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text:
Home Op-Ed Hey, press: Stop being a sitting duck for Trump
Hey, press: Stop being a sitting duck for Trump
(WhiteHouse.gov)
Is the press the enemy of the people? I think not, but President Donald Trump certainly gets people going when he says that. He's known for his rallies and talking about the three things that he knows gets a reaction: the press, the Democrats (and in particular "crooked Hillary," which begets chants of "Lock her up") and of course the wall that he wants built on the United States-Mexico border.
On Thursday, CNN's Jim Acosta asked White House Press Secretary Sarah Sanders about the press, and the exchange went like this:
Sanders: "The president is rightfully frustrated. Ninety percent of the coverage on him is negative, despite the fact that the economy is booming, ISIS is on the run, and American leadership is being reasserted around the world.
Just this week, the media refused to cover his remarks in Florida, highlighting efforts on workforce development. In fact, the pooler for the press said that there was no news made, despite the fact that the governor of the state joined with dozens of businesses across the state of Florida to announce thousands of new jobs.
That may not be news in Washington, D.C., but I can assure you that it's news in the state of Florida, that people that didn't have a job before this president took office have better opportunity and the opportunity to have a job moving forward. That's actually real news and something that people in the state of Florida and across this country appreciate. And that was totally ignored.
Not only that — before, a journalist on CNN claimed that the president hadn't taken questions in over a week, despite the fact that same journalist did a live shot from the two-and-two press conference that the president had with the prime minister of Italy just moments after making that accusation.
With this sort of misinformation and lack of interest that's so pervasive in the media, it's completely understandable for the president to be frustrated."
As I've stated in this column, I've been cleaning out things I've saved for years. I found lots of things from the Bill Clinton era, and the press was not very complimentary about Clinton, especially after the Monica Lewinsky scandal and the impeachment trial. However, no one took issue with the press. The press was just doing its job, which meant reporting on the news even if it made the leader of the free world, President Bill Clinton, not only look bad, but look like a jerk.
Fox News' Political Editor Chris Stirewalt said on Friday that news outlets should cease sending reporters to President Trump's rallies, stating their presence allows Trump to use them as a "prop."
"Everybody should stop having reporters penned up like veal in the back of those things for the president to use as a prop, and then some of the reporters exploit that for their own personal benefit." Stirewalt added, "This is not helping anybody. Get out of the hall. Leave the cameras, get the reporters out of the hall. Quit letting him use you as a foil."
Stirewalt is right. Several years ago I wrote about bringing back the morning gaggle — reporters who used to stand at the press secretary's desk (no cameras) — and everyone could ask a question. Former White House Press Secretary Dana Perino stopped the gaggle, saying the on-camera briefing was just a repeat of the morning. She was right … except people that normally did not get to ask questions at the briefing could speak.
It is time the press accesses who really is helpful to reporting —and stop being a prop and sitting duck for any president.
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Poll: Biden has an overwhelming lead among Democratic voters
Biden has an overwhelming lead in the first 3 nominating contests, polls say
Poll: Biden opens huge lead over Democratic primary rivals

redpajama_set_name: RedPajamaCommonCrawl


text:
import numpy as np
import malis as m
import h5py
np.set_printoptions(precision=4)

print "Can we make the `nhood' for an isotropic 3d dataset"
print "corresponding to a 6-connected neighborhood?"
nhood = m.mknhood3d(1)
print nhood

print "Can we make the `nhood' for an anisotropic 3d dataset"
print "corresponding to a 4-connected neighborhood in-plane"
print "and 26-connected neighborhood in the previous z-plane?"
nhood2 = m.mknhood3d_aniso(1,1.8)
print nhood2

segTrue = np.array([0, 1, 1, 1, 2, 2, 0, 5, 5, 5, 5],dtype=np.int32);
node1 = np.arange(segTrue.shape[0]-1,dtype=np.int32)
node2 = np.arange(1,segTrue.shape[0],dtype=np.int32)
nVert = segTrue.shape[0]
edgeWeight = np.array([0, 1, 2, 0, 2, 0, 0, 1, 2, 2.5],dtype=np.float32);
edgeWeight = edgeWeight/edgeWeight.max()
print segTrue
print edgeWeight

nPairPos = m.malis_loss_weights(segTrue, node1, node2, edgeWeight, 1)
nPairNeg = m.malis_loss_weights(segTrue, node1, node2, edgeWeight, 0)
print np.vstack((nPairPos,nPairNeg))
# print nPairNeg

idxkeep = (edgeWeight > 0).astype(np.int32)
cc = m.connected_components(nVert,node1,node2,idxkeep)
print cc

# node1, node2 = m.nodelist_like((2,3,4),-np.eye(3))
# print node1
# print node2

datadir = '/groups/turaga/turagalab/greentea/project_data/dataset_06/fibsem_medulla_7col/trvol-250-1-h5/'
print "Reading test volume from " + datadir
# hdf5_raw_file = datadir + 'img_normalized.h5'
hdf5_gt_file = datadir + 'groundtruth_seg.h5'
# hdf5_aff_file = datadir + 'groundtruth_aff.h5'

#hdf5_raw_file = 'zebrafish_friedrich/raw.hdf5'
#hdf5_gt_file = 'zebrafish_friedrich/labels_2.hdf5'

# hdf5_raw = h5py.File(hdf5_raw_file, 'r')
h5seg = h5py.File(hdf5_gt_file, 'r')
# hdf5_aff = h5py.File(hdf5_aff_file, 'r')

seg = np.asarray(h5seg['main']).astype(np.int32)
aff = m.seg_to_affgraph(seg,nhood)
cc,ccSizes = m.connected_components_affgraph(aff,nhood)
aff2 = m.seg_to_affgraph(cc,nhood)
cc2,ccSizes2 = m.connected_components_affgraph(aff2,nhood)

print "Comparing 'seg' and 'cc':"
frac_disagree = np.mean(seg.ravel()!=cc.ravel())
ri,fscore,prec,rec = m.rand_index(seg,cc)
V_rand,V_rand_split,V_rand_merge = m.compute_V_rand_N2(seg,cc)
print "Connected components disagree at %f%% locations" % (frac_disagree*100)
print "\tRand index: %f, fscore: %f, prec: %f, rec: %f" % (ri,fscore,prec,rec)
print "\tV_rand: %f, V_rand_split: %f, V_rand_merge: %f" % (V_rand,V_rand_split,V_rand_merge)

print "Comparing 'cc' and 'cc2':"
frac_disagree = np.mean(cc.ravel()!=cc2.ravel())
ri,fscore,prec,rec = m.rand_index(cc,cc2)
V_rand,V_rand_split,V_rand_merge = m.compute_V_rand_N2(cc,cc2)
print "Connected components disagree at %f%% locations" % (frac_disagree*100)
print "\tRand index: %f, fscore: %f, prec: %f, rec: %f" % (ri,fscore,prec,rec)
print "\tV_rand: %f, V_rand_split: %f, V_rand_merge: %f" % (V_rand,V_rand_split,V_rand_merge)

redpajama_set_name: RedPajamaGithub


text:
This directory contains files for making a device running UnetStack 4.x.x be able to communicate acoustically with a device running UnetStack 3.x.x .

## Eligibility

This is currently tested on Subnero WNC-M25M* devices only.

## Differences

The differences are in the default configuration of the PHYSICAL and BASEBAND services.

- `phy[].fec` : UnetStack 3.x.x uses an older set of FEC algorithms. UnetStack 4.x.x does support the older `XXXv3` algorithms, but those need to be choosen specifically.
- `bb[].preamble` : The preambles used for detection have changed between UnetStack 4.x.x and UnetStack 3.x.x.
- `phy[].frameLength` : The default length of a PHYSICAL frame was different on UnetStack 4.x.x
- `bb[].threshold` : The threshold of the detector needs to be updated to 0.25 for UnetStack 3.x.x

## Usage
- Copy the `compat.groovy` file into the `scripts` directory of the device running UnetStack 4.x.x.
- Run the command `compat` on the shell. The PHYSICAL and BASEBAND services will be configured to be compatible with UnetStack 3.x.x

If you need to have the `compat` command run at every boot add the following line to `startup.groovy`.

```
run('compat')
```


