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Vitello Tonnato
|Boneless veal leg
|1 1⁄2 Pound, rolled (675 Gram)
|Bay leaf
|1 , peeled and sliced
|1 , peeled and sliced
|Celery stick
|2 , scrubbed and chopped
|1 1⁄2 Cup (24 tbs)
|Canned tuna fish
|2 1⁄2 Ounce (1 Can)
|Anchovy fillets
|1 Can (10 oz), drained
|Olive oil
|1⁄4 Pint (150 Milliliter)
|Egg yolks
|Lemon juice
|15 Milliliter (1 Tablespoon)
|To Taste
|Ground black pepper
|To Taste
|2 Tablespoon (To Garnish:)
|Lemon slices
|5 (To Garnish:)
|Parsley sprigs
|6 (To Garnish:)
Place the veal in a saucepan with the bay leaf, peppercorns, vegetables and sufficient stock to cover barely.
Bring to the boil, remove the scum, cover and simmer gently for about 1 hour or until tender.
Drain and cool.
Meanwhile thoroughly mash the tuna fish with 4 anchovy fillets and 1 X 15 ml spoon (1 tablespoon) oil, then add the egg yolks and either press through a sieve or liquidise until very smooth.
Stir in the lemon juice and gradually beat in the remaining oil, a little at a time, until the sauce is smooth and has the consistency of thin cream.
Season to taste.
Slice the veal thinly and arrange in a shallow dish.
Spoon the sauce over to coat completely, cover the dish and chill overnight.
Before serving, garnish with the remaining anchovies, capers, lemon slices and parsley.


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The next book club will review the Roots of the Olive Tree written by Courtney Miller Santo. For more information call 215-886-8000
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Nosh on bagels and enjoy a discussion with the Brotherhood of Old York Road Temple-Beth Am at a 9:30 a.m. adult study session. No prior experience necessary
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subset: commoncrawl


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Troy, MO - United States
Member Since:
April 11th, 2011
About Sherry Hallemeier
Purple is Passion and Passion is my Photography...by s.hallemeier
Hi, my name is Sherry and I am a wife to a wonderful husband of 29 years, a mother to two grown children and a very proud grandmother to a beautiful baby girl. My passions are photography, creating art, boating and just being on the lake. I am the owner and photographer of Passions-Photography by s.hallemeier and now have my own personal website and on line store as lists below. My art has received awards, won contests and have been featured on websites including Fine Art America. Please, all art and photography are copyright protected from including but not limited to downloads, copies, duplications, borrowing etc. and require written authorization to be used in any way. I welcome any constructive critism, advice or information that anyone has as it has already helped me considerably in becoming who I am today. My camera of choice is a Canon Rebel EOS T1i, I love creating still life art and have just completed an in home studio. Please visit my website for more art -http://www.passions-photography by s.hallemeier
All artwork on this website is copyright protected. Please feel free to view the artwork at no cost, however using the artwork for any purpose, without permission including but not limited to digital downloads, image downloads, copying, pasting, marketing, personal use, etc. is NOT allowed. Please contact me if you would like special permission and thank you in advance for adhering to this matter.
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Daz is missing the following tools that it so desperately needs, also other programs that provide examples of what Daz should be able to do:
Fast Cloth Simulation -:- Marvelous Designer
Physics Simulations -:- Blender, iClone
Fluid Simulations -:- Blender
Animation Tools -:- iClone
—- Key frame drag movement
—- Motion blends and armature bone influence selection
Game engine -:- Blender, Unity, iClone
Selective bone skeleton import (only import part of pose, such as arms without legs).
Easy export of morphs created for legacy non weightmapped models such as V4.
Scene load times have become ridiculous in the most recent studio release, a scene that used to take 3 minutes to load pre 4.5 now takes 10 minutes to load.


text:
My name is Jesse. I know, you don't really care what my name is. Anyways, I like to play video games. Single player games are more my kind of thing. Ever since I wasted 5 years of my life on WoW, I haven't been able to get back into them. I like games such as Diablo 3, and DotA 2 though. Some of my favorite single player games include BioShock (1 & 2), The Assassin's Creed games, and The Elder Scrolls games. Annnnywayyyys. If you're interested in playing games together, and you're not completely terrible, just hit me up.
- Date joined:2012-06-01
- City:
- Gender:Male
- Alignment:PC
- Points:2 Points
- Ranked:Currently Disabled


text:
American Orthopaedic Association
Ortho Info—American Academy of Orthopaedic Surgeons
The Arthritis Society
Canadian Orthopaedic Association
Limb length discrepancy. American Academy of Orthopaedic Surgeons Ortho Info website. Available at:
http://orthoinfo.aaos.org/topic.cfm?topic=a00259. Updated July 2007. Accessed December 12, 2014.
Limb lengthening. International Deformity and Lengthening Institute website. Available at:
http://www.ilizarov.org/ll.pdf. Accessed December 12, 2014.
Limb lengthening. Scottish Rite Hospital for Children website. Available at:
http://www.tsrhc.org/limb-lengthening. Accessed December 12, 2014.
Paley D. Limb lengthening introduction. Limb Lengthening.us website. Available at:
http://www.limblengtheningdoc.org/limb%5Flengthening%5Fintro.html. Accessed December 12, 2014.
Rozbruch R. Limb lengthening: An overview. Hospital for Special Surgery website. Available at:
http://www.hss.edu/conditions%5Flimb-lengthening-overview.asp. Updated September 22, 2009. Accessed December 12, 2014.
This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.
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VIDEO: Paris Hilton Debuts Music Video for New Single 'Come Alive'
Paris Hilton has released a video for her new single "Come Alive," from Cash Money Records. Check it out below!
The reality TV star launched her music career in 2006 with the release of her full-length album "Paris," featuring the lead single "Stars Are Blind."
The album peaked at No. 6 on the Billboard 200 chart, and "Stars Are Blind" rose to No. 18 on the Billboard Hot 100. Hitlton followed it up in 2013 with the release of the single "Good Times," featuring Lil Wayne.
In 2003, Hilton starred in the reality television series The Simple Life alongside Nicole Richie. In the following years, she released her autobiography Confessions of an Heiress: A Tongue-in-Chic Peek Behind the Pose (2004), landed a supporting role in the horror filmHouse of Wax (2005).
Hilton returned to reality television with Paris Hilton's My New BFF (2008) and its two spin-offs Paris Hilton's British Best Friend (2009) and Paris Hilton's Dubai BFF (2009). She served as a voice actress in the TV movieThe Dog Who Saved Christmas Vacation (2010) and appeared in the Reality Show The World According to Paris (2011). She had a part in Sofia Coppola's independent film The Bling Ring (2013).
|Related Links
|Ed Sheeran to Co-Host 2015 MUCH MUSIC VIDEO AWARDS on Much, 6/21
March 31, 2015
About Author
- Casting Roundup: Sarah Chalke, Kim Raver Headline New Pilots
- ADVENTURE TIME Headed to the Big Screen?
- Pilot Season Roundup: Colm Feore, Daniel Stern, Dave Annable to Star in New Shows
- James Franco to Star in New Fox Comedy, WHY HIM?
- Christopher Meloni to Star in WGN America's Slave Drama UNDERGROUND
- Check Out Alex Dunphy's Full College Essay from Latest MODERN FAMILY Episode
- Photo Flash: HBO Reveals Key Art for GAME OF THRONES Season 5
- Syfy to Honor Leonard Nimoy with Special Programming This Sunday
- Grammy Winner Kelly Clarkson Exclusively Premieres New Music from New Album on MTV, VH1 & CMT First
- CONSTELLATIONS' Jake Gyllenhaal and Ruth Wilson Set for THEATER TALK This Weekend


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Need a mini-vacation close to home? Look no further than your own backyard.
Youll need a tent, sleeping bags or blankets maybe just a sheet if its too hot pillows, air mattresses (optional), lawn chairs and flashlights. Plan food that can be prepared over a campfire (or fire pit or grill), like hot dogs and marshmallows. If you cant build a fire, prepare dinner in the kitchen and bring it outside to eat. Ordering pizza is also an option! Add the classic dessert smores. (Try a different take on smores using the recipe in the 30 minutes or less category.)
Find a flat spot in your yard and pitch the tent before it gets dark. Set up your sleeping bags inside the tent. Arrange lawn chairs in a seating area or just lay out a blanket so everyone can cozy up.
As the sun sets, flick on flashlights and sit in a circle. Tell ghost stories, play games, sing fun camp songs or just gaze at the stars and enjoy time with your family. Tuck into the tent when kids get sleepy and tell more stories. (If temperatures are still soaring, a late-night retreat to the house isnt cheating. Finish your campout in the living room instead.)
One thing to keep in mind: You must have municipal permission before building a fire. According to Springfields fire code, you can build a recreational fire no bigger than 3 feet wide and stacked with dry seasoned firewood no higher than 2 feet. The fire must be at least 25 feet from any structure. Keep an eye on the fire at all times, have a means to extinguish the fire handy (hose, shovel or sand) and never build a fire if its windy. If you cant build a campfire, cook the hot dogs or burgers on the grill.
Want a cooler camping option close to home? Take kids in grades K-5 to a free indoor campout to sing songs and make crafts, beginning at 2 p.m. July 14 at the Library Center. Call 882-0714.


