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When it comes to predicting future costs associated with changes in the environment and natural resources, Robert Whaples says economists and policy makers have a spotty track record and should back off their pretensions of certainty. Economic models are "built on quicksand."
Whaples, who is co-editor and managing editor for The Independent Review says, "The economic projections are shaky" not because of whether or not the science is correct but "because estimates cannot account for future unknown factors." He says the historical record shows the unreliability of connecting an environmental change with an economic outcome. "Many pundits said $100 a barrel oil was here to stay, but globalized, integrated markets and new technologies blindsided these experts. These same forces make it nearly impossible to put a number – or even a ballpark range – to how much rising seas or climate change will cost our country."
Whaples can analyze issues ranging from employment trends to labor wages to worker productivity, and he isn't afraid to take a stand on the financial benefits of eliminating the penny. If the mint stopped making pennies, he argues the U.S. could save $900 million per year.
Having provided expert analysis for leading outlets such as The New York Times, Bloomberg News, Associated Press, U.S. News and World Report, and USA Today, Whaples can explain a wide range of policy issues such as eliminating trade barriers, mandating health insurance, subsidizing sports stadiums, and changing the income tax code to eliminate mortgage interest deductions.
Areas of Expertise (8)
Economic History of the U.S.
Employment and Unemployment
History of Labor Markets
Minimum Wage
Walmart and Big Box Retailers
Economics of Climate Change
Economics of Natural Resources
Elimination of the Penny
Education (2)
University of Pennsylvania: Ph.D., Economics 1990
University of Maryland-College Park: B.A., Economics and History 1983
Affiliations (3)
- EH.Net Encyclopedia of Economic and Business History: Editor
- Historical Perspectives on the American Economy (Book): Editor
- The Independent Review: Managing Editor Co-Editor
Media Appearances (5)
Two bills aim to raise minimum, subminimum wages
The Brown Daily Herald
While the majority of Americans are in consensus, economists seem divided on the issue, with 47 percent of economists with PhDs supporting the elimination of the minimum wage, 14 percent in favor of maintaining it at its current level and 38 percent in favor of increasing it, according to a 2006 survey by Robert Whaples, professor of economics at Wake Forest University...
Three myths of the Modern Age
The Real Truth
"And we're working a lot less than our grandparents, great grandparents and earlier generations. The average work week for a manufacturing employee in the 1860s was 62 hours, according to a paper from Robert Whaples, an economist at Wake Forest University."...
Would consumers lose money if U.S. dropped the penny?
The Wall Street Journal
However, in 2006, Robert M. Whaples, a Wake Forest University professor of economics, examined a week's worth of transactions at 20 gas stations and convenience stores in seven states, rounding cash purchases with tax to the nearest zero or five cents — and found that customers and merchants broken even. Mr. Whaples notes in his study that customers who purchase a single item with a price of less than $1 and ending in the nine digit were the "big losers," but in his sample, those types of purchases were atypical...
Is the US getting rid of the penny?
Fox Business
But, a more recent study from Wake Forest University economist Robert Whaples called those findings into question because they failed to account for factors that randomize the direction of rounding, such as sales tax and the purchase of multiple items. According to Whaples, consumers wouldn't see a price shift in either direction if the penny were eliminated...
Why we're working less than our parents did
CNN Money
And we're working a lot less than our grandparents, great grandparents and earlier generations. The average work week for a manufacturing employee in the 1860s was 62 hours, according to a paper from Robert Whaples, an economist at Wake Forest University. In the 1600s, there were actually laws requiring a minimum work day, wrote Whaples. In parts of the country, most people had to work sun up to sundown -- part of the Puritanical "idle-hands-are-the-devil's-workshop" ethos...
Articles (8)
The Independent Review's Winter 2016 symposium ponders the state of the economy fifty years from now. While our authors are largely optimistic, pointing to vast potential economic gains from new technologies and innovations, they also warn that government debt, regulation, and social problems could obstruct the arrival of a prosperous future.
The intellectual underpinning of a government-guaranteed basic income fails to overcome several objections on historical, economic, and moral grounds. But if it ever did, the adoption of a basic-income guarantee would deserve only cautious consideration because major policy changes always have numerous unknown and often irreversible consequences.
Old Hickory was a disaster for slaves and Native Americans, but from the perspective of the early-nineteenth-century electorate his policies were better than most. He curbed the growth of government, increased competition in the financial sector, and, most importantly, made resources more available to citizens by helping to put fertile land into the hands of the voting public.
Social Security funds and expenditures will become unsustainably large within the next fifty years if current policies remain unchanged. In addition, they may be reaching a consensus that increasing the normal retirement age is the best way to deal with this problem—but ...
This article examines where consensus does and does not exist among American economic historians by analyzing the results of a questionnaire mailed to 178 randomly selected members of the Economic History Association. The questions address many of ...
What do economic historians do? I analyze quantitatively The Journal of Economic History's contents since its founding, showing subfields, nations, and periods studied, and which scholars and universities have contributed. The timing, extent, and participants of ...
Over 70 years ago Samuel Gompers summarized the desires of American workers in one word: "more." Workers still want more—more money, more job security, larger benefits and pension packages, and more freedom on the job. Before World War II the demand for ...
The American workers' quest for an eight-hour day finally came to an end around 1919. I argue that the most important factors behind the rapid decline in manufacturing hours in the decade before 1919 include the rapid expansion of the economy, which increased ...


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Earlier in the week I heard Fergie was coming back which I love . Of course queen Nicki Minaj is featured on this track as well "You Already Know. " The beat is so dope, and Fergie vocals slay. Nicki rode the beat like a cruise ship.
What makes more sense than Taylor Swift making a comeback on the week rival Katy Perry drops her new music video for her diss to Taylor and Fergie makes a comeback.... None. Taylor has debuted a lyric video to her song "Look What You Made Me Do. With the split from Calvin Harris, and Kim Kardashian calling her out it fits. This single so far has mixed reviews. It is one of her darker songs. I'm interested to see the tone for the following single.


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[☆ The White Dragon || ↠ PDF Download by ✓ Anne McCaffrey] 458 Anne McCaffrey
Title: [☆ The White Dragon || ↠ PDF Download by ✓ Anne McCaffrey]
Posted by:
Published :2020-06-22T14:53:21+00:00
About "Anne McCaffrey"
356 thoughts on "The White Dragon"
Okay, wow, I had forgotten how unpleasant I find Jaxom about half the time He s a sympathetic character in that he gets to do all this cool stuff, but the internal monologue and motivations McCaffrey gives him are kind of tool y His distress over having no one real place where he fits is deeply appealing, but the way he whines about it is not Also, hi dodgy gender issues, how I didn t miss you They re prevalent enough in the Lessa books and the Menolly books, almost negligible in Piemur s book, [...]
No extra points in the rating for the awesome dragons and unique world this time around The shine of Pern has worn off, and all that s left is the author s writing In that regard, this book was pretty lackluster.I had a lot of hope for Jaxom and Ruth after Dragonquest I was pretty much completely disappointed Jaxom is a whiny, bratty kid that I had absolutely no investment in In fact, I actively want him to fail Characters that are special and wonderful at everything just for the sake of it anno [...]
