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Bolivia: A Glimpse of Freedom
The long, wide, bleak streets of cobblestones and tufts of petrified grass reach for the sacred mountain Illimani, whose pyramid of snow is like a watchtower. There was almost no life here when I first came to Bolivia as a young reporter -- only the freezing airport and its inviting oxygen tent; now almost a million people live in El Alto, the highest city in the world, the creation of modern capitalism.
Alto is as symbolic of Latin America today as Cerro Rico is of the past. A
hill almost solid with silver, it was mined by slave labour and served to
bankroll the Spanish empire for three centuries. Both places are in the
poorest country on a continent of 225 million inhabitants, half of whom
are poor. Debt bondage, even slavery, still exists secretly in Bolivia,
whose hill of silver now takes second place to other natural treasures of
gas and water.
Bolivia was second only to Chile as a laboratory of "neoliberalism", the jargon for capitalism in its pure, Hobbesian form. The Harvard economist Jeffrey Sachs designed the "shock therapy" that the IMF and World Bank administered in Bolivia, adding another dimension of poverty and suffering. With the privatization of the mines, tin finally collapsed, and the miners and their families headed for La Paz, settling on the bitter plain at El Alto, a thousand feet above the capital, without water and power and with little food. Farmers forced off their land by IMF diktats followed them, and their mass migration was typical of that of millions driven out of secure work by the foreign managers of the "Washington consensus", a fanaticism conceived at Bretton Woods in 1944 as a tool of empire. (Sachs sees himself as a liberal and is mentor to the gormless Bono, of Live Aid etcetera fame.)
Until now, Bolivia's modern presidents have all been rich, white men who ran the country on behalf of a tiny wealthy minority. Owners of vast tracts of land control the lowlands around Santa Cruz, reminiscent of their equivalent in South Africa. The pre-Inca indigenous majority were the "blacks" that were politically invisible, except as occasionally troublesome workers, especially the miners. People chewed coca leaves to relieve hunger; many died in their early middle years and their children were stunted. "My mother was worked to death on a big estate near Santa Cruz," a campesino told me. "If she was found learning to read, she was severely punished."
The last president but one, Sanchez de Lozada, a multimillionaire mine-owner now exiled in Maryland, had grown up in the United States and spoke better English than Spanish. He was known as "El Gringo." In colluding with the IMF and selling off the country's gas and water at knockdown prices to Brazilian, American and European multinationals, he fulfilled his role, like so many Latin American presidents, as Washington's viceroy. Indeed, Richard Nixon's contemptuous remark about Latin America -- "People don't give a shit about the place" -- was quite wrong; America's imperial design was inscribed on the lives of the people in its "backyard".
Last year, I interviewed Pablo Solon, son of the great Bolivian muralist Walter Solon, in an extraordinary room covered by his father's epic brush strokes. More visceral than Diego Rivera's images of the Mexican revolution, the pictures of injustice rage at you; the barbaric manipulation of people's lives shall not pass, they say. Pablo Solón, now an adviser to the government of Evo Morales, said: "The story of Bolivia is not unlike so many resource-rich countries where the majority are very poor. It is the story of the government behind the government and what the American embassy allows, for in that building is the true source of power in this country. The US doesn't have major investments here; what they fear is another Chavez; they don't want the 'bad example' to spread to Ecuador and beyond -- even to Nigeria, which might be inspired to tax the oil companies as never before. For the US, any genuine solution to poverty spells trouble."
"How much would it cost to solve the poverty of Bolivia?" I asked.
"A billion dollars; it's nothing. It's the example that matters, because that's the threat."
I drove out of El Alto with Juan Delfin, an indigenous church deacon, taxi driver and artist, who spoke about the conquistadores if they were within his memory. This is a society where a half-millennium of history is a presence and its subjugation and impoverishment are understood with anger. With Illimani looming ahead of us, a cemetery consumed the horizon. On the other side of the road was a small hill not of silver, but rubbish: a stinking, smoking, acrid hell of dust and dead dogs and wild pigs and women in traditional bowler hats digging with pickaxes for something, anything. "Here you have the symbol of everything we live and reject," said Delfin.
took me to a plaque with the names of 24 people shot to death by the army
in October 2003 when de Lozada tried to stop the people of El Alto
marching down to La Paz in protest against his selling-off of gas. Juan
Delfin linked their deaths to the lines of ordinary graves, many of them
children, "who also died violently, from poverty". A shepherd boy emerged
from a pile of stones where he lived, looking too small for his age.
Even the right to collect rainwater belonged to Bechtel. With an annual revenue of more than 17 billion dollars, the company's power is such that it expected and got (without the inconvenience of bidding) the contract to rebuild the US fortress in occupied Iraq. Yet, not only was Bechtel driven out of Bolivia in 2000, shortly followed by its mentor de Lozada, but the company has now dropped its compensation action against the government. It is a victory of huge significance, because it warns other multinationals in Bolivia (such as British Gas) that even if the government is prepared to compromise the wrath of the people, the movements are not.
It is
also a warning to Evo Morales, whose electoral victory in December remains
largely symbolic here. An indigenous man now leads Bolivia for the first
time; the checkered pre-Inca flags are proudly on high everywhere. "The
elections aren't something we asked for, ever," said Oscar Olivera, the
Cochabamba union leader who led the anti-Bechtel revolt. "What the social
movements need to do now is to continue accumulating popular forces, to
build up our ability to pressure whatever government that comes. A Morales
government would be less difficult to love, but it will still be
The likeable Evo is on notice above all with his own people, but also with the Americans, the "government behind the government". Unless Washington can "lobotomize him" (as it did with Jean-Bertrand Aristide in Haiti), it is likely to encourage a secessionist movement in the landowners' heartland of Santa Cruz, where the gas is and where the government has promised to redistribute unused land. Bolivia, like Venezuela, has glimpsed its freedom and demands our support.
John Pilger is an internationally renowned investigative journalist and documentary filmmaker. His newest book, Freedom Next Time, will be published in June by Bantam Press. Visit John Pilger's website: www.johnpilger.com. Thanks to Michelle Hunt at Granada Media.
Other Recent Articles by John Pilger
* The
Extraordinary Rise of a "True Democracy"
With the Enemy
* The Big Lie: WMDs Were Just a Pretext for Planned War on Iraq
* What Good Friends Left Behind in Afghanistan
* Iraq's Epic Suffering Is Made Invisible
* How Britain Exports Weapons of Mass Destruction
* The Unthinkable is Becoming Normal


