pred_label
stringclasses 2
values | pred_label_prob
float64 0.5
1
| wiki_prob
float64 0.25
1
| text
stringlengths 148
1.01M
| source
stringlengths 39
45
|
|---|---|---|---|---|
__label__cc
| 0.503627
| 0.496373
|
'); jQuery(".wpzoomSocial li a").attr("target","_blank"); });
Email us a tip
Yankees Are Ready For Astros Or Rays
October 10, 2019 6:58 PM·
By Rich Mancuso/ Sports Editor
Make all the comparisons, analyze all the stats and if the upset minded Rays don’t finish off the Astros we are back to a rematch in the Bronx and in Houston of a classic ALCS in a matter of days.
This will be no different. Seven games in October of 2017 determined the Astros would move on to the World Series. All seven won by the respective teams on their home field. And if it is Yankees-Astros again, as expected, home field goes to Houston.
Except, this time, the Yankees are different. Those that remain from that 2017 wild card team is not expecting a repeat as the division winner and not the wild card team out of the AL.
“We feel we can hang with anybody,” Brett Gardner said. “We’re going to have to play well if we’re going to stay alive. Only one team goes home happy at the end and hopefully it’s going to be us.”
Gardner is one of those who remain from that 2017 team. So does the veteran CC Sabathia who hopes to comprise the ALCS roster after being left out of the ALDS sweep over the Twins due to a sore left shoulder.
By chance, the Yankees would prefer the Tampa Bay Rays to visit the Bronx. They play well at home, 57-24, and won 12 of 19 games against the Rays this season. The Astros, four of seven won this season over the Yankees.
So you do the math as the Yankees prepare this week for their second ALCS in the last three years,
“We played both of them.”Aaron Boone said Thursday afternoon prior to his team having an official workout and waiting for the results of the Astros-Rays finale.
“We got confidence in ourselves to do our job,” he said. “ Yeah. I think both teams are great and present serious trouble, competition for us, and I know we’ll have to play really well to beat both teams, whoever it ends up being.”
Boone added,” Obviously with Tampa being in our division, we know them well. We know what makes them successful. You know, we know how difficult it can be when you go in there, and even though we had some success against them in the regular season this year, you always know how difficult it is and how well we had to play to have that success.”
Games 1 & 2, if in Houston, that is the task. And the Yankees most likely won’t face the Astros’ best. Justin Verlander and Gerrit Cole who finished out the series. A
Advantage, could go to the Yankees. But this is October baseball and pitching wins ball games.
So, a few years later, the situation for the Yankees would be the same. Win at least one of the two in Houston and return to the Bronx next week with a chance to advance and return to the Fall Classic for the first time since 2009 where they took it all.
Because pitching is so vital in the postseason, facing Verlander and Cole, two frontline starters, means the Yankees have to be savages in the box as they continued to do in their quick disposal of the Twins.
Reached Tuesday, hours after his team was eliminated, Twins reliever Sergio Romo said about the Yankees, “They attack and know how to keep attacking with their at bats. Slider, curve, fastball, just good all around hitters in that lineup.”
Monday night, and with Romo on the mound in the eighth inning, Cameron Maybin got hold of a breaking ball that went for a home run down the left field line that added cushion to the Yankees 5-1 win.
“You can throw Verlander, Cole, don’t matter, “ he said. “They know how to get on base.”
Advantage, though, again assuming it is the Astros are the Yankees using the home run ball as they finished second in baseball to the Twins in a record setting baseball season of balls going out of the yard.
Verlander has that tendency of giving up one too many, 36, second among starters in the American League.
But the Yankees relish the opportunity. They are ready for either the Astros or the Rays. This is what they played for and the gap in between series, as Boone said, will definitely help their bullpen which is considered one of the top three in baseball.
“I know out guys will use this as an opportunity,” Boone said. “To kind of recover a little bit, stay fresh, and I know we’ll come out and be focused and I feel like sharp when the bell rings.”
Comment: Ring786@aol.com Twitter@Ring786 Facebook.com/Rich Mancuso
You Should Read:
YANKEES SIGN RHP ADAM OTTAVINO TO THREE-YEAR CONTRACT Yankees Invite Additional Players To Spring Training Expectations For Second Half Domingo Should Be Yankees Ace
Tags: Hoston Astros, MLB, Yankees
Author: Rich Mancuso Rich has covered countless New York Mets and Yankees games along with some of the greatest boxing matches over the years. His award winning sports column has been in the Bronx News (which recently folded) for 28 years. Mancuso also has been a sports journalist for the Associated Press, New York Daily News, Gannett Westchester newspapers, Boxing Digest Magazine, The Sports Network and Latinosports.com. Bronxites will recall that Rich once hosted a sports talk television program, “Bronx Scoreboard” on Bronxnet Television. In addition, Mancuso recently concluded a four-year run hosting a sports talk program on the Whitney Broadcasting Network station WVOX.
SUPPORTING YOUR FELLOW CITIZENS
Copyright © 2020 — The Bronx Chronicle. All Rights Reserved | Design & Development by Tectonic Seven
|
cc/2020-05/en_middle_0097.json.gz/line35273
|
__label__wiki
| 0.668524
| 0.668524
|
The Edge of the Frame
A Look at the Oscars…and the Movies that Chase Them
Oscar Predix
2011 Film Index
2012 Films Index
My Ranked Films of 2015
March 26, 2016 thomasconroy Leave a comment
It’s hard to call one’s self a critic, or even an avid film enthusiast, without a top ten list to show for it at the end of the year. Granted, a year has not gone by in a couple of decades in which I haven’t put one together. However, if a list isn’t posted on the internet, does it really make a sound.
I originally intended for this to be smaller venture, but I couldn’t resist going a bit overboard. In result, I’ve done up a complete list counting down every movie that I’ve seen this year. It’s ranked, of course, since nothing seems to bring me better pleasure in life than ranking film-related material. It all leads up the my finalized top ten films of 2015. I’ve also thrown in an anecdote or two about each film, summing up what they all left me with.
Feel free to peruse, and stay tuned for the winners of the 6th Annual Edgy Awards in the coming week. Then, it’s officially on to 2016…
76. “San Andreas” – All of the endless forms of transportation utilized in this film couldn’t keep it from being the worst of the year. Too many ways to describe how horrid this film really is.
75. “Green Inferno” – What’s really hilarious is that this one of the better films I’ve seen by Eli Roth. Quite a curve he’s working on.
74. “Jupiter Ascending” – The apple falls very far from “The Matrix.” Creativity is abound, but any form of intelligence is out to lunch.
73. “The Cobbler” – Adam Sandler doesn’t need to cross his eyes or dress up like a woman for this film to be just as bad as the all the rest. Hard to believe the film’s writer/director created this mindless mess, while also helming one of the year’s best.
72. “Chappie” – One has to wonder exactly what happened to Neill Blomkamp’s talent, or if he ever had much to begin with? This film is pretentious in its own mindlessness and often times feels flat out alienating to its viewers.
71. “Blackhat” – The least thrilling thriller of the year. Sidebar: As a pioneer of digital filmmaking, why does Michael Mann insist in shooting with technologies that look like they’ve been dead for at least a decade?
70. “Aloha” – Cameron Crowe has really made himself the poster boy for “white people problem” movies. Emma Stone’s casting is just the icing on the cake.
69. “Serena” – An exhaustingly boring film to choke down. The magical chemistry of Cooper and Lawrence just could not bridge enough decades to fit this period piece.
68. “Goosebumps” – One couldn’t really go into this movie expecting a lot, but one could at least hope it could deliver a healthy dose of nostalgia. It did not.
67. “Poltergeist” – I’d like to think that Rosemary DeWitt and Sam Rockwell could have knocked this out with a better script, but this film starts out “meh” and get’s worse along the way.
66. “Hot Girls Wanted” – Call me a sexist, but this ultimately feels like a documentary about people with job remorse. They can somehow try to spin this as abuse, but ultimately these girls all made their beds and now don’t want to sleep in them.
65. “Maggie” – Believe it or not, this flop is not Arnold’s fault. He certainly gives it his all in a beautifully understated role, but the film seems to be lacking in nearly all other arenas.
64. “Ricki and the Flash” – Despite a few decent musical numbers and a few satisfying moments, this film is jumbled full of characters who just don’t make a lot of sense.
63. “Crimson Peak” – Designed within an inch of it’s life, and don’t get me wrong, it’s gorgeous. However, the over-the-top story and characters strongly reduce any creepy scares or tension.
62. “Stonewall” – I’m usually not one to complain about historical inaccuracies, because they’re ultimately unavoidable to create a story. However, in this case, they seem to really get in the way of the story rather than aid it.
61. “Burnt” – This just isn’t Bradley Cooper’s year. Much like “Chef” last year, this film seems far more interested in generating food porn than creating decent conflict for its characters.
60. “Legend” – Tom Hardy has had some great performances this year and this is certainly no exception. The film starts out strong, and then falls victim to severe repetition, making it feel at least 30 minutes too long.
59. “Child 44” – Speaking of overlong Tom Hardy movies, this film’s heart is in the right place. Yet, as a functioning mystery, it lacks a real drive towards finding a satisfying solution.
58. “Youth” – Easily one of the most ostentatious films I’ve ever seen in my life. Tries so hard to invoke a Felliniesque quality (for shame), but instead comes up cold and distant. However, it is highlighted by the performance of Harvey Keitel’s career.
57. “Southpaw” – Oh so very by the numbers boxing movie. Sure the template is effective, but it certainly doesn’t make it worth watching. If there were a reason, it’s Jake Gyllenhaal, who’s electric, once again.
56. “Mr Holmes” – The character element of an aging Sherlock Holmes is intriguing, and is a match made in heaven with Sir Ian McKellen. However, as a whole, the movie is ultimately a bore.
55. “The Wolfpack” – The film seems to want to keep everything as cut and dry as possible, but at least a little production value might have been an improvement. At times, I sometimes felt that weirdness of this family was really worthy of a feature-length doc.
54. “Digging for Fire” – I never was a fan of Joe Swanberg’s version of mumblecore. Here, he has by far the most elaborate cast and production and he just doesn’t seem to know what to do with it.
53. “Spy” – It’s no “The Heat” and certainly no “Bridesmaids”. There certainly are a flourish of funny moments, but not enough to make this film thoroughly worthwhile.
52. “The Hunting Ground” – Overall, this documentary is flawed and, honestly, more than a little irresponsible. The film functions 100% as an advocacy piece and purposely avoids opposing viewpoints or data. The strongest parts of the movie are the testimonials of the victims. Yet, the decision to prominently feature the widely discredited Erica Kinsman case and report it as virtual fact is detrimental to the impact of the other survivors’ stories.
51. “American Ultra” – Jesse Eisenberg proves once again that he can carry the weight of a variety of films. However, the absurdity of the plot cannot be balanced out with the sharp direction.
50. “Z for Zachariah” – When you set out to create a post-apocalyptic film on a low-key scale, you better have the story to back it up. This one does not quite pull it off, but does feature surprising performances by it’s three leads.
49. “Anomalisa” – Despite hovering around the middle of my list, I would probably consider this most disappointing film of the year, or at least the most overrated. A massive undertaking, but equally pretentious, as well as being the least entertaining film Charlie Kaufman has ever made.
48. “Trumbo” – Entertaining, insightful and finally featuring a breakout film role for Bryan Cranston. Still, I feel like this could have been much, much better.
47. “Truth” – Cate Blanchett gives a powerhouse performance. No surprise there. Yet, the film has a lot of difficulty maintaining a sense of tone and actually seems to contradict its own message.
46. “The Walk” – Gordon-Levitt’s goofy portrayal of Petit, as authentic as it may be, just grows irritating after a while. The actual rooftop scenes are more than a little harrowing, even with the outcome is already well documented.
45. “Tangerine” – Absolutely electric with live-wire energy, but it’s plot is really kind of apathetic towards its characters. One can only hope that the fantastic Mya Taylor is offered more well-deserved work in result of this.
44. “Everest” – Certain moments of the film are as harrowing as any you’ll see this year. Certain elements feel off kilter, though, in particular such an all star cast spread so thinly. Furthermore, the ending comes off less cathartic as it is straight-up depressing.
43. “Slow West” – A surprisingly colorful western with some fantastic set pieces that unfortunately feels like it is over before it even begins.
42. “Trainwreck” – It’s extremely refreshing to see a Judd Apatow film oozing with estrogen for a change. Amy Schumer carries the film well, though the weight really isn’t all that heavy.
41. “The Hateful Eight” – QT has never swung and missed completely, but in my mind, this is his second straight foul tip. The dialogue is not quite up to par for the auteur, and the film’s over the top nature nearly makes it irrelevant, anyway.
40. “99 Homes” – Garfield and Shannon do a decent job of playing off each others’ engaging talents. Yet, as the film tries to find a middling conclusion, that satisfaction is lost in the shuffle.
39. “Straight Outta Compton” – Music biopics have certainly a lot more generic in the past, and the timeliness is certainly a strong factor with this story. Yet, like many films this year, the ending feels rushed, which is strange for a 150+ minute film.
38. “Joy” – As it turns out, not everything David O’Russell touches turns to gold. While very entertaining at times, the film misses the mark on a number of levels, in particular, it doesn’t really feature a third act.
37. “Bone Tomahawk” – There’s really no reason this film should work, and yet, somehow it does succeed on multiple levels. It’s certainly not high art by any means, but puts an interesting horror spin on the average western with absolutely no punches pulled.
36. “Dope” – For most part, the film is a thoroughly played out story of a teen boy getting buried in shenanigans for his dream girls affection. It’s an original spin, but not anything earth-shaking. It does bring it all together with a hell of a closing statement.
35. “Cobain: Montage of Heck” – A highly insightful and educating documentary, but at times it is over the top, even for telling a life story such as this one.
34. “Clouds of Sils Maria” – I will admit that this film can be relentlessly tedious at times. However, it’s peppered with a handful of revelatory moments. Kristen Stewart gives, what hopefully will be a career turning performance.
33. “Creed” – I have to say, as someone who has not so much respect for “Rocky”, I wanted to dislike this movie more than I ended up. It’s still a pretty basic story and the performances are nowhere near as grand as made out to be, but it is well excecuted. The one take fight scene is remarkable.
32. “Grandma” – Lily Tomlin sets the place on fire in this film that unabashedly takes on women’s issues in ways most films don’t dare touch. I just wish the film wasn’t one and done in the time of some network TV pilots.
31. “The Danish Girl” – Eddie Redmayne simply is getting better and better as an actor which each performance, and here, I believe he may have reached a peak (though I hope not). The performers give it their all, as well as the design team, but the film still feels a bit on the surface, as well as unfortunately “safe.”
30. “Jurassic World” – I feel like this film has gone from anticipated to beloved to scrutinized to reviled by the general public. People just can’t let those heels rest. Without a doubt, the film has it’s flaws, but it’s still a rousing adventure with some legitimately thrilling scenes. Meanwhile, as Ray Arnold would say in the original: “It could have been worse…A LOT worse.”
29. “Suffragette” – This film really seemed to come and go without turning any heads. While not groundbreaking, it’s effective in a by-the-numbers fashion. Carey Mulligan gives a highly overlooked performance, as per usual. Her one on one with Brendan Gleason is dynamite acting.
28. “Love & Mercy” – Definitely the better of the two music biopics this year, with an interesting story structure. Paul Dano was passed over for what absolutely should have been his long time coming first Oscar nod. The movie could have done better than the “wrap-up” ending that it leaves you with.
27. “The Visit” – I have no shame counting myself among those believing M. Night Shymalan’s talent had gone the way of the Dodo. However, this surprising gem of genuine subjective filmmaking is as unnerving as it is hilarious (intentionally, this time).
26. “Black Mass” – It’s obvious that Scott Cooper is a director of extraordinary talents. I’ve often wished that his film’s scripts, whether self-written or not, measured up. Unfortunately, I’m still waiting after this film. What’s crucial here is possibly the best performance of Johnny Depp’s career. He electrifies every scene that he appears in.
25. “Ex Machina” – In some ways this little sci fi gem has a healthy dose of Hitchcock in it’s veins. Alicia Vikander has gotten all of the attention this year, for this performance or others, but Oscar Isaac is the true standout as J.D. Salinger meets Mark Zuckerberg.
24. “Me and Earl and the Dying Girl” – This film was heralded at Sundance as the second coming, so I was relieved to see it brought back down to earth by the mainstream critics. It’s certainly one of the best teen comedies to come out in the last decade, but at times, it feels more than a bit forced.
23. “Bridge of Spies” – I find it interesting how the 90-100 minutes of this film is nearly flawless. Everything is on point and the Tom Hanks embodies Jimmy Stewart even more than normal. However, during the third act, the once high stakes seem to drop through the floor.
22. “Beasts of No Nation” – The film does succeed in delivering several truly cathartic moments. Idris Elba nails his role as the sadistic, egocentric guerrilla leader. However, even a film like this should be able to deliver some entertainment value among all of the carnage.
21. “Cartel Land” – The perfect real-life counterpart for the similarly themed “Sicario”, succeeds very well. While the stories of the film’s two cross-border subjects. However, it’s the successes and horrors lived by the Mexican people as a whole that really stay with you.
20. “Diary of a Teenage Girl” – Glad I decided to check out the independent beauty of a film. While at times, the rough edges can get a little under the skin, it’s a quirky, if not raunchy look at female sexuality and independence. Bel Powley shines, but Alexander Skarsgard steals his fair share of scenes.
19. “It Follows” – Saying that this is the best horror film of the year is stating the obvious. Director Mitchell understands that the most essential tool that separates the men from the boys in the horror genre is solid tone. He maintains it with thick atmosphere, haunting music and some of the most nightmarish wide shots you’ll ever see.
18. “Winter on Fire: Ukraine’s Fight for Freedom” – Advocacy pieces tend to work a lot better when in your corner you have footage of thousands of peaceful protestors being massacred in the street. Hard to put up an argument against a doc like this. By the end, it’s hard not wanting to take up arms alongside these brave individuals no different from any one of us.
17. “The End of the Tour” – Unlike “Anomalisa,” this film crafts a moving and highly involving film about depression. Jason Segel confirms what many have alluded to that with a little effort, he could very well be the next Tom Hanks. For as much as he will warm your heart in this film, he will also break it if you let him.
16. “Steve Jobs” – Admittedly, this is actually a lesser work for Aaron Sorkin. Yet even minor Sorkin is better than 90% of other screenplays written this year or any other. Michael Fassbender and Kate Winslet absolutely tear up the scenery, as if either knew how to do anything less.
15. “The Look of Silence” – While, in my opinion, not as quite as groundbreaking or intense as its counterpart “The Act of Killing,” it still presents an searing human rights argument in ways that will leave you stunned and breathless.
14. “Carol” – The best gay-themed romance film since “Brokeback Mountain” (though not nearly on the same artistic level as the latter). It is so because, while the setting and times may not have been conducive, the gay love story is just that: a love story, without questions or inhibitions, it’s as true and natural as anything “straight” cinema has to offer.
13. “Amy” – After a lot of deliberation, this does remain the highest ranked documentary I’ve seen this year. While it may not tackle oppression, human rights, or even Wall Street, it does paint a beautiful portrait of a highly visible yet little known artist. Insightful as anything else produced this year and edited with such a fine and steady touch.
12. “The Martian” – It’s interesting that Ridley Scott’s best film in nearly a decade is maybe the least “Ridleyesque” that he’s ever made. In this case, the film’s greatness is less a question of style as pure skill. Mixed with the tangible and entertaining script and Matt Damon’s magnetic performance, it’s impossible not to recommend this movie to anyone.
11. “The Big Short” – Obviously, this extravaganza of a film just barely missed my final cut, but by narrow margins. I have to say I was surprised that McKay was able to pull off not only the movie’s comedic prowess, but it’s deep, cutting message. “Short” leaves it all on the field and strikes quite a nerve in its wake.
10. “Brooklyn”
Directed by John Crowley
Written by Nick Hornby
This film is a harkening back to the glory days of post-war America, capturing a time when possibilities and opportunity were boundless and the American dream was still plausible. In many ways, the filmmaking style is one in the same, embodying the simple but golden age of filmmaking. It succeeds on both fronts, and does not overreach for either goal. Saoirse Ronan is pitch perfect and Emory Cohen continues to make his case for better roles. A thoroughly satisfying film, start to finish.
9. “45 Years”
Written and Directed by
I had read one critical analysis of this film that compared it in so many ways to a ghost story. However, the characters are haunted by something much more real and tangible: the past. You feel it lurking in the wind, around the corner and up in that horrible, horrible attic. Saying this film is subtle is an understatement, and it takes an effort to let the film pay off. The rewards are as tragic and thought-provoking as anything you’ll see this year.
Directed by Alejandro Gonzalez Inarritu
Written by Alejandro Gonzalez Inarritu and Mark L. Smith
It’s hard to tell at this point whether this film is over or underrated, and I suppose it could swing both ways. The film had such high expectations, anything less than a masterpiece is a bit disappointing. A masterpiece it’s not, but still a magnificent example of filmmakers laying it all on the line to achieve their vision. Said vision is something that everyone who can stomach it should experience in all of it’s majesty. It somehow seems to expand the limits of what cinema can offer, mostly by using natural techniques. At the same time, the heavily computerized bear attack will go down as one of the most harrowing scenes in film history.
Directed by Denis Villeneuve
Written by Taylor Sheridan
Without a doubt, there is no filmmaker working today that I am more excited about than Denis Villeneuve. I am floored by the way he can captivate his audience. With this film, he touches on a level of intensity I’ve seldom, if ever seen, in American filmmaking. There is literally no point in this film in which any of the characters seem safe. Those are stakes often taken for granted in this day and age. Emily Blunt delivers a fine performance of grounded strength. Meanwhile, this may not be the undisputed finest role of Benicio’s career, but it’s definitely one for the books.
Directed by J.J. Abrams
Written by J.J. Abrams, Michael Arndt and Lawrence Kasdan
Let’s be frank about this: I am still pinching myself. Never in my life could I imagine that the single most anticipated sequel in cinematic history, of a series that is just about the most sacred form of nostalgia that I hold dear, would not only meet expectations, but in some ways surpass them. J.J. Abrams can go ahead and retire now, for it will be a tall order for him ever to top this achievement. Props furthermore for Disney for reinventing the film franchise without alienating it. Against all odds, we have a Star Wars installment to show future generations without it being prefaced by an apology.
Directed by Lenny Abrahamson
Written by Emma Donoghue
Even if this was a total bust (which, thankfully, it most certainly is not), it would still go down as the film that heralded Brie Larson as the best young actress working in Hollywood today. I was already on board after granting her my Best Actress Edgy award for “Short Term 12”, two years ago, however, it will be nice to know that we’re now all on the same page. The movie itself is a work of beauty, inspiration and life-affirmation. You would be hard-pressed not to break down into tears at least once during the runtime. A lot of credit is due to director Lenny Abrahamson. Without his steady hand, this could have easily slipped into Lifetime movie territory.
Directed by George Miller
Written by Nick Lathouris, Brendan McCarthy and George Miller
There is no film released last year that I have re-watched more times than this one. Through and through, my mind echoes the same sentiment as when I emerged from my first viewing: this may well be the best straight-up action film EVER made. Furthermore, no film from 2015 did more to subvert my own expectations, which bolsters the previous statement even more. How much can a self-respecting film aficionado anticipates brilliance from half-naked renegades performing drive-bys on each other in a post-apocalyptic expanse. Now, it’s a benchmark achievement. George Miller deserves every accolade that he received (as well as all those he didn’t), for helming this perfect storm of design, style, craft and controlled mayhem.
3. “Son of Saul”
Directed by Laszlo Nemes
Written by Laszlo Nemes and Clara Royer
Let’s preface by saying that I am still in the camp of “Schindler’s List” being a pure masterpiece in ever way, as well as the best film to date about the Holocaust, a mantel not likely to be toppled. However, for those that believe that this topic (really a genre, in itself) is one and done, this film will lay you out. Without a doubt, the most physically paralyzing and emotionally devastating film since at least “12 Years a Slave”, if not further from there. Debut filmmaker Nemes ought never make another film for this will be tough to top. Be prepared to leave this film with a heavy heart, for the bleeding from the scars of this inconceivable period of history will never stop, just as films like this should never stop being made.
Directed by Thomas McCarthy
Written by Thomas McCarthy and Josh Singer
Most years, my number one favorite film is a clear cut choice with no question. This year, it was a touch choice, and with not much more than a coin flip, this could be my Best Pic. Easily the best film about journalism since “All the President’s Men” almost 40 years prior. It’s importance lies not in its subject matter (which is both heartbreaking and galvanizing), but in its demand for an inquisitive and ruthless free press. This is old school filmmaking at its finest. “Spotlight” could have been made forty years ago or forty years from now and it would still have the same impact, because superior acting, direction and damn near perfect writing never go out of style.
Directed by Pete Docter
Written by Josh Cooley, Pete Docter and Meg LeFauve
This is the first time in not only my short lifetime, but in the entire breadth of cinema that I’ve been recording top ten lists, that an animated film has achieved my top spot for the year. This is no coincidence or chance, it’s simply that no animated film has ever reached the heights that this movie has. I recall being in the theater as the climax approached, and I found myself weeping. Not because of the film’s emotional impact (which is enough to weep gallons, on its own), but because I was floored at just how damn good it turned out to be.
Much like last year’s best film, “Boyhood”, this is a coming of age film. And just like its counterpart, “Inside Out” tackles the genre in ways you’ve never seen before. Both Riley’s story itself and the personification of her emotions are as intelligent as they are creative, and as hilarious as they are cathartic. This is the best film of 2015, the best film Pixar has ever produced, and quite possibly, the greatest animated movie in cinematic history.
Well, I must admit, that was a bit more of an undertaking than I had anticipated. Hope you all enjoyed it. Stay tuned for the winners of the 6th Annual Edgy Awards, coming soon…
Categories: Lists, Musings Tags: 2015, 45 years, amy, big short, brooklyn, carol, diary of a teenage girl, end of the tour, inside out, it follows, look of silence, mad max, martian, ranking, revenant, room, sicario, son of saul, spotlight, star wars, steve jobs, top ten list, winter on fire
The 6th Annual Edgy Award Nominations
After 2 years showing up really late to the party, I was determined to get these done on schedule this time around. Overall, a pretty great year for film, or at least a significant one, if nothing else. Plenty of achievements and landmarks to be seen and experienced, so it’s only right to award the best of the best.
To remind everyone, while there may only be five editions of the Edgies available online, the awards are cataloged by yours truly going all the way back to 1940. The recipients’ nomination and win counts are grouped according to each category, with the exception of the two music categories and the four acting categories being linked.
featured in “Ricki and the Flash”
Music and Lyrics by Jenny Lewis (1st nom) and Jonathan Rice (1st nom)
“It’s My Turn Now“
featured in “Dope”
Music and Lyrics by Pharrell Williams (1st nom)
“One Kind of Love“
featured in “Love and Mercy”
Music and Lyrics by Brian Wilson (1st nom)
“Simple Song #3“
featured in “Youth”
Music and Lyrics by David Lang
“Till It Happens to You“
featured in “The Hunting Ground”
Music and Lyrics by Lady Gaga (1st nom) and Diane Warren (4th nom, 1 win – “I Don’t Want to Miss a Thing”)
Carter Burwell (4th nom, 2 wins – “Fargo” and “Barton Fink”)
Michael Giacchino (2nd nom)
Junkie XL (1st nom)
Johann Johannsson (1st nom)
John Williams (28th nom, 10 wins – “Munich,” “Amistad,” “Schindler’s List,” “Empire of the Sun,” “Star Wars: Return of the Jedi,” “E.T.: The Extra-Terrestrial,” “Raiders of the Lost Ark,” “Star Wars: The Empire Strikes Back,” “Star Wars: A New Hope,” “Jaws”)
Gloria Pasqua Casny (1st nom) and Joel Harlowb (2nd nom)
Jan Sewell (1st nom)
Damian Martin (1st nom), Nadine Prigge (1st nom) and Lesley Vanderwalt (2nd nom)
Sian Grigg (2nd nom), Ducan Jarman (2nd nom) and Robert Pandini (1st nom)
Amanda Knight (2nd nom) and Lisa Tomblin (2nd nom)
Tim Alexander (3rd nom), Martyn Culpitt (1st nom), Michael Billette (1st nom)
Andrew Jackson (1st nom) Dan Oliver (1st nom) Andy Williams (1st nom) and Tom Wood (1st nom)
Anders Langlands (1st nom), Chris Lawrence (2nd nom, 1st win – “Gravity”), Richard Stammers (3rd nom) and Steven Warner (1st nom)
Richard McBride (1st nom), Matt Shumway (1st nom), Jason Smith (1st nom) and Cameron Waldbauer (2nd nom)
Chris Corbould (5th nom, 1 win – “Inception”), Roger Guyett (7th nom), Neal Scanlan (2nd nom, 1 win – “Babe”) and Pat Dubach (2nd nom)
BEST SOUND EFFECTS EDITING
Ren Klyce (4th nom, 1 win – “The Social Network”) and Shannon Mills (2nd nom)
Scott Hecker (2nd nom), Mark Mangini (4th nom) and Wayne Pashley (2nd nom)
Oliver Tarney (3rd nom, 1 win – “United 93”)
Alan Robert Murray (2nd nom)
David Acord (1st nom) and Matthew Wood (7th nom)
BEST SOUND EFFECTS MIXING
Christopher Boyes (7th nom, 1 win – “The Lord of the Rings: The Return of the King”) and Kirk Francis (4th nom, 1 win – “L.A. Confidential”)
Eugene Gearty (1st nom), Edward Tise (2nd nom) and Chris Jenkins (3rd nom)
Chris Jenkins (3rd nom), Ben Osmo (1st nom) and Gregg Rudloff (4th nom, 2 wins – “The Matrix” and “Glory”)
Chris Duestertiek (1st nom), Frank A. Montano (3rd nom), Jon Taylor (1st nom) and Randy Thom (7th nom, 3 wins – “Cast Away,” “Forrest Gump” and “The Right Stuff”)
Andy Nelson (22nd nom, 5 wins – “Les Miserables,” “Cloverfield,” “Munich,” “Saving Private Ryan” and “L.A. Confidential”), Chtistopher Scarabosio (3rd nom) and Stuart Wilson (2nd nom)
Odile Dicks-Mireaux (1st nom)
Sandy Powell (8th nom, 3 wins – “The Aviator,” “Gangs of New York” and “Interview with the Vampire”)
Paco Delgado (2nd nom)
Jenny Beaven (7th nom, 2 wins – “The Remains of the Day” and “A Room with a View”)
Jacqueline West (3rd nom)
Judy Becker (1st nom) and Heather Loeffler (1st nom)
Thomas E. Sanders (3rd nom, 1 win – “Saving Private Ryan”), Jeffrey A. Melvin (1st nom) and Shane Vieau (1st nom)
Eve Stewartb (3rd nom) and Michael Standish (1st nom)
Colin Gibson (1st nom) and Lisa Thompson (1st nom)
Rick Carter (5th nom, 1 win – “Lincoln”) and Lee Sandales (2nd nom)
Chris King (1st nom)
Kevin Nolting (1st nom)
Margaret Sixel (1st nom)
Pietro Scalia (5th nom, 2 wins – “Black Hawk Down” and “JFK”)
Tom McArdle (1st nom)
Robert Richardson (6th nom, 2 wins – “Born on the Fourth of July” and “Platoon”)
John Seale (5th nom)
Emmanuel Lubezki (6th nom, 3 wins – “Birdman or The Unexpected Virtue of Ignorance,” “The Tree of Life” and “Children of Men”)
Roger Deakins (14th nom, 4 wins – “O, Brother Where Art Thou?,” “Fargo,” “The Shawshank Redemption” and “Barton Fink”)
Matyas Erdely (1st nom)
James Gay-Rees (1st nom) and Asif Kapadia (1st nom)
Matthew Heineman (1st nom) and Tom Yellin (1st nom)
Brett Morgen (1st nom) and Danielle Renfrew (2nd nom)
Joshua Oppenheimer (2nd nom, 1 win – “The Act of Killing”)
“Winter on Fire: Ukraine’s Fight for Freedom“
Evgeny Afineevsky (1st nom) and Den Tolmer (1st nom)
Andrew Haigh (1st nom)
Nick Hornby (2nd nom)
Adam McKay (1st nom) and Charles Randolph (1st nom)
Emma Donoghue (1st nom)
Aaron Sorkin (5th nom, 3 wins – “Moneyball, “The Social Network” and “A Few Good Men”
Alex Garland (1st nom)
Josh Cooley (1st nom), Ronnie Del Carmen (1st nom), Pete Doctor (3rd nom) and Meg LeFauve (1st nom)
Jesse Andrews (1st nom)
Taylor Sheridan (1st nom)
Thomas McCarthy (3rd nom) and Josh Singer (1st nom)
BEST ENSEMBLE CAST PERFORMANCE
Christian Bale, Steve Carell, Karen Gillam, Ryan Gosling, Melissa Leo, Hamish Linklater, John Magaro, Billy Magnussen, Adepero Oduye, Brad Pitt, Rafe Spall, Jeremy Strong, Marisa Tomei, Finn Wittrock
Eva Birthistle, Jim Broadbent, Emory Cohen, Fiona Glasgow, Domhnall Gleason, Eileen O’Higgins, Eve Macklin, Samantha Munro, Nora Jane Noone, Emily Bett Rickards, Saoirse Ronan, Julie Walters
Zoe Bell, Demian Bichir, Bruce Dern, Walter Goggins, Dana Gourrier, Samuel L. Jackson, Gene Jones, Jennifer Jason Leigh, Michael Madsen, Tim Roth, Kurt Russell, Channing Tatum
Billy Crudup, Brian D’Arcy James, Michael Keaton, Rachel McAdams, Mark Ruffalo, Liev Schreiber, Jamey Sheridan, John Slattery, Stanley Tucci, Elena Wohl
Paul Giamatti, Elena Goode, Corey Hawkins, Aldis Hodge, O’Shea Jackson Jr., Jason Mitchell, Alexandra Shipp, R. Marcos Taylor, Marlon Yates Jr.
Rooney Mara – “Carol”
2nd nom
Kristen Stewart – “Clouds of Sils Maria”
1st nom
Mya Taylor – “Tangerine”
Julie Walters – “Brooklyn”
Kate Winslet – “Steve Jobs”
7th nom, 2 wins – “Little Children” and “Sense and Sensibility”
Paul Dano – “Love and Mercy”
Benicio Del Toro – “Sicario”
3rd nom, 1 win – “21 Grams”
Tom Hardy – “The Revenant”
Mark Ruffalo – “Spotlight”
3rd nom
Jason Segel – “The End of the Tour”
Brie Larson – “Room”
2nd nom, 1 win – “Short Term 12”
Carey Mulligan – “Suffragette”
3rd nom, 1 win – “An Education”
Charlotte Rampling – “45 Years”
Saoirse Ronan – “Brooklyn”
Lily Tomlin – “Grandma”
Johnny Depp – “Black Mass”
3rd nom, 1 win – “Edward Scissorhands”
8th nom, 1 win – “The Aviator”
3rd nom, 1 win – “12 Years a Slave”
Geza Rohrig – “Son of Saul”
Alejandro Gonzalez Inarritu – “The Revenant”
Tom McCarthy – “Spotlight”
George Miller – “Mad Max: Fury Road
Laszlo Neomes – “Son of Saul”
Denis Villeneuve – “Sicario”
BEST MOTION PICTURE OF THE YEAR
Tristan Goligher (1st nom)
Fiona Dwyer (2nd nom) and Amanda Posey (2nd nom)
Pete Doctor (1st nom) and Jonas Rivera (1st nom)
George Miller (2nd nom) and Doug Mitchell (2nd nom)
Steve Golin (5th nom, 1 win – “Eternal Sunshine of the Spotless Mind”), Alejandro Gonzalez Inarritu (4th nom), Arnon Milchan (3rd nom) and Mary Parent (1st nom)
Ed Guiney (1st nom)
Thad Luckinbill (1st nom) and Molly Smith (1st nom)
Laszlo Nemes (1st nom)
Steve Golin (5th nom, 1 win – “Eternal Sunshine of the Spotless Mind”), Nicole Rocklin (1st nom) and MIchael Sugar (1st nom)
J.J. Abrams (1st nom), Brian Burk (1st nom) and Kathleen Kennedy (9th nom)
NOMINATION TALLY
Mad Max: Fury Road – 11
The Revenant – 9
Sicario – 7
Star Wars: The Force Awakens – 7
Brooklyn – 6
Spotlight – 6
Inside Out – 5
Carol – 4
The Danish Girl – 4
Son of Saul – 4
45 Years – 3
Love and Mercy – 3
The Martian – 3
Room – 3
Steve Jobs – 3
Amy – 2
The Hateful Eight – 2
Jurassic World – 2
Stay tuned for for the winners to be announced, hopefully within the next week…
Categories: Lists, Musings, Oscars Tags: 45 years, black mass, brooklyn, carol, clouds of sils maria, danish girl, edgy awards, end of the tour, grandma, inside out, love and mercy, mad max, nominations, oscars, revenant, room, sicario, son of saul, spotlight, star wars, steve jobs, suffragette, tangerine, the big short
Predictions for the 90th Annual Academy Awards
The 7th Annual Edgy Award Winners
Predictions for the 89th Academy Awards
Critics Awards
127 hours 2010 2011 aaron sorkin academy awards albert brooks alice in wonderland amy adams andrew garfield anne hathaway annette bening awards best picture black swan brad pitt christian bale christopher nolan christopher plummer colin firth david fincher david o'russell drive edgy awards george clooney golden globes hfpa hugo inception inside job james franco jeff bridges jennifer lawrence jesse eisenberg john hawkes les miserables lincoln melissa leo Michelle Williams midnight in paris moneyball movie natalie portman new nominations Oscar oscars poster predictions review Ryan Gosling steven spielberg the artist the dark knight rises the descendants the edge of the frame the fighter the girl with the dragon tattoo the help the kids are all right the king's speech the social network the town the tree of life Thomas Conroy tinker tailor soldier spy tom hooper top ten toy story 3 trailer true grit viola davis war horse winners winter's bone zero dark thirty
Perfection can have that effect. twitter.com/jenelleriley/s… 4 hours ago
@NextBestPicture Same here. 7 hours ago
@EriktheMovieman If Bong wins the DGA though, everyone might need to make some revisions. Not saying it will happen… twitter.com/i/web/status/1… 7 hours ago
Wow. DGA is going to be High. Fucking. Noon. #ParasiteMovie 8 hours ago
RT @spacejamfan: My hot take about the MST3K discourse is that if you think MST3K trains people to think they’re better than the movies the… 12 hours ago
Follow @edgeoftheframe
Subscribe to The Edge of the Frame!
Enter your Email Address to receive notifications from The Edge of the Frame!
Subscribe to The Edge of the Frame
|
cc/2020-05/en_middle_0097.json.gz/line35278
|
__label__wiki
| 0.5366
| 0.5366
|
Our Creed
State House Reception
By Ashley Severs | In the News
[CREDIT: Leg. Press & Public Information Bureau] Rep. Eileen Naughton, left front, poses with guests at a reception welcoming Veterans Count to Rhode Island on Wednesday at the State House. From left are Secretary of Health and Human Services Elizabeth H. Roberts, Sen. Walter S. Felag Jr., Rep. Dennis M. Canario, House Veterans’ Affairs Committee Chairman Jan P. Malik, Director of Veterans’ Affairs Kasim Yarn and Veterans Count Chairman of the Board Jim Lawrence.
STATE HOUSE —Rep. Eileen S. Naughton (D-Dist 21, Warwick) hosted a reception in the State Room for representatives of Veterans Count, an organization that provides emergency aid and support to veterans and their families.
Veterans Count, a program of Easter Seals, is the philanthropic arm of Easter Seals Military and Veterans Services. It was conceived in 2007 when Easter Seals New Hampshire Board Member Mike Salter sought to bring comprehensive, emergency aid to veterans and their families whose quality of life was significantly impacted by deployment to war zones.
“It was a great pleasure to welcome Jim Lawrence, chairman of the board for Veterans Count Rhode Island,” said Representative Naughton, who serves on the Veterans Count Board of Directors. “It afforded us a wonderful opportunity to learn more about the organization and their efforts in Rhode Island. I am gratified to see the model which has worked so well in New Hampshire, Maine, New York and Vermont coming to Rhode Island.”
Funds raised through Veterans Count will provide services through Care Coordinators who work with military families in any situation to provide assistance for critical items such as transportation, housing, rent, fuel assistance, utilities, vehicle repair, gasoline, food, child care, tuition and medical bills.
Corner Bakery Café Hosts Benefit Night in Support of Veterans Count RI
Wakefield, RI— Enjoy dinner at Corner Bakery Café in Cranston, Warwick, and Middletown on Wednesday, March 30, from 4-9pm in support of Veterans Count Rhode Island.
Each restaurant will be donating 20% of sales, during the 4-9pm hours, to benefit veterans, service members, and their families.
In addition, local heroes—veterans of all eras—will be on hand to help serve our guests.
Corner Bakery Café locations can be found at 140 Hillside Road, Cranston; 21 Universal Boulevard, Warwick; and 11 East Main Road, Middletown. To view a complete menu please visit, www.cornerbakerycafe.com/menu.
About Veterans Count Rhode Island
Veterans Count is a philanthropic program of Easter Seals, which provides critical and timely financial assistance and services when no other resource is available to veterans, service members and their families, to ensure their dignity, health and overall well-being. To learn more about Veterans Count Rhode Island visit,www.vetscount.org/ri.
About Easter Seals RI
Easter Seals RI provides exceptional services to ensure that all children and young adults with disabilities or special needs and their families have an equal opportunity to live, learn, work and play in their communities. Last year, Easter Seals RI served nearly 500 children and their families through programs and services provided. For more information about Easter Seals RI, please call 401-284-1000 or visitwww.easterseals.com/rhodeisland.
Stay connected with Easter Seals RI on Facebook, Twitter, Instagram and Pinterest: @EasterSealsRI
Tiger Rug Co. Supports Veterans Count RI Through Rug Donation Program
Tiger Rug Co. of Warwick, RI is partnering with Veterans Count Rhode Island, a program of Easter Seals through a quarterly Rug Donation Program.
From January through March 31, 2016, Tiger Rug Co. will donate 10% of gross receipts from ANY rug sale to Veterans Count Rhode Island or Easter Seals RI, when either organization is mentioned by the client during the sale. In addition, for each sale made through the Rug Donation Program, Tiger Rug Co. will donate a like-sized carpet to a veteran’s household, to be determined by Veterans Count Rhode Island.
“My wife, Elizabeth, and I feel very strongly about giving back to our proud service men and women,” said Tiger Rug Co. Owner Stephen Putney. “Over the course of history, our freedoms have been hard-won. This is a small token of our appreciation for the dedication and sacrifice made every day by these men and women and their families to protect and defend our country.”
Tiger Rug Co. proudly sells hundreds of Tibetan oriental carpets for nearly two decades. Everyone is most welcome to visit their Warwick location at 380 Jefferson Boulevard.
About Tiger Rug Co.
Tiger Rug Co. is a purveyor of Tibetan hand-knotted oriental carpets. Since 2000, Tiger Rug Co. has been importing oriental carpets from Nepal that are made using the finest wool available in the world for the weaving of carpets. For more information about Tiger Rug Co. please visit them at www.tigerrug.net.
Veterans Count is a philanthropic program of Easter Seals, which provides critical and timely financial assistance and services when no other resource is available to veterans, service members and their families, to ensure their dignity, health and overall well-being. To learn more about Veterans Count Rhode Island visit,www.vetscount.org.
Easter Seals RI provides exceptional services to ensure that all children and young adults with disabilities or special needs and their families have equal opportunities to live, learn, work and play in their communities. To learn more about Easter Seals RI visit, www.easterseals.com/rhodeisland.
Easter Seals RI Launches Veterans Count Rhode Island
Wakefield, RI — Easter Seals RI will now provide assistance to Rhode Island service members, veterans of all eras, and their families with the launch of a Veterans Count Rhode Island.
Veterans Count began with a question: How Can We Help Veterans, Service Members and Their Families?
In 2007, Easter Seals NH Board Member sought to bring comprehensive emergency aid to veterans and their families whose quality of life was significantly impacted by deployment to war zones, and Veterans Count was born.
As the leading model in New Hampshire, Maine, New York, and Vermont, Veterans Count is expanding to Rhode Island to honor those who have served and those who continue to serve! Veterans Count cuts through the red tape to provide critical and timely financial assistance and access to services when no other resource is available.
Please join us at the Veterans Count Rhode Island Launch Party on Thursday, April 9, from 6:00-7:30pm at Iron Works Tavern in Warwick, RI, to learn more about Veterans Count Rhode Island.
Please RSVP to Judy at jfortier@eastersealsri.org to attend. Light refreshments and a cash bar will be available.
Volunteer as a board member, at an event, or help us raise awareness.
Your donation will make it possible for a Veteran, current Service Member, or a family member, to turn to us for help with:
Judy Fortier
jfortier@eastersealsri.org
© 2020 Vets Count Rhode Island. All Rights Reserved, VetsCount.org.
|
cc/2020-05/en_middle_0097.json.gz/line35285
|
__label__cc
| 0.548377
| 0.451623
|
850 — The Business Magazine of Northwest Florida - October-November 2016
Drone Detectives
Increasingly, individuals have become concerned about the possibility that they may be under surveillance by operators of drones. Gary Andrews is here to help. He has developed a drone-detecting app, available for free.
Port Panama City Seeks to Expand its Capacity
Expansion underway at Panama City’s deepwater port has been projected to generate an annual economic benefit of more than $125 million and create 63 jobs. In store is a new forest products terminal.
Jason Dehart,
Alignment Bay County
Patterned after a similar initiative in Nashville, a group made up of business leaders and educators is working to improve the chief product of Bay County schools: high school graduates.
Bay County Demographics
U.S. Navy photo by Jacqui Barker/Released Neil Patterson, a retired saturation diver now employed at the Naval Surface Warfare Division, Panama City Division, readies equipment for diving bell training procedures. POPULATION July 2015 (estimated) — 181,635 Percent change from 2010…
Site Staff,
Building a Workforce
Florida State University-Panama City, Gulf Coast State College and Haney Technical Center are all working to gear curriculum and degree and certificate programs to the anticipated needs of employers.
Google Guru
For anyone seeking a more formidable online presence, Mica Specialties is a one-stop shop. The business offers services ranging from website design and digital advertising to search engine optimization and social media marketing.
Matt Algarin,
Pier Park, on Panama City Beach, bills itself as the premier shopping, dining and entertainment district in Northwest Florida and one that has had both financial and social impacts.
Hannah Burke,
The Military Plays a Huge Role in The Economy of Bay County
Defense activities play a major role in Bay County’s economy — and that contribution is expected to grow. Overall in 2014, the military accounted for about $2.4 billion or 30.6 percent of the total gross regional product.
Jellyfish Health Plans Expansion in Panama City
The health care technology company, Jellyfish Health, has plans to create 100 news jobs with an average salary of $70,000 — and to do something about those insufferable lines in doctor’s offices.
Along I-10, Happenings
The Vintage Queen
Cindy Poire has an affinity for collecting old things because their history fascinates her. She’s turned her passion into successful businesses at Madison Antiques Market & Interiors and Marketplace of Madison — and she’s still shopping.
Tabitha Yang,
|
cc/2020-05/en_middle_0097.json.gz/line35290
|
__label__wiki
| 0.550518
| 0.550518
|
Sports, Music, Literature, Art, Science, and other clusters of Thought
MLB 2015 Predictions, Part 2: American League
Mookie Betts. Familiarize yourself. Say it over and over again. Mookie Betts. [AP photo]
Continuing along, a bit late, with my predictions for the new baseball season, using the Baseball Prospectus PECOTA projections for the 2015 season. Normally I like to get these out of the way before the season starts, but it's been an extremely busy time for me lately. Mostly because of this. (Once again, the win numbers at BP have inevitably changed slightly since I captured them here, they remain in flux as the season goes on.)
The American League saw so many big moves made over the winter that it's harder than ever to determine with any confidence how things may take shape. If every team had full health all around, there would likely be extreme parity in the AL with lots of teams finishing with win totals in the mid-80s. Out of 15 teams, I count only 3 that are good bets to be really bad: Twins, Astros, Rangers. Every other AL team expects to fight for a playoff spot. Every one of them is also constructed with obvious flaws or severely lopsided rosters.
These division standings could end up being jumbled into any combination imaginable and we oughtn't be surprised. The Rays and Yankees are most likely going to have down years, but both have enough talent on hand to conceivably compete, while the other three all have playoff aspirations.
1. Blue Jays
PECOTA: 80 wins
My pick: Over
With their best pitcher, Marcus Stroman, now out for the year with a torn ACL, I can't say that I've got a ton of confidence in this pick. But the addition of catcher Russell Martin alone makes the Jays a much better team and they were in the playoff race pretty much all of last season, only a terrible month of August (9-17 and outscored 132 to 86) knocked them out. Adding third baseman Josh Donaldson, one of the game's best all-around players the past two seasons (14.1 total fWAR, behind only Mike Trout and Andrew McCutchen) to an already powerful lineup certainly helps too.
Just like the Red Sox, the Jays are expected to have one of the highest-scoring offenses in the game, but the pitching, which features two late-career vets and three youngsters, has lots of question marks. Can R.A. Dickey harness his knuckleball well enough to pitch more like an above average starter than an amusing sideshow? Will 24-year-old Drew Hutchinson build on his solid first full season in 2014? Can the kids (Daniel Norris and Aaron Sanchez, both 22) handle a full season of pitching for a contending big league team?
It's a top-heavy roster and the bottom has enough youth for some breakout potential so there's plenty of reason for optimism. With the Royals ending their playoff drought last year, the longest streak of missing the postseason now belongs to the Blue Jays. I don't think that streak will carry much further.
2. Red Sox (Wild Card)
My pick: Under
Mookie Betts. The Red Sox have a budding young superstar named Mookie Betts. He is delightful. Mookie is listed at just 5'9 and 180 lbs but, at age 22, has not yet been overmatched at any professional level. Last year he was promoted to Double-A ball for the first time, he hit .355. Then he went up to Triple-A and hit .335. The Red Sox brought him up to the major leagues and he proceeded to hit .291/.368/.444 (AVG/OBP/SLG) in 52 games.
A versatile defensive player (he was a middle infielder in the minors but is the team's starting center fielder this year) and mature hitter at just 22 years old, Betts is an absolute gem and representative of the embarrassment of riches the Red Sox possess right now. They have another 5-foot-8 bopper, Cuban outfielder Rusney Castillo, who crushed the ball in limited action last year and had a fantastic spring training but who's stuck in the minors to start the year since there's no room for him on the major league roster right now. Don't forget about the other 5'8 line drive machine, Dustin "Laser Show" Pedroia, still one of the best all-around second basemen in the game though a wrist injury sapped his powers last year. I haven't even mentioned Big Papi, or the Boston return of Hanley Ramirez, or new third base upgrade Pablo Sandoval.
On the offensive side, the Red Sox are as stacked as any organization we've seen in recent years. There is no doubt they can withstand injuries and flukey off-years from key players should they occur. The problem is their pitching. They'll have a relatively low bar to clear since the offense ought to average upwards of 5 runs per game, but there's no ace on this staff and there isn't even really a viable #2 starter. It's a rotation full of low-end starters who keep the ball on the ground. With more hitters than they know what to do with, the Sox will probably trade for an ace eventually, but until then expect lots of back-and-forth, high-scoring games.
3. Orioles
After alternating between 93, 85, and 96 wins the last three years, perhaps the Orioles are veering toward an every other year success cycle just like the other orange-and-black uniformed team over in the NL. With the division rival Red Sox and Blue Jays bulking up, this could be a down year for the O's. They lost both Nelson Cruz and Nick Markakis in free agency and didn't make any significant pickups.
On the other hand, they were one of the best teams in baseball last year despite being without their starting catcher Matt Wieters, dealing with myriad other injuries to key players, and getting a terrible performance from first baseman Chris Davis (.704 OPS following a 1.004 breakout in 2013). They can expect to get Wieters back sometime soon and Davis has nowhere to go but up. This is also an organization that has consistently exceeded expectations the last few years with their manager Buck Showalter displaying an aptitude for platooning and generally extracting substantial production out of the roster he's given, no matter how bereft of stars. You can't count out the O's but I do think this is a year they'll be looking up at some of their rivals in the standings.
4. Rays
This 87-win PECOTA projection is a little extreme, mostly due to very optimistic individual projections for outfielders Steven Souza and Kevin Kiermaier who Prospectus expects to amass upwards of 3 WAR apiece. As much as I would love to see that happen (I've always had a soft spot for the Rays, they're a fun team to root for), it is unlikely. Combined, the two hitters haven't reached 500 at-bats in the majors yet and I imagine the more they'll play, the more pitchers will learn to exploit their weaknesses. The other projection systems out there aren't nearly as high on those two guys.
If either or both do somehow manage to play like All Stars then the Rays could contend for a Wild Card spot, if not the division title. Despite the team losing its manager, team president, and unloading some significant players (Ben Zobrist, Matt Joyce, Yunel Escobar, Wil Myers) over the winter, they still have plenty of pitching. Their all-under-30 rotation is likely the best in the division (though they're starting the season off with injury issues) and strong bullpens have long been a hallmark of the Rays.
The problem they've struggled with for years now is offense and once again it's not looking good beyond Evan Longoria. Desmond Jennings is a solid all-around player but hasn't developed into the kind of hitter he was expected to be and there isn't really anyone else in this lineup to be excited about. Except perhaps the unproven Souza and Kiermaier. I don't think it's too extreme to state that the Rays will sink or swim depending on the performance of those two.
5. Yankees
Let me start by saying something nice about this team: they'll likely have an excellent bullpen. They lost their closer David Robertson to free agency (how weird does that sound for the Yanks?), but solid pickups like Andrew Miller, David Carpenter, Justin Wilson and Andrew Bailey to go along with Dellin Betances make this a deep pen. Beyond that, there's little to be optimistic about with this team. The lineup has some firepower, but only one player is under 30 (Derek Jeter's replacement with the gorgeous name, Didi Gregorius), the rest are all in the midst of clearly defined declines. Carlos Beltran and Mark Teixeira are near locks to spend some time on the DL, Brian McCann seems to have fallen off a cliff, and while I'm hoping A-Rod plays great just to piss everybody off, he's about to turn 40 and took a year off, who knows what he's got left in the tank.
The rotation has some youth for once, headed by Michael Pineda and Masahiro Tanaka (both 26) but the latter is considered a ticking time bomb because of a frayed elbow ligament and the former has continually frustrated those tantalized by his elite stuff by getting injured all the time. Maybe new pickup Nathan Eovaldi turns into a nice pitcher, but I doubt it. It's amazing to consider that the Yankees aren't purposely tanking and yet they might still finish in last place.
1. Indians
It's hard not to buy into one of the preseason's popular breakout picks. Heck, I was intrigued by them at the end of last season and wrote them up as a team to look out for in 2015. The rotation is loaded with young talent, headed by reigning Cy Young winner Corey Kluber, the lineup is well-rounded with youth, speed, power, OBP and depth, and the bullpen looks better than average. A crappy defense remains the issue with this team, but they had an all-time great strikeout staff last year (23.4 K% as a team, tied with Rays for best in baseball, both tied for highest mark of all time---it is indeed The Era of Strikeouts) so it doesn't matter as much. The division is suddenly crowded with potential contenders but this will be the year the Indians finally unseat the Tigers and come out ahead of the pack.
2. Tigers (Wild Card)
A hard team to figure, they've got plenty of offensive firepower and some top-flight pitchers but the back of the rotation looks shaky and the bullpen could be terrible. This year could be the last hurrah for the current contending core of Tigers---their division rivals are quickly improving, David Price will be gone after this year, Justin Verlander's exhibited signs of fading, and their key hitters are getting toward their decline stage.
For this final run at a title they've assembled quite possibly the best lineup of the Dave Dombrowski era, with Miguel Cabrera and Victor Martinez now backed by two sluggers in J.D. Martinez and Yoenis Cespedes, speed atop the lineup from Anthony Gose and Ian Kinsler, and a rare sight for the Tigers in the emerging young hitter Nick Castellanos. They've also got one of the most exciting shortstops in the game, Jose Iglesias, back on the field after a lost year. With plenty of offense and Iglesias picking it at short, they'll be a fun team to watch, but sadly there's little hope for a World Series title in Detroit unless they can finally solve their bullpen conundrum.
3. White Sox
The Pale Hose went on a shopping spree this winter and practically became a new team. Last year they had two of the top players in all of baseball, newly arrived Cuban slugger Jose Abreu and long lanky mound master Chris Sale, yet still somehow lost 89 games. This year they've built a nice supporting cast around those two and could be in the mix for a Wild Card spot all year. Free agent pickups Adam LaRoche and Melky Cabrera are huge offensive upgrades and they'll be getting back promising outfielder Avisail Garcia. The rotation is now fronted by three formidable pitchers with Sale backed by right hander Jeff Samardzija and the quietly excellent young lefty Jose Quintana. Plus their horrendous bullpen was revamped with the addition of closer David Robertson at the back end. The ingredients for a contending team are here, it's just a matter of them mixing it all together effectively.
4. Royals
Here comes the hangover. While their division rivals beefed up, the Royals had a strange offseason in which they picked up two aging and unexciting hitters in Alex Rios and Kendrys Morales while saying goodbye to their best pitcher and team leader James Shields. While the bullpen and defense should be excellent once again, the Royals appear to be light on starting pitching and the offense will again be depending on the likes of disappointing youngsters Eric Hosmer and Mike Moustakas. I'll also be shocked if catcher Salvador Perez doesn't show signs of fatigue after playing far too many games last year in the regular season and playoffs. The experience of playoff success was probably edifying for this young squad and should help them succeed, but there's just not nearly enough production here for them to overtake the Tigers, White Sox, and Indians.
5. Twins
After four straight years at the bottom of the standings, the unremarkable Twinkies will spend yet another season in the basement. To be fair, they aren't the Phillies, stuck at the bottom with an old, expensive roster and a crappy farm system. The Twins have some solid young players on their roster right now---27-year-old second baseman Brian Dozier is a budding star with lots of pop, walks, and good defense; Kennys Vargas and Oswaldo Arcia are each under-25 and have displayed immense raw power; 24-year-old Danny Santana was phenomenal in limited action last year; Phil Hughes turned in his best season in 2014 and he's still just 28 despite entering his 9th big league season---and two super highly touted prospects coming through the minors in slugger Miguel Sano and baseball's #1 prospect Byron Buxton. But it's going to take some time before the kids mature into consistent major league contributors and the rest of this bunch does not have the makings of a team that can unseat any of the Royals, Indians, White Sox, or Tigers any time soon.
Like the AL East, so many flawed teams here, it's hard to pick one to win.
1. Mariners
Jack Z. in Seattle appears to have finally pieced together a team worthy of the playoffs. Last year they finished one game out and if you watched them play it was obvious that this pitching rich team was held back by an offense with two stars and little else. Robinson Cano and Kyle Seager played nearly every game and put up big numbers, but they couldn't carry this team to the playoffs on their own. Going into 2015, the two dependable left-handed hitters finally have some support. The big addition is Nelson Cruz, a one-dimensional slugger whose all-or-nothing style may not be a perfect fit for cavernous Safeco Field but is an above-average hitter nonetheless. Perhaps more significantly they added lefty Seth Smith, an on-base machine who fulfills the Mariners' biggest need. Plus they bring back center fielder Austin Jackson who, despite playing terribly in Seattle after arriving in a trade last year, is a good bet for a bounceback at 28 years old. He'll be in the leadoff spot in front of Cano, Seager, Cruz, Smith and the improving Logan Morrison who's still just 27. The young guys who've looked overmatched the last couple years---Mike Zunino, Dustin Ackley, Brad Miller---now get to figure things out batting 7-8-9. Suddenly this lineup doesn't look so bad anymore.
2. Athletics
The A's never cease to fascinate avid baseball geeks like me. With their most recent contending core showing signs of fading after last summer's swift descent in the standings, fearless roster-shuffler Billy Beane completely dismantled his team and built it back up again in the course of one winter. After trading away one of the game's best players, Josh Donaldson, on the heels of an great season, it seemed like Beane was simply gutting the team to prepare for a gradual rebuilding process. Instead the trades only kept coming and by the time the Hot Stove embers faded the A's looked like they might have a newly redesigned winner.
The new roster certainly has its share of holes---an offense short on power and relying on some undependable players like the capricious former Mets first baseman Ike Davis, unproven infielder Marcus Semien, a full staff of young or fragile pitchers, and the disappointing, oft-injured third baseman Brett Lawrie. But, as always with Beane's A's, they've got a ton of intriguing starting pitchers, a bullpen that could be fantastic, a strong defense, and a roster with plenty of depth and flexibility. With continued success through so many different roster iterations over the years, you eventually have to give credit to the organization itself; the front office decision makers, player development figures, and coaching staff. While formidable think tanks have developed in many organizations around the league over the years (due in large part to the influence of Moneyball), the consistently contending A's remain the gold standard. I'll be rooting for them hard this year, but I do think they'll end up finishing just outside the Wild Card race.
3. Angels
The success of last year's Angels kinda baffled me. Yes, they have the greatest baseball player in the world, Mike Trout. They've got some solid players around him and GM Jerry DiPoto built a nice bullpen on the fly after a few relievers tanked to start 2014. But that's basically it. The rotation looks like it could crumble any second now, with its top arms Jered Weaver and C.J. Wilson declining rapidly last year and the only saving grace being the out-of-nowhere success of 28-year-old rookie Matt Shoemaker. They will be getting last year's breakout phenom Garrett Richards back sometime soon, but that will give them exactly one top-notch starter and a presumably rusty one no less.
There are many flawed, unbalanced teams in the AL and the Angels are certainly one of them. But while the Blue Jays and Red Sox have deep, imposing lineups to counteract their questionable pitching, the Angels have a lineup of Mike Trout, a geriatric Albert Pujols, and a bunch of solid but unspectacular role players. I don't think they'll be bad, but it'll be surprising if they come anywhere near last year's 98 wins---88 wins seems more like it.
4. Astros
I had the privilege of watching the Astros in spring training last month. The second batter of the game, George Springer, crushed a triple off the wall before Chris Carter launched a homer into center field. There will be plenty of that this year. The Astros suddenly have an interesting team with tons and tons of power. Springer and Carter (combined 57 bombs last year) will be main sources and they've also now got the bare-handed beastly slugger Evan Gattis, all-or-nothing outfielder Colby Rasmus, and ferociously-swinging first baseman Jon Singleton in the mix. It'll be raining baseballs in the Crawford Boxes this year.
Houston developed two excellent starters out of nowhere last year, Dallas Keuchel and Collin McHugh, both of whom are just 27, and the peripheral stats (3.21 and 3.11 FIP respectively) suggest they weren't flukes. The team was intent on improving its atrocious bullpen over the offseason and it appears they've done just that, bringing on two of the game's most reliable and quietly dominant relievers in Luke Gregerson and Pat Neshek. This team will win some games this year, they might even flirt with .500 or, if all breaks right, a Wild Card spot. I'm confident that, at the very least, they'll once again finish ahead of the Rangers.
5. Rangers
After two straight World Series appearances followed by two straight excruciating late season slides, the Rangers have now fallen into a dead zone. Last year they were hexed, suffering a rash of injuries to nearly everybody and losing 95 games in a lost season. Before the 2015 regular season could even get started the injury bug bit again and now, despite having the great Adrian Beltre in the heart of the lineup, the Texas Rangers once again look poised to spend six months wandering in a desert of confused sadness, wondering where it all went wrong.
Posted by PQ at 11:47 AM
Labels: AL Central, AL East, AL West, baseball, Baseball Prospectus, sabermetrics, Season Preview, Sports
Austin by way of San Diego via Staten Island, United States
A 34-year-old native of Staten Island, New York, departed for the sunny shores of San Diego in 2008, bounced over to Austin, TX in 2011. Food-for-thought glutton, Baseball junkie, Hip Hop head, James Joyce enthusiast. "A Building Roam" is my vehicle for writing about all of that plus much more. Any comments, suggestions, or feedback of any kind is appreciated. You can email me HERE.
Finnegans, Wake!
Links to My Writing Elsewhere
16 Reasons Why James Joyce is the Greatest Writer Ever
Salvador Dali's essay "The Conquest of the Irrational"
Book Review: "Cardboard Gods" by Josh Wilker
Examining James Joyce/Stephen Dedalus' Esthetic Philosophy (part 1)
The Allure of Gravity's Rainbow and Its Mysterious Author
Retracing Recent Ramifications of Thought, Part 2 (Room 237 and beyond)
Read Before the Electronic Ink Evaporates: Illustrated Joyce (and some Dali too)
Retracing Recent Ramifications of Thought, Part 1 (VALIS, Duality and Finnegans Wake)
A Review of the First Half of the Madlib Medicine Show
Album Review: A sneak peek at the new Canibus & Br...
MLB 2015 Predictions, Part 1: National League
Gotta Read the Labels
Sports (145) books (134) baseball (130) music (108) James Joyce (99) literature (99) hip hop (89) art (68) random (62) sabermetrics (57) Finnegans Wake (55) Wu-Tang (51) Baseball Prospectus (50) ulysses (48) Season Preview (34) Mets (33) Bronze Nazareth (30) Kevlaar 7 (27) book reviews (27) The Wisemen (26) science (26) album review (25) Padres (24) Salvador Dali (24) cosmic consciousness (24) painting (24) video (24) film (23) astronomy (22) NL West (21) autobiographical (21) NL East (20) Madlib (19) Giants (18) synchronicity (18) Robert Anton Wilson (17) Rays (16) San Diego (16) jazz (16) AL Central (15) AL East (15) Basketball (15) NBA (15) AL West (14) Cardinals (14) Yankees (14) psychology (14) NL Central (13) Rza (13) A Portrait of the Artist as a Young Man (12) New York City (12) Red Sox (12) Tigers (12) philosophy (12) A's (11) Austin (11) Joseph Campbell (11) NHL (11) Rangers (11) lyrics (11) potent quotables (11) Angels (10) Dodgers (10) Marshall McLuhan (10) Orioles (10) Phillies (10) White Sox (10) Braves (9) Cubs (9) Gza (9) Hockey (9) Indians (9) MF Doom (9) Pirates (9) Staten Island (9) links (9) Blue Jays (8) Brewers (8) Killah Priest (8) Mariners (8) Rockies (8) poetry (8) soul (8) Marlins (7) Woodenchainz (7) earth (7) instrumentals (7) paranoiac-critical method (7) physics (7) "Thought Through My Eyes" (6) Astros (6) Bill James (6) Diamondbacks (6) FreeDarko (6) New York Knicks (6) Reds (6) Thirst for Knowledge Thursday (6) Timothy Leary (6) Twins (6) cosmos (6) history (6) photography (6) the moon (6) the universe (6) Bill Simmons (5) CG Jung (5) Friedrich Nietzsche (5) General (5) Inception (5) Josh Wilker (5) Masta Killa (5) Medicine Show (5) NFL football (5) Royals (5) Tragic Allies (5) football (5) graffiti (5) signs of my country's demise (5) street art (5) surrealism (5) 8-circuit brain (4) A Man Called Relik (4) Ghostface (4) Gustav Klimt (4) I-Ching (4) MC Escher (4) Nationals (4) Occupy Wall Street (4) Raekwon (4) introduction (4) mandala (4) travel (4) Alan Watts (3) Basketball Prospectus (3) Blake Griffin (3) Buckminster Fuller (3) Cilvaringz (3) Ezra Pound (3) Football Outsiders (3) Hell Razah (3) Herman Melville (3) Jacques Lacan (3) John Kidd (3) Moby-Dick (3) Noble Scity (3) Ol' Dirty Bastard (3) Olympics (3) Purpose (3) Rob Brezsny (3) San Diego Chargers (3) Stanley Kubrick (3) Sunz of Man (3) Texas (3) The Dead (3) astrology (3) lyric analysis (3) memories (3) mythology (3) reincarnation (3) the sun (3) 4th Disciple (2) Barcelona (2) Bill Murray (2) Blackhawks (2) Brooklyn Bridge (2) Cosmic Trigger (2) Django Unchained (2) Dubliners (2) Goldman Sachs (2) Istvan Orosz (2) Jorn Barger (2) Kings (2) Kobe Bryant (2) Kurt Vonnegut (2) Lakers (2) Lisbon (2) Lord Beatjitzu (2) Love (2) Manny Ramirez (2) Marcel Duchamp (2) Merc Versus (2) Moneyball (2) New York Jets (2) New York Rangers (2) Quentin Tarantino (2) Ralph Waldo Emerson (2) Red Wings (2) Roger Angell (2) San Francisco (2) Shakespeare (2) Stanislav Grof (2) Tim Lincecum (2) World Series (2) World Trade Center (2) chess (2) creation (2) piano (2) police brutality (2) pyramids (2) road trip (2) spacetime (2) the brain (2) writing (2) Aleister Crowley (1) Amare Stoudemire (1) Amy Winehouse (1) Antonio Gates (1) Arthur Schopenhauer (1) August (1) Billy Sunday (1) Book of Kells (1) Broncos (1) Bruins (1) CIA (1) Cappadonna (1) Charles Bukowski (1) Chicago Bears (1) Datsyuk (1) Double Feature (1) Egypt (1) Faust (1) Ferris Bueller (1) Fritjof Capra (1) Gang Starr (1) Giambattista Vico (1) Harriet Shaw Weaver (1) Holotropic Breathwork (1) Houston Rockets (1) Jacques Vallée (1) Jneiro Jarel (1) KRS-One (1) Ken Wilber (1) LeBron James (1) McFly (1) Michael Jordan (1) Milwaukee (1) Moondog (1) New Jersey (1) New Jersey Nets (1) Nina Simone (1) Paris (1) Philip K. Dick (1) Philip Rivers (1) Picasso (1) RIchard Tarnas (1) Remedios Varo (1) Richard Maurice Bucke (1) Roger Ebert (1) Room 237 (1) School for the Blindman (1) Seinfeld (1) Sigmund Freud (1) Stanley Cup (1) Stephen Wiltshire (1) Stevie Wonder (1) Sun Ra (1) Sylvia Beach (1) The Gutenberg Galaxy (1) Timbo King (1) Tracy McGrady (1) True Master (1) Tunc page (1) VALIS (1) Van Morrison (1) Vladimir Kush (1) Willie the Kid (1) animal slaughter (1) architecture (1) autistic savants (1) benjamin button (1) dentists (1) dreams (1) eastern religion (1) epiphanic morsels (1) military (1) propaganda (1) scultpure (1) stadiums (1) thunder (1) time (1) veganism (1) wisdom (1)
Banner by BC
Banner art designed by Bobby Campbell http://bobbycampbell.net
|
cc/2020-05/en_middle_0097.json.gz/line35293
|
__label__wiki
| 0.887743
| 0.887743
|
#GoodCops Sex Workers Rights
Sex worker jumps to her death after fleeing police
By Social Dissonance November 28, 2017
Leave a Comment on Sex worker jumps to her death after fleeing police
New York City- A sex worker jumped to her death from the third-story window in Queens rather than be arrested by cops during a sting operation, police said Sunday.
The 38-year-old sex worker made a deal to perform a sex act with an undercover cop while they were inside 135-32 40th Road in Flushing at 7:30 p.m. Saturday, according to officials.
When the officer called for backup, and the frightened woman leaped out the window, landing on the sidewalk below, police said.
She was taken to Booth Memorial Hospital, where she later died, officials said.
Cops have not released the woman’s name, but neighbors said she went by the name “C.C.” and worked inside a massage parlor there.
An unamed woman working at a nearby jewelry store said the victim had just gotten out of jail four months ago, but wanted to leave the industry. C.C. also confided to fellow massage-parlor workers that she would kill herself before being arrested again.
“It’s really horrible. I Saw the paddy wagon this morning and I knew,” said Rob, 42, who lives nearby and said he sometimes spoke with CC about her search for a new job.
The death comes as lawmakers grapple with the seedy massage parlor industry.
Queens Councilman Jose Peralta introduced a bill in October that would require massage parlor owners register with the Department of State and apply for special four-year licenses or face fines and potential jail time.
This is not the first time that a sex worker leaped and jumped out of a window to evade arrest.
According to a report on a Nigerian website called Pulse.ng, in May a Nigerian woman who went by the name Sophia, who worked as a commercial sex worker in Dubai, United Arab Emirates, jumped from her balcony to avoid getting caught by the authorities.
Previous Entry Facebook continues to create new ways to violate privacy
Next Entry Oklahoma gets new cameras to target drivers and increase revenue
|
cc/2020-05/en_middle_0097.json.gz/line35300
|
__label__wiki
| 0.941054
| 0.941054
|
The search for Green and Gold in the land of Scarlet and Gold
Giuliani associate: Trump had knowledge of Ukraine pressure
By MICHAEL BIESECKER, MARY CLARE JALONICK and ERIC TUCKER
WASHINGTON (AP) — A close associate of President Donald Trump’s personal lawyer says he delivered an ultimatum in May to the incoming president of Ukraine that no senior U.S. officials would attend his inauguration and all American aid to the war-torn country would be withheld if an investigation into Joe Biden wasn’t announced.
Lev Parnas, an associate of Rudy Giuliani, made several potentially explosive claims in a televised interview Wednesday night with MSNBC’s Rachel Maddow. The day after Parnas said he delivered the message, the U.S. State Department announced that Vice President Mike Pence would no longer be attending the inauguration of Ukrainian President Volodymir Zelenskiy.
Parnas alleged that Trump ordered Pence to stay away at the behest of Giuliani to send a clear message to the incoming Ukrainian administration that they needed to take seriously the demand for an investigation into Biden, a Democratic presidential candidate seen as a potential threat to Trump’s 2020 reelection.
Parnas said every communication he had with Zelenskiy’s team was at the direction of Giuliani, whom he regularly overheard briefing Trump about their progress by phone.
“President Trump knew exactly what was going on,” said Parnas, a Soviet-born Florida businessman facing a raft of criminal charges related to campaign finance violations. “He was aware of all my movements. I wouldn’t do anything without the consent of Rudy Giuliani, or the President.”
If true, Parnas’ account undercuts a key Republican defense of Trump deployed during the ongoing impeachment fight — that Trump’s withholding of vital military aid to Ukraine last summer wasn’t a quid pro quo for Biden investigations because Zelenskiy didn’t know the money was being held up.
Giuliani called Parnas’ statements “sad.”
“I feel sorry for him,” Giuliani said Wednesday in a text message to an AP reporter. “I thought he was an honorable man. I was wrong.”
Asked directly if Parnas was lying, Trump’s lawyer replied, “I’m not responding yet.”
Parnas said he also heard Giuliani and another Trump-aligned defense lawyer, Victoria Toensing, briefing Attorney General William Barr by phone about their efforts to pressure the Ukrainian government to announce the investigation into Biden and his son Hunter’s business dealings.
“Barr was basically on the team,” Parnas said.
The Justice Department said in September that Trump had not spoken to Barr about having Ukraine investigate the Bidens and that the attorney general had not discussed Ukraine with Giuliani. Justice Department spokeswoman Kerri Kupec said Wednesday that Parnas’ claims were “100% false.”
The new accusations came as House Democrats made public a trove of documents, text messages and photos from Parnas’ smartphones that appear to verify parts of his account.
A federal judge earlier this month ruled that Parnas could provide the materials to Congress as part of the impeachment proceedings. Democrats voted in December to impeach Trump for abuse of power and for obstruction of Congress.
A House committee chairman said Wednesday his panel will investigate what he says are “profoundly alarming” text messages among the newly disclosed materials that have raised questions about the possible surveillance of former Ambassador to Ukraine Marie Yovanovitch before she was ousted by the Trump administration last spring.
The messages show that a Robert F. Hyde, a Republican candidate for Congress from Connecticut, disparaged Yovanovitch in messages to Parnas and gave him updates on her location and cellphone use.
Rep. Eliot Engel, a New York Democrat who chairs the House Foreign Affairs Committee, said Wednesday that the messages are “profoundly alarming” and “suggest a possible risk” to Yovanovitch’s security in Kyiv before she was recalled from her post.
“These threats occurred at the same time that the two men were also discussing President Trump’s efforts, through Rudy Giuliani, to smear the ambassador’s reputation,” Engel said.
He said the committee staff flagged the information for the State Department’s Bureau of Diplomatic Security and is seeking assurances that proper steps have been taken to ensure the security of Yovanovitch and committee staff. He said he also wanted to know what, if anything, the State Department knew about the situation.
“This unprecedented threat to our diplomats must be thoroughly investigated and, if warranted, prosecuted to the fullest extent of the law,” Engel said.
Democrats released the files Tuesday and Wednesday as they prepared to send articles of impeachment to the Senate for Trump’s trial. The documents could add pressure on the Senate as it debates whether to hear witnesses in the trial.
The text and phone records show Parnas communicating with Giuliani multiple times a day before Yovanovitch’s removal, as well as a handwritten note that mentions asking Ukraine’s president to investigate “the Biden case.”
Among the documents is a screenshot of a previously undisclosed letter from Giuliani to Zelenskiy dated May 10, 2019, which was shortly after Zelenskiy was elected but before he took office. In the letter, Giuliani requests a meeting with Zelenskiy “as personal counsel to President Trump and with his knowledge and consent.”
The Associated Press reported in October that Zelenskiy had huddled three days earlier, on May 7, with a small group of key advisers in Kyiv to seek advice about how to navigate the insistence from Trump and Giuliani for a probe into the Bidens. He expressed his unease about becoming entangled in the American elections, according to three people familiar with the details of the three-hour meeting. They spoke on the condition of anonymity because of the diplomatic sensitivity of the issue, which has roiled U.S.-Ukrainian relations.
One of the documents released by Democrats is a handwritten note on stationery from the Ritz-Carlton Hotel in Vienna that says “get Zalensky to Annonce that the Biden case will be Investigated.”
Parnas told Maddow he took the notes as he was speaking by phone to Giuliani, receiving precise instructions about the demands Trump wanted to convey to Zelenskiy’s team.
Trump asked Zelenskiy in a July 25 call to investigate the Bidens. Hunter Biden served on the board of a gas company based in Ukraine.
The documents were sent to the House Judiciary Committee by three other House panels “to be included as part of the official record that will be transmitted to the Senate along with the Articles of Impeachment,” according to a statement. Some of the materials were made public while others were blacked out and marked as sensitive.
Parnas and his business partner, Igor Fruman, both U.S. citizens who emigrated from the former Soviet Union, were indicted last year on charges of conspiracy, making false statements and falsification of records. Prosecutors allege they made outsize campaign donations to Republican causes after receiving millions of dollars originating from Russia. The men have pleaded not guilty.
In several of the documents, Parnas communicated with Giuliani about the removal of Yovanovitch. The ambassador’s ouster, ordered by Trump, was at the center of the Democrats’ impeachment inquiry. Yovanovitch testified in the House impeachment hearings that she was the victim of a “smear campaign.”
Trump on the July call told Zelenskiy that Yovanovitch was “going to go through some things.” She had been recalled from her diplomatic post roughly three months earlier.
On April 23, just before Yovanovitch was directed to return to the United States, Giuliani texted Parnas, “He fired her again.” Parnas texted back, “I pray it happens this time I’ll call you tomorrow my brother.”
Parnas also received messages from Hyde, who referred to Yovanovitch as a “bitch.”
After texting about the ambassador, Hyde gave Parnas detailed updates that suggested he was watching her. In one text, Hyde wrote: “She’s talked to three people. Her phone is off. Her computer is off.” He said she was under heavy security and “we have a person inside.”
Hyde texted Parnas that ”they are willing to help if we/you would like a price,” and “guess you can do anything in Ukraine with money … is what I was told.”
Parnas texted back: “lol.”
Lawrence Robbins, an attorney for Yovanovitch, called for an investigation into the messages.
In a Twitter post Tuesday, Hyde called Parnas a “dweeb” and suggested the messages about surveilling the ambassador were a joke. He said he welcomed an investigation.
Parnas, in turn, also said Wednesday that Hyde’s texts shouldn’t be taken seriously.
The text messages show that Parnas consulted Giuliani in January 2019 after the U.S. denied a visa to former Ukrainian Prosecutor General Viktor Shokin. Giuliani replied: “I can revive it.”
The following day, Giuliani told Parnas, “It’s going to work I have no 1 in it.” Giuliani then predicted “he will get one,” before giving Parnas the phone number for Jay Sekulow, the leader of the president’s personal legal team. Sekulow is expected to be part of Trump’s legal team during the impeachment trial.
Trump has repeatedly denied knowing Parnas and Fruman, despite numerous photos that have emerged of the men together. Among the materials released from Parnas’ phone this week were more photos of him with Trump, as well as the president’s son Donald Trump Jr., first daughter Ivanka Trump, and her husband, Jared Kushner.
Asked by Maddow about Trump’s denials of knowing him, Parnas said he had spoken one-on-one with the president numerous times.
“He lied,” Parnas said of the president. “I mean, we’re not friends. Me and him didn’t watch football games together, we didn’t eat hot dogs. But he knew exactly who we were, who I was especially.”
Associated Press writers Michael Balsamo, Lisa Mascaro and Zeke Miller contributed to this report.
German parliament votes against new system for organ donors
3 African countries trying out 1st malaria vaccine in babies
AP Top Sports News at 5:46 a.m. EST
|
cc/2020-05/en_middle_0097.json.gz/line35314
|
__label__cc
| 0.690735
| 0.309265
|
How I Fell In Love And Jumped Into A Live-In With A Stranger In 7 Days
The lack of digital privacy and not respecting boundaries therein, led to the downfall of our relationship.
Part 1 - The Meeting
I have been in a live-in relationship for two years. And now I’m mentally prepping myself for a two year long distance one. Sigh! Before I fret about the physical distance, let me flashback to the summer of 2016, the first time I met my boyfriend Sammy. I had moved to Bangalore in March 2016. It took us less than 7 days to meet and start living together. At first, we didn’t even label it live-in. It happened organically.
In the first few weeks, we were just too busy falling in love to care about anything else. Our first conversation was on WhatsApp and it was just a whole lot of small trying-to-test-the-waters talk. But from there on, we went into details about our individual professions, favourite musicians, raves, college life in Bombay, drugs, likes, dislikes, food, travel destinations, how we had possibly been at the same rave in 2011 and so on. We had been texting for 72 hours straight. This even included him giving me a wake up call.
He lived at the other end of the city, two hours away at his parents place, but his office was about 15 minutes away from me. He wanted to meet me after work. I decided to play difficult and claimed to be busy, while I was secretly lounging on my bed, listening to Glass Animals in my underwear.
I was mentally freaking out, but still super excited about this extremely random, addictive, new found connection. Maybe he was my twin flame. Freakishly enough, our relationship defined a lot of characteristics associated with a twin flame experience. At least according to the internet:
Twin Flame - Unlike soul mates, twin flames are mirrors of ourselves. Twin flames experience intense passion, an instantaneous bond, a certain amount of intense pain looking into the eyes of your better (or other?) half and experiencing feelings of viewing them as a family member or your own child.
Whatever the label may be, this was a human connection I had never experienced before. Similar to a fantastic LSD trip.
Anyway we met. Dinner and drinks the night before a techno gig.
I told him he could stay at my place and he ought to carry some clothes with him. Sammy spent the next few hours on the phone with his best friend, debating whether I could be a serial killer or if this was just a one-off situation.
I walked into the restaurant wearing black tights, a black ganji, a multi-coloured tye-dye crop top pullover, paired with white Adidas sneakers. I had a tinge of lipstick on and my curls were let loose. I was ridiculously nervous. When I walked into the restaurant, Soum (Sammy) who had been waiting for 15 minutes, got up from the table. We grinned and gave each other an awkward, but enthusiastic half-hug.
Related: The Love Trip
As a journalist at a leading business daily, I tracked startups and technology companies out of Bangalore. But suddenly I found myself unable to accurately describe what I do, and all the characteristics that defined a startup versus any other company. We went from talking about startups to blowjobs, pork ribs, whiskey and dancing. Before I knew it, we were getting drinks, dancing to some techno and calling an Uber, planning to head home to my place. We smoked a doob and called it a night. Snuggling led to sex, after which he fell asleep.
Everything was happening too quickly.
I lay awake, staring at his face and then at the ceiling. I was petrified by all the emotions I was feeling. Was this a one night stand? Well, we still had the rave to go to the next day and he had no spare clothes.
Getting addicted. Image source: potentmedia.com
Everything was going unbelievably well. We were holding hands and acting like best friends who were falling in love. Later that night, our LSD trip ended with the music abruptly stopping in my room and us experiencing continuous “mindgasms” for three hours. Yes, no physical touching was required but it felt like our minds were fucking. It was overwhelming and more exhausting than physical fucking. We never experienced it again.
By the third day, we were farting and burping in front of each other, like it was no big deal. He went home, hung with his parents, picked up his clothes and returned a day later. We were inseparable and addicted to spending time with each other. We were officially in a live-in relationship without realising it. Both of us yearned for office hours to end, so that we could be in the same room again. Hours went by where we just stared at each other or remained lost in conversation.
One month flew by and we were gushing to our friends about how beautiful our significant others were. We were madly in love, but there was one enormous problem lurking around the corner. We were in a relationship without actually really knowing each other!
The end? Image source: fax.al
Part 2 - The Dark Side of Love
I lied about several tiny details from my past because of my own insecurities. The tiny details turned into a mountain of lies. However, I was honest with him about the fact that I had never been interested in relationships and flings usually worked for me. His entrance into my life was highly unexpected, but greatly appreciated. Sammy had been cheated on by his first lover during a long distance relationship. My lies only reinforced a strong level of distrust in him towards me.
While we lived together, I learnt more about myself than I ever had before. I realised that I didn't quite understand the concept of boundaries in a relationship. Boys whom I had slept with in the past were still very much a part of my life. Being in touch with exes did not seem to be a problem, till Sammy saw flirtatious messages being sent my way, which I often laughed off or ignored. Our relationship completely lacked digital privacy. Some of my lies were discovered when he was browsing through chats on my Whatsapp and Facebook account. I made it a point to read old messages between him and his ex lover and other women he had been flirtatious with. We were slowly killing the present with stories of our promiscuous past.
Related: How To Move On From A Toxic Relationship
Digital privacy was one factor, but the first cracks in our relationship emerged because of my lies. There were days when it felt like Sammy’s trust in me was completely broken. Our relationship had transitioned from constant affection to days filled with screaming, angry rants, binge drinking, excessive smoking, blocking each other’s phone numbers during office hours, verbally abusing each other and so on. Sometimes our fights were so loud that the landlord and flat mates had to intervene. And Sammy being extremely short tempered scared the shit out of me.
Emotional shitstorm. Image source: videoblocks.com
I began undoing my lies, but he was too angry by now. Everything was up and down. We spent nights crying and hating each other, despite still having days where we fucked four times a day. It was emotional chaos. I realised that my initial commitment phobia, along with the fear of him losing interest in the “real me” had led me to lie about the little things that I hated about myself. We broke up a million times and were constantly at each other’s throats. But we never left each other. Our relationship had all the signs of a classic abusive relationship.
Oddly enough, while my relationship hit rock bottom, my career was at an all time peak. I was breaking important news stories every week and the editors at my workplace were really starting to take notice of my work. Luckily for me, my absence from work was regarded as a young journalist being extremely busy with breaking news stories, developing secret sources and attending high profile meetings. In reality, I was most likely crying under my blanket after a terrible fight or getting high as a kite while smoking a bong.
Our lives together often felt like a recurring nightmare. The only peace and quiet we ever got was when we slept. Consciously or unconsciously we hugged each other tightly and slept through the night. Prior to meeting each other, neither of us were inclined towards any kind of body hugging while asleep. But somehow, sleeping in each other’s arms every night was something that happened automatically. Sometimes we would suddenly wake up in the morning, finding ourselves in each other’s arms. Then, one of us would snarl at the other and push away the individual, while remembering a fight from the previous night.
Then one day, I decided I had had enough. I packed my bags without informing Sammy and caught the first flight to Bombay, while he was in office. I sent him a long text before I boarded the flight, informing him that I was terribly hurt and had to go home and be around people I missed and loved. Before I knew it, he was going crazy. All he could keep saying was, “How could she leave me?” while he bawled on the phone to my best friend, pleading for me to return to Bangalore, promising that we would start afresh.
Alone again. Image source: YouTube.com
Part 3 – The Breakup
I returned home to my friends in Bombay and I was a complete mess. At first, I kept my phone switched off so he couldn’t reach me, but at the same time I ached to be back with him and make things work. After all, neither of us had fallen this madly in love with another person. Despite having run away, I knew I loved him and I longed to return to him. The day I left Bombay, was the day he flew to be with his best friend in Delhi. He claimed he did not know how to be in the same city without me. I understood that perfectly. I spent some time in Bombay with my closest friends. Over what felt like a hundred conversations in ten days and four flights back and forth between Bombay and Bangalore, we finally figured it out.
Acceptance and forgiveness was key, besides letting go of our past. Never again was I going to lie about stupid shit that made me insecure. If there was one thing we knew was real, it was the love we had for each other.
I came back to Bangalore and slowly learnt the importance of self love. He learnt how to control his temper and be calm. Every time we neared a disagreement about something irrelevant, one of us would laugh it off and hug the other or would walk into a separate room for a few minutes and cool off. We knew our arguments were not worth it. We were better than that. We had to be. The next four months we saw our fights go down dramatically. We went from fighting once a day to once a week, soon it was once a month, then suddenly there were no more fights. The fights were slowly replaced with laughs, giggles, hugs, kisses and sex a couple times a week, while we focused on our personal goals and ambitions.
Moving in. Image source: bymovers.com
Part 4 - A Long Distance Relationship
We went from living in a 3BHK with two other flatmates for over a year to renting out our first home together. That was no easy task. We met several brokers, most of whom told us to lie to the landlords, telling them we were engaged or married, otherwise we were not going to get a home. At first, we decided we wanted to be honest and tell them we were an unmarried couple, living together. That didn’t work out too well. We saw far too many rejections and eventually decided we would tell people we were engaged and would be married in one year. That worked.
Related: Why It's Okay To Have No Happily Ever After
We moved into a new home. After having spent one year obsessing over each other, it was time to go back to focusing on honing our individual skills and pursuing things we were passionate about, while being supportive of each other. The only kind of arguments we had were about the dirty dishes in the kitchen on a Sunday evening, clothes from the washing machine not being hung out to dry, serving dinner after work – all of the bickering typically associated with a married couple. We were truly at peace with each other.
I started taking yoga seriously and began working out. We made time for our girl and guy friends, having a girls or boys night out. There were long weekends when we took a trip together or just stayed in bed all day having a movie marathon, eating junk, smoking and having incredible sex. We no longer obsessively checked each others cellphones. Communicating with friends or acquaintances of the opposite sex was not equivalent to cheating on each other.
At peace. Image source: YouTube.com
Everything was perfect. We would dream of a future settling down in Bangalore. I loved travelling and having a father who had grown up in five different countries and travelled across the world, I yearned to live in different countries at some point too. Once Sammy realised I was serious about it, he decided to contact international recruiters. I was thrilled! In the last few weeks, a highly lucrative job offer came up from Singapore, which included being based out of Singapore and travelling across Southeast Asia on work, accompanied with a six figure annual salary. This meant he would have to leave before I had any solid plans of studying. After a lot of urging on my part, he finally accepted the offer.
Transitioning from a live-in to a long distance relationship is no easy task. The one way I plan to cope with it is through embracing the new experiences and learnings that come my way and by constantly keeping myself occupied reading, writing, learning different subjects, exercising and exploring new music. We have made a pact to meet once in four months so we have something to look forward to, besides weekly FaceTime video calls and texting, sharing photos through the day whenever we get the chance to do so.
We have convinced each other that this is only temporary and that we will get married in the next two years. For now I am going to be optimistic about the new, independent adventures that lie ahead of us, before we come together again. I promise to return with an update on our relationship status in 2020!
Disclaimer: The views expressed in this article are independent views solely of the author(s) expressed in their private capacity and do not in any way represent or reflect the views of 101india.com
By Sasha Klaatu
Cover photo credit: collegetimes.com
I’m A Woman And I Love Having Sex
I Came To Mumbai Looking For A Job – Found Love, Lost Love, Then...
Swingers and Threesomes – Recipe For A Happy Marriage?
I Looked Past The Barrel Of An Army Gun And Fell In Love With The...
A BDSM Play-Shop Opens Up The World Of Dominatrix And Submission To Me
Will Indian Porn Ever Come Of Age?
What It’s Like To Date A Musician
Borun and Mamota Yumnam: Mr. & Mrs. Bodybuilding | 101 Love In India
My Democratic Country Thinks It’s Okay To Kill Me For Being Gay
The Madam Of A Brothel Told Me, “All That Matters In Life Is Big...
The Big Fat Indian Wedding With A Gora
|
cc/2020-05/en_middle_0097.json.gz/line35316
|
__label__wiki
| 0.805668
| 0.805668
|
Formula: N2
Molecular weight: 28.0134
IUPAC Standard InChI:
InChI=1S/N2/c1-2
Download the identifier in a file.
IUPAC Standard InChIKey: IJGRMHOSHXDMSA-UHFFFAOYSA-N
CAS Registry Number: 7727-37-9
Chemical structure:
This structure is also available as a 2d Mol file or as a computed 3d SD file
The 3d structure may be viewed using Java or Javascript.
Other names: Nitrogen gas; N2; UN 1066; UN 1977; Dinitrogen; Molecular nitrogen; Diatomic nitrogen; Nitrogen-14
Permanent link for this species. Use this link for bookmarking this species for future reference.
Information on this page:
Gas phase thermochemistry data
Phase change data
Reaction thermochemistry data (reactions 1 to 50)
Mass spectrum (electron ionization)
Constants of diatomic molecules
Other data available:
Reaction thermochemistry data: reactions 51 to 100, reactions 101 to 150, reactions 151 to 156
Henry's Law data
Gas phase ion energetics data
Ion clustering data
Data at other public NIST sites:
Electron-Impact Ionization Cross Sections (on physics web site)
Computational Chemistry Comparison and Benchmark Database
Gas Phase Kinetics Database
Switch to calorie-based units
Data at NIST subscription sites:
NIST / TRC Web Thermo Tables, "lite" edition (thermophysical and thermochemical data)
NIST / TRC Web Thermo Tables, professional edition (thermophysical and thermochemical data)
NIST subscription sites provide data under the NIST Standard Reference Data Program, but require an annual fee to access. The purpose of the fee is to recover costs associated with the development of data collections included in such sites. Your institution may already be a subscriber. Follow the links above to find out more about the data in these sites and their terms of usage.
Go To: Top, Phase change data, Reaction thermochemistry data, Mass spectrum (electron ionization), Constants of diatomic molecules, References, Notes
Data compilation copyright by the U.S. Secretary of Commerce on behalf of the U.S.A. All rights reserved.
S°gas,1 bar 191.609 ± 0.004 J/mol*K Review Cox, Wagman, et al., 1984 CODATA Review value
S°gas,1 bar 191.61 J/mol*K Review Chase, 1998 Data last reviewed in March, 1977
Gas Phase Heat Capacity (Shomate Equation)
Cp° = A + B*t + C*t2 + D*t3 + E/t2
H° − H°298.15= A*t + B*t2/2 + C*t3/3 + D*t4/4 − E/t + F − H
S° = A*ln(t) + B*t + C*t2/2 + D*t3/3 − E/(2*t2) + G
Cp = heat capacity (J/mol*K)
H° = standard enthalpy (kJ/mol)
S° = standard entropy (J/mol*K)
t = temperature (K) / 1000.
View plot Requires a JavaScript / HTML 5 canvas capable browser.
View table.
Temperature (K)
100. - 500. 500. - 2000. 2000. - 6000.
28.98641 19.50583 35.51872
1.853978 19.88705 1.128728
-9.647459 -8.598535 -0.196103
16.63537 1.369784 0.014662
0.000117 0.527601 -4.553760
-8.671914 -4.935202 -18.97091
226.4168 212.3900 224.9810
Chase, 1998 Chase, 1998 Chase, 1998
Data last reviewed in March, 1977; New parameter fit January 2009 Data last reviewed in March, 1977; New parameter fit January 2009 Data last reviewed in March, 1977; New parameter fit January 2009
Go To: Top, Gas phase thermochemistry data, Reaction thermochemistry data, Mass spectrum (electron ionization), Constants of diatomic molecules, References, Notes
Data compiled as indicated in comments:
TRC - Thermodynamics Research Center, NIST Boulder Laboratories, Chris Muzny, director
AC - William E. Acree, Jr., James S. Chickos
Tboil 77.34 K N/A Jacobsen, Stewart, et al., 1986 TRC
Tboil 77.4 K N/A Streng, 1971 Uncertainty assigned by TRC = 0.3 K; TRC
Tfus 63.3 K N/A Streng, 1971 Uncertainty assigned by TRC = 0.3 K; TRC
Ttriple 63.14 K N/A Jacobsen, Stewart, et al., 1986 TRC
Ttriple 63.14 K N/A Angus, de Reuck, et al., 1979 Uncertainty assigned by TRC = 0.005 K; TRC
Ttriple 63.14 K N/A Henning and Otto, 1936 Uncertainty assigned by TRC = 0.06 K; temperature measured with He gas thermometer; TRC
Ttriple 63.13 K N/A Giauque and Clayton, 1933 Crystal phase 1 phase; Uncertainty assigned by TRC = 0.06 K; TRC
Ptriple 0.1252 bar N/A Jacobsen, Stewart, et al., 1986 Uncertainty assigned by TRC = 0.0005 bar; TRC
Ptriple 0.1253 bar N/A Angus, de Reuck, et al., 1979 Uncertainty assigned by TRC = 0.0002 bar; TRC
Ptriple 0.126 bar N/A Henning and Otto, 1936 Uncertainty assigned by TRC = 0.0007 bar; TRC
Ptriple 0.1253 bar N/A Giauque and Clayton, 1933 Crystal phase 1 phase; Uncertainty assigned by TRC = 0.0001 bar; Average Pressure; TRC
Tc 126.19 K N/A Jacobsen, Stewart, et al., 1986 Uncertainty assigned by TRC = 0.01 K; TRC
Tc 126.2 K N/A Angus, de Reuck, et al., 1979 Uncertainty assigned by TRC = 0.05 K; TRC
Tc 126.2 K N/A Weber, 1970 Uncertainty assigned by TRC = 0.2 K; IPTS-68, critical point not observed and Tc taken from literature but equation would allow pc to be calculated. Tc unct. several tenths K. "Ultra-high" purity nitrogen.; TRC
Tc 128.45 K N/A Cardoso, 1915 Uncertainty assigned by TRC = 0.5 K; TRC
Pc 33.978 bar N/A Jacobsen, Stewart, et al., 1986 Uncertainty assigned by TRC = 0.007 bar; TRC
Pc 34.00 bar N/A Angus, de Reuck, et al., 1979 Uncertainty assigned by TRC = 0.05 bar; TRC
Pc 3.0698 bar N/A Cardoso, 1915 Uncertainty assigned by TRC = 0.003 bar; TRC
c 11.18 mol/l N/A Jacobsen, Stewart, et al., 1986 Uncertainty assigned by TRC = 0.02 mol/l; TRC
c 11.2 mol/l N/A Angus, de Reuck, et al., 1979 Uncertainty assigned by TRC = 0.02 mol/l; TRC
Enthalpy of vaporization
vapH (kJ/mol)
6.1 78. Edejer and Thodos, 1967 Based on data from 63. - 126. K.; AC
5.6 77. Giauque and Clayton, 1933, 2 AC
Antoine Equation Parameters
log10(P) = A − (B / (T + C))
P = vapor pressure (bar)
T = temperature (K)
63.14 - 126. 3.7362 264.651 -6.788 Edejer and Thodos, 1967 Coefficents calculated by NIST from author's data.
63.14 - 78.00 3.63792 257.877 -6.344 Moussa, Muijlwijk, et al., 1966 Coefficents calculated by NIST from author's data.
In addition to the Thermodynamics Research Center (TRC) data available from this site, much more physical and chemical property data is available from the following TRC products:
SRD 103a – Thermo Data Engine (TDE) for pure compounds.
SRD 103b – Thermo Data Engine (TDE) for pure compounds, binary mixtures and chemical reactions
SRSD 2 – Web Thermo Tables (WTT), "lite" edition
SRSD 3 – Web Thermo Tables (WTT), professional edition
SRD 147 – Ionic Liquids Database
SRD 156 – Clathrate Hydrate Physical Property Database
Reaction thermochemistry data
Go To: Top, Gas phase thermochemistry data, Phase change data, Mass spectrum (electron ionization), Constants of diatomic molecules, References, Notes
M - Michael M. Meot-Ner (Mautner) and Sharon G. Lias
MS - José A. Martinho Simões
B - John E. Bartmess
ALS - Hussein Y. Afeefy, Joel F. Liebman, and Stephen E. Stein
Note: Please consider using the reaction search for this species. This page allows searching of all reactions involving this species. A general reaction search form is also available. Future versions of this site may rely on reaction search pages in place of the enumerated reaction displays seen below.
Reactions 1 to 50
+ = ( )
By formula: NO- + N2 = (NO- N2)
rH° 19. ± 1. kJ/mol PHPMS Hiraoka and Yamabe, 1989 gas phase; M
rH° 20. kJ/mol DT Gheno and Fitaire, 1987 gas phase; «DELTA»rS+-12. J/mol*K; M
rH° 18. kJ/mol HPMS Speller, Fitaire, et al., 1983 gas phase; Entropy change is questionable; M
rH° 22. kJ/mol HPMS Turner and Conway, 1976 gas phase; M
rH° 19. kJ/mol DT Johnsen, Huang, et al., 1975 gas phase; corrected for ln T by Keesee and Castleman, 1986; M
rS° 71.1 J/mol*K PHPMS Hiraoka and Yamabe, 1989 gas phase; M
rS° 57.7 J/mol*K DT Gheno and Fitaire, 1987 gas phase; «DELTA»rS+-12. J/mol*K; M
rS° 55.6 J/mol*K HPMS Speller, Fitaire, et al., 1983 gas phase; Entropy change is questionable; M
rS° 79.1 J/mol*K HPMS Turner and Conway, 1976 gas phase; M
rS° 65.7 J/mol*K DT Johnsen, Huang, et al., 1975 gas phase; corrected for ln T by Keesee and Castleman, 1986; M
Free energy of reaction
rG° (kJ/mol)
T (K)
2. 200. FA Dunkin, Fehsenfeld, et al., 1971 gas phase; M
By formula: N2+ + N2 = (N2+ N2)
rH° 102. - 102. kJ/mol RNG N/A Range of 6 values; Individual data points
rS° 87.9 J/mol*K PHPMS Hiraoka and Nakajima, 1988 gas phase; M
rS° 67.8 J/mol*K PHPMS Teng and Conway, 1973 gas phase; M
rS° 81.6 J/mol*K PHPMS Payzant and Kebarle, 1970 gas phase; M
rS° 46. J/mol*K DT Varney, 1968 gas phase; Entropy change is questionable; M
rS° -4. J/mol*K DT Varney, 1959 gas phase; Entropy change is questionable; M
By formula: O2+ + N2 = (O2+ N2)
rH° 21. ± 1. kJ/mol PHPMS Hiraoka and Nakajima, 1988 gas phase; M
rH° 22. kJ/mol HPMS Speller and Fitaire, 1983 gas phase; M
rH° 24. kJ/mol PHPMS Janik and Conway, 1967 gas phase; M
rS° 66.1 J/mol*K HPMS Speller and Fitaire, 1983 gas phase; M
rS° 79.1 J/mol*K PHPMS Janik and Conway, 1967 gas phase; M
0.0 296. FA Howard, Bierbaum, et al., 1972 gas phase; M
(HN2+ 4 ) + = (HN2+ 5 )
By formula: (HN2+ 4N2) + N2 = (HN2+ 5N2)
rH° 12. ± 1. kJ/mol PHPMS Hiraoka and Mori, 1989 gas phase; M
rH° 13. kJ/mol PHPMS Hiraoka, Saluja, et al., 1979 gas phase; Entropy change calculated or estimated; M
rS° 95.8 J/mol*K PHPMS Hiraoka and Mori, 1989 gas phase; M
rS° 84. J/mol*K N/A Hiraoka, Saluja, et al., 1979 gas phase; Entropy change calculated or estimated; M
5.9 92. PHPMS Hiraoka, Saluja, et al., 1979 gas phase; Entropy change calculated or estimated; M
( 7 ) + = ( 8 )
By formula: (O2- 7N2 O2) + N2 = (O2- 8N2 O2)
rH° 7. ± 1. kJ/mol PHPMS Hiraoka, 1988 gas phase; M
rH° 6.40 kJ/mol PHPMS Hiraoka, 1988 gas phase; Entropy change calculated or estimated; M
rS° 74.9 J/mol*K PHPMS Hiraoka, 1988 gas phase; M
rS° 75.3 J/mol*K N/A Hiraoka, 1988 gas phase; Entropy change calculated or estimated; M
By formula: (O2+ 2N2) + N2 = (O2+ 3N2)
rH° 15. kJ/mol HPMS Speller and Fitaire, 1983 gas phase; Entropy change is questionable; M
rS° 50.6 J/mol*K HPMS Speller and Fitaire, 1983 gas phase; Entropy change is questionable; M
( ) + = ( 2 )
By formula: (O2+ N2) + N2 = (O2+ 2N2)
By formula: (NO- N2) + N2 = (NO- 2N2)
C3N2NiO3 (solution) = C3NiO3 (solution) + (solution)
By formula: C3N2NiO3 (solution) = C3NiO3 (solution) + N2 (solution)
rH° 42. ± 4. kJ/mol KinS Turner, Simpson, et al., 1983 solvent: Liquid krypton; The reaction enthalpy relies on the experimental value for the activation enthalpy, 42. ± 4. kJ/mol, and on the assumption that the activation enthalpy for product recombination is negligible Turner, Simpson, et al., 1983.; MS
N+ + = (N+ )
By formula: N+ + N2 = (N+ N2)
rH° 249. kJ/mol N/A National Bureau of Standards, 1968 gas phase; from «DELTA»rH(f); M
rH° 250. kJ/mol EI Saporoschenko, 1965 gas phase; M
rH° 250. kJ/mol EI Franklin, Dibeler, et al., 1958 gas phase; M
Enthalpy of reaction
rH° (kJ/mol)
361. (+7.5,-0.) CID Haynes, Freysinger, et al., 1995 gas phase; guided ion beam CID; M
By formula: Cu+ + N2 = (Cu+ N2)
rH° 26. kJ/mol HPMS El-Shall, Schriver, et al., 1989 gas phase; Cu+ from laser desrption; M
rS° 67. J/mol*K HPMS El-Shall, Schriver, et al., 1989 gas phase; Cu+ from laser desrption; M
rG° 5.9 kJ/mol HPMS El-Shall, Schriver, et al., 1989 gas phase; Cu+ from laser desrption; M
rH° 16. kJ/mol PHPMS Hiraoka, Saluja, et al., 1979 gas phase; M
rS° 84. J/mol*K PHPMS Hiraoka, Saluja, et al., 1979 gas phase; M
(HN2+ ) + = (HN2+ 2 )
By formula: (HN2+ N2) + N2 = (HN2+ 2N2)
By formula: Na+ + N2 = (Na+ N2)
rH° 33. kJ/mol FA Perry, Rowe, et al., 1980 gas phase; M
rS° 77.8 J/mol*K FA Perry, Rowe, et al., 1980 gas phase; M
9.2 310. FA Perry, Rowe, et al., 1980 gas phase; M
8.4 310. DT Beyer and Keller, 1971 gas phase; low E/N; M
HN2+ + = (HN2+ )
By formula: HN2+ + N2 = (HN2+ N2)
rH° 66.9 kJ/mol PHPMS Hiraoka, Saluja, et al., 1979 gas phase; M
rH° 60.7 kJ/mol PHPMS Meot-Ner (Mautner) and Field, 1974 gas phase; M
rS° 100. J/mol*K PHPMS Hiraoka, Saluja, et al., 1979 gas phase; M
rS° 85.4 J/mol*K PHPMS Meot-Ner (Mautner) and Field, 1974 gas phase; M
C39H66N2O3P2W (solution) + (g) = C39H68O3P2W (solution) + (g)
By formula: C39H66N2O3P2W (solution) + H2 (g) = C39H68O3P2W (solution) + N2 (g)
rH° 18.4 ± 1.7 kJ/mol EqS Gonzalez and Hoff, 1989 solvent: Tetrahydrofuran; Temperature range: 288-308 K; MS
C39H66MoO3P3 (solution) + (g) = C39H66MoN2O3P2 (solution)
By formula: C39H66MoO3P3 (solution) + N2 (g) = C39H66MoN2O3P2 (solution)
rH° -37.7 ± 2.5 kJ/mol EqS Gonzalez and Hoff, 1989 solvent: Tetrahydrofuran; Temperature range: 294-308 K; MS
( 2 3 ) + = ( 3 3 )
By formula: (H3O+ 2N2 3H2O) + N2 = (H3O+ 3N2 3H2O)
rH° 5.0 kJ/mol DT Gheno and Fitaire, 1987 gas phase; «DELTA»rH, «DELTA»rS approximate; M
rS° 27. J/mol*K DT Gheno and Fitaire, 1987 gas phase; «DELTA»rH, «DELTA»rS approximate; M
rH° 11.3 ± 0.8 kJ/mol PHPMS Hiraoka and Nakajima, 1988 gas phase; M
3. 184. HPMS Speller and Fitaire, 1983 gas phase; M
By formula: (NO- 2N2) + N2 = (NO- 3N2)
4. 204. HPMS Speller, Fitaire, et al., 1983 gas phase; M
rH° 10. kJ/mol DT Gheno and Fitaire, 1987 gas phase; «DELTA»rH, «DELTA»rS approximate; M
( 9 ) + = ( 10 )
By formula: (NO- 9N2) + N2 = (NO- 10N2)
rH° 7.03 kJ/mol PHPMS Hiraoka and Yamabe, 1989 gas phase; Entropy change calculated or estimated; M
rS° 79. J/mol*K N/A Hiraoka and Yamabe, 1989 gas phase; Entropy change calculated or estimated; M
(HN2+ 10 ) + = (HN2+ 11 )
By formula: (HN2+ 10N2) + N2 = (HN2+ 11N2)
rH° 7.20 kJ/mol PHPMS Hiraoka and Mori, 1989 gas phase; Entropy change calculated or estimated; M
rS° 92. J/mol*K N/A Hiraoka and Mori, 1989 gas phase; Entropy change calculated or estimated; M
O3- + = (O3- )
By formula: O3- + N2 = (O3- N2)
rH° 11.3 ± 0.84 kJ/mol TDAs Hiraoka, 1988 gas phase; B,M
rG° -11.7 ± 2.1 kJ/mol TDAs Hiraoka, 1988 gas phase; B
(C2H5+ ) + = (C2H5+ 2 )
By formula: (C2H5+ N2) + N2 = (C2H5+ 2N2)
rH° 19. kJ/mol HPMS Speller, 1983 gas phase; deuterated, Entropy change is questionable; M
rS° 45.6 J/mol*K HPMS Speller, 1983 gas phase; deuterated, Entropy change is questionable; M
By formula: (N2+ N2) + N2 = (N2+ 2N2)
rH° 5.9 kJ/mol PI Linn, Ono, et al., 1981 gas phase; M
( ) + = ( )
By formula: (O2+ O2) + N2 = (O2+ N2 O2)
By formula: (Na+ N2) + N2 = (Na+ 2N2)
-1. 310. FA Perry, Rowe, et al., 1980 gas phase; M
(CH2N+ 2 ) + = (CH2N+ 3 )
By formula: (CH2N+ 2N2) + N2 = (CH2N+ 3N2)
+ 0.5 = + + 0.5
By formula: C4H4BrNO2 + 0.5H4N2 = HBr + C4H5NO2 + 0.5N2
rH° -260.3 ± 0.46 kJ/mol Cm Howard and Skinner, 1966 solid phase; solvent: Aqueous solution; Reanalyzed by Pedley, Naylor, et al., 1986, Original value = -261.7 ± 0.46 kJ/mol; ALS
rH° 25. ± 4.2 kJ/mol N/A Posey and Johnson, 1988 gas phase; B
rH° <56.90 kJ/mol IMRB Adams and Bohme, 1970 gas phase; N2..O2- + O2 -> O4-; B
C12H34P4Ru (solution) + (solution) = C12H32N2P4Ru (solution) + (solution)
By formula: C12H34P4Ru (solution) + N2 (solution) = C12H32N2P4Ru (solution) + H2 (solution)
rH° 16.3 kJ/mol PAC Belt, Scaiano, et al., 1993 solvent: Cyclohexane; The reaction enthalpy relies on 0.85 for the quantum yield of H2 dissociation.; MS
rH° 38. ± 11. kJ/mol DT Gheno and Fitaire, 1987 gas phase; M
rS° 119. J/mol*K DT Gheno and Fitaire, 1987 gas phase; M
(solution) + (solution) = C8H5N2O3V (solution) + (solution)
By formula: C9H5O4V (solution) + N2 (solution) = C8H5N2O3V (solution) + CO (solution)
rH° 27. ± 4. kJ/mol PAC Johnson, Popov, et al., 1991 solvent: Heptane; The reaction enthalpy relies on 0.80 for the quantum yield of CO dissociation.; MS
rH° 10.3 ± 0.8 kJ/mol PHPMS Hiraoka, 1988 gas phase; M
rH° 9.0 ± 0.8 kJ/mol PHPMS Hiraoka, 1988 gas phase; M
By formula: (O2- N2 O2) + N2 = (O2- 2N2 O2)
By formula: (H3O+ 2N2 H2O) + N2 = (H3O+ 3N2 H2O)
rH° 33. ± 8. kJ/mol DT Gheno and Fitaire, 1987 gas phase; M
rS° 92. J/mol*K DT Gheno and Fitaire, 1987 gas phase; M
( 2 ) + = ( 2 2 )
By formula: (H3O+ N2 2H2O) + N2 = (H3O+ 2N2 2H2O)
rH° 22. kJ/mol DT Gheno and Fitaire, 1987 gas phase; M
rS° 69.5 J/mol*K DT Gheno and Fitaire, 1987 gas phase; M
( 10 ) + = ( 11 )
By formula: (O2+ 10N2) + N2 = (O2+ 11N2)
rH° 6. ± 1. kJ/mol PHPMS Hiraoka and Nakajima, 1988 gas phase; M
By formula: (N2+ 10N2) + N2 = (N2+ 11N2)
rH° 6.9 ± 0.8 kJ/mol PHPMS Hiraoka and Nakajima, 1988 gas phase; M
Go To: Top, Gas phase thermochemistry data, Phase change data, Reaction thermochemistry data, Constants of diatomic molecules, References, Notes
Data compiled by: NIST Mass Spectrometry Data Center, William E. Wallace, director
Notice: This spectrum may be better viewed with a Javascript and HTML 5 enabled browser.
For Zoom
1.) Enter the desired X axis range (e.g., 100, 200)
2.) Check here for automatic Y scaling
3.) Press here to zoom
Help / Software credits
The interactive spectrum display requires a browser with JavaScript and HTML 5 canvas support.
Select a region with data to zoom. Select a region with no data or click the mouse on the plot to revert to the orginal display.
The following components were used in generating the plot:
jQuery UI
Plugins for Flot:
Resize (distributed with Flot)
Selection (distributed with Flot)
Axis labels
Labels ( Modified by NIST for use in this application)
Additonal code used was developed at NIST: jcamp-dx.js and jcamp-plot.js.
Use or mention of technologies or programs in this web site is not intended to imply recommendation or endorsement by the National Institute of Standards and Technology, nor is it intended to imply that these items are necessarily the best available for the purpose.
View image of digitized spectrum (can be printed in landscape orientation).
View spectrum image in SVG format.
Download spectrum in JCAMP-DX format.
NIST Mass Spectrometry Data Center
Collection (C) 2014 copyright by the U.S. Secretary of Commerce
on behalf of the United States of America. All rights reserved.
D.HENNEBERG, MAX-PLANCK INSTITUTE, MULHEIM, WEST GERMANY
NIST MS number
All mass spectra in this site (plus many more) are available from the NIST/EPA/NIH Mass Spectral Library. Please see the following for information about the library and its accompanying search program.
Go To: Top, Gas phase thermochemistry data, Phase change data, Reaction thermochemistry data, Mass spectrum (electron ionization), References, Notes
Data compiled by: Klaus P. Huber and Gerhard H. Herzberg
Data collected through February, 1977
Symbols used in the table of constants
State electronic state and / or symmetry symbol
Te minimum electronic energy (cm-1)
ωe vibrational constant – first term (cm-1)
ωexe vibrational constant – second term (cm-1)
ωeye vibrational constant – third term (cm-1)
Be rotational constant in equilibrium position (cm-1)
αe rotational constant – first term (cm-1)
γe rotation-vibration interaction constant (cm-1)
De centrifugal distortion constant (cm-1)
βe rotational constant – first term, centrifugal force (cm-1)
re internuclear distance (Å)
Trans. observed transition(s) corresponding to electronic state
ν00 position of 0-0 band (units noted in table)
Diatomic constants for 14N2
For a very detailed and critical review of the spectrum of nitrogen and its ions see the recent publication by Lofthus and Krupenie Lofthus and Krupenie, 1977. An Atlas of the VUV absorption spectrum 1060 - 1520 Å and table of absorption lines Tilford, Wilkinson, et al., 1966. Tables of band head wavelengths Wallace, 1962 Pearse and Gaydon, 1963 Lofthus and Krupenie, 1977. Photoionization and absorption cross sections Huffman, Tanaka, et al., 1963 Cook and Metzger, 1964 Carter, 1972. Potential functions Gilmore, 1965 Benesch, Vanderslice, et al., 1965 Gartner and Thrush, 1975 Lofthus and Krupenie, 1977.
Several Rydberg series (excitation of 1sN) with limit (K edge) at 409.5 eV.
↳Nakamura, Sasanuma, et al., 1969; Werme, Grennberg, et al., 1973; Vinogradov, Shlarbaum, et al., 1974; Vinogradov, Zimkina, et al., 1974
x" (1 u+) 1 x" X 405.59 $eV
x' (1 u) 2 x' X 400.84 $eV
Photoionization and dissociative photoionization processes corresponding to various excited states of N2+. 3
v 1 g 4 v X 253000
↳Lee, Wong, et al., 1975
u5 (183640) (2100) (15) 5 u5 X (183510)
↳Codling, 1966; Lee, Carlson, et al., 1973
Hopfield Hopfields Rydberg series converging to B 2 u+(v=0) of N2+:
...2 u1 u43 g2ns = 151233 - R/(m+0.141 - 0.199/m)2, m=3...11 (apparent emission series)6
↳Hopfield, 1930; missing citation; missing citation
...2 u1 u43 g2nd = 151233 - R/(m+0.070 - 0.041/m)2, m=3...20 (absorption series)7 8 9
Worley Worley's ("third") Rydberg series joining on to o3, o4, o5 and converging to A 2 u1/2(v=0) of N2+:
...2 u21 u33 g2ns = 134721 - R/(n - 1.06)2, n = 3...16.10 11 12 13
↳Worley, 1943; missing citation; missing citation
Ogawa Ogawa and Tanaka's Rydberg series joining on to O4, O5 and converging to A 2 u3/2(v=0) of N2+:
...2 u21 u33 g2ns = 134644 - R/(n*)2, n* = 2.84, 3.85, 4.86, ..., 14.91.10 11 12 13
↳missing citation; missing citation
Several dissociation continua in the region 100000 - 160000 cm-1.
↳Comes and Weber, 1969; Cook, Ogawa, et al., 1973
Several unidentified bands in the region 126100 - 131550 cm-1.
↳Ogawa, 1964
s 133355 14 1885 H (12) 15 s X 133119 H
133316 14 H ( ) 15 s X 133080 H
r 132878 14 1903 H (15) 16 r X R 132650 H
q 132136 14 1900 H (18) 17 q X 18 131906 H
p 129136 14 1869 H (10) 19 p X R 128892 H
o5 1 u (127868) (1935) 20 (19) o5 X R 127655 HQ
O5 (3 u) 127445 1925 HQ 18.4 O5 X R 127227 HQ
c'n and cn Rydberg series converging to X 2 g+(v=0) of N2+:
c'n 1 u+ 21 c'n X
↳Carroll and Yoshino, 1967; missing citation; Johns and Lepard, 1975
cn 1 u 22 cn a"
↳missing citation
cn 1 u 26 cn X 23 24 25
↳Worley and Jenkins, 1938; missing citation; missing citation; missing citation
o4 1 u 122419 [1824.1] H [1.7338] 27 [4E-6] [1.1784] o4 X R 122155.4 Z
↳Ogawa and Tanaka, 1962; Yoshino, Tanaka, et al., 1975
O4 (3 u) 121263 1982 H 27.0 O4 X R 121071.1 H
↳Ogawa and Tanaka, 1962
c'5 1 u+ (115876) [2221.8] Z 28 [1.345] 29 c'5 X R 115849.8 Z
↳Carroll and Collins, 1970; missing citation
c4 1 u 115635.9 2220.3 Z 19.4 [1.9261] 30 0.015 [6.3E-6] 30 1.116 c4 a" 16725.12 Z
c4 1 u 31 c4 X R 115565.53 Z
z 1 g (115435) (1700) 1.761 0.0153 1.169 z w V 43411.2 32 Z
↳Lofthus, 1957
y 1 g 114305.2 33 1906.43 33 37.51 33 1.739 33 34 0.017 33 (5.8E-6) 1.177 y w V 42467.5 35 Z
↳missing citation; Carroll and Subbaram, 1975
y a' V 46426.7 35 Z
k 1 g (113808) 36 [2182.32] 33 1.959 33 0.031 33 (5.9E-6) 1.109 k w V 41932.4 35 Z
k a' V 45891.7 35 Z
x 1 g- 113438.0 1910.0 Z 20.7 1.750 37 0.0225 (6E-6) 1.173 x a' V 45472.8 Z
↳Gaydon, 1944; missing citation; Rajan, 1974
d' 1 u- or 1 u [112500] 38 d' a 42373 H
↳Herman-Montagne, 1945; Gaydon and Herman, 1946; Dressler, 1969
o3 1 u 105869 39 1987.4 39 16.3 39 1.7339 39 0.0088 39 (5.3E-6) 1.1784 o3 a V 36731
↳Janin and Crozet, 1946; Janin, 1950
o3 X 40 R 105683
↳Worley, 1943; Yoshino, Tanaka, et al., 1975
H 3 u (105720) 924.21 Z 12.29 -0.173 1.0873 0.0191 [7.0E-6] 41 1.4881 (H ?) 42 12407.2 H
↳Herman, 1951; Carroll and Sayers, 1953
H G 43 V 17897.08 44 Z
↳Gaydon, 1944, 2; Herman-Montagne, 1945; Grun, 1954; missing citation
c'4 1 u+ 104519 45 2201.78 45 25.199 45 1.9612 45 0.0436 45 1.1080 c'4 a VR 35371.2 Z
c'4 X 46 R 104323.3 47 Z
↳Tilford and Wilkinson, 1964; Carroll and Yoshino, 1967; Carroll and Collins, 1969; Dressler, 1969; Carroll and Collins, 1970
c3 1 u 104476 2192.20 48 14.70 48 1.9320 48 0.0395 48 1.1163 c3 a RV (35187.0) (Z
↳Janin, 1950
c3 X 49 R 104138.2 50 Z
↳Carroll and Collins, 1969; Dressler, 1969
b' 1 u+ 104498 51 760.08 51 4.418 51 0.1093 1.1549 51 52 0.007387 51 -7.50E-5 1.4439 b' a R 53
b' X 49 R 103673.8 54 Z
↳Wilkinson and Houk, 1956; Carroll and Collins, 1970
D 3 u+ [104746.6] 55 [1.961] [20E-6] [1.1080] D B 56 V 44264.1 57 Z
↳Gero and Schmid, 1940
b 1 u (101675) [634.8] 58 [1.4483] 59 60 -0.00362 [29E-6] 61 1.2841 62 b a R (31865.7) Z
↳Gaydon, 1944; Herman-Montagne, 1945; Lofthus, 1957; Rajan, 1974
b X 49 R 100816.9 Z
↳Carroll and Collins, 1969; Yoshino, Tanaka, et al., 1975
a" 1 g+ [100016.0] [1.9133] 63 [6.2E-6] 63 [1.1218] a" X 64 98840.30 63 Z
↳Lutz, 1969
C' 3 u 98351 65 791 33.5 [1.04976] 66 [10.9E-6] 67 [1.5146] C' B R 38255.5 68 Z
↳missing citation; missing citation; missing citation
E 3 g+ (95858) [2185] H [1.927.3] [6.0E-6] [1.1177] E B V (36467.9) Z
↳Freund, 1969
E A V 46019.72 Z
E X 69
C" 5 u (93500) 70
C 3 u 89136.88 71 2047.178 Z 28.4450 72 1.82473 73 0.01868 74 1,14869 C B 75 76 V 29671.0 Z
↳Coster, Brons, et al., 1933; Dieke and Heath, 1959; missing citation; missing citation; missing citation
C X 77 R 88977.89 Z
↳Tanaka, 1955; Tanaka, Ogawa, et al., 1964; missing citation
G 3 g (87900) 78 [742.49] Z (11.85) H 0.9280 0.0161 [5.0E-6] 1.6107
↳Carroll, Collins, et al., 1972
A' 5 g+ (78800) 79 (650) 79 80 (1.55) 81
w 1 u 72097.4 1559.26 82 H 11.63 1.498 83 0.0166 1.268 w a 84 R 2747.29 Z
↳McFarlane, 1966
w X 77 85 R 71698.4 86 Z
↳Tanaka, Ogawa, et al., 1964; Chutjian, Cartwright, et al., 1973
a 1 g 69283.06 1694.208 Z 13.9491 87 7.935E-3 1.6169 88 0.01793 -2.93E-5 (5.89E-6) 1.2203 a a' 84 V 1212.28 Z
↳McFarlane, 1965; McFarlane, 1966, 2
a X 89 90 R 68951.20 Z
↳missing citation; Miller, 1970
a' 1 u- 68152.66 1530.254 Z 12.0747 91 .04129 1.4799 0.01657 2.41E-5 (5.55E-6) 1.2755 a' X 92 R 67739.31 Z
↳missing citation; missing citation; Campbell and Thrush, 1969; Golde, 1975; Chutjian, Cartwright, et al., 1973
B' 3 u- 66272.47 1516.88 Z 12.181 93 .04186 1.4733 94 0.01666 95 9E-6 (5.56E-6) 1.2784 B' B R (6545.5) Z
↳Carroll and Rubalcava, 1960; Dieke and Heath, 1960; Gartner and Thrush, 1975
B' X 96 R 65852.35 Z
↳missing citation; Wilkinson, 1960; missing citation; Golde and Thrush, 1972; Chutjian, Cartwright, et al., 1973
W 3 u 59808 (1501.4) Z 11.6 W B RV 73
↳Wu and Benesch, 1968; Saum and Benesch, 1970; Benesch and Saum, 1971; Covey, Saum, et al., 1973
W X 97 R 59380
↳missing citation; Chutjian, Cartwright, et al., 1973
B 3 g 59619.35 98 1733.39 Z 14.122 99 -0.0569 1.63745 100 0.01791 101 7.7E-5 [5.9E-6] 1.21260 B A 102 103 V 9552.03 Z
↳Dieke and Heath, 1959; Lofthus and Krupenie, 1977
B X 104 R 59306.81 Z
↳Wilkinson, 1962
A 3 u+ 50203.63 1460.64 Z 13.872 105 .0103 1.4546 106 0.0180 107 -8.8E-5 [6.15E-6] 1.2866 A X 108 104 R 49754.78 Z
↳Dieke and Heath, 1959; Miller, 1965; Miller, 1966
X 1 g+ 0 2358.57 Z 14.324 109 -2.26E-3 1.998241 110 0.017318 110 [5.76E-6] 1.097685 111
- pressure induced
↳Crawford, Welsh, et al., 1949; Bosomworth and Gush, 1965; Reddy and Cho, 1965; Shapiro and Gush, 1966; de Remigis, Welsh, et al., 1971; Sheng and Ewing, 1971; Buontempo, Cunsolo, et al., 1975
- el. field induced
↳Courtois and Jouve, 1975
Raman Spectra 112
↳Stoicheff, 1954; Butcher, Willetts, et al., 1971; Bendtsen, 1974
Mol. beam magn. reson. 113
1 X-ray absorption (3s 1sN).
2 X-ray absorption and emission (1 g 1sN), broad peak. 119
3 Absorption cross sections 140000-500000 cm-1 Lee, Carlson, et al., 1973, Watson, Lang, et al., 1973.
4 From high-energy electron impact spectroscopy.
5 First two members of Codling's Rydberg series. 120
6 Longward of the apparent emission "lines" are close-lying fairly sharp absorption "lines" Ogawa and Tanaka, 1962. Both features belong to the same Fano shape produced by the interaction of the series of Rydberg levels with the continuum joining on to the A 2 (or, less likely, X 2 ) limit.
7 Similar series with v'=1.
8 The first three members at 138330, 144090, 146690 cm-1 are very broad (presumably because of preionization), the higher members are sharper and shaded to the red. No rotational structure has been resolved. Preionization also observed by electron spectroscopy Hicks, Comer, et al., 1973, Wilden, Hicks, et al., 1976.
9 Oscillator strengths from absorption coefficients: f(m=3,4,..) = 0.0131, 0.0053, ... Cook and Ogawa, 1970.
10 Similar series for v'=l [observed to n=45 (2 1/2) and n*=40.2 (2 3/2)] and for v'=2...7 Yoshino, Ogawa, et al., 1976.
11 Corresponding series in 15N2 Ogawa, 1964.
12 Preionization observed in photoionization studies Cook and Ogawa, 1965, Comes and Weber, 1969, Carter and Berkowitz, 1973.
13 Preionization in absorption series having v'=1...4 was observed in active nitrogen using the photoionization technique Cook and McNeal, 1972.
14 These designations should not be confused with the older designations of component states of b 1 u and b' 1 u+.
15 Ogawa's "new progression 4" 12
16 Ogawa's "new progression 3" 12 122
18 Linelike, not shaded.
20 Vibrational intervals decrease irregularly: v=0 was shown [by electron spectroscopy Wilden, Hicks, et al., 1976] to be preionized.
21 ...1 u43 gnp 123 -Carroll and Yoshino's series joining on to c'4, c'5.
22 ...1 u43 gnp 123Ledbetters series c4, c5, c6.
23 Similar series with v'=1.
25 See 13.
26 - Worley and Jenkin's series joining on to c3, c4: = 125666.8124 - R/(m + 0.3697 - 0.3459/m + 0.532/m2 - 0.960/m4)2, m(=n-1) = 2...31.
27 Only v=0 [perturbed by c'6(v=1)] is sharp: bands with v'= 1,2,3 are diffuse owing to predissociation or preionization (levels with v > 2 are above the first ionization potential).
28 G(3/2) = 2119.7, see 29.
29 Strong homogeneous perturbations with the higher vibrational levels (v 18) of b' 1 u+ Carroll and Yoshino, 1972. The B0 value is an effective value at low J: Beff(v=1) = 1.285, Beff(v=2)= 1.173. In addition, there are heterogeneous interactions with the close- lying levels of c4 1 u. For deperturbed constants see Leoni and Dressler, 1972, Leoni, 1972.
30 Constants for - Ledbetter, 1972; B0( +) = 1.906. e from Carroll and Yoshino, 1972.
31 [A progression of six bands (v"=1-6) arises from c4(v'=0) a, Herman-Montagne, 1945 ]
32 Reevaluated from the origin of the 0-2 band. Lofthus, 1957 gives 43667.0 which was undoubtedly calculated with the constants of the a rather than of the w state.
33 Strong homogeneous interaction between k 1 g and y 1 g. The constants given are the deperturbed values from Carroll and Subbaram, 1975 and refer to -, the only component observed in k 1 g.
34 Predissociation of the + component above J=10 of v=0. -type doubling and predissociation discussed in Mulliken, 1976.
35 Not deperturbed.
36 From the deperturbed T00 = 113723.58.
37 0nly v'=0,1,2 observed. Predissociation (weakening of emission) at v'=2, J" l5 corresponding to the limit 2D+2D Lofthus, 1960; actual breaking off occurs at J'=25. See also Mulliken, 1976.
38 Only v'=0 observed
39 Deperturbed constants Yoshino, Tanaka, et al., 1975. Homogeneous interactions with levels (v > 6) of b 1 u and heterogeneous perturbations by b' 1 u+.
40 0scil1ator strengths Carter, 1972.
41 D1(E-6 cm-1)= 4.5 Carroll, Collins, et al., 1972, D2(E-6 cm-1)= 6.0 Carroll, Collins, et al., 1972, D3(E-6 cm-1)= 5.0 Carroll, Collins, et al., 1972. See, however, Veseth, 1973.
42 Fragment of near infrared spectrum, G"(1/2) 712.
43 Franck-Condon factors and r-centroids Mohamed and Khanna, 1974.
44 From a more detailed theoretical treatment Veseth, 1973 derives v00 = 17902.400 Veseth, 1973.
45 Deperturbed constants Leoni and Dressler, 1972, Leoni, 1972; eye= +0.7874. Strong perturbations produced by interaction with b' 1 u+; before these perturbations were recognized Dressler, 1969, Lefebvre-Brion, 1969 the vibrational levels were attributed to independent states called p', r', k, s', h, h', h", h'". The observed vibrational intervals (from band origins) and rotational constants for v = 0,1,2,3... are: G(v+1/2) = 2046.2, 2175.5, 2112.2, 2111.7 ...; Bv = 1.929, 1.711, 1.436, 1.594 ...
46 Radiative lifetime (v'=0) = 0.9 ns Hesser and Dressler, 1966, Hesser, 1968: oscillator strengths Lawrence, Mickey, et al., 1968, Carter, 1972.
47 Observed v00, not deperturbed.
48 deperturbed constants Leoni and Dressler, 1972, Leoni, 1972. Strong perturbations produced by interaction with b 1 u: the observed vibrational intervals (from band heads) and rotational constants for v=0,1,2,.., are: G(v+1/2) = 2401, 2146, 2103, 2042; Bv( -) = 1.516, 1.755, 1.813 [see Carroll and Collins, 1969, Leoni, 1972].
49 Oscillator strengths Lawrence, Mickey, et al., 1968, Carter, 1972.
50 missing note
51 Deperturbed constants Leoni and Dressler, 1972, Leoni, 1972; Strong perturbations on account of interactions with c'4, c'5 1 u+. Before these perturbations were recognized Carroll and Collins, 1969, Dressler, 1969, Hopfield, 1930O6a, Carroll and Collins, 1970 several of the vibrational levels were assumed to be independent states called b', g, f, r, s, t, u by Worley, 1943. The observed vibrational intervals (from band origins) and rotational constants for v= 0,1,2,3, ... are: G(v+1/2) = 744.9, 732.9, 717.6, 777.7, ... ; Bv = 1.1515, 1.15, 1.142, 1.152, .... The highest observed level is v=28. Intensity perturbations in the electron energy loss spectrum Geiger and Schroder, 1969.
52 The b' X absorption bands show diffuseness indicating predissociation for v'=20, 21, 22 Carroll and Collins, 1970. Emission bands have only been observed to v'=9. For v'= 5 and above J'=12 an intensity anomaly suggesting inverse predissociation has been observed in emission Tilford and Wilkinson, 1964, 2: it corresponds to the limit 4S + 2P. Selective emission from v'=0,2,7 in discharges in Ar and Kr with traces of N2 Tanaka and Nakamura, 1967.
53 Only the 7-0 band was observed at v0 = 40000.7 Lofthus, 1957.
54 0bserved band origin, not deperturbed.
55 Only v=0 is observed
56 Lifetime (v=0) = 14.1 ns Kurzweg, Egbert, et al., 1973. Franck Condon factors Hebert and Nicholls, 1969.
57 Extrapolated from Q2(3) of the 0-1 band.
58 G(3/2,5/2,...) = 700.0, 711.9, 685.2, 1151.4, 646.2, ... Carroll and Collins, 1969 [ Carroll and Collins, 1969, from band origins]. Leoni and Dressler, 1972, Leoni, 1972 give the deperturbed constants e = 461.01 Leoni and Dressler, 1972, Leoni, 1972, exe = -132.257 Leoni and Dressler, 1972, Leoni, 1972, eye = -35.005 Leoni and Dressler, 1972, Leoni, 1972, eze = +5.822 Leoni and Dressler, 1972, Leoni, 1972, ...; see 59.
59 Bv(v=1, 2, 3...) = 1.4086, 1.3872, 1.38l5, 1.42l3 ... Carroll and Collins, 1969: Leoni and Dressler, 1972, l52a give the deperturbed constants Be = 1.4601 Leoni and Dressler, 1972, Leoni, 1972, e= 0.02624 Leoni and Dressler, 1972, Leoni, 1972, ... Strong perturbations on account of interaction with the c3 1 u and o3 1 u Rydberg states. Before these perturbations were recognized Carroll and Collins, 1969, Dressler, 1969 several of the vibrational levels were assumed to be independent electronic states called i, j, b, l, m, p, q Worley, 1943. Intensity perturbations in the electron energy loss spectrum Meyer, Skerbele, et al., 1965, Geiger and Schroder, 1969.
60 The lines of absorption bands with v'= 0,2,3,4 are broadened on account of predissociation (especially v'=3); corresponding emission bands have not been observed. The state causing the predissociation is probably C' 3 u Carroll and Collins, 1969; see, however, Leoni and Dressler, 1971 who find that an additional diffuse level, very likely the still missing O3 3 u(v=0) level at ~103000 cm-1, is required to explain the broadening of v'= 3.
61 Effective (perturbed) D0 value.
62 From the deperturbed Be (see 59)
63 From Rydberg series having a" as lower state Ledbetter, 1972.
64 First thought to be observed as quadrupole absorption Dressler and Lutz, 1967, later recognized as pressure-induced dipole transition represented by a broad diffuse absorption band at ~99005 cm-1 Lutz, 1969: note the large pressure shift of +165 cm-1. The electron energy loss spectrum Lassettre, Skerbele, et al., 1966 shows a peak at 12.25 eV. Another 1 g+ state, non-Rydberg in character, is predicted to intersect a" not far from its minimum Michels, 1970.
65 A0 = 2.10 Ledbetter and Dressler, 1976, recalculated by Ledbetter and Dressler, 1976 from the data of Carroll, 1963 who obtained 1.15: A1 = 2.73 Ledbetter and Dressler, 1976, deperturbed value Ledbetter and Dressler, 1976.
66 B1(observed) = 1.2056, B1(deperturbed) = 1.026. Strong mixing of C'(v=1) with C(v=5). Deperturbed constants and RKR potential functions are given by Ledbetter and Dressler, 1976 who have analyzed in detail the C'(v=1) B(v=5) band for 14N2, 14N15N and 15N2. The perturbing level C(v=5) was recently observed by Ledbetter, 1977 in absorption from B(v=6).
67 H0 = 8.3E-10.
68 v00 = 38296.75 in Carroll, 1963 refers to the F1 component.
69 Resonance-like electron impact excitation function centered at 12.2 eV with a half-width of 0.4 eV Borst, 1972. Lifetime of the E state 190 s Borst and Zipf, 1971.
70 Arising from 4S + 2D; according to Carroll and Mulliken, 1965 responsible for the main predissociation in C 3 u.
71 A = 39.2 Budo, 1935.
72 eye= +2.08833. eze = -0.5350.