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i love this season. i love it, i love it, i love it! it is during this time of the year that i get so giddy i can hardly deal with the energy inside my chest! i love october. i love halloween. but really, i just love autumn. i feel so full of life during these next couple months. everything feels exciting. the colors are beautiful, and the time with family is always so necessary.
i just decorated my desk at work for halloween. i plan on buying a mum and putting it in here, as well. tonight, i am going to decorate my house, which means buying pumpkins and mums, making cider, and maybe even baking some cookies. i wish it were a little cooler outside so i could make chili. where we live, we don't really have a backyard, so i will be recruiting someone to donate their home and their time for roasting of marshmallows. i can't wait for sweatshirts, boots, and hats.
it really is an amazing time of the year. and God is so good to my family. this month my husband and i celebrate 4 years of "dating"….next month i celebrate my niece's birthday. she was a miracle baby, and i cannot believe she is about to be 4! my parents will celebrate 38 years of marriage! WOW!
let's just say that this season i will choose to be nothing but thankful. i will work hard not to complain. i will let praise come from my lips, and i will take time to LIVE…to really slow down and enjoy moments of life with people i love, as i know these moments are fleeting.
it's easy to get off track with posting. but something about this season just makes me want to create, bake, and share my joy for fall. it makes me so happy to see and feel it approaching. this season will be especially busy and joyful.
my second shooting business got much busier. i have a total of 7 weddings over the next 3 months! a year ago, i wouldn't have thought that this amazing opportunity would have fallen in my lap. i also have family vacation to Disney coming up! i haven't been to Disney in forever! and i can't wait. my husband has never even been to Florida. so, this will be an experience for him, as well. and we are going with my niece, who is almost 4, and i keep swearing she will have a mini-heart attack as soon as she walks in the front entrance. she's in love with her "princesses", so i imagine this will be quite the adventure.
i prefer this photo of them.
i am also getting super excited to go see Sigur Ros. if you have never heard of them, and you like ambient type music that is absolutely beautiful, you will love them. i am also taking hubbs to see Peter Pan!
basically, in a nutshell, i am thankful for my life, thankful for my job, and thankful for Dave Ramsey for helping my husband and i get our finances straight so that we can actually enjoy the money we are making.
welcome fall and all your feelings, smells, treats, and experiences.
we have celebrated many occasions since i last posted. in fact, right before my last post we celebrated Adam's birthday! he is the ripe 'ol age of 29 (last year of his 20's!). normally i would do a cake, but The Donut Den in Nashville makes giant birthday donuts! oh. my. gosh. yes please! we absolutely loved it. it was deeeelicious!
but let's not forget MY birthday! adam was so sweet. i was sick that day, which was no fun at all. it was the third day in a row of me feeling rotten. but we made the day special anyway. i had a meeting in the morning, then they took me out to brunch at Marche' in East Nashville. good grief, i had french toast and it was perfect to ease my sick self. then we went to coffee at Bongo Java East. i went home to lay down for a bit, but i refused to let the day be spoiled. i did an all natural remedy for my sinus infection, and took down some of my concoction (Bragg's Apple Cider Vinegar-2tbsp., local honey or grade B maple syrup-2tbsp., and warm water-6oz.) it helped perk me back up.
i ended up going to Chago's for margaritas with my friend Nikki. glad i didn't cancel because it ended up being a surprise thing with some other friends! it was so nice to hang out and drink several margaritas. not sure which helped me get back to my healthy state, the apple cider vinegar mixture, or the tequila.
then my sister picked me up and took me shopping. she bought me my now favorite pair of shoes! Minnetonka Moccasins!
lastly, i came home to my husband and best friend for cake and rest. adam made me a card, a cake, and bought me some vodka. what a man…..
it was an amazing day! and i woke up saturday feeling 100 times better!
of course, there is more…but that's all for today!


text:
AR Monster
The "AR" standing for "augmented reality" in this iPhone RPG from Hudson.
SAN FRANCISCO – June 18, 2010 – Hudson Soft, leading developer of games for consoles, cellular phones and smartphones, today announced the release of AR Monster, a role-playing game for iPhone TM . The launch of AR Monster follows the huge success of Hudson Soft's Bomberman series and the release of over 30 titles worldwide. The company also announced that a future update will feature monsters from Aurora Feint's recently released iPad game, Aurora Feint 3.
AR Monster is a role-playing game that integrates augmented reality technology. Players can discover more than 600 monsters with their iPhone's camera and battle in an augmented reality world. Players will discover more monsters by pointing their camera's view finder in different directions and by moving to new locations. AR Monster uses the iPhone's GPS system to make completely different monsters appear in different geographic locations!
"With its innovative augmented reality technology, AR Monster is a great addition to our iPhone game portfolio," said Masato Shibata, Smartphone Business Division President of Hudson Soft. "We think that we've created a fantastic role-playing game for our players, with over 600 fierce monsters to battle and 6 awesome battle weapons to choose from."
AR Monster also uses OpenFeint for its global leaderboards and achievements and connects its game players to the mobile social network's 26 million players.
"Hudson Soft is a great partner and we're honored that they'll be incorporating monsters from our Aurora Feint 3 title in an upcoming release of AR Monster," said Jason Citron, CEO and founder of Aurora Feint. "Hudson Soft is an innovative game developer and doesn't disappoint in this title - incorporating augmented reality technology and GPS-altered game play. We're proud that they're also partnering with us to integrate OpenFeint to help make a great online gaming experience."
AR Monster is now available in the iTunes store.
About Hudson Soft ( www.dothehudson.net/en/)
Hudson Soft develops and markets content for consoles, cellular phones and smartphones, including the mega hit series Bomberman. The company released games on the App Store at its launch, and currently offers more than 30 titles worldwide. Hudson Soft is primarily focused on developing game titles for the iPhone/iPad platform and will release more titles soon.
NOTE to Editors: Logos and screenshots are available at: http://www.game-newswire.com/index.php/the-news/203-hudson-soft-releases-augmented-reality-role-playing-game-ar-monster-.html
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Sony: We have not cut PS VR 2 production numbers
Sony reportedly halves PS VR2 shipping numbers


text:
Jamie Campbell Bower Age, Wiki, Biography, Wife, Height in feet, Net Worth & Many More -
Home Profiles Jamie Campbell Bower Age, Wiki, Biography, Wife, Height in feet, Net Worth & Many More
Jamie Campbell Bower Age, Wiki, Biography, Wife, Height in feet, Net Worth & Many More
Profiles By Trend Setter Live · August 17, 2022 · 0 Comment
James Metcalfe Campbell Bower is an English actor and singer who is known for acting in American films and television series. He was born on 22nd November 1988 in London, England. His mother is a music manager and his father works for the Gibson Guitar Corporation. His maternal great-great-great-great-grandfather was Sir John Campbell, of Airds, Lieutenant Governor of Saint Vincent and the Grenadines. He learned violin as a young child. He did his schooling at Bedales School. She was a former member of the National Youth Music Theatre and the National Youth Theatre.
He started his career in modelling.
He started his acting career in 1999 with his theatre show Honk! Later in 2002, he appeared in his second theatre show, The Dreaming. In 2007, he made his film debut with Sweeney Todd: The Demon Barber of Fleet Street. He also made his television debut with the television film The Dinner Party. In 2008, he appeared in two films, RocknRolla and Winter in Wartime. In 2009, he appeared in the popular film, The Twilight Saga: New Moon. He was seen in a television series, The Prisoner. In 2010, he was seen in two films, Harry Potter and the Deathly Hallows – Part 1 and London Boulevard.
Later, in 2011, he was seen in the television series, Camelot. He also appeared in two films, The Twilight Saga: Breaking Dawn – Part 1 and Anonymous. In 2012, he acted in the film, The Twilight Saga: Breaking Dawn – Part 2. In that year, he appeared in the music video, Florence and the Machine. The Mortal Instruments: City of Bones was his only released film in 2013. In 2015, he appeared in a stage show, Bend It Like Beckham, a film Thomas & Friends: Sodor's Legend of the Lost Treasure and a television series, Thomas & Friends. Will was his only released television series in 2017. In 2018, he was seen in the film, Fantastic Beasts: The Crimes of Grindelwald. In 2019, he appeared in the television series, Urban Myths. He also appeared in the film Six Days of Sistine in the same year. In 2022, he appeared as Henry Creel / One / Vecna Stranger Things and it was a breakthrough performance for him. He was praised for his performance.
Apart from acting, Jamie is also a musician. He is the frontman and singer for the band Counterfeit. They released their first album in March 2017. The band split in November 2020. He also sings several songs, Paralysed, Start the Fire, Crow, Devil In Me and Run On.
She did her engagement with actress Bonnie Wright in April 2011. But they ended their relationship on 30th June 2012.
Name James Metcalfe Campbell Bower
Nick Name Jamie Campbell Bower
Birth Place London, England
Hometown London, England
School Bedales Independent School, Hampshire, England, United Kingdom
Collage National Youth Music Theatre
The National Youth Theatre, London, England, United Kingdom
Debut Film– Sweeney Todd: The Demon Barber of Fleet Street (2007)
Television– The Dinner Party (2007)
Jamie Campbell Bower Career
He started his acting career in 1999 with his theatre show Honk! Later in 2002, he appeared in his second theatre show, The Dreaming.
In 2007, he made his film debut with Sweeney Todd: The Demon Barber of Fleet Street. He also made his television debut with the television film The Dinner Party.
In 2008, he appeared in two films, RocknRolla and Winter in Wartime.
In 2009, he appeared in the popular film, The Twilight Saga: New Moon. He was seen in a television series, The Prisoner.
In 2010, he was seen in two films, Harry Potter and the Deathly Hallows – Part 1 and London Boulevard.
In 2011, he was seen in the television series, Camelot. He also appeared in two films, The Twilight Saga: Breaking Dawn – Part 1 and Anonymous.
In 2012, he acted in the film, The Twilight Saga: Breaking Dawn – Part 2. In that year, he appeared in the music video, Florence and the Machine.
The Mortal Instruments: City of Bones was his only released film in 2013.
In 2015, he appeared in a stage show, Bend It Like Beckham, a film Thomas & Friends: Sodor's Legend of the Lost Treasure and a television series, Thomas & Friends.
Will was his only released television series in 2017.
In 2018, he was seen in the film, Fantastic Beasts: The Crimes of Grindelwald.
In 2019, he appeared in the television series, Urban Myths. He also appeared in the film Six Days of Sistine in the same year.
In 2022, he appeared as Henry Creel / One / Vecna Stranger Things.
Jamie Campbell Bower Family
Father Name David Bower
Mother Name Anne Elizabeth
Brother Samuel Bower
Jamie Campbell Bower Relationship / Marital Status & Many More
Affairs / Girlfriend Ruby Quilter, Lily Collins,
Wife/ Spouse N/A
Jamie Campbell Bower with his Girlfriend (Ruby Quilter)
Jamie Campbell Bower Physical Stats
Jamie Campbell Bower Favourite
Jamie Campbell Bower Education
Jamie Campbell Bower Net Worth
Some Unknown facts about Jamie Campbell Bower
He has a tattoo fetish.
He was featured in a 2012 music video for the song "Never Let Me Go" by Florence + the Machine.
He was briefly engaged to Harry Potter actress Bonnie Wright, but the couple separated in 2012.
He worked as a part-time model for the British company Select Model Management.
He also became the lead singer of The Darling Buds.
Jamie Campbell Bower Social Media Profile
Jamie Campbell Bower Instagram Profile
A post shared by ᴊᴀᴍɪᴇ ᴄᴀᴍᴘʙᴇʟʟ ʙᴏᴡᴇʀ (@bowerjamie)
American Actor English Actors