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Bee escape boards present you with a chemical-free, gentle means of separating your bees from the honey before you harvest. This article will explore what bee escape boards are, what they are useful for, alongside a comparison of four leading escape boards for you to consider when deciding on how this new technology can be used to advance your beekeeping efforts.
What is a Bee Escape Board?
The task of separating bees from their honey is ultimately the goal of the beekeeper, as without separation there is no sweet product to harvest. There are a variety of ways to separate bees from honey, generally either through physical or chemical methods, and those that are fast and expensive or slow and inexpensive. The former includes bee blowers, while the latter include bee escapes, including the bee escape board.
The Form and Function of the Escape Board
Bee escapes are the most effective means of separating bees from their honey inexpensively and without poor treatment of your bees. There are many designs for bee escapes, although generally they're mounted in or on boards known as "clearer boards" or "escape boards". Bee escape boards all perform the same fundamental function: they provide one-way passage so that upon leaving bees cannot return.
The alternative to the escape board is the removal of the honeycombs you wish to harvest one-by-one. Each time the honeycombs are removed, you must shake the bees from atop it, or brush them off, only to watch them again land upon the honeycomb to continue doing their work. Rather than this ongoing repetitive work, the use of the escape board allows the honeycomb to be mostly cleared out without any effort on your part beyond waiting.
The bee escapes are mounted in boards which are then placed between the honey supers and the hive. When the temperature drops at night, bees go through the escape and descend into the hive to form a cluster, and in the morning they're unable to get back into the super. It's important that the process is completed within 48 hours, as after this time the bees find solutions to get around the escape boards. Bees may learn their way back in, or may build bridge come in or around the board to make their way through.
Process Concerns
As mentioned, it is important to perform the separation process within 48 hours. The complete removal of bees may take 24-48 hours and may require a few visits to the apiary to ensure the escape boards are functioning effectively. The products explored below take between 2-48 hours to separate the bees from the honey, and it is important that they be monitored to ensure no problems develop.
There can be no cracks, openings, or holes above the escape boards. Such openings may be used by honey thieves such as yellow jackets, with a robbing frenzy denying you any of the sweet nectar. In the event robber bees are able to infiltrate the supers, the loss of honey may be complete, underlining the importance of effectively installing the bee escape board.
Escape Board Specs
What is unique about the escape board is its non-intrusive nature both in terms of the bees and also the honey. Chemical methods to separate bees from honey may lead to damage to the bees and a negative shift in the flavor of the honey. The more expensive bee blower method can dishevel the bees and even separate the queen from the hive to the detriment of your beekeeping efforts.
The bee escape board method is inexpensive and can be highly effective. However, there're many variations in the types of escape boards. Each type of escape board has a varying degree of effectiveness in both form and function. Following is a brief overview of the primary types of escape boards to provide us with sufficient background information before considering various options on the market for pre-fabricated bee escape boards.
Porter Bee Escape
This form of escape board is extremely inexpensive to produce, although is not particularly effective, and requires significant alteration to achieve top effectiveness. It is effectively a modified inner cover that is inserted in the hole of an inner cover, and then requires patience for the bees to leave, although they may not be comfortable doing so.
Triangle Escape Board
The triangle escape board works on similar principles to the Porter bee escape, although allows greater room for the bees to comfortably move. An overnight use often leaves no more than five or six bees in the super, on occasion none. It's important to maintain sufficient space below the escape board for the bees to go, and if the hive is especially crowded, adding an empty super below the escape bowl may help.
Escape boards can vary in price from a few dollars up to around twenty bucks depending upon their format and the materials used in construction. A variety of websites provide options for bee escape boards that will work for your personal setup and preferences for your bees. To frame the various options available, the following is a consideration of the specifications of a number of the top escape boards available on the market.
The Varieties of Bee Escape Boards
We picked a couple of similar escape boards available on the market to see how they compare. The bee escape boards presented below will be compared in relation to their ease of use, the materials used in their design and its overall appearance, as well as price. The varieties presented will make it clear that whatever sort of escape board you prefer, there are options available.
- 8 Way Bee Escape Board
- Bee Escape M00806
- Mann Lake Professional Bee Escape
- Brushy Mountain Bee Farm Bee Escape
The 8 Way Bee Escape Board is a beautifully designed wooden escape board with plastic attachments through which your bees may comfortably exit the honeycomb so you may harvest honey with minimal bother. When trying to remove the bees clustered on the honeycomb you wish to harvest honey from, there can be a number of headaches, with the 8 Way Bee Escape board solving the problem of pulling honeycombs individually and trying to get the bees off. This escape board is particularly effective, and after the requisite waiting time you may return to find a mostly empty box ready to be harvested.
Ease of Use
Simply place a bee escape below your box of honeycomb 24-48 hours before harvesting honey, with the maze side facing away from the honey, and return to find ideally a mostly empty box.
Assembly Time
Design Quality
The 8-Way Bee Escape Board is finely constructed of wood and plastic materials with a stylish aesthetic that will fit with any hive box.
The Bee Escape M00806 is a standard bee one-way door bee escape that allows the bees to leave, but not return. It is placed beneath the supers of honey to be removed, making the supers free of bees within 2-24 hours, all without the use of chemicals. Affixes to the center opening of an inner cover. The manufacture suggests that when removing more than one super of honey from within an individual hive, that you place an empty shallow super under the escape board to allow for more space.
Ease of Use
Upon attaching it to the center opening of the inner cover, simply put it into place and it is functional.
Assembly Time
Snaps simply into the center opening of an inner cover it fits with
Design Quality
Plastic and not aesthetically pleasing, but functional
The Mann Lake Professional Bee Escape is in the style of the 8-Way Bee Escape Board, constructed of wood and plastic. It is capable of clearing your supers in as few as 4 hours. As warned above, this manufacturer warns of the importance of not leaving the escape board in place for too long, as in time the industrious little creatures will figure out a way back in.
Ease of Use
Simply attach over the hole of the inner cover, set in place escape side down beneath the supers, and wait for the bees to clear.
Assembly Time
Design Quality
Constructed stylishly of wood and plastic
The Brushy Mountain Bee Farm Bee Escape functions much like the others in that it allows bees to exit while not allowing them to regain entry. This particular escape board is constructed of white plastic, and attached to the hole in an inner cover. The manufacturer suggests a longer waiting time of a few days may be necessary to clear the super of bees, although the warning of the potential of robber bees finding their way into the supers is again highlighted.
Ease of Use
Upon being clicked into the hole in an inner cover, it is functional.
Assembly Time
Must be clicked into the hole on an inner cover, beyond that it is pre-fabricated
Design Quality
Functional no-frills plastic design
Escape boards vary in their construction and formatting, but whatever their design, they are a chemical-free solution to separate your bees from the honey. In contrast to bee blowers, the cost is exponentially lower for escape boards, and the potential of damage to the hive is markedly lower, outside of the ever-present risk of robber bees.
In comparison to chemicals, escape boards provide a natural alternative that allows the bees to remove themselves. Rather than forcibly blowing the bees out from within the hive, with the risk of losing the queen and having to rebuild, the escape board allows you to transform your inner cover into a one-way street for the bees that enables them to freely move out of the supers you wish to harvest.
Price $$
The escape board provides an economical solution to separating bees from their honey without the use of physical force or chemical substances. Given the wide variety of formats currently available, explore the options through this article and then consider what your beekeeping practices are, and what types of escape boards may be best for your hives.
Depending upon whether you prefer a simple plastic insert that attaches into the hole of your inner door, or a wooden board with the insert containing the hole already designed into the product, you have choices. While the wooden designs are more appealing in terms of look, they may also be easier to use as they may simply be slipped between the super and the inner door to allow for the bees to begin moving and separating themselves from the honey.
Ease of Use
The bee escape boards reviewed are easy to install and begin to work immediately upon having been put in place. Through the use of the escape board, you will find a solution to bee from honey separation that is minimally invasive and chemical-free. Stay tuned to the Beekeeper Center for further tips on how to better care for your bees, and the tricks of the trade to do so naturally.

subset: commoncrawl


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25 Lessons from 25 Months of Content Marketing
Lists are a great way to check your strengths and weaknesses and this is a pretty comprehensive list
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6 Unconventional Ways to Come Up with Blog Post Ideas
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3 Obstacles Every Marketer Will Face in 2017
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15 Marketing Strategies That Inspire Strategic Thinkers
Marketing ideas with specific examples that can help you think out of the box. Marketing is all abo
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11 Reasons Why People Don't Like You—and 3 Ways to Win Them Over Now
If you want to succeed, learn from successful people. Leonard Kim grew his followers to 300K and is
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How to Write the Perfect Headline + 37 Templates to Get You Started
There are proven and measured techniques in getting attention in an exploding content world! The Hea
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You spend a lot of time, money and effort to get people to your landing pages, but how do you get th
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Great advice for finding top domains to link to you, clever messaging techniques, designing your lan
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Promotion is 80% of content marketing. Knowing how to promote is key to your success. When, should y
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Interactive content is a proven strategy for engaging users and capturing the interest and attention
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H.R.1505 - Protecting Family Resources and Training Options Act116th Congress (2019-2020) |
BillHide Overview
|Rep. Arrington, Jodey C. [R-TX-19] (Introduced 03/05/2019)
|House - Ways and Means
|Latest Action:
|House - 03/05/2019 Referred to the House Committee on Ways and Means. (All Actions)
This bill has the status Introduced
Here are the steps for Status of Legislation:
- Introduced
- Passed House
- Passed Senate
- To President
- Became Law
Subject — Policy Area:
- Social Welfare
- View subjects


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Fort Meigs. A condensed history of the most important military point in the Northwest, together with scenes and incidents connected with the sieges of 1813, and a minute description of the Old Fort and its surroundings, as they now appear.
Toledo, Ohio: Blade Printing and Paper Co., 1886. 8vo. 43 pp. FIRST EDITION. With 4 full page woodcuts (1 map). Original printed wrappers, illustrated with a woodcut of Fort Meigs. Front wrapper detached, small stamp of the Garrett Biblical Institute as well as their Sold stamp to front wrapper. Item #13008
First edition. Gives a brief historical sketch of Fort Meigs, including geographical information. The Seige of Fort Meigs, during the War of 1812, was considered an important American victory, and a turning point in the war on the northwest frontier.
Averill (fl. 1886) was a sergeant in the Ohio 21st Infantry.
Price: $250.00
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See all items by James P. AVERILL


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how do repair error message trap 0000000D GENERAL PROTECTION FAULT
Generally the error codes don't give enough information to know exactly what is wrong. Please supply the circumstances under which this is happening so I can try to send you in the correct direction. It could be failed hardware or a bad media disk, bad memory module or many other problems. You might try running ubuntu off of a cd-rom and see what kind of errors you get then.