The White Dragon wraps up the Dragonriders of Pern trilogy quite neatly however, pretty much everyone knows that it isn t the end for Pern Although the series got off to a slightly rough start, it actually got much better as it went on If you re a fan of science fiction, and you ve never read anything by Anne McCaffrey, what are you waiting for Give her books a chance
Sometimes the runt is important than anyone thought.
Oh, my gosh I read this over and over in sixth grade, giggling naughtily all the while Good grief, Jaxom and that buxom farmer s sister I think I read this before any of the other Pern books, though I had read DRAGONSINGER I loved Ruth, and the idea of a dragon who was just big enough to ride, but small enough to be kept at home.
As much as I loved the first two books of the Dragonriders of Pern series, The White Dragon remains my favorite And not because of Jaxom, whom I never liked as a lead character protagonist Ruth was my favorite character Ruth, the stunted runt totally unique White Dragon The archaeological discoveries on the Southern Continent at the original landing site are the most memorable and compelling parts of this installment in the saga of Pern And Ruth s abilities to manipulate time and space are unpar [...]
This is basically a review of the three books that make up the trilogy There actually was a book between books two and three that I m not counting, but which do introduce several characters in this book, but I m not counting it as one of the main books because that book was originally published as YA and it wasn t available at my local library.I prefer to review the books as they exist, and not the book I d wished someone had written I also think that if a book is part of a series that is than [...]
After Anne Mcaffrey died late 2011 I rooted around in my bookshelves for all my old pern paperbacks from the early 80 s I was utterly obsessed with these books when I was a young teenager, and they were extremely formative in my own history as a writer The first novel I ever wrote longhand, in mead spiralbound notebooks was a thin knockoff of Dragonflight I seem to remember it had unicorns, but I m so embarrassed by that book I haven t managed to actually read enough of it to check I reread all [...]
10 2014 Reread The continuing adventure with Don to rediscover Pern I love Ruth I love Jaxom They are pleased to see us in the air together Ramoth and Mnementh are very happy to see you on my back at last I am very happy Are you happier now And fire lizards I forgot how jam packed the Pern stories were Ruth and Jaxom s maturation is only a small portion of what happens as the politics expand, problems inflate and then are resolved, but really the bond between the two is what drove the book for m [...]
Summer Fantasy Fest read 25I think many of the ya audience would find the Ruth the white dragon dynamic fitting He s just not into it And that s ok He s absolutely lovely.
Oh Pern
As in the previous book in chronological order of this series Dragondrums this book supposed to be the last of a trilogy but is actually a stand alone novel Also like the previous book the protagonist is an angry teen thirsty for adult admission and hungry for sex, as most teenagers I think Of course, this teen is not an ordinary one as he is having many important responsibilities, to which he adds even as he tends to get involved where he does not have to With his ally the white dragon, howev [...]
This was my favorite of the first three Pern books I loved Jaxom and Ruth, and the scene where the dragons keep Robinton from leaving always has me in tears It was a fun way to spend the day.
I have said this before and I still think it s true, there are some books that are meant to be read at certain times And if you miss that particular time, then they just won t do it for you the way they might have I suspect that The White Dragon is just such a book I have found, and it seems to be often the case with science fiction fantasy novels, that I seem to have missed the space boat with McCaffrey s novel Back in the 80s, when I was in the midst of my science fiction binge, my best frien [...]
Hm, I don t remember Jaxom being so irritating before haha He whines and groans and talks a lot about how unfair things are, and yes, he has a lot of responsibility on his shoulders, but it doesn t stop me from wanting to smack him upside the head a few times It also doesn t help that his romantic attachments bore me to death, and that there is no rhyme or reason for Sharra view spoiler I felt like he fell into love with her too quickly and it came out of left field I felt nothing for her as a c [...]
As much of an Anne McCaffrey fan as I am, it s sad that I bought this over 5 years ago and just got around to listening to it But, as good a job as Dick Hill did in narrating the book, I can t say that it made the book any better than it was during my years long love of reading and re reading this, the 3rd of the Pern books Maybe it s just that the story can t get any better than it is, whether read or heard Fans of Pern and her dragons and dragonriders waited 7 long years from book 2,Dragonques [...]
The old saying goes, You can t judge a book by its cover I can still remember that summer day when I spotted the Michael Whelan cover on The White Dragon and how it caught my eye I remember picking it up, reading the blurb on the back cover and deciding I wanted to read it I was fourteen years old and I liked that the protagonist was around my age It was the last book of the Dragonriders of Pern series that introduced me to McCaffrey s world.But it was the story inside that cover that absolutely [...]
Yes by all means, judge a book set in a feudalistic world surrounded by dragon on your personal interpretation of feminism on Earth circa 2013 This makes no sense to me If you re going to read a book I think you should read a book and suspend your sense of self to really get a feel for the world that s being created Now yes McCaffrey wrote a lot of these books in the 60 s and 70 s and she did not write super liberated women, though for her time they would have seemed quite progressive no doubt H [...]
Okay this is the final book I have read in my recent Pern binge Definetly one of the best books in the series, though it may be a bit confusing as a first read as it requires a knowledge of the personalities of the major players on Pern.Anne McCaffrey has written some great scenes into the story I particular love reading as Jaxom develops from a boy into a man and into his role as Lord of Ruatha.
This is one of my favorites of the series Ruth and his rider are just plain nice people Both are disabled in their own way Ruth is the only white dragon on the planet Pern and Jaxom was born early from a mother who died at the time of his birth, and whose father died a short time later, making him the lord of Ruatha as an infant Both will have to prove themselves to the humans of Pern The dragons accept them as they are.
I think The White Dragon is my favorite of The Dragonriders of Pern trilogy In this story Jaxom, Lord Holder of Ruatha, has impressed Ruth, the only white dragon in existence Ruth is smaller than a typical dragon, but demonstrates special abilities and intelligence than a normal dragon.In The White Dragon, is discovered about the original colonists of Pern And I m off to continue my binge re read of the Pern books I do this every time
With this book, I have completed the original 3 book Dragon Riders of Pern series This was definitely not what I thought is was going to be I will go on and read other series someday, but what I will say is, if you like stories about dragons this is the series for you.
Jesus has McCaffrey never heard of a plot I mean, what is she waiting for, her grand finale Forget the characterization of Jaxom that everyone s complaining about he s barely sketched in enough to even be called a character and this strange fetish she has for men who force themselves on women let s just stick to the basic level of narrative, of plot mechanics, of conflict and a focused through line The biggest problem with this book is that, for hundreds of pages, basically NOTHING HAPPENS There [...]
Fantasy More dragonriding with some archeology thrown in for color and the first appearance by a female green dragonrider Except the text calls her a dragon girl and she doesn t get the honorific apostrophe like the men do and also no one likes her very much because she s bitchy We also get our first female crafter, a harper, but she s the appropriate combination of bossy and nurturing and everybody loves her If, on Pern, you are female and only bossy or only nurturing, then you re out of luck m [...]