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I am the lead programmer of a small indie game company caller Day Ja Voo Games. I can program in C# (for Unity3D), Java, Android, basic C++, and Ruby (for RPG Maker VX Ace).
No blog entries have been posted here. Boring yes, but as confucius says - if you have nothing good to say, why say anything at all? Check back later, perhaps something exciting will pop-up and be worth blogging about, like season 3 of the teletubbies.
Speak your mind, rant about games, mods and the development scene, it's simple and who knows maybe someone will read it and agree. It will feel right!


text:
The former host of "Safe Money Radio" and previous owner of Redwood Valley Interest in Redwood Falls has been indicted on 4 counts of wire fraud and 2 counts of mail fraud in federal court in connection with a scam that swindled nearly $2-million out of investors. 49-year-old Jeffrey Charles Rodd allegedly used the radio program to gain customer's trust and maintain a client base to solicit for his fraudulent annuity purchase program. Rodd reportedly raised at least $1.9-million from investors for his annuity program over a 2-year period, with the intent to use the money for his own personal and business expenses. He would reportedly only repay investors by soliciting money from new investors. He was ordered to halt the scheme and was fined $300,000 earlier this year by the state commerce department. Rodd still faces possible felony charges in Redwood County Court as well for writing bad checks.
Safe Money Radio Annuity Scam