text:
Dan Polydoris from The Chicago Toy Collector toyed with classic 80s Kenner Star Wars figures and reforged them as a set of Atari characters, similar to what you can see on the boxes.
A line-up of action figures (and maybe a few vehicles) based on these games could have been fun, sitting next to all the G.I. Joe and He-Man figures. Even though thanks to the Atari 2600's limited power you could only see them in the games as giant pixels.
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If you're in the middle of trying to decide what the best subwoofer to go for is I can help you with my short guide on what I believe are the best 10" size. While a 10 inch subwoofer is relatively small they can still be exceptionally powerful and one thing you won't want to compromise on is power!
If you're looking for strong bass performance then don't just buy the first subwoofer you come across, take into account all the benefits and features so you don't make the wrong decision. Size doesn't always mean quality and despite some people telling you that you get better sound with a larger subwoofer – if you choose a high quality piece of equipment you don't lose any of that powerful bass you crave. The following three 10 inch subwoofers are all available on Amazon.com and deliver a superior quality audio sound – trust me, I'm a music addict!
Pyle PLPW10D 1000 Watt 10 Inch Subwoofer
This is a handsome subwoofer and has a huge output of 1000 watts for a 10" piece of equipment and it's so affordable you could have more than one to really max out. This Pyle 10 inch subwoofer produces sound using the 2" single voice coil 4-Ohm and promises an outstanding audio experience whether you use it in your car or if you prefer, at home – even outdoors!
It's easy to connect, wire it to your amplifier with the spring-loaded speaker terminals to enjoy your music. Rubber suspension which is specially treated enhances the sound and a vented motor construction protects the subwoofer so it should last and last. There are many other advantages:
- Great value for money!
- 50oz magnet
- Black steel basket
- Non-press paper cone
- SPL 90dB
- Dual Ohm Impedance
- 500 watts RMS/1000 Watt max power
A couple of words of advice, if you're mounting in your car, get some brackets and use this subwoofer gently so don't crank up the volume immediately – do it gradually so as not to blow it out. The sound is good, you can hear the bass well – they aren't the best subwoofers on the market but they are very low price and you still get a quality product.
Kicker 10C104 Comp 10 Inch Subwoofer 4 Ohm
This is a slightly more expensive subwoofer than the Pyle version above but it delivers a solid sound with plenty of low tones and barely any distortion even on the highest volume so if I had to choose between this one or the Pyle I'd spend more cash and buy the Kicker 10 inch subwoofer.
The subwoofer comes with a coil-cooling venting to prevent overheating and it's made out of a stiff injection molded cone for strength. The voice coil is high temp and it also boasts Spiraled tinsel-lead technology for great staying power.
You can use this subwoofer in vented or sealed enclosures too and the mounting depth is 5". Really, there are no negatives you get a kick-ass bassline and pounding music for a great price.
For more information on what benefits the Kicker has see my list below:
- Reasonable value for money
- Loud, booming base
- Injection molded cone
- High temp coil wire
- Vented pole piece
- Steel basket
- Coil cooling perimeter venting
- Ribbed surround for extra strength
- Durable Spiralead technology tinsel leads
- Spring loaded terminals
Pioneer TS-W254R 10 Inch Component Subwoofer
Here's another budget price 10 inch subwoofer with all the power and it's easy on the pocket. If you want something which gives great tone, both high and low then you won't go wrong with the Pioneer. Delivering 1,100 watts max power it's a stylish looking piece which has a host of great features and benefits – additionally, everyone knows and respects Pioneer which is a trusted and reputable brand.
The subwoofer weighs 10lb and gives unbelievably strong output and an incredibly superior audio experience. For something that really rocks – this is it and it's really easy to install too even with a cheap 125W amp you get awesome sound. It is literally loaded with features and from what I hear from others who have it, it last for years (I've only had mine for a few months):
- Superb value for money
- Good looking sleek design
- 93Db sensitivity
- 20Hz-220Hz with 250W RMS
- 1100 watts of power
- Composite IMPP seamless cone
- 6 layer copper voice coil


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Beautiful location, quiet, and right in the heart of El Batey
- Mathhew Paulson
Quiet, tropical, poolside living in the very heart of the beautiful
resort town of Sosúa on the North Coast of the Dominican Republic. Condos is within an easy two to five minutes walking distance of beaches, banks, restaurants, shopping, and nightlife.
The official website of Condos Dominicano owners since 1998 is ©1998-2013 by C D Services and Xanadu Digital. All rights reserved.
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Convert the recipeto
another language. Works in most Browsers
Recipe by: Chef John V., A Good Cooking Recipe!
Serving size: 4
Preparation time: 0:30
2 whole bell peppers
1 tsp. of chopped garlic
1 tbsp. olive oil
1 tsp. of salt
1/4 tsp. ground white pepper
1/4 cup extra virgin olive oil
2 tsp. sugar
1 tbsp. cider vinegar
Wash 2 whole bell peppers, red, yellow, green or orange and dry. Cut in half and remove all the stem and seeds. Place the half peppers over an open flame on a gas stove, skin side down. With the flame on high, burn the skins until black and charred all over. When done place in a bowl and cover with plastic wrap to finish cooking and let the steam soften them. After 15 minutes rinse under a stream of cool running water. Rub slightly and the charred skins will wash off and you will be left with a perfect roasted pepper.
Cut into strips and marinate in vinaigrette.


text: 41 Fun and Easy DIY Arts Anyone Can Do A collection of Fun and Easy DIY Arts You Can Make. There are forty-one ideas for DIY Art Supplies, DIY Art To Sell, DIY Art Projects, Easy DIY Art, DIY Art Room, and much more.1. How Arts and Crafts Style Beautifies Today's InteriorsSource: houzz.com2. DIY Football Party Cups - Let's Mingle BlogSource: letsmingleblog.com3. DIY Party Photo Frame - From Under a Palm TreeSource: fromunderapalmtree.com 4. Make Paper From Plants - DIY - MOTHER EARTH NEWSSource: motherearthnews.com5. DIY Teacher Gift Idea: Yardstick USA Wall Art - Robb RestyleSource: robbrestyle.com6. Artist crafts stunning sculptures using old watchesSource: boredomtherapy.com 7. How to stop a DIY nightmare when starting a new life abroadSource: optima-translation.com8. An Earthy, Elegant DIY Holiday WreathSource: decoist.com9. 3 DIY Gifts to Start NOW to Have by Christmas!Source: thecozie.co 10. Curio Makeover Into Craft Storage – The Party Fetti BlogSource: partyfettiblog.com11. DIY Smart Home Project: Do-It-Yourselfer Designs and Installs His Own Whole-House Music System - Electronic HouseSource: electronichouse.com12. 4 DIY Insect Repellents - Gardening - Mother Earth LivingSource: motherearthliving.com13. Three times the fun: DIY Snowman Wall ArtSource: craftsncoffee.com14. DIY 13: 2016 Documentation - Opportunities - Live Art Development AgencySource: thisisliveart.co.uk15. Great days out Worcestershire with kids - Eastnor Castle - Craft with CartwrightSource: craftwithcartwright.co.uk16. DIY Wall Art from Old Potato Sacks - Crafting a Green WorldSource: craftingagreenworld.com17. DIY Valentine Decor ~ Watercolor Heart Artwork for your HomeSource: 3littlegreenwoods.com18. DIY Valentine's Day Crepe Paper Peony Flowers with Paper Mart - Chic StealsSource:chic-steals.com19. DIY Soda Can Art - Cottage in the OaksSource: cottageintheoaks.com20. Yarn Wrapped Hearts Craft - Valentines Day Crafts - Easy Peasy and FunSource: easypeasyandfun.com21. Dress your plants: DIY Washi Tape Planter ArtSource: thecozyhomechronicles.com22. DIY Football Party Cups - Let's Mingle BlogSource: letsmingleblog.com23. DIY Halloween Pop Up Cards for Kids - Red Ted Art's BlogSource: redtedart.com24. Hug a Book Toothless Bookmark DIY - Red Ted Art's BlogSource: redtedart.com25. DIY Weihnachtskarte mit Stoff - HANDMADE KulturSource: handmadekultur.de


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Save the Redwoods League and California State Parks are offering free, downloadable vehicle day-use passes to more than 40 redwood state parks for use on November 24, 2017. The passes are going quickly, so reserve and download yours today at RedwoodsFriday.org.
We are delighted to offer this free event for the third year in a row to celebrate California's unique and incredible redwood state parks. By offering free vehicle day-use passes, we hope to encourage everyone to go out and explore the parks with their friends and families and to inspire life-long connections with our public lands.
Save the Redwoods League and California State Parks have worked together to protect this network of parks for nearly a century and to encourage visitors from all over the world to experience these remarkable forests. Thanks to the generous support of the League's members, this year we were able to offer more than 2,500 free passes to over 40 redwood state parks for use on the day after Thanksgiving.
The downloadable passes cover day-use admission and parking fees. They are available on a first-come, first-served basis at RedwoodsFriday.org. Though they're going quickly, there's still space at many wonderful parks, including Wilder Ranch, Humboldt Redwoods, Jedediah Smith Redwoods and Calaveras Big Trees State Parks.
Please keep in mind:
- Passes are limited. They will be distributed on a first-come, first-served basis according to each park's capacity.
- Only one day-use pass is needed per vehicle, per park.
- The pass covers day-use admission and parking fees. Pass does not guarantee a parking space or entry if the park is full due to high demand.
- To ensure valid entry and avoid fines, printed passes must be presented to park staff members at entry gates or displayed on vehicle dashboards if no personnel are on duty.
- Electronic images of the pass will not be accepted.
- Consider visiting a state park during the off-peak hours – opening time to 11 a.m. and 3 p.m. to closing time.
- Visitors without passes are welcome, but must pay admission.
- We encourage all park visitors to review and obey park rules (external link).
- Share your experiences with us on social media using the hashtags #RedwoodsFriday and #CAStateParks.
Learn more about Redwoods Friday and reserve your free vehicle day-use pass today.