When I was very little I read all of the Pern books Now I remember little snippets and pieces so that the books have stopped being books and started being just one long and glorious plot line Now that I am rereading the books I have found that I actually remember whole quotes and can read one page and quote the beginning of the next page That is a little bit freaky.The plot is one of my favorites, however I strongly dislike Jaxom I was reading other people s reviews earlier and my view is wide s [...]
Sometimes, you read a book when you re thirteen, and you re all, Yeah, Jaxom No one understands what it s like to be stuck in between so many things except you and me I get this I want a dragon Then you read that same book again when you re 32, and you re all, Jaxom, you are an arrogant little snot Anne McCaffrey took the Dragonriders series down the coming of age trope storyline with the third installment She really does a marvelous job building that sense of self conscious egocentrism that pla [...]
Although I lost interest in the later books of the Pern series, the original trilogy and the Harper Hall books remain among my favorites in speculative fiction This is the third book in the series and you should read Dragonflight and Dragonquest first This book feels a little different with its focus on different characters Jaxom and his dragon Ruth Ruth comes across as a character in his own right than other Pern dragons, and he s an endearing one The plot has than enough twists and turns to [...]
After all these years i still love this series Jaxom grows up so fast in this book but Ruth is the star of the story He may have been the runt of the litter but he is smart and very fast I also think he is waiting to fly a gold dragon which is why he has no interest in the green and bronze as he points out he is the only white dragon on Pern, so why would he not hold out for gold.
After being disappointed with the first two Pern books I read Dragonflight and Dragonquest , I thoroughly enjoyed reading The White Dragon I think this book had great character development and a strong, likeable protagonist that were both lacking in the other two books IMO I also found the plot much enjoyable than the other two books.
For the nth time of reading, Jaxom is still wonderful Oh and so is Ruth


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Freaky Friday in the MiX Italo & Turbulentie with Mark van Dale
Let the weekend begin with RSDH in the MiX.
the best National and International Italo mix DJ's
8-11: pm CET
Play it loud! (rerun is saturday at 4pm CET)
DJ Feratho kicks off this weekend.
We didnt hear from him for a long time. Fer is a great mixer but also a producer. He loves the darker site of Italo and Electro and has a huuuuuge collection of vinyl.
So enjoy this mix, he used a and b sides and there are over 200 cuts in this rare electro mix!
Second in line-up a mix made in 2014 by our Spanish friens Sergi Elias. Let this mix warm you up for our next Top 100!. And Vote!!
Sergi Elias works for the Spanish label Blanco y Negro and is a mastermixer. 100 Tracks in one hour. The Top 100 2014 mix…
The last mix in this Line-up is from a new kid on the block. His real name is Patrick Camphens. Let's call him DJ Patrick.
Enjoy his Italo mix.
Aprox. 11:20 pm till 2:00 am CET Turbulentie with Mark van Dale & Joey Bananas. Deephouse sounds in the mix on your radio.


text: Organize a meeting Belgium Belgium venues and hotels Bruges venues and hotels - 49 Facilities Bedouk offers a variety of venues to organize corporate event. Discover a wide selection of hotels in Bruges for your next business trip, exhibition, seminar... For more details select an establishment and ask a quote for free. Lire My selection Bruges Delete all Affiner la catégorie Facilities 49 Suppliers 0 Agencies 2 Convention Bureaus 2 Sort your results by Standing guestrooms Meeting rooms Capacity Relevancy Boldershof ('T) Belgium - Bruges - 8020 Party and banquet room 't Boldershof provides weddings - receptions and banquets all kinds, and this already for the 4th generation. As a customer we will let you give a personal touch to your event. 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Business Internet Service in Woodberry Forest, VA
Call (855) 927-7423
Employees constantly communicate to one another through email, and many customers prefer to contact companies online; therefore, the internet is crucial to the survival of today's businesses whether or not they are online-based companies. With the number of business internet providers, choosing the right service provider can be difficult. MyRatePlan lets companies in Woodberry Forest, VA compare business internet service providers to find the best provider for their specific needs.
The Different Types of Business ISPs in Woodberry Forest, VA
Major advancements have occurred in the last 20 years in terms of internet provision options, and this advancement continues every year. For businesses in Woodberry Forest, VA that have stuck with the same option for many years, it's wise to shop around and see what new options are available, because there could be upgrades that offer dramatically improved performance and services. Each option has its own unique advantages and disadvantages, with one of the key factors in choosing an option being availability. There are efficient types of internet available that may not have enough network distribution to suffice. That's why it's important to research what's available in one's region. What are the most common types of internet? The current options are cable, DSL, fiber optic, T1, satellite and fixed wireless.
Business owners in Woodberry Forest, VA should keep in mind that most ISP providers offer more than just internet service, they offer packages with a wide range of available services. Finding a provider that offers a full package of services is convenient and it can save money. A full package includes web hosting, email and business phone service. Not only that, providers typically have a full service package that covers internet connectivity. This means that the provider handles service and support the business. Since the provider has experts available, it lowers the business's operating costs, since that business won't need to hire their own in-house expert.
Another key feature that business owners should look for is consultative services, which is when the provider's expert goes to the business's Woodberry Forest, VA office to determine its internet needs. The expert can then suggest possible improvements that will benefit the business, such as upgrading technology for better efficiency. The provider will also be able to calculate how much bandwidth the business will need by how many employees it has and the number of devices used in the office. The expert can even demonstrate how the business can remotely manage its devices.
Important Points to Think About with Business Internet Service in Woodberry Forest, VA
First and foremost, a business that's searching for a new business internet service plan in Woodberry Forest, VA needs to figure out how much speed it needs, and this is one area where it's smart to think ahead. The plan it chooses must have enough speed for the business's peak hours when there are many devices in use, and for the future as the business expands. It's never a good idea to try to save money by choosing a slower plan, because this can be very harmful to a business in the long run. Not only will slower speeds frustrate people and present an unprofessional image, but they will also lower productivity.
A business should make sure that it checks with the ISP it chooses about bandwidth caps and data throttling, as ISPs sometimes decrease download rates at specific times of the day. The business should ask about that and any other possible limitations, and look at the fine print of its contract before it signs on the dotted line.
It's almost never a good idea to go with an ISP that doesn't offer security protection. Any quality ISP should provide at least some form of protection from cyber threats, such as viruses, spyware, malware and spam. The business should get information on how much protection the ISP provides, whether that protection also extends to mobile devices connected to the business's network and what type of backup options are available in the event of data loss. If a business has a system crash, it's going to need to get back up as quickly as possible.
Choosing the Right Business Internet Plan in Woodberry Forest, VA
While every ISP has support available, the standard amount isn't sufficient for businesses that rely on the internet to conduct business. Any downtime for these types of businesses can result in a huge loss of sales and productivity. Those Woodberry Forest, VA businesses should make sure that their ISP has a Service Level Agreement, which guarantees a set amount of uptime. In the event that the ISP doesn't meet this guarantee, it provides a remedy, with the usual remedy being a bill credit.
The business should also look into what phone support options the ISP has, and specifically that it has support phone lines specifically for assisting its business customers. Besides that, the business must also research how effective the ISP's tech support is when it comes to resolving problems.
