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July 28th, 2016, 10:13 PMvfrn replied to a thread A Lot Can Happen In Sixty Years - Part 1 in Baby Name GamesYour Family: Roll a d10 to determine the family structure you had growing up. Married parents. Married parents. ...5 replies | 209 view(s)
July 28th, 2016, 10:10 PMvfrn started a thread A Lot Can Happen In Sixty Years - Part 1 in Baby Name GamesOur Protagonist Here are the dice I made this with, although if you prefer a different set, feel free to use what you want....5 replies | 209 view(s)
July 28th, 2016, 01:49 PMvfrn replied to a thread A Whole New World Story CAF, part 3 in Baby Name GamesWhen the ship reaches dry land, the location they find is hot and humid. This means that there is flourishing plant life and food is easy to come by,...11 replies | 4077 view(s)
July 28th, 2016, 12:15 PMvfrn replied to a thread A Whole New World Story CAF, part 2 in Baby Name GamesEarly on in the voyage, spirits are high and the crew and pilgrims are getting along well. A little too well, it turns out, leading to two unplanned...21 replies | 3405 view(s)
July 28th, 2016, 11:01 AMvfrn replied to a thread A Whole New World Story CAF, part 1 in Baby Name GamesShip Crew Captain : Phineas Harvey Dale, 40 – Until recently, he was the first mate, but then Trevor decided to switch as a semi-retirement. He...32 replies | 3505 view(s)
July 27th, 2016, 05:58 PMvfrn replied to a thread Superhero Family! in Baby Name GamesI am Skylar Ellery, with brown hair, brown eyes and the ability to fly. My superhero name is Stratosphere. My wife is Wanda Maximoff. (Mummy and Mama...32 replies | 3004 view(s)
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6 Edgecombe Avenue 5th Floor New York, New York 10030
Phone: 212-694-6040 Fax: 212-690-8056
Welcome Back Letter
September 2015
Dear Parents and School Community,
Welcome to the 2015-2016 school year! On behalf of the KAPPA IV community "thank you" for the opportunity to educate your children. Our quest of preparing our students for leadership and achievement is evidenced by our teachers unwavering commitment to recognize and celebrate all individual children's unique qualities. KAPPA IV's nurturing and challenging environment operates from a child-centered philosophy which explores all available options to provide our students with a quality education full of opportunities and possibilities. In keeping with a philosophy of enhancing our students' academic proficiency, individual development, and talents each and every day, we continue to use the Common Core aligned curriculum in all subject areas. Moreover, in order to help maximize both student academic and social capabilities we will continue to offer foreign language, art and music which will invariably provide your child with the necessary tools for college and career readiness.
We encourage you to check our website regularly in order to stay updated on the status of upcoming school events, important information and reminders. Finally, keep in mind that we strive to maximize our resources and efforts in order to provide each individual scholar with an opportunity to succeed. If you are interested in volunteering and/or have any ideas please be sure to share your comments with a member of the school community. On behalf of the KAPPA IV family we are looking forward to making the 2015-2016 school year a success for all!
Dr. J. Vives, Jr.
Monday, July 25, 2016

subset: commoncrawl


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Product Description
Front Porch Classics Reel 'Em In
This is an oversized and beautifully designed wooden brainteaser puzzle. Players move wood puzzle pieces and try to move fish from bottom to top and deposit wood ball bait into a hole. It's a great gift idea for every fisherman in the family. University Games was founded by Bob Moog and Cris Lehman, who recognized a developing niche in social interaction and learning games for adults and children. University Games creates educational board games designed so that players won't notice how much they are learning.
- Product Dimensions: 8 (L) x 6.75 (W) x 1.5 (H)
- Age: 3 years and up
Recommended Ages:3 and up
From the Manufacturer
Reel 'Em In, and reel in the fun, with this beautifully designed brainteaser puzzle from Front Porch Classics. Try to move the fish from bottom to top, and deposit the ''bait'' into the hole. The beautiful set has wooden puzzle pieces and an oversized game board. Great family fun suitable for anyone age 3 and over. Reel 'Em In is an unusual gift for your favorite fisherman. Measures 8'' x 6.75'' x 1.5''. Front Porch Classics offers "unplugged family entertainment." We're dedicated to bringing people together through play. Our games are designed to engage friends and the whole family around the coffee table, laughing, sharing and building memories. We build our core values into every toy and game we sell: rich storytelling, elegant design, ageless appeal and limitless play.


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From the Herb Garden: Tarragon
Tarragon is a low shrub native to Asia with flat, narrow, glossy-green leaves. It's actually a member of the lettuce family, and its tender leaves are quite tasty when raw! You can also find it as a dry spice, though the flavor is much diminished.
There are two main types of tarragon: French and Russian. We generally prefer to use French tarragon for its delicate, balanced flavor. Russian tarragon can be harsh-tasting and is significantly less aromatic.
The two most common uses for tarragon are in the French "fine herbes" blend and as part of a bearnaise sauce (hollandaise sauce with tarragon and shallots added). Tarragon is also often used as a flavoring for pickled vegetables.
Beyond that, we need to get a little creative! Since the leaves are so tender, they can be mixed in with other greens for salads or sprinkled over a finished dish much like parsley. The anise flavor goes well in tomato dishes, so we can see using it in panzanella and caprese salads, in tomato-based soups, or in tomato sauces for pasta. Used sparingly, tarragon makes a nice seasoning for fish and seafood dishes, or with eggs. Tarragon can also be muddled or infused into simple syrup for to use in cocktails and summer coolers!
We'd really love to start using more tarragon in our cooking. Please share your suggestions for using it!
Related: Tell Us: Is There An Herb You Can't Stand?
(Image: Artistic Gardens)


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First 250 Street Ferrari in Cavallino 213
It was one of Vignale's more bizarre creations, but still engaging nonetheless, but this Ferrari holds the distinction of being the first pure production road model to carry the soon-to-be-famous 250 power plant. Historian and researcher Alan Boe has a special affinity for these early cars,...Read More
Canadian GP: Sebastian Runner-Up
Vettel finishes second in Montreal, Raikkonen is sixth Sebastian Vettel drove a great race this afternoon in Montreal. The German took the chequered flag in the runner-up spot, having led the early stages thanks to a brilliant getaway off the line. Raikkonen, also on a two stop strategy, came home...Read More
Canadian GP: Vettel in the Top 3
Sebastian qualifies third, Kimi is sixth At the end of today's qualifying session at the Montreal circuit, Sebastian Vettel secured third place on the grid with a time of 1.12.990. Kimi Raikkonen was three places further back; sixth in 1.13.579. Starting the Grand Prix from pole tomorrow will be...Read More
The First Wing
From the Klemantaski Collection: In 1968 wings began to sprout on Formula 1 cars. One of the very first to appear was on the Ferrari 312F1 during practice for the Belgian Grand Prix at Spa-Francorchamps on Friday, June 7, 1968. Here is Ferrari's brilliant chief engineer Mauro Forghieri (left)...Read More
The Elégance of Pininfarina in Alassio
On June 6, 2016, The Concours d'Elégance Pininfarina in Alassio crowned its Queen. Winner of the prize for Best in Show at the Concours was the Ferrari 410 Superamerica Superfast, the 1956 masterpiece of the Robert M. Lee Collection and Anne Brockinton Lee. Chairman Paolo Pininfarina...Read More
Elegance Personified
From Gare d'Epoca: The Concorso d'Elaganza Villa d'Este was held for three days over the weekend of May 20 to 22, and as an exclusive event for exclusive cars in an appropriately exclusive setting, it did not disappoint. Among the events celebrating the charm of vintage cars, the Concorso...Read More
Exhaust Pipes Pipe Music
From The Exhaust of a Supercar, the Soundtrack of Our Own Passion Developed from an idea by Matteo Panini and the pencil of Mirco Pecorari, this is the first audio system for iPhones and iPods 100% made in Modena. Created thanks to the collaboration of entirely Modenese crafts workshops,...Read More
GTO Engineering Opens in Los Angeles
Vintage car enthusiasts and collectors gathered to celebrate the new Downtown Los Angeles location for GTO Engineering on Thursday, May 5th. The grand opening for the European Classic Ferrari Specialists featured a fleet of vintage Ferraris with some that have gone through GTO Engineering's...Read More
Business at Ferrari
From Bloomberg: Ferrari NV raised forecasts for 2016 after sales of new sports cars helped profit jump 11 percent in the first quarter, the Italian manufacturer's first as an independent company. Adjusted earnings before interest, taxes, depreciation and amortization will total at least...Read More
Monaco GP: Vettel Fourth, Raikkonen Retires
Sebastian so close to a podium, Kimi out after 10 laps Sebastian Vettel finished the Monaco Grand Prix in fourth place. The race was full of incident, after starting in heavy rain before drying out early on and staying that way to the chequered flag. Kimi Raikkonen retired after hitting the barriers...Read More
Monaco GP: Second and Third Row for Scuderia Ferrari
Sebastian Vettel fourth, Kimi Raikkonen sixth in qualifying Sebastian Vettel finished fourth in today's qualifying session with a time of 1.14.552. The German finished two places higher up the order than Kimi Raikkonen, who was sixth, 180 thousandths of a second slower than his team-mate....Read More
A short while ago, Ferrari hosted for two days their XX program and their F1 Clienti program for special drivers at the Mugello Circuit. In attendance were: XX: Eighteen FXX K Four 599XX Eleven 599XX EVO One FXX Formula 1: Thirteen F1, including two F2001, an F2002, an F2003-GA, an F2004, an F2005, a...Read More


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Designed for those shooting high-definition video with the Canon 5D Mark II and creating a finished product using Final Cut Pro.