text:
Holding Fast
By Billi Jean
Book 7 in the Love's Command series
Sara Stevens left her dreams behind long ago, but with William Bryson she can't stop wondering if they really can come true.
Will knew when he first met Sara Stevens that she was a temptation. He wasn't prepared for her, not six months ago in Wyoming, and certainly not now with the wild storm of the Sentinel drug still thrumming through him.
But life wasn't going to allow him the luxury of time. Not when Sara's threatened by Ashton Potter.
If Sara had learned one thing, it was that dreams were meant for fools. Life was raw and terrible. William Bryson was every girl's dream, which meant he wasn't to be trusted. But faced with an insane serial killer wanting to make her his next kill, she has no option but to let William close.
Only when she does, her fear switches from the evilness of the man chasing her, to the sexiness of the hero who held her close. He might protect her, but who will protect her heart from him?
General Release Date: 23rd May 2017
Sara stared down at the piece of paper in her hands. The insignificance was astonishing when she considered how hard she'd worked for it. What struck her wasn't that all her studies were over, or that she could now follow her dream of working with English language learners, it was that the registrar's certified letter wasn't even printed on high-quality paper. It was more like a receipt she'd get at some dry cleaners than proof that the last four years of attending classes, finishing assignments, passing exams, while holding two jobs, meant anything.
I'm done. It doesn't matter what it looks like. I'm a college graduate.
The graduation ceremony would have made more of an impact than the letter she held, but she'd been…unavailable.
Memories of those frightening days tried to swarm her. Sweat dampened her palms, so she straightened her shoulders and smiled at the student behind the registrar's counter.
Not thinking about that time.
"Thanks, this is great." She tried for a bright smile, but her lips were so numb she wasn't sure if she'd pulled it off.
The girl smiled back, though. She probably meant it, too. "It must be amazing to be done." She leaned on the counter. "I have two more years. It seems like forever."
"Enjoy it. This place rocks." A safe place. If I hadn't left here, I never would have gone to Wyoming, never would have taken a drug that changed everything. "I wish I had two more years," she added.
"The big bad world, huh? Yeah, I guess going to school isn't so hard, right?"
Hard doesn't even begin to describe it. Sara kept her thoughts to herself as she folded the paper carefully and tucked it away in her backpack. "Right. Now to go sell back my books, huh? Got to pay for this thing somehow." She waved the piece of paper and plastered on a smile again.
Stepping through the double doors and into the sunlight, she tried to slow her pounding pulse rate. The jitters had her in a stranglehold, but she'd been warned it wouldn't be easy getting back to life after Wyoming. Sara held the breath and counted to seven, then released it slowly counting to three, then repeated it until she could see past the shimmering brightness that often came with the nerves. The freakiest part of her mini-panic attacks was that they could be triggered by anything. It was never the same thing. She'd suddenly feel a sharp jab in her chest followed by the explosion of adrenaline. Her therapist, Cheryl, had taught her the breathing exercise. It seemed to do the trick.
Cheryl suggested stability would slowly put the past behind her. Getting a teaching job would help. When Sara found work and made money, paid for her apartment, and had what she needed, the events in Wyoming would slowly fade.
First, she needed stability, and to achieve that, she had to close the door on a few other things.
A shout in the distance caught her attention. A couple of college girls were taking the old wooden bridge that spanned the falls. They seemed oddly out of place. The campus was quiet, deserted in a way that made the laughing, playfulness of the girls stand out. Maybe everyone was in class, or it was that time of day to study and grab a coffee. Whatever the reason, Sara was thankful. She didn't want to run into anyone who might've kept her there answering too many questions.
When will I stand here again?
Not for a long time. Now, leaving, everything seemed so sharp and clear. The old brownstones were majestic. The enormous trees on either side provided comforting shade on hot summer days. She'd spent endless hours under them, studying for exams or reading. Everything, even the classrooms she'd spent so much time in along her left, held a special, safe spot in her heart. For the past four and a half years, all her focus had been on finishing her degree so she could begin a real life. Now that she held the paper to prove she'd managed it, an unexpected sadness struck her. The choked-up feeling tightened her throat, catching her by surprise as the beautiful scenery of the campus blurred.
"Crazy," she muttered, brushing tears off her cheeks. I should be happy, not sad.
No more classes, no more tutoring students in English after school and dancing all night, only to repeat the same thing the next day. Her beloved Swiss Army backpack held not only her degree but a brand-new teaching license.
I can start building a normal life. I can have a family. One of those families I always see through the windows, sitting at their table, eating a meal together.
A husband, children, a dog, maybe a cat, a house with a yard and summer vacations with their kids arguing while she and her husband wondered why they'd ever left the driveway.
Smiling at the silly dream, she tossed her hair out of her eyes and started walking. Before she could get on with her new life, she had to end the old one.
It shouldn't be too hard. Leaving things behind—or being left behind—was her specialty. She'd once dreamed of being a skater, like her friend, Paris. But that had proved impossible. Her mom had wanted her to have something different—so she'd taken Sara's skates away and given her ballet slippers instead. But when Sara had hit her teenage years, she'd quit ballet and joined a contemporary dance company. Her mom had been horrified. But what about her hadn't dismayed her prim and proper mom?
All those miserable memories clouded her thoughts as she walked across campus. She wondered what her mom would think of her now, but not enough to pick up a phone and call home. More likely than not, being a teacher, something so mundane, wouldn't impress her any more than how much money she'd made dancing.
It didn't matter. Trying to please her unhappy mother had fallen to the wayside years ago. They didn't speak, and when they did, it was usually because someone had asked about her and her mom felt guilty not being able to answer even the most basic question.
Thinking about those times brought back memories of pain when she knew she should be focusing on the future. When she did that, and worked at her dreams, anything was possible. At least she hoped it was.
Now a job as a teacher was her goal, and dance would fade away like skating had. The ice still called like an ache in her chest, until it grew impossible to ignore. Then she would lace up and spin in the frigid air until she couldn't breathe, but her heart felt right again each time. Now she had something else that did that—working with kids who didn't speak English.
But skating had turned her from a shy, insecure child to a person with confidence. Dance had taught her what a woman could do with her body. Both had given her the strength to understand that nothing she did would ever change her mother's misery, nor live up to some standard set by her.
So let it go.
Taking another deep breath, she willed herself to send those memories back where they belonged. The future has to be better, because the past sucks.
Her favorite motto brought a smile to her face. Yeah, eyes forward, and remember what you want.
One hour later Sara sat, more nervous than she'd thought she'd be, trying to explain to her soon-to-be ex-employer why she wouldn't be dancing for him any longer. It had seemed so simple when she'd practiced what she'd say, easy even. But face to face with Mr. Davis and his penetrating questions and she felt as if she'd walked onto the ice wearing her slipper socks.
"It's not the dancing, Mr. Davis." It was harder to explain to him than she'd thought it would be. Maybe that's because I barely understand the need to move on. "It's everything else."
Mr. Davis was the owner and operator of the burlesque club, Sweet Shady's Smile. She'd worked there three years to help pay for the cost of her tuition. Mr. Davis had given her a job without even seeing her dance. She'd been out on the ice, headphones on, her music filling her with the happiness she only found there. Right after she'd taken her skates off, Mr. Davis had walked up and made her an offer. She'd handed in her Applebee's apron the next day and tried on her first risqué costume.
"I see." He rested his large, tan hands on his desktop. The room was elegant, like the club. Everything was decorated like a 1920s joint. But in here, the dark, highly polished mahogany furnishings were rich with tones of red that matched the floor-to-ceiling bookcases. The shelves were lined with old leather-bound books that she itched to touch, but didn't dare. Still, the room was soothing to the senses, all except the man behind the enormous desk.
Mr. Davis.
He might wear elegant clothing, but he struck her as dangerous. It wasn't merely his sharp eyes and narrow face with the line of white slashed along his chin and continued on to wrap around his neck—a scar that the girls here all talked about. It was…him. He oozed deadly dangerous.
"Well, I can't lie. I had hoped to change your mind."
She dropped her gaze, unable to tolerate the intensity in his light gray eyes. His hands caught her attention. They were so beat up, they were at odds with the elegant charcoal-gray thin turtleneck and black trousers he wore. His hands weren't dirty—they were tough. His nails were cut short and orderly, but he couldn't straighten one finger so it angled upward. His joints were big, the knuckles scarred with traces of white lines that also appeared like faint ridges of scar tissue on the backs of his hands.
"Is it a customer? Or is it someone who works here—?"
She startled, realizing she'd been staring. She lifted her attention to his face. His dark eyebrows were slashed downward, a clear indication he wasn't pleased.
"No, it's nothing like that. Everyone is great, Mr. Davis, but…" She shrugged and twisted the material of her shirtsleeves, unsure how much to say. After Wyoming, she'd taken an extended sick leave. Mr. Davis had given it to her himself—no questions asked.
But she couldn't get into all that with him. She could barely talk to her therapist about it, and she wasn't strictly honest with her, either. Cheryl had been willing to do Skype sessions, only because Sara had lied and told them she was still in Canada. So, yeah, no one knew that today was the first time since Wyoming she'd left her apartment. And there was no way she was explaining that to this man. He might wear sophistication as if he'd been born with a silver spoon in his mouth, but she knew danger when she saw it, and Mr. Davis was dangerous. He probably had no idea what it was like to be afraid, so scared he couldn't leave his room for fear of what might be waiting outside the door.
"It's time to move on." New life. New job. New everything. Even me, I hope. "I've changed."
Surprising her, Mr. Davis didn't argue. She'd never spent much time with the man. He was too busy and more, too intense, for her to feel comfortable around. But he'd always been fair and he never hit on the girls—or allowed anyone else to, unless the girl was receptive to the attention. Over the past three years, she'd only spoken to him a handful of times. All had been over incidents in the club—fights mostly—that she'd witnessed.
"You have changed. I worried that someone had caused you harm, perhaps you were attacked, Ms. Stevens. Since you didn't come to me, it is clearly not my business. But whatever the case is, I fear someone has hurt you, am I correct?"
She licked her lips, suddenly feeling that rushing need to vomit hit her again. There was no room to not answer him, so she avoided the question. "I really want to teach, you know?"
Mr. Davis didn't answer for long enough that the room became uncomfortably silent. But since there wasn't a chance she'd explain what had happened to her, she couldn't say a word. The antique clock behind his desk ticked the seconds by. She even watched the narrow second hand move and could tell when the larger minute hand was tensing to click.
"Ah, I see, well, I have a suggestion for you. One I hope you'll take."
"Take a longer leave of absence. With your voice, and the way you dance, I'd offer you twice what you were making to stay on. But take some time, find a way to get through whatever happened to you this winter and move past it. Then give me a call on my private number." He handed her a crisp white business card with his cell number scrawled in bold lines on the back. "If you need anything, anything at all, or you want to take my offer, call me, Ms. Stevens."
Mr. Davis stood, ultra-polite, and as always, soft spoken. She got to her feet as well, already pocketing his number and knowing she wasn't going to need it. There were rumors about him, of course. Who didn't gossip about the boss? But if only half the whispers about him were true, she wasn't about to see if the interest in his light gray eyes went beyond her dancing on his stage.
"Ms. Stevens, are you forgetting something?" He held out an envelope with her last pay check in cash.
"Oh, yes, sorry, I guess I'm more nervous than I thought." She'd asked for her last pay check in cash. He hadn't asked why, and she was glad she didn't have to explain. Starting over meant more than a new address—cash would help, especially now.
"Take care of yourself, Ms. Stevens."
There's no one else who can, now is there? The truth of the thought brought the clarity she needed to walk away from Mr. Davis' offer of help.
Book Length: SUPER NOVEL
Genres: CONTEMPORARY
Billi Jean
Billi Jean was born in California but didn't stay put for long. She's lived in New York, Indiana, Missouri, Arizona, Colorado, Florida, Massachusetts and Vermont. She's lived in and worked from ranches to beach-side coffee shops to the woods in western Massachusetts. Now living and working in China, she continues to write for Totally Bound Publishing.
Billi Jean has been writing since high school when she couldn't wait for Robert Jordon to write his Wheel of Time series faster. As an adult, she still finds herself drawn to fantasy-adventure stories, but with an erotic romance flair. Her books are extremely hot, with a focus on strong characters that are shoved into fast-paced adventures. Her unique style of incredible journeys infused with hot passion leave her fans hoping for more.
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Other Books by Billi Jean
A Spartan's Kiss
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Sisterhood of Jade: Part Four: A Box Set
Golden's Rule
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Love's Command: Part One: A Box Set
The Promise of Love
Love's Command: Part Two: A Box Set


