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The election may be won or lost in suburban ridings around Toronto or Vancouver, but the federal parties are devoting this crucial second-last week of the campaign to ridings far from the city lights.
With Passover, Easter, the Stanley Cup and the royal wedding threatening to distract voters from election matters, victory in heavily populated areas could depend on which party is better able to dominate in local campaign organization and television advertising - not on big-ticket appearances by party leaders, who are spending time beyond the beltway.
The Conservatives: Off the highways
With the Conservatives only 12 seats shy of a majority government, every riding counts. And so Stephen Harper is travelling northwest to east in opposition-held ridings that lack freeways, where that elusive 12th seat may well be found.
After starting the week in Yellowknife - the heart of the NDP-held Western Arctic riding, where the Conservatives promised to complete the final 140 kilometres of the Dempster Highway that will link Inuvik with Tuktoyuktuk - Mr. Harper flew east to Thunder Bay, Ontario, where NDP-held Thunder Bay Rainy River and Thunder Bay-Superior North could both be up for grabs.
Here Mr. Harper stressed his party's opposition to the gun registry, the mere mention of which ensures lusty boos at Conservative rallies, while promising $100-million for brain research at the Thunder Bay Regional Research Institute.
Then if was off to Val D'Or, Quebec, for a Tuesday-evening rally in the riding of Abitibi, Baie-James-Nunavik-Eeyou, a rare Bloc Quebecois seat that the Tories believe could be vulnerable.
After overnighting in Riviere du Loup, where the Conservatives won a by-election in 2009 that they hope to retain, the campaign moves on to Atlantic Canada, where Mr. Harper will be making stops in winnable ridings in Newfoundland, Cape Breton and New Brunswick.
The Conservatives maintain that their ground game is better organized and better resourced than their Liberal and NDP opponents in the key urban battlegrounds. And they have already made the ad buys that, they say, will ensure anyone turning on a television in Ajax-Pickering or Vancouver South will hear the Tory message in the final week of the campaign.
The Liberals: Go East
The Ignatieff tour is following a similar trajectory to that of their Conservative rivals. Both leaders were in B.C. on Sunday, both leaders were in Yellowknife Monday and both are heading east for the rest of the week.
After a Tuesday-evening rally in Brampton - an area that will be watched closely on election night - Mr. Ignatieff heads to Saint John, followed by a rally in Yarmouth, Nova Scotia.
He's also expected to visit Prince Edward Island in the coming days, capping off a week in which he will have visited nine provinces and one territory.
The NDP: Country meet city
Jack Layton's cross-country tour has been targeting specific ridings, many of them rural, since the beginning of the campaign and party officials say that strategy will continue until election day.
On Tuesday, for instance, the NDP Leader was in Welland, in the Niagara Peninsula, where incumbent New Democrat Malcolm Allen is in a tough fight with both his Liberal and Conservative opponents.
On Wednesday, Mr. Layton will be in Essex, near Windsor, Ont., where the party believes Conservative MP Jeff Watson is vulnerable.
But the NDP's sites are on suburban and urban seats as well as those in agricultural areas and in the North.
Mr. Layton intends to spend at least some of the time before May 2 in Toronto, for instance, where there are a number of ridings along the Bloor subway line - Parkdale and Davenport and Beaches-East York - that are especially coveted by the New Democrats.
And, just as the NDP has done from the outset, they will be buying targeted ads - especially on radio - in areas visited by the national campaign that speak to local issues.


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When your windshield turns into Mother Nature's easel
Sweltering a bit after Seattle experiences its third consecutive day over 60 degrees? This ought to cool you off...
These interesting ice patterns were spotted on Ken Corkum's car Sunday morning.
The intricate patterns are caused as the water freezes onto the glass -- changes in temperature and wind can affect the progression of the water freezing into ice. The glass surface can also come into play if it's not either perfectly clean or has miniscule imperfections on the surface.
Add it all up, and you get a somewhat random freezing pattern that can turn oh, so gorgeous.
Here is a good explanation on how some of these patterns can form.
And here is another photo. Thanks Ken!