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Florsheim Men's Mogul Cap Toe Oxford Reviews
Rated 4.4 out of 5 by 5reviewers.
Rated 5 out of 5 by SaharaSara Loved the shore but needed B width Loved the shoe but needed a B width in a narrow. Famous Footwear don't sell B width. May 15, 2016
Rated 5 out of 5 by Bummer1234 Great Shoe !! I just love the quality of a Florshiem Shoe .... durable yet very stylish. The best part is that I could slip right into the shoe as if I had been wearing it for months. Looking forward to my next pair !!! May 9, 2016
Rated 4 out of 5 by john789 Good shoe, good price. These shoes are well made. They look good and they're comfortable. Not much to say after that. May 4, 2016
Rated 4 out of 5 by greatgrandpa This product was a good value. I have very narrow feet, so have trouble finding shoes that fit. These come very close to being narrow enough for me. March 18, 2016


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Eagle Pointe offers a variety of membership options. If you have any questions please contact the Pro Shop, at (812) 824-1100 Download Golf Membership Information.
The Clubhouse Bar is open from 11:00 - 9:00 Friday - Sunday
Please call (812) 824-4040 for reservations.
Comfortable 1-6 Bedroom Condominiums - Make Reservation
The 4 courts located behind the clubhouse are open to the public. Tennis lessons for beginners are available. For more information, please email firstname.lastname@example.com.


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India Outlines New Telecom Policy
By R. Jai Krishna
NEW DELHI – India Wednesday unveiled some points of a new telecommunications policy, including separating licenses from bandwidth and easing mergers and acquisition rules.
"This policy is announced and will operate from now," Communications Minister Kapil Sibal told reporters.
Read more here.


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In 1994, Driven to Distraction sparked a revolution in our understanding of attention deficit disorder. Widely recognized as the classic in the field, the book has sold more than a million copies. Now a second revolution is under way in the approach to ADD, and the news is great. Drug therapies, our understanding of the role of diet and exercise, ...
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In 1994, Driven to Distraction sparked a revolution in our understanding of attention deficit disorder. Widely recognized as the classic in the field, the book has sold more than a million copies. Now a second revolution is under way in the approach to ADD, and the news is great. Drug therapies, our understanding of the role of diet and exercise, even the way we define the disorder-all are changing radically. And doctors are realizing that millions of adults suffer from this condition, though the vast majority of them remain undiagnosed and untreated. In this new book, Drs. Edward M. Hallowell and John J. Ratey build on the breakthroughs of Driven to Distraction to offer a comprehensive and entirely up-to-date guide to living a successful life with ADD. As Hallowell and Ratey point out, "attention deficit disorder" is a highly misleading description of an intriguing kind of mind. Original, charismatic, energetic, often brilliant, people with ADD have extraordinary talents and gifts embedded in their highly charged but easily distracted minds. Tailored expressly to ADD learning styles and attention spans, Delivered from Distraction" "provides accessible, engaging discussions of every aspect of the condition, from diagnosis to finding the proper treatment regime. Inside you'll discover - whether ADD runs in families - new diagnostic procedures, tests, and evaluations - the links between ADD and other conditions - how people with ADD can free up their inner talents and strengths - the new drugs and how they work, and why they're not for everyone - exciting advances in nonpharmaceutical therapies, including changes in diet, exercise, and lifestyle - how to adapt the classic twelve-step program to treat ADD - sexual problems associated with ADD and how to resolve them - strategies for dealing with procrastination, clutter, and chronic forgetfulness ADD is a trait, a way of living in the world. It only becomes a disorder when it impairs your life. Featuring gripping profiles of patients with ADD who have triumphed, Delivered from Distraction" "is a wise, loving guide to releasing the positive energy that all people with ADD hold inside. If you have ADD or care about someone who does, this is the book you must read. "From the Hardcover edition."
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SherryLynne F
Dec 26, 2013
If you or anyone you know have ADD/ADHD you need to read this book! It is full of useful information that will help you not only understand the condition better, but also give you tips on how to deal with it in daily life!
Jan 20, 2011
What's great about this book is that both M.D. authors have ADD which gives us, the reader, true insight from specialists who live it thereby having an insight that others lack.
Dec 24, 2009
Delivered From Distraction is the most down-to-earth treatment of the ADD phenomenon that I've read to date. None of the associated difficulties are glossed over, yet the very real possibility of finding peace within yourself in spite of (and perhaps because of) the way in which you experience life as an 'ADDer' renews your mental and spiritual desire to see everything through to the end. I thought I was reading a book, but soon realized that I was reading my life story. The feeling of finally being 'understood' was just the beginning of the healing available in this book.
Jan 11, 2009
I am a occupational therapist and a mother of 2 ADD children. I've done my share of reading on the subject. I really like this one, even prefer it over "Driven..." which is also good. It is easily read by anyone but has enough details for the average professional The doctors are very sympathetic to the ADD condition. The chapters are broken down so that one can read the book a piece at a time. Good for all us ADDers!Good general info about ADD and useful specifics for adult ADD, even includes co-occuring diagnosis info and addiction; more about what ADD is about everyday than medical causes.I was lending my copy of this book to many of my adult clients in the field of addictions. But I was having difficulty getting it back because they were so "into" it. Some had actually been identified ADHD for years but didn't have this kind of info and understanding of their condition and what can be done. So now that there is a paperback I 'm ok asking them to buy their own after briefly looking at mine.