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I want to power up arduino through Vin port , what should be the input voltage ?
About 7.5V to 9V is best. A 9V battery is often not capable to supply enough current for an Arduino. Do you have a multimeter to measure the battery voltage drop when the Arduino is connected ?


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Tag Archives: summer fun
Do your Little Pnuts love ice cream? Ours certainly do, and what could be a better way to beat the summer heat than ice cream pretend play? Here are five ways we have used the Hape Ice Cream Shop from our recent Little Pnuts shipment for pretend play, sensory play, fine motor development, and FUN!
What You Will Need
- Hape Ice Cream Shop
- Cloud Dough (Recipe below)
- Sand
- Shaved Ice
- Homemade Syrup (Recipe below)
- Ice Cream Dough (Recipe below)
- Pom Poms in various sizes & colors
Variations of Play
Cloud Dough
Cloud dough, moon dough, snow dough –whatever you call it, this classic sensory medium makes the perfect pretend ice cream! To make it, simply combine 8 parts flour to one part vegetable oil (or any cooking oil). You can add Kool Aid, spices, or extracts to scent it and/or crushed chalk or powdered tempera paint to color it. The dough is soft and fluffy but can be molded like sand…so fun!
Take your Hape Ice Cream Shop to the sandbox – your Little Pnuts are guaranteed tons of fun with very little preparation!
Snow Cones with Homemade Syrup
Since the Hape Ice Cream Shop is BPA and phthalate free, your Little Pnuts can use it to make their own tiny snow cones! We used shaved ice and made homemade syrup with this easy recipe (LINK: http://nateandrachael.com/snow-cone-syrup-recipe/) and had a blast with our icy treat!
Ice Cream Dough
We stumbled upon this sensory play recipe from our friend over at Play Create Explore (LINK: http://www.playcreateexplore.org/2013/01/ice-cream-dough-new-play-recipe.html) and have been having tons of fun with it this summer! To make it, simply combine ¾ cup hair conditioner (or lotion, which is what we had on hand) and 1 ½ cups cornstarch. Add extracts and/or food coloring to make your perfect "flavor" and you have a fantastic dough that really and truly looks like ice cream!
Pom Poms
We have a giant stash of pom poms of all shapes, sizes, and colors that our Little Pnuts love to play with. They had a fabulous time scooping them out of the tub and "serving" their creations to the whole family one afternoon. This was an easy and awesome fine motor workout!
Developmental Milestones:
This activities focuses on the following Developmental Milestones for your Little Pnuts:
Exploration, Sensory Exploration & Development, Cognitive Development, Fine Motor Skill Development, Focus and Concentration, Creative Play, Pretend Play, Imaginative Play
—Stephanie Haass, Little Pnuts Early Childhood Activities Expert & Blogger, founder of www.two-daloo.com
Summer is the perfect time to get outdoors, play games and to get wet. Why not include a little balance and coordination to an afternoon of Gross Motor Play. Water Balloon Stomp is a fabulous way for your Little Pnuts to practice color recognition, build on counting skills, improve strategic thinking all while enjoying outdoor fun. A great water play activity for a play date or for individual play this activity is sure to elicit plenty of giggles.
What You Will Need
- Filled Water Balloons in a variety of colors, filled.
- A bucket filled with water
- A Timer for the variation on play
Get Ready…
Gather up some water balloons. We usually fill up a bucket(s) with water and then drop the water balloons in that to keep them safer longer.
Get Set…
Find a good place for your Little Pnut to "stomp". The beauty of this activity is you can do it just about anywhere outdoors. We did this activity on our deck but the yard, the driveway, or patio work great too. Gently lay out one or more water balloons on the ground.
You may have to demonstrate for your Little Pnut the action you are after but I promise you they will catch on quickly. Our 22 month old did! He had the best time trying to stomp on and break the water balloons with his feet. That alone is a good exercise in concentration and coordination. The older Little Pnuts will be a little more accurate and break the balloons more quickly but it may take the littles a few tries. Mix it up and make a color recognition game out of it for your Little Pnuts by laying out more than one balloon at a time and telling them what color balloon to stomp. Practice counting by challenging them to break a designated number of balloons.
For even older Little Pnuts write numbers on the balloons with a sharpie and see how many balloons they can break (ie. points they can score) in a designated time period. Older Little Pnuts will love the added element of a time challenge. The possibilities are almost endless. Most importantly though, have fun & get wet!
Happy Playing!
Developmental Milestones:
This activities focuses on the following Developmental Milestones for your Little Pnuts:
Gross Motor Skill Development, Focus and Concentration, Strategic Thinking, Balance, Coordination, Color Recognition, Number Recognition, Number Sequencing, Counting Skills, Cooperative Play, Cognitive Development, Group Play and Individual Play.—Jennifer Haas, founder of Plain Vanilla Mom.
It's the perfect weather for outdoor water play. Stay cool in the hot summer sun while introducing your Little Pnuts to the joy of fishing. A great game of strategy while encouraging concentration and focus. Perfect for a play date or for individual play, Fishing for Ping Pong Balls, will get your Little Pnuts excited about splashing around!
What You Will Need
- Ping Pong Balls (as many or as few as you like)
- Something to fish with like a butterfly or bug net or a kitchen strainer with a handle or even slotted spoon would work.
- A body of water. Think kiddie pool, bathtub, water table or large plastic container.
Set Up
Fill your designated container with water and drop in a few ping pong balls. We found that the 'more the merrier' in respect to the ping pong balls was especially true for this activity. Give your Little Pnut his fishing gear of choice. We used a kiddie sized butterfly net but a kitchen strainer with a handle works great too.
Let Them Fish!
See how many ping pong balls they can catch. Have them count them with you. If your Little Pnut is capable, challenge them to catch a particular number of ping pong balls. If you happen to have different colors of ping pong balls have them catch balls of a certain color. Ours were all white so we focused on making this a counting activity. For the littlest of Little Pnuts it's great hand-eye coordination just for them to catch the ping pong balls and throw them back in the water.
Happy Playing!
Developmental Milestones:
This activities focuses on the following Developmental Milestones for your Little Pnuts:
Gross Motor Skill Development, Fine Motor Skills, Focus and Concentration, Strategic Thinking, Problem Solving, Cognitive Development, Coordination, Cooperative Play, Group Play and Individual Play.—Jennifer Haas, founder of Plain Vanilla Mom.