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Press release from PR Newswire
Hain Celestial Announces Record First Quarter Fiscal Year 2013 Results
Thursday, November 01, 2012
Hain Celestial Announces Record First Quarter Fiscal Year 2013 Results16:10 EDT Thursday, November 01, 2012STRONG NET SALES FROM CONTINUING OPERATIONS UP 25.4% GAAP EPS FROM CONTINUING OPERATIONS OF $0.42 PER DILUTED SHARE; ADJUSTED EPS OF $0.40 PER DILUTED SHARE Enters into Letter of Intent to Acquire BluePrint?MELVILLE, N.Y., Nov. 1, 2012 /PRNewswire/ -- The Hain Celestial Group, Inc. (NASDAQ: HAIN), a leading natural and organic products company providing consumers with A Healthy Way of Life?, today reported its results for the first quarter ended September 30, 2012. Performance HighlightsNet sales from continuing operations up 25.4% over the same period in fiscal year 2012 GAAP net income from continuing operations up 56.6%; adjusted net income up 35.8% GAAP gross profit and adjusted gross profit up 19.3% GAAP diluted EPS from continuing operations of $0.42, up 50.0%; adjusted diluted EPS of $0.40, up 33.3% Operating free cash flow was $102.1 million for the trailing twelve months ended September 30, 2012, increasing 23.8% over the same period in fiscal year 2012The Company reported global net sales of $359.8 million from continuing operations, a 25.4% increase compared to net sales of $286.8 million in the first quarter of fiscal year 2012. The Company's first quarter net sales do not include $12.2 million of net sales in fiscal year 2013 and $5.5 million in fiscal year 2012 from discontinued operations. The Company's growth came from continued sales momentum in the natural and organic sector across various classes of trade including natural, grocery, mass-market retailers, club stores and e-tailers along with contributions from strategic acquisitions. Strong contribution came from our Celestial Seasonings®, Earth's Best®, Sensible Portions®, Spectrum®, MaraNatha®, The Greek Gods®, Terra®, Garden of Eatin'®, Arrowhead Mills®, Linda McCartney®, Alba Botanica®, Europe's Best®, New Covent Garden Soup Co.®, Johnson's Juice Co.® and Cully & Sully® brands. For the first quarter, the Company earned $19.8 million of net income from continuing operations as compared to $12.6 million in the prior year first quarter, a 56.6% increase from the prior year, and reported earnings per diluted share from continuing operations of $0.42 compared to $0.28 in the prior year first quarter. Adjusted earnings per diluted share was $0.40 on adjusted net income of $18.6 million in the fiscal year 2013 first quarter as compared to $0.30 per diluted share on adjusted net income of $13.7 million over the prior year first quarter. Adjusted net income and adjusted earnings per diluted share improved 35.8% and 33.3%, respectively, over the prior year first quarter. Adjusted net income excludes acquisition-related items and restructuring charges, discrete tax items and results of discontinued operations. "We had a strong start to our fiscal year with solid growth of our business led by Hain Celestial United States and with contributions from our expanded international operations during our first quarter. Our increased scale provided us the leverage for improved operating efficiencies across our global portfolio enabling us to deliver solid results from all of our segments. At the same time, our cash conversion cycle improved to 66 days compared 83 days during the first quarter last year," said Irwin D. Simon, Founder, President and Chief Executive Officer of Hain Celestial. Enters into Letter of Intent to Acquire BluePrint? In a separate press release, the Company announced it had entered into a letter of intent to acquire BluePrint?, a recognized leader in juice cleanses and single-serve raw juices based in New York City. The acquisition, which is expected to close by the end of calendar year 2012, is expected to be accretive to Hain Celestial's earnings in fiscal year 2013. Details of the transaction were not disclosed.Acquisition of Brands from Premier Foods In an October 29, 2012 press release, the Company also announced it had completed the strategic acquisition of Premier Foods' market-leading grocery brands including Hartley's®, Sun-Pat®, Gale's®, Robertson's® and Frank Cooper's® in the United Kingdom. The Company estimates that net sales during the eight month period from closing to June 30, 2013 will approximate $180 million with accretion in earnings per diluted share during that period of approximately $0.25 before acquisition related charges. These estimates are included in the Company's updated guidance below. The Company also announced that its Daily Bread sandwich business, which had been classified as a discontinued operation effective in the fourth quarter of fiscal year 2012, is expected to close tomorrow on its sale to Adelie Foods Group. Under the terms of the transaction the Company will acquire the prepared fruit products business of Adelie, which will be housed at Hain Daniels High Care, Fresh Innovation Center, specializing in healthy fruit and vegetable meal solutions. Fiscal Year 2013 Guidance The Company updated its annual guidance for fiscal year 2013 in connection with its recent acquisition of certain of the Premier Foods brands. Total net sales range of $1.780 billion to $1.795 billion. Earnings of $2.35 to $2.45 per diluted share.Guidance is provided for continuing operations on a non-GAAP basis and therefore excludes results of discontinued operations and acquisition and integration expenses that may be incurred during the Company's fiscal year 2013, which the Company will continue to identify when it reports its financial results. Guidance excludes the impact of any future acquisitions. Historically, the Company's sales and earnings are strongest in its second and third quarters, which is expected to continue with the acquisition of the brands from Premier Foods. Segment Results The Company's operations are organized into geographic segments: United States, United Kingdom and Rest of World. The following is a summary of first-quarter results by reportable segment. United StatesUnited KingdomRest of WorldCorporate/ OtherConsolidatedQ1 FY 2013 Net sales$ 252,647$ 57,948$ 49,212$ 359,807Q1 FY 2012 Net sales$ 233,642$ 11,238$ 41,957$ 286,837% change - 2013 vs. 20128.1%415.6%17.3%25.4%Q1 FY 2013 Operating profit (loss)$ 36,517$ (1,026)$ 4,406$ (7,621)$ 32,276Q1 FY 2012 Operating profit (loss)$ 31,732$ (1,122)$ 2,180$ (8,953)$ 23,837% change - 2013 vs. 201215.1%8.6%102.1%35.4%Q1 FY 2013 Operating profit (loss) margin14.5%-1.8%9.0%9.0%Q1 FY 2012 Operating profit (loss) margin13.6%-10.0%5.2%8.3%Webcast Hain Celestial will host a conference call and webcast at 4:30 PM Eastern Time today to review its first quarter fiscal year 2013 results. The conference call will be webcast and available under the Investor Relations section of the Company's website at www.hain-celestial.com.The Hain Celestial Group, Inc. The Hain Celestial Group (NASDAQ: HAIN), headquartered in Melville, NY, is a leading natural and organic products company in North America and Europe. Hain Celestial participates in many natural categories with well-known brands that include Celestial Seasonings®, Earth's Best®, Terra®, Garden of Eatin'®, Sensible Portions®, Health Valley®, Arrowhead Mills®, MaraNatha®, SunSpire®, DeBoles®, Gluten Free Café?, Hain Pure Foods®, Hollywood®, Spectrum Naturals®, Spectrum Essentials®, Walnut Acres Organic®, Imagine®, Almond Dream®, Rice Dream®, Soy Dream®, WestSoy®, The Greek Gods®, Ethnic Gourmet®, Yves Veggie Cuisine®, Europe's Best®, Cully & Sully®, New Covent Garden Soup Co.®, Johnson's Juice Co.®, Farmhouse Fare®, Hartley's®, Sun-Pat®, Gale's®, Robertson's®, Frank Cooper's®, Linda McCartney®, Lima®, Danival®, GG UniqueFiber®, Natumi®, JASON®, Zia® Natural Skincare, Avalon Organics®, Alba Botanica®, Queen Helene® and Earth's Best TenderCare®. Hain Celestial has been providing "A Healthy Way of Life?" since 1993. For more information, visit www.hain-celestial.com.Safe Harbor Statement This press release contains forward-looking statements under the Private Securities Litigation Reform Act of 1995. Words such as "plan," "continue," "expect," "expected," "anticipate," "estimate," "believe," "may," "potential," "can," "positioned," "should," "future," "look forward" and similar expressions, or the negative of those expressions, may identify forward-looking statements. These forward-looking statements include the Company's expectations relating to (i) the Company's guidance for net sales and earnings per diluted share in fiscal year 2013; (ii) the acquisition of certain brands from Premier Foods and the potential improvements to the Company's earnings resulting therefrom; and (iii) the potential acquisition of BluePrint. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those described in the forward-looking statements. These risks include but are not limited to the Company's ability to achieve its guidance for net sales and earnings per diluted share in fiscal year 2013 given the economic environment in the U.S. and other markets that it sells products as well as economic, political and business conditions generally and their effect on the Company's customers and consumers' product preferences, and the Company's business, financial condition and results of operations; the Company's ability to implement its business and acquisition strategy; the Company's ability to realize sustainable growth, execute productivity initiatives and manage its supply chain; the Company's ability to effectively integrate its acquisitions; competition; the success and cost of introducing new products as well as the Company's ability to increase prices on existing products; the Company's reliance on third party distributors, manufacturers and suppliers; the Company's ability to maintain existing customers and secure and integrate new customers; the Company's ability to respond to changes and trends in customer and consumer demand, preferences and consumption; international sales and operations; changes in fuel, raw materials and commodity costs; changes in, or the failure to comply with, government regulations; the availability of natural and organic ingredients; the loss of one or more of our manufacturing facilities; our ability to use our trademarks; reputational damage; product liability; seasonality; and those risks detailed from time-to-time in the Company's reports filed with the Securities and Exchange Commission, including the annual report on Form 10-K for the fiscal year ended June 30, 2012. As a result of the foregoing and other factors, no assurance can be given as to future results, levels of activity and achievements and neither the Company nor any person assumes responsibility for the accuracy and completeness of these statements.Non-GAAP Financial Measures This press release and the accompanying tables include non-GAAP financial measures, including adjusted net income, adjusted gross profit, adjusted diluted EPS, earnings before interest, taxes, depreciation, and amortization ("EBITDA"), adjusted EBITDA and operating free cash flow. The reconciliations of these non-GAAP financial measures to the comparable GAAP financial measures are presented in the tables "Consolidated Statements of Income with Adjustments" for the three months ended September 30, 2012 and 2011 and in the paragraphs below. Management believes that the non-GAAP financial measures presented provide useful additional information to investors about current trends in the Company's operations and are useful for period-over-period comparisons of operations. These non-GAAP financial measures should not be considered in isolation or as a substitute for the comparable GAAP measures. In addition, these non-GAAP measures may not be the same as similar measures provided by other companies due to potential differences in methods of calculation and items being excluded. They should be read only in connection with the Company's Consolidated Statements of Income presented in accordance with GAAP. The Company defines EBITDA as net income (a GAAP measure) before income taxes, net interest expense, depreciation and amortization, impairment of long lived assets, equity in the earnings of non-consolidated affiliates and stock based compensation. Adjusted EBITDA is defined as net income before income taxes, net interest expense, depreciation and amortization, impairment of long lived assets, equity in the earnings of non-consolidated affiliates, stock based compensation and acquisition-related expenses, including integration, and restructuring charges. The Company's management believes that these presentations provide useful information to management, analysts and investors regarding certain additional financial and business trends relating to its results of operations and financial condition. In addition, management uses these measures for reviewing the financial results of the Company as well as a component of performance-based executive compensation. For the three-month period ended September 30, 2012 and 2011, EBITDA and adjusted EBITDA were calculated as follows: Three MonthsTrailing 12 MonthsSep-12Sep-11Sep-12Sep-11Net Income16,38611,69083,92157,577Income taxes8,3367,71739,96237,861Interest expense, net3,4412,89915,61712,787Depreciation and amortization8,0096,31432,15524,495Impairment of long lived assets0015,0980Equity in earnings of non-consolidated affiliates738(68)(334)2,253Stock based compensation2,8921,7949,3899,075EBITDA39,80230,346195,808144,048Acquisition related expensesand restructuring charges6401,747(8,388)905Adjusted EBITDA40,44232,093187,420144,953 The Company defines Operating Free Cash Flow as cash provided from or used in operating activities (a GAAP measure) less capital expenditures. We view operating free cash flow as an important measure because it is one factor in evaluating the amount of cash available for discretionary investments. For the trailing twelve-month periods ended September 30, 2012 and 2011, operating free cash flow was calculated as follows: Twelve months 9/30/2012Twelve months 9/30/2011Cash flow provided by operating activities$128,293$93,957Purchases of property, plant and equipment(26,193)(11,497)Operating free cash flow$102,100$82,478 THE HAIN CELESTIAL GROUP, INC.Consolidated Balance Sheets(In thousands) September 30, June 30, 20122012 (Unaudited) ASSETSCurrent assets:Cash and cash equivalents$ 36,154$ 29,895Trade receivables, net181,575166,677Inventories199,916186,440Deferred income taxes17,25915,834Other current assets17,95419,864Assets of business held for sale2,87930,098Total current assets455,737448,808Property, plant and equipment, net154,111148,475Goodwill, net708,849702,556Trademarks and other intangible assets, net311,835310,378Investments and joint ventures46,29345,100Other assets22,58618,276Total assets $ 1,699,411$ 1,673,593LIABILITIES AND STOCKHOLDERS' EQUITYCurrent liabilities:Accounts payable and accrued expenses$ 205,192$ 184,103Income taxes payable5,0925,074Current portion of long-term debt252296Liabilities of business held for sale-13,336Total current liabilities210,536202,809Deferred income taxes 111,123107,633Other noncurrent liabilities8,5718,261Long-term debt, less current portion360,246390,288Total liabilities690,476708,991Stockholders' equity:Common stock465462Additional paid-in capital634,343616,197Retained earnings391,497375,111Treasury stock(24,862)(21,785)Accumulated other comprehensive income7,492(5,383)Total stockholders' equity1,008,935964,602Total liabilities and stockholders' equity$ 1,699,411$ 1,673,593THE HAIN CELESTIAL GROUP, INC. Consolidated Statements of Income (in thousands, except per share amounts) Three Months Ended September 30,20122011(Unaudited)Net sales$ 359,807$ 286,837Cost of sales264,595207,033Gross profit95,21279,804Selling, general and administrative expenses62,29554,437Acquisition related expenses including integration andrestructuring charges6411,531Operating income32,27623,836Interest expense and other expenses3,8923,548Income before income taxes and equity in earnings ofequity-method investees28,38420,288Income tax provision7,8587,717After-tax (income) loss of equity-method investees738(68)Income from continuing operations19,78812,639Loss from discontinued operations, net of tax(3,402)(949)Net income$ 16,386$ 11,690Basic net income per share: From continuing operations$ 0.44$ 0.29 From discontinued operations(0.08)(0.02)Net income per share - basic$ 0.36$ 0.27Diluted net income per share: From continuing operations$ 0.42$ 0.28 From discontinued operations(0.07)(0.02)Net income per share - diluted$ 0.35$ 0.26Weighted average common shares outstanding:Basic45,01743,930Diluted46,56945,356THE HAIN CELESTIAL GROUP, INC. Consolidated Statements of Income With Adjustments Reconciliation of GAAP Results to Non-GAAP Presentation (in thousands, except per share amounts) Three Months Ended September 30,2012 GAAPAdjustments2012 Adjusted2011 Adjusted(Unaudited)Net sales$ 359,807-$ 359,807$ 286,837Cost of Sales264,595-264,595207,033Gross profit95,212-95,21279,804Selling, general and administrative expenses62,295-62,29554,437Acquisition related expenses including integrationand restructuring charges641(641)--Operating income32,27664132,91725,367Interest and other expenses, net3,892(70)3,8223,419Income before income taxes and equity in earnings of equity-method investees28,38471129,09521,948Income tax provision7,8581,9199,7778,332After-tax (income) loss of equity-method investees738-738(68)Income from continuing operations19,788(1,208)18,58013,684Loss from discontinued operations, net of tax(3,402)3,402--Net income$ 16,386$ 2,194$ 18,580$ 13,684Basic net income per share$ 0.36$ 0.05$ 0.41$ 0.31Diluted net income per share$ 0.35$ 0.05$ 0.40$ 0.30Weighted average common shares outstanding:Basic45,01745,01743,930Diluted46,56946,56945,356FY 2013FY 2012Impact on Income Before Income TaxesImpact on Income Tax ProvisionImpact on IncomeBefore Income TaxesImpact on Income Tax Provision(Unaudited) Acquisition related fees and expenses and restructuring charges$ 641$ 109$ 631$ 236 Contingent consideration expense--900338Acquisition related expenses and restructuring charges6411091,531574 Accretion on acquisition related contingent consideration701712941Interest and other expenses, net701712941 Discrete tax benefit resulting from enacted tax rate change-1,793--Income tax provision-1,793-- Loss from discontinued operations3,402-949-Total adjustments$ 4,113$ 1,919$ 2,609$ 615SOURCE The Hain Celestial Group, Inc.For further information: Ira Lamel or Mary Anthes, The Hain Celestial Group, Inc., +1-631-730-2200


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Robinson's Arch is the same size as the men's and women's section since 70 A.D the men's and women's section has been open to to all people Jews and non-Jews alike (except for between 1948-67 and some other short periods of history) but all people must respect the holy site.I don't go in to a church and try a turn it in to a synagogue.If they want to open up a new synagogue they can do it in south part of the wall or the northern part of wall (in the northern part of the wall they might have to knock down some Arab homes).They have the Robinson's Arch for free which costs money for ALL other people to go to and they can pray at the women's section but they must respect the other women there. but all is that's not good enough for them they want Robinson's Arch and the women's section.
If selected for publication, it will appear as soon as possible on Haaretz.com.