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Fax: 0039 02 64442033
Original Article
Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia
An effective but myelosuppressive regimen to be offered to patients with advanced disease
Version of Record online: 5 JUL 2011
DOI: 10.1002/cncr.26303
Copyright © 2011 American Cancer Society
Volume 118, Issue 2, pages 434–443, 15 January 2012
Additional Information
How to Cite
Tedeschi, A., Benevolo, G., Varettoni, M., Battista, M. L., Zinzani, P. L., Visco, C., Meneghini, V., Pioltelli, P., Sacchi, S., Ricci, F., Nichelatti, M., Zaja, F., Lazzarino, M., Vitolo, U. and Morra, E. (2012), Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia. Cancer, 118: 434–443. doi: 10.1002/cncr.26303
Publication History
- Issue online: 5 JAN 2012
- Version of Record online: 5 JUL 2011
- Manuscript Accepted: 2 MAY 2011
- Manuscript Revised: 1 MAY 2011
- Manuscript Received: 21 MAR 2011
- Abstract
- Article
- References
- Cited By
- immunochemotherapy;
- fludarabine;
- cyclophosphamide;
- and rituximab;
- Waldenstrom macroglobulinemia;
- purine analogs
The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM).
Forty-three patients with symptomatic WM that was untreated or pretreated with 1 line of chemotherapy received rituximab 375 mg/m2 intravenously on day 1 and fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 intravenously on days 2 through 4. FCR was repeated every 28 days for up to 6 courses.
The overall response rate was 79%, and the major response rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good partial remissions. An amelioration of the quality of responses was observed during follow-up, leading to 18.6% of CRs. No differences in terms of responses were observed among previously treated or untreated patients. Among the clinical and laboratory features that were considered, only the β2-microglobulin level had a significant impact in terms of achieving a major response. The major toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and was the main reason for treatment discontinuation. After the end of treatment, 19 patients (44%) had long-lasting episodes of neutropenia. Three patients developed myelodysplastic syndrome during follow-up.
The FCR regimen was capable of neutralizing adverse prognostic factors and proved to be active in patients with WM, leading to rapid disease control and good-quality responses. Because myelosuppression was the main concern, further studies are warranted to optimize dosages and treatment duration. Cancer 2011;. © 2011 American Cancer Society.
Waldenstrom macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by bone marrow (BM) infiltration with lymphoplasmacytic cells along with the presence of a monoclonal immunoglobulin M (IgM) in serum.1 Over the last 20 years, purine nucleoside analogues have been used in monotherapy for the treatment of WM and have proven to be effective as both front-line and salvage therapy. In the largest studies, response rates of 30% to 40% and duration of response of 20 to 24 months have been reported with the use of fludarabine.2-6
Subsequent attempts to augment response rates have been made combining purine analogues with alkylating agents.7-10 Although the combination of fludarabine and cyclophosphamide has led to high overall response (OR) rates (range, 55%-85%), in all series, the responses have been categorized only as partial responses (PRs).
Rituximab, a chimeric monoclonal antibody that targets the B-lymphocyte antigen CD20, has been used successfully in the treatment of WM, because most tumor cells widely express CD20.11-14 Response rates to rituximab monotherapy reportedly vary between 20% and 50% irrespective of whether patients have been exposed previously to chemotherapy. An increase in the clinical activity of rituximab, mostly in terms of the time to progression, reportedly was observed using an extended schedule in which 8 infusions of 375 mg/m2 per week were administered in weeks 1 through 4 and weeks 12 through 16.15, 16
Preclinical data based on lymphoma cell lines indicated that rituximab sensitized cells to both fludarabine and cyclophosphamide, enhancing their cytotoxic activity.17, 18 Furthermore, in some cell lines, fludarabine exposure resulted in the down-regulation of complement-defense proteins CD55 and CD59.19, 20
Clinical trials in patients with WM produced a high response rate and long-lasting responses when rituximab was added to nucleoside analogues.10, 21, 22-26 Treon et al administered rituximab together with fludarabine to 43 patients with WM and obtained an objective response in 95.3% of patients with a median time to progression of 51.2 months.21 Similar response rates have been observed in smaller series of patients after the introduction of cyclophosphamide in regimens that contained either cladribine or pentostatine in association with rituximab (94% and 90%, respectively).10, 22
Experience with the combination of fludarabine, cyclophosphamide, and rituximab (FCR) in WM is limited.24-26 The only experience published in the literature is a report by Tam et al, who obtained a 56% PR rate with this regimen in 9 patients with WM.24 A better OR rate (79%) was achieved in our pilot study, which included heavily pretreated and untreated patients.26 Although no patients achieved complete remission (CR) after the first response evaluation, an improvement in the quality of response was observed in 66% of patients later during follow-up. To confirm the efficacy of the FCR regimen, we designed a multicenter, prospective clinical trial that included 43 patients with WM who were previously untreated or pretreated with 1 line of chemotherapy.
Patients with a diagnosis of WM who were symptomatic and required therapy based on the consensus recommendation of the Second International Workshop on Waldenstrom Macroglobulinemia27 and who had received ≤1 previous therapies were eligible for the study. Patients were excluded if they had received prior rituximab or concurrent fludarabine and cyclophosphamide. All patients provided informed written consent in accordance with the declaration of Helsinki and the institutional guidelines.
To be enrolled in the study, patients had to meet the following pretreatment laboratory criteria: alanine transaminase and aspartate transaminase levels ≤3 times the upper limit of normal; total bilirubin ≤2 times the upper limit of normal, unless clearly related to the disease; and a calculated or measured creatinine clearance ≥60 mL per minute. Baseline evaluation consisted of physical examination, blood counts, hepatic and renal function tests, serum and urine electrophoreses, quantification of serum immunoglobulins, β2-microglobulin level, BM aspiration and biopsy, and computed tomography scans of the chest, abdomen, and pelvis.
The FCR regimen consisted of rituximab 375 mg/m2 intravenously on day 1 and fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 intravenously on days 2 through 4. Rituximab premedication included intravenous diphenhydramine and oral acetaminophen. During treatment and for 6 months after the end of treatment, patients received prophylaxis for Pneumocystis carinii with oral trimethoprim-sulfamethoxazole thrice weekly and for herpes simplex and zoster infection with acyclovir 800 mg daily.
Courses were repeated every 28 days, depending on recovery of blood counts, for a maximum of 6 cycles. For episodes of grade 3/4 hematologic toxicity, treatment was withheld until the patient recovered to pretreatment baseline values. A 25% dose reduction of fludarabine and cyclophosphamide was allowed for grade 3/4 cytopenia, and a subsequent 25% further reduction was allowed for other episodes of grade 3/4 cytopenias. Erythropoietin administration was permitted during therapy. Granulocyte colony-stimulating factor administration was allowed at the physician's discretion either as prophylaxis or at the onset of neutropenia.
Before each course of treatment, 1 month after the completion of FCR, and every 3 months during follow-up, patients underwent physical examination, blood counts, hepatic and renal function tests, serum protein electrophoresis, and serum IgM quantification. The first disease reassessment, with BM evaluation and CT scans (for patients who had extramedullary disease at baseline), was performed after the third course of treatment; patients who had progressive disease at that assessment were removed from the study. BM evaluations and CT scans were performed to confirm response or progression after the end of treatment. During follow-up, restaging also consisted of BM biopsy and aspiration (to confirm CR or to evaluate a change in response), CT scans, or abdominal ultrasound studies at the physician's discretion.
Patients who received at least 1 day of FCR were eligible for the toxicity and response assessment, and the results were evaluated on an intent-to-treat basis. Toxicity was graded according to National Cancer Institute Common Toxicity Criteria. All adverse events and serious adverse events were recorded, and serious adverse events that were collected during treatment and 6 months post-treatment were reported to the local authorities.