text:
The Marine Corps Scholarship Foundation is the nation's oldest and largest need-based scholarship organization supporting U.S. military families. Since 1962, the Foundation has provided over 26,000 scholarships valued at more than $65 million, including nearly $5,000,000 to more than 1,600 students for the 2011-2012 academic year.
The Scholarship Foundation is proud to have been named by Independent Charities of America as 'Best in America' for demonstrating "the highest standards of public accountability, program effectiveness, and cost effectiveness."
For the Scholarship Foundation's most recent financial information, please visit our Reports and Publications page.
Provide educational opportunities to Marine Corps sons and daughters and Honor Marines by Educating Their Children today!
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text:
- Research article
- Open Access
- Published:
Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly
BMC Medical Genetics volume 8, Article number: 68 (2007)
7528 Accesses
15 Citations
3 Altmetric
Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, advanced bone age, characteristic facial features, and learning disabilities, caused by mutations or deletions of the NSD1 gene, located at 5q35. Sotos syndrome has been described in a number of patients with autism spectrum disorders, suggesting that NSD1 could be involved in other cases of autism and macrocephaly.
We screened the NSD1 gene for mutations and deletions in 88 patients with autism spectrum disorders and macrocephaly (head circumference 2 standard deviations or more above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions. Dosage analysis of NSD1 was carried out using multiplex ligation-dependent probe amplification.
We identified three missense variants (R604L, S822C and E1499G) in one patient each, but none is within a functional domain. In addition, segregation analysis showed that all variants were inherited from healthy parents and in two cases were also present in unaffected siblings, indicating that they are probably nonpathogenic. No partial or whole gene deletions/duplications were observed.
Our findings suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for NSD1 mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.
Sotos syndrome (MIM 117550) is a childhood overgrowth syndrome characterized by distinctive facial features including prominent forehead, down-slanted palpebral fissures and pointed chin, macrocephaly and learning disabilities. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor binding SET domain protein 1) gene [1], which encodes a coregulator of nuclear receptors that can activate or repress transcription [2]. Point mutations are identified in the majority of non-Japanese patients with Sotos syndrome (~80%), whereas 5q35 microdeletions encompassing NSD1 are the major cause among Japanese patients (>50%) [3, 4]. Most cases of Sotos syndrome are sporadic, but occasional familial cases have been reported, with dominant inheritance. Affected children usually exhibit developmental delay, and speech delay is common. In addition, autism spectrum disorders or autistic features have been described in a number of patients with Sotos syndrome [5–13].
Autism is a behaviorally defined neurodevelopmental syndrome characterized by social and communication deficits, and the presence of restricted and repetitive behaviors and interests, with onset in the first three years of life. Recent epidemiological studies indicate that autism is a common disorder, affecting as many as 2 in 1000 children [14]. The prevalence of all autism spectrum disorders, which include autism, pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger syndrome, is estimated at 6 per 1000 [14]. Autism is approximately four times more frequent in males than in females. Family and twin studies have shown that genetic factors play a major role in the susceptibility to autism [15] but genetic heterogeneity has made the identification of the genes involved difficult [16]. Monogenic disorders such as fragile X syndrome and other forms of X-linked mental retardation, tuberous sclerosis complex, neurofibromatosis, and various rare metabolic disorders are identified in a small percentage of patients [17]. Cytogenetically visible chromosomal aberrations are identified in approximately 5% of affected individuals [10], while recent higher-resolution whole-genome analyses using array-based technologies have revealed genomic imbalances in at least 10% of cases [18, 19]. However, the underlying cause remains unknown in the majority of patients.
Autism is associated with macrocephaly in approximately 20% of cases [20, 21]. Although macrocephaly is one of the most widely replicated neurobiological findings in autism, its pathogenesis remains unknown. The description of several cases of Sotos syndrome in patients with autism and macrocephaly [5–13] suggests that NSD1 could be involved in other cases of autism. Thus, the aim of this study was to assess the frequency of NSD1 mutations in cases of autism spectrum disorder associated with macrocephaly, defined as an occipitofrontal head circumference (HC) 2 SD or more above the mean. We screened NSD1 by direct sequencing in 88 subjects with autism spectrum disorder and macrocephaly. In addition, we searched for deletions of the NSD1 gene using multiplex ligation-dependent probe amplification (MLPA). Our results showed no point mutations or deletions of NSD1 , indicating that Sotos syndrome is a rare cause of autism spectrum disorders with macrocephaly.
A total of 88 patients with an autism spectrum disorder and macrocephaly (HC ≥+2 SD) were included in the study. Among these, 49 were recruited by the Paris Autism Research International Sibpair (PARIS) study at specialized clinical centers in France, Sweden, Norway, Italy, Belgium, Austria, and the United States, and 39 were collected at the Mount Sinai School of Medicine and/or the Autism Genetic Resource Exchange (AGRE) [22]. Patients were identified from a larger pool of 462 families for which head circumference measures were available. All patients with a HC ≥+2 SD were included in the study; in families with two or more siblings with an autism spectrum disorder and macrocephaly, one individual was chosen at random for the mutation screening.
The patients from the PARIS study included 45 males and 4 females from 16 multiplex families (with two or more affected siblings) and 33 simplex families (sporadic cases), with a mean age at the last evaluation of 10.5 ± 5.8 years (range 3.5–26). All patients were evaluated by experienced psychiatrists or child neurologists; diagnoses were based on clinical evaluation and DSM-IV and ICD-10 criteria. In addition, patients with autistic disorder were assessed with the Autism Diagnostic Interview-Revised (ADI-R) [23] and those with Asperger syndrome were assessed with the Asperger Syndrome Diagnostic Interview (ASDI) [24]. Forty-five individuals met criteria for autistic disorder, 2 for PDD-NOS and 2 for Asperger syndrome. There were 35 patients with mental retardation and 22 with limited or no language. Laboratory tests to rule-out medical causes of autism included standard karyotyping, fragile X testing, and metabolic screening; brain imaging and EEG were performed when possible. Patients diagnosed with medical disorders such as fragile X syndrome or chromosomal abnormalities were excluded from the study. There were 41 individuals of Caucasian origin, 2 Black, 1 Asian and 5 of mixed ethnicity. The study was approved by the research ethics boards of the collaborating institutions. Informed consent was obtained from all families participating in the study.
Thirty-nine patients were recruited by the Seaver Autism Research Center (SARC) at Mount Sinai, New York, co-recruited by the SARC and AGRE, or obtained from AGRE. The patients included 31 males and 8 females from 35 multiplex families and 4 simplex families, with a mean age at the last evaluation of 10.5 ± 4.2 years (range 5–24). The ADI-R was used to assess affected subjects. There were 35 individuals with autism, 1 with borderline autism, 2 with Asperger syndrome and 1 with PDD-NOS. The term 'borderline autism' (or 'not quite autism') refers to individuals who are no more than one point away from meeting autism criteria according to the ADI-R on any or all of the 3 main domains of autistic impairment – social, communication, and repetitive behavior – and meet the age of onset criterion (before 36 months); or individuals who meet criteria on all 3 domains but do not meet the age of onset criterion. Seventeen patients had mental retardation and 16 had limited or no language. Subjects with co-morbid genetic disorders (fragile X syndrome, tuberous sclerosis, or chromosomal anomalies) were excluded. There were 32 individuals of Caucasian origin, 1 Black, 1 Asian, and 5 of mixed or unknown ethnicity. All parents provided written informed consent. The study was approved by the local institutional review board.
HC among the 88 subjects included in the study ranged from +2 to +9.6 SD for age and sex. There were 68 subjects with a HC between +2 and +2.9 SD, 18 with a HC between +3 and +4 SD, and only 2 subjects with a HC greater than +4 SD. The patient with the largest HC (+9.6 SD) among all the study subjects was later found to have a PTEN mutation [25].
NSD1 mutation analyses
The NSD1 gene consists of 23 exons, the first of which is non coding. All exons (including exon 1), intron-exon boundaries and flanking intronic sequences were analyzed for mutations by direct sequencing of forward and reverse strands. When variants not described previously were detected, the DNA of parents and unaffected siblings (when available) was analyzed by direct sequencing for the specific base change identified in the proband.
NSD1 microdeletion analyses
In order to identify microdeletions of the NSD1 gene we performed MLPA [26] using a commercially available kit, according to the manufacturer's protocol (SALSA P026B Sotos; MRC-Holland, Amsterdam, The Netherlands). The P026B probe set contains 24 NSD1 probes, including one probe in the promoter region (1 Kb 5' of exon 1) and one probe for each of the 23 exons. The kit also contains six probes for five neighboring genes on 5q31-35 (IL4 , IL12B , FGFR4 , FLT4 and TRIM52 ), as well as 12 control probes in other chromosomes. Electrophoresis of PCR products was performed on an ABI 3730 sequencing platform (Applied Biosystems, Foster City, CA, USA) and the resultant traces were analyzed using the software GeneMarker (SoftGenetics, State College, PA, USA).
NSD1 mutation analyses
Genomic DNA from 88 unrelated individuals with autism spectrum disorders and macrocephaly was screened for intragenic NSD1 mutations by sequencing analysis. No frameshift or nonsense mutations were identified in any sample. Three missense variants, R604L, S822C and E1499G, were each identified in one individual (Table 1). R604L, in exon 5, was described previously in one patient referred for genetic testing of Sotos syndrome, and was classified as a variant of unknown significance [27]. S822C, also in exon 5, and E1499G in exon 10, have not been described previously. None of these variants is in a known functional domain of the protein [28]. Segregation analysis showed that all three variants were inherited from reportedly healthy parents and in two cases were present also in unaffected siblings, indicating that they are likely nonpathogenic. Furthermore, we identified two synonymous variants and two intronic substitutions present in one patient each, which were also inherited from unaffected parents. Table 1 shows all the sequence changes identified in our patients, including several new polymorphisms identified in this study.
NSD1 microdeletion analyses
There was no evidence for partial or whole gene deletions or duplications of the NSD1 gene in any of the patients screened with MLPA.
Screening of the NSD1 gene in a cohort of 88 familial and sporadic cases of autism and macrocephaly did not reveal any intragenic mutations or deletions, indicating that S otos syndrome is a rare cause of autism spectrum disorders. The three missense variants identified in one individual each (R604L, S822C and E1499G), were inherited from unaffected parents, suggesting that they are likely to be polymorphisms. In addition, none of these variants is located in a known functional domain [28], further suggesting that they are nonpathogenic. Previous studies have shown that missense mutations are pathogenic only if they occur within functional domains of the protein involved in chromatin regulation [4].
Our negative findings are in agreement with recent studies showing that virtually all patients with a NSD1 mutation or deletion have the characteristic facial features of Sotos syndrome (broad forehead, sparse frontotemporal hair, long narrow face, malar flushing, down-slanted palpebral fissures, prominent jaw, pointed chin) [4, 29, 30]. However, the facial features are subtle and are difficult to recognize by clinicians with limited experience with this condition. The patients in our study presumably did not have the facial gestalt of Sotos syndrome, although most had not been evaluated by a clinical geneticist and it is likely that the psychiatrists that evaluated the patients were not all familiar with Sotos syndrome because of the relative rarity of this condition.
The other key clinical features of Sotos syndrome are the macrocephaly and the developmental delay. HC and height are increased in the majority of children with Sotos syndrome. By adulthood, height may fall within normal limits, but macrocephaly usually persists. However, recent studies have shown that HC and height are normal in 10% of NSD1 mutation-positive patients, indicating that overgrowth, previously considered as a major criterion of the disorder, is not necessary for the diagnosis of Sotos syndrome [4].
Our series included a high proportion of familial cases of autism spectrum disorders, as compared to singletons (51 vs. 37). Because Sotos syndrome is mostly a sporadic disorder, this could have contributed to the negative results of this study. However, several familial cases of Sotos syndrome with NSD1 mutations have been described in the past years [4, 27, 30–35], suggesting that familial, usually milder, forms of the disorder might be underdiagnosed.
Besides Sotos syndrome, there are several other syndromes presenting with macrocephaly and developmental delay, which are sometimes associated with autism. Among the better known is the fragile X syndrome, which is the most frequent genetic disorder identified in patients with autism spectrum disorders, accounting for about 2% of cases [36]. Molecular analysis for fragile X is routinely performed in patients with autism and mental retardation, and was ruled out in the patients participating in our study. Another disorder associated with autism and macrocephaly is the PTEN hamartoma tumor syndrome, which includes Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. The PTEN gene has recently been found to be mutated in several children with autism spectrum disorders and macrocephaly [37–40]. We screened PTEN for mutations and deletions in the 88 individuals with autism spectrum disorders and macrocephaly reported in this study and identified one patient with extreme macrocephaly carrying a de novo missense mutation [25].
Other examples of disorders associated with macrocephaly which carry an increased risk for the development of autism include neurofibromatosis type I [41, 42] and 22q13 deletions [43]. In addition, there are several reports in the literature of cases with progressive postnatal macrocephaly with autism, marked speech delay and mental retardation, referred to as the Cole-Hughes macrocephaly syndrome [44, 45]. The Orstavik syndrome, described by Orstavik et al. [46], is characterized by macrocephaly, epilepsy, autism, mental retardation and dysmorphic features. Several other cases of the same syndrome were reported later by another group [47]. As Sotos syndrome, these disorders account for only a small number of patients with autism and macrocephaly.
The macrocephaly observed in about 20% of patients with autism appears to be an independent clinical trait, not related to sex, presence of morphological abnormalities, IQ, occurrence of seizures, or severity of autistic symptoms [20, 21]. Converging evidence from HC measurements, MRI studies and postmortem brain weight indicates that an even greater proportion of children with autism have an abnormal regulation of brain growth, resulting in enlarged brains during early childhood [48]. At birth, HC is typically normal or slightly reduced, followed by accelerated growth during the first years of life. This early phase of excessive growth is followed by slowed growth after 2–4 years of age, so that in adolescents and adults HC measures are usually within normal range [48]. Other studies, however, have found increased brain volume in older populations of individuals with autism [49, 50], so the timing of brain enlargement is not settled yet. Similarly, the pattern of enlargement across the brain lobes and cerebellum and the involvement of gray versus white matter remain unclear at present. Elucidation of the mechanisms involved in the pathological postnatal brain overgrowth may prove critical for understanding the emergence of autistic symptoms during the same time frame.
In conclusion, no NSD1 mutations, 5q35 microdeletions or partial NSD1 deletions were identified in this large sample of patients with autism spectrum disorders and macrocephaly. Our results suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for NSD1 mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.
- 1.
Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N: Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet. 2002, 30 (4): 365-366. 10.1038/ng863.
- 2.
Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R: Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators. Embo J. 1998, 17 (12): 3398-3412. 10.1093/emboj/17.12.3398.
- 3.
Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, Makita Y, Kondoh T, Ogata T, Hasegawa T, Nagai T, Ozaki T, Touyama M, Shenhav R, Ohashi H, Medne L, Shiihara T, Ohtsu S, Kato Z, Okamoto N, Nishimoto J, Lev D, Miyoshi Y, Ishikiriyama S, Sonoda T, Sakazume S, Fukushima Y, Kurosawa K, Cheng JF, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N: Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion. Hum Mutat. 2003, 22 (5): 378-387. 10.1002/humu.10270.
- 4.
Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S, Horn D, Hughes HE, Temple IK, Faravelli F, Waggoner D, Turkmen S, Cormier-Daire V, Irrthum A, Rahman N: Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005, 77 (2): 193-204. 10.1086/432082.
- 5.
Morrow JD, Whitman BY, Accardo PJ: Autistic disorder in Sotos syndrome: a case report. Eur J Pediatr. 1990, 149 (8): 567-569. 10.1007/BF01957694.
- 6.
Zappella M: Autistic features in children affected by cerebral gigantism. Brain Dysfunct. 1990, 3: 241–44-
- 7.
Trad PV, Schlefer E, Hertzig M, Kernberg PF: Treatment strategies for a case of concurrent pervasive developmental disorder and cerebral gigantism. J Am Acad Child Adolesc Psychiatry. 1991, 30 (3): 499-506. 10.1097/00004583-199105000-00024.
- 8.
Mouridsen SE, Hansen MB: Neuropsychiatric aspects of Sotos syndrome. A review and two case illustrations. Eur Child Adolesc Psychiatry. 2002, 11 (1): 43-48. 10.1007/s007870200007.
- 9.
Bolton PF, Veltman MW, Weisblatt E, Holmes JR, Thomas NS, Youings SA, Thompson RJ, Roberts SE, Dennis NR, Browne CE, Goodson S, Moore V, Brown J: Chromosome 15q11-13 abnormalities and other medical conditions in individuals with autism spectrum disorders. Psychiatr Genet. 2004, 14 (3): 131-137. 10.1097/00041444-200409000-00002.
- 10.
Kielinen M, Rantala H, Timonen E, Linna SL, Moilanen I: Associated medical disorders and disabilities in children with autistic disorder: a population-based study. Autism. 2004, 8 (1): 49-60. 10.1177/1362361304040638.
- 11.
Schaefer GB, Lutz RE: Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders. Genet Med. 2006, 8 (9): 549-556.
- 12.
Miles JH, Hillman RE: Value of a clinical morphology examination in autism. Am J Med Genet. 2000, 91: 245-253. 10.1002/(SICI)1096-8628(20000410)91:4<245::AID-AJMG1>3.0.CO;2-2.
- 13.
Battaglia A, Carey JC: Etiologic yield of autistic spectrum disorders: a prospective study. Am J Med Genet C Semin Med Genet. 2006, 142: 3-7.
- 14.
Chakrabarti S, Fombonne E: Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry. 2005, 162 (6): 1133-1141. 10.1176/appi.ajp.162.6.1133.
- 15.
Veenstra-Vanderweele J, Christian SL, Cook EH: Autism as a paradigmatic complex genetic disorder. Annu Rev Genomics Hum Genet. 2004, 5: 379-405. 10.1146/annurev.genom.5.061903.180050.
- 16.
Gupta AR, State MW: Recent advances in the genetics of autism. Biol Psychiatry. 2007, 61 (4): 429-437. 10.1016/j.biopsych.2006.06.020.
- 17.
Gillberg C, Coleman M: The Biology of the Autistic Syndromes. 2000, London, UK , Cambridge University Press
- 18.
Autism Genome Project Consortium: Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007, 39 (3): 319-328. 10.1038/ng1985.
- 19.
Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M: Strong association of de novo copy number mutations with autism. Science. 2007, 316 (5823): 445-449. 10.1126/science.1138659.
- 20.
Fombonne E, Roge B, Claverie J, Courty S, Fremolle J: Microcephaly and macrocephaly in autism. J Autism Dev Disord. 1999, 29 (2): 113-119. 10.1023/A:1023036509476.
- 21.
Miles JH, Hadden LL, Takahashi TN, Hillman RE: Head circumference is an independent clinical finding associated with autism. Am J Med Genet. 2000, 95 (4): 339-350. 10.1002/1096-8628(20001211)95:4<339::AID-AJMG9>3.0.CO;2-B.
- 22.
Geschwind DH, Sowinski J, Lord C, Iversen P, Shestack J, Jones P, Ducat L, Spence SJ: The Autism Genetic Resource Exchange: a resource for the study of autism and related neuropsychiatric conditions. Am J Hum Genet. 2001, 69 (2): 463-466. 10.1086/321292.
- 23.
Lord C, Rutter M, Le Couteur A: Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994, 24 (5): 659-685. 10.1007/BF02172145.
- 24.
Gillberg C, Gillberg C, Rastam M, Wentz E: The Asperger Syndrome (and high-functioning autism) Diagnostic Interview (ASDI): a preliminary study of a new structured clinical interview. Autism. 2001, 5 (1): 57-66. 10.1177/1362361301005001006.
- 25.
Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reichert J, Anckarsäter H, Råstam M, Smith CJ, Silverman JM, Hollander E, Leboyer M, Gillberg C, Verloes A, Betancur C: Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet B Neuropsychiatr Genet. 2007, 144 (4): 484-491.
- 26.
Douglas J, Tatton-Brown K, Coleman K, Guerrero S, Berg J, Cole TR, Fitzpatrick D, Gillerot Y, Hughes HE, Pilz D, Raymond FL, Temple IK, Irrthum A, Schouten JP, Rahman N: Partial NSD1 deletions cause 5% of Sotos syndrome and are readily identifiable by multiplex ligation dependent probe amplification. J Med Genet. 2005, 42 (9): e56-10.1136/jmg.2005.031930.
- 27.
Waggoner DJ, Raca G, Welch K, Dempsey M, Anderes E, Ostrovnaya I, Alkhateeb A, Kamimura J, Matsumoto N, Schaeffer GB, Martin CL, Das S: NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory. Genet Med. 2005, 7 (8): 524-533.
- 28.
Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N: Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Gene. 2001, 279 (2): 197-204. 10.1016/S0378-1119(01)00750-8.
- 29.
Cecconi M, Forzano F, Milani D, Cavani S, Baldo C, Selicorni A, Pantaleoni C, Silengo M, Ferrero GB, Scarano G, Della Monica M, Fischetto R, Grammatico P, Majore S, Zampino G, Memo L, Cordisco EL, Neri G, Pierluigi M, Bricarelli FD, Grasso M, Faravelli F: Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am J Med Genet A. 2005, 134 (3): 247-253.
- 30.
Saugier-Veber P, Bonnet C, Afenjar A, Drouin-Garraud V, Coubes C, Fehrenbach S, Holder-Espinasse M, Roume J, Malan V, Portnoi MF, Jeanne N, Baumann C, Heron D, David A, Gerard M, Bonneau D, Lacombe D, Cormier-Daire V, Billette de Villemeur T, Frebourg T, Burglen L: Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome. Hum Mutat. 2007, 28: 1098-107. 10.1002/humu.20568.
- 31.
Hoglund P, Kurotaki N, Kytola S, Miyake N, Somer M, Matsumoto N: Familial Sotos syndrome is caused by a novel 1 bp deletion of the NSD1 gene. J Med Genet. 2003, 40 (1): 51-54. 10.1136/jmg.40.1.51.
- 32.
Turkmen S, Gillessen-Kaesbach G, Meinecke P, Albrecht B, Neumann LM, Hesse V, Palanduz S, Balg S, Majewski F, Fuchs S, Zschieschang P, Greiwe M, Mennicke K, Kreuz FR, Dehmel HJ, Rodeck B, Kunze J, Tinschert S, Mundlos S, Horn D: Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. Eur J Hum Genet. 2003, 11 (11): 858-865. 10.1038/sj.ejhg.5201050.
- 33.
Tong TM, Hau EW, Lo IF, Chan DH, Lam ST: Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome. Chin Med J (Engl). 2005, 118 (18): 1499-1506.
- 34.
van Haelst MM, Hoogeboom JJ, Baujat G, Bruggenwirth HT, Van de Laar I, Coleman K, Rahman N, Niermeijer MF, Drop SL, Scambler PJ: Familial gigantism caused by an NSD1 mutation. Am J Med Genet A. 2005, 139 (1): 40-44.
- 35.
Tei S, Tsuneishi S, Matsuo M: The first Japanese familial Sotos syndrome with a novel mutation of the NSD1 Gene. Kobe J Med Sci. 2006, 52 (1): 1-8.
- 36.
Wassink TH, Piven J, Patil SR: Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet. 2001, 11 (2): 57-63. 10.1097/00041444-200106000-00001.
- 37.
Parisi MA, Dinulos MB, Leppig KA, Sybert VP, Eng C, Hudgins L: The spectrum and evolution of phenotypic findings in PTEN mutation positive cases of Bannayan-Riley-Ruvalcaba syndrome. J Med Genet. 2001, 38 (1): 52-58. 10.1136/jmg.38.1.52.
- 38.
Goffin A, Hoefsloot LH, Bosgoed E, Swillen A, Fryns JP: PTEN mutation in a family with Cowden syndrome and autism. Am J Med Genet. 2001, 105 (6): 521-524. 10.1002/ajmg.1477.
- 39.
Butler MG, Dasouki MJ, Zhou XP, Talebizadeh Z, Brown M, Takahashi TN, Miles JH, Wang CH, Stratton R, Pilarski R, Eng C: Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet. 2005, 42 (4): 318-321. 10.1136/jmg.2004.024646.
- 40.
Herman GE, Butter E, Enrile B, Pastore M, Prior TW, Sommer A: Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. Am J Med Genet A. 2007, 143 (6): 589-593.
- 41.
Gillberg C, Forsell C: Childhood psychosis and neurofibromatosis--more than a coincidence?. J Autism Dev Disord. 1984, 14 (1): 1-8. 10.1007/BF02408551.
- 42.
Williams PG, Hersh JH: Brief report: the association of neurofibromatosis type 1 and autism. J Autism Dev Disord. 1998, 28 (6): 567-571. 10.1023/A:1026012414193.
- 43.
Manning MA, Cassidy SB, Clericuzio C, Cherry AM, Schwartz S, Hudgins L, Enns GM, Hoyme HE: Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics. 2004, 114 (2): 451-457. 10.1542/peds.114.2.451.
- 44.
Cole TR, Hughes HE: Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?. Am J Med Genet. 1991, 41 (1): 115-124. 10.1002/ajmg.1320410128.
- 45.
Naqvi S, Cole T, Graham JM: Cole-Hughes macrocephaly syndrome and associated autistic manifestations. Am J Med Genet. 2000, 94 (2): 149-152. 10.1002/1096-8628(20000911)94:2<149::AID-AJMG7>3.0.CO;2-#.
- 46.
Orstavik KH, Stromme P, Ek J, Torvik A, Skjeldal OH: Macrocephaly, epilepsy, autism, dysmorphic features, and mental retardation in two sisters: a new autosomal recessive syndrome?. J Med Genet. 1997, 34 (10): 849-851.
- 47.
Steiner CE, Guerreiro MM, Marques-de-Faria AP: On macrocephaly, epilepsy, autism, specific facial features, and mental retardation. Am J Med Genet A. 2003, 120 (4): 564-565. 10.1002/ajmg.a.20032.
- 48.
Redcay E, Courchesne E: When is the brain enlarged in autism? A meta-analysis of all brain size reports. Biol Psychiatry. 2005, 58 (1): 1-9. 10.1016/j.biopsych.2005.03.026.
- 49.
Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, Folstein SE: Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry. 1997, 36 (2): 282-290. 10.1097/00004583-199702000-00019.
- 50.
Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P: A clinicopathological study of autism. Brain. 1998, 121 (Pt 5): 889-905. 10.1093/brain/121.5.889.
- 51.
Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N: NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet. 2003, 72 (1): 132-143. 10.1086/345647.
- 52.
Melchior L, Schwartz M, Duno M: dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the first 100 Sotos syndrome mutations. Ann Hum Genet. 2005, 69 (Pt 2): 222-226. 10.1046/j.1469-1809.2004.00150.x.
Pre-publication history
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/8/68/prepub
We are grateful to all the families that participated in this research. We thank the DNA and cell bank of the INSERM U679 (Hôpital Pitié-Salpêtrière) and the Centre d'Investigations Cliniques-Hôpital Robert Debré for processing the samples from the French families. We acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by the National Institute of Mental Health (grant MH64547 to Daniel H. Geschwind). This work was supported by the Beatrice & Samuel A. Seaver Foundation, the Milton & Miriam Handler Foundation, NIH (grants MH066673 and NS042165), INSERM, Assistance Publique-Hôpitaux de Paris, Fondation pour la Recherche Médicale, Fondation de France, Fondation France Télécom, and the Swedish Science Council. Dr. Joseph Buxbaum is the G. Harold and Leila Y. Mathers Research Professor at Mount Sinai School of Medicine.
Paris Autism Research International Sibpair Study: France : Marion Leboyer, Department of Psychiatry, Groupe Hospitalier Albert Chenevier – Henri Mondor, Créteil; Catalina Betancur, INSERM U513, Université Paris XII, Créteil; Pauline Chaste, Richard Delorme, Marie-Christine Mouren-Siméoni, Service de Psychopathologie de l'Enfant et l'Adolescent, Hôpital Robert Debré, Paris. Sweden : Christopher Gillberg, Maria Råstam, Carina Gillberg, Gudrun Nygren, Henrik Anckarsäter, Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg. Norway : Eili Sponheim, Centre for Child and Adolescent Psychiatry, University of Oslo, Oslo; Ola H. Skjeldal, Department of Pediatrics, Rikshospitalet, University of Oslo, Oslo. USA : Mary Coleman, Department of Pediatrics, Georgetown University School of Medicine, Washington D.C.; Philip L. Pearl, Children's National Medical Center, George Washington University School of Medicine, Washington, D.C.; Ira L. Cohen, John Tsiouris, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York. Italy : Michele Zappella, Divisione di Neuropsichiatria Infantile, Azienda Ospedaliera Senese, Siena. Austria : Harald Aschauer, Department of General Psychiatry, University Hospital, Vienna. Belgium : Lionel Van Maldergem, Centre de Génétique Humaine, Centre Hospitalier Universitaire du Sart Tilman, Université de Liège, Liège.
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Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
JDB and CB conceived the study, designed and coordinated it, performed part of the molecular genetic studies, and wrote the manuscript. GC and JG participated in the molecular genetic studies. GN, PC, RD, MR, JMS, EH, CG and ML participated in the recruitment of families. JMS, EH, CG and ML supervised the clinical evaluation of families. All authors read and approved the final manuscript.
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Buxbaum, J.D., Cai, G., Nygren, G. et al. Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly. BMC Med Genet 8, 68 (2007). https://doi.org/10.1186/1471-2350-8-68
- Autism Spectrum Disorder
- Head Circumference
- Asperger Syndrome
- Autistic Disorder
- Unaffected Sibling