Looking at what has worked for other businesses in the past is a smart way to choose an internet service plan. With MyRatePlan, Woodberry Forest, VA businesses can compare internet plan options in their areas by punching in their ZIP code. This is an easy way to check if there are any new service options available, so a business can make sure that it's not settling for less serviced than it should be getting.
Business Internet in Woodberry Forest, VA Requires Reliability and Flexibility
Your location determines a lot about the internet choices that are available. Even if you only have a handful of options available, it is important to carefully examine them before making the final choice. Make sure that you opt for the ISP that will adapt to any future changes in the internet and technological fields. A top-notch ISP will adjust their services and packages to reflect the changes in these areas.
Some of the changes we may expect to see in the future include the development of the IPv6. When the IPv6 is finished, it is expected to replace the currently used IPv4. This change is taking place since the IPv6 offers an unlimited number of IP addresses, and will make it easier than ever for devices to connect to the internet. The IPv6 should also lower the costs of internet connection for businesses, giving us hopes of lower prices in the future.
While it's impossible to find an internet service provider that is perfect, MyRatePlan can help you get as close as possible. Use the available tools to discover and compare existing business internet providers in the Woodberry Forest, VA area.
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ZIP Codes in Woodberry Forest, VA
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Russian Federal Space Agency (ROSCOSMOS) launch of a Soyuz-FG Rocket
Russian Federal Space Agency (ROSCOSMOS) was scheduled to launch a Soyuz-FG rocket as part of the Soyuz TMA-03M mission. The launch window for the Human Exploration mission was on Wed, Dec 21st, 2011, 8:16 AM EST from 1/5, Baikonur Cosmodrome, Kazakhstan. The status of the launch was Success. Don't miss this exciting rocket launch! Watch the launch video of the Soyuz-FG and experience the excitement for yourself.
Oleg KononenkoCommander - Russian
Oleg Dmitriyevich Kononenko (Russian: Олег Дмитриевич Кононенко) is a Russian cosmonaut. He has flown to the International Space Station three times, as a flight engineer for Expedition 17 aboard Soyuz TMA-12, as a flight engineer on Expedition 30 and commander of Expedition 31 aboard Soyuz TMA-03M, and as a flight engineer on Expedition 44 and Expedition 45 aboard Soyuz TMA-17M. Kononenko has accumulated over 533 days in orbit during three long duration flights to ISS.
André KuipersFlight Engineer - Dutch
André Kuipers is a Dutch physician and ESA astronaut. He became the second Dutch citizen, third Dutch-born and fifth Dutch-speaking astronaut upon launch of Soyuz TMA-4 on 19 April 2004. Kuipers returned to Earth aboard Soyuz TMA-3 11 days later. Kuipers is the first Dutch astronaut to return to space. On 5 August 2009, Dutch minister of economic affairs Maria van der Hoeven, announced Kuipers was selected as an astronaut for International Space Station (ISS) Expeditions 30 and 31. He was launched to space on 21 December 2011 and returned to Earth on 1 July 2012.
Donald PettitFlight Engineer - American
Donald Roy Pettit is an American chemical engineer and a NASA astronaut. He is a veteran of two long-duration stays aboard the International Space Station, one space shuttle mission and a six-week expedition to find meteorites in Antarctica. As of 2018, at age 63, he is NASA's oldest active astronaut.
Soyuz TMA-03M
Soyuz TMA-03M begins expedition 30 by carrying 3 astronauts and cosmonauts to the International Space Station. Russian Commander, cosmonaut Oleg Kononenko alongside Flight Engineers, André Kuipers (ESA) & Donald Pettit (NASA) will launch aboard the Soyuz spacecraft from the Baikonur Cosmodrome in Kazakhstan and then rendezvous with the station. It landed on 1 July 2012, 08:14 UTC
1/5, Baikonur Cosmodrome, Kazakhstan
The Soyuz FG rocket is an expendable launch vehicle most commonly known for carrying humans to the International Space Station today.Russian Federal Space Agency (ROSCOSMOS)
The Roscosmos State Corporation for Space Activities, commonly known as Roscosmos, is the governmental body responsible for the space science program of the Russian Federation and general aerospace research. Soyuz has many launch locations the Russian sites are Baikonur, Plesetsk and Vostochny however Ariane also purchases the vehicle and launches it from French Guiana.


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This 1969 Lotus Europa is a very special car, Lotus is a car manufacturer that cuts anything out of the vehicle to make it as light as possible, which generally leaves the vehicle simple with a minimal frame to hold the engine and a fiberglass cockpit for aerodynamics and look. There were under 10,000 units built and few survive to this day.
This particular one came in because the transmission box was continuously leaking gear oil and the shifter assembly broke. The transmission was resealed previously a few years ago by one of our techs, however the differential carrier assembly had too much play within the unit and had to be replaced to stop the leakage. A recycled transmission was sourced instead of rebuilding the unit, this choice was made due to difficulty finding parts to do a proper rebuild. The shifter assembly was welded and repaired due to the same issue of sourcing parts.
The most interesting part about this vehicle is that Lotus, in effort to save weight, decided to make the transmission a part of the vehicle's structure. This means that the transmission actually holds the rear suspension together. With the transmission removed, the vehicle cannot be lowered to the ground and pushed around, because the members holding the wheels are not supported.


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text:
Introduction: Pen Solder Feeder Hack
Hi! Today I have a special soldering quick tip for you: how to create an ultra cheap solder feeder. Once you start using it, it's much like with soldering fume extractor: you didn't know you needed one until you tried using it. And much like building a fume extractor, solder feeder is just as easy to make. All you need is a mechanical pencil and solder of matching diameter.
This hack does not only help with managing your solder wire but is also great for stabilizing your hand for times when you have to solder some tiny components like SMD chips. Without any further ado, lets get started.
Step 1: Building It
If you don't happen to have a mechanical pencil, take a walk to nearest office supply store. From then one, any will do. There are two factors to consider though: first is lead thickness for the pencil. It has to match the diameter of your solder wire. I used 0.5 mm pencil for 0.5 mm solder wire but you can pick any dimension so long as it matches your solder wire's thickness (0.7 mm and 1.0 mm are standard)
The second thing is to try and find a mechanical pencil that doesn't have "extend lead" button on the end but somewhere in the middle like what you can see on all above images. This will help you to extend solder wire more easily. If your local office supply store doesn't sell such pencils, buy one of these. If you don't want to spend any money, you can also use a regular mechanical pencil but that has some minor drawbacks.
Now that I covered the theory, let's get down to business. Take your pencil, open the lead compartment, remove cap, eraser and lead rods. Straighten your solder wire and insert it where lead rods should go. You will have to hold down "extend lead" button in order to get solder wire through point. Note that you may want to insert solder wire through a hole in pencil's cap before inserting it in pencil but that isn't crucial.
That is it. Now you have your own solder wire feeder!
Step 2: Conclusion
As I said in introduction, you don't realize you need one until you use one.
If you like it, favourite this Instructable and if you don't, give it a try. it only costs you a dollar to make one. And when you make it, come back to favourite this Ible :)
Also please vote for me for one or all of following contests:
- Unusual Uses Challenge
- Before and After Contest
And thank you all who voted for me in reuse contest! I got runner up prize. I am looking forward to scoring high in other contests as well!