Responses were assessed using modified consensus panel criteria from the Third International Workshop on Waldenstrom Macroglobulinemia.28 A CR was defined as the resolution of all symptoms, normalization of serum IgM levels with the complete disappearance of IgM paraprotein by immunofixation, no evidence of disease on BM examination, and the resolution of any adenopathy or splenomegaly. A very good PR (VGPR), a PR, and a minor response were defined as achieving a reductions in serum IgM levels >90%, 50% to 90%, and 25% to 50%, respectively. Stable disease was defined as a change in serum IgM level <25% in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WM. Progressive disease was defined as an increase in serum IgM level >25% from the lowest attained response value or progression of clinically significant disease-related symptoms. A major response was defined as the sum of all CRs, VGPRs, and PRs. Variables that were considered for a possible association with achieving an OR, major response, CR plus VGPR, developing major infections, and premature treatment discontinuation were age; sex; time from diagnosis to FCR treatment; pretreatment IgM value >7000 mg/dL; presence of light chain; percentage of BM involvement; extramedullary involvement; a platelet count <100 × 109/L; hemoglobin, albumin, and β2-microglobulin levels; the presence of Bence-Jones; and International Prognostic Scoring System for Waldenstrom Macroglobulinemia (IPSSWM) score.
Statistical Analysis
Differences in response rates were analyzed for statistical significance using the Fisher exact test, and associations of continuous or discrete variables were measured with the Wald test after logistic regression. Repeated-measures analyses of variance were used to evaluate variations in IgM levels within patients. Overall survival (OS) was measured from the start of FCR treatment to death because of any cause, progression-free survival (PFS) was measured from the end of FCR treatment to disease progression, and event-free survival (EFS) was measured in responding patients from the end of treatment to progression or death from any cause. OS, PFS, and EFS were analyzed with the Kaplan-Meier method, and differences were tested for statistical significance using the long-rank test. P values < .05 were considered statistically significant.
Clinical Characteristics
From February 2005 to April 2008, 43 patients were enrolled in this study. Baseline clinical and laboratory features are listed in Table 1. The median patient age was 65 years (range, 36-77 years).
|No. of Patients (%)
|Median [Range]
|Age, y
|65 [36-77]
|25 (58)
|18 (42)
|Time from diagnosis to FCR, mo
|25.5 [0.3-180.3]
|Disease status at treatment
|First-line treatment
|28 (65)
|12 (28)
|3 (7)
|IgM >7000 mg/dL
|5 (12)
|4380 [926-8500]
|Light chain
|34 (79)
|9 (21)
|Bone marrow involvement, %
|70 [10-95]
|Adenopathy, and/or splenomegaly, and/or extranodal involvement
|25 (58)
|β2-microglobulin, mg/dL
|2.97 [1.6-5.5]
|Hemoglobin <10 g/dL
|16 (37)
|Platelets <100×109/L
|1 (2)
|6 (15)
|Albumin, g/dL
|3.8 [2.73-5.5]
|IPSSWM score
|Low risk
|14 (33)
|Intermediate risk
|16 (38)
|High risk
|12 (29)
Most of patients (65%) received FCR as first line-treatment. Twenty-eight percent of patients were in relapse, and 7% had disease that was refractory to a previous line of treatment. Previous treatments included chlorambucil alone or with steroids in 8 patients and cyclophosphamide alone or with steroids in 7 patients. At the time of treatment, the median percentage of BM involvement with lymphoplasmacytic cells was 70% (range, 10%-95%), and the median serum IgM level was 4380 mg/dL (range, 926-8500 mg/dL). According to the IPSSWM score, the majority of patients presented with intermediate-risk or high-risk disease (67%). The primary reasons for initiating treatment, some of which overlapped, were: worsening cytopenia (n = 32); splenomegaly, lymphadenopathy, or organ involvement (n = 25) assessed by CT scan; symptoms and signs of hyperviscosity (n = 6); and peripheral neuropathy (n = 4).
All 43 enrolled patients received the first cycle of treatment and received a median of FCR 6 courses (range, 2-6 courses). Disease reassessment was performed in 39 patients, and the remaining 4 patients were not evaluated (all received <4 courses) were considered failures. On an intent-to treat basis, the OR rate evaluated at the end of therapy was 79% (95% confidence interval, 64%-90%), including 11.6% CRs, 20.9% VGPRs, 41.8% PRs, and 4.6% minor responses, for a major response rate of 74.4% (Table 2). Among responders, the median time to 25% and 50% reductions in serum monoclonal protein was 2 months and 3 months, respectively.
|No. of Patients (%)
|End of Treatment
|Best Response During Follow-Up
|Overall response rate
|34 (79)
|34 (79)
|Major response
|32 (74.4)
|33 (76.7)
|Complete remission
|5 (11.6)
|8 (18.6)
|Very good partial remission
|9 (20.9)
|6 (13.9)
|Partial remission
|18 (41.8)
|19 (44.1)
|Minor response
|2 (4.6)
|1 (2.3)
|Stable disease
|4 (9.3)
|4 (9.3)
|Progressive disease/failure
|1/4 (11.6)
|1/4 (11.6)
In 5 patients, an improved response was achieved during follow-up after a median of 6 months (range, 3-12 months). In 1 patient, a minor response converted to a PR, and 3 patients who were categorized with VGPRs achieved CR. Considering the best response, we observed a 76.7% major response rate (33 patients), including 18.6% CRs (8 patients), 13.9% VGPRs (6 patients), and 44.1% PRs. No statistical difference in terms of response was observed between pretreated and untreated patients, although, in naive patients, a trend was detected toward achieving a better quality of response (43% vs 14%; P = .086) (Table 3) 4.
|Response Category: P
|Overall Response (CR+VGPR+PR +Minor Response)
|Major Response (CR+VGPR+PR)
|Men vs womenb
|Time from diagnosis to FCR treatmenta
|Pretreated vs untreatedb
|IgM >7000 mg/dLb
|Light chain κ vs λb
|Bone marrow involvement, %a
|Adenopathy, and/or splenomegaly, and/or extranodal involvementb
|Hemoglobin <10 g/dLb
|Platelets <100×109/Lb
|Bence-Jones presenceb
|IPSSWM scorea
|Grade 1-2
|Grade 3-4
|Percentage of 43 Patients
|Percentage of 226 Cycles
|Percentage of 43 Patients
|Percentage of 226 Cycles
|Hematologic toxicity
|Extrahematologic toxicity
|Rituximab infusional reaction/hypersensitivity
|Biliary colic
|Cutaneous pemphigus vulgaris
Figure 1 illustrates the progressive, significant decrease in serum IgM levels observed from baseline and during treatment; a loss of significance was observed between IgM values detected between the sixth course and the final evaluation. A progressive, significant decrease in IgM levels was observed among responders between the end of therapy and up to 18 months of follow-up (P < .001) (Fig. 2). Furthermore, in patients who had the longest follow-up, reduced IgM levels still were detected after 48 months and 56 months.
Statistical analyses of clinical and laboratory features revealed that only the β2-microglobulin level (cutoff, ≤2.5 mg/dL) had a significant impact on the achievement of major response (Table 3). None of the other prognostic features that we considered in the study were predictive of achieving a response.
After a median follow-up of 37.2 months (range, 1.0-60.5 months), in total, 5 patients, including 2 treatment-naive patients and 3 previously treated patients, met the criteria for disease progression, and 1 patient required retreatment. No difference was observed in terms of PFS when we compared the patients who achieved CRs plus VGPRs versus patients who achieved PRs plus minor responses (Fig. 3). The median EFS was reached after 50.1 months (Fig. 4); however, even in this analysis, no difference was observed when patients were stratified according to the quality of response (CR plus VGPR vs PR plus minor response; log-rank test, P = .99).
After a median follow-up of 38.8 months (range, 6.6-58.2 months) 11 of 43 enrolled patients died, for an OS rate of 69.1%. The OS was 88.4% at 2 years and 69.1% at 4 years (Fig. 5). In 5 patients, including 4 nonresponders to FCR, death was related to disease progression. One patient died from conditions not related to disease or treatment complications. In 1 patient, death was secondary to the development of acute myeloid leukemia. One patient who had hypoplastic BM was lost to follow-up and died from an unknown cause. Deaths were related to pneumonia in 3 patients, including 1 patient who died 2 years after the end of treatment while in continuous CR.