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Research Staff
CTB employs more than 80 research professionals, psychometricians, statisticians, and educational measurement specialists. Meet a few of our senior staff members here.
Dr. Wim van der Linden
Wim van der Linden, Ph.D., is CTB's Chief Research Scientist. He leads CTB's research agenda and serves as a consultant on technical issues to CTB Research staff members.
Dr. van der Linden is an internationally-recognized expert in the field of psychometrics, with more than three decades of publications in the international literature. His vast knowledge in the art and science of educational assessment leads CTB's research agenda, and helps to shape the next generation of assessments.
Prior to joining CTB in 2008, Dr. van der Linden was Professor of Measurement and Data Analysis at the University of Twente in the Netherlands.
He has served on the editorial boards of Applied Psychological Measurement, Journal of Educational Measurement, Psychometrika, European Review of Applied Psychology, Dutch Journal of Education, Dutch Journal of Educational Research, and International Journal of Testing. In addition, he is a co-editor for the Springer Series on Statistics for Social and Behavioral Sciences, and has been a member of boards and committees of numerous national and international professional organizations.
He is co-editor of three published volumes: Handbook of Modern Item Response Theory (New York: Springer, 1997; with R. K. Hambleton), Computerized Adaptive Testing: Theory and Applications (Boston: Kluwer, 2000; with C. A. W. Glas), and its sequel Elements of Adaptive Testing (New York Springer, 2010; with C. A. W. Glas). He is also the author of Linear Models for Optimal Test Design published by Springer in 2005. Currently, he works on Introduction to Test Theory and its Applications, also to be published by Springer.
Ph.D., Psychometrics, University of Amsterdam
M.S., Psychology, University of Utrecht
M.S., Sociology, University of Utrecht
B.S., Psychology, University of Utrecht
B.S., Sociology, University of Utrecht
Awards and Recognitions
- E.F. Lindquist Award, American Educational Research Association, 2009
- Honorary Doctorate, Faculty of Social Sciences, Umeå University, Sweden, 2007
- Career Achievement Award, Association of Test Publishers (ATP), 2006
- Career Achievement Award, National Council on Measurement in Education (NCME), 2005
- Fellow of the Center for Advanced Study in the Behavorial Sciences, Stanford University, 2002-03
- Automated test assembly
- Test design
- Test theory (IRT)
- Optimal test assembly
- Response-time modeling
- Modeling response times on test items
- Equating methods
- Computer adaptive testing
- Bayesian methods
- Markov-chain Monte Carlo (MCMC) methods
- Cheating analysis
- Item and test security


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2010 GasGas 280 Economy Model - - What is it worth?????
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Joined: Mar 2006
Location: Black Bill Park
Oddometer: 360
No trials bike that I have ever ridden is "hard hitting" off idle. It defeats the purpose. You need to be able to roll on the throttle without breaking traction. At sea level the 280 will be pretty peppy, but trials motors are very linear. If you don't wind it up with the clutch in then dump it, it will be very smooth. Clutch and throttle control are key to trials. I don't think shimming the jug is a good idea...
Yes it would be a great starter bike. The parts are quite available, and there are lots of them around. As to price. I was considering a similar 07 300Pro for $4500, in like new condition, with no scratches on the skid plate.
As for what to look for. The suspension linkages in the back wear out. They are not cheap. If the rebound is gone in the rear shock. Not cheap. Shifter can bust, but if it does shift, you're probably ok. Shifting will feel crappy, compared to just about anything else you have ever ridden. They are just like that. These are astonishingly durable little machines. Unless it has been completely abused, and the oil never changed, it will probably serve you well. Rev it up, then cut the throttle. If you can hear piston clatter, it will need a top end, though some say run it till it blows, as these are generally low RPM machines, and it won't be catastrophic.
Then ride it till it dies.
ATGATT: When you fall off your motorcycle, you will be wearing what you were when you got on your motorcycle. Dress accordingly.
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Male Electrical Test Engineers number significantly more than their female counterparts, and average earnings in this role come out to $68K annually in the United States. Cash earnings of Electrical Test Engineers can occasionally include $6K each in bonuses and profit sharing proceeds; this strong performance component causes pay grades to stretch from approximately $49K to almost $99K. The majority of Electrical Test Engineers claim high levels of job satisfaction. Most enjoy medical while a large number get dental coverage. Vision coverage is also available to a majority. The data for this snapshot was collected from individuals who took PayScale's salary survey.
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It's not very common for Electrical Test Engineers to move on to become Senior Electrical Engineers. Average pay for a Senior Electrical Engineer is $95K annually. Becoming a Senior Test Engineer is, more often than not, the most common role that Electrical Test Engineers move into when they're ready for the next step in their career. The average salary for the position is $86K. Another frequent advance is for Electrical Test Engineers to assume an Electrical Design Engineer role; in this role, workers often earn $67K.
Survey results suggest that Electrical Test Engineers put a wide range of professional skills to use. Most notably, skills in C++, Project Management, Labview, and Test Engineering are correlated to pay that is above average. Skills that pay less than market rate include Windows Operating System General Use, Microsoft Word, and Matlab. Most people experienced in Microsoft Office also know Microsoft Excel.
Median of all compensation (including tips, bonus, and overtime) by years of experience.
Salaries of relatively inexperienced workers fall in the neighborhood of $62K, but folks who have racked up five to 10 years see a notably higher median of $75K. People with 10 to 20 years of experience make an average of about $82K in this role. Individuals who have achieved more than 20 years of experience don't seem to earn any more than people who have 10 to 20 years under their belts.
|Highly satisfied
Rated 4 out of 5
based on 53 votes.
7 %
93 %
|Medical: 89%
|Dental: 83%
|Vision: 67%
|None: 9%


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Images 05/18/2002: Steve McGee
This week's show is an Encore of a past interview with Steve McGee, the President of the Dona Ana Chapter of the National Alliance for the Mentally Ill.
Las Cruces, NM – First Aired 05/18/2002
This show received an award of merit from the Southern New Mexico Press Club in the Best Interview/Talk Category. Steve talked about his own experiences with those that are mentally ill, dispelled myths, provided new insights into this often misunderstood and misrespresented population.


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(FRIDAY, DECEMBER 9, 2011) Global HIV/AIDS prevention and treatment efforts are missing a major opportunity to significantly improve health conditions in poor countries by simply adding low-cost care for the many other chronic and disabling diseases routinely afflicting and often killing these same patients, according to a panel of disease experts who spoke at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).
"People want better health; they do not understand why we silo diseases," said Judd Walson, a global health and infectious disease expert at the University of Washington. "If you die from malaria, you don't care that your HIV was treated. Communities want us to leverage the resources we have to treat and prevent disease as effectively as possible."
Walson and his colleagues on the panel noted that many victims of HIV/AIDS also typically suffer from one or more of about 17 neglected, but burdensome, tropical diseases often called "diseases of poverty" because they prey on the "bottom billion"the world's poorest people. They include ailments such as trachoma, schistosomiasis, lymphatic filariasis, leishmaniasis, Chagas disease and onchocerciasis, all of which are either insect-borne disease, bacterial infections, or caused by parasitic worms.
Despite the illness and deaths attributable to these diseases, proposed US funding for fighting them was only about $155 million in 2011, or about 3 percent of the $5.6 billion invested in HIV/AIDS efforts. Moreover, the programs often exist in isolation from one another with, for example, many programs restricting support only to antiretroviral drugs to treat AIDS.
Yet tropical disease experts note that in places like sub-Saharan Africa, where neglected diseases affect 1.4 billion people, co-infections with HIV are common. And they see mounting evidence that dealing with multiple diseases at the same time and in the same place is more cost-effective a
|Contact: Preeti Singh
American Society of Tropical Medicine and Hygiene


