These participants were classified in the medicated hypertensive group. The remaining 15 participants in the vascular risk group who were not taking antihypertensive medication were classified in the unmedicated hypertensive group.
Participants were injected with a 370×106–Bq bolus of 18F-florbetapir. At 30 minutes postinjection, participants were positioned on the imaging table of a Siemens ECAT EXACT HR PET scanner. A 2-minute scout was acquired to ensure the brain was completely in the field of view and there was no rotation in either plane. A 2-frame × 5-minute dynamic emission acquisition began 50 minutes postinjection and immediately after an internal rod source transmission scan was acquired for 7 minutes. The transmission image was reconstructed using back projection and a 6-mm full-width-at-half-maximum gaussian filter. Emission images were processed by iterative reconstruction, 4 iterations and 16 subsets with a 3-mm full-width-at-half-maximum ramp filter.
Each participant's PET scan was spatially normalized to a florbetapir uptake template27 positioned in Montreal Neurological Institute space (2-mm3 voxels) using SPM8 (Wellcome Department of Cognitive Neurology) and in-house MATLAB (MathWorks Inc) scripts and visually inspected for registration quality. We computed standardized uptake value ratios (SUVRs) in 8 bilateral regions of interest, using a cerebellar reference region that excluded peduncles. Regions of interest and the reference region were defined by modifying automated anatomical labeling masks to minimize nonspecific white matter binding.27 Mean SUVR was calculated by averaging SUVRs in the 8 regions of interest: precuneus, posterior and anterior cingulate, temporal, dorsolateral prefrontal, orbital frontal, parietal, and occipital cortex.
To determine the effect of hypertension and APOE ϵ4 on Aβ burden, we used a generalized linear model with age as a continuous predictor and vascular risk (normotensive vs hypertensive) and genetic risk (APOE ϵ4+ vs APOE ϵ4−) as categorical predictors of amyloid burden (mean cortical SUVR). All possible interactions were tested and systematically removed from the final model if nonsignificant (P > .10). There was a significant effect of age (F1,113 = 5.22; P = .02) as amyloid burden increased with older age. The main effects of hypertension (F1,113 = 3.41; P = .06) and APOE ϵ4 (F1,113 = 3.52; P = .06) showed trend levels of significance, whereas the presence of an APOE ϵ4 allele, or having hypertension, was associated with greater Aβ deposition. Importantly, the APOE ϵ4 × hypertension interaction was significant (F1,113 = 3.90; P = .05) (Figure 1 shows the combined effect of hypertension and APOE genotype on cortical amyloid burden). Individuals who were both APOE ϵ4+ and had hypertension showed greater levels of amyloid burden than subjects with either a single risk factor or none at all.
Figure 1. β-Amyloid deposition by vascular and genetic risk groups. Individuals with hypertension and at least 1 apolipoprotein E (APOE) ϵ4 allele have greater β-amyloid deposition than all other groups. SUVR indicates standardized uptake value ratio. *Significant interaction (P = .05) between vascular risk and genetic status, with ϵ4+ participants with hypertension showing the greatest amounts of β-amyloid deposition.
To test the possibility that there were differing effects of medicated and unmedicated hypertension on Aβ deposition, we reconstructed the vascular risk variable into normotensive, medicated, and unmedicated hypertension and reestimated the effects on amyloid burden (see Table 2 for group demographics). We reproduced the significant effect of age (F1,109 = 12.98; P < .001) and found a main effect for APOE ϵ4 (F1,109 = 7.36; P < .001). Moreover, the APOE ϵ4 × vascular risk group interaction was significant (F1,109 = 4.01, P = .02), reflecting that unmedicated participants with hypertension and genetic risk showed higher levels of amyloid burden than all other groups (Figure 2).
Figure 2. Mean β-amyloid deposition by genetic risk and hypertensive subgroup. Individuals with uncontrolled hypertension and at least 1 apolipoprotein E (APOE) ϵ4 allele show greater β-amyloid deposition. SUVR indicates standardized uptake value ratio. *Significant interaction (P = .02) between vascular risk group and genetic status, with unmedicated ϵ4+ participants with hypertension showing the greatest amounts of β-amyloid deposition.