subset: commoncrawl


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With many drivers staying put for 2011 the most coveted place on the grid for next year is the second Renault seat. Speculation about who might take that place has come alive in the past week with the news that team principal Eric Boullier is planning to meet with Kimi R?�?�ikk?�?�nen. Is the 2007 world … Continue reading Should Renault sign R?�?�ikk?�?�nen? (Poll)
Day: October 2, 2010 articles archive
F1 Fanatic round-up: 2/10/2010
Posted on
It's the IndyCar title decider at Homestead tonight (if you're in Britain, at least, coverage here starts at 11:30pm) so I'm going to be watching that. Another title outcome to be decided this weekend is the inaugural Auto GP championship. Romain Grosjean is leading by one point going into this weekend's double-header at Monza – … Continue reading F1 Fanatic round-up: 2/10/2010


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American Tobacco Campus (ATC) is located in the heart of downtown Durham, and a strong case can be made that ATC is the heart of downtown Durham, after all, the revitalization of these old tobacco manufacturing buildings just over 10 years ago is what gave life back this once forgotten area and started to transform the entire city into what is now a true destination location.
Just over a decade later, ATC is one of Durham's most desirable places to visit, boasting theater and sports entertainment, fine dining and casual eating experiences, modern accommodations, and it's within walking distance to the best sites and spots in the Bull City.
Stay & Play
When looking for lodging, why not stay in the center of it all? Last August, ATC welcomed modern boutique hotel chain Aloft Durham Downtown. The hotel has comfortable rooms from standard sizes to larger suites and top-notch amenities like a bar and lounge, gym, and outdoor pool overlooking the iconic Lucky Strike tower.
The Aloft is attached to Durham's nationally acclaimed theater: Durham Performing Arts Center (DPAC), which attracts some of the best Broadway shows, musicians, performers and entertainers in the country to North Carolina, and is a major draw to the area. Recognized for its contemporary design, DPAC prides itself on presenting one-of-a-kind live entertainment that offers something for everyone, including families, couples and performing arts enthusiasts.
If theater isn't your cup of tea, you can always head over to the other side of ATC and catch a Durham Bulls game at the newly improved Durham Bulls Athletic Park. Tickets are affordable; the stadium is the perfect size for families of all ages, and it has its own onsite brewery (Bull Durham Beer Co.) along with many local Durham food vendors serving everything from empanadas to donuts.
Explore & Experience
ATC is even a fun place to stroll around and explore. In the center of the converted warehouse buildings (which are now mixed use office/businesses, housing, restaurants and event space) are beautifully landscaped grounds and water features. There's even a section that has hammocks for lounging, a gorgeous gas fire pit, and a life-sized Durham-themed outdoor chess set.
During the summer, ATC hosts the Back Porch Music on the Lawn series on Thursday evenings. People gather on the lawn under the Lucky Strike tower to enjoy the warm summer nights and listen to free live music.
ATC is also home to Full Frame Theater – a small, intimate theater that seats about 100 and offers year-round programming, screenings and classes. During the spring, it's one of the sites for the Full Frame Film Festival, showcasing some of the nation's best documentaries.
Eat & Indulge
There's no shortage of delicious restaurants in Durham within walking distance from ATC, and the campus itself is home to a variety of eateries from family-friendly joints to upscale dining establishments for date nights and celebrations.
For more upscale, date night dinners try two of ATC's newest restaurants: Basan Sushi and NanaSteak. Basan serves high quality sushi and creative Japanese cuisine in a modern and comfortable atmosphere. They also have an outdoor patio underneath the giant Bull's billboard right next to the ballpark. It's located just a few steps out the front door of the Aloft Hotel.
NanaSteak is a brand new addition to the scene, situated conveniently between the Aloft and DPAC. In an homage to Durham's long tobacco history, the bar top and tables are inlaid with real tobacco leaves. With a focus on locally sourced ingredients and a mouth-watering menu, this is a perfect place to impress your date.
For a more casual, family-friendly bite to eat before or after a game, head over to Only Burger for some seriously good combos of classic and specialty burgers and fries. Mellow Mushroom is also a great kid-friendly option, with pizzas that will satisfy both kids and parents.
For sports fans and late nights, Tyler's Restaurant & Taproom and Tobacco Road Sports Cafe have everything you need, including burgers, mac n' cheese, and plenty of beer. Both broadcast games on multiple screens in the restaurant and become popular hangouts in the evenings and during big sporting events. Tyler's overlooks the ATC lawn beneath the water tower, which is lively during the summer, and Tobacco Road overlooks the Bull's ballpark, providing a fun vantage point to catch the game while eating.
Whether you're coming to Durham for a vacation, festival or business trip, American Tobacco has it all in one convenient spot, from Broadway shows to sporting events to festivals and food. Located in the center of everything the Bull City has to offer, it's no wonder it's become a place so many people come to stay, play and enjoy.
Amber Watson is the creator and writer of the Durham-based food blog and website Bites of Bull City, where area residents and visitors can go to get insider local restaurant news and keep up with Durham's exciting and ever-expanding food scene.
Note: American Tobacco Campus and The Durham Bulls are owned by Capitol Broadcasting Co., which also owns WRAL.