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NFC Top Three Matchups- Week 4 Handicapping Report
- Updated: September 25, 2012
NFC Top Three Matchups- Week 4 Handicapping Report
With just three weeks in the books for the 2012 NFL regular season, parity has struck in the NFC with the Atlanta Falcons and the surprising Arizona Cardinals the only undefeated teams in the conference and the New Orleans Saints the only team at 0-3. The following is a handicapping guide for the top three division matchups in the NFC for this Sunday's games with lines provided by UcaBet.
Sunday, Sept. 30
Carolina Panthers vs. Atlanta Falcons (-6) Total Line: 50
A demoralized Cam Newton walked off the field last Thursday night in Carolina's 36-7 drubbing as a 2.5-point home favorite at the hands of the Giants. It will be interesting to see how the second-year quarterback responds in almost a must-win for his 1-2 Panthers.
Atlanta has risen to the top of the NFC South with a 3-0 start both straight-up and against the spread. Matt Ryan has the Falcons' offense firing on all cylinders and their defense looked sharp in holding San Diego to just three points in this past Sunday's win.
The Panthers are 1-6 both SU and ATS in their last seven games against the Falcons and the total has gone OVER in four of the last seven games. Atlanta won both games last season by the combined score of 62-40 to easily cover the spread in each. The total was split at 1-1.
Minnesota Vikings vs. Detroit Lions (-6) Total Line: OFF
Minnesota is another surprise team at 2-1 SU (1-2 ATS) after stunning San Francisco 24-13 as a 6.5-point home underdog this past Sunday. The total has stayed UNDER in its last two games. Christian Ponder is starting to come around at quarterback and the return of Adrian Peterson has revitalized the Vikings' running game.
Miscommunication on a fourth down snap in overtime led to a crushing 44-41 loss to Tennessee that dropped the Lions to 1-2 SU and 0-3 ATS. The total has gone 2-0-1 in their three games. Of greater concern is the health and playing status of quarterback Matthew Stafford, who left Sunday's game against the Titans with an injured leg. His status for this game is day-to-day.
The Vikings are 16-4 SU in their last 20 games against the Lions but they are winless in the last three meetings. The total has stayed UNDER in six of the last eight games overall and in four of the last five meetings in Detroit.
New York Giants vs. Philadelphia Eagles (-1) Total Line: 45.5
While it has not always looked pretty, the Giants are off to a 2-1 SU (1-2 ATS) start as Eli Manning keeps finding way to come up with a few big plays when his team has needed them the most. The total has stayed UNDER in two of their three games.
Philadelphia finally ran out of magic bullets against Arizona in a 27-6 loss as a four-point favorite on the road. This team has turned the ball over 12 times in its first three games and has continually shot itself in the foot at the worst possible times. Despite all this, the Eagles are 2-1 SU (0-3 ATS) in their first three games. The total has stayed UNDER in two of their three games.
New York is just 1-7 SU and ATS in the last eight meetings and the total has stayed UNDER in eight of the last 12 games. The Giants won 29-16 on the road last season as 7.5-point road underdogs but lost 17-10 at home later in the year as 5.5-point favorites. The total stayed UNDER in both of those games.
Dave Schwab
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- NBA Pick: New York Knicks vs. Brooklyn Nets - December 5, 2013
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Booker TBooker Tio Huffman, Jr.
- Birthdate: 03/01/1961 (age 54)
- Height: 6'3"
- Weight: 256 Ib
Booker is best known for his time in World Cham...
Read More »-- Booker T posted the following on Twitter last night…
"I guess you all no by now I'm going in the ( HALL OF FAME 2013 ) Just want to say there or no words but thanks to all me fans.#youdidit"
On the WWE App last night, Booker T said he's overwhelmed by the honor and teased that his days in the ring are not over. He then noted that we will see a Harlem Heat reunion at the Hall of Fame ceremony because his brother Stevie Ray will be there.
-- Here is Booker T's Hall of Fame video:


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Unfinished Business
Games I'm still working on.
Games I'm still working on.
I'm working feverishly to finish the first part of this game - The Journey - so I can start on The Answer. But I can only seem to play through 7 hours straight or so before the outside world comes knocking on my door. 'Time to turn off the cell phone, close the blinds, and shut down the PC, and use up some saved sick days.
A dungeon crawler fan's wettest dream...only in a portable format.
200+ hours and counting...
Use your keyboard!
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Birthstone jewelry
Commemorate your birth month with gorgeous birthstone rings and other birthstone jewelry featuring the signature style and quality you can get only from Helzberg Diamonds. From ruby to aquamarine, birthstone necklaces, charms, earrings and more are a beautiful way to express something uniquely you. Or, for that special someone, birthstone gifts are always a great choice.
January Birthstone
From garnet rings to garnet earrings and everything in between, browse beautifully handcrafted jewelry featuring this exquisite birthstone for January.
February Birthstone
Add a pop of vibrant color to any outfit with jewelry featuring the regal birthstone for February.
March Birthstone
March's elegant birthstone is sure to add sparkle to her day.
April Birthstone
Diamonds are a girl's best friend, especially those born in April.
May Birthstone
Known to be Cleopatra's gem of choice, the brilliant green emerald is the official May birthstone.
June Birthstone
Enjoy the captivating beauty of June's birthstone with everything from shimmering pearl earrings to iridescent pearl rings.
July Birthstone
Representing passion and romance, rubies make an unforgettable July birthday gift.
August Birthstone
Add a spritz of refreshing lime green to your look with peridot, August's official birthstone.
September Birthstone
A favorite among royals, the birthstone for September is also famous for its deep blue hue.
October Birthstone
Scintillating, irridescent, ever-changing. Discover the mysterious allure of the opal, the official birthstone for October.
November Birthstone
Fresh, eye-catching color makes citrine a modern favorite for November.
December Birthstone
Brighten up with blue topaz, December's official birthstone.
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Finlandia Swiss Cheese Biscuit
|1⁄4 Pound (Use 1 Stick)
|Egg yolks
|2 , well beaten
|Grated swiss cheese
|5 Ounce (Finlandia Brand)
|Prepared mustard
|1 1⁄2 Teaspoon
|Cayenne pepper
|1 Dash
|Sifted flour
|1 Cup (16 tbs)
1. Preheat the oven to 400 degree F
2. In a large bowl, add butter or margarine.
3. Beat the fat with a spatula or an electric mixture until it is light and creamy.
4. Add egg yolks, one at a time, beating into the fat until well blended.
5. Add cheese, mustard and cayenne and beat until well blended and creamy.
6. Gradually add flour, beating until the mixture binds to form dough and forms a ball.
7. Turn the dough out on a lightly floured surface.
8. Roll lightly with a rolling pin, into a large circle of 1/8 inch thickness.
9. Use a 21/2-inch round cookie cutter (plain or fluted) to cut the dough into biscuits.
10. Arrange the dough circles on baking sheets and place in hot oven
11. Bake the biscuits for about 10 to 12 minutes just until pale and dry.
12. Remove the baking sheets from the oven and loosen the biscuits with a spatula of pastry knife.
13. Slide them onto a wire rack and let them cool and harden.
14. Store the biscuits in a wax paper lined airtight container.
15. Serve the cheese biscuits as an accompaniment to dips, soups, stews or gravies or enjoy as an evening snack.


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We have been selected to be part of 100% Norway for the 2015 edition with the Lamaneurs and the Pathics. It will be from the 23 to the 26th of September 2015 in London.
The designs and art produced in Ideal Lab – Replanted Identity in 2014 has been selected to take part in the Biennale in 2015.
It will be shown in a dedicated exhibition of 110 m2 from the 12/3 to the 12/4 2015. Ralston & Bau curated and designed the scenography of the exhibition and is showing three new creations: Les Lamaneurs (urban furniture), Svele (serving plates) and Storm (vases).
We are very happy to announce the launch of our new furniture design collection for Vestnes Ocean: Keys. It is revealed to the public at the largest oil world fair ONS in Stavanger (Norway) as we speak.
At TEDxNantes, Birgitta Ralston talked about Ideal Lab', a program with the ambition to design beautiful meaning.
The Ideal Lab relocate the meaning of design to a social environment in mutation, to define future needs and realise future scenarios through tangible products and processes. She shows results from themes like elders participation, food waste and neighbourhood empathy.
Birgitta Ralston is a jury member for the design awards EDF Sustainable Design Challenge. The awards focuses on the materialisation of day-to-day energy efficient solutions for a better quality of life. On June 28th the award ceremony selecting the design most likely to "Encourage responsible energy behaviour for better living" takes place in London.


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Apr 16, 2015
Missing data issue in 3B42RT
IR fill-ins ceased when CPC Global 4 km Merged IR data dropped out, starting 14 April 17:00 UTC, apparently due to processing issues at NOAA. As a result, 3B41RT has no data and 3B42RT only has data in regions where microwave data are available.
The Hurricane Analysis Tool allows users to overlay various data products relevant in the study of hurricanes in an area plot, a time plot or animation using an interactive tool. The data products being offered include NCEP/CPC 4-km Global (60 deg N - 60 deg S) Merged IR Brightness Temperature Dataset, TRMM's product 3B42, TMI's sea surface temperature, NCEP Reanalysis sea level pressure and QuikScat's wind. This tool is beneficial for users to obtain a visualization comparison of two products during a hurricane event.
Hurricane Archive Gallery gets a face lift and is now dynamic! Check out the new gallery interface that allows you to select the year and hurricanes you want to view. Data access has also been added to the gallery along with QuikScat Wind and new CloudSat images! Take a look!
These are the latest images derived from the 3-hour near-real-time rainfall total (TMPA or 3B42RT) of the Atlantic and Gulf regions. The images created using the Giovanni analysis tool with the latest available data granules. These are generated and updated on a daily basis to observe current rainfall total activity. You can view more current images and animations of these and other parameters, such as AIRS temperature and Surface Pressure, by visiting the Image Gallery. A Past Hurricane Archive is also available to view animations of data set parameters of hurricanes that developed over the Atlantic region.
3-hourly near-real-time rainfall total of the Atlantic region derived from the TRMM Project Multi-Satellite
Precipitation Analysis (TMPA or 3B42RT. This image was created using the interactive Giovanni application.
Newsletter includes articles on crab plover research, Southern Ocean winds, and time-series data
Issue features an update on the development of Giovanni-4
Rain and snow data from microwave imager and precipitation radar
Issue features six interesting journal papers from the latter half of 2014
Precipitation data from the Global Precipitation Measurement (GPM) mission
+Hurricanes News Archive