text:
Sending reinforcements: women in combat deserve recognition
By Rae Hodge–
The good ol days are here again. As voices rise in opposition to Leon Panetta's recent decision to allow women to openly serve in combat roles, all the old arguments against women being in direct combat come fluttering down from our collective memory like so many bats from the attic. These arguments haven't seen much use in the past few years; they're in near-perfect condition after their storage. In fact, it's as though the last 50 or so years never happened at all.
Reading the arguments is like slipping a record onto the turntable and re-living the good old days when women knew their place, men did the heavy lifting, and all was right in heaven and on earth. All the greatest hits are breathed back to life in the hands of the newest players: religious opponents cite Biblical passages about the appropriate role of women in relation to men; would-be psychologists use outdated data to pronounce women unprepared for the mental rigors of combat; tee-totalers number the average differences in physical performances between the sexes; all while a chorus of neo-con women plead a case for sexism in their complicity with male military dictates, shaming female soldiers for ruining all the fun.
I guess, despite articles and documentaries from the New York Times, Washington Post, Huffington Post, National Public Radio and the Public Broadcast Service, no one heard the news: U.S. women have already been serving in combat positions for many years without training, recognition, proper compensation or psychological after care.
*Record scraaaaaatch*
Arguing that all women should be restricted from combat is just as pitifully behind the times as arguing that all women should be stay-at-home mothers. It's almost impossible to take these arguments seriously when they're built entirely on moot points. If these arguments should be taken seriously at all, it should be because of the willful ignorance and flippant disregard they display for the tremendous sacrifices made on their behalf by female soldiers.
Women soldiers are leading convoys in Afghanistan, raiding encampments in Iraq, and serving multiple tours of duty all over the globe with honor and distinction. They're engaging enemies in firefights, hauling the limp bodies of wounded male soldiers out of red zones, operating heavy weaponry and daily enduring unending physical and psychological trial. To claim that they endanger the lives of male soldiers ignores and insults the work they've done to save our sons.
By lifting the paper-only ban on women in combat, Panetta has not inserted some lone corset-wearing, 90-pound Barbie doll into a boys club; he has started a process of ensuring that the many women who endanger their lives for our freedom on a daily basis are allowed the proper training to prepare them, and the proper medals that they've risked their lives and earned. Those opposed to this preparation and compensation don't get to tie a yellow ribbon around any of their arguments: supporting the troops means supporting all of the troops, not just the ones that live in their imaginary Arlington of hetero-masculine war heroes.
Worst of all are the writers and pundits who banter on at length and feign concern for the delicate condition of women, the frail sex. All the precious chivalric sentiments of those who pretend to place women's lives on a pedestal (far above the deadly reaches of muddy male combat) wither feebly in the face of the flat truths: Where is the pedestal when women attempt to escape rising sexual assault rates in their non-combat military positions?Where is that pedestal when women require elevation in rank and pay?
Serving the United States of America in armed combat is either an honor or it's not. If it is an honor, then no one in this country has a right to take that honor away from women.
[email protected]
Photo: courtesy of Flickr/expertinfantry