Runner Up in the
Before and After Contest
Runner Up in the
Reuse Contest
Runner Up in the
Unusual Uses Challenge
3 People Made This Project!
- maidenkrystal made it!
- MoTinkerGNome made it!
- jbocek made it!
51 Discussions
I have worked in electronics since 1975 and made this Pens with solder in the 70's and 80's.
To in prove on your idea I would coil the solder to fit the inside of the barrel then feed it from the end of the coil down through the coil solder and out the end of the pen barrel. This keep the solder clean and easy to feed and handle
Great, thanks for sharing the idea!
this is awesome
I made several of these with .5 .7 and .9 sizes. They worked well for small solder joints but if you need to feed fast... oops, melt down. I love the idea but when I solder I feel the need, the need to feed. Still, I won't toss them, they will come in handy some day.
Also I have my solder on a homemade solder spool holder that hangs from the hutch on my desk and that works better for what I am doing.
Nice instructable, good info.
Worry not, my friend! I am working on "proper" solder feeder - one that will have switch on soldering iron and feeding mechanism standing on the table. To know what I am talking about, see this link (first recommended by MoTingerGNome): http://www.judepullen.com/designmodelling/solder-b...
With that difference that my version will leave one hand free. Stay tuned!
Scrap aluminum, scrap EMT, add two sheet metal screws and Voila ! !
Scrap aluminum, scrap EMT, add two sheet metal screws and Voila ! !
for got metals contest
tks, did not know that
I didn't. You can only apply for three contests with one instructable. Thank you for your concern though.
well done excelent idea and so useful thank you
First attempt to actually making an instructible. Worked perfectly. Anyone that sends negative comments on this, just like to make negative comments. It's simple and elegant and it works. what more need be said. you got my vote.
Wow, ingenious - the simplest things make the biggest difference! Added this to me Wire It Up! collection on Instructables.
genius :D
Great idea! I'm setting one up at my soldering station now.
Nice!, pitty that it wasnt your exact idea though, because kipkay had a video featuring this in april https://youtu.be/khu2MdYZOZo


text:
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Christmas Soups Recipes
Merry Christmas! Look at the best, easiest and healthiest Christmas recipes!
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Love Soup Mix in a Jar
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Slow Cooker Posole with Pork and Chicken
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Sweet Potato and Apple Soup
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Mom's Nova Scotia Seafood Chowder
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Slovak Sauerkraut Christmas Soup
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Dilled Vegetable Barley Soup
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Grandpa's Oyster Stew
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Brodetto (Fish Stew) Ancona-Style
Olive oil, Onion, chopped, Garlic, finely chopped and
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Christmas Clementine, Carrot and Coriander Soup W/ Citrus Twists
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Slovak Christmas Eve Mushroom Soup
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Christmas Corn Chowder
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Oyster and Wild Rice Bisque
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Cheesy Cream of Asparagus Soup
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Curried Pumpkin Apple Soup
Golden delicious apples, peeled and coarsely chopped and
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Golden Gouda Mushroom Soup
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Festive Corn Soup
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Roasted Tomato and Pepper Soup
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This complete series collection on Blu-ray from Shout! Factory looks gorgeous and is packed to the brim with special features.
Alien [40th Anniversary] (4K Ultra HD Blu-ray Review)
This new 4K Ultra HD remaster offers a stunning visual upgrade for this sci-fi/horror classic.
Star Blazers 2202: Part One [Limited Edition] (Blu-ray Review)
An action-packed space opera with gorgeous animation — but you made need to familiarize yourself with the franchise for full enjoyment.
2001: A Space Odyssey (1968) (TheaterByte Classic Film Review)
Visually striking, filled with symbolism, and a score culled from the world of classic and contemporary (at the time) classical music, '2001: A Space Odyssey' has become one of the must-see entries in the classic film canon.
Star Blazers 2199 – Part One [Limited Edition] (TheaterByte Blu-ray Review)
This beloved classic gets a well-made reboot that looks and sounds great in this part one limited edition set
Dark Matter: Season Two (TheaterByte Blu-ray Review)
SyFy's Canadian import sci-fi thriller delivers a knockout, binge-worthy second season that sets up its already off to a good start season three.
The Space Between Us (TheaterByte Blu-ray Review)
This film gets on space travel & colonization bandwagon while adding a touch of teen romance, but it does it with little success.


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"We need in the medium- to longer-term to go after the root causes that lead people to join these groups, whether it's lack of opportunity for jobs, whether . . . "
— Marie Harf, Deputy Spokesperson, U.S. State Department, Hardball with Chris Matthews, February 16, 2015
Given the relatively swank digs occupied by his family in the Colonial Shores neighborhood of Hixson, Tenn., it appears that "lack of opportunity for jobs" was not Mohammod Youssef Abdulazeez's affliction. The 24-year-old Kuwaiti immigrant who killed four Marines and wounded several others yesterday at two military recruitment centers in Chattanooga appears to have been amply provided for. "For more than a decade, Mr. Abdulazeez, his parents and his sisters had made their home in a subdivision called Colonial Shores, just across the Tennessee River from Chattanooga," writes the New York Times today. "It is a movie-set vision of American suburbia, almost surreally well-tended, with handsome middle-class homes of a late-1970s vintage." And Abdulazeez himself? As a kid he hung around with the other kids in the neighborhood, he wrestled in high school, he was friendly to his neighbors. He graduated from the University of Tennessee in 2012 with a degree in engineering. "He seemed to have been an all-American boy, handsome and polite, normally in a T-shirt and jeans."
Not impoverished, not deprived, not "minimized" or "marginalized." What possibly could have motivated Mohammod Youssuf Abdulazeez's murderous attack yesterday? What, in Ms. Harf's phrase, were the "root causes"?
The FBI's investigation is ongoing, but the early indications seem to be pointing in a predictable direction:
Mr. Abdulazeez maintained a blog where he posted about Islam, according to the SITE Intelligence Group, which tracks international terrorist groups. A July 13 post stated that "life is short and bitter" and that Muslims should not let "the opportunity to submit to Allah . . . pass you by."
Photographs posted on family Facebook pages show the once-clean-cut student recently grew a beard. A Hamilton County jail booking report posted on Chattanoogan.com shows that he was arrested on a charge of driving under the influence, a first offense.
In the last two or three months, Mr. Abdulazeez had begun showing up rather regularly at Friday Prayer at the Islamic Society of Greater Chattanooga, a large mosque and cultural center, said Dr. Azhar S. Sheikh, a founding member of the center's board.
Reuters reports that Abdulazeez last year traveled to Jordan, where he held citizenship, staying overseas for seven months. Authorities are trying to determine whether he made contact with local terrorist outfits or if he traveled to other countries — including Yemen, where al-Qaeda Arabian Peninsula (AQAP) has long been potent, and where the Islamic State has been gaining ground in recent months.
This story is not uncommon. In the Twin Cities, whence naturalized and second-generation Somalis are flocking to Somalia and Syria to join al-Shabaab and the Islamic State, deprivation can hardly be blamed. Burhan Hassan, a Minneapolis-area teenager killed in 2009 while fighting for al-Shabaab, was an honors student angling to attend Harvard. I'm no expert, but the job market in Mogadishu is not exactly booming.