73 Breaking-off on account of predissociation Buttenbender and Herzberg, 1935 in v' = 1, 2, 3, 4 above N' = 65, 55, 43, 28, respectively, yielding an accurate dissociation limit at 97938 cm-1 (4S + 2D). A second predissociation in high-pressure discharges (when the first predissociation disappears) has been found in v'=2 and 3 above N'= 80 and 67, respectively Hori and Endo, 1941. According to Carroll and Mulliken, 1965 the first predissociation is caused by C" 5 u, the second by C' 3 u. Predissociation in 15N2 Frackowiak, 1964. Intensity perturbations Coster, Brons, et al., 1933, Gero, 1935, Coster and Brons, 1935.
74 v= -0.00228(v+1/2)2 + 0.000733(v+1/2)3 - 0.000l5(v+1/2)4.
75 Lifetimes for v = 0,1,2 vary between 35 and 41 ns Johnson and Fowler, 1970, Imhof and Read, 1971, Dotchin and Chupp, 1973, Chen and Anderson, 1975, Osherovich and Gorshkov, 1976. For f values of C-B see Nicholls, 1963, Reis, 1964.
76 The head of the 0-0 band produces laser oscillation: high resolution measurements of the laser lines Parks, Rao, et al., 1968, see also Kasuya and Lide, 1967. An anomalous intensity alternation has been observed by Bleekrode, 1968, see also Fishburne, Lazdinis, et al., 1967. C(v=5) B(v=6) band in absorption Ledbetter, 1977. 14N15N and 15N2 isotope shifts Shvangiradze, Oganezov, et al., 1960. RKR Franck-Condon factors Zare, Larsson, et al., 1965, Benesch, Vanderslice, et al., 1966, dependence on rotation Shumaker, 1969. Integrated band intensities Tyte, 1962. Dependence of the electronic transition moment on r Shemansky and Broadfoot, 1971, Jain, 1972: absolute transition probabilities Shemansky and Broadfoot, 1971.
77 RKR Franck-Condon factors Zare, Larsson, et al., 1965, Benesch, Vanderslice, et al., 1966, 2, Lofthus and Krupenie, 1977.
78 A0 = -0.21, A1 = -0.25. All constants for this state are from H G Carroll, Collins, et al., 1972: for a more detailed theoretical treatment and somewhat different constants see Veseth, 1973.
79 From the predissociations in a and B Carroll, 1962: see also Oldenberg, 1957, Mulliken, 1962. The dissociation energy of this state is estimated to be between 850 and 1100 cm-1. According to Bayes and Kistiakowsky, 1960 the 5 g+ state plays an important role in the mechanism of the Lewis-Rayleigh afterglow of nitrogen.
80 For more recent results of an ab initio calculation see Krauss and Neumann, 1976.
82 Vibrational constants from the absorption spectrum Tanaka, Ogawa, et al., 1964, good agreement with band origin data for k w Carroll and Subbaram, 1975.
83 Rotational constants from y w Lofthus and Mulliken, 1957.
84 Appears in stimulated emission.
85 The w X Tanaka bands appear diffuse even under high resolution Tilford, Vanderslice, et al., 1979 indicating that this is a pressure-induced transition which has apparently no measurable spontaneous transition probability Tilford and Benesch, 1976. Observed in solid N2 by Roncin, Damany, et al., 1967.
86 From v00(a-X)+v00(w-a) McFarlane, 1966. The value from the w X absorption spectrum is 71740.3 (head) indicating a pressure shift of +40 cm-1; compare with a" X.
87 eze= +0.000291 Vanderslice, Tilford, et al., 1965: Lofthus and Krupenie, 1977 give very slightly different numbers.
88 -type doubling, |q0| = 0.00010 McFarlane, 1966. Breaking-off at low pressure above v=6, J=13 for both components because of predissociation Douglas and Herzberg, 1951. The state causing the predissociation is 5 g+ from 4S + 4S.
89 The lifetime is about 100 s but depends strongly on v. Non-exponential decay because of radiative interactions with a' 1 u- and w 1 u Freund, 1972. See also Ching, Cook, et al., 1967, Pilling, Bass, et al., 1971 who give f values.
90 This transition has both a magnetic dipole and an electric quadrupole component Wilkinson and Mulliken, 1957, Vanderslice, Wilkinson, et al., 1965, see also Pilling, Bass, et al., 1971. Observed in absorption in solid N2 by Roncin, Damany, et al., 1967. RKR Franck-Condon factors Zare, Larsson, et al., 1965, Benesch, Vanderslice, et al., 1966, 2, Lofthus and Krupenie, 1977. From intensity measurements and the Franck-Condon factors of Zare, Larsson, et al., 1965 it is concluded by McEwen and Nicholls, 1966 that the electronic transition moment can be considered as constant for most bands of this system. Comparison with intensities in the electron energy loss spectrum Lassettre, Meyer, et al., 1965.
91 eze = -0.000290 Tilford, Wilkinson, et al., 1965: Lofthus and Krupenie, 1977 give very slightly different numbers.
92 Franck-Condon factors: f00(a'-X) = 8.4E-11 Benesch, Vanderslice, et al., 1966, 2, Lofthus and Krupenie, 1977, corresponding to a lifetime of = 0.013 s Tilford and Benesch, 1976.
93 eze = -0.000732 Lofthus and Krupenie, 1977.
94 Spin splitting constants (v=5): = +0.66 Tilford, Vanderslice, et al., 1965, = -0.0030 Tilford, Vanderslice, et al., 1965.
95 Lofthus and Krupenie, 1977.
96 RKR Franck-Condon factors Benesch, Vanderslice, et al., 1966, 2, Lofthus and Krupenie, 1977. Rotational intensity distribution Kovacs, 1970.
97 Franck-Condon factors Saum and Benesch, 1970, 2.
98 Ae = 42.24 Bullock and Hause, 1971.
99 eze = +0.00361 Lofthus and Krupenie, 1977: slightly different constants are given by Artym, 1966, Bullock and Hause, 1971.
100 Predissociation above v=12,N=33 Van Der Ziel, 1934, Polak, Slovetskii, et al., 1972. The state causing the predissociation is probably A' 5 g+. Inverse predissociation A' 5 g+ B 3 g seems to be responsible for some of the phenomena in active nitrogen [see Becker, Fink, et al., 1972 and references quoted there]. The levels v'= 12,11,10 are preferably excited in the Lewis-Rayleigh afterglow: for excitation of other levels in the afterglow see Ung, 1976.
101 Lofthus and Krupenie, 1977: slightly different constants in Bullock and Hause, 1971.
102 Lifetime (v=0...12)= 5.0 s Chen and Anderson, 1975, 2: see also Jeunehomme, 1966. For B-A absorption f values (f ~0.0025) see Wurster, 1962, Dronov, Sobolev, et al., 1966, Cunio and Jansson, 1968.
103 Stimulated emission for some of the lines of the 4-2, 3-1, 2-0, 2-1, 1-0, 0-0, 0-1 bands has been observed Kasuya and Lide, 1967. RKR Franck-Condon factors Zare, Larsson, et al., 1965, Benesch, Vanderslice, et al., 1966, dependence on rotation Shumaker, 1969. Dependence of the electronic transition moment on r Shemansky and Broadfoot, 1971, Jain, 1972: absolute transition probabilities Kupriyanova, Kolesnikov, et al., 1969, Shemansky and Broadfoot, 1971.
104 Franck-Condon factors Benesch, Vanderslice, et al., 1966, 2, Lofthus and Krupenie, 1977. Rotational intensity distribution in the Vegard-Kaplan bands Miller, 1970, 2.
105 eze= -0.00197 Lofthus and Krupenie, 1977; slightly different constants in Artym, 1966, Bullock and Hause, 1971.
106 Spin-splitting constants (v=0): (v=0) = -1.33 Miller, 1965, (v=0) = -0.003 Miller, 1965; see also Bullock and Hause, 1971. The radio-frequency spectrum of this state was studied by the molecular beam magnetic resonance method Freund, Miller, et al., 1970, de Santis, Lurio, et al., 1973: magnetic hyperfine and electric quadrupole coupling constants.
107 Lofthus and Krupenie, 1977.
108 Lifetime = 1.3 s (F2) Shemansky, 1969, Shemansky and Carleton, 1969, Meyer, Klosterboer, et al., 1971, = 2.5 s (F1, F3) Shemansky, 1969, Shemansky and Carleton, 1969, Meyer, Klosterboer, et al., 1971 levels Shemansky, 1969, Shemansky and Carleton, 1969, Meyer, Klosterboer, et al., 1971; electronic transition moment, variation with r Chandraiah and Shepherd, 1968, Broadfoot and Maran, 1969, Shemansky, 1969.
109 eze = -0.00024 Lofthus and Krupenie, 1977. Bendtsen, 1974 gives G(1/2) = 2329.9168 and similar data for 14N15N and 15N2.
110 From B0 and B1 of Bendtsen, 1974 and using e = -0.000033 Lofthus and Krupenie, 1977.
111 Rot.-vibr.128 and rot. sp.:
112 Raman spectra of 14N15N and 15N2 Bendtsen, 1974, Butcher and Jones, 1974.
113 gJ(15N2) = 0.2593, sign not determined Chan, Baker, et al., 1964. For magnetic resonance spectra of metastable N2 in the A 3 u+ state see Freund, Miller, et al., 1970, de Santis, Lurio, et al., 1973.
114 From the predissociation in C 3 u assuming dissociation into 4S3/2 + 2D5/2. The latest ab initio calculation of the ground state gives De = 8.58 eV Dunning, Cartwright, et al., 1976.
115 From the Rydberg series.
116 Average of the two limits corresponding to 2 3/2 and 2 1/2.
117 From the data on N2+.
118 From x X of N2+ and I.P.(N2): the extrapolated K limit is 409.5 eV Nakamura, Sasanuma, et al., 1969.
119 Confirmed by electron-energy-loss measurements van der Wiel, El-Sherbini, et al., 1970. Preionization to X 2 g+ and A 2 u of N2+ observed by Auger electrons of 384.7 and 383.8 eV Carlson, Moddeman, et al., 1970.
120 This series, of which only two members have been observed, probably converges to C 2 u+ of N2+. In u4 v=1...13, in u5 v=3...8 have been observed, but the vibrational numbering in both states is uncertain. Evidence of preionization.
121 Interpreted as . ..nd by Lindholm, 1969.
122 Preionization also observed by electron spectroscopy Hicks, Comer, et al., 1973, Wilden, Hicks, et al., 1976.
123 For higher n values cn and c'n+l lie close together and interact strongly (l-uncoupling). Band structures for n = 5...12 have been discussed Carroll and Yoshino, 1972, Carroll, 1973, Johns and Lepard, 1975.
124 The limit according to Yoshino [see Lofthus and Krupenie, 1977] lies at 125667.5 cm-1 but is estimated Lofthus and Krupenie, 1977 to have an uncertainty of 5 cm-1.
125 A0...A3= -12.073 ... -12.094 Carroll, Collins, et al., 1972; see also Veseth, 1973.
126 Quoted from Lofthus and Krupenie, 1977; not deperturbed. Dressler, 1969 gives 104139.
127 Also referred to as "infrared afterglow bands".
128 Predicted transition moments for quadrupole vibration spectrum Cartwright and Dunning, 1974. The quadrupole moment in the v=0 level is measured to be -1.4E-26 e.s.u. cm2 Ketelaar and Rettschnick, 1963, Buckingham, Disch, et al., 1968.
Go To: Top, Gas phase thermochemistry data, Phase change data, Reaction thermochemistry data, Mass spectrum (electron ionization), Constants of diatomic molecules, Notes
Cox, Wagman, et al., 1984
Cox, J.D.; Wagman, D.D.; Medvedev, V.A., CODATA Key Values for Thermodynamics, Hemisphere Publishing Corp., New York, 1984, 1. [all data]
Chase, 1998
Chase, M.W., Jr., NIST-JANAF Themochemical Tables, Fourth Edition, J. Phys. Chem. Ref. Data, Monograph 9, 1998, 1-1951. [all data]
Jacobsen, Stewart, et al., 1986
Jacobsen, R.T.; Stewart, R.B.; Jahangiri, M., Thermodynamic properties of nitrogen from the freezing line to 2000 K at pressures to 1000 MPa., J. Phys. Chem. Ref. Data, 1986, 15(2), 735-909. [all data]
Streng, 1971
Streng, A.G., Miscibility and Compatibility of Some Liquid and Solidified Gases at Low Temperature, J. Chem. Eng. Data, 1971, 16, 357. [all data]
Angus, de Reuck, et al., 1979
Angus, S.; de Reuck, K.M.; Armstrong, B.; Jacobsen, R.T.; Stewart, R.B., International Thermodynamic Tables of the Fluid State - 6 Nitrogen, Pergamon, New York, 1979. [all data]
Henning and Otto, 1936
Henning, F.; Otto, J., Vapor pressure curves and triple points in the temperature region from 14 to 90 k, Phys. Z., 1936, 37, 633-8. [all data]
Giauque and Clayton, 1933
Giauque, W.F.; Clayton, J.O., Heat Capacity and Entropy of Nitrogen. Heat of Vaporization. Vapor Pressure of Solid and Liquid. The Reaction 1/2 N2 + 1/2 O2 = NO from Spectroscopic Data, J. Am. Chem. Soc., 1933, 55, 4875. [all data]
Weber, 1970
Weber, L.A., Some vapor pressure and P,V,T data on nitrogen in t he range 65 to 140 K, J. Chem. Thermodyn., 1970, 2, 839-846. [all data]
Cardoso, 1915
Cardoso, E., Study of the Critical Point of Several Difficultly LIquifiable Gases: Nitrogen, Carbon Monoxide, Oxygen and Methane, J. Chim. Phys. Phys.-Chim. Biol., 1915, 13, 312. [all data]
Edejer and Thodos, 1967
Edejer, Merardo P.; Thodos, George, Vapor pressures of liquid nitrogen between the triple and critical points, J. Chem. Eng. Data, 1967, 12, 2, 206-209, https://doi.org/10.1021/je60033a014 . [all data]
Giauque and Clayton, 1933, 2
Giauque, W.F.; Clayton, J.O., The Heat Capacity and Entropy of Nitrogen. Heat of Vaporization. Vapor Pressures of Solid and Liquid. The Reaction 1/2 N 2 + 1/2 O 2 = NO from Spectroscopic Data, J. Am. Chem. Soc., 1933, 55, 12, 4875-4889, https://doi.org/10.1021/ja01339a024 . [all data]
Moussa, Muijlwijk, et al., 1966
Moussa, M.R.; Muijlwijk, R.; van Dijk, H., The Vapour Pressure of Liquid Nitrogen, Physica (Amsterdam), 1966, 32, 5, 900-912, https://doi.org/10.1016/0031-8914(66)90021-8 . [all data]
Hiraoka and Yamabe, 1989
Hiraoka, K.; Yamabe, S., How are Nitrogen Molecules Bound to NO2+ and NO+?, J. Chem. Phys., 1989, 90, 6, 3268, https://doi.org/10.1063/1.455880 . [all data]
Gheno and Fitaire, 1987
Gheno, F.; Fitaire, M., Association of N2 with NH4+ and H3O+(H2O)n, n = 1,2,3, J. Chem. Phys., 1987, 87, 2, 953, https://doi.org/10.1063/1.453250 . [all data]
Speller, Fitaire, et al., 1983
Speller, C.V.; Fitaire, M.; Pointu, A.M., Three - Body Association Reactions of NO+ and O2+ with N2, J. Chem. Phys., 1983, 79, 5, 2190, https://doi.org/10.1063/1.446067 . [all data]
Turner and Conway, 1976
Turner, D.L.; Conway, D.C., Stability of the NO+.N2 Ion Cluster, J. Chem. Phys., 1976, 65, 10, 3944, https://doi.org/10.1063/1.432887 . [all data]
Johnsen, Huang, et al., 1975
Johnsen, R.; Huang, C.M.; Biondi, M.A., The Formation and Breakup of NO2+.N2 Clusters in N2 at Low Temperatures, J. Chem. Phys., 1975, 63, 8, 3374, https://doi.org/10.1063/1.431751 . [all data]
Keesee and Castleman, 1986
Keesee, R.G.; Castleman, A.W., Jr., Thermochemical data on Ggs-phase ion-molecule association and clustering reactions, J. Phys. Chem. Ref. Data, 1986, 15, 1011. [all data]
Dunkin, Fehsenfeld, et al., 1971
Dunkin, D.B.; Fehsenfeld, F.C.; Schelmetekopf, A.L.; Ferguson, E.E., Three-Body Association Reactions of NO+ with O2, N2, and CO2, J. Chem. Phys., 1971, 54, 9, 3817, https://doi.org/10.1063/1.1675432 . [all data]
Hiraoka and Nakajima, 1988
Hiraoka, K.; Nakajima, G., A Determination of the Stabilities of N2+(N2)n and O2+(N2)n with n = 1 - 11 from Measurements of the Gas - Phase Ion Equilibria, J. Chem. Phys., 1988, 88, 12, 7709, https://doi.org/10.1063/1.454285 . [all data]
Teng and Conway, 1973
Teng, H.H.; Conway, D.C., Ion - Molecule Equilibria in Mixtures of N2 and Ar, J. Chem. Phys., 1973, 59, 5, 2316, https://doi.org/10.1063/1.1680338 . [all data]
Payzant and Kebarle, 1970
Payzant, J.D.; Kebarle, P., Clustering Equilibrium N2+ + 2N2 = N4+ + N2 and the Bond Dissociation Energy of N4+, J. Chem. Phys., 1970, 53, 12, 4723, https://doi.org/10.1063/1.1674010 . [all data]
Varney, 1968
Varney, R.N., Equilibrium Constant and Rates for the Reversible Reaction N4+ -> N2+ + N2, Phys. Rev., 1968, 174, 1, 165, https://doi.org/10.1103/PhysRev.174.165 . [all data]
Varney, R.N., Molecular Ions, J. Chem. Phys., 1959, 31, 5, 1314, https://doi.org/10.1063/1.1730590 . [all data]
Speller and Fitaire, 1983
Speller, C.V.; Fitaire, M., Proceedings of the 16th International Conference on Phenomena of Ionized Gases, H. Boetticher, H. Wenk and E. Shulz - Gulde, ed(s)., ICPIG, Dusseldorf, 1983, 568. [all data]
Janik and Conway, 1967
Janik, G.S.; Conway, D.C., Bonding in Heteromolecular Ion Clusters. N2O2+, J. Phys. Chem., 1967, 71, 4, 823, https://doi.org/10.1021/j100863a007 . [all data]
Howard, Bierbaum, et al., 1972
Howard, C.J.; Bierbaum, V.M.; Rundle, H.W.; Kaufman, F., Kinetics and Mechanism of Formation of Water Cluster Ions from O2+ and H2O+, J. Chem. Phys., 1972, 57, 8, 3491, https://doi.org/10.1063/1.1678783 . [all data]
Hiraoka and Mori, 1989
Hiraoka, K.; Mori, T., Gas Phase Stabilities of the Cluster Ions H+(CO)2(CO)n, H+(N2)2(N2)n and H+(O2)2(O2)n with n = 1 - 14, Chem. Phys., 1989, 137, 1-3, 345, https://doi.org/10.1016/0301-0104(89)87119-8 . [all data]
Hiraoka, Saluja, et al., 1979
Hiraoka, K.; Saluja, P.P.S.; Kebarle, P., Stabilities of Complexes (N2)nH+, (CO)nH+ and (O2)nH+ for n = 1 to 7 Based on Gas Phase Ion Equilibrium Measurements, Can. J. Chem., 1979, 57, 16, 2159, https://doi.org/10.1139/v79-346 . [all data]
Hiraoka, 1988
Hiraoka, K., Determination of the Stabilities of O3-(N2)n, O3-(O2)n, and O4-(N2)n from Measurements of the Gas Phase Equilibria, Chem. Phys., 1988, 125, 2-3, 439, https://doi.org/10.1016/0301-0104(88)87096-4 . [all data]
Turner, Simpson, et al., 1983
Turner, J.J.; Simpson, M.B.; Poliakoff, M.; Maier II, W.B., J. Am. Chem. Soc., 1983, 105, 3898. [all data]
National Bureau of Standards, 1968
National Bureau of Standards, US, Technical Note 270 - 3 in The NBS Tables of Chemical Thermodynamic Properties, 1968. [all data]
Saporoschenko, 1965
Saporoschenko, M., Mobility of Mass Analyzed N+, N2+, N3+, and N4+ Ions in Nitrogen Gas, Phys. Rev. A, 1965, 139, 352. [all data]
Franklin, Dibeler, et al., 1958
Franklin, J.L.; Dibeler, V.H.; Reese, R.M.; Krauss, M., Ionization and dissociation of hydrazoic acid and methyl azide by electron impact, J. Am. Chem. Soc., 1958, 80, 298. [all data]
Haynes, Freysinger, et al., 1995
Haynes, C.L.; Freysinger, W.; Armentrout, P.B., Collision-induced dissociation of N3+(X3-) with Ne, Ar, Kr, and Xe, Int. J. Mass Spectrom. Ion Processes, 1995, 149/150, 267. [all data]
El-Shall, Schriver, et al., 1989
El-Shall, M.S.; Schriver, K.E.; Whetten, R.L.; Meot-Ner (Mautner), M., Ion/Molecule Clustering Thermochemistry by Laser Ionization High - Pressure Mass Spectrometry, J. Phys. Chem., 1989, 93, 24, 7969, https://doi.org/10.1021/j100361a002 . [all data]
Perry, Rowe, et al., 1980
Perry, R.A.; Rowe, B.R.; Viggiano, A.A.; Albritton, D.L.; Ferguson, E.E.; Fehsenfeld, F.C., Laboratory Measurements of Stratospheric Sodium Ion Measurements, Geophys. Res. Lett., 1980, 7, 9, 693, https://doi.org/10.1029/GL007i009p00693 . [all data]
Beyer and Keller, 1971
Beyer, R.A.; Keller, G.E., The Clustering of Atmospheric Gases to Alkali Ions, Trans. Am. Geophys. Union, 1971, 52, 303. [all data]
Meot-Ner (Mautner) and Field, 1974
Meot-Ner (Mautner), M.; Field, F.H., Kinetics and Thermodynamics of the Association of CO+ with CO and of N2+ with N2 between 120 and 650 K, J. Chem. Phys., 1974, 61, 9, 3742, https://doi.org/10.1063/1.1682560 . [all data]
Gonzalez and Hoff, 1989
Gonzalez, A.A.; Hoff, C.D., Inorg. Chem., 1989, 28, 4295. [all data]
Speller, 1983
Speller, C.V., Ph. D. Thesis, Universite de Paris Sud, 1983. [all data]
Linn, Ono, et al., 1981
Linn, S.H.; Ono, Y.; Ng, C.Y., Molecular Beam Photoionization Study of CO, N2, and NO Dimers and Clusters, J. Chem. Phys., 1981, 74, 6, 3342, https://doi.org/10.1063/1.441486 . [all data]
Speller, C.V.; Fitaire, M.; Pointu, A.M., H2CN+.nN2 Clustering Formation and the Atmosphere of Titan, Nature, 1982, 300, 5892, 507, https://doi.org/10.1038/300507a0 . [all data]
Howard and Skinner, 1966
Howard, P.B.; Skinner, H.A., Thermochemistry of some reactions of aqueous hydrazine with halogens, hydrogen halides and N-halogenosuccinimides, J. Chem. Soc. A, 1966, 1536-1540. [all data]
Pedley, Naylor, et al., 1986
Pedley, J.B.; Naylor, R.D.; Kirby, S.P., Thermochemical Data of Organic Compounds, Chapman and Hall, New York, 1986, 1-792. [all data]
Posey and Johnson, 1988
Posey, L.A.; Johnson, M.A., Pulsed Photoelectron Spectroscopy of Negative Cluster Ions: Isolation of Three Distinguishable Forms of N2O2-, J. Chem. Phys., 1988, 88, 9, 5385, https://doi.org/10.1063/1.454576 . [all data]
Adams and Bohme, 1970
Adams, N.G.; Bohme, D., Flowing Afterglow Studies of Formation and Reactions of Cluster Ions of O2+, O2-, and O-, J. Chem. Phys., 1970, 52, 6, 3133, https://doi.org/10.1063/1.1673449 . [all data]
Belt, Scaiano, et al., 1993
Belt, S.T.; Scaiano, J.C.; Whittlesey, M.K., J. Am. Chem. Soc., 1993, 115, 1921. [all data]
Johnson, Popov, et al., 1991
Johnson, F.P.A.; Popov, V.K.; George, M.W.; Bagratashvili, V.N.; Poliakoff, M.; Turner, J.J., Mendeleev Commun., 1991, 145.. [all data]
Lofthus and Krupenie, 1977
Lofthus, A.; Krupenie, P.H., The spectrum of molecular nitrogen, J. Phys. Chem. Ref. Data, 1977, 6, 113. [all data]
Tilford, Wilkinson, et al., 1966
Tilford, S.G.; Wilkinson, P.G.; Franklin, V.B.; Naber, R.H.; Benesch, W.; Vanderslice, J.T., Summary of observed absorption lines of room-temperature molecular nitrogen between 1060 and 1520 Å, Astrophys. J. Suppl. Ser., 1966, 13, 31. [all data]
Wallace, 1962
Wallace, L., A collection of the band-head wavelengths of N2 and N2+, Astrophys. J. Suppl. Ser., 1962, 6, 445. [all data]
Pearse and Gaydon, 1963
Pearse, R.W.B.; Gaydon, A.G., The identification of molecular spectra, Third Edition, Pub. John Wiley & Sons, Inc., New York, 1963, 0. [all data]
Huffman, Tanaka, et al., 1963
Huffman, R.E.; Tanaka, Y.; Larrabee, J.C., Absorption coefficients of nitrogen in the 1000-580 Å wavelength region, J. Chem. Phys., 1963, 39, 910. [all data]
Cook and Metzger, 1964
Cook, G.R.; Metzger, P.H., Photoionization and absorption cross sections of O2 and N2 in the 600- to 1000-A region, J. Chem. Phys., 1964, 41, 321. [all data]
Carter, 1972
Carter, V.L., High-resolution N2 absorption study from 730 to 980 Å, J. Chem. Phys., 1972, 56, 4195. [all data]
Gilmore, 1965
Gilmore, F.R., Potential energy curves for N2, NO, O2 and corresponding ions, J. Quant. Spectry. Radiative Transfer, 1965, 5, 369. [all data]
Benesch, Vanderslice, et al., 1965
Benesch, W.; Vanderslice, J.T.; Tilford, S.G.; Wilkinson, P.G., Potential curves for the observed states of N2 below 11 eV, Astrophys. J., 1965, 142, 1227. [all data]
Gartner and Thrush, 1975
Gartner, E.M.; Thrush, B.A., Infrared emission by active nitrogen. I. The kinetic behaviour of N2(B'3«SIGMA»u-), Proc. R. Soc. London A, 1975, 346, 103. [all data]
Nakamura, Sasanuma, et al., 1969
Nakamura, M.; Sasanuma, M.; Sato, S.; Watanabe, M.; Yamashita, H.; Iguchi, Y.; Ejiri, A.; Nakai, S.; Yamaguchi, S.; Sagawa, T.; Nakai, Y.; Oshio, T., Absorption structure near the K edge of the nitrogen molecule, Phys. Rev., 1969, 178, 80. [all data]
Werme, Grennberg, et al., 1973
Werme, L.O.; Grennberg, B.; Nordgren, J.; Nordling, C.; Siegbahn, K., Fine structure in the x-ray emission spectrum of N2, compared with electron spectroscopy, Nature (London), 1973, 242, 453. [all data]
Vinogradov, Shlarbaum, et al., 1974
Vinogradov, A.S.; Shlarbaum, B.; Zimkina, T.M., K-absorption spectrum of nitrogen in the N2 molecule, Opt. Spectrosc. Engl. Transl., 1974, 36, 383, In original 658. [all data]
Vinogradov, Zimkina, et al., 1974
Vinogradov, A.S.; Zimkina, T.M.; Akimov, V.N.; Shlarbaum, B., Structure of absorption spectra of the molecules N2, O2, and NF3 near the ionization thresholds of the inner atomic shells, Bull. Acad. Sci. USSR, Phys. Ser. Engl. Transl., 1974, 38, 69, In original 508. [all data]
Lee, Wong, et al., 1975
Lee, J.S.; Wong, T.C.; Bonham, R.A., Observation of a new electronic transition in N2 at 31.4 eV by means of high energy electron impact spectroscopy, J. Chem. Phys., 1975, 63, 1643. [all data]
Codling, 1966
Codling, K., Structure in the photo-ionization continuum of N, near 500 k, Astrophys., 1966, J.143, 552. [all data]
Lee, Carlson, et al., 1973
Lee, L.C.; Carlson, R.W.; Judge, D.L.; Ogawa, M., The absorption cross sections of N2, O2, CO, NO, CO2, N2O, CH4, C2H4, C2H6 and C4H10 from 180 to 700 Å, J. Quant. Spectrosc. Radiat. Transfer, 1973, 13, 1023. [all data]
Hopfield, 1930
Hopfield, J.J., New spectra in nitrogen, Phys. Rev., 1930, 36, 789-790. [all data]
Worley, 1943
Worley, R.E., Absorption spectrum of N2 in the extreme ultraviolet, Phys. Rev., 1943, 64, 207. [all data]
Comes and Weber, 1969
Comes, F.J.; Weber, K.W., Wirkungsquerschnitte der Photoabsorption und Photoionisation des N2-Molekuls, Z. Naturforsch. A, 1969, 24, 1941. [all data]
Cook, Ogawa, et al., 1973
Cook, G.R.; Ogawa, M.; Carlson, R.W., Photodissociation continuums of N2 and O2, J. Geophys. Res., 1973, 78, 1663. [all data]
Ogawa, 1964
Ogawa, M., Vibrational isotope shifts of absorption bands of N2 in the spectral region 720-830 Å, Can. J. Phys., 1964, 42, 1087. [all data]
Carroll and Yoshino, 1967
Carroll, P.K.; Yoshino, K., New Rydberg series of N2, J. Chem. Phys., 1967, 47, 3073. [all data]
Johns and Lepard, 1975
Johns, J.W.C.; Lepard, D.W., Calculation of rotation-electronic energies and relative transition intensities in diatomic molecules, J. Mol. Spectrosc., 1975, 55, 374. [all data]
Worley and Jenkins, 1938
Worley, R.E.; Jenkins, F.A., A new Rydberg series in N2, Phys. Rev., 1938, 54, 305. [all data]
Ogawa and Tanaka, 1962
Ogawa, M.; Tanaka, Y., Rydberg absorption series of N2, Can. J. Phys., 1962, 40, 1593. [all data]
Yoshino, Tanaka, et al., 1975
Yoshino, K.; Tanaka, Y.; Carroll, P.K.; Mitchell, P., High resolution absorption spectrum of N2 in the vacuum-UV region, O3,4 1«PI»u <-- X1«SIGMA»g+ bands, J. Mol. Spectrosc., 1975, 54, 87. [all data]
Carroll and Collins, 1970
Carroll, P.K.; Collins, C.P., The high energy 1«SIGMA»u+ states of N2, J. Phys. B:, 1970, 3, 127. [all data]
Lofthus, 1957
Lofthus, A., Emission band spectra of nitrogen. A study of some singlet systems, Can. J. Phys., 1957, 35, 216. [all data]
Carroll and Subbaram, 1975
Carroll, P.K.; Subbaram, K.V., Two new band systems in the near ultraviolet spectrum of N2, Can. J. Phys., 1975, 53, 2198. [all data]
Gaydon, 1944
Gaydon, A.G., The band spectrum of nitrogen: new singlet systems, Proc. R. Soc. London A, 1944, 182, 286. [all data]
Rajan, 1974
Rajan, K.J., The 1-0 band of the b1«PI»u - a1«PI»g transition and the 1-10 and 2-12 bands of the fifth positive system of N2: rotational analyses, Proc. R. Ir. Acad. Sect. A:, 1974, 74, 17-23. [all data]
Herman-Montagne, 1945
Herman-Montagne, R., Contribution a l'etude du spectre de la molecule d'azote, Ann. Phys. (Paris), 1945, 20, 241. [all data]
Gaydon and Herman, 1946
Gaydon, A.G.; Herman, R., Band systems in the spectrum of nitrogen, Proc. Phys. Soc. London, 1946, 58, 292. [all data]
Dressler, 1969
Dressler, K., The lowest valence and Rydberg states in the dipole-allowed absorption spectrum of nitrogen. A survey of their interactions, Can. J. Phys., 1969, 47, 547. [all data]
Janin and Crozet, 1946
Janin, J.; Crozet, A., Excitation du spectre de l'azote par passage de l'effluve electrique a travers le gaz ammoniac, Compt. Rend., 1946, 223, 1114. [all data]
Janin, 1950
Janin, J., Etude de certains systemes de simplets de la molecule d'azote, J. Rech. C.N.R.S., 1950, 3, 156. [all data]
Herman, 1951
Herman, R., Nouvelle transition interdite de la molecule N2, Compt. Rend., 1951, 233, 738. [all data]
Carroll and Sayers, 1953
Carroll, P.K.; Sayers, N.D., The band spectrum of nitrogen: new studies of the triplet systems, Proc. Phys. Soc. London Sect. A, 1953, 66, 1138. [all data]
Gaydon, 1944, 2
Gaydon, A.G., The band spectrum of N2: weak systems in the visible region, Proc. Phys. Soc. London, 1944, 56, 85. [all data]
Grun, 1954
Grun, A.E., Die Gaydon-Banden des N2, Z. Naturforsch. A, 1954, 9, 1017. [all data]
Tilford and Wilkinson, 1964
Tilford, S.G.; Wilkinson, P.G., The emission spectrum of molecular nitrogen in the region 900-1130 Å, J. Mol. Spectrosc., 1964, 12, 231. [all data]
Carroll, P.K.; Collins, C.P., High resolution absorption studies of the b1«PI»u <-- X1«SIGMA»g+ system of nitrogen, Can. J. Phys., 1969, 47, 563. [all data]
Wilkinson and Houk, 1956
Wilkinson, P.G.; Houk, N.B., Emission spectra of nitrogen in the vacuum ultraviolet, J. Chem. Phys., 1956, 24, 528. [all data]
Gero and Schmid, 1940
Gero, L.; Schmid, R., Rotationsanalyse der IV. Positiven banden des N2-molekuls, Z. Phys., 1940, 116, 598. [all data]
Lutz, 1969
Lutz, B.L., Pressure-induced a"1«SIGMA»g+ <-- X1«SIGMA»g+ absorption in the vacuum ultraviolet spectrum of molecular nitrogen, J. Chem. Phys., 1969, 51, 706. [all data]
Freund, 1969
Freund, R.S., Molecular-beam measurements of the emission spectrum and radiative lifetime of N2 in the metastable E3«SIGMA»g+ state, J. Chem. Phys., 1969, 50, 3734. [all data]
Coster, Brons, et al., 1933
Coster, D.; Brons, F.; van der Ziel, A., Die sogenannte zweite positive gruppe des stickstoffspektrums, Z. Phys., 1933, 84, 304. [all data]
Dieke and Heath, 1959
Dieke, G.H.; Heath, D.F., The first and second positive bands of N2, Rpt. Johns Hopkins Spectroscopic #17, 1959, 1-195. [all data]
Tanaka, 1955
Tanaka, Y., Absorption spectrum of nitrogen in the region from 1075 to 1650 A, J. Opt. Soc. Am., 1955, 45, 663. [all data]
Tanaka, Ogawa, et al., 1964
Tanaka, Y.; Ogawa, M.; Jursa, A.S., Forbidden absorption-band systems of N2 in the vacuum-ultraviolet region, J. Chem. Phys., 1964, 40, 3690. [all data]
Carroll, Collins, et al., 1972
Carroll, P.K.; Collins, C.C.; Murnaghan, J.T., Rotational studies of the Gaydon-Herman (green) bands of N2, J. Phys. B:, 1972, 5, 1634. [all data]
McFarlane, 1966
McFarlane, R.A., Measurements on the w1«DELTA»u --> a1«PI»g transition in molecular nitrogen, Phys. Rev., 1966, 146, 37. [all data]
Chutjian, Cartwright, et al., 1973
Chutjian, A.; Cartwright, D.C.; Trajmar, S., Excitation of the W3«DELTA»u, w1«DELTA»u, B'3«SIGMA»u-, and a'1«SIGMA»u- states of N2 by electron impact, Phys. Rev. Lett., 1973, 30, 195. [all data]
McFarlane, R.A., Observation of a 1«PI»-1«SIGMA»- transition in the N2 molecule, Phys. Rev. A: Gen. Phys., 1965, 140, 1070. [all data]
McFarlane, 1966, 2
McFarlane, R.A., 4B7-precision spectroscopy of new infrared emission systems of molecular nitrogen, IEEE J. Quantum Electron., 1966, 2, 229. [all data]
Miller, 1970
Miller, R.E., High-resolution emission Lyman-Birge-Hopfield bands of nitrogen, J. Opt. Soc. Am., 1970, 60, 171. [all data]
Campbell and Thrush, 1969
Campbell, I.M.; Thrush, B.A., Some new vacuum ultra-violet emissions of active nitrogen, Trans. Faraday Soc., 1969, 65, 32. [all data]
Golde, 1975
Golde, M.F., Vacuum UV emission by electronically excited N2: the collision-induced N2(a1«PI»g, v=0) = N2(a'1«SIGMA»u-, v=0) transition, Chem. Phys. Lett., 1975, 31, 348. [all data]
Carroll and Rubalcava, 1960
Carroll, P.K.; Rubalcava, H.E., Rotational analysis of the 5-1 band of the B'-B system of N2, Proc. Phys. Soc. London, 1960, 76, 337. [all data]
Dieke, G.H.; Heath, D.F., Structure of the infrared Y bands of N2, J. Chem. Phys., 1960, 33, 432. [all data]
Wilkinson, 1960
Wilkinson, P.G., Forbidden band systems in nitrogen. III. The Y3«SIGMA»u- <-- X1«SIGMA»g+ system in absorption, J. Chem. Phys., 1960, 32, 1061. [all data]
Golde and Thrush, 1972
Golde, M.F.; Thrush, B.A., Vacuum ultraviolet emission by active nitrogen. IV. The kinetic behaviour of N2(B'3«SIGMA»u-), Proc. R. Soc. London A, 1972, 330, 121. [all data]
Wu and Benesch, 1968
Wu, H.L.; Benesch, W., Evidence for the 3«DELTA»u --> B3«PI»g transition in N2, Phys. Rev., 1968, 172, 31. [all data]
Saum and Benesch, 1970
Saum, K.A.; Benesch, W.M., Infrared electronic emission spectrum of nitrogen, Appl. Opt., 1970, 9, 195. [all data]
Benesch and Saum, 1971
Benesch, W.M.; Saum, K.A., The w3«DELTA»u state of molecular nitrogen, J. Phys. B:, 1971, 4, 732. [all data]
Covey, Saum, et al., 1973
Covey, R.; Saum, K.A.; Benesch, W., Transition probabilities for the W3«DELTA»u - B3«PI»g system of molecular nitrogen, J. Opt. Soc. Am., 1973, 63, 5, 592-596. [all data]
Wilkinson, P.G., Some unsolved problems in the vacuum ultraviolet, J. Quant. Spectrosc. Radiat. Transfer, 1962, 2, 343. [all data]
Miller, R.E., High-resolution emission Vegard-Kaplan bands of nitrogen, J. Chem. Phys., 1965, 43, 1695. [all data]
Miller, R.E., The absolute energy of the A3«SIGMA»u+ state of nitrogen, J. Mol. Spectrosc., 1966, 19, 185. [all data]
Crawford, Welsh, et al., 1949
Crawford, M.F.; Welsh, H.L.; Locke, J.L., Infra-red absorption of oxygen and nitrogen induced by intermolecular forces, Phys. Rev., 1949, 75, 1607. [all data]
Bosomworth and Gush, 1965
Bosomworth, D.R.; Gush, H.P., Collision-induced absorption of compressed gases in the far infrared, Part II, Can. J. Phys., 1965, 43, 751. [all data]
Reddy and Cho, 1965
Reddy, S.P.; Cho, C.W., Induced infrared absorption of nitrogen and nitrogen-foreign gas mixtures, Can. J. Phys., 1965, 43, 2331. [all data]
Shapiro and Gush, 1966
Shapiro, M.M.; Gush, H.P., The collision-induced fundamental and first overtone bands of oxygen and nitrogen, Can. J. Phys., 1966, 44, 949. [all data]
de Remigis, Welsh, et al., 1971
de Remigis, J.; Welsh, H.L.; Bruno, R.; Taylor, D.W., Induced fundamental infrared band of nitrogen dissolved in solid argon, Can. J. Phys., 1971, 49, 3201. [all data]
Sheng and Ewing, 1971
Sheng, D.T.; Ewing, G.E., Collision induced infrared absorption of gaseous nitrogen at low temperatures, J. Chem. Phys., 1971, 55, 5425. [all data]
Buontempo, Cunsolo, et al., 1975
Buontempo, U.; Cunsolo, S.; Jacucci, G.; Weis, J.J., The far infrared absorption spectrum of N2 in the gas and liquid phases, J. Chem. Phys., 1975, 63, 2570. [all data]
Courtois and Jouve, 1975
Courtois, D.; Jouve, P., Electric field induced infrared spectrum of nitrogen. Vibrational polarizability matrix elements, J. Mol. Spectrosc., 1975, 55, 18. [all data]
Stoicheff, 1954
Stoicheff, B.P., High resolution Raman spectroscopy of gases. III. Raman spectrum of nitrogen, Can. J. Phys., 1954, 32, 630. [all data]
Butcher, Willetts, et al., 1971
Butcher, R.J.; Willetts, D.V.; Jones, W.J., On the use of a Fabry-Perot etalon for the determination of rotational constants of simple molecules - the pure rotational Raman spectra of oxygen and nitrogen, Proc. R. Soc. London A, 1971, 324, 231. [all data]
Bendtsen, 1974
Bendtsen, J., The rotational and rotation-vibrational Raman spectra of 14N2, 14N15N and 15N2, J. Raman Spectrosc., 1974, 2, 133. [all data]
Watson, Lang, et al., 1973
Watson, W.S.; Lang, J.; Stewart, D.T., Photoabsorption coefficients of molecular nitrogen in the 300-700 Å region, J. Phys. B:, 1973, 6, 148. [all data]
Hicks, Comer, et al., 1973
Hicks, P.J.; Comer, J.; Read, F.H., Autoionizing transitions in N2 and H2 produced by electron impact, J. Phys. B:, 1973, 6, 65. [all data]
Wilden, Hicks, et al., 1976
Wilden, D.G.; Hicks, P.J.; Comer, J., Autoionization of N2 studied using an electron time-of-flight coincidence spectrometer, J. Phys. B:, 1976, 9, 1959. [all data]
Cook and Ogawa, 1970
Cook, G.R.; Ogawa, M., Oscillator strengths of the Hopfield absorption series of N2, J. Chem. Phys., 1970, 53, 1292. [all data]
Yoshino, Ogawa, et al., 1976
Yoshino, K.; Ogawa, M.; Tanaka, Y., Extension of Rydberg absorption series of N2, A2«PI»u <-- X1«SIGMA»g+, J. Mol. Spectrosc., 1976, 61, 403. [all data]
Cook, G.R.; Ogawa, M., Photo-ionization of N2 in the 734-805 Å region, Can. J. Phys., 1965, 43, 256. [all data]
Carter and Berkowitz, 1973
Carter, V.L.; Berkowitz, J., Photoionization yields in N2 in the band series from 734 to 796 Å, J. Chem. Phys., 1973, 59, 4573. [all data]
Cook and McNeal, 1972
Cook, G.R.; McNeal, R.J., Photoionization of vibrationally excited nitrogen, J. Chem. Phys., 1972, 56, 1388. [all data]
Carroll, P.K.; Yoshino, K., The cn 1«PI»u and c'n 1«SIGMA»u+ Rydberg states of N2: high resolution studies, J. Phys. B:, 1972, 5, 1614. [all data]
Leoni and Dressler, 1972
Leoni, M.; Dressler, K., Deperturbation of the Worley-Jenkins Rydberg series of N2, Helv. Phys. Acta, 1972, 45, 959. [all data]
Leoni, 1972
Leoni, Dissertation, ETH Zurich, 1972, 1. [all data]
Ledbetter, 1972
Ledbetter, J.W., Jr., New Rydberg bands in the visible region and identification of the lowest 1«SIGMA»g+ Rydberg state of the N2 molecule, J. Mol. Spectrosc., 1972, 42, 100. [all data]
Mulliken, 1976
Mulliken, R.S., Predissociation and «LAMBDA»-doubling in the even-parity Rydberg states of the nitrogen molecule, J. Mol. Spectrosc., 1976, 61, 92. [all data]
Lofthus, A., A new predissociation in nitrogen, Nature (London), 1960, 186, 302. [all data]
Veseth, 1973
Veseth, L., On the calculation of molecular parameters for triplet states in diatomic molecules. The G3«DELTA»g and H3«PHI»u states of N2, Mol. Phys., 1973, 26, 101. [all data]
Mohamed and Khanna, 1974
Mohamed, K.A.; Khanna, B.N., Franck-Condon factors & r-centroids for the H3«phi»u-G3«DELTA»g (Gaydon-Herman) green band system of N2, Indian J. Pure Appl. Phys., 1974, 12, 77-78. [all data]
Lefebvre-Brion, 1969
Lefebvre-Brion, H., Theoretical study of homogeneous perturbations. II. Least-squares fitting method to obtain "deperturbed" crossing Morse curves. Application to the perturbed 1«SIGMA»u+ states of N2, Can. J. Phys., 1969, 47, 541. [all data]
Hesser and Dressler, 1966
Hesser, J.E.; Dressler, K., Radiative lifetimes of ultraviolet molecular transitions, J. Chem. Phys., 1966, 45, 3149. [all data]
Hesser, 1968
Hesser, J.E., Absolute Transition Probabilities in Ultraviolet Molecular Spectra, J. Chem. Phys., 1968, 48, 6, 2518, https://doi.org/10.1063/1.1669477 . [all data]
Lawrence, Mickey, et al., 1968
Lawrence, G.M.; Mickey, D.L.; Dressler, K., Absolute oscillator strengths of the strongest bands within the dipole-allowed absorption spectrum of nitrogen, J. Chem. Phys., 1968, 48, 1989. [all data]
Geiger and Schroder, 1969
Geiger, J.; Schroder, B., Intensity perturbations due to configuration interaction observed in the electron energy-loss spectrum of N2, J. Chem. Phys., 1969, 50, 7. [all data]
Tilford and Wilkinson, 1964, 2
Tilford, S.G.; Wilkinson, P.G., An inverse predissociation in molecular nitrogen, J. Mol. Spectrosc., 1964, 12, 347. [all data]
Tanaka and Nakamura, 1967
Tanaka, Y.; Nakamura, M., Selective enhancement of the b'1«SIGMA»u+ --> X1«SIGMA»g+ and g1«SIGMA»u+ --> X1«SIGMA»g+ band systems of N2 in the vacuum ultraviolet region, Sci. Light (Tokyo), 1967, 16, 73. [all data]
Kurzweg, Egbert, et al., 1973
Kurzweg, L.; Egbert, G.T.; Burns, D.J., Lifetime of the D3«SIGMA»u+ state of N2, J. Chem. Phys., 1973, 59, 2641. [all data]
Hebert and Nicholls, 1969
Hebert, G.R.; Nicholls, R.W., Franck-Condon factors for the v'=0 progression of the N2 fourth positive band system, J. Phys. B:, 1969, 2, 626. [all data]
Meyer, Skerbele, et al., 1965
Meyer, V.D.; Skerbele, A.; Lassettre, E.N., Intensity distribution in the N2 k(b1«PI»u)<--1«SIGMA»g+ transition, J. Chem. Phys., 1965, 43, 3769. [all data]
Leoni, M.; Dressler, K., Predissociation probabilities and determination of a repulsive potential in the N2 molecule, Z. Angew. Math. Phys., 1971, 22, 794. [all data]
Dressler and Lutz, 1967
Dressler, K.; Lutz, B.L., Optical identification of the 12.28-eV quadrupole transition in molecular nitrogen, Phys. Rev. Lett., 1967, 19, 1219. [all data]
Lassettre, Skerbele, et al., 1966
Lassettre, E.N.; Skerbele, A.; Meyer, V.D., Quadrupole-allowed transitions in the electron-impact spectrum of N2, J. Chem. Phys., 1966, 45, 3214. [all data]
Michels, 1970
Michels, H.H., Identification of two low-lying non-Rydberg states of the nitrogen molecule, J. Chem. Phys., 1970, 53, 841. [all data]
Ledbetter and Dressler, 1976
Ledbetter, J.W., Jr.; Dressler, K., Interaction of the C'3«PI»u and C3«PI»u states in 14N2, 14N15N, and 15N2, J. Mol. Spectrosc., 1976, 63, 370. [all data]
Carroll, 1963
Carroll, P.K., The structure of the Goldstein-Kaplan bands of N2, Proc. R. Soc. London A, 1963, 272, 270. [all data]
Ledbetter, J.W., Jr., A new band of N2 and identification of the lower vibronic level of the C', v=1 and the C, v=5 3«PI»u state interaction, J. Chem. Phys., 1977, 67, 3400. [all data]
Borst, 1972
Borst, W.L., Excitation of several important metastable states of N2 by electron impact, Phys. Rev. A: Gen. Phys., 1972, 5, 648. [all data]
Borst and Zipf, 1971
Borst, W.L.; Zipf, E.C., Lifetimes of metastable CO and N2 molecules, Phys. Rev. A: Gen. Phys., 1971, 3, 979. [all data]
Carroll and Mulliken, 1965
Carroll, P.K.; Mulliken, R.S., 3«PI» Levels and predissociations of N2 near the 12.135-eV dissociation limit, J. Chem. Phys., 1965, 43, 2170. [all data]
Budo, 1935
Budo, A., Uber die Triplett-Bandentermformel fur den allgemeinen intermediaren fall und anwendung derselben auf die B3«PI»-, C3«PI»-terme des N2-molekuls, Z. Phys., 1935, 96, 219. [all data]
Buttenbender and Herzberg, 1935
Buttenbender, G.; Herzberg, G., Uber die struktur der zweiten positiven stickstoffgruppe und die pradissoziation des N2-molekuls, Ann. Phys. (Neue Folge), 1935, 21, 577. [all data]
Hori and Endo, 1941
Hori, T.; Endo, Y., Uber die pradissoziation in der zweiten positiven stickstoffgruppe, Proc. Phys. Math. Soc. Jpn., 1941, 23, 834. [all data]
Frackowiak, 1964
Frackowiak, M., Predissociation in C3«PI»u state of 15N2, Bull. Acad. Pol. Sci., Ser. Sci. Math. Astron. Phys., 1964, 12, 361. [all data]
Gero, 1935
Gero, L., Zur deutung der storungen in den zweiten positiven stickstoffbanden, Z. Phys., 1935, 96, 669. [all data]
Coster and Brons, 1935
Coster, D.; Brons, F., Zur deutung der storungen in den zweiten positiven stickstoffbanden, Z. Phys., 1935, 97, 570. [all data]
Johnson and Fowler, 1970
Johnson, A.W.; Fowler, R.G., Measured lifetimes of rotational and vibrational levels of electronic states of N2, J. Chem. Phys., 1970, 53, 65. [all data]
Imhof and Read, 1971
Imhof, R.E.; Read, F.H., Measured lifetimes of the C3«PI»u state of N2 and the a3«SIGMA»g+ state of H2, J. Phys. B:, 1971, 4, 1063. [all data]
Dotchin and Chupp, 1973
Dotchin, L.W.; Chupp, E.L., Radiative lifetimes and pressure dependence of the relaxation rates of some vibronic levels in N2+, N2, CO+, and CO, J. Chem. Phys., 1973, 59, 3960. [all data]
Chen and Anderson, 1975
Chen, S.T.; Anderson, R.J., Excitation of the C3«PI»u state of N2 by electron impact, J. Chem. Phys., 1975, 63, 1250. [all data]
Osherovich and Gorshkov, 1976
Osherovich, A.L.; Gorshkov, V.N., Measurement of the radiation lifetimes of the C3«PI»u excited state of the N2 molecule and the B2«SIGMA»u+ excited state of the N2+ molecule by the phase-shift and delayed-coincidences methods, Opt. Spectrosc. Engl. Transl., 1976, 41, 92, In original 158. [all data]
Nicholls, 1963
Nicholls, R.W., Einstein A coefficients, oscillator strengths and absolute band strengths for the N2 second positive and N2+ first negative systems, J. Atmos. Terr. Phys., 1963, 25, 218. [all data]
Reis, 1964
Reis, V.H., Oscillator strengths for the N2 second positive and N2+ first negative systems from observations of shock layers about hypersonic projectiles, J. Quant. Spectrosc. Radiat. Transfer, 1964, 4, 783. [all data]
Parks, Rao, et al., 1968
Parks, J.H.; Rao, D.R.; Javan, A., A high-resolution study of the C3«PI»u --> B3«PI»g (O,O) stimulated transitions in N2, Appl. Phys. Lett., 1968, 13, 142. [all data]
Kasuya and Lide, 1967
Kasuya, T.; Lide, D.R., Jr., Measurements on the molecular nitrogen pulsed laser, Appl. Opt., 1967, 6, 69. [all data]
Bleekrode, 1968
Bleekrode, R., Contribution to the study of "abnormal" rotational energy distributions in the C3«PI»u-B3«PI»g bands of 14N2, J. Chem. Phys., 1968, 49, 951. [all data]
Fishburne, Lazdinis, et al., 1967
Fishburne, E.S.; Lazdinis, S.S.; Seibert, G.L., The N2 second positive system excited by impact with a metastable argon atom, J. Mol. Spectrosc., 1967, 23, 100. [all data]
Shvangiradze, Oganezov, et al., 1960
Shvangiradze, R.R.; Oganezov, K.A.; Chikhladze, B.Ya., Isotopic band shifts in the electronic-vibrational spectra of some diatomic molecules, Opt. Spectrosc. Engl. Transl., 1960, 8, 239. [all data]
Zare, Larsson, et al., 1965
Zare, R.N.; Larsson, E.O.; Berg, R.A., Franck-Condon factors for electronic band systems of molecular nitrogen, J. Mol. Spectrosc., 1965, 15, 117. [all data]
Benesch, W.; Vanderslice, J.T.; Tilford, S.G.; Wilkinson, P.G., Franck-Condon factors for permitted transitions in N2, Astrophys. J., 1966, 144, 408. [all data]
Shumaker, 1969
Shumaker, J.B., Jr., Franck-Condon factors for high rotational levels of nitrogen, J. Quant. Spectrosc. Radiat. Transfer, 1969, 9, 153. [all data]
Tyte, 1962
Tyte, D.C., The effect of helium on the intensity of the second positive system of nitrogen, Proc. Phys. Soc. London, 1962, 80, 1354. [all data]
Shemansky and Broadfoot, 1971
Shemansky, D.E.; Broadfoot, A.L., Excitation of N2 and N2+ systems by electrons. I. Absolute transition probabilities, J. Quant. Spectrosc. Radiat. Transfer, 1971, 11, 1385. [all data]
Jain, 1972
Jain, D.C., Transition moment variation in the first and second positive band systems of N2, J. Quant. Spectrosc. Radiat. Transfer, 1972, 12, 759. [all data]
Benesch, Vanderslice, et al., 1966, 2
Benesch, W.; Vanderslice, J.T.; Tilford, S.G.; Wilkinson, P.G., Franck-Condon factors for observed transitions in N2 above 6 EV, Astrophys. J., 1966, 143, 236. [all data]
Carroll, P.K., Note on the 5«SIGMA»g+ state of N2, J. Chem. Phys., 1962, 37, 805. [all data]
Oldenberg, 1957
Oldenberg, O., The 5«SIGMA» level of the nitrogen molecule in The Threshold of Space [The Proceedings of the Conference on Chemical Aeronomy, Zelikoff, ed(s)., Pergamon Press, Publications Division, New York, 1957, 180-185. [all data]
Mulliken, R.S., Low-energy 5«SIGMA»g+ states of the nitrogen molecule, J. Chem. Phys., 1962, 37, 809. [all data]
Bayes and Kistiakowsky, 1960
Bayes, K.D.; Kistiakowsky, G.B., On the mechanism of the Lewis-Rayleigh nitrogen afterglow, J. Chem. Phys., 1960, 32, 992. [all data]
Krauss and Neumann, 1976
Krauss, M.; Neumann, D.B., The 5«SIGMA»g+ states of N2, Mol. Phys., 1976, 32, 101. [all data]
Lofthus and Mulliken, 1957
Lofthus, A.; Mulliken, R.S., Emission band spectra of nitrogen. Kaplan's first and second systems, J. Chem. Phys., 1957, 26, 1010. [all data]
Tilford, Vanderslice, et al., 1979
Tilford; Vanderslice; Tanaka, Unpublished, quoted by Lofthus and Krupenie, 1977, cited in Huber and Herzberg, 1979, 1979, 425. [all data]
Tilford and Benesch, 1976
Tilford, S.G.; Benesch, W.M., Absorption oscillator strengths for the a'1«SIGMA»u--X1«SIGMA»g+ and w1«DELTA»u-X1«SIGMA»g+ transitions of molecular nitrogen, J. Chem. Phys., 1976, 64, 3370. [all data]
Roncin, Damany, et al., 1967
Roncin, J.-Y.; Damany, N.; Romand, J., Far ultraviolet absorption spectra of atoms and molecules trapped in rare gas matrices at low temperature, J. Mol. Spectrosc., 1967, 22, 154. [all data]
Vanderslice, Tilford, et al., 1965
Vanderslice, J.T.; Tilford, S.G.; Wilkinson, P.G., The high-resolution absorption spectrum of nitrogen from 1060 to 1520 Å. I. The a1«PI»g <-- X1«SIGMA»g+ system, Astrophys. J., 1965, 141, 395. [all data]
Douglas and Herzberg, 1951
Douglas, A.E.; Herzberg, G., Predissociation and dissociation of the N2 molecule, Can. J. Phys., 1951, 29, 294. [all data]
Freund, R.S., Radiative lifetime of N2(a1«PI»g) and the formation of metastable N2(a'1«SIGMA»u-), J. Chem. Phys., 1972, 56, 4344. [all data]
Ching, Cook, et al., 1967
Ching, B.K.; Cook, G.R.; Becker, R.A., Oscillator strengths of the a, w, and C bands of N2, J. Quant. Spectrosc. Radiat. Transfer, 1967, 7, 323. [all data]
Pilling, Bass, et al., 1971
Pilling, M.J.; Bass, A.M.; Braun, W., A curve of growth determination of the f-values for the fourth positive system of CO and the Lyman-Birge-Hopfield system of N2, J. Quant. Spectrosc. Radiat. Transfer, 1971, 11, 1593. [all data]
Wilkinson and Mulliken, 1957
Wilkinson, P.G.; Mulliken, R.S., An electric quadrupole electronic band system in molecular nitrogen, Astrophys. J., 1957, 126, 10. [all data]
Vanderslice, Wilkinson, et al., 1965
Vanderslice, J.T.; Wilkinson, P.G.; Tilford, S.G., Magnetic-dipole and electric-quadrupole transition moments for the a1«PI»g <-- X1«SIGMA»g+ transition in N2, J. Chem. Phys., 1965, 42, 2681. [all data]
McEwen and Nicholls, 1966
McEwen, D.J.; Nicholls, R.W., Intensity distribution of the Lyman-Birge-Hopfield band system of N2, Nature (London), 1966, 209, 902. [all data]
Lassettre, Meyer, et al., 1965
Lassettre, E.N.; Meyer, V.D.; Longmire, M.S., Relative intensities of Lyman-Birge-Hopfield bands in electron impact spectrum of nitrogen, J. Chem. Phys., 1965, 42, 807. [all data]
Tilford, S.G.; Wilkinson, P.G.; Vanderslice, J.T., The high-resolution absorption spectrum of nitrogen from 1060 to 1520 Å. II. The a'1«SIGMA»u- <-- X1«SIGMA»g+ system, Astrophys. J., 1965, 141, 427. [all data]
Tilford, S.G.; Vanderslice, J.T.; Wilkinson, P.G., The high resolution absorption spectrum of nitrogen from 1060 to 1520 Å. III. The B'3«SIGMA»u- <-- X1«SIGMA»g+ system, Astrophys. J., 1965, 141, 1226. [all data]
Kovacs, 1970
Kovacs, I., On an intercombination transition of the N2 molecule, Opt. Spectrosc. Engl. Transl., 1970, 28, 239, In original 444. [all data]
Saum and Benesch, 1970, 2
Saum, K.A.; Benesch, W.M., W3«DELTA»u-X1«SIGMA»g+ system of N2, Phys. Rev. A: Gen. Phys., 1970, 2, 1655. [all data]
Bullock and Hause, 1971
Bullock, L.E.; Hause, C.D., Molecular constants of the B3«PI» and A3«SIGMA» states of N2, J. Mol. Spectrosc., 1971, 39, 519. [all data]
Artym, 1966
Artym, R.I., Formula for the vibrational transitions of the triplet states B3«PI»g - A3u+ of nitrogen, Opt. Spectrosc. Engl. Transl., 1966, 2, 2, In original 4. [all data]
Van Der Ziel, 1934
Van Der Ziel, A., Predissociation in the first positive group of N2 and its bearing on the electronic level diagram of the nitrogen molecule, Physica (The Hague), 1934, 1, 353. [all data]
Polak, Slovetskii, et al., 1972
Polak, L.S.; Slovetskii, D.I.; Sokolov, A.S., Predissociation and quenching probabilities for the vibrational levels of the B3«PI»g state of molecular nitrogen, Opt. Spectrosc. Engl. Transl., 1972, 32, 247, In original 472. [all data]
Becker, Fink, et al., 1972
Becker, K.H.; Fink, E.H.; Groth, W.; Jud, W.; Kley, D., N2 formation in the Lewis-Rayleigh afterglow, Faraday Discuss. Chem. Soc., 1972, 53, 35. [all data]
Ung, 1976
Ung, A.Y.-M., Observations of the high vibrational levels of N2(B3«PI»g) in the Lewis-Rayleigh afterglow of nitrogen, J. Chem. Phys., 1976, 65, 2987. [all data]
Chen and Anderson, 1975, 2
Chen, S.T.; Anderson, R.J., Excitation of the B3«PI»g states of N2 by electron impact, Phys. Rev. A: Gen. Phys., 1975, 12, 468. [all data]
Jeunehomme, 1966
Jeunehomme, M., Transition moment of the first positive band system of nitrogen, J. Chem. Phys., 1966, 45, 1805. [all data]
Wurster, 1962
Wurster, W.H., Measured transition probability for the first-positive band system of nitrogen, J. Chem. Phys., 1962, 36, 2111. [all data]
Dronov, Sobolev, et al., 1966
Dronov, A.P.; Sobolev, N.N.; Faizullov, F.S., Determination of the electronic transition strength for the first positive band system of nitrogen. II, Opt. Spectrosc. Engl. Transl., 1966, 21, 301, In original 538. [all data]
Cunio and Jansson, 1968
Cunio, B.E.; Jansson, R.E.W., The electronic transition moment of the N2 first positive system (N2 1PG), J. Quant. Spectrosc. Radiat. Transfer, 1968, 8, 1763. [all data]
Kupriyanova, Kolesnikov, et al., 1969
Kupriyanova, E.B.; Kolesnikov, V.N.; Sobolev, N.N., Electronic band strengths of the first positive system of N2 and of the Mainel system of N2+-II, J. Quant. Spectrosc. Radiat. Transfer, 1969, 9, 1025. [all data]
Miller, 1970, 2
Miller, R.E., Rotational line intensities in 3«SIGMA»+-1«SIGMA»+ electronic transitions, Phys. Rev. A: Gen. Phys., 1970, 1, 590. [all data]
Freund, Miller, et al., 1970
Freund, R.S.; Miller, T.A.; de Santis, D.; Lurio, A., Radio-frequency spectrum of metastable N2(A 3«SIGMA»u+). I. Magnetic hyperfine and electric quadrupole constants, J. Chem. Phys., 1970, 53, 6, 2290-2303. [all data]
de Santis, Lurio, et al., 1973
de Santis, D.; Lurio, A.; Miller, T.A.; Freund, R.S., Radio-frequency spectrum of metastable N2(A3«SIGMA»u+). II. Fine structure, magnetic hyperfine structure, and electric quadrupole constants in the lowest 13 vibrational levels, J. Chem. Phys., 1973, 58, 4625. [all data]
Shemansky, 1969
Shemansky, D.E., N2 Vegard-Kaplan system in absorption, J. Chem. Phys., 1969, 51, 689. [all data]
Shemansky and Carleton, 1969
Shemansky, D.E.; Carleton, N.P., Lifetime of the N2 Vegard-Kaplan system, J. Chem. Phys., 1969, 51, 682. [all data]
Meyer, Klosterboer, et al., 1971
Meyer, J.A.; Klosterboer, D.H.; Setser, D.W., Energy transfer reactions of N2(A3«SIGMA»u+). IV. Measurement of the radiative lifetime and study of the interaction with olefins and other molecules, J. Chem. Phys., 1971, 55, 2084. [all data]
Chandraiah and Shepherd, 1968
Chandraiah, G.; Shepherd, G.G., Intensity measurements in emission of 18 Vegard-Kaplan bands of N2, Can. J. Phys., 1968, 46, 221. [all data]
Broadfoot and Maran, 1969
Broadfoot, A.L.; Maran, S.P., Electronic transition moment for the N2 Vegard-Kaplan bands, J. Chem. Phys., 1969, 51, 678. [all data]
Butcher and Jones, 1974
Butcher, R.J.; Jones, W.J., Study of the rotational Raman spectra of 14N15N and 15N2, using a Fabry-Perot etalon, J. Chem. Soc. Faraday Trans. 2, 1974, 70, 560. [all data]
Chan, Baker, et al., 1964
Chan, S.I.; Baker, M.R.; Ramsey, N.F., Molecular-beam magnetic-resonance studies of the nitrogen molecule, Phys. Rev., 1964, 136, 1224. [all data]
Dunning, Cartwright, et al., 1976
Dunning, T.H., Jr.; Cartwright, D.C.; Hunt, W.J.; Hay, P.J.; Bobrowicz, F.W., Generalized valence bond calculations on the ground state (X1«SIGMA»g+) of nitrogen, J. Chem. Phys., 1976, 64, 4755. [all data]
van der Wiel, El-Sherbini, et al., 1970
van der Wiel, M.J.; El-Sherbini, Th.M.; Brion, C.E., K shell excitation of nitrogen and carbon monoxide by electron impact, Chem. Phys. Lett., 1970, 7, 161. [all data]
Carlson, Moddeman, et al., 1970
Carlson, T.A.; Moddeman, W.E.; Pullen, B.P.; Krause, M.O., Identification of high energy lines in the K-LL Auger spectrum of N2, Chem. Phys. Lett., 1970, 5, 390. [all data]
Lindholm, 1969
Lindholm, E., Rydberg series in small molecules. III. Rydberg series in N2, Ark. Fys., 1969, 40, 111. [all data]
Carroll, P.K., Band structures in N2 Rydberg complexes, J. Chem. Phys., 1973, 58, 3597. [all data]
Cartwright and Dunning, 1974
Cartwright, D.C.; Dunning, T.H., Jr., Vibrational matrix elements of the quadrupole moment of N2(X1«SIGMA»g+), J. Phys. B:, 1974, 7, 1776. [all data]
Ketelaar and Rettschnick, 1963
Ketelaar, J.A.A.; Rettschnick, R.P.H., The quadrupole moment of nitrogen deduced from the pressure-induced rotational spectrum of nitrogen, Mol. Phys., 1963, 7, 191. [all data]
Buckingham, Disch, et al., 1968
Buckingham, A.D.; Disch, R.L.; Dunmur, D.A., The quadrupole moments of some simple molecules, J. Am. Chem. Soc., 1968, 90, 3104. [all data]
Huber and Herzberg, 1979
Huber, K.P.; Herzberg, G., Molecular Spectra and Molecular Structure. IV. Constants of Diatomic Molecules, Van Nostrand Reinhold Company, New York, 1979, 716. [all data]
Go To: Top, Gas phase thermochemistry data, Phase change data, Reaction thermochemistry data, Mass spectrum (electron ionization), Constants of diatomic molecules, References
Symbols used in this document:
Pc Critical pressure
Ptriple Triple point pressure
S°gas,1 bar Entropy of gas at standard conditions (1 bar)
T Temperature
Tboil Boiling point
Tc Critical temperature
Tfus Fusion (melting) point
Ttriple Triple point temperature
rG° Free energy of reaction at standard conditions
rH° Enthalpy of reaction at standard conditions
rS° Entropy of reaction at standard conditions
vapH Enthalpy of vaporization
c Critical density
Data from NIST Standard Reference Database 69: NIST Chemistry WebBook
The National Institute of Standards and Technology (NIST) uses its best efforts to deliver a high quality copy of the Database and to verify that the data contained therein have been selected on the basis of sound scientific judgment. However, NIST makes no warranties to that effect, and NIST shall not be liable for any damage that may result from errors or omissions in the Database.
Customer support for NIST Standard Reference Data products.
|
cc/2020-05/en_middle_0097.json.gz/line35326
|
__label__wiki
| 0.800498
| 0.800498
|
Funeral Crackdown in Iran
What the heck is going on in Iran? The Iranian regime put more constraints on its people and now they even have a problem burying their dead. On Thursday, more than 7 people were arrested while attending a funeral for the father of one of the reformist leaders Mir Hossein Mousavi.
The Green Movement website says that government security forces surrounded Mousavi’s home in Tehran as people were gathered for a funeral. It says that there was a confrontation between mourners and policemen in plain clothes who seized the coffin, forcefully placed it in a ambulance, and took it to a burial ceremony.
Furthermore it says, while a confrontation erupted between mourners and police forces, the police forces in plain clothes attacked mourners, beaten them up and arrested more than seven funeral attendants.
It has been since February 14 that opposition’s leaders Mir Hossein Mousavi and Mehdi Karroubi along with their wives have been put under house arrest, after they called for a rally in support of Egyptian uprising.
Labels:Green,Iran,Karroubi,Mousavi,Movement
Twitter and users
Happy Fifth Birthday Twitter!
The Middle East Doesn't mean Israel or Palestine a...
|
cc/2020-05/en_middle_0097.json.gz/line35332
|
__label__cc
| 0.55306
| 0.44694
|
DRC – Kinshasa
Reparations for Africa, A conversation worth revisiting?
In Africa, Slave Trade
Image Credit : American History USA
Reparations is a word that you and I be hearing often especially if we are trying to keep up with US politics. Since Candidates started announcing their intentions to run, there has been a buzz about reparations especially from the Democrats. Its a question that the get asked a lot and something that will likely be part of their top agenda.
What made it even more clearer was Trevor Noah’s segment on the Daily Show where he got to really explain what reparations were all about.
“……. Reparations, You are repairing something that you have broken, You are paying for something that you are supposed to pay for.
… If you are a black person in America, from Slavery, from day one, the number of injustices that have held black people back in America amount to an insurmountable…. you look at black peoples’ freedom, You look at back peoples land, … the amount of wealth you can acquire if you own land is exponential because you have the land, you have the fact that you can borrow based on the land, you have the fact that you can use the money that you have borrowed to grow more wealth, you can use it to grow your family’s wealth ….. just taking that away from black people is crippling them and so you combine that with slavery and you look at Jim Crow laws….. …” Trevor Noah March, 2019.
In July 2017, I had the very rare opportunity to travel to Banjul, the Gambia at the invitation of then UN Permanent Representative of the Gambia to the UN Dr Mamadou Tangara for an interesting discussion. The discussion was called : The Banjul International Colloquium on Slavery, Slave Trade & Colonialism.
Some of the speakers were Professor Jefferies now former Africa – American Professor of Black Studies City University of New York, His Wife Rosalind Jefferies : an African American Art Historian, Daughter of the Legendary Frantz Fanon – Mireille Fanon-Mendes-France and Dr Lang Fafa Dampha from the African Academy of Languages, African Union Commission in Bamako Mali.
Being in their midst for me was an honour, but also an awakening of a part of me that I never realised that I had. We visited Kuntah Kinteh Island and I was mad – the same mad you see people sharing about after watching When They See Us the 4 part series about the Central Park 5. Mad because Slave Trade was so inhumane. But even more mad because if you survived the Slave Trade journey then your only option was/ would be Slavery. I was invited to talk about the impact of Social Media in leading conversations such as this for the African people.
Dr Lang Fafa Dampha presented a paper citing reparations as a vital component to Africa’s healing economically and otherwise. He pointed out that conferences had been organised by the UN & its special institutions in 1978, 1983,2001, and 2009 on All were held in Geneva apart from the one in 2001 held in Durban, South Africa.
“Reparation claim for slavery and colonialism is not a new issue, because the African peoples both on the continent and in the Diaspora as well as other social groups in the Americas have a long history of demanding compensation for the wrongs inflicted on them, particularly in terms of slavery. For example, in the United States, the Black Panthers in the 1960s recalled the promise of “Forty Acres and a Mule.”” He said.
Mierille Fanon also made this argument for Reparations to be paid to Africa :
“Through reparation, the most important thing is to oblige the former colonizers from Trans – Atlantic trade slave, from enslavement and colonisation to colonialism to repair the situation which saw humanity be broken because of the development of capitalism in its most brutal aspects, which confirms today by the seizure of all the liberal capitalist machine on the state apparatus and is expressed by an endless war conducted against the people so that the system continues on and on, while garnering even more profits.”
The purpose of the said Colloquium was in the end : ‘to table a United Nations General Assembly resolution on Recognition, Restitution, Reparations () to mitigate the damages that slavery and colonialism have inflicted on African and People of the African Diaspora. This was to be backed by the now defunct government of President Yaya Jammeh. Such a resolution has to be backed by so many leaders of African Nations to be made visible at the UN. With Yaya Jammeh no longer in power, I wonder if the conversation will be continued any time soon.
The 2001 The World Conference Against Racism, Racial Discrimination, Xenophobia and Related Intolerance held in Durban was was a potential source of legal engagement to generate legal proceedings steering the conversations on reparations for Africa. However because the Western nations that were present refused to officially apologise even after they recognized the effects of Slavery, Slave trade & colonialism. Also, African leaders present then brought up other controversies like the existence of slaves in Present Day African countries like Sudan, Mauritania etc.
Then President Olusegun Obasanjo of Nigeria and Vice-President of South Africa Jacob Zuma felt that financial compensation was not a rational option, because it risked dividing Africans on the continent and those in the Diaspora.
President Wade of Senegal categorically dismissed the idea of financial compensation for the slave trade calling it “absurd,” because such a crime perpetrated cannot be compensated in monetary terms. Colin Powell also expressed the notion that Africans in demanding reparation are being “prisoners of the past”.
As I see Americans again bring up the conversations on reparations but for them, I ask myself : What about reparations for Africa?
More than the compensation, I would like to see an acknowledgement of wrongs done through Slavery, Slave Trade and Colonialism.
And so I ask: Is this a conversation worth visiting again, Can we sound the drums on this cause but also : Who would take the lead on this conversation? Is it in our interest?
Its important that Africans write this story their way. That school curricular has chapters of this covered in History classes because there is knowledge to be passed on.
African reparation requires Africans in the process to work according to their cultural values and the transformative aspects of these values. The individual African should be part of the collective Africa. The indispensable factors of African reparation in the larger context of socio-economic development are self discipline, self-respect, respect of African values, rigour, professionalism and genuine adherence to African sociocultural values. — Dr Lang Fafa Dampha
Month of Breast Protests in Uganda
Gender, Politics, Uganda
Democracy – the worst form of government…
Robert Mugabe and the Girl Called Zimbabwe
Africa, Democracy, Zimbabwe
Congolese Diaspora are Behind Belgium Success
Africa, DRC - Kinshasa
To regulate or not regulate social media - case in point : #UgandaDecides
Africa, Democracy, Media, Social Media, Uganda
Time for girls’ football
Gender, Tanzania
Africa Needs a Collective Thinking Space
Africa, Democracy, Development, Malawi, Politics, Social Media
El Adde Shows How Not To Fight Al Shabaab
Democracy, Development, Kenya
African Football.
Faure Gnassibé
Just Associates Southern Africa
Land Grab
Unionism
Zimbabwe Uganda Kenya Politics Zambia Tanzania ZANU PF Robert Mugabe Edgar Lungu Africa Malawi Uhuru Kenyatta Human rights Emmerson Mnangagwa Democracy John Magufuli Yoweri Museveni Zambia 2016 elections Raila Odinga South Africa Peter Mutharika Hakainde Hichilema Social Media Morgan Tsvangirai Elections freedom of expression Social DRC AfricaBlogging Morality Corruption Media Freedom MDC Burundi Economy Uganda elections UPND 2017 election internet shutdown Michael Sata Patriotic Front Development Zambia elections terrorism Press Freedom
About Africa Blogging
The international blogger network #AfricaBlogging is an online platform featuring a plurality of voices and views supporting democratic culture and debate in Sub-Saharan Africa.
Founded in 2015 in Johannesburg, its members believe that blogs play a major role in providing information and diversity of opinion in Africa and they are committed to encouraging open debate on matters not adequately covered by traditional media.
Media Program Sub-Saharan Africa
|
cc/2020-05/en_middle_0097.json.gz/line35333
|
__label__wiki
| 0.694822
| 0.694822
|
One Portwall Square
Clients: NORD
One Portwall Square is a new-build office for independent developer Nord on a site close to Bristol Temple Meads railway station. The site was originally part of 100 Temple Street, a large office building designed by John Wells-Thorpe during the 1970s including a raised squash court with parking below. The new-build scheme replaces the disused squash court with a six storey freestanding office building, set back from Portwall Lane to create a lively pocket square at ground level. The proximity to 100 Temple Street has been a key consideration in the building’s design, reflected in the high floor to floor levels which match those of its neighbour. The design uses a low spandrel that wraps around the building, forming the balustrade to the cantilevered south-facing terraces at each level and shading the storey below. A complementary palette of materials has been selected for the façade taking its cue from the neighbouring orange-red brick and pre-cast concrete buildings. Occupant comfort is at the forefront of the design, using energy efficient systems including smart ventilation and in-slab cooling. One Portwall Square will become the new Bristol base for AHMM, with the practice agreeing to pre-let a floor of the building - a space double that of the existing studio. This move will provide the opportunity to expand the Bristol team and accommodate new facilities, including a modelshop.
Morelands Rooftop
|
cc/2020-05/en_middle_0097.json.gz/line35334
|
__label__cc
| 0.719872
| 0.280128
|
5 PPC Questions Our Managed Services Team Gets Asked Everyday
Sandra Jimenez
As we dive head first into 2018, there are a few PPC questions we want to clarify that we get asked all the time. From Facebook ads to ad spend, many of you have common questions that deserve answers and you’re not alone! Since these topics keep coming up, we thought it would be a great idea to cover them on our blog. Here are the top 5 PPC questions we get asked everyday with the most thorough answers we can provide. Enjoy! But don’t hesitate to reach out to our managed services team if ever you have more questions on these topics or any others – we’re here to help.
1 Why Buy Facebook Ads Over Boosting a Post?
This is a very logical question that social media advertisers face on the regular and the answer takes a bit of explanation.
Anyone managing a brand’s Facebook page has seen the automatic prompts to boost a post. These prompts appear and remain at the bottom of updates added to a company’s feed as shown in the image below:
Boosting a post allows brands using Facebook to put their status update in front of more people than simply sharing on their wall would. Boosting allows advertisers to have their update appear on the desktop or mobile newsfeed, to choose from one of two objectives (website visits or engagements), to define an audience based on geography, age or their relationship with your page (has liked it or is friends with someone who liked it), and to determine a budget in a currency of their choice over the course of 1, 7 or 14 days of promotion. Once these parameters are set by the brand, Facebook will show the estimated reach and spend per day.
All of these option s available to advertisers when boosting a particular post are a lot like when a true Facebook ad is created. So what’s the difference? And why would anyone bother creating a Facebook ad when they could just boost a post?
The main reason is that advertisers can access many more options through Facebook ads than they could by boosting or promoting a post. When advertisers create a Facebook ad they can choose various ad formats, placements, select more goals or marketing objectives and access many more options for ad targeting. To elaborate more on the additional possibilities that running Facebook ads provides, lets drill down into each of these.
Facebook Ad Formats
Consider that brands can run an ad campaign with a photo, a video, a carousel of images, a slideshow or even a collection of products featured in one campaign when they use Facebook ads. Yes, a brand could create an image for a post that features many different products for example, but it wouldn’t have the same functionality of an ad featuring a collection. The image below demonstrates the Collection format of a Facebook ad where users can click on different products in a more engaging format than if it were just a boosted static image that led to one product page or another.
Facebook Placements
Advertisers can also place ads in different ad space around the Facebook ecosystem, whereas with a boosted post the only option is to show up in the mobile or desktop newsfeed. Facebook ad placements include inside newsfeeds (like with boosted posts), inside Facebook groups, in the right column of feeds (aka right-hand-rail), within Instant articles on the mobile app or messenger or within in-stream videos. Since Facebook owns Instagram, advertisers can also access this entirely other channel through Facebook ads, but that’s another story on its own.
Advertisers need to test which ad placement gets them the best results. For example, Lee Goldberg said in our Guide to Facebook Advertising Success that in his experience right column ads tend to get low click volume but have a high conversion rate. If the advertiser’s goal is to generate website conversions with a low budget, a Facebook ad campaign with right column placements may be the best fit – but again, always be testin!
Facebook Ad Goals
While we mentioned above that boosted posts allow brands to choose between the marketing objective of getting either website visits or engagements, Facebook ads allow for more types of objectives or goals. Brands running Facebook ads can create a campaign to get them attendees at an event, to generate video views, to incite app installs, to get likes for their brand’s Facebook page and of course for post engagement, and website clicks and website conversions. If the brand’s main goal was to get people to download their app, an ad campaign focusing on downloads as the end objective would be a more suitable option than simply boosting a post.
Facebook Ad Targeting
While boosting a Facebook post provides some targeting options for advertisers and brands like geography and age, Facebook ads have more advanced possibilities. Facebook ads allow advertisers to target by age, location, demographic, interests, behavior, device-type and even using custom lists from email marketing campaigns.
And with all of these additional capabilities, advertisers have a better chance of generating better campaign results and returns than if they had just boosted a post. Some brands may simply want to reach more people with an important news announcement rather than creating a whole ad campaign, and in this case boosting a post may be more appropriate. Otherwise Facebook ads is likely a better choice.
2 Why Can’t I See My Ad When I Google My Company Name?
The first thing we always tell clients is not to search for themselves because it creates false impressions and can temper campaign results. However, to answer the question, anyone running search ads knows that their ads appear in SERPs based on keywords selected by the advertiser in AdWords, Bing or another search engine. That means if the advertiser has not included their own company name or brand as a keyword in one of their ad groups, their ad will not show when anyone searches for their brand inside a search engine. In that case, brands can only hope that their website appears in the organic search results near the top of the page under the ad section. It is for this reason that we have been telling advertisers for some time to remember to create branded campaigns:
“When it comes to bidding on keywords, we can’t forget our own company identity. Don’t forget to bid on brand terms. Avery labels decreased their campaign costs by 51% by buying their own branded keywords. This also raised the cost of these keywords and stopped their competitors from bidding on them. PPC campaigns that bid intelligently on brand name keywords do better than those that don’t.”
If your brand doesn’t appear when you search for it, it’s because you haven’t included your own brand in your ad campaigns. Creating a branded ad group or simply adding branded keywords to existing campaigns will fix that instantly.
However, if you have created a branded ad group and you’re still not seeing your ad, there could be a few reasons why it isn’t showing including daily budget, the geographical target set, IP address and more. RevLocal elaborates a bit more about why certain ads don’t show in SERPs.
3 What is the Ideal Budget I Should Allocate for Adwords or Facebook?
This is certainly the million dollar question and the age old answer is that it depends. Unfortunately, there is no magic number to this question that can apply to all individual situations and ultimately it depends on how much budget an advertiser has to allocate to either channel in the first place. It also depends on your audience and campaign goals. Does your audience spend time on Facebook or are they more likely to convert through a search ad campaign?
If both channels are indeed an appropriate choice for your advertising goals and you just want to divide your budget between each, you could start off with an even split and see which channel performs best. If your ad campaign goal is to generate website conversions and you’re seeing more conversions come from Facebook than search for example, you may want to increase your budget in this channel incrementally until you find the right balance.
The problem is that both the search and social advertising ecosystems are dynamic and the results are subject to even more factors than an advertiser’s individual goals and circumstances. For example, one channel may perform better now than in 2 months as a result of seasonality. Due to the ongoing complexities of this dilemma that advertisers face, Acquisio developed a new AI algorithm that will distribute budget where it will perform best everyday. Anyone using the Acquisio platform can turn on this new algorithm and never have to think of this question again, while still getting optimal results.
4 How do Keywords Work and What Should I Pay for a Specific Keyword?
In general, keywords tell search engines which words you would like your ad to appear for. Advertisers should figure out how to select the best keywords for their campaign before deciding on which and what to bid on.
Determining what advertisers should pay for a specific keyword is another “it depends” type of question. First of all, in search ads advertisers bid on specific keywords, which is different from what they end up paying in the end for each, otherwise known as their cost-per-click (CPC). So what anyone should pay for a specific keyword isn’t the right question to ask, rather they should ask, ‘what should I bid?’.
Bidding can be complex and is again why Acquisio has developed 30 different AI algorithms for bid and budget management. Prices per keyword vary depending on how many people are bidding on the same keyword and how much they’re bidding, yet it’s almost impossible for advertisers to have this competitive data. Publishers like AdWords provide a suggested bid, but it doesn’t guarantee results. In fact, bids need to be modified throughout the day according to ongoing fluctuations in the auction to generate optimal results. From this respect, determining the answer to what to bid per keyword becomes a full time job.
To know what to bid at a keyword level, advertisers have to understand how the auction works and modify bids accordingly. The bid given by the advertiser determines what position they will show up in within ad results embedded in SERPs for various keywords. If the bid isn’t high enough for a particular keyword, they won’t show up at all as we explained in a past post on automation.
“An effective bid can be the difference between being the first ad to appear on search and not appearing on the page at all. An optimal bid is one that generates a higher return on investment (ROI). The best bids are those that cost less and generate more engagement. Manually figuring out the right bid at the ad group and keyword level requires a lot of work, analysis and time, and it’s not something campaign managers can realistically handle at scale.”
Again, the answer to this question is quite complex and yet so fundamental to PPC success. We recommend that anyone having difficulty answering this question for themselves, either hire a PPC expert or use Acquisio Turing for artificially intelligent bid and budget management.
5 What’s my Position Compared to my Competitors?
If you’re an advertiser and you want to know where your ad stands compared to your competitors, you can simply open up an incognito window in your browser and type in the keyword you’re looking to shed light on. You’ll see your ad in relation to all of the competitors bidding on this keyword. However, as you know from previous answers above, your position for a particular keyword can vary throughout the day, week, month etc., as other variables like competitor bids and quality score in the auction fluctuate. In some circumstances your ad may not appear at all.
Looking at your ad rank and average position is a better overall indicator of where you stand. Checkout this AdWords Competition Guide to discover 4 tools that will help you figure out how your competitors are performing, like using the Auction Insights Report to determine their average position.
Feature Image: Unsplash/Climate KIC
Screenshots 1-2 by Sandra Jimenez. Taken December 2017 from Facebook.
Image 3: Screenshot by Sandra Jimenez. Taken December 2017 from Facebook Business.
Keywords PPC 101 PPC Marketing Social Media
With nearly a decade of experience in marketing, Sandra has spent the last seven years focused on digital marketing, including email marketing, data management, SEM, affiliate marketing and more. Having worked at Cyrpa Media and Binbit International, Sandra is now the Operations Manager with the Acquisio Trading Desk. As part of Acquisio's display team, Sandra has managed media buys that resulted in a performance record of 1000% return on ad spend for several campaigns.
The 7 Don’t-Miss PPC Events of 2018
The State of PPC Report 2017-2018
eBook: Facebook Advertising Success
Increase CTR From Facebook Ads by 20% With One Click!
|
cc/2020-05/en_middle_0097.json.gz/line35341
|
__label__wiki
| 0.929492
| 0.929492
|
Tag: Thibaut Courtois
Chelsea goalkeeper Thibaut Courtois shows class in penalty shootout
July 22, 2016 Vincent Van Genechten
Thibaut Courtois is eager to show Antonio Conte and Chelsea fans he’s better than the goalkeeper that endured a very rocky Premier League season. The Belgium international performed well at Euro 2016 and showed his penalty-stopping skills in a one-on-one game with Chicago Bulls basketball player Nikola Mirotic. Aquí tenéis el resultado del reto… gracias @thibautcourtois por el buen rato y a la @SeFutbol por sus campos! pic.twitter.com/zwe4bBYC5R — Nikola Mirotic (@threekola) 19 juli 2016
Chelsea, Premier League, VideoChelsea, Thibaut Courtois
Chelsea in talks with French star goalkeeper
Chelsea have begun talks with Marseille goalkeeper Steve Mandanda as they look to make him Thibaut Courtois’s understudy at Stamford Bridge. According to a report by The Guardian, the 31-year-old is set to leave Marseille after a very poor season when his contract ends this month. He played nine years at the Stade Vélodrome and has expressed an interest in pursuing his career in the Premier League, after once having an unsuccessful trial with Aston Villa. Mandanda is currently France’s second goalkeeper at Euro 2016, backing up Tottenham’s Hugo Lloris. He’s been…
Chelsea, Ligue 1, NewsNow, Premier LeagueChelsea, Marseille, Steve Mandanda, Thibaut Courtois
Chelsea have offered star player to Barcelona for huge fee
Speculation regarding Chelsea goalkeeper Thibaut Courtois’s future at the West London club has grown strong in the recent weeks. The Belgian goalkeeper has repeatedly been linked with a move back to the Spanish La Liga, and now according to Spanish publication Mundo Deportivo, the Blues have offered their star player to Barcelona for £50 million. Meaning Courtois will become the most expensive goalkeeper in football history, as Juventus paid £40 million for Gianluigi Buffon to Parma in 2001. The Belgium international, who recently refused to commit his long-term future to the…
Barcelona, Chelsea, La Liga, Ligue 1, NewsNow, Premier League, PSG, Real MadridBarcelona, Chelsea, Real Madrid, Thibaut Courtois
Chelsea star free to leave Stamford Bridge on one condition
April 30, 2016 Vincent Van Genechten
Incoming coach Antonio Conte has reportedly given the green light to Chelsea’s management to sell goalkeeper Thibaut Courtois, according to The Times. The 23-year-old has enjoyed a disappointing season at Stamford Bridge, as he missed three months of football after suffering a training ground injury in the first half of the season. Following his return from injury, he has not been at his best and produced some questionable performances. He has also received a couple of red cards in the Premier League this season. Recently, when asked about his future, he…
Barcelona, Chelsea, La Liga, NewsNow, Premier League, Real MadridChelsea, Thibaut Courtois
Chelsea star interested in Real Madrid move
April 21, 2016 Vyom Chaudhary
Chelsea might have a battle on their hands in keeping hold of their first-choice goalkeeper Thibaut Courtois in the summer. The Belgian goalkeeper has recently been linked with a move to Real Madrid, and famous football journalist Duncan Castles has further fuelled the rumours by claiming that Courtois is open to a move to the La Liga giants. Castles writes in One World Sports that Courtois will be ready to join Real if the La Liga club manage to agree terms with Chelsea in the summer. The 23-year-old has enjoyed a…
Barcelona, Chelsea, La Liga, NewsNow, Premier League, Real MadridChelsea, Real Madrid, Thibaut Courtois
Chelsea are ready to axe star goalkeeper for reserve
April 9, 2016 April 9, 2016 Vincent Van Genechten
Asmir Begovic will be handed starts between now and the end of the season as Chelsea consider selling Thibaut Courtois and making the Serbian their number one goalkeeper next season, according to The Daily Mail. The Blues could place the Belgian international on the bench against Swanesa to allow Begovic the chance to audition to become Antonio Conte’s man between the sticks next season. Courtois has endured a mixed season at Stamford Bridge and has refused to state he’s going to stay at Chelsea after the current season ends. He is thought…
Chelsea, NewsNow, Premier LeagueAsmir Begovic, Chelsea, Thibaut Courtois
Belgian looks to be most crazy goalkeeper on the planet [Video]
March 25, 2016 Vincent Van Genechten
The Premier League has been able to watch two talented Belgian goalkeepers as of late: Chelsea’s Thibaut Courtois and Liverpool’s Simon Mignolet. However, both Belgium internationals are fellow countryman of possibly the most crazy goalkeeper on the planet. Glenn Verbauwhede used to play in the Belgium top flight with Club Brugge, Kortrijk and Westerlo. The 30-year-old moved to South-Africa in the summer of 2013 and has played for Sundowns, FS Stars, and currently Maritzburg United, who are ranked last in the ABSA Premiership. Now, the Belgian, who has been capped 62 times…
Chelsea, Featured Column, Liverpool, NewsNow, VideoGlenn Verbauwhede, Simon Mignolet, Thibaut Courtois
Chelsea put world-record price tag on star player
March 23, 2016 March 23, 2016 Vincent Van Genechten
Chelsea have put a world-record price tag of £73 million on star goalkeeper Thibaut Courtois in an attempt to ward off interest from Spanish giants Real Madrid, according to the Evening Standard. At the moment, Juventus legend Gianluigi Buffon is still the most expensive goalkeeper in football history. The Old Lady payed nearly £40 million to Parma for his services in 2001. However, if Courtois is sold by the Blues at their current price tag, he would overtake Buffon in this regard. The report claims that the 23-year-old Belgium international wants a return to the…
Chelsea, La Liga, NewsNow, Premier LeagueAtletico Madrid, Chelsea, Premier League, Thibaut Courtois
Chelsea fans regret selling star player and want him back [Tweets]
March 21, 2016 Vyom Chaudhary
Chelsea sold their long-serving goalkeeper Petr Cech to Arsenal last summer. The Czech goalkeeper had fallen behind Thibaut Courtois in the pecking order at Stamford Bridge and wanted a move to the North London club. He was granted his wish by Chelsea owner Roman Abramovich due to his cordial relationship with the Blues. Cech seems to have settled quite well at the Emirates Stadium, while at the same time, Courtois has suffered from a drop in his form. Following the Belgian’s performance in the draw against West Ham, many Chelsea fans…
Arsenal, Chelsea, Featured Column, Premier Leaguearsenal, Chelsea, Petr Cech, Thibaut Courtois
Courtois: “Confidence back, but top four is not possible for Chelsea”
February 7, 2016 Vyom Chaudhary
Chelsea goalkeeper Thibaut Courtois admits that a top-finish is out of reach for the Blues this season. The Belgian, however, insists that under interim manager Guus Hiddink, Chelsea are again playing with confidence. The West London club lost nine of their first 16 league fixtures under former manager Jose Mourinho, but following the arrival of Dutch manager, they are unbeaten in eight games. Courtois claims that the Blues have a lot to fight for this season as they are still competing in the FA Cup and the Champions League. He concedes…
Chelsea, NewsNow, Premier LeagueChelsea, Premier League, Thibaut Courtois
Belgians and Chelsea rule Premier League’s most valuable XI
January 28, 2016 January 29, 2016 Vincent Van Genechten
The winter transfer market is nearing its close. Some Premier League teams made a couple of moves, while others seem to be happy with their current squad. Big names usually don’t change teams during January. Therefore, we’ll be looking at the highest rated XI in the Premier League, using a 4-3-3 formation. Note: it’s never easy to put an accurate market value on a player, but Transfermarkt does a pretty good job at it. KEEPER No matter what formation we use, Thibaut Courtois is our goalkeeper. The Chelsea man is rated at…
Arsenal, Chelsea, Everton, Featured Column, Manchester City, NewsNow, Premier Leaguearsenal, Cesar Azpilicueta, Cesc Fabregas, Chelsea, Eden Hazard, Everton, Kevin de Bruyne, Manchester City, Mesut Ozil, Nemanja Matic, Nicolas Otamendi, Premier League, Seamus Coleman, Thibaut Courtois, Vincent Kompany
Chelsea gossip: Mourinho given vote of confidence as Courtois steps up recovery
October 6, 2015 Steve Green
Tuesday’s biggest Chelsea news and transfer gossip. Some Chelsea fans actually claimed Eva Carneiro had placed a curse on their side as they lost 3-1 to Southampton on Saturday, the Metro reports. Carneiro, of course, left her position as the Blues’ first-team doctor on September 22 after Jose Mourinho was accused discriminatory comments towards her. Jose Mourinho has been charged by the FA with misconduct for claiming referees are afraid to give penalties to Chelsea, the Daily Mirror reports. The under-pressure Chelsea boss made the claim in several interviews on…
Chelsea, Premier LeagueEva Carniero, Jose Mourinho, Roman Abramovic, Thibaut Courtois
Jose Mourinho expects Thibaut Courtois to return for Chelsea’s clash with Man United
Chelsea boss Jose Mourinho has given Blues fans a lift by claiming that goalkeeper Thibaut Courtois is in line for a return from injury in December, the Daily Express reports. The Belgian custodian went under the knife in Spain in September after tearing his meniscus in training (via Express). However, Mourinho has moved to bring in a back up while Courtois is on the sidelines in the shape of former Italian international Marco Amelia (via Express). But despite that, Mourinho is confident that Courtois should be back in line for…
Chelsea, Manchester United, Premier LeagueThibaut Courtois
Chelsea gossip: Costa dropped from Spain squad but Porto star targeted
Friday’s biggest Chelsea news and transfer rumours. Jose Mourinho has confirmed Chelsea are in the process of signing veteran Italian goalkeeper Marco Amelia as cover for current no.2 stopper Asmir Begovic, according to the Daily Star. Begovic, who moved to Stamford Bridge this summer from Stoke, is currently deputising for Thibaut Courtois, who is on the sidelines with a knee injury. Diego Costa has been dropped from Spain’s squad for their final two Euro 2016 qualifying fixtures – with Vicente Del Bosque critical of the striker’s antics against Arsenal, the…
Chelsea, Featured Column, Premier LeagueDiego Costa, Giannelli Imbula, Jose Mourinho, Marco Amelia, Thibaut Courtois
Chelsea gossip: Blues target gets confirmed exit and Mourinho vows to stay at Stamford Bridge
September 12, 2015 Steve Green
Saturday’s biggest Chelsea news and transfer rumour roundup. Chelsea boss Jose Mourinho says it was not his decision to sign defender Papy Djilobodji, 26, from Nantes on transfer deadline day, The Independent reports. The 26-year-old moved to Stamford Bridge in a £4m deal in an effort to bolster the Blues’ defensive options after they failed to sign Everton centre back John Stones, despite tabling several bids for the Englishman. Tottenham Hotspur are open to entering a Wembley ground share agreement with Chelsea to avoid the London clubs trying to outbid…
Chelsea, Everton, Premier League, Tottenham HotspurJohn Stones, Jose Mourinho, Papy Djilobodji, Thibaut Courtois, Wembley
Chelsea rule out signing emergency loan goalkeeper after Courtois injury
Chelsea have confirmed that they have no plans to sign a goalkeeper on an emergency loan deal despite losing Thibaut Courtois to a knee injury, the Daily Express reports. Jose Mourinho told reporters that the Belgian international will be on the sidelines for “quite a long time” after sustaining an injury to his right knee in training on Wednesday (via Express). That means that summer arrival Asmir Begovic will be handed the chance to shine against Everton this weekend, with youngster Jamal Blackman backing him up from the bench. And Mourinho…
Chelsea, Featured Column, NewsNow, Premier LeagueAsmir Begovic, Jamal Blackman, Jose Mourinho, Thibaut Courtois
Chelsea gossip: Courtois out for “a long time” but Brazilian defender back on Blues’ radar
Friday’s biggest Chelsea news and transfer gossip. Chelsea goalkeeper Thibaut Courtois, 23, is set for an extended spell on the sidelines after injuring a knee in training, the London Evening Standard reports. That means deputy Asmir Begovic will now get the opportunity to shine in his absence. Courtois also requires knee surgery and will be out for “quite a long time”, manager Jose Mourinho has confirmed, the BBC reports. The 23-year-old Belgium international damaged his medial ligaments during training on Wednesday. Chelsea transfer target Marquinhos is growing increasingly unsettled at…
Chelsea, Everton, Ligue 1, Premier League, PSGJose Mourinho, Marquinhos, Papy Djilobodji, Radamel Falcao, Thibaut Courtois
Chelsea predicted line-up vs Everton: Thibaut Courtois to miss clash through injury
September 11, 2015 September 10, 2015 Jordan Harris
After the start they made to the new season, Chelsea would have probably been quite grateful for the international break, as it allowed Jose Mourinho the time to assess how the Blues are going to get their Premier League title defence off and running. Three points on Saturday is arguably a must, even at this early stage of the season, but the Toffees will fancy their chances, especially if they can keep things tight at the back, as the champions have conceded at least two goals in everyone of their…
Chelsea, Everton, Featured Column, Premier LeagueAsmir Begovic, Branislav Ivanovic, Cesar Azpilicueta, Cesc Fabregas, Diego Costa, Eden Hazard, Gary Cahill, John Terry, Nemanja Matic, Pedro, Thibaut Courtois, Willian
Chelsea star a doubt for Everton clash after picking up knee injury
Chelsea may have to play their next clash with Everton without goalkeeper Thibaut Courtois, after the Belgian sustained a knee injury in training, the Daily Express report. The 23-year-old returned from international duty without any problems, but picked up the knock in training (via Express), and now may be forced to watch the Blues from the sidelines. The Express suggest, however, that Jose Mourinho is willing to give the Belgian every chance to prove his fitness before deciding whether to start the game at Goodison Park with either his number…
Chelsea, Everton, Featured Column, NewsNow, Premier LeagueThibaut Courtois
Chelsea news: Stones move could now be easier, and Pogba reportedly agrees pre-contract move
September 10, 2015 Jordan Harris
Here is Thursday’s news and gossip concerning Chelsea: The Blues have been dealt a major blow in their pursuit of Paul Pogba, after the Daily Express suggested that the Juventus man had reportedly agreed a pre-contract deal with Barcelona. The Catalan side’s transfer ban means that a deal can only go through in January. John Stones could be about to sign a new contract with Everton, but the 21-year-old is keen to ensure that the fresh terms make a Stamford Bridge switch easier, according to the Daily Mirror. The England international…
Barcelona, Chelsea, Europe, Everton, Juventus, La Liga, Premier League, Serie AJohn Stones, Louis van Gaal, Paul Pogba, Thibaut Courtois, Wembley
FIFA 16 player rankings 40-31: Chelsea stopper ranked higher than Man United striker Wayne Rooney
On Wednesday, we brought you the first in a series of lists concerning the player rankings on FIFA 16. And today we continue that run down with numbers 40-31, and though there are no major shocks, the placement of certain names will no doubt ruffle a few feathers amongst fans. 40. Gerard Pique – Barcelona Rating: 85 The Barca defender is still in good nick despite having a quiet season by his own standards. 39. Mats Hummels – Borussia Dortmund Rating: 86 Linked with United over the summer, and we…
Barcelona, Bayern Munich, Borussia Dortmund, Bundesliga, Chelsea, Featured Column, Juventus, La Liga, Manchester United, Premier League, Serie AArturo Vidal, Gerard Pique, Karim Benzema, Marco Reus, Mats Hummels, Paul Pogba, Thibaut Courtois, Thomas Muller, Wayne Rooney
Jose Mourinho wants 11 defenders at Chelsea
August 29, 2015 Steve Green
Chelsea boss Jose Mourinho is so worried about his side leaking so many goals so far this season that he has told his squad that they are all defenders, The Sun reports. The defending Premier League champions have already conceded seven goals in their opening three games this term, but the 52-year-old is refusing to lay the blame solely on his back four. “You cannot blame defenders for goals conceded. A team is a team. A good team defends as a team,” he said. “I worked the team. You have…
Chelsea, Premier LeagueJohn Terry, Jose Mourinho, Thibaut Courtois
Chelsea gossip: Pogba named as definitive #1 target and midfielder set to become latest Turkish export
Friday’s biggest Chelsea news and transfer rumour roundup. Chelsea will pursue signing 22-year-old France midfielder Paul Pogba from Juventus over the remainder of the transfer window, The Independent reports. The France international will represent a huge coup for The Blues, but could raise doubts over the future of either Cesc Fabregas or Nemanja Matic. England defender John Stones was targeted by Everton fans at his home in Widnes after handing in a transfer request and is now staying in a hotel, The Sun reports. This comes after he handed in…
Chelsea, Europe, Everton, Featured Column, Juventus, Premier League, Serie AJohn Stones, Jon Obi Mikel, Paul Pogba, Pedro, Thibaut Courtois
Chelsea gossip: Blues to embark on £100m spending spree and winger wanted by Prem giants
Friday’s biggest Chelsea news and transfer rumour roundup. Everton defender John Stones, 21, will put in a transfer request in an attempt to force through a move to Premier League champions Chelsea, The Sun reports. However, Stones is part of a potential £100m double deal for the Blues, who are also keen to sign Juventus and France midfielder Paul Pogba, 22, the Daily Star reports. Chelsea winger Victor Moses, 24, is wanted by Aston Villa and Tottenham, according to the Daily Telegraph. Chelsea goalkeeper Thibaut Courtois, 23, says former Manchester…
Barcelona, Chelsea, Everton, Juventus, La Liga, Premier League, Serie AJohn Stones, Paul Pogba, Pedro, Thibaut Courtois, Victor Moses
Chelsea gossip: Higuain asks to leave Napoli, while two Ligue 1 defenders targeted
Here is Wednesday’s news and gossip concerning Chelsea: Reported Blues target Gonzalo Higuain has asked to leave Napoli this summer, according to the Metro. However, the Premier League champions will have to activate his release clause if they wish to sign him. That would mean paying the Serie A club an eye-watering £66m. Chelsea are also targeting a move for Paris Saint-Germain right-back Gregory van der Wiel, according to the Metro. The approach comes just days after Branislav Ivanovic endured a torrid time against Swansea City winger Jefferson Montero on…
Chelsea, Europe, Ligue 1, Manchester City, Premier League, PSG, Serie AEva Carneiro, Gonzalo Higuain, Gregory van der Wiel, Layvin Kurzawa, Thibaut Courtois
|
cc/2020-05/en_middle_0097.json.gz/line35345
|
__label__wiki
| 0.647309
| 0.647309
|
Iran Reports
Persian/فارسی
2 days ago-Ukrainian unions oppose anti-worker labour law reform
4 days ago-Union calls for increased security as four teachers are killed in the first weeks of 2020
1 weeks ago-unions demand transparent investigation into plane crash
2 weeks ago-IASWI’s Statement on Assassination of Qasem Soleimani and its Aftermath: "Say no categorically and proactively to US warmongering and stand firmly in solidarity with the working class and the poor and oppressed people of Iran, and not the tyrannical Iranian regime, and help strengthen anti-capitalist, anti-poverty and social and economic justice movements in Iran and across the region."
3 weeks ago-McDonald's Peru: 12-hour shifts and death by electrocution
4 weeks ago-The brutal exploitation behind premium priced certified coffee from Brazil
4 weeks ago-STATEMENT: Brazilian National Contact Point fails workers and justice after dam disaster
4 weeks ago-Bonsecours Market employees have no reason to celebrate as the year draws to a close
4 weeks ago-Kazakh leader remains in custody on politically motivated charges
4 weeks ago-Coalition of Ontario unions to launch Charter challenge
Education union reports terrible toll of Turkish military aggression in Northeastern Syria
Syria: Education union reports terrible toll of Turkish military aggression in Northeastern Syria According to one of Education International’s affiliates in Iraq, the Kurdistan Teachers’ Union, the Turkish attack in Northeastern Syria has already caused immense loss, with 18 teachers…
Bangladesh: Farmers, agricultural workers continue their fight to block commercial release of genetically-engineered rice
The IUF-affiliated Bangladesh Agricultural Farm Labour Federation (BAFLF) and National Women Farmers and Workers’ Association (NWFA) jointly organized a public meeting at the National Press Club in Dhaka on 17 October 2019 to demand the government rescind its decision to…
education nurtures informed, engaged and empowered citizens
In the era of fake news, media literacy is essential for democracies the world over. Educators play a crucial role in helping their students become responsible and discerning citizens who can navigate the increasingly complex media landscape and make informed…
IndustriALL rejects violence and repression against the people of Chile
According to the National Institute of Human Rights, a further 173 people have suffered firearm injuries, while thousands more have been arrested in the anti-government protests. The disturbances in Chile began when President Sebastián Piñera announced an increase in the price…
Workers’ Rights Act amendments a victory for Mauritius unions
Under the act workers will get benefits in insolvencies, and portable retirement gratuity schemes will be introduced. The gratuity is an additional benefit to existing pension funds. The new law allows workers to carry their pensions and retirement benefits to…
Ukrainian miners demand payment of wage arrears
On 29 October, coal miners will come to Kiev from all regions of Ukraine to picket the parliament until their demands to eliminate wage arrears are met. Two IndustriALL affiliates in Ukraine, the Independent Trade Union of Miners of Ukraine and the Trade Union…
About IASWI
The International Alliance in Support of Workers’ in Iran (IASWI) was formed in January 2000, with labour endorsements, particularly from Canadian labour movement, to launch and organize collaborative international solidarity campaigns in support of workers’ rights and struggles in Iran. The lack of free and independent labour organizations, and the lack of the right to strike in Iran, have created great obstacles for workers in their struggles for the realization of their rights and demands. The working class in Iran needs the international support of the workers and their organizations in other parts of the world in its struggle.
>>To support workers’ struggle in Iran for better working conditions and living standards;
>>To advocate for workers’ movement demands in Iran, including the right to organize free and independent labour organizations and the right to strike;
>>To strive for an absolute end to the systematic repression, persecution, imprisonment, torture, assassination and execution of labour activists and political opponents in Iran;
>>To promote the implementation and enforcement of internationally recognized human and
workers’ rights and freedoms for all people in Iran.
Ukrainian unions oppose anti-worker labour law reform
Union calls for increased security as four teachers are killed in the first weeks of 2020
unions demand transparent investigation into plane crash
IASWI’s Statement on Assassination of Qasem Soleimani and its Aftermath: “Say no categorically and proactively to US warmongering and stand firmly in solidarity with the working class and the poor and oppressed people of Iran, and not the tyrannical Iranian regime, and help strengthen anti-capitalist, anti-poverty and social and economic justice movements in Iran and across the region.”
McDonald’s Peru: 12-hour shifts and death by electrocution
The brutal exploitation behind premium priced certified coffee from Brazil
STATEMENT: Brazilian National Contact Point fails workers and justice after dam disaster
International Alliance in Support of Workers in Iran © 2017 All Rights Reserved.
|
cc/2020-05/en_middle_0097.json.gz/line35350
|
__label__wiki
| 0.679048
| 0.679048
|
The first ever funny rhyme by the world-famous creators of The Gruffalo. The book where it all started! But how will this daft story end…? The old lady’s house is poky and small. Gosh, what a squash! What a squeeze! But with a cow on the table, a goat on the bed and a pig in the larder munching her bread… not to mention a big flapping hen, can she make her house feel big and empty again? A hoot of a story, bursting with comic energy and with a feelgood lesson tucked inside. Squash up and enjoy!
The first story by the star team behind The Gruffalo
A laugh-aloud rhyming classic full of animal antics
Julia and Axel are the UK’s top picture book team
Valuable message about appreciating what you have
“My readers collapsed in heaps, and then had to have it read again. And again.” Vivian French, Guardian
most of you liked this
How can they fit . Hee
loobyloulou123
Cheerforevers
This is about a lady whos animals trash her house.
We liked the pig because he was funny.
We liked the chicken because it flew out the window.
We liked the cow because it was too big for the house.
LilaWonderful
This book is a squash and a squeeze. well this book a got a lot of UGH GET OUT OF MY HOUSE ad this book is really,really amazing.
unicorn3
Meme30
ellielin
Dumbo123
Raccoon11
Julia Donaldson is one of the UK’s best loved authors, known for brilliant picture books like The Gruffalo, Room on the Broom and Stick Man. She was also the Children’s Laureate 2011-2013.
Julia has won many major book prizes, including the Smarties and Blue Peter Awards for The Gruffalo, the Blue Peter and Sheffield Children’s Book Prizes for Room on the Broom, the British Book Awards Children’s Book of the Year for The Gruffalo’s Child and the Red House Award for Super Worm. Julia was also the Children’s Laureate 2011-2013.
Axel is the illustrator of The Gruffalo and many other favourite picture books.
Axel has won many of the major book prizes, including the Smarties and Bluue Peter Awards for The Gruffalo, the Blue Peter and Sheffield Children’s Book Prizes for Room on the Broom, the British Book Awards Children’s Book of the Year for The Gruffalo’s Child and the Red House Award for Super Worm.
|
cc/2020-05/en_middle_0097.json.gz/line35351
|
__label__cc
| 0.637397
| 0.362603
|
Bulgaria rejects an offer to join NATO Black Sea fleet
SOFIA, Bulgaria — PM of Bulgaria Boyko Borissov announced on Thursday that Bulgaria will not join NATO flotilla consisting of Turkey and Romania naval forces.
Sofia – Capital of Bulgaria (Image:en.wikipedia.org)
Bulgarian Prime Minister contradicted previous statements in favor of joining NATO Black Sea fleet made by the President of Bulgaria and the Defense Minister, arguing that he doesn’t want to see military ships in the coastline resorts that Bulgaria invested so much in.
Boyko Borissov – Prime Minister of Bulgaria (Image:en.wikipedia.org)
Borissov, the leader of the GERB (Citizens for European Development of Bulgaria) party, found himself in the middle of the tensions between Russia and Turkey. Turkey repeatedly requested more NATO presence in the Black Sea – calling it “Russian Lake”. Russia on the other side warned Bulgaria against any military build-up in the Black Sea.
Romanian president Klaus Iohannis, who visited Bulgaria on Wednesday and Thursday this week, and proposed the initiative of NATO fleet in the Black Sea to the Bulgarian PM denied that NATO has any intentions or enough resources to create and maintain the fleet.
Iohannis explained to the press that the “sole purpose” of the initiative is “practical cooperation in joint exercise” of Bulgarian, Romanian and Turkish forces.
Tensions between Turkey – a NATO member and Russia started in November of last year, when Turkey shot down a Russian jet that violated its airspace Turkish air space.
Tensions between Russia and NATO escalated last week when United States’ warship USS Porter entered Black Sea, triggering a response from Moscow which promised “response measures”, and warned Bulgaria against any build up in the region.
Washington responded with a statement noting that the US will maintain its presence in the Black Sea despite the warnings from Kremlin. Officials of the US Navy explained that the main reason of US presence in the Black Sea is “to deter potential aggression”.
NATO Black Sea fleet is a project of possible joint task naval force consisting of three NATO member states: Turkey, Romania and Bulgaria, initiated in spring of 2014 after annexation of Crimea by Russia. Ukraine, a non-member of NATO expressed willingness to join as well.
It is expected that Black Sea fleet will be discussed on upcoming NATO Summit in Warsaw.
Dejan Scepanovic
based in Bosnia and Herzegovina. BA in political science, columnist.
06/18/2016 Bulgaria / Black Sea, Black Sea fleet, Boyko Borissov, Bulgaria, Klasu Iohannes, NATO, Romania, Turkey. Russia, United States
At least 10 people killed, 24 injured in fighting near Somali capital
Schoolgirls released by Boko Haram reunited with parents
A suspected U.S. surveillance drone crashes in Somalia
At least 10 people killed, 24 injured in fighting near Somali capital 10/17/2016
Schoolgirls released by Boko Haram reunited with parents 10/17/2016
A suspected U.S. surveillance drone crashes in Somalia 10/16/2016
Afghan vice-president survives the Taliban ambush 10/16/2016
Montenegro: 20 citizens of Serbia arrested on terrorism charges on Election Day 10/16/2016
|
cc/2020-05/en_middle_0097.json.gz/line35362
|
__label__cc
| 0.594591
| 0.405409
|
A dangerous unpunished push by Zaha – changed this game as he deliberately pushed Pepe into Torreira who was injured…
The similarities between Arsenal’s performances in the Chelsea and United games were striking. Energy and zest in the first half…
Good start – bad finish. Mikel Arteta said there was a difference in the fitness of the two teams –…
The two that got away
Solid and encouraging performance in this 1-1 draw at Bournemouth. Arsenal could have won three precious points if Lacazette had…
Round | Arteta’s press performance | ASA demands
Steve Round, part of Mikel Arteta’s backroom staff has good experience particularly in defence. He worked in the England set-up…
More posts and stories…
Arsenal’s most successful manager was superb for most of the 12 seasons analysed in this insightful and detailed paperback. Yes, Arsene Wenger changed English football. This essential Arsenal book is now available from Amazon and is also available from
iTunes for the iPhone, iPad or iPod touch. Cost: £6.99.
|
cc/2020-05/en_middle_0097.json.gz/line35363
|
__label__wiki
| 0.796142
| 0.796142
|
Opinions differ on downtown Aspen noise
Karl Herchenroeder
Vanessa Vieni, left, and Katie Kowalski have a drink Monday evening on the Square Grouper patio.
Karl Herchenroeder/The Aspen Times |
Both Karen Day and Mari Peyton have lived in downtown Aspen for 32 years. Day lives in a condominium adjacent to Rubey Park Transit Center, next to McDonald’s, while Peyton lives in an apartment on the Cooper Avenue pedestrian mall.
Both are aware of ambient noise coming from the mall, particularly from the Red Onion, where local musicians gather for weekly open-mic nights. They’re also both aware of the Aspen City Council’s desire to boost allowable noise levels and extend nighttime noise hours, with an official vote expected in June. But Day and Peyton differ on what they’d like to see from the vote’s outcome.
The proposed changes stem, in part, from a dispute that played out in Aspen Municipal Court in January between the Aspen Brewing Co. and downtown penthouse owners Michael Sedoy and Natalia Shvachko. The couple phoned police 23 times between late December 2012 and early September 2013 to complain about sounds coming from the East Hopkins Avenue bar. Although the brewer received three separate citations from the city, a six-person jury absolved the restaurant of any wrongdoing.
Peyton — a former member of the Planning and Zoning Commission and an Aspen Times proofreader for 20 years, who retired after selling her wholesale tour operation to Ski.com — is disappointed with council members. She said they are acting on the assumption that all downtown residents are “spoiled, newcomer” billionaires living in penthouses.
“That is not the case,” Peyton said, adding that she knows plenty of others like her who have worked hard to make the core their home. “This one couple has created a mess for all of us.”
Day said that noise is the price she pays for living in the core. When she moved here, she had a parking space for her Rubey Park condo, where she and her late husband, Sterling Greenwood, published the Aspen Free Press.
“There’s so many benefits to living downtown that it’s not fair for me to complain about any noise at all,” said Day, who retired after running her own interior-design business.
For Jesse Wey, co-owner of The Square Grouper, a restaurant adjacent to the Aspen Brewing Co., upping the decibel level is a move that has been a long time coming.
“It’s a call that should have been made a while ago, especially given the nature of this block,” he said, speculating that the lobby of the Pitkin County Library can get louder than the city’s allowable volume. “The decibel level was far too low to begin with.”
Peyton would like to see the noise ordinance kept as is, while Day said she is OK with all of the proposed changes. The majority of the council’s desire is to boost allowable volume at night from 60 decibels to 65 decibels and extend “nighttime noise” hours from 9 p.m. to 11 p.m. A 10-decibel increase equates to “double the loudness,” according to Environmental Health Director C.J. Oliver.
The council also expressed interest in changing the way police take sound readings, which Peyton takes issue with. If approved, police would conduct “closed building” measurements, meaning all windows and doors would need to be shut at the time of the reading.
“The reading when your windows are open is the reading that affects the people, not the reading when it’s in an artificial situation,” Peyton said. “Nobody can keep their doors and windows shut in the summer. They’re not going to be able to breathe.”
Peyton has spoken with others who share her opinion, saying that even people living on the perimeter to the downtown core have trouble sleeping at night with the current ordinance.
“And they feel that the city is saying, ‘We don’t care about you. We don’t care if you sleep,’” she said.
Day said that if she had to complain about anything, it would be about the noise from amplifiers at the Food & Wine Classic in Wagner Park and from World Cup events on Aspen Mountain. Her three skylights — in the kitchen, living room and bathroom — are particularly susceptible to the loudspeakers.
“The worst is the World Cup because those speakers run for 10 solid days, and you can’t possibly shut them out,” she said.
Regardless, she said she’s fine with whatever direction council takes.
“My feeling is I want what’s best for the town,” Day said. “And the joy I have of living downtown, the convenience of living downtown, outweighs that aggravation.”
herk@aspentimes.com
City of Aspen
Government Job Opportunities at City of Aspen in ASPEN
Now Hiring! Utilities Resource Manager Records Manager Business Analyst II Mechanic II Early Childhood Teacher…
Town Engineer at Town Of Eagle in EAGLE
Town Engineer $81,941-$98,329 Requires: - 5-10 yrs experience - Civil Eng Degree - PE Certification…
Full & Part Time Club Assistants (Driver/Bellman) at The Timbers Club in SNOWMASS VILLAGE
Now Accepting Applications for the following positions: Full & Part Time Club Assistants (Driver/Bellman) Must…
Line Cook/Pantry Cook/Dishwasher at Jimmy's in ASPEN
Line Cook/Pantry Cook/Dishwasher Jimmy'sFT/PT, PM shifts, will train. $18+/hr with experience Jimmy's Aspen area preferred.…
Starwood Metropolitan District
Security Officer at Starwood Metropolitan District in ASPEN
Security Officer Starwood Metropolitan District is seeking a FT security officer for the gatehouse to…
Temporary Info Center Host at Town of Eagle in EAGLE
Temporary Info Center Host $13 – $14/hr. Temporary position for December & January works Fri,…
|
cc/2020-05/en_middle_0097.json.gz/line35366
|
__label__wiki
| 0.51325
| 0.51325
|
Relocation & Help Moving to Vietnam
Couriers & Delivery Services
Freight Forwarding & Shipping
IT, Security & Network Installations
Web Site Design & Hosting
Vietnamese Lessons & Language Schools
Party & Wedding Planners
Baby Sitting & Nanny Services
Investments in Vietnam
Bakers, Cakes & Pastries
Breweries & Brewhouses
Cafes & Coffee Bars
Butchers & Meat Suppliers
Cosmetic Surgery & Treatments
Physiotherapy, Osteopathy & Chiropractors
Weight Loss, Slimming & Nutrition
Doctors & Medical Practitioners
Hairdressers, Manicure & Pedicure
Spas, Massage & Beauty Treaments
Air Conditioning & Fans
Domestic Services, Maids & Cleaners
Ayasan Vietnam
Property Rental & Housing Agents
Kitchen & Catering Equipment
Supermarkets & Grocery Shops
Sports Clubs & Associations
HCMC Blogs & Websites
Ferries & Cruises
Vietnam Web Portals
Exhibitions & Art
Saigon Book
Stocks a comprehensive range of books and magazines with a range in English. Has online ordering and home delivery. 474-476 Nguyen Thi Minh Khai St., Dist. 3 and 217/4 No Trang Long St., Dist. Binh Thanh, Ho Chi Minh City
CALL (08) 38355907
RMIT Library
Provides a wide range of books, videos, DVDs, CDs and magazines. Services include a computer centre for research and public internet access. 702 Nguyen Van Linh St., Dist. 7, Ho Chi Minh City
University of Social Sciences and Humanities Library
Offering a range of specialised education and research materials. Translation, counselling and training classes also available. 10-12 Dinh Tien Hoang St., Dist. 1, Ho Chi Minh City
The Alcove Library Hotel
With a wide range of services including airport shuttle service, currency exchange, restaurant and a bar. A library is also available at the main reception. 133A Nguyen Dinh Chinh St., Phu Nhuan Dist., Ho Chi Minh City.
Nguyen Hue Bookstore
Offering a range of Vietnamese and English books, magazines, DVDs and souvenirs. 40 Nguyen Hue St., Dist. 1, Ho Chi Minh City
Agriculture and Forestry University Library
Learning centre of Agriculture and Forestry University, offering a range of materials and data for reading and research purposes. Tan Phu St., Thu Duc Dist., Ho Chi Minh City
Hub Cafe
Coffeehouse with more than 10,000 books including fiction and non-fiction in Vietnamese and English. 18A Cong Hoa St., Tan Binh Dist., Ho Chi Minh City
Phuong Nam Bookstore
Has more than 30 bookstores in Vietnam and offers a wide range of books and magazines, Phuong Nam bookstores are one of the leading retail chains in Vietnam. 2nd Floor, Parkson Center, 35 and 45 Le Thanh Ton, St. Dist. 1, Ho Chi Minh City
General Science Library
The biggest library in Ho Chi Minh City with more than 500,000 books and 100,0000 magazines offering professional services such as loan services, computer centre and reading rooms. 69 Ly Tu Trong St., Dist. 1, Ho Chi Minh City
Me & Con Bookstore
Children bookstore, offering a range of books and products suitable for parents and children. 46 Le Loi St., Dist. 1, Ho Chi Minh City
Banking University Library and Information Center
Offering a wide range of education and research materials for students to access on and offline. 39 Ham Nghi St., Dist. 1, Ho Chi Minh City
Architecture University Library
Offering a range of education and research materials for architecture students. 196 Pasteur St., Dist. 3, Ho Chi Minh City
Ho Chi Minh City - Change Location
|
cc/2020-05/en_middle_0097.json.gz/line35370
|
__label__cc
| 0.683273
| 0.316727
|
Joel Oppenheimer, Inc.
Conservation Affiliates Program
System of Anatomical Plates of the Human Body
Lizars Pl. 16, View of the Deeper Muscles, Blood...
https://www.audubonart.com/shop/product/oeli-016-lizars-pl-16-view-of-the-deeper-muscles-blood-5472
$ 50.00 $ 50.00 50.0 USD
Published by Oppenheimer Editions, 2016
Oppenheimer Editions Print
Blind embossed with the Oppenheimer Editions logo
A System of Anatomical Plates of the Human Body—Published by Oppenheimer Editions
John Lizars (1787—1860) was a Scottish surgeon, anatomist and medical author. A System of Anatomical Plates of the Human Body was originally issued in 12 parts from 1822 to 1826 and is comprised of 101 hand-colored engravings. William Home Lizars (1788—1859) a painter and well-known engraver in Edinburgh, engraved his bothers plates. William Home Lizars is well-known for engraving John James Audubon’s earliest plates from The Birds of America. John Lizar's "superb atlas is certainly one of the most elegant works [on anatomy] of the nineteenth century " (Heirs of Hippocrates, Richard Eimas, 1436).
Established in 1999, Oppenheimer Editions has partnered with prestigious museums to make prints from their holdings. Works from the New-York Historical Society’s unrivaled collections of John James Audubon’s watercolors and the Hudson River School paintings are examples of art that otherwise would be unobtainable. Among the institutional collections we have partnered with are the American Museum of Natural History, the Field Museum, and Royal Botanic Gardens, Kew. These are not mere reproductions. They are limited-edition fine art prints made with the finest quality archival pigments on rag watercolor paper and executed to exacting standards.
Click here for more Lizars prints from A System of Anatomical Plates of the Human Body published by Oppenheimer Editions
Specifications for Lizars Pl. 16, View of the Deeper Muscles, Blood...
Type of Artwork Oppenheimer Editions Print
Framed Option Available After Adding Item to Cart
Joel Oppenheimer, Inc. - About us
Joel Oppenheimer in his historic gallery
Joel Oppenheimer Inc. is located in Chicago’s historic Tree Studios. We are passionate about natural history art, offering superb examples of rare works by John J. Audubon, Mark Catesby, Alexander Wilson, Pierre-Joseph Redouté, Dr. Robert Thornton, Basilius Besler, John Gould, Edward Lear, and other important natural history artists.
Copyright © Joel Oppenheimer, Inc.
|
cc/2020-05/en_middle_0097.json.gz/line35372
|
__label__wiki
| 0.722281
| 0.722281
|
ReviewsMovie Review
In Free Solo, thrilling climb footage fights for time with pat psychologizing
Vikram Murthi
Filed to:Movie Review
Photo: National Geographic Documentary FIlms
Elizabeth Chai Vasarhelyi, Jimmy Chin
Select theaters September 28
Alex Honnold is a climber, but not the ordinary kind: He free solo climbs extremely high, very dangerous big walls. Free soloing is a form of climbing that entails scaling a surface alone and without the assistance of any protective equipment. There is essentially no margin of error in free solo ascents; any mistake can prove to be fatal. Many professional climbers have fallen to their deaths while soloing, and while that might prevent some people from continuing the practice, it barely fazes Honnold. He intimately understands the risks, but forges forward anyway, partially because soloing makes life feel more immediate. It’s the thrill of the climb that keeps him alive.
Elizabeth Chai Vasarhelyi and Jimmy Chin’s documentary Free Solo chronicles Honnold’s groundbreaking free solo climb of El Capitan in Yosemite National Park, a 3,300-foot slab of granite that has been a popular climbing site for years. Armed with a team of professional climbers doubling as cinematographers, Chin and Vasarhelyi intimately capture Honnold’s various solo climbs and practice runs before the major ascent. Free Solo’s climbing footage reliably provokes awe and wonder, not to mention terror, and certain high-angle shots emphasize the obvious borderline-suicidal danger of Honnold’s raison d’être. He’s most compelling as an interview subject when he dives deep into the machinations of soloing—feet placement, complicated hand movements to ensure stability, the numerous obstacles unique to certain pitches on a climb, his assessment of risk. Generally speaking, Free Solo excels whenever it focuses on process and Honnold’s actual climbs, which also highlight Chin and Vasarhelyi’s filmmaking craft. (Free Solo is one of the few documentaries in recent memory to justifiably employ drone cameras, mainly to capture certain angles that no person on the ground could secure on their own.)
Unfortunately, Free Solo suffers when Vasarhelyi and Chin psychologize Honnold or attempt to explain his drive for death-defying climbs. It’s understandable why the filmmakers would want to examine Honnold’s psyche, given that his Spock-like demeanor and curiously casual approach to soloing does raise certain questions about his mental stability or lack thereof. Yet every “answer” they ascribe to him (or he ascribes to himself) feels pat and unconvincing. Honnold mentions his father, who was emotionally unavailable to Honnold’s mother but also spurred his son’s interest in climbing. He describes his “dark soul” as a child and his “bottomless pit of self-loathing.” There’s some talk about being a loner in school. Yet none of those explanations are as persuasive as an MRI diagnosis that simply concludes he requires more stimulus than most people. Similarly, Free Solo’s fixation on how soloing affects Honnold’s relationship with his girlfriend feels transported from a more banal film altogether. At best, this material is uninteresting filler, and at worst, it’s a distraction.
While the psychological analysis fails to captivate, Free Solo gets interesting when actively interrogating the ethics of filming Honnold on his climbs. Vasarhelyi and Chin correctly identify the queasy voyeurism of filming such stunts, given that their subject could fall to his death at any moment. Their concerns only increase when Honnold voices trepidation at being filmed on El Capitan at all after an anxious practice run. (His awareness of being filmed affects his confidence on the climb.) As a result, Honnold’s solo climb up El Capitan, a disappointingly brief section of the film, is understandably circumscribed to ensure his safety. Chin and Vasarhelyi keep cutting away from Honnold to the cameramen on the ground, who provide nervous spectator commentary, constantly reiterating the danger that Honnold faces every time he surpasses a new pitch. It’s a needless effort to explicate the stakes, but one that makes sense considering that a more in-your-face method might fatally disturb Honnold. It’s easy to imagine an exposition-free, process-focused version of Free Solo that exclusively follows the El Capitan climb, which would enthrall entirely on the basis of Honnold’s physical prowess. As it stands, however, Free Solo still has plenty to offer in the edge-of-your-seat department.
The mountain climbers of extreme sports doc Meru are either brave or insane
Expert recreations add suspense to this mountain-climbing disaster doc
Everest will make you want to stay indoors
Vikram Murthi is a freelance writer and critic currently based out of Brooklyn.
|
cc/2020-05/en_middle_0097.json.gz/line35378
|
__label__cc
| 0.608557
| 0.391443
|
What is engagement?
To continue with our recommended settings, please click 'Accept'. This will apply cookies that are non-essential for the website's core functionality. Essential cookies are mandatory as the website cannot function properly without these.
To edit your settings or for more information on the non-essential cookies we use, please click 'View Options'.
If you have previously visited this site, cookie options may have already been saved on your browser. These settings will need to be removed before your new choices can take effect. Please see our cookie policy for more information about how to do this.
Preferences* - These cookies remember the settings you have chosen in previous site visits, facilitating the personalisation of your user experience. Analytics - These cookies allow us to make informed decisions about how best to improve the experience you have on our website. Marketing - These cookies let us deliver content that you want to see and allows us to contact you if legitimate interest is shown in the services we offer.
*Please note that preference cookies for videos embedded on our website are set by a third-party, therefore cannot be disabled by opting out. For more information about how to prevent these cookies from being set on your browser, please see our cookie policy for 'do not track' (DNT) instructions.
To review cookie options in the future, this banner can be found within the footer area of our website.
Home » Company Profile
Latest BCI Score
Lingerie and Swimwear Manufacturer
http://www.wacoal-europe.com
The Corsetry Factory, Rothwell Road, Desborough, Northants, NN14 2PG
About Wacoal Europe
Wacoal Europe, based in Northamptonshire, are leaders in the A-K cup, 28-48 back size intimate-apparel market. They offer a whole family of brands, each with their own personality and position in the market.
The company’s strength is in realising that one size does not fit all: every woman differs in her size, shape, taste and how she feels. The company offers high-quality, fashion-conscious lingerie and bra-sized swimwear stocked in over 5,000 retailers in more than 30 countries.
Under Chief Executive Officer Geoff Embley, around 465 people work in the UK office, production centres and sales offices across the world. Materials are responsibly sourced from trusted suppliers around the globe in more than 30 countries. They’re manufactured with rigorously applied employee-welfare policies and practices.
The firm has made huge efforts to reduce their ‘bra miles’ and are shrinking their carbon footprint more by constantly challenging the supply chain and adopting both local and international improvement initiatives.
What is it like to work for Wacoal Europe
69% of staff agreed:
I have confidence in the leadership skills of the senior management team
Leaders lead with their behaviours. They talk and listen to all, accept that no idea is a bad idea and are open, participative and respectful of individuals. The CEO is always available, will talk with anyone and is committed to taking the corporate message around the globe.
67% of staff disagreed:
My health is suffering because of my work
Wacoal offer support for paid time off for all for NHS health screening. This support is offered on an individual basis, depending on need and circumstances.
I believe I can make a valuable contribution to the success of this organisation
The company aims to help women express their beauty. Core values are to act with ‘mutual trust’ and honesty and integrity, live by the laws of the land and report any wrongdoing. Workshops for all help create a vision of the future.
Learn more about the 8 factors of workplace engagement here
At least 20% of staff are known to undertake charitable activities during business hours without incurring financial loss
At least 40% of senior managers are women
Earning £35,000+:
Male : Female:
Staff Turnover:
UK sites:
Average Age:
Want to get on the list or be accredited?
Start your engagement journey today and find out what you need to do to earn a Best Companies accreditation or a place on the Best Companies lists.
For a better workplaceTM
© Copyright Best Companies 2020
|
cc/2020-05/en_middle_0097.json.gz/line35381
|
__label__cc
| 0.5445
| 0.4555
|
South Dakota Trails
Rapid City Blog: Crazy Horse Memorial
Lisa Jhung
We got a little lost on our drive to Crazy Horse Memorial (but what’s a road trip without an unplanned detour?), so when we got there, Mark and I chuckled about the low-lying clouds covering the massive sculpture seeming fittingly humorous. But we were optimistic, and figured the clouds would move out, so we took the kids into the Visitor Center that doubles as the Indian Museum of North America. We marveled at all the American Indian artifacts, the beautiful wood interior, and teepee replica. The kids enjoyed exploring what Indians used for toys and tools.
The four of us then sat down in a nice auditorium for a short movie about the history of the memorial—how one man, an Irish/Polish sculptor named Korczak Ziolkowski, took on the project at the asking of Lakota Chief Standing Bear. “My fellow chiefs and I would like to white man to know the red man has great heroes, also,” wrote the chief, referencing nearby Mount Rushmore. Starting in 1947, at age 40, Korczak worked on Crazy Horse for the rest of his life.
It might have been the footage of blasting dynamite, but my boys stayed glued to the screen for the whole 20 minutes. We learned that, to this day, the memorial works off of private funding and donations only—no government grants—so the process is slow-going. We learned that Korczak and his wife Ruth had 10 children, and most of them dedicated their lives to the Memorial. I felt moved by the meaning of all of it, and grateful that my kids were exposed to the history of the American Indian people and the hard work and dedication necessary to keep the work on the memorial going.
When the film ended, we exited the auditorium into a room with large picture windows. And, what do you know? The fog had lifted, and there was Crazy Horse in his glory.
Rapid City Trails
Rapid City Blog: Mount Rushmore & Crazy Horse
Rapid City Blog: Family Shenanigans
Rapid City Blog: Oh, the Granite
Rapid City Blog: Impressive Learning Center
Rapid City Blog: Downtown Trails and Recreation
Rapid City Blog: Jewels Above and Below Ground
Rapid City Blog: Custer State Park Safari
Rapid City Blog: The Opposite of Camping Can be Fun
Rapid City Blog: Badlands
|
cc/2020-05/en_middle_0097.json.gz/line35383
|
__label__wiki
| 0.640899
| 0.640899
|
BAE Systems Announces Proposed acquisition of Collins Aerospace’s Military Global Positioning System Business and Raytheon’s Airborne Tactical Radios Business Jan 20 2020
What we doProducts & ServicesRadar Operations, Maintenance and Sustainment
Radar Operations, Maintenance, and Sustainment
We develop and manufacturer precision instrumentation radar systems and electro-optical tracking systems and are a recognised leader in test and evaluation, training range operations and maintenance, as well as design and manufacture.
In 1974, BAE Systems introduced a computer-based, precision tracking range instrumentation radar, which offered flexibility and capability not previously available in support of TSPI. Since then, BAE Systems has continued to enhance its computer-based radar systems, with each delivery, and offers a field-proven, TSPI solution for future test range requirements. Today, BAE Systems continues to build the range instrumentation systems sought for modernization programs on test and training ranges around the world.
Test range instrumentation equipment includes:
Integrated optical tracking systems
TSPI tracking systems, range control centers
Flight termination systems
Wideband imaging radar systems
Test range instrumentation
BAE Systems provides the test and training range community a variety of products, capabilities and services to replace, enhance, upgrade, modify and sustain range instrumentation systems and subsystems. Over 90 percent of the BAE Systems’ TSPI systems, produced over the last 30 years, are still in use today, and actively supported and sustained via various sustainment programs within BAE Systems. BAE Systems has low cost, field-proven solutions that can be provided in fixed, transportable and/or mobile configurations, which leverage leading edge technology and are logistically supportable.
|
cc/2020-05/en_middle_0097.json.gz/line35385
|
__label__wiki
| 0.854795
| 0.854795
|
Antonio Castilla on choreographing My First Ballet: Swan Lake
Image: Choreographer Antonio Castilla in rehearsals for My First Ballet: Swan Lake © Photography by ASH.
Ahead of My First Ballet: Swan Lake opening in London today, we sat down with Antonio Castilla, English National Ballet’s Ballet Master and Repetiteur. Hear more about this brand new version of the classic ballet which he has choreographed especially for children aged three upwards.
Can you tell us about the My First Ballet series?
English National Ballet and English National Ballet School’s My First Ballet series takes popular ballets and adapts them especially for young audiences. This year we have created a new version of the well-known classical ballet, Swan Lake.
Can you tell us about your choreography background?
I started choreographing in San Francisco for a small professional company and also San Francisco Ballet School. Then, when I moved to London I created pieces for Ballet Central and later the Royal Ballet School.