Overall, 226 courses of FCR treatment were administered. The toxicities observed during treatment are listed in Table 3. In 15 patients (35%), <6 courses were administered for the following reasons: disease progression (1 patient), pneumonia (2 patients), fever of unknown origin associated with neutropenia (1 patient), development of hemolytic anemia (1 patient), rituximab hypersensitivity (1 patient), and medical decision based on persisting cytopenia that required continuous supportive treatment with granulocyte colony-stimulating factor (9 patients).
The first rituximab administration was associated with grade 1/2 infusional symptoms in 18 patients, and 2 patients developed grade 3 hypotension. In the subsequent FCR courses, only 9 episodes of grade 1/2 infusional symptoms were observed. One patient discontinued treatment after the fourth cycle because of a grade 3 cutaneous rash, which was categorized as rituximab hypersensitivity.
No patients experienced an increase in serum monoclonal protein levels after the first course of treatment. Grade 3/4 neutropenia occurred in 44.6% courses, at least 1 episode developing in 38 patients. Granulocyte colony-stimulating factor was administered in 68.5% of courses. In 19 patients (44%), long-lasting episodes of neutropenia, alternating in grade, that persisted after the last course of treatment for a median of 7 months (range, 3-24 months) were recorded. Two patients developed grade 4 thrombocytopenia, which resolved in both patients after the administration of steroids because of a suspicion of autoimmune phenomena. Hemolysis leading to severe grade 4 anemia was observed in 1 patient.
Three patients who were heavily pretreated with alkylating agents developed myelodysplastic syndrome with a complex karyotype after 5 months, 24 months, and 60 months, respectively. One of those patients died from acute myeloid leukemia evolution. None of the patients developed high-grade non-Hodgkin lymphoma.
Severe extrahematologic toxicity (grade 3/4) occurred in 2 patients, both of whom required hospitalization because of cutaneous pemphigus vulgaris in 1 patient and hypotension with lipothymia in the other. Fever of unknown origin was recorded in 7 patients (9 episodes) during treatment and in 3 patients (6 episodes) during follow-up.
Nine infectious episodes, including 3 minor episodes and 6 major episodes, that occurred along with neutropenia were documented during treatment and during the first 6 months of follow-up. The 6 major infections, which developed in 5 patients (12%), were characterized by 5 pneumonias (only radiologically documented) and 1 sepsis sustained by Enterococcus faecalis. In 2 of these patients, pneumonia was the cause of treatment discontinuation. Minor infections consisted of 2 urinary tract infections and 1 herpes zoster.
Three major infections (only radiologically documented pneumonias) were observed after 6 months of follow-up in 3 patients. In 2 of these patients, infection developed during tardive neutropenia. None of the clinical or disease variables that were analyzed and no previous treatments had any prognostic significance for the development of delayed neutropenia, major infections, or premature treatment discontinuation.
Because of its activity, tolerance, and synergy with other agents, rituximab is now a component of most frontline and salvage regimens in WM. The combinations of rituximab with cyclophosphamide and dexamethasone29; or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)30, 31; and, more recently, with bendamustine32 have produced promising results. Furthermore, Buske et al reported a significantly superior response rate (94%) and time to treatment failure in patients with WM and lymphoplasmocytoid lymphoma who received R-CHOP compared with patients who did not receive the monoclonal antibody (69%).33
Several studies have assessed the activity of the combination of purine analogues and rituximab in WM. The addition of rituximab to fludarabine determined a high rate of response with a long time to progression, especially in patients who achieved at least a VGPR.21 A high remission rate with good-quality responses and mild toxicities also were achieved with the administration of 4 courses of rituximab and subcutaneous 2-chloro-2′-deoxyadenosine.23 Similarly, in smaller series of patients, cladribine and pentostatine in combination with cyclophosphamide and rituximab produced OR rates of 94% and 76.9%, respectively, including 18% and 15.3% CR rates, respectively.10, 22 In the literature, many trials have reported high efficacy and an increase in the quality of responses after FCR in patients with indolent B-cell malignancies and chronic lymphocytic leukemia.24, 34-36 To our knowledge, ours is the first study directed specifically at a large population of patients with WM to assess the efficacy of the FCR regimen.
On an intent-to-treat basis, we observed an OR rate of 79%, which is in line with other results reported in literature from larger series of patients with WM who received rituximab-containing combination chemotherapy regimens. Treon et al,21 in their series of 43 patients, obtained a major response rate of 86% with combined fludarabine and rituximab, which is slightly superior to the rate we achieved with the same drugs plus cyclophosphamide. However, in contrast to Treon et al, we observed a progressive improvement in responses during follow-up, leading to a higher CR rate (19% vs 5%). Furthermore, it is noteworthy that the inclusion of cyclophosphamide allowed us to achieve similar response rates while administering a lower cumulative dose of fludarabine (450 mg vs 750 mg) without increasing infective toxicity. This is an important issue when considering recently reported concerns regarding the use of purine analogues in WM.37
Even if the OR rate obtained in this study may be considered similar to the rate reported by Tamburini et al with the same chemotherapeutic regimen without the addition of the rituximab monoclonal antibody (77.6%; all PRs),9 it is important to note that, in our patients, the addition of rituximab improved of the quality of response, and 33% achieved at least a VGPR. The importance of achieving a good-quality response has been reported recently by Treon et al21 in a series of 43 patients who received fludarabine and rituximab; because, in that study, after a long follow-up of 40.3 months, the time to progression was significantly shorter in patients who attained less than a VGPR. In our current study, the follow-up was too short to determine whether the good quality of response may translate into longer PFS or OS.
The FCR regimen was effective in obtaining rapid responses, because the median time to achieving 25% and 50% reductions in monoclonal protein was shorter than what has been reported with other regimens or immunomodulatory agents in combination with rituximab.21, 29, 38, 39 Furthermore, none of our patients had a paradoxical increase in serum IgM levels after the initiation treatment. These data suggest that the concomitant administration of both fludarabine and cyclophosphamide may prevent the flare phenomena and that the FCR regimen should be considered for patients who require rapid disease control.
Hematologic toxicity was considerable, and we observed a high percentage of grade 3/4 neutropenia. A high incidence of neutropenia, leading to treatment delays or dose reductions, also has been reported using other immunochemotherapeutic regimens with or without purine analogs. Grade 3/4 granulocytopenia occurred in 72% of patients who received R-CHOP patients,33 and numerous episodes of grade 4 neutropenia were observed after patients received combined fludarabine and rituximab.21 It should be stressed that myelosuppression after FCR contributed to a high rate of premature discontinuation of intended therapy and led to prolonged episodes of neutropenia in 44% of patients.
In our study, the infectious episodes observed during treatment and during the first 6 months of follow-up were in line with those observed using other schedules that included rituximab.29 The long-lasting tardive neutropenia and the well known immunosuppression related to purine analogs led to a high incidence of major infections, which were fatal in 2 patients. Therefore, accurate follow-up of patients and prolonged prophylaxis are warranted in patients who receive combined FCR.
The phenomenon of late-onset neutropenia, which usually occurs several months after the administration of rituximab or rituximab-based therapies, is well known.40 The high incidence of delayed neutropenia observed may raise the question whether the intended therapy should be limited to 4 courses of therapy or whether the doses of fludarabine and cyclophosphamide should be reduced, as reported recently in patients with chronic lymphocytic leukemia (FCR lite).41 Although the patient numbers were small, in our series, we observed similar response rates between patients who completed 6 courses and patients who completed only 4 or 5 courses. This observation and the progressive amelioration of responses during follow-up are in favor of reducing the cumulative doses of fludarabine, cyclophosphamide, and rituximab administered to patients with WM.
Because an objective of our study was the evaluation of PFS, further chemotherapy to attempt stem cell harvesting was not allowed by study design. Although the role of autologous stem cell transplantation in WM has not yet been established, treatment strategies that include high-dose chemotherapy in young patients with poor prognostic features may be considered.42, 43 From the pronounced and prolonged myelosuppression associated with BM hypocellularity observed after treatment, we speculate that stem cell mobilization may be impaired after FCR.