Deere & Company - Exit Before Earnings?
"Armchair Trader" Members Up 45% Potential Profit Already On This Options Trade!
Deere & Company shares have sunk – but will it last after earnings on Friday morning. This put options trade was recommended to ""Armchair Trader" Members" of Stock Options Made Easy on Monday morning; now up 45% potential profits in two days; more is likely; is it time to exit?
Or should you hold until after the earnings report due out Friday, before the market opens to obtain the 100% originally aimed for?
…….from……"Armchair Trader Series" Recommendations - Week Beginning Monday, August 13, 2018.
Deere & Company (NYSE:DE), engaged in equipment operations, will report earnings on Friday, August 17, 2018, before the market opens. Equities research analysts forecast that Deere & Company (NYSE:DE) will report $2.76 earnings per share for the current fiscal quarter. Five analysts have issued estimates for Deere & Company's earnings, with the lowest EPS estimate coming in at $2.61 and the highest estimate coming in at $2.84. Deere & Company reported earnings per share of $1.97 in the same quarter last year.
Also, Wall Street brokerages predict that Deere & Company will announce sales of $9.20 billion for the current quarter. Five analysts have provided estimates for Deere & Company's earnings, with estimates ranging from $9.19 billion to $9.21 billion. Deere & Company posted sales of $6.83 billion in the same quarter last year.
In the past three months, Deere's 100-day moving average price has fallen from $157.80 to $146.60, which indicates a downward trend in the stock.
Deere stock has fallen 9.2% year-to-date.
UBS analysts said the stocks in their coverage universe most impacted by trade tensions have underperformed the S&P 500 by about 4.5 percent since trade frictions began to intensify in mid-March…continue reading…..
** OPTION TRADE: Buy the DE SEPT 21 2018 135.000 PUT at approximately $4.40. Place a pre-determined sell at $8.80.
Also include a protective stop loss of $1.75.
Shares of Deere & Company sunk over 2% through early afternoon trading Wednesday in a sign that investors might be nervous about the firm ahead of its quarterly earnings release. But unfortunately, Deere's dip is part of a much larger decline over the last six months.
The reason to be wary her is that many analysts predict that Deere's top and bottom lines are projected to soar this quarter.
Deere did report a GAAP net loss of $535.1 million in its first fiscal quarter of 2018, which the company said was mainly due to the massive U.S. tax reforms. And the agricultural and construction equipment powerhouse has been negatively impacted by the ongoing trade disputes between the U.S. and China, as investors worry the company's costs could climb.
However, the firm reported net income of $1.21 billion, with revenues up 29%, in its second quarter.
More recently, the company's upbeat outlook is based on higher housing starts in the U.S. and an improved oil and gas sector. Deere also noted that it expects its June 2017 acquisition of the German-headquartered manufacturer of road construction equipment, Wirtgen Group, to have a positive impact on its sales. Furthermore, the economic environment for the construction, forestry, and road building industries look strong.
But DE stock is up just 7% over the last year, which lags the S&P's 15% climb. Much worse still, shares of Deere have plummeted by more than 13% since the start of the year.
So, for "Armchair Trader" members who managed to execute this trade recommended by Stock Options Made Easy; and wish to take potential profits now, 45%, at last look, was available.
Entering the option trade at a cost of $4.40 or less; and now as high as $6.40; one options contract would provide a profit of $200; or 45% Potential Profit.
This trade has been very profitable in a short time and it is very possible that further profit can be made from this put options trade, but as they say, "a bird-in-the-hand is better than two-in-the-bush".
Back to Stock Options Made Easy Home Page from Deere & Company - Exit Before Earnings?