Victor Gonzalez Perez, Valerio Zaffalon and Antonio Castilla in rehearsals for My First Ballet: Swan Lake © Photography by ASH.
What do you enjoy about choreographing?
I enjoy the process of creation. It is a voyage that starts in the studio and continues all the way to the stage. The aim is to be really committed to the trip and hope that audiences will get on board.
What made you want to choreograph this new version of My First Ballet: Swan Lake?
It’s the first year I’ve choreographed a ballet for the series and I’m thrilled to be involved. Swan Lake is one of my favourite ballets and the opportunity to work with English National Ballet School and a great artistic team to recreate it for children was an opportunity I welcomed.
Antonio Castilla coaching Beatriz Kuperus in the promotional photo shoot for My First Ballet: Swan Lake © Photography by ASH.
What is it like creating a ballet that’s especially for younger audiences? Can you tell us about what you must keep in mind during the creative process?
Children are truly honest which means they can be one of the toughest audiences! For me this means I also want to be truly honest – with both the story and the choreography. It’s a challenge but also very rewarding.
Can you tell us a bit about this new version of My First Ballet: Swan Lake specifically? What have been your priorities when you have been developing this version?
In this new version of My First Ballet: Swan Lake, we have put the focus on Odile, rather than Odette, with the narrative following her journey and the difficult decision she must make, allowing us to explore important themes of friendship, forgiveness and honesty.
What do the English National Ballet School students gain from performing in My First Ballet?
English National Ballet School students get to experience working at a professional level. Through choreography and direction, we are giving them the opportunity to embrace the work and grow as dancers and performers.
What are your personal highlights of working on My First Ballet?
I really enjoy helping students develop their talents, that is very special. I’ve also really valued the experience of working with both a dramaturg and a narrator. Our dramaturg works with me as I choreograph to help give a narrative to the ballet. During the show, a narrator will be on stage guiding the audience through the story.
English National Ballet School students in My First Ballet: Swan Lake © Laurent Liotardo.
I’m very much looking forward to taking My First Ballet: Swan Lake on tour to audiences around the country. For me, brilliant dancing, beautiful costumes, and of course Tchaikovsky’s wonderful music mean that this production is the perfect introduction to ballet and the joy it can bring!
My First Ballet: Swan Lake opens in London from 29 March – 7 April, then tours nationally to Bromley, Oxford, Manchester, Blackpool, Woking and Torquay until 20 May. Get your tickets.
Eric Snyder and his princely turn in My First Ballet: Sleeping Beauty
American dancer Eric Snyder, a second-year student at English National Ballet School, is performing as Prince Désiré in My First Ballet: Sleeping Beauty. We caught up with him to see how he first started dancing, and what it's been like performing in this new version of the fairy tale classic for children as young as three.
Great reviews for My First Ballet: Swan Lake
The swans of My First Ballet: Swan Lake have been flying across the country on a National tour this past month. Introducing the magic of ballet to children as young as three, this newly adapted version, choreographed by Antonio Castilla and performed by students of English National Ballet School, has cast its spell on audiences and critics of all ages.
Black swan – Beatriz Kuperus on playing Odile in My First Ballet: Swan Lake
As My First Ballet: Swan Lake continues its national tour – heading to Oxford this weekend – catch up with Beatriz Kuperus, an English National Ballet School student dancing the fiery role of Odile in this adaptation for young children.
Harvey Littlefield on performing as Prince Siegfried in My First Ballet: Swan Lake
My First Ballet: Swan Lake is commencing its national tour this weekend, following sold out performances in London. We caught up with Harvey Littlefield, a student of English National Ballet School, on what it’s like performing the dashing role of Prince Siegfried in this shortened version especially for children aged three upwards.
Chloe Keneally on dancing role of Odette in My First Ballet: Swan Lake
Following the opening of My First Ballet: Swan Lake in London last week, hear from one of its stars, English National Ballet School student Chloe Keneally. She performs the iconic role of Odette in this version of the classic ballet for young children.
We’re very excited to announce our 2018-19 season, featuring Lest We Forget, Kenneth MacMillan’s Manon, Derek Deane’s Swan Lake, Wayne Eagling’s Nutcracker, She Persisted (a triple bill of works by Stina Quagebeur, Annabelle Lopez Ochoa and Pina Bausch) and Christopher Wheeldon’s Cinderella in-the-round.
|
cc/2020-05/en_middle_0097.json.gz/line35387
|
__label__wiki
| 0.817639
| 0.817639
|
Home News & Community Changing Suit
Changing Suit
A Baltimore brainstorming session yields better protection for Ebola caregivers.
By Amy Mulvihill - March 2015
A Hopkins Hackathon Leads to Improved Ebola Suit
-Photography by Christopher Myers
In late October, 65 people from all walks of life convened at The Johns Hopkins University for a weekend hackathon. But rather than debugging the latest software, the task at hand was designing a better personal protective equipment (PPE) suit.
The suits, used in medical emergencies such as the recent Ebola outbreak in West Africa, have many virtues, but many flaws as well. They are incredibly hot, difficult to put on and take off, provide poor visibility, and have coverage gaps that can expose health-care workers to pathogens.
Dr. Harshad Sanghvi, vice president of innovations and medical director at the Hopkins-affiliated global health organization Jhpiego, was especially concerned after learning that 16 health-care workers trained by Jhpiego had died in the Ebola outbreak. "We felt that if we are going to send some of the brightest of our people to fight any disease, we have an incredible responsibility to make sure they remain safe," he says.
Jhpiego teamed up with Hopkins' Center for Bioengineering Innovation & Design (CBID) to host the hackathon, welcoming participants from the fields of public health, technology, academia, and fashion, among others. At the end of the weekend, the group had a suit that was cooler, easier to don and doff, and more protective.
Admits Youseph Yazdi, the executive director of CBID: "I was amazed. I wasn't sure that the hackathon event would come up with anything new." The result was entered in a design competition sponsored by U.S. Agency for International Development (USAID), and announced as a winner in December.
Now they are further testing the suit and will start production soon. Both Sanghvi and Yazdi attribute the breakthrough to what Sanghvi terms a "meeting of unlike minds." Agrees Yazdi: "If you want something new, you have to ask a broader group of people with fresh ideas."
News & Community The Johns Hopkins University Ebola Jhpiego
Give Baltimore Guide 2019
A special section for the season of charity.
The Chatter
National Aquarium and Other Attractions Offer $1 Admission This Weekend
Here’s where to go and what to see without breaking the bank.
Cardinal Shehan Choir Heads Back to ‘The View’ on MLK Day
This time, the group will be joined by Krieger Schechter and sing with Billy Porter.
The Life of Reilly
From a secret backroom location, we sit down with the one-time nun-in-training, former Romper Room teacher, and still-serious poker player.
Redefining Music Education in Baltimore
The Baltimore School of Music shares their top community initiatives and how they extend music appreciation to all ages.
Why This Former Orioles Prospect Decided to Start a CBD Company
Steve Bumbry, the son of O’s Hall-of-Famer, Al, knows about pain and recovery.
Signal Station North Hopes to Light Up the Neighborhood at Night
New initiative aims to draw foot traffic by illuminating artwork and businesses.
Cameo: Andy Cook
We sit down with the campaign director for Made in Baltimore.
Meet the Ravens’ 25-Year-Old, Number-Crunching Whiz Who Has John Harbaugh’s Ear: Park School alum Daniel Stern helps call the game-changing shots for his hometown team.
|
cc/2020-05/en_middle_0097.json.gz/line35388
|
__label__wiki
| 0.853161
| 0.853161
|
Alan Peter Porciello reads a statement during his sentencing in Deschutes County Circuit Court on Tuesday, Jan. 14, 2020.
Garrett Andrews/The Bulletin
Alan Peter Porciello, left, arrives at his sentencing in Deschutes County Circuit Court on Tuesday.
Jenny Cashwell is flanked by her daughters, Kayla, 11, left, and Piper, 8.
Bend man gets 9 years in first-date killing
Alan Porciello: 'I know I deserve punishment'
By GARRETT ANDREWS The Bulletin
Garrett Andrews
Alan Peter Porciello, 37, who pleaded guilty last month to second-degree manslaughter, was sentenced Tuesday in Deschutes County Circuit Court to 9 years in prison, nearly a year to the day after shooting Jenny Cashwell on a first date gone horribly wrong.
Judge Wells Ashby went along with the conditions of a plea deal, to the frustration of numerous friends and relatives who felt the sentence was too light.
Cashwell, 37, was an insurance agent in Sisters with daughters, 8 and 11. She was a gifted powerlifter, a volunteer firefighter and a lifelong animal lover.
She had divorced in 2018 after her husband twice cheated on her, her parents wrote in a letter to the court. According to friends, she’d recently started dating again after taking some time to herself.
Porciello was on disability after suffering two traumatic brain injuries in two different car crashes.
Several years earlier, Porciello had been engaged to a woman named Shalonda McColm, who was prepared to testify for the state had the case gone to trial. McColm said that once during an argument Porciello had pointed a gun at her and released the safety, but had not pulled the trigger, according to court documents. The incident caused him to see the risk he posed to others, and in response, he got rid of all his guns.
But at the time of shooting, all was not well with Alan Porciello. On Jan. 10 — two days before the shooting — Bend Police issued a safety alert to officers to be on the lookout for Porciello. Police had been contacted by care providers who believed his “anger and agitation were ramping up and they were concerned.” Police were told Porciello owned “many” handguns and rifles.
“He is described as having explosive anger issues, being obsessive about his rights and recently disengaged with private care providers because of his behaviors,” according to court documents.
It was Cashwell who reached out to Porciello on the Plenty of Fish dating platform. The two spent five days texting to get to know each other and planning their upcoming date.
One thing they found they had in common was an interest in firearms. Cashwell had a concealed carry permit and was known to carry a 9 mm handgun in her purse. She and Porciello discussed possibly going to a gun range on their date.
On Jan. 12 — a Saturday — the two met at Porciello’s apartment around 12:30 p.m. They picked up lunch at a restaurant on U.S. Highway 20, then drove through a coffee stand on their way to Pine Nursery Park trail system for a hike they previously discussed.
As they hiked, Cashwell let her feelings be known to a friend.
“This shouldn’t take too long,” she texted. “He’s not really my type.”
At 3:22, they arrived back at Cedar West Apartments. Evidence shows they both went up to Porciello’s apartment but it’s not known why. In the back seat of Cashwell’s car, police would later find her purse, her handgun still inside.
At 3:46 p.m., a panicked Porciello called 911. He told the operator he was “being facetious, pretending like I was going to shoot her, and accidentally did.”
He told police he believed his Springfield semi-automatic XDS 9 mm wasn’t loaded when he pulled the trigger.
“There was in fact a bullet inside,” said prosecutor Dan Reesor. It passed through Cashwell’s chest and struck her spine and, eventually, it killed her.
Porciello was arrested at the scene.
“I can’t believe what I have done now,” officers overhead him say. “After this I am definitely getting rid of my guns.”
The state submitted more than 20 letters to the court from friends and relatives of Cashwell for the judge to consider at sentencing.
Christy Shores Rumgay wrote of the urge she still feels every day to pick up her phone and text her only sister.
“This nightmare that we will never awake from has shaken our family and our community to the core,” she wrote. “Jenny was my best friend, closest confidant and my blood. My heart is broken and part of my soul is missing forever.”
Many letter-writers were angry with the perceived light sentence in the plea deal. One called it a “travesty of justice,” another a “slap in the face” to Cashwell’s daughters.
According to Porciello’s lawyer, Peter Parnickis, the defense would have argued at trial that two pieces of evidence show Porciello didn’t act with extreme indifference, which is required to prove first-degree manslaughter.
Madras woman facing charges for biting son on cheek
Bend man suspected of exploiting 13 local children, possibly dozens more, in child porn case
Bend Police Chief Porter explains decision to retire
County steps up pressure on man after blaze exposes firefighters to explosions
One piece of evidence is the 911 call Porciello made moments after he shot Cashwell.
“It is heart-wrenching to listen to,” Parnickis said.
Parnickis brought the other piece of evidence to the hearing — a prayer Porciello wrote and crumpled up when investigators left him alone in an interview room with a pen and pad of paper.
The paper was retrieved from the garbage by police.
“Father God, I beg of you to forgive my stupidity,” it read. “I can’t believe I was so dumb. I pray for your will. I know that Jenny is your daughter. Please keep her safe. Save her, I beg of you.”
Parnickis said that because of Porciello’s brain injuries, he sees the world “more in black and white.”
“He’s not a person that can deny or deceive, and he hasn’t done that at any point in this case,” Parnickis said. “He does have a genuine moral compass.”
Porciello read a statement for the court.
“Your Honor, I take 100% of the blame because I broke the cardinal rule of responsible gun ownership and I made the biggest mistake of my life,” he said. “You might not see my emotions due to my two TBI’s but trust me, I feel it. It’s there. I know I deserve punishment. No matter how badly I wish I could undo it, it breaks my heart the way I’ve robbed you all of a very wonderful woman. The main reason I feel this way is her daughters have to grow up without their great mom.”
The judge spoke last.
“There is never a sentence that this court could impose that would properly honor Jenny Cashwell’s life or square the ledger on her death. That’s because justice in a courtroom is imperfect and the tools that we have are very crude,” Ashby said. “I read the letters that were angry, that our justice system is broken and that there needs to be a longer sentence. And if I wasn’t a judge today, I would write the same letter. That’s how we feel.”
Reporter: 541-383-0325,
gandrews@bendbulletin.com
Alan Peter Porciello
Jenny Cashwell
Bend Police
Wells Ashby
Deschutes County Circuit Court
Follow Garrett Andrews
|
cc/2020-05/en_middle_0097.json.gz/line35394
|
__label__cc
| 0.691984
| 0.308016
|
Saved Listings 0
Hi Guest No Account? Sign Up
Saved Searches and Alerts
Change Search Filter
Search Radius 5 Miles 10 Miles 15 Miles 20 Miles 25 Miles 30 Miles 35 Miles 50 Miles 75 Miles 100 Miles 150 Miles 200 Miles 300 Miles ALL
Make Any Acura Alfa Romeo Aston Martin Audi Bentley BMW Buick Cadillac Chevrolet Chrysler Daewoo Datsun Dodge Eagle Ferrari Fiat Ford Genesis Geo GMC Honda Hummer Hyundai Infiniti International Isuzu Jaguar Jeep Kia Lamborghini Land Rover Lexus Lincoln Lotus Maserati Maybach Mazda Mercedes-Benz Mercury MG Miata MINI Mitsubishi Nissan Oldsmobile Plymouth Pontiac Porsche RAM Rolls-Royce Saab Saturn Scion Smart Studebaker Subaru Suzuki Tesla Toyota Triumph Volkswagen Volvo
Model Any
Type & Style Any Convertible Coupe Electric Hatchback Hybrid Passenger Sedan SUV Pickup Truck Van & Minivans Station Wagon
Price Min Any $1,000 $2,000 $3,000 $5,000 $8,000 $10,000 $14,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $50,000 $100,000
Price Max Any $1,000 $2,000 $3,000 $5,000 $8,000 $10,000 $14,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $50,000 $100,000
Show only cars with prices
Year Min Any 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 1979 1978 1977 1976 1975 1974 1973 1972 1971 1970 1969 1968 1967 1966 1965 1964 1963 1962 1961 1960 1959 1910
Year Max Any 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 1979 1978 1977 1976 1975 1974 1973 1972 1971 1970 1969 1968 1967 1966 1965 1964 1963 1962 1961 1960 1959
Mileage Any Less than 10,000 Less than 100,000 Less than 120,000 Less than 150,000 Less than 20,000 Less than 30,000 Less than 40,000 Less than 50,000 Less than 60,000 Less than 70,000 Less than 80,000 Less than 90,000
Sold By Owners & Dealers Sale by Owners Sale by Dealers
Cars Added in the Last 24 Hours. (8,788 Added)
Search Recent Price Drops
Only Certified Pre-Owned
Recently Added Cars
Recently Added Cars Under $1,000
Cars for Sale in Arvada, CO
Showing 1 - 6 of 6 Listings
Sort By Best Match Best Deal First Model (A-Z) Price (low to high) Price (high to low) Year (newer to older) Year (older to newer) Mileage (low to high) Mileage (high to low) Newest Listings First Oldest Listings First Sale by Owner First
1946 Ford 2 door coupe
Owner Says:
Only 6,500 since built has a 429 big block ford engine ..c6 auto transmission ..posi rear end ..4 wheel disc brakes
2007 Chevrolet Impala LT 3.5 Flex Fuel
(make me a respectable offer I'll negotiate want to get rid of this car ASAP ) 2007 Impala LT 3.5 flex fuel engine, has
2006 Jeep Grand Cherokee SRT
Excellent condition with a few upgrades. AFE cold air intake, resonator delete, drilled/slotted rotors with stoptech
This is a great little car that is a very usable and desirable time capsule of history. It is now 91 years old and runs
2012 Volkswagen CC
2011 Subaru Impreza WRX
2011 white Subaru WRX sedan for sale. This has around 76,500 miles on it, and is not being used as a daily driver right
Search Near Arvada »
Share Car Listings:
Cars for Sale in Near Cities
Aurora CO
37 New 337 Ads 337 Listings337 Listings, 20 for sale by owner. 12 Good, Great and Best Deals
1 New 41 Ads Save $1,08041 for Sale by Owner Listings. Save $1,080 with 19 Good, Great and Best Deals in Denver, CO.
Littleton CO
1 New 15 Ads Save $83915 for Sale by Owner Listings. Save $839 with 4 Good, Great Deals in Littleton, CO.
11 Ads Save $60511 for Sale by Owner Listings. Save $605 with 6 Good, Great and Best Deals in Brighton, CO.
Parker CO
9 Ads Save $1,6629 for Sale by Owner Listings. Save $1,662 with 5 Good, Great and Best Deals in Parker, CO.
Golden CO
2 New 6 Ads Save $1,7436 Listings with 1 recent price drop, 1 for sale by owner. Save $1,743 with 2 Deals in Golden, CO.
Cars for Sale by Owner in Arvada
Cars & Trucks Sale by Owner
Copyright © 2020 BestCarFinder.com. All rights reserved. Sitemap | Terms of Use | Privacy Policy
|
cc/2020-05/en_middle_0097.json.gz/line35398
|
__label__cc
| 0.555839
| 0.444161
|
Companies of Manufacturing in Taguig
With active offers (24)
DEL MONTE PHILS. INC.
Del Monte Philippines, Inc. (DMPI) is a leading producer of pineapple and other food products. The company markets...
Taguig, National Capital Region
Coca-Cola Far East Ltd.
Global Business Services (GBS) Coca-Cola Far East Ltd., is a wholly-owned subsidiary of The Coca-Cola Company and is...
NEWMATIC PTE LTD
Newmatic is a Singapore company specializing in built-in kitchen appliances that are designed to be novel and...
Snow Mountain Dairy Corporation
SNOW MOUNTAIN DAIRY CORPORATION (SMDC) is the Milk Business Unit of the Century Pacific Foods Inc., which was...
Vynex Signs Philippines, Inc.
Vynex Signs Philippines, Inc. (“Vynex” or the “company”) was incorporated in March 1993. By 1995, it became a...
W Group Inc.
Our Company has continuously innovated blending and compounding food stabilizers and binders using carrageenan as base...
ASSISTCO ENERGY & INDUSTRIAL CORPORATION
ASSISTCO was primarily engaged in the distribution of thermal insulating products in 1970 exclusively distributed the...
Puratos Philippines, Inc.
Puratos Philippines, Inc. is a wholly owned subsidiary of Puratos NV/SA, with headquarters at Brussels, Belgium....
Knauf Gypsum Philippines, Inc.
Knauf, a family name, and a corporate group of global dimensions. At the same time synonymous with a type of corporate...
Duralco, Inc.
Duralco is the Philippine's premiere manufacturer of a comprehensive range of Aluminum Windows & Doors, Security...
Holcim East Asia Business Service Centre B.V. - Philippine ROHQ
Holcim East Asia Business Service Center B.V. – Philippine ROHQ is the regional IT and Business Shared Service Center...
Ecolab Philippines, Inc.
Ecolab is the global leader in water, hygiene and energy technologies and services. Around the world businesses in...
Puratos Philippines Inc.
Puratos Phils. Inc. The Puratos Group is a Belgian privately owned enterprise, with headquarters close to Brussels,...
Filsung Technology Resources, Inc.
Filsung is established as a Korean company under the BOI's status in June 29, 2000. FIlsung has the breakthrough...
ESTA FINE COLOR CORPORATION
Esta Fine Color Corporation was established in 1976 as a joint venture corporation between Esta Trading Corporation...
CEMPC
We are committed in providing world-class sheet metal fabricating services for you and your company. We accept...
Air Liquide Philippines, Inc
World leader in gases, technologies and services for Industry and Health, Air Liquide is present in 80 countries with...
Coca Cola Beverages Philippines, Inc.
Strive to exceed the world’s ever-changing expectations because our quality promise of delivering safe and refreshing...
ANGELS CONNECTIONS CORPORATION
The Company is a manufacturing of food inredients. They expanded its product lines and ventured into the food grade...
|
cc/2020-05/en_middle_0097.json.gz/line35399
|
__label__wiki
| 0.998322
| 0.998322
|
Hereford & Worcester selected
Hereford & Worcester
Worcester City's Lee Smith warned after race tweets probe
https://www.bbc.com/news/uk-england-hereford-worcester-15848162
No further action is to be taken over claims a Worcester City footballer posted an allegedly racist remark on Twitter, police have confirmed.
Lee Smith was suspended by the club last week amid claims a post he tweeted on 11 November was "spreading hatred".
The 28-year-old striker was arrested earlier on suspicion of having committed a public order offence.
Gloucestershire Police said it had advised him about his behaviour and no further action was now required.
Ch Insp Derek Jones added: "The individual involved has been spoken to by officers about the content of his 'tweets' and given strong words of advice about his behaviour.
"The Twitter account has since been removed and no further police action will be taken against the man."
Carl Heeley, Worcester City Football Club's manager, said on Tuesday the club would release a statement in due course.
Worcester footballer Lee Smith in 'racist tweet' probe
Police probe into Worcester City footballer Lee Smith tweet
Worcester sign Nuneaton's Smith
Worcester City Football Club
|
cc/2020-05/en_middle_0097.json.gz/line35402
|
__label__cc
| 0.747031
| 0.252969
|
Fruits of the knowledge and skill of our Manufacture, our constant pursuit of excellence and the creative spirit of our watchmakers and craftsmen, Blancpain timepieces express the values that inspire us: authenticity, passion and emotion.
Founded in 1735 in the Swiss Jura by Jehan-Jacques, Blancpain is the world’s oldest watchmaking...
Blancpain and its President CEO, Marc A. Hayek, are proud to unveil the world premiere of their...
Blancpain has re-interpreted one of its core timepieces, the three-hand model of the Fifty...
Born in the late 1950s from a desire to offer a diver’s watch in a size suited to daily wear, the...
Blancpain presents its new Bathyscaphe Flyback Chronograph Blancpain Ocean Commitment II
The Bathyscaphe is a legendary name at Blancpain. Three years after the 1953 debut of the...
All the latest innovations from Blancpain unveiled at Baselworld 2016.
Discover more on :...
Innovation is our Tradition - Short version
Innovation is our Tradition - 3 mn
Blancpain presents Fifty Fathoms collection
The Fifty Fathoms collection embodies Blancpain’s passion for the underwater world that was...
(30 seconds) Collection Women | Quantième rétrograde
Developed in a resolutely romantic and contemporary spirit, the Retrograde Calendar is a perfect...
(37 in all)
|
cc/2020-05/en_middle_0097.json.gz/line35405
|
__label__cc
| 0.620186
| 0.379814
|
Britain: 'Megxit' and the crisis of the Monarchy 16 January
Interview with Russian school student activist: “the future belongs to us!” 15 January
French strike passes 40th day as workers reject Macron's manoeuvre 14 January
Britain: Labour leadership election – go on the offensive against the right wing! 14 January
Protests show deep crisis of Iranian regime after Ukraine aircraft shot down 12 January
Russia: the nature of the Putin regime 10 January
WWI and the German Revolution
The Russian Revolution
Chinese Revolution
Spanish Revolution
Revolutionary 1968
The Iranian Revolution
Ireland and Republicanism
British Labour History
Cuban Revolution
Publication announcements
Historical Materialism
Women's Emancipation
In defence of genuine Marxism
The Ted Grant archive
National question
International Marxist Tendency
Articles about the IMT
All other languages
فرنسا: العمال يرفضون مناورة ماكرون والإضراب العام يتجاوز يومه الأربعين 20 January
Mais de 40 dias de greve na França e rejeição das manobras de Macron 20 January
Το εργατικό κίνημα της Γαλλίας συνεχίζει τον αγώνα 20 January
Frankrijk: staking gaat ook na 40 dagen door, manoeuvers Macron worden verworpen 20 January
Il pensiero rivoluzionario di Antonio Gramsci 17 January
Indija: 250 miliona se pridružuje generalnom štrajku u usponu masovnog pokreta protiv drakonskog zakona o državljanstvu 17 January
Salvini, les « sardines » et la lutte des classes 17 January
National Congresses
International Schools and Congresses
Solidarity activities
France: for a workers' government!
Révolution (editorial)
France Featured
The power of the yellow vests movement never ceases to surprise – and intimidate – its adversaries. Of course, the bourgeois and their lackeys (in politics and the media) know that poverty exists. They hear about it, distantly, but they are totally disconnected from the real living conditions of the people, their suffering and their problems. Then, from their lofty position of privilege, with all their power and their fortune, they said to themselves: “a little more or a little less austerity, what difference will that make?” The answer hit them like a ton of bricks.
This is an editorial if the French Marxist journal, Révolution, originally published on 1 Feb 2019
The depth of the movement
The movement seized on a day of action scheduled by the CGT, February 5, as the starting point of an "unlimited general strike" / Image: fair use
Revolution has said time and again in recent years: no political regime can impose a permanent social regression without causing an explosion of the class struggle at a certain stage. It is a law of history that admits of no exception. Another law: the longer the masses wait, suffer, endure, the more powerful is their revolt when the time comes. But it is a fact that millions of exploited and oppressed people have suffered in silence for decades. They went out of their way to pay the rent, the bills, taxes, for food - in short, the basic necessities for survival. And over the years, they have faced more and more trouble making ends meet.
The trade union movement had almost no hold on these layers of workers, who, in turn, watched with scepticism (at best) the ritual "struggles" organised by the union confederations, without any result. For a divorced mother whose survival depends on a precarious job in which she is brutally exploited, trade unions’ "days of action" with no long-term plan and no effect are of no interest. These are a luxury she cannot afford. And that goes for millions of workers.
It is precisely these poor employees who alongside pensioners, the unemployed, small traders, etc. form the backbone of the movement of yellow vests. Their combativeness is commensurate with the amount of anger and frustration they have accumulated. Police and judicial repression, of unprecedented brutality, do not make them falter. On the contrary, it reinforces their determination to get rid of a government that is based only on the "democratic" virtues of truncheons, tear gas, flash-balls and arbitrary arrests.
A point of no return has been crossed by the powers that be which, unceasingly mutilate and imprison the populace. Who still supports Macron and his clique? The big bourgeoisie and its media cronies (though not without apprehension), as well as a few thousand "red scarves" who embarrassed themselves in the streets of Paris, on 27 January. That is about it. Since May 68, never has a French government been so weak and discredited.
The general strike
The yellow vests' combativeness is commensurate with the amount of anger and frustration they have accumulated / Image: fair use
Everyone understood that the "big debate" organised by the government has the sole purpose of weakening the mobilisations on the streets and at roundabouts. The experience of the last 12 weeks has convinced the vast majority of yellow vests that it is necessary to carry on the fight within workplaces themselves, in the form of massive and unlimited strikes. The movement has seized on a day of action scheduled by the CGT, February 5, as the starting point of an "unlimited general strike".
This is the key to victory. The government is determined to "hold" against Saturday's protests. Macron expects fatigue and exhaustion. And it is clear that, if the movement does not move forward, it will fall back. On the other hand, a vast movement of unlimited strikes would deal a fatal blow to the government. Macron would be obliged, at a minimum, to dissolve the National Assembly, in the hope of defusing the development of a revolutionary crisis.
It is impossible to predict what will happen on 5 February and the following days. France is the country of June ‘36 and May ‘68: two general strikes that erupted from below, against the will of the union leadership. Anything is possible. The course of events depends in particular on the initiatives taken, in the field, by the most combative union activists, in connection with the yellow vests. However, it must be admitted that the passivity of the confederal leadership of the CGT (to say nothing of the other unions) is a major obstacle to the organisation of a powerful movement of unlimited strikes.
There is no doubt that many workers support the idea of a general strike against the Macron government. But they know that it is not enough for one sector to go on strike and wait for others to follow. Dockers, refinery workers and railway workers – among others – have had bitter experiences in 2010, 2016 and 2017. The confederal leaders of the unions did not lift a finger to extend the strike to other sectors. Isolated, these strikes failed. With this experience in mind, many workers look to trade union assemblies and say: "These people do not seem ready to extend and generalise a strike movement. If we start, we risk being isolated.” This is a serious obstacle. But it's an obstacle relative to the pressure from the rank and file. And so, sooner or later, the leadership will yield.
Against capitalism!
The dissolution of the National Assembly would be a first victory. But then what? What kind of government do we need? The yellow vests say, "Power to the people!" We agree! But what does that mean, concretely? For the "power of the people" to be real and effective, this presupposes the transfer of economic and political power to the hands of the workers, that is to say, those who produce all the wealth. This means the expropriation of the parasites who hold the main levers of the economy: the banks, industry, energy, transport, pharmaceuticals, the media, etc.
The yellow vests are fighting to get rid of a government that is based on the "democratic" virtues of truncheons, tear gas, flash-balls and arbitrary arrests / Image: Olivier Ortelpa
All of these large companies must be nationalised and placed under the democratic control of employees. Then, as part of a democratic planning of production, it will be possible to satisfy the needs of the majority – instead of satisfying the thirst for profits of a small minority, as is the case today. At the same time, it will be possible to guarantee much better conditions for small traders, artisans and farmers, who are presently crushed by big capital.
At this stage, the movement of the yellow vests has not raised these questions. This is not surprising, since the left and the labour movement have themselves evacuated this issue from their speeches and programmes for decades. It is time for this to change. France Insoumise and the CGT, in particular, that Macron works for the capitalist class. They should strive to link the struggle of the yellow vests with the objective of genuine workers' government: that is to say, a revolutionary, socialist transformation of society. No doubt this would be a powerful battle cry for millions of young people and workers.
Originally published 1 Feb 2019
This website uses cookies, you can find out more and set your preferences here.
By continuing to use this website, you agree to our Privacy Policy
|
cc/2020-05/en_middle_0097.json.gz/line35413
|
__label__cc
| 0.547039
| 0.452961
|
Long Lost: Book summary and reviews of Long Lost by Harlan Coben
Summary | Reviews | More Information | More Books
Myron Bolitar Series #9
by Harlan Coben
Readers' rating:
Published in USA Mar 2009
Genre: Thrillers
Myron Bolitar hasn’t heard from Terese Collins since their torrid affair ended ten years ago, so her desperate phone call from Paris catches him completely off guard. In a shattering admission, Terese reveals the tragic story behind her disappearance — her struggles to get pregnant, the greatest moment of her life when her baby was born … and the fatal accident that robbed her of it all: her marriage, her happiness and her beloved only daughter.
Now a suspect in the murder of her ex-husband in Paris, Terese has nowhere else to turn for help. Myron heeds the call. But then a startling piece of evidence turns the entire case upside down, laying bare Terese’s long-buried family secrets … and the very real possibility that her daughter may still be alive.
In grave danger from unknown assailants in a country where nothing is as it seems, Myron and Terese race to stay a step ahead of Homeland Security, Interpol, and Mossad. Soon they are working at breakneck pace, not only to learn what really happened to Terese’s long-lost little girl — but to uncover a sinister plot with shocking global implications.
Click to the right or left of the sample to turn the page.
(If no book jacket appears in a few seconds, then we don't have an excerpt of this book or your browser is unable to display it)
"[A] fast-paced ninth thriller ... Bolitar fans will cheer their hero every step of the way." - Publishers Weekly.
"Starred Review. Fans are strongly advised to leave plenty of time to plow through the case at one sitting, as any delay would be fatal to the suspension of disbelief it demands. On the other hand, those few hours will leave the easy chair smoking." - Kirkus Reviews.
"Coben puts a wicked topical spin on Children of the Corn in an action-packed thriller with a horrific yet credible premise." - Booklist.
"This is sure to please both Bolitar fans and those who have only read Coben's roller coaster-ride thrillers." - Library Journal.
The information about Long Lost shown above was first featured in "The BookBrowse Review" - BookBrowse's online-magazine that keeps our members abreast of notable and high-profile books publishing in the coming weeks. In most cases, the reviews are necessarily limited to those that were available to us ahead of publication. If you are the publisher or author of this book and feel that the reviews shown do not properly reflect the range of media opinion now available, please send us a message with the mainstream media reviews that you would like to see added.
Click here and be the first to review this book!
Harlan Coben Author Biography
Harlan Coben was born and raised in New Jersey. After graduating from Amherst College as political science major, he worked in the travel industry. He now lives in New Jersey with his wife, Anne Armstrong-Coben MD, a pediatrician, and their four children.
Coben is the first author to win all three of the most coveted literary awards: the Edgar Award, Shamus Award and Anthony Award. His books include the Myron Bolitar series, as well as other standalone novels, including Play Dead, Miracle Cure. Tell No One, Gone for Good, No Second Chance, Just One Look, The Innocent, The Wods, Hold Tight, and Caught. Harlan Coben's books have been published in more than twenty-two languages.
Link to Harlan Coben's Website
Other books by Harlan Coben at BookBrowse
Readers Also Browsed . . .
The Plea by Steve Cavanagh
Heaven, My Home by Attica Locke
The Truants by Kate Weinberg
Rust & Stardust by T Greenwood
The Smiling Man by Joseph Knox
Her Kind of Case by Jeanne Winer
Confessions of an Innocent Man by David R. Dow
After She's Gone by Camilla Grebe
more thrillers...
|
cc/2020-05/en_middle_0097.json.gz/line35414
|
__label__wiki
| 0.753496
| 0.753496
|
Bill Downs, War Correspondent
1942. Britain Rejects American Criticism of the War Effort
Home Secretary Morrison Responds to Critics
"A British patrol is on the lookout for enemy movements over a valley in the Western Desert, on the Egyptian side of the Egypt-Libya border, in February of 1942" (source)
Bill Downs
CBS London
There was neither confirmation nor denial from the United States Army headquarters in London this morning that General Eisenhower was to be recalled to Washington for consultation. The report came from the Associated Press bureau in Washington. The official statement from General Eisenhower's headquarters is a cryptic "no comment."
Herbert Morrison, the British Home Secretary, said some things in a speech yesterday that should have been said a long time ago. Paradoxically, though, his speech was made in answer to people who have been damning the British—not in Germany, but in America.
Mr. Morrison frankly took the British light from under its traditional self-effacing bushel and said that Britain need not apologize to anyone for its prosecution of the war for the past three years. Then he said, "We have made mistakes and suffered ill fortune, but happily we owe no one an explanation on that account except ourselves."
Mr. Morrison pointed out that, at the time Britain stood alone before the massed armies of Hitler, "a large proportion of the world was generous with its applause."
"Today," he continued, "it seems to be rather a different story. We are having critical shafts directed at us from various points of the compass. We are being pressed to do various things, military and political, now and after the war."
The British Home Secretary did not say Britain was above criticism. He said, however, that the people who have most right to urge Britain on are the exiled governments who have been forced to sit and watch Hitler enslave their people. These governments have not complained about the British war effort, Mr. Morrison said, probably because they can see for themselves the effort Britain is making.
"And perhaps too," he continued, "because their memories are not too short and they look back when we stood their only comrade in arms, the only friend who offered them not merely friendship but a strong right arm bent up to strike in their cause."
Mr. Morrison said Britain during the past three years has fought a hard and honorable war. He reiterated the victories over the Italian army in Abyssinia—the defeat of the German air force in the Battle of Britain—the ordinary man's victory over the intense German bombings of Coventry, London, Plymouth, and other towns. He said Britain has nothing to be ashamed of in her attempted defense of Greece.
And about India, the Home Secretary said that nation was made a fair offer of independence, an offer designed to cause no rift in the war effort. This offer has not yet been accepted, he said, adding, "This is not the moment to stop to consider why. In any case, I hope and believe that in the end the substance of the offer will be accepted."
Perhaps it was by coincidence that Ambassador Winant also made a speech last night which has a direct bearing on the question of British and American relations. Mr. Winant said that the human race must go forward together or not at all. "If our two nations ever become divided in their purpose, it is hard to see how the world can find a way out from its present misery or realize a basis for a lasting collaboration and peace program."
But the main point of all these speeches and criticisms and agitations and appeals for unity is that they are going to sound pretty good to Herr Goebbels. Nazi propagandists know that the surest way to lick a combined enemy is to get that enemy fighting among themselves.
However, the most important fact to emerge from all of this talk of dislike and criticism between the British and United States is that the ordinary Britisher here doesn't quite know or understand what all the shouting is about. The little people of Britain like the Americans and show it every day in their treatment of our soldiers. He wants the Americans to like him.
But whether the people of the United States love him or despise him is not important to the British man on the street. The important thing is to get on with the war and victory.
There is a standard joke on this side of the Atlantic which the British repeat whenever the question of British-American relations comes up. The Britisher will put down his pint of beer, grin and say, "You know, it appears that your people in America only like us when we're suffering or being bombed or something."
About Bill Downs
1950. West Germany Celebrates Holiday as the East ...
1970. The Environmental Crisis Facing the Planet
1942. Berlin and Vichy Worry About the Allies' Nex...
1942. Eleanor Roosevelt Visits Wartime England
1950. Western Occupation Powers Consider German Ro...
1945. Howard K. Smith Describes the German Surrend...
1949. Simmering Tensions Over the Ruhr
1942. Two Ignominious Anniversaries for Fascist It...
1967. Public Confidence in Congress Continues to D...
1940. New York Times: What Would a Nazi Invasion o...
1942. RAF Strikes Northern Italy, Eighth Army Figh...
1970. The Soviet Union and West Germany Sign the T...
1967. Leaders Gather for Inter-American Summit in ...
1950. East German Lieutenant Testifies Soviets Bui...
1949. General Clay to Step Down as American Milita...
1942. Britain Rejects American Criticism of the Wa...
1967. President Johnson and Ho Chi Minh Exchange P...
1950. Political Reshuffling on Both Sides of Germa...
1945. Charles Collingwood's Eyewitness Account of ...
1967. The Growing Polarization of Congress
1949. Son of Communist Leader Max Reimann Escapes ...
1968. Defense Secretary Robert McNamara's Farewell...
1937. The New York Times Criticizes American Isola...
1949. U.S. Officials Appeal to Soviets to Release ...
1948. Western Allied Commanders Convene on the Eve...
1970. Fragile Ceasefire in the Arab-Israeli Confli...
1970. Ralph Nader's Crusade for Corporate Responsi...
1949. Partial Blockade Slows Traffic to Berlin
1948. Signs of Economic Difficulty Reported in the...
1970. Bill Downs Recalls Hiroshima and Nagasaki
The Murrow Boys
1944: The Murrow Boys on D-Day
1944: Rare Footage of the Murrow Boys During World War II
1950: The CBS News Mid-Century Roundup
1955: The Murrow Boys on the Cold War
1958: Edward R. Murrow's "Wires and Lights in a Box" Speech
1961: The Debate Over Editorialization
The Murrow-Cronkite Rivalry
Featured World War II Posts
1943: The Aftermath in Stalingrad
1943: Blood at Babi Yar: Kiev's Atrocity Story
1943: Stories from the Eastern Front
1943: War Correspondents vs. Soviet Censors
1944: The Heroes of Normandy
1944: The Battle of Nijmegen Bridge
1944-1945: Dispatches from the Western Front
1945: American Humor on the Western Front
1945: The German Surrender at Lüneburg Heath
Bill Downs Reports from the Front Lines
1943: The Moscow Reports
1944: Reports from Western Europe
1948-1950: The Berlin Blockade Reports
Ernest Hemingway's World War II Essays (1944)
The New York Times on the Rise and Fall of Fascism (1922-1945)
Collier's Magazine's History of World War III (1951)
|
cc/2020-05/en_middle_0097.json.gz/line35418
|
__label__wiki
| 0.89809
| 0.89809
|
USFDA approves Daiichi Sankyo and AstraZeneca’s breast cancer drug
Japan | News | 0 Comment | 26 Dec, 2019
Daiichi Sankyo and AstraZeneca have announced that the U.S. Food and Drug Administration (FDA) has approved ENHERTU® (fam-trastuzumab deruxtecan-nxki), a HER2 directed antibody drug con...Read more
Gilead, Eisai to co-promote drug in Japan for RA treatment
Gilead Sciences, Inc. and Eisai Co., Ltd. have announced that Gilead Sciences K.K. and Eisai have entered into an agreement for the distribution and co-promotion of filgotinib, an investiga...Read more
Eisai gets USFDA nod for insomnia drug
Eisai has announced that the U.S. Food and Drug Administration (FDA) approved DAYVIGO™ (lemborexant) 5 mg and 10 mg for the treatment of adult patients with insomnia, characteriz...Read more
Towa to acquire Esteve’s generic division for 320M euros
Japan based TOWA PHARMACEUTICAL CO., LTD. and Spain based pharma company ESTEVE have announced that TOWA will acquire 100% of Pensa Investments, SL (Pensa), the generic division of the Span...Read more
Takeda, Turnstone Biologics to develop novel viral immunotherapies
US based Turnstone Biologics, a biotechnology company pioneering the development of engineered viral immunotherapies, has announced a strategic collaboration with Japan based Tak...Read more
FDA grants accelerated approval to Astellas' and Seattle Genetics' PADCEV
Astellas Pharma Inc. and Seattle Genetics, Inc. have announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval to PADCEV™ for the treatme...Read more
PHC Corporation makes investment in Kakehashi
Japan based PHC Corporation has announced it was taking a stake in KAKEHASHI Inc., based on a share purchase agreement with the company. Kakehashi developed Musubi, a next-generation elect...Read more
AMED awards 3 joint projects with A*STAR
Japan Agency for Medical Research and Development (AMED) and Singapore’s Agency for Science, Technology and Research (A*STAR) have jointly selected three outstanding R&D projects ...Read more
Pfizer, Astellas' Xtandi Gets FDA nod
Pfizer and Japan based Astellas Pharma have announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for XTANDI® (enzaluta...Read more
PENTAX Medical gets CE Mark for AI aided Polyp Detector
PENTAX Medical, a division of the HOYA Group which is a global med-tech company based in Tokyo, Japan, has cleared CE mark for DISCOVERY™, an innovative Artificial Intelligence (AI) a...Read more
AstraZeneca, Daiichi Sankyo’s trastuzumab shows promise in Phase II Trial
AstraZeneca and Daiichi Sankyo Company presented positive detailed data from the global pivotal Phase II single-arm DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201), a HER2-target...Read more
Eisai breaks ground for global drug discovery centre
Japan based Eisai Co., Ltd. has had a groundbreaking ceremony for a major renovation of its Tsukuba Research Laboratories (Ibaraki, Japan) as part of strategic investment to realize Eisai&r...Read more
FUJIFILM sets manufacturing facility for liposome formulation
FUJIFILM Toyama Chemical has announced the construction completion of a new manufacturing facility (facility name: 701) within its Toyama Second Fact...Read more
Solasia enters new license alliance with Maruho
Japan based Solasia Pharma K.K. has announced that it has entered into an exclusive license agreement with Maruho Co., Ltd. for the commercialization of Solasia’s product SP-04 (PledO...Read more
Takeda, Enzyre to develop diagnostic device for hemophilia patients
Enzyre based in The Netherlands, which is developing breakthrough ambulant diagnostic technology for coagulation testing, has announced that it has entered into a research collaboration agr...Read more
Takeda presents Phase III Trial results in patients with amyloidosis
Japan based Takeda Pharmaceutical Company Limited announced the presentation of the results of tourmaline-AL1 trial in an oral session at the 61 to annual meeting of the American ...Read more
Hitachi to provide CNAO with Proton Therapy System
Japan headquartered Hitachi, Ltd. has entered into an agreement to provide Centro Nazionale di Adroterapia Oncologica (CNAO) with its proton therapy system. In the comprehensive public ten...Read more
BitBiome to analyse gut bacteria related to cancer
bitBiome, Inc., a start-up company from Waseda University in Japan, and National Cancer Center of Japan have signed a collaborative research agreement on the analysis of...Read more
|
cc/2020-05/en_middle_0097.json.gz/line35419
|
__label__wiki
| 0.824756
| 0.824756
|
Home > Research > TSRC > Research > Service delivery > Commissioning
Explore Research
Spotlight on Research
Hydrogen-powered train
Birmingham Centre for Railway Research and Education’s (BCRRE) research into the application of fuel cells and hydrogen in railway traction system design stretches back over the last decade and beyond.
Quantum Technologies
Developing the use of sensors and clocks in innovative, ground-breaking technologies to change the future landscapes of healthcare, transport, defence, civil engineering and more.
Academia partnering with business, investigating, developing and co-creating robust and innovative solutions to achieve responsible business success. Building the foundations for a more responsible and sustainable future.
We are working with partners across the globe to understand how to save lives at risk from poor air quality.
Superdiversity
Challenging established views and policy responses to migration and its impact on societies in a rapidly changing world.
Global Ethics
Birmingham academics work on major issues in international ethics and global justice and train the next generation of students to tackle these issues.
Birmingham has been at the forefront of transplants since the pioneering work of Sir Peter Medawar. Our researchers are continuing his legacy.
Explore our Spotlights
Enter researcher name
Arts and Law
Life and Environmental Sciences
Medical and Dental Sciences
Languages, Cultures, Art History and Music
We explore what it means to be human – in historical and cultural contexts, within ethical and legal norms and through languages and communication.
Explore all Arts and Law Research
Electronic, Electrical and Systems Engineering
Healthcare Technologies Institute
Institute for Gravitational Wave Astronomy
Metallury and Materials
Quantum Technology Hub
From atoms to astronomy, computers to cars and robots to robust materials, our goal is to transform our understanding of the world to make life easier, healthier and more sustainable.
Explore all Engineering and Physical Sciences Research
Across the breadth of life and environmental sciences we discover, apply and translate science, forging major advances in human and environmental health.
Explore all Life and Environmental Sciences Research
Institute of Applied Health Research
Institute of Cancer and Genomic Sciences
Institute of Cardiovascular Sciences
Institute of Clinical Sciences
Institute of Immunology and Immunotherapy
Institute of Inflammation and Ageing
Institute of Metabolism and Systems Research
Institute of Microbiology and Infection
With over 1,000 academic staff researchers and around £80 million new research funding per year, we are dedicated to performing world-leading research with the ultimate goal of improving human health.
Explore all Medical and Dental Sciences Research
We address the challenges facing society and the economy, from shedding light on the refugee crisis, to character education in schools, through to developing leaders in the NHS.
Explore all Social Sciences Research
In 'Service delivery'
Releasing the Community Investment potential of social housing organisations
Self-help Housing
Third sector partnerships for service delivery
Back to 'Research'
Commissioning has become an increasingly important issue in UK public services, and its implications are being hotly debated. Many suggest that the third sector is well placed to take advantage of opportunities presented by competitive commissioning arrangements, the opening up of public services to new providers, and the Social Value Act 2012. But there is also concern that efficiency will take precedence over social value, possibly jeopardising the ‘comparative advantage’ of TSOs in this context.
Commissioning is not new but has been given a big push by the Coalition Government. The 2011 Open Public Services White Paper set out an increased emphasis on commissioning, and greater use of Payment by Results and outcomes based commissioning. It is closely linked to mechanisms such as Social Return on Investment and Social Impact Bonds. But there is still much confusion about what exactly commissioning is, and whether it is deeply embedded in different service areas and levels of government.
Researchers at TSRC are interested in understanding the reality and diversity of commissioning; its implications for those voluntary organisations that are directly affected, and its implications for the future of public services. Throughout our research we explore whether public sector commissioning is successfully engaging with TSOs to deliver integrated and holistic outcomes.
What is commissioning in different service areas, and what is the experience of third sector organisations in commissioning arrangements?
How do understandings of commissioning differ between commissioners, TSOs, and potentially, users?
Is it possible to identify good practice in commissioning?
How should we define success? How can social value be recognised alongside economic value in commissioning process? What are the ingredients of successful commissioning?
How does commissioning relate to the specification and measurement of outcomes?
Projects currently underway include:
Introduction to commissioning and the Third Sector, James Rees
Academic Literature Review, Ross Millar, James Rees, David Mullins, Rosie Meek
Commissioning and Mental Health, Robin Miller
Mental Health Project, James Rees, Robin Miller, Ross Millar
Commissioning and Measurement, Jenny Harlock
Evaluations and social value, Malin Arvidson and Helen Kara
Transparency and the open public service agenda: implications for the third sector, Malin Arvidson
Research report 86: Commissioning across government: review of evidence (August 2012) A report commissioned by the National Audit Office, looking at current models of commissioning, their effects, and the changes being considered by government departments.
In the coming six months, we will publish a number of Working Papers related to commissioning on the TSRC website, as well as articles in peer-reviewed journals. We are also planning to host a one-day conference to discuss research findings, and engage with other academics and practitioners that share an interest in this topical and important area of research.
From Autumn 2012, a core team (Rees, Miller and Millar) will be conducting a project on mental health and commissioning in the West Midlands. The research will focus on commissioning of services to support people with mental health difficulties. It will explore commissioning practice and experience in four Local Authority areas based around the West Midlands
Ross Millar
David Mullins
Tony Bovaird
Rosie Meek
Jenny Harlock
Malin Arvidson
Fergus Lyon
Policy Experts Guide
Our impact: find out about recent advances
Explore our Research Spotlights
|
cc/2020-05/en_middle_0097.json.gz/line35420
|
__label__cc
| 0.621579
| 0.378421
|
Anstey College of physical training
Principals and heads of department
Photographs and visual images
The Anstey College of Physical Training was founded by Rhoda Anstey in 1897. It was the second women's physical training college to be established after Hampstead Training College (later Dartford College) which was founded by the Swedish physical educationalist Madame Bergman Österberg where Rhoda Anstey herself trained in 1893 to 1895. Anstey's first location was at the Leasowes a house in Halesowen formerly the home of the poet and landscape gardener William Shenstone (1714 to 1763). In 1907 Rhoda Anstey moved the college to Yew Tree House on the Chester Road in Erdington, where it remained until 1981.
From its outset the college forged close links with Birmingham University for students to receive instruction in Anatomy and Physiology and also with local schools where students undertook teaching practice and from where pupils came to the college to be taught physical education and remedial gymnastics. In the early days the college trained women professionals in: ''….Educational Gymnastics, Medical Gymnastics, Anatomy, Physiology, Hygiene, Dancing, Swimming and Games and …. (aimed to) prepare girls to take up the work of Physical Education in Schools'' (Rhoda Anstey, Founder /Principal 1904, College Magazine 1, p3). The archive is ongoing and further contributions are welcome. More material is continually being added to the collection.
The college had to move in 1981 as part of the Department of Education and Science's restructuring, and became the Anstey School of Physical Education within the Birmingham Polytechnic on Westbourne Road, Edgbaston. The college finally closed in 1984.
Throughout its history and still with us today there is a dynamic Anstey Association of former students and staff who have lovingly collected and safe guarded the custodial history of the college in this archive. They have also retained other memorabilia and larger scale items in the Anstey Room in Ravensbury House, Westbourne Road, which is part of the Birmingham City University (formerly Birmingham Polytechnic, then University of Central England). Regular gatherings of the Anstey Association continue to foster the ethos of the college to physical educationalists world wide.
Next page Principals and heads of department
Archives of Soho
Benjamin Stone collection
Birmingham industrial exhibition (1886)
Birmingham music venues
Birmingham newscuttings collection
Bournville Village Trust archive
George Cadbury
George Lempriére collection
Helen Caddick and her diaries
History of Curzon Street station
History of lawn tennis
LGBT heritage resources
Peaky Blinders - gangs of Birmingham
Raymond Crompton Rhodes
Records of Birmingham Photographic Society
The Birmingham Collection
The Irish Experience - oral history project
Unlocked - hidden stories
World War two - oral history project
|
cc/2020-05/en_middle_0097.json.gz/line35421
|
__label__wiki
| 0.73187
| 0.73187
|
Security Guards at Target Force 20-Year Old Black Woman to Expose Herself to Prove She Didn’t Steal a Bikini
Ashanae Davis, the African American woman accused of stealing a bikini at Target
Detroit, MI — Ashanae Davis, a 20-year old Black woman from Michigan, is filing a lawsuit against Target after being a victim of racial profiling when she was falsely accused of stealing a bikini from a store in Detroit. She said that the security guards dragged her while yelling loudly that she stole bikini panties. What’s more, she was asked to strip to check if she wasn’t really wearing a stolen bikini!
Davis recalled what happened last May 22 on the Target store in Southfield in Detroit, Michigan. She said she was about to get out of the store when a security guard, who was Black, grabbed her and stopped her from leaving.
Another security guard, who was white, came to handcuff her and dragged her while yelling loudly that she was wearing stolen bikini panties underneath her clothing.
“He said that over and over. Loud enough for other customers to hear and loud enough to publicly humiliate our client,” Davis’ lawyer Jasmine Rand said. They called the humiliating practice the “Target Walk of Shame.”
Afterwards, Davis was escorted to a room where she was asked to pull up her shirt and bring her pants down. A white female manager was there with the two security guards. When they have proven that Davis didn’t stole anything, she was allowed to leave.
“At first I was in shock, of course, and it was just very humiliating,” Davis said. “I felt degraded. It was sad. I was very upset.”
On Tuesday, Target issued an apology statement and said that the Black security worker has already been fired.
“We want everyone who shops at Target to feel welcomed and respected and take any allegations of mistreatment seriously,” the company said in a statement. “We’re sorry for the actions of our former team member, who created an experience we don’t want any guest to have at Target. Upon reviewing our team’s actions, we terminated the team member who was directly involved and are addressing the situation with the security team at the store.”
Target also added that the reason why Davis was stopped was a bikini with tags still attached spotted in her bag. Apparently, it was from a different store and not from Target.
However, Rand thinks that how Target responded was not yet enough.
“If only one employee was held accountable for the incident, and that employee was fired on the day we held the press conference, I find Target’s efforts disingenuous,” she told the Huffington Post in a statement. “If Target fired only the African American male employee, I find the effort a compounding act of racial discrimination. Hate can’t drive out hate from corporate culture.”
|
cc/2020-05/en_middle_0097.json.gz/line35425
|
__label__wiki
| 0.774454
| 0.774454
|
English for young learners (3-17 years)
myClass English courses for adults
How do I book a course?
Why study with the British Council?
Exam preparation courses: IELTS
Our work in Arts and the Creative Industries
Our work in education, science and society
EUNIC and the British Council
myClass Portal
FameLab is designed to inspire, motivate and develop young scientists and engineers to actively engage with the public and stakeholders.
Effective science communication has the potential to alter stereotypes, create excitement and interest, and ultimately justify public funding for scientific research.
UK involvement
The UK is a centre of excellence for science communication and recognises that science accessibility to a non-scientific audience is an ever-growing priority for researchers worldwide.
Each year the FameLab International final is held at The Times Cheltenham Science Festival in the UK. National winners from across the globe flock to the festival to prove their science communication prowess, engage with other enthusiastic science communicators, and to learn from UK experts in the field.
Since its birth at The Times Cheltenham Science Festival in 2005 FameLab has grown into the world leading science communication competition.
The partnership with the British Council, begun in 2007, has seen the competition go global, with more than 5000 young scientists and engineers participating in over 25 different countries. 2015 sees FameLab’s growth set to continue, with the addition of even more countries to the competition.
More information about the FameLab competition.
Skip Facebook content
FameLab Portugal
80 years in Portugal
Equal opportunity and diversity
Statements and reflections on UK Referendum
InEnglish Digital magazine
Courses and professional development
English and training for schools
Professional associations and networks
|
cc/2020-05/en_middle_0097.json.gz/line35432
|
__label__wiki
| 0.767506
| 0.767506
|
The Five Best Concerts in South Florida This Week
Miami's Cool Uncle Bobby Caldwell on Show Business, Japan, and Three Generations of Fans
Johnny Marr Is the Quintessential 1980s Guitarist
David Von Bader
David Von Bader | November 15, 2013 | 8:37am
The excess that characterized the 1980s has since been, decried, extolled, and examined ad nauseam. The musical landscape that developed during that decade was one of the most compelling in history, not necessarily based on the content that flowed through the mainstream (which was unique in its own right), but for the alternative art and music made in objection to the over-the-top schtick and fodder that had become the standard. Post-rock, post-punk, art-pop, shoegaze, and the lion's share of styles that now inform and cue the sounds and aesthetics of today's hype-makers emerged in the '80s.
Of all the bands that spawned amid the chaos and hair product of the era, few have gained the sort of following of the Smiths. And their fans are rarely the casual type. While Morrissey's inimitable voice and personality quirks cannot be minimized in any way when discussing the success of the Smiths, Johnny Marr's guitar work and compositional sense were a defining feature that was entirely necessary to the Smith's sound, making Marr a quintessential guitarist of that era.
While the archetype of the '80s guitarist was defined in the minds of most by Eddie Van Halen -- who fought to progress technique and athleticism with mind-boggling licks and tricks that humbled even the most respected of the period's shredders -- Marr's understated arrangements and style choices were the reset button many musicians were looking for.
Armed with vintage gear that defied the trends of the time, Marr built a foundation for Morrissey's soaring croons and melodies with the jangle and clang of 12-string Rickenbackers, classic Fender and Gibson guitars, and buxom '60s Fender amps. While those choices might appear quite normal to the layman, most guitarists at the time were knee-deep in the muck of locking whammy bars and pointy headstocks, and running amps with as much distortion possible to match the feeling provided by the cocaine flowing through their veins.
Marr has spoken about his preference for undistorted tones, explaining that if one is always shouting, there is nowhere further to go dynamically =- just one of the many pearls of wisdom this anti-hero has provided guitarists with over the years. Beyond basic tonal choices, Marr approached the guitar in a way that defied the trappings of most lead guitarists, utilizing unique tunings, off kilter chord voicings, and mod-inspired rhythms to round out the Smith's sound. Though it is the most frequently referenced of Marr's countless earthshaking musical contributions, the melange of churning tremolo (created by sequencing the tremolo effect of four Fender amps at once) and the haunting slide guitar of "How Soon Is Now" is more than enough to cement Marr as an unsung legend of the guitar.
Hawthorne Heights and Emery
Monday, Jan. 20, 2020 / 6:30pm @ Culture Room 3045 N Federal Hwy Fort Lauderdale FL 33306
3045 N Federal Hwy, Fort Lauderdale FL 33306
Tuesday, Jan. 21, 2020 / 7:30pm @ Amaturo Theater at Broward Ctr For The Perf Arts 201 Sw 5th Avenue Fort Lauderdale FL 33312
201 Sw 5th Avenue, Fort Lauderdale FL 33312
Tuesday, Jan. 21, 2020 / 8:00pm @ King Center For The Performing Arts 3865 N Wickham Road Melbourne FL 32935
3865 N Wickham Road, Melbourne FL 32935
Marr has transcended his place as an icon of '80s guitar in maintaining relevance through the years and never shying away from opportunities with younger groups. Marr has performed with fresh bands like the Cribs and Modest Mouse, always adding his own flare to the established sounds of the artists without changing the entity all together. While the media already spends far too much time making verbal Venn diagrams of the Marr-Morrissey relationship, it is important to note that Marr -- beyond being Moz's former musical foil -- really has become the anti-Morrissey in his dealings with the media and fans, maintaining a reputation as one of the friendliest legends in music.
As Marr's first solo performance in South Florida approaches, one should take the time to delve deeply into the guitarist's massive catalog and understand the genius of Johnny Marr beyond the Smiths. Perhaps begin with The Messenger, Marr's first proper solo release, and a far more listenable record than anything Moz has released in recent memory.
Johnny Marr with Alamar. 7:30 p.m., Tuesday, November 26, at Culture Room, 3045 N. Federal Hwy., Fort Lauderdale. Tickets cost $25 plus fees. Call 954-564-1074, or visit cultureroom.net.
Follow @CountyGrind
Trina and Trick Daddy Kick Off 2020 With 99 Jamz Radio Show
Billy Joel Begins the Decade With a Show in South Florida
|
cc/2020-05/en_middle_0097.json.gz/line35435
|
__label__wiki
| 0.714102
| 0.714102
|
HomeWelcome to the BSHS Website The British Society for the History of Science (BSHS) is the main organisation in the British Isles working to bring together people with an interest in the histories of science, technology and medicine and their changing relationship with society.As you will know from the last issue of Viewpoint membership rates have increased slightly this year but we are sure that you will still find membership excellent value for money. In addition to regular issues of Viewpoint and the British Journal for the History of Science, and our active conference programme, membership benefits will shortly be expanded to include a dedicated members’ area of the BSHS website.» Learn more about the BSHS here
The BSHS
Policy: Statement on Equality and Diversity
International Advisers
Updates from the BSHS President
Policy: Social Media Guidelines
Website Writing and Image Guidelines
BJHS
BJHS Themes
BSHS Monographs
BSHS Translations
Education Forum Archive
About BSHS Membership
BSHS Policies
Policy: Guidance for Chairs
Policy: Guidance for Speakers
ConferencesForthcoming Meetings Organised or Supported by the BSHS24th International Congress of History of Science, Technology and Medicine, 2013, Manchester2011 BSHS Annual Conference, 14-17 July 2011, University of Exeter Recent Meetings Organised by the BSHS2011 BSHS Postgraduate Conference, 4-6 January 2011, University of Manchester2010 BSHS Annual Conference, 22-25 July 2010, University of AberdeenBSHS Meeting Information and ArchivesAnnual Conference: the largest event in the BSHS calendar, the annual summer meeting was re-established in 2003 and welcomes contributors from all areas of the profession.Postgraduate Conference: an equally important Society institution, the Postgraduate Conference takes place early in the calendar year and is organised entirely by, and for, graduate students.Other Meetings: details of more specialised conference events, plus joint meetings with other societies, including the four-yearly Three Societies Meeting.Interested in organising a meeting?If you have a suggestion for a possible future conference, symposium or public lecture which you think would benefit from BSHS support, we’d like to hear it. The BSHS may be involved at a variety of levels ranging from overall organization to financial or in-kind sponsorship. See BSHS Support for Events for further details.
Twitter Conference
Postgraduate Conferences
Three Societies Meeting
Other BSHS Meetings
Support for Events
GrantsThe British Society for the History of Science operates the following grants schemes:Master’s Degree Bursaries: bursaries of £1,000 to support students taking taught Master’s courses in the history of science or technology. Non-members of the Society are eligible. Deadline: 30 September each year.Research Grants: small grants for specific research purposes, from £50 to £500. There are two cycles per year. Only members of the Society are eligible. Deadlines: 30 September and 31 March each year.Butler-Eyles Travel Grants: grants of up to £100 to assist with the travel costs of attending a BSHS conference. This grant is open to independent scholars and student members of the Society only. There are multiple cycles: candidates should apply by the registration deadline for the relevant conference.Special Projects Grants: grants, usually from £50 to £1500 in value, to fund ‘special projects’ which promote the general aims of the BSHS. There are two cycles per year. Only members of the Society are eligible. Deadlines: 30 September and 31 March each year.Care Grants: grants of up to £100 towards delegates’ care arrangements during the BSHS Annual Conference.The Society also supports the organisation of conferences and events, but not through these grants schemes. For more details of the…
Butler-Eyles Travel Grants
Carer Grants
Engagement Fellowships
Master’s Degree Bursaries
Outreach and Engagement Project Grants
Undergraduate Dissertation Archive Grants
PrizesThe BSHS encourages good quality history of science by organising and judging three prestigious biennial prizes, two of which are awarded by the Society:The Singer Prize is awarded by the BSHS every two years to the author of an unpublished essay based on original research into any aspect of the history of science, technology, or medicine. The Prize is intended for younger scholars or entrants into the profession.The Dingle Prize is awarded to the best book in the history of science (broadly construed) published in English and which is accessible to a wide audience of non-specialists. The winner of the 2009 competition was Thomas Dixon, Science and Religion: A Very Short Introduction (Oxford University Press, 2008).The BSHS Slade Prize was awarded biennially between 1999 and 2009 to the writer of an essay (published or unpublished) that made the best critical study of an episode in the history of science focused on conceptual innovation or scientific methodology. Details of the winners are available here.
BSHS Singer Prize
BSHS Hughes Prize
BSHS Pickstone Prize
BSHS Ayrton Prize
BSHS Great Exhibitions Prize
Postgraduate Hub
Leaving a Legacy to the BSHS
Faking It: Forgery and Fabrication in Late Medieval and Early Modern Culture (August 2019)
Home/News/Conferences, Symposia & Workshops/Faking It: Forgery and Fabrication in Late Medieval and Early Modern Culture (August 2019)
The University of Gothenburg, Sweden, 15-17th August 2019
What is real and what is fake? And why does it matter? As soon as objects, texts and utterances (be they pragmatic or artistic) become imbued with a sense of authority or authenticity, there is a potential to produce other objects, texts and utterances which mimic and attempt to siphon off that authority and authenticity. In late medieval and early modern European culture (1400–1750), this potential was realized in new and unprecedented ways. Social, technological, and intellectual developments forever altered many activities which fall under the remit of forgery and fabrication, spurring lively debate about truth and falsity. The printing press transformed the production, distribution and marketing of texts and images. Heightened interest in classical antiquity changed how scholars interacted with and assigned value to artefacts originating in past cultures. Legal developments altered how artworks and documents were policed, and how authorship and authenticity were instantiated.
The conference Faking it. Forgery and Fabrication in Late Medieval and Early Modern Culture, held in Gothenburg from the 15th to the 17th of August 2019, seeks to explore the many and varying ways in which legitimate forms of production spawned illegitimate ones in late medieval and early modern culture. The conference is hosted by The Early Modern Seminar at The University of Gothenburg. We welcome proposals on all types of cultural production stemming from all cultural ambits, provided that they are connected with the later medieval and early modern world.
Confirmed keynote speakers:
Patricia Pires Boulhosa (Department of Anglo-Saxon, Norse, and Celtic, University of Cambridge)
Ingrid Rowland (The University of Notre Dame School of Architecture)
Earle A. Havens (Department of German and Romance Languages, John Hopkins University)
Christopher S. Wood (Department of German, New York University)
Topics may include, but are not limited to:
The terminology of spuriosity
Developments in criticism as a response to forgery
The fake as a foil to the authentic
Connections between literary forgery and forgery in the visual arts
The relationship between lying and forgery
Grey areas: where production becomes fabrication
Legal and economic perspectives on fabrication
Fakes and fabrications in arts and sciences
The personality cult of the forger
We invite abstracts of up to 250 words, accompanied by a title and a 50-word biographical statement, to be sent to [email protected] Note that presentations must last no more than 20 minutes. The deadline for submitting an abstract is the 30th of January, 2019. Enquiries may be sent to the same address or made directly to Matilda Amundsen Bergström ([email protected]) or Philip Lavender ([email protected]).
Website: http://lir.gu.se/forskning/forskningssamverkan/tidigmoderna-seminariet
By Nicola.Sugden|2018-11-01T20:44:10+00:00October 1st, 2018|Conferences, Symposia & Workshops, News|Comments Off on Faking It: Forgery and Fabrication in Late Medieval and Early Modern Culture (August 2019)
About the Author: Nicola.Sugden
Follow @BSHSNews
BSHS
@BSHSNews
The @royalsociety Lisa Jardine Grant Scheme, which supports travel and expenses for research trips and events, is o… https://t.co/rjx3oLaOdg
RT @BSECS: In case the Oxford conference just wasn't enough, we're now announcing our 2020 postgraduate/ECR conference CfP... details are h…
BSHS Executive Secretary (for current mailing address please contact by email in the first instance)
Web: Official BSHS Website
Copyright 2017 | The British Society for the History of Science | All Rights Reserved.
30% discount off Royal Society Notes and Records
BSHS members get an exclusive 30% off a personal subscription to Notes and Records.
20% discount off Ashgate publications
BSHS members get an exclusive 20% off all Ashgate publications.
Visit Ashgate
|
cc/2020-05/en_middle_0097.json.gz/line35436
|
__label__wiki
| 0.932778
| 0.932778
|
Online Streams
Improve Reception
Report Reception & Streaming Issues
BPR News
About BPR News
Local & NC News
BPR Classic
About BPR Classic
Open Air Brevard
Monthly Sustainer
Stock and IRA Rollover Gifts
Local Business Partner Program
Business Sponsorship Directory
About BPR
People of BPR
Careers at BPR
Local Content & Services
BPR Tech Blog
Studio/ISDN Rental
Daniel Estrin
The 'Losing Lawyer' In Israel Who Defends Palestinians Charged With Violence
By Daniel Estrin • Jan 15, 2020
Her Israeli critics have called her a traitor and devil's advocate for representing Palestinians facing terrorism charges in Israeli courts. She calls herself a "losing lawyer," losing case after case, defending Palestinian suspects for nearly five decades.
Now the fiery Lea Tsemel, 75, is the subject of an award-winning documentary — and a target in the latest battle between Israel's liberal filmmakers and right-wing activists led by the country's nationalist culture minister.
Oscar-Shortlisted Israeli Documentary 'Advocate' Faces Backlash
MICHEL MARTIN, HOST:
Global Reactions To Soleimani Killing
By Daniel Estrin & Eleanor Beardsley • Jan 4, 2020
Now let's get reaction from around the globe. I'm joined now by NPR correspondent Deborah Amos in Beirut, Daniel Estrin in Jerusalem and Eleanor Beardsley in Paris.
Bethlehem Tourism Reaches Record High As Palestinians See Hope For Peace Dimming
By Daniel Estrin • Dec 24, 2019
AILSA CHANG, HOST:
Syrians Say U.S. Helicopter Fire Killed Civilians During The Raid On Baghdadi
By Daniel Estrin & Lama Al-Arian • Dec 4, 2019
A Syrian farmer says his arm was blown off and his two friends were killed by U.S. helicopter fire in the village where American special forces were attacking the compound of ISIS leader Abu Bakr al-Baghdadi in October.
Lebanon's Anti-Government Protesters View Army As Unifying Force
By Daniel Estrin • Nov 15, 2019
'We Didn't See A Body': Baghdadi's Death Draws Doubts In Lands Where ISIS Ruled
By Fatma Tanis, Jane Arraf, Daniel Estrin, Lama Al-Arian & Alex Leff • Oct 29, 2019
Updated on Wednesday at 5:30 p.m. ET
In Iraq and Syria, news of ISIS leader Abu Bakr al-Baghdadi's death has stirred a mix of responses — from joy to disbelief to dread.
Since President Trump announced this weekend that Baghdadi died during a U.S. military operation in Syria, analysts have been grappling with the implications for the militant organization that has now lost its main chief in addition to all the territory it once held in Iraq and Syria.
Lebanese Prime Minister Resigns
By Daniel Estrin & David Greene • Oct 29, 2019
DAVID GREENE, HOST:
After weeks of raucous, jubilant protests and sometimes violent attempts to quell them, there was celebration in the streets of Beirut today.
(SOUNDBITE OF ARCHIVED RECORDING)
UNIDENTIFIED CROWD: (Chanting in foreign language).
Syrians React To Death Of ISIS Leader Abu Bakr al-Baghdadi
By Daniel Estrin • Oct 28, 2019
MARY LOUISE KELLY, HOST:
Anti-Government Protests Continue In Lebanon And Move To Include Hezbollah Leader
AUDIE CORNISH, HOST:
'Baby Shark,' Drinks And Dancing: Lebanon's Protests Are Unlike Any Other
By Daniel Estrin & Lama Al-Arian • Oct 23, 2019
Lebanon's mass street protests resemble other outpourings of anger in places like Chile and Ecuador. But the Lebanese never miss an excuse to party.
Faced with years of war, Lebanese have coped with strife by using satire, humor and lots of dancing. This thawra or revolution, as anti-government protesters in Lebanon call it, is no different. It's accompanied by clever handwritten signs, profanity-laced chants and even "Baby Shark" singalongs.
Hundreds Of Thousands Of Protesters Fill Main Squares In Lebanon
ARI SHAPIRO, HOST:
This is what Lebanon sounds like tonight.
(SOUNDBITE OF PROTEST)
UNIDENTIFIED PROTESTERS: (Chanting in foreign language).
Kurdish General Slams U.S.-Syria Policy; Gen. Petraeus Calls Withdrawal 'A Betrayal'
By Jenny Gathright, Daniel Estrin & Lama Al-Arian • Oct 19, 2019
As the five-day cease-fire along Turkey's border with Syria continues to falter, the commander of the Kurdish-led Syrian Democratic Forces (SDF) tells NPR he thinks the deal is "really terrible."
Reporters' Notebook: The Moment Everything Changed In Syria
Our small NPR reporting team arrived in Syria just in time to witness a historic moment in the long-running civil war. But we didn't think we would have to rush out so quickly.
Kurds Align With Syria After U.S. Withdrawal
As U.S. Troops Prepare To Withdraw From Syria, Kurds Seek New Ally
By Daniel Estrin & Peter Kenyon • Oct 14, 2019
NOEL KING, HOST:
The United States military and Kurdish militias were allies for five years fighting against ISIS. Now that has changed. President Trump unexpectedly pulled U.S. troops from near the Syria-Turkey border, and the Kurds were left to fend for themselves.
Turkey Claims To Have Won A Key Syrian Border Town From Kurdish Forces
By Vanessa Romo & Daniel Estrin • Oct 12, 2019
Turkey's defense ministry says the country's forces have captured a Syrian border city after clashes with Kurdish-led militias. But a Syrian monitoring group said the fight was still ongoing.
Turkish officials said on state media Saturday that the strategic town of Ras al-Ayn, which sits on the northeastern part of the border, has been "brought under control." Several surrounding villages have also been overtaken, the officials said.
Turkey Launches Offensive Against Kurds In Northern Syria
RACHEL MARTIN, HOST:
Netanyahu Fights To Hang On In Another Israeli Election. Here's What To Know
By Daniel Estrin • Sep 16, 2019
Benjamin Netanyahu, Israel's longest-serving prime minister, faces his toughest political battle for survival in years, as the country holds unprecedented repeat elections Tuesday.
This is the second time Israelis are going to the polls in less than six months. Netanyahu, 69, forced the do-over in a last-minute move, just weeks after April elections, because he secured a narrow win but failed to build a parliament majority.
Arab Israelis Hope Their Votes Will Help To Oust Netanyahu
There's A Growing Sore Spot In Israeli-U.S. Relations: China
By Daniel Estrin & Emily Feng • Sep 11, 2019
The Trump administration has shown unwavering support for the Israeli government, except for one major criticism: China's growing influence in the Israeli economy.
Chinese companies have invested in strategic Israeli infrastructure, from shipping to electricity to public transportation, and they have bought up millions of dollars in stakes in cutting-edge technology startups.
Where Israel sees an opportunity to access the world's second-largest economy, the United States sees security threats posed by its main adversary.
Israel Appears To Intensify Its Campaign Against Iranian Forces
By Daniel Estrin • Aug 26, 2019
Face Recognition Lets Palestinians Cross Israeli Checkposts Fast, But Raises Concerns
It takes a few seconds: Palestinians place electronic ID cards on a sensor, stare at the aperture of a small black camera, then walk past panels fanning open to let them through.
Israel is upgrading its West Bank checkpoints with facial recognition technology to verify Palestinians' identities as they cross into Israel. The new system, which began rolling out late last year, eases their passage with shorter wait times — but is drawing criticism about the role the controversial technology plays in Israel's military control over Palestinians.
Reversing Earlier Ban, Israel Permits Limited Visit For Rep. Rashida Tlaib
Here's What Tourists Might See If They Were Allowed To Visit Gaza
By Daniel Estrin • Aug 9, 2019
It's not easy to find a tour guide in Gaza. Even clerks at the local Tourism Ministry, a vestige of the 1990s that remarkably still exists, struggle to recommend professional guides, before suggesting a man who hasn't led tourists around for 20 years.
Ayman Hassouna seems delighted to spend a sweltering day in a suit jacket, showing off the historical sites, colorful markets and delicious grilled fish of his native Gaza — among other unexpected gems made even more precious by the reality that most people in the world are unable to experience them.
Here's What Tourists Might See If They Were Allowed To Visit The Gaza Strip
Now for a view of the Gaza Strip that few people get. It's what a tourist might see if tourists were allowed; they haven't been since Hamas militants took over Gaza 12 years ago.
The Doctor Who Helped Israeli Spies Catch Eichmann But Refused Recognition For It
By Daniel Estrin • Jul 16, 2019
The fake license plates, forged passports and concealed surveillance camera were locked away in the musty archives of Israel's Mossad intelligence agency for 50 years. Now they are touring the U.S. in a traveling exhibition about the Mossad's legendary capture of Nazi officer Adolf Eichmann.
But one object crucial to the mission's success is not on display: the needle used to inject a sedative into Eichmann's arm before he was smuggled onto a plane back to Israel to stand trial.
Israeli Education Minister Causes Uproar, Endorses Discredited Gay Conversion Therapy
In Israel, the new education minister has caused an uproar by saying gay conversion therapy works. The practice has been widely discredited. NPR's Daniel Estrin reports from Jerusalem.
'I Want To Get The Hell Out Of Here': Thousands Of Palestinians Are Leaving Gaza
By Daniel Estrin • Jul 4, 2019
For over a decade, the Gaza Strip — controlled by the Islamist militant group Hamas, blockaded by its neighbors, difficult to leave — has amounted to an experiment in human isolation.
Now there is a new escape route. Egypt suddenly opened its border with Gaza in May 2018, and, facing increasingly unbearable living conditions, tens of thousands of Gazans are believed to have crossed that border and scattered across the world, in the latest chapter in a mass exodus of migrants out of the troubled Middle East.
U.S. Mideast Plan Rejected By Palestinian Leaders, Panned By Former U.S. Envoys
By Daniel Estrin • Jun 24, 2019
The White House on Saturday published one-half of its long-awaited Israeli-Palestinian peace plan — a multibillion-dollar proposal to upgrade the Palestinian economy. The Palestinian leadership has already rejected it, and so far, it has been widely panned by former U.S. envoys and Mideast policy experts.
© 2020 BPR
|
cc/2020-05/en_middle_0097.json.gz/line35441
|
__label__cc
| 0.714962
| 0.285038
|
Joe Scarborough: Glenn Beck's Border Gesture 'Christ-like,' Out of 'Jesus' Handbook'
On his Thursday “Morning Joe” broadcast, host Joe Scarborough applauded Glenn Beck for his efforts in shipping truckloads of soccer balls and hot meals to the border, which is taking on an influx of unaccompanied Central American youth.
Scarborough likened Beck to Jesus Christ and attacked conservatives for their criticism of Beck’s gesture.
“A lot of people are saying that he’s actually playing into Barack Obama’s hands, that he’s playing by Obama’s handbook,” Scarborough said. “He’s actually playing by another person’s handbook, Jesus’ handbook. I mean, this is — Jesus was very clear. He said the people that are blessed are those that understand I was hungry, and you fed me. I was thirsty, and you gave me something to drink. I needed clothing, and you gave me clothes.”
“What Glenn Beck is doing is the most Christ-like thing anybody can do, and so for a lot of people on the right who may call themselves Christians, to attack Glenn Beck for doing exactly what Jesus says a Christian has to do, which is to be the Good Samaritan. I think the fact he is sending down tractor-trailer loads of food and clothes and toys and soccer balls to these poor children despite the fact he opposes the type of immigration reform the president is pushing right now makes it an even more noble gesture.”
Follow Jeff Poor on Twitter @jeff_poor
ClipsGlenn BeckJoe Scarborough
Waters on Hunter Biden Testifying: GOP 'Can Call Whomever They Want'
|
cc/2020-05/en_middle_0097.json.gz/line35442
|
__label__wiki
| 0.770218
| 0.770218
|
Lithuania urges Walmart to drop Soviet-themed shirts
Vilnius (AFP) – Lithuania on Friday urged American retail giant Walmart to stop selling T-shirts and hoodies with Soviet hammer and sickle symbols, insisting that the image insults victims of often deadly Soviet-era persecution.
“We sent a letter to Walmart requesting the withdrawal of products with Soviet symbols and we are still waiting for a reaction,” Lithuanian Ambassador to the US Rolandas Krisciunas told AFP.
The hammer and sickle symbol is banned in Lithuania, a European Union member of 2.9 million that was the first republic to secede from the Soviet Union as it began to crumble in 1990.
The Baltic state’s Foreign Minister Linas Linkevicius tweeted: “You wouldn’t buy Nazi-themed clothing, would you?
“We trust Walmart’s moral stance & call to withdraw products with the symbols of mass murders.”
Vilnius estimates that more than 50,000 Lithuanians died in camps, prisons, and during deportations in 1944-1953, while another 20,000 partisans and supporters were killed in anti-Soviet guerilla fighting.
Walmart is selling red-hooded sweatshirts and T-shirts emblazoned with the yellow hammer and sickle symbol over the caption “CCCP”, which means “USSR” in the Cyrillic alphabet.
Hoodies described as “cool” on Walmart’s website cost $29.95 (25.70 euros) while the T-shirts go for $18.00.
The Soviet-inspired style has become trendy in recent years as Russian designers make their mark.
Walmart did not immediately respond when contacted by AFP, but guidelines posted on its website prohibit the sale of products related to “any historical or news event” that could be considered “offensive”.
Politicians in neighbouring Baltic states Estonia and Latvia, where people also suffered decades of Soviet occupation, joined the call for the world’s biggest retailer to pull the Soviet-themed merchandise from its shelves.
Walmart is present in 28 countries, but not in the Baltic states or other eastern European countries dominated by the former Soviet Union.
Lithuania, which joined both the EU and NATO in 2004, was a battleground between Nazi and Soviet troops during World War II.
It was seized by Moscow in 1940 under a secret pact with Adolf Hitler, and within a decade, some 300,000 Lithuanians had been deported, mostly to Siberia, or killed in insurgent fighting.
WAPO Presents Virginia Gun Rally to be Charlottesville 2.0
Two Officers Dead in Honolulu Shooting
Sen. Brown on Impeachment Witnesses: 'Fine' to Hear from Hunter Biden
|
cc/2020-05/en_middle_0097.json.gz/line35443
|
__label__wiki
| 0.78715
| 0.78715
|
Clerk of Council
Records Management Division
Resources Available at the Records Center
The Records Center houses a variety of records generated by departments and divisions of the City of Charleston, which may be of use for both historical and contemporary research. These records document the City's organizational history and provide important insight into the social, political, and economic history of Charleston.
In 2002, the City transferred some of its older collections to the Charleston County Public Library (CCPL) in order to make the documents more widely available. A list of these records is located on the library website at City of Charleston Records.
The following gives a broad overview of the records held by the City of Charleston and available for research at the Records Center at 2 George Street. Researchers are welcome to make appointments to view many of our records; however, some research requests may require a Freedom of Information Act (FOIA) request.
Council Records
Board, Committee, and Commission Minutes, 1790 to 2015 (PDF) (with early gaps)
Special Committee, Subcommittee, and Public Hearing Minutes, 1886 to 2015 (PDF) (with early gaps)
Ledgers of City Council Minutes, 1865 to 1908
Indexes to City Council Ledgers, 1865 to 1919
Journals of the City Council of Charleston, 1865 to 2002
Ledgers of Ways and Means Committee Minutes, 1897
Executive & Legislative Files
Mayoral Records, 1879 to present
Mayoral Scrapbooks, 1931 to 1999
Codes of Ordinances of the City of Charleston, 1783 to present
Ordinances, Resolutions, and Proclamations, 1800 to 2015 (with gaps)
Departmental Records, including the following collections of note:
Business License Registers, Street Lists, and Applications, 1872 to 2015
Clerk of Council Letterpress Copybooks, 1935 to 1994 (microfilm only)
City Treasurer and Assessor Files, 1884 to 1960
Engineering Records, 1867 to 1979 (PDF)
Fire Department Records, 1848 to 1979 (PDF)
Public Service Records, 1916 to 1983
Sewerage Department Records, 1895 to 1924
Surveyor Records, 1813 to 1916 (PDF)
General Research Files
These files are a useful source of knowledge for anyone seeking a broad overview of a particular subject, person, or place of significance to the City. While largely a collection of newspaper clippings, the General Files also contain many original City documents.
The General Files of the City Records Center contain information on:
City Streets
Events Relevant to the History of Charleston
Noteworthy Persons
Institutional Records
Alms House Records, 1801 to 1917 (Microfilm only. CCPL holds original records)
Orphan House and Oak Grove Files, 1803 to 1979
In 2002, many Charleston Orphan House records over seventy-five years were transferred to the South Carolina Room of the CCPL, where records are processed and open to researchers. Records that were less than seventy-five years old at the time remain with the City's Records Management Division. Depending on age, the records on file at the Records Center are subject to the following restrictions:
To protect the privacy of former residents, access to these files is restricted until the records reach seventy-five years of age. Contact Records Management for more information on accessing these records. The records may be viewed at Records Management, or redacted photocopies may be obtained:
By a former resident, upon presentation of a photo ID
By a relative of a deceased former resident, upon presentation of a photo ID and a copy of the death certificate of the former resident
By a relative of a living former resident, upon presentation of a photo ID and a power of attorney from the former resident
By other persons with a court order allowing access to the records upon presentation of a photo ID and a copy of the court order
Land & Property Records
Building Permits, 1932 to 2016
Certificates of Occupancy, 1978 to 2015
Elevation Certificates, circa the 1980s to present
Maps and Plats, 1698 to 1989
Through the courtesy of the Charleston County Register of Deeds (ROD), digital images of more than 800 archival maps and plats, many drawn by the City Surveyor or City Engineer, are available online at City of Charleston Archival Maps and Plats.
Please note that the City does not retain plans for private property longer than one year after an issuance of a Certificate of Occupancy.
Publications & Printed Material
City of Charleston Yearbooks, 1880 to 1951
Pamphlet Collection, 1782 to 1991 (PDF)
Plans and Studies, 1895 to 2009 (PDF)
Records Not held by the City of Charleston
Many of the public records frequently requested from the City Records Center are actually issued by other government agencies.
The South Carolina Department of Health and Environmental Control, Vital Records: Issues birth certificates, death certificates, marriage licenses, and reports of divorce. Phone: 843-953-0032
The Charleston County Clerk of Court: Issues divorce decrees. Phone: 843-958-5000
The Charleston County Register of Deeds (ROD): Retains deeds, mortgages, and plats for real property located in the City of Charleston. Phone: 843-958-4800
Rebecca Schultz
2 George Street
2 George Street Charleston SC 29407
Historical City Information
Intendants and Mayors
Historical City Records
Mayoral Records
Hurricane Hugo 30th Anniversary
|
cc/2020-05/en_middle_0097.json.gz/line35448
|
__label__wiki
| 0.914513
| 0.914513
|
Truck, train collide; man airlifted
Authorities say a Pomeroy man failed to yield at a crossing at a private drive off Three Locks Road.
Truck, train collide; man airlifted Authorities say a Pomeroy man failed to yield at a crossing at a private drive off Three Locks Road. Check out this story on chillicothegazette.com: http://ohne.ws/2bFm5C6
Chris Balusik, Reporter Published 4:39 p.m. ET Aug. 18, 2016 | Updated 6:56 p.m. ET Aug. 19, 2016
A train collided with a dump truck Thursday along the 6000 block of Three Locks Road where the private drive to Three Locks Gravel Co. crosses the railroad tracks.(Photo: Jess Grimm/Gazette)Buy Photo
CHILLICOTHE - A Pomeroy man was airlifted to a Columbus hospital Thursday afternoon after the dump truck he was driving collided with a train on a private drive leading to the Three Locks Gravel Co.
According to Lt. Mike Preston, with the Ross County Sheriff's Office, the call for emergency services came in shortly after 4 p.m. Crews responded to the crossing located at 6580 Three Locks Road to find the badly damaged truck on the eastern side of the railroad tracks, with the view of the vehicle blocked from passing Three Locks Road traffic by a stopped Norfolk & Southern train.
The truck's driver, Marty Chasteen, 62, was trapped inside the vehicle and had to be mechanically extricated by emergency crews. When he was brought to the Scioto Township Squad for transport to a MedFlight landing zone that was set up in the area in front of Open Door Church, he was strapped down to keep him immobilized. Preston said he was awake and responsive, but that no further information on the severity of his injuries was available.
Chasteen was flown to Ohio State University's Wexner Medical Center for treatment.
Preston said Chasteen was westbound on the private drive heading toward Three Locks Road when he reached the tracks and "failed to yield to a southbound train."
The lengthy train was hauling tractor-trailers that were stacked two high on each flatcar.
Representatives of the Ross County Sheriff's Office, Ohio State Highway Patrol and Norfolk & Southern were taking measurements and continuing their investigation into the early evening at the scene. Preston initially said it was too early into the investigation to determine how fast the train had been going at the time of the impact. Crews from Scioto Valley Fire and EMS, the VA Fire Department and representatives from the railroad each played a role in the response.
Live Blog #cgnow: Updates and developing stories from our social media network
Read or Share this story: http://ohne.ws/2bFm5C6
|
cc/2020-05/en_middle_0097.json.gz/line35451
|
__label__wiki
| 0.606989
| 0.606989
|
Commerce Secretary Wilbur Ross predicts Trump and China will reach a trade deal — ‘even shooting wars end in negotiations’ – CNBC
June 11, 2019 by Zettan
Commerce Secretary Wilbur Ross predicted on Tuesday that the U.S. and China will successfully negotiate a trade deal.
“Eventually, this will end in negotiation,” Ross said on CNBC’s “Squawk Box.” “Even shooting wars end in negotiations.”
With questions circulating about whether President Donald Trump and Chinese leader Xi Jinping would meet on trade at the G-20 meeting later this month, the U.S. president told CNBC on Monday he would place additional tariffs on Chinese goods if Xi does not attend.
“The China deal is going to work out. You know why? Because of tariffs,” Trump said in a “Squawk Box” call with CNBC’s Joe Kernen. “Right now, China is getting absolutely decimated by companies that are leaving China, going to other countries, including our own, because they don’t want to pay the tariffs.”
Ross, who has spoken out in favor of Trump’s tariff strategy, warned that trade deals are not made at summits. He said any talks between Trump and Xi would lay the groundwork for a possible agreement.
In May, Trump increased tariff rates on $200 billion worth of Chinese goods and threatened to put levies on another $300 billion, effectively the rest of China’s imports in the United States.
An agreement with China would have to fix all the violations that the U.S. alleges, otherwise making a deal would not make any sense, said Ross, who before joining the White House, made a fortune in the investment world, running W.L. Ross & Co., and buying stakes in distressed assets.
“Either we will collect more and more tariffs on more and more products or we’ll back an arrangement with them,” Ross said, while warning investors not to get too “trigger happy” when Trump threatens tariffs.
After the president warned Mexico on May 30 that he would put a 5% tariff on all Mexican goods if they did not take actions to help curb undocumented migrants from coming into the U.S., Ross said that “people were getting hysterical” and the markets got “a little too jumpy.” The day after the proposed tariffs were announced, the Dow Jones Industrial Average plunged more than 350 points.
“Judge this administration by results,” Ross said. “Don’t judge it by interim soundbites.” Late Friday, the president called off the Mexico tariffs, saying the U.S. and Mexico agreed to follow through on earlier concessions it had made on immigration.
In Monday’s CNBC interview, Trump said the deal came together in just two days because Mexico’s leaders knew the alternative would have been worse.
“We got everything we wanted and we’re going to be a great partner to Mexico now because now they respect us,” Trump said. “They didn’t even respect us. They couldn’t believe how stupid we were with everything that’s going on where somebody comes in from Mexico and just walks right into our country and we’re powerless to do anything.”
Watch the full CNBC interview with Commerce Secretary Wilbur Ross
Filed Under: Commerce, Secretary Tagged With: Commerce, Secretary
|
cc/2020-05/en_middle_0097.json.gz/line35452
|
__label__cc
| 0.690382
| 0.309618
|
Google Fiber is leaving Louisville, so what should customers do?
Google Fiber is leaving Louisville, where it had installed internet in Portland, Newburg and Strathmoor. If you're a customer, here's what to know
Google Fiber is leaving Louisville, so what should customers do? Google Fiber is leaving Louisville, where it had installed internet in Portland, Newburg and Strathmoor. If you're a customer, here's what to know Check out this story on cincinnati.com: https://www.courier-journal.com/story/money/companies/2019/02/07/google-fiber-leaving-louisville-what-customers-should-know/2803780002/
Thomas Novelly, Louisville Courier Journal Published 3:33 p.m. ET Feb. 7, 2019 | Updated 6:45 p.m. ET Feb. 7, 2019
Google Fiber on Thursday announced it would be leaving Louisville behind. So what does that mean if you're a Google Fiber customer?
From how long Google Fiber will be available to what other services you can switch to, here's what you need to know:
Which neighborhoods are affected?
Google Fiber was set to provide internet for the Portland, Newburg and Strathmoor neighborhoods.
When will my service end?
Google Fiber said it would end service on April 15, 2019.
Read this: Mayor considers Louisville Metro's first tax increase, budget cuts
AT&T Fiber and other internet options
AT&T says it offers comparable fiber service at nearly 175,000 Louisville area homes and small businesses. As of September, AT&T listed the following areas having access to 1Gbps service:
Clarksville, Indina
Jeffersonville, Indiana
New Albany, Indiana
Shively
Oldham County.
You can see which AT&T services are offered at your home byclicking here. AT&T customers get 1 Gbps service for $90 per month and 100 Mbps for $50 per month.
Spectrum has also been offering 1 Gbps download speeds throughout Louisville since October, spokesman Mike Pedelty said.
While the underlying technology is different — the fiber optic cables don't extend all the way to individual homes — the resulting service is essentially the same, with no modem fees or data caps. Spectrum customers pay $124.99 for 1 Gbps service and $64.99 for 200 Mbps service. You can check its offerings by clicking here.
Another option is local company IgLou, which resells bandwidth from AT&T minus the data caps the bigger company imposes. IgLou customers pay $89.95 per month for 1 Gbps service, $69.95 per month for 100 Mbps and $49.95 for 50 Mbps.
How much will I have to pay?
Google Fiber said the next two months before it shuts off internet service will be free for existing customers. Customers had been paying $50 per month for 100 Mbps service and $70 per month for 1 Gbps service.
What do I need to do my Google Fiber equipment?
Customers do not need to return any of the equipment that came with installation, including Google Wifi and Nvidia Shield.
These devices can be used with any Internet service provider. However, if they no longer want them, they can safely recycle them at Louisville's Electronics Recycling Center. They should perform a factory reset beforehand to protect their personal information.
Google Fiber said Louisville was a trial experiment. And it said the company encountered a lot of problems. Namely "a different type of construction method," which involved "placing fiber in much shallower trenches than we’ve done elsewhere."
Is there a chance Google Fiber could be salvaged in Louisville?
It's not likely.
That seems unlikely.
-Tom, the Google Fiber team
— Google Fiber (@googlefiber) February 7, 2019
Will your cloud storage be affected?
Any additional storage Google Fiber customers have purchased will stay with their account. All the information will be maintained on Google Drive. But you may not be able to move anything else on to that Drive.
Will YouTube TV be affected?
Google Fiber said this will not affect YouTube TV, but you may not be able to stream services through Google Fiber anymore.
Are people in Louisville angry?
For some that would be an understatement. Google Fiber was answering questions on Twitter from some irate residents. Some were, uh, pretty rough.
"You messed up my road...you tore up my lawn," Twitter user Craig said. "Job well done. Not sure who was in charge of managing the project, but how are they still employed?"
You messed up my road...you tore up my lawn. Job well done. Not sure who was in charge of managing the project, but how are they still employed?
— Craig (@dcs722) February 7, 2019
Alfred Miller contributed reporting. Reach Thomas Novelly at 502-582-4465 or by email at tnovelly@courier-journal.com. Follow him on twitter @TomNovelly.
Read or Share this story: https://www.courier-journal.com/story/money/companies/2019/02/07/google-fiber-leaving-louisville-what-customers-should-know/2803780002/
|
cc/2020-05/en_middle_0097.json.gz/line35455
|
__label__wiki
| 0.575642
| 0.575642
|
Bigelow receives Childspring award
The Bigelow family hosted Makenge Chacha, who was in the U.S. for treatment.
Bigelow receives Childspring award The Bigelow family hosted Makenge Chacha, who was in the U.S. for treatment. Check out this story on cincinnati.com: http://cin.ci/1FOm5pC
Makenge Chacha and Victoria Bigelow holding the Dr. George B. Wirth Global Spirit Award Bigelow received from Childspring International.(Photo: Provided)
Indian Hill resident Victoria Bigelow was awarded the Childspring International Seventh Annual Dr. George B. Wirth Global Spirit Award in Atlanta. The award was in recognition of her dedication, faithful support exemplary service which have changed the lives of children around the world forever.
The Bigelow family hosted one of Childspring International’s children, Makenge Chacha, who was in the U.S. for treatment following a horrific hyena attack three years ago in his Tanzanian village. As a result of the attack, he lost both hands and was scalped. Shriner’s Hospital in Lexington fitted Makenge with prosthetic hands, which dramatically changed his life. Shriner’s Hospital in Cincinnati miraculously repaired Makenge’s scalp, leaving him with a full head of hair, and the confidence of a young man who has a beautiful life ahead of him, something he never thought he would ever have again.
In addition to other families who hosted Makenge for his first year in the United States, as well as the East End Adult Learning Center who provided him with tutors to help him learn English, Makenge will return to Tanzania with a love and appreciation for so many Cincinnatians who were there to help him grow, heal, and become whole again.
For more information about Childspring International and the incredible work they do to provide treatment for children all over the world, visit www.childspringintl.org.
Read or Share this story: http://cin.ci/1FOm5pC
|
cc/2020-05/en_middle_0097.json.gz/line35456
|
__label__wiki
| 0.992188
| 0.992188
|
UC lock for NCAAs after Tulsa win, ESPN's Lunardi says
An NCAA men's basketball tournament bid may well have been secured by UC on Wednesday.
UC lock for NCAAs after Tulsa win, ESPN's Lunardi says An NCAA men's basketball tournament bid may well have been secured by UC on Wednesday. Check out this story on cincinnati.com: https://cin.ci/1BJLHnb
Tom Groeschen, tgroeschen@enquirer.com Published 11:17 p.m. ET March 4, 2015 | Updated 10:39 a.m. ET March 5, 2015
Cincinnati Bearcats guard Farad Cobb (21) hits a 3-point shot against South Florida in February. Cobb scored XX points in Wednesday night's game.(Photo: Enquirer file)
TULSA, Okla. – This may have done it. An NCAA men's basketball tournament bid may well have been secured here Wednesday night by the University of Cincinnati.
In fact, ESPN bracketologist Joe Lunardi responded to a Twitter question after the game by saying UC was now a lock for the NCAA field after beating Tulsa 56-47. Lunardi confirmed via text to The Enquirer that he now considers UC certain to make the NCAAs.
“@KamChance: Is Cincinnati now a lock for NCAAs with its 6th top 50 RPI win? @ESPNLunardi” Yes. More Skyline!!
— Joe Lunardi (@ESPNLunardi) March 5, 2015
UC (21-9, 12-5 American Athletic Conference) beat league leader Tulsa (21-8, 14-3 AAC) on its home floor, apparently lifting the Bearcats off the NCAA bubble. UC entered with a No. 49 ranking in the daily NCAA RPI, with Tulsa at No. 31.
Junior guard Farad Cobb scored 22 points, and UC took a huge step toward securing its fifth straight NCAA bid with the victory before 5,840 fans at Reynolds Center.
Takeaways from UC-Tulsa: Bearcats rated lock for NCAAs
Does this indeed put UC into the NCAA field?
"I hope so," Cobb. "Oh yeah. We should be."
Box score: UC 56, Tulsa 47
UC finishes the regular season at home Sunday against Memphis (noon), followed by the AAC tournament March 12-15 in Hartford, Conn.
UC associate head coach Larry Davis, who has been reluctant to talk about the NCAA tournament, said it will be hard to deny the Bearcats now.
"In my mind, the only way we can guarantee ourselves, and there's obviously no guarantee until the committee picks them, but we've got to go beat Memphis on Sunday," Davis said. "And then I think it's going to be hard for them to keep us out."
CBS Sports Network analyst Pete Gillen, the former Xavier coach who was on hand to do color commentary for UC-Tulsa, was among those saying before the game that his sense was UC would clinch an NCAA bid by beating Tulsa.
"Everybody says 'Oh, you're in the tournament now, you're in the tournament now,' " Davis said. "All I know is if we beat Memphis, that gets us one step closer. This is a big win. Coming here on the road and beating (Tulsa) is huge.
UC's Cronin: Pizza coming for RallyCats
"This is a big win for us. We had to have this win. If we wanted to have a real, real shot to go on to play in the tournament, we had to have this win."
Sophomore point guard Troy Caupain, who backed Cobb with 12 points, also was asked if he thought UC is in the NCAA field now.
"I hope so," Caupain said. "We're really just focused on one game at a time. We've still got a lot of games ahead of us before we get to the dance. We've got one more game in the regular season before we get to the conference (tournament)."
UC already had been projected to reach the NCAA field by forecasters including Jerry Palm of CBS Sports (No. 10 seed), Lunardi of ESPN (11 seed) and Shelby Mast of USA Today (11 seed). And that was before the win at Tulsa.
Palm had listed UC among teams that are, "In for now" entering Wednesday.
Palm had said UC should be OK if it splits its last two regular season games. Step one is accomplished.
"Cincinnati took care of business against Tulane (last Saturday)," Palm wrote in his latest analysis. "With their good wins, the Bearcats are close to getting off this (bubble) page."
Wednesday's victory over Tulsa is as good a win as UC has had this season.
For UC, Cobb's 22 points were two behind his career high. Caupain added 12 points and six rebounds for UC, while junior forward Octavius Ellis had seven points, 13 rebounds and four blocks. Sophomore guard Kevin Johnson had eight points, and freshman forward Gary Clark had seven points and eight rebounds.
UC out-shot Tulsa 46 percent to 34 percent from the field and out-rebounded the Golden Hurricane 40-30.
The Bearcats entered Wednesday also hopeful of landing as high as a No. 3 seed for the AAC tournament. The win over Tulsa clinched a first round AAC tournament bye for UC.
At this point, if UC were to win its last two games (mission accomplished at Tulsa, then Memphis on Sunday), it would be the No. 3 seed in the AAC tournament. If the Bearcats lose Sunday, its AAC seed may depend on how other teams in their AAC standings vicinity fare.
UC has now won four straight games overall, and broke a four-game Tulsa winning streak.
Tulsa would have clinched a share of the AAC title by beating UC. The Golden Hurricane were led by Rashad Ray with 15 points and James Woodard with 12.
NICE HALF: UC led 27-20 at halftime, after leading by as much as 12 points before the break (25-13).
The Bearcats were led by Cobb and Johnson with seven points each in the first half.
DOWN THE STRETCH: UC pushed its lead out to 33-22 early in the second half, and led 35-25 with 13:50 to go.
Tulsa answered with a 6-0 run to come within 35-31 moments later. The Golden Hurricane crowd suddenly was back in it, after sitting on their hands much of the first half.
Cobb banged in consecutive 3-pointers to lift UC to a 43-36 lead with 8:15 left. Tulsa got as close as three points with 6:10 left but could draw no closer.
Cronin: Cameo possible, coaching unlikely until '15-16
|
cc/2020-05/en_middle_0097.json.gz/line35457
|
__label__cc
| 0.565907
| 0.434093
|
Home / Car News / Lexus RC F disguised as an Aussie police officer
Lexus RC F disguised as an Aussie police officer
A few weeks ago we have told you that the Victoria Police has managed to get a Mercedes-AMG GLE63 S Coupe as an operational highway patrol car. Now, the NSW police has also an interesting new colleague. We are talking about the all-new Lexus RC.
The car is powered by that impressive V8 in F specs and will be a multi-purpose vehicle. It will have an active role in roadside campaigns to promote road safety.
The new Aussie police officer has made its public debut last week during the Bathurst Six Hours where it was the new race control vehicle. The car will also be shown in various motorsport events.
Most of the time, the new Lexus RC F will be on NSW Police’s Southern Region service and will play an important role to promote safety on the roads. As you probably read, the RC F comes equipped with a 5.0 liter V8 engine naturally aspirated that can deliver 467 horsepower.
Source: Lexus
PREVIOUS 27 Mar 2016
Mini John Cooper Works Convertible - Pictures and details
NEXT 28 Mar 2016
Skoda celebrates 25 years under Volkswagen umbrella
|
cc/2020-05/en_middle_0097.json.gz/line35462
|
__label__wiki
| 0.759932
| 0.759932
|
Brother Wolf plans cat cafe
Downtown Commission approves wording change to zoning ordinance, plans move forward
Brother Wolf plans cat cafe Downtown Commission approves wording change to zoning ordinance, plans move forward Check out this story on citizen-times.com: http://avlne.ws/1Ml6IqR
Beth Walton, bwalton@citizen-times.com Published 5:00 p.m. ET July 10, 2015 | Updated 9:42 a.m. ET Sept. 8, 2015
Three kittens needing adoption at Brother Wolf Animal Rescue. The nonprofit no-kill shelter received unanimous approval from the city’s Downtown Commission Friday morning to amend the wording of a zoning ordinance to open a cat cafe.(Photo: Brother Wolf Animal Rescue / Special to the Citizen-Times)
ASHEVILLE – If Brother Wolf gets its way, downtown Asheville will soon be as welcoming for cats as it is for dogs.
A cat cafe proposal heads to City Council for consideration at tonight's meeting. In July, the no-kill animal shelter received unanimous approval from the city’s Downtown Commission to amend the wording of a zoning ordinance to open the cafe.
“Cat cafes are being built all over the country,” said Denise Bitz, president and founder of Brother Wolf Animal Rescue. “This is going to happen. We have been planning this for at least two years.”
Brother Wolf intends to rent space downtown where tourists and passersby can stop to enjoy a cup of coffee and a cat or two. The goal is to open the cafe by fall.
“We’re a very dog-centered town; you can bring your dogs everywhere, but there is not a lot for cats,” said Bitz.
The cafe will likely have two rooms divided by a clear wall, she said. One side will be set up similar to coffee shop where people can enjoy drinks, prepackaged baked goods and pastries. The other side will have between 20 and 25 cats needing adoption.
“The key point is to keep the food and animals separate,” Bitz said.
By bringing cats out of its noisy shelter on Glendale Avenue and into the public’s eye, the cafe will give Brother Wolf heightened visibility and increase its ability to find more homes for abandoned animals, Bitz said.
“Cats are a special breed and they need to be tended to and they need their own space in a quiet, calm environment,” said Bitz. “Many people won’t come to a shelter because it’s too emotional for them. This will be a warm, inviting place.”
Brother Wolf anticipates more than 500 abandoned felines will be adopted each year because of the initiative. In July, Brother Wolf had around 400 cats and kittens needing adoption.
There are limited uses for having living animals in Asheville’s downtown commercial district, said Vaidila Satvika, an urban planner for the city. Kennels are prohibited because of the loud noise made by barking dogs.
Abandoned cats in the care of an animal shelter are less of a problem, he said. The unified development ordinance is meant to be reviewed regularly to meet changing economic and cultural needs.
“This will support the vibrancy of downtown by allowing yet another use that is interesting, creative and complementary,” said Satvika. “I think it’s great idea. This is a new thing that is happening. Brother Wolf is at the forefront by trying to bring this to Asheville.”
Brother Wolf Animal Rescue is hosting a contest to name the new cafe. Send submissions to Denise Bitz at denise@bwar.org. More information at www.bwar.org.
Read or Share this story: http://avlne.ws/1Ml6IqR
|
cc/2020-05/en_middle_0097.json.gz/line35463
|
__label__wiki
| 0.779201
| 0.779201
|
Montana man canoeing East Coast missing in NC
The overturned canoe of a Montana man who was canoeing down the East Coast has been found
Montana man canoeing East Coast missing in NC The overturned canoe of a Montana man who was canoeing down the East Coast has been found Check out this story on citizen-times.com: http://avlne.ws/1zQaTV6
AP Published 9:49 a.m. ET Dec. 3, 2014 | Updated 10:13 a.m. ET Dec. 3, 2014
Authorities say the overturned canoe of a Montana man who was canoeing down the East Coast has been found in eastern North Carolina.(Photo: Special to the Citizen-Times)
ELIZABETH CITY Authorities say the overturned canoe of a Montana man who was canoeing down the East Coast has been found in eastern North Carolina.
Pasquotank County Sheriff Randy Cartwright tells area media outlets that a canoe belonging to 63-year-old Richard Conan was found overturned in a creek near Elizabeth City last Saturday. Cartwright says the canoe was found by duck hunters and had Conan's gear inside.
Media outlets report that Conan flew from Bozeman, Montana to upstate New York several months ago. He started his trek down the East Coast from Lake Champlain near the Canadian border.
Cartwright says the North Carolina Wildlife Resources Commission is searching area waterways while the U.S. Coast Guard has conducted searches from the air.
WNC high school sports: Friday night box scores
WNC high school basketball: Boys scoring leaders
|
cc/2020-05/en_middle_0097.json.gz/line35464
|
__label__wiki
| 0.985484
| 0.985484
|
SPECIAL REPORT: Bury North candidates set out election promises
By Brad Marshall @bradmarshBT News Reporter
The Houses of Parliament in Westminster, central London
WITH just one week to go until Bury goes to the polls a tight contest is developing for the borough's two constituencies.
This week the Bury Times spoke with each of the Bury North Parliamentary candidates to find out why they think they should get your vote.
James Frith — Labour Party
JAMES Frith is the former Bury North MP after first winning the seat in 2017. He is also a former Elton councillor and founder of an education social enterprise.
He asked that voters to keep their faith in him and says he has delivered on a number of his policy priorities, including saving Bury’s walk-in centres, protecting the greenbelt and securing flood defences.
If re-elected Mr Frith says he will work to get football back at Gigg Lane, adding that his priorities will include a plan for social care, involving integration of hospice work into NHS for continuing health care. He also pledges that Labour will invest in new NHS staff, nurses and doctors and create a specialist “National Care Service”.
On education he wants “real terms” investment in schools and return to support services giving head teachers resources to commission support needed such as teaching assistants and special educational needs coordinators
He is also seeking to tackle exclusion rates in Bury’s schools and says Labour will create a “National Education Service” to give children the “best start to life and entitlement to lifelong learning”. To tackle anti-social behaviour and crime Mr Frith says he wants to see a return to community policing which would put officers “back on the streets of Bury”.
Town regeneration is also another of Mr Frith’s priorities which he says would see improved highstreets and retail offers and would get broadband to everyone in the borough.
To achieve this he wants to give the constituency’s towns greater capacity to make decisions for themselves over regeneration projects and their investment needs and priorities.
On the environment, Mr Frith said the “state of climate crisis cannot be understated”, adding that to tackle the problem and reach carbon neutral target by 2030s he is seeking a green industrial revolution, promoting “economic as well as environmental renewal” through renewable energy, jobs and wealth creation.
And on Brexit Mr Frith is in favour of “final say referendum” and does not endorse Boris Johnson’s deal which he believes should go “back to the people”.
He argued that Mr Johnson’s deal divides UK, puts trade barriers between NI and rest of UK, and does not protect environment standards, workers rights or the NHS from Trump trade deal.
“When the Tories talk about getting Brexit done it is a lie and a myth. It is not done. It might go to the next round of this process but the exit will take ages but the entry to new markets will take even longer,” he added. Instead he suggested a deal struck by the Labour party would be a “customs union Brexit”.
James Daly — Conservative Party
JAMES Daly is a partner in a small business, a councillor for North Manor and leader of the Bury Conservative Group.
He says his knowledge and experience from living, working and representing the town make him the ideal candidate, adding: “I have a vision to transform our town for the better.”
If elected he pledged to encourage the council to look to their borrowing powers and play the “honest broker” to ensure the future of Bury FC — claiming that this would “not cost council tax payers a penny”.
His other priorities include big investment in the NHS, policing and education services, with especial focus on supporting children with special educational needs, adding that he would aim to play a role in every Bury North school to ensure money for schools the NHS and policing is “actually used to deliver”.
He said: “If I was elected MP and every school in Bury was not rated “Outstanding” by the time I left office I would be very disappointed.”
Mr Daly is opposed to the GMSF and he would instead push for a new plan utilising Government funding and “local partners” to build “affordable” homes. On Brexit Mr Daly supports Boris Johnson’s deal and wants the UK to leave the EU by the end of January 2020. He says he will then work to get a free trade deal, with open access to the EU and other countries, which gets more, better paid and higher skilled jobs in the borough.
And on the environment he said: “Climate change is an issue that affects us all and we all need to work together to come up with solutions, support experts and reduce carbon emissions to ensure that we have a better world going forward.”
However he argued that certain sectors, such as taxis, should be exempt from the proposed regional clean air zone and called for better support for taxi drivers — including a second MOT centre in the borough.
Gareth Lloyd-Johnson — Liberal Democrats
GARETH Lloyd-Johnson is a campaigns officer for the Liberal Democrats, the secretary of Hollins Community Centre and was born and raised in Bury North.
He says his is the “only out-and-out Remain party” committed to revoking Article 50, which he claims is the best way to protect Bury from ‘potential damage’ resulting from Brexit.
“I am absolutely unequivocal that stopping Brexit would be good for Bury North,” he said.
If the Liberal Democrats do not form the next Government, however, Mr Lloyd-Johnson says he will campaign for a “people’s vote” with “proper legal standing” to resolve if and how we are going to leave the EU.
Any future deal brokered on leaving the EU should be as close to the current relationship, such as remaining in the single market and retaining freedom of movement, he added.
As a lifelong Bury FC fan, Mr Lloyd-Johnson says he will work to ensure the town has a football club playing at Gigg Lane. His priorities for Bury North include protecting the constituency’s independent businesses including an overhaul of business rates and raising the income tax threshold “to put money back in people’s pockets”
Mr Lloyd-Johnson is opposed to GMSF and wants to protect green spaces while building eco-friendly and affordable homes and infrastructure, adding that greater action must be taken to tackle climate change, including a green economy of businesses and technologies.
He also pledged to fight the “crisis in eduction” and declining standards in the borough’s schools which he says desperately need proper resources.
Mr Lloyd-Johnson said he would like to see a 10-year funding plan for the NHS and social care, with spending used “correctly”, more control given to medical professionals, and mental health to be given parity with physical health.
Charlie Allen — Green Party
CHARLIE Allen is a project manager at the University of Manchester, former community teacher of adult numeracy in Bury and a Bury North resident of 15 years.
She says that addressing climate issues must be the priority in Bury and across the country and claims The Green Party is the only party that will address the climate change “crisis” with a comprehensive environmental plan.
To tackle this she is seeking to plant more trees in the borough and stop expansion of Manchester Airport and scrap the HS2 high speed rail link.
Ms Allen described Bury’s transport system as “shocking” and says she would work for a cheaper, more efficient and more integrated transport system for the borough and Greater Manchester which will help to tackle climate change and address air pollution levels.
Further she also aims to fix roads across the borough to improve the network but is also keen to get more cars off the roads.
Other priorities for Ms Allen include addressing “slipping” education standards in Bury’s schools and increased spending on police with “a lot more community policing” where people know their local officer and they are visible and seen as part of the community.
Social care has been “woefully funded and it is time now that that is addressed,” she argued and says she would seek more money for the NHS to ensure there are enough doctors and nurses on the frontline and in the social care sector to make the two work together.
On housing she pledged to confront the “desperate need” for affordable and social housing particularly for young people and families.
To do this Ms Allen is in favour utilising brownfield sites and opposed to building “fancy houses” on greenbelt land “where the developers make a lot of money out of them”.
On Brexit she says she and her party want to remain in the EU and is in favour of a “people’s vote” to put the issue back to the electorate because “things have changed and moved on so much”.
Alan McCarthy — Brexit Party
ALAN McCarthy is a Rochdale councillor of 20 years, representing West Heywood, and defected to the Brexit Party from Labour earlier this year. He is also a forklift truck driver and former commercial inspection and construction diver and former computer engineer who has lived in Bury for 27 years.
He says the people of Bury North should elect him as his is the “only party standing up for the democratic decision made in 2016”, and pledges to “build a future together and change politics for good”. He added: “As a parent and grandparent our job is to give our today for tomorrow’s generation.”
On Brexit he says he will pursue a “clean break” from the EU which would allow decisions to be made in the UK, the protection of British industry and investment in the NHS.
This increased funding for the health service and social care is one of his top priorities, and he he further pledges to protect the NHS from privatisation and bring in house any private initiative which have failed, and prevent “health tourism”.
Education is another of Mr McCarthy’s top priorities and he says he aims to stop the “unfair funding” of schools and increase cash required in several areas, including for pupils with special educational needs.
On housing he is opposed to building on the greenbelt which he wants to protect and instead favours building on brownfield sites.
He is also proposing to cancel business rates in the town to foster town regeneration.
And on the environment and tackling climate change, Mr McCarthy says his position is to: “Get out of the EU and set policies which we can decide that protect our UK and the world to save our planet for our children’s future.”
Previously, Mr McCarthy has said his other policies include House of Lords reform, the scrapping of the HS2 high speed rail link, halving the UK’s foreign aid spending, cutting student loan interest, and reforming the BBC and scrapping the TV licence fee.
Bus driver helps 80-year-old man with Alzheimer's get home safely
|
cc/2020-05/en_middle_0097.json.gz/line35471
|
__label__wiki
| 0.905414
| 0.905414
|
Home > Transport
Nearly 80 still missing in Indonesian ferry accident
Sun, Dec 20, 2015 - 6:42 PM
[SIWA, Indonesia] Nearly 80 people are still missing nearly 24 hours after a ferry ran into trouble in rough seas off the coast of Indonesia's Sulawesi, with authorities not ruling out the possibility of a sinking.
The transport ministry has confirmed three people, including two children, have been found dead, while 39 others have been pulled from the water alive, some after desperately clinging to fishing buoys for hours in the huge swell until help arrived.
Search and rescue teams have still not found the stricken vessel, police told AFP, which was ferrying 118 people around Sulawesi island when it sent out a distress signal late Saturday afternoon.
The whereabouts of the remaining 76 people is also still unclear, with search and rescue teams being hampered by rough conditions and waves up to five metres high as daylight hours dwindle.
When asked whether the boat had sank, South Sulawesi police spokesman Frans Barung told AFP: "Maybe yes, maybe no".
Differing prospects for Asean telcos in 5G rollout: DBS
"The boat has not been found, because the weather has not been good," he added, saying the boat was constructed from fibre glass and was therefore difficult to sink.
Authorities lost contact with the ferry late Saturday afternoon, and it failed to arrive at its destination in Siwa across the Bay of Bone as scheduled.
Officials dismissed initial reports the boat had sunk, instead claiming it was adrift, having lost engine power.
Police, national search and rescue teams and the navy have been scouring the seas for survivors ever since but have been battling harsh elements.
Local search and rescue head Roki Asikin said powerful waves meant it took three hours to evacuate some survivors to shore.
"These waves were very high," he said.
There had been warnings about extreme weather in the area in the days leading up to the accident, with strong winds and rough seas.
The Indonesian archipelago of more than 17,000 islands is heavily dependent on ferry services but the industry has a poor safety record and fatal accidents are common.
Just this week a Danish cargo ship collided with a tanker and sank in Indonesia's west, with some crew still missing.
High hopes as Austria's new night train sets off for Brussels
Canada says still no firm plans for downloading crashed jet's flight data
Mitsuoka Motor gets ready to rock
|
cc/2020-05/en_middle_0097.json.gz/line35476
|
__label__cc
| 0.686428
| 0.313572
|
Tax queries
Vikas (Accountant) 10 December 2016
Is it mandatory to claim depreciation under the income tax act 1961? Can I pay income tax without claiming benefit of depreciation under income tax act, 1961?
Sanjay S (Chartered Accountant) 11 December 2016
Sanjay S
140 likes 1370 points
No. It is not possible to compute tax liability without claiming depreciation. Depreciation as per Income Tax Act is a mandatory deduction to be applied in Income Tax computation.
Legal Provisions:
I. With reference to Explanation 5 to Section 32(1) of the Income Tax Act, 1961, Depreciation shall be allowed to the assessee whether or not the assessee has claimed deduction in respect of depreciation in computing his Total Income.
II. Besides, a plain-reading of section 32(1):
"32. Depreciation
(1) In respect of depreciation of buildings, machinery, plant or furniture owned by the assessee and used for the purposes of the business or profession, the following deductions SHALL, subject to the provisions of section 34, be allowed-"
The Act uses the word 'shall'. Hence it again proves the point.
Hope this clarifies the issue.
Gstr 2a reconciliation
CSR expenditure
PTEC Entry no Schedule
|
cc/2020-05/en_middle_0097.json.gz/line35478
|
__label__wiki
| 0.572604
| 0.572604
|
Insights:
What you need to know about ad viewability
Viewability has become one of the hot button issues for the digital advertising sector but is it the silver bullet the industry is looking for?
Brad Howarth (CMO)
If a television ad ran for less than a second, without sound, and was partly or completely obscured on the screen, you could safely assume the advertiser would want their money back.
For advertisers on digital channels, such scenarios are commonplace, with the majority of ad impressions failing to even achieve these basic requirements for viewability.
Not surprisingly then, viewability has become one of the hot-button issues in the digital advertising industry, as more and more marketers come to realise many of the page impressions they are buying will never be seen by human eyes.
Using the US Media Rating Council (MRC) standard for viewability, Integral Ad Science’s (IAS) latest Media Quality Report for Australia found only 42 per cent of the local pool of digital inventory can be classed as viewable. That result rises by just three percentage points for ads placed directly with publishers. And the MRC standards are hardly onerous, requiring that just half of the ad must be viewable for at least one second, or for two seconds for video.
“Still, you are looking at 60 per cent of the ads that are paid for never materialising as illuminated pixels on a screen,” says IAS’s managing director for Australia and New Zealand, James Diamond. “And if it is not given the opportunity to be seen, it just cannot contribute to the success of a marketing campaign – be that a performance campaign or a brand campaign.”
Seeking accountability
Figures such as these have led some advertisers to seek guaranteed minimum viewability levels. Kellogg Company’s media and connection manager for Australia, Alastair Jones, says Kellogg will be making viewable CPM its standard cost metric, with a benchmark of 50 per cent and an operating target of 70 per cent.
“Back in the day there was an assumption that you put an ad out there and people saw it,” Jones says. “But if the publisher who is selling you this inventory knows that their ad units are ‘below the fold’, and the majority of the inventory served on that page will not be viewable, is that a fair way of selling inventory?
“What it really represents is leakage of our media investment. And if the national averages of viewability are true, am I really throwing 50 per cent of my digital investment out the window?”
Read more How to strengthen customer relationships with insight
Kellogg is one example of a brand choosing the tackle the challenge head-on, having also invested in a data management platform (DMP) from Krux to better understand the performance of its digital spend. Its response is representative of a growing awareness among Australian marketers that there is more they can do to extract value from that spend.
“I think it is going to become more front and centre, especially as you have to justify investment a lot more and become accountable,” Jones says. “It’s an area which is only going to grow in momentum to get this reviewed by publishers.”
Diamond agrees the number of advertisers taking viewability into account is growing, albeit from a small base.
“Increasingly now, we are working much more directly with advertisers,” Diamond says. “There is a whole transparency debate unfolding in the market, and often advertisers want to have some sort of level of visibility over the quality of the media they are getting.”
Read more Report: A/NZ marketers behind global marketers for end-to-end customer approach
That has also increasingly led to advertisers negotiating viewability targets for their media buys. But ironically, Diamond says this might actually be exacerbating issues for the broader pool of advertisers.
“Viewability percentages have not really changed much since we stated measuring it in Australia,” he says. “That is a bit concerning, because we know that some advertisers via their agencies now have a viewability metric as part of their trading agreement, so publishers are responding to those requests and trying to provide that level of viewability.
“But overall viewability hasn’t gone up. What that means is it is happening at someone else’s expense. So for advertisers who are not taking a proactive approach on this, their performance is actually dropping, because the viewable stuff is just being consumed by people who are a little bit ahead of them.”
The rising interest in viewability among Australian marketers has also been noted by CEO of the Australian Marketing Institute, Lee Tonitto, who says viewability figures are not moving in the direction they would hope. By global standards, Australia actually ranks behind many other nations in terms of the performance of digital industry, with IAS’ estimate of 45 per cent viewability for publisher-direct ads well behind the 54 per cent it reports from the US.
Read more How a social engagement program has helped Barilla's bottom line
Numerous factors contribute to poor viewability, including robots and other forms of ad fraud, which represent 5.1 per cent of impressions in Australia (but well under the 10.5 per cent reported in the US).
“Advertisers are starting to realise how important it is to buy good quality media and so demand for viewable, fraud-free and brand-safe media is rising,” Tonitto says. “Publishers will start to respond to that soon. You can expect to see CPMs go up as media quality improves.
“The shift from a served impression to a viewable impression is yet another step to greater accountability in digital media. Marketers, agencies and publishers determined that guaranteeing the ‘Opportunity to See’ for all ads made digital even more accountable and also laid the foundation for greater comparability with other media channels.”
Diamond believes another issue is the sheer number of ads that publishers place on their pages.
Read more Account-based marketing gets boost with vendor alliance
“Publishers have put a lot of ads on their pages because they can sell them all,” he claims. “We are trying to point out the ads that add value because they come into view. The rest are slowing down the Internet, and incentivising people to install ad blockers.
“If we were to get rid of those, we could increase the price on the ads that do add value, and the whole ecosystem would be better off.”
Long-term implications
Those advertisers buying on viewability may not be placated in the long term, however. A survey of advertisers by IAS found more than half believed the US MRC’s standard for viewability was too low.
Read more 4 tips to boost your content marketing game
The situation is further confused by a lack of consistency among the tools used to measure viewability, with MRC-accredited tools from suppliers such as IAS, Moat and ComScore all capable of producing different results. For instance, when measuring ad duration, the timer might start either when the page loads or when the creative appears on the page. A 200ms difference between these events might see one tool reporting an ad as viewable whereas another one might not.
Viewability is a key concern for peak body for digital publishers, IAB Australia, which has been working to develop a robust digital measurement currency.
“The end game is that media can be planned, bought and evaluated using common metrics,” says IAB Australia CEO, Alice Manners. “Viewability is the foundation for measurement transformation and globally, the IAB has supported this drive and is focused on the end goal.”
But that means overcoming a large number of technological challenges first, including the fact that not all ads can be measured for viewability.
Read more IAB launches inaugural ad viewability data benchmarks
“Reasonable expectations should be set in monitoring viewable impressions,” Manners says. “As long as there are still major amounts of inventory that cannot be measured accurately, it is difficult to trade fairly. Different ad units, browsers, ad placements, vendors and measurement methodologies are yielding different viewability numbers, and this needs to be addressed. Measurement and technology improvements are essential if we are to strive for 100 per cent viewability.”
Account director at ad tech platform TubeMogul A/NZ, Ash Cooper, describes the reaction from publishers as positive.
“On the one hand, viewability reporting has allowed publishers to understand the true value of their inventory by measuring what impressions drive the highest levels of viewability to which they charge a premium for,” Cooper says. “The flip side is that it can expose potentially poor viewability scores that may devalue a publisher’s offering, and there is still a large percentage of online video impressions that are not measured for viewability.”
Cooper also cautions that viewability is not the silver bullet to measuring the effectiveness of an online campaign.
Read more P&G brand chief calls out 'murky' and 'fraudulent' digital marketing practices
“It is merely a metric that should be used to complement other metrics that allow marketers to build a clear picture of their campaign performance,” he says. “My advice to advertisers is to embrace viewability as a metric, but thorough testing must be undertaken to understand the true value and impact of this metric.
“Through testing, we have been able to measure the positive impact viewability has on brand lift as well as its ability to drive more cost efficient conversions vs impressions that were not seen. Viewability means a lot of different things to different people. What’s key is applying it to your specific business objective.”
Growing the definition
According to the head of interactive for OMD Australia, Dan Robins, the next step will be to expand the definition of viewability to take into account the actual intentions of advertisers. This makes the MRC standards just the starting point in a much longer journey.
“When there is already lots of confusion, at least 50 per cent of the ad in view is a start point, and cuts out all the other ads that never had a cat’s chance in hell of being seen because they were so far down the page or tucked away,” Robins says. “When everyone is on board we can all play within it and expand it and go to 100 per cent of pixels and more seconds.
“But just getting an ad in view isn’t the be all and end all. Yes, it is important, but what’s more important is driving business outcomes. If it is for direct response, we want to drive sales and leads and volume; if it is for branding, we want to drive engagement and for people to actually feel the love.
“But just forcing it in front of somebody isn’t the point.”
Follow CMO on Twitter: @CMOAustralia, take part in the CMO conversation on LinkedIn: CMO ANZ, join us on Facebook: https://www.facebook.com/CMOAustralia, or check us out on Google+: google.com/+CmoAu
Tags: digital marketingdigital advertisingad viewability
Report: Artificial intelligence driving best customer service
Customer advocacy drives new free energy switch service ...
5 CMOs reflect on 2019, achievements and lessons ...
Aussie marketing leader to become customer chief at ...
Analysis: Is the proof of influencer marketing in the pudding?
The secret ingredient in Mr. Beer's customer engagement plan
Report: Confusion still rife over CDPs
Concerns raised for embattled media industry as Google turns off third-party cookies
Report: Future 100 highlights top tech, brand and culture trends of the next decade
Tweets by @CMOAustralia
State of the CMO 2019
CMO’s State of the CMO is an annual industry research initiative aimed at understanding how ...
Transforming the modern marketing function
How have leading CMOs gone about realigning their marketing teams, approach and leadership skills in ...
Sustainability trends brands can expect in 2020
Marketers have made strides this year in sustainability with the number of brands rallying behind the Not Business As Usual alliance for action against climate change being a sign of the times. While sustainability efforts have gained momentum this year, 2020 is shaping up to be the year brands are really held accountable for their work in this area.
Ben King
CSR manager & sustainability expert, Finder
The trouble with Scotty from Marketing
As a Marketer, the ‘Scotty from Marketing’ meme troubles me.
Natalie Robinson
Director of marketing and communications, Melbourne Polytechnic
How do we break out of our marketing echo chambers?
Clients and agencies can get stuck into a particular way of behaving and viewing the world, but there are ways to break out of our marketing echo chamber.
Steve O'Farrell
Managing Partner, The Royals
If you think it can benefit both consumer and seller then it would be great
Simon Bird
Why Ford is counting on the Internet of Things to drive customer engagement
It's a good idea. Customers really should control their data. Now I understand why it's important.
Elvin Huntsberry
Salesforce CMO: Modern marketers have an obligation to give customers control of their data
Instagram changes algorithms every time you get used to them. It really pisses me off. What else pisses me off? The fact that Instagram d...
Instagram loses the like in Australia; industry reacts positively
I tried www.analisa.io to see my Instagram Insight
Dina Rahmawati
7 marketing technology predictions for 2016
The saying is pretty tongue in cheek. It's not saying that marketers are bad people, nor that they don't take themselves seriously. There...
LYF Solutions
The trouble with Scotty from Marketing - The CMO view - CMO Australia
CMO Webinar | Creating memorable customer experiences: The who, what and how
Lessons from the best: Modern marketing leadership strategy from the CMO50
Getting Intimate with CX bonus episode: Louise Eyres on showing customer centricity
In this bonus last episode of this new podcast series, BrandHook MD, Pip Stocks, talks with former ANZ group general manager of marketing, Louise Eyres, talks about the importance of thinking like a customer and using intuition to solve customer painpoints.
Play podcast
About us | Contact us | Privacy Policy | RSS
Copyright 2020 IDG Communications. ABN 14 001 592 650. All rights reserved.
Reproduction in whole or in part in any form or medium without express written permission of IDG Communications is prohibited.
IDG Sites: CIO | PC World | Computerworld Australia | CSO Online | Techworld | ARN | GoodGearGuide | CIO Executive Council
|
cc/2020-05/en_middle_0097.json.gz/line35483
|
__label__wiki
| 0.841599
| 0.841599
|
2015.3.21 Aaron Pexa Albert Paley Anna Mlasowsky Artist (Job Title) Artist-in-residence Barbara Idzikowska Corning Incorporated Elinor Portnoy Emma Stein Fred Kahl Glass Art (Type Of Museum) Helen Tegeler Ingalena Klenell Jackie Pancari Judy Tuwaletstiwa Justin Ginsberg Karlyn Sutherland Marta Ramirez Min Jeong Song Namdoo Kim Paley Rui Sasaki Shelley James Specialty Glass Specialty Glass Residency The Studio Yuka Otani art artist artist in residence artist:name=ShelleyJames artistsatthestudio east meets west exhibition flameworking fredrik nielsen glass art glass artist glassblowing glassmaking studio 134326 134330 134333 138379
Aaron Pexa | Artist-in-Residence at The Studio
Aaron Pexa's work spans multiple mediums, from video and installation to sculpture and performance, and his goal is always to create a sense of bewilderment. He takes everyday environments and subverts them by introducing new artifacts and narratives that stimulate wonder and “bring people out
Fred Kahl | Artist-in-Residence at The Studio
"The way the work is with the CNC carved molds is this perfect blend of scientific and mechanical precision and total fudge factor working in front of the furnaces and that is a lot about who I am as an artist, embracing the chaos of the universe." — Fred Kahl Working at the intersection
Artist-in-Residence: Justin Ginsberg
With a material as fragile and unpredictable as glass, artists need to be flexible—and it’s exactly that flexibility that intrigues Justin Ginsberg. A visual artist, Ginsberg investigates the “unusual properties” of glass, and its “extraordinary ability to flex and bend when made very thin.” His
Artist-in-Residence: Yuka Otani
You might not look at glass and candy and think they have similar properties, but Yuka Otani does. “Those two materials share many characteristics,” she says. “But what if they are made into a unified object?” During her artist residency at The Studio of The Corning Museum of Glass, Otani created a
Specialty Glass Residency with Albert Paley
Albert Paley is the first artist selected to participate in a new Specialty Glass Residency program offered by The Corning Museum of Glass and Corning Incorporated. Read the blog post: Specialty Glass Residency: New Materials Open Up New Possibilities.
Artist-in-Residence: Min Jeong Song (October 2011)
"I want the viewer to expereince the process of blurring boundaries between cultures by looking at my work." Min Jeong Song studies ornamental styles across time periods and geography, and her work explores how certain attributes of glass can be used to create ambivalent objects: objects
Artist-in-Residence: Ingalena Klenell
In her May 2012 Residency at The Studio, Ingalena Klenell worked on a project called Travelers. The project is based on the history of cultural exchange in trade relations between Venice and Egypt, inspired by a collection of glass shards found in Egypt that date from 1100 A.D. to 1400 A.D.
Artist-in-Residence: Marta Ramírez
In her May 2012 Residency at The Studio, Marta Ramírez interpreted the works of Shinichi Maruyama, a Japanese artist and photographer who has developed an artistic body of work called Water Sculptures.
Artist-in-Residence: Barbara Idzikowska
Barbara Idzikowska has been fascinated by glass for more than 20 years. Living and working in Wrocław, Poland, she seeks to give ideas material form through her work in glass. In 2004, she established Atelier Si, Pb..., a studio of drawing on glass, with the graphic designer Eugeniusz Get
Artist-in-Residence: Shelley James
Shelley James' work is the result of practiced technical precision and researched techniques. Over the past six years, she has focused her work on "combining the optical qualities of glass with the graphic range of print to explore the dialogue between eye and brain." James studied
Artist-in-Residence: Alison Lowry
Hear from Irish artist Alison Lowry about her Residency at The Studio.
Artist-in-Residence: Emma Stein
Emma Stein in inspired by patterns and circularity as they relate to nature and human history. As a teenager, she visited The Corning Museum of Glass, where she witnessed glassblowing for the first time. It ignited a passion that led to a life of exploring the material, focusing her work on the
Artist-in-Residence: Jackie Pancari
Jackie Pancari loves discovering the ways glass and light interact. She thinks of her studio as “a laboratory where curiosity and imagination lead to experimentation and discovery.” With an MFA from Alfred University School of Art, Pancari has exhibited her work across the U.S. and in Japan. She
Artist-in-Residence: Helen Tegeler
Helen Tegeler is inspired by the transitional properties of plants, and extrapolates upon that in her work. From growth patterns and branching to surface textures and patterns, she feels there are infinite design possibilities when interpreting plants in glass. She loves exploring seeds, and the
Artist-in-Residence: Rui Sasaki
Rui Sasaki is a Japanese conceptual artist whose work centers around the exploration and discovery of subtle intimacy in unfamiliar and familiar spaces, which she refers to as “empty space.” After moving to the U.S. in 2007, she experienced sensations of lost memories, nostalgia, and homesickness.
Elinor Portnoy | Artist-in-Residence
The way I usually go is to follow my curiosity. If I'm curious about a material and I'm wondering how it will behave, the curiosity is strong and I want to test things out. Elinor Portnoy ’s work examines the fluidness of material. She designs processes that demonstrate the natural
Karlyn Sutherland | Artist-in-Residence at The Studio
"I wanted to create an experience where it was about the light and the sound of the water and you're really aware of the context in the surroundings." Dr. Karlyn Sutherland is inspired by the bond between people and place. Autobiographical in nature, her work explores this dialogue
Michael Rogers and Judy Tuwaletstiwa | Artist-in-Residence at The Studio
Hear from artists Michael Rogers and Judy Tuwaletstiwa about their collaborative work as artists-in-residence at The Studio.
Anna Mlasowsky Specialty Glass Residency
"Even though I know glass well, and I've worked with it so much, I feel like I'm completely a beginner again—a beginner with knowledge—and I think this is a very different way of working then I've done so far," says artist Anna Mlasowsky about the Special Glass Residency, a
Namdoo Kim | Artist-in-Residence at The Studio
Children in Korea today are like mass produced toys. They are meant to be all exactly alike, lacking individuality and quality of character, a whole society of people who are easily replaceable and hold little value as individuals, just like mass produced plastic toys or paper dolls
Fredrik Nielsen | Artist-in-Residence at The Studio
I like to see it as, I know how to play, but I choose not to play the way that I learned. Fredrik Nielsen is a Swedish artist with a unique flair for experimentation, combining aspects of pop culture such as graffiti, music, videos, and performance into his glass art. His strong desire to push the
|
cc/2020-05/en_middle_0097.json.gz/line35484
|
__label__wiki
| 0.855773
| 0.855773
|
story from Business
LocalBitcoins Starts Manufacturing Low-Cost Bitcoin ATM
Feb 18, 2014 at 14:07 UTC Updated Mar 20, 2015 at 15:52 UTC
Joon Ian Wong
Bitcoin marketplace LocalBitcoins.com has produced a bitcoin ATM and is preparing to mass-manufacture the machine, which was launched on 17th February.
The Helsinki-based company said the machine can perform two-way conversions between bitcoin and fiat currency. Each unit is priced at €1,990 (approx $2,732) and the firm has built five so far.
LocalBitcoins founder Jeremias Kangas said:
“We have a pretty good chance of entering [the ATM market]. Of course there are existing companies but our model is much more cost-effective.”
The LocalBitcoins machine will also obtain its conversion rates differently from existing two-way machines. A Robocoin ATM, for example, takes its rates from a large exchange like Bitstamp through an internet connection.
The ATM can operate offline, and transactions must be completed through the LocalBitcoins website.