An increased incidence of Richter transformation and the development of myelodysplastic syndrome/acute myeloid leukemia in patients with WM who received nucleoside analog-containing regimens, independent from previous alkylator therapy, have been recently reported.37 Although the median follow-up of our study was shorter than the follow-up in studies that revealed the long-term consequences of these agents,21, 37 3 of our patients developed myelodysplastic syndrome. These patients had been heavily pretreated with chlorambucil; thus, it is plausible that the alkylator played a role in the occurrence of myelodysplastic syndrome.
In conclusion, the current results demonstrate that FCR produces rapid responses with high rates of CR and VGPR in patients with WM. Because myelosuppression was the most common cause of early discontinuation an d led to a high incidence of prolonged episodes of neutropenia, further studies are needed to optimize the doses and duration of this combined treatment regimen.
By modulating doses and therapy duration, FCR may be considered an effective salvage regimen capable of neutralizing adverse prognostic factors in patients with WM. On the basis of the potential risk of secondary malignancies and the myelosuppressive effects of this regimen, FCR should be avoided as first-line treatment in younger patients.
This study was supported by "Associazione Malattie del Sangue," Milano, Italy.
The authors made no disclosures.
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- 32Bendamustine plus rituximab versus CHOP plus rituximab in the first-line treatment of patients with Waldenstrom's macroglobulinemia: first interim results of a randomized phase III study of the Study Group Indolent Lymphomas (StiL). Paper presented at: Fifth International Workshop on Waldenstrom's Macroglobulinemia; October 15-19, 2008; Stockholm, Sweden. Abstract 139., , , et al.
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- 34Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005; 23: 4079-4088., , , et al.
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Man City boss Manuel Pellegrini rules Sergio Aguero out of Southampton game; Will be fit for Liverpool [Video]
- By Dov Rawson
- April 4, 2014
- Comments0
Manchester City boss Manuel Pellegrini has a tough game this weekend, hosting Mauricio Pochettino's in-form Southampton to the Etihad.
Star striker Sergio Aguero has struggled with injury this year and hasn't featured since City were eliminated by barcelona in the Champions League.
In his Friday press conference, Pellegrini said "Sergio is OK but he needs more work to be 100% fit".
Ruling Aguero out of the Southampton game, Pellegrini said "Next week against Liverpool he will not have any problems".
The South American manager believes the title race will go to the final day of the season. Watch the presser below.
Bet on Manchester City & claim a £50 free bet.
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ViewSonic ViewPad P100 pictures and hands-onPocket-lint
ViewSonic has certainly been busy on the tablet front at Mobile World Congress 2012 and, while it's all been about Android 4.0 Ice Cream Sandwich, there was a cameo from Windows with the arrival of the ViewSonic ViewPad P100
The P100 sports a Windows 7 OS on a 10-inch IPS 1280 x 800 display panel. Using an Intel N2600 dual-core processor running at 1.6GHz, it should be suitable for Windows 8 when it arrives. The device itself is a bit of a beast, feeling a lot more like a computer with the keyboard hacked off than a tablet in its own right.
The enormous dock connector at the bottom is probably the main culprit here but with every other kind of port and socket under the sun stuck on to the rim somewhere, it was never going to be a lightweight thing of beauty. There are external speakers, a lock button, a flap where you can stick a SIM and SD card, two USB ports, headphones jack, power adapter, volume rocker, home and menu buttons and more. A lot. And that might explain the £520 price tag for the Wi-Fi version with £645 if you want 3G too.
The harder part to understand is why you really want to have Windows 7 on a tablet at all. It's not much fun to use. The screen is okay - not super responsive, just okay - and it's all a bit fiddly trying to translate your finger touch to that of a pin-point cursor.
At the same time, with Windows 8 fast approaching, there seemed to be some suggestion from ViewSonic that, indeed, the P100 might never in fact make it to market at all. Not the biggest shame as far as we're concerned.
Best smartphone battery packs: Pokemon power and more
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New ink promotes new world tour.
New Little One For Little Big Town
Little Big Town's Phillip Sweet and his wife Rebecca welcomed their first child, daughter Penelopi Jane, over the Christmas holidays, Dec. 27.
Penelopi Jane was born at Baptist Hospital in Nashville at 5:47 p.m. and has curly brown hair. "We never knew we could love someone so much," says Phillip. "We are truly blessed!" The band is currently on the road with George Strait through March.
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The Gambler's Last Deal begins May 13 in Mahnomen, Minn.
Video features his Wife Alex and Dog Writer as the main characters.
Sam Hunt leads the field with nods in three categories.
New single, "Outskirts of Heaven," has youngsters thinking.
The faith-fueled tune is part of Blake's new album, "If I'm Honest."


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vehicle maintenance mechanic jobs near Tooele, UT
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Diesel Mechanic Technician
Ace Recycling and Disposal - Utah
Correcting vehicle deficiencies; Verifies vehicle performance by conducting test drives; Determines vehicle condition by conducting inspections and diagnostic...
Automotive Technician / Automotive Mechanic / Entry Level Tech
Chrysler Dealer - Tooele, UT
Perform vehicle inspections, basic maintenance, minor repairs, and documenting repairs. Work alongside skilled technicians to learn how to perform quality...
Automotive Technician / Automotive Mechanic /Apprentice Tech
Chrysler Dealer - Tooele, UT
Perform vehicle inspections, basic maintenance, minor repairs, and documenting repairs. Work alongside skilled technicians to learn how to perform quality...
Motorcycle/ATV Mechanic
Powersports Plus - United States
Motorcycle or ATV Mechanic:. Routinely kneel-down and bend-over powersports vehicles. Inspect vehicles, and identify additional recommended services....
Diesel Technician/Mechanic II
Penske - West Valley City, UT
This is a great opportunity for someone who may be looking to learn the fundamentals of preventative maintenance on diesel vehicles and grow in a diesel career...
Customer Service Representative (Fueler/Washer/Detailer)
Penske - West Valley City, UT
The duties may consist of vehicle inspections, fueling and washing of vehicles, pick-up and delivery of vehicles and parts, tire changes, daily rental check in...
HEMTT Mechanic
STS Technical Services - Tooele Army Depot, UT
HEMTT Mechanic experience:. Works for HEMTT Mechanic Lead. This project involves heavy vehicle maintenance and fault repair on a large fleet of US Army HEMTT's...
Vehicle Maintenance Mechanic
Clean Harbors - Tooele, UT
The Vehicle Maintenance Mechanic will be responsible for conducting maintenance on our fleet of company vehicles, trucks, and heavy equipment....
Light-Wheel Vehicle Mechanic
National Guard - Tooele, UT
As a Light-Wheel Vehicle Mechanic, you will have the opportunity to supervise and perform unit maintenance and recovery operations on gasoline - and diesel -...


text: Hi all, as you might have noticed, we (finally) ship firefox-3.0 based on xulrunner-1.9 in gutsy universe. We did this not only to ship the latest firefox beta, but more importantly to allow upstream developers to take a glance at the new xulrunner, how its packaged, how the new gecko API feels like and finally to give them a chance to adapt their code-base in time for hardy. So, if you maintain a gecko embedding package, _please_ point your upstream devs to the xulrunner-1.9(-dev) packages available in gutsy and ask them to report any issues they might have as a bug against xulrunner-1.9. If you or your upstreams need help or have questions on xulrunner-1.9 and how to upgrade, feel free to join #ubuntu-mozillateam on freenode or the mozillateam mailing list (ubuntu-mozillateam at lists.ubuntu.com - subscription required!). Thanks, - Alexander


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Two Polish football freestylers work in tandem to create a special skills video
- February 24, 2014
- Comments0
YouTube channel BeFreestyle are dedicated to uploading the best football freestyler videos onto the internet, and their latest video is something out of the ordinary.