text:
As you all probably know I am a great Poetry fan,
I came across this sweet little verse a while ago,
I liked it so much that put it my special little,
ABCW book of ideas,
to use at an appropriate time, as now.
I do hope you like it.
DREAMS..... by Langston Hughes.
Hold fast to dreams
for if dreams die,
Life is a broken winged bird
That cannot fly
Hold fast to dreams
For when dreams go.
Life is a barren field
frozen with snow.
Childhood Dreams.
When I was a small child
I used to DREAM of
Tinkerbell said to Peter Pan
'You know the place between sleep and wake,
the place where you still can remember DREAMING,
that's where I'll always love you,
That's where I'll be waiting'.
It was a place where children never
grew up and had wonderful adventures
The story is the classic children's story
called Peter Pan, written by J.M. Barrie.
Peter was a boy who refused to grow up.
he would fly out of his bedroom window
taking with him a few friends he also had a special
friend in Tinkerbell the fairy.
They had many adventures in Neverland and
Peter had several skirmishes with Captain Hook
and a ticking crocodile.
|Peter fighting with Captain Hook.
|Statue of Peter Pan in Kensington palace Gardens, London.
Thanks to Denise Roger and Leslie, along with the special team of helpers for keeping this well loved meme running for a decade or more.
Best wishes to you all,
ABCW team.
Best wishes to you all,
ABCW team.