Scotland is the true home of good whisky, but with five regions to choose from, where does one begin to look for the best Scotch?
Obviously this question is very subjective, depending on whether you like light floral undertones or heavy peated bass notes, but many drammers turn to Speyside for their tipple of choice.
Speyside, despite its somewhat small surface area, is the most densely populated region in terms of distilleries, with eighty-four working in total. It is truly the heart of whisky production in Scotland.
It is also home to some of the big names in the Scotch game, including Glenfiddich, Glenlivet and The Macallan. These are names that have gathered near legendary status, both at home and abroad, with Glenfiddich and Glenlivet being the biggest selling scotches worldwide.
The region is not only famous for its malts, but also for its glorious natural beauty.
The magnificent River Spey, lending its name to the region and also the second longest in Scotland, runs through the rolling heather hills and deep green valleys of this part of Scotland.
The land is the epitome of outstanding beauty and compliments the exceptional whisky that is made here.
The river is also the main water source for many of the distilleries found here. Many Speyside fans attribute the overall success of Speyside malts to the fantastic water quality that comes from the river.
But the beautiful surroundings and exceptional quality of the region's natural resources are not the only things to know about Speyside.
The malts produced here tend to be light and floral in profile. Age is a massive contributor to the high quality of these malts, especially when matured in sherry casks, a common practice in Speyside.
A delicate fruitiness is also very common in Speyside malts, with apples and pears making an appearance, tied in with subtle honeyed sweetness and exquisite vanilla highlights.
One needs only look to the Glenfiddich range to find an exceptional expression each of these flavours.
The malts of this region are a movement away from the deeply peated whiskies of the Highlands and Islands and the sea salted coarseness of the Lowlands, with a sweet lightness being the biggest expression found here.
That doesn't mean that peated whiskies are not available here, with distilleries such as BenRiach and Tomintoul producing some very fine peated malts.
As discussed, the high water quality of the River Spey has massive effects on the malt produced from it.
This malt tends to be smooth, carrying the rich, fragrant flavours delicately and easily across the taste buds, a smoothness that perfectly combines with its lightness.
Speyside lives up to the hype. The brands produced here are of consistently high quality and do not let their region down.
So the next time you're wondering about where the best scotch is from, why not pick up a bottle of Glenfiddich, or a dram of Glen Livet, and experience the Speyside region for yourself?
Next ArticleGreatDrams wins UK Food And Drink Blog of the Year 2017!


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Your Perfect Peru
About Peru
Release the Environmental Scientist in You
As you read this, there are myriad scientists conducting field research expeditions that tackle critical environmental challenges around the globe—from climate change to ocean health, human-wildlife conflict, and more. How would you like to join them?
Thanks to the efforts of the Earthwatch Institute, you can. Earthwatch provides ordinary citizens—no scientific knowledge or experience necessary–with the opportunity to work alongside leading scientists to combat some of the planet's most pressing environmental issues.
Earthwatch is an international nonprofit organization that has been connecting "civilians" with scientists since 1971. Since then, the organization has enabled over 100,000 people from all walks of life to join leading scientists working on crucial environmental research projects locally and globally. Earthwatch currently supports about 60 projects in nearly 40 countries, including Peru.
Earthwatch does not consider itself a voluntourism, ecotourism, or adventure travel company, because its volunteers experience real, hands-on scientific fieldwork in some of the most astounding locations in the world. Volunteers have ranged in age from 10 to over 80. The organization's standard expeditions have a minimum age of 18 except for volunteers accompanied by a parent or legal guardian, in which case the minimum age for most expeditions is 15.
Earthwatch is currently operating two conservation projects in Peru. The first is the 4-day Amazon Riverboat Exploration, where you'll help survey the area's wildlife to develop conservation strategies for the region and the people who inhabit it. To learn more about this expedition, click here.
The second opportunity takes place on the north coast of Peru, where Earthwatch scientists are monitoring the health and well-being of giant manta rays. Join this expedition, and you will have the chance to snorkel alongside these beautiful behemoths, photograph them, document markers such as scars, take measurements and more.
While at sea, you'll also document seabirds and marine megafauna—whale sharks, dolphins, humpback whales, and sea turtles—that can help give scientists a more complete picture of the larger Pacific Ocean ecosystem.
Join Earthwatch in Peru, and you can help make a difference in some of the most astounding areas of the country. You'll meet a community of like-minded travelers and return home with stories filled with adventure.
25% OFF Explora Valle Sagrado
5% OFF Trail of the Incas Volunteer Adventure
14 Days North Peru, The Mayo & Huallaga Valleys
© Copyright 2017 PromPeru.


iRadioPhilly's live broadcast from the Field Stage at the 4th annual Haverford Music Festival. Includes interviews between sets from performers on all stages.
Beatlemania NOW closes the evening.
Self Indulgence Band features covers and original tunes. After the set Paul Kelly interviews brilliant Russian classical crossover singer Marina Cruzo after her first US performance at the Haverford Music Festival.
Chaquis Maliq, a one woman show featuring Urban Folk, Soul and Acoustic Pop. After her performance, Paul Kelly interviews Chaquis Maliq about her influences and style.
Green Eggs and Jam fills the air with Jazz-Funk Rock. After their performance Paul Kelly interviews David Falcone and Nixon's Head after their performances on other stages. Paul also interviews Green Eggs and Jam.
The End of America, an emerging new Philly band with amazing 3 part harmonies and Folk Rock. Al Clay interviews band members after their performance.
Haverford Music Festival opening with Paul Mariani III singing the national anthem. Hevertown's own Electric Oracle performed the first set of the day. After the set, Al Clay interviews the band.


text:
Don't fear my robots, says the Boston Dynamics founder who makes machines that drive the internet wild
Isobel Asher Hamilton
Boston DynamicsBoston Dynamics robot 'SpotMini.'
Boston Dynamics has sent the internet into meltdown by creating robot dogs that can open doors and a back-flipping humanoid.
The machines have provoked quips about it being the end of human civilisation, but CEO Marc Raibert has sought to reassure people, according to Associated Press.
Boston Dynamics did not, however, rule out the possibility of weaponizing its robots.
Robotics firm Boston Dynamics has sent the internet into meltdown with robot dogs that can open doors and a back-flipping humanoid. The advances provoked quips about it being the end of human civilisation and even inspired a dystopian episode of Netflix show "Black Mirror" with killer robo-dogs.
But CEO Marc Raibert has played down fears about his machines, according to an Associated Press report. At a robotics conference in late May, Raibert told the AP that technological advances come with risk – but that's because of humans, not machines.
"We think about that, but that's also true for cars, aeroplanes, computers, lasers," said Raibert. "Every technology you can imagine has multiple ways of using it. If there's a scary part, it's just that people are scary. I don't think the robots by themselves are scary."
His comments come as "SpotMini," a dog-like Boston Dynamics robot, is slated for commercial release next year, with plans to manufacture 1,000 annually.
It weighs as much as a Labrador and is able to navigate autonomously, climb stairs, and open doors. The machine will apparently be sold to businesses as a camera-equipped security guard. The price is yet to be announced.
Videos of "SpotMini" have also shown the robot being poked with hockey sticks and tugged around by engineers to test its "robustness." While it can take a kicking, there's no evidence yet to suggest it could fight back.
Boston Dynamics' broader plans remain murky, according to the AP, and it has not ruled out military applications for its technology.
Founded in 1992, previously Boston Dynamics' focus was more on research than commercial demands. It initially received military funding from the Defence Advanced Research Projects Agency (DARPA). A federal contracting database lists more than $US150 million (£186 million) in funding allotted to Boston Dynamics since 1994, the AP said.
YouTube/Boston Dynamics'Atlas' sticks the landing after performing a backflip.
In 2013 Google acquired Boston Dynamics and was keen to shift emphasis away from military applications. But in 2016, Google sold the company to Japanese conglomerate SoftBank.
SoftBank said nothing about its plans for Boston Dynamics when contacted by AP, but its approach has been interpreted as more commercially minded by people familiar with the company. While Raibert has played down fears about his creations, weaponizing them for revenue is not completely off the table.
black mirror boston dynamics dogs google robots sai-us softbank