Two Polish football freestylers have worked in tandem to create an incredible skills video that will leave you very impressed.
Combining football skills with juggling and throwing, the end result is perfection.
Watch two Polish football freestylers working in tandem to create a special skills video below.
Grab more information on: Football skills


text:
Fit and finish. It's a Motor City term for how well a car goes together — do the hood and fenders blend together seamlessly? Does the dashboard rattle and shake? Was the carpet installed without seams showing, or was it thrown down as an afterthought? What's evident during the Steelers' offseason practices is that coach Mike Tomlin didn't like the fit and finish of his 2012 model team.
Robinson: Steelers Coach Tomlin Says It's Time to Shape Up
From TribLive.com
Use your ← → (arrow) keys to browse more stories
Gregory Shamus/Getty Images


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Timothy Adam teaches people how to use Etsy.com through his web- site Handmadeology.com. He is a self-taught metal artist and modern metal furniture designer, and since 2007, his products have sold around the world through his successful Etsy shop.
How to Make Money Using Etsy: A Guide to the Online Marketplace for Crafts and Handmade Productsby Timothy Adam
View All Available Formats & Editions
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In a world where most products are manufactured by machines, Etsy offers an online platform for makers of handmade products and crafts to market and sell their goods to a vast network of buyers who demand unique, genuine products. To date, the site has attracted over 400,000 sellers who collectively have sold over 30 million items, generating more than $180.6 million in revenue. The only resource of its kind, How to Make Money Using Etsy--written by Tim Adam who has successfully been selling his products all over the world through his Etsy shop since 2007--guides readers step-by-step through the many stages of selling online. How-to topics include:
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- Effectively photograph your products
- Post your products to optimize visibility and increase sales
- Brand your business
- Use social media like blogs, Twitter, and Facebook to connect with buyers and grow your business
Product Details
- 9781118033845
- Publisher:
- Wiley
- Publication date:
- 02/23/2011
- Sold by:
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- Format:
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Meet the Author
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What was your response to the Budget? We asked readers on social media what the most important decisions were for them.
For Peter Curnow-Ford it was the stamp duty cut: Read more
What was your response to the Budget? We asked readers on social media what the most important decisions were for them.
For Peter Curnow-Ford it was the stamp duty cut: Read more
David Cameron and Nick Clegg were this morning falling over themselves to claim the credit for helping "hard working families" with news of a new voucher scheme that could be worth up to £1,200 per child.
After weeks of wrangling, the coalition was finally ready to press the button on a tax-free childcare scheme to replace the current "employer supported childcare" system. The new scheme will eventually reach up to 2.5m families – compared with the 450,000 who access the current voucher system – and include the self-employed. Read more
Some fascinating economic research by Ipsos Mori, published today, shows that George Osborne is the least popular chancellor in nearly a decade, with net approval ratings of -33. Nobody has had such bad ratings since Ken Clarke in the early 1990s.
At first sign this is unsurprising: this is the first recession we've had since the early 1990s (if you take 2008-now as one recession). But actually when you plot the popularity of chancellor's against economic growth, the two are surprisingly unconnected.
Plotting chancellors' approval ratings since 1976 tells us a few things: Read more
I've updated this post at the bottom in light of this afternoon's parliamentary debate on the issue.
As the Tories contemplate the fallout from coming third in the Eastleigh byelection, different ministers have been floating different ideas for recapturing the votes lost to Ukip. One such idea is banning newly-arrived migrants from accessing certain benefits and NHS services.
Polls suggest immigration is a major reason for voters choosing Ukip, and Conservatives worry that trend will only accelerate when limits on movement from Bulgaria and Romania to elsewhere in the EU are removed.
A cabinet sub-committee has been convened to look into the policy options, but in the face of EU rules forbidding discrimination between citizens of different European countries, is there anything they can do, or is this empty populist rhetoric? Read more
This June, George Osborne will unveil his spending review for the financial year 2015/16. The chancellor is expecting to have to make around £10bn of cuts to Whitehall departments, which, as we revealed in the FT a few weeks ago, would mean some departments taking a particularly heavy whack.
Our figures show that cutting at the same pace as the government has done so far, which is what Osborne has promised, would mean another £1bn taken out of both the business department and the money that goes to local government. The defence budget, possibly the most sensitive of budgets, at least within the Conservative party, would fall by nearly £770m. Read more
Ed Miliband's announcement that Labour backs a mansion tax on properties over £2m, with the money used to fund a new 10p rate of income tax, has left the two coalition parties scrambling to trump the opposition with their own progressive tax plans.
For the Lib Dems, this meant leaking a tax document* being prepared in advance of the party's spring conference. The paper proposed extending the mansion tax from people's first properties to apply also to additional properties and any other land they may own. It also suggested the more radical idea of taxing assets such as paintings, jewellery and even record and book collections – although this was quickly dismissed by Vince Cable.
The Tories offered their own response on Sunday evening, when Tory chairman Grant Shapps appeared on BBC 5 Live's Pienaar's Politics. Shapps told the programme the Tories were considering pushing the income tax allowance beyond the £10,000 level currently planned – something that could go into the party's 2015 manifesto. Read more
Today's exchanges at PMQs sounded fairly hackneyed and well-worn. Ed Miliband chose to ask about the economy, and the usual argument took place – the Labour leader accused the coalition of stifling growth, the prime minister said it was all Labour's fault for borrowing too much.
But Miliband did give one revealing answer during the debate. The Labour leader pointed out:
[Cameron] is borrowing £212bn more than he promised.
We reported this morning that Tory MPs are trying to make sure that the MoD doesn't suffer further cuts at this year's spending review. Mark Pritchard, a Tory backbencher, summed up the feeling of many of his colleagues when he told us:
Colleagues have, to date, reluctantly backed reductions in the MoD budget. However, any additional cuts to the defence, beyond those already agreed, will create a substantial political backlash. In short, the MoD budget has been cut enough, and the Treasury needs to look elsewhere for savings.
Pritchard and his colleagues should be on safe ground: the prime minister himself said that the defence settlement signed in 2010 would require "year-on-year real-terms growth in the defence budget in the years beyond 2015". Read more
The UK government has revealed the planned route of the second stage of the proposed high speed rail link from London to the north of England. Lex's Stuart Kirk and Oliver Ralph discuss who'll invest in a project where any returns would be a long way off.
Amid all the debate about the economic viability of an independent Scotland, one element of the debate has been left behind, namely what Scottish independence would mean for the rest of the UK.
Martin Beck of Capital Economics has sought to remedy that today, putting out a 12-page briefing note on whether the rest of the UK would suffer if Scotland went it alone. Many of the conclusions are speculative: an awful lot depends on what the independence settlement looks like and what happens to the economy after 2014. But there are some interesting points definitely worth pulling out: Read more
The coalition's mid-term "mid-term" parliamentary programme – which is hogging the headlines today – may seem rather thin compared with the original coalition agreement of 2010, which ran into hundreds of pledges.
What's striking is today's PR stunt (sorry, renewal of political vows) also includes one or two areas where an agreement is by no means pinned down between the Tories and Lib Dems.
One of these is the attempt by George Osborne and others to inject billions of pounds into the road network, preferably by a privatisation of the motorways and trunk roads. Read more
Welcome to our rolling coverage of the Autumn Statement.
George Osborne has missed his fiscal targets and cut corporation tax.
We'll bring you all the day's developments live. By Tom Burgis and Ben Fenton.
15.45: We're winding up the blog now, but you can follow events as they unfold through constantly updating stories on the front page of FT.com
15.31: A representation of the "flamethrower of uncertainty" can be found in the documentation of the OBR. It is also known as a "fan chart". I doubt George Osborne is a fan of it, though.