The hold of religion is deep, and does not acquiesce to jobs programs or tax credits.
Well, depending on the position. There are plenty of open roster slots on the global jihad "JV team," which has been recruiting heavily of late.
What induces a person to shoot up a military recruiting center in middle America is surely a complex of factors. But the same network of politicians and media who absurdly attributed Dylann Roof's murder to the presence of a flag on state property 120 miles away — that is, to the deep and abiding menace of structural racism, "interpersonal and structural . . . current and historical . . . explicit and implicit . . . articulated and silent," in Charles Blow's perfectly nebulous formulation — are hesitant to blame terrorism on any "structure" or "institution" not amenable to a stimulus package.
#related#But, as the literary critic Irving Babbitt observed in his 1924 book Democracy and Leadership: "When studied with any degree of thoroughness, the economic problem will be found to run into the political problem, the political problem in the philosophical problem, and the philosophical problem itself to be almost indissolubly bound up at last with the religious problem." Talk about lack of jobs, if you like — or rampant inflation, unaffordable housing, &c. — but eventually you have to go deeper. Marx was wrong. Men are not explained solely by their economic circumstances.
The hold of religion is deep, and does not acquiesce to jobs programs or tax credits. Until our leaders acknowledge that squarely, we'll continue to blame earned income for the problems of Islam — and continue to be surprised that we're in the crosshairs.


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14 Jan 2018 14:01
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According to an article from the Yorkshire Evening Post, it is now a legal requirement to perform a risk assessment of both hot and cold water systems to check the threat of Legionella bacteria.
"This is the latest in a series of tougher laws with the aim of driving up safety standards in a fast-growing sector – handing the legal duty for doing so to agents and landlords," said Jon Oldroyd, managing director of Ignite Gas Care.
"Gas safety checks and the testing of electrics have long played a key role in keeping tenants safe. But the Legionella assessment, coupled with the mandatory introduction of smoke alarms and carbon monoxide monitors later this year, will now give them ultimate peace of mind."
Some Legionella safeguards may include disinfecting water systems, cleaning shower heads, and multiple other methods.
To read more about this story, please click here.


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Gonzaga's Josh Perkins, Brandon Clarke add to record collection in win over Florida State
UPDATED: Fri., March 29, 2019
Josh Perkins keeps adding to his record collection.
The senior point guard surpassed Matt Santangelo as the program's single-season assists leader. Perkins had five assists against Florida State on Thursday, bumping his season total to 228, three more than Santangelo in 1999-2000. Perkins moved past Santangelo as the school's career assists leader during the regular season.
Perkins has played in 15 NCAA Tournament games, another GU mark. Silas Melson is second at 14. Perkins is now the 11th Zags player to hit 100 career points in tourney games. He has 134 career wins, three shy of former teammate Przemek Karnowski's Division I record of 137.
Junior forward Brandon Clarke rejected five shots against FSU, bringing his season total to 115. He's the new WCC single-season blocks leader, edging past San Francisco 7-footer Hondre Brewer's 114 in 1999.
Clarke became the first player with at least 15 points and five or more blocks in consecutive NCAA Tournament games since Kansas center Jeff Withey in 2013.
Follow along with the Zags
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NIkki Stark
My feedback
705 votes75 comments · WooCommerce » Extension - WooCommerce Subscriptions · Flag idea as inappropriate… · Admin →
An error occurred while saving the commentNIkki Stark commented
How is this not a core function? Product prices change and price increases must be passed on to the customer. There should be a way to bulk increase and then notify the customer of the change and if they do not like the new price they can cancel their subscription. I could even live with it if price increases were reflected when a subscription expires and a customer resubscribes. But right from their My Account page they can resubscribe at the OLD price. At the very least give us the option to increase to current prices when they resubscribe or make it easy to remove the resubscribe option from the My Account page. The way it is currently set up is a mess. Any business owner knows you have to increase prices to match your increased cost for the item over time. Business 101 folks.NIkki Stark supported this idea ·


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Rachael Reviewed on Apr 12, 2019, 6:39 PM
My experience is always awesome! Got there to pick up vehicle one they had on lot had a tire that needed changed. So they upgraded my vehicle at no extra charge, even let me keep it extra hrs. Because I couldnt make to normal drop off time due to traffic issues construction !


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As I tried to immortalize her
at the peak of her might,
I realized that the beauty I hold in sight
is nothing but a facade she gathers,
to hide everything from light.
But what? Struggle, Internal fight?
Making me feel anxious but not bothered,
as it only intensified her and made her bright;
empowering herself with every right,
taking over my mind with every tide
of mystery that emanated from inside.
A mind that holds so much with pride.
Oh such secrecy, only made her rise,
elevating her beauty to a state of praise;
where even gods would kneel in a blaze,
looking down feeling unworthy of such eyes;
which hold hidden more than Pandora's gaze.
Such is her mystery,
which I observed as I painted her history
in a canvas that was meant to contain wholly.
But all tries ended up being folly,
as no art could ever be worthy
of immortalizing something so holy.


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All posts tagged "Boys Swimming"
Swimming/ 1 year ago
Zapatka wins 1,500 meter race at Futures Championship with personal-best time
GENEVA, Ohio, August 1 – Avon's Adam Zapatka finished first in the men's 1,500 meter freestyle race at the Futures Championships...
News/ 1 year ago
Seven Avon High athletes earn All-State honors this winter
AVON, April 1 – Five swimmers and two wrestlers earned All-State honors competing for Avon High this winter. Chris Gens (220...
Canton High swimmer Will Gallant qualifies for 2020 U.S. Olympic trials
ST. PETERSBURG, Fla., March 28, 2019 – Canton High senior Will Gallant already has an invitation for a place to visit...
Jaremko sweeps two events, Richard wins 50 free for third time at CCC North meet
WETHERSFIELD, March 2 – Avon's Maksymilian Jaremko won two events to help lead the Avon High boys swimming team to a...
Avon's 200 freestyle relay finishes tenth at State Open with new school record
NEW HAVEN, March 15 – Earlier this week, Avon's 200-yard freestyle relay team became the first Falcon boys swimming relay team...
Jaremko, Falcon relay team win state titles at Class M championships
MIDDLETOWN, March 11 – A week ago, Avon High's 200-yard freestyle relay team set a new school record while finishing second...
Northwestern breaks Avon's hold on Splash Classic championship
WEST HARTFORD, February 23 – It's been a long time since a team other than Avon raised the Splash Classic trophy...
Avon/ 2 years ago
Three Avon High athletes earn All-State honors
Three Avon High athletes earned All-State honors for their play this winter. Avon High senior Peter Hoffman earned All-State honors for...
Swimming/ 3 years ago
Falcons swimmers set two new school records at State Open championships
NEW HAVEN, March 17 – Two new school records were set by the Avon High boys swim team at the State...
Swimming/ 3 years ago
Richard, Downey each finish third at Class M meet for 2nd straight year
WEST HARTFORD, March 14 – Andre Richard and Brendan Downey each finished third in their respective events as the Avon High...