In addition to testing the categorical effects of hypertension, we also examined whether a dose-response effect existed between elevation in blood pressure and elevated cortical amyloid level. We repeated the generalized linear model approach using age and PP as continuous predictors and APOE status as a categorical predictor of mean cortical SUVR. We observed significant effects of APOE group (F1,113 = 6.63; P = .01), PP (F1,113 = 6.40; P = .01), and a trend level effect of age (F1,113 = 3.54; P = .06) on mean cortical SUVR. A significant interaction of APOE group × PP (F1,113 = 9.52; P = .003) indicated that increased PP was predictive of greater amyloid burden in the genetic risk group, whereas this effect was not apparent in individuals who were APOE ϵ4− (Figure 3).
Figure 3. Association of pulse pressure and β-amyloid deposition. Increased pulse pressure is associated with increased β-amyloid deposition in individuals with genetic risk for Alzheimer disease (ie, apolipoprotein E (APOE) ϵ4+).
Our study demonstrates that hypertension, a prevalent vascular risk factor in aging populations, interacts with APOE ϵ4 genotype to increase amyloid deposition in cognitively healthy middle-aged and older adults. Individuals with vascular or genetic risk alone do not show elevated mean cortical amyloid burden when compared with a group with neither risk factor. We additionally show that in healthy individuals with genetic risk for late-onset AD (ie, presence of an APOE ϵ4 allele), unmedicated hypertension is associated with the greatest risk for accumulating Aβ. Participants with controlled hypertension, however, show significantly less amyloid burden than the unmedicated group and only a slight elevation compared with participants without hypertension. Beyond these categorical differences, we further demonstrate a dose-response effect of increases in PP with increases in cortical amyloid load. For ϵ4+ individuals, increases in PP reliably predicted elevated amyloid burden. All of these effects are beyond the significant effect of age on amyloid,27 underscoring the importance of individual differences in health and genetic risk factors in brain aging.
The present results are in accord with previous research demonstrating the impact of blood pressure elevations on AD diagnosis. Large-scale epidemiological studies have demonstrated that midlife increases in blood pressure predict the development of dementia later in the life span.16 Further, a recent report showed that individuals with the highest diastolic blood pressure elevations in midlife showed the strongest associations between plasma amyloid levels (Aβ1-40 and Aβ1-42) and risk for later AD.18 Thus, blood pressure elevation appears to increase the risk for AD. Our study extends this literature by directly measuring in vivo amyloid plaque in nonpathological aging and suggests that in persons with genetic risk for AD, blood pressure elevations are associated with increased amyloid accumulation even in cognitively normal adults.
Studies directly investigating the association of vascular health and in vivo amyloid deposition in the human brain are limited and findings thus far have been equivocal. One recent study investigating the link between cerebrovascular disease, defined by high white matter hyperintensities, and amyloid positivity in healthy adults found no relationship between the two, although individuals with both cerebrovascular disease and amyloid positivity showed poorer executive function performance.32 In agreement with the present findings, the Framingham Coronary Risk Profile score (an index of elevated cholesterol level, diabetes, hypertension, and smoking) has been associated with increased amyloid burden in a sample of normal controls, participants with mild cognitive impairment, and participants with AD.33 In a subset of participants with APOE genotyping, no interaction of Framingham Coronary Risk Profile score with APOE positivity was detected,33 although low power constrained interpretation of those findings.
Interestingly, the detrimental effect of hypertension and its interaction with APOE genotype on brain aging may not be limited to amyloid burden. A significant body of work has documented the deleterious effects of hypertension and other vascular risk factors on both normal and abnormal cognitive and brain aging,23,34 as well as its interaction with various genetic risk factors for cognitive decline beyond APOE.24- 26,35- 37 This literature highlights the complex nature of vascular and genetic effects on neurocognitive aging and suggests the synergistic effect of vascular compromise and genetic risk results in increased susceptibility to both the accumulation of neural insults and associated cognitive decline with aging. Understanding the time course, mechanism, and for whom the aging process becomes pathological is an open question in need of further study.