Customers buying bitcoin through the ATM, for example, would deposit cash in the machine and receive a redeemable code. The customer would then enter this code on LocalBitcoins.com to complete the transaction.
Customers selling bitcoin would transfer coins into a LocalBitcoins wallet and specify the amount of fiat currency they wish to withdraw. This would then generate a redeemable code which can be inputted into the ATM – the machine would then produce the cash.
LocalBitcoins will charge a 1% transaction fee for using the ATM. This fee would be on top of the premium on conversions set by the ATM’s operator. Kangas said he expected the machines to be a hit among active LocalBitcoin traders:
“[LocalBitcoins.com] is already a world-leading website for finding [bitcoin to cash] exchangers, so an ATM makes sense. We can distribute ATMs to our traders. Many will be interested. We have traders in at least 150 countries.”
Kangas said the first batch of machines are designed to be used with an attendant monitoring them. Currently, they do not have any customer identification features, he added.
A blogpost on the LocalBitcoins website announcing the machines called the units “experimental” and offered a full refund if customers found any technical problems.
LocalBitcoins is planning to develop two types of machines, one priced at €1,500 to €2,000 and a more advanced model at €2,500 to €3,000, according to Kangas.
The machines can accept more than 100 currencies. They also contain a bank-note recycler, which reduces the need for the operator to monitor and top-up the amount of cash in the machine.
Although the company has not sold any units yet, it confirmed that it has received various inquiries. Kangas said he expected the first machine to be acquired and installed within a month.
Earlier this month Florida police arrested a LocalBitcoins user in a sting operation where an undercover agent attempted to convert $30,000 into bitcoin. Police said the user flouted Florida’s anti-money laundering laws. Kangas said his firm had not formulated a response to these scenarios yet. He said:
“We are thinking about what to do with the situation, how to deal with this kind of activity in the future.”
The ATM space is evolving quickly as operators begin to move upstream with their own exchanges, as in the case of Vancouver’s Bitcoiniacs, while marketplace owners like LocalBitcoins begin manufacturing operations.
Manufacturing incumbents Lamassu and Robocoin meanwhile, continue to take orders from customers worldwide, even as new makers like Bit Access enter the scene.
ATMsExchangesLocalBitcoins.comRobocoinStartupsTechnologyLocalBitcoinsBitcoin ATMsBitcoinNewsCompaniesTechnology News
|
cc/2020-05/en_middle_0097.json.gz/line35487
|
__label__wiki
| 0.979529
| 0.979529
|
ABC cancels "Roseanne" after Barr's racist tweet
By Andrea Park
May 30, 2018 / 2:25 AM / CBS News
ABC cancels "Roseanne"
Stellar ratings and an apology weren't enough to mitigate Roseanne Barr's racist comments, and now ABC is pulling the plug on "Roseanne." ABC Entertainment president Channing Dungey confirmed the network has decided to cancel the "Roseanne" reboot following Barr's tweet comparing former Obama White House aide Valerie Jarrett to an ape.
Jimmy Kimmel calls for compassion in wake of Roseanne Barr controversy
Dungey said in a statement, "Roseanne's Twitter statement is abhorrent, repugnant and inconsistent with our values, and we have decided to cancel her show." In 2016, Dungey made headlines when she became the first African-American to run the entertainment division of a major broadcast television network.
Bob Iger, chairman and CEO of The Walt Disney Company, which owns ABC, shared Dungey's statement on Twitter and added the comment, "There was only one thing to do here, and that was the right thing."
From Channing Dungey, President of ABC Entertainment: "Roseanne's Twitter statement is abhorrent, repugnant and inconsistent with our values, and we have decided to cancel her show."
There was only one thing to do here, and that was the right thing.
— Robert Iger (@RobertIger) May 29, 2018
Although Barr had earlier tweeted that she was leaving Twitter, she returned Tuesday night. She retweeted some support she had received -- as well wrote she thought Jarrett was "Saudi" -- and then she issued a statement.
Don't feel sorry for me, guys!!-I just want to apologize to the hundreds of people,and wonderful writers (all liberal) and talented actors who lost their jobs on my show due to my stupid tweet. I will be on Joe Rogan's podcast friday.
— Roseanne Barr (@therealroseanne) May 30, 2018
Roseanne also tweeted at Jarrett that she was "very sorry to have hurt you. I hope you can accept this sincere apology!"
@ValerieJarrett I want to apologize to you. I am very sorry to have hurt you. I hope you can accept this sincere apology!
Barr continued to tweet into the night, retweeting a statement she said she sent BuzzFeed News West Coast correspondent Kate Aurthur.
Here's @therealroseanne's apology. pic.twitter.com/YWZ6i6WWq7
— Kate Aurthur (@KateAurthur) May 30, 2018
Barr also tweeted "hey guys, don't defend me" and that she "went 2 far." She claimed she was "ambien tweeting" when she posted about Jarrett.
hey guys, don't defend me, it's sweet of you 2 try, but...losing my show is 0 compared 2 being labelled a racist over one tweet-that I regret even more.
guys I did something unforgiveable so do not defend me. It was 2 in the morning and I was ambien tweeting-it was memorial day too-i went 2 far & do not want it defended-it was egregious Indefensible. I made a mistake I wish I hadn't but...don't defend it please. ty
But she also retweeted tweets from her supporters that seemed to contradict the earlier statements, including comments that "leftist" celebrities wouldn't have gotten the same treatment.
TV & Streaming More
New Netflix show shines light on kids' social anxiety
Ken Jennings wins "Jeopardy! The Greatest of All Time" tournament
HBO to develop "Parasite" limited series
Barack and Michelle Obama's Netflix documentary scores Oscars nod
"The Price Is Right" specials coming to CBS primetime in spring
More in TV & Streaming
ICM Partners, the talent agency that represents Barr, also dropped her as a client. The company sent an email to all of its employees saying, "We are all greatly distressed by the disgraceful and unacceptable tweet from Roseanne Barr this morning. What she wrote is antithetical to our core values, both as individuals and as an agency. Consequently, we have notified her that we will not represent her. Effective immediately, Roseanne Barr is no longer a client."
Reruns of the show also took an immediate hit, with Viacom announcing that it would drop the series from all its channels.
Earlier on Tuesday, Barr apologized for the racist tweet about Valerie Jarrett, a former senior advisor to President Barack Obama, in which Barr compared Jarrett, who is black, to an ape.
Barr's tweet about Jarrett said, "muslim brotherhood & planet of the apes had a baby=vj."
After initially pushing back against criticism of the comment, Barr admitted her "joke" was in "bad taste." She said she was sorry and that she was leaving Twitter.
"I apologize to Valerie Jarrett and to all Americans. I am truly sorry for making a bad joke about her politics and her looks. I should have known better. Forgive me-my joke was in bad taste." But the apology was clearly not enough for ABC.
I apologize. I am now leaving Twitter.
I apologize to Valerie Jarrett and to all Americans. I am truly sorry for making a bad joke about her politics and her looks. I should have known better. Forgive me-my joke was in bad taste.
Earlier, Barr had rebuffed accusations of racism by insisting that "Islam is not a race." But her eventual admission that the joke was about Jarrett's "looks" seemed to confirm that the ape comment was indeed about Jarrett's appearance.
Jarrett, in her first comments about the incident, said, "We have to turn it into a teaching moment." She spoke at an MSNBC town hall event, "Everyday Racism in America."
"I'm fine," Jarrett said, adding, "I'm worried about all the people out there who don't have a circle of friends and followers who come right to their defense. The person who's walking down the street minding their own business and they see somebody cling to their purse, or want to cross the street, or every black parent I know who has a boy who has to sit down and have a conversation, 'the talk' as we call it, and as you say, those ordinary examples of racism that happen every single day."
The offending tweet came late Monday night, amid a series of tweets referring to George Soros as a Nazi and Chelsea Clinton as a Soros family member (Barr apologized and took it back, then attacked the family of Clinton's husband, Marc Mezvinsky, instead).
Barr is a vocal President Trump supporter, as is her character on the "Roseanne" revival on ABC. Mr. Trump called Barr to congratulate her after the first episode of the reboot scored record ratings.
Before the show was canceled, comedian Wanda Sykes, a consulting producer on the show, tweeted that she would not be returning in the wake of Barr's comments.
I will not be returning to @RoseanneOnABC.
— Wanda Sykes (@iamwandasykes) May 29, 2018
First published on May 29, 2018 / 1:55 PM
Andrea Park
Andrea is an entertainment producer at CBSNews.com
More World
Watch live: Third all-female spacewalk
NASA is in the process of replacing aging solar array batteries with more powerful lithium-ion replacements
"It brings me great sadness that it has come to this," the 35-year-old said in an emotional speech Sunday night.
updated 26M ago
The world's 2,153 billionaires have as much wealth as 60% of the world's population, anti-poverty group Oxfam says.
More U.S.
The White House is due to submit its formal legal brief for opening arguments in President Trump's impeachment trial by noon.
Governor Ralph Northam declared a state of emergency, temporarily banning all weapons on capitol grounds.
Motive unknown; lounge was holding celebration of Kansas City Chiefs victory that sent them to Super Bowl.
2 killed, 5 injured after patron opens fire at San Antonio bar
A suspect opened fire on patrons at the Ventura, a music venue and bar located along the Museum Reach portion of the San Antonio River Walk.
The paper gave its thumbs-up to Elizabeth Warren and Amy Klobuchar, both senators who represent divergent strains in the Democratic Party
Bloomberg says his life would be different "if I had been black"
The former New York City mayor was in Tulsa on Sunday to unveil an ambitious policy proposal aimed at delivering economic justice for black Americans.
Warren criticizes Bloomberg for financial disclosure extension
Bloomberg was given a 45-day extension to file his personal financial disclosure with the FEC, which means his financial filings won't be public until after Super Tuesday.
They warmly congratulated each other. The win for "Parasite" launched it into best picture Oscar talk, and Robert De Niro ripped into Trump.
Singer David Olney dies at 71 after collapsing onstage
Olney, a native of Rhode Island, was part of the music scene in Nashville, Tennessee, for decades and had recorded more than 20 albums.
Harry & Meghan to begin new life with queen's blessing
Prince Harry and wife Meghan’s bombshell declaration of independence now has the official blessing of Queen Elizabeth. Harry is expected to join his wife and son, Archie, in British Columbia soon. But the family’s royal separation comes at a cost — and new criticism from Meghan’s estranged father. Imtiaz Tyab reports.
8H ago 02:04
The "Road to the Grammys" on "CBS This Morning"
All this week on "CBS Morning," preview "The Gayle King Grammy Special" as King goes one-on-one in a series of intimate interviews with Lizzo, the Jonas Brothers, Blake Shelton and Gwen Stefani and Billie Eilish.
11H ago 00:20
Almanac: Neon lights
On January 19, 1915, French inventor Georges Claude received a U.S. patent for his "System of Illuminating by Luminescent Tubes" ... tubes filled with neon gas
SpaceX deliberately destroys boosters in dramatic test
The test was the last major hurdle before the Crew Dragon blasts off with astronauts aboard.
Kidnapped 14-year-old girl alerted friends of her location on Snapchat
"Where am I?" the girl messaged friends.
Lawsuit demands Zuckerberg give up control of Facebook
Anti-trust suit by stalled rivals calls Facebook "one of the largest unlawful monopolies ever seen in the United States."
Turning an ocean menace into a meal
As kelp forests off America's West Coast are being decimated by voracious urchins, threatening other species' survival, a unique partnership between scientists and a seafood company hopes to turn a menace into a delicacy
SpaceX delays dramatic Crew Dragon abort test
Dramatic SpaceX in-flight abort test is intended to clear the way to send astronauts to the International Space Station.
Court tosses out kids' climate-change lawsuit
Three-judge panel rules that the questions brought up in the case are best dealt with by legislators, not courts.
As Australia burns, it's Murdoch vs. Murdoch on climate change
Media mogul's son is the latest to accuse him of downplaying the role of global warming in the lethal blazes.
More in Science
Premature births: One of the biggest public health threats facing the U.S.
One in 10 births in this country is premature, one of the highest rates in the industrialized world; author Sarah DiGregorio says we must do better
One psychiatrist's long-forgotten idea on giving support to those hospitalized or treated for depression or attempting suicide is being revived, and is finding positive results in an era of texting
Teen suicide: Risk factors, warning signs and prevention
Resources for teens and parents offering important information and support
Four teachers sue Delta Air Lines over California fuel dump
At a news conference, the teachers described the fuel as drizzling down like raindrops with "overwhelming" fumes.
More MoneyWatch
A fruitful life: Remembering Frieda Caplan, the exotic fruit lady
The entrepreneur, who died Saturday at age 96, made a number of exotic fruits and vegetables, from kiwi to ginger, household names
Trump finds campaign foe in "Mini" Mike Bloomberg
Despite his seeming long-shot chances for the presidency, Bloomberg has become a favorite target for President Trump on Twitter
U.S. Treasury to soon begin selling 20-year bonds
The new offering between 10-year and 30-year bonds could help finance U.S.'s enormous $1 trillion annual deficits.
Why wine sales are falling for the first time in 25 years
Wine consumption in the U.S. slowed for the first time in 25 years, thanks in part to young adults' changing tastes.
More in MoneyWatch
Flames destroyed several homes; suspect, two women unaccounted for but likely in home that burned, police said.
Texas woman convicted in husband's murder: "He wasn't supposed to die"
In her first TV interview, the Texas woman at the center of a case prosecutors say was all about "sex, lies, money, and murder" tells "48 Hours" what happened the night of the murder.
Woman convicted in suicide texting case to be released from jail
Inside the groundbreaking case of a crime of the digital age — a young woman convicted of involuntary manslaughter because she used text messages to encourage a friend to take his own life.
More in Crime
More Space
SpaceX deliberately destroyed a Falcon 9 booster Sunday in a spectacular high-altitude conflagration moments after an unpiloted Crew Dragon astronaut ferry ship shot away in a critical test of its emergency escape system, propelled to safety with a rush of fiery exhaust from eight powerful abort engines. CBS News senior space consultant Bill Harwood joins CBSN's Omar Villafranca from the Kennedy Space Center in Florida with the latest.
Mysterious objects found orbiting supermassive black hole: study
Are they just gas, or are they stars? Astronomers now believe the unusual objects may be a hybrid of both.
More in Space
More Latest Galleries
Claude Monet: The Truth of Nature
The Denver Art Museum presents the country's largest Monet exhibit in more than two decades, exploring the Impressionist's fascination with light, and how tragedy colored his work
Jan 19 14 photos
Surprising stars who have never won an Oscar
No thanks to the Academy.
Animals doing people things
A gorilla looking at iPhone photos, an elk drinking red wine... the line between human activity and animal behavior is furrier than one might think
Animals in the wrong place at the wrong time
A hippo at a Swatch store, a squirrel in the Phillies dugout — you won't believe where these animals have popped up ...
Meghan Markle's style, from "Suits" to the royal family
Whatever's next for the the Duchess of Sussex, she's sure to do it in royal fashion.
More in Latest Galleries
Harry and Meghan in “uncharted territory”
Prince Harry is speaking publicly for the first time about his and Meghan Markle's unprecedented decision to give up their royal duties. As part of the deal, Harry and Meghan will lose their most prestigious royal titles and will no longer receive public funds. Roya Nikkhah reports on why the couple can’t continue serving in a royal capacity.
updated 4M ago 04:01
Jeff Flake's advice to party ahead of trial
As the impeachment trial of President Trump gets underway this week, Senate Minority Leader Chuck Schumer says he'll force votes to call four witnesses at the trial if Majority Leader Mitch McConnell doesn't do so. Democrats will need the votes of four Republicans. Republican Jeff Flake of Arizona, who served in the Senate from 2013 until last year, joins “CBS This Morning” with his advice for members of his party.
updated 10M ago 04:37
All that matters in 90 seconds
A look back at what we've been covering on "CBS This Morning."
Spread of deadly virus in China a concern
A dangerous virus is spreading rapidly in China, and U.S. officials are worried it will come to America. China has more than 200 confirmed cases of coronavirus, which produces pneumonia like symptoms. Three people have died from the illness, which has spread to at least three other Asian countries. Ramy Inocencio reports from Wuhan, China, considered Ground Zero for the outbreak.
Cutting royal ties was only option for Harry
In his first public comments since announcing a plan to withdraw from official duties, Prince Harry says he had "no other option" but to cut most of his royal ties. Charlie D’Agata reports on the emotional speech Harry gave Sunday night, after Queen Elizabeth announced the highly anticipated details of the new arrangement for him and his wife Meghan.
More in Popular
Copyright © 2020 CBS Interactive Inc. All rights reserved.
View CBS News In
CBS News App Open
Chrome Safari Continue
|
cc/2020-05/en_middle_0097.json.gz/line35493
|
__label__wiki
| 0.68046
| 0.68046
|
Special Report | Syria: Deciphering the Propaganda War over the Ghouta Massacre
The politicised debate over the realities of last month's chemical attack in Ghouta is a further manifestation of a propaganda war - being fought on all sides and for competing national and geopolitical interests - that shows scant regard for the human cost of the conflict.
New in Ceasefire, Special Reports - Posted on Friday, September 20, 2013 22:27 - 19 Comments
By Nafeez Mosaddeq Ahmed
If there is anything to learn from the Syrian conflict, it is that, in the fog of war, truth really is the first casualty. Narratives and counter-narratives of the conflict have plagued media accounts and the blogosphere ever since peaceful protests erupted on the streets of Syria over two years ago, and increasingly so in the wake of the Ghouta chemical weapons attack of the 21st August.
While the West’s case against Assad in this respect appears politicised and less than conclusive, the same, if not worse, can be said about the case against the rebels. Almost every single piece of evidence that has been put forward to support that case has been disputed at the very least, or proved entirely false. And the politicisation of Russian and Iranian intelligence, the role of Assad in spearheading propaganda, has been overlooked.
From the White House dossier to the United Nations report, from Syrian nuns to revelations from former and active intelligence officials, the propaganda war between pro and anti-interventionists to control the paradigm through which we understand the conflict – manifesting itself in Bashar al-Assad’s latest call for a ceasefire – may be feeding into little-known strategic imperatives that see the Syrian people as mere pawns in a wider gambit.
The Ghouta verdict
On September 16th, a UN investigation released its interim findings on the chemical weapons incident in Ghouta, Damascus of August 21st, stating that:
“… the environmental, chemical and medical samples, we have collected, provide clear and convincing evidence that surface-to-surface rockets containing the nerve agent sarin were used in Ein Tarma, Moadamiyah and Zamalka in the Ghouta area of Damascus.”
But there were faultlines. Acknowledging that the investigation would not have been possible without the consent of both the Syrian government and on-the-ground cooperation of opposition forces, the report is fully cognisant of potential efforts to manipulate evidence at the various sites of the attack. In Moadamiya (p. 18), the report notes that: “The sites have been well travelled by other individuals both before and during the investigation. Fragments and other possible evidence have clearly been handled/moved prior to arrival of the investigation team.”
And in Zamalka and Ein Tarma (p. 22), the report flags up similar reservations that “the locations have been well travelled by other individuals prior to the arrival of the Mission” Even while the inspectors were present, “individuals arrived carrying other suspected munitions indicating that such potential evidence is being moved and possibly manipulated”:
These caveats are important, but they should not be overblown. That the inspection team recognised these issues and took them into account in assessing the implications of the physical evidence mitigates against jumping quickly to the sort of simplistic counter-conclusion opportunistically (and misleadingly) misinterpreted by the likes of Iran’s state-controlled ‘Press TV’. On the other hand, the fact that the UN team documented efforts by individuals at these rebel-controlled areas to “possibly manipulate” some “potential evidence” at the sites is a concern.
But the UN report was also corroborated by independent experts. Dan Kaszeta, a chemical weapons specialist formerly with the U.S. Army Chemical Corps who had previous expressed doubt about the attacks due to inconsistencies in symptoms and other issues, nevertheless assessed that the UN report had identified “conclusive evidence” from environmental and medical data that this was a Sarin gas attack. Kaszeta pointed out that to address the limitations identified, the inspection team utilised a range of controls to ensure a lack of cross-contamination, and obtained a variety of different samples from in and around sites to avoid potential effects of tampering. An earlier Human Rights Watch (HRW) investigation undertaken with support from independent experts noted that the nature of the munitions, their trajectories, as well as the testimony from victims and eyewitnesses, pointed to a sophisticated operation most “likely” to have been carried out by the Syrian military via a regime-held base.
Counter-posed to these assessments is a barely-literate, self-contradictory “report” based essentially on analysis of YouTube videos by an unidentified “investigative team” headed up by Sister Agnes Miriam de la Croix, a Carmelite nun based in Syria who has long openly supported Assad. If there remain questions about the UN’s findings (itself arguable), this report is far worse, making a large number of interlinked and largely spurious claims implying that there was no chemical weapons attack at all, and the Ghouta massacre was entirely staged by the rebels with the complicity of international news media. Agnes Miriam, however, has a track record of unreliability and unverifiable accusations, explicable in the context of being close to Assad’s security services—so close, that according to the Committee for the Protection of Journalists (CPJ), the nun was complicit in a successful regime plot to kill international journalists. Unfortunately, that dearth of credibility has not prevented outlets like ‘Russia Today‘ from broadcasting the nun and her claims on satellite television. That’s not entirely surprising though, because Russian ‘intelligence’ attributing the attack to the rebels appears to be based exactly on such speculative partisan online analysis proven wrong in the past.
Dodgy Dossier?
Not surprisingly, the White House moved quickly to stating that the UN’s findings vindicated its case that the attacks were carried out by Assad’s forces. On Aug. 30, the White House had published a document squarely attributing the Aug. 21 use of chemical weapons in Ghouta to the Syrian military. The document described itself as a U.S. “government assessment“, encapsulating “an unclassified summary of the U.S. intelligence community’s analysis” of the attack. But the document admitted to falling short of conclusive “confirmation.”
Less than a week after the White House assessment was published, on Sept. 6, an open letter to president Barack Obama signed by a respected group of retired US intelligence officers claimed that active U.S. intelligence community officials disagreed with the White House assessment. The memo by the group known as Veteran Intelligence Professionals for Sanity (VIPS)—led by 27-year CIA analyst Ray McGovern who chaired National Intelligence Estimates and prepared the President’s Daily Brief—opens as follows:
“… our former co-workers are telling us, categorically, that contrary to the claims of your administration, the most reliable intelligence shows that Bashar al-Assad was NOT responsible for the chemical incident that killed and injured Syrian civilians on August 21, and that British intelligence officials also know this.”
The veterans group does have a solid track record, having addressed its first memo to President George W. Bush warning presciently that Secretary of State Colin Powell’s notorious 2003 UN speech on Iraq’s weapons of mass destruction intelligence was fraudulent. The group’s other members include well-known former intelligence officers from the CIA, State Department and National Security Agency.
They wrote that “CIA officers working on the Syria issue” told them that Syria’s chemical incident was “not the result of an attack by the Syrian Army using military-grade chemical weapons from its arsenal.” On the contrary: “They tell us that CIA Director John Brennan is perpetrating a pre-Iraq-War-type fraud on members of Congress, the media, the public—and perhaps even you.”
The memo describes the White House report as “a political, not an intelligence document.” It cites Middle East sources linked to the Syrian opposition confirming that “the August 21 chemical incident was a pre-planned provocation by the Syrian opposition and its Saudi and Turkish supporters”, designed precisely to “bring the United States into the war.”
The memo quickly went viral online. If the VIPS account is accurate, of course, then it raises serious questions not just about the White House assessment that it contested, but also about the possibility that the rebels’ supporters could have interfered with evidence critical to the integrity of the UN investigation.
So who is right?
Politicisation of Intelligence
Backing up the VIPS’ case, other intelligence experts have stated that the very nature of the White House document probably means it does not represent the untarnished conclusions of the US intelligence community.
One anonymous ex-senior intelligence official who held dozens of security classifications over a decades-long career said that the language used by the White House “means that this is not an intelligence community document.” He had “never seen a document about an international crisis at any classification described/slugged as a U.S. government assessment.” This means that the administration “decided on a position and cherry-picked the intelligence to fit it… The result is not a balanced assessment of the intelligence.”
Paul Pillar, a former National Intelligence Council (NIC) officer who participated in drafting national intelligence estimates, described the White House report as “evidently an administration document.” Even if senior intelligence officials signed off on the document at some stage, he said, the White House may have drafted its own paper to “avoid attention to analytic differences within the intelligence community.”
Others have pointed out that the document appears to mislead on its sources of information. At one point, for instance, it claims:
“We have a body of information, including past Syrian practice, that leads us to conclude that regime officials were witting of and directed the attack on August 21. We intercepted communications involving a senior official intimately familiar with the offensive who confirmed that chemical weapons were used by the regime on August 21 and was concerned with the UN inspectors obtaining evidence.”
However, as noted by former British Ambassador Craig Murray who headed the British Foreign Office’s Cyprus section in the 1990s, the Mount Troodos listening post in Cyprus responsible for monitoring all electronic communications across the Middle East on behalf of both U.S. and British intelligence (which share all this information as a matter of protocol) did not appear to have picked up these intercepts. Murray’s intelligence sources told him that such intercepts “were not available to the UK Joint Intelligence Committee” – but if they had been picked up, they should have been. The only explanation was that the alleged intercept evidence was provided by Mossad, he said—but the fact that Troodos did not pick up on it suggests Mossad may have doctored the intercepts.
On the other hand, German intelligence picked up intercepts showing that Syrian military officers had been requesting Assad permission to use chemical weapons for over the preceding four months—but crucially that Assad himself had always denied permission up to and including the Ghouta attack.
Dodgier Dossier?
So at first glance, the VIPS memo’s core contention that U.S. intelligence is being politicized over Syria, as happened in the run-up to the 2003 Iraq War, appears compelling.
But a deeper look reveals that the VIPS memo fails to withstand the same level of scrutiny and verifiability it demands from the Obama administration. From where, for instance, does its narrative of the Aug. 21 attack actually come from?
Disturbingly, certain sections of the VIPS letter to Obama seem to plagiarise verbatim an older article by Yossef Bodanksy, former Director the U.S. Congressional Task Force on Terrorism and Unconventional Warfare of the U.S. House of Representatives, published in the Washington DC journal Defense & Foreign Affairs. The latter, a publication of the International Strategic Studies Association (ISSA)—a private intelligence group providing consultancy services for the U.S. and other governments and corporations—attributed the chemical weapon attacks to the rebels.
Here are some extracts from the VIPs memo and the Bodanksy article—published about a week before the former (and available online here)—which are almost exactly the same (added emphasis ours):
Bodansky:
There is a growing volume of new evidence from numerous sources in the Middle East—mostly affiliated with the Syrian opposition and its sponsors and supporters—that makes a very strong case, based on solid circumstantial evidence, that the August 21, 2013, chemical strike in Damascus suburbs was indeed a pre-meditated provocation by the Syrian opposition.
VIPS:
There is a growing body of evidence from numerous sources in the Middle East—mostly affiliated with the Syrian opposition and its supporters—providing a strong circumstantial case that the August 21 chemical incident was a pre-planned provocation by the Syrian opposition and its Saudi and Turkish supporters. The aim is reported to have been to create the kind of incident that would bring the United States into the war.
Western-sponsored opposition forces in Turkey started advance preparations for a major and irregular military surge. Initial meetings between senior opposition military commanders and representatives of Qatari, Turkish and US intelligence took place at the converted Turkish military garrison in Antakya, Hatay Province, used as the command center and headquarters of the Free Syrian Army (FSA) and their foreign sponsors. Very senior opposition commanders who had arrived from Istanbul briefed the regional commanders of an imminent escalation in the fighting due to “a war-changing development” which would, in turn, lead to a U.S.-led bombing of Syria.
In addition, we have learned that on August 13-14, 2013, Western-sponsored opposition forces in Turkey started advance preparations for a major, irregular military surge. Initial meetings between senior opposition military commanders and Qatari, Turkish and U.S. intelligence officials took place at the converted Turkish military garrison in Antakya, Hatay Province, now used as the command center and headquarters of the Free Syrian Army (FSA) and their foreign sponsors.
Senior opposition commanders who came from Istanbul pre-briefed the regional commanders on an imminent escalation in the fighting due to “a war-changing development,” which, in turn, would lead to a U.S.-led bombing of Syria.
The opposition forces had to quickly prepare their forces for exploiting the US-led bombing in order to march on Damascus and topple the Bashar al-Assad Government, the senior commanders explained. The Qatari and Turkish intelligence officials assured the Syrian regional commanders that they would be provided with plenty of weapons for the coming offensive.
Indeed, unprecedented weapons distribution started in all opposition camps in Hatay Province on August 21-23, 2013. In the Reyhanli area alone, opposition forces received well in excess of 400 tons of weapons, mainly anti-aircraft weaponry from shoulder-fired missiles to ammunition for light-guns and machine guns. The weapons were distributed from store-houses controlled by Qatari and Turkish intelligence under the tight supervision of U.S. intelligence.
Opposition leaders were ordered to prepare their forces quickly to exploit the U.S. bombing, march into Damascus, and remove the Bashar al-Assad government.
The Qatari and Turkish intelligence officials assured the Syrian regional commanders that they would be provided with plenty of weapons for the coming offensive. And they were. A weapons distribution operation unprecedented in scope began in all opposition camps on August 21-23. The weapons were distributed from storehouses controlled by Qatari and Turkish intelligence under the tight supervision of U.S. intelligence officers.
I queried several VIPS signatories regarding their alleged sources for this narrative. Ex-NSA senior executive Thomas Drake described the sources as “sensitive” but attributed primary authorship of the memo to Ray McGovern—Bodansky’s article, of course, being available for free online is hardly a “sensitive source.”
Former CIA and State Department counter-terrorism officer Larry Johnson said that he had obtained some information related to this account from one “highly reliable and trusted” source, rather than multiple sources. When asked if the source was based in the Middle East or Syrian opposition, as claimed in the memo, Johnson said he would not divulge any other information about this source.
Further, when pressed to elaborate on the nature of their sources, VIPS chair McGovern referred to: “Senior officials in the U.S. intelligence community with access to this information.”
However, their real—unacknowledged—source is Bodanksy’s article, as the clear textual evidence of blatant plagiarism above reveals. But Bodansky is not a senior official in the U.S. intelligence community. VIPS do not have on the ground sources in the Middle East or among the Syrian opposition at all. Rather than learning the lesson of the plagiarised British dossier on Iraq’s (non-existent) WMD, the VIPS memo replicates it in a misguided effort to oppose an intervention.
When I then put the charge of plagiarism to VIPS, McGovern responded by saying: “Sorry if I did not make it clear. ‘Senior officials’ and Bodansky are two separate and distinct things. The former have nothing to do with the latter. Were it not for the former, we would not have written the piece.” The former CIA analyst added:
“If, as we are told by people we trust (amid suspicions from a whole array of other circumstantial evidence) that the government is not telling the truth, then, in essence we have (or almost had) Iraq Part II, as far as fraudulent intelligence is concerned.”
I asked him why VIPS needed to rely on Bodansky’s narrative if their U.S. intelligence sources were privy to information proving Assad’s innocence, and whether they had verified Bodanksy’s own alleged sources, but received no further comment.
Vacuous Viral Memes
The contradictory White House and VIPS memos are part of an ongoing propaganda war to ‘fix’ the intelligence on Syria for partisan interests, well meaning or not. They illustrate how difficult it is to make sense of the situation in Syria for outside observers due to inherently politicised, conflicting reports. Neither the U.S. and British, nor Iranian and Russian media are impartial sources of information.
Is it possible to assess whether Bodansky’s claims have any merit? Although he has been right in the past, his services having been sought as a U.S. government defence consultant, he has also been ridiculously wrong. In relation to Syria, Bodansky is openly supportive of Bashar al-Assad’s regime, as well as of Alawite domination of Syria. He specifically supported Assad’s uncle Rifaat, who led the 1982 massacre in Hama. So his alleged sources might well also be partisan. (Bodansky could not be reached for comment on his relationship with the Assad regime or the reliability of his own alleged sources, and my email to him on these issues received no response.)
Are VIPS being too credulous about pro-Assad propaganda? Responding to questions about sources over Twitter, Thomas Drake replied with a link to another viral article by Jordan-based Dale Gavlak, a veteran Middle East correspondent for Associated Press, co-writing with on-the-ground reporter Yahya Ababneh. The report cited interviews with mostly unnamed “doctors, Ghouta residents, rebel fighters and their families” saying that the Aug. 21 attack was conducted accidentally by rebels supplied with chemical weapons by Saudi intelligence chief, Prince Bandar bin Sultan. Bandar reportedly provided the weapons to the rebels via the al-Qaeda affiliated al-Nusra Front. But the article, published by a little-known alternative news outlet known as ‘Mint Press News’, came with the following caveat: “Some information in this article could not be independently verified. Mint Press News will continue to provide further information and updates.”
Subsequently, the integrity of the report was completely thrown into question when its purported lead author, Gavlak, issued a statement confirming that she had, in fact, nothing to do with the authorship of the article, and had repeatedly requested Mint Press News to remove her name from the piece without success:
“To date, Mint Press News has refused to act professionally or honestly in regards to disclosing the actual authorship and sources for this story. I did not travel to Syria, have any discussions with Syrian rebels, or do any other reporting on which the article is based. The article is not based on my personal observations and should not be given credence based on my journalistic reputation. Also, it is false and misleading to attribute comments made in the story as if they were my own statements.”
Worse, the story is disputed by accounts obtained by London’s Independent from Ghouta residents who “repeatedly recounted separate landings of ‘chemicals’ at Kafr Batna, Zayina, Ein Tarma, Zamalka, Ain Tarma and Moadamiyeh Al Sham, at varying times, pointing out that a single home-made rocket could not have carried out multiple strikes.” While tunnels in Ghouta do exist, “any chemical accidents in them would not have reached the areas affected, the residents insisted.” Additionally, al-Nusra “has no presence of any significance in Ghouta”, with the largest Islamist group in the area being Liwa al-Islam, who “are not as hardline.”
How to explain the discrepancy between the two stories? The Houla massacre provides a clue—in that case, Assad agents were bribing poor Syrians to spread propaganda blaming the rebels for the killings. The propaganda even made news attributed to so-called Syrian “opposition sources”, but was eventually discredited by UN investigators. The simple physical and eyewitness evidence at the sites of multiple surface-to-surface rocket attacks also undermines the Mint Press News’ claims about an accidental underground detonation.
Another viral story blaming the rebels for the Aug. 21 attacks cites two Belgian and Italian writers who had been taken hostage by Syrian rebel forces for five months. After their release on 8th September, they described overhearing a conversation between their captors saying the rebels had launched the attack to trigger a Western intervention. Compelling? The Italian journalist later emphasised he did not know the rebels were responsible for the chemical attack, as he could not tell whether the overheard conversation was based on real events as opposed to discussion of rumour or hearsay, and could not even confirm the exact identities of its participants.
Proxy War
The ongoing war of words illustrates that Syria is not just a civil war, but a propaganda war being fought for competing geopolitical interests. The end-result of this tug of war between pro-interventionist and anti-interventionist narratives has been the victory of neither, and thus, the entrenchment of violence amidst a Syrian stalemate.
Unfortunately, some parties see this stalemate as a strategic boon. Noting “the synergy between the Israeli and American positions”, the New York Times recently reported that: “For Jerusalem, the status quo, horrific as it may be from a humanitarian perspective, seems preferable to either a victory by Mr. Assad’s government and his Iranian backers or a strengthening of rebel groups, increasingly dominated by Sunni jihadis.” In this context, the threat of “limited” military strikes is more about sending a message to Iran and Syria, rather than about decisively defeating Assad—which may be because “the West needs more time to prop up opposition forces it finds more palatable.”
This coheres uncannily well with a 2008 U.S. Army-funded RAND report tasked with setting out strategic options for regional policy, whose key objective it describes as protecting Western access to Persian Gulf oil supplies. This requires “shoring up the traditional Sunni regimes in Saudi Arabia, Egypt, and Pakistan as a way of containing Iranian power and influence in the Middle East and Persian Gulf”, as well as “exploiting fault lines” between jihadist groups “to turn them against each other and dissipate their energy on internal conflicts.” This is now well underway in Syria, where al-Qaeda and Hizbullah are being dragged into a spiral of mutually-debilitating violence.
Another strategic upshot is the sidelining of longstanding regional pipeline plans that could challenge U.S. aspirations to become a major gas exporter to European markets, directly competing with Russian hegemony. With Qatar and Iran at loggerheads over potential Syria-crossing transit routes designed to supply gas to Europe (with Assad favouring the Iran-backed route based on utilising the Russian-controlled Syrian port of Tartus), the civil war stalemate prevents both from materialising, giving the U.S. an unexpected edge as its shale gas production booms.
In short, the U.S. gets to sideline its gas export competitors while undermining Iranian influence; Israel gets its regional enemies embroiled in war-without-end; Russia gets its arms sales to Iran and Syria; Saudi Arabia and Qatar get to escalate their game of geopolitical brinkmanship; and even the UN gets to rack up its depleted ‘peacekeeping’ credentials over self-congratulatory chemical weapons negotiations. And as the world has watched the debate over intervention drag on like an obscene international game of ping pong, the military-industrial complex rakes in huge profits from rocketing share prices.
Meanwhile, Syrian civilians continue to be killed largely by conventional, not chemical, weapons. According to the latest UN human rights report, both Syrian government forces and Free Syrian Army rebels—and not just those affiliated to al-Qaeda—have committed war crimes, although government forces are culpable in the vast bulk of the violence including at least eight massacres. But under the feel-good smokescreen of chemical ‘peacemaking’ resulting in the rightly-lauded framework agreement, the U.S. and Russia are still fuelling the conflict by stepping up military support to their favoured sides.
Despite the heavy-handed moral rhetoric from all quarters, it seems that everyone is jockeying in pursuit of their own interests, the Syrian people be damned.
Nafeez Ahmed is an investigative journalist, bestselling author and international security scholar. He has contributed to two major terrorism investigations in the US and UK, the 9/11 Commission and the 7/7 Coroner's Inquest, and has advised the Royal Military Academy Sandhust, British Foreign Office and US State Department, among other government agencies. His new novel, ZERO POINT, predicted a US-UK re-invasion of Iraq to put down an Islamist insurgency there. He is a regular contributor to The Guardian where he writes about the geopolitics of interconnected environmental, energy and economic crises via his Earth Insight global column. He has also written for The Independent, Sydney Morning Herald, The Age, The Scotsman, Foreign Policy, The Atlantic, Quartz, Prospect, New Statesman, Le Monde Diplomatique, among many others.
« Previous: Politics | Chile’s 9/11: “Forty years on, we haven’t received any form or type of justice.” [VIDEO]
Next: Analysis | The Long Walk: Talha Ahsan and the Politics of Racialisation »
Harel B
Along with some good analysis, Mr. Ahmed’s piece contains some very misleading statements. He writes: “the integrity of the report was completely thrown into question when its purported lead author, Gavlak, issued a statement confirming that he had, in fact, nothing to do with the authorship” Like others, Ahmed was in such a rush to dismiss this report that he didn’t even take 10 seconds to find out Gavlak is a she and not a “he”
While Gavlak’s gender is not central, it illustrates the glee with which evidence pointing at rebel use of chemical weapons (CW) is dismissed with no more than a cursory glance. Those who click the link Ahmed provides, discover it is in fact not a direct statement by Gavlak but a page by a blogger who claims to be sharing an email sent by Gavlak. It might be true but is unverified. Even if true, the fact is that several others have posted copies of their own emails form Gavlak, two weeks ago, and she told them she helped Ababneh write the article and said not one word to distance herself from co-authorship. She is believed to have known Ababneh (which MintPress made clear was responsible for the interviews) for some three years at the time, so presumably her choice to help him write it up was based on respect for his work she had by them developed.
It speaks volumes that Gavlak remained silent for 3 weeks and even more, what the alleged recent statement does not say. Does Gavlak say the story isn’t true? No. Does she say she has reason to doubt Ababneh or his interviewing? No. Does she say she has reason to doubt what the Ghouta residents testified to Ababneh? Again, no. Sympathies are due Gavlak; it does not take great imagination to see the immense pressure anyone is under when an article they helped someone else write goes viral which reports unpleasant things Ghouta residents have said about a Saudi Billionaire prince, let alone one which questions the narrative of the world’s most powerful state. Understandable if true, that she wishes her name was not on the piece she helped Ababneh write; the issue for those who claim to care about the victims remains elsewhere: the testimonies Ghouta area rebels and residents gave, pointing at rebel use of CW.
Aside: Mother Agnes who Ahmed tells us ” has long openly supported Assad” is on record calling the Assad government “totalitarian” This is hardly “supporting” Assad, and that fact is not changed by the fact that her own experiences and those testimonies given to her suggest many of the rebels are as or more totalitarian and brutal. She’s on record wanting a change of government from the “obsolete” totalitarian present model, but just happens to believe that funding brutally murderous jihadists, bandits, and Al Qaeda groups to tear the country to shreds is not the way to do it:”Now, this totalitarianism is not good, and it’s obsolete but if the armed insurrection is implementing another totalitarianism, which is maybe
worse, because there is blood, they can behead you, they can cut – last week, in our village, they cut the fingers of a so-called ‘collaborator’, then they behead him, and they cut him in pieces,and they left him, in the street, where even children would see..” (2:03min at YsK-12Q6rBU on YT)
Most stunning is Ahmed’s dismissal of what two pro-rebel journalists held hostage by rebels overheard, in English, in an adjacent room to where they were held. Though Ahmed does not bother repeating the words, here is Domenico Quirico’s description of what the man they knew as rebel commander, and two others, said: “During the Skype conversation, they said that the gas attack on the two neighborhoods in Damascus [Ghouta] had been carried out by rebels as a provocation, to push the West towards a military intervention” Not a commander saying he “conjectures” that but saying it “was carried out”. The other hostage Piccinin heard the same. The fact that they can’t be 100% sure of it as proof, is apparently reason enough to dismiss it entirely, and move on to other matter, rather than to call for a vigorous investigation.
One can imagine in some “opposite” parallel universe, in which two pro-Assad journalists are taken hostage, clearly held by Assad forces, and overhear such a conversation with direct CW admission by an Assad commander. Perhaps some pro-Assad hack journalist would say it’s not “compelling”, after all, since the former hostages cannot “even” be 100% certain of the identities of their captors and it “might be” a rumor – surely no one else, certainly no serious journalist, no Western journalist, would react the same way – demands for a full investigation (if not dropping bombs) would be step 1.
Surely at the very least if we care about the dead children, we should demand an investigation into these testimonies. In the actual universe, they will be brushed under the rug –what Piccinin and Quirico overheard, what Ghouta rebels and family told Ababneh– unless the public bands together to insist on an impartial inquiry into the many lines of evidence pointing at rebel use of chemical weapons. The victims deserve nothing less.
Nafeez Ahmed
@HarelB begins his comment with a veiled ad hominem: ‘Ahmed was in such a rush to dismiss this report that he didn’t even take 10 seconds to find out Gavlak is a she and not a “he”… While Gavlak’s gender is not central, it illustrates the glee with which evidence pointing at rebel use of chemical weapons (CW) is dismissed with no more than a cursory glance.’
That error has been corrected. It seems the aim here is to imply that I had a pre-ordained stance on the Mint Press News article which caused me to “rush” into dismissing it.
I think anyone with a half a brain reading this piece will quickly realise 1) I am not particularly gleeful about anything going in Syria, nor any arguments either way 2) I did not rush into any conclusions but rather have conducted a painstaking investigation of the arguments and counterarguments. 3) my dismissal of the Mint Press News report claiming that the Ghouta attack was carried out by rebels is based fundamentally on the fact that firstly the account is disputed by a far more reputable newspaper publication (let’s note that The Independent is also owned by a Russian oligarch), and secondly that the physical evidence at the multiple sites of the attack completely contradicts the therefore implausible scenario put forth in this article, which the HarelB bends over backwards to try to rehabilitate.
In any case, I was in no “rush” to dismiss the Mint Press article. This could have been verified by a quick google of my writings on Syria such as here:
http://www.nafeezahmed.com/2013/08/special-report-syria-intervention-plans.html
where early after the attack I have referenced multiple sources raising questions about the official account., including keeping an open mind about the Mint Press News report.
@HarelB says: “Those who click the link Ahmed provides, discover it is in fact not a direct statement by Gavlak but a page by a blogger who claims to be sharing an email sent by Gavlak. It might be true but is unverified.”
That’s a bit of a rich observation coming from someone clinging obsessively to an article which itself says some of its contents (without specifying which contents exactly) “cannot be independently verified.”
As for the blog where Dale Gavlak’s statement is posted (and I am about to notify you of some interesting updates in this regard), for those who don’t know, the Brown Moses blog is highly regarded and is a reliable source of coverage on Syria by a citizen journo with a pretty decent track record http://www.channel4.com/news/brown-moses-blog-syria-arms-weapons-croatia
@HarelB: “Even if true, the fact is that several others have posted copies of their own emails form Gavlak, two weeks ago, and she told them she helped Ababneh write the article and said not one word to distance herself from co-authorship. She is believed to have known Ababneh (which MintPress made clear was responsible for the interviews) for some three years at the time, so presumably her choice to help him write it up was based on respect for his work she had by them developed. It speaks volumes that Gavlak remained silent for 3 weeks and even more, what the alleged recent statement does not say. Does Gavlak say the story isn’t true? No. Does she say she has reason to doubt Ababneh or his interviewing? No. Does she say she has reason to doubt what the Ghouta residents testified to Ababneh? Again, no. Sympathies are due Gavlak; it does not take great imagination to see the immense pressure anyone is under when an article they helped someone else write goes viral which reports unpleasant things Ghouta residents have said about a Saudi Billionaire prince, let alone one which questions the narrative of the world’s most powerful state. Understandable if true, that she wishes her name was not on the piece she helped Ababneh write; the issue for those who claim to care about the victims remains elsewhere: the testimonies Ghouta area rebels and residents gave, pointing at rebel use of CW.”
What HarelB doesn’t seem to understand, is that for any impartial observer, there is simply no way to take the Mint Press News article seriously anymore. The idea that we can rely on this report as a credible source it just silly.
More than that, the totality of the information revealed about the Gavlak clearly and consistently raises a whole host of disturbing questions about the origins of the whole story. Mint Press News is continuing to claim that Gavlak “wrote the article in it’s entirety as well as conducted the research.” http://www.mintpressnews.com/official-statement-on-dale-gavlaks-involvement-in-syria-exclusive/169507/
Note how carefully worded this is – now compare it to Gavlak’s further statement which clarifies her exact role in the piece:
“Email correspondence between Ms. Gavlak and Mint Press News that began on August 29 and ended on September 2 clearly show that from the beginning Ms. Gavlak identified the author of the story as Yahya Ababneh, a Jordanian journalist. She also made clear that only his name should appear on the byline and the story was submitted only in his name. She served as an editor of Ababneh’s material in English as he normally writes in Arabic. She did not travel to Syria and could not corroborate his account.
“Dale Gavlak specifically stated in an email dated August 29 ‘Pls find the Syria story I mentioned uploaded on Google Docs. This should go under Yahya Ababneh’s byline. I helped him write up his story but he should get all the credit for this.’
“Ms. Gavlak supplied the requested bio information on Mr. Ababneh later that day and had further communications with Mint Press News’ Mnar Muhawesh about the author’s background. There was no communication by Mint Press News to Ms. Gavlak that it intended to use her byline. Ms. Muhawesh took this action unilaterally and without Ms. Gavlak’s permission.
“After seeing that her name was attached to the article, Dale Gavlak demanded her name be removed. However, Ms. Muhawesh stated: ‘We will not be removing your name from the byline as this is an existential issue for MintPress and an issue of credibility as this will appear as though we are lying’.”
http://brown-moses.blogspot.co.uk/2013/09/more-from-dale-gavlak-on-mint-press.html
So it does seem that Gavlak made clear her byline shouldn’t be on the piece. It also seems that she admits to helping write up the story as a friend to Ababneh, and even pitching the piece – and it’s plausible that she might have tried to check with colleagues and officials as Mint Press News claims to see if there was any corroboration of Ababneh’s reporting. Either way, what does seem clear that Gavlak was not responsible for the fundamental content of the piece, and the attribution to her is dishonest.
While I have no doubt that Gavlak probably is under immense pressure, her specific account that she had from the beginning made clear to not use her byline because she was not responsible for the content of the piece seems increasingly plausible in the context of new evidence of Mint Press News’ dubious background, along with the dubious behaviour of the other primary author of the piece Yahya Ababneh.
The New York Times has investigated the issue further and discovered that Mint Press News’ financial backers and advisers included the website editor’s father, an ethnic Jordanian of Shi’a persuasion. http://thelede.blogs.nytimes.com/2013/09/21/reporter-denies-writing-article-that-linked-syrian-rebels-to-chemical-attack/?_r=0 Now that in itself would not be important except 1) sectarian issues have become extremely polarised and polarising with respect to the Syrian conflict and stances supporting and opposing intervention and 2) the NYT found evidence of vehemently sectarian and anti-Saudi anti-Wahabi sentiments linked to her father’s role in Mint Press News. So Mint Press News. For a news site that is supposed to have a semblance of impartiality doing exclusive reporting on Syria, I’m sorry but this is pretty fatal. (also see http://www.al-bab.com/blog/2013/september/syria-rebel-chemicals-story-gets-weirder.htm#sthash.6FIm6srs.dpbs)
It gets worse. An investigation by Brian Whitaker, former Mideast editor at the Guardian, has found compelling circumstantial evidence that Ababneh’s real name is Yan Barakat, has lied about his journalistic credentials, and that the whole story blaming rebels for the chemical weapons attack may have derived from a Russian source in Damascus http://www.al-bab.com/blog/2013/september/yahya-ababneh-exposed.htm#sthash.OTfitqYd.dpbs
No wonder “some” of the information “could not be independently verified.” Anyone claiming that we should now continue to applaud this article and, on its basis, call for an investigation due to its “testimonies”, should take a good look in the mirror to admire their ability to undertake the most profound sorts of mental gymnastics.
HarelB says: “Aside: Mother Agnes who Ahmed tells us ” has long openly supported Assad” is on record calling the Assad government “totalitarian” This is hardly “supporting” Assad, and that fact is not changed by the fact that her own experiences and those testimonies given to her suggest many of the rebels are as or more totalitarian and brutal.”
More admirable mental gymnastics follows as HarelB completely ignores all the evidence I’ve provided proving quite clearly that “Mother Agnes” is utterly compromised, demonstrably close to “Assad’s security forces”, and lauded his so-called “reforms”, not to mention, according to independent journalists, apparently worked with Assad’s forces to have a bunch of them exterminated (successfully). She denies this, unsurprisingly, but the journalists on the ground who witnessed it with their own eyes hold fast to their very plausible and harrowing account.
Harel B ignores all of that, and misquotes “Mother Agnes'” by quoting, not Mother Agnes, but an article by Robert Moynihan, who writes, “Yes, Syria’s president Assad is no democrat; he is a powerful totalitarian leader.” Moynihan then cites an interview in Ha’aretz with the nun titled ‘On visit to Israel, Syrian-based nun backs beleaguered President Assad’, where she says:
“She believes the Assad regime is the only thing that can save Syria from a takeover by Al-Qaida, and that most Syrians support the present regime.”
I have not found a single source where the nun actually describes Assad as “totalitarian” herself.
I myself was taken in by the nun and quoted her in the past. But we do not need “Mother Agnes” discredited pro-Assad ramblings and unverifiable claims of rebel atrocities to be aware of the danger of the Islamist forces therein, and the atrocities they have carried out, a matter I have documented at length elsewhere.
@HarelB says: “Most stunning is Ahmed’s dismissal of what two pro-rebel journalists held hostage by rebels overheard, in English, in an adjacent room to where they were held…. The fact that they can’t be 100% sure of it as proof, is apparently reason enough to dismiss it entirely, and move on to other matter, rather than to call for a vigorous investigation.”
I should call for a vigorous investigation into what exactly? Into a skype conversation overheard by journalists where one of them explicitly admits that he wasn’t sure whether the conversation was about something that had actually happened, or was a conversation about a rumour of what may have happened, and that even if the conversants were clearly amongst the rebel forces, he wasn’t sure precisely who they actually were?
An investigation by the UN is already underway. I’d suggest waiting for the results of that before jumping up and down about the allegedly groundbreaking implications of a vague report such as this in the hope it might prove your suspicions. People are free to make up their own minds, but this report, again, offers no firm ground to draw any meaningful conclusions either way to the available evidence. NOTE: I have not said the account is false. Just that with added caveats, it’s no longer compelling.
“One can imagine in some ‘opposite’ parallel universe, in which two pro-Assad journalists are taken hostage, clearly held by Assad forces, and overhear such a conversation with direct CW admission by an Assad commander. Perhaps some pro-Assad hack journalist would say it’s not “compelling”, after all, since the former hostages cannot “even” be 100% certain of the identities of their captors and it “might be” a rumor – surely no one else, certainly no serious journalist, no Western journalist, would react the same way – demands for a full investigation (if not dropping bombs) would be step 1.”
Interesting that HarelB thinks we should adhere to the standards of the Western journos and govts who might demand “dropping bombs” on Assad on the basis of such poor evidence. He completely ignores the fact that I’ve already looked that the dubious and politicised nature of the way the US government has utilised “intelligence” in relation to the CW issue. So no, we shouldn’t adopt that standard in this case and use it as a basis to think such thin evidence justifies jumping to conclusions.
“Surely at the very least if we care about the dead children, we should demand an investigation into these testimonies.”
Again, difficult to understand what is being expected here. We should all start “demanding” investigation “into these testimonies.” What HarelB clearly fails to grasp from the article is that these testimonies are a dead-end. They do not offer or open up lines of inquiry in themselves that actually lead anywhere. They are vacuous. They might be true. They might not be true. We don’t know. We might never know. Because in one case – e.g. Mint Press News – we now have a body of compelling evidence that the “report” is just garbage Russian propaganda swallowed by an amateur overly-credulous Jordanian journo looking for a scoop, and backed up by a somewhat foolish AP correspondent who tried to help him get it published without wanting to sully her name with such an evidently dubious piece. So maybe we should “investigate” the Belgian and Italian journos’ story even though their whole story is inherently unverifiable because we can’t track down the rebels that took them hostage to ask them what they were conversing about and whether or not they were discussing rumours and who exactly they were.
“In the actual universe, they will be brushed under the rug –what Piccinin and Quirico overheard, what Ghouta rebels and family told Ababneh– unless the public bands together to insist on an impartial inquiry into the many lines of evidence pointing at rebel use of chemical weapons. The victims deserve nothing less.”
What the victims deserve is not to have the public trumping up bullshit lines of inquiry as if they are made of evidentiary gold.
I remain open-minded about the CW issue and as the article above shows, have drawn no specific conclusions either way. But what I have done is shown how all parties, even so-called anti-war activists and journos who really should no better, are politicising the facts.
My full response to this absurd comment is in this link after UPDATE http://www.nafeezahmed.com/2013/09/special-report-fixing-intelligence-on.html
Nafeez Ahmed On Syria: Deciphering the Propaganda War over the Ghouta Massacre | Stop Making Sense
[…] Nafeez Ahmed for Ceasefire Magazine: […]
Syria: Deciphering the Propaganda War over the ...
Sep 26, 2013 2:56
[…] The politicised debate over the realities of last month's chemical attack in Ghouta is a further manifestation of a propaganda war – being fought on all sides and for competing national and geopolitical interests – that shows scant regard for the… […]
Syria: Deciphering the Propaganda War over the Ghouta Massacre | Idler on a hammock
[…] via Syria: Deciphering the Propaganda War over the Ghouta Massacre | Ceasefire Magazine. […]
Syricide
Fog of war significantly dissipates when you dampen down the deliberate dissonance.
MSM = main stream media = multi-sensory-manipulation.
Your blog does better than most to cover as much of the conflicting factors that have ‘manifested’. But it still has managed to miss at least 3 key incidents/revelations.
1.Quirrico and Piccinin. We we should all know by the latter’s testimony about the rebels “skype call” that was overheard by both of the hostages. What we have as a riposte from the anti-Assad fraternity is an attempt to invalidate the pertinence of this incident by trumpeting the fact that Quirrico contested the validity of what they heard.
But when you pause to analyse this you realise it DOES NOT MATTER that one of the hostages questions the merits of it. The key fact is they BOTH correlated that a call was overheard by them that related to ghouta massacre. Once you accept this then you have only 2 scenarios as to why this call occurred.
a) The call was part of an elaborate hoax for them to overhear, which implies the kidnapping was also part of the plan by undercover Assad agents posing as FSA. A hoax 5 months in the planning just so they could overhear this so when they were released they would point the finger away from Assad or..
b) The FSA or associated brigades were complicit in launching the chemical weapons attack.
2.Gas missiles ‘were not sold to Syria’ http://www.independent.co.uk/voices/comment/gas-missiles-were-not-sold-to-syria-8831792.html
Interestingly this bombshell is not taken up by any other western-oriented news source.
And this little gem..
3.Who attacked Ghouta? http://www.whoghouta.blogspot.co.il/2013/09/umlaca-simulation.html
Whats most important about this is … you cant fight the math. Science is impervious to politics.
The suspect munition trumpeted by western media, human rights watch and self pronounced twitter munitions expert “Brown Moses” as his “UMLACA” invalidates all insinuations.
Are you ready for this? The very same missile COULD NOT have travelled the 9km from Regime positions. Even if we err on the side of a 50% miscalculation it COULD NOT have travelled the distance trajectory that is being exhorted by the anti-Assad entities.
Like I said the fog of war significantly dissipates when you dampen down the deliberate dissonance. Step away from the noise, redeem your own logic and reason that MSM compels you to suspend and ask a simple question of yourself.
Cui Bono? Who benefits?
Structural Inclinations – The Leaning Tower of Propaganda: Chemical Weapons Attacks In Ghouta, Syria
[…] energy and economic crises, provided a reasonable assessment of the evidence on September 20, here. Ahmed later commented on responsibility for the […]
Structural Inclinations – The Leaning Tower of Propaganda: Chemical Weapons Attacks In Ghouta, Syria | Syria Solidarity Movement
The leaning tower of propaganda: what the media said about chemical weapons in Syria
fadi harb
Establishing oneself as a dissident is by no means an evidence of one really being so. No one can prove that Chomsky, Zinn, pilger etc. r/were real dissidents. Orwell was an imperialist racist savage pig, the absence of africans and asians in his novels and writings is striking. Living in the west makes u a savage wanting to keep your privileges, this implies integrating and adopting the west’s methods. Being a dissident in the west is no danger to it. On the contrary it strengthens the class called the mind control laborers. This is not about winning souls and minds, this is about the west having the maxim gun and the others not. This is about winning bellies. This is the bottom line.
Oorlog en waarheid. - Ook jij telt mee
[…] betreft? Daarmee is ook van alles aan de hand, zoals stap voor stap uit de doeken wordt gedaan in dit artikel van Nafeez Mossadeq Ahmed. Zijn eindconclusie: ‘t eerste slachtoffer in een oorlog is de waarheid en geen enkel […]
Oorlog en waarheid. (2). - Ook jij telt mee
[…] we nog ‘s teruggaan naar ‘t artikel van Nafeez Mossadeq Ahmed, waarin ie betoogt dat “in de mist van de oorlog, de waarheid ‘t eerste slachtoffer […]
Nov 9, 2013 20:58
[…] Nafeez Mossadeq Ahmed onderwerpt vervolgens ‘t memo van de VIPS aan een nader onderzoek en weet overtuigend aan te tonen dat de opstellers een eerder verschenen artikel geplagieerd hebben van Yossef Bodansky, een ‘Israeli American‘ politiek wetenschapper en voormalig ‘Director of the U.S. Congressional Task Force on Terrorism and Unconventional Warfare of the U.S. House of Representatives’. […]
Structural Inclinations – The Leaning Tower of Propaganda: Chemical Weapons Attacks In Ghouta, Syria » My WordPress Website
Orphan In Needs » Structural Inclinations – The Leaning Tower of Propaganda: Chemical Weapons Attacks In Ghouta, Syria
Oorlog en waarheid. (3). - Quantralef
|
cc/2020-05/en_middle_0097.json.gz/line35497
|
__label__cc
| 0.503645
| 0.496355
|
Foothills Parkway to be closed Saturday, Sunday…
Boulder Area news
Foothills Parkway to be closed Saturday, Sunday for bridge removal
From 7 a.m. Saturday to 7 p.m. Sunday Foothills Parkway will be closed from Baseline Road to Arapahoe Avenue
By Kristina Pritchett | kpritchett@prairiemountainmedia.com |
PUBLISHED: October 29, 2019 at 4:22 pm | UPDATED: October 29, 2019 at 4:22 pm
Foothills Parkway will be closed Saturday and Sunday due to a planned bridge removal, Boulder announced this week.
From 7 a.m. Saturday to 7 p.m. Sunday, Foothills Parkway will be closed from Baseline Road to Arapahoe Avenue.
The work is part of the Foothills Parkway underpass project on Colo. 157, just south of Colorado Avenue, which is projected to be completed in a year.
The new underpass will replace the existing bridge and provide a safer route for cyclists and pedestrians.
Part of the construction includes removing the existing bridge over Foothills Parkway.
A detour will be in place from Baseline Road or Arapahoe Avenue to U.S. 36/28th Street. The pedestrian and bicycle detour will be signed along the route and available at bit.ly/FoothillsUnderpass.
Park East Park will remain open, but the basketball court will be fenced off and closed to play Friday through Nov. 8. The city recommended Emma Gomez Martinez Park, Greenleaf Park or the East Boulder Community Center and Park as alternate locations for basketball.
Following this weekend’s closure, construction of the underpass on the west side of Foothills Parkway will begin. Four lanes of Foothills Parkway will remain open with occasional off-peak time lane closures.
For more information, visit bit.ly/FoothillsUnderpass or contact Noreen Walsh at 303-441-4301 or walshn@bouldercolorago.gov.
Kristina Pritchett
More in Boulder Area news
BVSD moves ‘newcomers’ program from a central location to two high schools
Boulder Library civil rights event allows young to teach their elders
Broomfield Women’s March honors 19th Amendment, MLK Jr. Day
Longmont period kit making event aims to help women in need
|
cc/2020-05/en_middle_0097.json.gz/line35502
|
__label__wiki
| 0.958316
| 0.958316
|
Columbia Valley Rockies
Wartime Wednesdays
Columbia Valley Map Book
Place a Cheers/Jeers
An Air Canada Boeing 737 Max 8 parked at Toronto’s Pearson International Airport in May 2018. (Nicholas Pescod/News Bulletin)
Experts question security, passenger safety after sleeping woman left on plane
Tiffani Adams fell asleep on a quick flight from Quebec City to Toronto and woke up in the dark
Aviation experts are raising security and passenger safety concerns after a woman was left sleeping on a parked Air Canada aircraft with the lights turned off and crew gone.
“It was just a total screw up,” said Ross Aimer, CEO of Aero Consulting Experts and a former airline captain, of the woman’s ordeal.
Tiffani Adams fell asleep during a roughly 90-minute Air Canada flight from Quebec City to Toronto, according to a friend’s recounting of the experience in a Facebook post on the airline’s social media page.
When Adams woke up a few hours after the flight landed, she realized she was alone on a dark plane. Her phone died shortly after, so Adams found a flashlight in the cockpit and attempted to send an SOS signal through one of the plane’s windows.
She then unbolted three latches on the main door, opened it and flagged down a nearby baggage cart operator, who rescued her.
Aimer, who has roughly four decades of aviation service, said he’s never heard of such a situation and that multiple errors would have to be madeto overlook a passenger during disembarking.
It’s likely the flight crew was on the tail end of a multi-day set of flights and were anxious to get home as soon as possible, he said.
Typically, crew must look up and down the cabin as they leave the plane, checking for people or any items passengers may have left behind, he said.
Sometimes the crew will do a cursory clean, as well, he said, or a cleaning crew will arrive to do a more thorough job before a morning flight.
Neither of those things seem to have happened here, Aimer said, and it’s possible the crew failed to check all the seats in their excitement to leave.
“So, it was kind of multiple screw ups that caused this.”
Air Canada, which has confirmed the incident happened, did not immediately respond to a request for additional comment.
Aimer said a cleaning, catering or flight crew would have discovered Adams in the morning had she not been so proactive, but it’s possible someone with malicious intent could hide on a plane in this manner.
“It’s much easier to miss a person that is basically hiding under the seats,” said Aimer.
In that scenario, a person who is trained to fly planes could possibly attempt to hijack the aircraft, he said, pointing to a recent incident out of Seattle.
In 2018, a 29-year-old airport worker named Richard Russell stole a Horizon Air Bombardier Q400 plane and took it for a 75-minute flight that ended with his death in a fiery crash. While Russell’s joy ride didn’t hurt anyone else, there was a nearby sold-out Pearl Jam concert that could have been a potential target.
However, other airport security measures, like a constant police and security presence monitoring the grounds, would likely hinder a hijacking, said Aimer.
Adams’s experience is a freak accident, said Gabor Lukacs, an air passenger rights activist.
His biggest concern would be if the airline had left an ill or otherwise incapacitated passenger behind, who could be much more vulnerable in that situation.
The frequent airline industry critic said he appreciates Air Canada’s willingness to assume responsibility and wishes they were more forthcoming in other situations.
Aleksandra Sagan, The Canadian Press
First Nations included in latest Columbia River Treaty talks
Four-year-old boy assaulted at B.C. soccer game
Jumbo saga reaches finale
A three-decade long disagreement comes to a close.
Former Waterside property to be rezoned?
Invermere residents supported rezoning Waterside property.
Angel Flight
Flights take patients for medical appointments.
Potential pints and a paroled peacock
Radium council discussed a micro-brewery and one of the village’s wildlife mascots.
Explore The Columbia Valley Pioneer
ABERDEEN PUBLISHING INC.
Invermere News
Invermere Weather
Invermere Classifieds
Pick us up!
©2020, The Columbia Valley Pioneer Aberdeen Publishing Inc.
|
cc/2020-05/en_middle_0097.json.gz/line35504
|
__label__wiki
| 0.845421
| 0.845421
|
Home >> US News >> Attorney For Suspected Cop Shooter Says ‘Four-Way Conversation’ With Philadelphia AG, Police Commissioner Helped
Attorney For Suspected Cop Shooter Says ‘Four-Way Conversation’ With Philadelphia AG, Police Commissioner Helped
Posted by: Evie Fordham in US News August 15, 2019 Comments Off on Attorney For Suspected Cop Shooter Says ‘Four-Way Conversation’ With Philadelphia AG, Police Commissioner Helped
The attorney for a suspected shooter said a “four-way” conversation contributed to the end of an hours-long standoff in northern Philadelphia after six Philadelphia police officers had been shot Wednesday.
“There was four-way conversation between [suspect Maurice] Hill, [Police Commissioner Richard] Ross, [District Attorney Larry] Krasner, and myself, trying to figure out a way to do this where there were no injuries to anyone, no further injuries, and I certainly did not want my client to be injured as he was taken into custody,” lawyer Shaka Johnson told Action News on Thursday.
Ross described the four-way call as “unorthodox,” but the suspect’s lawyer, who has a years-long relationship with the suspect, said he was in a special position to help both sides avoid loss of life. Johnson and Hill call each other “uncle” and “nephew” even though they have no relation, reported Action News.
“I told him, ‘I’m not going to be on this television, man, and watch you on this TV, on social media, and watch you go out in a blaze of glory. I’m not going to be a part of that. So if you’re not coming out of that house, I’m going to hang up this phone and I’m going to turn the TV off because I’m not going to watch you get killed,’” Johnson said.
Krasner said the gunman was in a “very excited and animated, frankly, dangerous state” when he got on the phone with him and the other men. But the gunman was motivated to work with the authorities to emerge unscathed because of his newborn daughter, reported Action News.
Six officers were shot and wounded Wednesday. The suspect was forced out by tear gas from the home where he was hiding, and he was still carrying a firearm when police apprehended him.
“I thank the Philadelphia Police Department for being very patient. This could have gone a very different way much earlier in the day, especially with the community putting pressure on them to resume their normal lives. Just standing around and being patient, I’m sure that’s not what a lot of officers wanted, but I thank from command on down for instituting some patience and allowing myself and Mr. Krasner a chance to get here and talk him out,” Johnson said.
Johnson expects Hill to be arraigned on charges including attempted murder, aggravated assault and recklessly endangering another person, reported Action News. He could end up in prison for life, Krasner said. Hill had a history of previous gun convictions, according to The Washington Post. Officers attempted to serve an arrest warrant, leading to the standoff.
Hill was born April 26, 1983. Several men in the Philadelphia and Pennsylvania criminal database share his name, according ABC 6.
Content created by The Daily Caller News Foundation is available without charge to any eligible news publisher that can provide a large audience. For licensing opportunities of our original content, please contact [email protected]
Evie Fordham
Previous: Philadelphia CBP Seizes Nearly $1 Million in Counterfeit Smartphones from China
Next: American Flags Lowered To Half-Staff On Epstein’s ‘Pedophile Island’
About Evie Fordham
KilgoreHoover on Today’s Democrat Party, Complicit Media Are the Enemy of the People
|
cc/2020-05/en_middle_0097.json.gz/line35506
|
__label__cc
| 0.682461
| 0.317539
|
Recognized as 2019 Gartner Peer Insights Customers' Choice for WCM
Contenstack is the leading choice.
For IT & Developers
CMS Guides
In order to proceed, please accept our terms by checking the box here.
Blog / How Modern Marke ...
How Modern Marketers Can Implement AI for Content
Dec 18th 2019, Brent Heslop
The field of artificial intelligence has grown leaps and bounds since Logic Theorist, the first program to mimic human problem-solving skills, was built in 1955 by Herbert Simon, Allen Newell, and John Shaw.
Not even a century after its unveiling at the 1956 Dartmouth Summer Research Project on Artificial Intelligence conference—where the term “artificial intelligence” was coined—AI-powered computers are already writing sci-fi screenplays from scratch and “robot journalists” are creating content in record time for the Associated Press.
AI and content are a winning combination for any modern marketing department that needs to crank up the quantity of their content without sacrificing its quality. Keep reading to learn more about the practical applications of AI for content marketing and how to get it right.
Artificial Intelligence and Its Place in Content Marketing
Artificial intelligence, or AI, refers to the capability of a machine to mimic human cognitive activities. AI is an umbrella term that covers several different technologies, including machine learning (automatic “learning” without being programmed to do so), natural language processing (“reading” human language), natural language generation (“writing” and “speaking” human language), and more. The overarching theme is that all of these systems use similar AI practices to perform various cognitive processes as well as—or better than—humans. Additionally, they typically improve with time and experience.
And it’s clearly in high demand, considering predictions that the global artificial intelligence software market is going to grow by over 594% between 2020 and 2025.
The growth of AI is excellent news for content marketers. Why? Just think of all those manual, menial marketing tasks you could spend entire days on—not anymore with the help of artificial intelligence. How? Keep reading to learn the practical applications of AI for content marketing.
AI for Content: Practical Applications for Marketers
Marketers can effectively and efficiently plan and create content, predict and personalize content that resonates with each consumer, and even automate engagement—all by using AI.
Content Planning and Creation at Any Scale
“Tuesday was a great day for W. Roberts, as the junior pitcher threw a perfect game to carry Virginia to a 2-0 victory over George Washington at Davenport Field.” Did a human or a computer write that sentence? If you can’t tell, it doesn’t matter. (It wasn’t a human.) Big content producers like Yahoo and even the Associated Press have been using AI to write stories—like the sentence above, referencing W. Roberts—for years.
But if full-on robot writers aren’t your style, try implementing AI in your content creation workflow to help write short-form content such as ad copy and even nail those emails and subject lines the first time around.
AI can also be used to analyze consumer behavior and generate recommendations to the content that is most applicable to the person as they continue on their customer journey.
Effective Content Personalization
As the most critical marketing trend of this century, personalization is extremely important for the modern content marketer. And there is almost no way to execute personalized content at any valuable scale without the assistance of automation and artificial intelligence.
Computers armed with machine learning collect data from consumers that they then use to create individual profiles and generate recommendations on how to personalize content for each.
Around-the-Clock Engagement
That little box that pops up at the bottom right corner when you visit a website? It probably isn’t a real agent offering to help you—that’s a chatbot.
Chatbot software employs artificial intelligence to mimic human conversation. Chatbots enable businesses to provide around-the-clock customer service, automatically share just-right promotional and educational content, and empower consumers to self-serve as they see fit. Aside from doing all of the above to boost engagement, chatbots also streamline the customer support process to increase average resolution time and decrease costs.
How to Implement AI for Content
As we’ve explored, AI for content has several essential applications in the business world. The marketer that wants to keep their company relevant and competitive would be wise to tackle this new frontier as quickly and seamlessly as possible.
The key to implementing AI for content marketing lies in separating that content from other business assets, and enabling the filtering of the content through cutting-edge AI-powered tools for analysis, optimization, and publication across various channels.
How? With a headless content management system (CMS). The bleeding edge in content marketing, headless CMS is a purpose-built platform for compartmentalizing content creation, display, and functionality. That means that any piece of content in the CMS can be personalized and optimized for chatbot use, and otherwise updated seamlessly and infinitely.
If you’re ready to implement the AI tools you need for large-scale content planning and creation, flawless personalization, and engaging chatbot automation; it’s time to move your content management program over to Contentstack—the only headless CMS designed specifically for integrations, such as AI and personalization integrations. Contentstack includes pre-built integrations for leading AI solutions, such as IBM Watson and MonkeyLearn.
Learn more about headless CMS, and use our ROI calculator to see how you could be saving hundreds of thousands of dollars on content management, or get in touch today to try Contentstack for free!
|
cc/2020-05/en_middle_0097.json.gz/line35507
|
__label__wiki
| 0.648017
| 0.648017
|
The Siberian Dilemma (The Arkady Renko Novels #9) (Hardcover)
By Martin Cruz Smith
On Our Shelves Now at Some of Our Stores
On hand as of Jan 19 5:30pm
(NEW HARDCOVER FICTION)
This is book number 9 in the The Arkady Renko Novels series.
#1: Gorky Park (The Arkady Renko Novels #1) (Mass Market): $9.99
#2: Polar Star: A Novel (Arkady Renko #2) (Paperback): $17.00
#3: Red Square: A Novel (Arkady Renko #3) (Paperback): $16.00
#4: Havana Bay: An Arkady Renko Novel (Paperback): $17.00
#5: Wolves Eat Dogs (The Arkady Renko Novels #5) (Paperback): $16.99
#6: Stalin's Ghost: An Arkady Renko Novel (The Arkady Renko Novels #6) (Paperback): Email or call for price
#7: Three Stations: An Arkady Renko Novel (The Arkady Renko Novels #7) (Paperback): Email or call for price
#8: Tatiana: An Arkady Renko Novel (The Arkady Renko Novels #8) (Paperback): $17.00
From the award-winning, bestselling author of Gorky Park and Tatiana comes a breathtaking new novel about investigator Arkady Renko—“one of the most compelling figures in modern fiction” (USA TODAY)—who travels deep into Siberia to find missing journalist Tatiana Petrovna.
Journalist Tatiana Petrovna is on the move. Arkady Renko, iconic Moscow investigator and Tatiana’s part-time lover, hasn’t seen her since she left on assignment over a month ago. When she doesn’t arrive on her scheduled train, he’s positive something is wrong. No one else thinks Renko should be worried—Tatiana is known to disappear during deep assignments—but he knows her enemies all too well and the criminal lengths they’ll go to keep her quiet.
Renko embarks on a dangerous journey to find Tatiana and bring her back. From the banks of Lake Baikal to rundown Chita, Renko slowly learns that Tatiana has been profiling the rise of political dissident Mikhail Kuznetsov, a golden boy of modern oil wealth and the first to pose a true threat to Putin’s rule in over a decade. Though Kuznetsov seems like the perfect candidate to take on the corruption in Russian politics, his reputation becomes clouded when Boris Benz, his business partner and best friend, turns up dead. In a land of shamans and brutally cold nights, oligarchs wealthy on northern oil, and sea monsters that are said to prowl the deepest lake in the world, Renko needs all his wits about him to get Tatiana out alive.
The Washington Post has said “Martin Cruz Smith is that rare phenomenon: a popular and well-regarded crime novelist who is also a writer of real distinction.” In the latest continuation of his unforgettable series, he brings us to the inside world of shadowy political figures and big wig oil oligarchs providing us with an authentic view of contemporary Russia, infused with his trademark wit.
Martin Cruz Smith’s novels include Gorky Park, Stallion Gate, Nightwing, Polar Star, Stalin’s Ghost, Rose, December 6, Tatiana, The Girl from Venice, and The Siberian Dilemma. He is a two-time winner of the Hammett Prize, a recipient of the Mystery Writers of America’s Grand Master Award and Britain’s Golden Dagger Award, and a winner of the Premio Piemonte Giallo Internazionale. He lives in California.
“This is Smith at his absolute best: black humor, brown bears, and gray souls.”
“[A] must for any crime fiction fan interested in the underside of Putin’s Russia.”
“Everything just feels Russian, as though the author hikes to his hut from the taiga, warms his frozen fingers at the wood stove, pours himself a vodka, and sits down to type. This is vintage Martin Cruz Smith. Fans of Arkady Renko will be pleased.”
"The master of the international thrillier."
"A huge inspiration for me."
"Martin Cruz Smith and Detective Arkady Renko are irresistible."
"Renko is one of the most compelling figures in modern fiction."
"Along with icons like Sherlock Holmes, Philip Marlowe, and Sam Spade, Arkady Renko has become one of the finest fictional detectives to prowl the literary landscape."
"What ultimately sets the Renko books apart is the careful writing, and, more important, the knowledge of the human heart."
—Chicago Tirbune
"A continuing adventure that in terms of popular fiction is surely a work of art."
"Not merely. . . our best writer of suspense, but one of our best writers, period."
—The New York Times Book Review
Publisher: Simon & Schuster
Series: The Arkady Renko Novels
Fiction / Thrillers / Espionage
Fiction / Historical
CD-Audio (November 5th, 2019): $29.99
|
cc/2020-05/en_middle_0097.json.gz/line35511
|
__label__cc
| 0.686583
| 0.313417
|
Teenage Confusion
by Tricia Johnson MBACP (Senior Accredited) Counsellor, Supervisor and Trainer, listed counsellor/therapist
How many parents despair of the mess they find upon opening their teenager’s bedroom door? How often do they shout and nag ‘And tidy your bedroom up!’? How many parents wrestle with a sense of failure as they wonder where they can possibly have gone wrong?
Yet, this problem hits all families, and generally speaking no matter how hard the parents try, the result is the same; they might manage to get their teenager to tidy their room up – but it isn’t long before it is back in a mess, maybe even worse than it was originally!
However, it may be worth considering that perhaps there may be a very good reason why teenagers in particular have messy bedrooms.
Very often the state of the individual's bedroom can be a reflection of how they feel about themselves. The bedroom is a personal space; rarely will anyone else enter it except those we deeply trust. It is here that we feel safe to be at our most vulnerable. Therefore, how we feel about this space indicates how we feel about ourselves and our own vulnerability. If we are confused and struggling to work out who we really are, then our bedroom will be confused and a mess. If we are content and secure in ourselves, then our bedroom will be a space we will delight in and it will reflect our tastes and personality in its décor and furnishings.
So, what about teenagers? If the above is true then, judging by their bedrooms, teenagers are totally confused and internally disturbed. Could this be the case?
Developmentally, during early teens, youngsters are asking the same questions that they asked when they were first born. Who am I? Whom can I trust? What am I allowed/able to do? How do I fit into this new world? When first born, the baby is seeking answers to these questions as he/she comes into the world from the womb. Teenagers are asking these questions as they move from childhood to adulthood.
Unfortunately, the society within which we live is confused in terms of how they see these young people, as reflected by the minimum ages at which they are allowed to do things. For example, a young person, at
10 can get locked up for killing someone
13 can be found guilty of rape and other sex offences
can work part-time
14 can have an air rifle or pistol
can be found guilty of any crime
15 pays full price at the cinema
can be sent to young offenders institution or prison
16 pays full price on public transport
can leave home with parents’ permission
can have sex with someone else
can get married or become Civil Partners with parents’ consent
can sign medical consent forms
17 can drive a car
can leave home without parents’ consent
18 can vote
can change his/her name
can act as executor of a person’s will
can serve on a jury
can borrow money
can drive a London Underground train
can get married
can have his/her own credit card
21 can drive a bus or a big lorry
22 can demand National Minimum wage
This is just a sample of the things that can be done at the different ages. I wonder what message all of this gives to our young people. At 16 they are considered old enough to leave home, marry, have sex, sign consent forms and pay full fare on public transport but they can’t have credit cards, can’t drive or vote and are not entitled to National Minimum wage!
It is small wonder that so many of our young people feel confused and disorientated not knowing fully who they are and how they fit in to wider society. And as a result their bedrooms will be a confused mess, reflecting the inner turmoil that they are experiencing.
With the best will in the world it is almost impossible for the conscientious parent to help their offspring to negotiate the transition from childhood to adulthood without some trauma. With so many confused messages from society around them, they are seriously limited with regards to how much responsibility and freedom they can allow them to assume. As a result, the frustrated teenager will show signs of this confusion. All a parent can hope to do is allow freedom and responsibility as and when it’s appropriate and keep communicating to their youngsters that it is frustrating, but it won’t last for ever. Furthermore, accepting that their bedroom will reflect this confusion and being patient with them will go a long way to alleviate some of the pressure that they are experiencing. In time they will deal with this as they, hopefully, become content in who they are and how they fit in.
If you are struggling with this, either as a parent or a teenager, and feel you need additional help to navigate these choppy waters, then perhaps counselling will be able to offer the support that you need.
Relationship problemsChild related issuesFamily issues
About Tricia Johnson
Hello and welcome to my page.I have been helping people with psychological issues for over 30 years, and originally went for counselling training because others would often seek me out to listen to their problems and difficulties. My own background and past difficulties mean that I have a good understanding of where others may be coming from.I use a designated room in my home which is comfortable … Read more
Located in Alford.
Relationships and Ambivalence (Part 2) Boundaries
Abuse Relationship problems Sexual abuse
Emma: I am not a victim. I am a survivor.
In 1981, I was sexually abused by the restaurant owner who had befriended my family on...
Anxiety Depression Relationship problems Low self-confidence Low self-esteem Alcoholism
Louise Thompson: Anxiety, depression and codependency
Louise Thompson, known for the glamour and glitz of Made in Chelsea, is more than meets...
Relationship problems Sex problems
Sex and intimacy in intimate relationships
By Pasquale Forcellati PGdip, NCS Accred Relationship and Psychosexual Therapist
Is sex enough to create intimacy in committed, long-term relationships? Sex in a...
Relationship problems Anxiety
Relationship problems Depression Low self-esteem
|
cc/2020-05/en_middle_0097.json.gz/line35517
|
__label__wiki
| 0.730394
| 0.730394
|
Board index Caribbean Regional Airline News Montserrat Airways Ltd. / Fly Montserrat
Fly Montserrat: Business as Usual After The Fatal Crash
Web site: http://www.flymontserrat.com/
Unread post by bimjim » Sun May 17, 2015
http://www.mnialive.com/articles/fly-mo ... atal-crash
Fly Montserrat and The Governor:
Business as Usual After The Fatal Crash
Jeevan A. Robinson
The formal investigation of the airline began in April 2014, when ASSI contracted an Investigation and Enforcement Officer from the CAA's Office of the General Counsel, Des Nelhams. As an experienced Detective Superintendent of Scotland Yard, Mr. Nelhams proceeded to interview and collect written statements "that would stand up in court" or other legal proceedings.
What is the relationship between Governor Davis & Fly Montserrat's management?
It seems reasonable to expect the accident and resulting deaths of 3 people would have a profound effect on how the airline and the Governor carried on the business of air safety - them becoming far more safety conscious. However, it appears just the opposite occurred.
Update: The Governor has responded yet again to our second article. You will want to pause here, and read his latest comments and our reply (available here) before proceeding as it impacts upon this article.
In our first installment of this series, we exposed how the UK's regulator, acting as advisor to the Governor of Montserrat, was eventually forced to recommend action against the airline. A lengthy investigation resulted in many pilots, passengers and airport staff coming forward with their personal experiences. These written statements were protected by the UK Civil Aviation Authority's (CAA) whistle-blower protection, but copies of the statements were passed directly to the airline.
Additionally and as recently as January 2015, even after the latest round of sanctions were in place, the British Governor forwarded formal and confidential e-mail from citizens to the airline, resulting in threats of punitive legal action against this group by the airline's lawyers.
Now that these statements are no longer confidential, we can relay some of the accounts of the airline's practices that finally led Air Safety Support International (ASSI) to insist on changes in operational management at Fly Montserrat.
A small sample of the findings include:
A pilot's girlfriend, who was not a commercial pilot, listed in the log as a pilot (dressed in a pilot's uniform while occupying the co-pilot seat) and flying with passengers onboard in order to gain flying experience. This incident was first reported to the Eastern Caribbean Aviation Authority (ECCAA) in Antigua by an SVG pilot, Ted (Teddy) Thomas. (later confirmed through ASSI investigation of log book entries);
A very experienced pilot quitting after only 11 days sighting dangerous safety practices;
Management encouraging pilots to fly in winds greater than the aircraft's limits (confirmed through testimony of a private pilot and tower staff);
Pilots and engineers encouraged not to write aircraft defects in logs because the airline was only a small carrier and pilots "needed to be reasonable". All aircraft defects must be addressed within a given period of time, categorised by severity. Repairs cannot be postponed past the stipulated timeframe, hence the request to not record issues. When defects are hidden, unsuspecting passengers are flying on planes that are technically, and legally, grounded.
After discussions about how to keep a defective aircraft flying (repeated and consistent failure to start left engine on VP-MNI), the repair centre in Anguilla sent a message to remind the airline, "Please be advised that this aircraft cannot operate commercially if there is a known problem. Arrangements should be made to bring this aircraft to main base for rectification or support from main base go to MNI to assist in rectifying problem."
Regarding a different defect (malfunctioning generator and the aircraft's inability to balance the load between the generators), the airline sent e-mail messages describing how the grounded aircraft, VP-MNI, could be kept flying from the date of the message, August 26, 2014, to the plane's scheduled maintenance in October, nearly 3 months away. As a result of our investigation, MNI Alive has received internal e-mail messages of these incidents and discussions.
In one of the most horrific accounts of the findings, a young pilot was forced to land in Montserrat without functioning flaps because the airline's management was allegedly not willing to pay for hotel rooms for some of the passengers onboard. When the plane finally came to a stop and could turn back towards the terminal, the wing was "hanging over the edge of the cliff" during the turn. The frightened pilot apologised profusely to Canadian passengers who later reported this incident.
Clearly, ASSI found a preponderance of evidence against the airline, concluding "As a result of our investigation, the operator has been subject to close monitoring and the renewal periods for its operating certificate have also been reduced whilst we track progress against various actions... A number of significant changes have been introduced to the FM management structure, ...[and] further changes are to be implemented by April 2015 and we will continue to closely monitor the operator until at least mid-2015" (ASSI CEO, Jan 5, 2015).
As a result of the investigation, Nigel Harris was forced to step-down as the airline's Chief Pilot and Accountable Manager (or in his words - put a transition plan in place).
The airline's second largest private shareholder was put forward as the new Accountable Manager who must "demonstrate the ability to direct the activities of the organisation, ...[has] ultimate responsibility for operational standards and compliance with the relevant regulations, ...[has] appropriate authority for human resources matters, ...[and] has corporate authority for ensuring that all operations and maintenance system activities can be financed and carried out to the standard required" (OTAC 119-1, CAP 789).
The glaring oversight in appointing this shareholder to the Accountable Manager position is that he lives and works in the US. The old management is still in place, and if you have travelled through Montserrat you know this to be true.
Either directly on-the-ground or via Skype from their home a few miles away, the same 2 people run all aspects of daily operations of the airline they formed in 1989. (see article here)
The other glaring failure of this smoke-and-mirrors game is the airline has been given time to become familiar with, and incorporate, ASSI regulations to improve the firm's safety culture. Really? So how did Nigel Harris own and operate no fewer than 7 previous airline companies in the UK while not being fully aware of the industry's regulations? (Companies listed show last registered and historical names in parenthesis - i.e. name changed.)
• London Flight Centre (Headcorn) Limited - (Loop Venture Limited)
• Love Air Limited
• London Flight Centre (Stansted)
• Stansted Aviation Centre Limited - (Action Forward Limited)
• London Flight Centre (Training) Limited - (London Flight Centre (LYDD) Limited)
• London Flight Centre (Engineering) Limited - (London Flight Centre (Bristol) Limited)
• London Flight Centre (Air Charter) Limited - (Altair Aviation Limited)
In an interview with Management Today, Nigel Harris is reported to have all his 65 staff transfer operations between the UK and Caribbean twice a year. (see article here) Really? He had a staff of 65 and is still unaware of industry compliance rules?
In terms of shedding light on the management culture at Fly Montserrat, one of the most telling pieces of information in the written statements collected in 2014 and 2015 were threats made to pilots about ruining their future employment prospects if they went to authorities regarding the safety practices at the airline. These threats turned to action during Nigel Harris' tenure as Accountable Manager, and the practice continues even after ASSI claims a "new management team" is in charge.
In an e-mail obtained during our investigations, the Managing Director at SVG Air, Grenadine Airways, ABM Air, OECS Aircraft Maintenance, Paul Gravel, stated he "got a call from MNI to warn me about your lack of airmanship and how you landed Runway 28 after having to overshoot it and on the second attempt you landed long and blew the tires. What is the true story?" (Paul Gravel, February 26, 2015)
The pilot who agreed to be named in this article, Abe Ayyad, was the subject of these exchanges and has over 30 years of flying experience, is a long-time flight trainer and who, only days before this fabricated incident, was complemented on his handling of his plane in windy conditions by ASSI regulators during their inspections in February 2015. Abe stated Mr. Harris' telephone call was silly since any such incident would force tower staff to send a Mandatory Occurrence Report to ASSI, and of course, no such report was filed.
Fortunately, the ability of authorities to subpoena telephone records of both Nigel Harris and Paul Gravel would put an end to denials of such behaviour and clearly show the call took place. Additionally, similar incidents took place on at least 2 other occasions, again one after the "new management team" was in place, highlighting a continuing pattern of such behaviour. Not only is the airline willing to suppress information through threats, the firm is also more than happy to fabricate the information entirely in its bid to silence experienced pilots from exposing wrong-doing in the airline's practices.
The Governor of Montserrat, Adrian Davis, first made citizens aware of the CAA's whistle-blower protection in an email dated February 6, 2014, and the initial message in the thread contained statements that clearly fell within the whistle-blower policy. Strangely however, the Governor copied his reply to the head of the DFID organization on the island who was also a board member of the Montserrat Development Corporation (MDC). MDC is a major shareholder in the airline, and we have confirmed this message was passed along to the airline.
Similarly and even after the most recent sanctions against the airline, it is likely Adrian Davis passed along confidential and protected messages directly to the airline on or about January 21, 2015. We know this because the Chief Operating Officer at ASSI confirmed he and his organisation did not forward the message, the only other recipients. The deliberate breach of the CAA's policy resulted in the airline launching threats of punitive legal action, directly referring to information contained in the confidential report.
Having been aware of the CAA policy and privy to the threats contained in testimony, Governor Davis as the aviation "competent authority" for the Territory, continued to provide direct and illegal support to the airline. (Yes, it is illegal to violate the whistle-blower protection.)
In light of the Governor's continued support of the airline after the crash, was the airline emboldened to continue such illegal safety practices? After all, the company was untouchable, was it not?
The Governor continues to deny he is the "competent authority" for air safety on the island, deny he has the power to alter or suppress information, claims there is no record of Air Traffic Controllers submitting Mandatory Occurrence Reports they clearly state were submitted before the crash, and he continues to provide material support to the airline.
His protection of the airline and the absence of a report on the "fully investigated" 2010 mid-air engine failure must be seen as directly contributing to the deaths of 3 innocent passengers. In this regard, both the airline's management and the British Government, through the actions of its Governor, must be seen as culpable in the deaths.
What will it take before the British Government begins a formal and public enquiry into the deaths and continued dangerous practices of the airline?
Again, why does The Civil Aviation (Investigation of Air Accidents And Incidents) Regulations (S.R.O. 72/2007) of Montserrat give the Governor the power to alter and thereby suppress any and all air safety issues on the island?
Why can he exempt companies or individuals form mandatory reporting of incidents under the Air Navigation (Overseas Territories) Order of 2007?
Why is Fly Montserrat allowed to carry passengers after allowing inexperienced pilots to fly VP-MON after its 2010 mid-air engine failure and while continuing to threaten pilots in a bid to suppress willful action at circumventing safety regulations?
Where does the Premier, Donaldson Romeo, stand on the call for a UK public enquiry and a repeal of the 2 Acts that provide the Governor these powers? As Opposition Leader, Mr. Romeo was the only politician who spoke of the need to investigate problems at the airline.
What will it take before Montserratians rise up and demand the repeal of the Governor's powers and call for direct protection under the UK's professional regulators, who must have complete and unfettered jurisdiction in protecting passengers?
Return to “Montserrat Airways Ltd. / Fly Montserrat”
|
cc/2020-05/en_middle_0097.json.gz/line35520
|
__label__wiki
| 0.575863
| 0.575863
|
South East Asia | John-Alex Mason ECS Scholarship Recipient 2015
Jessica L. James, Director of Communications and Advancement
Kristi Tilghman, a senior at The Colorado Springs School (CSS) will participate in the Sojourn in South East Asia: Past and Present Vietnam and Cambodia as the 2015 recipient of the John-Alex Mason Experience Centered Seminar (ECS) Scholarship. As a CSS alumnus of the Class of 1994, John-Alex Mason had been active in the life of the school and even planned and led a Blues ECS alongside faculty. As a student, John-Alex’s passions were explored and nurtured at CSS. His family credits CSS for offering transformative educational experiences such as ECSs that allowed John-Alex to pursue his music career and become a well-known Blues musician. After John-Alex’s passing in October of 2011, memorial gifts from family and friends established a scholarship fund to fully fund an ECS experience for a deserving student.
Imaging herself as a modern Indiana Jones, Kristi looks to fully embrace the adventure to Cambodia and Vietnam. But as a more serious scholar, Kristi first became intrigued with this part of the world during her Advanced Placement History Class in which she studied the Vietnam War. She recalls being “absolutely struck” by a series of letters a soldier had written about the horrors of war. Her vivid imagination wants to take those words off the pages and experience the country and culture first hand in the present day.
She has furthered her interest in this subject through her Advanced Placement Comparative Politics course this year. The three-week ECS seminar will now give her the opportunity to delve deeper into the political and economic challenges faced by these countries as well as explore cultural and environmental wonders. An element of service runs deep for Kristi as she serves as a member of the National Honor Society. Her humanity attracts her to the service component of this ECS. Students will help build a shaded outdoor reading space at a local Vietnamese school. The reading shelter will provide a respite from the sun for those students wishing to read while outside.
With an optimistic outlook and a fervor for life, Kristi aspires to study international business in college and is eager to make her college decision. She has already received many college acceptances and Trinity and Lake Forest are two schools among the top of her choices. As a thespian at CSS, Kristi starred as Belle in the school’s musical production of Beauty and the Beast last spring and this year she will explore a new stage on Boddington Field as she has decided to play soccer for the first time this spring. Kristi also played volleyball for the Kodiaks and recently earned a Scholastic Art Award for a charcoal figure-drawing. She is an active member of KICS, a philanthropy club at school and Upstagers, the drama club.
Kristi is a veteran student at CSS having embraced a love for experiential learning and seminars since preschool. As a high school student she has previously participated in the Desert Solitaire ECS, The Brain ECS, and the Marine Biology ECS in Bonaire.
Interested in the continued adventures of the Experience Centered Seminar program? Follow the ECS Blogs.
MORE ABOUT THE SOJOURN IN SOUTH EAST ASIA: PAST AND PRESENT VIETNAM AND CAMBODIA
Recently recovering from decades of war and isolation, Vietnam today has become a country renowned for its tremendous economic growth, welcoming people, and rich history. We explore Vietnam’s rich and diverse cultures and history from 15th century port villages like Hoi An, to capital city, Hanoi, which recently celebrated it’s first millennium in 2010. We delve deeply into the history of the Vietnam war, visiting sites like the Hoa Loa Prison (Hanoi Hilton), the tunnels of Cu Chi, and the War Remnants museum in Saigon. We also learn about Vietnam’s rich environmental wonders as we explore the Mekong Delta and paddle in the world class kayak destination of Ha Long Bay. Our group works hands-on with at least one NGO that has worked to combine historic and cultural preservation with the goals of economic development. We wrap up our experience with the powerful comparisons and contrasts of Cambodia, where we spend 5 days immersing ourselves in local culture. From the world famous temple at Angkor Wat to the Killing Fields and Genocide Museum in Phnom Penh, students delve deeply into Cambodia’s beautiful and tragic past.
MORE ABOUT EXPERIENCE CENTERED SEMINARS (ECSes)
Experience Centered Seminars (ECSes) are an integral part of the Upper School program and give our students the skills necessary to conduct large-scale investigations in college and beyond. Each March, our students participate in a three- to four-week-long study that immerses them in academic subjects through a hands-on, interdisciplinary approach. ECS’s approach broad, interdisciplinary questions to optimize the teaching of critical thinking, organized inquiry, in-depth analysis, and synthesis of information. They demand direct active participation and primary research in an environment outside of the classroom. Academic requirements include oral and written presentations, term papers, group work and projects, or final exams. The ECS experience sets our students apart as they move into the collegiate world and beyond.
MORE ABOUT THE JOHN-ALEX MASON ECS SCHOLARSHIP
Established by friends and family of alumnus, John Alex-Mason ‘94, the John-Alex Mason ECS Scholarship is a full, merit-based memorial scholarship for a deserving student to explore their passion through an ECS. John-Alex Mason played an active role in the life pf the school and even planned and led a Blues ECS alongside faculty. As a student, John-Alex’s passions were explored and nurtured at CSS. His family credits CSS for offering transformative educational experiences such as ECSs that allowed John-Alex to pursue his music career and become a well-known Blues musician. An application and essay are submitted by students and reviewed by a scholarship committee.
2013: Travis McDowell - The Blues
2014: Carl Churchill - Peru
2015: Kristi Tilghman - Sojourn in South East Asia
ABOUT THE COLORADO SPRINGS SCHOOL (CSS)
CSS offers an experiential educational curriculum for PreKindergarten – 12th graders. Through superior academics and mentoring, The Colorado Springs School prepares students to think independently and to meet the needs of a dynamic world with leadership, ingenuity, problem-solving skills, and personal integrity. Learn more at www.css.org or visit us on Facebook at www.facebook.com/TheColoradoSpringsSchool
|
cc/2020-05/en_middle_0097.json.gz/line35526
|
__label__cc
| 0.732765
| 0.267235
|
JMA raises the roof with reading
Readers Raise the Roof is one of several Reads to Lead initiatives
JMA raises the roof with reading Readers Raise the Roof is one of several Reads to Lead initiatives Check out this story on CurrentArgus.com: http://c-cargus.co/2c4O0f5
DeJanay Booth, Carlsbad Current-Argus Published 4:29 p.m. MT Aug. 27, 2016
Books and apple(Photo: Getty Images/iStockphoto)
CARLSBAD — Jefferson Montessori Academy hosted Readers Raise the Roof on Friday to help students build their reading skills.
The workshop, which JMA reading coach Jean Appell said is held at other schools as part of the state's Reads to Lead program, offered parents a chance to be involved with their kids in reading.
Appell said although the workshop was geared toward students in kindergarten through third grade, any JMA student was welcome to attend.
"The workshop gives parents support and strategies for reading practices at home," Appell said.
Families who attended the event engaged in role playing and students created book worms out of pipe cleaners. Teachers also taught students a song about reading.
Appell said the main goal of the event was for students to not only work on their reading but also to create working relationship between parents, students and teachers.
"It gives the parent more activities to work with their child on specific skills like to conduct a conversation," Appell said. "Students don't have to only read in school. (At home), a parent can listen to their child read and help them if they stumble on a word. When (the students) go to college, will they be able to read an application?"
Appell, who organized the event at the school, said it was the first held at JMA. She said a second event is planned for February.
"Reading doesn't have to be boring. It can be something fun," Appell said.
DeJanay Booth can be reached at 575-628-5546.
Read or Share this story: http://c-cargus.co/2c4O0f5
|
cc/2020-05/en_middle_0097.json.gz/line35527
|
__label__wiki
| 0.955011
| 0.955011
|
Lisa May finishes her last day on radio with…
Lisa May finishes her last day on radio with KLOS team Frosty, Heidi and Frank
Lisa May helps host KROQ’s annual Kevin & Bean’s April Foolishness at Gibson Amphitheatre in April 2013. (Photo by KELLY A. SWIFT, FOR THE REGISTER)
By Peter Larsen | plarsen@scng.com | Orange County Register
There were tears, as she’d predicted, but the final moments on the air for radio personality Lisa May also unfolded with laughter, music, and a whole lot of love on Friday morning.
May, whose career on Los Angeles radio included the last five years on KLOS-FM/95.5 and nearly 25 years on KROQ-FM/106.7, announced recently that she was leaving the airwaves for a new chapter as the owner and operator of a fitness center in the Coachella Valley.
Comedian Brad Williams gives KROQ’s Lisa May a lap dance so, as he put it, she would have something to remember from KROQ’s 2012 April Foolishness show at the Gibson Amphitheare in Universal City in 2012. (Photo by ARMANDO BROWN, FOR THE ORANGE COUNTY REGISTER)
Lisa May and Brittany, the reigning Miss Double D-cember, introduce comedian Reggie Watts during KROQ 106.7 FM’s annual Kevin & Bean’s April Foolishness show at the Shrine Auditorium in Los Angeles in 2014. (Photo by ARMANDO BROWN, FOR THE REGISTER)
Kevin and Bean Show team members Lisa May, Chip, and Christine, from left, introduce comedian Doug Benson during KROQ’s annual April Foolishness show at the Shrine Auditorium in Los Angeles in 2014. (Photo by ARMANDO BROWN, FOR THE REGISTER)
Lisa May (Courtesy photo)
Longtime L.A. radio personality Lisa May is leaving KLOS-FM and radio on Friday, Dec. 13, 2019 to embark on a new chapter as the owner-operator of a fitness studio in the Coachella Valley. (Photo courtesy of Lisa May)
Comedian Brad Williams had the audience in stitches while giving KROQ’s Lisa May an alleged lap dance during KROQ’s April Foolishness show at the Gibson Amphitheare in Universal City in 2012. (Photo by ARMANDO BROWN, FOR THE ORANGE COUNTY REGISTER)
As her day on the Frosty, Heidi and Frank Show neared its 10 a.m. finish on Friday, things mostly turned to tributes from the KLOS team as well as calls from longtime listeners.
“You’re making me cry,” she said soon after the champagne bottles got uncorked and the toasting began.
“She’s the first human being I see every day besides the guy who works at 7/11,” said show producer Erik Smith before the regular New Music Friday bit for which he’d picked a pair of songs in May’s honor.
“The first one is called ‘I Made It’ (by Manafest), and it’s just for you,” Smith said. “Because you hear a lot in this industry (that) you never know if or when you’ve made it.
“We’re here to tell you you made it,” he continued. “You have done this job with grace, you have done this job with kindness, and nobody in this building can say a bad word about Lisa.”
A truck driver named Sam called to thank May for “your love of the traffic” through which he drives every day.
“Your traffic [report] really uplifts me, your voice uplifts me,” he told her.
“Thank you, and man, a guy in a truck, that is rough in L.A.,” May replied.
Caller Doug noted that he’d met her at a pet adoption event a few years ago, which gave Frosty, Heidi and Frank an opportunity to tease her one more time.
“Which cage were you in, Lisa?” one of the guys asked.
“Yeah, we adopted her from KROQ,” the other chimed in.
“She stayed with me awhile,” Heidi added. “I fostered her.”
Frosty then sang her a song he’d written back when Frosty, Heidi and Frank were leaving their former radio home — that included lyrics he said were appropriate to be “saying goodbye to our dear friend that we’re going to miss, that we spent so many years or our lives with.”
The song included lines such as “I never thought you’d be leaving this soon,” and “I hope you find what you’re looking for,” and finally, “Goodbye to you.”
It’s radio, of course, but you could sense the studio was getting a little bit tearier from the audible sniffing you could hear at the finish.
“Losing you in our life, we’ve all lost people and said goodbye to people we never thought we’d say goodbye to so soon,” Frosty said.
“She’s not dying!” Heidi joked.
“I might be,” May countered.
Caller Jerry came on the line that thank Lisa for the traffic report that helped him find his future wife. He’d been stuck in traffic, heard May’s report and her suggested alternate route one day seven or so years ago.
“I ended up getting rear-ended,” Jerry said of the woman he met that morning thanks to listening to Lisa. “I ended up talking to her, and seven years later we’re still married.”
Smith’s final song for May closed out the show, a Trampled By Turtles cover of the Warren Zevon song, “Keep Me In Your Heart,” which is truly one of the most beautiful and emotional farewell songs you could ever hope to cry along to.
“If I leave, it doesn’t mean I loved you any less,” one verse goes before the chorus enters with “Keep me in your heart for a while.”
As the chorus repeated at the end of the song the studio mics went live again and you could hear the crew singing along.
Then laughter: Apparently some kind of sign was displayed in the room that read “Lisa May, 1988-2019,” like a gravestone.
“Oh, you guys, I love you,” May said.
“Lisa, we love you too,” one of the guys said.
As did a whole, whole lot of other people around Southern California for the last three decades.
Ska Parade radio show celebrates 30 years on air with anniversary tour
Remembering Don Imus, the Riverside-born radio host who found fame and scandal on the East Coast
Radio game show ‘Says You!’ will tape in San Bernardino on Jan. 25
Richard Blade remembers KROQ DJ Raymond ‘Ramondo’ Banister, his former radio partner
Appointments cancelled at Kaiser Woodland Hills due to water main break – Daily News
Pier 1 closing 7 stores in LA County, nearly 20 in all for Southern California – Daily News
John Racz convicted of murdering his wife – Daily News
Stephen Colbert’s act will liven up presidential race – Daily News
Health a key concern for Lakers – Daily News
Peter Larsen
Peter Larsen has been the Pop Culture Reporter for the Orange County Register since 2004, finally achieving the neat trick of getting paid to report and write about the stuff he's obsessed about pretty much all his life. He regularly covers the Oscars and the Emmys, goes to Comic-Con and Coachella, reviews pop music, and conducts interviews with authors and actors, musicians and directors, a little of this and a whole lot of that. He grew up, in order, in California, Arkansas, Kentucky and Oregon. Graduated from Lewis and Clark College in Portland, Ore. with degrees in English and Communications. Earned a master's degree at the Medill School of Journalism at Northwestern University. Earned his first newspaper paycheck at the Belleville (Ill.) News-Democrat, fled the Midwest for Los Angeles Daily News and finally ended up at the Orange County Register. He's taught one or two classes a semester in the journalism and mass communications department at Cal State Long Beach since 2006. Somehow managed to get a lovely lady to marry him, and with her have two daughters. And a dog named Buddy. Never forget the dog.
Follow Peter Larsen @PeterLarsenBSF
More in Radio
|
cc/2020-05/en_middle_0097.json.gz/line35529
|
__label__cc
| 0.528542
| 0.471458
|
All About Damian
Blog: Fan Fun with Damian Lewis
"actor, dad, redhead and ping pong champion"
Categories Events Helen Personal and Family Life Philanthropy Summertime Video
Video: Damian and Helen Attend Circus Gala – May 10, 2018
Posted On May 10, 2018 August 1, 2018 Written By Gingersnap Comments Off on Video: Damian and Helen Attend Circus Gala – May 10, 2018
by Gingersnap | damian-lewis.com | May 10, 2018
Damian Lewis and Gala Ambassador Helen McCrory attended the Circus Gala 2018 titled ‘Expect the Unexpected‘ in London on Thursday, May 10, 2018. The Gala is a fundraising event to help raise money to support the next generation of circus artists and will celebrate and ignite the future of the art-form.
This year, the National Centre for Circus Arts Gala partnered with Chef Ben Spalding to offer a unique and unexpected three course dinner, along with cocktails, silent and live auctions and other fundraising games.
For more information about the National Centre for Circus Arts organization, please visit their website here.
Gala ambassador Helen McCrory & husband @lewis_damian arriving earlier. pic.twitter.com/akZE01NkVV
— National Circus (@NationalCircus) May 10, 2018
Great picture of me partying with Brody from Homeland and Anna Karenina (aka Damian Lewis and Helen McCrory). Yup, you can just about make out the back of their heads! Fab night @NationalCircus pic.twitter.com/v2XR9kUTn6
— Lebby Eyres (@LebbyE) May 11, 2018
Tags Circus Gala CircusGala2018 Damian Lewis Helen McCrory National Centre for Circus Arts National Circus
Previous PostDeep State’s Mark Strong on Playing Footie with Damian Lewis – May 10, 2018
Next PostFrom the Trader’s Desk: Recapping Billions S3 E7 – May 11, 2018
Fan Fun with Damian Lewis is thrilled to run Damian-Lewis.com, a fan site dedicated to the brilliant actor Damian Lewis. As we keep writing all about Damian on Fan Fun, we aim to share the latest news along with an extensive gallery and a comprehensive media archive here.
We cannot express our gratitude enough to all those who poured their hearts and souls into the site over the years. We will do our best to preserve their legacy and keep up the good work.
As Damian once said “best journeys are shared.” It is a true privilege to share this journey with you. We hope you enjoy both sites, come visit us often and spread the word!
Latest Gallery Photo Albums
Voices of London
Evening Standard Theatre Awards
Lord Mayor’s Show & Silent Ceremony
Damian’s Twitter Feed
Once Upon a Time in…Hollywood - July 26, 2019
Out on DVD
A TV actor and his stunt double embark on an odyssey to make a name for themselves in the film industry during the Charles Manson murders in 1969 Los Angeles.
Damian Lewis: Spy Wars - October 7, 2019
Host Reporter/Presenter
Airing on History Channel UK
An eight part docudrama series on History Channel UK that tells the unbelievable true stories behind some of the most important international spy operations of the last 40 years. The show will use reconstructions of real-life events, with Lewis acting as the guide throughout each episode, telling a different spy story from the Cold War through to the ‘War on Terror’ and the renewed espionage hostilities of the present day. It will feature experts and former spies including ex-Mossad, ex-CIA, ex-KGB and ex-MI6, and will be shot on location in Moscow, Israel and London.
Dream Horse - April 17, 2020 UK & May 1, 2020 USA
Howard Davies, Accountant
World Premiere - Sundance
Based on true story of how against all the odds, an ordinary woman inspires her Welsh community to go on the ride of a lifetime and rediscover a sense of hope.
Damian Supports
Subscribe to damian-lewis.com
Enter your email address and find Damian in your inbox every time we post the news!
Search Website Select Category Announcement (28) Appearances (79) Audio Books (4) A Delicate Truth (1) The Love Book (1) Awards (66) Academy Award/Oscars (3) Award Submissions (3) BAFTA Awards (1) Britannia Award (3) Critic’s Choice (1) Emmy (8) For Your Consideration (2) GLAAD Awards (1) Gold Derby (1) Golden Globes (1) London Power 100 (1) Nomination (11) SAG Award (1) Satellite Awards (1) Behind the Scenes (81) Birthday (8) Blue Carpet (1) Books (9) Cannes Film Festival (3) Charity (42) Damian Lewis (2) Twitter (2) Dining Guide (3) Download (104) Events (177) Facebook (1) Fan Questionnaire (4) Fanart (6) Fanvid (1) Fashion and Style (27) Food/Dining (5) Gallery (487) Candids (8) on set (8) Photoshoots (26) Screencaptures (4) Guest Appearances (46) HIGNFY (13) Helen (104) Holiday (10) Christmas (6) Halloween (2) In Development/ Pre-Production (37) Interviews (188) Locations Guide (3) Magazine (21) Media (1,317) Audio (30) Broadcast Media (249) Podcast (23) Press Conference (4) Print Media (728) Trailer (44) Video (390) memory lane (20) Merchandise (35) Messages (52) Misc (15) Music (15) News (123) Owen Teale (1) Personal and Family Life (153) Philanthropy (54) Poetry (19) Newsnight Review (7) Poll (57) Premiere (9) Radio (52) Ratings (5) Readings (22) Recap (168) Red Carpet (12) Review (74) Rock Star (5) Rookery Productions (1) Rumored (15) Screenings (26) Site (36) Social Media (22) Sports (73) Boxing (1) Cricket (12) Cycling (2) Football/Soccer (35) Golf (7) Hockey (1) Horse Racing (2) Ping-Pong (1) Surfing (1) Tennis (6) Summertime (50) Sundance Film Festival (1) Supported Causes (26) Theatre (114) American Buffalo (26) Hamlet (6) Pillars of the Community (1) The Goat or Who is Sylvia? (19) The Misanthrope (44) Whodunnit (2) TV/Film Projects (1,542) Alone (1) An Unfinished Life (3) Band of Brothers (77) Richard Winters (15) Bill (2) Billions (643) Chromophobia (5) Colditz (1) Desire (8) Dream Horse (6) Dreamcatcher (7) Driven (4) Forsyte Saga (1) Friends & Crocodiles (1) Have I Got News For You (3) Hearts & Bones (4) Homeland (378) Keane (10) Life (89) Love and Virtue (1) Man Is Wolf to Man (2) Once Upon a Time in Hollywood (47) Our Kind of Traitor (14) Phineas & Ferb (1) Queen of the Desert (9) Romeo and Juliet (14) Run This Town (11) Spy Wars (19) Stolen (35) Stormbreaker (3) The Baker (45) The Escapist (62) The Forsyte Saga (19) The Silent Storm (10) The Situation (5) The Sweeney (17) To Appomattox (1) Warriors (3) Will (27) Wolf Hall (77) Your Highness (38) Twitter (11) Uncategorized (677) Voice Work (26) Narrator (3) WebChat (1) Welcome (1)
Launched: 13 July 2006
Staff: Damianista, Gingersnap, and Lewisto since September 2017
© 2017 Damian-Lewis.com | Theme by MonicaNDesign | Powered by WordPress
Damian-Lewis.com is an unofficial non-profit fan site that is in no way affiliated with Damian Lewis or his management. All media are copyright to their respective owners, no copyright infringement is ever intended. If you wish for anything to be removed, please contact us at admin@damian-lewis.com.
|
cc/2020-05/en_middle_0097.json.gz/line35531
|
__label__wiki
| 0.514168
| 0.514168
|
Kerato acanthoma =القرنوم الشائك
Kerato acanthoma Proliferating phase early development = القرنوم الشائك مرحلة مبكرة
Keratoacanthoma is a common epithelial tumor of the skin characterized by rapid growth, histopathologic features similar to those of cutaneous squamous cell carcinoma, and a certain tendency toward spontaneous regression. The exact nosology and classification of keratoacanthoma are a matter of debate. Some authors regard keratoacanthoma as a benign cutaneous tumor that is the prototype of a “pseudomalignant” tumor of the skin, whereas others maintain that it is a malignant neoplasm and should be regarded as a variant of cutaneous squamous cell carcinoma.
The authors of this chapter believe that keratoacanthoma represents a peculiar variant of squamous cell carcinoma, based on the rare but wellknown potential for distant metastases, and the capability for local destruction of important structures.
The exact incidence of keratoacanthoma is unknown. The tumor is more frequent in light-skinned persons, and rarer in dark-skinned and Japanese persons. The relative frequency in comparison with squamous cell carcinoma of the skin is controversial, but most studies show a lower incidence of keratoacanthoma than of squamous cell carcinoma. Discordant results may be explained, at least in part, by differences in classification of these lesions.
Studies on gender distribution reveal that both sexes are affected equally, possibly with a slight predilection for men. Keratoacanthoma occurs mostly in adult life, with a peak between the ages of 55 and 65 years; it has been observed rarely in younger patients. The familial type of keratoacanthoma occurs often during adolescence, and a neonatal case has been reported. Although the incidence was thought to remain stable after a peak in the sixth decade, a study conducted in a defined population in Hawaii revealed that keratoacanthoma increases with age, in a fashion similar to that observed for cutaneous basal and squamous cell carcinomas.
Relationship to Squamous Cell Carcinoma
The authors of earlier reports considered keratoacanthoma to be a form of epithelial cancer of the skin, and named it accordingly. However, since the introduction of the concept of keratoacanthoma as a benign, self-healing neoplasm distinct from squamous cell carcinoma, the relationship between these two epithelial tumors has been the subject of debate. In their paper published in 1950, Rook and Whimster wrote, “This disease is evidently not cancerous or precancerous.”2 On the other hand, Kwittken, in 1975, stated, “I have come to the firm conclusion that all of these lesions are malignancies and that the formerly accepted concept of a self-healing squamous cell carcinoma of the skin is a correct one,” and in 1979, even Rook amended his initial concept by writing, “…transformation from keratoacanthoma to squamous cell carcinoma occurs frequently.”11 Cases of typical keratoacanthoma with metastases have been observed,12 and four possible explanations for this phenomenon have been suggested: an initial misdiagnosis of keratoacanthoma; the presence of both keratoacanthoma and squamous cell carcinoma in the same lesion; the malignant transformation of keratoacanthoma into squamous cell carcinoma; and, finally, the possibility that keratoacanthoma may be a peculiar variant of squamous cell carcinoma.13 The debate is not settled yet, and some authors still maintain that keratoacanthoma represents a benign epithelial tumor, distinct from squamous cell carcinoma,14 whereas others hold that it is a variant of squamous cell carcinoma with tendency to spontaneous regression, but with the potential for giving rise to lethal distant metastases.15 Two studies of large numbers of cases highlighted the impossibility of reliably differentiating keratoacanthoma from squamous cell carcinoma using histopathologic criteria alone.16,17 Recently, a patient under infliximab therapy developed multiple squamous cell carcinomas as well as keratoacanthomas, suggesting a common pathogenetic pathway on immunosuppression.18 In addition, multiple keratoacanthomas and multiple squamous cell carcinomas may be observed at the same skin site (“field cancerization”) . Keratoacanthomas have a higher proliferation rate than squamous cell carcinomas.19 Other investigations pointed at similarities among squamous cell carcinoma and keratoacanthoma in the expression of oncogenetic and cell-cycle-regulating proteins as well as regarding the presence of trisomy 7 in a subset of tumors in both groups, thus suggesting a close relationship between these two entities.20-25 On the other hand, studies on loss of heterozygosity, on expression of angiotensin type 1 receptor and of desmogleins 1 and 2, on adhesion molecules vascular cellular adhesion molecule and intercellular adhesion molecule, on telomerase activity, on apoptotic and cell adhesion markers, and on chromosomal aberrations assessed by comparative genomic hybridization showed differences among keratoacanthomas and squamous cell carcinomas.26-32 Using different molecular techniques, both similarities and differences between keratoacanthoma and squamous cell carcinoma have been recently demonstrated.33 In short, at present, and in spite of the great amount of clinical and experimental data collected over the decades, the exact nosology of keratoacanthoma is not clear, and the term abortive malignancy has been proposed.34
KERATOACANTHOMA AT A GLANCE
ETIOLOGY AND PATHOGENESIS
Different etiologic factors are probably involved in the development of keratoacanthomas in different patients, and it seems likely that these different factors act synergistically to induce the onset of a lesion in a given patient. The role of chronic ultraviolet (UV) light exposure in the etiology of keratoacanthoma is well documented by the frequent occurrence on sun-exposed areas, as well as by the presence of keratoacanthomas in patients with xeroderma pigmentosum and after prolonged psoralen and UVA light (PUVA) treatment. In patients with multiple keratoacanthomas, PUVA treatment accelerates the development of the tumors, but the risk for keratoacanthoma after therapy with PUVA seems lower than that for squamous or basal cell carcinoma. An etiologic link to UV light has been confirmed also by experimental studies in mice.
The relationship of keratoacanthoma to chemical carcinogens has been well documented in humans and in several animals.37 In fact, the incidence of keratoacanthoma is higher in industrial towns, and among industrial workers coming in contact with pitch, mineral oils, and tar. Chemical carcinogens may act in conjunction with UV rays to induce the onset of keratoacanthomas. Smokers seem also to be more affected than nonsmokers.37
Keratoacanthomas have been reported at the site of injury. The association with trauma is also documented by the report of cases occurring after skin grafting, at both the donor and the recipient sites, and at the site of arterial puncture and vaccination.38, 39, 40 The role of human papillomavirus (HPV) remains controversial. Recently, evidence of HPV infection was documented by the highly sensitive polymerase chain reaction technique,41,42 but other studies failed to detect viral material within lesions of keratoacanthoma.43 Some studies found an association with HPV-25, and HPV-19 and HPV-48 have been isolated in a lesion arising in a human immunodeficiency virus (HIV) patient.44,45 Several other types of HPV have been linked to keratoacanthoma, including types 6, 9, 14, 16, 19, 35, 37, 58, and 61.
Genetic factors probably play a major role in the familial type of keratoacanthoma. In the other variants of keratoacanthoma, it seems likely that genetic aspects interplay with other etiologic factors (i.e., UV rays, trauma, infections) by providing the genetic predisposition for the development of the tumor. Keratoacanthomas are commonly observed in patients with Muir-Torre syndrome, suggesting that the genetic defect(s) of this syndrome also plays a role in the development of keratoacanthoma.46, 47, 48, 49 In addition, keratoacanthomas have been observed in patients affected by a variety of skin diseases including psoriasis, lupus erythematosus, lichen planus, atopic dermatitis, herpes zoster, acne conglobata, and pemphigus foliaceus, among others.38
Keratoacanthomas also have been observed in patients under immunosuppression as a result of bone marrow transplantation, cyclosporine treatment, or infection with HIV, thus suggesting that immunosuppression may play an etiologic role in some cases. In these patients, most lesions of keratoacanthoma tested for presence of HPV proved positive, suggesting that immunosuppression may contribute by decreasing the immune response against possible causative agents.50 Similarly, UV light may act not only by direct carcinogenesis, but also by virtue of the local immunosuppression caused by sun exposure .
Little is known about the pathogenesis of keratoacanthoma, and about the exact mechanisms of regression in the absence of any treatment. Studies on p53 oncoprotein expression and p53 gene mutations revealed expression of p53 oncoprotein in the great majority of tested cases, and association with a point mutation in the p53 gene in slightly more than 10 percent of these cases, suggesting a possible role of p53 gene in the development of some keratoacanthomas.
Multiple keratoacanthomas of the Ferguson-Smith type show a familial distribution and are transmitted in an autosomal dominant fashion. The gene responsible for this syndrome is localized to chromosome 9q. The majority of the cases have been described in some Scottish families, and in these patients, the syndrome is thought to be caused by a single genetic mutation that occurred before 1790.
Keratoacanthomas occur mostly on sun-exposed skin of the face, forearms, and dorsal aspects of the hands . Actinic damage is commonly found in the surrounding skin. In most instances, they are located on hairy skin, but lesions with similar clinicopathologic aspects have been described in the oral cavity, the subungual region, the genital mucosa, and the conjunctiva.
The stereotypic example of keratoacanthoma is represented by a solitary lesion growing rapidly within a few weeks, and subsequently showing a slow involution over a period of a few months. Three clinical stages have been described: proliferative, mature, and resolving.38 Lesions in the proliferative stage are rapidly enlarging erythematous papules that grow up to a dimension of 1 to 2 cm or more. In this stage, the lesions are symmetric and firm and show a smooth surface. In the mature stage there are symmetric, firm, erythematous or skin-colored nodules with a central keratotic core (see Fig. 117-2). The central part can appear crateriform if the keratotic core is removed. Ghadially divided mature keratoacanthomas into three main morphologic types: type 1, or bud-shaped; type 2, or dome-shaped;
and type 3, or berry-shaped.39 Regressing lesions are characterized by a keratotic, partly necrotic nodule that becomes progressively flat upon elimination of the keratotic plug, eventually leaving a hypopigmented scar (Fig. 117-3; Box 117-1).
Systemic Associations
Keratoacanthomas may be associated with multiple internal cancers in patients with Muir-Torre syndrome and the related hereditary nonpolyposis colorectal cancer syndrome. Patients with multiple keratoacanthomas should always be evaluated for the presence of typical traits of Muir-Torre syndrome, where cutaneous sebaceous tumors and low-grade visceral malignancies can be observed (most commonly carcinomas of the gastrointestinal tract, but also carcinomas of the lung and genitourinary system, and, occasionally, colonic polyps). It has been suggested that at least some of the patients with multiple keratoacanthomas of the Ferguson-Smith type may have an incomplete form of the Muir-Torre syndrome.
Keratoacanthomas may also occur in patients with xeroderma pigmentosum and, rarely, in patients with lymphomatoid papulosis .
Clinical Differential Diagnosis of Keratoacanthoma
Most Likely
· Squamous cell carcinoma
· Well-developed tumors
o Common warts
o Molluscum contagiosum
o Prurigo nodularis
o Metastatic carcinoma
· Regressing tumors
o Regressing lesions of lymphomatoid papulosis
o Regressing lesions of anaplastic large cell lymphoma
o Amelanotic melanoma
Several variants of keratoacanthoma have been described, and different morphologic types of keratoacanthoma have been observed in a single patient.
Giant Keratoacanthoma
In some instances, keratoacanthomas may reach dimensions of several centimeters (see eFig. 117-3.1 in on-line edition), and even a tumor reaching 15 cm in its diameter has been observed. Giant keratoacanthomas show a predilection for the nose and the dorsum of the hands. In some cases, the growth of the tumor may be associated with destruction of underlying tissues .
Keratoacanthoma Centrifugum Marginatum
Keratoacanthoma centrifugum marginatum is characterized by multiple tumors growing on a localized area, usually on the face, trunk, or extremities . Tumors are annular, polycyclic, or circular in morphology. The area affected may reach 20 cm in diameter, and resolution may be slower than in solitary keratoacanthoma.
Multiple Keratoacanthomas of the Ferguson-Smith Type
The Ferguson-Smith type is a familial form of keratoacanthoma that affects both sexes with approximately equal severity, which is characterized by the appearance of multiple, sometimes hundreds of keratoacanthomas, each with the clinicopathologic aspects of a solitary keratoacanthoma. The disorder is inherited in an autosomal-dominant manner, and the majority of the cases have been described in a few Scottish families. Patients develop keratoacanthomas during adolescence and early adulthood, but onset during childhood is not infrequent. It has been suggested that at least some of these patients may have an incomplete form of the Muir-Torre syndrome.
Generalized Eruptive Keratoacanthomas of Grzybowski
Keratoacanthomas of Grzybowski is a variant characterized by the presence of hundreds to thousands of tiny follicular keratotic papules disseminated all over the body, with predominance on sun-exposed areas. Facial involvement is usually severe, and coalescence of lesions around the eyes may cause ectropion. The mucosal regions (oral, genital) may be affected, whereas palms and soles are usually not involved. The age of onset is similar to that of solitary keratoacanthoma, and clustering in families has not been observed.
Subungual Keratoacanthoma
Subungual keratoacanthoma (see eFig. 117-5.1 in on-line edition) differs from the other types of keratoacanthoma by being persistent and often causing destruction of the underlying bone. The tumor originates in the distal nail bed, separating the nail plate from the nail bed, and can grow rapidly causing destruction of the entire phalanx.
Keratoacanthoma of the Mucosal Regions
Keratoacanthomas have been described in the oral mucosa, the conjunctiva, the nasal mucosa, and the genital mucosa. In fact, involvement of the oral and genital mucosa is common in the generalized eruptive keratoacanthomas of the Grzybowski type. Keratoacanthomas arising on mucosal regions, especially on the oral mucosa, present clinically as slowly growing crateriform lesions that tend to persist for many months or years.
The histopathologic diagnosis of keratoacanthoma rests mainly on the silhouette of the tumor as assessed at scanning magnification; inadequate specimens (i.e., punch biopsies, shave biopsies, curettage) do not allow a diagnosis and differentiation from squamous cell carcinoma. Two large studies on the histopathologic criteria for diagnosis of keratoacanthoma emphasized the overlapping features between this tumor and squamous cell carcinoma, which render differentiation very difficult or even impossible in given cases.
The histopathologic features of keratoacanthoma depend on the stage of evolution of the tumor. In early, proliferative lesions, the epithelium is markedly hyperplastic, and the central keratotic plug is not as pronounced as in fully developed lesions. The lesion has an overall symmetric aspect . Although atypical cells do not represent the majority of the cells in typical keratoacanthoma, there may be atypical keratinocytes and mitoses, especially at the lower margin of the tumor. Nests of epithelial cells may detach from the main tumor mass and be found in the superficial reticular dermis. Fully developed, mature lesions are characterized by a large central core of keratin surrounded by a well-differentiated proliferation of squamous epithelium that in some cases may resemble squamous cell carcinoma . The epidermis at both sides of the central core extends over the keratotic area in a fashion that has been described as “lipping” or “buttressing,” giving a distinct crateriform appearance to the lesion. Nests and strands of keratinocytes may be found apart from the main bulk of the tumor but usually do not extend lower than the level of sweat glands .
Cytomorphologically, large keratinocytes with eosinophilic cytoplasm are commonly observed, together with atypical cells and mitoses . An inflammatory infiltrate containing lymphocytes, plasma cells, histiocytes, eosinophils, and neutrophils is a common feature, and in some instances may be conspicuous. Neurotropism and even vascular invasion can be observed in otherwise typical keratoacanthomas, but the prognosis does not seem to be affected by these histopathologically worrisome features .
Solitary keratoacanthoma behaves as a benign tumor in the majority of the cases, but lymph node and visceral metastases have been observed in a small number of patients. Central facial keratoacanthoma may behave aggressively. There are no clear-cut features to predict the biologic behavior of a given tumor, but persistent and recurrent lesions should be managed by complete surgical excision. Histopathologic features that are associated with a poor prognosis in common squamous cell carcinoma, such as neurotropism and vascular invasion,
do not seem to have prognostic implications in keratoacanthomas. Ungual keratoacanthomas do not show a tendency to spontaneous regression and often are the cause of massive bone destruction. In spite of aggressive local behavior, however, distant metastases have not been observed in ungual and mucosal types of keratoacanthoma.
Histopathologic Differential Diagnosis of Keratoacanthoma
Regressing Tumors: Consider
· Other regressing epithelial tumors
· Regressing lesions of lymphomatoid papulosis
· Regressing lesions of anaplastic large cell lymphoma
Keratoacanthomas show a tendency to spontaneous regression, and, in typical cases, an acceptable therapeutic option may be to adopt the so-called watchful waiting strategy. However, because of the uncertainty regarding the exact nosology of this tumor, as well as the difficulty to differentiate it clinically from squamous cell carcinoma, complete conservative excision is advised in most cases, especially in those of solitary keratoacanthoma and in keratoacanthoma of the face. Removal by shave excision below the base to preserve architecture for diagnostic purposes followed by electrodesiccation and curettage are being increasingly performed for keratoacanthoma. Punch biopsies never allow differentiation of keratoacanthoma from well-differentiated squamous cell carcinoma and should be avoided. For diagnostic purposes, a longitudinal biopsy that includes normal skin at both margins of the lesion as well as the underlying fat tissues is acceptable. Mohs micrographic surgery has been adopted for difficult cases such as recurrent lesions, lesions in the central facial area, giant lesions, or lesions of keratoacanthoma centrifugum marginatum that may cover a large area of the body. Therapy by laser vaporization, electrodesiccation, and cryosurgery with liquid nitrogen does not allow the histopathologic verification of the clinical diagnosis.
Treatment for Keratoacanthoma
· Complete surgical excision
· Curettage followed by electrodesiccation
· Radiotherapy
· Intralesional chemotherapeutic agents, intralesional interferon
· Oral retinoids
· Photodynamic therapy
Keratoacanthomas have been treated by radiotherapy (electron beam, or the voltage radiation, superficial x-ray) with excellent results. This type of treatment is particularly indicated for lesions that can be difficult to manage surgically. Intralesional instillation of chemotherapeutic agent (methotrexate, bleomycin, and 5-fluorouracil) has also proved therapeutically successful,and 5-fluorouracil has been applied also topically. Some keratoacanthomas have been treated by intralesional injection of interferon-α 2a,66,67 and others have been successfully treated with intralesional application of triamcinolone. Successful topical treatment has been performed with podophyllin, either alone or in combination with other treatment modalities. However, podophyllin is also capable of inducing keratoacanthomas. Multiple keratoacanthomas have been treated successfully with oral retinoids in several cases, but larger studies have not been performed. Systemic treatments include chemotherapy with methotrexate, cyclophosphamide, or 5-fluorouracil.
A further treatment option for keratoacanthoma of both solitary and multiple types is represented by photodynamic therapy with δ-aminolevulinic acid . The treatment is simple and has been shown to achieve good therapeutic and cosmetic results. Topical imiquimod has been reported to induce regression of keratoacanthoma.
▪ PREVENTION
Preventive measures against the development of keratoacanthomas are similar to those applied for basal and squamous cell carcinoma of the skin. In predisposed subjects (i.e., fair skin, history of multiple actinic keratoses, basal and/or squamous cell carcinomas, Muir-Torre syndrome), avoidance of direct sun exposure should be achieved, and skin protection creams applied.
|
cc/2020-05/en_middle_0097.json.gz/line35534
|
__label__wiki
| 0.987114
| 0.987114
|
Simpson College students demand action after professor uses racial slur
A retired professor working part-time at Simpson College said the incident is "something that I deeply regret."
Simpson College students demand action after professor uses racial slur A retired professor working part-time at Simpson College said the incident is "something that I deeply regret." Check out this story on desmoinesregister.com: https://www.desmoinesregister.com/story/news/2019/11/16/simpson-college-students-demand-action-after-professor-uses-slur/4205805002/
Danielle Gehr, Des Moines Register Published 3:50 p.m. CT Nov. 16, 2019 | Updated 9:44 p.m. CT Nov. 19, 2019
A Simpson College associate professor is facing student backlash after using a racial slur, causing some to leave the class. He said he regrets using the word but was just trying to prove a point.
John Bolen, a retired professor working part-time at Simpson, said he was trying to prove the severity of the word redskin, a slur against Native Americans still used for sports team nicknames, including the NFL's Washington Redskins. Students say Bolen's point could have been made without the word.
"I wish I hadn't done it because it communicated the wrong thing to students," Bolen said. "I always believed in equal rights for humans. I've fought for that and campaigned for that. I know it's been very hard on some students, and I feel bad about that. It's been hard on me as well."
Simpson College is opening its doors to scores of low-income Iowa students with a new initiative that will cover their tuition announced Monday Nov. 6, 2017, by Simpson President Jay Simmons at a press conference in Indianola, Iowa. (Photo: Rodney White/The Register)
Simpson President Jay Simmons said the university could not speak about Bolen, citing personnel privacy restrictions, but he noted that the college is taking steps to better educate their faculty on bias issues.
Saturday morning Bolen said he will complete the class as an online course and will no longer be teaching with the college for future semesters. Bolen retired about three years ago after 25 years with Simpson.
He said this is the first time he's used the slur in his career, and in an emailed apology to his philosophy class, Bolen assured he wouldn't use the word again, nor the "R-word."
"The sad thing is the intention I felt was a good intention, just was a poor decision-making process on my part," Bolen said. "I still think the argument I made was a good one because I'm just as offended by the R-word we hear every NFL Sunday."
Within a 3-minute period, Bolen said, he lost his reputation.
Students call for university action
Campus leaders quickly mobilized after the incident came to light. One student began recording after Bolen said the slur the first time, ending with a second usage and an attempted explanation by Bolen.
"I think I have what I need," the student says before ending the recording, according to a transcript.
The transcript of the recording was shared online by the Simpson College Student Government Association. Simmons said he heard the recording and confirmed the context of the incident.
The transcript quoted Bolen as saying, "It would be the same thing as having a team called like, uh, the Florida n------."
Simpson College students called for more transparency after a professor used the N-word to his students. President Jay Simmons said because of personnel policy his hands are tied. (Photo: Rodney White/The Register)
The transcript shows students in the class immediately speaking out against his use of the word saying, "You can't say that as a white man," and "You could have had the same effect without saying it."
Student Government President Jailyn Seabrooks equipped herself with Bolen's apology letter to the class and the transcript as she and fellow student leaders set up in a student center to answer students' questions and receive input for several hours Thursday.
"This is an important discussion to be had in terms of we should be talking about how Native American slurs can be harmful," Seabrooks said. "We think we can do that without using racial slurs."
From the student input, Student Government and the Black Student Union issued a resolution in response to the incident. Members of the Black Student Union weren't available for comment Friday evening.
"I think as a Student Government, our first concern is always students," Seabrooks said.
The resolution asks the school to require mandatory bias training of faculty and staff, draft a clear policy for handling incidents of racism and bias, and dismiss Bolen.
Seabrooks felt it was important to note the professor's use of the slur was during a tangent before class and unrelated to the course.
(4) This is the transcript of the recording provided. It was changed in the use of the R-word. Every time the full R-word was used, it was correct to [R-word] due to the word being a derogatory slur. https://t.co/ijZiRp29WGpic.twitter.com/yiYhhVpiEZ
— Simpson College SGA (@SimpCoSGA) November 14, 2019
The Simpson College employee handbook protects teachers with educational freedom — though there are limitations.
"The teacher is entitled to freedom in the classroom in discussing his/her subject, but he/she should be careful not to introduce into his/her teaching controversial matter that has no relation to his/her subject," the handbook states.
If a dismissal is not possible, the students asked that Bolen be given suspension without pay or agree in writing that he will issue a sincere apology to the student body and complete bias training.
Seabrooks said Student Government members looked to other similar situations at institutions around the country when deciding how to address the situation. She said they found other professors had been let go or suspended.
"This is not as uncommon as we'd like it to be," Seabrooks said.
The students wanted a more timely response from the administration, Seabrooks said. She also noted the students have clear standards on issues of bias. The student handbook includes a section on bias. The faculty handbook does not.
"I think part of what we asked for in our resolution was to develop some more concrete policies around this," Seabrooks said. "I think in general we as a college haven't done a good job of saying when things like this happen how should we react."
Simmons said the college will be looking to expand its already existing cultural competency training and its diversity committee will seek areas that need improvement.
"We all strive to do better," Simmons said. "We take it very seriously and we are working to respond to it."
Bolen said he still believes in the argument he made. He has had connections with the Meskwaki people, who explained their experience with the slur. While he does not pretend to be a minority, he said he can be "offended as a human being."
"It's something that I deeply regret. Nobody's responsible but me," Bolen said. "I was trying to make a point about how there are other racist issues that for some reason in this culture we're not ready to deal with. By saying the N-word, I ended up completely losing the argument I was trying to make."
Danielle Gehr is a breaking news reporter at the Des Moines Register. She can be reached by email at dgehr@dmreg.com, by phone at 515-284-8367 or on Twitter at @Dani_Gehr.
Your subscription makes work like this possible. Join today at DesMoinesRegister.com/Deal.
Read or Share this story: https://www.desmoinesregister.com/story/news/2019/11/16/simpson-college-students-demand-action-after-professor-uses-slur/4205805002/
|
cc/2020-05/en_middle_0097.json.gz/line35536
|
__label__wiki
| 0.637445
| 0.637445
|
Q&A: Plan International CEO on a pervasive obstacle to gender equality
By Amy Lieberman // 10 October 2019
Social/Inclusive Development
Anne-Birgitte Albrectse, CEO at Plan International. Photo by: @FNsambandet via Twitter
NEW YORK — Progress on girls and young women’s empowerment and inclusion has one big challenge not tracked by the Sustainable Development Goals: media representation.
Women and girls in leadership positions are four times more likely than men to be shown wearing revealing clothing in films, according to new findings by Plan International and Geena Davis Institute on Gender in Media, a nonprofit that researches gender representation in media. Women in leadership positions are also more likely to be sexually objectified than men, according to the organizations, which analyzed the 56 top-grossing movies in 2018 in 20 countries.