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1Department of Pediatrics, College of Medicine, Yeungnam University, Daegu, Korea.
2Department of Pediatrics, Daegu Fatima Hospital, Daegu, Korea.
3Department of Clinical Pathology, Kyungpook National University School of Medicine, Daegu, Korea.
4Department of Laboratory Medicine, College of Medicine, Yeungnam University, Daegu, Korea.
Invasive fungal infections (IFIs) are a life-threatening problem in immunocompromised patients. Despite timely diagnosis and appropriate antifungal therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment with a combination of antifungal agents. Therefore, childhood leukemic patients treated with voriconazole plus caspofungin were evaluated for the safety and efficacy of the combination antifungal therapy to treat IFIs.
In this retrospective study, medical records were retrieved for patients admitted to the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between April 2009 and May 2013. Medical records of 22 patients were analyzed.
Of the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and 13 (59%) with possible IFI. All patients, except one, were already receiving antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis of IFI was confirmed, antifungal monotherapy was replaced with combination therapy. The study's overall response rate was 90.9%, with complete responses in 86.3% of the patients. Two patients experienced a side effect of a small increase in liver enzyme levels.
Voriconazole plus caspofungin combination therapy is an effective and safe treatment for serious IFI in pediatric patients with acute leukemia.
Treatment outcomes for childhood leukemia have improved over time. With recent advances in chemotherapy and supportive care, the overall survival rates of children with newly diagnosed acute lymphoblastic leukemia (ALL) and of those with myeloid neoplasms are now as high as 80% and 50%, respectively [12]. The development of supportive therapy has played an important role in the improvement of treatment outcomes.
Invasive fungal infections (IFIs) are significant causes of morbidity and mortality in pediatric cancer patients. Development of new antifungal drugs has remarkably improved the success rate of treatments; however, the mortality rate of IFI patients remains high. In addition, the efficacy of current antifungal drugs is suboptimal [3]. The development of a new antifungal drug requires considerable time; however, antifungal combination therapy (ACT) can be used as a complementary therapy to current IFI treatment. In vitro studies on ACT have shown that it is more effective than monotherapy; yet, ACT has been shown to have limitations when used in a practical clinical setting. In the study by Nivoix et al. [4], six refractory cases of invasive aspergillosis were treated with combination therapy, which likely caused one patient to develop hepatotoxicity.
Echinocandin antifungal agents, such as caspofungin (CAS), damage fungal cell walls by inhibiting beta-1,3-D-glucan synthase, and azole antifungal agents, such as voriconazole (VRC), are known to inhibit the synthesis of cell membranes. Studies have suggested that a combination of drugs from each of these classes would produce a synergistic effect because of their varied targets [567]. In addition, there have been case reports and a recently published prospective study from the Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne (SEIFEM) group that evaluated the use of ACT to treat IFI in adults [8]. Further, the use of ACT based on CAS for pediatric hematology patients has been reported [459]. However, there have been no studies conducted in children with a single ACT (CAS+VRC).
A total of 30 patients who had received a combination of CAS plus VRC for IFI were identified among 79 patients diagnosed with pediatric acute leukemia from April 2009 to May 2013 in the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea. Of the patients who were initially identified, three were excluded from the study because they had been subsequently diagnosed with pneumonia not attributable to an IFI, and an additional five were excluded because they were diagnosed with non-infectious pulmonary infiltration. Medical records of the remaining 22 patients were retrospectively reviewed, and the following data were analyzed: demographic characteristics, underlying disease and disease states, radiological findings, and outcomes. None of the patients underwent stem cell transplantation before diagnosis of IFI. The study protocol was approved by the Institutional Review Board of Yeungnam University Hospital (IRB File No 2016-12-024).
Diagnosis of IFI was based on the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group (EORTC/MSG) [12]. Patients were allocated to groups according to a diagnosis of proven, probable, or possible IFI. Patients with a positive serum galactomannan test result were classified as having invasive aspergillosis (IA). The day of diagnosis was defined as the day that the clinical team confirmed diagnosis of IFI.
According to the institutional guidelines, empirical antifungal treatment was initiated if fever persisted for more than 48 hours after initiation of empiric antibacterial treatment. ACT was initiated based on the patient's condition and clinician's subjective decision. Response to antifungal treatment was defined according to the current standard definition, which states that both complete responses (CR) and partial responses (PR) are considered as successful treatment, while all other responses are classified as treatment failures [13].
An enzyme immunoassay to detect
Comparison of overall response rate, overall survival rate and possible risk factors were estimated using Fisher's exact test. Overall survival was calculated using the Kaplan-Meier method from the date of diagnosis of IFI to the date of death from any cause or to the date of last follow-up. For all calculations, a
The demographic characteristics of the patients are presented in Table 1. The study group was comprised of 11 boys and 11 girls, with a mean age of 5.3 years (range, 0.8–13.3 yrs); 11 patients had ALL, and 11 had acute myeloid leukemia (AML). None of the patients had undergone hematopoietic stem cell transplantation or immunosuppressive treatment prior to IFI onset. IFI diagnoses were classified as probable in nine patients (41%) and possible in 13 (59%) patients. Table 2 presents the patients' statuses for IFI diagnostic criteria.
All patients, with the exception of one, received empirical antifungal monotherapy with conventional amphotericin B, liposomal amphotericin B, or fluconazole (range of treatment duration, 1–21 days) before starting VRC plus CAS combination therapy. The remaining patient had already started combination antifungal therapy. Of the 22 patients, 21 patients received VRC plus CAS simultaneously, but one patient received the therapies consecutively, with 1–6 days between treatments. This patient was treated with VRC monotherapy, but the clinical symptoms did not improve and CAS was added.
When IFI was detected, 16 patients (nine ALL, seven AML) were in complete hematological remission (CHR). Of these 16 CHR patients, two had positive minimal residual disease, and they underwent re-induction chemotherapy at the time of IFI diagnosis. The remaining six patients (four ALL, two AML) had active hematological disease. Of the 22 patients, only two patients with ALL were diagnosed with IFI during maintenance chemotherapy. Of the remaining 20 patients, 18 (90.9%) were receiving intensive chemotherapy when IFI was detected. Of the patients with AML, six were diagnosed with IFI during induction therapy (Table 1). The median time between diagnosis of leukemia and the day of IFI diagnosis was 136.5 days (range, 12–1431 days).
After diagnosis of IFI, all 22 patients had severe neutropenia (absolute neutrophil count [ANC] <500 cells/µL), the median duration of which was 24.5 days (range, 3–91 days). The mean neutropenia (<500 cells/µL) duration of ALL and AML were 21±21 days and 35 days, respectively (
Nodules (38.1%) and consolidations (33.3%) were the most frequent radiologic findings in patients. A serum galactomannan (GM) assay was performed on 21 patients. Of these, nine patients had a GM index greater than 0.5, and the maximum GM index was 6.96. At diagnosis of IFI, the median C-reactive protein level was 7.8 mg/dL (range, 0.1–37.3 mg/dL) (Table 3).