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Harrison Mixbus 32C v3.7.27.WiN
Harrison Mixbus 32C v3.7.27 WiN | 83 Mb
Harrison Mixbus32C is as relevant today as the first Harrison 32 series consoles were 40 years ago. Harrison consoles are dynamically mature products - products that retain the benefits of long, successful experience while incorporating the best of all the new technology. Mixbus32C is designed in the most operationally ergonomic manner possible.
Operational Advantages
Because of the way the Mixbus32C mixer page is laid out, the most commonly used controls are displayed and are accessible at all times using a rich, high contrast, GUI design that gracefully and accurately emulates the original hardware version of the Harrison 32C console. This traditional layout not only looks good but allows the engineer to approach the console as if it were a musical instrument, directly affecting the art of mixing and contributing greatly to the success of any given mix.
Analog Performance
Harrison has pioneered the use of high performance computer technology over the last 20 years to provide unmatched processing power in the world's largest mixing environments. By keeping up with these incremental technological steps through the decades, Harrison can now faithfully emulate the beautifully designed analog signal processing designs of the past and incorporate them into a full function "True Analog" mixing console within the digital audio workstation environment.
More Equalization
Each Mixbus32C channel strip incorporates an exact emulation of the original Harrison 32C parametric four-band sweepable EQ with a separately switchable filter section including second order high-pass and low-pass filters. Every resistor, capacitor, and transistor was modeled. To run this complex DSP on every channel strip was impossible just 5 years ago.
More Buses
Mixbus32C provides 12 stereo mix buses, each with individual level control, latency compensation, and associated master channel incorporating the highly successful Harrison tape saturation, bus compression, and tone control functionality.
Download link:
Links are Interchangeable - No Password - Single Extraction


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9 persons, including Malladi Vishnu booked in cheap liquor case - Tv9
Tue, Dec 08, 2015, 02:08 PM
The Krishnalanka police have filed FIRs against nine persons, including Congress leader Malladi Vishnu, whose name has appeared as ninth in the list. Cases have been booked against Rajapureddy, Mallakonda Reddy, T. Venkateshwar Rao, Nunna Venkateshwar Rao and Malladi Vishnu. Bar license holder Bhagavantula Sarathchandra has been named a A1 accused. His partners, Kavuri Purnachandra Sarma, Kavuri Lakshmi, Malladi Balatripura Sundari and Kalidasu Venkataramana have also been booked.