“We find that what girls see in movies, which pull in a lot of viewers and a lot of money, shape women’s leadership in a way that turns off women from pursuing leadership.”
— Anne-Birgitte Albrectse, CEO, Plan International
The focus on media might seem outside the realm of typical development work, but the findings reveal an important obstacle that could discourage the 76% of girls and young women who aspire to be leaders in their work, according to Plan International.
Devex spoke with Plan International CEO Anne-Birgitte Albrectsen about what can be done to counter this trend.
This conversation has been lightly edited for length and clarity.
You have a new partnership with the Geena Davis Institute on Gender in Media. How does this intersect with your own work at Plan International?
Girls and young women's leadership is a key part of our global strategy, and efforts of challenging stereotypes is an equally important part.
Opinion: Rewriting the headlines for gender equality
It's time to shed more light on progress being made toward gender equality — and use those successes to inform the G-7. Dr. Joannie Marlene Bewa, founder of the Young Beninese Leaders Association, explains.
Many of us in the development sector have been working tirelessly for years to make sure our efforts are gender-aware and transformative. Our goal is to make sure that everything we do creates lasting systemic change that leads to gender equality. Increasingly, we are finding our efforts have less impact than we would have hoped because we are constantly battling the windmill of the negative stereotypes of the social norms of how women are perceived in society and the roles they are supposed to play or not play.
Media advertisements have an incredible role in shaping their image. Unfortunately, we find that what girls see in movies, which pull in a lot of viewers and a lot of money, shape women’s leadership in a way that turns off women from pursuing leadership.
How much influence can development work on girls' leadership actually have when you are working against all these other factors?
If we look at girls’ education generally across the world, we all know the numbers have been improving in primary and secondary education. But we are not seeing the same impact in women’s participation in the labor force. What we are up against there collectively is the overarching social norm that when a woman gets married or has a child she stops working, or that there are certain jobs that are just not for women.
We really have to find ways of busting those social norms. We are hearing from the girls themselves that they want to lead in their communities, they want to take charge of change projects, and they would like executive roles in the labor market. But they are afraid based on what they have seen in real life and movies — that they will be objectified and subject to harassment.
Unfortunately, what we have also seen is those taking small baby steps into the political arena or leadership often specifically drop out because they are subject to harassment when they do step up.
What do you think should be done among development leaders to help reverse these trends?
Working together as a sector and with media companies can help retell the story of what a young woman can be. I am personally a huge believer in the fact that what you see day-on-day is what you believe, whether it is fiction or reality.
All of those that are investing a lot in education have to demand that textbooks depict girls and women in a different way. I have often used the example of primary school textbooks in India that do not have a single picture of a woman in an executive position. They always show women as parents, carers, teachers, and if that is what you grow up with, that is what you think you should be.
We could probably change social norms a lot faster than we think if we made a concerted effort in the educational system and in the film industry that has such tremendous impacts on how an individual sees herself.
Gender Equality and Social Inclusion (GESI) Specialist
Employment Training Officer
East and Southeast Asia Chapter Program Associate
Some gender equality progress 'slipping away,' says former Global Fund for Women CEO
Gender data is moving forward — with a new set of challenges
Q&A: Stretching gender norms without breaking relationships
How the Solomon Islands improved working conditions for women
|
cc/2020-05/en_middle_0097.json.gz/line35538
|
__label__wiki
| 0.861292
| 0.861292
|
Huge US star confirmed to headline Glastonbury festival on Sunday
The singer tweeted: "I'm ecstatic to tell you that I'll be headlining Glastonbury on its 50th anniversary – See you there!"
Richard BoothEditor
Global pop sensation Taylor Swift has been announced as one of the headliners at next year's Glastonbury. The star will take to the stage as the main act on the Sunday line-up.
Glastonbury organiser Michael Eavis said in a video posted on Twitter: "I'm so pleased to announce Taylor Swift will be headlining the Sunday at Glastonbury 2020.
"She's one of the biggest stars in the world and her songs are absolutely amazing. We're so delighted."
Festival co-organiser Emily Eavis added: "Taylor is one of the biggest and best artists on the planet, and we’re just so pleased that she’s coming here to Worthy Farm to join us for our fiftieth birthday celebrations."
locked up 2019
The singer recently released her brand new, highly-anticipated album Lover and is expected to perform a dazzling set-list and medley of her greatest hits.
She released her new album Lover at the end of August and it shot straight to the top of the charts in the US.
Rumours of her headlining Glastonbury Festival circulated after the Shake It Off singer released her first tour dates and fans noticed a Glastonbury-sized hole in the list.
Swift, who performed on this weekend's Strictly Come Dancing final, joins previously-announced Saturday night headliner Paul McCartney; and Motown star Diana Ross, who will play the Sunday afternoon "legends slot".
Devon NewsPedestrian, 80, in life-threatening condition after crash in TavistockHe was airlifted to Derriford Hospital
Traffic & TravelVan crashes in ditch and wipes out telegraph poles - live updatesLocals have been left without phone signal
CrimeSwede lobbed by 'idiots' shatters armed police car windscreenThe windscreen of the car was destroyed on the A380 between Torquay and Newton Abbot - the latest in a string on incidents involving large vegetables
In the NewsToday is Blue Monday and Devon and Cornwall is looking awfulPhotos of glorious sunrise will help blow the blues away
|
cc/2020-05/en_middle_0097.json.gz/line35539
|
__label__cc
| 0.735059
| 0.264941
|
Numeric Catalogue
The letters of Casa Ricordi are an invaluable resource not only for the history of music and especially of opera, but also for our understanding of the complicated rapport between the worlds of art and commerce. Indeed, the company’s ability to strike and safeguard a delicate balance between artistic and business concerns was one of the principal reasons for its success. Throughout its history there has been ample evidence of the tremendous time and energy Casa Ricordi dedicated to relationships with those creative artists whose original work was essential to the publisher’s economic viability and independence; but also with others who shared and helped disseminate the fruits of their labor, including theatres, performers, and music periodicals, not to mention the vast market of consumers both public and private. The autograph letters presented here range from the beginning of its activity until 1948, when Tito II’s resignation marked the end of the family’s stewardship.
Copybooks indexes
Private copybooks
Correspondence Bellini-Ricordi
Addresees (A. de Halffter)
A. de Halffter (4)
s.l. (4)
Named people
Named works
Named places
Named theatres
lettera (4)
Ricordi > A. de Halffter
No place LLET025355 > 26/11/1953
No place LLET025358 > 4/3/1954
No place LLET025360 > 24/3/1954
|
cc/2020-05/en_middle_0097.json.gz/line35544
|
__label__wiki
| 0.843519
| 0.843519
|
How Sindh is struggling to respond to climate change challenges
Zulfiqar KunbharUpdated March 22, 2018
Women carrying pitchers filled with the water near a remote village in Thar. Women in the desert have to walk miles every day to fetch water for their families. ─ Photo by author
A recent report by Germanwatch listed Pakistan as 7th in the countries most affected by climate change from 1997 to 2016 recently.
Within Pakistan, though, Sindh is the worst affected by extreme weather events that are the classic manifestations of climate change.
From the Germanwatch Global Climate Risk Index 2018
Sindh witnessed massive floods in 2010 and 2011, and severe drought in Thar Desert, Achhro Thar, Nara Desert, Kachho region, and Kohistan since 2013.
The 2010 floods alone caused an estimated $9.7 billion in damage, twice that of the massive 2005 earthquake in the Kashmir region.
One initiative to deal with this has been a $120 million World Bank (WB) Sindh Resilience Project (SRP), to mitigate drought and flood risks of Sindh.
Under the project, a total of 15 small recharge dams will be constructed in Tharparkar, Thatta, Dadu, Jamshoro, and Karachi districts.
Young girls at a well in a remote village near Thano Bula Khan in Jamshoro District near Karachi. Kohistan is an arid region that has suffered severe droughts for many years. Photo by author.
"The construction of small rainwater-fed recharge dams will contribute to recharging underwater aquifers to provide water to nearby communities and contribute to livelihood," a WB spokesperson told thethirdpole.net.
Under the SRP more than 5m people from floods and drought conditions will be direct beneficiaries. The infrastructure investments will further protect more than 517,000 hectares of land from floods and drought events.
The former director general of the Pakistan Meteorological Department (PMD), who also served as special adviser to the secretary general of the UN World Meteorological Organization for Asia, Qamar-uz-Zaman Chaudhry, approved of the idea of dams.
Quoting PMD data, he suggested that the change in rainfall patterns, which had led to extremes of either too much water in too little time (resulting floods) and too little rainfall for longer and longer periods (leading to droughts) needed to be offset.
The records reveal that in last two decades rain patterns have been squeezed into a narrower window in Pakistan.
Earlier the monsoon rains would last from July to September, but now they occur only from July to August. But while the number of rainy days has come down, the intensity of rainfall has increased in Pakistan.
One way of dealing with these severe outliers was the construction of small dams as an aid to resilience in Sindh and Balochistan.
The problem is that the dams also need to be filled.
A stream flowing from Karoonjhar Hills in Thar Desert near the Indian border in Sindh. ─ Photo by author
"The erratic rain pattern indicates that in Sindh there is decline of rainfall whereas there is an in Punjab and Khyber Pakhtunkhwa provinces," Ghulam Rasul, the current DG PMD told thethirdpole.net.
The question is that with this decline, where is the water to fill these dams going to come from?
The Sindh government has constructed thirty nine small dams in the province. According to Sindh Chief Minister Syed Murad Ali Shah, 14 small dams have been completed in district Jamshoro and six such dams have been constructed in Thar Desert including in Nangarparkar area.
However scarcity of rains in recent years has not allowed existing small dams to be filled.
As per PMD record, for last 15 years, the Thar Desert faced frequent droughts. 2011 was exceptional year when the desert received 1,200 millimetres of rainfall in the monsoon against Thar’s average annual rainfall of 200 millimetres.
The 2011 rains enhanced the storage to six months collected in Thar’s ‘tarayoon’ (natural depression ponds between sand dunes), weirs, and dams. This water is used for both drinking purposes and small scale agriculture.
Livestock drinking water at the small dam constructed by the Sindh government in Thar Desert in 2011. ─ Photo by author
Since 2011 though, the scarcity of rainfall has not allowed these dams to be filled. The result is that area people are facing acute drinking water shortage.
For instance Ranpur Dam situated around 25km away from Nagarparkar located in the extreme south of Thar Desert near the Indian border is suffering water scarcity for more than a decade.
In the past few years locals are struggling to find drinking water.
Last year Ranpur Dam was partially filled after moderate rains. But the water lasted only for two months because people used for agriculture purpose.
Locals say at one hand where Sindh government has constructed small dams to recharge the groundwater, while on other it has also started open pit mining in search of 175bn tonnes of lignite coal reserves inside layers of aquifers for its Thar Coal Project. This is also causing the depletion of groundwater level from the area.
Sindh Engro Coal Mining Company (SECMC), a joint venture with the Sindh government in excavation at Block-II site, disputes this, though.
"Considering the scale of mining operations and potential of underground water in Thar, Block-II is only dewatering 0.04 per cent of total Thar underground water per year for an area of 9,100 square km and this percentage would exponentially decrease to around 0.02pc,” a SECMC statement said.
Maybe the one issue that nobody seems to be addressing is the access to water is often dependent on wealth and social position.
Despite the declining rainfall in Sindh, it has the best water infrastructure in Pakistan, and yet very high poverty rates.
Infrastructure tweaks may not be the end of the story, or even what is most needed by the most marginalised.
This article originally appeared on Thirdpole.net and has been reproduced with permission.
Guava production in Larkana tumbles to all-time low
Ex-minister Syed Ali Mardan Shah dies of cardiac arrest
Comments (3) Closed
Even then, PPP wins in SINDH ?????
May be Rehman will help in affected areas.
The names of the persons who will fight climate change in Sindh are Asif Ali Zardari and Bilawal Bhutto Zardari. Good luck fighting climate change!
|
cc/2020-05/en_middle_0097.json.gz/line35549
|
__label__wiki
| 0.759435
| 0.759435
|
Associations, Events
The Toy Association Talks Top Toy Tech Trends
Mattel’s Hello Barbie Hologram
By Laurie Chartorynsky
Judging from the multitude of fascinating tech toys showcased at the 114th North American International Toy Fair in February, tech-savvy kids have a lot to look forward to in 2017. At a Toy Trends Briefing hosted by The Toy Association’s trend experts at the show, toys with an interactive tech component were among the top trends announced for 2017.
U.S. sales of toys that include technology continue to grow – according to The NPD Group, the youth electronics super-category was up three percent last year, reaching $610 million in sales. The U.S. toy industry now stands at $26 billion with overall domestic toy sales rising five percent in 2016, says NPD.
Sales growth in the tech category reflects the manner in which toy companies are continuing to innovate by incorporating cutting-edge technology in their toys and games. “Tech is not replacing classic play, but in fact enhancing it,” said Adrienne Appell, The Toy Association’s toy trends specialist. “A new generation of toys and playthings with digital aspects continues to become more affordable and accessible to kids. Current trends include toys that incorporate virtual and augmented reality, robotics, and toys that marry traditional play with new technology.”
Laurie Chartorynsky Author's page
Laurie Chartorynsky is a communication specialist and content developer at The Toy Association, a nonprofit organization that represents all businesses that design, produce, license, and deliver toys and youth entertainment products for kids of all ages.
Open Connectivity Foundation Introduces International Standard for Smart Homes
Z-Wave Alliance & Silicon Labs to Expand Smart Home Ecosystem
ADL’s Technology Awards Gala Set for Nov. 9 in NYC
‘NEXTGEN TV’ Name, Logo To Mark ATSC 3.0-Enabled Tech Devices
NKBA to Host First Global Connect Business Summit
|
cc/2020-05/en_middle_0097.json.gz/line35553
|
__label__cc
| 0.740526
| 0.259474
|
Risk Intelligence publishes Strategic Insights maritime security 2017 forecast issue
Maritime securityShipping on 3rd March 2017
Many of the areas reviewed in this concluding issue of Risk Intelligence’s Strategic Insights series will be familiar to maritime operators and long-time readers of Strategic Insights: Somalia and Nigeria, for example. But there are also new areas of concern emerging, as well as the return of power politics.
One of the themes of this issue, which looks ahead to the challenges in 2017 and beyond, is that developments on land can ‘trickle down’ to the maritime domain. But this is not always the case, and each environment needs to be analysed on a case-by-case basis to completely understand the threat, and if it will affect maritime operations.
Overall, threats may be changing, with new locations emerging and new dynamics affecting operations. There are a number of trends at the macro and micro levels that will have implications in 2017 and beyond. But risks can still be mitigated and the starting point is information – assessments of threats and accompanying analysis. Risk Intelligence continues to provide global overviews on incidents and threats through its upgraded MaRisk 2.0 portal. As well, the PortRisk platform now provides full assessments of the threat environment for 170 ports around the world, and is continuing to add more.
Strategic Insights download
The free download of the latest Strategic Insights issue is available here. More information about Risk Intelligence and the services offered are available on the company website.
Tags : maritime domainmaritime operationsNigeriaRisk IntelligenceSomalia
Risk Intelligence publishes Nigeria maritime security forecast for 2017
International Harbour Masters’ Association invites presentations for 2018 congress
State of Piracy report 2018 published
More than just seapower – interview about maritime security
IMB piracy report 2018 shows increase in attacks
Dirk Siebels
Received my PhD in maritime security, now putting research into practical work at Risk Intelligence. Read, speak and write on most things related to maritime matters in Africa.
Academic profiles
On Twittter
|
cc/2020-05/en_middle_0097.json.gz/line35558
|
__label__wiki
| 0.956833
| 0.956833
|
Crane killer has probation revoked
Shooter of whooping cranes squanders second chance.
Crane killer has probation revoked Shooter of whooping cranes squanders second chance. Check out this story on caller.com: http://callertim.es/2uJJ5JX
David Sikes, Corpus Christi Caller-Times Published 3:09 p.m. CT July 19, 2017 | Updated 4:21 p.m. CT July 19, 2017
The endangered whooping crane is internationally protected and harming one is a violation of the U.S. Migratory Bird Treaty Act.(Photo: COURTESY BECKY JOHNSON)
When a federal judge in Beaumont slapped a harsh sentence on a teen who shot two whooping cranes last year, public reaction was unexpectedly mixed.
Trey Frederick, who was 19 at the time, was ordered to pay $25,850 in restitution, and sentenced to 200 hours of community service and five years probation. He also could not possess a firearm or a hunting license in any state for five years.
Some folks felt this sentence was disproportionate to the crime, suggesting lesser punishments are administered for violent crimes against humans. I hear the same reaction following harsh judgments against egregious animal abusers.
But mostly, the public applauded U.S. Magistrate Judge Zack Hawthorn for sticking it to Frederick for shooting the cranes with a rifle while they stood in a field. He later claimed the act was an innocent mistake.
Frederick first told federal authorities he thought the birds were snow geese, which were in season at the time in Jefferson County where the incident occurred. Later, he told a biologist with the International Crane Foundation in a Beaumont courthouse that he mistook the birds for sandhill cranes, which are not legal to hunt in Jefferson County.
He initially pleaded not guilty to violating the Migratory Bird Treaty Act, then changed his plea on a lesser charge to avoid a jury trial.
None of this matters now.
I learned this week that Frederick shot a feral hog in February, while seated in his pickup one night in Jefferson County. I learned this from a Texas Monthly story by Sonia Smith. But it's all supported by court affidavits.
Frederick and several friends got permission to hunt the property its ownerm the story stated. The unsavory details of that night included Frederick, now 20, seeing a possum near a convenience story, grabbing it and "smashing it repeatedly against the concrete," according to Smith's magazine story.
How do we know all this? Because a confidential informant told Texas game warden Daniel Pope, who subsequently reported Frederick to federal authorities.
Of course, Frederick's probation was revoked. He's been in custody since June and faced Judge Hawthorn earlier this month. Yes, Hawthorn was not happy to see him in court again. And yes, Frederick was equally unhappy to see his hunting partners testify against him.
The hearing also revealed Frederick had not reported regularly to his probation officer, not paid any restitution, tried to purchase a gun and applied for a Montana hunting license.
Did he apologize to the court for these transgressions? No. Instead he said the testimony against his was untrue.
Hawthorn sentenced the young unapologetic poacher to 11 months in prison, followed by one year of supervised release.
TPW Game Warden Col. Craig Hunter applauded the court's decision. Tim Grunewald, the Crane Foundation's North American Program director, said the judge's ruling is justified.
"We want people in society to know this is a serious offense," Grunewald said. "Now it's up to this young man to decide what he wants to do with his life."
The two birds Frederick killed were not part of the 300 or so whooping cranes that migrate from Canada to South Texas annually. The sub-adult male and female whoopers he shot were part of an experimental Louisiana population of domestically hatched birds introduced into the wild. Technically, cranes within this nonmigratory flock are not considered endangered, but certainly are highly protected by law.
As I've mentioned before, for us to dismiss Frederick's behavior as a senseless prank not worthy of condemnation is to ignore the potential damage these acts inflict on the reputation of legitimate hunters and hunting.
Frederick, through Facebook at least, pretended to be a hunter. We must always challenge this claim made by poachers. Frederick is an outlaw. And he is not us.
Please join me in making this distinction clear to those who are unaware.
David Sikes’ Outdoors columns appear Thursday and Sunday. Contact David at 361-886-3616 or david.sikes@caller.com.
David Sikes (@davidoutdoors) | Twitter
|
cc/2020-05/en_middle_0097.json.gz/line35562
|
__label__wiki
| 0.961623
| 0.961623
|
Former X Factor singer Danny Tetley admits child sexual exploitation of seven teenage boys
The charges relate to him inducing teenage boys to send indecent images to him for money
Lauren Ballinger
Ella Pengelly
Danny Tetley in Ibiza for the Judges Houses stage on the ITV1 talent show, The X Factor (Image: PA)
Former X Factor contestant Danny Tetley has pleaded guilty to a series of child sexual exploitation charges.
The charges against the singer from Bradford relate to him inducing teenage boys to send indecent images to him for money.
Previously the 39-year-old’s court case was subject to a court order preventing publication of his previous guilty pleas to similar offending, but today the Recorder of Bradford Judge Jonathan Durham Hall QC lifted the restriction after the singer admitted five more allegations.
Tetley, of St Enoch’s Road, Bradford, was being held in custody before he was brought to the city’s crown court and formally entered his guilty pleas.
Today, December 13, he pleaded guilty to five charges of causing sexual exploitation of a child relating to five teenage boys aged 15 and 16.
It can now be reported that at a previous hearing Tetley admitted four other allegations understood to have involved similar offending with two 14-year-olds, Examiner Live reports.
None of the complainants in the case can be identified for legal reasons.
X Factor star Danny Tetley (Image: ITV)
The charges he admitted today cover a period between October 2018 and August this year.
Prosecutor Michael Smith told the judge that the Crown would not seek to try Tetley on other outstanding allegations to which he had pleaded not guilty and the case was now ready for sentence.
“The investigation is complete and the victims have been identified,” said Mr Smith.
Some of the charges faced by Tetley include allegations that he tried to induce two boys to send him indecent images which would be in the most serious category for such offences.
Barrister Andrew Dallas, for Tetley, asked for the sentence to be adjourned so that the defence had time to consider “well over 10,000” text messages or WhatsApp messages which had been served.
Judge Durham Hall fixed the sentence hearing for January 24 next year and said the case would go ahead on that day barring an exceptional problem.
Tetley, who appeared in the dock wearing a black short-sleeve t-shirt and pale blue jeans, was remanded back into custody until next month.
Tetley reached the semi-finals of the popular show in 2018 and finished sixth.
Boris Johnson makes first speech as Prime Minister after winning general election and says 'I will never take your support for granted'
Instagram top nine 2019: How to see your best posts from this year
|
cc/2020-05/en_middle_0097.json.gz/line35565
|
__label__wiki
| 0.806993
| 0.806993
|
MATCH PREVIEW: OXFORD UNITED
Cambridge United are back in Sky Bet League Two action today at the Abbey Stadium and face an Oxford United side who look certain to be within the automatic promotion places come the end of the season.
Following a 3-0 defeat to third placed Bristol Rovers on Good Friday, the U’s now taken on second in the division and will need to dig deep to secure a winning result on a wet and windy afternoon.
The U’s will still be without Greg Taylor, Barry Corr, Conor Newton and Ryan Donaldson who continue their respective recoveries, whilst Ryan Ledson and Shane O’Neill are also unavailable on international duty.
However, an exciting opening display from Hull City loanee Max Clark at the Memorial Stadium gives the U’s boss food for thought in midfield, with the 20-year old likely to make his first appearance at the Abbey Stadium today.
Meanwhile, with a six point buffer inside the automatic play-off places ahead of the Easter period, Michael Appleton’s Oxford United have epitomized consistency so far this term and look almost certain to be plying their trade in League One next season.
Lead goalscorer Kemar Roofe (21 goals) has certainly played a major role in Oxford’s triumphs, whilst Liam Sercombe (13) and Danny Hylton (12) have also contributed on the goals front.
A single goal from Ryan Taylor split today’s sides when they met at the Kassam Stadium earlier this season and United will be hoping for a reverse result this afternoon if they too are to stay in promotion contention.
The visitors edge the overall head to head records by 11 wins to nine, but following yesterday’s triumph for Cambridge in the University Boat Race, the U’s will be eager to make it a duo of wins over Oxford this Easter.
Tickets can be bought online for the match here.
|
cc/2020-05/en_middle_0097.json.gz/line35566
|
__label__cc
| 0.596239
| 0.403761
|
Engaging ideas, transforming minds
Health Promotion and Quality of Life in Canada
Essential Readings
By Dennis Raphael
Canadian Scholars’ Press
Health Promotion / Health Studies / Social Determinants of Health / Sociology / Sociology of Health
Print ISBN: 9781551303673
Health and quality of life are vital social reflections. The way a society distributes resources amongst its population tells us a great deal about the society itself. This unique volume unites readings that explore the integral link between quality of life and public policy choices.
The first section discusses individual perspectives on health promotion and quality of life and provides a conceptual basis for determining an individual's or community's standard. The next section addresses community and policy perspectives to show how quality of life is related both to the health of the population as a whole, and to collective choices that determine how material resources are distributed in society.
Part three places quality of life and population health within a political economy framework and uses the social determinants of health concept to illustrate how societies differ in their willingness to support their members' quality of life and health. Part four examines vulnerable populations and their issues: the Indigenous community, persons with disabilities, women and the gender gap, and the effects of race and immigrant status on employment opportunities.
The final section suggests ways in which health promotion, quality of life, and the social determinants of health agendas can come together. It provides an up-to-date analysis of the barriers facing those attempting to improve quality of life and health, as well as the means to accomplish those goals.
Population Health in Canada
Ivy Lynn Bourgeault, Ronald Labonté, Corinne Packer, Vivien Runnels
Health Promotion in Canada, Fourth Edition
Irving Rootman, Ann Pederson, Katherine Frohlich, Sophie Dupéré
Social Determinants of Health, Third Edition
Dennis Raphael
Health Promotion in Canada, Third Edition
Irving Rootman, Sophie Dupéré, Ann Pederson, Michel O'Neill
Staying Alive, Second Edition
Toba Bryant, Dennis Raphael, Marcia Rioux
Social Determinants of Health, 2nd Edition
Chapter 1: Setting the Stage: Why Quality of Life? Why Health Promotion? - Dennis Raphael
Part I: Individual Perspectives
Chapter 2: Quality of Life Indicators and Health - Dennis Raphael, Rebecca Renwick, Ivan Brown, and Irving Rootman
Chapter 3: Quality of Life: What Are the Implications for Health Promotion? - Dennis Raphael, Ivan Brown, Rebecca Renwick, and Irving Rootman
Chapter 4: The Quality of Life Profile--Adolescent Version - Dennis Raphael, Ellen Rukholm, Ivan Brown, Pat Hill-Bailey, and Emily Donato
Chapter 5: Measuring the Quality of Life of Older Persons - Dennis Raphael, Ivan Brown, Rebecca Renwick, Maureen Cava, Nancy Weir, and Kit Heathcote
Part II: Community and Policy Perspectives
Chapter 6: Making the Links between Community Structure and Individual Well-being - Dennis Raphael, Rebecca Renwick, Ivan Brown, Brenda Steinmetz, Hersh Sehdev, and Sherry Phillips
Chapter 7: Community Quality of Life in Low-income Neighbourhoods - Dennis Raphael, Rebecca Renwick, Ivan Brown, Sherry Phillips, Hersh Sehdev, and Brenda Steinmetz
Chapter 8: What Do Canadian Seniors Say Supports Their Quality of Life - Toba Bryant, Ivan Brown, Tara Cogan, Clemence Dallaire, Sophie Laforest, Patrick McGowan, Dennis Raphael, Lucie Richard, Loraine Thompson, and Joyce Wong
Chapter 9: The Welfare State as a Determinant of Women's Health - Dennis Raphael and Toba Bryant
Part III: The Role of the Social Determinants of Health
Chapter 10: Bridging the Gap between Research Findings and Public Policy - Dennis Raphael
Chapter 11: Present Status, Unanswered Questions, and Future Directions - Dennis Raphael
Chapter 12: Maintaining Population Health in a Period of Welfare State Decline - Dennis Raphael
Chapter 13: The State's Role in Promoting Population Health - Dennis Raphael and Toba Bryant
Part IV: Vulnerable Populations
Chapter 14: Indigenous Well-being in Four Countries - Martin Cooke, Francis Mitrou, David Lawrence, Eric Guimond, and Dan Beavon
Chapter 15: The Impact of Race and Immigrant Status on Employment Opportunities and Outcomes in Canada - Cheryl Teelucksingh and Grace-Edward Galabuzi
Chapter 16: Employment and Persons with Disabilities in Canada - Canadian Council on Social Development
Chapter 17: A Call to Combat Poverty and Exclusion of Canadians with Disabilities - Council of Canadians with Disabilities
Chapter 18: Economic Gender Equality Indicators 2000 - Warren Clark
Part V: Moving Towards Action
Chapter 19: Barriers to Addressing the Social Determinants of Health - Dennis Raphael, Ann Curry-Stevens, and Toba Bryant
Chapter 20: Income and Health in Canada - Dennis Raphael, Ronald Labonte, Ronald Colman, Karen Hayward, Renee Torgerson, and Jennifer Macdonald
Chapter 21: Identifying and Strengthening the Structural Roots of Urban Health in Canada - Toba Bryant, Dennis Raphael, and Robb Travers
Chapter 22: Getting Serious about the Social Determinants of Health - Dennis Raphael
Chapter 23: Can Increasing Concern with Quality of Life Encourage Health Promoting Public Policy? - Dennis Raphael
Copyright Acknowledgments
Dennis Raphael is a Professor of Health Policy and Management at York University, whose areas of interest include topics in public policy, poverty, and social determinants of health.
Social Determinants of Health, 2nd Edition, Health Promotion and Quality of Life in Canada, Poverty in Canada, Second Edition, Social Determinants of Health, Third Edition, Staying Alive, Second Edition, Tackling Health Inequalities, Immigration, Public Policy, and Health, Staying Alive, Third Edition, The Politics of Health in the Canadian Welfare State, Poverty in Canada, Third Edition
"This synthesis is long overdue and will contribute to advancing the field. The introduction of quality of life into this volume represents a new conceptualization."
Kim Raine, School of Public Health, University of Alberta
"The articles are well written, making the work easily accessible to a variety of audiences, including students, practitioners, and researchers. This reader will encourage a broader view of the impact of health determinants on quality of life as experienced in day-to-day living."
Linda Reutter, Faculty of Nursing, University of Alberta
"This urgently needed book will be an excellent addition to current literature in Canada. It will make quite a splash in the somewhat stagnant waters of many current health promotion writings and teachings, and will be very relevant to all who concern themselves with moving a social change agenda forward in Canada."
— Linda Reutter, Faculty of Nursing, University of Alberta
General Student Resource - Download
Print - $61.95
Follow us with:
Spring 2020 Catalogue
Canadian Scholars
Women’s Press
Web Development by Isnor Creative
|
cc/2020-05/en_middle_0097.json.gz/line35569
|
__label__wiki
| 0.622947
| 0.622947
|
Late Effects of Treatment for Childhood Cancer (PDQ®)–Health Professional Version
General Information About Late Effects of Treatment for Childhood Cancer
Subsequent Neoplasms
Late Effects of the Cardiovascular System
Late Effects of the Central Nervous System
Late Effects of the Digestive System
Late Effects of the Endocrine System
Late Effects of the Immune System
Late Effects of the Musculoskeletal System
Late Effects of the Reproductive System
Late Effects of the Respiratory System
Late Effects of the Special Senses
Late Effects of the Urinary System
Changes to This Summary (11/26/2019)
About This PDQ Summary
Go to Patient Version
During the past five decades, dramatic progress has been made in the development of curative therapy for pediatric malignancies. Long-term survival into adulthood is the expectation for more than 80% of children with access to contemporary therapies for pediatric malignancies.[1,2] The therapy responsible for this survival can also produce adverse long-term health-related outcomes, referred to as late effects, which manifest months to years after completion of cancer treatment.
A variety of approaches have been used to advance knowledge about the very long-term morbidity associated with childhood cancer and its contribution to early mortality. These initiatives have utilized a spectrum of resources including investigation of data from the following:
Population-based registries.[3-5]
Self-reported outcomes (provided through large-scale cohort studies).[6,7]
Medical assessments.[8,9]
Studies reporting outcomes in survivors who have been well characterized regarding clinical status and treatment exposures, and comprehensively ascertained for specific effects through medical assessments, typically provide the highest quality data to establish the occurrence and risk profiles for late cancer treatment–related toxicity. Regardless of study methodology, it is important to consider selection and participation bias of the cohort studies in the context of the findings reported.
Prevalence of Late Effects in Childhood Cancer Survivors
Late effects are commonly experienced by adults who have survived childhood cancer; the prevalence of late effects increases as time from cancer diagnosis elapses. Population-based studies support excess hospital-related morbidity among childhood and young adult cancer survivors compared with age- and sex-matched controls.[3-5,10-14]
Research has demonstrated that among adults treated for cancer during childhood, late effects contribute to a high burden of morbidity, including the following:[6,8,9,15-18]
60% to more than 90% develop one or more chronic health conditions.
20% to 80% experience severe or life-threatening complications during adulthood.
Using the cumulative burden metric—which incorporates multiple health conditions and recurrent events into a single metric that takes into account competing risks—by age 50 years, survivors in the St. Jude Lifetime Cohort experienced an average of 17.1 chronic health conditions, 4.7 of which were severe/disabling, life threatening, or fatal.[17] This is in contrast to the cumulative burden in matched community controls who experienced 9.2 chronic health conditions, 2.3 of which were severe/disabling, life threatening, or fatal (refer to Figure 1).[17]
Figure 1. Figure shows distribution of cumulative burden by age among childhood cancer survivors of specific pediatric cancer subtypes and community controls participating in the St. Jude Lifetime Cohort Study. The cumulative burden at age 30 years and rate of cumulative burden growth is variable across cancer subtypes and organ systems. Reprinted from The Lancet, Volume 390, Issue 10112, Bhakta N, Liu Q, Ness KK, Baassiri M, Eissa H, Yeo F, Chemaitilly W, Ehrhardt MJ, Bass J, Bishop MW, Shelton K, Lu L, Huang S, Li Z, Caron E, Lanctot J, Howell C, Folse T, Joshi V, Green DM, Mulrooney DA, Armstrong GT, Krull KR, Brinkman TM, Khan RB, Srivastava DK, Hudson MM, Yasui Y, Robison LL, The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE), Pages 2569–2582, Copyright (2017), with permission from Elsevier.
The variability in prevalence is related to differences in the following:
Age and follow-up time of the cohorts studied.
Methods and consistency of assessment (e.g., self-reported vs. risk-based medical evaluations).
Treatment intensity and treatment era.
Childhood Cancer Survivor Study (CCSS) investigators demonstrated that the elevated risk of morbidity and mortality among aging survivors in the cohort increases beyond the fourth decade of life. By age 50 years, the cumulative incidence of a self-reported severe, disabling, life-threatening, or fatal health condition was 53.6% among survivors, compared with 19.8% among a sibling control group. Among survivors who reached age 35 years without a previous severe, disabling, life-threatening, or fatal health condition, 25.9% experienced a new grade 3 to grade 5 health condition within 10 years, compared with 6.0% of healthy siblings (refer to Figure 2).[6]
The presence of serious, disabling, and life-threatening chronic health conditions adversely affects the health status of aging survivors, with the greatest impact on functional impairment and activity limitations. Predictably, chronic health conditions have been reported to contribute to a higher prevalence of emotional distress symptoms in adult survivors than in population controls.[19] Female survivors demonstrate a steeper trajectory of age-dependent decline in health status than do male survivors.[20] The even-higher prevalence of late effects among clinically ascertained cohorts is related to the subclinical and undiagnosed conditions detected by screening and surveillance measures.[9]
Figure 2. Cumulative incidence of chronic health conditions for (A) grades 3 to 5 chronic health conditions, (B) multiple grade 3 to 5 conditions in survivors, (C) multiple grade 3 to 5 conditions in siblings, (D) conditioned based on no previous grade 3 to 5 conditions among survivors by ages 25, 35, or 45, and (E) conditioned based on no previous grade 3 to 5 conditions among siblings by ages 25, 35, or 45. Gregory T. Armstrong, Toana Kawashima, Wendy Leisenring, Kayla Stratton, Marilyn Stovall, Melissa M. Hudson, Charles A. Sklar, Leslie L Robison, Kevin C. Oeffinger; Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study; Journal of Clinical Oncology, volume 32, issue 12, pages 1218-1227. Reprinted with permission. © (2014) American Society of Clinical Oncology. All rights reserved.
CCSS investigators also evaluated the impact of race and ethnicity on late outcomes by comparing late mortality, subsequent neoplasms, and chronic health conditions in Hispanic (n = 750) and non-Hispanic black (n = 694) participants with non-Hispanic white participants (n = 12,397).[21] The following results were observed:
Cancer treatment did not account for disparities in mortality, chronic health conditions, or subsequent neoplasms observed among the groups.
Differences in socioeconomic status and cardiovascular risk factors affected risk. All-cause mortality was higher among non-Hispanic black participants than among other groups, but this difference disappeared after adjustment for socioeconomic status.
Risk of developing diabetes was elevated among racial/ethnic minority groups even after adjustment for socioeconomic status and obesity.
Non-Hispanic blacks had a higher likelihood of reporting cardiac conditions, but this risk diminished after adjusting for cardiovascular risk factors.
Nonmelanoma skin cancer was not reported by non-Hispanic blacks, a finding that has been replicated by others,[22] and Hispanic participants had a lower risk than did non-Hispanic white participants.
Recognition of late effects, concurrent with advances in cancer biology, radiological sciences, and supportive care, has resulted in a change in the prevalence and spectrum of treatment effects. In an effort to reduce and prevent late effects, contemporary therapy for most pediatric malignancies has evolved to a risk-adapted approach that is assigned based on a variety of clinical, biological, and sometimes genetic factors. The CCSS reported that with decreased cumulative dose and frequency of therapeutic radiation use over treatment decades from 1970 to 1999, survivors have experienced a significant decrease in risk of subsequent neoplasms.[23] With the exception of survivors requiring intensive multimodality therapy, sometimes including hematopoietic cell transplantation, for aggressive or refractory/relapsed malignancies, life-threatening treatment effects are relatively uncommon after contemporary therapy in early follow-up (up to 10 years after diagnosis). However, survivors still frequently experience life-altering morbidity related to effects of cancer treatment on endocrine, reproductive, musculoskeletal, and neurologic function.
A CCSS investigation examined temporal patterns in the cumulative incidence of severe to fatal chronic health conditions among survivors treated from 1970 to 1999. The 20-year cumulative incidence of at least one grade 3 to 5 chronic condition decreased significantly, from 33.2% for survivors diagnosed between 1970 and 1979, to 29.3% for those diagnosed between 1980 and 1989, to 27.5% for those diagnosed between 1990 and 1999, compared with a 4.6% incidence in a sibling cohort. The overall decrease in incidence of chronic conditions across the three treatment decades was, in part, because of a substantial reduction of endocrinopathies, subsequent malignant neoplasms, musculoskeletal conditions, and gastrointestinal conditions, whereas the cumulative incidence of hearing loss increased during this time. Declines in morbidity were not uniform across the diagnosis groups or condition types because of differences in treatment and survival patterns over time (refer to Figure 3 for more information).[24]
Figure 3. Cumulative incidence of grade 3–5 chronic health conditions in 5-year survivors of childhood cancer by diagnosis decade and siblings. (A) Cumulative incidence of a first grade 3–5 condition. (B) Cumulative incidence of two or more grade 3–5 conditions. The shaded area represents the 95% confidence interval (CI). The number of participants at risk (number censored) at each 5-year interval post-diagnosis is listed below the x-axis. The number censored does not include those who experienced a competing risk event (death from a cause other than a grade 5 chronic condition). Reprinted from The Lancet Oncology, Volume 19, Issue 12, Todd M Gibson, Sogol Mostoufi-Moab, Kayla L Stratton, Wendy M Leisenring, Dana Barnea, Eric J Chow, Sarah S Donaldson, Rebecca M Howell, Melissa M Hudson, Anita Mahajan, Paul C Nathan, Kirsten K Ness, Charles A Sklar, Emily S Tonorezos, Christopher B Weldon, Elizabeth M Wells, Yutaka Yasui, Gregory T Armstrong, Leslie L Robinson, Kevin C Oeffinger, Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort. Pages 1590-1601, Copyright (2018), with permission from Elsevier.
Late effects also contribute to an excess risk of premature death among long-term survivors of childhood cancer as observed in the following:
Several studies of very large cohorts of survivors have reported early mortality among individuals treated for childhood cancer compared with age- and sex-matched general population controls. Relapsed/refractory primary cancer remains the most frequent cause of death, followed by excess cause-specific mortality from subsequent primary cancers, and cardiac and pulmonary toxicity.[25-31]
An analysis of the CCSS and Surveillance, Epidemiology, and End Results (SEER) data that evaluated conditional survival demonstrated a subsequent 5-year survival rate of 92% or higher among most diagnoses at 5 years, 10 years, 15 years, and 20 years. Among those who had survived at least 5 years from diagnosis, the probability of all-cause mortality in the next 10 years was 8.8% in the CCSS and 10.6% in the SEER study, with neoplasms accounting for cause of death in approximately 75% of survivors.[32]
Despite high premature morbidity rates, overall mortality has decreased over time.[25,33-35] This reduction is related to a decrease in deaths from the primary cancer without an associated increase in mortality from subsequent cancers or treatment-related toxicities. The former reflects improvements in therapeutic efficacy, and the latter reflects changes in therapy made subsequent to studying the causes of late effects. The expectation that mortality rates in survivors will continue to exceed those in the general population is based on the long-term sequelae that are likely to increase with attained age. If patients treated on therapeutic protocols are followed up for long periods into adulthood, it will be possible to evaluate the excess lifetime mortality in relation to specific therapeutic interventions.
Survivors of adolescent and young adult cancers
Little information is available on the conditional probabilities of death among adolescent and young adult cancer patients who survive more than 5 years after their diagnosis. Using SEER data, conditional relative survival up to 25 years after diagnosis was studied in a cohort of adolescent and young adult patients (N = 205,954) diagnosed with a first malignant cancer (thyroid, melanoma, testicular, breast, lymphoma, leukemia, and central nervous system [CNS] tumors). For all cancer types combined, among individuals who survived up to 5 years, subsequent 5-year relative survival exceeded 95% by 7 years after diagnosis. According to this study, most adolescent and young adult cancer patients who survived at least 7 years after diagnosis experienced little difference in survival from that of the general population. For specific cancer types, including CNS tumors, female breast cancer, Hodgkin lymphoma, and leukemia, evidence of excess mortality risk persisted, or re-emerged, more than 10 years after a cancer diagnosis. Conditional relative survival was lowest for adolescent and young adult patients with CNS tumors, although patients aged 15 to 29 years demonstrated a higher survival rate than did patients aged 30 to 39 years at the time of diagnosis of their CNS tumors.[36]
Monitoring for Late Effects
Recognition of both acute and late modality–specific toxicity has motivated investigations evaluating the pathophysiology and prognostic factors for cancer treatment–related effects. The results of these studies have played an important role in the following areas:[25,33]
Changing pediatric cancer therapeutic approaches to reduce treatment-related mortality among survivors treated in more recent eras.
The development of risk counseling and health screening recommendations for long-term survivors by identifying the clinical and treatment characteristics of those at highest risk of treatment complications.
The common late effects of pediatric cancer encompass several broad domains, including the following:
Growth and development.
Organ function.
Reproductive capacity and health of offspring.
Secondary carcinogenesis.
Psychosocial sequelae related to the primary cancer, its treatment, or maladjustment associated with the cancer experience.
Late sequelae of therapy for childhood cancer can be anticipated based on therapeutic exposures, but the magnitude of risk and the manifestations in an individual patient are influenced by numerous factors. Factors that should be considered in the risk assessment for a given late effect include the following:
Tumor-related factors
Tumor location.
Direct tissue effects.
Tumor-induced organ dysfunction.
Mechanical effects.
Treatment-related factors
Radiation therapy: Total dose, fraction size, organ or tissue volume, type of machine energy.
Chemotherapy: Agent type, dose-intensity, cumulative dose, schedule.
Surgery: Technique, site.
Hematopoietic cell transplantation.
Use of combined modality therapy.
Blood product transfusion.
Management of chronic graft-versus-host disease.
Host-related factors
Genetic predisposition.
Premorbid health state.
Developmental status.
Age at diagnosis.
Time from diagnosis/therapy.
Inherent tissue sensitivities and capacity for normal tissue repair.
Hormonal milieu.
Function of organs not affected by cancer treatment.
Socioeconomic status.
Health habits.
Resources to Support Survivor Care
Risk-based screening
The need for long-term follow-up for childhood cancer survivors is supported by the American Society of Pediatric Hematology/Oncology, the International Society of Pediatric Oncology, the American Academy of Pediatrics, the Children’s Oncology Group (COG), and the Institute of Medicine. A risk-based medical follow-up is recommended, which includes a systematic plan for lifelong screening, surveillance, and prevention that incorporates risk estimates based on the following:[37]
Previous cancer.
Cancer therapy.
Lifestyle behaviors.
Comorbid conditions.
Part of long-term follow-up is also focused on appropriate screening of educational and vocational progress. Specific treatments for childhood cancer, especially those that directly impact nervous system structures, may result in sensory, motor, and neurocognitive deficits that may have adverse consequences on functional status, educational attainment, and future vocational opportunities.[38] In support of this, a CCSS investigation observed the following:[39]
Treatment with cranial radiation doses of 25 Gy or higher was associated with higher odds of unemployment (health related: odds ratio [OR], 3.47; 95% confidence interval [CI], 2.54–4.74; seeking work: OR, 1.77; 95% CI, 1.15–2.71).
Unemployed survivors reported higher levels of poor physical functioning than employed survivors, had lower education and income, and were more likely to be publicly insured than unemployed siblings.
These data emphasize the importance of facilitating survivor access to remedial services, which has been demonstrated to have a positive impact on education achievement,[40] which may in turn enhance vocational opportunities.
In addition to risk-based screening for medical late effects, the impact of health behaviors on cancer-related health risks is also emphasized. Health-promoting behaviors are stressed for survivors of childhood cancer. Targeted educational efforts appear to be worthwhile in the following areas:[41]
Abstinence from smoking, excess alcohol use, and illicit drug use to reduce the risk of organ toxicity and, potentially, subsequent neoplasms.
Healthy dietary practices and active lifestyle to reduce treatment-related metabolic and cardiovascular complications.
Proactively addressing unhealthy and risky behaviors is pertinent, as several research investigations confirm that long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects.[41-43]
Access to risk-based survivor care
Most childhood cancer survivors do not receive recommended risk-based care. The CCSS observed the following:
88.8% of survivors reported receiving some form of medical care.[44]
31.5% reported receiving care that focused on their previous cancer (survivor-focused care).[44]
17.8% reported receiving survivor-focused care that included advice about risk reduction and discussion or ordering of screening tests.[44]
Surveillance for new cases of cancer was very low in survivors at the highest risk of colon, breast, or skin cancer, suggesting that survivors and their physicians need education about the risk of subsequent neoplasms and recommended surveillance.[45]
Sociodemographic factors have been linked to declining rates of follow-up care over time from diagnosis. CCSS participants who were male, had a household income of less than $20,000 per year, and had lower educational attainment (high school education or less) were more likely to report no care at their most recent follow-up survey. This trend is of concern because the prevalence of chronic health conditions increases with longer elapsed time from cancer diagnosis in adults treated for cancer during childhood.[46]
Access to health insurance appears to play an important role in risk-based survivor care.[47,48] Lack of access to health insurance affects the following:
Cancer-related visits. In the CCSS, uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted relative risk [RR], 0.83; 95% CI, 0.75–0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71–0.98). Uninsured survivors had lower levels of utilization in all measures of care than privately insured survivors. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11–1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18–1.70) than were privately insured survivors.[47]
Health care outcomes. In a study comparing health care outcomes for long-term survivors of adolescent and young adult (AYA) cancer with young adults who have no cancer history, the proportion of uninsured survivors did not differ between the two groups.[49]
Financial burden. Subgroups of AYA survivors may be at additional risk of facing health care barriers. Younger survivors (aged 20–29 years), females, nonwhites, and survivors reporting poorer health faced more cost barriers, which may inhibit the early detection of late effects.[49]
Overall, lack of health insurance remains a significant concern for survivors of childhood cancer because of health issues, unemployment, and other societal factors.[50,51] Legislation, including the Health Insurance Portability and Accountability Act (HIPAA),[52,53] has improved access and retention of health insurance among survivors, although the quality and limitations associated with these policies have not been well studied.
Transition to Survivor Care
Long-term follow-up programs
Transition of care from the pediatric to adult health care setting is necessary for most childhood cancer survivors in the United States.
When available, multidisciplinary long-term follow-up programs in the pediatric cancer center work collaboratively with community physicians to provide care for childhood cancer survivors. This type of shared care has been proposed as the optimal model to facilitate coordination between the cancer center oncology team and community physician groups providing survivor care.[54]
An essential service of long-term follow-up programs is the organization of an individualized survivorship care plan that includes the following:
Details about therapeutic interventions undertaken for childhood cancer and their potential health risks (e.g., chemotherapy type and cumulative dose, radiation treatment fields and dose, surgical procedures, blood product transfusions, and hematopoietic cell transplantation).
Personalized health screening recommendations.
Information about lifestyle factors that modify risks.
A CCSS investigation that evaluated perceptions of future health and cancer risk highlighted the importance of continuing education of survivors during long-term follow-up evaluations. A substantial subgroup of adult survivors reported a lack of concern about future health (24%) and subsequent cancer risks (35%), even after exposure to treatments associated with increased risks. These findings present concerns that survivors may be less likely to engage in beneficial screenings and risk-reduction activities.[55]
For survivors who have not been provided with this information, the COG offers a template that can be used by survivors to organize a personal treatment summary (refer to the COG Survivorship Guidelines, Appendix 1).
COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers
To facilitate survivor and provider access to succinct information to guide risk-based care, COG investigators have organized a compendium of exposure- and risk-based health surveillance recommendations, with the goal of standardizing the care of childhood cancer survivors.[56]
The compendium of resources includes the following:
Long-Term Follow-Up Guidelines. COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers are appropriate for asymptomatic survivors presenting for routine exposure-based medical evaluation 2 or more years after completion of therapy.
Health Links. Patient education materials called Health Links provide detailed information on guideline-specific topics to enhance health maintenance and promotion among this population of cancer survivors.[57]
Comprehensive reviews. Multidisciplinary system-based (e.g., cardiovascular, neurocognitive, and reproductive) task forces who are responsible for monitoring the literature, evaluating guideline content, and providing recommendations for guideline revisions as new information becomes available have published several comprehensive reviews that address specific late effects of childhood cancer.[58-70]
Information concerning late effects is summarized in tables throughout this summary.
Several groups have undertaken research to evaluate the yield from risk-based screening as recommended by the COG and other pediatric oncology cooperative groups.[9,71,72] Pertinent considerations in interpreting the results of these studies include:
Variability in the cohort’s age at treatment.
Age at screening.
Time from cancer treatment.
Participation bias.
Collectively, these studies demonstrate that screening identifies a substantial proportion of individuals with previously unrecognized, treatment-related health complications of varying degrees of severity. Study results have also identified low-yield evaluations that have encouraged revisions of screening recommendations. Ongoing research is evaluating cost effectiveness of screening in the context of consideration of benefits, risks, and harms.
Jemal A, Siegel R, Xu J, et al.: Cancer statistics, 2010. CA Cancer J Clin 60 (5): 277-300, 2010 Sep-Oct. [PUBMED Abstract]
Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2010. Bethesda, Md: National Cancer Institute, 2013. Also available online. Last accessed March 7, 2019.
Lorenzi MF, Xie L, Rogers PC, et al.: Hospital-related morbidity among childhood cancer survivors in British Columbia, Canada: report of the childhood, adolescent, young adult cancer survivors (CAYACS) program. Int J Cancer 128 (7): 1624-31, 2011. [PUBMED Abstract]
Mols F, Helfenrath KA, Vingerhoets AJ, et al.: Increased health care utilization among long-term cancer survivors compared to the average Dutch population: a population-based study. Int J Cancer 121 (4): 871-7, 2007. [PUBMED Abstract]
Rebholz CE, Reulen RC, Toogood AA, et al.: Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 29 (31): 4181-8, 2011. [PUBMED Abstract]
Armstrong GT, Kawashima T, Leisenring W, et al.: Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol 32 (12): 1218-27, 2014. [PUBMED Abstract]
Oeffinger KC, Mertens AC, Sklar CA, et al.: Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355 (15): 1572-82, 2006. [PUBMED Abstract]
Geenen MM, Cardous-Ubbink MC, Kremer LC, et al.: Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA 297 (24): 2705-15, 2007. [PUBMED Abstract]
Hudson MM, Ness KK, Gurney JG, et al.: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 309 (22): 2371-81, 2013. [PUBMED Abstract]
Sun CL, Francisco L, Kawashima T, et al.: Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood 116 (17): 3129-39; quiz 3377, 2010. [PUBMED Abstract]
Kurt BA, Nolan VG, Ness KK, et al.: Hospitalization rates among survivors of childhood cancer in the Childhood Cancer Survivor Study cohort. Pediatr Blood Cancer 59 (1): 126-32, 2012. [PUBMED Abstract]
Zhang Y, Lorenzi MF, Goddard K, et al.: Late morbidity leading to hospitalization among 5-year survivors of young adult cancer: a report of the childhood, adolescent and young adult cancer survivors research program. Int J Cancer 134 (5): 1174-82, 2014. [PUBMED Abstract]
Sørensen GV, Winther JF, de Fine Licht S, et al.: Long-Term Risk of Hospitalization Among Five-Year Survivors of Childhood Leukemia in the Nordic Countries. J Natl Cancer Inst 111 (9): 943-951, 2019. [PUBMED Abstract]
Norsker FN, Rechnitzer C, Cederkvist L, et al.: Somatic late effects in 5-year survivors of neuroblastoma: a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study. Int J Cancer 143 (12): 3083-3096, 2018. [PUBMED Abstract]
Berbis J, Michel G, Chastagner P, et al.: A French cohort of childhood leukemia survivors: impact of hematopoietic stem cell transplantation on health status and quality of life. Biol Blood Marrow Transplant 19 (7): 1065-72, 2013. [PUBMED Abstract]
Phillips SM, Padgett LS, Leisenring WM, et al.: Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev 24 (4): 653-63, 2015. [PUBMED Abstract]
Bhakta N, Liu Q, Ness KK, et al.: The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet 390 (10112): 2569-2582, 2017. [PUBMED Abstract]
Salloum R, Chen Y, Yasui Y, et al.: Late Morbidity and Mortality Among Medulloblastoma Survivors Diagnosed Across Three Decades: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 37 (9): 731-740, 2019. [PUBMED Abstract]
Vuotto SC, Krull KR, Li C, et al.: Impact of chronic disease on emotional distress in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 123 (3): 521-528, 2017. [PUBMED Abstract]
Hudson MM, Oeffinger KC, Jones K, et al.: Age-dependent changes in health status in the Childhood Cancer Survivor cohort. J Clin Oncol 33 (5): 479-91, 2015. [PUBMED Abstract]
Liu Q, Leisenring WM, Ness KK, et al.: Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study. J Clin Oncol 34 (14): 1634-43, 2016. [PUBMED Abstract]
Ehrhardt MJ, Bhakta N, Liu Q, et al.: Absence of Basal Cell Carcinoma in Irradiated Childhood Cancer Survivors of Black Race: A Report from the St. Jude Lifetime Cohort Study. Cancer Epidemiol Biomarkers Prev 25 (9): 1356-60, 2016. [PUBMED Abstract]
Turcotte LM, Liu Q, Yasui Y, et al.: Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015. JAMA 317 (8): 814-824, 2017. [PUBMED Abstract]
Gibson TM, Mostoufi-Moab S, Stratton KL, et al.: Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 19 (12): 1590-1601, 2018. [PUBMED Abstract]
Armstrong GT, Pan Z, Ness KK, et al.: Temporal trends in cause-specific late mortality among 5-year survivors of childhood cancer. J Clin Oncol 28 (7): 1224-31, 2010. [PUBMED Abstract]
Bhatia S, Robison LL, Francisco L, et al.: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Blood 105 (11): 4215-22, 2005. [PUBMED Abstract]
MacArthur AC, Spinelli JJ, Rogers PC, et al.: Mortality among 5-year survivors of cancer diagnosed during childhood or adolescence in British Columbia, Canada. Pediatr Blood Cancer 48 (4): 460-7, 2007. [PUBMED Abstract]
Tukenova M, Guibout C, Hawkins M, et al.: Radiation therapy and late mortality from second sarcoma, carcinoma, and hematological malignancies after a solid cancer in childhood. Int J Radiat Oncol Biol Phys 80 (2): 339-46, 2011. [PUBMED Abstract]
Prasad PK, Signorello LB, Friedman DL, et al.: Long-term non-cancer mortality in pediatric and young adult cancer survivors in Finland. Pediatr Blood Cancer 58 (3): 421-7, 2012. [PUBMED Abstract]
Youn P, Milano MT, Constine LS, et al.: Long-term cause-specific mortality in survivors of adolescent and young adult bone and soft tissue sarcoma: a population-based study of 28,844 patients. Cancer 120 (15): 2334-42, 2014. [PUBMED Abstract]
Reulen RC, Winter DL, Frobisher C, et al.: Long-term cause-specific mortality among survivors of childhood cancer. JAMA 304 (2): 172-9, 2010. [PUBMED Abstract]
Mertens AC, Yong J, Dietz AC, et al.: Conditional survival in pediatric malignancies: analysis of data from the Childhood Cancer Survivor Study and the Surveillance, Epidemiology, and End Results Program. Cancer 121 (7): 1108-17, 2015. [PUBMED Abstract]
Yeh JM, Nekhlyudov L, Goldie SJ, et al.: A model-based estimate of cumulative excess mortality in survivors of childhood cancer. Ann Intern Med 152 (7): 409-17, W131-8, 2010. [PUBMED Abstract]
Armstrong GT, Chen Y, Yasui Y, et al.: Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer. N Engl J Med 374 (9): 833-42, 2016. [PUBMED Abstract]
Fidler MM, Reulen RC, Winter DL, et al.: Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain: population based cohort study. BMJ 354: i4351, 2016. [PUBMED Abstract]
Anderson C, Smitherman AB, Nichols HB: Conditional relative survival among long-term survivors of adolescent and young adult cancers. Cancer 124 (14): 3037-3043, 2018. [PUBMED Abstract]
McCabe MS, Partridge AH, Grunfeld E, et al.: Risk-based health care, the cancer survivor, the oncologist, and the primary care physician. Semin Oncol 40 (6): 804-12, 2013. [PUBMED Abstract]
Hudson MM, Mulrooney DA, Bowers DC, et al.: High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance. J Clin Oncol 27 (14): 2405-14, 2009. [PUBMED Abstract]
Kirchhoff AC, Leisenring W, Krull KR, et al.: Unemployment among adult survivors of childhood cancer: a report from the childhood cancer survivor study. Med Care 48 (11): 1015-25, 2010. [PUBMED Abstract]
Mitby PA, Robison LL, Whitton JA, et al.: Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 97 (4): 1115-26, 2003. [PUBMED Abstract]
Nathan PC, Ford JS, Henderson TO, et al.: Health behaviors, medical care, and interventions to promote healthy living in the Childhood Cancer Survivor Study cohort. J Clin Oncol 27 (14): 2363-73, 2009. [PUBMED Abstract]
Schultz KA, Chen L, Chen Z, et al.: Health and risk behaviors in survivors of childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 55 (1): 157-64, 2010. [PUBMED Abstract]
Tercyak KP, Donze JR, Prahlad S, et al.: Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) program. Pediatr Blood Cancer 47 (6): 825-30, 2006. [PUBMED Abstract]
Nathan PC, Greenberg ML, Ness KK, et al.: Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 26 (27): 4401-9, 2008. [PUBMED Abstract]
Nathan PC, Ness KK, Mahoney MC, et al.: Screening and surveillance for second malignant neoplasms in adult survivors of childhood cancer: a report from the childhood cancer survivor study. Ann Intern Med 153 (7): 442-51, 2010. [PUBMED Abstract]
Casillas J, Oeffinger KC, Hudson MM, et al.: Identifying Predictors of Longitudinal Decline in the Level of Medical Care Received by Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study. Health Serv Res 50 (4): 1021-42, 2015. [PUBMED Abstract]
Casillas J, Castellino SM, Hudson MM, et al.: Impact of insurance type on survivor-focused and general preventive health care utilization in adult survivors of childhood cancer: the Childhood Cancer Survivor Study (CCSS). Cancer 117 (9): 1966-75, 2011. [PUBMED Abstract]
Keegan TH, Tao L, DeRouen MC, et al.: Medical care in adolescents and young adult cancer survivors: what are the biggest access-related barriers? J Cancer Surviv 8 (2): 282-92, 2014. [PUBMED Abstract]
Kirchhoff AC, Lyles CR, Fluchel M, et al.: Limitations in health care access and utilization among long-term survivors of adolescent and young adult cancer. Cancer 118 (23): 5964-72, 2012. [PUBMED Abstract]
Crom DB, Lensing SY, Rai SN, et al.: Marriage, employment, and health insurance in adult survivors of childhood cancer. J Cancer Surviv 1 (3): 237-45, 2007. [PUBMED Abstract]
Pui CH, Cheng C, Leung W, et al.: Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 349 (7): 640-9, 2003. [PUBMED Abstract]
Park ER, Kirchhoff AC, Zallen JP, et al.: Childhood Cancer Survivor Study participants' perceptions and knowledge of health insurance coverage: implications for the Affordable Care Act. J Cancer Surviv 6 (3): 251-9, 2012. [PUBMED Abstract]
Warner EL, Park ER, Stroup A, et al.: Childhood cancer survivors' familiarity with and opinions of the Patient Protection and Affordable Care Act. J Oncol Pract 9 (5): 246-50, 2013. [PUBMED Abstract]
Oeffinger KC, McCabe MS: Models for delivering survivorship care. J Clin Oncol 24 (32): 5117-24, 2006. [PUBMED Abstract]
Gibson TM, Li C, Armstrong GT, et al.: Perceptions of future health and cancer risk in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 124 (16): 3436-3444, 2018. [PUBMED Abstract]
Landier W, Bhatia S, Eshelman DA, et al.: Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 22 (24): 4979-90, 2004. [PUBMED Abstract]
Eshelman D, Landier W, Sweeney T, et al.: Facilitating care for childhood cancer survivors: integrating children's oncology group long-term follow-up guidelines and health links in clinical practice. J Pediatr Oncol Nurs 21 (5): 271-80, 2004 Sep-Oct. [PUBMED Abstract]
Castellino S, Muir A, Shah A, et al.: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children's Oncology Group. Pediatr Blood Cancer 54 (5): 663-9, 2010. [PUBMED Abstract]
Henderson TO, Amsterdam A, Bhatia S, et al.: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152 (7): 444-55; W144-54, 2010. [PUBMED Abstract]
Jones DP, Spunt SL, Green D, et al.: Renal late effects in patients treated for cancer in childhood: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (6): 724-31, 2008. [PUBMED Abstract]
Liles A, Blatt J, Morris D, et al.: Monitoring pulmonary complications in long-term childhood cancer survivors: guidelines for the primary care physician. Cleve Clin J Med 75 (7): 531-9, 2008. [PUBMED Abstract]
Nandagopal R, Laverdière C, Mulrooney D, et al.: Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. Horm Res 69 (2): 65-74, 2008. [PUBMED Abstract]
Nathan PC, Patel SK, Dilley K, et al.: Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: a report from the Children's Oncology Group. Arch Pediatr Adolesc Med 161 (8): 798-806, 2007. [PUBMED Abstract]
Ritchey M, Ferrer F, Shearer P, et al.: Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children's Oncology Group. Pediatr Blood Cancer 52 (4): 439-46, 2009. [PUBMED Abstract]
Shankar SM, Marina N, Hudson MM, et al.: Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group. Pediatrics 121 (2): e387-96, 2008. [PUBMED Abstract]
Wasilewski-Masker K, Kaste SC, Hudson MM, et al.: Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics 121 (3): e705-13, 2008. [PUBMED Abstract]
Metzger ML, Meacham LR, Patterson B, et al.: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol 31 (9): 1239-47, 2013. [PUBMED Abstract]
Kenney LB, Cohen LE, Shnorhavorian M, et al.: Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children's Oncology Group. J Clin Oncol 30 (27): 3408-16, 2012. [PUBMED Abstract]
Effinger KE, Migliorati CA, Hudson MM, et al.: Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report. Support Care Cancer 22 (7): 2009-19, 2014. [PUBMED Abstract]
Bass JK, Knight KR, Yock TI, et al.: Evaluation and Management of Hearing Loss in Survivors of Childhood and Adolescent Cancers: A Report From the Children's Oncology Group. Pediatr Blood Cancer 63 (7): 1152-62, 2016. [PUBMED Abstract]
Landier W, Armenian SH, Lee J, et al.: Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines. J Clin Oncol 30 (35): 4401-8, 2012. [PUBMED Abstract]
Wasilewski-Masker K, Mertens AC, Patterson B, et al.: Severity of health conditions identified in a pediatric cancer survivor program. Pediatr Blood Cancer 54 (7): 976-82, 2010. [PUBMED Abstract]
Subsequent neoplasms (SNs), which may be benign or malignant, are defined as histologically distinct neoplasms developing at least 2 months after completion of treatment for the primary malignancy. Childhood cancer survivors have an increased risk of developing SNs that varies according to the following:
Host factors (e.g., genetics, immune function, hormone status).
Primary cancer therapy.
Environmental exposures.
Lifestyle factors.
SNs are the leading cause of nonrelapse late mortality (standardized mortality ratio, 15.2; 95% confidence interval [CI], 13.9–16.6).[1] The Childhood Cancer Survivor Study (CCSS) reported the following 30-year cumulative incidence rates:[2]
All SNs: 20.5% (95% CI, 19.1%–21.8%).
Nonmelanoma skin cancer (NMSC): 9.1% (95% CI, 8.1%–10.1%).
SNs with malignant histologies (excluding NMSC): 7.9% (95% CI, 7.2%–8.5%).
Meningioma: 3.1% (95% CI, 2.5%–3.8%).
This represents a sixfold increased risk of SNs among cancer survivors, compared with the general population.[2]
The excess risk of SNs has been described in several studies.[3]
Evidence (excess risk of SN after age 40 years):
In a CCSS cohort, at the age of 55 years, the cumulative incidence of any new SN (including malignant neoplasms, NMSCs, benign meningiomas, and other benign neoplasms) occurring after age 40 years was 34.6%. The incidence of malignant SNs was 16.3%. Female sex and therapeutic radiation exposure were associated with an increased risk of developing SNs in multivariate analysis. Moreover, prolonged follow-up has established that multiple SNs are common among aging childhood cancer survivors.[4,5]
The CCSS also reported that individuals treated in more recent treatment eras experienced decreased risk of SNs (including subsequent malignancies, NMSCs, and benign meningiomas) compared with those treated earlier, and this was associated with decreased exposure to therapeutic radiation; however, individuals treated in the 1990s remain at increased risk of SNs compared with the general population.[6]
A follow-up CCSS study evaluated morbidity and mortality associated with meningioma among 4,221 participants treated with cranial radiation therapy.[7]
The cumulative incidence of subsequent meningioma by age 40 years was 5.6% in this group of patients, and the incidence was without demonstrable plateau.
Risk factors for subsequent meningioma included female sex (hazard ratio [HR], 1.7; 95% CI, 1.2–2.3) and higher cranial radiation dose (HR, 2.6; 95% CI, 1.6–4.2 after 30 Gy or higher).
Among survivors reporting meningiomas, the risk of neurologic sequelae occurring 5 or more years after primary cancer diagnosis was increased for seizures (HR, 10.0; 95% CI, 7.0–15.3); auditory-vestibular-visual sensory deficits (HR, 2.3; 95% CI, 1.3–4.0); focal neurologic dysfunction (HR, 4.9; 95% CI, 3.2–7.5); and severe headaches (HR, 3.2; 95% CI, 1.9–5.4).
With a median follow-up of 72 months after meningioma diagnosis, 13% of the patients had died, with six deaths attributed to meningioma.
Dutch investigators evaluated the contribution of chemotherapy to solid cancer risk in a large cohort of childhood cancer survivors diagnosed between 1963 and 2001 (median follow-up, 20.7 years).[8]
The 25-year cumulative SN incidence was 3.9% and did not change across decades.
Survivors treated with doxorubicin exhibited a dose-dependent increased risk of all solid cancers and breast cancer.
Among female survivors who did not receive chest radiation or total-body irradiation (TBI) (n = 31, breast cancer), HRs for doxorubicin dose tertiles were 1.3 (95% CI, 0.3–6.1), 5.6 (95% CI, 1.9–16.2), and 9.9 (95% CI, 4.2–23.8).
The doxorubicin–breast cancer dose response was stronger in survivors with Li-Fraumeni syndrome–associated childhood cancers (leukemia, central nervous system [CNS], and sarcomas other than Ewing) than in survivors of other cancers.
Study findings also confirmed those of previous SN investigations that have demonstrated a dose-response relationship with cyclophosphamide and subsequent sarcoma, particularly bone sarcoma. The HR for subsequent sarcoma was 3.1 (95% CI, 1.5–6.0) for survivors who received cyclophosphamide at a dose greater than 9,400 mg/m2 and 2.6 (95% CI, 1.3–5.2) for those who received ifosfamide.
St. Jude Lifetime Cohort Study investigators assessed the contribution of pathogenic and likely pathogenic mutations in cancer predisposition genes to SN risk in childhood cancer survivors.[9]
Of 3,006 study participants (median age, 35.6 years) evaluated by whole-genome sequencing (30-fold), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 pathogenic or likely pathogenic mutations were identified in 5.8% of survivors; the prevalence of a pathogenic or likely pathogenic mutation among nonirradiated survivors with SNs was much higher at 18%.
Mutations were associated with significantly increased rates of breast cancer (relative risk [RR], 13.9) and sarcoma (RR, 10.6) among irradiated survivors and with developing any SN (RR, 4.7), breast cancer (RR, 7.7), nonmelanoma skin cancer (RR, 11), and two or more histologically distinct SNs (RR, 18.6).
Mutation carriers did not have an increased rate of meningioma or thyroid cancer.
A study of 4,905 1-year survivors of allogeneic hematopoietic cell transplantation (HCT) who underwent transplant between 1969 and 2014 for malignant or nonmalignant diseases and followed for a median 12.5 years, demonstrated a strong effect of TBI dose and dose fractionation on risk of SNs.[10]
There were 581 SNs (excluding squamous and basal cell carcinomas of the skin) that developed in 499 individuals.
The cumulative incidence of SN by 30 years after HCT was 22.0%.
SN risk was highest in survivors exposed to high-dose unfractionated (600–1,200 cGy) or very high-dose fractionated (1,440–1,750 cGy) TBI.
With low-dose TBI (200–450 cGy), the SN risk was comparable to the risk with chemotherapy alone, although still twofold higher than in the general population.
The development of an SN is likely multifactorial in etiology and results from a combination of influences including gene-environment and gene-gene interactions. Outcome after the diagnosis of an SN is variable, as treatment for some histological subtypes may be compromised if childhood cancer therapy included cumulative doses of agents and modalities at the threshold of tissue tolerance.[11]
The incidence and type of SNs depend on the following:
Primary cancer diagnosis.
Type of therapy received.
Presence of genetic conditions.
Unique associations with specific therapeutic exposures have resulted in the classification of SNs into the following two distinct groups:
Chemotherapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML).
Radiation-related solid SNs.
Therapy-Related Myelodysplastic Syndrome and Leukemia
Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) has been reported after treatment of Hodgkin lymphoma (HL), acute lymphoblastic leukemia (ALL), and sarcomas, with the cumulative incidence approaching 2% at 15 years after therapy.[12-16]
Characteristics of t-MDS/AML include the following:[12,17,18]
A short latency (<10 years from primary cancer diagnosis). The risk of t-MDS/AML plateaus after 10 to 15 years. Although the risk of subsequent leukemia remains significantly elevated beyond 15 years from primary diagnosis (standardized incidence ratio [SIR], 3.5; 95% CI, 1.9–6.0), these events are relatively rare, with an absolute excess risk of 0.02 cases per 1,000 person-years.[18]
An association with alkylating agents and/or topoisomerase II inhibitors.
t-MDS/AML is a clonal disorder characterized by distinct chromosomal changes. The following two types of t-MDS/AML are recognized by the World Health Organization classification:[19]
Alkylating agent-related type: Alkylating agents associated with t-MDS/AML include cyclophosphamide, ifosfamide, mechlorethamine, melphalan, busulfan, nitrosoureas, chlorambucil, and dacarbazine.[20]
The risk of alkylating agent–related t-MDS/AML is dose dependent, with a latency of 3 to 5 years after exposure; it is associated with abnormalities involving chromosomes 5 (-5/del(5q)) and 7 (-7/del(7q)).[20]
Topoisomerase II inhibitor–related type: Topoisomerase II inhibitor agents include etoposide, teniposide, and anthracycline-related drugs.
Most of the translocations observed in patients exposed to topoisomerase II inhibitors disrupt a breakpoint cluster region between exons 5 and 11 of the band 11q23 and fuse mixed lineage leukemia with a partner gene.[20] Topoisomerase II inhibitor–related t-AML presents as overt leukemia after a latency of 6 months to 3 years and is associated with balanced translocations involving chromosome bands 11q23 or 21q22.[21]
Therapy-Related Solid Neoplasms
Therapy-related solid SNs represent 80% of all SNs and demonstrate a strong relationship with radiation exposure and are characterized by a latency that exceeds 10 years. The risk of solid SNs continues to increase with longer follow-up. The risk of solid SNs is highest when the following occur:[2,16]
Radiation exposure at a younger age.
High total dose of radiation.
Longer period of follow-up after radiation exposure.
The histological subtypes of solid SNs encompass a neoplastic spectrum ranging from benign and low-grade malignant lesions (e.g., NMSC, meningiomas) to high-grade malignancies (e.g., breast cancers, glioblastomas).[2,14,22-26]
Solid SNs in childhood cancer survivors most commonly involve the following: [2,12,14,16,23,27,28]
Breast.
Thyroid.
CNS.
Bone and soft tissue.
With more prolonged follow-up of adult survivors of childhood cancer cohorts, epithelial neoplasms have been observed in the following:[2,12,22,29]
Lung.
Gastrointestinal tract.
Genitourinary system.
Benign and low-grade SNs, including NMSCs and meningiomas, have also been observed with increasing prevalence in survivors who were treated with radiation therapy for childhood cancer.[2,23,24]
In addition to radiation exposure, exposure to certain anticancer agents may result in solid SNs. In recipients of an HCT conditioned with high-dose busulfan and cyclophosphamide (Bu-Cy), the cumulative incidence of new solid cancers appears to be similar regardless of exposure to radiation. In a registry-based, retrospective, cohort study, Bu-Cy conditioning without TBI was associated with higher risks of solid SNs than in the general population. Chronic graft-versus-host disease increased the risk of SNs, especially those involving the oral cavity.[30]
Some well-established solid SNs are described in the following sections.[31]
Breast cancer is the most common therapy-related solid SN after HL, largely due to the high dose of chest radiation used to treat HL (SIR of subsequent breast cancer, 25–55).[12,32] The following has been observed in female survivors of childhood HL:
Excess risk of breast cancer has been reported in female HL survivors treated with high-dose, extended-volume radiation at age 30 years or younger.[33] Emerging data indicate that females treated with low-dose, involved-field radiation also exhibit excess breast cancer risk.[34]
Patients with HL who received supradiaphragmatic radiation therapy (excluding the axillae) had a significantly lower risk of subsequent breast cancers than did patients who received mantle-field radiation therapy.[35]
For female HL patients treated with radiation therapy to the chest before age 16 years, the cumulative incidence of breast cancer approaches 20% by age 45 years.[12]
The latency period after chest irradiation ranges from 8 to 10 years, and the risk of subsequent breast cancer increases in a linear fashion with radiation dose (P for trend < .001).[36]
Radiation-induced breast cancer has been reported in one population-based study to have more adverse clinicopathological features, as evidenced by a twofold increased risk of estrogen receptor–negative, progesterone receptor–negative breast cancer observed among 15-year HL survivors, compared with women who had sporadic breast cancer.[37] Several studies that have investigated the clinical characteristics of subsequent breast cancers arising in women treated with radiation for childhood cancer have observed a higher proportion of more histologically aggressive subtypes (e.g., triple-negative breast cancer) than age-matched sporadic invasive cancers.[38,39] These findings are in contrast to other smaller hospital-based, case-control studies of breast cancer among HL survivors that have not identified a significant variation in hormone receptor status when compared with primary breast cancer controls. Previous studies have also not demonstrated significant difference in overall risk of high-grade versus low-grade tumors.[40-42]
Treatment of childhood HL with higher cumulative doses of alkylating agents and ovarian radiation of 5 Gy or higher (exposures predisposing to premature menopause) have been correlated with reductions in breast cancer risk, underscoring the potential contribution of hormonal stimulation on breast carcinogenesis.[35,43,44]
Most data describing the risk of radiation-associated breast cancer are based on patients treated for HL, with doses ranging from 15 Gy to 50 Gy. However, the risk of breast cancer was also increased in the following studies that used lower radiation doses to treat cancer metastatic to the chest/lung (e.g., Wilms tumor, sarcoma) and exposed the breast tissue:
In 116 children in the CCSS cohort treated with 2 Gy to 20 Gy to the lungs (median, 14 Gy), the SIR for breast cancer was 43.6 (95% CI, 27.1–70.1).[45]
A report of 2,492 female participants in the National Wilms Tumor Studies 1 through 4 (1969–1995) addressed the excess risk of breast cancer.[46]
Sixteen of 369 women who received chest irradiation for metastatic Wilms tumor developed invasive breast cancer (cumulative risk at age 40 years, 14.8% [95% CI, 8.7–24.5]). The SIR of 27.6 (95% CI, 16.1–44.2) was based on 5,010 person-years of follow-up.
Of the 369 patients, radiation doses to the chest were less than 12 Gy in 4%, 12 Gy in 64%, 13 Gy to 15 Gy in 19%, and more than 15 Gy in 13% of patients.
For all patients who developed breast cancer (with or without chest irradiation), the median age at first breast cancer diagnosis was 34.3 years (range, 15.5–48.4) and the median time from Wilms tumor diagnosis was 27.1 years (range, 7.9–35.7).
Although currently available evidence is insufficient to demonstrate a survival benefit from the initiation of breast cancer surveillance in women treated with radiation therapy to the chest for childhood cancer, interventions to promote detection of small and early-stage tumors may improve prognosis, particularly for those who may have more limited treatment options because of previous exposure to radiation or anthracyclines.
Childhood sarcoma or leukemia survivors not exposed to chest radiation also have an increased risk of breast cancer at a young age.[47]
CCSS investigators observed a fourfold excess risk (SIR, 4.0; 95% CI, 3.0–5.3) of breast cancer compared with rates in the general population among 3,768 female participants who did not receive chest radiation.
Breast cancer risk was highest among sarcoma (SIR, 5.3; 95% CI, 3.6–7.8) and leukemia (SIR, 4.1; 95% CI, 2.4–6.9) survivors, for whom the cumulative incidence of breast cancer was estimated to be 5.8% and 6.3%, respectively, by age 45 years.
Treatment with alkylating agents and anthracyclines increased the risk of breast cancer in a dose-dependent manner.
Dutch investigators evaluated the contribution of chemotherapy to solid cancer risk in a large cohort of childhood cancer survivors diagnosed between 1963 and 2001.[8]
Survivors treated with doxorubicin exhibited a dose-dependent increased risk of breast cancer (HR, 3.1; 95% CI, 1.4–6.5 among survivors treated with anthracycline doses of 250 mg/m2 or higher).
The doxorubicin–breast cancer dose response was stronger for survivors of Li-Fraumeni–associated cancers (leukemia, CNS, and sarcomas other than Ewing) than for survivors of other cancers.
The St. Jude Lifetime Cohort Study assessed 1,467 women cancer survivors for the risk of developing subsequent breast cancer and evaluated whether surveillance imaging affects breast cancer outcomes.[48]
In women who did not receive chest radiation and did not receive anthracyclines, the cumulative incidence of breast cancer was 2% at age 35 years and 15% at age 50 years. For women who were treated with 250 mg/m2 or higher of anthracyclines, the rates were 7% at age 35 years and 46% at age 50 years.
Anthracycline doses of 250 mg/m2 or higher remained significantly associated with increased risk of breast cancer in models, excluding survivors with cancer predisposition gene mutations, chest radiation of 10 Gy or higher, or both.
Breast cancers detected by imaging and/or prophylactic mastectomy were more likely to be in situ carcinomas, be smaller masses, have no lymph node involvement, and be treated without chemotherapy, compared with breast cancers detected by physical findings.
On the basis of these findings, the authors recommend screening survivors who were treated with higher doses of anthracyclines in a manner consistent with those who have received radiation affecting the breast and/or have a known breast cancer predisposition mutation (e.g., BRCA1/BRCA2). In addition, dual imaging with mammography and breast magnetic resonance imaging (MRI) is a sensitive and specific approach to identifying breast cancers that require less aggressive therapy than breast cancers detected by physical findings.
In a study of female participants in the CCSS who were subsequently diagnosed with breast cancer (n = 274) and matched to a control group of women (n = 1,095) with de novo breast cancer, survivors of childhood cancer were found to have elevated mortality rates (HR, 2.2; 95% CI, 1.7–3.0) even after adjusting for breast cancer treatment. Survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4–9.0). The cumulative incidence of a second asynchronous breast cancer was elevated significantly compared with controls (at 5 years, 8.0% among childhood cancer survivors vs. 2.7% among controls; P < .001).[49]
Thyroid cancer is observed after the following:[2,12,50]
Neck radiation therapy for HL, ALL, and brain tumors.
Iodine I 131-metaiodobenzylguanidine (131I-MIBG) treatment for neuroblastoma.
TBI for hematopoietic stem cell transplantation.
The risk of thyroid cancer among survivors of Hodgkin disease has been reported to be 18-fold that of the general population.[51] Significant modifiers of the radiation-related risk of thyroid cancer include the following:[52,53]
Female sex.
Younger age at exposure.
Longer time since exposure.
Radiation dose. A linear dose-response relationship between radiation exposure and thyroid cancer is observed up to 29 Gy, with a decline in the odds ratio (OR) at higher doses, especially in children younger than 10 years at treatment, demonstrating evidence for a cell kill effect.[52,54]
(Refer to the Thyroid nodules section of this summary for information on detecting thyroid nodules and thyroid cancer.)
CNS tumors
Brain tumors develop after cranial irradiation for histologically distinct brain tumors [23] or for management of disease among ALL or non-Hodgkin lymphoma patients.[13,55] SIRs reported for subsequent CNS neoplasms after treatment for childhood cancer range from 8.1 to 52.3 across studies.[56]
The risk of subsequent brain tumors demonstrates a linear relationship with radiation dose.[2,23]
The risk of meningioma after radiation not only increases with radiation dose but also with increased dose of intrathecal methotrexate.[57]
Cavernomas have also been reported with considerable frequency after CNS irradiation but have been speculated to result from angiogenic processes as opposed to true tumorigenesis.[58-60]
Despite the well-established increased risk of subsequent CNS neoplasms among childhood cancer survivors treated with cranial irradiation, the current literature is insufficient to evaluate the potential harms and benefits of routine screening for these lesions.[56]
Bone and soft tissue tumors
Survivors of hereditary retinoblastoma, Ewing sarcoma, and other malignant bone tumors are at a particularly increased risk of developing subsequent bone and soft tissue tumors.[61-65]
A population-based study of 69,460 5-year survivors of cancer diagnosed before age 20 years observed the following:
The risk of subsequent primary bone cancer was 22-fold greater than that of the general population, with an estimated 45-year cumulative incidence of 0.6%, compared with an expected rate of 0.03% in the general population.[63] The observed excess numbers of subsequent primary bone cancer declined with both age and years from diagnosis.
In the same cohort, the risk of subsequent soft tissue sarcoma was almost 16-fold higher than the general population, with an estimated 45-year cumulative incidence of 1.4%, compared with an expected rate of 0.1%.[64] The median time from diagnosis to occurrence of a soft tissue sarcoma was 19 years.
The most commonly observed soft tissue sarcomas were leiomyosarcoma, fibromatous neoplasms, and malignant peripheral nerve sheath tumors. The SIR for subsequent fibromatous primary sarcomas decreased with increasing years from diagnosis and attained age, whereas the SIR for leiomyosarcoma and malignant peripheral nerve sheath tumors remained consistently high across all years from diagnosis and at all attained ages.
Notably, absolute excess risks of all sarcoma subtypes were generally low, except for leiomyosarcoma that followed a retinoblastoma diagnosis (absolute excess risks, 52.7 per 10,000 person-years among survivors 45 years or more from diagnosis). The risk of developing a leiomyosarcoma was 30-fold higher among survivors of childhood cancer, compared with an excess risk of 0.7 for the general population. Retinoblastoma survivors were at the highest risk (SIR, 342.9), followed by Wilms tumor survivors (SIR, 74.2). Ninety percent of leiomyosarcomas observed after a Wilms tumor diagnosis developed within the irradiated tissue.
Radiation therapy is associated with a linear dose-response relationship.[61,66] After adjustment for radiation therapy, treatment with alkylating agents has also been linked to bone cancer, with the risk increasing with cumulative drug exposure.[61] These data from earlier studies concur with the following data observed by the CCSS and other investigators:
In a CCSS cohort, an increased risk of subsequent bone or soft tissue sarcoma was associated with radiation therapy, a primary diagnosis of sarcoma, a history of other SNs, and treatment with higher doses of anthracyclines or alkylating agents.[67] The 30-year cumulative incidence of subsequent sarcoma in CCSS participants was 1.08% for survivors who received radiation therapy and 0.5% for survivors who did not receive radiation therapy.[67]
Dose-risk modeling was used to study the risk of bone sarcoma in a retrospective cohort of 4,171 survivors of a childhood solid cancer treated between 1942 and 1986 (median follow-up, 26 years).[66]
Dose-risk modeling demonstrated that the risk of bone sarcoma increased slightly up to a cumulative organ-absorbed radiation dose of 15 Gy (HR, 8.2; 95% CI, 1.6–42.9) and then rapidly increased for higher radiation doses (HR for 30 Gy or more, 117.9; 95% CI, 36.5–380.6), compared with patients not treated with radiation therapy.
The excess RR per Gy in this model was 1.77 (95% CI, 0.62–5.94).
Dutch investigators studied the risk of sarcoma in a large cohort of childhood cancer survivors diagnosed between 1963 and 2001.[8]
The use of cyclophosphamide, an alkylating agent, was found to increase the risk of sarcoma, particularly bone sarcoma, in a dose-dependent manner (HR, 3.1; 95% CI, 1.5–6.0 among survivors treated with cyclophosphamide doses of 9,400 mg/m2 or higher).
In survivors of bilateral retinoblastoma, the most common SNs seen are sarcomas, specifically osteosarcoma.[68-71] The contribution of chemotherapy to solid malignancy carcinogenesis was highlighted in a long-term follow-up study of 906 5-year hereditary retinoblastoma survivors who were diagnosed between 1914 and 1996 and observed through 2009.[62]
Treatment with alkylating agents significantly increased risk of subsequent bone tumors (HR, 1.60; 95% CI, 1.03–2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22–5.85) among members of the cohort.
Leiomyosarcoma occurrence was more common after treatment with alkylating agent chemotherapy and radiation therapy compared with radiation therapy alone (5.8% vs. 1.6% at age 40 years; P = .01).
Soft tissue sarcomas can be of various histologic subtypes, including nonrhabdomyosarcoma soft tissue sarcomas, rhabdomyosarcoma, malignant peripheral nerve sheath tumors, Ewing/primitive neuroectodermal tumors, and other rare types. The CCSS reported the following on 105 cases and 422 matched controls in a nested case-control study of 14,372 childhood cancer survivors:[72]
Soft tissue sarcomas occurred at a median of 11.8 years (range, 5.3–31.3 years) from original diagnoses.
Any exposure to radiation was associated with increased risk of soft tissue sarcoma (OR, 4.1; 95% CI, 1.8–9.5), which demonstrated a linear dose-response relationship.
Anthracycline exposure was associated with soft tissue sarcoma risk (OR, 3.5; 95% CI, 1.6–7.7), independent of radiation dose.
Nonmelanoma skin cancers (NMSCs) represent one of the most common SNs among childhood cancer survivors and exhibit a strong association with radiation therapy.[73] The CCSS has observed the following:
Compared with participants who did not receive radiation therapy, CCSS participants treated with radiation therapy had a 6.3-fold increase in risk of NMSC (95% CI, 3.5–11.3).[74]
Ninety percent of tumors occurred within the radiation field.[74]
A CCSS case-control study of the same cohort reported on subsequent basal cell carcinomas (BCCs). Children who received 35 Gy or more to the skin site had an almost 40-fold excess risk of developing BCCs (OR, 39.8; 95% CI, 8.6–185), compared with those who did not receive radiation therapy; results were consistent with a linear dose-response relationship, with an excess OR per Gy of 1.09 (95% CI, 0.49–2.64).[74]
These data underscore the importance of counseling survivors about sun protection behaviors to reduce ultraviolet radiation exposure that may exacerbate this risk.[24]
In 5,843 childhood cancer survivors in the Dutch Childhood Oncology Group (DCOG)-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs. After a first BCC diagnosis, 46.7% of patients had more BCCs later. This risk was associated with any radiation therapy to the original radiation field (HR,14.32) and with estimated percentage of in-field skin surface area (26%–75%: HR, 1.99; 76%–100%: HR, 2.16 vs. 1%–25% exposed; Ptrend among exposed = .002). BCC risk was not associated with prescribed radiation dose and likelihood of sun-exposed skin area. Of all chemotherapy groups examined, only vinca alkaloids increased the BCC risk (HR, 1.54).[75]
The occurrence of an NMSC as the first SN has been reported to identify a population at high risk of a future invasive malignant SN.[4] CCSS investigators observed a cumulative incidence of a malignant neoplasm of 20.3% (95% CI, 13.0%–27.6%) at 15 years among radiation-exposed survivors who developed NMSC as a first SN compared with 10.7% (95% CI, 7.2%–14.2%) whose first SN was an invasive malignancy.
Malignant melanoma has also been reported as an SN in childhood cancer survivor cohorts, although at a much lower incidence than NMSCs. A systematic review including data from 19 original studies (total N = 151,575 survivors; median follow-up of 13 years) observed an incidence of 10.8 cases of malignant melanoma per 100,000 childhood cancer survivors per year.[76]
Risk factors for malignant melanoma identified among these studies include the following:[76]
Radiation therapy.
Combination of alkylating agents and antimitotic drugs.
Melanomas most frequently developed in survivors of HL, hereditary retinoblastoma, soft tissue sarcoma, and gonadal tumors, but the relatively small number of survivors represented in the relevant studies preclude assessment of melanoma risk among other types of childhood cancer.[76]
CCSS investigators observed an approximate 2.5-fold increased risk (SIR, 2.42; 95% CI, 1.77–3.23) of melanoma among members of their cohort (median time to development, 21.0 years). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% (95% CI, 0.37%–0.73%), and absolute excess risk was 0.10 per 1,000 person-years (95% CI, 0.05–0.15). Family history of cancer, demographic, or treatment-related factors did not predict risk of melanoma.[77]
Lung cancer: Among childhood cancer survivor cohorts, lung cancer represents a relatively uncommon SN; the 30-year cumulative incidence of lung cancer among CCSS participants was 0.1% (95% CI, 0.0%–0.2%).[2] The following has been observed in adult survivors of childhood HL:[78]
Lung cancer has been reported after chest irradiation for HL. The risk increases in association with longer elapsed time from diagnosis.
Smoking has been linked with the occurrence of lung cancer that develops after radiation therapy for HL. The increase in risk of lung cancer with increasing radiation dose is greater among patients who smoke after exposure to radiation than among those who refrain from smoking (P = .04).
Gastrointestinal (GI) cancer
There is substantial evidence that childhood cancer survivors develop GI malignancies more frequently and at a younger age than the general population.[12,79-82]
The following has been observed in adult survivors of childhood cancer:
The Late Effects Study Group reported a 63.9-fold increased risk of gastric cancers and 36.4-fold increased risk of colorectal cancers in adult survivors of childhood HL. In addition to previous radiation therapy, younger age (0–5 years) at the time of the primary cancer therapy significantly increased risk.[12]
In a French and British cohort-nested, case-control study of childhood solid cancer survivors diagnosed before age 17 years, the risk of developing an SN in the digestive organs varied with therapy. The following was also observed:[79]
The risk of GI cancer was 9.7-fold higher than in population controls.
The SNs most often involved the colon/rectum (42%), liver (24%), and stomach (19%).
A strong radiation dose-response relationship, with an OR of 5.2 (95% CI, 1.7–16.0) for local radiation doses between 10 Gy and 29 Gy and 9.6 (95% CI, 2.6–35.2) for doses of 30 Gy and above, compared with the dose response in survivors who had not received radiation therapy.
Chemotherapy alone and combined-modality therapy were associated with a significantly increased risk of developing a GI SN (SIR, 9.1; 95% CI, 2.3–23.6; SIR 29.0; 95% CI, 20.5–39.8).
CCSS investigators reported a 4.6-fold higher risk of GI SNs among their study participants than in the general population (95% CI, 3.4–6.1). They also reported the following:[80]
The SNs most often involved the colon (39%), rectum/anus (16%), liver (18%), and stomach (13%).
The SIR for colorectal cancer was 4.2 (CI, 2.8–6.3).
The most prevalent GI SN histology was adenocarcinoma (56%).
The highest risk of GI SNs was associated with abdominal irradiation (SIR, 11.2; CI, 7.6–16.4), but survivors not exposed to radiation also had a significantly increased risk (SIR, 2.4; CI, 1.4–3.9).
High-dose procarbazine (RR, 3.2; CI, 1.1–9.4) and platinum drugs (RR, 7.6; CI, 2.3–25.5) independently increased the risk of GI SNs.
St. Jude Children's Research Hospital investigators observed that the SIR for subsequent colorectal carcinoma was 10.9 (95% CI, 6.6–17.0) compared with U.S. population controls. Investigators also observed the following:[81]
Incidence of a subsequent colorectal carcinoma increased steeply with advancing age, with a 40-year cumulative incidence of 1.4% ± 0.53% among the entire cohort (N = 13,048) and 2.3% ± 0.83% for 5-year survivors.
Colorectal carcinoma risk increased by 70% with each 10 Gy increase in radiation dose, and increasing radiation volume also increased risk.
Treatment with alkylating agent chemotherapy was also associated with an 8.8-fold excess risk of subsequent colorectal carcinoma.
A multi-institutional prospective study observed that potentially precancerous neoplastic polyps were found in 27.8% of childhood cancer survivors who received radiation to the abdomen/pelvis at least 10 years earlier and who had colonoscopic screening between age 35 and 49 years.[83]
This polyp prevalence is at least as high as that previously reported for the average-risk population older than 50 years and is similar to the 24% incidence rate for patients with hereditary non-polyposis colon cancer; polyp prevalence rates in the general population for people aged 35 to 49 years are unclear.
A DCOG-LATER record linkage study evaluated the risk of histologically confirmed colorectal adenomas among 5,843 5-year childhood cancer survivors followed for a median of 24.9 years.[84]
The cumulative incidence of colorectal adenoma by age 45 years was 3.6% among survivors who received abdominal pelvic radiation versus 2.0% for survivors who did not receive abdominal pelvic radiation, versus 1.0% among siblings.
Factors associated with adenoma risk were abdominal pelvic radiation (HR, 2.1), TBI (HR, 10.6), cisplatin (HR, 2.1 for <480 mg/m2; HR, 3.8 for ≥480 mg/m2), diagnosis of hepatoblastoma (HR, 27.1), and family history of early-onset colorectal cancer (HR, 20.5).
Procarbazine exposure was also associated with an increased risk among survivors not exposed to abdominal pelvic radiation or TBI (HR, 2.7).
In a large series from two institutions, 2,053 patients with retinoblastoma (diagnosed between 1914 and 2016) were identified.[85]
Most deaths occurred in hereditary retinoblastoma patients more than 70 years from diagnosis (518 of 1,129), and 267 of these deaths were caused by secondary cancers.
Increased risk of death resulting from cancers of the pancreas, large intestines, and kidney were reported.
Overall risk of subsequent cancer was higher for patients who were treated with radiation therapy and chemotherapy than for patients treated with radiation therapy alone, although patterns varied by organ site.
Based on a new cohort of 143 retinoblastoma survivors diagnosed between 1997 and 2006, continued improvements in mortality were observed.
For patients with nonhereditary retinoblastoma, only 27 deaths in 924 patients were attributed to second malignancies.
Collectively, these studies support the need for initiation of colorectal carcinoma surveillance at a young age among survivors receiving high-risk exposures.[12,79-81,86]
Renal carcinoma
Consistent with reports among survivors of adult-onset cancer, an increased risk of renal carcinoma has been observed in survivors of childhood cancer.[29,87,88]
CCSS investigators reported a significant excess of subsequent renal carcinoma among 14,358 5-year survivors in the cohort (SIR, 8.0; 95% CI, 5.2–11.7) compared with the general population.[87] The reported overall absolute excess risk of 8.4 per 105 person-years indicates that these cases are relatively rare. Highest risk was observed among the following:
Neuroblastoma survivors (SIR, 85.8; 95% CI, 38.4–175.2).[87] Radiation has been hypothesized to predispose children with high-risk neuroblastoma to renal carcinoma.[89]
Those treated with renal-directed radiation therapy of 5 Gy or higher (RR, 3.8; 95% CI, 1.6–9.3).[87]
Those treated with platinum-based chemotherapy (RR, 3.5; 95% CI, 1.0–11.2).[87] Cases of secondary renal carcinoma associated with Xp11.2 translocations and TFE3 gene fusions have also been reported and suggest that cytotoxic chemotherapy may contribute to renal carcinogenesis.[90,91]
Underlying genetic predisposition may also play a role because rare cases of renal carcinoma have been observed in children with tuberous sclerosis.[87]
Subsequent Neoplasms and Genetic Susceptibility
Literature clearly supports the role of chemotherapy and radiation therapy in the development of SNs. However, interindividual variability exists, suggesting that genetic variation has a role in susceptibility to genotoxic exposures, or that genetic susceptibility syndrome confers an increased risk of cancer, such as Li-Fraumeni syndrome.[92,93] Previous studies have demonstrated that childhood cancer survivors with a family history of Li-Fraumeni syndrome in particular, or a family history of cancer, carry an increased risk of developing an SN.[94,95]
The risk of SNs could potentially be modified by mutations in high-penetrance genes that lead to these serious genetic diseases (e.g., Li-Fraumeni syndrome).[95] However, the attributable risk is expected to be very small because of the extremely low prevalence of mutations in high-penetrance genes.
Table 1 summarizes the spectrum of neoplasms, affected genes, and Mendelian mode of inheritance of selected syndromes of inherited cancer predisposition.
Table 1. Selected Syndromes of Inherited Cancer Predispositiona
Major Tumor Types
Affected Gene
AML = acute myeloid leukemia; MDS = myelodysplastic syndromes; WAGR = Wilms tumor, aniridia, genitourinary anomalies, mental retardation.
aAdapted from Strahm et al.[96]
bDominant in a fraction of patients, spontaneous mutations can occur.
Adenomatous polyposis of the colon Colon, hepatoblastoma, intestinal cancers, stomach, thyroid cancer APC Dominant
Ataxia-telangiectasia Leukemia, lymphoma ATM Recessive
Beckwith-Wiedemann syndrome Adrenal carcinoma, hepatoblastoma, rhabdomyosarcoma, Wilms tumor CDKN1C/NSD1 Dominant
Bloom syndrome Leukemia, lymphoma, skin cancer BLM Recessive
Diamond-Blackfan anemia Colon cancer, osteogenic sarcoma, AML/MDS RPS19 and other RP genes Dominant, spontaneousb
Fanconi anemia Gynecological tumors, leukemia, squamous cell carcinoma FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG Recessive
Juvenile polyposis syndrome Gastrointestinal tumors SMAD4/DPC4 Dominant
Li-Fraumeni syndrome Adrenocortical carcinoma, brain tumor, breast carcinoma, leukemia, osteosarcoma, soft tissue sarcoma TP53 Dominant
Multiple endocrine neoplasia 1 Pancreatic islet cell tumor, parathyroid adenoma, pituitary adenoma MEN1 Dominant
Multiple endocrine neoplasia 2 Medullary thyroid carcinoma, pheochromocytoma RET Dominant
Neurofibromatosis type 1 Neurofibroma, optic pathway glioma, peripheral nerve sheath tumor NF1 Dominant
Neurofibromatosis type 2 Vestibular schwannoma NF2 Dominant
Nevoid basal cell carcinoma syndrome Basal cell carcinoma, medulloblastoma PTCH Dominant
Peutz-Jeghers syndrome Intestinal cancers, ovarian carcinoma, pancreatic carcinoma STK11 Dominant
Retinoblastoma Osteosarcoma, retinoblastoma RB1 Dominant
Tuberous sclerosis Hamartoma, renal angiomyolipoma, renal cell carcinoma TSC1/TSC2 Dominant
von Hippel-Lindau syndrome Hemangioblastoma, pheochromocytoma, renal cell carcinoma, retinal and central nervous system tumors VHL Dominant
WAGR syndrome Gonadoblastoma, Wilms tumor WT1 Dominant
Wilms tumor syndrome Wilms tumor WT1 Dominant
Xeroderma pigmentosum Leukemia, melanoma XPA, XPB, XPC, XPD, XPE, XPF, XPG, POLH Recessive
Drug-metabolizing enzymes and DNA repair polymorphisms
The interindividual variability in risk of SNs is more likely related to common polymorphisms in low-penetrance genes that regulate the availability of active drug metabolites or are responsible for DNA repair. Gene-environment interactions may magnify subtle functional differences resulting from genetic variations.
Drug-metabolizing enzymes
Metabolism of genotoxic agents occurs in two phases.
Phase I involves activation of substrates into highly reactive electrophilic intermediates that can damage DNA, a reaction principally performed by the cytochrome p450 (CYP) family of enzymes.
Phase II enzymes (conjugation) function to inactivate genotoxic substrates. The phase II proteins comprise the glutathione S-transferase (GST) enzymes, NAD(P)H:quinone oxidoreductase-1 (NQO1) enzyme, and others.
The balance between the two sets of enzymes is critical to the cellular response to xenobiotics; for example, high activity of a phase I enzyme and low activity of a phase II enzyme can result in DNA damage.
DNA repair polymorphisms
DNA repair mechanisms protect somatic cells from mutations in tumor suppressor genes and oncogenes that can lead to cancer initiation and progression. An individual’s DNA repair capacity appears to be genetically determined.[97] A number of DNA repair genes contain polymorphic variants, resulting in large interindividual variations in DNA repair capacity.[97] Evaluation of the contribution of polymorphisms influencing DNA repair to the risk of SN represents an active area of research.
Screening and Follow-up for Subsequent Neoplasms
Vigilant screening is important for childhood cancer survivors at risk.[98] Because of the relatively small size of the pediatric cancer survivor population and the prevalence and time to onset of therapy-related complications, undertaking clinical studies to assess the impact of screening recommendations on the morbidity and mortality associated with the late effect is not feasible.
Well-conducted studies on large populations of childhood cancer survivors have provided compelling evidence linking specific therapeutic exposures and late effects. This evidence has been used by several national and international cooperative groups (Scottish Collegiate Guidelines Network, Children’s Cancer and Leukaemia Group, Children's Oncology Group [COG], DCOG) to develop consensus-based clinical practice guidelines to increase awareness and standardize the immediate care needs of medically vulnerable childhood cancer survivors.[99]
All pediatric cancer survivor health screening guidelines employ a hybrid approach that is both evidence-based (utilizing established associations between therapeutic exposures and late effects to identify high-risk categories) and grounded in the collective clinical experience of experts (matching the magnitude of the risk with the intensity of the screening recommendations). The screening recommendations in these guidelines represent a statement of consensus from a panel of experts in the late effects of pediatric cancer treatment.[98,99]
The COG Guidelines for malignant SNs indicate that certain high-risk populations of childhood cancer survivors merit heightened surveillance because of predisposing host, behavioral, or therapeutic factors.[98]
Screening for leukemia: t-MDS/AML usually manifests within 10 years after exposure. Recommendations include monitoring with history and physical examination for signs and symptoms of pancytopenia for 10 years after exposure to alkylating agents or topoisomerase II inhibitors.
Screening after radiation exposure: Most other SNs are associated with radiation exposure and usually manifest more than 10 years after exposure. Screening recommendations include careful annual physical examination of the skin and underlying tissues in the radiation field.
Specific comments about screening for more common radiation-associated SNs are as follows:
Screening for early-onset skin cancer: Annual dermatological exam focusing on skin lesions and pigmented nevi in the radiation field is recommended. Survivors are counseled about the following:
Increased risk of skin cancer.
Potential exacerbation of risk through tanning.
Benefits of adhering to behaviors to protect the skin from excessive ultraviolet radiation exposure.
Screening for early-onset breast cancer: Because outcome after breast cancer is directly linked to stage at diagnosis, close surveillance resulting in early diagnosis may confer survival advantage.[100] Several pediatric cancer groups have endorsed the recommendation for early (before population breast cancer screening) initiation of breast cancer surveillance using mammography, breast MRI, or both imaging modalities in young women who were treated with chest irradiation.[101]
Mammography, the most widely accepted screening tool for breast cancer in the general population, may not be the ideal screening tool by itself for radiation-related breast cancers occurring in relatively young women with dense breasts. On the basis of research among young women with inherited susceptibility to breast cancer, dual-imaging modalities may enhance early detection related to the higher sensitivity of MRI in detecting lesions in premenopausal dense breasts and the superiority of mammography in identifying ductal carcinoma in situ;[102-104] therefore, the American Cancer Society recommends including adjunct screening with MRI.[105] The high sensitivity and specificity in detecting early-stage lesions with dual-imaging surveillance is offset by a substantial rate of additional investigations attributable to false-positive results.[104]
Many clinicians are concerned about potential harms related to radiation exposure associated with annual mammography in these young women. In this regard, it is important to consider that the estimated mean breast dose with contemporary standard two-view screening mammograms is about 3.85 mGy to 4.5 mGy.[106-108] Thus, 15 additional surveillance mammograms from age 25 to 39 years would increase the total radiation exposure in a woman treated with 20 Gy of chest radiation to 20.05775 Gy. The benefits of detection of early breast cancer lesions in high-risk women must be balanced by the risk predisposed by a 0.3% additional radiation exposure.
To keep young women engaged in breast health surveillance, the COG Guideline recommends the following for females who received a radiation dose of 20 Gy or higher to the mantle, mediastinal, whole lung, and axillary fields:
Monthly breast self-examination beginning at puberty.
Annual clinical breast examinations beginning at puberty until age 25 years.
A clinical breast examination every 6 months, with annual mammograms and MRIs beginning 8 years after radiation therapy or at age 25 years (whichever occurs later).
The risk of breast cancer in patients who received less than 20 Gy of radiation with potential impact to the breast is of a lower magnitude compared with those who received more than 20 Gy. Monitoring of patients treated with less than 20 Gy of radiation with potential impact to the breast is determined on an individual basis after a discussion with the provider regarding the benefits and risk/harms of screening. If a decision is made to screen, the recommendations for women exposed to more than 20 Gy are used.
Screening for early-onset colorectal cancer: Screening of those at risk of early-onset colorectal cancer (i.e., radiation doses of 30 Gy or higher to the abdomen, pelvis, or spine) includes colonoscopy every 5 years beginning at age 35 years or 10 years after radiation therapy (whichever occurs later).[83]
Mertens AC, Liu Q, Neglia JP, et al.: Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 100 (19): 1368-79, 2008. [PUBMED Abstract]
Friedman DL, Whitton J, Leisenring W, et al.: Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 102 (14): 1083-95, 2010. [PUBMED Abstract]
Turcotte LM, Whitton JA, Friedman DL, et al.: Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort. J Clin Oncol 33 (31): 3568-75, 2015. [PUBMED Abstract]
Armstrong GT, Liu W, Leisenring W, et al.: Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 29 (22): 3056-64, 2011. [PUBMED Abstract]
van Eggermond AM, Schaapveld M, Lugtenburg PJ, et al.: Risk of multiple primary malignancies following treatment of Hodgkin lymphoma. Blood 124 (3): 319-27; quiz 466, 2014. [PUBMED Abstract]
Bowers DC, Moskowitz CS, Chou JF, et al.: Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 35 (14): 1570-1576, 2017. [PUBMED Abstract]
Teepen JC, van Leeuwen FE, Tissing WJ, et al.: Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy. J Clin Oncol 35 (20): 2288-2298, 2017. [PUBMED Abstract]
Wang Z, Wilson CL, Easton J, et al.: Genetic Risk for Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer. J Clin Oncol 36 (20): 2078-2087, 2018. [PUBMED Abstract]
Baker KS, Leisenring WM, Goodman PJ, et al.: Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation. Blood 133 (26): 2790-2799, 2019. [PUBMED Abstract]
Milano MT, Li H, Gail MH, et al.: Long-term survival among patients with Hodgkin's lymphoma who developed breast cancer: a population-based study. J Clin Oncol 28 (34): 5088-96, 2010. [PUBMED Abstract]
Bhatia S, Yasui Y, Robison LL, et al.: High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: report from the Late Effects Study Group. J Clin Oncol 21 (23): 4386-94, 2003. [PUBMED Abstract]
Bhatia S, Sather HN, Pabustan OB, et al.: Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. Blood 99 (12): 4257-64, 2002. [PUBMED Abstract]
Hijiya N, Hudson MM, Lensing S, et al.: Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 297 (11): 1207-15, 2007. [PUBMED Abstract]
Bhatia S, Krailo MD, Chen Z, et al.: Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group. Blood 109 (1): 46-51, 2007. [PUBMED Abstract]
Mauch PM, Kalish LA, Marcus KC, et al.: Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: long-term analysis of risk factors and outcome. Blood 87 (9): 3625-32, 1996. [PUBMED Abstract]
Berger C, Trombert-Paviot B, Casagranda L, et al.: Second malignant neoplasms following childhood cancer: a study of a recent cohort (1987-2004) from the childhood cancer registry of the Rhône-Alpes region (ARCERRA) in France. Pediatr Hematol Oncol 28 (5): 364-79, 2011. [PUBMED Abstract]
Nottage K, Lanctot J, Li Z, et al.: Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood 117 (23): 6315-8, 2011. [PUBMED Abstract]
Tefferi A, Vardiman JW: Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22 (1): 14-22, 2008. [PUBMED Abstract]
Thirman MJ, Larson RA: Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 10 (2): 293-320, 1996. [PUBMED Abstract]
Pedersen-Bjergaard J, Philip P: Balanced translocations involving chromosome bands 11q23 and 21q22 are highly characteristic of myelodysplasia and leukemia following therapy with cytostatic agents targeting at DNA-topoisomerase II. Blood 78 (4): 1147-8, 1991. [PUBMED Abstract]
Bassal M, Mertens AC, Taylor L, et al.: Risk of selected subsequent carcinomas in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24 (3): 476-83, 2006. [PUBMED Abstract]
Neglia JP, Robison LL, Stovall M, et al.: New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98 (21): 1528-37, 2006. [PUBMED Abstract]
Perkins JL, Liu Y, Mitby PA, et al.: Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the childhood cancer survivor study. J Clin Oncol 23 (16): 3733-41, 2005. [PUBMED Abstract]
Boukheris H, Stovall M, Gilbert ES, et al.: Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 85 (3): 776-83, 2013. [PUBMED Abstract]
Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
Ronckers CM, Sigurdson AJ, Stovall M, et al.: Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res 166 (4): 618-28, 2006. [PUBMED Abstract]
Fidler MM, Frobisher C, Guha J, et al.: Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study. Br J Cancer 112 (12): 1857-65, 2015. [PUBMED Abstract]
Reulen RC, Frobisher C, Winter DL, et al.: Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA 305 (22): 2311-9, 2011. [PUBMED Abstract]
Majhail NS, Brazauskas R, Rizzo JD, et al.: Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117 (1): 316-22, 2011. [PUBMED Abstract]
Bhatia S, Sklar C: Second cancers in survivors of childhood cancer. Nat Rev Cancer 2 (2): 124-32, 2002. [PUBMED Abstract]
Kenney LB, Yasui Y, Inskip PD, et al.: Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med 141 (8): 590-7, 2004. [PUBMED Abstract]
Travis LB, Hill D, Dores GM, et al.: Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J Natl Cancer Inst 97 (19): 1428-37, 2005. [PUBMED Abstract]
O'Brien MM, Donaldson SS, Balise RR, et al.: Second malignant neoplasms in survivors of pediatric Hodgkin's lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol 28 (7): 1232-9, 2010. [PUBMED Abstract]
Schaapveld M, Aleman BM, van Eggermond AM, et al.: Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma. N Engl J Med 373 (26): 2499-511, 2015. [PUBMED Abstract]
Inskip PD, Robison LL, Stovall M, et al.: Radiation dose and breast cancer risk in the childhood cancer survivor study. J Clin Oncol 27 (24): 3901-7, 2009. [PUBMED Abstract]
Dores GM, Anderson WF, Beane Freeman LE, et al.: Risk of breast cancer according to clinicopathologic features among long-term survivors of Hodgkin's lymphoma treated with radiotherapy. Br J Cancer 103 (7): 1081-4, 2010. [PUBMED Abstract]
Horst KC, Hancock SL, Ognibene G, et al.: Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma. Ann Oncol 25 (4): 848-51, 2014. [PUBMED Abstract]
Demoor-Goldschmidt C, Supiot S, Mahé MA, et al.: Clinical and histological features of second breast cancers following radiotherapy for childhood and young adult malignancy. Br J Radiol 91 (1086): 20170824, 2018. [PUBMED Abstract]
Castiglioni F, Terenziani M, Carcangiu ML, et al.: Radiation effects on development of HER2-positive breast carcinomas. Clin Cancer Res 13 (1): 46-51, 2007. [PUBMED Abstract]
Gaffney DK, Hemmersmeier J, Holden J, et al.: Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2. Int J Radiat Oncol Biol Phys 49 (2): 539-46, 2001. [PUBMED Abstract]
Janov AJ, Tulecke M, O'Neill A, et al.: Clinical and pathologic features of breast cancers in women treated for Hodgkin's disease: a case-control study. Breast J 7 (1): 46-52, 2001 Jan-Feb. [PUBMED Abstract]
Travis LB, Hill DA, Dores GM, et al.: Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290 (4): 465-75, 2003. [PUBMED Abstract]
van Leeuwen FE, Klokman WJ, Stovall M, et al.: Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease. J Natl Cancer Inst 95 (13): 971-80, 2003. [PUBMED Abstract]
Moskowitz CS, Chou JF, Wolden SL, et al.: Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol 32 (21): 2217-23, 2014. [PUBMED Abstract]
Lange JM, Takashima JR, Peterson SM, et al.: Breast cancer in female survivors of Wilms tumor: a report from the national Wilms tumor late effects study. Cancer 120 (23): 3722-30, 2014. [PUBMED Abstract]
Henderson TO, Moskowitz CS, Chou JF, et al.: Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 34 (9): 910-8, 2016. [PUBMED Abstract]
Ehrhardt MJ, Howell CR, Hale K, et al.: Subsequent Breast Cancer in Female Childhood Cancer Survivors in the St Jude Lifetime Cohort Study (SJLIFE). J Clin Oncol 37 (19): 1647-1656, 2019. [PUBMED Abstract]
Moskowitz CS, Chou JF, Neglia JP, et al.: Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 37 (24): 2120-2130, 2019. [PUBMED Abstract]
van Santen HM, Tytgat GA, van de Wetering MD, et al.: Differentiated thyroid carcinoma after 131I-MIBG treatment for neuroblastoma during childhood: description of the first two cases. Thyroid 22 (6): 643-6, 2012. [PUBMED Abstract]
Sklar C, Whitton J, Mertens A, et al.: Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 85 (9): 3227-32, 2000. [PUBMED Abstract]
Bhatti P, Veiga LH, Ronckers CM, et al.: Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat Res 174 (6): 741-52, 2010. [PUBMED Abstract]
Michaelson EM, Chen YH, Silver B, et al.: Thyroid malignancies in survivors of Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 88 (3): 636-41, 2014. [PUBMED Abstract]
Sigurdson AJ, Ronckers CM, Mertens AC, et al.: Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet 365 (9476): 2014-23, 2005 Jun 11-17. [PUBMED Abstract]
Neglia JP, Friedman DL, Yasui Y, et al.: Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst 93 (8): 618-29, 2001. [PUBMED Abstract]
Bowers DC, Nathan PC, Constine L, et al.: Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review. Lancet Oncol 14 (8): e321-8, 2013. [PUBMED Abstract]
Taylor AJ, Little MP, Winter DL, et al.: Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 28 (36): 5287-93, 2010. [PUBMED Abstract]
Faraci M, Morana G, Bagnasco F, et al.: Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study. Pediatr Blood Cancer 57 (2): 240-6, 2011. [PUBMED Abstract]
Vinchon M, Leblond P, Caron S, et al.: Radiation-induced tumors in children irradiated for brain tumor: a longitudinal study. Childs Nerv Syst 27 (3): 445-53, 2011. [PUBMED Abstract]
Koike T, Yanagimachi N, Ishiguro H, et al.: High incidence of radiation-induced cavernous hemangioma in long-term survivors who underwent hematopoietic stem cell transplantation with radiation therapy during childhood or adolescence. Biol Blood Marrow Transplant 18 (7): 1090-8, 2012. [PUBMED Abstract]
Hawkins MM, Wilson LM, Burton HS, et al.: Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst 88 (5): 270-8, 1996. [PUBMED Abstract]
Wong JR, Morton LM, Tucker MA, et al.: Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. J Clin Oncol 32 (29): 3284-90, 2014. [PUBMED Abstract]
Fidler MM, Reulen RC, Winter DL, et al.: Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe. J Natl Cancer Inst 110 (2): , 2018. [PUBMED Abstract]
Bright CJ, Hawkins MM, Winter DL, et al.: Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe. J Natl Cancer Inst 110 (6): 649-660, 2018. [PUBMED Abstract]
Chaussade A, Millot G, Wells C, et al.: Correlation between RB1germline mutations and second primary malignancies in hereditary retinoblastoma patients treated with external beam radiotherapy. Eur J Med Genet 62 (3): 217-223, 2019. [PUBMED Abstract]
Schwartz B, Benadjaoud MA, Cléro E, et al.: Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment. Radiat Environ Biophys 53 (2): 381-90, 2014. [PUBMED Abstract]
Henderson TO, Whitton J, Stovall M, et al.: Secondary sarcomas in childhood cancer survivors: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 99 (4): 300-8, 2007. [PUBMED Abstract]
Shinohara ET, DeWees T, Perkins SM: Subsequent malignancies and their effect on survival in patients with retinoblastoma. Pediatr Blood Cancer 61 (1): 116-9, 2014. [PUBMED Abstract]
MacCarthy A, Bayne AM, Brownbill PA, et al.: Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004. Br J Cancer 108 (12): 2455-63, 2013. [PUBMED Abstract]
Yu CL, Tucker MA, Abramson DH, et al.: Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst 101 (8): 581-91, 2009. [PUBMED Abstract]
Temming P, Arendt M, Viehmann A, et al.: Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center. Pediatr Blood Cancer 64 (1): 71-80, 2017. [PUBMED Abstract]
Henderson TO, Rajaraman P, Stovall M, et al.: Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int J Radiat Oncol Biol Phys 84 (1): 224-30, 2012. [PUBMED Abstract]
Daniëls LA, Krol AD, Schaapveld M, et al.: Long-term risk of secondary skin cancers after radiation therapy for Hodgkin's lymphoma. Radiother Oncol 109 (1): 140-5, 2013. [PUBMED Abstract]
Watt TC, Inskip PD, Stratton K, et al.: Radiation-related risk of basal cell carcinoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 104 (16): 1240-50, 2012. [PUBMED Abstract]
Teepen JC, Kok JL, Kremer LC, et al.: Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study. J Natl Cancer Inst : , 2019. [PUBMED Abstract]
Braam KI, Overbeek A, Kaspers GJ, et al.: Malignant melanoma as second malignant neoplasm in long-term childhood cancer survivors: a systematic review. Pediatr Blood Cancer 58 (5): 665-74, 2012. [PUBMED Abstract]
Pappo AS, Armstrong GT, Liu W, et al.: Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study. Pediatr Blood Cancer 60 (3): 461-6, 2013. [PUBMED Abstract]
van Leeuwen FE, Klokman WJ, Stovall M, et al.: Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease. J Natl Cancer Inst 87 (20): 1530-7, 1995. [PUBMED Abstract]
Tukenova M, Diallo I, Anderson H, et al.: Second malignant neoplasms in digestive organs after childhood cancer: a cohort-nested case-control study. Int J Radiat Oncol Biol Phys 82 (3): e383-90, 2012. [PUBMED Abstract]
Henderson TO, Oeffinger KC, Whitton J, et al.: Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med 156 (11): 757-66, W-260, 2012. [PUBMED Abstract]
Nottage K, McFarlane J, Krasin MJ, et al.: Secondary colorectal carcinoma after childhood cancer. J Clin Oncol 30 (20): 2552-8, 2012. [PUBMED Abstract]
Allodji RS, Haddy N, Vu-Bezin G, et al.: Risk of subsequent colorectal cancers after a solid tumor in childhood: Effects of radiation therapy and chemotherapy. Pediatr Blood Cancer 66 (2): e27495, 2019. [PUBMED Abstract]
Daly PE, Samiee S, Cino M, et al.: High prevalence of adenomatous colorectal polyps in young cancer survivors treated with abdominal radiation therapy: results of a prospective trial. Gut 66 (10): 1797-1801, 2017. [PUBMED Abstract]
Teepen JC, Kok JL, van Leeuwen FE, et al.: Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study. J Natl Cancer Inst 110 (7): 758-767, 2018. [PUBMED Abstract]
Kleinerman RA, Tucker MA, Sigel BS, et al.: Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914-2016. J Natl Cancer Inst 111 (9): 961-969, 2019. [PUBMED Abstract]
Rigter LS, Spaander MCW, Aleman BMP, et al.: High prevalence of advanced colorectal neoplasia and serrated polyposis syndrome in Hodgkin lymphoma survivors. Cancer 125 (6): 990-999, 2019. [PUBMED Abstract]
Wilson CL, Ness KK, Neglia JP, et al.: Renal carcinoma after childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 105 (7): 504-8, 2013. [PUBMED Abstract]
de Vathaire F, Scwhartz B, El-Fayech C, et al.: Risk of a Second Kidney Carcinoma Following Childhood Cancer: Role of Chemotherapy and Radiation Dose to Kidneys. J Urol 194 (5): 1390-5, 2015. [PUBMED Abstract]
Fleitz JM, Wootton-Gorges SL, Wyatt-Ashmead J, et al.: Renal cell carcinoma in long-term survivors of advanced stage neuroblastoma in early childhood. Pediatr Radiol 33 (8): 540-5, 2003. [PUBMED Abstract]
Hedgepeth RC, Zhou M, Ross J: Rapid development of metastatic Xp11 translocation renal cell carcinoma in a girl treated for neuroblastoma. J Pediatr Hematol Oncol 31 (8): 602-4, 2009. [PUBMED Abstract]
Argani P, Laé M, Ballard ET, et al.: Translocation carcinomas of the kidney after chemotherapy in childhood. J Clin Oncol 24 (10): 1529-34, 2006. [PUBMED Abstract]
Archer NM, Amorim RP, Naves R, et al.: An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-Based Evidence for a Cancer Predisposition Syndrome? Pediatr Blood Cancer 63 (2): 196-201, 2016. [PUBMED Abstract]
Wang X, Sun CL, Hageman L, et al.: Clinical and Genetic Risk Prediction of Subsequent CNS Tumors in Survivors of Childhood Cancer: A Report From the COG ALTE03N1 Study. J Clin Oncol 35 (32): 3688-3696, 2017. [PUBMED Abstract]
Andersson A, Enblad G, Tavelin B, et al.: Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma. Br J Cancer 98 (5): 1001-5, 2008. [PUBMED Abstract]
Hisada M, Garber JE, Fung CY, et al.: Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90 (8): 606-11, 1998. [PUBMED Abstract]
Strahm B, Malkin D: Hereditary cancer predisposition in children: genetic basis and clinical implications. Int J Cancer 119 (9): 2001-6, 2006. [PUBMED Abstract]
Collins A, Harrington V: Repair of oxidative DNA damage: assessing its contribution to cancer prevention. Mutagenesis 17 (6): 489-93, 2002. [PUBMED Abstract]
Kremer LC, Mulder RL, Oeffinger KC, et al.: A worldwide collaboration to harmonize guidelines for the long-term follow-up of childhood and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Pediatr Blood Cancer 60 (4): 543-9, 2013. [PUBMED Abstract]
Diller L, Medeiros Nancarrow C, Shaffer K, et al.: Breast cancer screening in women previously treated for Hodgkin's disease: a prospective cohort study. J Clin Oncol 20 (8): 2085-91, 2002. [PUBMED Abstract]
Mulder RL, Kremer LC, Hudson MM, et al.: Recommendations for breast cancer surveillance for female survivors of childhood, adolescent, and young adult cancer given chest radiation: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 14 (13): e621-9, 2013. [PUBMED Abstract]
Kriege M, Brekelmans CT, Boetes C, et al.: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351 (5): 427-37, 2004. [PUBMED Abstract]
Leach MO, Boggis CR, Dixon AK, et al.: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 365 (9473): 1769-78, 2005 May 21-27. [PUBMED Abstract]
Tieu MT, Cigsar C, Ahmed S, et al.: Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging. Cancer 120 (16): 2507-13, 2014. [PUBMED Abstract]
Saslow D, Boetes C, Burke W, et al.: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57 (2): 75-89, 2007 Mar-Apr. [PUBMED Abstract]
Berrington de Gonzalez A, Berg CD, Visvanathan K, et al.: Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. J Natl Cancer Inst 101 (3): 205-9, 2009. [PUBMED Abstract]
Young KC, Burch A, Oduko JM: Radiation doses received in the UK Breast Screening Programme in 2001 and 2002. Br J Radiol 78 (927): 207-18, 2005. [PUBMED Abstract]
Spelic DC: Trends in Mammography Dose and Image Quality 1974-2005. Silver Spring, Md: U.S. Food and Drug Administration, 2006. Available online. Last accessed April 17, 2019.
Cardiovascular disease, after recurrence of the original cancer and development of second primary cancers, has been reported to be the leading cause of premature mortality among long-term childhood cancer survivors.[1-5]
Evidence (excess risk of premature cardiovascular mortality):
Among more than 20,000 North American 5-year survivors of childhood cancer (in the Childhood Cancer Survivor Study [CCSS]) treated from 1970 to 1986, participants had a standardized mortality ratio of 7.0 (95% confidence interval [CI], 5.9–8.2) for cardiac mortality, which translated to 0.36 excess deaths per 1,000 person-years.[1]
All-cause circulatory disease was associated with an absolute excess risk of 3.4% (95% CI, 2.8%–4.2%) among nearly 18,000 5-year survivors in the British CCSS who were diagnosed with cancer between 1950 and 1991. Individual standardized mortality ratios for cardiac, cerebrovascular, and other circulatory diseases ranged from 3.5 to 5.2.[2]
By age 45 years, the overall cumulative incidence of severe, life-threatening, or fatal cardiac events has been reported to be approximately 5% for coronary artery disease and heart failure separately and 1% to 2% for valve disorders and arrhythmias.[6] Compared with siblings, 5-year survivors had relative risks (RRs) approaching, if not exceeding, tenfold for heart failure, coronary artery disease, and cerebrovascular disease.[7] The burden of subclinical disease is likely much greater.[8]
The specific late effects covered in this section include the following:
Cardiomyopathy/heart failure.
Ischemic heart disease.
Pericardial heart disease.
Valve disease.
Conduction disorders.
Cerebrovascular disease.
Venous thromboembolism.
The section will also briefly discuss the influence of related conditions such as hypertension, dyslipidemia, and diabetes in relation to these late effects, but not directly review in detail those conditions as a consequence of childhood cancer treatment. A comprehensive review on long-term cardiovascular toxicity in childhood and young adult survivors of cancer, issued by the American Heart Association, has been published.[5]
Overall, there has been a wealth of studies focused on the topic of cardiac events among childhood cancer survivors. In addition to many smaller studies not covered in detail here, the literature includes very large cohort studies that are either hospital based,[6,8-12] clinical trial based,[13,14] or population based,[2,4] many with up to several decades of follow-up. However, even with decades of follow-up, the average age of these populations may still be relatively young (young or middle adulthood). And while the risk of serious cardiovascular outcomes may be very high relative to the age-matched general population, the absolute risk often remains low, limiting the power of many studies. Among the very large studies featuring thousands of survivors, the main limitation has been inadequate ability to clinically ascertain late cardiovascular complications, with a greater reliance on either administrative records (e.g., death registries) and/or self-report or proxy-report.
While each study design has some inherent biases, the overall literature, based on a combination of self-reported outcomes, clinical ascertainment, and administrative data sources, is robust in concluding that certain cancer-related exposures predispose survivors toward a significantly greater risk of cardiovascular morbidity and mortality. Although late effects research often lags behind changes in contemporary therapy, many therapies linked to cardiovascular late effects remain in common use today.[15,16] Ongoing research will be important to ensure that newer targeted agents being introduced today do not result in unexpected cardiovascular effects.[17]
Evidence (selected cohort studies describing cardiovascular outcomes):
In the CCSS, data from 24,214 5-year survivors diagnosed between 1970 and 1999 were used to assess the impacts of radiation therapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk of late-onset cardiac disease.[18]
The cumulative incidence of cardiac disease (any cardiac disease, coronary artery disease, and heart failure) 30 years from diagnosis was 4.8%. Male survivors were more likely to develop coronary artery disease and less likely to develop heart failure than were female survivors. Non-Hispanic black survivors were more likely to develop any cardiac disease than were non-Hispanic white survivors.
Low-to-moderate radiation therapy doses (5.0–19.9 Gy) to large cardiac volumes (>50% of the heart) were associated with a 1.6-fold increased risk of cardiac disease compared with survivors who did not have any cardiac radiation therapy exposure.
High doses (>20 Gy) to small cardiac volumes (0.1%–29.9%) were associated with an elevated rate of cardiac disease compared with unexposed survivors.
A dose-response relationship was observed between anthracycline exposure and heart failure, with younger children (<13 years) at the greatest risk of heart failure after comparable dosing.
A multicenter French cohort of 3,162 5-year survivors treated between 1942 and 1986 were monitored for a median of 26 years.[12]
The cumulative incidence of any cardiac disease (ischemic heart disease, heart failure, arrhythmia, or valve and pericardial diseases) by age 40 years was 11% (7% if restricted to those that warranted medical intervention).
Risk increased with higher anthracycline and radiation doses, particularly anthracycline doses of 250 mg/m2 or more and heart radiation doses of 15 Gy or higher.
A significant interaction was identified between radiation dose, anthracycline exposure, and attained age.
A Dutch hospital-based cohort of 1,362 5-year childhood cancer survivors (median attained age, 29.1 years) were monitored from diagnosis for a median of 22.2 years.[11]
The 30-year cause-specific cumulative incidence of symptomatic cardiac events (congestive heart failure, cardiac ischemia, valve disease, arrhythmia, and/or pericarditis) was significantly increased after treatment with both anthracyclines and cardiac radiation (12.6%; 95% CI, 4.3%–20.3%), anthracyclines alone (7.3%; 95% CI, 3.8%–10.7%), and cardiac radiation alone (4.0%; 95% CI, 0.5%–7.4%) compared with other treatments.
The CCSS demonstrated that the cumulative incidence of serious cardiac events (myocardial infarction, congestive heart failure, pericardial disease, and valvular abnormalities) continued to increase beyond age 45 years.[6]
The risk of these events was potentiated (i.e., beyond what would be expected by an additive model) by the presence of concurrent, but potentially modifiable, conditions such as obesity, dyslipidemia, diabetes, and, particularly, hypertension.
Hypertension was independently associated with all serious cardiac outcomes (RRs, sixfold to 19-fold), even after adjustment for anthracycline use and chest irradiation.
Of 670 survivors of Hodgkin lymphoma (HL) who were treated at St. Jude Children’s Research Hospital (SJCRH) and have lived 10 or more years, 348 patients were clinically assessed in the St. Jude Lifetime Cohort Study.[19]
Overall, survivors had a higher cumulative burden (a novel measurement of disease burden that incorporates multiple health conditions and recurrent events into a single metric) than did community controls, with the total grade 3 to 5 cumulative burden among survivors at age 30 years being comparable to that of community controls at 50 years.
At age 50 years, the cumulative incidence of those survivors experiencing at least one grade 3 to grade 5 cardiovascular condition was 45.5% (95% CI, 36.6%–54.3%), compared with 15.7% (95% CI, 7.0%–24.4%) in community controls.
Myocardial infarction and structural heart defects were the major contributors to the excess grade 3 to grade 5 cumulative burden in survivors, whereas there was no notable difference in survivors and community controls at age 50 years for grades 3 to 5 cumulative burden of dyslipidemia and essential hypertension.
Another St. Jude Lifetime Cohort Study compared the prevalence of major and minor electrocardiography (ECG) abnormalities among 2,715 participants and 268 community controls.[20]
Major ECG abnormalities were significantly more prevalent in survivors (10.7%) than in controls (4.9%); the most common abnormalities included isolated ST-T wave abnormalities (7.2%), evidence of myocardial infarction (3.7%), and left ventricular hypertrophy with strain pattern (2.8%).
Treatment exposures predicting increased risk of major abnormalities were anthracycline doses of 300 mg/m2 or greater (odds ratio [OR], 1.7; 95% CI, 1.1–2.5) and cardiac radiation (OR, 2.1; 95% CI, 1.5–2.9 [1–1,999 cGy]; OR, 2.6; 95% CI, 1.6–3.9 [2,000–2,999 cGy]; OR, 10.5; 95% CI, 6.5–16.9 [≥3,000 cGy]).
Major ECG abnormalities were predictive of all-cause mortality (HR, 4.0; 95% CI, 2.1–7.8).
In the Teenage and Young Adult Cancer Survivor Study, cardiac mortality was investigated in more than 200,000 5-year survivors of adolescent and young adult cancer (aged 15–39 years).[21]
Age at diagnosis and type of cancer were identified as being important in determining risk of cardiac mortality.
The standardized mortality ratios (SMR) for all cardiac disease combined was greatest for individuals diagnosed at age 15 to 19 years (4.2), decreasing to 1.2 for individuals aged 35 to 39 years (2P for trend < .0001). This age effect was most apparent for survivors of Hodgkin lymphoma, who were also found to be at greatest risk overall.
Limitations of this study included lack of detailed information on exposures to radiation therapy (doses, fields), exposures to chemotherapy (primarily anthracycline dose), and cardiovascular risk factors (e.g., smoking, obesity, hypertension, diabetes, family history).
Using data from four large, well-annotated childhood cancer survivor cohorts (CCSS, National Wilms Tumor Study Group, the Netherlands, and SJCRH), a heart failure risk calculator based on readily available demographic and treatment characteristics has been created and validated, which may provide more individualized clinical heart failure risk estimation for 5-year survivors of childhood cancer who have recently completed therapy and up through age 40 years. One limitation of this estimator is that because of the young age of participants at the time of baseline prediction (5-year survival), information on conventional cardiovascular conditions such as hypertension, dyslipidemia, or diabetes could not be incorporated.[22]
In another collaborative study, data from the CCSS, Netherlands, and SJCRH were used to develop risk-prediction models for ischemic heart disease and stroke among 5-year survivors of childhood cancer through 50 years. Risk scores derived from a standard prediction model that included sex, chemotherapy exposure, and radiation therapy exposure identified statistically distinct low-risk, moderate-risk, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were less than 5%, compared with approximately 20% for high-risk groups and only 1% for siblings.[23]
Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-aged survivors of childhood cancer, as demonstrated by a CCSS investigation that constructed prediction models accounting for cardiotoxic cancer treatment exposures, combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes. Risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes showed good performance (area under the receiver operating characteristic curve [AUC] and concordance [C] statistics ≥0.70) for predicting cardiovascular events in the models applied to the discovery and replication cohorts. The most influential exposures were anthracycline, radiation therapy, diabetes, and hypertension.[24]
Treatment Risk Factors
Chemotherapy (in particular, anthracyclines and anthraquinones) along with radiation therapy both independently and in combination, increase the risk of cardiovascular disease in survivors of childhood cancer and are considered to be the most important risk factors contributing to premature cardiovascular disease in this population (refer to Figure 4).[11]
Figure 4. (A, B) Marginal (Kaplan-Meier) and (C–E) cause-specific (competing risk) cumulative incidence of cardiac events (CEs) in childhood cancer survivors stratified according to different treatment groups. (A) Marginal cumulative incidence for all CEs, stratified according to potential cardiotoxic (CTX) therapy or no CTX therapy, log-rank P < .001. (B) Marginal cumulative incidence for all CEs, stratified according to different CTX therapies, log-rank P < .001. (C) Cause-specific cumulative incidence for congestive heart failure, stratified according to different treatment groups, log-rank P < .001. (D) Cause-specific cumulative incidence for cardiac ischemia, stratified according to cardiac irradiation (RTX) or no RTX, log-rank P = .01. (E) Cause-specific cumulative incidence for valvular disease, stratified according to RTX or no RTX, log-rank P < .001. The shaded colorized background areas refer to the 95% CIs. Ant, anthracycline. Helena J. van der Pal, Elvira C. van Dalen, Evelien van Delden, Irma W. van Dijk, Wouter E. Kok, Ronald B. Geskus, Elske Sieswerda, Foppe Oldenburger, Caro C. Koning, Flora E. van Leeuwen, Huib N. Caron, Leontien C. Kremer, High Risk of Symptomatic Cardiac Events in Childhood Cancer Survivors, Journal of Clinical Oncology, volume 30, issue 13, pages 1429-1437. Reprinted with permission. © (2012) American Society of Clinical Oncology. All rights reserved.
Anthracyclines and related agents
Anthracyclines (e.g., doxorubicin, daunorubicin, idarubicin, and epirubicin) and anthraquinones (e.g., mitoxantrone) are known to directly injure cardiomyocytes through the formation of reactive oxygen species and inducing mitochondrial apoptosis.[5,25] The downstream results of cell death are changes in heart structure, including wall thinning, which leads to ventricular overload and pathologic remodeling that, over time, leads to dysfunction and eventual clinical heart failure.[26-29]
Risk factors for anthracycline-related cardiomyopathy include the following:[18,30]
Cumulative dose, particularly greater than 250 mg/m2 to 300 mg/m2.
Younger age at time of exposure, particularly children younger than 5 years.
Increased time from exposure.
Among these factors, cumulative dose appears to be the most significant (refer to Figure 5).[9] While it is not completely certain whether there is a truly safe lower dose threshold, doses in excess of 250 mg/m2 to 300 mg/m2 have been associated with a substantially increased risk of cardiomyopathy, with cumulative incidences exceeding 5% after 20 years of follow-up, and in some subgroups, reaching or exceeding 10% cumulative incidence by age 40 years.[9,10,22,27,29] Concurrent chest or heart radiation therapy also further increases risk of cardiomyopathy,[11,12,22] as does the presence of other cardiometabolic traits such as hypertension.[6,31] While development of clinical heart failure can occur within a few years after anthracycline exposure, in most survivors, even those who received very high doses, clinical manifestations may not occur for decades.
Figure 5. Risk of anthracycline-induced clinical heart failure (A-CHF) according to cumulative anthracycline dose. Reprinted from European Journal of Cancer, Volume 42, Elvira C. van Dalen, Helena J.H. van der Pal, Wouter E.M. Kok, Huib N. Caron, Leontien C.M. Kremer, Clinical heart failure in a cohort of children treated with anthracyclines: A long-term follow-up study, Pages 3191-3198, Copyright (2006), with permission from Elsevier.