The median duration of VRC plus CAS combination therapy was 45 days (range, 5–99 days). The median duration of the combination therapy in the 20 survivors was 50 days, while the median duration of the combination therapy in the two patients who died was 12 days (Table 3). One of the survivors was unresponsive to ACT and received a posaconazole replacement treatment. The loading and maintenance doses of CAS were 63.1±7.7 mg/m2 and 47.2±6.0 mg/m2, respectively. The loading and maintenance doses of VRC were 5.9±0.5 mg/kg and 3.6±0.6 mg/kg, respectively. The first patient who died had AML and was diagnosed with IFI during the consolidation phase, whereas the second patient who died had ALL and was diagnosed with IFI during the chemotherapy induction phase. None of the other patients experienced IFI relapse after remission during chemotherapy.
The 100-day survival rate after initiation of combination therapy was 90.9% (Fig. 1). Of the 22 patients, 20 (90.9%) responded to combination therapy (19 responded completely and one partially). The one patient with partial response received posaconazole replacement treatment. After 30 days of treatment, this patient showed a complete response. The remaining two patients died as a result of IA progression. Therefore, the 100-day treatment failure was three cases in total, and the 100-day IFI-free survival was 86.3%. An additional three patients subsequently died, with one fatality resulting from
VRC plus CAS combination therapy was well tolerated, except by two patients who had elevated liver enzyme levels, classified as grade 1 adverse event according to the Common Terminology Criteria for Adverse Events (CTCAE v4.03). The VRC dose was therefore reduced for one of these patients, although the other patient continued treatment without a reduction in antifungal drug dose. Neither patient stopped treatment because of side effects. While receiving VRC plus CAS combination therapy, 16 patients continued with anti-leukemic therapy. Of these 16 patients, the dose of anti-leukemic drugs was reduced for two patients.
IFI is a life-threatening infection in immunocompromised patients. Despite timely diagnosis and antifungal therapy, clinical outcomes of IFI are disappointing. The treatment success rate for IFI is 60% [14], while IFI-related mortality is 43–87.5% [151617]. The benefits of combination ACT for IFI are increased drug synergy and efficacy, and decreased resistance to antifungal drugs. The effectiveness of ACT has been proven in many recent experimental clinical studies. Arikan et al. [18] reported synergy of CAS plus amphotericin B (AMB), and Kirkpatrick et al. [19] reported that simultaneous VRC plus liposomal AMB was more effective than liposomal AMB alone. Cesaro et al. [5] used CAS-based ACT on 40 children and adolescents, and reported a favorable response in 53% of the patients and a 100-day survival rate of 70%.
Echinocandins are semisynthetic lipopeptide antifungal compounds that inhibit synthesis of β-1,3-D-glucan, an important component of cell walls in fungi. Therefore, echinocandins have the advantage of not affecting human cells without cell walls. In contrast, azole antifungals inhibit 14-α demethylase, suppressing the synthesis of ergosterol, a structural component of fungal membranes; as a result, membrane permeability increases, and fungal growth is inhibited. Thus, a synergistic effect has been predicted for ACT with these two antifungal agents because of their different mechanisms of action.
This study used VRC plus CAS combination therapy. In vitro and experimental animal model studies have reported that CAS plus VRC is more effective than monotherapy [620]. Lellek et al. [21] used CAS plus posaconazole therapy on adult patients and reported a favorable response in 77% of patients. Raad et al. [22] conducted a clinical study that used a single combination of CAS plus VRC therapy in IA. Herbrecht et al. [23] reported 59 proven, 178 probable, and 106 possible IA patients who underwent VRC vs. AMP monotherapy, with a 12-week response rate of 54.7% vs. 29.9%, respectively. In Candoni et al. [3], an 80% (28/35) overall response rate in CAS plus VRC, 70% (14/20) in CAS plus AMP and 73% (11/15) in VRC plus CAS were obtained. To date, there has been no clinical study on CAS plus VRC for children with IA. Given the synergistic effect of CAS plus VRC combination, the reduction in drug resistance and excellent expected therapeutic effect, the combination of both agents has been used to treat IFI in pediatric cancer patients.
In the present study, IFI-related death mortality was 9%, and the 100-day survival rate after initiation of combination therapy was 90.9%. ACT did not result in IFI control in only in 3 of the 22 patients. To the best of our knowledge, these values are considerably better than those reported in other studies. Data from L'Associazione Italiana ematologia ed Oncologia Pediatrica (AIEOP) showed that the overall mortality rate from fungal infections in children with cancer was 28%. Moreover, in patients with deep tissue mycoses, the mortality rate was 59% in children with probable invasive infection and 30% in those with possible invasive infection. ACT was used to treat 49% of the fungal infection cases [24]. In patients treated with ACT, there was a favorable response rate of 53% and the 100-day survival rate was 70% [5]. The same team also reported that the risk of death was higher (3.8-fold) in patients already receiving antifungal therapy at the time of diagnosis. In this study, all patients, with the exception of one, received antifungal monotherapy at the time of diagnosis. Nevertheless, this study's survival rates after implementing ACT were higher than those in previous studies.
Neutropenia is a risk factor for IFI, and the longer the duration of neutropenia, the higher the risk of IFI. The duration of neutropenia affects the response and mortality rate of IFI [25]. In this study, the median duration of neutropenia was 37±33 days. Raad et al. [22] reported that the median duration of neutropenia was 15 days (1–50 days) in primary therapy and 21 days (2–70 days) in salvage therapy. Caillot et al. [26] reported that the median duration of neutropenia was 15 days (3–58 days) in L-AMB monotherapy vs. 31.5 days (3–115 days) in L-AMB plus CAS ACT. Therefore, in this study, ACT could be considered to have better therapeutic results despite the longer duration of neutropenia, as compared with previous studies. However, the citations mentioned above mostly refer to studies in adults. Hence, this is a limitation as we cannot generalize our results to children.
Recently, other studies have explored differences in the effectiveness of treatments according to dosage and have devised measures to minimize drug toxicity, while conducting ACT along with therapeutic drug monitoring [2728]. Unfortunately, a pharmacological study to determine the optimal dosage to minimize the side effects of CAS plus VRC ACT could not be conducted simultaneously with our study. Regardless, we observed only minimal adverse effects during ACT. In previous studies, hypokalemia, as well as liver, renal, and neurologic toxicity were mentioned as side effects of ACT. We had chosen to use VRC because of concerns about severe nephrotoxicity of amphotericin B [2329].
This study has several limitations. First, this was a retrospective study with no uniform application criteria. Second, the study only reports results from a single institute. Lastly, there is a lack of microbiological confirmation of non-aspergillosis fungal infection. However, other studies have reported the results of treatment for small numbers of patients using various combinations of antifungal agents. Nevertheless, this is the first study that evaluated the efficacy and safety of ACT with CAS plus VRC. No previous study has reported treatment results and safety of this ACT in pediatric leukemia patients.
In conclusion, VRC plus CAS combination therapy is an effective and safe treatment for serious invasive fungal infection in pediatric acute leukemia patients. However, prospective studies on this ACT that include more pediatric patients with IFI are needed.
The 100-day survival rate after initiation of combination therapy was 90.9%.