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NEW YORK ( TheStreet) -- U.S. stock futures pointed to a higher Wall Street open Tuesday, following the upside action in global markets which got a boost from U.S. retail sales that came in better than expected. European stocks were rising while Asian shares finished Tuesday's trading session with gains. Japan's Nikkei 225 index rose 1.4% to close at 8,701.31
The economic calendar in the U.S. Tuesday includes the consumer price index for September at 8:30 a.m. EDT, industrial production and capacity utilization data for September at 9:15 a.m., and the National Association of Home Builders housing market index for October at 10 a.m.
U.S. stocks on Monday closed higher after retail sales for September exceeded expectations and Citigroup ( C) delivered above-consensus earnings. The Dow Jones Industrial Average rose more than 95 points, or 0.72%, to finish at 13,424.
President Obama and Mitt Romney face-off Tuesday in the second presidential debate at Hofstra University on New York's Long Island. The 90-minute debate, which begins at 9 p.m., will be conducted in a town-hall format. Obama is looking to perform better than in the first debate, at which Romney was viewed as the clear victor.
Goldman Sachs ( GS), the investment bank, is expected by analysts Tuesday to report third-quarter earnings of $2.12 a share on revenue of $7.30 billion.
Health care company Johnson & Johnson ( JNJ) is expected Tuesday to post third-quarter profit of $1.21 a share on revenue of $16.95 billion.
Tech giants IBM ( IBM) and Intel ( INTC) post numbers after Tuesday's closing bell. Wall Street is looking for earnings of $3.62 a share from IBM on revenue of $25.38 billion, while analysts see Intel, the No. 1 chipmaker, posting quarterly profit of 49 cents a share on revenue of $13.23 billion. .
Coca-Cola ( KO) and UnitedHealth ( UNH) also are highlights of Tuesday's earnings calendar. Other notables before the bell include Domino's Pizza ( DPZ), Forest Laboratories ( FRX), Mattel ( MAT), Omnicom ( OMC), PNC Financial ( PNC), State Street ( STT), W.W. Grainger ( GWW), and Wolverine World Wide ( WWW). Companies reporting after Tuesday's closing bell include Apollo Group ( APOL), Cree ( CREE), CSX Corp. ( CSX), Intuitive Surgical ( ISRG), Sonic Corp. ( SONC), and United Rentals ( URI).
Yahoo! ( YHOO) has tabbed Henrique de Castro, one of Google's ( GOOG)top advertising executives for the past two years, as the Internet company's chief operating officer.
Starbucks ( SBUX)will begin selling its new Verismo coffee and espresso brewer in U.S. stores on Tuesday.
-- Written by Joseph Woelfel >To contact the writer of this article, click here: Joseph Woelfel >To submit a news tip, send an email to: email@example.com.
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Turn to our expert staff for restaurant reservations within the hotel and throughout Bangkok, as well as arranging tickets to cultural events such as performances at the beautiful Patravadi Theatre Bangkok or popular sporting events like Thai Kick Boxing matches. Allow them to suggest itineraries for tours and excursions to the many nearby temples, historical sites and museums. Of course, they are always happy to recommend the best markets and shopping districts for local crafts, original artifacts and treasured souvenirs.
From flight reservations to limousine service, they will handle all of your transportation needs with a meticulous attention to detail. Furthermore, they are pleased to organise the delivery of floral arrangements, cellular phone rentals, shipping and packaging, luggage storage, laundry services, shoeshine, medical services and so much more.
For more information or to make any arrangements prior to your arrival, please contact them at: firstname.lastname@example.com.