Anthracycline dose equivalency
It remains unclear how best to add together doses of different anthracycline agents. A variety of anthracycline equivalence formulas (in relation to doxorubicin) have been used; however, they are largely based on hematologic toxicity equivalence, and may not necessarily be the same for cardiac toxicity.[22,32,33] Most pediatric professional societies and groups have generally considered daunorubicin equivalent, or near equivalent, to doxorubicin, although historically lower ratios have been proposed as well.[34] A large analysis of over 15,000 childhood cancer survivors who were monitored to age 40 years found that daunorubicin may be significantly less cardiotoxic than doxorubicin (equivalence ratio, 0.5 [95% CI, 0.2–0.7]).[35]
Other agents such as idarubicin, epirubicin, and mitoxantrone (an anthraquinone) were designed to reduce cardiac toxicity while maintaining similar antitumor effect, although data supporting this are primarily limited to adult cancer patients.[36] Similarly, data on whether liposomal formulations of anthracyclines reduce cardiac toxicity in children also are limited.[36]
Anthracycline cardioprotection
Cardioprotective strategies that have been explored include the following:
New, less cardiotoxic agents and liposomal formulations.
Prolonged infusion time. Prolonged infusion time has been associated with reduced heart failure in adult patients but not in children.[37,38]
Concurrent administration of cardioprotectants. A variety of agents have been tested as cardioprotectants (amifostine, acetylcysteine, calcium channel blockers, carvedilol, coenzyme Q10, and L-carnitine), but none have been definitively shown to be beneficial and are not considered standard of care.[39,40]
There are more data for dexrazoxane as a cardioprotectant, but again, mainly in adult cancer patients, for whom it is approved by the U.S. Food and Drug Administration for women with metastatic breast cancer who have received 300 mg/m2 of anthracyclines and who may benefit from further anthracycline-based therapy.[39] Pediatric data show that dexrazoxane may ameliorate some markers of early cardiac toxicity up to 5 years after therapy.[41-44] Dexrazoxane may be associated with an increased risk of acute toxicities in some regimens, however.[45] While these data suggest that dexrazoxane does protect the heart in the short term, there are not yet long-term data showing the impact of dexrazoxane on cardiac health.
As a topoisomerase inhibitor, dexrazoxane’s association with secondary cancers, particularly secondary leukemia, remains controversial.[44,46] One report that described the use of concurrent etoposide and doxorubicin observed an increased risk of acute myeloid leukemia (AML) among patients treated with dexrazoxane.[47] However, all other pediatric randomized controlled and nonrandomized studies have not observed an increased risk of subsequent malignant neoplasms in conjunction with dexrazoxane,[44] and the risk of secondary AML was not increased among children treated with dexrazoxane who were registered in the Pediatric Health Information Systems database.[48] Another randomized trial reported an increased risk of secondary brain tumors among survivors treated with cranial irradiation, but this risk did not differ among patients who did and did not receive dexrazoxane.[43]
While anthracyclines directly damage cardiomyocytes, radiation therapy primarily affects the fine vasculature of affected organs.[5]
Late effects of radiation therapy to the heart specifically include the following:
Delayed pericarditis, which can present abruptly or as a chronic pericardial effusion.
Pancarditis, which includes pericardial and myocardial fibrosis, with or without endocardial fibroelastosis.
Cardiomyopathy (in the absence of significant pericardial disease), which can occur even without anthracycline exposure.
Functional valve injury, often aortic.
Conduction defects.
These cardiac late effects are related to the following:
Individual radiation fraction size.
Volume of the heart that is exposed to radiation.[18]
Total radiation dose. Various studies have demonstrated a substantially increased risk of these outcomes with higher radiation doses, particularly doses to the heart exceeding 35 Gy (refer to Figure 6).[10-12,14,49,50] At higher radiation doses, rates of heart failure, pericardial disease, and valvular disease have been reported to exceed 10% after 20 to 30 years. Although some studies suggest that doses less than 5 Gy may be associated with an increased risk of cardiovascular disease, the RR is small (i.e., 2.5) and the 95% CI is large (i.e., 0.2–41.5); moreover, the dosimetric analyses are generally estimations of incidental cardiac exposure.[3,10-12] Low-to-moderate radiation therapy doses (5.0–19.9 Gy) to large cardiac volumes (>50% of the heart) are associated with an increased rate of cardiac disease (i.e., 1.6) compared with survivors who did not have any cardiac radiation therapy exposure. High doses of radiation (>20 Gy) to small cardiac volumes (0.1%–29.9%) are associated with an elevated rate of cardiac disease (2.4).[18] Consequently, additional confirmatory data are needed for an accurate assessment of risk at very low cardiac doses.
Figure 6. Cumulative incidence of cardiac disorders among childhood cancer survivors by average cardiac radiation dose. BMJ 2009; 339:b4606. © 2009 by British Medical Journal Publishing Group.
Similar to anthracyclines, manifestation of these late effects may take years, if not decades, to present. Finally, patients who were exposed to both radiation therapy affecting the cardiovascular system and cardiotoxic chemotherapy agents are at even greater risk of late cardiovascular outcomes.[12,18]
Cerebrovascular disease after radiation therapy exposure is another potential late effect for survivors. While brain tumor survivors have had traditionally the greatest risk, other survivors exposed to cranial irradiation (≥18 Gy) and neck irradiation (≥40 Gy), such as leukemia and lymphoma survivors, have also been reported to be at increased risk.[51-54] In lymphoma survivors who only received chest and/or neck radiation therapy, cerebrovascular disease is thought to be caused by large-vessel atherosclerosis and cardiac embolism.[52]
As with cardiac outcomes, risk increases with cumulative dose received. One study (N = 325) reported that the stroke hazard increased by 5% (hazard ratio [HR], 1.05; 95% CI, 1.01–1.09; P = .02), with each 1 Gy increase in the radiation dose, leading to a cumulative incidence of 2% for the first stroke after 5 years and 4% after 10 years.[55] Survivors who experienced stroke were then at significantly greater risk of experiencing recurrent strokes.
Evidence (selected studies describing prevalence of and risk factors for cerebrovascular [CVA]/vascular disease):
In a multicenter retrospective Dutch study, among 2,201 5-year survivors of HL diagnosed before age 51 years (25% pediatric-aged patients), with a median follow-up of 18 years, 96 patients developed cerebrovascular disease (CVA and transient ischemic attacks [TIA]).[52]
Most ischemic events were from large-artery atherosclerosis (36%) or cardiac embolism (24%).
The cumulative incidence of ischemic CVA or TIA 30 years after lymphoma treatment was 7%.
The overall standardized incidence ratio (SIR) was 2.2 for CVA and 3.1 for TIA. However, SIR estimates appeared to be greater among childhood cancer survivors, with SIRs of 3.8 for CVA and 7.6 for TIA.
Irradiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (HR, 2.5; 95% CI, 1.1–5.6) versus no radiation therapy. Treatment with chemotherapy was not associated with increased risk.
Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease.
French investigators observed a significant association between radiation dose to the brain and long-term cerebrovascular mortality among 4,227 5-year childhood cancer survivors (median follow-up, 29 years).[53]
Survivors who received more than 50 Gy to the prepontine cistern had an HR of 17.8 (95% CI, 4.4–73.0) for death from cerebrovascular disease, compared with those who had not received radiation therapy or who had received less than 0.1 Gy in the prepontine cistern region.
A retrospective, single-center, cohort study of 325 survivors of pediatric cancer treated with cranial irradiation or cervical irradiation determined that cranial irradiation put survivors at a high risk of first and recurrent strokes.[55]
The cumulative incidence of first stroke was 4% (95% CI, 2.0%–8.4%) at 10 years after radiation therapy. The stroke hazard increased by 5% (HR, 1.05; 95% CI, 1.01–1.09; P = .02) with each 1 Gy increase in the radiation dose.
The cumulative incidence of recurrent stroke was 38% (95% CI, 17%–69%) at 5 years and 59% (95% CI, 27%–92%) at 10 years after the first stroke.
CCSS investigators evaluated the rates and predictors of recurrent stroke among participants who reported a first stroke.[56]
Among responding participants (329 of 443), 271 confirmed a first stroke (at median age, 19 years) and 70 reported a second stroke (at median age, 32 years).
Independent predictors of recurrent stroke included treatment with a cranial radiation therapy dose of 50 Gy or higher (vs. no cranial radiation therapy), history of hypertension, and age 40 years or older at first stroke (vs. age 0–17 years).
The 10-year cumulative incidence of late recurrent stroke was 21% overall, and 33% for those treated with 50 Gy or higher of cranial radiation therapy.
A retrospective study of 3,172 5-year survivors of childhood cancer monitored for a mean time of 26 years was constituted from the Euro2K cohort, which included eight centers in France and the United Kingdom. Radiation doses to the Circle of Willis were estimated for each of the 2,202 children who received radiation therapy.[57]
Patients who received radiation therapy had an 8.5-fold increased risk (95% CI, 6.3–11.0) of stroke in contrast to a nonelevated risk for patients not receiving radiation therapy.
The RR was 15.7 (95% CI, 4.9–50.2) for doses of 40 Gy or higher.
At age 45 years, the cumulative incidence was 11.3% (95% CI, 7.1%–17.7%) in patients who received 10 Gy or higher to the Circle of Willis, compared with 1% in the general population.
Investigators from the Teenage and Young Adult Cancer Survivor Study (N = 178,962) evaluated the risk of hospitalization for a cerebrovascular event among 5-year survivors of cancer diagnosed between age 15 and 39 years.[58]
The investigators found that survivors of adolescent and young adult cancers had a 40% increased risk of hospitalization for cerebrovascular event compared with the general population.
Survivors of central nervous system (CNS) tumors (standardized hospitalization ratios [SHR], 4.6), head and neck tumors (SHR, 2.6), and leukemia (SHR, 2.5) had the highest risk of hospitalization for a cerebrovascular complication.
Males had significantly higher absolute excess risks than did females, especially among head and neck tumor survivors. By age 60 years, 9% of CNS tumor survivors, 6% of head and neck tumor survivors, and 5% of leukemia survivors had been hospitalized for a cerebrovascular event.
The risk of hospitalization for a cerebral infarction was particularly increased among survivors of a CNS tumor older than 60 years, whereas this risk was increased across all ages in survivors of head and neck tumors.
Children with cancer have an excess risk of venous thromboembolism within the first 5 years after diagnosis; however, the long-term risk of venous thromboembolism among childhood cancer survivors has not been well studied.[59] CCSS investigators evaluated self-reported late-onset (5 or more years after cancer diagnosis) venous thromboembolism among cohort members (median follow-up, 21.3 years). The 35-year cumulative incidence of venous thromboembolism among survivors was 4.9%, which represented a more-than-twofold-higher risk compared with a sibling cohort (RR, 2.2; 95% CI, 1.7–2.8). Risk factors for venous thromboembolism among survivors included female sex, treatment with cisplatin or asparaginase, obesity or underweight, and recurrent primary or subsequent cancer. The risk of late venous thromboembolism was higher among survivors of lower-extremity osteosarcoma treated with limb-sparing surgery compared with patients treated with any amputation, possibly resulting from alterations in peripheral vascular anatomy and homeostasis. Venous thromboembolism was associated with an almost-twofold increased risk of late mortality (RR, 1.9; 95% CI, 1.6–2.3).[60]
Conventional cardiovascular conditions
Various cancer treatment exposures may also directly or indirectly influence the development of hypertension, diabetes mellitus, and dyslipidemia.[5] These conditions remain important among cancer survivors, as they do in the general population, in that they are independent risk factors in the development of cardiomyopathy, ischemic heart disease, and cerebrovascular disease.[6,52,61-64]
Childhood cancer survivors should be closely screened for the development of these cardiovascular conditions because they represent potentially modifiable targets for intervention. This includes being aware of related conditions such as obesity and various endocrinopathies (e.g., hypothyroidism, hypogonadism, growth hormone deficiency) that may be more common among subsets of childhood cancer survivors; if these conditions are untreated/uncontrolled, they may be associated with a metabolic profile that increases cardiovascular risk.[8,65]
Other Risk Factors
Some, but not all, studies suggest that female sex may be associated with a greater risk of anthracycline-related cardiomyopathy.[5] In addition, there is emerging evidence that genetic factors, such as single nucleotide polymorphisms in genes regulating drug metabolism and distribution, could explain the heterogeneity in susceptibility to anthracycline-mediated cardiac injury.[66-71] However, these genetic findings still require additional validation before being incorporated into any clinical screening algorithm.[72]
In a study of solid organ transplants in 13,318 survivors in the CCSS, 62 survivors had end-stage heart failure that warranted heart transplants, 37 of whom received a heart transplant. At 35 years after cancer diagnosis, the cumulative incidence of heart transplant was 0.30%, and the cumulative incidence of being placed on the waiting list or receiving a heart was 0.49%. The 5-year survival rate from heart transplant was 80.6%, which is similar to the outcome in the general population of the same age range.[73]
Knowledge Deficits
While much knowledge has been gained over the past 20 years in better understanding the long-term burden and risk factors for cardiovascular disease among childhood cancer survivors, many areas of inquiry remain, and include the following:
Radiation may have both direct and indirect effects on vascular endothelium, contributing to vascular damage beyond the primary radiation field.[74]
The long-term effects of lower radiation doses, particularly in light of newer technology that allows radiation oncologists to reduce the dose to critical organs outside of the tumor field, remain to be determined.[75]
The long-term effects of many newer anticancer agents that are based on molecular targets remains unclear, although some of them are known to have shorter-term cardiac toxicity.[17]
The efficacy of cardioprotective strategies, including the use of alternative anthracycline formulations that appear promising in adults, requires further study in children.[40]
Screening, Surveillance, and Counseling
Various national groups, including the National Institutes of Health–sponsored COG (refer to Table 2), have published recommendations regarding screening and surveillance for cardiovascular and other late effects among childhood cancer survivors.[76-80] Professional groups (both pediatric and adult) have developed evidence-based health surveillance recommendations and have identified knowledge deficits to help guide future studies.[30,81] Adult oncology professional and national groups have also issued recommendations related to cardiac toxicity monitoring.[82]
At this point, there is no clear evidence (at least through age 50 years or 30–40 years posttreatment) that there is a plateau in risk that occurs after a certain time among survivors exposed to cancer treatments associated with cardiovascular late effects.[3,4,10,11,51,83] Thus, some form of life-long surveillance is recommended, even if the cost-effectiveness of certain screening strategies remains unclear.[30,84-86]
However, a growing amount of literature is beginning to establish the yield from these screening studies, which will help inform future guidelines.[8,87-89] In these studies, for example, among adult-aged survivors of childhood cancer, evidence for cardiomyopathy on the basis of echocardiographic changes was found in approximately 6% of at-risk survivors. Overall, in a cohort of more than 1,000 survivors (median age, 32 years), nearly 60% of screened at-risk survivors had some clinically ascertained cardiac abnormality identified.[8]
Given the growing evidence that conventional cardiovascular conditions such as hypertension, dyslipidemia, and diabetes substantially increase the risk of more serious cardiovascular disease among survivors, clinicians should carefully consider baseline and follow-up screening and treatment of these comorbid conditions that impact cardiovascular health (refer to Table 2).[6,52,61,62]
There is also emerging evidence that adoption of healthier lifestyle factors may decrease future cardiovascular morbidity in at-risk survivors.[90] Thus, similar to the general population, survivors are counseled about maintaining a healthy weight, participating in regular physical activity, adhering to a heart-healthy diet, and abstaining from smoking.
In addition to releasing a comprehensive, publicly available (online) set of guidelines, the COG has also put together a series of handouts on cardiovascular and related topics, including lifestyle choices written for a lay audience, available on the same website.
Table 2. Cardiovascular Late Effectsa,b
Predisposing Therapy
Potential Cardiovascular Effects
aThe Children's Oncology Group (COG) guidelines also cover other conditions that may influence cardiovascular risk also exist, such as obesity and diabetes mellitus/impaired glucose metabolism.
bAdapted from the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.
Any anthracycline and/or any radiation to the heart Cardiac toxicity (arrhythmia, cardiomyopathy/heart failure, pericardial disease, valve disease, ischemic heart disease) Yearly medical history and physical exam
Electrocardiogram at entry into long-term follow-up
Echocardiogram at entry into long-term follow-up, periodically repeat based on previous exposures and other risk factors
Radiation to the area (≥40 Gy) Carotid and/or subclavian artery disease Yearly medical history and physical exam; consider Doppler ultrasound 10 years after exposure
Radiation to the brain/cranium (≥18 Gy) Cerebrovascular disease (cavernomas, Moyamoya, occlusive cerebral vasculopathy, stroke) Yearly medical history and physical exam
Radiation to the abdomen Diabetes Diabetes screen every 2 years
Total-body irradiation Dyslipidemia; diabetes Fasting lipid profile and diabetes screen every 2 years
Heavy metals (carboplatin, cisplatin), ifosfamide, and methotrexate exposure; radiation to the kidneys; hematopoietic cell transplantation; nephrectomy Hypertension (as a consequence of renal toxicity) Yearly blood pressure and urinalysis; renal function laboratory studies at entry into long-term follow-up
Tukenova M, Guibout C, Oberlin O, et al.: Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol 28 (8): 1308-15, 2010. [PUBMED Abstract]
Kero AE, Järvelä LS, Arola M, et al.: Cardiovascular morbidity in long-term survivors of early-onset cancer: a population-based study. Int J Cancer 134 (3): 664-73, 2014. [PUBMED Abstract]
Lipshultz SE, Adams MJ, Colan SD, et al.: Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation 128 (17): 1927-95, 2013. [PUBMED Abstract]
Armstrong GT, Oeffinger KC, Chen Y, et al.: Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 31 (29): 3673-80, 2013. [PUBMED Abstract]
van Dalen EC, van der Pal HJ, Kok WE, et al.: Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. Eur J Cancer 42 (18): 3191-8, 2006. [PUBMED Abstract]
Mulrooney DA, Yeazel MW, Kawashima T, et al.: Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339: b4606, 2009. [PUBMED Abstract]
van der Pal HJ, van Dalen EC, van Delden E, et al.: High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 30 (13): 1429-37, 2012. [PUBMED Abstract]
Haddy N, Diallo S, El-Fayech C, et al.: Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study. Circulation 133 (1): 31-8, 2016. [PUBMED Abstract]
Green DM, Grigoriev YA, Nan B, et al.: Congestive heart failure after treatment for Wilms' tumor: a report from the National Wilms' Tumor Study group. J Clin Oncol 19 (7): 1926-34, 2001. [PUBMED Abstract]
Schellong G, Riepenhausen M, Bruch C, et al.: Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies. Pediatr Blood Cancer 55 (6): 1145-52, 2010. [PUBMED Abstract]
Green DM, Kun LE, Matthay KK, et al.: Relevance of historical therapeutic approaches to the contemporary treatment of pediatric solid tumors. Pediatr Blood Cancer 60 (7): 1083-94, 2013. [PUBMED Abstract]
Hudson MM, Neglia JP, Woods WG, et al.: Lessons from the past: opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies. Pediatr Blood Cancer 58 (3): 334-43, 2012. [PUBMED Abstract]
Moslehi JJ: Cardiovascular Toxic Effects of Targeted Cancer Therapies. N Engl J Med 375 (15): 1457-1467, 2016. [PUBMED Abstract]
Bates JE, Howell RM, Liu Q, et al.: Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study. J Clin Oncol 37 (13): 1090-1101, 2019. [PUBMED Abstract]
Bhakta N, Liu Q, Yeo F, et al.: Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma: an analysis from the St Jude Lifetime Cohort Study. Lancet Oncol 17 (9): 1325-34, 2016. [PUBMED Abstract]
Mulrooney DA, Soliman EZ, Ehrhardt MJ, et al.: Electrocardiographic abnormalities and mortality in aging survivors of childhood cancer: A report from the St Jude Lifetime Cohort Study. Am Heart J 189: 19-27, 2017. [PUBMED Abstract]
Henson KE, Reulen RC, Winter DL, et al.: Cardiac Mortality Among 200 000 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The Teenage and Young Adult Cancer Survivor Study. Circulation 134 (20): 1519-1531, 2016. [PUBMED Abstract]
Chow EJ, Chen Y, Kremer LC, et al.: Individual prediction of heart failure among childhood cancer survivors. J Clin Oncol 33 (5): 394-402, 2015. [PUBMED Abstract]
Chow EJ, Chen Y, Hudson MM, et al.: Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer. J Clin Oncol 36 (1): 44-52, 2018. [PUBMED Abstract]
Chen Y, Chow EJ, Oeffinger KC, et al.: Traditional cardiovascular risk factors and individual prediction of cardiovascular events in childhood cancer survivors. J Natl Cancer Inst : , 2019. [PUBMED Abstract]
Zhang S, Liu X, Bawa-Khalfe T, et al.: Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18 (11): 1639-42, 2012. [PUBMED Abstract]
Silber JH, Cnaan A, Clark BJ, et al.: Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol 22 (5): 820-8, 2004. [PUBMED Abstract]
Lipshultz SE, Lipsitz SR, Sallan SE, et al.: Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 23 (12): 2629-36, 2005. [PUBMED Abstract]
Hudson MM, Rai SN, Nunez C, et al.: Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. J Clin Oncol 25 (24): 3635-43, 2007. [PUBMED Abstract]
van der Pal HJ, van Dalen EC, Hauptmann M, et al.: Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch Intern Med 170 (14): 1247-55, 2010. [PUBMED Abstract]
Armenian SH, Hudson MM, Mulder RL, et al.: Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 16 (3): e123-36, 2015. [PUBMED Abstract]
Armenian SH, Sun CL, Vase T, et al.: Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease. Blood 120 (23): 4505-12, 2012. [PUBMED Abstract]
Children's Oncology Group: Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, Version 4.0. Monrovia, Ca: Children's Oncology Group, 2013. Available online. Last accessed April 17, 2019.
Le Deley MC, Leblanc T, Shamsaldin A, et al.: Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Société Française d'Oncologie Pédiatrique. J Clin Oncol 21 (6): 1074-81, 2003. [PUBMED Abstract]
Keefe DL: Anthracycline-induced cardiomyopathy. Semin Oncol 28 (4 Suppl 12): 2-7, 2001. [PUBMED Abstract]
Feijen EA, Leisenring WM, Stratton KL, et al.: Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart Failure in Survivors of Childhood Cancer. J Clin Oncol 33 (32): 3774-80, 2015. [PUBMED Abstract]
van Dalen EC, Michiels EM, Caron HN, et al.: Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev (5): CD005006, 2010. [PUBMED Abstract]
van Dalen EC, van der Pal HJ, Caron HN, et al.: Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev (4): CD005008, 2009. [PUBMED Abstract]
Lipshultz SE, Giantris AL, Lipsitz SR, et al.: Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol 20 (6): 1677-82, 2002. [PUBMED Abstract]
Hensley ML, Hagerty KL, Kewalramani T, et al.: American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 27 (1): 127-45, 2009. [PUBMED Abstract]
van Dalen EC, Caron HN, Dickinson HO, et al.: Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev (6): CD003917, 2011. [PUBMED Abstract]
Wexler LH, Andrich MP, Venzon D, et al.: Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol 14 (2): 362-72, 1996. [PUBMED Abstract]
Lipshultz SE, Scully RE, Lipsitz SR, et al.: Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol 11 (10): 950-61, 2010. [PUBMED Abstract]
Asselin BL, Devidas M, Chen L, et al.: Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children's Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Oncol 34 (8): 854-62, 2016. [PUBMED Abstract]
Shaikh F, Dupuis LL, Alexander S, et al.: Cardioprotection and Second Malignant Neoplasms Associated With Dexrazoxane in Children Receiving Anthracycline Chemotherapy: A Systematic Review and Meta-Analysis. J Natl Cancer Inst 108 (4): , 2016. [PUBMED Abstract]
Schwartz CL, Constine LS, Villaluna D, et al.: A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood 114 (10): 2051-9, 2009. [PUBMED Abstract]
Chow EJ, Asselin BL, Schwartz CL, et al.: Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group. J Clin Oncol 33 (24): 2639-45, 2015. [PUBMED Abstract]
Tebbi CK, London WB, Friedman D, et al.: Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol 25 (5): 493-500, 2007. [PUBMED Abstract]
Walker DM, Fisher BT, Seif AE, et al.: Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid leukemia from 1999 and 2009: analysis of a national cohort of patients in the Pediatric Health Information Systems database. Pediatr Blood Cancer 60 (4): 616-20, 2013. [PUBMED Abstract]
Galper SL, Yu JB, Mauch PM, et al.: Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. Blood 117 (2): 412-8, 2011. [PUBMED Abstract]
Mulrooney DA, Nunnery SE, Armstrong GT, et al.: Coronary artery disease detected by coronary computed tomography angiography in adult survivors of childhood Hodgkin lymphoma. Cancer 120 (22): 3536-44, 2014. [PUBMED Abstract]
Bowers DC, Liu Y, Leisenring W, et al.: Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24 (33): 5277-82, 2006. [PUBMED Abstract]
De Bruin ML, Dorresteijn LD, van't Veer MB, et al.: Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma. J Natl Cancer Inst 101 (13): 928-37, 2009. [PUBMED Abstract]
Haddy N, Mousannif A, Tukenova M, et al.: Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain 134 (Pt 5): 1362-72, 2011. [PUBMED Abstract]
van Dijk IW, van der Pal HJ, van Os RM, et al.: Risk of Symptomatic Stroke After Radiation Therapy for Childhood Cancer: A Long-Term Follow-Up Cohort Analysis. Int J Radiat Oncol Biol Phys 96 (3): 597-605, 2016. [PUBMED Abstract]
Mueller S, Sear K, Hills NK, et al.: Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys 86 (4): 643-8, 2013. [PUBMED Abstract]
Fullerton HJ, Stratton K, Mueller S, et al.: Recurrent stroke in childhood cancer survivors. Neurology 85 (12): 1056-64, 2015. [PUBMED Abstract]
El-Fayech C, Haddy N, Allodji RS, et al.: Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries. Int J Radiat Oncol Biol Phys 97 (2): 278-286, 2017. [PUBMED Abstract]
Bright CJ, Hawkins MM, Guha J, et al.: Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study). Circulation 135 (13): 1194-1210, 2017. [PUBMED Abstract]
Walker AJ, Grainge MJ, Card TR, et al.: Venous thromboembolism in children with cancer - a population-based cohort study. Thromb Res 133 (3): 340-4, 2014. [PUBMED Abstract]
Madenci AL, Weil BR, Liu Q, et al.: Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol : JCO2018784595, 2018. [PUBMED Abstract]
Mueller S, Fullerton HJ, Stratton K, et al.: Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 86 (4): 649-55, 2013. [PUBMED Abstract]
Lipshultz SE, Landy DC, Lopez-Mitnik G, et al.: Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. J Clin Oncol 30 (10): 1050-7, 2012. [PUBMED Abstract]
Chao C, Xu L, Bhatia S, et al.: Cardiovascular Disease Risk Profiles in Survivors of Adolescent and Young Adult (AYA) Cancer: The Kaiser Permanente AYA Cancer Survivors Study. J Clin Oncol 34 (14): 1626-33, 2016. [PUBMED Abstract]
Winther JF, Bhatia S, Cederkvist L, et al.: Risk of cardiovascular disease among Nordic childhood cancer survivors with diabetes mellitus: A report from adult life after childhood cancer in Scandinavia. Cancer 124 (22): 4393-4400, 2018. [PUBMED Abstract]
Lipshultz SE, Lipsitz SR, Kutok JL, et al.: Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer 119 (19): 3555-62, 2013. [PUBMED Abstract]
Visscher H, Ross CJ, Rassekh SR, et al.: Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer 60 (8): 1375-81, 2013. [PUBMED Abstract]
Wang X, Liu W, Sun CL, et al.: Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children's oncology group. J Clin Oncol 32 (7): 647-53, 2014. [PUBMED Abstract]
Wang X, Sun CL, Quiñones-Lombraña A, et al.: CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study. J Clin Oncol 34 (8): 863-70, 2016. [PUBMED Abstract]
Aminkeng F, Bhavsar AP, Visscher H, et al.: A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer. Nat Genet 47 (9): 1079-84, 2015. [PUBMED Abstract]
Visscher H, Rassekh SR, Sandor GS, et al.: Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children. Pharmacogenomics 16 (10): 1065-76, 2015. [PUBMED Abstract]
Davies SM: Getting to the heart of the matter. J Clin Oncol 30 (13): 1399-400, 2012. [PUBMED Abstract]
Dietz AC, Seidel K, Leisenring WM, et al.: Solid organ transplantation after treatment for childhood cancer: a retrospective cohort analysis from the Childhood Cancer Survivor Study. Lancet Oncol 20 (10): 1420-1431, 2019. [PUBMED Abstract]
Brouwer CA, Postma A, Hooimeijer HL, et al.: Endothelial damage in long-term survivors of childhood cancer. J Clin Oncol 31 (31): 3906-13, 2013. [PUBMED Abstract]
Maraldo MV, Jørgensen M, Brodin NP, et al.: The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma. Pediatr Blood Cancer 61 (4): 717-22, 2014. [PUBMED Abstract]
Skinner R, Wallace WH, Levitt GA, et al.: Long-term follow-up of people who have survived cancer during childhood. Lancet Oncol 7 (6): 489-98, 2006. [PUBMED Abstract]
Morris B, Partap S, Yeom K, et al.: Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology 73 (22): 1906-13, 2009. [PUBMED Abstract]
Sieswerda E, Postma A, van Dalen EC, et al.: The Dutch Childhood Oncology Group guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors. Ann Oncol 23 (8): 2191-8, 2012. [PUBMED Abstract]
Armenian SH, Lacchetti C, Barac A, et al.: Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35 (8): 893-911, 2017. [PUBMED Abstract]
Lenihan DJ, Oliva S, Chow EJ, et al.: Cardiac toxicity in cancer survivors. Cancer 119 (Suppl 11): 2131-42, 2013. [PUBMED Abstract]
Chen AB, Punglia RS, Kuntz KM, et al.: Cost effectiveness and screening interval of lipid screening in Hodgkin's lymphoma survivors. J Clin Oncol 27 (32): 5383-9, 2009. [PUBMED Abstract]
Wong FL, Bhatia S, Landier W, et al.: Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure. Ann Intern Med 160 (10): 672-83, 2014. [PUBMED Abstract]
Yeh JM, Nohria A, Diller L: Routine echocardiography screening for asymptomatic left ventricular dysfunction in childhood cancer survivors: a model-based estimation of the clinical and economic effects. Ann Intern Med 160 (10): 661-71, 2014. [PUBMED Abstract]
Ramjaun A, AlDuhaiby E, Ahmed S, et al.: Echocardiographic Detection of Cardiac Dysfunction in Childhood Cancer Survivors: How Long Is Screening Required? Pediatr Blood Cancer 62 (12): 2197-203, 2015. [PUBMED Abstract]
Spewak MB, Williamson RS, Mertens AC, et al.: Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation. Pediatr Blood Cancer 64 (6): , 2017. [PUBMED Abstract]
Jones LW, Liu Q, Armstrong GT, et al.: Exercise and risk of major cardiovascular events in adult survivors of childhood hodgkin lymphoma: a report from the childhood cancer survivor study. J Clin Oncol 32 (32): 3643-50, 2014. [PUBMED Abstract]
Neurocognitive
Neurocognitive late effects are most commonly observed after treatment of malignancies that require central nervous system (CNS)–directed therapies. While considerable evidence has been published about this outcome, its quality is often limited by small sample size, cohort selection and participation bias, cross-sectional versus longitudinal evaluations, and variable time of assessment from treatment exposures. CNS-directed therapies include the following:
Cranial radiation therapy.
Systemic therapy with high-dose methotrexate or cytarabine.
Intrathecal chemotherapy.
Children with brain tumors or acute lymphoblastic leukemia (ALL) are most likely to be affected. Risk factors for the development of neurocognitive late effects include the following:[1-7]
Younger age at the time of treatment.
Higher cranial radiation dose.
Treatment with cranial radiation therapy and/or chemotherapeutic agents (systemic or intrathecal).
The cognitive phenotypes observed in childhood survivors of ALL and CNS tumors may differ from traditional developmental disorders. For example, the phenotype of attention problems in ALL and brain tumor survivors appears to differ from developmental attention-deficit/hyperactivity disorder in that few survivors demonstrate significant hyperactivity/impulsivity, but instead have associated difficulties with processing speed and executive function.[8,9]
In addition to the direct effects of neurotoxic therapies like cranial radiation, Childhood Cancer Survivor Study (CCSS) investigators observed that chronic health conditions resulting from non-neurotoxic treatment exposures (e.g., thoracic radiation) can adversely impact neurocognitive function.[10] They hypothesized that chronic cardiopulmonary and endocrine dysfunction that develops after therapy mediates and may exacerbate the impact of neurotoxic exposures on neurocognitive function, underscoring the importance of promoting interventions to support healthy brain aging in long-term survivors.
Neurocognitive outcomes in brain tumor survivors
Survival rates have increased over recent decades for children with brain tumors; however, long-term cognitive effects caused by illness and associated treatments are a well-established morbidity in this group of survivors. In childhood and adolescent brain tumor survivors, risk factors for adverse neurocognitive effects include the following:
Cranial radiation therapy. Cranial radiation therapy has been associated with the highest risk of long-term cognitive morbidity, particularly in younger children.[11] There is an established dose-response relationship, with patients who receive higher-dose cranial radiation therapy consistently performing more poorly on intellectual measures.[12] Radiation dose to specific regions of the brain, including the temporal lobes and hippocampi, have been shown to significantly impact longitudinal intelligence quotient (IQ) scores and academic achievement scores among children treated with craniospinal irradiation for medulloblastoma.[13]
Tumor site.[11,14]
Shunted hydrocephalus.[11,15,16]
Postsurgical cerebellar mutism.[17]
Auditory difficulties, including sensorineural hearing loss.[15,18]
History of stroke.[19]
Seizures.[14,20]
The negative impact of radiation treatment has been characterized by changes in IQ scores, which have been noted to drop about 2 to 5 years after diagnosis; the decline continues 5 to 10 years afterward, although less is known about potential stabilization or further decline of IQ scores several decades after diagnosis.[21-23] The decline in IQ scores over time typically reflects the child’s failure to acquire new abilities or information at a rate similar to that of his or her peers, rather than a progressive loss of skills and knowledge.[12] Affected children also may experience deficits in other cognitive areas, including academic difficulties (reading and math) and problems with attention, processing speed, memory, and visual or perceptual motor skills.[22,24,25]
These changes in cognitive functioning may be partially explained by radiation-induced reduction of normal-appearing white matter volume or integrity of white matter pathways, as evaluated through magnetic resonance imaging (MRI).[26-28] In fact, reduced white matter integrity has been directly linked to slowed cognitive processing speed in survivors of brain tumors,[29] while greater white matter volume has been associated with better working memory, particularly in females.[28] It should be noted that data emerging from contemporary protocols show that using lower doses of cranial radiation and more targeted treatment volumes appears to reduce the severity of neurocognitive effects of therapy.[14,16,30]
Data are emerging regarding cognitive outcomes after proton radiation to the CNS.[31-33] To date, these studies largely describe IQ changes during early (less than 5 years from radiation) follow-up and are limited by retrospective analysis of cognitive outcomes among relatively small clinically heterogeneous pediatric brain tumor cohorts and use of historically treated photon patients or population standards as comparison groups. Study results demonstrating lack of difference in slopes of IQ change among photon- and proton-treated patients [31] and significant declines in cognitive processing speed among patients treated with proton radiation [32] underscore the importance of longitudinal follow-up to determine whether proton radiation provides a clinically meaningful benefit in sparing cognitive function compared with photon radiation.
In addition, studies are beginning to examine cognitive outcomes in histologically distinct subtypes of brain tumors. For example, data from a sample of 121 medulloblastoma patients demonstrated variation in cognitive outcomes by four distinct molecular subgroups and differences in patterns of change over time.[34] This study highlights the need for future research to consider neurocognitive outcomes across biologically distinct subtypes of childhood brain tumors.
Longitudinal cohort studies have provided insight into the trajectory and predictors of cognitive decline among survivors of CNS tumors.
Evidence (predictors of cognitive decline among survivors of CNS tumors):
St. Jude Children’s Research Hospital (SJCRH) studied 78 children younger than 20 years (mean, 9.7 years) diagnosed with low-grade glioma.[35]
Cognitive decline after 54 Gy of conformal cranial radiation therapy was noted (refer to Figure 7).
Age at time of cranial irradiation was more important than was cranial radiation dose in predicting cognitive decline, with children younger than 5 years estimated to experience the greatest cognitive decline.
Figure 7. Modeled intelligence quotient (IQ) scores after conformal radiation therapy (CRT) by age for pediatric low-grade glioma. Age is measured in years, and time is measured in months after the start of CRT. Thomas E. Merchant, Heather M. Conklin, Shengjie Wu, Robert H. Lustig, and Xiaoping Xiong, Late Effects of Conformal Radiation Therapy for Pediatric Patients With Low-Grade Glioma: Prospective Evaluation of Cognitive, Endocrine, and Hearing Deficits, Journal of Clinical Oncology, volume 27, issue 22, pages 3691-3697. Reprinted with permission. © (2009) American Society of Clinical Oncology. All rights reserved.
In a study of 51 children with low-grade gliomas and low-grade glioneural tumors diagnosed within the first year of life, the mean IQ score was 75.5; 75% of the children had IQ scores lower than 85. Predictors of low IQ included a supratentorial location of the primary tumor and treatment with more chemotherapy regimens, but not radiation use. The child’s ability to complete age-appropriate tasks was as affected as IQ scores.[36]
A study of 126 medulloblastoma survivors treated with 23.4 Gy or 36 Gy to 39.6 Gy of craniospinal radiation (with a conformal boost dose of 55.8 Gy to the primary tumor bed) assessed processing speed, attention, and memory performance.[37]
Processing speed scores declined significantly over time, while less decline was observed in attention and memory performance. Higher doses of radiation and younger age at diagnosis predicted slower processing speed over time.
Studies of working memory and academic achievement in patients enrolled on the same medulloblastoma trial (SJCRH SJMB03 [NCT00085202]) indicated that performance was largely within the age-expected range up to 5 years postdiagnosis,[38,39] although in both studies, posterior fossa syndrome, higher cranial radiation dose, and younger age at diagnosis predicted worse performance over time. In addition, serious hearing loss was associated with intellectual and academic decline over time.[39]
A prospective study compared 36 pediatric medulloblastoma patients who experienced posterior fossa syndrome with 36 medulloblastoma patients who did not experience posterior fossa syndrome but were matched on treatment and age at diagnosis.[40]
The posterior fossa syndrome group demonstrated lower mean scores at 1, 3, and 5 years postdiagnosis on general intellectual ability, processing speed, working memory, and spatial relations compared with the non–posterior fossa syndrome group.
The group who experienced posterior fossa syndrome showed little recovery over time and further decline over time in some domains (attention and working memory), compared with the non–posterior fossa syndrome group.
Canadian investigators evaluated the impact of radiation (dose and boost volume) and neurologic complications on patterns of intellectual functioning in a cohort of 113 medulloblastoma survivors (mean age at diagnosis, 7.5 years; mean time from diagnosis to last assessment, 6 years).[41]
Survivors treated with reduced-dose craniospinal radiation therapy plus tumor bed boost showed stable intellectual functioning.
Neurological complications, such as hydrocephalus requiring cerebrospinal fluid diversion and mutism, and treatment with higher doses and larger boost volumes of radiation resulted in intellectual declines with distinctive trajectories.
Although adverse neurocognitive outcomes observed 5 to 10 years after treatment are presumed to be pervasive, and potentially worsen over time, few empirical data are available regarding the neurocognitive functioning in very long-term survivors of CNS tumors.
Among adult survivors participating in the CCSS, CNS tumor survivors (n = 802) self-reported significantly more problems with attention/processing speed, memory, emotional control, and organization than did survivors of non-CNS malignancies (n = 5,937) and sibling controls (n = 382).[4] Moreover, a large proportion of CNS tumor survivors treated with cranial irradiation reported impairment on measures of attention/processing speed (42.9%–73.3%) and memory (14.3%–37.4%), with differences observed by diagnosis and cranial radiation dose.[42]
A study of 224 adult survivors of pediatric brain tumors participating in the St. Jude Lifetime Cohort Study revealed that 20% to 30% of the survivors demonstrated severe neurocognitive impairment (defined as at least two standard deviations below normative mean) on tests of intelligence, memory, and executive function (e.g., planning, organization, and flexibility).[14] Among adults in the general population, the expected impairment rate at this threshold is 2%. Survivors who received whole-brain cranial irradiation were 1.5 to 3 times more likely to have severe neurocognitive impairment than were survivors who did not receive any cranial irradiation. Hydrocephalus with shunt placement and seizures were also associated with increased risk of impairment. Importantly, this study relied on direct assessment of neurocognitive skills while the previous CCSS report relied on self-report of problems.[14]
In the CCSS, investigators compared long-term neuropsychological and socioeconomic status outcomes of 181 adult survivors of pediatric low-grade gliomas with the outcomes of an age-matched and sex-matched sibling comparison group. Survivors who were treated with surgery and radiation therapy (median age at diagnosis, 7 years; median age at assessment, 41 years) scored lower on estimated IQ than did survivors who were treated with surgery only, who scored lower than siblings (surgery and radiation therapy, 93.9; surgery only, 101.2; siblings, 108.5; all P values < .0001). Younger age at diagnosis was predictive of low scores for all neuropsychological outcomes except for attention/processing speed. Survivors who were treated with surgery and radiation therapy had more-than-twofold-lower occupation scores, income, and education than did survivors who were treated with surgery only.[43]
The neurocognitive consequences of CNS disease and treatment may have a considerable impact on functional outcomes for brain tumor survivors.
In childhood and adolescence, neurocognitive deficits have been associated with poor social adjustment, including problems with peer relations, social withdrawal, and reduced social skills.[44,45]
CNS tumor survivors are more likely to need special education services than are survivors of other malignancies.[46]
Adult CNS tumor survivors are less likely to live independently, marry, and graduate from college than are survivors of other malignancies and siblings.[46-48]
Neurocognitive outcomes in acute lymphoblastic leukemia (ALL) survivors
The increase in cure rates for children with ALL over the past decades has resulted in greater attention to the neurocognitive morbidity and quality of life of survivors. The goal of current ALL treatment is to minimize adverse late effects while maintaining high survival rates. To minimize the risk of late sequelae, patients are stratified for treatment according to their risk of relapse. Cranial irradiation is reserved for the fewer than 20% of children who are considered at high risk for CNS relapse.[49]
Although low-risk, standard-risk, and most high-risk patients are treated with chemotherapy-only protocols, early reports of neurocognitive late effects for ALL patients were based on heterogeneously treated groups of survivors who received combinations (simultaneously or sequentially) of intrathecal chemotherapy, radiation therapy, and high-dose chemotherapy, making it difficult to differentiate the impact of the individual treatment components. However, outcome data are increasingly available regarding the risk of neurocognitive late effects in survivors of childhood ALL treated with chemotherapy only.
ALL and cranial radiation
In survivors of ALL, cranial radiation therapy may result in clinical and radiographic neurologic late sequelae, including the following:
Clinical leukoencephalopathy. Clinical leukoencephalopathy characterized by spasticity, ataxia, dysarthria, dysphagia, hemiparesis, and seizures is uncommon after contemporary ALL therapy. In contrast, neuroimaging frequently demonstrates white matter abnormalities among survivors treated with cranial irradiation and/or high-dose methotrexate. Radiographic leukoencephalopathy has been reported in up to 80% of children on some treatment regimens. Higher doses and more courses of intravenous methotrexate have been reported to increase risk of leukoencephalopathy.[50] In many patients, white matter anomalies are transient and decrease in prevalence, extent, and intensity with longer elapsed time from completion of therapy.[50] Leukoencephalopathy results in smaller white matter volumes that have been correlated with cognitive deficits. Although these abnormalities are mild among the irradiated patients (overall IQ fall of approximately 10 points), those who have received higher doses at a young age may have significant learning difficulties.[51,52]
Neuropsychological deficits. Deficits in neuropsychological functions such as visual-motor integration, processing speed, attention, and short-term memory are reported in children treated with 18 Gy to 24 Gy.[51,53,54] Females and children treated at a younger age are more vulnerable to the adverse impact of cranial radiation on the developing brain.[55] The decline in intellectual functioning appears to be progressive, showing more impairment of cognitive function with increasing time since radiation therapy.[55,56] Limited studies suggest that long-term survivors of childhood ALL treated with cranial irradiation are at risk of progressive decline consistent with early-onset mild cognitive impairment; this risk is most prominent among those treated with cranial radiation doses of 24 Gy.[57,58]
ALL and chemotherapy-only CNS therapy
Because of its penetrance into the CNS, systemic methotrexate has been used in a variety of low-dose and high-dose regimens for leukemia CNS prophylaxis. Systemic methotrexate in high doses with or without radiation therapy can lead to an infrequent but well-described leukoencephalopathy, which has been linked to neurocognitive impairment.[50] When neurocognitive outcomes after radiation therapy and chemotherapy-only regimens are directly compared, the evidence suggests a better outcome for those treated with chemotherapy alone, although some studies show no significant difference.[59,60] In a longitudinal analysis of 210 childhood ALL survivors, the development of acute leukoencephalopathy during chemotherapy-only CNS therapy predicted higher risks of developing long-term neurobehavioral problems (e.g., deficits in organization and task initiation [components of executive function]) and reduced white matter integrity in frontal brain regions.[61]
Compared with cranial irradiation, chemotherapy-only CNS-directed treatment produces neurocognitive deficits involving processes of attention, speed of information processing, memory, verbal comprehension, visual-spatial skills, visual-motor functioning, and executive functioning; global intellectual function is typically preserved.[53,59,62-65] Few longitudinal studies evaluating long-term neurocognitive outcome report adequate data for a decline in global IQ after treatment with chemotherapy alone.[63] The academic achievement of ALL survivors in the long term seems to be generally average for reading and spelling, with deficits mainly affecting arithmetic performance.[59,66,67] Risk factors for poor neurocognitive outcome after chemotherapy-only CNS-directed treatment are younger age and female sex.[65,68,69]
Reduced cognitive status has been observed in association with reduced integrity in neuroanatomical regions essential in memory formation (e.g., reduced hippocampal volume with increased activation and thinner parietal cortices). However, the long-term impact of these prevalent neurocognitive and neuroimaging abnormalities on functional status in aging adults treated for childhood ALL, particularly those treated with contemporary approaches using chemotherapy alone, remains an active area of research.
Evidence (neurocognitive functioning in large pediatric cancer survivor cohorts):
The CCSS examined parent-reported cognitive, behavior, and learning problems from 1,560 adolescent survivors of childhood ALL who were treated with chemotherapy alone between 1970 and 1999.[70]
Survivors treated with cranial irradiation had significantly higher frequency of problems in anxiety-depression, inattention-hyperactivity, and social withdrawal than did patients who were not treated with cranial irradiation.
Compared with siblings, survivors treated with chemotherapy only were more likely to demonstrate headstrong behavior (19% of survivors vs. 14% of siblings, P = .010), inattention-hyperactivity (19% vs. 14%, P < .0001), social withdrawal (18% vs. 12%, P = .002), and had higher rates of learning problems (28% vs. 14%, P < .0001).
In multivariable models among survivors, increased cumulative dose of intravenous methotrexate (i.e., >4.3 g/m2) conferred increased risk of inattention-hyperactivity (relative risk [RR], 1.53).
Adolescent survivors with cognitive or behavior problems and those with learning problems were less likely to graduate from college as young adults than adolescent survivors without cognitive or behavior problems.
Inattention and hyperactivity problems were associated with the highest risk of special education placement during adolescence. Participation in special education during adolescence did not improve adult educational attainment.
In the SJCRH Total XV (NCT00137111) trial, which omitted prophylactic cranial irradiation, comprehensive cognitive testing of 243 participants at week 120 revealed the following:[71]
A higher risk for below-average performance on a measure of sustained attention but not on measures of intellectual functioning, academic skills, or memory.
The risk of cognitive deficits correlated with treatment intensity but not with age at diagnosis or sex.
Prolonged follow-up (average, 7.7 years from diagnosis) of this cohort demonstrated that intelligence was within normal limits compared with population expectations, but measures of executive function, processing speed, and memory were less than population means. Higher plasma methotrexate was associated with executive dysfunction, thicker cerebral cortex, and higher activity in frontal brain regions on functional MRI.
These results underscore the need for continued follow-up as this population ages to better characterize the prevalence and magnitude of cognitive deficits after CNS-directed therapy with chemotherapy alone.[72]
In a large prospective study of neurocognitive outcomes in children with newly diagnosed ALL, 555 children were randomly assigned to receive CNS-directed therapy according to risk group.[73]
Low-risk group: Intrathecal methotrexate versus high-dose methotrexate.
High-risk group: High-dose methotrexate versus 24 Gy of cranial radiation therapy.
A significant reduction in IQ scores (4–7 points) was observed in all patient groups when compared with controls, regardless of the CNS treatment delivered.
Children younger than 5 years at diagnosis were more likely to have IQs below 80 at 3 years posttherapy than were children older than 5 years at diagnosis, irrespective of treatment allocation, suggesting that younger children are more vulnerable to treatment-related neurologic toxic effects.
Persistent cognitive deficits and progressive intellectual decline have been observed in cohorts of adults treated for ALL during childhood and associated with reduced educational attainment and unemployment.[52,55,58] The results of a study of more than 500 adult survivors of childhood ALL (average, 26 years postdiagnosis) showed the following:[52]
Survivors demonstrated increased rates of impairment across all neurocognitive domains (ranging from 28.6%–58.9% for each domain).
Rate of severe impairment increased as a function of cranial radiation dose, but was common among survivors treated with lower doses of cranial irradiation and chemotherapy only.
Impairment in executive function skills increased with time since diagnosis in a cranial radiation dose-dependent manner; impairment in intellect, academics, and memory progressively increased with younger age at treatment in a cranial radiation dose-dependent manner; and neurocognitive impairment was related to functional outcomes as adults, including reduced likelihood of college graduation and full-time employment.
Continued monitoring by health professionals is needed to identify neurocognitive problems that may emerge over time.
ALL and steroid therapy
The type of steroid used for ALL systemic treatment may affect cognitive functioning. In a study that involved long-term neurocognitive testing (mean follow-up, 9.8 years) of 92 children with a history of standard-risk ALL who had received either dexamethasone or prednisone during treatment, no meaningful differences in mean neurocognitive and academic performance scores were observed.[74] In contrast, in a study of 567 adult survivors of childhood leukemia (mean age, 33 years; mean time since diagnosis, 26 years) dexamethasone exposure was associated with increased risk of impairment in attention (RR, 2.12; 95% confidence interval [CI], 1.11–4.03) and executive function (RR, 2.42; 95% CI, 1.20–4.91), independent of methotrexate exposure. Intrathecal hydrocortisone also increased risk of attention problems (RR, 1.24; 95% CI, 1.05–1.46).[52]
Neurocognitive abnormalities have been reported in other groups of cancer survivors. In a study of adult survivors of childhood non-CNS cancers (including ALL, n = 5,937), 13% to 21% of survivors reported impairment in task efficiency, organization, memory, or emotional regulation. This rate of impairment was approximately 50% higher than that reported in the sibling comparison group. Factors such as diagnosis before age 6 years, female sex, cranial radiation therapy, and hearing impediment were associated with impairment.[54] In addition, emerging data suggest that the development of chronic health conditions in adulthood may contribute to cognitive deficits in long-term survivors of non-CNS cancers.
Neurocognitive abnormalities have been reported for the following cancers:
Osteosarcoma. In a study evaluating neurocognitive function among 80 long-term survivors of osteosarcoma (mean time since diagnosis, 24.7 years), survivors demonstrated lower mean scores in reading skills, attention, memory, and processing speed than did community controls. The presence of cardiac, pulmonary, and endocrine conditions were significantly associated with worse performance on measures of memory and processing speed.[75]
Retinoblastoma. Early studies of intellectual functioning in survivors of retinoblastoma suggested above average intelligence among bilateral survivors compared with unaffected siblings and the general population, especially those who were blind as a result of their disease.[76-78]
Later studies have yielded mixed results. For example, serial assessment of cognitive and adaptive functioning in a group of survivors younger than 6 years revealed declines in developmental functioning over time. The most pronounced declines were observed in patients with 13q deletion.[79] In contrast, a study of long-term adult survivors, who were on average 33 years postdiagnosis, demonstrated largely average cognitive functioning across domains of intelligence, memory, attention, and executive function.[80] These conflicting findings may be attributed, in part, to the low test-retest reliability of measures used to assess cognitive outcomes at a very young age, as well as temporal differences in treatment exposures.
Lymphoma. Survivors of lymphoma have not historically been considered at risk of developing neurocognitive late effects. However, reports suggest that more than two-thirds of survivors of childhood non-Hodgkin lymphoma experience at least mild neurocognitive impairment, including severe deficits in executive function (13%), attention (9%), and memory (4%).[81] Similarly, in a study of 62 adult survivors of childhood Hodgkin lymphoma, survivors demonstrated worse performance on measures of sustained attention, short- and long-term memory, and cognitive fluency when compared with national normative data.[82] Importantly, measures of cardiac and pulmonary function also were associated with neurocognitive impairment in this group of survivors.
Cognitive and academic consequences of stem cell transplantation in children have also been evaluated and include, but are not limited to, the following:
In a report from SJCRH in which 268 patients were treated with stem cell transplantation, minimal risk of late cognitive and academic sequelae was observed.[83]
Subgroups of patients were at relatively higher risk, including patients who underwent unrelated donor transplantation, received total-body irradiation, and developed graft-versus-host disease (GVHD). However, these differences were small relative to differences in premorbid functioning, particularly those associated with socioeconomic status.
In a series of 38 patients who underwent hematopoietic stem cell transplantation (HSCT) and received intrathecal chemotherapy, significant declines in visual motor skills and memory scores were noted within the first year posttransplant.[84]
By 3 years posttransplant, there was an improvement in visual motor development scores and memory scores, but new deficits were evident in long-term memory scores.
By 5 years posttransplant, there were progressive declines in verbal skills and performance skills, and new deficits were seen in long-term verbal memory scores.
The greatest decline in neurocognitive function occurred in patients who received cranial irradiation, either as part of their initial therapy or as part of their HSCT conditioning.
Most neurocognitive late effects after stem cell transplantation are thought to be related to white matter damage in the brain. This was investigated in children with leukemia who were treated with HSCT. In a series of 36 patients, performance on neurocognitive measures typically associated with white matter was compared with performance on measures thought to correlate with gray matter function. Composite white matter scores were significantly lower than composite gray matter scores, thereby supporting the belief that white matter damage contributes to neurocognitive late effects in this population.[85]
Neurologic Sequelae
Risk of neurologic complications may be predisposed by the following:
Neurosurgery.
Specific neurotoxic chemotherapeutic agents.
In children with CNS tumors, mass effect, tumor infiltration, and increased intracranial pressure may result in motor or sensory deficits, cerebellar dysfunction, and secondary effects such as seizures and cerebrovascular complications. Numerous reports describe abnormalities of CNS integrity and function, but such studies are typically limited by small sample size, cohort selection and participation bias, cross-sectional ascertainment of outcomes, and variable time of assessment from treatment exposures. In contrast, relatively few studies comprehensively or systematically ascertain outcomes related to peripheral nervous system function.
CNS tumor survivors remain at higher risk of new-onset adverse neurologic events across their lifetimes than siblings. No plateau has been reached for new adverse sequelae, even 30 years from diagnosis, according to a longitudinal study of 1,876 5-year survivors of CNS tumors from the CCSS. The median time from diagnosis was 23 years and the median age of the patients studied was 30.3 years.[86]
Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset neurologic sequelae (seizures, focal neurologic dysfunction, and neurosensory abnormalities).
This finding supports the need to monitor these patients carefully with continued neurologic follow-up within or in close association with a multidisciplinary cancer survivor clinic.
Neurologic complications that may occur in survivors of childhood cancer include the following:
Seizures. The development of seizures may occur secondary to tumor mass effect within the CNS and/or as a result of neurotoxic CNS-directed therapies.
In 1,876 5-year survivors of CNS tumors from the CCSS, the incidence of seizures increased from 27% in survivors 5 years from diagnosis to 41% in survivors 30 years from diagnosis. Late-onset seizures were associated with frontal lobe radiation of 50 Gy (hazard ratio [HR], 1.8) and temporal lobe radiation in a dose-dependent fashion (HR, 1.9 for 1–49 Gy; HR, 2.2 for >50 Gy). Other risk factors associated with late-onset seizures included recurrence (HR, 2.3), development of meningioma (HR, 2.6), and history of stroke (HR, 2.0). The risk of seizures was elevated for survivors compared with siblings (HR, 12.7).[86]
Among survivors of childhood leukemia in the CCSS (N = 4,151; 64.5% treated with cranial irradiation), 6.1% reported the development of a seizure disorder, and seizures occurred more than 5 years after diagnosis in 51% of these patients.[87]
Leukoencephalopathy. Clinical or radiographic leukoencephalopathy has been reported after cranial irradiation and high-dose systemic methotrexate administration. Younger patients and those treated with cranial radiation doses higher than 24 Gy are more vulnerable to reduced white matter volumes associated with leukoencephalopathy.[53,58,88,89] White matter changes may be accompanied by other neuroimaging abnormalities, including dystrophic calcifications, cerebral lacunae, and cerebral atrophy.
Peripheral neuropathy. Vinca alkaloid agents (vincristine and vinblastine) and cisplatin may cause peripheral neuropathy.[90-92] This condition presents during treatment and appears to improve or clinically resolve after completion of therapy.[90] However, higher cumulative doses of vincristine and/or intrathecal methotrexate have been linked to neuromuscular impairments in long-term survivors of childhood ALL, which suggests that persistent effects of these agents may affect functional status in aging survivors.[90]
Among adult survivors of extracranial solid tumors of childhood (median time from diagnosis, 25 years), standardized assessment of neuromuscular function disclosed motor impairment in association with vincristine exposure and sensory impairment in association with cisplatin exposure.[91] Survivors with sensory impairment demonstrated a higher prevalence of functional performance limitations related to poor endurance and mobility restrictions. These studies underscore the importance of assessment and referral to rehabilitative services to optimize functional outcomes among long-term survivors.
Stroke. Childhood CNS tumor survivors have a 43-fold elevated risk of stroke compared with siblings.[42,93] Cranial radiation therapy (dose dependent), baseline atherosclerosis, hypertension, and African American ethnicity are identified risk factors.[94-96] (Refer to the Cerebrovascular disease section of this summary for information on stroke.)
Hypersomnia (daytime sleepiness) or narcolepsy. In a retrospective review of brain tumor patients treated at SJCRH, investigators identified 39 of 2,336 patients who were diagnosed with hypersomnia/narcolepsy, for a prevalence rate of 1,670 cases per 100,000, which is much higher than a prevalence rate of 20 to 50 cases per 100,000 reported in the general population. This may be an underestimate in childhood brain tumor survivors because many patients with mild-to-moderate symptoms, such as fatigue and sleep disturbances, may not be recognized or referred to a sleep specialist. Hypersomnia/narcolepsy was diagnosed at a median of 6 years (range, 0.4–13.2 years) from tumor diagnosis and 4.7 years (range, 1.5–10.4 years) from cranial radiation. Midline tumor location and antiepilepsy drug use correlated with hypersomnia/narcolepsy, while radiation dose higher than 30 Gy trended toward significance. Posterior fossa tumor location was associated with a reduced risk of hypersomnia. Treatment of hypersomnia/narcolepsy should be individualized and pharmacologic intervention with stimulants may be beneficial.[97]
In a baseline evaluation of 82 childhood CNS tumor survivors (median age, 13.8 years) participating in a randomized controlled trial of neurofeedback, 48% of survivors endorsed sleep problems and scored significantly worse than the norm on the Sleep Disturbance Scale for Children in the subscales for initiating and maintaining sleep, excessive somnolence, and total scale. Emotional problems and/or hyperactivity/inattention were independent potential risk factors for sleep problems. Sleep problems were also associated with worse, parent-reported executive functioning.[98]
Other neurologic sequelae. In a report from the CCSS that compared self-reported neurologic late effects among 4,151 adult survivors of childhood ALL with siblings, survivors were at elevated risk for late-onset coordination problems, motor problems, seizures, and headaches. The overall cumulative incidence was 44% at 20 years. Serious headaches were most common, with a cumulative incidence of 25.8% at 20 years, followed by focal neurologic dysfunction (21.2%) and seizures (7%). Children who were treated with regimens that included cranial irradiation for ALL and those who suffered relapse were at increased risk for late-onset neurologic sequelae.[87]
In a cross-sectional study that evaluated neurologic morbidity and quality of life in 162 survivors of childhood ALL (median age at evaluation, 15.7 years; median time from completion of therapy, 7.4 years) in concert with a clinical neurologic exam, neurologic symptoms were present in 83% of survivors, but symptom-related morbidity was low and quality of life was high in most survivors. The most commonly reported symptoms included neuropathy (63%), headache (46.9%), dizziness (33.3%), and back pain (22.8%). Female sex, ten doses or more of intrathecal chemotherapy, cranial irradiation, CNS leukemia at diagnosis, and history of ALL relapse were associated with neurologic morbidity.[7]
Neuroimaging studies of irradiated and nonirradiated ALL survivors demonstrate a variety of CNS abnormalities, including leukoencephalopathy, cerebral lacunes, cerebral atrophy, and dystrophic calcifications (mineralizing microangiopathy). Among these, abnormalities of cerebral white matter integrity and volume have been correlated with neurocognitive outcomes.[50,58,88,89]
Cavernomas have also been observed in ALL survivors treated with cranial irradiation. They have been speculated to result from angiogenic processes as opposed to tumorigenesis.[99]
In 1,876 5-year survivors of CNS tumors from the CCSS, the cumulative incidence of headaches increased from 38% at 5 years to 53% at 30 years from diagnosis. Similarly, coordination problems increased from 21% at 5 years to 53% at 30 years from diagnosis, and motor impairment increased from 21% to 35% during this time period. Increased risk of motor impairment was associated with tumor recurrence (HR, 2.6), development of a meningioma (HR, 2.3), and stroke (HR, 14.9). Adverse neurosensory outcomes also increased during this period; the cumulative incidence of hearing loss increased from 9% at 5 years to 23% at 30 years, cumulative incidence of tinnitus increased from 8% at 5 years to 21% at 30 years, and cumulative incidence of vertigo increased from 9% at 5 years to 17% at 30 years. Risks of motor impairment (HR, 7.6) and hearing loss (HR, 18.4) were elevated compared with siblings.[86]
Table 3 summarizes CNS late effects and the related health screenings.
Table 3. Central Nervous System Late Effectsa
Neurologic Effects
IQ = intelligence quotient; IT = intrathecal; IV = intravenous.
aAdapted from the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.
Platinum agents (carboplatin, cisplatin) Peripheral sensory neuropathy Neurologic exam
Plant alkaloid agents (vinblastine, vincristine) Peripheral sensory or motor neuropathy (areflexia, weakness, foot drop, paresthesias) Neurologic exam
Methotrexate (high dose IV or IT); cytarabine (high dose IV or IT); radiation impacting the brain Clinical leukoencephalopathy (spasticity, ataxia, dysarthria, dysphagia, hemiparesis, seizures); headaches; seizures; sensory deficits History: cognitive, motor, and/or sensory deficits, seizures
Neurologic exam
Radiation impacting cerebrovascular structures Cerebrovascular complications (stroke, Moyamoya disease, occlusive cerebral vasculopathy) History: transient/permanent neurological events
Neurosurgery–brain Motor and/or sensory deficits (paralysis, movement disorders, ataxia, eye problems [ocular nerve palsy, gaze paresis, nystagmus, papilledema, optic atrophy]); seizures Neurologic exam
Neurology evaluation
Neurosurgery–brain Hydrocephalus; shunt malfunction Abdominal x-ray
Neurosurgery evaluation
Neurosurgery–spine Neurogenic bladder; urinary incontinence History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
Neurosurgery–spine Neurogenic bowel; fecal incontinence History: chronic constipation, fecal soiling
Predisposing Therapy Neuropsychological Effects Health Screening
Methotrexate (high-dose IV or IT); cytarabine (high-dose IV or IT); radiation impacting the brain; neurosurgery–brain Neurocognitive deficits (executive function, memory, attention, processing speed, etc.); learning deficits; diminished IQ; behavioral change Assessment of educational and vocational progress
Formal neuropsychological evaluation
Psychosocial
Many childhood cancer survivors report reduced quality of life or other adverse psychosocial outcomes. Evidence for adverse psychosocial adjustment after childhood cancer has been derived from a number of sources, ranging from patient-reported or proxy-reported outcomes to data from population-based registries. The former may be limited by small sample size, cohort selection and participation bias, and variable methods and venues (clinical vs. distance-based survey) of assessments. The latter is often not well correlated with clinical and treatment characteristics that permit the identification of survivors at high risk of psychosocial deficits.
Survivors with neurocognitive deficits are particularly vulnerable to adverse psychosocial outcomes that affect achievement of expected social outcomes during adulthood.
In a population-based study of adult survivors of CNS tumors diagnosed in childhood or adolescence, survivors had significantly poorer self-perception and self-esteem than did individuals in the general population. Female sex, persistent visible physical sequelae, specific tumor type, and treatment with cranial radiation therapy predicted poor self-perception outcomes.[100]
In a series of CNS malignancy survivors (n = 802) reported from the CCSS, adverse outcome on multiple indicators of successful adult adjustment (educational achievement, income, employment, and marital status) were most prevalent among survivors who reported neurocognitive dysfunction.[4]
Collectively, studies evaluating psychosocial outcomes among CNS tumor survivors indicate deficits in social competence that worsen over time.[101] This includes problems with peer rejection and isolation in childhood/adolescence, as well as the inability to develop friendships and romantic relationships as adults.
In a CCSS study that evaluated predictors of independent living status across diagnostic groups, adult survivors of childhood cancer with neurocognitive, psychological, or physical late effects were less likely to live independently as adults than were siblings in the comparison group.[47]
In a St. Jude Lifetime Cohort study of 224 survivors of CNS tumors (median current age, 26 years; median time from diagnosis, 18 years), neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living.[14]
In a series of 1,560 adolescent survivors of childhood ALL treated with chemotherapy alone, the CCSS identified a significant proportion of survivors who still experienced problems with headstrong behavior, inattention-hyperactivity, and social withdrawal, which were associated with an increased risk of special education placement and predicted reduced adult educational attainment.[70]
Childhood cancer survivors are also at risk of developing symptoms of psychological distress. In a longitudinal study of more than 4,500 survivors, subgroups of survivors were found to be at risk of developing persistent and increasing symptoms of anxiety and depression during a 16-year period. Survivors who reported pain and worsening health status were at the greatest risk of developing symptoms of anxiety, depression, and somatization over time.[102]
Adult survivors of childhood cancer are also at risk of suicide ideation compared with siblings, with survivors of CNS tumors being most likely to report thoughts of suicide. In a CCSS study that evaluated the prevalence of recurrent suicidal ideation among 9,128 adult long-term survivors of childhood cancer, survivors were more likely to report late suicidal ideation (odds ratio [OR], 1.9; 95% CI, 1.5–2.5) and recurrent suicidal ideation (OR, 2.6; 95% CI, 1.8–3.8) compared with siblings. History of seizure was associated with a twofold increased likelihood of suicide ideation in survivors.[103] In a population-based study that evaluated suicide among adults treated for cancer before age 25 years, the absolute risk of suicide was low (24 cases among 3,375 deaths), but the HR of suicide was increased among individuals treated for cancer in childhood (0–14 years; HR, 2.5; 95% CI, 1.7–3.8) and in adolescence and young adulthood (15–24 years; HR, 2.3; 95% CI, 1.2–4.6).[104]
The presence of chronic health conditions can also impact aspects of psychological health. In a study that evaluated psychological outcomes among long-term survivors treated with HSCT, 22% of survivors and 8% of sibling controls reported adverse outcomes. Somatic distress was the most prevalent condition and affected 15% of HSCT survivors, representing a threefold higher risk compared with siblings. HSCT survivors with severe or life-threatening health conditions and active chronic GVHD had a twofold increased risk of somatic distress.[105] A report from the CCSS revealed that the presence of chronic pulmonary, endocrine, and cardiac conditions was associated with increased risk of psychological distress symptoms in a sample of 5,021 adult survivors of childhood cancer.[106]
In a CCSS investigation that evaluated long-term psychological and educational outcomes among survivors of neuroblastoma, survivors demonstrated elevated risks of psychological impairment, which was associated with the use of special education services and lower educational attainment. The presence of two or more chronic health conditions, but not common treatment exposures, predicted psychological impairment. Specifically, pulmonary disease predicted impairment in all five psychological domains, whereas endocrine disease and peripheral neuropathy each predicted impairment in three domains.[107]
Incorporation of psychological screening into clinical visits for childhood cancer survivors may be valuable; however, limiting such evaluations to those returning to long-term follow-up clinics may result in a biased subsample of survivors with more difficulties, and precise prevalence rates may be difficult to establish. A review of behavioral, emotional, and social adjustment among survivors of childhood brain tumors illustrates this point, with the prevalence of psychological maladjustment ranging from 25% to 93%.[108] In a study of 101 adult cancer survivors of childhood cancer, psychological screening was performed during a routine annual evaluation at the survivorship clinic at the Dana Farber Cancer Institute. On the Symptom Checklist 90 Revised, 32 subjects had a positive screen (indicating psychological distress), and 14 subjects reported at least one suicidal symptom. Risk factors for psychological distress included subjects’ dissatisfaction with physical appearance, poor physical health, and treatment with cranial irradiation. In this study, the instrument was shown to be feasible for use in the clinic visit setting because the psychological screening was completed in less than 30 minutes. In addition, completion of the instrument itself did not appear to cause distress in the survivors in 80% of cases.[109] These data support the feasibility and importance of consistent assessment of psychosocial distress in a medical clinic setting.
(Refer to the PDQ summary on Adjustment to Cancer: Anxiety and Distress for more information about psychological distress and cancer patients.)
Post-traumatic stress after childhood cancer
Despite the many stresses associated with the diagnosis of cancer and its treatment, studies have generally shown low levels of post-traumatic stress symptoms and post-traumatic stress disorder (PTSD) in children with cancer, typically no higher than those in healthy comparison children.[110] Patient and parent adaptive style appear to be significant determinants of PTSD in the pediatric oncology setting.[111,112]
The prevalence of PTSD and post-traumatic stress symptoms has been reported in 15% to 20% of young adult survivors of childhood cancer, with estimates varying based on criteria used to define these conditions.[113]
Survivors with PTSD reported more psychological problems and negative beliefs about their illness and health status than did those without PTSD.[114,115]
A subset of adult survivors (9%) from the CCSS reported functional impairment and/or clinical distress in addition to the set of symptoms consistent with a full diagnosis of PTSD. This was significantly more prevalent in survivors than in sibling comparisons.[116] In this study, PTSD was significantly associated with being unmarried, having an annual income of less than $20,000, being unemployed, having a high school education or less, and being older than 30 years. Survivors who were treated with cranial irradiation before age 4 years were at particularly high risk for PTSD. Intensive cancer-directed therapy was also associated with increased risk of full PTSD.
Because avoidance of places and persons associated with the cancer is part of PTSD, the syndrome may interfere with obtaining appropriate health care. Those with PTSD perceive greater current threats to their lives or the lives of their children. Other risk factors include poor family functioning, decreased social support, and noncancer stressors.[117]
Psychosocial outcomes among childhood, adolescent, and young adult cancer survivors
Most research on late effects after cancer has focused on individuals with a cancer manifestation during childhood. Little is known about the specific impact of a cancer diagnosis with an onset in adolescence or the impact of childhood cancer on adolescent and young adult (AYA) psychosocial outcomes.
Evidence (psychosocial outcomes in AYA cancer survivors):
Adult survivors of cancer diagnosed during adolescence (aged 15–18 years) (N = 825) were compared with an age-matched sample from the general population and a comparison group of adults without cancer.[118]
Female survivors of adolescent cancers achieved fewer developmental milestones related to their psychosexual development, such as having their first boyfriend, or they reached these milestones later.
Male survivors were more likely to live with their parents than were same-sex controls.
Adolescent cancer survivors were less likely to have ever married or have had children. Survivors were significantly older at their first marriage and at the birth of their first child than were their age-matched samples.
Survivors in this cohort were also significantly less satisfied with their general and health-related life than were people in a community-based control group. Impaired general and health-related life satisfaction were associated with somatic late effects, symptoms of depression and anxiety, and lower rates of posttraumatic growth.[119]
A survey of 4,054 AYA cancer survivors and 345,592 respondents who had no history of cancer reported the following:[120]
AYA cancer survivors were more likely to smoke (26% vs. 18%), be obese (31% vs. 27%), and have chronic conditions such as cardiovascular disease (14% vs. 7%), hypertension (35% vs. 9%), asthma (15% vs. 8%), disability (36% vs. 18%), and poor mental health (20% vs. 10%).
They were also less likely to receive medical care because of cost (24% vs. 15%).
The CCSS evaluated outcomes of 2,979 adolescent survivors and 649 siblings of childhood cancer survivors to determine the incidence of difficulty in six behavioral and social domains (depression/anxiety, being headstrong, attention deficit, peer conflict/social withdrawal, antisocial behaviors, and social competence).[121]
Survivors were 1.5 times (95% CI, 1.1–2.1) more likely than siblings to have symptoms of depression/anxiety and 1.7 times (95% CI, 1.3–2.2) more likely than siblings to have antisocial behaviors.
Scores in the depression/anxiety, attention deficit, and antisocial domains were significantly elevated in adolescents treated for leukemia or CNS tumors, compared with the scores in siblings.
In addition, survivors of neuroblastoma had difficulty in the depression/anxiety and antisocial domains.
CNS-directed treatments (cranial radiation therapy and/or intrathecal methotrexate) were specific risk factors for adverse behavioral outcomes.
Another CCSS study evaluated psychological and neurocognitive function in 2,589 long-term cancer survivors who were diagnosed during adolescence and young adulthood.[122]
Compared with a sibling cohort, survivors diagnosed during adolescence and young adulthood reported higher rates of depression (OR, 1.55; 95% CI, 1.04–2.30) and anxiety (OR, 2.00; 95% CI, 1.17–3.43) and reported more cognitive problems affecting task efficiency (OR, 1.72; 95% CI, 1.21–2.43), emotional regulation (OR, 1.74; 95% CI, 1.26–2.40), and memory (OR, 1.44; 95% CI, 1.09–1.89).
Survivors of lymphoma and sarcoma diagnosed during later adolescence were at reduced risk of psychosocial and neurocognitive problems than were those diagnosed before age 11 years. These outcomes did not differ by age at diagnosis among CNS tumor and leukemia survivors.
Survivors diagnosed during adolescence and young adulthood were also significantly less likely than sibling controls to have attained a post–high school education, be working full time, be married, or be living independently; inferior social outcomes were related to neurocognitive symptoms.
A follow-up CCSS study evaluated profiles of symptom comorbidities in 3,993 adolescents (aged 13–17 years) treated for cancer.[123] Latent profile analysis identified four symptom profiles:
No significant symptoms.
Elevated internalizing symptoms (anxiety and/or depression, social withdrawal, and attention problems).
Elevated externalizing symptoms (headstrong behavior and attention problems).
Elevated internalizing and externalizing symptoms.
Overall results support that behavioral, emotional, and social symptoms frequently co-occur in adolescent survivors and are associated with treatment exposures (cranial radiation, corticosteroids, and methotrexate) and late effects (obesity, cancer-related pain, and sensory impairments).
The diagnosis of childhood cancer may also affect psychosocial outcomes and the expected attainment of functional and social independence in adulthood. Several investigations have demonstrated that survivors of pediatric CNS tumors are particularly vulnerable.[124,125]
Evidence (functional and social independence):
In a study of 665 survivors of CNS tumors (54% male; 52% treated with cranial radiation therapy; median age, 15 years; and 12 years from diagnosis), CCSS investigators observed the following:[124]
Almost 50% of survivors experienced social difficulties related to peer relationships that exceeded those of survivors of solid tumors and sibling controls.
Cranial radiation exposure predicted social and peer relationships; cognitive impairment mediated the association between all social outcomes and cranial radiation.
A St. Jude Lifetime Cohort Study investigated functional and social independence in 306 CNS tumor survivors (astrocytoma [n = 130], medulloblastoma [n = 77], ependymoma [n = 36], and other [n = 63]; median age, 25 years; and time since diagnosis, 16.8 years).[125]
Only 40% of long-term survivors in the study cohort achieved complete independence as adults.
Predictors of nonindependence included treatment with craniospinal irradiation, history of hydrocephalus with shunting, and younger age at diagnosis.
Beyond impaired IQ scores, functional limitations in aerobic capacity, flexibility, and adaptive physical function were significantly associated with nonindependence.
Social withdrawal in adolescence has been associated with adult obesity and physical inactivity.[126] As a result, these psychological problems may increase future risk for chronic health conditions and support the need to routinely screen and treat psychological problems after cancer therapy.
Because of the challenges experienced by adolescents and young adults at cancer diagnosis and during long-term follow-up, this group may benefit from access to programs to address the unique psychosocial, educational, and vocational issues that impact their transition to survivorship.[127,128]
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for CNS and psychosocial late effects information, including risk factors, evaluation, and health counseling.
Robinson KE, Kuttesch JF, Champion JE, et al.: A quantitative meta-analysis of neurocognitive sequelae in survivors of pediatric brain tumors. Pediatr Blood Cancer 55 (3): 525-31, 2010. [PUBMED Abstract]
Reeves CB, Palmer SL, Reddick WE, et al.: Attention and memory functioning among pediatric patients with medulloblastoma. J Pediatr Psychol 31 (3): 272-80, 2006. [PUBMED Abstract]
Ellenberg L, Liu Q, Gioia G, et al.: Neurocognitive status in long-term survivors of childhood CNS malignancies: a report from the Childhood Cancer Survivor Study. Neuropsychology 23 (6): 705-17, 2009. [PUBMED Abstract]
Butler RW, Fairclough DL, Katz ER, et al.: Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy. Life Sci 93 (17): 611-6, 2013. [PUBMED Abstract]
Patel SK, Mullins WA, O'Neil SH, et al.: Neuropsychological differences between survivors of supratentorial and infratentorial brain tumours. J Intellect Disabil Res 55 (1): 30-40, 2011. [PUBMED Abstract]
Khan RB, Hudson MM, Ledet DS, et al.: Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study. J Cancer Surviv 8 (4): 688-96, 2014. [PUBMED Abstract]
Krull KR, Khan RB, Ness KK, et al.: Symptoms of attention-deficit/hyperactivity disorder in long-term survivors of childhood leukemia. Pediatr Blood Cancer 57 (7): 1191-6, 2011. [PUBMED Abstract]
Kahalley LS, Conklin HM, Tyc VL, et al.: ADHD and secondary ADHD criteria fail to identify many at-risk survivors of pediatric ALL and brain tumor. Pediatr Blood Cancer 57 (1): 110-8, 2011. [PUBMED Abstract]
Cheung YT, Brinkman TM, Li C, et al.: Chronic Health Conditions and Neurocognitive Function in Aging Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 110 (4): 411-419, 2018. [PUBMED Abstract]
Reimers TS, Ehrenfels S, Mortensen EL, et al.: Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors. Med Pediatr Oncol 40 (1): 26-34, 2003. [PUBMED Abstract]
Palmer SL, Goloubeva O, Reddick WE, et al.: Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis. J Clin Oncol 19 (8): 2302-8, 2001. [PUBMED Abstract]
Merchant TE, Schreiber JE, Wu S, et al.: Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma. Int J Radiat Oncol Biol Phys 90 (3): 554-61, 2014. [PUBMED Abstract]
Brinkman TM, Krasin MJ, Liu W, et al.: Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study. J Clin Oncol 34 (12): 1358-67, 2016. [PUBMED Abstract]
Armstrong GT, Conklin HM, Huang S, et al.: Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro Oncol 13 (2): 223-34, 2011. [PUBMED Abstract]
Di Pinto M, Conklin HM, Li C, et al.: Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma. Int J Radiat Oncol Biol Phys 84 (3): e363-9, 2012. [PUBMED Abstract]
Ris MD, Walsh K, Wallace D, et al.: Intellectual and academic outcome following two chemotherapy regimens and radiotherapy for average-risk medulloblastoma: COG A9961. Pediatr Blood Cancer 60 (8): 1350-7, 2013. [PUBMED Abstract]
Orgel E, O'Neil SH, Kayser K, et al.: Effect of Sensorineural Hearing Loss on Neurocognitive Functioning in Pediatric Brain Tumor Survivors. Pediatr Blood Cancer 63 (3): 527-34, 2016. [PUBMED Abstract]
Nassar SL, Conklin HM, Zhou Y, et al.: Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia. Pediatr Blood Cancer 64 (8): , 2017. [PUBMED Abstract]
Mabbott DJ, Spiegler BJ, Greenberg ML, et al.: Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J Clin Oncol 23 (10): 2256-63, 2005. [PUBMED Abstract]
Brière ME, Scott JG, McNall-Knapp RY, et al.: Cognitive outcome in pediatric brain tumor survivors: delayed attention deficit at long-term follow-up. Pediatr Blood Cancer 50 (2): 337-40, 2008. [PUBMED Abstract]
Edelstein K, Spiegler BJ, Fung S, et al.: Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes. Neuro Oncol 13 (5): 536-45, 2011. [PUBMED Abstract]
Mulhern RK, Merchant TE, Gajjar A, et al.: Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 5 (7): 399-408, 2004. [PUBMED Abstract]
Mulhern RK, White HA, Glass JO, et al.: Attentional functioning and white matter integrity among survivors of malignant brain tumors of childhood. J Int Neuropsychol Soc 10 (2): 180-9, 2004. [PUBMED Abstract]
Reddick WE, White HA, Glass JO, et al.: Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer 97 (10): 2512-9, 2003. [PUBMED Abstract]
Brinkman TM, Reddick WE, Luxton J, et al.: Cerebral white matter integrity and executive function in adult survivors of childhood medulloblastoma. Neuro Oncol 14 (Suppl 4): iv25-36, 2012. [PUBMED Abstract]
Jacola LM, Ashford JM, Reddick WE, et al.: The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy. J Neurooncol 119 (1): 197-205, 2014. [PUBMED Abstract]
Palmer SL, Glass JO, Li Y, et al.: White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor. Neuro Oncol 14 (9): 1185-93, 2012. [PUBMED Abstract]
Ris MD, Packer R, Goldwein J, et al.: Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study. J Clin Oncol 19 (15): 3470-6, 2001. [PUBMED Abstract]
Kahalley LS, Ris MD, Grosshans DR, et al.: Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors. J Clin Oncol 34 (10): 1043-9, 2016. [PUBMED Abstract]
Pulsifer MB, Sethi RV, Kuhlthau KA, et al.: Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors. Int J Radiat Oncol Biol Phys 93 (2): 400-7, 2015. [PUBMED Abstract]
Pulsifer MB, Duncanson H, Grieco J, et al.: Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors. Int J Radiat Oncol Biol Phys 102 (2): 391-398, 2018. [PUBMED Abstract]
Moxon-Emre I, Taylor MD, Bouffet E, et al.: Intellectual Outcome in Molecular Subgroups of Medulloblastoma. J Clin Oncol 34 (34): 4161-4170, 2016. [PUBMED Abstract]
Merchant TE, Conklin HM, Wu S, et al.: Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits. J Clin Oncol 27 (22): 3691-7, 2009. [PUBMED Abstract]
Liu APY, Hastings C, Wu S, et al.: Treatment burden and long-term health deficits of patients with low-grade gliomas or glioneuronal tumors diagnosed during the first year of life. Cancer 125 (7): 1163-1175, 2019. [PUBMED Abstract]
Palmer SL, Armstrong C, Onar-Thomas A, et al.: Processing speed, attention, and working memory after treatment for medulloblastoma: an international, prospective, and longitudinal study. J Clin Oncol 31 (28): 3494-500, 2013. [PUBMED Abstract]
Knight SJ, Conklin HM, Palmer SL, et al.: Working memory abilities among children treated for medulloblastoma: parent report and child performance. J Pediatr Psychol 39 (5): 501-11, 2014. [PUBMED Abstract]
Schreiber JE, Gurney JG, Palmer SL, et al.: Examination of risk factors for intellectual and academic outcomes following treatment for pediatric medulloblastoma. Neuro Oncol 16 (8): 1129-36, 2014. [PUBMED Abstract]
Schreiber JE, Palmer SL, Conklin HM, et al.: Posterior fossa syndrome and long-term neuropsychological outcomes among children treated for medulloblastoma on a multi-institutional, prospective study. Neuro Oncol 19 (12): 1673-1682, 2017. [PUBMED Abstract]
Moxon-Emre I, Bouffet E, Taylor MD, et al.: Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma. J Clin Oncol 32 (17): 1760-8, 2014. [PUBMED Abstract]
Armstrong GT, Liu Q, Yasui Y, et al.: Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst 101 (13): 946-58, 2009. [PUBMED Abstract]
Ris MD, Leisenring WM, Goodman P, et al.: Neuropsychological and socioeconomic outcomes in adult survivors of pediatric low-grade glioma. Cancer 125 (17): 3050-3058, 2019. [PUBMED Abstract]
Brinkman TM, Palmer SL, Chen S, et al.: Parent-reported social outcomes after treatment for pediatric embryonal tumors: a prospective longitudinal study. J Clin Oncol 30 (33): 4134-40, 2012. [PUBMED Abstract]
Moyer KH, Willard VW, Gross AM, et al.: The impact of attention on social functioning in survivors of pediatric acute lymphoblastic leukemia and brain tumors. Pediatr Blood Cancer 59 (7): 1290-5, 2012. [PUBMED Abstract]
Kunin-Batson A, Kadan-Lottick N, Zhu L, et al.: Predictors of independent living status in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 57 (7): 1197-203, 2011. [PUBMED Abstract]
Janson C, Leisenring W, Cox C, et al.: Predictors of marriage and divorce in adult survivors of childhood cancers: a report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 18 (10): 2626-35, 2009. [PUBMED Abstract]
Pui CH, Howard SC: Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol 9 (3): 257-68, 2008. [PUBMED Abstract]
Reddick WE, Glass JO, Helton KJ, et al.: Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 26 (5): 1263-9, 2005. [PUBMED Abstract]
Waber DP, Queally JT, Catania L, et al.: Neuropsychological outcomes of standard risk and high risk patients treated for acute lymphoblastic leukemia on Dana-Farber ALL consortium protocol 95-01 at 5 years post-diagnosis. Pediatr Blood Cancer 58 (5): 758-65, 2012. [PUBMED Abstract]
Krull KR, Brinkman TM, Li C, et al.: Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study. J Clin Oncol 31 (35): 4407-15, 2013. [PUBMED Abstract]
Reddick WE, Shan ZY, Glass JO, et al.: Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer 106 (4): 941-9, 2006. [PUBMED Abstract]
Kadan-Lottick NS, Zeltzer LK, Liu Q, et al.: Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers. J Natl Cancer Inst 102 (12): 881-93, 2010. [PUBMED Abstract]
Krull KR, Zhang N, Santucci A, et al.: Long-term decline in intelligence among adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation. Blood 122 (4): 550-3, 2013. [PUBMED Abstract]
Annett RD, Hile S, Bedrick E, et al.: Neuropsychological functioning of children treated for acute lymphoblastic leukemia: impact of whole brain radiation therapy. Psychooncology 24 (2): 181-9, 2015. [PUBMED Abstract]
Schuitema I, Deprez S, Van Hecke W, et al.: Accelerated aging, decreased white matter integrity, and associated neuropsychological dysfunction 25 years after pediatric lymphoid malignancies. J Clin Oncol 31 (27): 3378-88, 2013. [PUBMED Abstract]
Armstrong GT, Reddick WE, Petersen RC, et al.: Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy. J Natl Cancer Inst 105 (12): 899-907, 2013. [PUBMED Abstract]
Spiegler BJ, Kennedy K, Maze R, et al.: Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate. J Clin Oncol 24 (24): 3858-64, 2006. [PUBMED Abstract]
Campbell LK, Scaduto M, Sharp W, et al.: A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 49 (1): 65-73, 2007. [PUBMED Abstract]
Cheung YT, Sabin ND, Reddick WE, et al.: Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. Lancet Haematol 3 (10): e456-e466, 2016. [PUBMED Abstract]
Mennes M, Stiers P, Vandenbussche E, et al.: Attention and information processing in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Pediatr Blood Cancer 44 (5): 478-86, 2005. [PUBMED Abstract]
Jansen NC, Kingma A, Schuitema A, et al.: Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia. J Clin Oncol 26 (18): 3025-30, 2008. [PUBMED Abstract]
Iyer NS, Balsamo LM, Bracken MB, et al.: Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis. Blood 126 (3): 346-53, 2015. [PUBMED Abstract]
Jacola LM, Krull KR, Pui CH, et al.: Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol. J Clin Oncol 34 (11): 1239-47, 2016. [PUBMED Abstract]
Espy KA, Moore IM, Kaufmann PM, et al.: Chemotherapeutic CNS prophylaxis and neuropsychologic change in children with acute lymphoblastic leukemia: a prospective study. J Pediatr Psychol 26 (1): 1-9, 2001 Jan-Feb. [PUBMED Abstract]
Kaemingk KL, Carey ME, Moore IM, et al.: Math weaknesses in survivors of acute lymphoblastic leukemia compared to healthy children. Child Neuropsychol 10 (1): 14-23, 2004. [PUBMED Abstract]
Buizer AI, de Sonneville LM, Veerman AJ: Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: a critical review of the literature. Pediatr Blood Cancer 52 (4): 447-54, 2009. [PUBMED Abstract]
von der Weid N, Mosimann I, Hirt A, et al.: Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences. Eur J Cancer 39 (3): 359-65, 2003. [PUBMED Abstract]
Jacola LM, Edelstein K, Liu W, et al.: Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study. Lancet Psychiatry 3 (10): 965-972, 2016. [PUBMED Abstract]
Krull KR, Cheung YT, Liu W, et al.: Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia. J Clin Oncol 34 (22): 2644-53, 2016. [PUBMED Abstract]
Conklin HM, Krull KR, Reddick WE, et al.: Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia. J Natl Cancer Inst 104 (18): 1386-95, 2012. [PUBMED Abstract]
Halsey C, Buck G, Richards S, et al.: The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI. J Hematol Oncol 4: 42, 2011. [PUBMED Abstract]
Kadan-Lottick NS, Brouwers P, Breiger D, et al.: A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood 114 (9): 1746-52, 2009. [PUBMED Abstract]
Edelmann MN, Daryani VM, Bishop MW, et al.: Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma. JAMA Oncol 2 (2): 201-8, 2016. [PUBMED Abstract]
Levitt EA, Rosenbaum AL, Willerman L, et al.: Intelligence of retinoblastoma patients and their siblings. Child Dev 43 (3): 939-48, 1972. [PUBMED Abstract]
Eldridge R, O'Meara K, Kitchin D: Superior intelligence in sighted retinoblastoma patients and their families. J Med Genet 9 (3): 331-5, 1972. [PUBMED Abstract]
Williams M: Superior intelligence of children blinded from retinoblastoma. Arch Dis Child 43 (228): 204-10, 1968. [PUBMED Abstract]
Willard VW, Qaddoumi I, Chen S, et al.: Developmental and adaptive functioning in children with retinoblastoma: a longitudinal investigation. J Clin Oncol 32 (25): 2788-93, 2014. [PUBMED Abstract]
Brinkman TM, Merchant TE, Li Z, et al.: Cognitive function and social attainment in adult survivors of retinoblastoma: a report from the St. Jude Lifetime Cohort Study. Cancer 121 (1): 123-31, 2015. [PUBMED Abstract]
Ehrhardt MJ, Sandlund JT, Zhang N, et al.: Late outcomes of adult survivors of childhood non-Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 64 (6): , 2017. [PUBMED Abstract]
Krull KR, Sabin ND, Reddick WE, et al.: Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma. J Clin Oncol 30 (29): 3618-24, 2012. [PUBMED Abstract]
Phipps S, Rai SN, Leung WH, et al.: Cognitive and academic consequences of stem-cell transplantation in children. J Clin Oncol 26 (12): 2027-33, 2008. [PUBMED Abstract]
Shah AJ, Epport K, Azen C, et al.: Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies. J Pediatr Hematol Oncol 30 (6): 411-8, 2008. [PUBMED Abstract]
Anderson FS, Kunin-Batson AS, Perkins JL, et al.: White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood. Neuropsychiatr Dis Treat 4 (1): 283-8, 2008. [PUBMED Abstract]
Wells EM, Ullrich NJ, Seidel K, et al.: Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors: a Childhood Cancer Survivor Study report. Neuro Oncol 20 (1): 132-142, 2018. [PUBMED Abstract]
Goldsby RE, Liu Q, Nathan PC, et al.: Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28 (2): 324-31, 2010. [PUBMED Abstract]
Khong PL, Leung LH, Fung AS, et al.: White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function. J Clin Oncol 24 (6): 884-90, 2006. [PUBMED Abstract]
Zeller B, Tamnes CK, Kanellopoulos A, et al.: Reduced neuroanatomic volumes in long-term survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 31 (17): 2078-85, 2013. [PUBMED Abstract]
Jain P, Gulati S, Seth R, et al.: Vincristine-induced neuropathy in childhood ALL (acute lymphoblastic leukemia) survivors: prevalence and electrophysiological characteristics. J Child Neurol 29 (7): 932-7, 2014. [PUBMED Abstract]
Ness KK, Jones KE, Smith WA, et al.: Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study. Arch Phys Med Rehabil 94 (8): 1451-7, 2013. [PUBMED Abstract]
Kandula T, Farrar MA, Cohn RJ, et al.: Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes. JAMA Neurol 75 (8): 980-988, 2018. [PUBMED Abstract]
Gurney JG, Kadan-Lottick NS, Packer RJ, et al.: Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 97 (3): 663-73, 2003. [PUBMED Abstract]
Ullrich NJ, Robertson R, Kinnamon DD, et al.: Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 68 (12): 932-8, 2007. [PUBMED Abstract]
Wang C, Roberts KB, Bindra RS, et al.: Delayed cerebral vasculopathy following cranial radiation therapy for pediatric tumors. Pediatr Neurol 50 (6): 549-56, 2014. [PUBMED Abstract]
Khan RB, Merchant TE, Sadighi ZS, et al.: Prevalence, risk factors, and response to treatment for hypersomnia of central origin in survivors of childhood brain tumors. J Neurooncol 136 (2): 379-384, 2018. [PUBMED Abstract]
van Kooten JAMC, Maurice-Stam H, Schouten AYN, et al.: High occurrence of sleep problems in survivors of a childhood brain tumor with neurocognitive complaints: The association with psychosocial and behavioral executive functioning. Pediatr Blood Cancer 66 (11): e27947, 2019. [PUBMED Abstract]
Hörnquist L, Rickardsson J, Lannering B, et al.: Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population. Neuro Oncol 17 (5): 733-40, 2015. [PUBMED Abstract]
Schulte F, Barrera M: Social competence in childhood brain tumor survivors: a comprehensive review. Support Care Cancer 18 (12): 1499-513, 2010. [PUBMED Abstract]
Brinkman TM, Zhu L, Zeltzer LK, et al.: Longitudinal patterns of psychological distress in adult survivors of childhood cancer. Br J Cancer 109 (5): 1373-81, 2013. [PUBMED Abstract]
Brinkman TM, Zhang N, Recklitis CJ, et al.: Suicide ideation and associated mortality in adult survivors of childhood cancer. Cancer 120 (2): 271-7, 2014. [PUBMED Abstract]
Gunnes MW, Lie RT, Bjørge T, et al.: Suicide and violent deaths in survivors of cancer in childhood, adolescence and young adulthood-A national cohort study. Int J Cancer 140 (3): 575-580, 2017. [PUBMED Abstract]
Sun CL, Francisco L, Baker KS, et al.: Adverse psychological outcomes in long-term survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study (BMTSS). Blood 118 (17): 4723-31, 2011. [PUBMED Abstract]
Zheng DJ, Krull KR, Chen Y, et al.: Long-term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study. Cancer 124 (15): 3220-3230, 2018. [PUBMED Abstract]
Fuemmeler BF, Elkin TD, Mullins LL: Survivors of childhood brain tumors: behavioral, emotional, and social adjustment. Clin Psychol Rev 22 (4): 547-85, 2002. [PUBMED Abstract]
Recklitis C, O'Leary T, Diller L: Utility of routine psychological screening in the childhood cancer survivor clinic. J Clin Oncol 21 (5): 787-92, 2003. [PUBMED Abstract]
Phipps S, Klosky JL, Long A, et al.: Posttraumatic stress and psychological growth in children with cancer: has the traumatic impact of cancer been overestimated? J Clin Oncol 32 (7): 641-6, 2014. [PUBMED Abstract]
Phipps S, Larson S, Long A, et al.: Adaptive style and symptoms of posttraumatic stress in children with cancer and their parents. J Pediatr Psychol 31 (3): 298-309, 2006. [PUBMED Abstract]
Phipps S, Jurbergs N, Long A: Symptoms of post-traumatic stress in children with cancer: does personality trump health status? Psychooncology 18 (9): 992-1002, 2009. [PUBMED Abstract]
Stuber ML, Meeske KA, Leisenring W, et al.: Defining medical posttraumatic stress among young adult survivors in the Childhood Cancer Survivor Study. Gen Hosp Psychiatry 33 (4): 347-53, 2011 Jul-Aug. [PUBMED Abstract]
Rourke MT, Hobbie WL, Schwartz L, et al.: Posttraumatic stress disorder (PTSD) in young adult survivors of childhood cancer. Pediatr Blood Cancer 49 (2): 177-82, 2007. [PUBMED Abstract]
Schwartz L, Drotar D: Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. J Pediatr Psychol 31 (4): 356-66, 2006. [PUBMED Abstract]
Stuber ML, Meeske KA, Krull KR, et al.: Prevalence and predictors of posttraumatic stress disorder in adult survivors of childhood cancer. Pediatrics 125 (5): e1124-34, 2010. [PUBMED Abstract]
Hobbie WL, Stuber M, Meeske K, et al.: Symptoms of posttraumatic stress in young adult survivors of childhood cancer. J Clin Oncol 18 (24): 4060-6, 2000. [PUBMED Abstract]
Dieluweit U, Debatin KM, Grabow D, et al.: Social outcomes of long-term survivors of adolescent cancer. Psychooncology 19 (12): 1277-84, 2010. [PUBMED Abstract]
Seitz DC, Hagmann D, Besier T, et al.: Life satisfaction in adult survivors of cancer during adolescence: what contributes to the latter satisfaction with life? Qual Life Res 20 (2): 225-36, 2011. [PUBMED Abstract]
Tai E, Buchanan N, Townsend J, et al.: Health status of adolescent and young adult cancer survivors. Cancer 118 (19): 4884-91, 2012. [PUBMED Abstract]
Schultz KA, Ness KK, Whitton J, et al.: Behavioral and social outcomes in adolescent survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 25 (24): 3649-56, 2007. [PUBMED Abstract]
Prasad PK, Hardy KK, Zhang N, et al.: Psychosocial and Neurocognitive Outcomes in Adult Survivors of Adolescent and Early Young Adult Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 33 (23): 2545-52, 2015. [PUBMED Abstract]
Brinkman TM, Li C, Vannatta K, et al.: Behavioral, Social, and Emotional Symptom Comorbidities and Profiles in Adolescent Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 34 (28): 3417-25, 2016. [PUBMED Abstract]
Schulte F, Brinkman TM, Li C, et al.: Social adjustment in adolescent survivors of pediatric central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer 124 (17): 3596-3608, 2018. [PUBMED Abstract]
Brinkman TM, Ness KK, Li Z, et al.: Attainment of Functional and Social Independence in Adult Survivors of Pediatric CNS Tumors: A Report From the St Jude Lifetime Cohort Study. J Clin Oncol 36 (27): 2762-2769, 2018. [PUBMED Abstract]
Krull KR, Huang S, Gurney JG, et al.: Adolescent behavior and adult health status in childhood cancer survivors. J Cancer Surviv 4 (3): 210-7, 2010. [PUBMED Abstract]
Freyer DR: Transition of care for young adult survivors of childhood and adolescent cancer: rationale and approaches. J Clin Oncol 28 (32): 4810-8, 2010. [PUBMED Abstract]
Nathan PC, Hayes-Lattin B, Sisler JJ, et al.: Critical issues in transition and survivorship for adolescents and young adults with cancers. Cancer 117 (10 Suppl): 2335-41, 2011. [PUBMED Abstract]
Chemotherapy, radiation therapy, and local surgery can cause multiple cosmetic and functional abnormalities of the oral cavity and dentition. The quality of current evidence regarding this outcome is limited by retrospective data collection, small sample size, cohort selection and participation bias, and heterogeneity in treatment approach, time since treatment, and method of ascertainment.
Oral and dental complications reported in childhood cancer survivors include the following:
Abnormalities of tooth development.
Salivary gland dysfunction.
Abnormalities of craniofacial development.
Osteoradionecrosis and second cancers in the oral cavity also occur.
Abnormalities of tooth development
Abnormalities of dental development reported in childhood cancer survivors include the following:[1-11]
Absence of tooth development.
Hypodontia.
Microdontia.
Enamel hypoplasia.
Root malformation.
The prevalence of hypodontia has varied widely in series depending on age at diagnosis, treatment modality, and method of ascertainment.
Cancer treatments that have been associated with dental maldevelopment include the following:[3,11]
Head and neck radiation therapy.
Any chemotherapy.
Hematopoietic stem cell transplantation (HSCT).
Children younger than 5 years are at greatest risk for dental anomalies, including root agenesis, delayed eruption, enamel defects, and/or excessive caries related to disruption of ameloblast (enamel producing) and odontoblast (dentin producing) activity early in life.[3]
Key findings related to cancer treatment effect on tooth development include the following:
Radiation therapy. Radiation directed at oral cavity or surrounding structures increases the risk of dental anomalies because ameloblasts can be permanently damaged by doses as low as 10 Gy.[3,5,6,12] However, the most significant degree of tooth aplasia or delayed eruption occurs in younger children (aged <4 years) who are exposed to radiation doses of 20 Gy or higher.[13]
Developing teeth may be irradiated in the course of treating head and neck sarcomas, Hodgkin lymphoma, neuroblastoma, central nervous system leukemia, nasopharyngeal cancer, brain tumors, and as a component of total-body irradiation (TBI). Doses of 10 Gy to 40 Gy can cause root shortening or abnormal curvature, dwarfism, and hypocalcification.[14] Significant dental abnormalities, including mandibular or maxillary hypoplasia, increased caries, hypodontia, microdontia, root stunting, and xerostomia have been reported in more than 85% of survivors of head and neck rhabdomyosarcoma treated with radiation doses higher than 40 Gy.[4,5]
Chemotherapy. Chemotherapy, especially exposure to alkylating agents, can affect tooth development.[3,6,7] Chemotherapy for the treatment of leukemia or neuroblastoma is associated with shortening and thinning of the premolar roots and enamel abnormalities.[15-17] Childhood Cancer Survivor Study (CCSS) investigators identified age younger than 5 years and increased exposure to cyclophosphamide as significant risk factors for developmental dental abnormalities in long-term survivors of childhood cancer.[3]
HSCT. HSCT conditioning, especially regimens containing TBI, may result in tooth agenesis and root malformation. Younger children who have not developed secondary teeth are most vulnerable.[1,2,6] Children who undergo HSCT with TBI may develop short V-shaped roots, microdontia, enamel hypoplasia, and/or premature apical closure.[1,2,8] The younger a patient is when treated with HSCT, the more severely disturbed dental development will be and the more deficient vertical growth of the lower face will be. These high-risk patients require close surveillance and appropriate interventions.[9] Dental abnormalities have been reported in patients who underwent HSCT without TBI, particularly in patients younger than 2 years at the time of the transplant.[18]
Salivary gland dysfunction
Xerostomia, the sensation of dry mouth, is a potential side effect after head and neck irradiation or HSCT that can severely impact quality of life. Complications of reduced salivary secretion include the following:[19,20]
Increased caries.
Susceptibility to oral infections.
Sleep disturbances.
Difficulties with chewing, swallowing, and speaking.
The prevalence of salivary gland dysfunction after cancer treatment varies based on measurement techniques (patient report vs. stimulated or unstimulated salivary secretion rates).[21] In general, the prevalence of self-reported persistent posttherapy xerostomia is low among childhood cancer survivors. In the CCSS, the prevalence of self-reported xerostomia in survivors was 2.8% compared with 0.3% in siblings, with an increased risk in survivors older than 30 years.[3]
Key findings related to cancer treatment effect on salivary gland function include the following:
Radiation therapy. Salivary gland irradiation incidental to treatment of head and neck malignancies or Hodgkin lymphoma causes a qualitative and quantitative change in salivary flow, which can be reversible after doses of less than 40 Gy but may be irreversible after higher doses, depending on whether sensitizing chemotherapy is also administered.[19]
HSCT. HSCT recipients are at increased risk of salivary gland dysfunction related to transplant conditioning or graft-versus-host disease (GVHD). GVHD can cause hyposalivation and xerostomia with resultant dental disease. In a study of pediatric HSCT survivors, 60% of those exposed to a conditioning regimen with cyclophosphamide and 10 Gy single-dose TBI had decreased salivary secretion rates, compared with 26% in those who received cyclophosphamide and busulfan.[22] In contrast, in another study, the prevalence of reduced salivary secretion did not differ among long-term survivors on the basis of the conditioning regimen (single-dose TBI, 47%; fractionated TBI, 47%; busulfan, 42%).[23]
Chemotherapy. The association of chemotherapy alone with xerostomia remains controversial.[19] Only one study of pediatric patients demonstrated an excess risk (odds ratio, 12.32 [2.1–74.4]) of decreased stimulated saliva flow rates among patients treated with cyclophosphamide; however, an increase in dental caries was not noted and patient-reported xerostomia was not evaluated.[7]
The impact of infectious complications and alterations in the microflora during and after therapy is not known.[6]
Abnormalities of craniofacial development
Craniofacial maldevelopment is a common adverse outcome among children treated with high-dose radiation therapy to the head and neck that frequently occurs in association with other oral cavity sequelae such as dental anomalies, xerostomia, and trismus.[5,24,25] The extent and severity of musculoskeletal disfigurement is related to age at treatment and radiation therapy volume and dose, with higher risk observed among younger patients and those who received 30 Gy or more.
Osteoradionecrosis of the jaw is a rare complication observed in childhood survivors treated with high-dose craniofacial radiation (>40 Gy), particularly after dental extractions in irradiated mandibles.[26,27]
Remediation of cosmetic and functional abnormalities often requires multiple surgical interventions.
Posttherapy management
Some studies suggest that fluoride products or chlorhexidine rinses may be beneficial in patients who have undergone radiation therapy.[28] Dental caries are a problematic consequence of reduced salivary quality and flow. The use of topical fluoride can dramatically reduce the frequency of caries, and saliva substitutes and sialagogues can ameliorate sequelae such as xerostomia.[20]
It has been reported that the incidence of dental visits for childhood cancer survivors falls below the American Dental Association's recommendation that all adults visit the dentist annually.[29] The Children’s Oncology Group Long-term Follow-Up Guidelines recommend biannual dental cleaning and exams for all survivors of childhood cancer. These findings give health care providers further impetus to encourage routine dental care and dental hygiene evaluations for survivors of childhood treatment. (Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information about oral complications in cancer patients.)
Table 4 summarizes oral and dental late effects and the related health screenings.
Table 4. Oral/Dental Late Effectsa
Oral/Dental Effects
Health Screening/Interventions
CT = computed tomography; GVHD = graft-versus-host disease; MRI = magnetic resonance imaging.
Any chemotherapy; radiation impacting oral cavity Dental developmental abnormalities; tooth/root agenesis; microdontia; root thinning/shortening; enamel dysplasia Dental evaluation and cleaning every 6 months
Regular dental care including fluoride applications
Consultation with orthodontist experienced in management of irradiated childhood cancer survivors
Baseline Panorex x-ray before dental procedures to evaluate root development
Radiation impacting oral cavity Malocclusion; temporomandibular joint dysfunction Dental evaluation and cleaning every 6 months
Referral to otolaryngologist for assistive devices for jaw opening
Radiation impacting oral cavity; hematopoietic cell transplantation with history of chronic GVHD Xerostomia/salivary gland dysfunction; periodontal disease; dental caries; oral cancer (squamous cell carcinoma) Dental evaluation and cleaning every 6 months
Supportive care with saliva substitutes, moistening agents, and sialogogues (pilocarpine)
Referral for biopsy of suspicious lesions
Radiation impacting oral cavity (≥40 Gy) Osteoradionecrosis History: impaired or delayed healing after dental work
Exam: persistent jaw pain, swelling or trismus
Imaging studies (x-ray, CT scan and/or MRI) may assist in making diagnosis
Surgical biopsy may be needed to confirm diagnosis
Consider hyperbaric oxygen treatments
Digestive Tract
The gastrointestinal (GI) tract is sensitive to the acute toxicities of chemotherapy, radiation therapy, and surgery. However, these important treatment modalities can also result in some long-term issues in a treatment- and dose-dependent manner. Reports published about long-term GI tract outcomes are limited by retrospective data collection, small sample size, cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment.
Treatment-related late effects include the following:
Upper and lower digestive tract late effects associated with dose intensity of chemotherapy and/or abdominal radiation.
Adhesions secondary to abdominal surgery predisposing to postoperative bowel obstruction.
Digestive tract–related late effects include the following:
Esophageal dysmotility.
Esophageal stricture.
Gastroesophageal reflux.
Gastritis, enteritis, or colitis.
GI motility dysfunction (diarrhea, constipation, encopresis, bowel obstruction).
Subsequent malignant neoplasms
GI outcomes from selected cohort studies
Evidence (GI outcomes from selected cohort studies):
Among 5-year childhood cancer survivors participating in the CCSS, the cumulative incidence of self-reported GI conditions was 37.6% at 20 years from cancer diagnosis (25.8% for upper GI complications and 15.5% for lower GI complications), representing an almost twofold excess risk of upper GI complications (relative risk [RR], 1.8; 95% confidence interval [CI], 1.6–2.0) and lower GI complications (RR, 1.9; 95% CI, 1.7–2.2), compared with sibling controls.[30]
Factors predicting higher risk of specific GI complications include the following:
Older age at diagnosis.
Intensified therapy (anthracyclines for upper GI complications and alkylating agents for lower GI complications).
Abdominal radiation therapy.
Abdominal surgery.
A cohort study of children treated for acute myeloid leukemia with chemotherapy alone found that GI disorders were relatively rare and not significantly different from those reported by sibling controls.[31]
Late radiation injury to the digestive tract is attributable to vascular injury. Necrosis, ulceration, stenosis, or perforation can occur and are characterized by malabsorption, pain, and recurrent episodes of bowel obstruction, as well as perforation and infection.[32-34]
In general, fractionated radiation doses of 20 Gy to 30 Gy can be delivered to the small bowel without significant long-term morbidity. Doses greater than 40 Gy are associated with a higher risk of bowel obstruction or chronic enterocolitis.[35] Sensitizing chemotherapeutic agents such as dactinomycin or anthracyclines can increase this risk.
Impact of cancer histology on GI outcomes
Intra-abdominal tumors represent a relatively common location for several pediatric malignancies, including rhabdomyosarcoma, Wilms tumor, lymphoma, germ cell tumors, and neuroblastoma. Intra-abdominal tumors often require multimodal therapy, occasionally necessitating resection of bowel, bowel-injuring chemotherapy, and/or radiation therapy. Thus, these tumors would be expected to be particularly prone to long-term digestive tract issues.
A limited number of reports describe GI complications in pediatric patients with genitourinary solid tumors treated with radiation therapy:[36-40]
One study comprehensively evaluated intestinal symptoms in 44 children with cancer who underwent whole-abdominal (10–40 Gy) and involved-field (25–40 Gy) radiation therapy and received additional interventions predisposing them to GI tract complications, including abdominal laparotomy in 43 patients (98%) and chemotherapy in 25 patients (57%).[36]
Late small-bowel obstruction was observed in 36% of patients surviving for 19 months to 7 years, which was uniformly preceded by small bowel toxicity during therapy.
The CCSS evaluated the incidence and risk of late-occurring intestinal obstruction requiring surgery in 12,316 5-year survivors (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 siblings. The most common diagnoses among survivors with abdominopelvic tumors were Wilms tumors and neuroblastomas but also included soft tissue sarcomas, lymphomas, and bone tumors.[41]
The cumulative incidence of late intestinal obstruction requiring surgery at 35 years was 5.8% among survivors with abdominopelvic tumors, 1.0% among those without abdominopelvic tumors, and 0.3% among siblings.
Elevated risk of intestinal obstruction requiring surgery was associated with presence of an abdominopelvic tumor (adjusted rate ratio [ARR], 3.6; P < .001) and exposure to abdominal or pelvic radiation therapy within 5 years of cancer diagnosis (ARR, 2.4; P < .001).
Among survivors of abdominopelvic tumors, the median time from diagnosis to the first late intestinal obstruction requiring surgery was 12 years (range, 8–19 years).
Lymphoma resulted in the highest cumulative incidence of late-occurring intestinal obstruction requiring surgery (7.2% at 35 years after diagnosis).
Childhood cancer survivors are at increased risk of late anorectal disease after pelvic radiation exposure. A report from the CCSS demonstrated the following results:[42]
Among survivors, pelvic radiation therapy higher than 30 Gy within 5 years of cancer diagnosis was associated with late-onset anorectal disease (ARR for 30–49.9 Gy vs. none, 1.6; ARR for ≥50 Gy vs. none, 5.4).
The most frequent anorectal disease reported was fistula-in-ano, followed by stricture and anorectal subsequent malignant neoplasm.
Late-onset anorectal disease was associated with psychological impairment in all domains, as characterized by increased emotional distress and impaired quality of life.
Reports from the Intergroup Rhabdomyosarcoma Study evaluating GI toxicity in long-term survivors of genitourinary rhabdomyosarcoma infrequently observed abnormalities of the irradiated bowel.[37,38,40]
Radiation-related complications occurred in approximately 10% of long-term survivors of paratesticular and bladder/prostate rhabdomyosarcoma and included intraperitoneal adhesions with bowel obstruction, chronic diarrhea, and stricture or enteric fistula formation.
Table 5 summarizes digestive tract late effects and the related health screenings.
Table 5. Digestive Tract Late Effectsa
Gastrointestinal Effects
GVHD = graft-versus-host disease; KUB = kidneys, ureter, bladder (plain abdominal radiograph).
Radiation impacting esophagus; hematopoietic cell transplantation with any history of chronic GVHD Gastroesophageal reflux; esophageal dysmotility; esophageal stricture History: dysphagia, heart burn
Esophageal dilation, antireflux surgery
Radiation impacting bowel Chronic enterocolitis; fistula; strictures History: nausea, vomiting, abdominal pain, diarrhea
Serum protein and albumin levels yearly in patients with chronic diarrhea or fistula
Surgical and/or gastroenterology consultation for symptomatic patients
Radiation impacting bowel; laparotomy Bowel obstruction History: abdominal pain, distention, vomiting, constipation
Exam: tenderness, abdominal guarding, distension (acute episode)
Obtain KUB in patients with clinical symptoms of obstruction
Surgical consultation in patients unresponsive to medical management
Pelvic surgery; cystectomy Fecal incontinence History: chronic constipation, fecal soiling
Hepatic complications resulting from childhood cancer therapy are observed primarily as acute treatment toxicities.[43] Because many chemotherapy agents and radiation are hepatotoxic, transient liver function anomalies are common during therapy. Severe acute hepatic complications rarely occur. Survivors of childhood cancer can occasionally exhibit long-standing hepatic injury.[44]
Some general concepts regarding hepatotoxicity related to childhood cancer include the following:
The risk of long-term hepatotoxicity is not well defined.
Children with primary liver tumors requiring significant liver resection, or even transplant, are at higher risk of liver injury.
Children receiving radiation therapy to the liver are at higher risk of liver injury.
Children undergoing bone marrow transplant are at higher risk of liver injury.
Certain factors, including the type of chemotherapy, the dose and extent of radiation exposure, the influence of surgical interventions, and the evolving impact of viral hepatitis and/or other infectious complication, need additional attention in future studies.
Types of hepatobiliary late effects
Asymptomatic elevation of liver enzymes is the most common hepatobiliary complication.
Asymptomatic elevation of liver enzymes. Liver injury related to treatment for childhood cancer is often asymptomatic and indolent in course. While elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) levels can reflect transient acute liver injury during chemotherapy, they are not predictive of late hepatic dysfunction or cirrhosis.
Dutch investigators observed hepatobiliary dysfunction in 8.7% of 1,362 long-term survivors (median follow-up, 12.4 years since diagnosis) evaluated by ALT for hepatocellular injury and GGT for biliary tract injury. Cases with a history of viral hepatitis and a history of veno-occlusive disease were excluded. Predictors for elevated ALT and GGT by multivariable analysis included treatment with radiation therapy involving the liver, higher body mass index (BMI), higher alcohol intake, and longer follow-up time; older age at diagnosis was only significantly associated with elevated GGT levels.[45] In a CCSS report, survivors of childhood cancer were more than two times more likely to report a hepatic-related health issue and were nearly nine times more likely to report cirrhosis, compared with sibling controls.[30]
Less commonly reported hepatobiliary complications include the following:
Cholelithiasis. In limited studies, an increased risk of cholelithiasis has been linked to ileal conduit, parenteral nutrition, abdominal surgery, abdominal radiation therapy, and HSCT.[46,47] Gallbladder disease was the most frequent late-onset liver condition reported among participants in the CCSS, with a twofold excess risk compared with sibling controls (RR, 2.0; 95% CI, 2.0–40.0).[30]
Focal nodular hyperplasia. Lesions made up of regenerating liver called focal nodular hyperplasia have been incidentally noted on screening imaging studies after chemotherapy or HSCT.[48,49]
These lesions are thought to be iatrogenic benign manifestations of vascular damage and have been associated with veno-occlusive disease, high-dose alkylating agents (e.g., busulfan and melphalan), and liver irradiation. The prevalence of this finding is unknown; while noted at less than 1% in some papers,[49] this is likely an underestimate. In one study of patients who were followed by magnetic resonance imaging (MRI) after transplant to assess liver iron stores, the cumulative incidence was 35% at 150 months posttransplant.[48]
The lesions can mimic metastatic or subsequent tumors, but MRI imaging has a characteristic pattern and is generally diagnostic. Biopsy or resection is usually unnecessary unless the lesions grow or patients have worrisome symptoms.
Nodular regenerative hyperplasia.[50] Nodular regenerative hyperplasia is a rare condition characterized by the development of multiple monoacinar regenerative hepatic nodules and mild fibrosis. The pathogenesis is not well established but may represent a nonspecific tissue adaptation to heterogeneous hepatic blood flow.[51] Nodular regenerative hyperplasia has rarely been observed in survivors of childhood cancer treated with chemotherapy, with or without liver irradiation.[52,53]
Biopsy may be necessary to distinguish nodular regenerative hyperplasia from a subsequent malignancy.
Microvesicular fatty change.[50] In a cohort who recently completed intensified therapy for acute lymphoblastic leukemia, histologic evidence of fatty infiltration was noted in 93% and siderosis in up to 70% of patients.[54] Fibrosis developed in 11% and was associated with higher serum low-density lipoprotein (LDL) cholesterol. Fatty liver with insulin resistance has also been reported to develop more frequently in long-term childhood cancer survivors treated with cranial radiation therapy before allogeneic stem cell transplantation who were not overweight or obese.[55] Prospective studies are needed to define whether acute posttherapy fatty liver change contributes to the development of late steatohepatitis or the metabolic syndrome in this population.
Transfusion-related iron overload. Red blood cell transfusion can result in an accumulation of excess iron due to disruption of the homeostasis of iron storage and distribution when exogenous iron is loaded into organs. Transfusional iron overload has been reported in pediatric oncology patients, but its prevalence, organ distribution, and severity remain incompletely characterized.
MRI has emerged as an accurate, noninvasive means for measuring iron in multiple organ systems.[56,57] In a cross-sectional study of 75 patients (4.4 years of median follow-up time; 4.9 years since last transfusion), MRI iron concentrations were elevated in the liver (49.3%) and pancreas (26.4%), but not in the heart.
In a multivariable analysis, cumulative packed red blood cell volume and older age at diagnosis predicted elevated liver iron concentration.[56] Receipt of allogeneic transplantation is a significant risk factor.[58] A study of 116 childhood cancer survivors identified three patients (2.6%) with ferritin greater than 500 ng/mL. The total packed red blood cell volume correlated with elevated ferritin (r = 0.74; P < .0001).[59] Additional research is needed to better characterize survivors at risk of clinically significant transfusion-related iron overload who warrant interventions to reduce iron burden and organ dysfunction.
Treatment-related risk factors for hepatobiliary late effects
The type and intensity of previous therapy influences risk for late-occurring hepatobiliary effects. In addition to the risk of treatment-related toxicity, recipients of HSCT frequently experience chronic liver dysfunction related to microvascular, immunologic, infectious, metabolic, and other toxic etiologies.
Key findings related to cancer treatment effect on hepatobiliary complications include the following:
Chemotherapy. Chemotherapeutic agents with established hepatotoxic potential include antimetabolite agents like 6-mercaptopurine, 6-thioguanine, methotrexate, and rarely, dactinomycin. Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) and cholestatic disease have been observed after thiopurine administration, especially 6-thioguanine. Progressive fibrosis and portal hypertension have been reported in a subset of children who developed VOD/SOS after treatment with 6-thioguanine.[60-62] Acute, dose-related, reversible VOD/SOS has been observed in children treated with dactinomycin for pediatric solid tumors.[63,64]
In the transplant setting, VOD/SOS has also been observed after conditioning regimens that have included cyclophosphamide/TBI, busulfan/cyclophosphamide, and carmustine/cyclophosphamide/etoposide.[65] High-dose cyclophosphamide, common to all of these regimens, is speculated to be a potential causative factor.
Radiation therapy. Acute radiation-induced liver disease also causes endothelial cell injury that is characteristic of VOD/SOS.[66] In adults, the whole liver has tolerance up to 30 Gy to 35 Gy with conventional fractionation, the prevalence of radiation-induced liver disease varies from 6% to 66% based on the volume of liver involved and on hepatic reserve.[66,67]
Radiation hepatopathy after contemporary treatment appears to be uncommon in long-term survivors without predisposing conditions such as viral hepatitis or iron overload.[68] The dose threshold for irreversible injury is uncertain, but is being examined by the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative. The risk of injury in children increases with radiation dose, hepatic volume, younger age at treatment, previous partial hepatectomy, and concomitant use of radiomimetic chemotherapy such as dactinomycin and doxorubicin.[69-72] Survivors who received radiation doses of 40 Gy to at least one-third of liver volume, doses of 30 Gy or more to whole abdomen, or an upper abdominal field involving the entire liver are at highest risk for hepatic dysfunction.[44]
HSCT. Chronic liver dysfunction in patients after HSCT is multifactorial in etiology. The most common etiologies for chronic liver dysfunction include iron overload, chronic GVHD, and viral hepatitis.[73] Patients with chronic GVHD of the GI tract who exhibit an elevated bilirubin have a worse prognosis and quality of life.[74] While chronic liver dysfunction may be seen in more than half of long-term stem cell transplantation survivors, and the course of the disease appears to be indolent, continued follow-up is needed to establish its long-term impact on survivor health.[75]
Infectious risk factors for hepatobiliary late effects
Viral hepatitis B and C may complicate the treatment course of childhood cancer and result in chronic hepatic dysfunction. Hepatitis B tends to have a more aggressive acute clinical course and a lower rate of chronic infection. Hepatitis C is characterized by a mild acute infection and a high rate of chronic infection. The incidence of transfusion-related hepatitis C in childhood cancer survivors has ranged from 5% to 50% depending on the geographic location of the reporting center.[76-82]
Chronic hepatitis predisposes the childhood cancer survivor to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Concurrent infection with hepatitis B and C in combination or in co-occurrence with other hepatotrophic viruses accelerates the progression of liver disease.
Because most patients received some type of blood product during childhood cancer treatment and many are unaware of their transfusion history, screening on the basis of date of diagnosis/treatment is recommended unless there is absolute certainty that the patient did not receive any blood or blood products.[83] Therefore, all survivors of childhood cancer who received treatment before 1972 should be screened for hepatitis B, and those who received treatment before 1993 should be screened for hepatitis C and referred for discussion of treatment options if screening results are positive.
Survivors with liver dysfunction should be counseled regarding risk-reduction methods to prevent hepatic injury. Standard recommendations include maintenance of a healthy body weight, abstinence from alcohol use, and immunization against hepatitis A and B viruses. In patients with chronic hepatitis, precautions to reduce viral transmission to household and sexual contacts should also be reviewed.
Table 6 summarizes hepatobiliary late effects and the related health screenings.
Table 6. Hepatobiliary Late Effectsa
Hepatic Effects
ALT = alanine aminotransferase; AST = aspartate aminotransferase; HSCT = hematopoietic stem cell transplantation.
Methotrexate; mercaptopurine/thioguanine; HSCT Hepatic dysfunction Lab: ALT, AST, bilirubin levels
Ferritin in those treated with HSCT
Mercaptopurine/thioguanine; HSCT Veno-occlusive disease/sinusoidal obstructive syndrome Exam: scleral icterus, jaundice, ascites, hepatomegaly, splenomegaly
Lab: ALT, AST, bilirubin, platelet levels
Radiation impacting liver/biliary tract; HSCT Hepatic fibrosis/cirrhosis; focal nodular hyperplasia Exam: jaundice, spider angiomas, palmar erythema, xanthomata hepatomegaly, splenomegaly
Lab: ALT, AST, bilirubin levels
Prothrombin time for evaluation of hepatic synthetic function in patients with abnormal liver screening tests
Screen for viral hepatitis in patients with persistently abnormal liver function or any patient transfused before 1993
Gastroenterology/hepatology consultation in patients with persistent liver dysfunction
Hepatitis A and B immunizations in patients lacking immunity
Consider phlebotomy and chelation therapy for iron overload
Radiation impacting liver/biliary tract Cholelithiasis History: colicky abdominal pain related to fatty food intake, excessive flatulence
Exam: right upper quadrant or epigastric tenderness (acute episode)
Consider gallbladder ultrasound in patients with chronic abdominal pain
The pancreas has been thought to be relatively radioresistant because of a paucity of information about late pancreatic-related effects. However, children and young adults treated with TBI or abdominal irradiation are known to have an increased risk of insulin resistance and diabetes mellitus.[84-86] While corticosteroids and asparaginase are associated with acute toxicity to the pancreas, late sequelae in the form of exocrine or endocrine pancreatic function for those who sustain acute injury have not been reported.
Evidence (risk of diabetes mellitus):
A retrospective cohort study, based on self-reports of 2,520 5-year survivors of childhood cancer treated in France and the United Kingdom, investigated the relationship between radiation dose to the pancreas and risk of a subsequent diabetes mellitus diagnosis.[87]
Sixty-five cases of diabetes mellitus were validated; the risk increased with radiation therapy to the tail of the pancreas, where the islets of Langerhans are concentrated. Risk increased up to 20 to 29 Gy and then plateaued. The estimated RR at 1 Gy was 1.61.
Radiation dose to other parts of the pancreas did not have a significant effect.
Compared with patients who did not receive radiation therapy, the RR of diabetes mellitus was 11.5 in patients who received more than 10 Gy to the pancreas.
Children younger than 2 years at the time of radiation therapy were more sensitive than were older patients (RR at 1 Gy was 2.1 for the young age group vs. 1.4 for older patients).
For the 511 patients who received more than 10 Gy, the cumulative incidence of diabetes mellitus was 16%.
Another study evaluated the risk of diabetes mellitus in 2,264 5-year survivors of Hodgkin lymphoma (42% younger than 25 years at diagnosis) after a median follow-up of 21.5 years.[88]
The cumulative incidence of diabetes mellitus was 8.3% (95% CI, 6.9%–9.8%) for the overall cohort and 14.2% (95% CI, 10.7%–18.3%) for those treated with more than 36 Gy para-aortic radiation.
Survivors treated with more than 36 Gy of radiation to the para-aortic lymph nodes and spleen had a 2.3-fold increased risk of diabetes mellitus compared with those who did not receive radiation therapy.
The risk of diabetes mellitus increased with higher doses to the pancreatic tail.
CCSS investigators evaluated the risk of diabetes mellitus among 20,762 5-year childhood cancer survivors and 4,853 siblings.[89]
Survivors exposed to abdominal radiation (n = 4,568) were almost three times more likely to develop diabetes than were siblings and 1.6 times more likely than survivors who were not exposed to abdominal radiation.
Among survivors treated with abdominal radiation therapy, multivariable modeling identified independent risk factors for developing diabetes, which included older attained age, higher BMI, and increasing dose to the pancreatic tail.
A significant interaction was also identified between younger age (<10 years) at cancer diagnosis and higher mean pancreatic tail dose.
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for digestive system late effects information including risk factors, evaluation, and health counseling.
Hölttä P, Alaluusua S, Saarinen-Pihkala UM, et al.: Agenesis and microdontia of permanent teeth as late adverse effects after stem cell transplantation in young children. Cancer 103 (1): 181-90, 2005. [PUBMED Abstract]
Hölttä P, Hovi L, Saarinen-Pihkala UM, et al.: Disturbed root development of permanent teeth after pediatric stem cell transplantation. Dental root development after SCT. Cancer 103 (7): 1484-93, 2005. [PUBMED Abstract]
Kaste SC, Goodman P, Leisenring W, et al.: Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study. Cancer 115 (24): 5817-27, 2009. [PUBMED Abstract]
Paulino AC: Role of radiation therapy in parameningeal rhabdomyosarcoma. Cancer Invest 17 (3): 223-30, 1999. [PUBMED Abstract]
Paulino AC, Simon JH, Zhen W, et al.: Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 48 (5): 1489-95, 2000. [PUBMED Abstract]
Maciel JC, de Castro CG, Brunetto AL, et al.: Oral health and dental anomalies in patients treated for leukemia in childhood and adolescence. Pediatr Blood Cancer 53 (3): 361-5, 2009. [PUBMED Abstract]
Hsieh SG, Hibbert S, Shaw P, et al.: Association of cyclophosphamide use with dental developmental defects and salivary gland dysfunction in recipients of childhood antineoplastic therapy. Cancer 117 (10): 2219-27, 2011. [PUBMED Abstract]
Dahllöf G: Oral and dental late effects after pediatric stem cell transplantation. Biol Blood Marrow Transplant 14 (1 Suppl 1): 81-3, 2008. [PUBMED Abstract]
Hölttä P, Alaluusua S, Saarinen-Pihkala UM, et al.: Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation. Bone Marrow Transplant 29 (2): 121-7, 2002. [PUBMED Abstract]
Kang CM, Hahn SM, Kim HS, et al.: Clinical Risk Factors Influencing Dental Developmental Disturbances in Childhood Cancer Survivors. Cancer Res Treat 50 (3): 926-935, 2018. [PUBMED Abstract]
Fromm M, Littman P, Raney RB, et al.: Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature. Cancer 57 (10): 2070-6, 1986. [PUBMED Abstract]
Thompson RF, Schneider RA, Albertini F, et al.: Dose to the developing dentition during therapeutic irradiation: organ at risk determination and clinical implications. Int J Radiat Oncol Biol Phys 86 (1): 108-13, 2013. [PUBMED Abstract]
Maguire A, Craft AW, Evans RG, et al.: The long-term effects of treatment on the dental condition of children surviving malignant disease. Cancer 60 (10): 2570-5, 1987. [PUBMED Abstract]
Alpaslan G, Alpaslan C, Gögen H, et al.: Disturbances in oral and dental structures in patients with pediatric lymphoma after chemotherapy: a preliminary report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87 (3): 317-21, 1999. [PUBMED Abstract]
Kaste SC, Hopkins KP, Jones D, et al.: Dental abnormalities in children treated for acute lymphoblastic leukemia. Leukemia 11 (6): 792-6, 1997. [PUBMED Abstract]
O'Sullivan EA, Duggal MS, Bailey CC: Changes in the oral health of children during treatment for acute lymphoblastic leukaemia. Int J Paediatr Dent 4 (1): 31-4, 1994. [PUBMED Abstract]
Elzembely MM, Dahlberg AE, Pinto N, et al.: Late effects in high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell rescue. Pediatr Blood Cancer 66 (1): e27421, 2019. [PUBMED Abstract]
Jensen SB, Pedersen AM, Vissink A, et al.: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18 (8): 1039-60, 2010. [PUBMED Abstract]
Jensen SB, Pedersen AM, Vissink A, et al.: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer 18 (8): 1061-79, 2010. [PUBMED Abstract]
Garming Legert K, Remberger M, Ringdèn O, et al.: Salivary secretion in children after fractionated or single-dose TBI. Bone Marrow Transplant 47 (3): 404-10, 2012. [PUBMED Abstract]
Dahllöf G, Wondimu B, Barr-Agholme M, et al.: Xerostomia in children and adolescents after stem cell transplantation conditioned with total body irradiation or busulfan. Oral Oncol 47 (9): 915-9, 2011. [PUBMED Abstract]
Garming-Legert K, Remberger M, Ringdén O, et al.: Long-term salivary function after conditioning with busulfan, fractionated or single-dose TBI. Oral Dis 17 (7): 670-6, 2011. [PUBMED Abstract]
Raney RB, Asmar L, Vassilopoulou-Sellin R, et al.: Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group. Med Pediatr Oncol 33 (4): 362-71, 1999. [PUBMED Abstract]
Gevorgyan A, La Scala GC, Neligan PC, et al.: Radiation-induced craniofacial bone growth disturbances. J Craniofac Surg 18 (5): 1001-7, 2007. [PUBMED Abstract]
Sulaiman F, Huryn JM, Zlotolow IM: Dental extractions in the irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results. J Oral Maxillofac Surg 61 (10): 1123-31, 2003. [PUBMED Abstract]
Vissink A, Jansma J, Spijkervet FK, et al.: Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med 14 (3): 199-212, 2003. [PUBMED Abstract]
Hong CH, Napeñas JJ, Hodgson BD, et al.: A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer 18 (8): 1007-21, 2010. [PUBMED Abstract]
Yeazel MW, Gurney JG, Oeffinger KC, et al.: An examination of the dental utilization practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Public Health Dent 64 (1): 50-4, 2004. [PUBMED Abstract]
Goldsby R, Chen Y, Raber S, et al.: Survivors of childhood cancer have increased risk of gastrointestinal complications later in life. Gastroenterology 140 (5): 1464-71.e1, 2011. [PUBMED Abstract]
Skou AS, Glosli H, Jahnukainen K, et al.: Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study. Pediatr Blood Cancer 61 (9): 1638-43, 2014. [PUBMED Abstract]
Bölling T, Willich N, Ernst I: Late effects of abdominal irradiation in children: a review of the literature. Anticancer Res 30 (1): 227-31, 2010. [PUBMED Abstract]
Churnratanakul S, Wirzba B, Lam T, et al.: Radiation and the small intestine. Future perspectives for preventive therapy. Dig Dis 8 (1): 45-60, 1990. [PUBMED Abstract]
Sher ME, Bauer J: Radiation-induced enteropathy. Am J Gastroenterol 85 (2): 121-8, 1990. [PUBMED Abstract]
Emami B, Lyman J, Brown A, et al.: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21 (1): 109-22, 1991. [PUBMED Abstract]
Donaldson SS, Jundt S, Ricour C, et al.: Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management. Cancer 35 (4): 1167-78, 1975. [PUBMED Abstract]
Heyn R, Raney RB, Hays DM, et al.: Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. J Clin Oncol 10 (4): 614-23, 1992. [PUBMED Abstract]
Hughes LL, Baruzzi MJ, Ribeiro RC, et al.: Paratesticular rhabdomyosarcoma: delayed effects of multimodality therapy and implications for current management. Cancer 73 (2): 476-82, 1994. [PUBMED Abstract]
Paulino AC, Wen BC, Brown CK, et al.: Late effects in children treated with radiation therapy for Wilms' tumor. Int J Radiat Oncol Biol Phys 46 (5): 1239-46, 2000. [PUBMED Abstract]
Raney B, Heyn R, Hays DM, et al.: Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. Cancer 71 (7): 2387-94, 1993. [PUBMED Abstract]
Madenci AL, Fisher S, Diller LR, et al.: Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 33 (26): 2893-900, 2015. [PUBMED Abstract]
Madenci AL, Dieffenbach BV, Liu Q, et al.: Late-onset anorectal disease and psychosocial impact in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 125 (21): 3873-3881, 2019. [PUBMED Abstract]
Mulder RL, van Dalen EC, Van den Hof M, et al.: Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database Syst Rev (7): CD008205, 2011. [PUBMED Abstract]
Mulder RL, Kremer LC, Koot BG, et al.: Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors. Eur J Cancer 49 (1): 185-93, 2013. [PUBMED Abstract]
Mahmoud H, Schell M, Pui CH: Cholelithiasis after treatment for childhood cancer. Cancer 67 (5): 1439-42, 1991. [PUBMED Abstract]
Safford SD, Safford KM, Martin P, et al.: Management of cholelithiasis in pediatric patients who undergo bone marrow transplantation. J Pediatr Surg 36 (1): 86-90, 2001. [PUBMED Abstract]
Sudour H, Mainard L, Baumann C, et al.: Focal nodular hyperplasia of the liver following hematopoietic SCT. Bone Marrow Transplant 43 (2): 127-32, 2009. [PUBMED Abstract]
Lee MH, Yoo SY, Kim JH, et al.: Hypervascular hepatic nodules in childhood cancer survivors: clinical and imaging features. Clin Imaging 36 (4): 301-7, 2012 Jul-Aug. [PUBMED Abstract]
Castellino SM, Hudson MM: Late gastrointestinal and hepatic effects. In: Schwartz CL, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood and Adolescent Cancer: A Multidisciplinary Approach. 3rd ed. Cham, Switzerland: Springer International Publishing, 2015, pp 229-52.