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https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMzM0NjA3LW92ZXJ2aWV3
Drugs & Diseases > Rheumatology
Author: Mujahed M Alikhan, MD; Chief Editor: Herbert S Diamond, MD more...
Sections Paget Disease
Approach Considerations
Urinary Markers
Radiographs
Bone Scans
CT and MRI
Histologic Findings
Bisphosphonates and Calcitonin Analogues
Neoplasm
Spinal Disease
Diet and Activity
Long-Term Monitoring
Guidelines Summary
Paget's Association
Endocrine Society Guidelines
Medication Summary
Metabolic & Endocrine, Other
Paget disease is a localized disorder of bone remodeling that typically begins with excessive bone resorption followed by an increase in bone formation. [1] This osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. [2]
The English surgeon Sir James Paget first described chronic inflammation of bone as osteitis deformans in 1877. [3] Paget disease, as the condition came to be known, is the second most common bone disorder (after osteoporosis) in elderly persons.
Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:
Bone pain (the most common symptom)
Secondary osteoarthritis (when Paget disease occurs around a joint)
Bony deformity (most commonly bowing of an extremity)
Excessive warmth (due to hypervascularity)
Neurologic complications (caused by the compression of neural tissues)
Paget disease may involve a single bone but is more frequently multifocal. [4] It has a predilection for the axial skeleton (ie, spine, pelvis, femur, sacrum, and skull, in descending order of frequency), but any bone may be affected. After onset, Paget disease does not spread from bone to bone, but it may become progressively worse at preexisting sites.
Sarcomatous degeneration of pagetic bone is an uncommon but often deadly complication. Pagetic sarcoma is malignant, and the course usually is rapid and fatal
Although the etiology of Paget disease is unknown, both genetic and environmental contributors have been suggested. Ethnic and geographic clustering of Paget disease is well described. Paget disease is common in Europe (particularly Lancashire, England), North America, Australia, and New Zealand. It is rare in Asia and Africa. In the United States, most, although not all, individuals with Paget disease are white. (See Epidemiology.)
A familial link for Paget disease was first reported by Pick in 1883, who described a father-daughter pair with Paget disease. This was followed shortly thereafter with a sibling case of Paget disease described by Lunn in 1885. Approximately 40% of persons with Paget disease report a family history of the disease, although the true prevalence of the disease is likely higher.
Some studies suggest a genetic linkage for Paget disease located on chromosome arm 18q. This has not been demonstrated in most families with Paget disease, however, which suggests genetic heterogeneity.
An environmental trigger for Paget disease has long been considered but never proven. Bone biopsies in patients with Paget disease have demonstrated antigens from several different Paramyxoviridae viruses, including measles virus and respiratory syncytial virus, located within osteoclasts. However, the putative antigen or antigens remain unknown.
Measurement of serum alkaline phosphatase—in some cases, bone-specific alkaline phosphatase (BSAP)—along with several urinary markers, can be useful in the diagnosis of Paget disease. Plain radiographs and bone scanning should be performed upon initial diagnosis. (See Workup.) Medical therapy is principally with bisphosphonates; surgical therapy may be indicated. (See Treatment and Medication.)
Three phases of Paget disease have been described: lytic, mixed lytic and blastic, and sclerotic. In an individual patient, different skeletal lesions may progress at different rates. Thus, at any one time, multiple stages of the disease may be demonstrated in different skeletal regions.
Paget disease begins with the lytic phase, in which normal bone is resorbed by osteoclasts that are more numerous, are larger, and have many more nuclei (up to 100) than normal osteoclasts (5-10 nuclei). Bone turnover rates increase to as much as 20 times normal.
The second phase, the mixed phase, is characterized by rapid increases in bone formation from numerous osteoblasts. Although increased in number, the osteoblasts remain morphologically normal. The newly made bone is abnormal, however, with collagen fibers deposited in a haphazard fashion rather than linearly, as with normal bone formation. As the osteoclastic and osteoblastic activities of bone destruction and formation repeat, a high degree of bone turnover occurs.
In the final phase of Paget disease, the sclerotic phase, bone formation dominates and the bone that is formed has a disorganized pattern (woven bone) and is weaker than normal adult bone. This woven bone pattern allows the bone marrow to be infiltrated by excessive fibrous connective tissue and blood vessels, leading to a hypervascular bone state.
After a variable amount of time, osteoclastic activity may decrease, but abnormal bone formation continues. Some pockets of normal-appearing lamellar bone may replace immature woven bone. Eventually, osteoblastic activity also declines, and the condition becomes quiescent. This is the sclerotic, or burned-out, phase. Continued bone resorption and formation are minimal or absent.
Paget disease can affect every bone in the skeleton, but it has an affinity for the axial skeleton, long bones, and the skull. The skeletal sites primarily affected include the pelvis, lumbar spine, femur, thoracic spine, sacrum, skull, tibia, and humerus. The hands and feet are very rarely involved.
Complications of Paget disease depend on the site affected and the activity of the disease. When Paget disease occurs around a joint, secondary osteoarthritis may ensue. Skull involvement may lead to the following:
Dental malocclusion
Basilar invagination
Cranial nerve disorders
Frequently, erythema is present over the affected bone area, which is due to the increased hypervascularity. In patients with Paget disease who have extensive bony involvement, this increased bone vascularity may cause high-output cardiac failure and an increased likelihood of bleeding complications following surgery.
Vertebral involvement of Paget disease may be associated with serious complications, including nerve root compressions and cauda equina syndrome. Fractures, which are the most common complication of Paget disease, may occur and may have potentially devastating consequences. Rarely, pagetic bone may undergo a sarcomatous transformation.
Standard serum chemistry values, including serum calcium, phosphorus, and parathyroid hormone levels, are normal in persons with Paget disease. However, hypercalcemia may complicate the course of Paget disease, most frequently in the setting of immobilization. Elevated levels of uric acid and an increased prevalence of gout have been reported in patients with Paget disease.
Levels of bone turnover markers (including markers of bone formation and resorption) are elevated in patients with active Paget disease and may be used to monitor the course of disease. The degree of elevation of these biomarkers helps identify the extent and severity of bone turnover.
Markers of bone turnover that are useful to monitor in persons with Paget disease include the following:
Bone-specific alkaline phosphatase (marker of bone formation)
Deoxypyridinoline (marker of bone resorption)
N -Telopeptide of type I collagen (marker of bone resorption)
Alpha-alpha type I C-telopeptide fragments
Alpha-alpha type I C-telopeptide fragments are sensitive markers of bone resorption for assessing disease activity and monitoring treatment efficacy in persons with Paget disease. [5] Serum osteocalcin, a marker of bone formation, is not a useful parameter to assess in persons with Paget disease. Upon successful treatment of Paget disease, the level of these bone markers is expected to decrease.
The juvenile form of Paget disease differs greatly from the adult version. Juvenile Paget disease is characterized by widespread skeletal involvement and has distinctly different histologic and radiologic features. [6]
The cause of Paget disease is unknown. Both genetic and environmental factors have been implicated.
The geographic distribution of the disease may be explained by genetic transmission and dissemination by population migration. Studies have found a positive family history in 12.3% of 788 patients in the United States, 13.8% of 407 patients in Great Britain, and 22.8% of 658 patients in Australia. In the former 2 studies, a 7- to 10-fold increase in the incidence of Paget disease was observed in relatives of patients diagnosed with the condition, compared with control groups.
In one study, 15-40% of affected patients had a first-degree relative with Paget disease. Numerous other studies have described families exhibiting autosomal dominant inheritance.
Studies of potential genetic markers for Paget disease have found an association between human leukocyte antigen–A (HLA-A), HLA-B, and HLA-C (class I) and clinical evidence of disease. Two studies reported an increased frequency of DQW1 and DR2 antigens (class II HLA). The studies on HLA have not been conclusive, however; variation among families tested suggests that genetic heterogeneity is likely. [7]
Subsequent genome linkage studies identified several loci associated with Paget disease. Mutations in the sequestosome SQSTM1/p62 gene were identified in 30% of familial Paget cases. The SQSTM1/p62 protein is a selective activator of NFB (nuclear factor kappa-B) transcription factor, which is involved in osteoclast differentiation and activation in response to the cytokines interleukin-1 (IL-1) and RANKL (receptor activator of nuclear factor kappa-B ligand). How germline DNA mutations can cause bone disease that is focal in nature remains unclear.
Alterations in cytokine expression have been found in persons with Paget disease [8] : elevated interleukin-6 (IL-6) levels are found in bone marrow plasma and peripheral blood in patients with Paget disease but not in healthy controls. One hypothesis is that some unidentified viral infection up-regulates IL-6 and the IL-6 receptor genes; however, this has not been shown conclusively. [9, 10]
Osteoclast precursors in patients with Paget disease also appear to be hyperresponsive to vitamin D (specifically, 1,25(OH)2 D3, the active form of vitamin D3 [11] ) and calcitonin and have up-regulation of the c-fos proto-oncogene [12] and BC12, the antiapoptosis gene. Treatment efficacy of bisphosphonates in Paget disease may be due to suppression of RANKL-induced bone resorption, with decreases in RANKL and increased osteoprotegerin production.