The neural mechanisms underlying the specific effect of hypertension and APOE ϵ4 on amyloid accumulation is unknown, although the animal literature offers some insight. Previous work in a mouse model of arterial hypertension suggested that chronic hypertension may increase blood-brain barrier permeability and result in Aβ deposition.38 Further examination of Aβ plaque in another murine model of hypertension showed that hypoperfusion and neuroinflammation in the cortex and hippocampus preceded the development of amyloid deposition.39 Mechanistically, APOE (a major cholesterol transport protein in the brain) has been linked to AD and Aβ deposition via cholesterol metabolism.40
The present study should be interpreted in the context of its limitations. The cross-sectional design of our study prohibits the delineation of cause-effect relationships among variables. The findings are additionally limited in their generalization to the full population of middle-aged and older adults by design, as we focus on a highly screened sample of healthy aging. Consequently, the sample is free from clinically significant vascular disease. While this does not allow us to study the spectrum of vascular effects, it does allow for a relatively focused study of the effects of hypertension compared with an index-based approach where the significance of individual factors is less clear. However, because the study was not prospectively selected to study hypertension directly, the findings should not be overinterpreted. Because the prevalence of hypertension increases with age, the normotensive group was younger than the hypertensive group. To address this possible age confound, we matched the age range of the groups and explicitly modeled age in all analyses. Additionally, given the relatively low prevalence of the APOE ϵ4 allele in the general population12 (approximately 24%), which was mirrored in our sample, the analyses were differentially powered in comparisons of vascular and genetic risk groups. Future prospective studies with selective case-control recruiting on vascular and genetic risk factors are needed to replicate and extend the present findings.
Our findings advance the existing literature in several important ways. First, our study focuses on a group of healthy and cognitively normal middle-aged and older adults, which enables the examination of risk factors and amyloid burden before the development of mild cognitive impairment and possibly preclinical dementia. Of course, long-term longitudinal follow-up (which we are pursuing) is needed to determine which proportion of the sample will ultimately develop pathology. Second, we used a highly selected sample of adults screened against significant cardiovascular disease, which lends confidence to the specificity of the hypertension findings. Third, in addition to examining categorical factors, we substantiate and extend that approach with actual blood pressure measurements across multiple occasions, which allows for the examination of a dose-response relationship and provides a more direct and nuanced study of hypertension effects than diagnostic group comparisons alone.
In sum, our results show that hypertension may modify the impact of genetic risk for AD on Aβ accumulation in healthy adults. Interestingly, these initial findings suggest that individuals with an APOE ϵ4 allele may be able to attenuate their likelihood for amyloid accumulation through proper control of blood pressure. However, future studies with larger sample sizes that examine additional factors, such as duration of hypertension treatment, are needed to support these findings. The identification of hypertension as an additional risk factor for amyloid plaque deposition is encouraging as we may be able to prevent, or at least slow, pathological aging in some individuals through lifestyle modification or pharmacological intervention.
Correspondence: Karen M. Rodrigue, PhD, Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, 1600 Viceroy Dr, Ste 800, Dallas, TX (email@example.com).
Accepted for Publication: October 9, 2012.
Published Online: March 18, 2013. doi:10.1001/jamaneurol.2013.1342
Author Contributions: Dr Rodrigue had full access to all the data in the study and takes responsibility for the integrity of the data. Study concept and design: Rodrigue, Kennedy, Devous, and Park. Acquisition of data: Rodrigue, Rieck, Kennedy, Devous, and Diaz-Arrastia. Analysis and interpretation of data: Rodrigue, Devous, Diaz-Arrastia, and Park. Drafting of the manuscript: Rodrigue, Rieck, and Devous. Critical revision of the manuscript for important intellectual content: Rodrigue, Kennedy, Devous, Diaz-Arrastia, and Park. Statistical analysis: Rodrigue and Devous. Obtained funding: Rodrigue, Kennedy, Diaz-Arrastia, and Park. Administrative, technical, and material support: Rieck and Diaz-Arrastia. Study supervision: Kennedy, Diaz-Arrastia, and Park.