15.24: Chote speaks of the "flamethrower of uncertainty"- a favourite phrase, unsettlingly enough, of the OBR, which is a chart showing forecasts in a wide range that makes the chart lines look like a firebreathing dragon.
15.18: Chote says that the variation in the possible range in the forecast of net debt figures for the UK is a large number, but is "dwarfed by the scale of uncertainties" on the issuance of debt. I think that's the second time he has said that in his address.
15.12: The Spectator is running a rather scary chart showing the lost output of the current "seven-year slump" in the UK.
15.07: Robert Chote, director of the Office for Budget Responsibility, is live now, going through his department's figures that underpinned the bad news Mr Osborne has just had to deliver.
15.05: Gavyn Davies has blogged for the FT with his view on the autumn statement while the FT's Lucy Warwick-Ching has collated some very interesting instant reaction from personal finance experts.
14.49: Hannah Kuchler on the FT's UK desk has been keeping an eye on business reaction to the autumn statement.
She says:
The CBI, the employer's organisation, urged the government to stick to its guns on deficit reduction to retain international credibility, saying it was no surprise that austerity would last longer than expected.
John Cridland, director-general, welcomed investment in infrastructure and support for exports, but said the proof was in the delivery. He said:
"Businesses need to see the Chancellor's words translated into building sites on the ground."
But the British Chambers of Commerce was less positive, declaring the statement not good enough for a country meant to be in a state of "economic war".
The government is just "tinkering around the edges", John Longworth, the BCC's director general said, adding: "The Budget next March must make truly radical and large-scale choices that support long-term growth and wealth creation. That means reconsidering the 'sacred cows' of the political class, including overseas aid and the gargantuan scale of the welfare state. Only a wholesale re-prioritisation of resources, to unlock private sector finance, investment and jobs, will be enough to win the 'economic war' we are facing. The danger is that our political class is sleepwalking with its eyes open."
14.40: Lionel Barber, the FT's editor, just passed by the live news desk so we asked him what he thought of the autumn statement.
The Chancellor is in a hole, but the good news is that he's stopped digging. The FT supports the government's fiscal stance, but is there more to be done on monetary policy to boost growth? That's the question.
14.26 Who says the British don't like doing things the French way? Might we surmise from this tweet from the BBC's Robert Peston's interview with Danny Alexander, Osborne's Lib Dem No2, that the UK's crediworthiness might be going to way of its Gallic cousins'?
[blackbirdpie url="https://twitter.com/Peston/statuses/276330461142327296"]
Others are more chipper:
[blackbirdpie url="https://twitter.com/MJJHunter/statuses/276330252601524225"]
Being prepared for big economic statements, such as tomorrow's Autumn Statement, is a must, given the quantity of information released in such a short time. Even though this will be the 41st Budget, Autumn Statement or pre-Budget report I have covered, I try not to be complacent.
Here's what I think is important (sorry about the length), what type of analysis is relevant to understanding Britain's economy and public finances, and at the bottom is a moan about the way in which George Osborne has decided to follow Gordon Brown down the road of playing games with numbers.
Back in September, Nick Clegg said he would block any attempt by George Osborne to freeze benefits in this week's autumn statement. This put the chancellor in something of a quandary. He had been hoping to save several billions with the move, as well as winning the support of a public that is increasingly hostile to people who are claimants.
Another option remains on the table, however, is to allow benefits to rise, but not by as much as they would normally do if the link with inflation is kept. New analysis from the Institute of Public Policy Research suggests there could still be a fair amount of savings to be gained, for example, by increasing them by just 1 per cent.
The IPPR has produced a table of savings from possible options open to the chancellor: Read more
Mark Hoban, the employment minister, has just suffered a bit of a torrid press conference with the assorted ranks of the British press after the Department for Work and Pensions admitted its £5bn back-to-work scheme has fallen well short of its own targets.
The government's figures show the scheme had found sustained employment (six months for most, three months for those most difficult to help) for just 2.3 per cent of people. The department had set a minimum performance level for itself of 5.5 per cent.
Why is it failing? There are many reasons, but here are the main ones:
1) The economy is worse than expected. The original assumptions built into the scheme were that the UK economy would be growing at 2 per cent. Of course, it is not, which means there are fewer jobs around to be had.
2) The targets were too high. As a way of getting the Treasury to cough up the cash needed for the scheme, the department for work and pensions set very aggressive targets for providers. This has been a concern right from the start of the scheme, as the FT's former public policy editor, wrote last year. Read more
Ministers have been urged to consider imposing severe restrictions on new out-of-town retail developments to save town centres against a backdrop of mass closures of high street shops.
The radical suggestion was first put forward nearly a year ago by Mary Portas, the government's retail tsar, in a review into how to stem the decline of Britain's small shops.
The government has accepted many of the report's 28 recommendations, including setting up a Distressed Retail Property Taskforce that will be unveiled on Monday to combat growing numbers of boarded-up shops.
Yet ministers shied away from her idea that all out-of-town applications should automatically be called in by ministers.
Chris Wade, chief executive of the charity Action for Market Towns, urged ministers to revisit the idea. "That was quite a bold recommendation, but it was never accepted," he said. "We would want to see that happen."
For now, the government has reaffirmed its previous "town centre first" policy in its recently condensed national planning policy framework – namely that retailers should only be able to consider edge-of-town or out-of-town locations if town centre options are not possible. Read more
This morning's research from the IPPR lays out in thorough detail just how difficult George Osborne will find it to meet his fiscal rules when announcing his spending review for the period 2015-2017 next year.
The think tank has analysed the forecasts from the OBR and the Treasury and calculated the cuts needed to make sure the current structural deficit is cleared by the end of the five-year period and debt is falling as a ratio of GDP by 2015.
Firstly, let's assume no cuts are made to welfare. If that is the case, the chancellor needs to make average savings of 3.8 per cent from departmental budgets. If spread equally among the departments, that would mean hugely controversial measures such as cutting the NHS budget by nearly £8bn a year and education by nearly £4bn.
The Lib Dem conference, which starts on Saturday, could be an awkward affair for the party leadership. It is the first conference when Nick Clegg has been faced with members of his own parliamentary party calling for his resignation, and the second successive one where the party has been languishing in the polls.
The agenda for the conference shows the party leadership willing to give the faithful some red meat in the form of Tory-bashing motions. There is a motion insisting on national pay bargaining, one recommitting the party to Lords reform and one resisting any attempts to expand Heathrow.
But the biggest problem could come during the debate on the economy, when an amendment will be discussed calling for the government to rip up its fiscal mandate and take immediate measures to stimulate the economy. Read more
As I reported today, the Treasury is looking seriously into the idea of adopting German-style "mini jobs", a scheme long championed by free market Conservative MPs. The model is that workers can earn up to €400, or £314, tax free each month, while their employers benefit from flexible labour with minimal bureaucracy: they pay a flat rate of wage taxes, insurance and pension contributions.
It is easy to see why companies and jobseekers might be clamouring for the government to pick this up, but there is actually a serious political case as well. Tories who were frustrated by the Liberal Democrats' opposition to radical labour market reforms put forward by Adrian Beecroft have been calling for ministers to come forward with some new deregulation measures for some time.
The Lib Dems themselves are keen not to be seen as too obstructionist on this issue given the drive for growth, and party officials have assured me that they are not pushing back against the mini jobs idea. Could this be the middle way? Read more
Prime ministers aren't supposed to engage in reshuffle speculation. Once they answer one question about a reshuffle, not only have they admitted it is going to happen, they invite a whole load of others.
But David Cameron seems to have been sufficiently spooked by recent speculation surrounding his chancellor that he felt moved to say the following to Sky's Kay Burley:
KB: The economy will pick up, and George Osborne, his job will be safe?
DC: George Osborne is doing an excellent job in very difficult circumstances and he has my full support in going on and doing that job.
KB: And he'll still be the chancellor at the next election?
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