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One sunny morning in 1969, near the end of her first trip to Miami, twenty-six-year-old Frances Ellerby finds herself in a place called Stiltsville, a community of houses built on pilings in the middle of Biscayne Bay.
It's the first time the Atlanta native has been out on the open water, and she's captivated. On the dock of a stilt house, with the dazzling skyline in the distance and the unknowable ocean beneath her, she meets the house's owner, Dennis DuVal—and… (more)
Publisher: HarperCollins e-books (August 03, 2010)
Format: EPUB
Page count: 320 pages
File size: 992 KB
Protection: DRM
Language: English
Awards: PEN/Robert W. Bingham Prize 2011 winner


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Are you H Riehm?Claim your profile
Publications (188)915.1 Total impact
- SourceAvailable from: Myriam Campbell
Article: Intensive Chemotherapy for Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Intercontinental Trial ALL IC-BFM 2002[Show abstract] [Hide abstract]
ABSTRACT: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.Journal of Clinical Oncology 12/2013; 32(3). DOI:10.1200/JCO.2013.48.6522 · 17.88 Impact Factor
Article: Die West-Berliner Studie zur Behandlung der akuten lymphoblastischen Leukämie des Kindes - Erfahrungsbericht nach 6 Jahren*Klinische Pädiatrie 05/2013; 225(S 01):S16-S29. DOI:10.1055/s-0033-1337959 · 1.90 Impact Factor
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ABSTRACT: Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche Krebshilfe and others.).New England Journal of Medicine 04/2012; 366(15):1371-81. DOI:10.1056/NEJMoa1110169 · 54.42 Impact Factor
Article: Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia.[Show abstract] [Hide abstract]
ABSTRACT: In the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features. Cytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95. The 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect. Selective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.Haematologica 01/2012; 97(7):1048-56. DOI:10.3324/haematol.2011.047613 · 5.87 Impact Factor
Article: Low platelet counts after induction therapy for childhood acute lymphoblastic leukemia are strongly associated with poor early response to treatment as measured by minimal residual disease and are prognostic for treatment outcome[Show abstract] [Hide abstract]
ABSTRACT: Numerous reports have been published on the association between kinetics of leukemic cells during early treatment of childhood acute lymphoblastic leukemia and therapeutic outcome. In contrast, little is known about the prognostic relevance of normal blood counts in this setting. Normal hematopoiesis during and after induction treatment (days 8, 15 and 33) was correlated with therapeutic outcome in a cohort of 256 children with acute lymphoblastic leukemia treated in one of three consecutive ALL-BFM trials at a single institute. Replication analysis of positive findings was performed in an independent cohort of 475 patients from the ALL-BFM 2000 multicenter trial. A platelet count in the first quartile on treatment day 33 and a neutrophil count above the median on day 8 were significantly associated with treatment outcome, conferring multivariate risk ratios for an event of 3.27 (95% confidence interval 1.60-6.69) and 2.26 (95% confidence interval 1.23-4.29), respectively. Replication analysis confirmed the prognostic effect of platelet count on treatment day 33 and demonstrated a strong association with minimal residual disease-based risk group distribution (P<0.00001). Platelet counts after induction treatment may improve treatment stratification for patients with childhood acute lymphoblastic leukemia and be of particular interest in non-minimal residual disease-based trials. (ALL-BFM 2000 is registered at: ClinicalTrials.gov: NCT00430118. National Cancer Institute: Protocol ID 68529).Haematologica 11/2011; 97(3):402-9. DOI:10.3324/haematol.2011.045229 · 5.87 Impact Factor
Article: Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000[Show abstract] [Hide abstract]
ABSTRACT: Between 1981 and 2000, 6609 children (<18 years of age) were treated in five consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria and Switzerland. Probability of 10-year event-free survival (EFS) (survival) improved from 65% (77%) in study ALL-BFM 81 to 78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: (1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk (HR) ALL patients, and eliminated in non- HR non-T-ALL patients, if it was replaced by high-dose and intrathecal (IT) MTX; (2) omission of delayed re-intensification severely impaired outcome of low-risk patients; (3) 6-month-less maintenance therapy caused an increase in systemic relapses; (4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; (5) condensed induction therapy resulted in significant improvement of outcome; (6) the daunorubicin dose in induction could be safely reduced in low-risk patients and (7) intensification of consolidation/re-intensification treatment led to considerable improvement of outcome in HR patients.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2009; 24(2):265-84. DOI:10.1038/leu.2009.257 · 9.38 Impact Factor
Article: Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols.[Show abstract] [Hide abstract]
ABSTRACT: Thiopurine methyltransferase (TPMT)is involved in the metabolism of thiopurines such as 6-mercaptopurine and 6-thioguanine. TPMT activity is significantly altered by genetics, and heterozygous and even more homozygous variant people reveal substiantially decreased TPMT activity. Treatment for childhood acute lymphoblastic leukemia (ALL) regularly includes the use of thiopurine drugs. Importantly, childhood ALL patients with low TPMT activity have been considered to be at increased risk of developing therapy-associated acute myeloid leukemia and brain tumors. In the present study, we genotyped 105 of 129 patients who developed a secondary malignant neoplasm after ALL treatment on 7 consecutive German Berlin-Frankfurt-Münster trials for all functionally relevant TPMT variants. Frequencies of TPMT variants were similarly distributed in secondary malignant neoplasm patients and the overall ALL patient population of 814 patients. Thus, TPMT does not play a major role in the etiology of secondary malignant neoplasm after treatment for childhood ALL, according to Berlin-Frankfurt-Münster strategies.Blood 07/2009; 114(7):1314-8. DOI:10.1182/blood-2008-12-193250 · 10.43 Impact Factor
Article: Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.[Show abstract] [Hide abstract]
ABSTRACT: The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (+/- 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (+/- 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (+/- 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non-T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (+/- 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.Blood 06/2008; 111(9):4477-89. DOI:10.1182/blood-2007-09-112920 · 10.43 Impact Factor
Article: Prevalence, Clinical Pattern, and Outcome of CNS Involvement in Childhood and Adolescent Non-Hodgkin's Lymphoma Differ by Non-Hodgkin's Lymphoma Subtype: A Berlin-Frankfurt-Münster Group Report[Show abstract] [Hide abstract]
ABSTRACT: We analyzed the prevalence, clinical pattern, and prognostic impact of CNS involvement in a large cohort of children and adolescents diagnosed with non-Hodgkin's lymphoma (NHL), with special attention to differences according to NHL subtype. From October 1986 to December 2002, 2,381 patients (median age, 9.37 years; range, 0.2 to 23.8 years; female-to-male ratio, 1:2.7) from Germany, Austria, and Switzerland were registered. A total of 2,086 patients were eligible for the consecutive multicenter protocols NHL-Berlin-Frankfurt-Münster [BFM] -86, NHL-BFM-90, and NHL-BFM-95, and could be evaluated for outcome. CNS involvement was diagnosed in 141 (5.9%) of 2,381 patients and was associated with an advanced stage of NHL. The percentage of CNS-positive patients was 8.8% for Burkitt's lymphoma/Burkitt's leukemia (BL/B-ALL), 5.4% for precursor B-lymphoblastic lymphoma (pB-LBL), 3.3% for anaplastic large-cell lymphoma, 3.2% for T-cell-LBL, 2.6% for diffuse large B-cell lymphoma, and 0% for primary mediastinal large B-cell NHL (P < .001). Most CNS-positive patients with pB-LBL, T-LBL, or BL/B-ALL had meningeal disease. The probability of event-free survival (pEFS; +/- SE) at 5 years was 85% +/- 1% for the 2,086 protocol patients (median follow-up, 6.5 years; range, 0.3 to 17.7 years). For the 112 CNS-positive patients, pEFS was 64% +/- 5%, compared with 86% +/- 1% for the 1,927 CNS-negative patients (P < .001). Although CNS disease had no impact on pEFS for advanced-stage T-LBL patients, CNS-positive patients with BL/B-ALL had a worse average outcome than CNS-negative patients with stage IV BL/B-ALL (60% +/- 5% v 81% +/- 3%; P < .001). In multivariate analysis, CNS disease was the strongest predictor for relapse in BL/B-ALL patients with advanced-stage disease. Six percent of childhood/adolescent NHL patients were CNS positive. However, the prevalence, pattern, and prognostic impact of CNS involvement differed among NHL subtypes.Journal of Clinical Oncology 10/2007; 25(25):3915-22. DOI:10.1200/JCO.2007.11.0700 · 17.88 Impact Factor
Article: Integrating molecular information into treatment of childhood acute lymphoblastic leukemia - A perspective from the BFM Study Group[Show abstract] [Hide abstract]
ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and is treated with chemotherapy alone or, in particular subgroups, with additional radiation therapy and/or stem cell transplantation. The treatment intensity is adjusted according to prognostic factors associated with the risk of ALL recurrence. On Berlin-Frankfurt-Münster (BFM) protocols, the widely applicable early in vivo response to treatment as measured by the reduction of leukemic cells in the blood or bone marrow is currently the most important prognostic factor. However, although overall long-term cure rates for childhood ALL treated on risk-adapted protocols have dramatically improved over the last decades and, to date, are higher than 75%, a significant number of patients still die due to recurrent disease or the toxicity of treatment applied. One goal in future BFM trials will be to take advantage of a better molecular understanding of leukemia and host characteristics to dissect the mechanisms underlying the differences in treatment response. This short review focuses on the evolution of treatment response in BFM trials and provides a perspective on our strategy for improving molecular characterization of childhood ALL and implementing more individualized and novel therapeutic approaches.Blood Cells Molecules and Diseases 09/2007; 39(2):160-3. DOI:10.1016/j.bcmd.2007.04.005 · 2.33 Impact Factor
Article: Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial[Show abstract] [Hide abstract]
ABSTRACT: Studies in the 1970s and 1980s suggested that the outcome of childhood acute lymphoblastic leukaemia (ALL) could be improved by intensification of conventional continuation chemotherapy with pulses of vincristine sulfate and steroids. We aimed to investigate the efficacy and toxic effects of vincristine-dexamethasone pulses as an addition to the continuation-therapy phase in a large cohort of children with intermediate-risk disease who were treated with the Berlin-Frankfurt-Münster (BFM) treatment strategy. 3109 children, diagnosed with ALL and intermediate-risk features, were enrolled by eight participating organisations in eleven countries. All were treated with very similar protocols based on the BFM treatment strategy, which included induction, consolidation, reinduction, and continuation-therapy phases. At the beginning of the continuation-therapy phase, those patients in complete remission were randomly assigned to either a treatment or a control group. Control patients were given conventional mercaptopurine and methotrexate chemotherapy only. Patients in the treatment arm were also given pulses of vincristine (1.5 mg/m2 weekly for 2 weeks) and dexamethasone (6 mg/m2 daily for 7 days) every 10 weeks for six cycles. The primary outcome measure was disease-free survival. Analysis was by intention to treat. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00411541. 174 patients (5.6%) relapsed or died in complete remission before randomisation. Of the remaining 2935 patients, 2618 (89.2%) were randomly assigned: 1325 to the treatment group and 1293 to the control group. With median follow-up of 4.8 years, 240 children in the treatment group and 241 in the control group had relapses; 15 in the treatment group and 14 controls died in complete remission or developed second malignant neoplasms. The 5-year and 7-year disease-free survival estimates were 79.8% (SE 1.2) and 77.5% (1.5) in the treatment group and 79.2% (1.2) and 78.4% (1.3) in the control group, respectively. Treatment with pulses of vincristine and dexamethasone was associated with a non-significant 3% relative-risk reduction (hazard ratio 0.97; 95% CI 0.81-1.15; p=0.70). Children with intermediate-risk ALL who received intensive chemotherapy based on BFM protocols did not benefit from intensification of the continuation-therapy phase with a schedule of pulses of vincristine and dexamethasone.The Lancet 02/2007; 369(9556):123-31. DOI:10.1016/S0140-6736(07)60073-7 · 45.22 Impact Factor
Article: Superiority of Allogeneic Hematopoietic Stem-Cell Transplantation Compared With Chemotherapy Alone in High-Risk Childhood T-Cell Acute Lymphoblastic Leukemia: Results From ALL-BFM 90 and 95[Show abstract] [Hide abstract]
ABSTRACT: The role of hematopoietic stem-cell transplantation (SCT) in first complete remission (CR1) for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is still under critical discussion. In the ALL-Berlin-Frankfurt-Münster (BFM) 90 and ALL-BFM 95 trials, 387 patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell ALL (T-ALL) patients with poor in vivo response to initial treatment represented the largest homogeneous subgroup within VHR patients. Of 191 high-risk (HR) T-ALL patients, 179 patients (94%) achieved CR1. Twenty-three patients received an MSD-SCT. Furthermore, in trial ALL-BFM 95, eight matched unrelated donors (MUDs) and five mismatched family donors (MMFDs) were used. The median time to SCT was 5 months (range, 2.4 to 10.8 months) from diagnosis. The 5-year disease-free survival (DFS) was 67% +/- 8% for 36 patients who received an SCT in CR1 and 42% +/- 5% for the 120 patients treated with chemotherapy alone having an event-free survival time of at least the median time to transplantation (Mantel-Byar, P = .01). Overall survival (OS) rate for the SCT group was 67% +/- 8% at 5 years, whereas patients treated with chemotherapy alone had an OS rate of 47% +/- 5% at 5 years (Mantel-Byar, P = .01). Outcome of patients who received MSD-SCT versus MUD-/MMFD-SCT was comparable (DFS, 65% +/- 10% v 69% +/- 13%, respectively). However, relapses only occurred after MSD-SCT (eight of 23 patients), whereas treatment-related mortality only occurred after MUD-/MMFD-SCT (four of 13 patients). SCT in CR1 is superior to treatment with chemotherapy alone for childhood HR-T-ALL.Journal of Clinical Oncology 01/2007; 24(36):5742-9. DOI:10.1200/JCO.2006.06.2679 · 17.88 Impact Factor
Article: Impact of Cranial Radiotherapy on Central Nervous System Prophylaxis in Children and Adolescents With Central Nervous System–Negative Stage III or IV Lymphoblastic Lymphoma[Show abstract] [Hide abstract]
ABSTRACT: In the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) 95 trial, we tested, against the historical control of the combined trials NHL-BFM90 and NHL-BFM86, whether prophylactic cranial radiotherapy (PCRT) can be omitted for CNS-negative patients with stage III or IV lymphoblastic lymphoma (LBL) with sufficient early response. Apart from the removal of PCRT in NHL-BFM95, the chemotherapy of the three trials was identical except for the amount of l-asparaginase and daunorubicin during induction. The therapy in NHL-BFM95 was accepted to be noninferior when compared with trials NHL-BFM90/86 if the lower limit of the one-sided 95% CI for the difference in the 2-year probability of event-free-survival (pEFS) between target patients of NHL-BFM95 and the historical controls of NHL-BFM90/86 did not exceed -14%. The target patient group consisted of stage III and IV patients who were CNS negative and responded well to induction therapy. The number of target patients was 156 in NHL-BFM95 (median age, 8.6 years; range, 0.2 to 19.5 years) and 163 in NHL-BFM90/86 (median age, 8.4 years; range, 0.6 to 16.6 years). For the target group, the pEFS rates at 2 and 5 years were 86% +/- 3% and 82% +/- 3%, respectively, in NHL-BFM95 (median follow-up time, 5.1 years; range, 2.1 to 9.1 years) compared with 91% +/- 2% and 88% +/- 3%, respectively in NHL-BFM90/86 (median follow-up time, 10.7 years; range, 5 to 15.4 years). The lower limit of the one-sided 95% CI for the difference in pEFS was -11% at 2 years and -13% at 5 years. In NHL-BFM95, one isolated and two combined CNS relapses occurred compared with one combined CNS relapse in NHL-BFM90/86. Five-year disease-free-survival rate was 88% +/- 3% in NHL-BFM95 compared with 91% +/- 2% in NHL-BFM90/86. For CNS-negative patients with stage III or IV LBL and sufficient response to induction therapy, treatment without PCRT may be noninferior to treatment including PCRT.Journal of Clinical Oncology 02/2006; 24(3):491-9. DOI:10.1200/JCO.2005.02.2707 · 17.88 Impact Factor
Chapter: Akute lymphoblastische Leukämie[Show abstract] [Hide abstract]
ABSTRACT: Häufigkeit: Die akute lymphoblastische Leukämie (ALL) ist mit 30% die häufigste maligne Erkrankung des Kindesalters.12/2005: pages 5404-5426;
Chapter: Akute lymphoblastische Leukämien[Show abstract] [Hide abstract]
ABSTRACT: Die akute lymphoblastische Leukämie ist die häufigste Krebserkrankung bei Kindern und Jugendlichen. Die Entwicklung der intensiven Polychemotherapie seit Anfang der 70er-Jahre und die konsequente Mitbehandlung der so genannten Extrakompartimente (in erster Linie des Zentralnervensystems) hat zu der entscheidenden Verbesserung der Heilungsrate geführt. Neue präzise Methoden zur Bestimmung der In-vivo-Therapieresistenz erlauben eine zuverlä ssigere Aussage zur Prognose als die meisten Parameter zum Zeitpunkt der Diagnose. Das bessere Verständnis der Biologie der Leukämiezelle lässt Rückschlüsse auf die Pathogenese zu, trägt aber auch zur Entwicklung spezifischer Therapieansätze bei. Trotz aller Fortschritte ist die erste Behandlung bei einem Viertel der Kinder nicht erfolgreich. Darüber hinaus ist die derzeit verfügbare Therapie durch die Therapiedauer und durch einzelne, teilweise schwerwiegende und unerwartete Nebenwirkungen sehr belastend.12/2005: pages 656-679;
Article: Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials[Show abstract] [Hide abstract]
ABSTRACT: A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Münster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 50+/-2, 61+/-3 and 57+/-2%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapy-related death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with >70 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.Leukemia 12/2005; 19(12):2030-42. DOI:10.1038/sj.leu.2403920 · 9.38 Impact Factor
Article: Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: Data from the trials ALL-BFM 86, 90, and 95[Show abstract] [Hide abstract]