Wanless IR: Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology 11 (5): 787-97, 1990. [PUBMED Abstract]
Brisse H, Servois V, Bouche B, et al.: Hepatic regenerating nodules: a mimic of recurrent cancer in children. Pediatr Radiol 30 (6): 386-93, 2000. [PUBMED Abstract]
Chu WC, Roebuck DJ: Nodular regenerative hyperplasia of the liver simulating metastases following treatment for bilateral Wilms tumor. Med Pediatr Oncol 41 (1): 85-7, 2003. [PUBMED Abstract]
Halonen P, Mattila J, Ruuska T, et al.: Liver histology after current intensified therapy for childhood acute lymphoblastic leukemia: microvesicular fatty change and siderosis are the main findings. Med Pediatr Oncol 40 (3): 148-54, 2003. [PUBMED Abstract]
Tomita Y, Ishiguro H, Yasuda Y, et al.: High incidence of fatty liver and insulin resistance in long-term adult survivors of childhood SCT. Bone Marrow Transplant 46 (3): 416-25, 2011. [PUBMED Abstract]
Ruccione KS, Wood JC, Sposto R, et al.: Characterization of transfusion-derived iron deposition in childhood cancer survivors. Cancer Epidemiol Biomarkers Prev 23 (9): 1913-9, 2014. [PUBMED Abstract]
Vag T, Kentouche K, Krumbein I, et al.: Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results. Pediatr Radiol 41 (8): 980-4, 2011. [PUBMED Abstract]
Schempp A, Lee J, Kearney S, et al.: Iron Overload in Survivors of Childhood Cancer. J Pediatr Hematol Oncol 38 (1): 27-31, 2016. [PUBMED Abstract]
Trovillion EM, Schubert L, Dietz AC: Iron Overload in Survivors of Childhood Cancer. J Pediatr Hematol Oncol 40 (5): 396-400, 2018. [PUBMED Abstract]
Broxson EH, Dole M, Wong R, et al.: Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6-thioguanine during maintenance therapy. Pediatr Blood Cancer 44 (3): 226-31, 2005. [PUBMED Abstract]
De Bruyne R, Portmann B, Samyn M, et al.: Chronic liver disease related to 6-thioguanine in children with acute lymphoblastic leukaemia. J Hepatol 44 (2): 407-10, 2006. [PUBMED Abstract]
Rawat D, Gillett PM, Devadason D, et al.: Long-term follow-up of children with 6-thioguanine-related chronic hepatoxicity following treatment for acute lymphoblastic leukaemia. J Pediatr Gastroenterol Nutr 53 (5): 478-9, 2011. [PUBMED Abstract]
Green DM, Norkool P, Breslow NE, et al.: Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study. J Clin Oncol 8 (9): 1525-30, 1990. [PUBMED Abstract]
Sulis ML, Bessmertny O, Granowetter L, et al.: Veno-occlusive disease in pediatric patients receiving actinomycin D and vincristine only for the treatment of rhabdomyosarcoma. J Pediatr Hematol Oncol 26 (12): 843-6, 2004. [PUBMED Abstract]
McDonald GB: Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology 51 (4): 1450-60, 2010. [PUBMED Abstract]
Dawson LA, Ten Haken RK: Partial volume tolerance of the liver to radiation. Semin Radiat Oncol 15 (4): 279-83, 2005. [PUBMED Abstract]
Milano MT, Constine LS, Okunieff P: Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol 17 (2): 131-40, 2007. [PUBMED Abstract]
Pan CC, Kavanagh BD, Dawson LA, et al.: Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76 (3 Suppl): S94-100, 2010. [PUBMED Abstract]
Bhanot P, Cushing B, Philippart A, et al.: Hepatic irradiation and adriamycin cardiotoxicity. J Pediatr 95 (4): 561-3, 1979. [PUBMED Abstract]
Flentje M, Weirich A, Pötter R, et al.: Hepatotoxicity in irradiated nephroblastoma patients during postoperative treatment according to SIOP9/GPOH. Radiother Oncol 31 (3): 222-8, 1994. [PUBMED Abstract]
Kun LE, Camitta BM: Hepatopathy following irradiation and adriamycin. Cancer 42 (1): 81-4, 1978. [PUBMED Abstract]
Tefft M: Radiation related toxicities in National Wilms' Tumor Study Number 1. Int J Radiat Oncol Biol Phys 2 (5-6): 455-63, 1977 May-Jun. [PUBMED Abstract]
Levitsky J, Sorrell MF: Hepatic complications of hematopoietic cell transplantation. Curr Gastroenterol Rep 9 (1): 60-5, 2007. [PUBMED Abstract]
Pidala J, Chai X, Kurland BF, et al.: Analysis of gastrointestinal and hepatic chronic graft-versus-host [corrected] disease manifestations on major outcomes: a chronic graft-versus-host [corrected] disease consortium study. Biol Blood Marrow Transplant 19 (5): 784-91, 2013. [PUBMED Abstract]
Tomás JF, Pinilla I, García-Buey ML, et al.: Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients. Bone Marrow Transplant 26 (6): 649-55, 2000. [PUBMED Abstract]
Aricò M, Maggiore G, Silini E, et al.: Hepatitis C virus infection in children treated for acute lymphoblastic leukemia. Blood 84 (9): 2919-22, 1994. [PUBMED Abstract]
Castellino S, Lensing S, Riely C, et al.: The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St Jude Children's Research Hospital hepatitis C seropositive cohort. Blood 103 (7): 2460-6, 2004. [PUBMED Abstract]
Cesaro S, Petris MG, Rossetti F, et al.: Chronic hepatitis C virus infection after treatment for pediatric malignancy. Blood 90 (3): 1315-20, 1997. [PUBMED Abstract]
Fink FM, Höcker-Schulz S, Mor W, et al.: Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients. Eur J Pediatr 152 (6): 490-2, 1993. [PUBMED Abstract]
Locasciulli A, Testa M, Pontisso P, et al.: Hepatitis C virus genotypes and liver disease in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 19 (3): 237-40, 1997. [PUBMED Abstract]
Locasciulli A, Testa M, Pontisso P, et al.: Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood 90 (11): 4628-33, 1997. [PUBMED Abstract]
Paul IM, Sanders J, Ruggiero F, et al.: Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease. Blood 93 (11): 3672-7, 1999. [PUBMED Abstract]
Lansdale M, Castellino S, Marina N, et al.: Knowledge of hepatitis C virus screening in long-term pediatric cancer survivors: a report from the Childhood Cancer Survivor Study. Cancer 116 (4): 974-82, 2010. [PUBMED Abstract]
van Waas M, Neggers SJ, Raat H, et al.: Abdominal radiotherapy: a major determinant of metabolic syndrome in nephroblastoma and neuroblastoma survivors. PLoS One 7 (12): e52237, 2012. [PUBMED Abstract]
Neville KA, Cohn RJ, Steinbeck KS, et al.: Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors. J Clin Endocrinol Metab 91 (11): 4401-7, 2006. [PUBMED Abstract]
Baker KS, Ness KK, Steinberger J, et al.: Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood 109 (4): 1765-72, 2007. [PUBMED Abstract]
de Vathaire F, El-Fayech C, Ben Ayed FF, et al.: Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Lancet Oncol 13 (10): 1002-10, 2012. [PUBMED Abstract]
van Nimwegen FA, Schaapveld M, Janus CP, et al.: Risk of diabetes mellitus in long-term survivors of Hodgkin lymphoma. J Clin Oncol 32 (29): 3257-63, 2014. [PUBMED Abstract]
Friedman DN, Moskowitz CS, Hilden P, et al.: Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus. J Natl Cancer Inst : , 2019. [PUBMED Abstract]
Endocrine dysfunction is very common among childhood cancer survivors, especially those treated with surgery or radiation therapy that involves hormone-producing organs and those receiving alkylating agent chemotherapy.
Figure 8. Prevalence of endocrine disorders at the last follow-up visit, by sex. Copyright © 2013, European Society of Endocrinology.
The prevalence of specific endocrine disorders is affected by the following:[1-3]
Patient factors (e.g., age at treatment and sex).
Treatment factors (e.g., radiation dose and treatment volume).
Time from radiation exposure (typically increases with longer time from radiation exposure [refer to Figure 8]).
Endocrinologic late effects can be broadly categorized as those resulting from hypothalamic/pituitary injury or from peripheral glandular compromise.[4,5] The former are most common after treatment for central nervous system (CNS) tumors, where the prevalence was reported to be 24.8% in a nationwide cohort study of 718 survivors who lived longer than 2 years and all hypothalamic/pituitary axes were effected.[3]
The following sections summarize research that characterizes the clinical features of survivors at risk of endocrine dysfunction that impacts pituitary, thyroid, adrenal, and gonadal function.
Thyroid dysfunction is a common delayed effect of radiation therapy fields that include the thyroid gland incidental to treating Hodgkin lymphoma (HL), brain tumors, head and neck sarcomas, and acute lymphoblastic leukemia (ALL). There is considerable evidence linking radiation exposure to thyroid abnormalities, but the prevalence of specific conditions varies widely because studies are limited by cohort selection and participation bias, heterogeneity in radiation treatment approach, time since radiation exposure, and method of ascertainment (e.g., self-report vs. clinical or diagnostic imaging assessment).
Thyroid abnormalities observed in excess in childhood cancer survivors include the following:
Primary hypothyroidism.
Hyperthyroidism.
Goiter.
Nodules.
Of children treated with radiation therapy, most develop hypothyroidism within the first 2 to 5 years posttreatment, but new cases can occur later. Reports of thyroid dysfunction differ depending on the dose of radiation, the length of follow-up, and the biochemical criteria utilized to make the diagnosis.[6] The most frequently reported abnormalities include:
Elevated thyroid-stimulating hormone (TSH).
Depressed thyroxine (T4).
Elevated TSH and depressed T4.
Compensated hypothyroidism includes an elevated TSH with a normal T4 and is asymptomatic. The natural history is unclear, but most endocrinologists support treatment. Uncompensated hypothyroidism includes both an elevated TSH and a depressed T4. Thyroid hormone replacement is beneficial for correction of the metabolic abnormality, and has clinical benefits for cardiovascular, gastrointestinal, and neurocognitive function.
An increased risk of hypothyroidism has been reported among childhood cancer survivors treated with head and neck radiation exposing the thyroid gland, especially among survivors of HL.
Evidence (prevalence of and risk factors for hypothyroidism):
The German Group of Paediatric Radiation Oncology reported on 1,086 patients treated at 62 centers, including 404 patients (median age, 10.9 years) who received radiation therapy to the thyroid and/or pituitary gland.[7] Follow-up information was available for 264 patients (60.9%; median follow-up, 40 months), with 60 patients (22.7%) showing pathologic values.
In comparison to patients treated with prophylactic cranial irradiation (median dose, 12 Gy), patients treated with radiation doses of 15 Gy to 25 Gy to the thyroid gland had a hazard ratio (HR) of 3.072 (P = .002) for the development of pathologic thyroid blood values.
Patients treated with more than 25 Gy of radiation to the thyroid gland had an HR of 3.769 (P = .009), and patients treated with craniospinal irradiation had an HR of 5.674 (P < .001).
The cumulative incidence of thyroid hormone substitution therapy did not differ between defined subgroups.
In a cohort of childhood HL survivors treated between 1970 and 1986, survivors were evaluated for thyroid disease by use of a self-report questionnaire in the Childhood Cancer Survivor Study (CCSS).[8]
Among 1,791 survivors, 34% reported that they had been diagnosed with at least one thyroid abnormality.
For hypothyroidism, there was a clear dose response (refer to Figure 9), with a 20-year risk of:
20% for those who received less than 35 Gy of radiation to the thyroid gland.
30% for those who received 35 Gy to 44.9 Gy of radiation to the thyroid gland.
50% for those who received more than 45 Gy of radiation to the thyroid gland.
Compared to a sibling control group, the relative risk (RR) was 17.1 for hypothyroidism; 8.0 for hyperthyroidism; and 27.0 for thyroid nodules.
Elapsed time since diagnosis was a risk factor for both hypothyroidism and hyperthyroidism, with the risk increasing in the first 3 to 5 years postdiagnosis. For nodules, the risk increased beginning at 10 years postdiagnosis. Females were at increased risk for hypothyroidism and thyroid nodules.
Figure 9. Probability of developing hypothyroidism according to radiation dose in 5-year survivors of childhood cancer. Data from the Childhood Cancer Survivor Study. Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, Greffe B, Wolden S, Robison L: Abnormalities of the Thyroid in Survivors of Hodgkin's Disease: Data from the Childhood Cancer Survivor Study. The Journal of Clinical Endocrinology and Metabolism 85 (9): 3227-3232, September 1, 2000. Copyright 2000, The Endocrine Society.
In a more recent report from the CCSS that compared self-reported data from 14,290 survivors with data from 4,031 sibling controls.[2]
The RR was 3.8 for hypothyroidism and 2.5 for hyperthyroidism; the RR for both remained significantly higher in survivors when compared with controls even in the absence of radiation therapy to the thyroid or pituitary.
These results indicate the need for continued and individualized long-term monitoring strategies in childhood cancer survivors.
Any radiation field that includes the thyroid is associated with an excess risk of thyroid neoplasms, which may be benign (usually adenomas) or malignant (most often differentiated papillary carcinoma).[2,8-12] The clinical manifestation of thyroid neoplasia among childhood cancer survivors ranges from asymptomatic, small, solitary nodules to large, intrathoracic goiters that compress adjacent structures. CCSS investigators performed a nested case-control study to evaluate the magnitude of risk for thyroid cancer over the therapeutic radiation dose range of pediatric cancers. The risk of thyroid cancer increased with radiation doses up to 20 Gy to 29 Gy (odds ratio [OR], 9.8; 95% confidence interval [CI], 3.2–34.8), but declined at doses higher than 30 Gy, consistent with a cell-killing effect.[12]
The following factors are linked to an increased risk of thyroid nodule development:
Time from diagnosis, female sex, and radiation dose. In a study of HL survivors, CCSS investigators identified time from diagnosis, female sex, and radiation dose of 25 Gy or higher as significant risk factors for thyroid nodule development.[8] Based on a cohort of 3,254 2-year childhood cancer survivors treated before 1986 and monitored for 25 years, the risk of thyroid adenoma increased with the size of the radiation dose to the thyroid during childhood cancer treatment and plateaued at doses exceeding 10 Gy.[10]
Age at time of radiation therapy. Based on the same cohort of 3,254 2-year childhood cancer survivors, the risk of thyroid adenoma per unit of radiation dose to the thyroid was higher if radiation therapy had been delivered before age 5 years; the risk was also higher in individuals who were younger than 40 years at the time of the study.[10] Younger age at radiation therapy has also been linked to an excess risk of thyroid carcinoma.[9-12]
Exposure to iodine I 131-metaiodobenzylguanidine (131I-MIBG). During childhood and adolescence, there is an increased incidence of developing thyroid nodules, and potentially thyroid cancer, for patients exposed to 131I-MIBG. Children who have been treated with 131I-MIBG should undergo lifelong monitoring, not only for thyroid function but also for the development of thyroid nodules and thyroid cancer.[13]
Chemotherapy. Whereas the risk of thyroid cancer is known to be increased by exposure to radiation therapy and 131I-MIBG, an increased risk of thyroid nodules and cancer has also been observed in association with chemotherapy, independent of radiation exposure.[2,9,10]
In a pooled study of two cohorts of 16,757 survivors that included 187 patients with secondary thyroid cancer, treatments with alkylating agents, anthracyclines, or bleomycin were associated with a significantly increased risk of thyroid cancer in individuals not exposed to radiation therapy.[14] In the CCSS, the RR of developing thyroid cancer was 2.5 (P < .01) in survivors not treated with thyroid radiation when compared with sibling controls.[2] Defining the precise role of exposure to chemotherapy and developing risk prediction models for thyroid cancer in childhood cancer survivors on the basis of demographic and treatment-related risk factors are areas of active research.[15]
Several investigations have demonstrated the superiority of ultrasound to clinical exam for detecting thyroid nodules and thyroid cancers and characterized ultrasonographic features of nodules that are more likely to be malignant.[16-18] However, primary screening for thyroid neoplasia (beyond physical exam with thyroid palpation) remains controversial because of the lack of data indicating a survival benefit and quality-of-life benefit associated with early detection and intervention. In fact, because these lesions tend to be indolent, are rarely life-threatening, and may clinically manifest many years after exposure to radiation, there are significant concerns regarding the costs and harms of overscreening.[19] Expert panels have refrained from specifically endorsing or discouraging the use of ultrasound as a screening tool for thyroid cancer and this continues to be an active area of investigation.[20] Following a systematic assessment of the evidence, the International Guideline Harmonization Group concluded that initiation of surveillance and the type of surveillance modality (thyroid palpation vs. ultrasound) should be determined by shared decision-making between the health care provider and survivor after carefully considering the benefits and harms. A decision aid to facilitate discussion accompanies their recommendations.[21]
(Refer to the Subsequent Neoplasms section of this summary for information about subsequent thyroid cancers.)
Posttransplant thyroid dysfunction
Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at increased risk of thyroid dysfunction, with the risk being much lower (15%–16%) after fractionated total-body irradiation (TBI), as opposed to single-dose TBI (46%–48%). Non–TBI-containing regimens historically were not associated with an increased risk. However, in a report from the Fred Hutchinson Cancer Research Center, the increased risk of thyroid dysfunction did not differ between children receiving a TBI-based or busulfan-based regimen (P = .48).[22] Other high-dose therapies have not been studied.
TSH deficiency (central hypothyroidism) is discussed with late effects that affect the pituitary gland.
Table 7 summarizes thyroid late effects and the related health screenings.
Table 7. Thyroid Late Effectsa
Endocrine/Metabolic Effects
131I-MIBG = Iodine I 131-metaiodobenzylguanidine; T4 = thyroxine; TSH = thyroid-stimulating hormone.
Radiation impacting thyroid gland; thyroidectomy Primary hypothyroidism TSH level
Radiation impacting thyroid gland Hyperthyroidism Free T4 level
TSH level
Radiation impacting thyroid gland, including 131I-MIBG Thyroid nodules Thyroid exam
Thyroid ultrasound
Survivors of childhood cancer are at risk of developing a spectrum of neuroendocrine abnormalities, primarily because of the effect of radiation therapy on the hypothalamus. In addition, tumor development or surgical resection close to the hypothalamus and/or pituitary gland may induce direct anatomical damage to these structures and result in hypothalamic/pituitary dysfunction. Essentially all of the hypothalamic-pituitary axes are at risk.[4,23-25]
Although the quality of the literature regarding pituitary endocrinopathy among childhood cancer survivors is often limited by retrospective data collection, small sample size, cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment, the evidence linking this outcome with radiation therapy, surgery, and tumor infiltration is quite compelling because affected individuals typically present with metabolic and developmental abnormalities early in follow-up.
Central diabetes insipidus
Central diabetes insipidus may herald the diagnosis of craniopharyngioma, suprasellar germ cell tumor, or Langerhans cell histiocytosis.[26-28] In these conditions, diabetes insipidus may occur as an isolated pituitary deficiency, although additional pituitary hormone deficiencies may develop with tumor progression. More commonly, however, diabetes insipidus occurs in the context of panhypopituitarism caused by the presence of a tumor in close proximity to the sellar region or as a consequence of surgical procedures undertaken for local tumor control.
Central diabetes insipidus has not been reported as a late effect of cranial irradiation in childhood cancer survivors.
Anterior pituitary hormone deficiency
Deficiencies of anterior pituitary hormones and major hypothalamic regulatory factors are common late effects among survivors treated with cranial irradiation.
Evidence (prevalence of anterior pituitary hormone deficiency):
In a single-institution study, 1,713 adult survivors of childhood cancers and brain tumors (median age, 32 years) were monitored for a median follow-up of 25 years.[25]
The prevalence of hypothalamic-pituitary axis disorders was 56.4% in individuals exposed to cranial radiation therapy at doses of 18 Gy or higher.
A study of 748 childhood cancer survivors treated with cranial irradiation and observed for a mean of 27.3 years reported the following:[5]
The estimated point prevalence for anterior pituitary hormone deficiency was 46.5% for growth hormone deficiency, 10.8% for luteinizing/follicle stimulating hormone deficiency, 7.5% for thyroid-stimulating hormone deficiency, and 4% for adrenocorticotropin deficiency; the cumulative incidence increased with follow-up.
The six anterior pituitary hormones and their major hypothalamic regulatory factors are outlined in Table 8.
Table 8. Anterior Pituitary Hormones and Major Hypothalamic Regulatory Factors
Pituitary Hormone
Hypothalamic Factor
Hypothalamic Regulation of the Pituitary Hormone
(–) = inhibitory; (+) = stimulatory.
Growth hormone (GH) Growth hormone–releasing hormone +
Somatostatin –
Prolactin Dopamine –
Luteinizing hormone (LH) Gonadotropin-releasing hormone +
Follicle-stimulating hormone (FSH) Gonadotropin-releasing hormone +
Thyroid-stimulating hormone (TSH) Thyroid-releasing hormone +
Adrenocorticotropin (ACTH) Corticotropin-releasing hormone +
Vasopressin +
Growth hormone deficiency
Growth hormone deficiency is the earliest hormonal deficiency associated with cranial radiation therapy in childhood cancer survivors. The risk increases with radiation dose and time since treatment. Growth hormone deficiency is sensitive to low doses of radiation. Other hormone deficiencies require higher doses, and their time to onset is much longer than for growth hormone deficiency.[29] The prevalence in pooled analysis was found to be approximately 35.6%.[30]
Growth hormone deficiency is commonly observed in these long-term survivors because of radiation doses used in the treatment of childhood brain tumors. Approximately 60% to 80% of irradiated pediatric brain tumor patients who received doses higher than 30 Gy will have impaired serum growth hormone response to provocative stimulation, usually within 5 years of treatment. The dose-response relationship has a threshold of 18 Gy to 20 Gy; the higher the radiation dose, the earlier that growth hormone deficiency will occur after treatment.
Evidence (radiation-dose response relationship of growth hormone deficiency):
A study of conformal radiation therapy (CRT) in children with CNS tumors indicates that growth hormone insufficiency can usually be demonstrated within 12 months of radiation therapy, depending on hypothalamic dose-volume effects.[31]
In a report featuring data from 118 patients with localized brain tumors who were treated with radiation therapy, peak growth hormone was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus.[32]
The average patient was predicted to develop growth hormone deficiency with the following combinations of time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 Gy to 30 Gy; and 60 months and 15 Gy to 20 Gy.
A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of growth hormone deficiency at 5 years (TD50/5) (refer to Figure 10).
Figure 10. Peak growth hormone (GH) according to hypothalamic mean dose and time after start of radiation. According to equation 2, peak GH = exp{2.5947 + time × [0.0019 − (0.00079 × mean dose)]}. Thomas E. Merchant, Susan R. Rose, Christina Bosley, Shengjie Wu, Xiaoping Xiong, and Robert H. Lustig, Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors, Journal of Clinical Oncology, volume 29, issue 36, pages 4776-4780. Reprinted with permission. © (2011) American Society of Clinical Oncology. All rights reserved.
Children treated with CNS-directed therapy for leukemia are also at increased risk of growth hormone deficiency.
Evidence (risk of growth deficits in childhood ALL survivors):
One study evaluated 127 patients with ALL treated with 24 Gy, 18 Gy, or no cranial radiation therapy.[33]
The change in height, compared with population norms expressed as the standard deviation score (SDS), was significant for all three groups, with a dose response of -0.49 ± 0.14 for the group that did not receive radiation therapy, -0.65 ± 0.15 for the group that received 18 Gy of radiation therapy, and -1.38 ± 0.16 for the group that received 24 Gy of radiation therapy.
Another study found similar results in 118 ALL survivors treated with 24 Gy of cranial radiation, in which 74% had an SDS of -1 or higher and the remainder had scores of -2 or higher.[34]
Survivors of childhood ALL who are treated with chemotherapy alone are also at increased risk for adult short stature, although the risk is highest for those treated with cranial and craniospinal radiation therapy at a young age.[35] In this cross-sectional study, attained adult height was determined for 2,434 ALL survivors participating in the CCSS.
All survivor treatment exposure groups (chemotherapy alone and chemotherapy with cranial or craniospinal radiation therapy) had decreased adult height and an increased risk of adult short stature (height SDS < -2), compared with siblings (P < .001).
Compared with siblings, the risk of short stature for survivors treated with chemotherapy alone was elevated (OR, 3.4; 95% CI, 1.9–6.0).
Among survivors, significant risk factors for short stature included diagnosis of ALL before puberty, higher-dose cranial radiation therapy (≥20 Gy vs. <20 Gy), any radiation therapy to the spine, and female sex.
The impact of chemotherapy alone on growth in 67 survivors treated with contemporary regimens for ALL was statistically significant at -0.59 SD. The loss of growth potential did not correlate with growth hormone status in this study, further highlighting the participation of other factors in the growth impairments observed in this population.[36]
In a longitudinal study of 372 survivors of ALL who were treated on a single-institution chemotherapy-only trial, the following was observed:[37]
Height z scores declined during treatment and improved after therapy.
Younger age at diagnosis (2 to <10 years), or low-risk ALL status, or white blood cell count below 50 × 109/L at diagnosis, or CNS-negative status were associated with significant improvements in z scores for height during the off-therapy period compared with those older at diagnosis (age ≥10 years), or with standard-risk/high-risk ALL status, or a white blood cell count of 50 × 109/L or higher, or CNS-positive status.
The loss in height potential in older patients was attributed to attenuation of the growth spurt during treatment without improvement after therapy and to chemotherapy intensity in patients with standard- or high-risk disease features.
Children who undergo HSCT with TBI have a significant risk of both growth hormone deficiency and the direct effects of radiation on skeletal development. The risk is increased with single-dose TBI as opposed to fractionated TBI, pretransplant cranial irradiation, female sex, and posttreatment complications such as graft-versus-host disease (GVHD).[38-40] Hyperfractionation of the TBI dose markedly reduces risk in patients who have not undergone pretransplant cranial irradiation for CNS leukemia prophylaxis or therapy.[41] Regimens containing busulfan and cyclophosphamide appear to increase risk in some studies,[40,42] but not others.[43]
Evidence (growth hormone deficiency in childhood HSCT survivors):
The late effects that occur after HSCT have been studied and reviewed by the Late Effect Working Party of the European Group for Blood and Marrow Transplantation. Among 181 patients with aplastic anemia, leukemias, and lymphomas who underwent HSCT before puberty, the following results were observed:[44,45]
An overall decrease in final height-SDS value was found, compared with height at transplant and genetic height. The mean loss of height is estimated to be approximately 1 height-SDS (6 cm), compared with the mean height at time of HSCT and mean genetic height.
The type of transplantation, GVHD, and growth hormone or steroid treatment did not influence final height.
TBI (single-dose radiation therapy more than fractionated-dose radiation therapy), male sex, and young age at transplant were found to be major factors for long-term height loss. Most patients (140 of 181) reached adult height within the normal range of the general population.
Growth hormone deficiency replacement therapy
Growth hormone deficiency replacement therapy provides the benefit of optimizing height outcomes among children who have not reached skeletal maturity. Treatment with recombinant growth hormone (rGH) replacement therapy is generally delayed until 12 months after successful completion of cancer or brain tumor treatments and after a multidisciplinary discussion involving the prescribing pediatric endocrinologist, the primary oncologist, and other providers selected by the patient or family.[46] Safety concerns pertaining to the use of rGH in childhood cancer survivors have primarily been related to the mitogenic potential of the growth hormone stimulating tumor growth in a population with an increased risk of second neoplasms.[47] Most studies that report these outcomes, however, are limited by selection bias and small sample size.
The following study results have been reported in survivors who did or did not receive treatment with growth hormone.
Evidence (growth hormone deficiency replacement therapy):
One study evaluated 361 growth hormone-treated cancer survivors enrolled in the CCSS and compared risk of recurrence, risk of subsequent neoplasm, and risk of death among survivors who did and did not receive treatment with growth hormone.[48]
The RR of disease recurrence was 0.83 (95% CI, 0.37–1.86) for growth hormone-treated survivors. Growth hormone-treated subjects were diagnosed with 15 subsequent neoplasms, all solid tumors, for an overall RR of 3.21 (95% CI, 1.88–5.46), mainly because of a small excess number of subsequent neoplasms observed in survivors of acute leukemia.[48] With prolonged follow-up, the elevation of subsequent cancer risk resulting from growth hormone diminished.[49]
Compared with survivors not treated with growth hormone, those who were treated had a twofold excess risk of developing a subsequent neoplasm (RR, 2.15; 95% CI, 1.33–3.47; P < .002); meningiomas were the most commonly observed neoplasms (9 of 20 tumors).[48]
A review of existing data suggests that treatment with growth hormone is not associated with an increased risk of CNS tumor progression or recurrence, or new or recurrent leukemia.[50]
A study from the CCSS reported specifically on the risk of subsequent CNS neoplasms after a longer period of follow-up.[51]
The adjusted rate ratio of meningioma and gliomas in growth hormone-treated survivors of CNS tumors was 1.0 (95% CI, 0.6–1.8; P = .94) when compared with CNS tumor survivors who were not treated with growth hormone, thus indicating negligible differences between the two groups for this particular risk.
In general, the data addressing subsequent malignancies should be interpreted with caution given the small number of events.[46-48]
Disorders of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
Pubertal development can be adversely affected by cranial radiation therapy. Doses higher than 18 Gy can result in central precocious puberty, while doses higher than 30 Gy to 40 Gy may result in LH and FSH deficiency.[52]
Central precocious puberty
Central precocious puberty is defined by the onset of pubertal development before age 8 years in girls and 9 years in boys as a result of the premature activation of the hypothalamic-pituitary-gonadal axis. Aside from the adjustment and psychosocial challenges associated with early pubertal development, precocious puberty can lead to the rapid closure of the skeletal growth plates and short stature. This deleterious effect can be further potentiated by growth hormone deficiency.[53,54] The increased growth velocity induced by pubertal development can mask concurrent growth hormone deficiency with seemingly normal growth velocity; this occurrence may mislead care providers. It is also important to note that the assessment of puberty cannot be performed using testicular volume measurements in boys exposed to chemotherapy or direct radiation to the testes, given the toxic effect of these treatments on germ cells and repercussions on gonadal size. The staging of puberty in males within this population relies on the presence of other signs of virilization, such as the presence of pubic hair and the measurement of plasma testosterone levels.[53]
Children who have tumors that grow near the hypothalamus/pituitary or optic pathways (including those with neurofibromatosis type 1) have the highest risk of developing central precocious puberty.[54,55] Hydrocephalus also seems to increase the risk of this complication.[55] Central precocious puberty has been reported in some children receiving cranial irradiation in doses of 18 Gy or higher.[54,56,57] The impact of central precocious puberty on linear growth can be ascertained by assessing the degree of skeletal maturation (or bone age) using an x-ray of the left hand.[58]
When appropriate, delaying the progression of puberty relies on the use of various gonadotropin-releasing hormone agonist preparations, an approach that has been shown to improve growth prospects—especially when other pituitary abnormalities, including growth hormone deficiency, are concurrently treated.[59]
LH/FSH deficiency
LH/FSH deficiency (also referred to as hypogonadotropic hypogonadism) can manifest through pubertal delay, arrested puberty, or symptoms of decreased sex hormone production, depending on age and pubertal status at the time of diagnosis. The risk of LH/FSH deficiency is highest among patients treated with cranial radiation at doses greater than or equal to 30 Gy; LH/FSH deficiency following the exposure to lower doses can occur at delayed time points.[5] With higher doses of cranial radiation therapy (>35 Gy), deficiencies in LH/FSH can be seen, with a cumulative incidence of 10% to 20% at 5 to 10 years posttreatment.[60,61]
The treatment of LH/FSH deficiency relies on sex-hormone replacement therapy adjusted to age and pubertal status.
TSH deficiency
TSH deficiency (also referred to as central hypothyroidism) in survivors of childhood cancer can have profound clinical consequences and be underappreciated. Symptoms of central hypothyroidism (e.g., asthenia, edema, drowsiness, and skin dryness) may have a gradual onset and go unrecognized until thyroid replacement therapy is initiated. In addition to delayed puberty and slow growth, hypothyroidism may cause fatigue, dry skin, constipation, increased sleep requirement, and cold intolerance. Individuals with TSH deficiency have low plasma free T4 levels and either low or inappropriately normal TSH levels.
The risk of TSH deficiency is highest among patients treated with cranial radiation at doses of 30 Gy or higher; TSH deficiency following the exposure to lower doses can occur at delayed time points.[5] Radiation dose to the hypothalamus in excess of 42 Gy is associated with an increased risk of developing TSH deficiency (44% ± 19% for dose of ≥42 Gy and 11% ± 8% for dose of <42 Gy).[62] It occurs in as many as 65% of survivors of brain tumors, 43% of survivors of childhood nasopharyngeal tumors, 35% of bone marrow transplant recipients, and 10% to 15% of leukemia survivors.[63,64]
Mixed primary and central hypothyroidism can also occur and reflects separate injuries to the thyroid gland and the hypothalamus (e.g., radiation injury to both structures). TSH values may be elevated and, in addition, the secretory dynamics of TSH are abnormal, with a blunted or absent TSH surge or a delayed peak response to TSH-releasing hormone (TRH).[65] In a study of 208 childhood cancer survivors referred for evaluation of possible hypothyroidism or hypopituitarism, mixed hypothyroidism was present in 15 patients (7%).[65] Among patients who received TBI (fractionated total doses of 12–14.4 Gy) or craniospinal radiation therapy (fractionated total cranial doses higher than 30 Gy), 15% had mixed hypothyroidism. In one study of 95 patients with medulloblastoma who received craniospinal irradiation, overall 35% of the patients developed hypothyroidism. Median time to last thyroid assessment was 3.8 years for the proton radiation group and 9.6 years for the photon radiation group. Primary hypothyroidism developed in 12 of 54 patients (22%) after photon radiation therapy and 3 of 41 patients (7%) after proton radiation therapy (HR, 2.1; P = .27). Central hypothyroidism developed in 13 of 54 patients (24%) after photon radiation therapy and 4 of 41 patients (10%) after proton radiation therapy (HR, 2.16, P = .18).[66] In a larger study of 189 children and young adults (aged <26 years) with brain tumors who were treated with proton radiation therapy, the actuarial rate of hypothyroidism was 20.1%, with 90% central TSH deficiency. This is concordant with previous studies.[62] However, the cumulative incidence of primary hypothyroidism was 3% after craniospinal irradiation and 1.6% overall and is substantially lower than previous reports of 56% to 65% incidence after craniospinal irradiation with photons.[62,67,68]
Thyroid hormone replacement therapy using levothyroxine represents the mainstay of treatment of TSH deficiency. The dose of levothyroxine needs to be adjusted solely using plasma free T4 levels; the levels of TSH are expected to remain low during therapy, given the central nature of this deficiency.
Adrenal-corticotropin (ACTH) deficiency
ACTH deficiency is less common than other neuroendocrine deficits but should be suspected in patients who have a history of brain tumor (regardless of therapy modality), cranial radiation therapy, growth hormone deficiency, or central hypothyroidism.[29,62,69-71] Although uncommon, ACTH deficiency can occur in patients treated with intracranial radiation doses of less than 24 Gy and has been reported to occur in fewer than 3% of patients after chemotherapy alone.[71]
The diagnosis should be suspected when low plasma levels of morning cortisol are measured (a screening cortisol level collected at 8 a.m. that is 10 µg/dL or more is reassuring for ACTH sufficiency, whereas a value of 5 µg/dL or lower is suspicious for insufficiency). Confirmation is necessary using dynamic testing such as the low-dose ACTH stimulation test.[70] Because of the substantial risk of central adrenal insufficiency among survivors treated with cranial radiation doses exceeding 30 Gy to the hypothalamic-pituitary axis, endocrine monitoring with periodic dynamic testing as clinically indicated is recommended for this high-risk group.
Patients with partial ACTH deficiency may have only subtle symptoms unless they become ill. Illness can disrupt these patients’ usual homeostasis and cause a more severe, prolonged, or complicated course than expected. As in complete ACTH deficiency, incomplete or unrecognized ACTH deficiency can be life-threatening during concurrent illness.
The treatment of ACTH deficiency relies on replacement with hydrocortisone, including stress dosing in situations of illness to adjust to the body’s physiologically increased need for glucocorticoids.
Hyperprolactinemia has been described in patients who received radiation therapy to the hypothalamus in doses higher than 50 Gy or who underwent surgery that disrupted the integrity of the pituitary stalk. Primary hypothyroidism may lead to hyperprolactinemia as a result of hyperplasia of thyrotrophs and lactotrophs, presumably due to TRH hypersecretion. The prolactin response to TRH is usually exaggerated in these patients.[29,72]
In general, hyperprolactinemia may result in delayed puberty, galactorrhea, menstrual irregularities, loss of libido, hot flashes, infertility, and osteopenia. However, hyperprolactinemia resulting from cranial radiation therapy is rarely symptomatic and is frequently associated with hypogonadism (both central and primary).
Hyperprolactinemia rarely requires treatment.
Table 9 summarizes pituitary gland late effects and the related health screenings.
Table 9. Pituitary Gland Late Effectsa
BMI = body mass index; FSH = follicle-stimulating hormone; LH = luteinizing hormone; T4 = thyroxine; TSH = thyroid-stimulating hormone.
bTesticular volume measurements are not reliable in the assessment of pubertal development in boys exposed to chemotherapy or direct radiation to the testes.
cAppropriate only at diagnosis. TSH levels are not useful for follow-up during replacement therapy.
Tumor or surgery affecting hypothalamus/pituitary. Radiation impacting hypothalamic-pituitary axis. Growth hormone deficiency Assessment of nutritional status
Height, weight, BMI, Tanner stageb
Tumor or surgery affecting hypothalamus/pituitary or optic pathways; hydrocephalus. Radiation impacting hypothalamic-pituitary axis. Precocious puberty Height, weight, BMI, Tanner stageb
FSH, LH, estradiol, or testosterone levels
Tumor or surgery affecting hypothalamus/pituitary. Radiation impacting hypothalamic-pituitary axis. Gonadotropin deficiency History: puberty, sexual function
Exam: Tanner stageb
FSH, LH, estradiol or testosterone levels
Tumor or surgery affecting hypothalamus/pituitary. Radiation impacting hypothalamic-pituitary axis. Central adrenal insufficiency History: failure to thrive, anorexia, episodic dehydration, hypoglycemia, lethargy, unexplained hypotension
Endocrine consultation for those with radiation dose ≥30 Gy
Radiation impacting hypothalamic-pituitary axis. Hyperprolactinemia History/exam: galactorrhea
Prolactin level
Radiation impacting hypothalamic-pituitary axis. Overweight/obesity Height, weight, BMI
Components of metabolic syndrome (abdominal obesity, hypertension, dyslipidemia, impaired glucose metabolism) Fasting blood glucose level and lipid profile
Tumor or surgery affecting hypothalamus/pituitary. Radiation impacting hypothalamic-pituitary axis. Central hypothyroidism TSHc free thyroxine (free T4) level
Testis and Ovary
Testicular and ovarian hormonal functions are discussed in the Late Effects of the Reproductive System section of this summary.
An increased risk of metabolic syndrome or its components has been observed among cancer survivors. The evidence for this outcome ranges from clinically manifested conditions that are self-reported by survivors to retrospectively assessed data in medical records and hospital registries to systematic clinical evaluations of clinically well-characterized cohorts. Studies have been limited by cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment. Despite these limitations, compelling evidence indicates that metabolic syndrome is highly associated with cardiovascular events and mortality.
Definitions of metabolic syndrome are evolving but generally include a combination of central (abdominal) obesity with at least two of the following features:
Hypertension.
Atherogenic dyslipidemia (elevated triglycerides, reduced high-density lipoprotein [HDL] cholesterol).
Abnormal glucose metabolism (fasting hyperglycemia, hyperinsulinism, insulin resistance, diabetes mellitus type 2).[73]
Evidence (prevalence of and risk factors for metabolic syndrome in childhood cancer survivors):
A study monitored 784 long-term childhood ALL survivors (median age, 31.7 years) for a median follow-up of 26.1 years.[74]
The prevalence of metabolic syndrome was 33.6%, which was significantly higher than that in a cohort of age-, sex-, and race-matched controls (n = 777) from the National Health and Nutrition Examination Survey (RR, 1.43; 95% CI, 1.22–1.69).
Risk factors associated with metabolic syndrome in this study included older age and past exposures to cranial radiation therapy.
Components of metabolic syndrome with significantly higher prevalence in ALL survivors than in controls included obesity, insulin resistance, hypertension, and decreased HDL levels.
French investigators evaluated the overall and age-specific prevalence of and risk factors for metabolic syndrome and its components among 650 adult survivors of childhood leukemia treated without hematopoietic stem cell transplantation.[75]
The overall prevalence of the condition was 6.9%, with the following age-specific cumulative prevalence:
20 years—1.3%.
30 years—10.8%.
The prevalence of individual components of the metabolic syndrome was as follows:
Increased fasting glucose—5.8%.
Increased triglycerides—11.7%.
Increased abdominal circumference—16.7%.
Decreased high-density lipoprotein cholesterol—26.8%.
Increased blood pressure—36.7%.
Clinical factors significantly predicting the risk of metabolic syndrome included male sex (OR, 2.64; 95% CI, 1.32–5.29), age at last evaluation (OR, 1.10; 95% CI, 1.04–1.17) and body mass index (BMI) at diagnosis (OR, 1.15; 95% CI, 1.01–1.32), but not cumulative steroid dose. Irradiated and nonirradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in nonirradiated patients.
Abdominal irradiation is an additional risk factor for metabolic syndrome. Survivors of developmental or embryonal tumors treated with abdominal irradiation are also at an increased risk of developing components of metabolic syndrome. In a prospective study of 164 long-term survivors (median follow-up, 26 years), nephroblastoma (OR, 5.2) and neuroblastoma (OR, 6.5) survivors had more components of metabolic syndrome than did controls.[76]
Compared with nonirradiated survivors, survivors treated with abdominal irradiation had higher blood pressure, triglycerides, low-density lipoprotein (LDL) cholesterol, and total fat percentage, which were assessed by dual-energy x-ray absorptiometry.
Long-term survivors of ALL, especially those treated with cranial radiation therapy, may have a higher prevalence of some potentially modifiable risk factors for cardiovascular disease such as impaired glucose tolerance or overt diabetes mellitus, dyslipidemia, hypertension, and obesity.[74,77-82] The contribution of modifiable risk factors associated with metabolic syndrome to the risk of major cardiac events suggests that survivors are good candidates for targeted screening and lifestyle counseling regarding risk-reduction measures.[83]
Several studies have provided support for the potential benefits of lifestyle modifications in reducing cardiovascular disease risk.
Evidence (lifestyle modifications to reduce cardiovascular risk in childhood cancer survivors):
Survivors participating in the St. Jude Lifetime Cohort Study who were adherent to a heart-healthy lifestyle had a lower risk of metabolic syndrome. Females (RR, 2.4; 95% CI, 1.7–3.3) and males (RR, 2.2; 95% CI, 1.6–3.0) in the cohort who did not follow recommended dietary and physical activity guidelines had a more than twofold excess risk of having clinical features of the metabolic syndrome.[84]
A CCSS investigation evaluated the impact of exercise on cardiovascular disease risk among survivors of HL.[85]
Vigorous exercise was associated with a lower risk of cardiovascular events in a dose-dependent manner, independent of cardiovascular risk profile and treatment.
Survivors who were adherent to national vigorous-intensity exercise guidelines had a 51% reduction in the risk of any cardiovascular event compared with those not meeting the guidelines.
Another CCSS investigation evaluated the association of exercise with mortality in adult survivors of childhood cancer.[86]
After adjusting for chronic health conditions and treatment exposures, all-cause mortality was inversely associated with survivor-reported exercise quartiles (0, 3–6, 9–12, and 15–21 metabolic equivalent task [MET] hours/week).
Survivors who endorsed recommended levels of vigorous exercise (≥9 MET hours/week) in early adulthood and those who increased exercise over 8 years had a lower risk of mortality.
Abnormal glucose metabolism
Abdominal radiation therapy and TBI are increasingly recognized as independent risk factors for diabetes mellitus in childhood cancer survivors.[2,76,78,82,87-91]
Evidence (risk factors for diabetes mellitus in childhood cancer survivors):
A single-center cohort study of 532 long-term (median follow-up, 17.9 years) adult (median age, 25.6 years) survivors observed the following:[89]
Treatment, but not genetic variation, was strongly associated with the occurrence of the components of metabolic syndrome.
Metabolic syndrome was more frequent in cranially (23.3%, P = .002) and abdominally (23.4%, P = .009) irradiated survivors than in nonirradiated survivors (10.0%).
A cross-sectional study evaluated cardiovascular risk factors and insulin resistance in a clinically heterogeneous cohort of 319 childhood cancer survivors 5 or more years since diagnosis and 208 sibling controls.[92]
Insulin resistance was significantly higher in survivors treated with cisplatin plus cranial irradiation (92% brain tumors) and in those who received steroids but no cisplatin (most leukemia survivors), compared with siblings.
Insulin resistance did not differ between survivors treated with surgery alone and siblings.
Among survivors, analysis of individual chemotherapy agents failed to find associations with cardiovascular risk factors or insulin resistance. However, compared with siblings, nearly all chemotherapeutic agents, when examined individually, seemed to be associated with a high cardiovascular risk profile, characterized by lower total lean body mass, higher percentage fat mass, and insulin resistance.
In a European multicenter cohort of 2,520 childhood cancer survivors (median follow-up, 28 years), significant associations were found between diabetes mellitus and increasing doses of radiation therapy to the tail of the pancreas. These data support the contribution of radiation-induced islet cell injury to impairments of glucose homeostasis in this population.[90]
A report from the CCSS compared 8,599 childhood cancer survivors with 2,936 randomly selected sibling controls, and adjusted for age, BMI, and several demographic factors.[93]
The risk of diabetes mellitus was 1.8 times higher in survivors (95% CI, 1.3–2.5; P < .001).
Significant associations were found between diabetes mellitus and young age at diagnosis (0–4 years), the use of alkylating agents and abdominal radiation therapy or TBI.
Survivors were significantly more likely to be receiving medication for hypertension, dyslipidemia, and/or diabetes mellitus than were sibling controls.
Table 10 summarizes metabolic syndrome late effects and the related health screenings.
Table 10. Metabolic Syndrome Late Effectsa
Potential Late Effects
BMI = body mass index.
Abdominal irradiation. Total-body irradiation. Components of metabolic syndrome (abdominal obesity, hypertension, dyslipidemia, impaired glucose metabolism) Height, weight, BMI, blood pressure
Labs: fasting glucose and lipids
Body Composition: Underweight, Overweight, and Obesity
Childhood cancer survivors are at risk of experiencing abnormal body composition, which includes being underweight (BMI, <18.5), overweight (BMI, >25.0 to BMI, <30.0), or obese (BMI, ≥30.0). BMI at diagnosis has been identified as a significant predictor of being underweight or overweight at follow-up, suggesting that genetic or environmental factors contribute to the development or persistence of abnormal body composition.[94,95]
CCSS investigators identified treatment-related risk factors for being underweight, including TBI (females) or abdominal irradiation (males), use of alkylating agents, and use of anthracyclines.[95] Among a cohort of 893 Dutch childhood cancer survivors monitored for a median of almost 15 years, being underweight was linked to a high prevalence of moderate to extreme adverse health statuses and reports of a major medical condition.[94]
To date, cancer patients with an increased incidence of being overweight and obese are primarily ALL [94,96-102] and CNS tumor [4,23] survivors who were treated with cranial radiation therapy.[95,103] The development of obesity after cranial radiation therapy is multifactorial and includes the following:[99,104,105]
Growth hormone deficiency.
Leptin sensitivity.
Reduced levels of physical activity and energy expenditure.
The cumulative glucocorticoid dose received during therapy does not affect the risk of long-term childhood cancer survivors being overweight, as investigated in Swiss childhood cancer survivors with ALL, non-Hodgkin lymphoma, and Hodgkin lymphoma. In a study of 1,936 childhood cancer survivors surveyed at a median of 17 years from diagnosis and compared with siblings and the general population, there was no evidence of a relationship between cumulative glucocorticoid dose and being overweight. Additionally, there was no evidence that the use of cranial radiation therapy modified the effect of the cumulative glucocorticoid dose on being overweight.[106]
Also, craniopharyngioma survivors have a substantially increased risk of extreme obesity because of the tumor location and the hypothalamic damage resulting from surgical resection.[107-112]
In addition to treatment factors, lifestyle factors and medication use can also contribute to the risk of obesity. CCSS investigators reported the following independent risk factors for obesity in childhood cancer survivors:[113]
Cancer diagnosed at ages 5 to 9 years (RR, 1.12; 95% CI, 1.01–1.24).
Abnormal physical functioning (RR, 1.19; 95% CI, 1.06–1.33).
Hypothalamic/pituitary radiation dose of 20 Gy to 30 Gy (RR, 1.17; 95% CI, 1.05–1.3; P = .01).
Specific antidepressant use (paroxetine) (RR, 1.29; 95% CI, 1.08–1.54).
Survivors who adhered to the U.S. Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82–0.97; P = .01) and who had a medium amount of anxiety (RR, 0.86; 95% CI, 0.75–0.99; P = .04) had a lower risk of obesity.[113]
Body composition alterations after childhood ALL
Moderate-dose cranial radiation therapy (18–24 Gy) among ALL survivors is associated with obesity, particularly in females treated at a young age.[79,97,99,114] Female adult survivors of childhood ALL who were treated with cranial radiation therapy of 24 Gy before age 5 years are four times more likely to be obese than are women who have not been treated for a cancer.[97] In addition, women treated with 18 Gy to 24 Gy cranial radiation therapy before age 10 years have a substantially greater rate of increase in their BMI through their young adult years than do women who were treated for ALL with only chemotherapy or women in the general population.[99] It appears that these women also have a significantly increased visceral adiposity and associated insulin resistance.[115,116]
These outcomes are attenuated in males. However, a study of long-term male survivors of ALL (mean age, 29 years) observed significantly higher body adiposity than in age-matched controls, despite normal weight and BMI. Potential indicators of increased adiposity included high leptin and low sex hormone–binding globulin levels. Serum testicular endocrine markers (testosterone, FSH, or inhibin B) did not correlate with body adiposity.[117]
ALL therapy regimens are associated with increases in BMI shortly after completion of therapy, and possibly with a higher risk of obesity in the long term.[100-102,118,119] Several studies have reported that survivors of childhood ALL treated with chemotherapy alone also exhibit long-term changes in body composition, with relative increases in body fat [116,120-122] and visceral adiposity in comparison to lean mass.[115] These changes cannot be detected if BMI alone is used in the assessment of metabolic risk in this population.
Evidence (body composition changes in adult survivors of childhood ALL):
A cohort study of 365 adult survivors of ALL (149 treated with cranial radiation therapy and 216 treated without cranial radiation therapy) compared body composition, energy balance, and fitness with age-, sex-, and race-matched peers.[123]
Female survivors who were not exposed to cranial irradiation had comparable body composition values to that of peers. However, waist circumference, waist-to-height ratio, and total and percent fat mass were higher among male survivors and cranial radiation–exposed female survivors than among comparison group members.
Survivors of both sexes exposed to cranial radiation therapy had higher BMI and percent body fat than did survivors not exposed to cranial radiation therapy.
Although survivors who did not receive cranial radiation therapy had energy balance similar to the matched peer group, they had significantly higher measures of impaired fitness (impaired flexibility, peripheral sensorimotor deficits, proximal muscle weakness, and poor exercise tolerance).
These results suggest that elimination of cranial radiation from ALL therapy has improved, but not eliminated, adverse body composition outcomes and underscores the importance of attention to interventions to preserve function in this group as they age.
In contrast, in a report from the CCSS, adult survivors of childhood ALL treated with chemotherapy alone did not have significantly higher rates of obesity than did sibling controls,[97] nor were there differences in BMI changes between these groups after a subsequent period of follow-up that averaged 7.8 years.[99]
Results from the CCSS, however, were based on self-reported height and weight measurements. Likewise, Children’s Oncology Group investigators also did not observe an increased risk of being overweight and obese based on BMI measurements in 269 patients with standard-risk ALL (age, 3.5 years at diagnosis and 13.3 years at follow-up) compared with peers without cancer. Again, these variable outcomes likely relate to the use of BMI as the metric for abnormal body composition, which does not adequately assess visceral adiposity that can contribute to metabolic risk in this population.[124]
Body composition alterations after treatment for CNS tumors
Among brain tumor survivors treated with higher doses of cranial radiation therapy, only females treated at a younger age appear to be at increased risk for obesity.[125]
Body composition alterations after hematopoietic cell transplantation
Survivors of childhood cancer treated with TBI in preparation for an allogeneic HSCT have increased measures of body fatness (percent fat) while often having a normal BMI.[87,91,126,127] Longitudinal decline in BMI related to substantial decrease in lean mass has been observed among survivors of hematological malignancies treated with allogeneic HSCT. This finding was largely attributable to TBI conditioning and severity of chronic GVHD.[128]
Body composition and frailty
Young adult childhood cancer survivors have a higher-than-expected prevalence of frailty, a phenotype characterized by low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Individuals are termed prefrail if they have two of these five characteristics and frail if they have three or more of these characteristics. The frailty phenotype increases in prevalence with aging, and has been associated with excess risk of mortality and onset of chronic conditions.[129] Ongoing research aims to elucidate the pathophysiology of frailty and develop/test interventions to prevent or reverse this condition.
Table 11 summarizes body composition late effects and the related health screenings.
Table 11. Body Composition Late Effectsa
Cranial radiation therapy Overweight/obesity Height, weight, BMI, blood pressure
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for endocrine and metabolic syndrome late effects information, including risk factors, evaluation, and health counseling.
Endocrine Effects in Survivors of Cancer in Adolescence and Young Adulthood
In one of the first studies of late effects in survivors of adolescent and young adult (AYA) cancers, based on 32,548 AYA 1-year cancer survivors from the Danish Patient Registry, investigators found that AYA cancer survivors are at 73% higher risk of developing endocrine disease than are the general population. The dominating endocrine diseases are thyroid diseases, testicular dysfunction, and diabetes, which reflect the most common cancers in the AYA population and treatment during the time period of 1975 to 2009. This study highlights the importance of counseling and monitoring of AYA cancer survivors to guide future preventive measures.[130]
Brignardello E, Felicetti F, Castiglione A, et al.: Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics. Eur J Endocrinol 168 (3): 465-72, 2013. [PUBMED Abstract]
Mostoufi-Moab S, Seidel K, Leisenring WM, et al.: Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 34 (27): 3240-7, 2016. [PUBMED Abstract]
Clement SC, Schouten-van Meeteren AY, Boot AM, et al.: Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study. J Clin Oncol 34 (36): 4362-4370, 2016. [PUBMED Abstract]
Constine LS, Woolf PD, Cann D, et al.: Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 328 (2): 87-94, 1993. [PUBMED Abstract]
Chemaitilly W, Li Z, Huang S, et al.: Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study. J Clin Oncol 33 (5): 492-500, 2015. [PUBMED Abstract]
Gleeson HK, Darzy K, Shalet SM: Late endocrine, metabolic and skeletal sequelae following treatment of childhood cancer. Best Pract Res Clin Endocrinol Metab 16 (2): 335-48, 2002. [PUBMED Abstract]
Bölling T, Geisenheiser A, Pape H, et al.: Hypothyroidism after head-and-neck radiotherapy in children and adolescents: preliminary results of the "Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence" (RiSK). Int J Radiat Oncol Biol Phys 81 (5): e787-91, 2011. [PUBMED Abstract]
Haddy N, El-Fayech C, Guibout C, et al.: Thyroid adenomas after solid cancer in childhood. Int J Radiat Oncol Biol Phys 84 (2): e209-15, 2012. [PUBMED Abstract]
Veiga LH, Lubin JH, Anderson H, et al.: A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer. Radiat Res 178 (4): 365-76, 2012. [PUBMED Abstract]
Kovalchik SA, Ronckers CM, Veiga LH, et al.: Absolute risk prediction of second primary thyroid cancer among 5-year survivors of childhood cancer. J Clin Oncol 31 (1): 119-27, 2013. [PUBMED Abstract]
Vivanco M, Dalle JH, Alberti C, et al.: Malignant and benign thyroid nodules after total body irradiation preceding hematopoietic cell transplantation during childhood. Eur J Endocrinol 167 (2): 225-33, 2012. [PUBMED Abstract]
Li Z, Franklin J, Zelcer S, et al.: Ultrasound surveillance for thyroid malignancies in survivors of childhood cancer following radiotherapy: a single institutional experience. Thyroid 24 (12): 1796-805, 2014. [PUBMED Abstract]
Brignardello E, Felicetti F, Castiglione A, et al.: Ultrasound surveillance for radiation-induced thyroid carcinoma in adult survivors of childhood cancer. Eur J Cancer 55: 74-80, 2016. [PUBMED Abstract]
Metzger ML, Howard SC, Hudson MM, et al.: Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma. Pediatr Blood Cancer 46 (3): 314-9, 2006. [PUBMED Abstract]
Francis GL, Waguespack SG, Bauer AJ, et al.: Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 25 (7): 716-59, 2015. [PUBMED Abstract]
Clement SC, Kremer LCM, Verburg FA, et al.: Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Cancer Treat Rev 63: 28-39, 2018. [PUBMED Abstract]
Sanders JE, Hoffmeister PA, Woolfrey AE, et al.: Thyroid function following hematopoietic cell transplantation in children: 30 years' experience. Blood 113 (2): 306-8, 2009. [PUBMED Abstract]
Sklar CA: Growth and neuroendocrine dysfunction following therapy for childhood cancer. Pediatr Clin North Am 44 (2): 489-503, 1997. [PUBMED Abstract]
Ramelli GP, von der Weid N, Stanga Z, et al.: Suprasellar germinomas in childhood and adolescence: diagnostic pitfalls. J Pediatr Endocrinol Metab 11 (6): 693-7, 1998 Nov-Dec. [PUBMED Abstract]
Vinchon M, Baroncini M, Leblond P, et al.: Morbidity and tumor-related mortality among adult survivors of pediatric brain tumors: a review. Childs Nerv Syst 27 (5): 697-704, 2011. [PUBMED Abstract]
Fahrner B, Prosch H, Minkov M, et al.: Long-term outcome of hypothalamic pituitary tumors in Langerhans cell histiocytosis. Pediatr Blood Cancer 58 (4): 606-10, 2012. [PUBMED Abstract]
Darzy KH, Shalet SM: Hypopituitarism following radiotherapy. Pituitary 12 (1): 40-50, 2009. [PUBMED Abstract]
Mulder RL, Kremer LC, van Santen HM, et al.: Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review. Cancer Treat Rev 35 (7): 616-32, 2009. [PUBMED Abstract]
Merchant TE, Goloubeva O, Pritchard DL, et al.: Radiation dose-volume effects on growth hormone secretion. Int J Radiat Oncol Biol Phys 52 (5): 1264-70, 2002. [PUBMED Abstract]
Merchant TE, Rose SR, Bosley C, et al.: Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol 29 (36): 4776-80, 2011. [PUBMED Abstract]
Sklar C, Mertens A, Walter A, et al.: Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation. J Pediatr 123 (1): 59-64, 1993. [PUBMED Abstract]
Schriock EA, Schell MJ, Carter M, et al.: Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia. J Clin Oncol 9 (3): 400-5, 1991. [PUBMED Abstract]
Chow EJ, Friedman DL, Yasui Y, et al.: Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Pediatr 150 (4): 370-5, 375.e1, 2007. [PUBMED Abstract]
Vandecruys E, Dhooge C, Craen M, et al.: Longitudinal linear growth and final height is impaired in childhood acute lymphoblastic leukemia survivors after treatment without cranial irradiation. J Pediatr 163 (1): 268-73, 2013. [PUBMED Abstract]
Browne EK, Zhou Y, Chemaitilly W, et al.: Changes in body mass index, height, and weight in children during and after therapy for acute lymphoblastic leukemia. Cancer 124 (21): 4248-4259, 2018. [PUBMED Abstract]
Ogilvy-Stuart AL, Clark DJ, Wallace WH, et al.: Endocrine deficit after fractionated total body irradiation. Arch Dis Child 67 (9): 1107-10, 1992. [PUBMED Abstract]
Willi SM, Cooke K, Goldwein J, et al.: Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia. J Pediatr 120 (5): 726-32, 1992. [PUBMED Abstract]
Wingard JR, Plotnick LP, Freemer CS, et al.: Growth in children after bone marrow transplantation: busulfan plus cyclophosphamide versus cyclophosphamide plus total body irradiation. Blood 79 (4): 1068-73, 1992. [PUBMED Abstract]
Huma Z, Boulad F, Black P, et al.: Growth in children after bone marrow transplantation for acute leukemia. Blood 86 (2): 819-24, 1995. [PUBMED Abstract]
Bernard F, Bordigoni P, Simeoni MC, et al.: Height growth during adolescence and final height after haematopoietic SCT for childhood acute leukaemia: the impact of a conditioning regimen with BU or TBI. Bone Marrow Transplant 43 (8): 637-42, 2009. [PUBMED Abstract]
Chemaitilly W, Sklar CA: Endocrine complications of hematopoietic stem cell transplantation. Endocrinol Metab Clin North Am 36 (4): 983-98; ix, 2007. [PUBMED Abstract]
Socié G, Salooja N, Cohen A, et al.: Nonmalignant late effects after allogeneic stem cell transplantation. Blood 101 (9): 3373-85, 2003. [PUBMED Abstract]
Cohen A, Rovelli A, Bakker B, et al.: Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT. Blood 93 (12): 4109-15, 1999. [PUBMED Abstract]
Raman S, Grimberg A, Waguespack SG, et al.: Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee. J Clin Endocrinol Metab 100 (6): 2192-203, 2015. [PUBMED Abstract]
Chemaitilly W, Robison LL: Safety of growth hormone treatment in patients previously treated for cancer. Endocrinol Metab Clin North Am 41 (4): 785-92, 2012. [PUBMED Abstract]
Sklar CA, Mertens AC, Mitby P, et al.: Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 87 (7): 3136-41, 2002. [PUBMED Abstract]
Ergun-Longmire B, Mertens AC, Mitby P, et al.: Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 91 (9): 3494-8, 2006. [PUBMED Abstract]
Bogarin R, Steinbok P: Growth hormone treatment and risk of recurrence or progression of brain tumors in children: a review. Childs Nerv Syst 25 (3): 273-9, 2009. [PUBMED Abstract]
Patterson BC, Chen Y, Sklar CA, et al.: Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J Clin Endocrinol Metab 99 (6): 2030-7, 2014. [PUBMED Abstract]
Chemaitilly W, Sklar CA: Endocrine complications in long-term survivors of childhood cancers. Endocr Relat Cancer 17 (3): R141-59, 2010. [PUBMED Abstract]
Chemaitilly W, Merchant TE, Li Z, et al.: Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes. Clin Endocrinol (Oxf) 84 (3): 361-71, 2016. [PUBMED Abstract]
Gan HW, Phipps K, Aquilina K, et al.: Neuroendocrine Morbidity After Pediatric Optic Gliomas: A Longitudinal Analysis of 166 Children Over 30 Years. J Clin Endocrinol Metab 100 (10): 3787-99, 2015. [PUBMED Abstract]
Didcock E, Davies HA, Didi M, et al.: Pubertal growth in young adult survivors of childhood leukemia. J Clin Oncol 13 (10): 2503-7, 1995. [PUBMED Abstract]
Shalet SM, Crowne EC, Didi MA, et al.: Irradiation-induced growth failure. Baillieres Clin Endocrinol Metab 6 (3): 513-26, 1992. [PUBMED Abstract]
Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of Hand and Wrist. 2nd ed. Stanford, Ca: Stanford University Press, 1959.
Gleeson HK, Stoeter R, Ogilvy-Stuart AL, et al.: Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. J Clin Endocrinol Metab 88 (8): 3682-9, 2003. [PUBMED Abstract]
Chow EJ, Friedman DL, Yasui Y, et al.: Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 50 (4): 854-8, 2008. [PUBMED Abstract]
Armstrong GT, Whitton JA, Gajjar A, et al.: Abnormal timing of menarche in survivors of central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer 115 (11): 2562-70, 2009. [PUBMED Abstract]
Laughton SJ, Merchant TE, Sklar CA, et al.: Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol 26 (7): 1112-8, 2008. [PUBMED Abstract]
Rose SR: Cranial irradiation and central hypothyroidism. Trends Endocrinol Metab 12 (3): 97-104, 2001. [PUBMED Abstract]
Cheuk DK, Billups CA, Martin MG, et al.: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117 (1): 197-206, 2011. [PUBMED Abstract]
Rose SR, Lustig RH, Pitukcheewanont P, et al.: Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. J Clin Endocrinol Metab 84 (12): 4472-9, 1999. [PUBMED Abstract]
Bielamowicz K, Okcu MF, Sonabend R, et al.: Hypothyroidism after craniospinal irradiation with proton or photon therapy in patients with medulloblastoma. Pediatr Hematol Oncol 35 (4): 257-267, 2018. [PUBMED Abstract]
Paulino AC: Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy. Int J Radiat Oncol Biol Phys 53 (3): 543-7, 2002. [PUBMED Abstract]
Vatner RE, Niemierko A, Misra M, et al.: Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors. J Clin Oncol 36 (28): 2854-2862, 2018. [PUBMED Abstract]
Patterson BC, Truxillo L, Wasilewski-Masker K, et al.: Adrenal function testing in pediatric cancer survivors. Pediatr Blood Cancer 53 (7): 1302-7, 2009. [PUBMED Abstract]
Kazlauskaite R, Evans AT, Villabona CV, et al.: Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 93 (11): 4245-53, 2008. [PUBMED Abstract]
Rose SR, Danish RK, Kearney NS, et al.: ACTH deficiency in childhood cancer survivors. Pediatr Blood Cancer 45 (6): 808-13, 2005. [PUBMED Abstract]
Constine LS, Rubin P, Woolf PD, et al.: Hyperprolactinemia and hypothyroidism following cytotoxic therapy for central nervous system malignancies. J Clin Oncol 5 (11): 1841-51, 1987. [PUBMED Abstract]
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106 (25): 3143-421, 2002. [PUBMED Abstract]
Nottage KA, Ness KK, Li C, et al.: Metabolic syndrome and cardiovascular risk among long-term survivors of acute lymphoblastic leukaemia - From the St. Jude Lifetime Cohort. Br J Haematol 165 (3): 364-74, 2014. [PUBMED Abstract]
Saultier P, Auquier P, Bertrand Y, et al.: Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study. Haematologica 101 (12): 1603-1610, 2016. [PUBMED Abstract]
Chow EJ, Simmons JH, Roth CL, et al.: Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 16 (12): 1674-81, 2010. [PUBMED Abstract]
Surapolchai P, Hongeng S, Mahachoklertwattana P, et al.: Impaired glucose tolerance and insulin resistance in survivors of childhood acute lymphoblastic leukemia: prevalence and risk factors. J Pediatr Hematol Oncol 32 (5): 383-9, 2010. [PUBMED Abstract]
Veringa SJ, van Dulmen-den Broeder E, Kaspers GJ, et al.: Blood pressure and body composition in long-term survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 58 (2): 278-82, 2012. [PUBMED Abstract]
Steinberger J, Sinaiko AR, Kelly AS, et al.: Cardiovascular risk and insulin resistance in childhood cancer survivors. J Pediatr 160 (3): 494-9, 2012. [PUBMED Abstract]
Gurney JG, Ness KK, Sibley SD, et al.: Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer 107 (6): 1303-12, 2006. [PUBMED Abstract]
Oudin C, Simeoni MC, Sirvent N, et al.: Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood 117 (17): 4442-8, 2011. [PUBMED Abstract]
Smith WA, Li C, Nottage KA, et al.: Lifestyle and metabolic syndrome in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Cancer 120 (17): 2742-50, 2014. [PUBMED Abstract]
Scott JM, Li N, Liu Q, et al.: Association of Exercise With Mortality in Adult Survivors of Childhood Cancer. JAMA Oncol 4 (10): 1352-1358, 2018. [PUBMED Abstract]
van Waas M, Neggers SJ, Uitterlinden AG, et al.: Treatment factors rather than genetic variation determine metabolic syndrome in childhood cancer survivors. Eur J Cancer 49 (3): 668-75, 2013. [PUBMED Abstract]
Armenian SH, Chemaitilly W, Chen M, et al.: National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Cardiovascular Disease and Associated Risk Factors Working Group Report. Biol Blood Marrow Transplant 23 (2): 201-210, 2017. [PUBMED Abstract]
Baker KS, Chow EJ, Goodman PJ, et al.: Impact of treatment exposures on cardiovascular risk and insulin resistance in childhood cancer survivors. Cancer Epidemiol Biomarkers Prev 22 (11): 1954-63, 2013. [PUBMED Abstract]
Meacham LR, Chow EJ, Ness KK, et al.: Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev 19 (1): 170-81, 2010. [PUBMED Abstract]
van Santen HM, Geskus RB, Raemaekers S, et al.: Changes in body mass index in long-term childhood cancer survivors. Cancer 121 (23): 4197-204, 2015. [PUBMED Abstract]
Meacham LR, Gurney JG, Mertens AC, et al.: Body mass index in long-term adult survivors of childhood cancer: a report of the Childhood Cancer Survivor Study. Cancer 103 (8): 1730-9, 2005. [PUBMED Abstract]
Mayer EI, Reuter M, Dopfer RE, et al.: Energy expenditure, energy intake and prevalence of obesity after therapy for acute lymphoblastic leukemia during childhood. Horm Res 53 (4): 193-9, 2000. [PUBMED Abstract]
Oeffinger KC, Mertens AC, Sklar CA, et al.: Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 21 (7): 1359-65, 2003. [PUBMED Abstract]
Sklar CA, Mertens AC, Walter A, et al.: Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation. Med Pediatr Oncol 35 (2): 91-5, 2000. [PUBMED Abstract]
Garmey EG, Liu Q, Sklar CA, et al.: Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 26 (28): 4639-45, 2008. [PUBMED Abstract]
Chow EJ, Pihoker C, Hunt K, et al.: Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer 110 (10): 2313-20, 2007. [PUBMED Abstract]
Withycombe JS, Post-White JE, Meza JL, et al.: Weight patterns in children with higher risk ALL: A report from the Children's Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer 53 (7): 1249-54, 2009. [PUBMED Abstract]
Dalton VK, Rue M, Silverman LB, et al.: Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment. J Clin Oncol 21 (15): 2953-60, 2003. [PUBMED Abstract]
Nathan PC, Jovcevska V, Ness KK, et al.: The prevalence of overweight and obesity in pediatric survivors of cancer. J Pediatr 149 (4): 518-25, 2006. [PUBMED Abstract]
Oeffinger KC: Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of cardiovascular disease? Pediatr Blood Cancer 50 (2 Suppl): 462-7; discussion 468, 2008. [PUBMED Abstract]
Brennan BM, Rahim A, Blum WF, et al.: Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity? Clin Endocrinol (Oxf) 50 (2): 163-9, 1999. [PUBMED Abstract]
Belle FN, Kasteler R, Schindera C, et al.: No evidence of overweight in long-term survivors of childhood cancer after glucocorticoid treatment. Cancer 124 (17): 3576-3585, 2018. [PUBMED Abstract]
Sahakitrungruang T, Klomchan T, Supornsilchai V, et al.: Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery. Eur J Pediatr 170 (6): 763-9, 2011. [PUBMED Abstract]
Müller HL: Childhood craniopharyngioma: current controversies on management in diagnostics, treatment and follow-up. Expert Rev Neurother 10 (4): 515-24, 2010. [PUBMED Abstract]
Simoneau-Roy J, O'Gorman C, Pencharz P, et al.: Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma. Clin Endocrinol (Oxf) 72 (3): 364-70, 2010. [PUBMED Abstract]
May JA, Krieger MD, Bowen I, et al.: Craniopharyngioma in childhood. Adv Pediatr 53: 183-209, 2006. [PUBMED Abstract]
Müller HL, Gebhardt U, Teske C, et al.: Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up. Eur J Endocrinol 165 (1): 17-24, 2011. [PUBMED Abstract]
Tosta-Hernandez PDC, Siviero-Miachon AA, da Silva NS, et al.: Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center. Horm Metab Res 50 (9): 675-682, 2018. [PUBMED Abstract]
Green DM, Cox CL, Zhu L, et al.: Risk factors for obesity in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 30 (3): 246-55, 2012. [PUBMED Abstract]
Didi M, Didcock E, Davies HA, et al.: High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood. J Pediatr 127 (1): 63-7, 1995. [PUBMED Abstract]
Janiszewski PM, Oeffinger KC, Church TS, et al.: Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab 92 (10): 3816-21, 2007. [PUBMED Abstract]
Oeffinger KC, Adams-Huet B, Victor RG, et al.: Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 27 (22): 3698-704, 2009. [PUBMED Abstract]
Jahnukainen K, Heikkinen R, Henriksson M, et al.: Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia. Horm Res Paediatr 84 (2): 108-15, 2015. [PUBMED Abstract]
Kohler JA, Moon RJ, Wright S, et al.: Increased adiposity and altered adipocyte function in female survivors of childhood acute lymphoblastic leukaemia treated without cranial radiation. Horm Res Paediatr 75 (6): 433-40, 2011. [PUBMED Abstract]
Zhang FF, Rodday AM, Kelly MJ, et al.: Predictors of being overweight or obese in survivors of pediatric acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 61 (7): 1263-9, 2014. [PUBMED Abstract]
Warner JT, Evans WD, Webb DK, et al.: Body composition of long-term survivors of acute lymphoblastic leukaemia. Med Pediatr Oncol 38 (3): 165-72, 2002. [PUBMED Abstract]
Miller TL, Lipsitz SR, Lopez-Mitnik G, et al.: Characteristics and determinants of adiposity in pediatric cancer survivors. Cancer Epidemiol Biomarkers Prev 19 (8): 2013-22, 2010. [PUBMED Abstract]
Jarfelt M, Lannering B, Bosaeus I, et al.: Body composition in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol 153 (1): 81-9, 2005. [PUBMED Abstract]
Ness KK, DeLany JP, Kaste SC, et al.: Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia. Blood 125 (22): 3411-9, 2015. [PUBMED Abstract]
Lindemulder SJ, Stork LC, Bostrom B, et al.: Survivors of standard risk acute lymphoblastic leukemia do not have increased risk for overweight and obesity compared to non-cancer peers: a report from the Children's Oncology Group. Pediatr Blood Cancer 62 (6): 1035-41, 2015. [PUBMED Abstract]
Gurney JG, Ness KK, Stovall M, et al.: Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study. J Clin Endocrinol Metab 88 (10): 4731-9, 2003. [PUBMED Abstract]
Nysom K, Holm K, Michaelsen KF, et al.: Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant 27 (8): 817-20, 2001. [PUBMED Abstract]
Ketterl TG, Chow EJ, Leisenring WM, et al.: Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 24 (3): 622-626, 2018. [PUBMED Abstract]
Inaba H, Yang J, Kaste SC, et al.: Longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol 30 (32): 3991-7, 2012. [PUBMED Abstract]
Ness KK, Krull KR, Jones KE, et al.: Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study. J Clin Oncol 31 (36): 4496-503, 2013. [PUBMED Abstract]
Jensen MV, Rugbjerg K, Licht SDF, et al.: Endocrine late effects in survivors of cancer in adolescence and young adulthood: a Danish population-based cohort study. JAMA Netw Open 1 (2): e180349, 2018. Also available online. Last accessed April 17, 2019.
Late effects of the immune system have not been well studied, especially in survivors treated with contemporary therapies. Reports published about long-term immune system outcomes are limited by retrospective data collection, small sample size, cohort selection and participation bias, heterogeneity in treatment approach, time since treatment, and method of ascertainment.
Asplenia
Surgical or functional splenectomy increases the risk of life-threatening invasive bacterial infection:[1]
Although staging laparotomy is no longer standard practice for pediatric Hodgkin lymphoma, patients from earlier treatment periods have ongoing risks.[2,3]
Children may be rendered asplenic by radiation therapy to the spleen in doses greater than 30 Gy.[4,5] Low-dose involved-field radiation therapy (21 Gy) combined with multiagent chemotherapy did not appear to adversely affect splenic function, as measured by pitted red blood cell assays.[5] No other studies of immune status after radiation therapy are available.
Functional asplenia (with Howell-Jolly bodies, reduced splenic size and blood flow) after hematopoietic stem cell transplantation (HSCT) has been attributed to graft-versus-host disease (GVHD).
Childhood Cancer Survivor Study investigators observed a significantly increased risk of late infection-related mortality among survivors who were treated with splenectomy (relative risk [RR], 7.7; 95% confidence interval [CI], 3.1–19.1). Splenic radiation was also associated with a dose-related risk of late infection-related mortality (0.1–9.9 Gy: RR, 2.0; 95% CI, 0.9–4.5; 10.0–19.9 Gy: RR, 5.5; 95% CI, 1.9–15.4; >20.0 Gy: RR, 6.0; 95% CI, 1.8–20.2). However, the low cumulative incidence of infection-related late mortality of 1.5% at 35 years after splenectomy and 0.6% after splenic radiation indicates that these are rare events.[6] These data underscore the importance of counseling at-risk survivors about immunizations and other measures to reduce infection risk.
Individuals with asplenia, regardless of the reason for the asplenic state, have an increased risk of fulminant bacteremia, especially associated with encapsulated bacteria, which is associated with a high mortality rate. The risk of bacteremia is higher in younger children than in older children, and this risk may be higher during the years immediately after splenectomy. Fulminant septicemia, however, has been reported in adults up to 25 years after splenectomy.
Bacteremia may be caused by the following organisms in asplenic survivors:
Streptococcus pneumoniae. The most common pathogen that causes bacteremia in children with asplenia.
Other streptococci.
Haemophilus influenzae type b (Hib).
Neisseria meningitidis.
Escherichia coli; Staphylococcus aureus.
Gram-negative bacilli, such as the Salmonella species, the Klebsiella species, and Pseudomonas aeruginosa.
Individuals with functional or surgical asplenia are also at increased risk of fatal malaria and severe babesiosis.
Clinicians should consider and encourage the administration of inactivated vaccines (e.g., influenza) and vaccines made of purified antigens (e.g., pneumococcus), bacterial components (e.g., diphtheria-tetanus-pertussis), or genetically engineered recombinant antigens (e.g., hepatitis B) in all cancer and transplant survivors according to recommended doses and schedules.[7-9]
Two primary doses of quadrivalent meningococcal conjugate vaccine should be administered 2 months apart to children with asplenia, from age 2 years through adolescence, and a booster dose should be administered every 5 years.[10] (Refer to the Immunization Schedules for 2019 section of the Red Book for more information.) However, the efficacy of meningococcal vaccines in children with asplenia has not been established. (Refer to the Meningococcal Infections section of the Red Book for more information.) No known contraindication exists to giving these vaccines at the same time as other required vaccines, in separate syringes, at different sites.
Pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPSV) are indicated at the recommended age for all children with asplenia. Following the administration of the appropriate number of doses of PCV13, PPSV23 should be administered starting at age 24 months. A second dose should be administered 5 years later. For children aged 2 to 5 years with a complete PCV7 series who have not received PCV13, a supplemental dose of PCV13 should be administered. For asplenic individuals aged 6 to 18 years who have not received a dose of PCV13, a supplemental dose of PCV13 should be considered.[11,12] (Refer to the Pneumococcal Infections section of the Red Book for more information.) Hib immunization should be initiated at age 2 months, as recommended for otherwise healthy young children and for previously unimmunized children with asplenia.[11] (Refer to the Immunization Schedules for 2019 section of the Red Book for more information.)
Daily antimicrobial prophylaxis against pneumococcal infections is recommended for young children with asplenia, regardless of their immunization status. Although the efficacy of daily antimicrobial prophylaxis has been proven only in patients with sickle cell anemia, this experience has been extended to other high-risk children, including asplenic children with a history of malignant neoplasms or thalassemia. In general, antimicrobial prophylaxis (in addition to immunization) should be considered for all children with asplenia younger than 5 years and for at least 1 year after splenectomy.
The age at which antimicrobial prophylaxis is discontinued is an empiric decision. On the basis of a multicenter study in sickle cell disease, prophylactic penicillin can be discontinued at age 5 years among those who are receiving regular medical attention and who have not had a severe pneumococcal infection or surgical splenectomy. The appropriate duration of prophylaxis is unknown for children with asplenia attributable to other causes. Some experts continue prophylaxis throughout childhood and into adulthood for particularly high-risk patients with asplenia.
Table 12 summarizes spleen late effects and the related health screenings.
Table 12. Spleen Late Effectsa
Immunologic Effects
GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation; IgA = immunoglobulin A; T = temperature.
Radiation impacting spleen; splenectomy; HSCT with currently active GVHD Asplenia/hyposplenia; overwhelming post-splenectomy sepsis Blood cultures during febrile episodes (T >38.5°C); empiric antibiotics
Immunization for encapsulated organisms (pneumococcal, Haemophilus influenzae type b, and meningococcal vaccines)
HSCT with any history of chronic GVHD Immunologic complications (secretory IgA deficiency, hypogammaglobulinemia, decreased B cells, T cell dysfunction, chronic infections [e.g., conjunctivitis, sinusitis, and bronchitis associated with chronic GVHD]) History: chronic conjunctivitis, chronic sinusitis, chronic bronchitis, recurrent or unusual infections, sepsis
Exam: attention to eyes, nose/sinuses, and lungs
Refer to the Centers for Disease Control and Prevention (CDC) Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients for more information on posttransplant immunization.
Although the immune system appears to recover from the effects of active chemotherapy and radiation therapy, there is some evidence that lymphoid subsets do not normalize in all survivors. Innate immunity, thymopoiesis, and DNA damage responses to radiation were shown to be abnormal in survivors of childhood leukemia.[13] Defects in immune recovery characterized by B-cell depletion have been observed in 2-year survivors of standard-risk and intermediate-risk acute lymphoblastic leukemia (ALL).[14] Antibody levels to previous vaccinations are also reduced in patients off therapy for ALL for at least 1 year,[15,16] suggesting abnormal humoral immunity [17] and a need for revaccination in such children. Survivors of childhood cancer may remain susceptible to vaccine-preventable infections. Treatment intensity, age at diagnosis, and time from treatment are associated with the risk of losing pre-existing immunity.[18,19]
While there is a paucity of data regarding the benefits of administering active immunizations in this population, reimmunization is necessary to provide protective antibodies. The recommended reimmunization schedule will depend on previously received vaccinations and on the intensity of therapy.[20,21] In some children who received intensive treatment, consideration may be given to evaluating the antibodies against common vaccination antigens to determine the need for revaccination. (Refer to the Immunization Schedules for 2019 section of the Red Book for more information.)
Immune status is also compromised after HSCT, particularly in association with GVHD.[22] In a prospective, longitudinal study of 210 survivors treated with allogeneic HSCT, antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favorable. Factors associated with vaccine failure include older age at immunization; lower CD3, CD4, or CD19 count; higher immunoglobulin M concentration; positive recipient cytomegalovirus serology; negative titer before immunization; history of acute or chronic GVHD; and radiation conditioning.[23]
Follow-up recommendations for transplant recipients have been published by the major North American and European transplant groups, the CDC, and the Infectious Diseases Society of America.[24,25]
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for immune system late effects information including risk factors, evaluation, and health counseling.
Immunization in special circumstances. In: Kimberlin DW, Brady MT, Jackson MA, et al., eds.: Red Book: 2018–2021 Report of the Committee on Infectious Diseases. 31st ed. Itasca, Ill: American Academy of Pediatrics, 2018, pp 67-111.
Kaiser CW: Complications from staging laparotomy for Hodgkin disease. J Surg Oncol 16 (4): 319-25, 1981. [PUBMED Abstract]
Jockovich M, Mendenhall NP, Sombeck MD, et al.: Long-term complications of laparotomy in Hodgkin's disease. Ann Surg 219 (6): 615-21; discussion 621-4, 1994. [PUBMED Abstract]
Coleman CN, McDougall IR, Dailey MO, et al.: Functional hyposplenia after splenic irradiation for Hodgkin's disease. Ann Intern Med 96 (1): 44-7, 1982. [PUBMED Abstract]
Weiner MA, Landmann RG, DeParedes L, et al.: Vesiculated erythrocytes as a determination of splenic reticuloendothelial function in pediatric patients with Hodgkin's disease. J Pediatr Hematol Oncol 17 (4): 338-41, 1995. [PUBMED Abstract]
Weil BR, Madenci AL, Liu Q, et al.: Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol 36 (16): 1571-1578, 2018. [PUBMED Abstract]
National Center for Immunization and Respiratory Diseases: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 60 (RR02): 1-60, 2011. Available online Last accessed April 17, 2019.
Bridges CB, Coyne-Beasley T; Advisory Committee on Immunization Practices: Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older: United States, 2014. Ann Intern Med 160 (3): 190, 2014. [PUBMED Abstract]
Rubin LG, Levin MJ, Ljungman P, et al.: 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 58 (3): 309-18, 2014. [PUBMED Abstract]
Centers for Disease Control and Prevention (CDC): Recommendation of the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MenACWY-D) among children aged 9 through 23 months at increased risk for invasive meningococcal disease. MMWR Morb Mortal Wkly Rep 60 (40): 1391-2, 2011. [PUBMED Abstract]
Kimberlin DW, Brady MT, Jackson MA, et al., eds.: Red Book: 2018–2021 Report of the Committee on Infectious Diseases. 31st ed. Itasca, Ill: American Academy of Pediatrics, 2018. Also available online. Last accessed April 11, 2019.
Centers for Disease Control and Prevention (CDC): Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 62 (25): 521-4, 2013. [PUBMED Abstract]
Schwartz C L, Hobbie WL, Constine LS, et al., eds.: Survivors of Childhood Cancer: Assessment and Management. St. Louis, Mo: Mosby, 1994.
Koskenvuo M, Ekman I, Saha E, et al.: Immunological Reconstitution in Children After Completing Conventional Chemotherapy of Acute Lymphoblastic Leukemia is Marked by Impaired B-cell Compartment. Pediatr Blood Cancer 63 (9): 1653-6, 2016. [PUBMED Abstract]
Leung W, Neale G, Behm F, et al.: Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia. Cancer Epidemiol 34 (3): 303-8, 2010. [PUBMED Abstract]
Aytac S, Yalcin SS, Cetin M, et al.: Measles, mumps, and rubella antibody status and response to immunization in children after therapy for acute lymphoblastic leukemia. Pediatr Hematol Oncol 27 (5): 333-43, 2010. [PUBMED Abstract]
Brodtman DH, Rosenthal DW, Redner A, et al.: Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens. J Pediatr 146 (5): 654-61, 2005. [PUBMED Abstract]
Fayea NY, Fouda AE, Kandil SM: Immunization status in childhood cancer survivors: A hidden risk which could be prevented. Pediatr Neonatol 58 (6): 541-545, 2017. [PUBMED Abstract]
Bochennek K, Allwinn R, Langer R, et al.: Differential loss of humoral immunity against measles, mumps, rubella and varicella-zoster virus in children treated for cancer. Vaccine 32 (27): 3357-61, 2014. [PUBMED Abstract]
Ruggiero A, Battista A, Coccia P, et al.: How to manage vaccinations in children with cancer. Pediatr Blood Cancer 57 (7): 1104-8, 2011. [PUBMED Abstract]
Patel SR, Chisholm JC, Heath PT: Vaccinations in children treated with standard-dose cancer therapy or hematopoietic stem cell transplantation. Pediatr Clin North Am 55 (1): 169-86, xi, 2008. [PUBMED Abstract]
Olkinuora HA, Taskinen MH, Saarinen-Pihkala UM, et al.: Multiple viral infections post-hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts. Pediatr Transplant 14 (2): 242-8, 2010. [PUBMED Abstract]
Inaba H, Hartford CM, Pei D, et al.: Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation. Br J Haematol 156 (1): 109-17, 2012. [PUBMED Abstract]
Rizzo JD, Wingard JR, Tichelli A, et al.: Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT). Bone Marrow Transplant 37 (3): 249-61, 2006. [PUBMED Abstract]
Tomblyn M, Chiller T, Einsele H, et al.: Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15 (10): 1143-238, 2009. [PUBMED Abstract]
The musculoskeletal system of growing children and adolescents is vulnerable to the cytotoxic effects of cancer therapies, including surgery, chemotherapy, and radiation therapy. Documented late effects include the following:
Bone and joint (abnormal bone and/or muscle growth) problems.
Deformity and functional loss associated with amputation/limb-sparing surgery, joint contracture, osteoporosis/fractures, and osteonecrosis.
Changes in body composition (obesity and loss of lean muscle mass).
While these late effects are discussed individually, it is important to remember that the components of the musculoskeletal system are interrelated. For example, hypoplasia to a muscle group can negatively affect the function of the long bones and the resultant dysfunction can subsequently lead to disuse and osteoporosis.
The major strength of the published literature documenting musculoskeletal late effects among children and adolescents treated for cancer is that most studies have clearly defined outcomes and exposures. However, many studies are observational and cross-sectional or retrospective in design. Single-institution studies are common, and for some outcomes, only small convenience cohorts have been described. Thus, it is possible that studies either excluded patients with the most severe musculoskeletal effects because of death or inability to participate in follow-up testing, or oversampled those with the most severe musculoskeletal late effects because these patients were accessible as they returned for complication-related follow-up. Additionally, some of the results reported in adult survivors of childhood cancer may not be relevant to patients currently being treated because the delivery of anticancer modalities, particularly radiation therapy, has changed over the years in response to documented toxicities.[1,2]
Abnormal Bone Growth
The effect of radiation on bone growth depends on the sites irradiated, as follows:
Head and brain.
Spine and long bones.
Radiation to the head and brain
In an age- and dose-dependent fashion, radiation can inhibit normal bone and muscle maturation and development. Radiation to the head (e.g., cranial, orbital, infratemporal, or nasopharyngeal radiation therapy) can cause craniofacial abnormalities, particularly in children treated before age 5 years who received radiation doses of 20 Gy or higher [3-8] or who were treated with concomitant chemotherapy.[9] Soft tissue sarcomas such as orbital rhabdomyosarcoma and retinoblastoma are two of the more common cancer types treated with these radiation fields. Often, in addition to the cosmetic impact of the craniofacial abnormalities, there can be related dental and sinus problems.
Cranial radiation therapy damages the hypothalamic-pituitary axis in an age- and dose-response fashion and can result in growth hormone deficiency.[10-13] If the growth hormone deficiency is not treated during the growing years and, sometimes, even with appropriate treatment, it leads to a substantially lower final height. Patients with a central nervous system (CNS) tumor [10,14] or acute lymphoblastic leukemia (ALL) [15-17] treated with 18 Gy or higher of cranial radiation therapy are at highest risk. Patients treated with total-body irradiation (TBI), particularly single-fraction TBI,[18-21] and those treated with cranial radiation for non-CNS solid tumors [22] are also at risk of growth hormone deficiency. If the spine is also irradiated (e.g., craniospinal radiation therapy for medulloblastoma or early ALL therapies in the 1960s), growth can be affected by two separate mechanisms—growth hormone deficiency and direct damage to the spine.
Radiation to the spine and long bones
Radiation therapy can also directly affect the growth of the spine and long bones (and associated muscle groups) and can cause premature closure of the epiphyses, leading to the following:[23-31]
Short stature.
Asymmetric growth (scoliosis/kyphosis).
Limb-length discrepancy.
Orthovoltage radiation therapy, commonly used before 1970, delivered high doses of radiation to bone and was commonly associated with subsequent abnormalities in bone growth. However, even with contemporary radiation therapy, if a solid tumor is located near an epiphysis or the spine, alterations in normal bone development can be difficult to avoid.
The effects of radiation therapy administered to the spine on stature in survivors of Wilms tumor have been assessed.
Evidence (effect of radiation therapy on the spine and long bones):
In the National Wilms Tumor Study (NWTS), studies 1 through 4, stature loss in 2,778 children was evaluated.[24] Repeated height measurements were collected during long-term follow-up. The effects of radiation dosage, age at treatment, and chemotherapy on stature were analyzed using statistical models that accounted for the normal variation in height with sex and advancing age. Predictions from the model were validated by descriptive analysis of heights measured at ages 17 to 18 years for 205 patients.
For those younger than 12 months at diagnosis who received more than 10 Gy of radiation therapy, the estimated adult-height deficit was 7.7 cm when compared with the nonradiation therapy group.
For those who received 10 Gy, the estimated trunk shortening was 2.8 cm or less.
Among those whose height measurements in the teenage years were available, patients who received more than 15 Gy of radiation therapy were 4 to 7 cm shorter on average than their nonirradiated counterparts, with a dose-response relationship evident.
Chemotherapy did not confer additional risk.
The effect of radiation therapy on the development of scoliosis has also been re-evaluated. In a group of 42 children treated for Wilms tumor from 1968 to 1994, scoliosis was seen in 18 patients, with only one patient needing orthopedic intervention.[32]
Median time to development of scoliosis was 102 months (range, 16–146 months).
A clear dose-response relationship was seen; children treated with lower doses (<24 Gy) of radiation had a significantly lower incidence of scoliosis than those who received more than 24 Gy of radiation.
There was also a suggestion that the incidence was lower in patients who received 10 to 12 Gy, the dosages currently used for Wilms tumor, although the sample size was small.
Osteoporosis and Fractures
Although increased rates of fracture are not reported among long-term survivors of childhood cancer,[33] maximal peak bone mass is an important factor influencing the risk of osteoporosis and fracture among older patients. Treatment-related factors that affect bone mineral loss include the following:
Chemotherapy. Methotrexate has a cytotoxic effect on osteoblasts, resulting in a reduction of bone volume and formation of new bone.[34,35] This effect may be exacerbated by the chronic use of corticosteroids, another class of agents routinely used in the treatment of hematological malignancies and in supportive care for a variety of pediatric cancers.
Radiation therapy. Radiation-related endocrinopathies, such as growth hormone deficiency or hypogonadism, may contribute to ongoing bone mineral loss.[36-39]
Nutrition and activity. Suboptimal nutrition and physical inactivity may further predispose to deficits in bone mineral accretion.
Most of our knowledge about cancer and treatment effects on bone mineralization has been derived from studies of children with ALL.[34,40] In this group, the leukemic process, and possibly vitamin D deficiency, may play a role in the alterations in bone metabolism and bone mass observed at diagnosis.[41] Antileukemic therapy causes additional bone mineral density loss,[42] which has been reported to normalize over time [43,44] or to persist for many years after completion of therapy.[45,46] Clinical factors predicting higher risk of low bone mineral density include treatment with the following:[38,45,47-49]
High cumulative doses of methotrexate (>40 g/m2).
High cumulative doses of corticosteroids (>9 g/m2).
Cranial radiation therapy or craniospinal radiation therapy.
More potent glucocorticoids such as dexamethasone.
The development of osteonecrosis during treatment for ALL also predicts higher risk of low bone density.[50]
Clinical assessment of bone mineral density in adults treated for childhood ALL indicates that most bone mineral deficits normalize over time after discontinuing osteotoxic therapy.
Evidence (low bone mineral density):
A cohort of 845 adult survivors of childhood ALL were evaluated at a median age of 31 years.[38]
Very low bone mineral density was relatively uncommon, with only 5.7% and 23.8% of patients demonstrating bone mineral density z-scores consistent with osteoporosis and osteopenia, respectively.
Cranial radiation dose of 24 Gy or higher, but not cumulative methotrexate or prednisone equivalent doses, was associated with a twofold elevated risk of bone mineral density z-scores of -1 or lower.
In a subset of 400 survivors with longitudinal bone mineral density evaluations, bone mineral density z-scores tended to improve from adolescence to young adulthood.
Among 862 ALL survivors (median age, 31.3 years) evaluated by quantitative computed tomography of L1 through L2 vertebrae, 30% of survivors had low bone mineral density (z-score below -1) and 18.6% met criteria for frailty or prefrailty.[51]
The prefrail phenotype is characterized by having two of five characteristics (low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness) and the frail phenotype is characterized by having three or more of these characteristics. Modifiable factors such as growth hormone deficiency, smoking, and alcohol consumption were significant predictors for these outcomes, with varying impact on the basis of sex. These data underscore the importance of lifestyle counseling and screening for hormonal deficits during long-term survivors' follow-up evaluations.
Bone mineral density deficits that are likely multifactorial in etiology have been reported in allogeneic hematopoietic stem cell transplantation (HSCT) recipients conditioned with TBI.[52,53] French investigators observed a significant risk of lower femoral bone mineral density among adult survivors of childhood leukemia treated with HSCT who had gonadal deficiency.[54] Hormonal therapy has been shown to enhance the bone mineral density of adolescent girls diagnosed with hypogonadism after HSCT.[55]
Despite disease-related and treatment-related risks of bone mineral density deficits, the prevalence of self-reported fractures among Childhood Cancer Survivor Study (CCSS) participants was lower than that reported by sibling controls. Predictors of increased prevalence of fracture by multivariable analyses included the following:[33]
Among female survivors, increasing age at follow-up, white race, methotrexate treatment, and balance difficulties.
Among male survivors, smoking history and white race.
Radiation-induced fractures can occur with doses of radiation of 50 Gy or higher, as is often used in the treatment of Ewing sarcoma of the extremity.[56,57]
Data from the St. Jude Lifetime Cohort (development) and Erasmus Medical Center (validation) in the Netherlands were used to develop and validate prediction models for low and very low bone mineral density on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry. Low bone mineral density was defined as lumbar spine bone mineral density and/or total-body bone mineral density Z score of -1 or lower; very low bone mineral density was defined as a Z score of -2 or lower. Low bone mineral density was present in 51% and 45% of St. Jude Lifetime and Dutch participants, represented by survivors of both hematologic and solid malignancies, respectively, and very low bone mineral density was present in 20% and 10%, respectively. The model, which included male sex, height, weight, attained age, current smoking status, and cranial irradiation, showed good performance for predicting risk of low bone mineral density (areas under the curve of 0.72 in the St. Jude Lifetime Cohort and 0.69 in the Dutch cohort). The model, which included male sex, height, weight, attained age, cranial irradiation, and abdominal irradiation, showed good performance for predicting risk of very low bone mineral density (areas under the curve of 0.76 in the St. Jude Lifetime Cohort and 0.75 in the Dutch cohort). These models correctly identified bone mineral density status in most white adult survivors through age 40 years using easily measured patient and treatment characteristics.[58]
Osteonecrosis (also known as aseptic or avascular necrosis) is a rare, but well-recognized skeletal complication observed predominantly in survivors of pediatric hematological malignancies treated with corticosteroids.[59-61] The prevalence of osteonecrosis has varied from 1% to 22% based on the study population, treatment protocol, method of evaluation, and time from treatment.[61-67]
The condition is characterized by death of one or more segments of bone that most often affects weight-bearing joints, especially the hips and knees. Longitudinal cohort studies have identified a spectrum of clinical manifestations of osteonecrosis, ranging from asymptomatic, spontaneously-resolving imaging changes to painful progressive articular collapse requiring joint replacement.[68,69] Symptomatic osteonecrosis characterized by pain, joint swelling, and reduced mobility typically presents during the first 2 years of therapy, particularly in patients with ALL. These symptoms may improve over time, persist, or progress in the years after completion of therapy.[70] In one series, 60% of patients continued to have symptoms at a median follow-up of 4.9 years after diagnosis of osteonecrosis.[71] Surgical procedures, including core decompression, osteotomy, and joint replacements, are sometimes performed in those with persistently severe symptoms.[71]
Factors that increase the risk of osteonecrosis include the following:
Exposure to corticosteroids and, possibly, methotrexate and concurrent asparaginase. The most important treatment factor associated with the development of osteonecrosis is prolonged exposure to corticosteroids, which is typical in treatment regimens used for ALL, non-Hodgkin lymphoma, and HSCT.[64,67,72,73]
Osteonecrosis risk may be related to type of corticosteroid, with some studies in patients with ALL indicating increased risk with the use of dexamethasone compared with prednisone.[74,75]
Corticosteroid dosing schedule also appears to impact the risk of developing osteonecrosis. In the Children’s Oncology Group (COG) 1961 trial for newly diagnosed high-risk ALL, patients were randomly assigned to receive either continuous (daily) dexamethasone or an alternate-week schedule of dexamethasone during the delayed intensification phase; the alternate-week schedule was associated with a lower incidence of osteonecrosis.[61]
In addition to corticosteroids, exposure to methotrexate and concurrent asparaginase may contribute to the development of osteonecrosis.[76,77]
Development of thromboembolism during antileukemic therapy. In a retrospective review of 208 children treated for ALL, investigators at McMaster University reported a 5.21-fold (95% CI, 1.82–14.91) increased odds of osteonecrosis among children who experienced thromboembolism during antileukemic therapy than among those who did not have a thromboembolism, even after accounting for age and asparaginase exposure.[77]
HSCT conditioning and course. In a large case-control study that evaluated risk factors for osteonecrosis using data from the Center for International Blood and Marrow Transplant Research, lower risks of osteonecrosis were seen in patients with nonmalignant diseases and in those who had received reduced-intensity conditioning regimens for malignant diseases than were seen in patients receiving myeloablative regimens for malignant diseases.[78] Several studies have reported an increased risk of osteonecrosis in association with chronic graft-versus-host disease (GVHD).[65,72,78]
Age at time of diagnosis or transplant. Several studies have demonstrated that age at diagnosis (or at time of transplant) is a significant independent predictor of osteonecrosis.[61,62,67,71,72,74,78] Osteonecrosis is significantly more common in older children and adolescents than in younger children. In the COG-1961 trial for high-risk ALL, the 5-year cumulative incidence of symptomatic osteonecrosis was 1.0% for patients aged 1 to 9 years, 9.9% for patients aged 10 to 15 years, and 20% for patients aged 16 to 21 years (P < .0001).[61]
Race. Osteonecrosis also occurs more frequently in white patients than in black patients.[73,79]
Genetic factors. Genetic factors influencing folate metabolism, glucocorticoid metabolism, and adipogenesis have been linked to excess risk of osteonecrosis among survivors.[73,80,81]
Two candidate gene studies indicate that children homozygous for a 28–base pair repeat within the 5’ untranslated region of the TS gene are at increased risk of osteonecrosis.[73,81] This gene is associated with folate production and replacement and is inhibited by methotrexate.
St. Jude Children's Research Hospital investigators observed an almost sixfold (odds ratio, 5.6; 95% confidence interval, 2.7–11.3) risk of osteonecrosis among survivors with polymorphism of the ACP1 gene, which regulates lipid levels and osteoblast differentiation.[66]
Genome-wide association studies have identified potential risk variants in BMP7, PROX1-AS1, GRID2 (children younger than 10 years), and GRIN3A, which are all associated with glucocorticoid receptor activity.[80,82]
Studies evaluating the influence of sex on the risk of osteonecrosis have yielded conflicting results, with some suggesting a higher incidence in females [68,71,79] that has not been confirmed by others.[60,68]
Osteochondromas are benign boney protrusions that can be spontaneous or associated with radiation therapy. They generally occur as a single lesion; however, multiple lesions may develop in the context of hereditary multiple osteochondromatosis.[83] Approximately 5% of children undergoing myeloablative HSCT will develop osteochondroma, which most commonly presents in the metaphyseal regions of long bones.[83,84]
Evidence (risk of osteochondroma):
A large Italian study reported a 6.1% cumulative risk of developing osteochondroma at 15 years posttransplant, with increased risk associated with younger age at transplant (≤3 years) and use of TBI.[85]
Osteochondromas have been reported in patients with neuroblastoma who received local radiation therapy, anti-GD2 monoclonal antibody therapy, and isotretinoin. [86]
Osteochondromas occurred at a median of 8.2 years from diagnosis, and the cumulative incidence rate was 4.9% at 10 years from diagnosis among 362 patients younger than 10 years.
In this series, most of the osteochondromas were unrelated to radiation and had features characteristic of benign developmental osteochondroma.
The pathogenic role for chemotherapy, anti-GD2 monoclonal antibody therapy, or isotretinoin in the development of osteochondroma remains speculative.
Growth hormone therapy may influence the onset and pace of growth of osteochondromas.[21,87]
Because malignant degeneration of these lesions is exceptionally rare, clinical rather than radiological follow-up is most appropriate.[88] Surgical resection is only necessary when the lesion interferes with joint alignment and movement.[89]
Amputation and Limb-Sparing Surgery
Amputation and limb-sparing surgery prevent local recurrence of bone tumors by removal of all gross and microscopic disease. If optimally executed, both procedures accomplish an en bloc excision of tumor with a margin of normal uninvolved tissue. The type of surgical procedure, the primary tumor site, and the age of the patient affect the risk of postsurgical complications.[40] Complications in survivors treated with amputation include prosthetic fit problems, chronic pain in the residual limb, phantom limb pain, and bone overgrowth.[90,91] While limb-sparing surgeries may offer a more aesthetically pleasing outcome, complications have been reported more frequently in survivors who underwent these procedures than in those treated with amputation. Complications after limb-sparing surgery include non-union, pathologic fracture, aseptic loosening, limb-length discrepancy, endoprosthetic fracture, and limited joint range of motion.[90,92] Occasionally, refractory complications develop after limb-sparing surgery and require amputation.[93,94]
A number of studies have compared functional outcomes after amputation and limb-sparing surgery, but results have been limited by inconsistent methods of functional assessment and small cohort sizes. Overall, data suggest that limb-sparing surgery results in better function than amputation, but differences are relatively modest.[90,94,95] Similarly, long-term quality of life outcomes among survivors undergoing amputation and limb sparing procedures have not differed substantially.[93] A longitudinal analysis of health status among extremity sarcoma survivors in the CCSS indicates an association between lower extremity amputation and increasing activity limitations with age, and an association between upper extremity amputation and lower educational attainment.[96]
Joint Contractures
HSCT with any history of chronic GVHD is associated with joint contractures.[97-99]
Table 13 summarizes bone and joint late effects and the related health screenings.
Table 13. Bone and Joint Late Effectsa
Musculoskeletal Effects
CT = computed tomography; DXA = dual-energy x-ray absorptiometry; GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation.
Radiation impacting musculoskeletal system Hypoplasia; fibrosis; reduced/uneven growth (scoliosis, kyphosis); limb length discrepancy Exam: bones and soft tissues in radiation fields
Radiation impacting head and neck Craniofacial abnormalities History: psychosocial assessment, with attention to: educational and/or vocational progress, depression, anxiety, posttraumatic stress, social withdrawal
Head and neck exam
Radiation impacting musculoskeletal system Radiation-induced fracture Exam of affected bone
Methotrexate; corticosteroids (dexamethasone, prednisone); radiation impacting skeletal structures; HSCT Reduced bone mineral density Bone mineral density test (DXA or quantitative CT)
Corticosteroids (dexamethasone, prednisone) Osteonecrosis History: joint pain, swelling, immobility, limited range of motion
Musculoskeletal exam
Radiation with impact to oral cavity Osteoradionecrosis History/oral exam: impaired or delayed healing after dental work, persistent jaw pain or swelling, trismus
Amputation Amputation-related complications (impaired cosmesis, functional/activity limitations, residual limb integrity, chronic pain, increased energy expenditure) History: pain, functional/activity limitations
Exam: residual limb integrity
Prosthetic evaluation
Limb-sparing surgery Limb-sparing surgical complications (functional/activity limitations, fibrosis, contractures, chronic infection, chronic pain, limb length discrepancy, increased energy expenditure, prosthetic malfunction [loosening, non-union, fracture]) History: pain, functional/activity limitations
Radiograph of affected limb
Orthopedic evaluation
HSCT with any history of chronic GVHD Joint contracture Musculoskeletal exam
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for musculoskeletal system late effects information, including risk factors, evaluation, and health counseling.
Green DM: 11th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer. Forward. Pediatr Blood Cancer 58 (1): 111, 2012. [PUBMED Abstract]
Estilo CL, Huryn JM, Kraus DH, et al.: Effects of therapy on dentofacial development in long-term survivors of head and neck rhabdomyosarcoma: the memorial sloan-kettering cancer center experience. J Pediatr Hematol Oncol 25 (3): 215-22, 2003. [PUBMED Abstract]
Karsila-Tenovuo S, Jahnukainen K, Peltomäki T, et al.: Disturbances in craniofacial morphology in children treated for solid tumors. Oral Oncol 37 (7): 586-92, 2001. [PUBMED Abstract]
Choi SY, Kim MS, Yoo S, et al.: Long term follow-up results of external beam radiotherapy as primary treatment for retinoblastoma. J Korean Med Sci 25 (4): 546-51, 2010. [PUBMED Abstract]
Raney RB, Anderson JR, Kollath J, et al.: Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: Report from the Intergroup Rhabdomyosarcoma Study (IRS)-III, 1984-1991. Med Pediatr Oncol 34 (6): 413-20, 2000. [PUBMED Abstract]
Shildkrot Y, Kirzhner M, Haik BG, et al.: The effect of cancer therapies on pediatric anophthalmic sockets. Ophthalmology 118 (12): 2480-6, 2011. [PUBMED Abstract]
Sklar CA, Constine LS: Chronic neuroendocrinological sequelae of radiation therapy. Int J Radiat Oncol Biol Phys 31 (5): 1113-21, 1995. [PUBMED Abstract]
Brownstein CM, Mertens AC, Mitby PA, et al.: Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study. J Clin Endocrinol Metab 89 (9): 4422-7, 2004. [PUBMED Abstract]
Kiehna EN, Merchant TE: Radiation therapy for pediatric craniopharyngioma. Neurosurg Focus 28 (4): E10, 2010. [PUBMED Abstract]
Packer RJ, Boyett JM, Janss AJ, et al.: Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. J Clin Oncol 19 (2): 480-7, 2001. [PUBMED Abstract]
Bongers ME, Francken AB, Rouwé C, et al.: Reduction of adult height in childhood acute lymphoblastic leukemia survivors after prophylactic cranial irradiation. Pediatr Blood Cancer 45 (2): 139-43, 2005. [PUBMED Abstract]
Leung W, Ahn H, Rose SR, et al.: A prospective cohort study of late sequelae of pediatric allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore) 86 (4): 215-24, 2007. [PUBMED Abstract]
Sanders JE: Growth and development after hematopoietic cell transplant in children. Bone Marrow Transplant 41 (2): 223-7, 2008. [PUBMED Abstract]
Sanders JE, Guthrie KA, Hoffmeister PA, et al.: Final adult height of patients who received hematopoietic cell transplantation in childhood. Blood 105 (3): 1348-54, 2005. [PUBMED Abstract]
Shalitin S, Laur E, Lebenthal Y, et al.: Endocrine complications and components of the metabolic syndrome in survivors of childhood malignant non-brain solid tumors. Horm Res Paediatr 81 (1): 32-42, 2014. [PUBMED Abstract]
Fletcher BD: Effects of pediatric cancer therapy on the musculoskeletal system. Pediatr Radiol 27 (8): 623-36, 1997. [PUBMED Abstract]
Hogeboom CJ, Grosser SC, Guthrie KA, et al.: Stature loss following treatment for Wilms tumor. Med Pediatr Oncol 36 (2): 295-304, 2001. [PUBMED Abstract]
Merchant TE, Nguyen L, Nguyen D, et al.: Differential attenuation of clavicle growth after asymmetric mantle radiotherapy. Int J Radiat Oncol Biol Phys 59 (2): 556-61, 2004. [PUBMED Abstract]
Willman KY, Cox RS, Donaldson SS: Radiation induced height impairment in pediatric Hodgkin's disease. Int J Radiat Oncol Biol Phys 28 (1): 85-92, 1994. [PUBMED Abstract]
Wallace WH, Shalet SM, Morris-Jones PH, et al.: Effect of abdominal irradiation on growth in boys treated for a Wilms' tumor. Med Pediatr Oncol 18 (6): 441-6, 1990. [PUBMED Abstract]
Silber JH, Littman PS, Meadows AT: Stature loss following skeletal irradiation for childhood cancer. J Clin Oncol 8 (2): 304-12, 1990. [PUBMED Abstract]
Hartley KA, Li C, Laningham FH, et al.: Vertebral body growth after craniospinal irradiation. Int J Radiat Oncol Biol Phys 70 (5): 1343-9, 2008. [PUBMED Abstract]
Paulino AC, Nguyen TX, Mai WY: An analysis of primary site control and late effects according to local control modality in non-metastatic Ewing sarcoma. Pediatr Blood Cancer 48 (4): 423-9, 2007. [PUBMED Abstract]
de Jonge T, Slullitel H, Dubousset J, et al.: Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J 14 (8): 765-71, 2005. [PUBMED Abstract]
Wilson CL, Dilley K, Ness KK, et al.: Fractures among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 118 (23): 5920-8, 2012. [PUBMED Abstract]
Davies JH, Evans BA, Jenney ME, et al.: Skeletal morbidity in childhood acute lymphoblastic leukaemia. Clin Endocrinol (Oxf) 63 (1): 1-9, 2005. [PUBMED Abstract]
van der Sluis IM, Boot AM, Hop WC, et al.: Long-term effects of growth hormone therapy on bone mineral density, body composition, and serum lipid levels in growth hormone deficient children: a 6-year follow-up study. Horm Res 58 (5): 207-14, 2002. [PUBMED Abstract]
van der Sluis IM, van den Heuvel-Eibrink MM, Hählen K, et al.: Bone mineral density, body composition, and height in long-term survivors of acute lymphoblastic leukemia in childhood. Med Pediatr Oncol 35 (4): 415-20, 2000. [PUBMED Abstract]
Gurney JG, Kaste SC, Liu W, et al.: Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 61 (7): 1270-6, 2014. [PUBMED Abstract]
Siegel DA, Claridy M, Mertens A, et al.: Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
Oeffinger KC, Hudson MM, Landier W: Survivorship: childhood cancer survivors. Prim Care 36 (4): 743-80, 2009. [PUBMED Abstract]
van der Sluis IM, van den Heuvel-Eibrink MM, Hählen K, et al.: Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia. J Pediatr 141 (2): 204-10, 2002. [PUBMED Abstract]
Arikoski P, Komulainen J, Riikonen P, et al.: Reduced bone density at completion of chemotherapy for a malignancy. Arch Dis Child 80 (2): 143-8, 1999. [PUBMED Abstract]
Brennan BM, Mughal Z, Roberts SA, et al.: Bone mineral density in childhood survivors of acute lymphoblastic leukemia treated without cranial irradiation. J Clin Endocrinol Metab 90 (2): 689-94, 2005. [PUBMED Abstract]
Kadan-Lottick N, Marshall JA, Barón AE, et al.: Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998. J Pediatr 138 (6): 898-904, 2001. [PUBMED Abstract]
Kaste SC, Jones-Wallace D, Rose SR, et al.: Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development. Leukemia 15 (5): 728-34, 2001. [PUBMED Abstract]
Warner JT, Evans WD, Webb DK, et al.: Relative osteopenia after treatment for acute lymphoblastic leukemia. Pediatr Res 45 (4 Pt 1): 544-51, 1999. [PUBMED Abstract]
Mandel K, Atkinson S, Barr RD, et al.: Skeletal morbidity in childhood acute lymphoblastic leukemia. J Clin Oncol 22 (7): 1215-21, 2004. [PUBMED Abstract]
Holzer G, Krepler P, Koschat MA, et al.: Bone mineral density in long-term survivors of highly malignant osteosarcoma. J Bone Joint Surg Br 85 (2): 231-7, 2003. [PUBMED Abstract]
den Hoed MA, Klap BC, te Winkel ML, et al.: Bone mineral density after childhood cancer in 346 long-term adult survivors of childhood cancer. Osteoporos Int 26 (2): 521-9, 2015. [PUBMED Abstract]
den Hoed MA, Pluijm SM, te Winkel ML, et al.: Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia. Haematologica 100 (12): 1564-70, 2015. [PUBMED Abstract]
Wilson CL, Chemaitilly W, Jones KE, et al.: Modifiable Factors Associated With Aging Phenotypes Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia. J Clin Oncol 34 (21): 2509-15, 2016. [PUBMED Abstract]
Benmiloud S, Steffens M, Beauloye V, et al.: Long-term effects on bone mineral density of different therapeutic schemes for acute lymphoblastic leukemia or non-Hodgkin lymphoma during childhood. Horm Res Paediatr 74 (4): 241-50, 2010. [PUBMED Abstract]
McClune BL, Polgreen LE, Burmeister LA, et al.: Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients. Bone Marrow Transplant 46 (1): 1-9, 2011. [PUBMED Abstract]
Le Meignen M, Auquier P, Barlogis V, et al.: Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities. Blood 118 (6): 1481-9, 2011. [PUBMED Abstract]
Kodama M, Komura H, Shimizu S, et al.: Efficacy of hormone therapy for osteoporosis in adolescent girls after hematopoietic stem cell transplantation: a longitudinal study. Fertil Steril 95 (2): 731-5, 2011. [PUBMED Abstract]
Paulino AC: Late effects of radiotherapy for pediatric extremity sarcomas. Int J Radiat Oncol Biol Phys 60 (1): 265-74, 2004. [PUBMED Abstract]
Wagner LM, Neel MD, Pappo AS, et al.: Fractures in pediatric Ewing sarcoma. J Pediatr Hematol Oncol 23 (9): 568-71, 2001. [PUBMED Abstract]
van Atteveld JE, Pluijm SMF, Ness KK, et al.: Prediction of Low and Very Low Bone Mineral Density Among Adult Survivors of Childhood Cancer. J Clin Oncol 37 (25): 2217-2225, 2019. [PUBMED Abstract]
Sala A, Mattano LA, Barr RD: Osteonecrosis in children and adolescents with cancer - an adverse effect of systemic therapy. Eur J Cancer 43 (4): 683-9, 2007. [PUBMED Abstract]
Elmantaser M, Stewart G, Young D, et al.: Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukaemia. Arch Dis Child 95 (10): 805-9, 2010. [PUBMED Abstract]
Mattano LA, Devidas M, Nachman JB, et al.: Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial. Lancet Oncol 13 (9): 906-15, 2012. [PUBMED Abstract]
Bürger B, Beier R, Zimmermann M, et al.: Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95. Pediatr Blood Cancer 44 (3): 220-5, 2005. [PUBMED Abstract]
Karimova EJ, Rai SN, Howard SC, et al.: Femoral head osteonecrosis in pediatric and young adult patients with leukemia or lymphoma. J Clin Oncol 25 (12): 1525-31, 2007. [PUBMED Abstract]
Karimova EJ, Wozniak A, Wu J, et al.: How does osteonecrosis about the knee progress in young patients with leukemia?: a 2- to 7-year study. Clin Orthop Relat Res 468 (9): 2454-9, 2010. [PUBMED Abstract]
Campbell S, Sun CL, Kurian S, et al.: Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantation. Cancer 115 (18): 4127-35, 2009. [PUBMED Abstract]
Kawedia JD, Kaste SC, Pei D, et al.: Pharmacokinetic, pharmacodynamic, and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia. Blood 117 (8): 2340-7; quiz 2556, 2011. [PUBMED Abstract]
Girard P, Auquier P, Barlogis V, et al.: Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood. Haematologica 98 (7): 1089-97, 2013. [PUBMED Abstract]
Aricò M, Boccalatte MF, Silvestri D, et al.: Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia. Haematologica 88 (7): 747-53, 2003. [PUBMED Abstract]
Ribeiro RC, Fletcher BD, Kennedy W, et al.: Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma. Leukemia 15 (6): 891-7, 2001. [PUBMED Abstract]
Padhye B, Dalla-Pozza L, Little D, et al.: Incidence and outcome of osteonecrosis in children and adolescents after intensive therapy for acute lymphoblastic leukemia (ALL). Cancer Med 5 (5): 960-7, 2016. [PUBMED Abstract]
te Winkel ML, Pieters R, Hop WC, et al.: Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia. J Clin Oncol 29 (31): 4143-50, 2011. [PUBMED Abstract]
Faraci M, Calevo MG, Lanino E, et al.: Osteonecrosis after allogeneic stem cell transplantation in childhood. A case-control study in Italy. Haematologica 91 (8): 1096-9, 2006. [PUBMED Abstract]
Relling MV, Yang W, Das S, et al.: Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. J Clin Oncol 22 (19): 3930-6, 2004. [PUBMED Abstract]
Vrooman LM, Stevenson KE, Supko JG, et al.: Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol 31 (9): 1202-10, 2013. [PUBMED Abstract]
Hyakuna N, Shimomura Y, Watanabe A, et al.: Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group. J Pediatr Hematol Oncol 36 (1): 22-9, 2014. [PUBMED Abstract]
Yang L, Panetta JC, Cai X, et al.: Asparaginase may influence dexamethasone pharmacokinetics in acute lymphoblastic leukemia. J Clin Oncol 26 (12): 1932-9, 2008. [PUBMED Abstract]
Badhiwala JH, Nayiager T, Athale UH: The development of thromboembolism may increase the risk of osteonecrosis in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 62 (10): 1851-4, 2015. [PUBMED Abstract]
Li X, Brazauskas R, Wang Z, et al.: Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents. Biol Blood Marrow Transplant 20 (4): 587-92, 2014. [PUBMED Abstract]
Mattano LA, Sather HN, Trigg ME, et al.: Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group. J Clin Oncol 18 (18): 3262-72, 2000. [PUBMED Abstract]
Karol SE, Mattano LA, Yang W, et al.: Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood 127 (5): 558-64, 2016. [PUBMED Abstract]
Finkelstein Y, Blonquist TM, Vijayanathan V, et al.: A thymidylate synthase polymorphism is associated with increased risk for bone toxicity among children treated for acute lymphoblastic leukemia. Pediatr Blood Cancer 64 (7): , 2017. [PUBMED Abstract]
Karol SE, Yang W, Van Driest SL, et al.: Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood 126 (15): 1770-6, 2015. [PUBMED Abstract]
Bovée JV: Multiple osteochondromas. Orphanet J Rare Dis 3: 3, 2008. [PUBMED Abstract]
Danner-Koptik K, Kletzel M, Dilley KJ: Exostoses as a long-term sequela after pediatric hematopoietic progenitor cell transplantation: potential causes and increase risk of secondary malignancies from Ann & Robert H. Lurie Children's Hospital of Chicago. Biol Blood Marrow Transplant 19 (8): 1267-70, 2013. [PUBMED Abstract]
Faraci M, Bagnasco F, Corti P, et al.: Osteochondroma after hematopoietic stem cell transplantation in childhood. An Italian study on behalf of the AIEOP-HSCT group. Biol Blood Marrow Transplant 15 (10): 1271-6, 2009. [PUBMED Abstract]
Kushner BH, Roberts SS, Friedman DN, et al.: Osteochondroma in long-term survivors of high-risk neuroblastoma. Cancer 121 (12): 2090-6, 2015. [PUBMED Abstract]
Bordigoni P, Turello R, Clement L, et al.: Osteochondroma after pediatric hematopoietic stem cell transplantation: report of eight cases. Bone Marrow Transplant 29 (7): 611-4, 2002. [PUBMED Abstract]
Taitz J, Cohn RJ, White L, et al.: Osteochondroma after total body irradiation: an age-related complication. Pediatr Blood Cancer 42 (3): 225-9, 2004. [PUBMED Abstract]
King EA, Hanauer DA, Choi SW, et al.: Osteochondromas after radiation for pediatric malignancies: a role for expanded counseling for skeletal side effects. J Pediatr Orthop 34 (3): 331-5, 2014 Apr-May. [PUBMED Abstract]
Nagarajan R, Neglia JP, Clohisy DR, et al.: Limb salvage and amputation in survivors of pediatric lower-extremity bone tumors: what are the long-term implications? J Clin Oncol 20 (22): 4493-501, 2002. [PUBMED Abstract]
Aulivola B, Hile CN, Hamdan AD, et al.: Major lower extremity amputation: outcome of a modern series. Arch Surg 139 (4): 395-9; discussion 399, 2004. [PUBMED Abstract]
Kaste SC, Neel MN, Rao BN, et al.: Complications of limb-sparing procedures using endoprosthetic replacements about the knee for pediatric skeletal sarcomas. Pediatr Radiol 31 (2): 62-71, 2001. [PUBMED Abstract]
Eiser C, Darlington AS, Stride CB, et al.: Quality of life implications as a consequence of surgery: limb salvage, primary and secondary amputation. Sarcoma 5 (4): 189-95, 2001. [PUBMED Abstract]
Renard AJ, Veth RP, Schreuder HW, et al.: Function and complications after ablative and limb-salvage therapy in lower extremity sarcoma of bone. J Surg Oncol 73 (4): 198-205, 2000. [PUBMED Abstract]
Fernandez-Pineda I, Hudson MM, Pappo AS, et al.: Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study. J Cancer Surviv 11 (1): 1-12, 2017. [PUBMED Abstract]
Marina N, Hudson MM, Jones KE, et al.: Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study. Arch Phys Med Rehabil 94 (6): 1062-73, 2013. [PUBMED Abstract]
Antin JH: Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 347 (1): 36-42, 2002. [PUBMED Abstract]
Beredjiklian PK, Drummond DS, Dormans JP, et al.: Orthopaedic manifestations of chronic graft-versus-host disease. J Pediatr Orthop 18 (5): 572-5, 1998 Sep-Oct. [PUBMED Abstract]
Inamoto Y, Storer BE, Petersdorf EW, et al.: Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood 121 (25): 5098-103, 2013. [PUBMED Abstract]
Surgery, radiation therapy, or chemotherapy that negatively affects any component of the hypothalamic-pituitary axis or gonads may compromise reproductive outcomes in childhood cancer survivors. Evidence for this outcome in childhood cancer survivors is limited by studies characterized by small sample size, cohort selection and participation bias, cross-sectional assessment, heterogeneity in treatment approach, time since treatment, and method of ascertainment. In particular, the literature is deficient regarding hard outcomes of reproductive potential (e.g., semen analysis in men, primordial follicle count in women) and outcomes after contemporary risk-adapted treatment approaches.[1,2]
The risk of infertility is generally related to the tissues or organs involved by the cancer and the specific type, dose, and combination of cytotoxic therapy.
Orchiectomy or oophorectomy performed for the management of pediatric germ cell tumors may reduce germ cell numbers.
Alkylating agents and similar DNA interstrand cross-linking agents used in the treatment of pediatric cancers are the primary chemotherapeutic agents associated with a high risk of infertility. Factors influencing the risk of gonadal injury in children treated with alkylating agent chemotherapy include the following:
Cumulative dose.
Earlier studies used the alkylating agent dose to define dose levels associated with the risk of gonadal toxicity within a specific study cohort. Childhood Cancer Survivor Study (CCSS) investigators developed the cyclophosphamide equivalent dose, which is a metric for normalization of the cumulative doses of various alkylating agents that is independent of the study population. The alkylating agent dose and cyclophosphamide equivalent dose perform similarly when used in several models for different survivor outcomes that include treatment exposures, but only the cyclophosphamide equivalent dose permits comparison across variably treated cohorts. Investigations that evaluate risk factors for gonadal toxicity vary in the use of cumulative doses based on individual alkylating agents, the alkylating agent dose, and the cyclophosphamide equivalent dose.[3]
The specific alkylating agent.
The length of treatment.
Age at treatment.
The risk of radiation injury to the hypothalamic-pituitary axis or gonads is related to the treatment volume, total dose, fractionation schedule, and age at treatment.
In addition to anticancer therapy, age at treatment, and sex, it is likely that genetic factors influence the risk of permanent infertility. It should be noted that pediatric cancer treatment protocols often prescribe combined-modality therapy; thus, the additive effects of gonadotoxic exposures may need to be considered in assessing reproductive potential. Detailed information about the specific cancer treatment modalities including specific surgical procedures, the type and cumulative doses of chemotherapeutic agents, and radiation treatment volumes and doses are needed to estimate risks for gonadal dysfunction and infertility.
Cancer treatments that may impair testicular and reproductive function include the following:
Surgery (orchiectomy, retroperitoneal lymph node dissection, extensive pelvic dissection).
Radiation therapy (exposing the hypothalamic-pituitary axis or testes).
Chemotherapy (alkylating agents and similar DNA interstrand cross-linking agents such as procarbazine).
Surgery affecting testicular function
Patients who undergo unilateral orchiectomy for testicular torsion may have subnormal sperm counts at long-term follow-up.[4,5] Retrograde ejaculation is a frequent complication of bilateral retroperitoneal lymph node dissection performed on males with testicular neoplasms,[6,7] and erectile dysfunction may occur after extensive pelvic dissections to remove a rhabdomyosarcoma of the prostate.[8,9]
Radiation affecting testicular function
Among men treated for childhood cancer, the potential for gonadal injury exists if radiation treatment fields include the pelvis, gonads, or total body. The germinal epithelium is more sensitive to radiation injury than are the androgen-producing Leydig cells. A decrease in sperm counts can be seen 3 to 6 weeks after such irradiation, and depending on the dosage, recovery may take 1 to 3 years. The germinal epithelium is damaged by much lower dosages (<1 Gy) of radiation than are Leydig cells (20–30 Gy). Irreversible germ cell failure may occur with fractionated radiation doses of greater than 2 Gy to 4 Gy.[10] Administration of higher radiation doses, such as 24 Gy, which was used for the treatment of testicular relapse of acute lymphoblastic leukemia (ALL), results in both germ cell failure and Leydig cell dysfunction.[11]
Radiation injury to Leydig cells is related to the dose delivered and age at treatment. Testosterone production may be normal in prepubertal boys treated with less than 12 Gy fractionated testicular irradiation, but elevated plasma concentrations of luteinizing hormone observed in this group suggest subclinical injury. Gonadal failure typically results when prepubertal boys are treated with more than 20 Gy of radiation to the testes; androgen therapy is required for masculinization. Leydig cell function is usually preserved in sexually mature male patients if radiation doses do not exceed 30 Gy. Although available data suggest that Leydig cells are more vulnerable when exposed to radiation before puberty, confounding factors, such as the age at testing and the effects of both orchiectomy and chemotherapy, limit the reliability of this observation.[12]
Chemotherapy affecting testicular function
Cumulative alkylating agent (e.g., cyclophosphamide, mechlorethamine, dacarbazine) dose is an important factor in estimating the risk of testicular germ cell injury, but limited data are available that correlate results of semen analyses in clinically well-characterized cohorts.[13] In general, Leydig cell function is preserved, but germ cell failure is common in men treated with high cumulative doses of cyclophosphamide (7,500 mg/m2 or more) and more than 3 months of combination alkylating agent therapy. Most studies suggest that prepubertal males are not at lower risk for chemotherapy-induced testicular damage than are postpubertal patients.[14-17]
Studies of testicular germ cell injury, as evidenced by oligospermia or azoospermia, after alkylating agent administration with or without radiation therapy, have reported the following:
Cyclophosphamide:
Male survivors of non-Hodgkin lymphoma who received a cumulative cyclophosphamide dose of greater than 9.5 g/m2 and underwent pelvic radiation therapy were at increased risk for failure to recover spermatogenesis.[18]
In survivors of Ewing sarcoma and soft tissue sarcoma, treatment with a cumulative cyclophosphamide dose of greater than 7.5 g/m2 was correlated with persistent oligospermia or azoospermia.[19]
Cyclophosphamide doses exceeding 7.5 g/m2 and ifosfamide doses exceeding 60 g/m2 produced oligospermia or azoospermia in most exposed individuals.[20-22]
A small cohort study reported normal semen quality in adult long-term survivors of childhood ALL treated with 0 to 10 g/m2 of cyclophosphamide and cranial irradiation, whereas no spermatozoa were detected in semen samples from survivors treated with more than 20 g/m2 of cyclophosphamide.[23]
Treatment with a cyclophosphamide equivalent dose of less than 4 g/m2 results in infrequent azoospermia or oligospermia, with 88.6% of 31 men treated being normospermic.[24]
Spermatogenesis was present in 67% of 15 men who received 200 mg/kg of cyclophosphamide before undergoing HSCT for aplastic anemia.[25]
Dacarbazine:
The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) produced oligospermia or azoospermia in adults frequently during the course of treatment. However, recovery of spermatogenesis occurred after treatment was completed, in contrast to the experience reported after treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP).[26]
Alkylating agent plus procarbazine:
Most studies suggest that combination chemotherapy with an alkylating agent and procarbazine causes severe damage to the testicular germinal epithelium that is irreversible at high cumulative doses.[14,27-30]
Azoospermia occurred less frequently in adults after treatment with two, rather than six, cycles of MOPP.[31]
Elevation of the basal follicle-stimulating hormone (FSH) level, which may reflect impaired spermatogenesis, was less frequent among patients receiving two courses of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) than among those who received two courses of OPPA in combination with two or more courses of cyclophosphamide, vincristine, procarbazine and prednisone (COPP).[32]
Low-dose cranial radiation plus alkylating agents:
In a cross-sectional study that included male adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without cranial radiation, St. Jude Children's Research Hospital investigators demonstrated that cranial radiation at doses lower than 26 Gy has no demonstrable independent effect on spermatogenesis.[33]
Testicular function after hematopoietic stem cell transplantation (HSCT)
The risk of gonadal dysfunction and infertility related to conditioning with total-body irradiation (TBI), high-dose alkylating agent chemotherapy, or both is substantial. Because transplantation is often undertaken for relapsed or refractory cancer, previous treatment with alkylating agent chemotherapy or hypothalamic-pituitary axis or gonadal radiation therapy may confer additional risks. Age at treatment also influences the risk of gonadal injury. Young boys and adolescents treated with high-dose cyclophosphamide (200 mg/kg) will generally maintain Leydig cell function and testosterone production, but germ cell failure is common. After TBI conditioning, most male patients retain their ability to produce testosterone but will experience germ cell failure.[34]
Limited data suggest that a greater proportion of boys will retain germinal function or recovery of spermatogenesis (based on pubertal progress and gonadotropin levels) after reduced-intensity conditioning with fludarabine/melphalan than will those treated with myeloablative conditioning with busulfan/cyclophosphamide.[35]
Recovery of gonadal function
Recovery of gonadal function after cytotoxic chemotherapy and radiation therapy is possible. Dutch investigators used inhibin B as a surrogate marker of gonadal function in a cross-sectional, retrospective study of 201 male survivors of childhood cancer, with a median follow-up of 15.7 years (range, 3–37 years) from diagnosis. The median inhibin B level among the cohort increased based on serial measurements performed over a median of 3.3 years (range, 0.7–11.3 years). The probability of recovery of the serum inhibin B level was significantly influenced by baseline inhibin B level, but not age at diagnosis, age at study evaluation, interval between discontinuation of treatment and study evaluation, gonadal irradiation, and alkylating agent dose score. These results suggest that recovery can occur but not if inhibin B is already at a critically low level.[36]
Inhibin B and FSH levels are correlated with sperm concentration and often used to estimate the presence of spermatogenesis; however, limitations in the specificity and positive predictive value of these tests have been reported.[37] Hence, male survivors should be advised that semen analysis is the most accurate assessment of adequacy of spermatogenesis.
Cancer treatments that may impair ovarian function/reserve include the following:
Surgery (oophorectomy).
Radiation therapy (exposing the hypothalamic-pituitary axis or ovaries).
Chemotherapy (alkylating agents, similar DNA interstrand cross-linking agents like procarbazine).
HSCT.
Surgery affecting ovarian function
Oophorectomy performed for the management of germ cell tumors may reduce ovarian reserve. Contemporary treatments utilize fertility-sparing surgical procedures combined with systemic chemotherapy to reduce this risk.[38]
Radiation affecting ovarian function
In women treated for childhood cancer, the potential for primary gonadal injury exists if treatment fields involve the lumbosacral spine, abdomen, pelvis, or total body. The frequency of ovarian failure after abdominal radiation therapy is related to both the age of the woman at the time of irradiation and the radiation therapy dose received by the ovaries. The ovaries of younger individuals are more resistant to radiation damage than are those of older women because of their greater complement of primordial follicles.
Whole-abdomen irradiation at doses of 20 Gy or greater is associated with the highest risk of ovarian dysfunction. Seventy-one percent of women in one series failed to enter puberty, and 26% had premature menopause after receiving whole-abdominal radiation therapy doses of 20 Gy to 30 Gy.[39] Other studies reported similar results in women treated with whole-abdomen irradiation [40] or craniospinal irradiation [41,42] during childhood.
Chemotherapy affecting ovarian function
Ovarian function may be impaired after treatment with combination chemotherapy that includes an alkylating agent and procarbazine. In general, girls maintain gonadal function at higher cumulative alkylating agent doses than do boys. Most female childhood cancer survivors who are treated with risk-adapted combination chemotherapy retain or recover ovarian function. However, the risk of acute ovarian failure and premature menopause is substantial if treatment includes combined-modality therapy with alkylating agent chemotherapy and abdominal or pelvic radiation therapy or dose-intensive alkylating agents for myeloablative conditioning before HSCT.[43-47]
Premature ovarian failure
Premature ovarian failure is well documented in childhood cancer survivors, especially in women treated with both an alkylating agent and abdominal radiation therapy.[43,47-49]
Studies have associated the following factors with an increased rate of premature ovarian failure (acute ovarian failure and premature menopause):
Age at the time of treatment and attained age.
Increasing doses of abdominal-pelvic radiation therapy.
Exposure to alkylating agents and/or procarbazine.
Oophorectomy.
The presence of apparently normal ovarian function at the completion of chemotherapy should not be interpreted as evidence that no ovarian injury has occurred.
Evidence (acute ovarian failure and premature menopause in childhood cancer survivors):
Of 3,390 eligible participants in the CCSS, 215 (6.3%) developed acute ovarian failure (defined as never having menses or ceased having menses within 5 years of diagnosis).[44]
Survivors with acute ovarian failure were older (aged 13–20 years vs. aged 0–12 years) at cancer diagnosis and more likely to have been diagnosed with Hodgkin lymphoma or to have received abdominal or pelvic radiation therapy than were survivors without acute ovarian failure.
Of survivors who developed acute ovarian failure, 75% had received abdominal-pelvic radiation therapy. Radiation doses to the ovary of at least 20 Gy were associated with the highest rate of acute ovarian failure, with over 70% of such patients developing acute ovarian failure.
In a multivariable logistic regression model, increasing doses of ovarian radiation, exposure to procarbazine at any age, and exposure to cyclophosphamide at ages 13 to 20 years were independent risk factors for acute ovarian failure.
The menopausal status of 2,930 survivors participating in the CCSS was compared with that of 1,399 siblings. Nonsurgical premature menopause was defined as sustained menses cessation occurring for more than 6 months beginning 5 years after the cancer diagnosis but before age 40 years that was not caused by pregnancy, surgery, or medications. In 110 survivors who developed nonsurgical premature menopause, the prevalence was 9.1% at age 40 years in a population with a median age of 34 years.[47]
In multivariable analyses, significant independent risk factors for the development of nonsurgical premature menopause were exposure to a dose of procarbazine greater than 4,000 mg/m2 (odds ratio [OR], 8.96; 95% confidence interval [CI], 5.02–16.00 [P < .0001]), any dose of radiation therapy to the ovaries (OR, 2.73 [95% CI, 1.33–5.61; P = .0062] for a dose of less than 500 cGy and OR, 8.02 [95% CI, 2.81–22.85; P < .0001] for a dose of greater than 500 cGy), and receipt of stem cell transplant (OR, 6.35; 95% CI, 1.19–33.93 [P = .0307]). A cyclophosphamide equivalent dose of 6,000 mg/m2 or higher that included procarbazine was significant in the univariate analysis, but did not achieve significance in the multivariable analysis.
For survivors who received more than 4,000 mg/m2 of procarbazine, the prevalence of nonsurgical premature menopause at age 40 years was 39.7%, compared with 4.2% among those who did not receive any procarbazine (P < .0001). Radiation exposure to the ovaries of greater than 500 cGy resulted in a prevalence of nonsurgical premature menopause at age 40 years of 24.1%, compared with a prevalence of 3.0% in those who did not receive radiation (P < .0001).
Cyclophosphamide exposure (at any dose), unilateral oophorectomy, smoking status, and body mass index (BMI) were not found to be significant for the risk of nonsurgical premature menopause.
Compared with survivors who did not develop nonsurgical premature menopause, those who developed nonsurgical premature menopause were less likely to ever be pregnant or to have a live birth between the ages of 31 and 40 years. There was no difference in the pregnancy and live birth rates before the age of 30 years for survivors who ultimately developed nonsurgical premature menopause and those who do not.
A French cohort study of 1,109 female survivors of childhood solid cancer identified the following risk factors for nonsurgical menopause:[49]
Exposure to and dose of alkylating agents, especially during adolescence.
Radiation dose to the ovaries.
Women treated with alkylating agents after the onset of puberty, either alone (relative risk [RR], 9.0; 95% CI, 2.7–28.0; P = .0003) or associated with even a low dose of radiation to the ovaries (RR, 29; 95% CI, 8–108; P < .0001), had the highest risk ratio for nonsurgical menopause.
The overall rate of nonsurgical menopause by age 40 years was only 2.1% and substantially lower than the CCSS and European Organization for Research and Treatment of Cancer cohort studies that include survivors of hematological malignancies.
Unilateral oophorectomy was associated with a 7-year-earlier age at menopause.
In Europe, survivors of Hodgkin lymphoma treated between the ages 15 years and 40 years and who were not receiving hormonal contraceptives were surveyed for the occurrence of premature ovarian failure.[48]
In 460 women, premature ovarian failure was mainly influenced by alkylating chemotherapy use with a linear dose relationship between alkylating chemotherapy and premature ovarian failure occurrence. Premature ovarian failure risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy before age 32 years and at age 32 years or older, cumulative premature ovarian failure risks were 3% and 9%, respectively.
If menstruation returned after treatment, cumulative premature ovarian failure risk was independent of age at treatment.
Among women who ultimately developed premature ovarian failure, 22% had one or more children after treatment, compared with 41% of women without premature ovarian failure who had one or more children after treatment. This report indicates that women with proven fertility after treatment can still face infertility problems at a later stage.