Conflict of Interest Disclosures: The radiotracer was provided at no cost to the study by Avid Radiopharmaceuticals Inc. Dr Devous serves on the advisory board of Avid Radiopharmaceuticals. Avid Radiopharmaceuticals is supporting a longitudinal component of this study.
Funding/Support: This study was supported by National Institutes of Health grants 5R37AG-006265-25, 3R37AG-006265-25S1, and P30AG12300 and Alzheimer's Association grant IIRG-09-135087 (Dr Park). Dr Rodrigue was supported in part by National Institute on Aging grant 1K99-AG-036848-2.
Additional Contributions: We thank Michael Viguet, BS, ARRT(N), for assistance with positron emission tomography scanning, Chris Paliotta, BA, for collecting blood samples, and Prasanna Tamil, MS, and Erin Wooden, BS, for participant testing and scheduling.
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In brief: Kerry: Obama didn't order all NSA spying
Kerry: Obama didn't order all NSA spying
WASHINGTON -- Secretary of State John Kerry said his counterparts in other nations know President Barack Obama didn't order up all the snooping that the National Security Agency conducted abroad.
While traveling in the United Arab Emirates, Kerry told the BBC that his foreign counterparts have been understanding about the recent revelations of widespread National Security Agency surveillance, and know that the Obama administration is trying to find a way forward that can fight terrorism in a way that respects privacy.
Kerry said Obama didn't personally order all the various types of snooping that have been revealed by former NSA systems analyst Edward Snowden -- that the scope of the NSA work evolved over a long period of time.
U.S., China to begin joint disaster exercise
HONOLULU -- Army officials from China and the U.S. are meeting in Hawaii for an annual disaster relief exercise that will include field training for the first time this year.
Specifics of the exercise scenario starting today have not been publicly released. U.S. Army Pacific officials have only described it as a humanitarian assistance and disaster relief operation requiring military cooperation between the United States and China in a fictional third country.
On Thursday, U.S. and Chinese soldiers will train in a field exercise at Bellows Air Force Base, on a Marine Corps training area on the east side of Oahu.
Col. Bill Florig, chief of civil military operations for U.S. Army Pacific, said in announcing the exercises in October that the event is the largest between the United States and China armies.
The exchange is an annual exercise that is part of a security cooperation agreement established in 1998.
Amazon, Postal Service to deliver Sundays
NEW YORK -- Amazon said it is teaming up with the U.S. Postal Service to deliver packages on Sundays.
The Seattle company said Sunday delivery will be available to customers in the New York and Los Angeles metropolitan areas at first. Amazon and the Postal Service plan to roll out service to "a large portion of the U.S. population" in 2014, including Dallas, Houston, New Orleans, and Phoenix.
Amazon expects Sunday delivery to be popular with members of its Prime service, which costs $79 a year and comes with free two-day shipping on many items on the site as well as access to Amazon's TV and movie streaming service.
But Sunday delivery will be available to all Amazon customers.
Ohio casino pays homage to 'A Christmas Story'
CLEVELAND -- Cleveland's casino will mark the 30th anniversary of the movie "A Christmas Story," parts of which were filmed in the department store that now houses the casino.
The Horseshoe Casino Cleveland opened in 2012 in the old Higbee building downtown. It said the movie will be highlighted throughout the casino during the season.
The Higbee building and its holiday-decorated windows had a starring role in the 1983 film. This year, the casino will re-create the nostalgic animatronic holiday scenes that adorned the store's street-level windows back in the day.
Cleveland also is home to "A Christmas Story" House and Museum. That's the house where hero Ralphie Parker lived in the movie.
The museum also is planning 30th anniversary events.
-- from wire reports