text:
Every week I sew some sort of project but what I haven't been showing is how I am altering and tweaking the pattern before I start filming. I've nearly got my upper body pattern just how I want it, so this week, that's my focus. I'm going to get it right once and for all.
I fixed up the body piece but also made patterns for both the short and long sleeves.
I can proudly say I got it all right and now, I always have a base to work off of. I can make t-shirts, button-ups, sweaters, polos and, well, you name it really. If it's a top, I've got a pattern to work off of now. Yay me.


text:
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Bertolino LLP provides comprehensive legal services related to probate and estates, including the distribution of assets, payment of estate debts, tax issues, dispute resolution, notice to creditors, and filing of required documents with the probate court. The law firm can also help you with any disputes that arise during the process or, separately, represent persons who think they have a claim for a portion of the probate estate that is not being adequately handled by the personal representative of the estate.
The attorneys at Bertolino LLP also handle guardianship cases involving designating a legal guardian, which can also sometimes involve child custody-related issues. Whatever probate or estate-related issue you need help with in Texas, the Bertolino Law Firm is ready to go to work for you.
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text:
I know I bang on a bit about the linguistic incompetence of the English, but toady I read something on the train to London that pushed all my prejudice buttons.
In today's Guardian Jonathan Freedland has a good go at the (usually untested) arguments for the massive pay differentials in some of our businesses. The usual rationale has something to do with the assumption that our 'best' talent would go abroad if we brought what the boss of Barclays called the 'compensation' levels down to something that resembled 'earnings'. In other words, we would be left with second-division executives who lack the ambition or the hunger to up sticks and emigrate.
He responds to this by recognising that rare skills can legitimately demand rare salaries – but also that the skills of those who earn huge amounts are not exactly rare.
?… Our objection to telephone-number salaries goes deeper. What it comes down to is desert – a notion so deeply ingrained that, yes, even a seven-year-old can grasp it: the belief that people should deserve the rewards they get.
… Most people have long accepted that there will be a differential in pay that, in the hoary example, the brain surgeon will earn more than the dustman. People understand that some skills are rare and therefore command a greater premium. They even accept that this can result in extreme outcomes, with the likes of Wayne Rooney trousering £250,000 a week. But none of that logic applies to the current state of corporate pay.
Rooney is truly a one in a hundred million talent; there might be just two dozen people in the world who could match his skills. But with all due respect to Bob Stack, that is not true of him. Nor can it possibly be true of the 2,800 staff in 27 UK-based banks who, according to the Financial Services Authority, received more than £1m each in 2009. Whatever these people are able to do, it's clearly not rare.
Ah, comes the reply, but these are the cream of the international crop, among the very best bankers in the world. The commission report blows a hole in that tired argument, revealing there's hardly any cross-border poaching of corporate talent. Not many of our monolingual high earners could work abroad and even fewer would want to. They like it here and do not have to be paid lottery jackpot money to stay.
Notice the (almost) aside? 'Monolingual' high earners? We consistently underestimate the economic cost of our linguistic incompetence – to say nothing of the cultural and experiential deficit.
So, those are the buttons Freedland pressed for me: critique of the absurd and unjustifiable differentials, a sideswipe at our linguistic incompetence, and some myth-busting about the 'market'.
And beneath all the fun a serious question about how we value people, what they do, why it matters, and how we need to recover some connection between work and reward.


text:
Steve Round says:
"The big test will be if we get promoted. There are tiers in the Premier League. But the owner has always said it's a stage process.
"You cannot go historically from promotion to, for example, sixth in the Premier League straight away.
"You have to step up the ladder incrementally. That's the plan and aim. It's incremental rises all the time.
"When I came in, we were third bottom. We are now second. It's taken almost 18 months to get there.
"It's making sure we can get this club over the line in terms of getting promoted, that is our sole focus on the field at the moment then we need push on from there."