St. Jude Lifetime Cohort investigators evaluated the prevalence of and risk factors for premature ovarian insufficiency in 921 female childhood cancer survivor participants. Premature ovarian insufficiency was clinically assessed and defined by persistent amenorrhea combined with an FSH level of 30 IU/L or higher before age 40 years.[50]
The prevalence of premature ovarian insufficiency was 10.9% among women who were a median age of 31.7 years at study assessment and a median 24 years from cancer diagnosis.
Independent risk factors for premature ovarian insufficiency included ovarian radiation therapy at any dose and cyclophosphamide equivalent dose of 8,000 mg/m2 or higher.
Obesity (BMI of 30 kg/m2 or higher) at assessment was associated with a lower risk of premature ovarian insufficiency (HR, 0.36). Survivors with premature ovarian insufficiency had increased odds of low bone mineral density (OR, 5.07) and frailty (OR, 3.5) than did those without premature ovarian insufficiency.
Ovarian function after HSCT
The preservation of ovarian function among women treated with HSCT is related to age at treatment, receipt of pretransplant alkylating agent chemotherapy and abdominal-pelvic radiation therapy, and transplant conditioning regimen.[45,51]
Evidence (ovarian function among women treated with HSCT):
Girls and young women conditioned with TBI or busulfan-based regimens appear to be at equally high risk of declining ovarian function and premature menopause compared with patients conditioned with cyclophosphamide only.[45] All women who received high-dose (50 mg/kg/day x 4 days) cyclophosphamide before HSCT for aplastic anemia developed amenorrhea after transplantation.
In another series, 36 of 43 women with aplastic anemia conditioned with cyclophosphamide (200 mg/kg) had recovery of normal ovarian function 3 to 42 months after transplantation, including all of the 27 patients who were between ages 13 and 25 years at the time of HSCT.[46]
TBI is especially damaging when given in a single fraction.[45] Most postpubertal women who receive TBI before HSCT develop amenorrhea.
In one series, recovery of normal ovarian function occurred in only 9 of 144 patients and was highly correlated with age at time of radiation therapy in patients younger than 25 years.[46]
Among women with leukemia, cranial irradiation before transplantation further decreased the possibility of retaining ovarian function.[45]
Ovarian function may be better preserved (based on pubertal progress and gonadotropin levels) in females undergoing HSCT with reduced-intensity conditioning using fludarabine/melphalan than in those undergoing conditioning with myeloablative busulfan/cyclophosphamide.[35]
Infertility remains one of the most common life-altering treatment effects experienced by long-term childhood survivors. Pediatric cancer cohort studies have demonstrated the impact of cytotoxic therapy on reproductive outcomes. CCSS investigations have elucidated factors contributing to subfertility among childhood cancer survivors.[52,53]
Fertility was evaluated in 10,938 CCSS participants (5,640 males, 5,298 females) and 3,949 siblings.[52]
At a median follow-up of 8 years from cohort entry, 38% of survivors reported having or siring a pregnancy, resulting in at least one live birth in 83% of those survivors. Among siblings monitored for a median of 10 years, 62% reported having or siring a pregnancy, resulting in at least one live birth in 90% of those siblings. Multivariable analysis confirmed that survivors had significantly decreased likelihood of siring or having a pregnancy (hazard ratio [HR], 0.63 in males and 0.87 in females) or of having a live birth (HR, 0.63 in males and 0.82 in females) than did siblings.
Greater doses of alkylating drugs (HR, 0.82 per 5,000 mg/m2 increments) and cisplatin reduced the likelihood of siring pregnancy among male survivors, but only busulfan and higher doses (>411 mg/m2) of lomustine significantly reduced pregnancy among females. Reassuringly, the risk of reduced likelihood of pregnancy in women was observed only at the highest cyclophosphamide equivalent dose (HR, 0.85 for upper quartile [≥11,295 mg/m2] vs. no exposure).
HRs (95% CIs) for the likelihood of reporting first pregnancy by cyclophosphamide equivalent dose for male and female survivors are summarized in Table 14:
Table 14. Cyclophosphamide Equivalent Dose by Tertile and Sex
Cyclophosphamide Equivalent Dose by Tertile
HR (95% CI)
CI = confidence interval; HR = hazard ratio.
Lower (<4,897 mg/m2) 1.14 (1.00–1.30) .045 0.97 (0.86–1.08) .55
Middle (4,897–9,638 mg/m2) 0.79 (0.68–0.91) .0010 0.98 (0.87–1.11) .76
Upper (≥9,639 mg/m2) 0.55 (0.47–0.64) <.0001 0.90 (0.79–1.01) .07
Similar relationships were observed for live birth outcomes.
Fertility may be impaired by factors other than the absence of sperm and ova. Conception requires delivery of sperm to the uterine cervix, patency of the fallopian tubes for fertilization to occur, and appropriate conditions in the uterus for implantation.[6,7,54]
Retrograde ejaculation occurs with a significant frequency in men who undergo bilateral retroperitoneal lymph node dissection.[6,7]
Uterine structure may be affected by abdominal irradiation. A study demonstrated that uterine length was significantly shorter in ten women with ovarian failure who had been treated with whole-abdomen irradiation. Endometrial thickness did not increase in response to hormone replacement therapy in three women who underwent weekly ultrasound examination. No flow was detectable with Doppler ultrasound through either uterine artery of five women, and through one uterine artery in three additional women.[54]
In a study of menopausal status on reproductive outcomes in 2,930 survivors from the CCSS, investigators found that for those who ultimately developed nonsurgical premature menopause, rates of pregnancy and live birth were substantially reduced before nonsurgical premature menopause between the ages of 31 and 40 years. However, pregnancy and live birth rates did not differ for those aged 21 to 30 years on the basis of ultimate menopausal status. Treatment variables significant for developing nonsurgical premature menopause by multivariable analyses included exposure to procarbazine doses higher than 4,000 mg/m2, any ovarian irradiation, and stem cell transplant.[47] A cyclophosphamide equivalent dose of 6,000 mg/m2 or higher that included procarbazine was significant in the univariate analysis, but did not achieve significance in the multivariable analysis.[47]
For survivors who maintain fertility, numerous investigations have evaluated the prevalence of and risk factors for pregnancy complications in adults treated for cancer during childhood. Pregnancy complications including hypertension, fetal malposition, fetal loss/spontaneous abortion, preterm labor, and low birth weight have been observed in association with specific diagnostic and treatment groups.[55-59]
Evidence (pregnancy complications in adults treated for childhood cancer):
In a study of 4,029 pregnancies among 1,915 women followed in the CCSS, there were 63% live births, 1% stillbirths, 15% miscarriages, 17% abortions, and 3% unknown or in gestation.[55]
Risk of miscarriage was 3.6-fold higher in women treated with craniospinal irradiation and 1.7-fold higher in those treated with pelvic irradiation. Chemotherapy exposure alone did not increase risk of miscarriage.
Survivors were less likely to have live births, more likely to have medical abortions, and more likely to have low-birth-weight babies than were siblings.
Disruption of normal uterine function after radiation therapy or other treatment that results in reduced uterine volume and impaired uterine blood flow appears to be the underlying pathophysiology for many of these adverse obstetrical events.[60]
In the National Wilms Tumor Study, records were obtained for 1,021 pregnancies of more than 20 weeks duration. In this group, there were 955 single live births.[61]
Hypertension complicating pregnancy, early or threatened labor, malposition of the fetus, lower birth weight (<2,500 g), and premature delivery (<36 weeks) were more frequent among women who had received flank irradiation, in a dose-dependent manner.
Another CCSS study evaluated pregnancy outcomes of partners of male survivors.[56]
Among 4,106 sexually active males, 1,227 reported they sired 2,323 pregnancies, which resulted in 69% live births, 13% miscarriages, 13% abortions, and 5% unknown or in gestation at the time of analysis.
Compared with partners of male siblings, there was a decreased incidence of live births (RR, 0.77), but no significant differences of pregnancy outcome by treatment.
Results from a Danish study confirm the association of uterine irradiation with spontaneous abortion, but not other types of abortion. Thirty-four thousand pregnancies were evaluated in a population of 1,688 female survivors of childhood cancer in the Danish Cancer Registry. The pregnancy outcomes of survivors, 2,737 sisters, and 16,700 comparison women in the population were identified.[57]
No significant differences were seen between survivors and comparison women in the proportions of live births, stillbirths, or all types of abortions combined.
Survivors with a history of neuroendocrine or abdominal radiation therapy had an increased risk of spontaneous abortion.
Thus, the pregnancy outcomes of survivors were similar to those of comparison women with the exception of spontaneous abortion.
In a retrospective cohort analysis from the CCSS of 1,148 men and 1,657 women who had survived cancer, there were 4,946 pregnancies.[58]
Irradiation of the testes in men and pituitary gland in women and chemotherapy with alkylating drugs were not associated with an increased risk of stillbirth or neonatal death.
Uterine and ovarian irradiation significantly increased the risk of stillbirth and neonatal death at doses higher than 10 Gy.
For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1 Gy to 2.49 Gy significantly increased the risk of stillbirth or neonatal death.
Most pregnancies reported by HSCT survivors and their partners result in live births.[59]
In female HSCT survivors who were exposed to TBI, there appears to be an increased risk of preterm delivery of low-birth-weight infants.
Female HSCT survivors are at higher risk of needing cesarean delivery than are the normal population (42% vs. 16%).
Preservation of fertility and successful pregnancies may occur after HSCT, although the conditioning regimens that include TBI, cyclophosphamide, and busulfan are highly gonadotoxic. One study evaluated pregnancy outcomes in a group of females treated with HSCT.[62]
Among 708 women who were postpubertal at the time of transplant, 116 regained normal ovarian function and 32 became pregnant.
Among 82 women who were prepubertal at the time of transplant, 23 had normal ovarian function and nine became pregnant.
Of the 72 pregnancies in these 41 women, 16 occurred in those treated with TBI and 50% resulted in early termination.
Among the 56 pregnancies in women treated with cyclophosphamide without either TBI or busulfan, 21% resulted in early termination.
There were no pregnancies among the 73 women treated with busulfan and cyclophosphamide, and only one retained ovarian function.
A German study demonstrated that the rate of childbearing for female survivors of Hodgkin lymphoma was similar to that of the general population, although the rate of childbearing was lower for survivors who received pelvic radiation therapy.[63]
British CCSS investigators evaluated pregnancy and labor complications among female survivors of childhood cancer treated with abdominal radiation by linking British CCSS cohort data to a national hospital registry.[64]
Survivors treated with abdominal radiation had a significantly higher risk (RR, 2.1) of pregnancy complications than did survivors who did not receive abdominal radiation.
Risks were elevated for hypertension complicating pregnancy among Wilms tumor survivors (RR, 3.29) treated with abdominal radiation and for gestational diabetes mellitus (RR, 3.35) and anemia (RR, 2.10) among all survivors treated with abdominal radiation.
A systematic review compared the data from published pregnancy and child health outcomes for pediatric and young adult leukemia and lymphoma survivors with the data from controls who did not have a history of cancer.[65]
No higher risks of spontaneous abortions, maternal diabetes and anemia, stillbirth, birth defects, or childhood cancer in offspring were observed in survivors compared with controls.
Live birth rates were lower, while risks of preterm birth and low birth weight were modestly higher in survivors than in controls.
Progress in reproductive endocrinology has resulted in the availability of several options for preserving or permitting fertility in patients about to receive potentially toxic chemotherapy or radiation therapy.[66] For males, cryopreservation of spermatozoa before treatment is an effective method to circumvent the sterilizing effect of therapy. Although pretreatment semen quality in patients with cancer has been shown to be less than that noted in healthy donors, the percentage decline in semen quality and the effect of cryodamage to spermatozoa from patients with cancer is similar to that of normal donors.[67,68] For those unable to bank sperm, newer technologies such as testicular sperm extraction may be an option. Further micromanipulative technologic advances such as intracytoplasmic sperm injection and similar techniques may be able to render sperm extracted surgically, or even poor-quality cryopreserved spermatozoa from cancer patients, capable of successful fertilization.[69]
For females, the most successful assisted-reproductive techniques depend on harvesting and banking the postpubertal patient’s oocytes and cryopreserving unfertilized oocytes or embryos before gonadotoxic therapy.[70] Options for prepubertal patients are limited to investigational ovarian tissue cryopreservation for later autotransplantation, which may be offered to girls with nonovarian, nonhematologic cancers.[71]
Offspring of childhood cancer survivors
For childhood cancer survivors who have offspring, there is concern about congenital anomalies, genetic disease, or risk of cancer in the offspring. Children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parents' exposure to mutagenic cancer treatments.
Evidence (children of cancer survivors not at significantly increased risk of congenital anomalies):
A retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female participants of the CCSS observed the following:[72]
No significant associations between gonadal radiation therapy or cumulative exposure to alkylating agents and congenital anomalies in offspring.
A study compared 2,198 offspring of adult survivors treated for childhood cancer between 1945 and 1975 with 4,544 offspring of sibling controls.[73]
There were no differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations.
There was similarly no effect of type of childhood cancer treatment on the occurrence of genetic disease in the offspring.
A population-based study of 2,630 live-born offspring of childhood cancer survivors versus 5,504 live-born offspring of the survivors' siblings found no differences in proportion of abnormal karyotypes or incidence of Down syndrome or Turner syndrome between survivor and sibling offspring.[74]
In the same population-based cohort, survivors treated with abdominal radiation therapy and/or alkylating agents did not have an increased risk of offspring with genetic disease, compared with survivors not exposed to these agents.
In a study of 5,847 offspring of survivors of childhood cancers treated in five Scandinavian countries, in the absence of a hereditary cancer syndrome (such as hereditary retinoblastoma), there was no increased risk of cancer.[75] Data from the five-center study also indicated no excess risk of single-gene disorders, congenital malformations, or chromosomal syndromes among the offspring of former patients compared with the offspring of siblings.[76]
In a study that evaluated pregnancy outcomes in 19,412 allogeneic and 17,950 autologous transplant patients, European Group for Blood and Marrow Transplantation investigators did not observe an increased risk of birth defects, developmental delay, or cancer among offspring of male and female HSCT recipients.[59]
A nationwide Finnish population-based registry study compared the risk of congenital anomalies in the offspring of 6,862 long-term survivors of childhood, adolescent, and young adult cancer treated between 1953 and 2004 with the risk of congenital anomalies in the offspring of 35,690 siblings.[77]
The study did not find a significant excess risk of congenital anomalies among childhood and adolescent survivors (prevalence ratio [PR], 1.17; 95% CI, 0.92–1.49) and young adult survivors (PR, 1.17; 95% CI, 0.83–1.23) compared with siblings.
There was an association between parent cancer and congenital anomalies in the offspring of survivors who were diagnosed in the earlier decades (1955–1964: PR, 2.77; 95% CI, 1.26–6.11; and 1965–1974: PR, 1.55; 95% CI, 0.94–2.56).
Table 15 summarizes reproductive late effects and the related health screenings.
Table 15. Reproductive Late Effectsa
Reproductive Late Effects
AMH = anti-mullerian hormone; FSH = follicle-stimulating hormone; LH = luteinizing hormone.
Alkylating agents; gonadal irradiation Testicular hormonal dysfunction: Testosterone deficiency/insufficiency; delayed/arrested puberty Tanner stage
Morning testosterone
Impaired spermatogenesis: Reduced fertility; oligospermia; azoospermia; infertility Semen analysis
Inhibin B
Ovarian hormone deficiencies: Delayed/arrested puberty; premature ovarian insufficiency/premature menopause. Reduced ovarian follicular pool: Diminished ovarian reserve; infertility. Tanner stage
Menstrual cycle history
Antral follicle count
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for reproductive late effects information including risk factors, evaluation, and health counseling.
van Dorp W, Mulder RL, Kremer LC, et al.: Recommendations for Premature Ovarian Insufficiency Surveillance for Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Report From the International Late Effects of Childhood Cancer Guideline Harmonization Group in Collaboration With the PanCareSurFup Consortium. J Clin Oncol 34 (28): 3440-50, 2016. [PUBMED Abstract]
Skinner R, Mulder RL, Kremer LC, et al.: Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Lancet Oncol 18 (2): e75-e90, 2017. [PUBMED Abstract]
Green DM, Nolan VG, Goodman PJ, et al.: The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 61 (1): 53-67, 2014. [PUBMED Abstract]
Arap MA, Vicentini FC, Cocuzza M, et al.: Late hormonal levels, semen parameters, and presence of antisperm antibodies in patients treated for testicular torsion. J Androl 28 (4): 528-32, 2007 Jul-Aug. [PUBMED Abstract]
Tryfonas G, Violaki A, Tsikopoulos G, et al.: Late postoperative results in males treated for testicular torsion during childhood. J Pediatr Surg 29 (4): 553-6, 1994. [PUBMED Abstract]
Narayan P, Lange PH, Fraley EE: Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J Urol 127 (4): 685-8, 1982. [PUBMED Abstract]
Nijman JM, Jager S, Boer PW, et al.: The treatment of ejaculation disorders after retroperitoneal lymph node dissection. Cancer 50 (12): 2967-71, 1982. [PUBMED Abstract]
Schlegel PN, Walsh PC: Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol 138 (6): 1402-6, 1987. [PUBMED Abstract]
Frees S, Rubenwolf P, Ziesel C, et al.: Erectile function after treatment for rhabdomyosarcoma of prostate and bladder. J Pediatr Urol 12 (6): 404.e1-404.e6, 2016. [PUBMED Abstract]
Hahn EW, Feingold SM, Simpson L, et al.: Recovery from aspermia induced by low-dose radiation in seminoma patients. Cancer 50 (2): 337-40, 1982. [PUBMED Abstract]
Blatt J, Sherins RJ, Niebrugge D, et al.: Leydig cell function in boys following treatment for testicular relapse of acute lymphoblastic leukemia. J Clin Oncol 3 (9): 1227-31, 1985. [PUBMED Abstract]
Izard MA: Leydig cell function and radiation: a review of the literature. Radiother Oncol 34 (1): 1-8, 1995. [PUBMED Abstract]
Romerius P, Ståhl O, Moëll C, et al.: High risk of azoospermia in men treated for childhood cancer. Int J Androl 34 (1): 69-76, 2011. [PUBMED Abstract]
Shafford EA, Kingston JE, Malpas JS, et al.: Testicular function following the treatment of Hodgkin's disease in childhood. Br J Cancer 68 (6): 1199-204, 1993. [PUBMED Abstract]
Whitehead E, Shalet SM, Jones PH, et al.: Gonadal function after combination chemotherapy for Hodgkin's disease in childhood. Arch Dis Child 57 (4): 287-91, 1982. [PUBMED Abstract]
Aubier F, Flamant F, Brauner R, et al.: Male gonadal function after chemotherapy for solid tumors in childhood. J Clin Oncol 7 (3): 304-9, 1989. [PUBMED Abstract]
Jaffe N, Sullivan MP, Ried H, et al.: Male reproductive function in long-term survivors of childhood cancer. Med Pediatr Oncol 16 (4): 241-7, 1988. [PUBMED Abstract]
Pryzant RM, Meistrich ML, Wilson G, et al.: Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin's lymphomas. J Clin Oncol 11 (2): 239-47, 1993. [PUBMED Abstract]
Meistrich ML, Wilson G, Brown BW, et al.: Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer 70 (11): 2703-12, 1992. [PUBMED Abstract]
Kenney LB, Laufer MR, Grant FD, et al.: High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 91 (3): 613-21, 2001. [PUBMED Abstract]
Garolla A, Pizzato C, Ferlin A, et al.: Progress in the development of childhood cancer therapy. Reprod Toxicol 22 (2): 126-32, 2006. [PUBMED Abstract]
Williams D, Crofton PM, Levitt G: Does ifosfamide affect gonadal function? Pediatr Blood Cancer 50 (2): 347-51, 2008. [PUBMED Abstract]
Jahnukainen K, Heikkinen R, Henriksson M, et al.: Semen quality and fertility in adult long-term survivors of childhood acute lymphoblastic leukemia. Fertil Steril 96 (4): 837-42, 2011. [PUBMED Abstract]
Green DM, Liu W, Kutteh WH, et al.: Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Lancet Oncol 15 (11): 1215-23, 2014. [PUBMED Abstract]
Sanders JE, Buckner CD, Leonard JM, et al.: Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation. Transplantation 36 (3): 252-5, 1983. [PUBMED Abstract]
Viviani S, Santoro A, Ragni G, et al.: Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD. Eur J Cancer Clin Oncol 21 (5): 601-5, 1985. [PUBMED Abstract]
Mackie EJ, Radford M, Shalet SM: Gonadal function following chemotherapy for childhood Hodgkin's disease. Med Pediatr Oncol 27 (2): 74-8, 1996. [PUBMED Abstract]
Sherins RJ, Olweny CL, Ziegler JL: Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin's disease. N Engl J Med 299 (1): 12-6, 1978. [PUBMED Abstract]
Dhabhar BN, Malhotra H, Joseph R, et al.: Gonadal function in prepubertal boys following treatment for Hodgkin's disease. Am J Pediatr Hematol Oncol 15 (3): 306-10, 1993. [PUBMED Abstract]
Heikens J, Behrendt H, Adriaanse R, et al.: Irreversible gonadal damage in male survivors of pediatric Hodgkin's disease. Cancer 78 (9): 2020-4, 1996. [PUBMED Abstract]
da Cunha MF, Meistrich ML, Fuller LM, et al.: Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2 (6): 571-7, 1984. [PUBMED Abstract]
Brämswig JH, Heimes U, Heiermann E, et al.: The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence. Cancer 65 (6): 1298-302, 1990. [PUBMED Abstract]
Green DM, Zhu L, Wang M, et al.: Effect of cranial irradiation on sperm concentration of adult survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude Lifetime Cohort Study†. Hum Reprod 32 (6): 1192-1201, 2017. [PUBMED Abstract]
Ishiguro H, Yasuda Y, Tomita Y, et al.: Gonadal shielding to irradiation is effective in protecting testicular growth and function in long-term survivors of bone marrow transplantation during childhood or adolescence. Bone Marrow Transplant 39 (8): 483-90, 2007. [PUBMED Abstract]
Panasiuk A, Nussey S, Veys P, et al.: Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan. Br J Haematol 170 (5): 719-26, 2015. [PUBMED Abstract]
van Dorp W, van der Geest IM, Laven JS, et al.: Gonadal function recovery in very long-term male survivors of childhood cancer. Eur J Cancer 49 (6): 1280-6, 2013. [PUBMED Abstract]
Green DM, Zhu L, Zhang N, et al.: Lack of specificity of plasma concentrations of inhibin B and follicle-stimulating hormone for identification of azoospermic survivors of childhood cancer: a report from the St Jude lifetime cohort study. J Clin Oncol 31 (10): 1324-8, 2013. [PUBMED Abstract]
Tangir J, Zelterman D, Ma W, et al.: Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary. Obstet Gynecol 101 (2): 251-7, 2003. [PUBMED Abstract]
Wallace WH, Shalet SM, Crowne EC, et al.: Ovarian failure following abdominal irradiation in childhood: natural history and prognosis. Clin Oncol (R Coll Radiol) 1 (2): 75-9, 1989. [PUBMED Abstract]
Scott JE: Pubertal development in children treated for nephroblastoma. J Pediatr Surg 16 (2): 122-5, 1981. [PUBMED Abstract]
Hamre MR, Robison LL, Nesbit ME, et al.: Effects of radiation on ovarian function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group. J Clin Oncol 5 (11): 1759-65, 1987. [PUBMED Abstract]
Wallace WH, Shalet SM, Tetlow LJ, et al.: Ovarian function following the treatment of childhood acute lymphoblastic leukaemia. Med Pediatr Oncol 21 (5): 333-9, 1993. [PUBMED Abstract]
Sklar CA, Mertens AC, Mitby P, et al.: Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 98 (13): 890-6, 2006. [PUBMED Abstract]
Chemaitilly W, Mertens AC, Mitby P, et al.: Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 91 (5): 1723-8, 2006. [PUBMED Abstract]
Vatanen A, Wilhelmsson M, Borgström B, et al.: Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence. Eur J Endocrinol 170 (2): 211-8, 2014. [PUBMED Abstract]
Sanders JE, Buckner CD, Amos D, et al.: Ovarian function following marrow transplantation for aplastic anemia or leukemia. J Clin Oncol 6 (5): 813-8, 1988. [PUBMED Abstract]
Levine JM, Whitton JA, Ginsberg JP, et al.: Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 124 (5): 1044-1052, 2018. [PUBMED Abstract]
van der Kaaij MA, Heutte N, Meijnders P, et al.: Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study. J Clin Oncol 30 (3): 291-9, 2012. [PUBMED Abstract]
Thomas-Teinturier C, El Fayech C, Oberlin O, et al.: Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature. Hum Reprod 28 (2): 488-95, 2013. [PUBMED Abstract]
Chemaitilly W, Li Z, Krasin MJ, et al.: Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 102 (7): 2242-2250, 2017. [PUBMED Abstract]
Bresters D, Emons JA, Nuri N, et al.: Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood. Pediatr Blood Cancer 61 (11): 2048-53, 2014. [PUBMED Abstract]
Chow EJ, Stratton KL, Leisenring WM, et al.: Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 17 (5): 567-76, 2016. [PUBMED Abstract]
Armuand G, Skoog-Svanberg A, Bladh M, et al.: Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study. J Clin Oncol 35 (14): 1577-1583, 2017. [PUBMED Abstract]
Critchley HO, Wallace WH, Shalet SM, et al.: Abdominal irradiation in childhood; the potential for pregnancy. Br J Obstet Gynaecol 99 (5): 392-4, 1992. [PUBMED Abstract]
Green DM, Kawashima T, Stovall M, et al.: Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 27 (16): 2677-85, 2009. [PUBMED Abstract]
Green DM, Kawashima T, Stovall M, et al.: Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 28 (2): 332-9, 2010. [PUBMED Abstract]
Winther JF, Boice JD, Svendsen AL, et al.: Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol 26 (26): 4340-6, 2008. [PUBMED Abstract]
Signorello LB, Mulvihill JJ, Green DM, et al.: Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet 376 (9741): 624-30, 2010. [PUBMED Abstract]
Salooja N, Szydlo RM, Socie G, et al.: Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey. Lancet 358 (9278): 271-6, 2001. [PUBMED Abstract]
Beneventi F, Locatelli E, Giorgiani G, et al.: Adolescent and adult uterine volume and uterine artery Doppler blood flow among subjects treated with bone marrow transplantation or chemotherapy in pediatric age: a case-control study. Fertil Steril 103 (2): 455-61, 2015. [PUBMED Abstract]
Green DM, Lange JM, Peabody EM, et al.: Pregnancy outcome after treatment for Wilms tumor: a report from the national Wilms tumor long-term follow-up study. J Clin Oncol 28 (17): 2824-30, 2010. [PUBMED Abstract]
Sanders JE, Hawley J, Levy W, et al.: Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood 87 (7): 3045-52, 1996. [PUBMED Abstract]
Brämswig JH, Riepenhausen M, Schellong G: Parenthood in adult female survivors treated for Hodgkin's lymphoma during childhood and adolescence: a prospective, longitudinal study. Lancet Oncol 16 (6): 667-75, 2015. [PUBMED Abstract]
Reulen RC, Bright CJ, Winter DL, et al.: Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study. J Natl Cancer Inst 109 (11): , 2017. [PUBMED Abstract]
Shliakhtsitsava K, Romero SAD, Dewald SR, et al.: Pregnancy and child health outcomes in pediatric and young adult leukemia and lymphoma survivors: a systematic review. Leuk Lymphoma 59 (2): 381-397, 2018. [PUBMED Abstract]
Loren AW, Mangu PB, Beck LN, et al.: Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31 (19): 2500-10, 2013. [PUBMED Abstract]
Agarwa A: Semen banking in patients with cancer: 20-year experience. Int J Androl 23 (Suppl 2): 16-9, 2000. [PUBMED Abstract]
Müller J, Sønksen J, Sommer P, et al.: Cryopreservation of semen from pubertal boys with cancer. Med Pediatr Oncol 34 (3): 191-4, 2000. [PUBMED Abstract]
Hsiao W, Stahl PJ, Osterberg EC, et al.: Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: the Weill Cornell experience. J Clin Oncol 29 (12): 1607-11, 2011. [PUBMED Abstract]
Domingo J, Ayllón Y, Domingo S, et al.: New approaches to female fertility preservation. Clin Transl Oncol 11 (3): 154-9, 2009. [PUBMED Abstract]
Oktay K, Karlikaya G: Ovarian function after transplantation of frozen, banked autologous ovarian tissue. N Engl J Med 342 (25): 1919, 2000. [PUBMED Abstract]
Signorello LB, Mulvihill JJ, Green DM, et al.: Congenital anomalies in the children of cancer survivors: a report from the childhood cancer survivor study. J Clin Oncol 30 (3): 239-45, 2012. [PUBMED Abstract]
Winther JF, Boice JD, Mulvihill JJ, et al.: Chromosomal abnormalities among offspring of childhood-cancer survivors in Denmark: a population-based study. Am J Hum Genet 74 (6): 1282-5, 2004. [PUBMED Abstract]
Winther JF, Olsen JH, Wu H, et al.: Genetic disease in the children of Danish survivors of childhood and adolescent cancer. J Clin Oncol 30 (1): 27-33, 2012. [PUBMED Abstract]
Sankila R, Olsen JH, Anderson H, et al.: Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology. N Engl J Med 338 (19): 1339-44, 1998. [PUBMED Abstract]
Byrne J, Rasmussen SA, Steinhorn SC, et al.: Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am J Hum Genet 62 (1): 45-52, 1998. [PUBMED Abstract]
Seppänen VI, Artama MS, Malila NK, et al.: Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors. Int J Cancer 139 (8): 1721-30, 2016. [PUBMED Abstract]
Respiratory function may be compromised in long-term survivors of childhood cancer who were treated with the following therapies:
Specific chemotherapeutic agents.
Thoracic radiation therapy.
Pulmonary/chest wall surgery.
The effects of early lung injury from cancer treatment may be exacerbated by the decline in lung function associated with normal aging, other comorbid chronic health conditions, or smoking. The quality of current evidence regarding this outcome is limited by retrospective data collection, small sample size, cohort selection and participation bias, description of outcomes following antiquated treatment approaches, and variability in time since treatment and method of ascertainment. No large cohort studies have been performed that include clinical evaluations coupled with functional and quality-of-life assessments.
The true prevalence or incidence of pulmonary dysfunction in childhood cancer survivors is not clear. For children treated with HSCT, significant clinical disease has been observed.
Evidence (selected cohort studies describing long-term pulmonary function outcomes):
The incidence of self-reported pulmonary dysfunction among adults treated for central nervous system malignancies with craniospinal irradiation (per 1,000 person-years) was 9.1 (95% confidence interval, 7.8–10.6) for emphysema/obliterative bronchiolitis and more than 3.0 for asthma, chronic cough, and the need for extra oxygen. High rates of late onset pulmonary dysfunction occurring more than 5 years after diagnosis were also observed.[1]
Dutch investigators reported outcomes of 193 childhood cancer survivors evaluated by pulmonary function testing at a median follow-up of 18 years after diagnosis.[2]
Pulmonary function impairment (Common Terminology Criteria for Adverse Events grade 2 or higher) was identified in 85 patients (44.0%) and included obstructive deficits (2.1%), restrictive deficits (17.6%), and decreased carbon monoxide diffusion capacity (39.9%).
Multivariate logistic regression models showed that treatment with radiation therapy, radiation therapy combined with bleomycin, and radiation therapy combined with surgery were associated with the highest risk of pulmonary function impairment when compared with bleomycin treatment only.
In a longitudinal study evaluating the magnitude and trajectory of pulmonary dysfunction among 121 childhood cancer survivors (median time from diagnosis to last evaluation, 17.1 years) treated with potentially pulmonary-toxic therapy (e.g., bleomycin, busulfan, pulmonary radiation therapy), survivors were significantly more likely to have restrictive and diffusion defects than were healthy controls.[3]
Age younger than 16 years at diagnosis and exposure to more than 20 Gy of chest radiation were associated with increased odds of restrictive defects, whereas female sex and chest radiation dose were associated with diffusion abnormalities.
Decline in pulmonary function over time was largely related to changes in diffusion capacity. The odds of decline in diffusion function over time showed a fourfold increase among females and 24-fold increase among survivors treated with more than 20 Gy of chest radiation. Compared with survivors with normal diffusion, those with diffusion defects were significantly more likely to be symptomatic and have poorer health-related quality-of-life scores, with decreases in the domains of physical functioning, role limitation as a result of physical health, and low energy/increased fatigue.
Childhood Cancer Survivor Study investigators compared self-reported pulmonary outcomes and their impact on daily activities among 5-year cancer survivors (median, 25 years from diagnosis) and a sibling cohort.[4]
Survivors were more likely to report chronic cough, the need for oxygen, lung fibrosis, and recurrent pneumonia than were siblings despite lower rates of smoking.
By age 45 years, the cumulative incidence of any pulmonary condition was 29.6% for survivors. Survivors with chronic pulmonary conditions (e.g., chronic cough) were more likely to report activity limitations than were those without these conditions.
Pulmonary complications contributed to an almost sixfold excess risk of death among survivors and demonstrated significant associations with exposure to platinum and lung radiation.
Respiratory complications after radiation therapy
Radiation therapy that exposes the lung parenchyma can result in pulmonary dysfunction related to reduced lung volume, impaired dynamic compliance, and deformity of both the lung and chest wall. The potential for chronic pulmonary sequelae is related to the radiation dose administered, the volume of lung irradiated, and the fractional radiation therapy doses.[5] Combined-modality therapy including radiation therapy and pulmonary toxic chemotherapy or thoracic/chest wall surgery increases the risk of pulmonary function impairment.[2,6]
Chronic pulmonary complications reported after treatment for pediatric malignancies include restrictive or obstructive chronic pulmonary disease, pulmonary fibrosis, and spontaneous pneumothorax.[7] These sequelae are uncommon after contemporary therapy, which most often results in subclinical injury that is detected only by imaging or formal pulmonary function testing.
Evidence (selected cohort studies describing pulmonary outcomes):
A study of 48 survivors of pediatric malignant solid tumors followed for a median of 9.7 years after median whole-lung radiation doses of 12 Gy (range, 10.5–18 Gy) reported the following:[8]
Only nine patients (18.8%) reported respiratory symptoms. However, abnormalities in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity, and diffusion capacity were common (58%–73%).
Focal-boost radiation therapy was significantly associated with additional abnormalities.
Reducing the size of the daily radiation fractions (e.g., from 1.8 Gy per day to 1.5 Gy per day) decreases this risk.[9,10]
For survivors of pediatric Hodgkin lymphoma, the prevalence of pulmonary symptoms using contemporary involved-field techniques is reported to be low. However, many exhibit substantial subclinical dysfunction.[11]
Changes in lung function have been reported in children treated with whole-lung radiation therapy for metastatic Wilms tumor.[9,10]
A dose of 12 Gy to 14 Gy reduced total lung capacity and vital capacity to about 70% of predicted values, and even lower if the patient had undergone thoracotomy.
Administration of bleomycin alone can produce pulmonary toxicity and, when combined with radiation therapy, can heighten radiation reactions. Chemotherapeutic agents such as doxorubicin, dactinomycin, and busulfan are radiomimetic agents and can reactivate underlying radiation damage.[9,10,12]
Respiratory complications after chemotherapy
Chemotherapy agents with potential pulmonary toxic effects commonly used in the treatment of pediatric malignancies include bleomycin, busulfan, and the nitrosoureas (carmustine and lomustine). These agents induce lung damage on their own or potentiate the damaging effects of radiation to the lung. Combined-modality therapy including pulmonary toxic chemotherapy and thoracic radiation therapy or thoracic/chest wall surgery increases the risk of pulmonary function impairment.[2]
Evidence (outcomes among cohorts treated with pulmonary toxic chemotherapy):
The development of bleomycin-associated pulmonary fibrosis with permanent restrictive disease is dose dependent, usually occurring at doses greater than 200 U/m2 to 400 U/m2, higher than those used in treatment protocols for pediatric malignancies.[12-14]
More current pediatric regimens for Hodgkin lymphoma using radiation therapy and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) have shown a significant incidence of asymptomatic pulmonary dysfunction after treatment, which appears to improve with time.[15-17] However, grades 3 and 4 pulmonary toxicity was reported in 9% of children receiving 12 cycles of ABVD followed by 21 Gy of extended-field radiation.[14]
ABVD-related pulmonary toxic effects may result from fibrosis induced by bleomycin or radiation recall pneumonitis related to administration of doxorubicin.
Pulmonary veno-occlusive disease has been observed rarely and has been attributed to bleomycin chemotherapy.[18]
Respiratory complications associated with HSCT
Patients undergoing HSCT are at increased risk of pulmonary toxic effects related to the following:[19-21]
Preexisting pulmonary dysfunction (e.g., asthma, pretransplant therapy).
Conditioning regimens, including cyclophosphamide, busulfan, or carmustine.
Total-body irradiation.
Graft-versus-host disease (GVHD).
Although most survivors of transplant are not clinically compromised, restrictive lung disease may occur and has been reported to increase in prevalence with increasing time from HSCT, based on limited data from longitudinally followed cohorts.[22,23] Obstructive disease is less common, as is late onset pulmonary syndrome, which includes the spectrum of restrictive and obstructive disease. Bronchiolitis obliterans with or without organizing pneumonia, diffuse alveolar damage, and interstitial pneumonia may occur as a component of this syndrome, generally between 6 and 12 months posttransplant. Cough, dyspnea, or wheezing may occur with either normal chest x-ray or diffuse/patchy infiltrates; however, most patients are symptom free.[20,24,25]
Other factors associated with respiratory late effects
Additional factors contributing to chronic pulmonary toxic effects include superimposed infection, underlying pneumonopathy (e.g., asthma), chest wall abnormalities, respiratory toxic effects, chronic GVHD, and the effects of chronic pulmonary involvement by tumor or reaction to tumor.[6] Lung lobectomy during childhood appears to have no significant impact on long-term pulmonary function,[26] but the long-term effect of lung surgery for children with cancer is not well defined.
Pulmonary complications may also be exacerbated by smoking cigarettes or other substances. While smoking rates in survivors of childhood cancer tend to be lower than the general population, it is still important to prevent initiation of smoking and promote cessation in this distinct population.[27]
Evidence (pulmonary dysfunction in former or current smokers):
Pulmonary function evaluations of 433 adult childhood cancer survivors treated with pulmonary toxic modalities demonstrated significantly higher risk of pulmonary dysfunction in smokers than in nonsmokers.[28]
FEV1/FVC median values among current and former smokers were lower than those who had never smoked.
Median FEV1/FVC values were lower among those who smoked less than 6 pack-years and those who smoked 6 pack-years or more compared with those who had never smoked, suggesting that survivors who are former or current smokers have an increased risk of future obstructive and restrictive lung disease.
Table 16 summarizes respiratory late effects and the related health screenings.
Table 16. Respiratory Late Effectsa
Respiratory Effects
DLCO = diffusing capacity of the lung for carbon monoxide; GVHD = graft-versus-host disease.
Busulfan; carmustine (BCNU)/lomustine (CCNU); bleomycin; radiation impacting lungs; surgery impacting pulmonary function (lobectomy, metastasectomy, wedge resection) Subclinical pulmonary dysfunction; interstitial pneumonitis; pulmonary fibrosis; restrictive lung disease; obstructive lung disease History: cough, shortness of breath, dyspnea on exertion, wheezing
Pulmonary exam
Pulmonary function tests (including DLCO and spirometry)
Counsel regarding tobacco avoidance/smoking cessation
In patients with abnormal pulmonary function tests and/or chest x-ray, consider repeat evaluation before general anesthesia
Pulmonary consultation for patients with symptomatic pulmonary dysfunction
Influenza and pneumococcal vaccinations
Hematopoietic cell transplantation with any history of chronic GVHD Pulmonary toxicity (bronchiolitis obliterans, chronic bronchitis, bronchiectasis) History: cough, shortness of breath, dyspnea on exertion, wheezing
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for respiratory late effects information including risk factors, evaluation, and health counseling.[29]
Huang TT, Chen Y, Dietz AC, et al.: Pulmonary outcomes in survivors of childhood central nervous system malignancies: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 61 (2): 319-25, 2014. [PUBMED Abstract]
Mulder RL, Thönissen NM, van der Pal HJ, et al.: Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax 66 (12): 1065-71, 2011. [PUBMED Abstract]
Armenian SH, Landier W, Francisco L, et al.: Long-term pulmonary function in survivors of childhood cancer. J Clin Oncol 33 (14): 1592-600, 2015. [PUBMED Abstract]
Dietz AC, Chen Y, Yasui Y, et al.: Risk and impact of pulmonary complications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 122 (23): 3687-3696, 2016. [PUBMED Abstract]
Huang TT, Hudson MM, Stokes DC, et al.: Pulmonary outcomes in survivors of childhood cancer: a systematic review. Chest 140 (4): 881-901, 2011. [PUBMED Abstract]
Kasteler R, Weiss A, Schindler M, et al.: Long-term pulmonary disease among Swiss childhood cancer survivors. Pediatr Blood Cancer 65 (1): , 2018. [PUBMED Abstract]
Josephson MB, Goldfarb SB: Pulmonary complications of childhood cancers. Expert Rev Respir Med 8 (5): 561-71, 2014. [PUBMED Abstract]
Motosue MS, Zhu L, Srivastava K, et al.: Pulmonary function after whole lung irradiation in pediatric patients with solid malignancies. Cancer 118 (5): 1450-6, 2012. [PUBMED Abstract]
McDonald S, Rubin P, Maasilta P: Response of normal lung to irradiation. Tolerance doses/tolerance volumes in pulmonary radiation syndromes. Front Radiat Ther Oncol 23: 255-76; discussion 299-301, 1989. [PUBMED Abstract]
McDonald S, Rubin P, Phillips TL, et al.: Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys 31 (5): 1187-203, 1995. [PUBMED Abstract]
Venkatramani R, Kamath S, Wong K, et al.: Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation. Pediatr Blood Cancer 61 (7): 1277-81, 2014. [PUBMED Abstract]
Kreisman H, Wolkove N: Pulmonary toxicity of antineoplastic therapy. Semin Oncol 19 (5): 508-20, 1992. [PUBMED Abstract]
Bossi G, Cerveri I, Volpini E, et al.: Long-term pulmonary sequelae after treatment of childhood Hodgkin's disease. Ann Oncol 8 (Suppl 1): 19-24, 1997. [PUBMED Abstract]
Fryer CJ, Hutchinson RJ, Krailo M, et al.: Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional radiation in advanced Hodgkin's disease in children: a report from the Children's Cancer Study Group. J Clin Oncol 8 (12): 1971-80, 1990. [PUBMED Abstract]
Hudson MM, Greenwald C, Thompson E, et al.: Efficacy and toxicity of multiagent chemotherapy and low-dose involved-field radiotherapy in children and adolescents with Hodgkin's disease. J Clin Oncol 11 (1): 100-8, 1993. [PUBMED Abstract]
Hunger SP, Link MP, Donaldson SS: ABVD/MOPP and low-dose involved-field radiotherapy in pediatric Hodgkin's disease: the Stanford experience. J Clin Oncol 12 (10): 2160-6, 1994. [PUBMED Abstract]
Marina NM, Greenwald CA, Fairclough DL, et al.: Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Cancer 75 (7): 1706-11, 1995. [PUBMED Abstract]
Polliack A: Late therapy-induced cardiac and pulmonary complications in cured patients with Hodgkin's disease treated with conventional combination chemo-radiotherapy. Leuk Lymphoma 15 (Suppl 1): 7-10, 1995. [PUBMED Abstract]
Cerveri I, Fulgoni P, Giorgiani G, et al.: Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed? Chest 120 (6): 1900-6, 2001. [PUBMED Abstract]
Leiper AD: Non-endocrine late complications of bone marrow transplantation in childhood: part II. Br J Haematol 118 (1): 23-43, 2002. [PUBMED Abstract]
Marras TK, Chan CK, Lipton JH, et al.: Long-term pulmonary function abnormalities and survival after allogeneic marrow transplantation. Bone Marrow Transplant 33 (5): 509-17, 2004. [PUBMED Abstract]
Inaba H, Yang J, Pan J, et al.: Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Cancer 116 (8): 2020-30, 2010. [PUBMED Abstract]
Frisk P, Arvidson J, Hedenström H: A longitudinal study of pulmonary function after stem cell transplantation, from childhood to young adulthood. Pediatr Blood Cancer 58 (5): 775-9, 2012. [PUBMED Abstract]
Uderzo C, Pillon M, Corti P, et al.: Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties. Bone Marrow Transplant 39 (11): 667-75, 2007. [PUBMED Abstract]
Yoshihara S, Yanik G, Cooke KR, et al.: Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 13 (7): 749-59, 2007. [PUBMED Abstract]
Kreisel D, Krupnick AS, Huddleston CB: Outcomes and late complications after pulmonary resections in the pediatric population. Semin Thorac Cardiovasc Surg 16 (3): 215-9, 2004. [PUBMED Abstract]
Gibson TM, Liu W, Armstrong GT, et al.: Longitudinal smoking patterns in survivors of childhood cancer: An update from the Childhood Cancer Survivor Study. Cancer 121 (22): 4035-43, 2015. [PUBMED Abstract]
Oancea SC, Gurney JG, Ness KK, et al.: Cigarette smoking and pulmonary function in adult survivors of childhood cancer exposed to pulmonary-toxic therapy: results from the St. Jude lifetime cohort study. Cancer Epidemiol Biomarkers Prev 23 (9): 1938-43, 2014. [PUBMED Abstract]
Hearing loss as a late effect of therapy can occur after exposure to platinum compounds (cisplatin and carboplatin), cranial radiation therapy, or both. These therapeutic exposures are most common in the treatment of central nervous system (CNS) and non-CNS solid tumors. Children are more susceptible to otologic toxic effects from platinum agents than are adults.[1,2] A report from the Swiss Childhood Cancer Survivor Study (CCSS) (N = 2,061) estimated the prevalence of hearing loss in survivors at 10%, compared with 3% in siblings. Hearing loss was most common in survivors of CNS tumors (25%), neuroblastoma (23%), hepatic tumor (21%), germ cell tumor (20%), bone tumor (16%), and soft tissue sarcoma (16%).[3] Data from the Swiss CCSS indicate that the relative rate of first occurrence of auditory complications (problems hearing sounds, tinnitus, hearing loss, deafness) is greatest in the time period from diagnosis to 5 years postdiagnosis; however, during the period of 5 or more years postdiagnosis, the risk of developing such conditions for survivors remained significantly higher than for siblings.[4]
Risk factors associated with hearing loss include the following:
Younger age at treatment.
Higher cumulative dose of platinum-based chemotherapy (≥300 mg/m2).[5]
Exposure to cisplatin combined with carboplatin.[5]
CNS tumors.
Hearing loss and platinum-based therapy
Platinum-related sensorineural hearing loss develops as an acute toxicity that is generally irreversible and bilateral. Hearing loss manifests initially in the high frequencies and progresses to the speech frequencies with increasing cumulative exposure. The prevalence of hearing loss has varied widely per series and is based on platinum treatment (e.g., platinum type, dose, infusion duration); host factors (e.g., age, genetic susceptibility, renal function); receipt of additional ototoxic therapy (cranial radiation therapy, aminoglycosides, loop diuretics), and the grading criteria used to report prevalence and severity of hearing loss.[5,6]
Cisplatin-induced hearing loss involving the speech frequencies (500–2,000 Hz) usually occurs with cumulative doses that exceed 400 mg/m2 in pediatric patients.[7,8] Prolonging the duration of infusion or splitting the dose has been reported to reduce the risk of significant hearing loss.[9]
In a randomized trial that compared cisplatin alone with cisplatin plus delayed administration of sodium thiosulfate, the administration of sodium thiosulfate 6 hours after cisplatin chemotherapy resulted in a 48% lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma and did not jeopardize overall survival or event-free survival.[10]
Exposure to cisplatin combined with myeloablative carboplatin significantly increases the risk of severe hearing loss.[8] Otologic toxic effects after platinum chemotherapy have been reported to worsen years after completion of therapy.[11]
Radiation therapy to the posterior fossa inclusive of the eighth cranial nerve (suggestive of damage to the cochlea at the end of therapy) increases the risk of late-onset hearing loss in survivors treated with cisplatin.[12]
Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[13] However, delayed-onset hearing loss has been reported in the following populations:
In a cross-sectional, multicenter analysis that included 451 Dutch childhood cancer survivors who received platinum agents but not cranial radiation therapy, the incidence of ototoxicity (defined as Münster grade >2b [>20 dB at ≥4–8kHz]) associated with the use of carboplatin given alone (n = 112) was 17%.[5]
A single study of otologic toxic effects after non–stem cell transplant dosing of carboplatin for retinoblastoma reported that 8 of 175 children developed hearing loss. For seven of the eight children, the onset of the otologic toxic effects was delayed a median of 3.7 years.[14]
Another study that evaluated audiological outcomes among 60 retinoblastoma survivors treated with nonmyeloablative systemic carboplatin and vincristine estimated a cumulative incidence of hearing loss of 20.3% at 10 years. Among the ten patients (17%) who developed sustained grade 3 or grade 4 hearing loss, nine were younger than 6 months at the start of chemotherapy. Younger age at the start of treatment was the only significant predictor of hearing loss; the cumulative incidence of hearing loss was 39% for patients younger than 6 months versus only 8.3% for patients aged 6 months and older.[15]
The use of a carboplatin conditioning regimen for hematopoietic stem cell transplantation, particularly in combination with previous carboplatin or cisplatin therapy, may cause significant otologic toxic effects.[7,8]
Hearing loss and cranial radiation therapy
Cranial radiation therapy, when used as a single modality, may result in otologic toxic effects that may be gradual in onset, manifesting months to years after exposure. The threshold dose for auditory toxicity after radiation therapy alone is in the range of 35 to 45 Gy for children.[16] High-frequency sensorineural hearing loss is uncommon at cumulative radiation doses below 35 Gy, and is rarely severe below doses of 45 Gy.[17] The exception is for patients with supratentorial tumors and ventriculoperitoneal shunts, in whom doses below 30 Gy may be associated with intermediate frequency (1,000–2,000 Hz) hearing loss.[16,18] To reduce the risk of hearing loss, the average cochlear dose should not exceed 30 to 35 Gy, delivered over 6 weeks. Young patient age and presence of a brain tumor and/or hydrocephalus can increase susceptibility to hearing loss.
Sensorineural hearing loss after cranial radiation therapy can progress over time. In a study of 235 pediatric brain tumor patients treated with conformal or intensity-modulated radiation therapy (without cisplatin or pre-existing hearing loss) and monitored for a median of 9 years, sensorineural hearing loss was prevalent in 14% of patients, with a median time to onset of 3.6 years from radiation therapy. Follow-up evaluations among 29 patients identified continued decline in hearing sensitivity. Risk factors for cranial radiation–associated sensorineural hearing loss included younger age at initiation of radiation, higher cochlear radiation dose, and cerebrospinal fluid shunting.[19]
When used concomitantly with cisplatin, radiation therapy can substantially exacerbate the hearing loss associated with platinum chemotherapy.[16,20-22] In a report from the CCSS, 5-year survivors were at increased risk of problems with hearing sounds (relative risk [RR], 2.3), tinnitus (RR, 1.7), hearing loss requiring an aid (RR, 4.4), and hearing loss in one or both ears not corrected by a hearing aid (RR, 5.2), compared with siblings. Temporal lobe irradiation (>30 Gy) and posterior fossa irradiation (>50 Gy but also 30–49.9 Gy) were associated with these adverse outcomes. Exposure to platinum was associated with an increased risk of problems with hearing sounds (RR, 2.1), tinnitus (RR, 2.8), and hearing loss requiring an aid (RR, 4.1).[4]
Hearing loss and quality of life
Importantly, children treated for malignancies may be at risk of early- or delayed-onset hearing loss that can affect learning, communication, school performance, social interaction, and overall quality of life.
Among 137 child survivors of neuroblastoma (aged 8–17 years), hearing loss was associated with problems with reading and math skills, as well as higher risk of learning disability and/or special education needs. In addition, hearing loss was associated with poorer school-related quality of life.[23]
Serial neurocognitive and audiology evaluations were performed on 260 children and young adults with embryonal brain tumors who were enrolled on a treatment protocol that consisted of surgery, risk-adapted cranial spinal irradiation, and chemotherapy. The 64 children with severe sensorineural hearing loss exhibited greater reading difficulties over time compared with the group of children with normal or mild-to-moderate sensorineural hearing loss. Specifically, these children with severe sensorineural hearing loss seemed to struggle most with phonological skills and processing speed, which affect higher level skills such as reading comprehension.[24]
In a study of adult survivors of pediatric CNS tumors (n = 180) and non-CNS solid tumors (n = 226) who were treated with potentially ototoxic cancer therapy, serious hearing loss (requiring aid or resulting in deafness) was associated with a twofold increased risk of nonindependent living and unemployment or not graduating from high school.[25]
The Children’s Oncology Group has published recommendations for the evaluation and management of hearing loss in survivors of childhood and adolescent cancers to promote early identification of at-risk survivors and timely referral for remedial services.[26]
Table 17 summarizes auditory late effects and the related health screenings.
Table 17. Auditory Late Effectsa
Potential Auditory Effects
FM = frequency modulated.
Platinum agents (cisplatin, carboplatin); radiation impacting the ear Otologic toxic effects; sensorineural hearing loss; tinnitus; vertigo; dehydrated ceruminosis; conductive hearing loss History: hearing difficulties, tinnitus, vertigo
Otoscopic exam
Audiology evaluation
Amplification in patients with progressive hearing loss
Speech and language therapy for children with hearing loss
Otolaryngology consultation in patients with chronic infection, cerumen impaction, or other anatomical problems exacerbating or contributing to hearing loss
Educational accommodations (e.g., preferential classroom seating, FM amplification system, etc.)
Orbital and Optic
Orbital complications are common after radiation therapy for retinoblastoma and after total-body irradiation (TBI) and in children with head and neck sarcomas and CNS tumors.
For survivors of retinoblastoma, a small orbital volume may result from either enucleation or radiation therapy. Age younger than 1 year may increase risk, but this finding is not consistent across studies.[27,28] Progress has been made in the management of retinoblastoma, with better enucleation implants, intravenous chemoreduction, and intra-arterial chemotherapy in addition to thermotherapy, cryotherapy, and plaque radiation therapy. Longer follow-up is needed to assess the impact on vision in patients undergoing these more contemporary treatment modalities.[27,29,30] Previously, tumors located near the macula and fovea were associated with an increased risk of complications leading to vision loss, although treatment of these tumors with foveal laser ablation has shown promise in preserving vision.[31-34]
(Refer to the PDQ summary on Retinoblastoma Treatment for more information on the treatment of retinoblastoma.)
Survivors of orbital rhabdomyosarcoma are at risk of dry eye, cataract, orbital hypoplasia, ptosis, retinopathy, keratoconjunctivitis, optic neuropathy, lid epithelioma, and impairment of vision after radiation therapy doses of 30 Gy to 65 Gy. The higher dose ranges (>50 Gy) are associated with lid epitheliomas, keratoconjunctivitis, lacrimal duct atrophy, and severe dry eye. Retinitis and optic neuropathy may also result from doses of 50 Gy to 65 Gy and even at lower total doses if the individual fraction size is higher than 2 Gy.[35] Cataracts are reported after lower doses of 10 Gy to 18 Gy.[36-38]
(Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information on the treatment of rhabdomyosarcoma in children.)
Low-grade optic pathway glioma and craniopharyngioma
Survivors of optic pathway glioma and craniopharyngioma are also at risk of visual complications, resulting in part from tumor proximity to the optic nerve.
In a retrospective cohort study of 59 pediatric patients with sporadic optic pathway gliomas diagnosed between 1990 and 2014 (median follow up, 5.2 years), there was a significant burden of long-term visual impairment. The findings showed that more than two-thirds of the patients had evidence of long-term vision loss, more than one-half had severe vision loss in at least one eye, and one-quarter of the patients had severe bilateral vision loss. Identified risk factors for poor visual outcome were postchiasmal involvement, younger age, and optic nerve pallor at presentation.[39]
Longitudinal follow-up (mean, 9 years) of 21 patients with optic pathway gliomas indicated that before treatment, 81% of patients had reduced visual acuity, 81% had optic nerve pallor, and all had reduced visual evoked potentials in one or both eyes. Treatment arrested acuity loss for 4 to 5 years. Visual acuity was stable or improved in 33% of patients at last follow-up; however, it declined on average. Visual acuity at follow-up was related to tumor volume at initial presentation.[40]
In a study of 51 children with low-grade gliomas and low-grade glioneural tumors diagnosed within the first year of life, visual acuity was decreased in 27 of 48 patients (56%), 13 (27%) of whom were legally blind. The tumor location (hypothalamic or optic pathway) was significantly associated with decreased visual acuity (P = .002).[41]
In a study of 25 patients diagnosed with craniopharyngioma, 67% had visual complications at a mean follow-up of 11 years.[42] A retrospective review of 30 children with craniopharyngioma revealed that 19 patients had vision loss before surgery; 21 patients had postsurgical vision loss. Preoperative vision loss was predicative of postoperative vision loss.[43]
CCSS investigators evaluated the impact of impaired vision on cognitive and psychosocial outcomes among 1,233 adult survivors of childhood low-grade gliomas. Some degree of visual impairment was prevalent in 22.5% of patients, and 3.8% of patients were blind in both eyes. Survivors who were blind in both eyes were more likely to be unmarried, live dependently, and be unemployed than were survivors with unimpaired vision. However, bilateral blindness did not impact self-reported cognitive or emotional outcomes. Impaired (with some remaining) vision was not associated with psychological or economic outcomes.[44]
Treatment-specific effects
Survivors of childhood cancer are at increased risk for ocular late effects related to both glucocorticoid and radiation exposure to the eye.
Evidence (ocular effects of radiation exposure):
The CCSS reported that survivors who were 5 or more years from diagnosis were at increased risk of developing cataracts (RR, 10.8), glaucoma (RR, 2.5), legal blindness (RR, 2.6), double vision (RR, 4.1), and dry eye (RR, 1.9), compared with siblings.[45]
The 15-year cumulative incidence of cataract was 4.5% among 517 survivors of childhood acute lymphoblastic leukemia (median, 10.9 years from diagnosis), systematically evaluated by slit lamp examination. CNS radiation therapy was the only treatment-related risk factor identified for cataract development, which occurred in 11.1% of irradiated survivors, compared with 2.8% of those who were not irradiated.[46]
A report from the CCSS provides additional data on the interval from radiation therapy and the radiation dose associated with the development of cataracts.[47]
Among 13,902 study participants, 3.5% developed cataracts (41% within 5 years of radiation therapy), with a median time to onset of 9.6 years and a maximum time of 37 years. Lens radiation doses were associated with an increased prevalence: 1.3% if less than 0.5 Gy, 6.1% after 2.5 to 3.49 Gy, and 40.6% after 20 to 60 Gy.
Higher doses were associated with a shorter time interval to diagnosis.
Of the group with cataracts, 31% reported having cataract surgery, supporting the clinical consequences.
Cytosine arabinoside (odds ratio [OR], 1.5) and doxorubicin (OR, 1.5) were independently associated with cataract development, methotrexate was inversely associated (OR, 0.6), and no positive interaction between the use of corticosteroids and radiation therapy was observed.
Ocular complications, such as cataracts and dry eye syndrome, are common after stem cell transplantation in childhood.
Evidence (ocular effects of stem cell transplantation):
Compared with patients treated with busulfan or other chemotherapy, patients treated with single-dose or fractionated TBI are at increased risk of cataracts. Risk ranges from approximately 10% to 60% at 10 years posttreatment, depending on the total dose and fractionation, with a shorter latency period and more severe cataracts noted after single fraction and higher dose or dose-rate TBI.[48-51]
Patients receiving TBI doses of less than 40 Gy have a less than 10% chance of developing severe cataracts.[51]
Corticosteroids and graft-versus-host disease may further increase risk.[48,52]
The prevalence of cataracts, evaluated by serial slit lamp testing, among 271 participants (mean follow-up, 10.3 years) in the Leucémie Enfants Adolescents (LEA) program was 41.7%, with 8.1% requiring surgical intervention.[53] In this cohort, the cumulative incidence of cataracts among those treated with TBI increased over time from 30% at 5 years to 70.8% at 15 years and 78% at 20 years. The lack of a plateau in cataract incidence suggests that nearly all patients treated with TBI will develop cataracts as follow-up increases. In contrast, the 15-year cumulative incidence of cataracts was 12.5% among those conditioned with busulfan. Multivariable analysis identified high cumulative steroid dose as a potential cofactor with TBI for cataract risk.
Dry eye syndrome has been shown to be more common if the patient was exposed to repeated high trough levels of cyclosporine.[54]
Table 18 summarizes ocular late effects and the related health screenings.
Table 18. Ocular Late Effectsa
Ocular/Vision Effects
GVHD = graft-versus-host disease; 131I = iodine I 131.
Busulfan; corticosteroids; radiation impacting the eye Cataracts History: decreased acuity, halos, diplopia
Eye exam: visual acuity, funduscopy (yearly)
Ophthalmology consultation
Radiation impacting the eye, including radioiodine (131I) Ocular toxicity (orbital hypoplasia, lacrimal duct atrophy, xerophthalmia [keratoconjunctivitis sicca], keratitis, telangiectasias, retinopathy, optic chiasm neuropathy, enophthalmos, chronic painful eye, maculopathy, papillopathy, glaucoma) History: visual changes (decreased acuity, halos, diplopia), dry eye, persistent eye irritation, excessive tearing, light sensitivity, poor night vision, painful eye
Hematopoietic cell transplantation with any history of chronic GVHD Xerophthalmia (keratoconjunctivitis sicca) History: dry eye (burning, itching, foreign body sensation, inflammation)
Enucleation Impaired cosmesis; poor prosthetic fit; orbital hypoplasia Ocular prosthetic evaluation
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for information on the late effects of special senses, including risk factors, evaluation, and health counseling.
Grewal S, Merchant T, Reymond R, et al.: Auditory late effects of childhood cancer therapy: a report from the Children's Oncology Group. Pediatrics 125 (4): e938-50, 2010. [PUBMED Abstract]
Li Y, Womer RB, Silber JH: Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer 40 (16): 2445-51, 2004. [PUBMED Abstract]
Weiss A, Sommer G, Kasteler R, et al.: Long-term auditory complications after childhood cancer: A report from the Swiss Childhood Cancer Survivor Study. Pediatr Blood Cancer 64 (2): 364-373, 2017. [PUBMED Abstract]
Whelan K, Stratton K, Kawashima T, et al.: Auditory complications in childhood cancer survivors: a report from the childhood cancer survivor study. Pediatr Blood Cancer 57 (1): 126-34, 2011. [PUBMED Abstract]
Clemens E, de Vries AC, Pluijm SF, et al.: Determinants of ototoxicity in 451 platinum-treated Dutch survivors of childhood cancer: A DCOG late-effects study. Eur J Cancer 69: 77-85, 2016. [PUBMED Abstract]
Brock PR, Knight KR, Freyer DR, et al.: Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. J Clin Oncol 30 (19): 2408-17, 2012. [PUBMED Abstract]
Kushner BH, Budnick A, Kramer K, et al.: Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma. Cancer 107 (2): 417-22, 2006. [PUBMED Abstract]
Landier W, Knight K, Wong FL, et al.: Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales--a report from the Children's Oncology Group. J Clin Oncol 32 (6): 527-34, 2014. [PUBMED Abstract]
Lewis MJ, DuBois SG, Fligor B, et al.: Ototoxicity in children treated for osteosarcoma. Pediatr Blood Cancer 52 (3): 387-91, 2009. [PUBMED Abstract]
Brock PR, Maibach R, Childs M, et al.: Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med 378 (25): 2376-2385, 2018. [PUBMED Abstract]
Bertolini P, Lassalle M, Mercier G, et al.: Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss. J Pediatr Hematol Oncol 26 (10): 649-55, 2004. [PUBMED Abstract]
Kolinsky DC, Hayashi SS, Karzon R, et al.: Late onset hearing loss: a significant complication of cancer survivors treated with Cisplatin containing chemotherapy regimens. J Pediatr Hematol Oncol 32 (2): 119-23, 2010. [PUBMED Abstract]
Fouladi M, Gururangan S, Moghrabi A, et al.: Carboplatin-based primary chemotherapy for infants and young children with CNS tumors. Cancer 115 (14): 3243-53, 2009. [PUBMED Abstract]
Jehanne M, Lumbroso-Le Rouic L, Savignoni A, et al.: Analysis of ototoxicity in young children receiving carboplatin in the context of conservative management of unilateral or bilateral retinoblastoma. Pediatr Blood Cancer 52 (5): 637-43, 2009. [PUBMED Abstract]
Qaddoumi I, Bass JK, Wu J, et al.: Carboplatin-associated ototoxicity in children with retinoblastoma. J Clin Oncol 30 (10): 1034-41, 2012. [PUBMED Abstract]
Hua C, Bass JK, Khan R, et al.: Hearing loss after radiotherapy for pediatric brain tumors: effect of cochlear dose. Int J Radiat Oncol Biol Phys 72 (3): 892-9, 2008. [PUBMED Abstract]
Bhandare N, Jackson A, Eisbruch A, et al.: Radiation therapy and hearing loss. Int J Radiat Oncol Biol Phys 76 (3 Suppl): S50-7, 2010. [PUBMED Abstract]
Merchant TE, Gould CJ, Xiong X, et al.: Early neuro-otologic effects of three-dimensional irradiation in children with primary brain tumors. Int J Radiat Oncol Biol Phys 58 (4): 1194-207, 2004. [PUBMED Abstract]
Bass JK, Hua CH, Huang J, et al.: Hearing Loss in Patients Who Received Cranial Radiation Therapy for Childhood Cancer. J Clin Oncol 34 (11): 1248-55, 2016. [PUBMED Abstract]
Merchant TE, Hua CH, Shukla H, et al.: Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 51 (1): 110-7, 2008. [PUBMED Abstract]
Paulino AC, Lobo M, Teh BS, et al.: Ototoxicity after intensity-modulated radiation therapy and cisplatin-based chemotherapy in children with medulloblastoma. Int J Radiat Oncol Biol Phys 78 (5): 1445-50, 2010. [PUBMED Abstract]
Gurney JG, Tersak JM, Ness KK, et al.: Hearing loss, quality of life, and academic problems in long-term neuroblastoma survivors: a report from the Children's Oncology Group. Pediatrics 120 (5): e1229-36, 2007. [PUBMED Abstract]
Olivier TW, Bass JK, Ashford JM, et al.: Cognitive Implications of Ototoxicity in Pediatric Patients With Embryonal Brain Tumors. J Clin Oncol 37 (18): 1566-1575, 2019. [PUBMED Abstract]
Brinkman TM, Bass JK, Li Z, et al.: Treatment-induced hearing loss and adult social outcomes in survivors of childhood CNS and non-CNS solid tumors: Results from the St. Jude Lifetime Cohort Study. Cancer 121 (22): 4053-61, 2015. [PUBMED Abstract]
Kaste SC, Chen G, Fontanesi J, et al.: Orbital development in long-term survivors of retinoblastoma. J Clin Oncol 15 (3): 1183-9, 1997. [PUBMED Abstract]
Peylan-Ramu N, Bin-Nun A, Skleir-Levy M, et al.: Orbital growth retardation in retinoblastoma survivors: work in progress. Med Pediatr Oncol 37 (5): 465-70, 2001. [PUBMED Abstract]
Shields CL, Shields JA: Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Curr Opin Ophthalmol 21 (3): 203-12, 2010. [PUBMED Abstract]
Abramson DH, Dunkel IJ, Brodie SE, et al.: Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology 117 (8): 1623-9, 2010. [PUBMED Abstract]
Shields CL, Shields JA: Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabismus 36 (1): 8-18; quiz 35-6, 1999 Jan-Feb. [PUBMED Abstract]
Shields CL, Shields JA, Cater J, et al.: Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology 108 (11): 2116-21, 2001. [PUBMED Abstract]
Shields JA, Shields CL: Pediatric ocular and periocular tumors. Pediatr Ann 30 (8): 491-501, 2001. [PUBMED Abstract]
Schefler AC, Cicciarelli N, Feuer W, et al.: Macular retinoblastoma: evaluation of tumor control, local complications, and visual outcomes for eyes treated with chemotherapy and repetitive foveal laser ablation. Ophthalmology 114 (1): 162-9, 2007. [PUBMED Abstract]
Kline LB, Kim JY, Ceballos R: Radiation optic neuropathy. Ophthalmology 92 (8): 1118-26, 1985. [PUBMED Abstract]
Oberlin O, Rey A, Anderson J, et al.: Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop. J Clin Oncol 19 (1): 197-204, 2001. [PUBMED Abstract]
Wan MJ, Ullrich NJ, Manley PE, et al.: Long-term visual outcomes of optic pathway gliomas in pediatric patients without neurofibromatosis type 1. J Neurooncol 129 (1): 173-8, 2016. [PUBMED Abstract]
Kelly JP, Leary S, Khanna P, et al.: Longitudinal measures of visual function, tumor volume, and prediction of visual outcomes after treatment of optic pathway gliomas. Ophthalmology 119 (6): 1231-7, 2012. [PUBMED Abstract]
Poretti A, Grotzer MA, Ribi K, et al.: Outcome of craniopharyngioma in children: long-term complications and quality of life. Dev Med Child Neurol 46 (4): 220-9, 2004. [PUBMED Abstract]
Fisher PG, Jenab J, Gopldthwaite PT, et al.: Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 14 (10): 558-63, 1998. [PUBMED Abstract]
de Blank PM, Fisher MJ, Lu L, et al.: Impact of vision loss among survivors of childhood central nervous system astroglial tumors. Cancer 122 (5): 730-9, 2016. [PUBMED Abstract]
Whelan KF, Stratton K, Kawashima T, et al.: Ocular late effects in childhood and adolescent cancer survivors: a report from the childhood cancer survivor study. Pediatr Blood Cancer 54 (1): 103-9, 2010. [PUBMED Abstract]
Alloin AL, Barlogis V, Auquier P, et al.: Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study. Br J Haematol 164 (1): 94-100, 2014. [PUBMED Abstract]
Chodick G, Sigurdson AJ, Kleinerman RA, et al.: The Risk of Cataract among Survivors of Childhood and Adolescent Cancer: A Report from the Childhood Cancer Survivor Study. Radiat Res 185 (4): 366-74, 2016. [PUBMED Abstract]
Ferry C, Gemayel G, Rocha V, et al.: Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies. Bone Marrow Transplant 40 (3): 219-24, 2007. [PUBMED Abstract]
Fahnehjelm KT, Törnquist AL, Olsson M, et al.: Visual outcome and cataract development after allogeneic stem-cell transplantation in children. Acta Ophthalmol Scand 85 (7): 724-33, 2007. [PUBMED Abstract]
Gurney JG, Ness KK, Rosenthal J, et al.: Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood: results from the Bone Marrow Transplant Survivor study. Cancer 106 (6): 1402-8, 2006. [PUBMED Abstract]
Kal HB, VAN Kempen-Harteveld ML: Induction of severe cataract and late renal dysfunction following total body irradiation: dose-effect relationships. Anticancer Res 29 (8): 3305-9, 2009. [PUBMED Abstract]
Holmström G, Borgström B, Calissendorff B: Cataract in children after bone marrow transplantation: relation to conditioning regimen. Acta Ophthalmol Scand 80 (2): 211-5, 2002. [PUBMED Abstract]
Horwitz M, Auquier P, Barlogis V, et al.: Incidence and risk factors for cataract after haematopoietic stem cell transplantation for childhood leukaemia: an LEA study. Br J Haematol 168 (4): 518-25, 2015. [PUBMED Abstract]
Fahnehjelm KT, Törnquist AL, Winiarski J: Dry-eye syndrome after allogeneic stem-cell transplantation in children. Acta Ophthalmol 86 (3): 253-8, 2008. [PUBMED Abstract]
Acute toxicity of the urinary system from cancer therapy is well known. Less is known about the genitourinary outcomes in long-term survivors.[1] The evidence for long-term renal injury in childhood cancer survivors is limited by studies characterized by small sample size, cohort selection and participation bias, cross-sectional assessment, heterogeneity in time since treatment, and method of ascertainment. In particular, the inaccuracies of diagnosing chronic kidney dysfunction by estimating equations of glomerular dysfunction should be considered.[2] Cancer treatments predisposing to renal injury and/or high blood pressure later in life include the following:
Chemotherapeutic drugs (cisplatin, carboplatin, ifosfamide, methotrexate).
Renal radiation therapy.
Nephrectomy.
The risk and degree of renal dysfunction depend on type and intensity of therapy, and the interpretation of the studies is compromised by variability in testing.
Few large-scale studies have evaluated late renal-health outcomes and risk factors for renal dysfunction among survivors treated with potentially nephrotoxic modalities.
Evidence (renal dysfunction in childhood cancer survivors):
In a large, cross-sectional study of 1,442 childhood cancer survivors (median attained age, 19.3 years; median time from diagnosis, 12.1 years), Dutch investigators assessed the presence of albuminuria, hypomagnesemia, hypophosphatemia, and hypertension, and they estimated glomerular filtration rate (GFR) among survivors treated with ifosfamide, cisplatin, carboplatin, high-dose cyclophosphamide (>1 g/m2 or more per course), or high-dose methotrexate (>1 g/m2 or more per course), radiation therapy to the kidney region, total-body irradiation (TBI), or nephrectomy.[3]
At least one abnormality of renal function or hypertension was detected in 28.1% of survivors.
History of nephrectomy (odds ratio [OR], 8.6; 95% confidence interval [CI], 3.4–21.4) had the strongest association with a GFR of less than 90 mL/min per 1.73 m2.
The prevalence of decreased GFR was highest among those treated with multimodality therapy including nephrectomy, nephrotoxic chemotherapy, and abdominal radiation therapy. Nearly 5% of these survivors had a GFR of less than 90 mL/min per 1.73 m2.
Abdominal irradiation was the only significant treatment-related risk factor for hypertension (OR, 2.5; 95% CI, 1.4–4.5).
Therapy-related factors affecting the kidney
Cancer treatments predisposing to late renal injury and hypertension include the following:[4-6]
Nephrectomy. Survivors of childhood cancer who have undergone nephrectomy are at risk of hyperfiltration injury. Compensatory hypertrophy of the remaining kidney typically occurs after nephrectomy, but over time, renal injury may manifest as reduced glomerular filtration, microalbuminuria and proteinuria, hypertension, and, rarely, focal glomerulosclerosis leading to chronic renal failure.
In a cross-sectional study of 1,442 5-year childhood cancer survivors (median 12.1 years from diagnosis), 28.1% of all survivors had at least one renal adverse effect, with hypertension (14.8%) and albuminuria (14.5%) being the most prevalent. Survivors who had undergone nephrectomy had the highest risk of diminished renal function (OR, 8.6; 95% CI, 3.4–21.4).[3,5] However, patients with nonsyndromic unilateral Wilms tumor treated with unilateral radical nephrectomy without nephrotoxic chemotherapy or ionizing radiation therapy appear to be at low risk of developing significant long-term renal dysfunction.[7]
Chemotherapy.
Cisplatin. Cisplatin can cause glomerular and tubular damage resulting in a diminished GFR and electrolyte wasting (particularly magnesium, calcium, and potassium).[8-10]
Acute cisplatin-related nephrotoxicity has been reported in 30% to 100% of exposed children.[11] However, the prevalence of persistent renal dysfunction in long-term survivors appears to be considerably lower.
Among 63 children treated with platinum agents, GFR was less than 60 mL/min per 1.73 m2 in 11% of children and hypomagnesemia requiring oral supplements occurred in 7% of children at 10 years from completion of therapy. Among 651 sarcoma patients evaluated after cessation of antineoplastic therapy (median follow-up, 2 years), hypomagnesemia occurred in 12.1% of patients after cisplatin therapy and in 15.6% after carboplatin therapy, compared with 4.5% who did not receive any platinum derivatives. In all groups, the frequency of hypomagnesemia decreased with ongoing follow-up, but serum magnesium remained lower in platinum-treated patients throughout the study period.[10,12]
Carboplatin. Carboplatin is a cisplatin analog and is less nephrotoxic than cisplatin. In a prospective, longitudinal, single-center, cohort study of children monitored for more than 10 years after cisplatin or carboplatin therapy, older age at treatment was found to be the major risk factor for nephrotoxicity, especially for patients receiving carboplatin, while cisplatin dose schedule and cumulative carboplatin dose were also important predictors of toxicity. Platinum nephrotoxicity did not change significantly over 10 years.[10]
The combination of carboplatin and ifosfamide may be associated with more renal damage than the combination of cisplatin and ifosfamide.[8-10]
Additional follow-up in larger numbers of survivors treated with carboplatin (without other nephrotoxic agents and modalities) must be evaluated before potential renal toxicity can be better defined.
Ifosfamide. Ifosfamide can also cause glomerular and tubular toxicity, with renal tubular acidosis and Fanconi syndrome, a proximal tubular defect characterized by impairment of resorption of glucose, amino acids, phosphate, and bicarbonate. Ifosfamide doses greater than 60 g/m2, age younger than 5 years at treatment, and combination with cisplatin and carboplatin increase the risk of ifosfamide-associated renal tubular toxicity.[13-15]
A French study that evaluated the prevalence of late renal toxicity after ifosfamide reported normal tubular function in 90% of pediatric cancer survivors (median follow-up, 10 years); 79% of the cancer survivors had normal GFR, and all survivors had normal serum bicarbonate and calcium.[15] Hypomagnesemia and hypophosphatemia were seen in 1% of cancer survivors. Glycosuria was detected in 37% of cancer survivors but was mild in 95% of cases. Proteinuria was observed in 12% of cancer survivors. In multivariate analysis, ifosfamide dose and interval from therapy were predictors of tubulopathy, and older age at diagnosis and interval from therapy were predictors of abnormal GFR.
High-dose methotrexate. High-dose methotrexate (1,000–33,000 mg/m2) has been reported to cause acute renal dysfunction in up to 12.4% of patients. Long-term renal sequelae have not been described.[5,16]
Radiation therapy. Radiation therapy to the kidney can result in radiation nephritis or nephropathy after a latent period of 3 to 12 months. The kidney is relatively radiosensitive, with a tolerance dose of 20 Gy.[17] Doses of 18 Gy are considered unlikely to cause severe or chronic renal sequelae. In contrast, up to 50% of individuals treated with 20 Gy may develop glomerular dysfunction or hypertension within 20 years.[18]
Specific quantitative data are sparse, but a study of 108 children treated for Wilms tumor who had undergone unilateral nephrectomy showed that 41% of children who received less than 12 Gy of radiation to the contralateral remaining kidney, 56% of children who received 12 Gy to 24 Gy, and 91% of children who received more than 24 Gy had a decreased creatinine clearance (GFR <63 mL/min/m2).[19]
In a report from the German Registry for the Evaluation of Side Effects after Radiation in Childhood and Adolescence (RISK consortium), 126 patients who underwent radiation therapy to parts of the kidneys for various cancers were evaluated. All patients had also received potentially nephrotoxic chemotherapy. Whole-kidney volumes exposed to greater than 20 Gy (P = .031) or 30 Gy (P = .003) of radiation were associated with a greater risk of nephrotoxicity.[20]
Risk factors for radiation nephritis include the following:
Age at time of radiation therapy. Neonates appear to have an increased sensitivity to radiation therapy; doses of 12 Gy to 24 Gy at 1.25 Gy to 1.5 Gy per fraction to the entire kidney were associated with a decreased GFR. However, for older children, there is no convincing evidence that age at the time of radiation therapy is related to renal injury.[21]
Unilateral versus bilateral radiation therapy. In the National Wilms Tumor Study experience, renal failure was more common in children with bilateral tumors than in children with unilateral tumors.[22] The effects of radiation also depend on whether partial or whole-kidney radiation therapy is administered. Renal failure is rare after the administration of partial-volume radiation doses between 12 Gy and 27 Gy.[23] When certain agents such as cyclosporine and teniposide are not used, total-body irradiation doses of up to 13 Gy are associated with a less than 8% incidence of kidney toxicity.[24]
Hematopoietic stem cell transplantation (HSCT). Chronic kidney disease is a long-term complication of HSCT that has been variably associated with acute kidney injury, lower pretransplant renal function, TBI, conditioning regimens such as fludarabine, graft-versus-host disease, and use of calcineurin inhibitors.[25-27]
Most reports of renal outcomes among long-term survivors of childhood cancer treated with HSCT are limited to descriptive outcomes of very small cohorts.
Refer to the Urinary System Late Effects section of the Childhood Hematopoietic Cell Transplantation summary for more information.
Genetic factors predisposing to renal dysfunction
Many childhood survivors of Wilms tumor who develop chronic renal failure have syndromes accompanying WT1 mutations or deletions that predispose to renal disease. Data from the National Wilms Tumor Study Group and the U.S. Renal Data System indicate that the 20-year cumulative incidence of end-stage renal disease in children with unilateral Wilms tumor and Denys-Drash syndrome is 74%, 36% for those with WAGR (Wilms tumor, aniridia, genitourinary abnormalities, mental retardation) syndrome, 7% for male patients with genitourinary anomalies, and 0.6% for patients with none of these conditions.[28] For patients with bilateral Wilms tumors, the incidence of end-stage renal disease is 50% for Denys-Drash syndrome, 90% for WAGR, 25% for genitourinary anomaly, and 12% for others.[28,29] End-stage renal disease in patients with WAGR and genitourinary anomalies tended to occur relatively late, and often during or after adolescence.[28]
Therapy-related bladder complications
Pelvic or central nervous system surgery, alkylator-containing chemotherapy such as cyclophosphamide or ifosfamide, pelvic radiation therapy, and certain spinal and genitourinary surgical procedures have been associated with urinary bladder late effects, as follows:[30]
Chemotherapy. The oxazophorine alkylating agents (cyclophosphamide and ifosfamide) and radiation therapy exposing the bladder have been implicated in the development of hemorrhagic cystitis. Chemotherapy-associated hemorrhagic cystitis presents as an acute toxicity and appears to be a rare persistent effect among clinically well characterized long-term survivor cohorts.[31,32]
In a study of 6,119 children treated between 1986 and 2010 (mean age, 12.2 years ± 6.3 standard deviation), 1.6% of patients (n = 97) developed hemorrhagic cystitis (manifesting at mean 2.7 months after transplant induction therapy and mean 12.4 months after pelvic radiation), most of whom (75%) had severity scores of II or III (scale, I–IV). Patients with radiological evidence of renal or bladder calculi or tumors invading the bladder wall were excluded from the study. Older age, previous bone marrow or peripheral stem cell transplantation, and BK virus in the urine were risk factors for hemorrhagic cystitis and were associated with a higher severity score.[33]
Previous exposure to cyclophosphamide has been linked to risk of bladder carcinoma. An excess prevalence of bladder tumors has also been observed in survivors of specific diagnostic types (e.g., heritable retinoblastoma) supporting the contribution of genetic factors in the development of subsequent neoplasms.[34,35]
Radiation therapy. Pelvic radiation therapy is also associated with an increased risk of hemorrhagic cystitis that may be either acute or chronic in presentation. The risk of radiation-induced hemorrhagic cystitis is greatest among survivors treated with radiation doses of more than 30 Gy to the whole bladder or more than 60 Gy to a portion of the bladder. Long-term bladder fibrosis and contracture may result as sequelae from hemorrhagic cystitis or radiation therapy.[30]
Surgery. Surgical procedures involving the lower genitourinary tract have the potential to impair normal function of the bladder and normal voiding mechanisms. Likewise, any cancer therapy or tumor infiltration that disrupts innervation of the bladder can have deleterious effects on bladder function that may manifest as impaired bladder storage, inability to void, and/or incontinence.
Children who have undergone ileal enterocystoplasty for bladder augmentation are at risk of developing a vitamin B12 deficiency. Serum B12 levels decrease over time after the procedure, with the greatest risk occurring 7 years postoperatively.[36]
In a study of solid organ transplants in 13,318 survivors in the Childhood Cancer Survivor Study, 71 survivors had end-stage kidney disease that warranted kidney transplants, 50 of whom received a kidney transplant. At 35 years after cancer diagnosis, the cumulative incidence of a kidney transplant was 0.39%, and the cumulative incidence of being placed on the waiting list or receiving a kidney was 0.54%. Exposure to ifosfamide and receiving TBI were associated with the highest hazard ratio for being placed on the waiting list or receiving a kidney transplant. The 5-year survival rate from the time of kidney transplant was 93.5%, which is similar to that of the general population in the same age range.[37]
Table 19 summarizes kidney and bladder late effects and the related health screenings.
Table 19. Kidney and Bladder Late Effectsa
Renal/Genitourinary Effects
BUN = blood urea nitrogen; NSAIDs = nonsteroidal anti-inflammatory drugs; RBC/HFP = red blood cells per high-field power (microscopic exam).
Cisplatin/carboplatin; ifosfamide; calcineurin inhibitors Renal toxicity (glomerular injury, tubular injury [renal tubular acidosis], Fanconi syndrome, hypophosphatemic rickets) Blood pressure
BUN, Creatinine, Na, K, Cl, CO2, Ca, Mg, PO4 levels
Electrolyte supplements for patients with persistent electrolyte wasting
Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
Methotrexate; radiation impacting kidneys/urinary tract Renal toxicity (renal insufficiency, hypertension) Blood pressure
Nephrectomy Renal toxicity (proteinuria, hyperfiltration, renal insufficiency) Blood pressure
Discuss contact sports, bicycle safety (e.g., avoiding handlebar injuries), and proper use of seatbelts (i.e., wearing lap belts around hips, not waist)
Counsel to use NSAIDs with caution
Nephrectomy; pelvic surgery; cystectomy Hydrocele Testicular exam
Cystectomy Cystectomy-related complications (chronic urinary tract infections, renal dysfunction, vesicoureteral reflux, hydronephrosis, reservoir calculi, spontaneous neobladder perforation, vitamin B12/folate/carotene deficiency [patients with ileal enterocystoplasty only]) Urology evaluation
Vitamin B12 level
Pelvic surgery; cystectomy Urinary incontinence; urinary tract obstruction History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
Counsel regarding adequate fluid intake, regular voiding, seeking medical attention for symptoms of voiding dysfunction or urinary tract infection, compliance with recommended bladder catheterization regimen
Urologic consultation for patients with dysfunctional voiding or recurrent urinary tract infections
Cyclophosphamide/Ifosfamide; radiation impacting bladder/urinary tract Bladder toxicity (hemorrhagic cystitis, bladder fibrosis, dysfunctional voiding, vesicoureteral reflux, hydronephrosis) History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
Urine culture, spot urine calcium/creatinine ratio, and ultrasound of kidneys and bladder for patients with microscopic hematuria (defined as ≥5 RBC/HFP on at least 2 occasions)
Nephrology or urology referral for patients with culture-negative microscopic hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio
Urology referral for patients with culture negative macroscopic hematuria
Refer to the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers for urinary late effects information including risk factors, evaluation, and health counseling.
Shnorhavorian M, Friedman DL, Koyle MA: Genitourinary long-term outcomes for childhood cancer survivors. Curr Urol Rep 10 (2): 134-7, 2009. [PUBMED Abstract]
Green DM: Evaluation of renal function after successful treatment for unilateral, non-syndromic Wilms tumor. Pediatr Blood Cancer 60 (12): 1929-35, 2013. [PUBMED Abstract]
Knijnenburg SL, Jaspers MW, van der Pal HJ, et al.: Renal dysfunction and elevated blood pressure in long-term childhood cancer survivors. Clin J Am Soc Nephrol 7 (9): 1416-27, 2012. [PUBMED Abstract]
Dekkers IA, Blijdorp K, Cransberg K, et al.: Long-term nephrotoxicity in adult survivors of childhood cancer. Clin J Am Soc Nephrol 8 (6): 922-9, 2013. [PUBMED Abstract]
Mulder RL, Knijnenburg SL, Geskus RB, et al.: Glomerular function time trends in long-term survivors of childhood cancer: a longitudinal study. Cancer Epidemiol Biomarkers Prev 22 (10): 1736-46, 2013. [PUBMED Abstract]
Interiano RB, Delos Santos N, Huang S, et al.: Renal function in survivors of nonsyndromic Wilms tumor treated with unilateral radical nephrectomy. Cancer 121 (14): 2449-56, 2015. [PUBMED Abstract]
Marina NM, Poquette CA, Cain AM, et al.: Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas. J Pediatr Hematol Oncol 22 (2): 112-8, 2000 Mar-Apr. [PUBMED Abstract]
Hartmann JT, Fels LM, Franzke A, et al.: Comparative study of the acute nephrotoxicity from standard dose cisplatin +/- ifosfamide and high-dose chemotherapy with carboplatin and ifosfamide. Anticancer Res 20 (5C): 3767-73, 2000 Sep-Oct. [PUBMED Abstract]
Skinner R, Parry A, Price L, et al.: Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors. Eur J Cancer 45 (18): 3213-9, 2009. [PUBMED Abstract]
Skinner R, Kaplan R, Nathan PC: Renal and pulmonary late effects of cancer therapy. Semin Oncol 40 (6): 757-73, 2013. [PUBMED Abstract]
Stöhr W, Paulides M, Bielack S, et al.: Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: a report from the late effects surveillance system. Pediatr Blood Cancer 48 (2): 140-7, 2007. [PUBMED Abstract]
Skinner R, Cotterill SJ, Stevens MC: Risk factors for nephrotoxicity after ifosfamide treatment in children: a UKCCSG Late Effects Group study. United Kingdom Children's Cancer Study Group. Br J Cancer 82 (10): 1636-45, 2000. [PUBMED Abstract]
Stöhr W, Paulides M, Bielack S, et al.: Ifosfamide-induced nephrotoxicity in 593 sarcoma patients: a report from the Late Effects Surveillance System. Pediatr Blood Cancer 48 (4): 447-52, 2007. [PUBMED Abstract]
Oberlin O, Fawaz O, Rey A, et al.: Long-term evaluation of Ifosfamide-related nephrotoxicity in children. J Clin Oncol 27 (32): 5350-5, 2009. [PUBMED Abstract]
Widemann BC, Balis FM, Kim A, et al.: Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol 28 (25): 3979-86, 2010. [PUBMED Abstract]
Cohen EP, Robbins ME: Radiation nephropathy. Semin Nephrol 23 (5): 486-99, 2003. [PUBMED Abstract]
Dawson LA, Kavanagh BD, Paulino AC, et al.: Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys 76 (3 Suppl): S108-15, 2010. [PUBMED Abstract]
Mitus A, Tefft M, Fellers FX: Long-term follow-up of renal functions of 108 children who underwent nephrectomy for malignant disease. Pediatrics 44 (6): 912-21, 1969. [PUBMED Abstract]
Bölling T, Ernst I, Pape H, et al.: Dose-volume analysis of radiation nephropathy in children: preliminary report of the risk consortium. Int J Radiat Oncol Biol Phys 80 (3): 840-4, 2011. [PUBMED Abstract]
Peschel RE, Chen M, Seashore J: The treatment of massive hepatomegaly in stage IV-S neuroblastoma. Int J Radiat Oncol Biol Phys 7 (4): 549-53, 1981. [PUBMED Abstract]
Ritchey ML, Green DM, Thomas PR, et al.: Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 26 (2): 75-80, 1996. [PUBMED Abstract]
Paulino AC, Wilimas J, Marina N, et al.: Local control in synchronous bilateral Wilms tumor. Int J Radiat Oncol Biol Phys 36 (3): 541-8, 1996. [PUBMED Abstract]
Cheng JC, Schultheiss TE, Wong JY: Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. Int J Radiat Oncol Biol Phys 71 (5): 1436-43, 2008. [PUBMED Abstract]
Hoffmeister PA, Hingorani SR, Storer BE, et al.: Hypertension in long-term survivors of pediatric hematopoietic cell transplantation. Biol Blood Marrow Transplant 16 (4): 515-24, 2010. [PUBMED Abstract]
Abboud I, Porcher R, Robin M, et al.: Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 15 (10): 1251-7, 2009. [PUBMED Abstract]
Ellis MJ, Parikh CR, Inrig JK, et al.: Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 8 (11): 2378-90, 2008. [PUBMED Abstract]
Breslow NE, Collins AJ, Ritchey ML, et al.: End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol 174 (5): 1972-5, 2005. [PUBMED Abstract]
Hamilton TE, Ritchey ML, Haase GM, et al.: The management of synchronous bilateral Wilms tumor: a report from the National Wilms Tumor Study Group. Ann Surg 253 (5): 1004-10, 2011. [PUBMED Abstract]
Riachy E, Krauel L, Rich BS, et al.: Risk factors and predictors of severity score and complications of pediatric hemorrhagic cystitis. J Urol 191 (1): 186-92, 2014. [PUBMED Abstract]
Kersun LS, Wimmer RS, Hoot AC, et al.: Secondary malignant neoplasms of the bladder after cyclophosphamide treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 42 (3): 289-91, 2004. [PUBMED Abstract]
Frobisher C, Gurung PM, Leiper A, et al.: Risk of bladder tumours after childhood cancer: the British Childhood Cancer Survivor Study. BJU Int 106 (7): 1060-9, 2010. [PUBMED Abstract]
Rosenbaum DH, Cain MP, Kaefer M, et al.: Ileal enterocystoplasty and B12 deficiency in pediatric patients. J Urol 179 (4): 1544-7; discussion 1547-8, 2008. [PUBMED Abstract]
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text about the mortality results of a study of female participants in the Childhood Cancer Survivor Study (CCSS) who were subsequently diagnosed with breast cancer and matched to a control group of women with de novo breast cancer (cited Moskowitz et al. as reference 49).
Added text to state that traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-aged survivors of childhood cancer. Also added text about a CCSS investigation that constructed prediction models accounting for cardiotoxic cancer treatment exposures, combined with information on traditional cardiovascular risk factors (cited Chen et al. as reference 24).
Added Heart Transplant as a new subsection.
Late Effects of the Central Nervous System (CNS)
Added text to state that in a baseline evaluation of 82 childhood CNS tumor survivors participating in a randomized controlled trial of neurofeedback, 48% of survivors endorsed sleep problems and scored significantly worse than the norm on the Sleep Disturbance Scale for Children in the subscales for initiating and maintaining sleep, excessive somnolence, and total scale. Emotional problems and/or hyperactivity/inattention were independent potential risk factors for sleep problems. Sleep problems were also associated with worse, parent-reported executive functioning (cited van Kooten et al. as reference 98).
Added text about a CCSS study that demonstrated that childhood cancer survivors are at increased risk of late anorectal disease after pelvic radiation exposure (cited Madenci et al. as reference 42).
Added text about the results of a CCSS investigation that evaluated the risk of diabetes mellitus among 20,762 5-year childhood cancer survivors and 4,853 siblings (cited Friedman et al. as reference 89).
Added text about how prediction models for low and very low bone mineral density were developed and validated using data from the St. Jude Lifetime Cohort and Erasmus Medical Center in the Netherlands (cited van Atteveld et al. as reference 58).
Added Kidney Transplant as a new subsection.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the late effects of treatment for childhood cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
be discussed at a meeting,
be cited with text, or
replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Late Effects of Treatment for Childhood Cancer are:
Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)
Melissa Maria Hudson, MD (St. Jude Children's Research Hospital)
Nita Louise Seibel, MD (National Cancer Institute)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Late Effects of Treatment for Childhood Cancer. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/childhood-cancers/late-effects-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389273]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.
|
cc/2020-05/en_middle_0097.json.gz/line35570
|
__label__cc
| 0.571644
| 0.428356
|
No one forgets the first time they visit Provincetown. The narrow and vibrant streets of Provincetown offer a cosmopolitan mix of people, restaurants and stores; the Harbor is bustling with fishing boats and whale watches; and the dunes and beaches beckon the adventurous with bike trails and romantic sunsets. Cape Cod Realtors offers best real estate property in Provincetown.
Flying Kites in Provincetown. Photo by Doug Azarian
The Pilgrims landed here first, then left for Plymouth in search of fresh water. Later, “P-town”, as it known today, was settled by early colonial settlers, and later, Portuguese immigrants, who came here in large numbers to work in the fishing industry.
Still later, Provincetown became, and still is, an artist’s colony. The thriving gay and lesbian community of Provincetown is a cornerstone of this town’s vibrant culture.
Many visitors to the Cape make a day trip to Provincetown to go on a whale watch and to see the Pilgrim Monument; others show up after sunset for the nightlife.
Day or night, Provincetown is a very popular destination for all.
Provincetown (pop. 2,950 off season, 60,000 in the summer) is where the Pilgrims first touched ground in 1620 and wrote America’s first constitution, the “Mayflower Compact”. After staying for 5 weeks they decided to travel on and ended up in Plymouth.
The town’s principal industries were whaling and deep-water fishing and it was called “Helltown”by locals. By 1921 the whaling industry came to an end. Today this offbeat town is a haven for artists and alternative culture. It has over 100 motels and inns and in the summer, its population swells to over 60,000.
Colorful Provincetown Harbor. Photo by Doug Azarian.
Over 30 miles of beach front include:
Race Point
Harbor Beach on Commercial Street
Long Point which is accessible by boat or, if ambitious, a 2 hour walk
If you enjoy the outdoors, you’ll love Provincetown! Cruise down Commercial Street taking in the sights or head out to the Cape Cod National Seashore for a real adventure. At the seashore, take a break from hiking and biking on the expansive paths and visit the Provincelands Visitors Center, Race Point Lighthouse (see calendar for tour dates) and the Race Point Life-Saving Station.
Lovers of history and the arts are in luck. Along with trendy shops and restaurants, Provincetown’s streets are packed with galleries featuring fabulously talented artists working in a variety of media.
Museums including the Pilgrim Monument & Provincetown Museum, the Provincetown Art Association & Museum and Expedition Whydah and other cultural centers including the Fine Arts Work Center, Provincetown Theater and Waters Edge Cinema, offer a variety of exhibits, programs, workshops, screenings and live shows.
Throughout the season, people from all walks of life head to Provincetown for some of the most interesting festivals in the area including the Provincetown Portuguese Festival & Blessing of the Fleet and Provincetown International Film Festival in June, Carnival Week in August and the Provincetown Tennessee Williams Theater Festival in September.
Streets of Provincetown. Photo by Doug Azarian. Information via CapeCodTravel.com
|
cc/2020-05/en_middle_0097.json.gz/line35572
|
__label__wiki
| 0.604135
| 0.604135
|
Palace of the Vampire Queen (Classic Reprint)
Precis Intermedia
Precis Intermedia brings back the first known commercially-published adventure for the original Roleplaying Game (First Edition/OD&D/0E; B/X recommended). Originally released in 1976 by Wee Warriors, Palace of the Vampire Queen is a 5-level dungeon with what was called pre-factored creatures and treasures (in other words, this is essentially a stocked dungeon). While hit points are provided for the creatures, the First Edition RPG or an OSR equivalent is required for actual rules and their descriptions.
For three centuries, the peasants of the Dwarvish island of Baylor have feared the raids of the Vampire Queen and her minions. Sweeping down at night from the palace in the shrouded peaks of the island, they range ever farther in their search for blood. The most recent victim was the Princess of Baylor, daughter of King Arman, who was taken in a midnight raid. King Arman has offered fabulous riches and land holdings with titles to the person or persons who can brave the stronghold of the Vampire Queen and return his daughter to him alive and well.
This piece of gaming history is a must for collectors and old school gamers. With the original on the extremely rare list, this classic reprint of Palace of the Vampire Queen has been remastered for a clean print, and is readily available at a low cost.
Note: SFW (safe for work) version of cover image is displayed by default, but NSFW (not safe for work) image can be toggled in the PDF (requires Adobe Reader or other PDF viewer that can handle layers).
Wee Warriors and Palace of the Vampire Queen are trademarks of Precis Intermedia. All rights reserved.
Preview this item before you buy!
Swords & Wizardry
Other OSR Games
Peter Kerestan, Judy Kerestan
D&D-OGL
Classic D&D/AD&D
1e (AD&D)
Basic/BECMI or OD&D
PLIWW003
This title was added to our catalog on December 12, 2019.
|
cc/2020-05/en_middle_0097.json.gz/line35578
|
__label__wiki
| 0.887712
| 0.887712
|
Ceres Negros finally wins in 7's FL
Home 7's Football League Bohemian Ceres football Ghana H&J All-Stars Super Eagles Tondo Ceres Negros finally wins in 7's FL
By Dugout Philippines
TAGUIG – Thrilling matches in the men’s seniors division highlighted Match Day 6 of the Season 3 Philam Life 7s Football League at the McKinley Hill Stadium.
After struggling to get the precious three points in the team standings for five straight weeks, Ceres-Negros Youth F.C. finally achieved a breakthrough win at the expense of Stallion Laguna, while Bohemian Sporting Club, H&J All Stars and Tondo F.C. all bounced back from previous losses with close victories.
Season 2 finalists Super Eagles and Ghana F.C. remain neck-and-neck at the top of the standings after successful outings yet again.
The two undefeated teams have been rivals from the beginning of the league, and the race to determine who the better team continues halfway in the elimination round.
Ghana F.C. routed Real Amigos, 6-2 while Super Eagles survived a brave stand from Delimondo-Laro F.C., 2-1.
“Like what I have said before, we know how to play, but as it stands now, we do have a lot of injured players on our list and with the way we played the games today, I know there are still a lot of work to do, we still have a lot of things to improve but I’m still going to assure that we will remain undefeated. We are the defending champions and we will still be the champions,” said Super Eagles head coach Danny Kross.
“We are not under pressure at all. We are not even thinking about Super Eagles, we are thinking about us. We don’t have competition; we are competing with ourselves. We make sure that every game, we play to our best knowledge. We have had lapses (last time) so we really prepared for this game, talked to every player that we have to step up. We controlled the game from the start, until the end, we didn’t underestimate our opponent” said Ghana F.C. head coach Ayi Bimbo.
After absorbing a tough loss against Futbol Funatics last week, Bohemian Sporting Club returned to winning form by defeating Matu Deportivo for a hard-fought, come-from-behind 2-1 win.
“We dominated most of the possession. Most of the game was played in Matu’s half. We just had to continue, take some more shots, try to open them up because they had all their seven players in their own half. Our wingers played wise, created more space and then just continue with our game plan,” said B.S.C. head coach Mikee Carrion.
The H&J All Stars recorded a hard-earned win over Superbad, 2-1, while Tondo F.C. relied on their rock-solid defense to escaped Futbol Funatics, 2-1.
Tondo opened the match scoring the first two goals and was close to tallying a shut-out as they deflected many of their opponents’ attempts in the second half.
A last-minute conversion from a bicycle kick by Abel Gboko prevented a clean sheet, but it wasn’t enough for Futbol Funatics.
“We talked about it in the huddle that this game is going to be a tough game. It is about toughness and durability so I shared to them a mantra that I also use during the game which is COCARECO, it means cool, calm, relaxed, and composed. I want them to play that constantly in their heads so that they can stay in focus,” said Tondo F.C.’s Peter Amores.
Ceres-Negros Youth F.C. ended their Season 3 drought with a 4-2 win over Stallions Laguna.
The match was tied 2-2 at the half before the eventual winners put on a show in the second half for their maiden win in the tournament.
“In training, we were told to work harder as a team. Being in a tournament such as this one, which is organized by some Azkals players, it motivates us to become better players, to become better for the upcoming leagues, it gives us the possibilities to join the big clubs such as Ceres and Kaya. Even if you lose some, you win some – it’s all part of the game, at the end it’s just a question of whether you give up or stand back up,” said Ceres Youth F.C. player Gael Papillon.
The 7s Youth League also kicked off with a brand new tournament featuring U9 and U13 teams, with eight playing in each age bracket.
Follow the site on Twitter: @DugoutPH
7's Football League Bohemian Ceres football Ghana H&J All-Stars Super Eagles Tondo
|
cc/2020-05/en_middle_0097.json.gz/line35585
|
__label__cc
| 0.60229
| 0.39771
|
RENAULT FLEET 2019
An incentive for a car manufacturer, Renault Italy, used to pamper and privilege its sales force. An award tool established over the years that allowed Renault to motivate and strengthen its team in a virtuous and original way.
Ega has created a unique and exclusive experience for the client in Lisbon, one of the most dynamic and evolving capitals of Europe. In just three days a complete itinerary was created allowing the Renault staff to visit all the most significant places in the city and also some unforgettable neighboring areas such as Sintra and Cascais.
The customer Renault Italy, having to reward an increasing number of segments of the sales force, found itself having to face a significant budget reduction, but with the necessity of maintaining the standard of an unforgettable experience.
Ega carried out numerous briefings with all the people involved in the decision-making process aimed to defining the incentive: purchasing department, marketing department, segment managers; establishing a daily collaboration that allowed the travel programme to be shaped on the authentic expectations of the participant . The result was to put on the field all the attention and some little tricks that made the team feel pampered.
Renault Italy had only 3 days to give its participants a unique experience in Lisbon, with a calibrated but not too stressful program.
Ega has designed and implemented a programme that allowed people to visit this wonderful city in its entirety, allowing the group to visit the most significant places in the Portuguese capital but in a comfortable and original way. Comfortable tours have been privileged, such as those through dedicated fascinating transport: old trams and boats, the original tuck tuck, on which small refreshments were always offered with typical Portuguese products. The group enjoyed the beauty of the metropolis to the full and without stress.
Renault Italia paid particular attention to the Gala evening in which the awarding of the sellers has taken place, with the need of a prize representative of the destination and also an original and aesthetically beautiful.
Ega came up with a venue that represents all the traditional and folkloristic soul of Portugal. The choice was the Pateo Alfacinha, a place that elegantly and accurately recreates a typical Portuguese village. A real village festival was staged with the band and the traditional dances with participants directly involved. For the prize was created a typical Portuguese azulejo, Portuguese tile, hand-decorated with the event logo and the name of the winner.
BEST SALES MAN
AMAZING DESTINATION: LISBON
Let’s build together your event, contact us
|
cc/2020-05/en_middle_0097.json.gz/line35589
|
__label__cc
| 0.713115
| 0.286885
|
Anna McKay
Thesis title: Textiles and Female Spirituality in Medieval English and Scottish Literature
PhD English Literature
Year of study: 3
School of Literatures, Languages and Cultures
Email: Anna.McKay@ed.ac.uk
PhD supervisor:
Dr Sarah Dunnigan
Anna is a third year PhD candidate working under the supervision of Dr. Sarah Dunnigan. Her research explores the significance of textiles as vessels for female devotional and artistic authority in the English and Scottish literature of the medieval period.
MScR English Literature (Distinction) - The University of Edinburgh
MA(Hons) English Literature (First Class) - The University of Edinburgh
Death and the Supernatural. The Third Annual Conference of Late Antique and Medieval Postgraduate Society at the University of Edinburgh. 16 June 2017. Organiser.
Papers delivered
"Thread and Blood: Weaving Christ's Body in John Lydgate's Lyf of Our Lady." International Congress on Medieval Studies 2019, Western Michigan University. 9-12th May 2019.
"'blessedly clothed with gems of virtue': Clothing and Female Reclusion in The Life of Christina Markyate and The Life of Mary of Egypt." International Anchoritic Society Conference 2018, University of East Anglia. 27-29th June 2018.
"'There is no friend like a sister': Rewriting the Medieval Minstrelsy Tradition in Christina Rossetti's 'Goblin Market' and Adelaide Procter's 'A Legend of Provence'." International Medieval Congress 2018, University of Leeds. 2nd-5th July 2018.
"Society's Cast-Offs: Material Culture and Female Reclusion in Medieval Hagiography." Scottish Graduate School of Arts and Humanities Symposium 2018: Alienation, Communication, Co-Existence, The University of Glasgow. 18th June 2018.
“The Veil of Veronica: the Imago Christi and Textile Culture in Anglo-Saxon Exeter." Late Antique and Medieval Postgraduate Society Autumn Seminar Series, University of Edinburgh. 28th November 2016.
This article was published on 16 May, 2019
|
cc/2020-05/en_middle_0097.json.gz/line35593
|
__label__wiki
| 0.615266
| 0.615266
|
by eplmatches · Published October 6, 2012 · Updated October 6, 2012
Manchester City returned to form with a deserved victory over Sunderland thanks to goals from Aleksandar Kolarov, Sergio Aguero and James Milner.
Watch English Premier League match, Man City Vs Sunderland highlights here.
Venue: Etihad Stadium
Date: Saturday, 6 October
Kick off: 12:45
1-0 Kolarov 5′
2-0 Aguero 60′
3-0 Milner 89′
Sunderland were the only team to come away unbeaten from the Etihad Stadium in last season’s Premier League after a 3-3 draw. They were the only top-flight team not to lose to City in 2011-12.
Before last season’s draw, Sunderland had lost on their previous seven visits to City.
Sunderland have never won a Premier League match at Manchester City. Their last away victory in this fixture came at Maine Road in January 1998, when Kevin Phillips scored the only goal of a second-tier game.
Manchester City are looking for back-to-back league wins for the first time this season.
Roberto Mancini’s side dropped just two points at home last season; they have already dropped the same number after just three home games in this campaign.
City and Sunderland are two of the three top-flight clubs not to have suffered a league defeat this season.
City are the first reigning champions in Premier League history to concede in each of their first six matches of the season.
Gareth Barry could make his 550th club career start.
Just as they did last season, Sunderland had to wait until their fifth league game for a victory – but, unlike in 2011-12, the Black Cats are unbeaten in their first five league matches.
Steven Fletcher, who was recalled to the Scotland squad earlier this week, has scored all five of Sunderland’s league goals so far.
The Black Cats’ victory over Wigan ended a run of 12 Premier League games without a win, Martin O’Neill’s worst run as a manager in the division.
Sunderland are the only team in the Premier League that have not gone a goal behind in any of their matches this season.
Tags: Manchester CitySunderland
Man City 0-0 Liverpool Highlights
Liverpool 2-2 Man City Highlights – Carling Cup
by eplmatches · Published January 25, 2012 · Last modified January 27, 2012
Club America 0-2 Man City Highlights
by eplmatches · Published July 17, 2011
Next story Chelsea 4-1 Norwich Highlights
Previous story West Ham 1-3 Arsenal Highlights
|
cc/2020-05/en_middle_0097.json.gz/line35594
|
__label__cc
| 0.621571
| 0.378429
|
How I Dress now: Charlie Siem
By The Fashion Editors
Marco Negri
From the March 2013 issue
The only downside to playing the violin is that you never know when you're going to be asked to play. I could be out to dinner or having a drink at a bar, and someone could just give me a violin and I've got to be ready to play. I'm always on duty, so I tend to wear suits. I've got double-breasted and single-breasted, mostly dark blues and grays. I'm obsessed with them, and I always have been.
I've also always had very specific tastes in terms of how those suits should look and feel. Where I went to school, Eton College, we had to wear dark trousers, a tailcoat, and a stiff, starched collar every day, and that was fine with me: Part of the reason I wanted to go there was because I've always loved dressing up. But I didn't necessarily like wearing those kind of suits — I wanted to wear my kind of suit. They had a thing at Eton called "formal change," which was when your tail suit had to be mended and you got to wear a blazer and a tie, or a suit if you had one. I always tried to wear one of my suits instead of my school dress. That was my way of expressing myself. That was my rebellion.
There was only one problem with my preference for dressing up all the time: To play the violin, I had to wear badly fitted jackets that allowed me to move the way I needed to move. And because I loved clothes and I loved to perform, this was a big problem. So when I was 19, I went to a tailor to get a proper tailor-made suit — something that would fix this problem of mine. And the suits he made me... no luck. So I went to another tailor a few years later — someone who made clothes for people who shoot and hunt — and he found a way to make me a structured, fairly close-fitting jacket with a slit in the back so that I could have full mobility in my shoulders to perform. It made all the difference in the world.
Right now I've got about 12 suits, and I'm quite simplistic in how I wear them. I wear white or pale-blue shirts and black knit ties: They don't draw attention to me in any kind of peacockish way. It's like I'm back wearing a uniform again, except this time it's one that I chose.
Carhartt WIP's New Collaboration With Awake
Where to Get This Week's Biggest Sneaker Releases
14 Shoes You Need Before Summer Starts
The 15 Best Chambray Shirts to Buy Now
At Pitti Uomo, the Fashion Shows Tell a Story
6 Accessories That'll Easily Enhance Your Outfit
Created for From Esquire for Created by Esquire for
These Boots Will Make You Look Forward to Rain
Jonah Hill Officially Confirms Adidas Partnership
Suitsupply's Outlet Sale Is Back
The Man Who Dresses the NBA Will Now Be Dressing You
Style Don'ts On Display in New Dumb and Dumber To Movie Poster
Style Across America: Palm Springs
Help, We're in a Living Hell and Don't Know How to Get Out
How to Make Pancakes from Scratch
How to Art Direct a Rock Star
|
cc/2020-05/en_middle_0097.json.gz/line35601
|
__label__wiki
| 0.937061
| 0.937061
|
Home » Modular Bridge to Reconnect Communities in Puerto Rico
TransportationSoutheast Construction News
Modular Bridge to Reconnect Communities in Puerto Rico
Six months after Hurricane Maria hit Puerto Rico on Sept. 20, landslides, broken traffic lights and reconstruction traffic make Edgar Iñesta’s commute halfway across the 100-mile-wide island a slow crawl.
PHOTO BY SCOTT BLAIR FOR ENR
Pam Radtke Russell and Scott Blair
KEYWORDS Bridge Construction / Modular Construction / Puerto Rico
Six months after Hurricane Maria hit Puerto Rico on Sept. 20, landslides, broken traffic lights and reconstruction traffic make Edgar Iñesta’s commute halfway across the 100-mile-wide island a slow crawl. It takes him five hours to make the round trip to Morovis, where he serves as project manager on a new bridge being built across the Manati River.
Iñesta is hardly alone. Of the 30 men at Del Valle Group working to replace the reinforced concrete bridge that was washed 300 ft downriver by the swollen river, several would normally have used the bridge in their daily commute, Iñesta says. Now, they, like the residents of Morovis, must either take treacherous hairpin-turn roads through the mountains to get to the site or ford the river.
In the days after Hurricane Maria, desperate residents walked across the river, carrying the sick residents of Morovis on their backs to hospitals.
It’s not simply the work that keeps the workers coming every morning. A sense of purpose and drive to restore the tropical paradise for its 3.4 million people may be the biggest motivator.
“This is a way to build back, but better,” says Carmelo Calderón, Del Valle vice president. “The community really appreciates our efforts here.” So much so that local residents have prepared lunch for the crew each day they’ve been on site since early January, he adds.
The $4.7 million bridge is built 1 ft above the river's 200-year-flood level and is built to withstand floodwaters. Del Valle President Humberto Reynolds says he took stock of what materials were on hand and told the designer to use those materials. In the days and weeks after the storm, lack of power stilled the production of aggregate and asphalt.
Though the bridge is considered a temporary structure by U.S. Department of Transportation, which took charge of the damaged local bridges and roads, it is built to last. The 8-meter-wide, three-span modular steel bridge, manufactured in Ohio by U.S. Bridge, was shipped in 17 containers to the site and assembled atop 40-ft-deep drilled shaft foundations using two cranes.
The trusses were aligned using digital surveying and workers had to check and double check the alignment before putting the sections together. "It was a challenge," Iñesta says. "There was no way of going back."
Employing design-build delivery, Del Valle changed the original foundation design to help speed construction, allowing the bridge to open in early April, Calderón says.
“The collaborative effort from, the contractors, the U.S. Government, and the people of Puerto Rico, has made this an extremely fulfilling project," said Todd Carpenter, bridge superintendent at U.S. Bridge, which built the Manati bridge and three others for the territory. "Knowing that our bridges are being used for connecting communities that were shattered, is something I’ll never forget. And these communities will use these bridges for generations to come.”
By Pam Radtke Russell and Scott Blair
Related Article: Six Months Later, Puerto Rico Recovery Inches On
Recent Articles by Pam Radtke Russell
John Abrera: Engineer Has Put Technology in Context for Water Plant Operators
Doug Houseman: Power Sector Veteran Has Pushed to Share Knowledge With A New Generation
Cris B. Liban: Sustainability Advocate Worked Nonstop to Prepare Infrastructure for the Future
Deputy Editor Pam Radtke Russell is a New Orleans-based journalist with more than a decade covering energy, environment and climate for ENR, Platts, CQ Roll Call in Washington D.C. and the Times-Picayune in New Orleans. She was part of the Times-Picayune team that worked from Baton Rouge after Hurricane Katrina and was awarded two Pulitzer Prizes for journalism in 2006 for public service and breaking news.
Blair manages day-to-day operations of the ENR editorial team to ensure brand quality, further best practices and support the editor-in-chief. He spearheads ENR's various competitions, including Best Projects and the Award of Excellence, and organizes editorial content at events including the Global Construction Summit. A Jesse H. Neal, Construction Media Alliance and AZBEES-award-winning writer and videographer, Blair frequently contributes to ENR’s burgeoning video channel with project tour videos and interviews with industry leaders. He is also a frequent speaker and moderator on topics such as design and jobsite technology, construction means and methods and marketing.
Texans Begin to Assess 'Breathtaking' Damage From Harvey
$2.5B Worth of Flood Control Work Underway in Puerto Rico
Kris Caldwell: Getting Power Back to the People in Puerto Rico
|
cc/2020-05/en_middle_0097.json.gz/line35606
|
__label__wiki
| 0.822767
| 0.822767
|
Home » John Lavelle: Engineer CEO Led GE Team Launch of 'Gamechanging' Offshore Wind Turbine
Top 25 NewsmakersAwards2019Power & IndustrialSustainabilityCompaniesEnvironmentProjectsRisk
ENR 2019 Top 25 Newsmakers
John Lavelle: Engineer CEO Led GE Team Launch of 'Gamechanging' Offshore Wind Turbine
Lavelle addresses press conference at GE’s Francebased manufacturing plant flanked by the 600-tonne nacelle of the firm’s giant 12-MW Haliade-X offshore wind turbine launched last year. The nacelle’s thrust generation “is equal to a Boeing 737 with four engines,” says the CEO of GE’s offshore wind production unit.
IMAGES COURTESY GE RENEWABLES
Debra K. Rubin
KEYWORDS ENR Newsmakers
John Lavelle, a 37-year veteran of U.S. manufacturing pioneer General Electric, admits the behemoth’s move into clean energy manufacturing “is not for the faint of heart.”
But the CEO of its growing offshore wind unit has high hopes the corporation’s $400-million investment in the record-setting Haliade-X giant offshore wind turbine will net big rewards in carving a role for GE in what is seen as a $30.5-billion global turbine market by 2025, and as an emerging design and construction arena in the U.S. and abroad.
While the aviation and power sector innovator has had its financial challenges in recent years, Lavelle says GE is betting on its R&D and manufacturing prowess in clean energy.
“Not many companies can do this, but we can do it with confidence because we have done it before,” says the mechanical engineer. "While it’s been a challenge designing a turbine that has the largest rotor and biggest blades on the market, it’s been a much more manageable challenge because we’ve been able to draw on the research and engineering capabilities of all of GE ... to bring the Haliade-X from design to reality."
Lavelle took over the offshore unit in 2016 and led a 600-person corporate team launch of the nearly 850-ft-tall turbine with three rotors each spanning about 720 ft. and an industry leading capacity factor of 63%, he says.
"The ability to produce more power from a single turbine means a smaller number of turbines in the total farm, which translates to less expenditure for the plant and reduced risk in project execution, as installation time is reduced," Lavalle notes. "It also simplifies operation and maintenance. All of this reduces the investment and operation cost for developers, makes offshore wind projects more profitable, and ultimately lowers the cost of electricity for consumers."
Said Lavelle atr a recent industry event: “Haliade-X’s thrust generation is equivalent to a Boeing 737 with four engines." GE estimates that a single turbine can power up to 15,000 homes.
The mega-machine now is being subject to tough operating tests in Holland, the U.K. and at Boston’s Clean Energy Center. Once testing is complete, GE expects to begin serial manufacturing in time to ship orders in 2021 for wind farms in the U.S. and elsewhere that are set to begin commercial operation in 2022. Lavalle says GE is "on track" to gain all certifications needed to commercialize Haliade-X by next year.
The turbine, whose names derives from Greek mythology, already is winning more current plaudits, including its selection by Time magazine in 2019 as one of the world’s best inventions, with the media outlet terming it “a piece in the puzzle to slow global heating.”
More critically, Haliade-X and GE are moving the U.S. into the European-dominated turbine marketplace.
The machine will make its global commercial debut in America, purchased by mega-developer Orsted to power two East Coast wind farms, including the 1,100-MW Ocean Wind project in offshore New Jersey.
“Addition of 12-MW turbines … positions us to further improve reliability of energy produced by green, offshore wind in the U.S.,” says Orsted North America President Thomas Brostrom.
The turbine’s appeal also crossed the Atlantic, with its selection last year to power the U.K.’s record 3.6-GW Dogger Bank project. GE also has committed to build a new Haliade-X manufacturing plant in China.
Right Time
Lavalle credits past senior roles at GE such as managing its Global Project Organization's $75-billion backlog that have helped him "better understand the global characteristics of the offshore world market and recognize the important role that game-changing technologies, such as the Haliade-X, can make in positioning GE" to serve worldwide customers.
"Growth will be driven by the compelling value proposition of offshore wind, which is a clean, renewable source of reliable power near high concentrations of population in coastal cities that need power and are particularly sensitive to the impact of climate change," says Lavelle "Technology step changes like the Haliade-X are driving down the cost of generating power from offshore wind dramatically, further helping it to compete with other sources of power generation."
GE has been selected preferred wind turbine supplier for 4.8GW of potential projects, "which demonstrates the confidence they have in this new technology," the CEO contends. "This is one more sign that the Haliade-X is the right turbine at the right time."
Even with competitive pressure keener and returns far out, market analyst Wood Mackenzie sees recent Haliade-X deals as a “promising restart” for GE in a new power sector.
For Lavelle, a Holyoke, Mass., native now based in Nantes, France, “this business is a personal as well as a professional endeavor. I want to leave an energy system to my children and grandchildren that is cleaner, safer and more sustainable.”
Back to ENR's 2019 Top 25 Newsmakers
Recent Articles by Debra Rubin
Ryan Keith Cox: Va. Beach City Employee Died Leading Coworkers to Escape Workplace Terror
The Biggest Construction Stories of the Decade
As ENR Editor-at-Large for Management, Business and Workforce, Debra K. Rubin has a broad vantage for news, issues and trends in global engineering, architecture and construction—from corporate finance and executive management to regulation and risk, next-generation workforce and developing markets such as offshore wind energy.
Debra also launched and manages ENR's Top 200 Environmental Firms ranking, which defines a $51-billion global market; is editor of ENR WorkforceToday e-newsletter on industry talent management; and supervises content for the Industry Buzz page, which leads ENR’s monthly Contractor Business Strategy report. She also is an organizer of ENR's annual Groundbreaking Women in Construction conference, a major AEC industry forum for talent management and women's career advancement.
Click here for more detail on the 2019 conference in May in San Francisco and plans in formation for the 2020 event.
Debra's reporting for ENR on the 2001 Ground Zero attack damage, response and recovery earned a Jesse B. Neal award from B2B media giant Connectiv and is featured in the National September 11 Memorial & Museum in New York City.
Design Firm CEO Leads Team to 'Super Bowl' of Dam Projects in Missouri
Startup of First U.S. Offshore Wind Farm Propels Domestic Market
Expert Crossed the Pond to Build America's First Offshore Wind Farm
A Golden Age? Energy Outlook 2019
|
cc/2020-05/en_middle_0097.json.gz/line35607
|
__label__cc
| 0.706874
| 0.293126
|
Wendi Lou Lee
{Featured}
Devotionals Daily
Let the redeemed of the Lord tell their story,
those He redeemed from the hand of the foe.
— Psalm 107:2 NIV
In our Western culture we seldom have enemies hunting us down. At least not the kind of enemies we read about in the stories of the Bible — Pharaoh pursuing the Israelites or Saul chasing David. What we do have is troubles — relationship troubles, health problems, loss and grief, feelings of loneliness and hopelessness. At times our troubles can seem so overwhelming that we wonder where God is and what possible purpose He could have. Our faith dwindles as we envision a grim future or a poor outcome.
Surrender the Fight
In 2015, I found myself face-to-face with an enemy I never expected. Only 38 years old and with two young children, I sat in the doctor’s office trying to absorb the diagnosis: the excruciating headaches, deep fatigue, confusion and dizziness — a brain tumor. The tumor had to come out and quick, with further testing needed to reveal whether it was cancerous. From the get-go, I had a decision to make: rail against God and attempt to power through in my own strength or accept God’s sovereign will, surrendering the fight to the One who held my future in His hands.
My foe appeared powerful, but it didn’t compare to the God of the universe beside me.
As I lay my troubles at His feet, an unexpected calm enveloped me. It’s tempting to clench onto our lives, to grasp for what our hands can never hold. Scripture tells us that God alone holds the world together, in hands big enough to change the course of history through His Son. He cared enough to redeem us, and He cares enough to hold us right alongside the stars and galaxies.
Pry open your clenched hands. Surrender to His ways, even when they don’t make sense. We can rest assured that God’s plan is perfect; His promises prove true (Psalm 18:30). Then wait and watch the story of His love and grace unfold.
As my hospital bed rolled into the operating room, the peace of God filled my heart. Surrendering the outcome to His perfect will freed me to breathe easy and trust that He was in control. I woke up grateful to be alive, grateful to remember my family and friends, but most of all, grateful to have a story of His faithfulness. Even while we waited for the biopsy results, God was faithful — yet again.
Share with Courage
God redeems even the internal villains of our lives, writing a story so grand we stand in awe, and then He gives us the courage to share our story. Telling others encourages them to trust their troubles to Jesus, the One who stands beside us.
Written for Devotionals Daily by Wendi Lou Lee, author of A Prairie Devotional.
What foes are you battling? How can you release your grip of control and surrender your future to God? What story of God’s faithfulness does your friend or neighbor need to hear? Come share with us on our blog. We want to hear from you! ~ Devotionals Daily
Relive Little House on the Prairie nostalgia with the original Baby Grace
photo credit: Jackie Juchniewicz
For Wendi Lou Lee,the four seasons she spent on Little House on the Prairie playing Baby Grace Ingalls alongside her twin sister Brenda are among God’s greatest blessings. Her good but hard life resembles what the Ingalls family experienced—great joys and sorrows. In 2015, Wendi was diagnosed with a brain tumor. Her surgery and recovery led to a newfound freedom. Sharing her story of God’s goodness through life’s most difficult circumstances brings Wendi the most joy. Learn more about Wendi through her website (wendiloulee.com) or by reading her new book, A Prairie Devotional!
Wendi Lou Lee is a Jesus follower, an actress, and a brain surgery survivor. The four seasons she spent on Little House on the Prairie playing Baby Grace Ingalls are among God’s greatest blessings. Her good but hard life resembles what the Ingalls family experienced—great joys and sorrows. In 2015, Wendi was diagnosed with a brain tumor. Her surgery and recovery led to a newfound freedom. Sharing her story of God’s goodness through life’s most difficult circumstances brings Wendi the most joy.
Follow Wendi Lou Lee on: Facebook Website
Like the article? Share it!
Gluten-Free Pasta: The Failure of Perfection
3 Devotions You Can Read In 3 Minutes from Anne Graham Lotz
I’m Scared to Pray Boldly
|
cc/2020-05/en_middle_0097.json.gz/line35612
|
__label__wiki
| 0.909641
| 0.909641
|
As it happened: Erdogan wins Turkey presidential election
Recep Tayyip Erdogan will be Turkey’s next president after being declared the winner of the country’s presidential election. With more than 50% of the vote in his favour, there will be no need for a second round run-off vote.
Erdogan’s main opposition rival Ekmeleddin Ihsanoglu (CHP and MHP) has conceded defeat and congratulated Erdogan, the current Turkish Prime Minister, who has won around 52 percent of the vote according to the latest results, 13 percent more than Ihsanoglu. Selehattin Demirtas (People’s Democratic Party) is in third place with less than 10 percent of the vote.
Follow all the updated results and reaction below.
Ekrem Imamoğlu easily elected new mayor of Istanbul after repeat poll
Turkish opposition: Nothing will be the same after Istanbul win
UK general election 2019: What are the key seats to watch?
Turkish Presidential Election 2014
|
cc/2020-05/en_middle_0097.json.gz/line35614
|
__label__cc
| 0.504111
| 0.495889
|
EUSEM Membership
We invite you to join the growing community of those committed to promoting and improving Emergency Medicine in Europe.
8 Good reasons to become an EUSEM member
1. Become closely involved in the development of the specialty of Emergency Medicine in Europe
2. Discounts on registration fees at EUSEM congresses and other events proposed by EUSEM
3. Reduced fees for participation in EUSEM training courses
4. Reduced fees when you apply for EBEEM (European Board Examination in Emergency Medicine)
5. Free access to EUSEM Academy, EUSEM's e-learning platform
6. Free access to the presentations of the congress
7. Annual online subscription to the European Journal of Emergency Medicine
8. Participation in EUSEM scientific activities, including positions in Sections and Working groups
Apply for membership!
Current Fellows and Honorary Fellows
Membership Category Fee Category Fee (annual)
Member * Member without Journal €100
Member + Online Journal €175
Member + Hard copy of Journal €225
Member in training without Journal €50
Member in training + Online Journal €90
Member in training + Hard copy of Journal €140
Currency-restricted European countries ¹ Member without Journal €50
Currency-restricted European countries ¹ Member + Online Journal €90
Currency-restricted European countries ¹ Member + Hard copy of Journal €140
Currency-restricted European countries ¹ Member in training without Journal €25
Currency-restricted European countries ¹ Member in training + Online Journal €54
Currency-restricted European countries ¹ Member in training + Hard copy of Journal €104
Associate Member ** Associate Member without Journal €100
Associate Member + Online Journal €175
Associate Member + Hard copy of Journal €225
Currency-restricted European countries ¹ Associate Member without Journal €50
Currency-restricted European countries ¹ Associate Member + Online Journal €90
Currency-restricted European countries ¹ Associate Member + Hard copy of Journal €140
Nurse, Paramedic, EM-technician without Journal €25
Nurse, Paramedic, EM-technician + Online Journal €54
Nurse, Paramedic, EM-technician + Hard copy of Journal €104
Medical student without Journal €25
Medical student + Online Journal €54
Medical student + Hard copy of Journal €104
Fellow *** Fellow + Online Journal €260
Fellow + Hard copy of Journal €310
Currency-restricted European countries ¹ Fellow + Online Journal €135
Currency-restricted European countries ¹ Fellow + Hard copy of Journal €185
* Physicians who work within a structure providing pre-, inter-, and/or in-hospital emergency medical care in Europe (including Israel) and physicians in training in EM or interested in EM.
** Physicians and non-physicians who are interested in the practice of Emergency Medicine and who are not eligible for any other category OR physicians practising outside Europe who work within a structure providing pre-, inter-, and/or in-hospital emergency medical care. Associate members do not have voting rights.
*** For details on eligibility for EUSEM Fellowship, please click here.
¹ Albania, Armenia, Azerbaijan, Belarus, Bosnia & Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Kazakhstan, Latvia, Lithuania, Macedonia (FYR), Moldova, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, Turkey, Ukraine
Please note that ‘currency-restricted country’ refers to the country in which you are currently working and not to your country of origin.
Your membership begins on the day of your first payment and ends one year later.
You may cancel your membership at any time by writing to This email address is being protected from spambots. You need JavaScript enabled to view it.. Fees already received will not be refunded. We therefore recommend that you take advantage of your membership benefits until the end of your membership year. As long as no cancellation notice has been received, you will continue to be considered a member of EUSEM.
A reminder to pay your next year’s membership fee will be sent to you well in advance of the end of the current membership year.
Becoming a Fellow of the European Society for Emergency Medicine (FESEM)
In 2010, a new category of membership of the European Society for Emergency Medicine was introduced, namely ‘Fellowship of the European Society for Emergency Medicine’. This new category of ‘Fellowship’ is in keeping with the practice of other medical Colleges and Societies worldwide and is intended to recognise those long standing full members of EUSEM who have made substantial contributions of distinction to the Society and to the community of European Emergency Medicine. (Associate members are not eligible)
Prospective Fellows will be entitled to apply for election after no less than five (5) years of continuous Membership. Candidates for Fellowship will be expected to demonstrate their substantial contributions to European emergency medicine (such activities may include national EM development in Europe; development of teaching or research in their country or Europe-wide; significant contributions to European EM work such as curriculum development; or significant and sustained contributions to the European Journal of Emergency Medicine).
All applications for Fellowship will be assessed by the Fellowship Committee. Applicants who are not successful in their application will be permitted to re-apply not less than two years after their previous application.
Fellows will be entitled to
Use the post-nominal letters FESEM
Have their names listed on the EUSEM website as Fellows
Eligible for (an encouragement to lead and participate in) sections and working groups and committees
Applicants who are successfully elected to the Fellowship will be expected to continue to pay their appropriate annual subscription.
To apply for Fellowship of EUSEM, please fill in the application form that you can find here, and email it to This email address is being protected from spambots. You need JavaScript enabled to view it..
Honorary Fellowship of the European Society for Emergency Medicine (Hon FESEM)
In 2010, a new category of membership of the European Society for Emergency Medicine was introduced, namely ‘Fellowship of the European Society for Emergency Medicine’. In line with this, the current category of ‘Honorary Membership’ will be replaced with the category of ‘Honorary Fellowship of the European Society for Emergency Medicine’ in keeping with the practice of other medical Colleges and Societies worldwide.
The purpose of the Honorary Fellowship is to recognise a significant and sustained contribution to the development of EUSEM.
Honorary Fellows will be intitled to:
Use the post-nominal letters HonFESEM
Have their names listed on the EUSEM website as Honorary Fellows
No membership fee for EUSEM for life
Free registration for the EUSEM Congress in the year of the Honorary Fellowship award
Have a reduced rate for EUSEM Congress registration, namely the standard EUSEM member discount
New Honorary Fellows shall receive a Certificate of Honorary Fellowship of EUSEM signed by the President and Secretary of EUSEM at the following Annual General Meeting.
Current Fellows of EUSEM Country Since
Professor Diana Cimpoesu Romania May 2014
Dr Thomas Fleischmann Germany October 2013
Dr Christian Hohenstein Germany July 2013
Dr Luc Mortelmans Belgium October 2011
Professor Joseph Osterwalder Switzerland February 2013
Professor Riccardo Pini Italy September 2018
Dr Jana Seblova Czech Republic September 2018
Professor Ives Hubloue Belgium October 2019
Assoc. Prof. Lars Petter Bjoernsen Norway October 2019
Professor Mikkel Brabrand Denmark October 2019
Current Honorary Fellows of EUSEM Country Since
Professor Helen Askitopoulou Greece October 2010
Dr Gautam Bodiwala United Kingdom October 2011
Professor Francesco Della Corte Italy
Professor Herman Delooz Belgium February 2005
Professor Wolfgang Dick Germany
Professor Juliusz Jakubaszko Poland October 2010
Dr Keith Little United Kingdom
Professor Patrick Plunkett Ireland October 2012
Dr David Williams United Kingdom September 2008
Professor David Yates United Kingdom October 2006
Professor Marc Sabbe Belgium September 2017
Professor Gunnar Ohlen Sweden 2014
Dr Barbara Hogan Germany September 2018
Professor Abdelouahab Bellou France September 2018
Dr Roberta Petrino Italy October 2019
Professor Colin Graham Hong Kong October 2019
|
cc/2020-05/en_middle_0097.json.gz/line35615
|
__label__wiki
| 0.895755
| 0.895755
|
Paekakariki
NZ String Quartet | Celebrate 400
Sun 1 Dec 2019, 3:00pm–4:30pm
Where: Paekakariki Memorial Hall, 98 The Parade, Paekakariki, Kapiti Coast
Adult: $38.88 ($35.00 + $3.88 fees)
Concession: $33.75 ($30.00 + $3.75 fees)
Student: $16.38 ($15.00 + $1.38 fees)
Child: $5.12 ($5.00 + $0.12 fees)
Adult group concession: $38.88 ($35.00 + $3.88 fees)
Eventfinda tickets no longer on sale
New Zealand String Quartet
Listed by: New Zealand String Quartet
400 years ago – before the birth of Bach, Vivaldi, or Handel – the renowned instrument-maker Nicolò Amati crafted an exquisite viola in his Italian workshop. Is this marvellous Amati viola now the oldest string instrument in New Zealand? The New Zealand String Quartet believe so!
Now played by the New Zealand String Quartet’s violist, Gillian Ansell, the ensemble will give two concerts in Wellington and Paekakariki in November and December to celebrate this astonishingly rare instrument’s 400 years. Performing works by Mozart, Brahms, Beethoven, Vieuxtemps, and New Zealand composers Jack Body and Salina Fisher, join the NZSQ to experience history in action. After the concert, join the NZSQ for tea and cake to celebrate this unique occasion.
With a gloriously sweet sound, the Amati viola is a joy for Gillian to play. She explains ‘I would love to know everything about its history, who has played it and where, in which European court orchestras – maybe it was involved in the first performance of a Bach cantata, Mozart opera or a Beethoven symphony!’
The Amati viola arrived in New Zealand in 2017 and is generously loaned to the New Zealand String Quartet by the Adam Foundation.
Praised as "a quartet to match the finest anywhere" (The Australian), the New Zealand String Quartet has gained an international reputation in its 32-year history for insightful interpretations, compelling communication, and dynamic performing style. The NZSQ perform nation-wide each year and regular worldwide tours have included prestigious concerts at London’s Wigmore Hall, New York’s Frick Museum, and Washington’s Library of Congress. The NZSQ are Quartet-in-Residence at the New Zealand School of Music and have recorded extensively for Naxos.
Mozart String Quartet No. 23 in F Major, K 590: Movement 1, Allegro Moderato
Henri Vieuxtemps 'Capriccio' for solo viola
Beethoven String Quartet No. 16 in F Major, Op. 135: Movement 1, Allegretto
Salina Fisher, 'Reflect' for solo viola
Brahms String Quartet No. 3, Op. 67: Movement 3, Agitato
Beethoven String Quartet No. 10 in E-flat Major, Op. 74 “Harp”: Movement 2
Jack Body 'Three Transcriptions'
Beethoven String Quartet No. 9 in C Major, Op. 59/3: Finale
Concert duration - 1.5 hours (no interval)
General admission - no pre-allocated seating
Concerti Grossi - Southern Baroque Ensemble
St Patrick’s Church, Greymouth, Grey
Mon 17 Feb 7:30pm
St Lukes Anglican Church, Oamaru, North Otago
Sat 15 Feb 6:00pm
St Pauls Cathedral, Dunedin, Otago
St Mary's Basilica, Invercargill, Southland
Thu 13 Feb 7:30pm
The Piano: Centre for Music and the Arts, Christchurch
|
cc/2020-05/en_middle_0097.json.gz/line35617
|
__label__wiki
| 0.65961
| 0.65961
|
NovemberNov 20, 1991
Roubaix, France
NovemberNov 20, 1991 (age 28)
Born in Roubaix, France#2
28 Year Old Soccer Player#37
Soccer Player Born in France#43
Scorpio Named Anthony#8
Attacking midfielder who was named the Young Player of the Year after scoring the Goal of the Season for Leicester City in 2013.
He played 12 seasons of youth soccer before making his professional debut with Guingamp at age 18.
He played internationally for France at the U20 and U21 levels.
He was raised in Roubaix, France with three siblings.
He became teammates with David Nugent on Leicester City FC in 2012.
Anthony Knockaert Popularity
Anthony Knockaert Is A Member Of
Brighton & Hove Albion F.C.
First Name Anthony
Anthony Knockaert Fans Also Viewed
Soccer Player Trivia Games
More November 20 Birthdays
Michael Clifford
November 20 Birthdays
More Scorpios
RiceGum
Scorpios
|
cc/2020-05/en_middle_0097.json.gz/line35619
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.