ABSTRACT: Large progress has been made in the treatment of acute lymphoblastic leukemia (ALL) of childhood and adolescence over the past 30 years. Eighty percent of the patients can be cured, but clinical subgroups with a dismal outcome can still be identified. In this study, we investigated the association of age with prognosis in 5 181 patients with ALL under 18 years (y) of age enrolled in the three consecutive treatment trials ALL-BFM 86, 90 and 95 in more than 80 centers. Event-free survival (pEFS) of the total group was significantly associated with age. The most unfavorable outcome was found in infancy and the best results were achieved at toddler and pre-school age. Beyond 5 y of age, survival probability decreased (pEFS at 8 y: < 1 y = 0.45; 1-5 y = 0.82; 6-9 y = 0.75; 10-14 y = 0.63; > or = 15 y = 0.59). The proportion of T-ALL as compared to precursor B-cell ALL (pB-ALL) was lower in younger children, due to an incidence peak of pB-ALL in toddlers and at pre-school age compared to a constant incidence of T-ALL. Within the T-ALL group, no correlation of age with sex, initial white blood cell count, CNS disease, or early treatment response was found. Children under 10 y of age had a slightly lower relapse rate compared to older patients. Within pB-ALL patients, the proportion as well as the absolute incidence of TEL/AML1 rearrangement and DNA index of > or = 1.16 was higher in the younger children. A lower proportion of BCR/ABL-positive ALL was observed in the age group of < 6 y when compared to patients aged > or = 6 y, but the absolute incidence was constant across the age groups after the first year of life. More than half of the infants had a CD10-negative pB-ALL. The incidence was constant after a peak in the first year of life, yet the percentage of CD10 negativity increased with rising age in this subgroup. Adolescents with pB-ALL had a significantly higher proportion of prednisone poor-responders. Accordingly, outcome was worse in older patients. This pattern was also evident in the biologically heterogeneous group of patients with a DNA index of > or = 1.16. In contrast, no significant age-related outcome differences could be shown within TEL/AML1- or BCR/ABL-positive patients, as well as within CD10-negative pB-ALL beyond infant age. Analysis of the pB-ALL group in a Cox's regression model including age and the above-listed biological factors revealed age < 1 year and > or = 10 years as independent risk factors. This is in line with the poorer prognosis of these age groups in the pB-ALL subgroup without specific biological characteristics. This subgroup also had an incidence peak at toddler age, presumably containing other favorable biological subsets. An independent prognostic impact of age in pediatric ALL cannot be excluded by this study. However, our analyses show that the age-associated different prognosis in childhood ALL is at least partly related to the different distribution of relevant prognostic subgroups between the age groups.Klinische Pädiatrie 11/2005; 217(6):310-20. DOI:10.1055/s-2005-872515 · 1.90 Impact Factor
Article: The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence[Show abstract] [Hide abstract]
ABSTRACT: We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non-Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin-Frankfurt-Münster (BFM) multicentre protocols NHL-BFM-86, -90 and -95. Median age at diagnosis was 8.0 years for 97 precursor B-lymphoblastic lymphoma (pB-LBL) patients, 8.8 years for 335 T-lymphoblastic lymphoma (T-LBL) patients, 8.4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B-AL) patients, 11.4 years for 173 diffuse large B-cell lymphoma (centroblastic subtype) (DLBCL-CB) patients, 13.2 years for 40 primary mediastinal large B-cell lymphoma (PMLBL) patients and 10.8 years for 215 anaplastic large-cell lymphoma (ALCL) patients (P < 0.00001). The male:female ratio was 0.9:1 for pB-LBL and PMLBL, 1.7:1 for DLBCL-CB, 1.8:1 for ALCL, 2.5:1 for T-LBL and 4.5:1 for BL/B-AL (P < 0.00001). The probability of event-free survival at 5 years (5-year pEFS) was 85 +/- 1% for all 2084 patients [median follow-up 5.7 (0.1-15.9) years], and was significantly superior for male T-LBL and DLBCL-CB patients. Comparing age-groups 0-4, 5-9, 10-14 and 15-18 years, pEFS was inferior for the youngest patients only in the pB-LBL- and ALCL-groups. T-LBL and DLBCL-CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL-subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL-subtype but also according to gender in some subtypes.British Journal of Haematology 10/2005; 131(1):39-49. DOI:10.1111/j.1365-2141.2005.05735.x · 4.96 Impact Factor
Article: The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95[Show abstract] [Hide abstract]
ABSTRACT: In the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster 95 (NHL-BFM95) study, we tested by randomization whether for patients with B-cell neoplasms methotrexate as intravenous infusion over 4 hours (MTX-4h) is not inferior to, but less toxic than, a 24-hour intravenous infusion (MTX-24h). Second, we investigated against the historical control of study NHL-BFM90, whether for patients with moderate tumor mass MTX can be reduced from 5 g/m(2) to 1 g/m(2). Patients received 2 5-day therapy courses in risk group R1 (resected), 4 in R2 (lactate dehydrogenase [LDH] < 500 U/L), 5 in R3 (LDH > 500 to < 1000 U/L) and 6 in R4 (LDH > 1000 U/L and/or central nervous system [CNS] disease). Courses contained MTX 1 g/m(2) in R1 + R2 and 5 g/m(2) in R3 + R4. Of 505 patients (April 1996 to March 2001), 364 were randomized to receive MTX-4h or MTX-24h. Failure-free survival (pFFS, 1 year) for arm MTX-4h versus MTX-24h, respectively, was 95% +/- 5% (n = 20) versus 100% (n = 19) in R1, 94% +/- 2% (n = 88) versus 96% +/- 2% (n = 95) in R2, and 77% +/- 5% (n = 62) versus 93% +/- 3% (n = 69) in R3 +/- R4 (per-protocol analysis). Incidence of mucositis grade III/IV was significantly lower with MTX-4h in all risk groups. For patients in R2, event-free survival (pEFS) was 95% +/- 2% (n = 222) in NHL-BFM95 (MTX 1 g/m(2)) and 97% +/- 1% (n = 154) in NHL-BFM90 (MTX 5 g/m(2)). In conclusion, MTX-4h was less toxic than MTX-24h. MTX-4h was noninferior to MTX-24h for limited stage B-cell non-Hodgkin lymphoma (B-NHL) but not for advanced disease. For limited disease, MTX 1 g/m(2) is noninferior to 5 g/m(2).Blood 03/2005; 105(3):948-58. DOI:10.1182/blood-2004-03-0973 · 10.43 Impact Factor
Article: Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome.[Show abstract] [Hide abstract]
ABSTRACT: Additional chromosomal aberrations occur frequently in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) of childhood. The treatment outcome of these patients is heterogeneous. This study assessed whether such clinical heterogeneity could be partially explained by the presence and characteristics of additional chromosomal abnormalities. Cytogenetic descriptions were available for 249 of 326 children with Ph+ ALL, diagnosed and treated by 10 different study groups/large single institutions from 1986 to 1996. Secondary aberrations were present in 61% of the cases. Chromosomes 9, 22, 7, 14, and 8 were most frequently abnormal. Most (93%) karyotypes were unbalanced. Three main cytogenetic subgroups were identified: no secondary aberrations, gain of a second Ph and/or >50 chromosomes, or loss of chromosome 7, 7p, and/or 9p, while other secondary aberrations were grouped as combinations of gain and loss or others. Of the three main cytogenetic subgroups, the loss group had the worst event-free survival (P=0.124) and disease-free survival (P=0.013). However, statistical significance was not maintained when adjusted for other prognostic factors and treatment. Karyotypic analysis is valuable in subsets of patients identified by molecular screening, to assess the role of additional chromosomal abnormalities and their correlation with clinical heterogeneity, with possible therapeutic implications.Leukemia 05/2004; 18(4):693-702. DOI:10.1038/sj.leu.2403324 · 9.38 Impact Factor
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- Klinische Pädiatrie (37)
- Blood (18)
- Haematology and blood transfusion (18)
- Leukemia (7)
- Monatsschrift Kinderheilkunde (6)
Hannover Medical School
Hanover, Lower Saxony, Germany
- Department of Paediatric Haematology and Oncology
Hochschule HannoverHanover, Lower Saxony, Germany
University Medical Center Schleswig-Holstein
Kiel, Schleswig-Holstein, Germany
- Department of Pediatrics
University Hospital EssenEssen, North Rhine-Westphalia, Germany
Justus-Liebig-Universität Gießen
Gießen, Hesse, Germany
- Department of Pediatric Hematology and Oncology
Humboldt-Universität zu BerlinBerlín, Berlin, Germany
University of FreiburgFreiburg, Baden-Württemberg, Germany
University of Iowa Children's HospitalIowa City, Iowa, United States
Universitätsklinikum TübingenTübingen, Baden-Württemberg, Germany
St Anna's KinderspitalWien, Vienna, Austria
Universität des SaarlandesSaarbrücken, Saarland, Germany
Michiana Hematology OncologyIndiana, Pennsylvania, United States
University of HamburgHamburg, Hamburg, Germany
Dutch Childhood Oncology GroupRotterdam, South Holland, Netherlands
Freie Universität Berlin
Berlín, Berlin, Germany
- Department of Hematology
Azienda Ospedaliera San GerardoMonza, Lombardy, Italy
University of TuebingenTübingen, Baden-Württemberg, Germany
Universitäts-Herzzentrum Freiburg - Bad Krozingenباد کروزینگن, Baden-Württemberg, Germany


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Gun Carry Laws Challenged in Florida
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Servers were so pleasant and interacted with our kids well. Food was all delicious. Reasonable prices for the portions you get. Clean, fast and efficient--service with a smile :-)
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