Macrophage-colony stimulating factor (M-CSF) may play a role in Paget disease. M-CSF is a growth factor produced by many cells, including osteoblasts and marrow fibroblasts. Significantly high levels of M-CSF have been found in patients with untreated Paget disease; however, its exact role remains to be determined.
The development of Paget disease of bone may be related to a deregulation of autophagy, a catabolic process responsible for the degradation of damaged organelles, cytoplasmic proteins, and protein aggregates. Structures observed in the cytoplasm of many osteoclasts in Paget disease may be protein aggregates that would normally be degraded via autophagy. [13]
Variants of several genes involved in the process of autophagy, such as SQSTM1, VCP, and OPTN have been linked with Paget disease. For example, 20–40% of patients with a positive family history of Paget disease and 5–10% of patients with sporadic Paget disease are carriers of a mutation in SQSTM1. [13]
A missense mutation in the zinc finger protein 687 gene (ZNF687) has been found in Paget disease–affected members of a large family, several of whom had giant cell tumors of bone associated with Paget disease. ZNF687 wasalso upregulated in the peripheral blood of Paget disease–affected family members with and without mutations in SQSTM1. [14]
A study of ATG genes, which code for proteins involved in autophagy, found that persons who are carriers of the C allele of the ATG16L1 rs2241880 and the G allele of ATG5 rs2245214 polymorphisms were associated with an increased risk of developing Paget disease, whereas carriers of the T allele of ATG10 rs1864183 polymorphism were at decreased risk. [13]
Environmental factors also may contribute to the pathogenesis of Paget disease. Supporting observations include the variable penetrance of Paget disease within families with a genetic predisposition; the fact that the disease remains highly localized to a particular bone or bones rather than affecting the entire skeleton; and data that reveal a declining incidence and severity of the disease over the past 20-25 years.
The leading hypothesis for an infectious etiology in Paget disease is the slow virus theory. According to this hypothesis, bone marrow cells (the progenitors of osteoclasts) are infected by a virus, causing an abnormal increase in osteoclast formation. Clinical expression of these viral infections may take years, which may account for the advanced age of most people diagnosed with Paget disease. Familial and geographic clustering also may support the theory of a viral process.
Suspected viruses are paramyxoviruses, such as measles or canine distemper viruses. Respiratory syncytial virus also is suspected; however, no virus has been cultured from pagetic tissue, and extracted ribonucleic acid (RNA) has not confirmed a viral presence.
Some studies have found viral inclusion particles in pagetic osteoclasts. [15] Measles virus messenger RNA sequences have been found in osteoclasts and other mononuclear cells of pagetic bones. Canine distemper virus nucleocapsid antigens have also been found in osteoclasts from patients with Paget disease. However, the presence of these paramyxovirus-like nuclear inclusions does not prove that these are responsible for the development of pagetic lesions; rather, these inclusions may be markers of the disease itself.
Other suggested etiologies
The possibility of an inflammatory cause of Paget disease is supported by evidence of clinical improvement after treatment with anti-inflammatory medications. Elevated parathyroid hormone in Paget disease also has been observed, but no firm evidence links the 2 disorders, and one case of Paget disease was diagnosed in a patient with idiopathic hypoparathyroidism. An osteogenic mechanism also has been proposed. Autoimmune, connective tissue, and vascular disorders are proposed as other possible etiologies.
United States statistics
Paget disease is estimated to affect 1 to 3 million people in the United States. Epidemiologic studies are inherently imprecise, however, because many individuals with Paget disease are asymptomatic.
According to a 2000 study by Altman et al, the prevalence of pelvic Paget disease in the United States was 0.71% ± 0.18%, based on data from the National Health and Nutrition Examination Survey I (NHANES I, 1971-1975). The male-to-female ratio was 1.2:1, and the prevalence of pelvic Paget disease was the same in white persons and black persons.
The prevalence of pelvic Paget disease increases with age, with the highest prevalence in persons older than 65 years. A survey study suggested that the prevalence in the United States is 2.3% of the population between ages 65 and 74 years. [16] Paget disease is estimated to occur in 1-3% of individuals older than 45-55 years and in up to 10% of persons older than 80 years. Geographically, pelvic Paget disease was least common in the southern United States and most common in the northeastern United States. [16]
International statistics
The prevalence of Paget disease varies greatly in different areas of the world. The highest prevalence is in Europe (predominantly England, France, and Germany). [17] The United States, Australia, and New Zealand have high prevalence rates because of significant populations with northern European ancestry and a large population of British immigrants. [18] The disease is rare in Asian countries, especially China, India, and Malaysia, and in the Middle East and Africa.
Prevalence may vary even within the same country. [19] A prevalence of 2% in certain British cities can be contrasted with rates in Lancaster, England, which had a prevalence of 8.3%. [20]
In Europe, the prevalence rates of Paget disease appear to decrease from north to south, with the exception of Norway and Sweden, which both have very low rates (0.3%). The highest prevalence in Europe is found in England (4.6%) and France (2.4%) in hospitalized patients older than 55 years. Other European countries, such as Ireland, Spain, Germany, Italy, and Greece, report prevalence rates of Paget disease that range from 0.5% to approximately 2%. The prevalence rates of Paget disease in Australia and New Zealand range from 3-4%.
The prevalence of Paget disease in sub-Saharan Africa is 0.01-0.02%. In Israel, Paget disease is predominantly found in Jews; however, cases have recently been reported in Israeli Arabs.
In South America, the incidence of Paget disease is relatively high in Argentina (around Buenos Aires), which was settled by Spanish and Italian immigrants, and lower in Chile and Venezuela.
Research from Europe and New Zealand indicates that the prevalence of Paget disease has decreased since the 1980s but that increased incidence with age has been maintained. [21] The estimated prevalence of Paget's disease in patients aged 55 years or older has decreased to approximately 2%.
Race-, sex-, and age-related differences in incidence
Paget disease is not known to demonstrate a predilection for any race. Nevertheless, unusual patterns of prevalence have been noted. Paget disease is more common in males than females. The male-to-female ratio is approximately 1.8:1.
Paget disease is distinctly rare in persons younger than 25 years and increases in frequency with increasing age. Paget disease is believed to develop in persons in the fifth decade of life and is most commonly diagnosed in the sixth decade. The incidence of Paget disease in persons older than 80 years is approximately 10%. There is a juvenile form of Paget disease, but it is very different from the adult form. [22]
The general outlook for patients with Paget disease is good, especially if treatment is administered before major changes have occurred in the bones. Treatment does not cure Paget disease, but it can control it. Patients with severe polyostotic Paget disease have a less favorable prognosis than those with monostotic disease. Patients with polyostotic disease are at higher risk for complications.
Morbidity from Paget disease can be extensive. The excessive remodeling of bone associated with Paget disease may result in pain, fractures, and bone deformities. Complications associated with fractures, such as articular and neurologic problems, may increase mortality in patients with Paget disease. The hypervascularity of bone that may result from Paget disease may cause excessive bleeding following fractures or surgery.
The prognosis is extremely unfavorable if the patient has any type of sarcomatous degeneration, especially if there is multicentricity. The 5-year survival rate for a patient with Paget disease and sarcoma is 5-7.5%; however, it may be as high as 50% for those who undergo operative tumor ablation and chemotherapy before metastases occur. The 5-year survival rate for elderly patients with primary nonpagetic sarcoma is 37%.
Higher doses of radiation may be delivered if the neoplasm is located on the limb. Consequently, a more central lesion carries a less favorable prognosis.
Patient education about the pathophysiology of Paget disease and its complications is essential. The patient needs to understand the importance of proper posture, body mechanics, and avoidance of trauma. Precautions against falling should be reinforced. At the same time, the hazards of immobility increase greatly with Paget disease. The patient should understand the necessity of staying active.
Knowledge of the signs and symptoms of complications is important. For instance, increased local pain with soft tissue mass should be reported to a physician immediately, as this may represent a sarcoma.
Understanding the potential side effects of medications is helpful and reassuring to the patient. For example, patients taking bisphosphonates should be aware of the potential for osteonecrosis of the jaw.
Patient education about delayed bone healing and the long rehabilitation process is important in situations of fracture and postsurgery. Reinforcement about the importance of careful, prolonged, protected weight bearing is crucial because the pagetic bone is abnormal and weak. Nonunion and refracture rates are high among patients with Paget disease.
Family members should be informed of the increased incidence of Paget disease in families. Proper patient education on the nature of Paget disease is essential. For patient education information, see Paget's Disease. In addition, The Paget Foundation for Paget's Disease of Bone and Related Disorders (telephone: 800-237-2438) can provide useful information for patients.
Bouchette P, Boktor SW. Paget Disease. 2018 Jan. [Medline]. [Full Text].
Lalam RK, Cassar-Pullicino VN, Winn N. Paget Disease of Bone. Semin Musculoskelet Radiol. 2016 Jul. 20 (3):287-299. [Medline].
Paget J. On a form of chronic inflammation of bones. Medico-chirurgical Transactions. 1877;65:37-63:
Senthil V, Balaji S. Monostotic Paget Disease of the Lumbar Vertebrae: A Pathological Mimicker. Neurospine. 2018 Jun. 15 (2):182-186. [Medline]. [Full Text].
Alexandersen P, Peris P, Guañabens N, Byrjalsen I, Alvarez L, Solberg H, et al. Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone. J Bone Miner Res. 2005 Apr. 20(4):588-95. [Medline].
Polyzos SA, Cundy T, Mantzoros CS. Juvenile Paget disease. Metabolism. 2017 Nov 22. [Medline].
Hughes AE, Shearman AM, Weber JL, Barr RJ, Wallace RG, Osterberg PH, et al. Genetic linkage of familial expansile osteolysis to chromosome 18q. Hum Mol Genet. 1994 Feb. 3(2):359-61. [Medline].
Neale SD, Schulze E, Smith R, Athanasou NA. The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease. QJM. 2002 Apr. 95(4):233-40. [Medline].
Hoyland JA, Freemont AJ, Sharpe PT. Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget's disease. J Bone Miner Res. 1994 Jan. 9(1):75-80. [Medline].
Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Löwik CW, Papapoulos SE. Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate. J Bone Miner Res. 1995 Jun. 10(6):956-62. [Medline].
Menaa C, Barsony J, Reddy SV, Cornish J, Cundy T, Roodman GD. 1,25-Dihydroxyvitamin D3 hypersensitivity of osteoclast precursors from patients with Paget's disease. J Bone Miner Res. 2000 Feb. 15(2):228-36. [Medline].
Hoyland J, Sharpe PT. Upregulation of c-fos protooncogene expression in pagetic osteoclasts. J Bone Miner Res. 1994 Aug. 9(8):1191-4. [Medline].
Usategui-Martín R, García-Aparicio J, Corral-Gudino L, Calero-Paniagua I, Del Pino-Montes J, González Sarmiento R. Polymorphisms in autophagy genes are associated with paget disease of bone. PLoS One. 2015. 10 (6):e0128984. [Medline].
Divisato G, Formicola D, Esposito T, Merlotti D, Pazzaglia L, Del Fattore A, et al. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor. Am J Hum Genet. 2016 Feb 4. 98 (2):275-86. [Medline]. [Full Text].
Rebel A, Basle M, Pouplard A, Malkani K, Filmon R, Lepatezour A. Towards a viral etiology for Paget's disease of bone. Metab Bone Dis Relat Res. 1981. 3(4-5):235-8. [Medline].
Altman RD, Bloch DA, Hochberg MC, Murphy WA. Prevalence of pelvic Paget's disease of bone in the United States. J Bone Miner Res. 2000 Mar. 15(3):461-5. [Medline].
Poór G, Donáth J, Fornet B, Cooper C. Epidemiology of Paget's disease in Europe: the prevalence is decreasing. J Bone Miner Res. 2006 Oct. 21(10):1545-9. [Medline].
Cooper C, Dennison E, Schafheutle K, Kellingray S, Guyer P, Barker D. Epidemiology of Paget's disease of bone. Bone. 1999 May. 24(5 Suppl):3S-5S. [Medline].
Guañabens N, Garrido J, Gobbo M, Piga AM, del Pino J, Torrijos A, et al. Prevalence of Paget's disease of bone in Spain. Bone. 2008 Dec. 43(6):1006-9. [Medline].
Barker DJ, Chamberlain AT, Guyer PB, Gardner MJ. Paget's disease of bone: the Lancashire focus. Br Med J. 1980 Apr 26. 280(6222):1105-7. [Medline]. [Full Text].
Doyle T, Gunn J, Anderson G, Gill M, Cundy T. Paget's disease in New Zealand: evidence for declining prevalence. Bone. 2002 Nov. 31(5):616-9. [Medline].
Bouchette P, Boktor SW. Paget Disease. 2017 Jun. [Medline]. [Full Text].
Dove J. Complete fractures of the femur in Paget's disease of bone. J Bone Joint Surg Br. 1980 Feb. 62-B(1):12-7. [Medline].
Mangham DC, Davie MW, Grimer RJ. Sarcoma arising in Paget's disease of bone: declining incidence and increasing age at presentation. Bone. 2009 Mar. 44(3):431-6. [Medline].
Goldman AB, Bullough P, Kammerman S, Ambos M. Osteitis deformans of the hip joint. AJR Am J Roentgenol. 1977 Apr. 128(4):601-6. [Medline].
Lluberas-Acosta G, Hansell JR, Schumacher HR Jr. Paget's disease of bone in patients with gout. Arch Intern Med. 1986 Dec. 146(12):2389-92. [Medline].
Alvarez L, Guañabens N, Peris P, Monegal A, Bedini JL, Deulofeu R, et al. Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. J Bone Miner Res. 1995 Mar. 10(3):458-65. [Medline].
Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008 Sep. 83(9):1032-45. [Medline]. [Full Text].
Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics. 2002 Sep-Oct. 22(5):1191-216. [Medline].
Seitz S, Priemel M, Zustin J, Beil FT, Semler J, Minne H, et al. Paget's disease of bone: histologic analysis of 754 patients. J Bone Miner Res. 2009 Jan. 24(1):62-9. [Medline].
Lyles KW, Siris ES, Singer FR, Meunier PJ. A clinical approach to diagnosis and management of Paget's disease of bone. J Bone Miner Res. 2001 Aug. 16(8):1379-87. [Medline].
Corral-Gudino L, Tan AJ, Del Pino-Montes J, Ralston SH. Bisphosphonates for Paget's disease of bone in adults. Cochrane Database Syst Rev. 2017 Dec 1. 12:CD004956. [Medline].
Silverman SL. Paget disease of bone: therapeutic options. J Clin Rheumatol. 2008 Oct. 14(5):299-305. [Medline].
Abelson A. A review of Paget's disease of bone with a focus on the efficacy and safety of zoledronic acid 5 mg. Curr Med Res Opin. 2008 Mar. 24(3):695-705. [Medline].
Woitge HW, Oberwittler H, Heichel S, Grauer A, Ziegler R, Seibel MJ. Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone. Clin Chem. 2000 May. 46(5):684-90. [Medline].
Reid IR, Wattie D, Gamble GD, Kalluru R, Cundy T. Long-Term Effects of Intravenous Ibandronate in Paget's Disease of Bone. Calcif Tissue Int. 2017 Mar. 100 (3):250-254. [Medline].
González DC, Mautalen CA. Short-term therapy with oral olpadronate in active Paget's disease of bone. J Bone Miner Res. 1999 Dec. 14(12):2042-7. [Medline].
Miller PD, Brown JP, Siris ES, Hoseyni MS, Axelrod DW, Bekker PJ. A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget's disease of bone. Paget's Risedronate/Etidronate Study Group. Am J Med. 1999 May. 106(5):513-20. [Medline].
Roux C, Gennari C, Farrerons J, Devogelaer JP, Mulder H, Kruse HP, et al. Comparative prospective, double-blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget's disease of bone. Arthritis Rheum. 1995 Jun. 38(6):851-8. [Medline].
Siris E, Weinstein RS, Altman R, Conte JM, Favus M, Lombardi A, et al. Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone. J Clin Endocrinol Metab. 1996 Mar. 81(3):961-7. [Medline].
Al-Rashid M, Ramkumar DB, Raskin K, Schwab J, Hornicek FJ, Lozano-Calderón SA. Paget Disease of Bone. Orthop Clin North Am. 2015 Oct. 46 (4):577-85. [Medline].
Walsh JP, Ward LC, Stewart GO, Will RK, Criddle RA, Prince RL. A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone. Bone. 2004 Apr. 34(4):747-54. [Medline].
Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med. 2005 Sep 1. 353(9):898-908. [Medline].
Langston AL, Campbell MK, Fraser WD, MacLennan GS, Selby PL, Ralston SH. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone. J Bone Miner Res. 2010 Jan. 25(1):20-31. [Medline].
Tan A, Hudson J, Walker A, Fraser W, MacLennan G, Ralston S. Intensive bisphosphonate therapy increases the risk of fracture and requirement for orthopaedic surgery in Paget's disease: the PRISM-EZ study. ECTS-IBMS Abstracts. 2015. [Full Text].
Cundy T, Maslowski K, Grey A, Reid IR. Durability of response to zoledronate treatment and competing mortality in Paget's disease of bone. J Bone Miner Res. 2016 Nov 3. [Medline].
Merlotti D, Gennari L, Martini G, Valleggi F, De Paola V, Avanzati A, et al. Comparison of different intravenous bisphosphonate regimens for Paget's disease of bone. J Bone Miner Res. 2007 Oct. 22(10):1510-7. [Medline].
Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD. Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. J Bone Miner Res. 2007 Jan. 22(1):142-8. [Medline].
Reid IR, Lyles K, Su G, Brown JP, Walsh JP, del Pino-Montes J. A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res. 2011 Sep. 26(9):2261-70. [Medline].
Devogelaer JP, Geusens P, Daci E, Gielen E, Denhaerynck K, Macdonald K, et al. Remission over 3 years in patients with Paget disease of bone treated with a single intravenous infusion of 5 mg zoledronic acid. Calcif Tissue Int. 2014 Mar. 94(3):311-8. [Medline].
Cronin O, Forsyth L, Goodman K, et al. Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone. BMJ Open. 2019 Sep 4. 9 (9):e030689. [Medline]. [Full Text].
Parvizi J, Klein GR, Sim FH. Surgical management of Paget's disease of bone. J Bone Miner Res. 2006 Dec. 21 Suppl 2:P75-82. [Medline].
Jorge-Mora A, Amhaz-Escanlar S, Lois-Iglesias A, Leborans-Eiris S, Pino-Minguez J. Surgical treatment in spine Paget's disease: a systematic review. Eur J Orthop Surg Traumatol. 2015 Jul 1. [Medline].
[Guideline] Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, et al. Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline. J Bone Miner Res. 2019 Apr. 34 (4):579-604. [Medline]. [Full Text].
[Guideline] Singer FR, Bone HG 3rd, Hosking DJ, Lyles KW, Murad MH, Reid IR, et al. Paget's Disease of Bone: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014 Dec. 99(12):4408-22. [Medline].
Rasmusson L, Abtahi J. Bisphosphonate associated osteonecrosis of the jaw: an update on pathophysiology, risk factors, and treatment. Int J Dent. 2014. 2014:471035. [Medline]. [Full Text].
Radiograph showing a 44-year-old African American man with characteristic changes of Paget disease in the left hemipelvis.
Radiograph showing a 72-year-old white woman with Paget disease of the lower leg and typical bowing.
Dual-energy x-ray absorptiometry scan of a 72-year-old white woman with Paget disease of the lower leg and typical bowing (same patient as in Image 2).
Mujahed M Alikhan, MD Rheumatologist
Mujahed M Alikhan, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology
Karen Driver, MS Medical Writer, Procter and Gamble Company
Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine
Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology
Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa
Laura D Carbone, MD, MS Professor of Medicine, Division of Connective Health Diseases, Director, Memphis Metabolic Bone Center, Department of Medicine, University of Tennessee Health Science Center College of Medicine
Laura D Carbone, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Rheumatology, American Medical Women's Association, American Society for Bone and Mineral Research; and International Society for Clinical Densitometry
Disclosure: Novartis Honoraria Consulting, Speaking and teaching; P&G Honoraria Consulting, Speaking and teaching
Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Marlon J Navarro, MD Fellow, Department of Rheumatology, University of Tennessee at Memphis
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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