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extreme long range hunting shows?
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June 29, 2013, 06:18 PM
math teacher
Senior Member
Join Date: February 5, 2012
Location: Southwest WA Coast
Posts: 524
I have a couple of gripes with the long range hunting shows. There seems to be a preponderance of them lately. It tends to make people who have never practiced at over a hundred yards or from field conditions think that it is OK to take extreme long shots. I am not criticizing those who have put in their time to learn the art.
Secondly the theme of some of those shows is just long range shots at animals. They never try to get closer, nor do they show them taking an animal they happen on at 50 yards. It is the current emphasis on long range hunting that I object to.
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Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL) (PCYC-1104-CA)
This study has been completed.
Pharmacyclics LLC.
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
First received: October 18, 2010
Last updated: August 24, 2015
Last verified: August 2015
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Detailed Description:
The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL.
The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.
|Mantle Cell Lymphoma
|Drug: PCI-32765
|Phase 2
|Study Type:
|Study Design:
|Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:
|Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma
Resource links provided by NLM:
MedlinePlus related topics: Lymphoma
Drug Information available for: IbrutinibU.S. FDA Resources
Further study details as provided by Pharmacyclics LLC.:
Primary Outcome Measures:
- Percentage of Participants Achieving Response [ Time Frame: The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months ]The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a >/= 50% decrease in the sum of the product of diameters of the target lesions, and >/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions.
Secondary Outcome Measures:
- Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure ]Number of participants who had experienced at least one treatment emergent AE
- PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765 [ Time Frame: Performed During the First Month of Receiving PCI-32765 ]Area under the plasma concentration-time curve using data collected at 0, 1, 2, 4, 6-8, and 24 hours post dose (AUC0-24h)
- Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score [ Time Frame: From Baseline to Cycle 5 (Week 20) ]Mean change from baseline to Cycle 5 in the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) Global Health Status Score according to EORTC QLQ-C30 Scoring Manual (3rd Edition, 2001). For global health status, positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. A change in 5 to 10 points in either direction represents a small change; 10 to 20 points represents a moderate change and greater than 20 points represents a large change.
|Study Start Date:
|February 2011
|Study Completion Date:
|January 2014
|Primary Completion Date:
|January 2014 (Final data collection date for primary outcome measure)
|Assigned Interventions
Experimental: Participants received PCI-32765 560 mg daily
Participants were enrolled and received 560 mg/day dose, stratified into 2 groups based on prior bortezomib exposure.
Drug: PCI-32765
560 mg daily
Detailed Description:
This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects with histologically documented MCL who have relapsed after ≥ 1 (but not > 5) prior treatment regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable toxicity, or enrollment in a long-term extension study, whichever occurs earlier.
|Ages Eligible for Study:
|18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Men and women ≥ 18 years of age
- ECOG performance status of ≤ 2
- Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in the longest diameter and measurable in 2 perpendicular dimensions
- Documented failure to achieve at least partial response (PR) with, or documented disease progression disease after, the most recent treatment regimen
- At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects having received ≥2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.)
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)
Major exclusion criteria:
- Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug
- Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement
- Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
- Creatinine > 2.0 x ULN
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01236391
Please refer to this study by its ClinicalTrials.gov identifier: NCT01236391
|United States, California
|Stanford University School of Medicine
|Stanford, California, United States, 94305
|United States, New Jersey
|Hackensack University Medical Center
|Hackensack, New Jersey, United States, 07601
|United States, New York
|Cll Research and Treatment Program
|New Hyde Park, New York, United States, 11042
|New York Presbyterian Hospital/Cornell Medical Center
|New York, New York, United States, 94305
|United States, Ohio
|The Ohio Sate university
|Columbus, Ohio, United States, 43210
|United States, Oregon
|Oregon Health & Science University
|Portland, Oregon, United States, 97239
|United States, Texas
|MD Anderson Cancer Center
|Houston, Texas, United States, 77030
|United States, Virginia
|University of Virginia School of Medicine Hospital
|Charlottesville, Virginia, United States, 22908
|United States, Wisconsin
|University of Wisconsin
|Madison, Wisconsin, United States, 53792
|Klinikum der Universitat Munchen - Campus Grosshadern
|Munchen, Germany, D - 81377
|Universitatsklinikum Ulm, Klinik fur Innere Medizin II
|ULM, Germany, 89081
|Oddzail Kliniczny Onkologil
|Bydgoszcz, Poland, 85-796
|Malopolskie Centrum Medyczne
|Krakow, Poland, 30-510
|MTZ Clinical Research Sp. z o.o.
|Warsaw, Poland, 02-106
|United Kingdom
|Centre for Experimental Cancer Medicine
|London, United Kingdom, EC1M6BQ
|Christie Hospital
|Manchester, United Kingdom, M20 4BX
|Derriford Hospital
|Plymouth, United Kingdom, PL6 8DH
|Southampton General Hospital
|Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Pharmacyclics LLC.
Janssen Pharmaceuticals
|Study Director:
|Darrin Beaupre, MD, PhD
|Pharmacyclics LLC.
More Information
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Keywords provided by Pharmacyclics LLC.:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 21, 2017
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Zhang L, Baher L, Cheng M, Lee D, Beaupre DM, Rule S. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015 Aug 6;126(6):739-45. doi: 10.1182/blood-2015-03-635326. Epub 2015 Jun 9.
Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.
Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.
|Responsible Party:
|Pharmacyclics LLC.
|ClinicalTrials.gov Identifier:
|NCT01236391 History of Changes
|Other Study ID Numbers:
PCI-32765 ( Other Identifier: Pharmacyclics )
|Study First Received:
|October 18, 2010
|Results First Received:
|February 12, 2015
|Last Updated:
|August 24, 2015
Keywords provided by Pharmacyclics LLC.:
Mantle Cell
Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
ClinicalTrials.gov processed this record on September 21, 2017


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Enthusiastic Leeds post-punk five-piece Eagulls caused a stir after posting an open letter on their blog calling out various indie tropes (eg, "disgusting Afrobeat sounds mixed with your mock American singing" and "promoters clueless to the band's music but very bothered by the amount of Facebook likes"), before concluding: "Gary Numan would knock ALL of your dads out!"
Amusing as it was, some commentators were upset at their suggestion that female band members were used as some groups' "golden ticket" and that it failed to lay out any solution other than "f**k rite off".
"To be honest, it was more a joke that got misconstrued," groans guitarist Mark Goldsworthy (aka Goldy). "I didn't even know what an open letter was until that got posted. It was just on our blog that had about 20 people checking it, and it's got blown out of proportion."
The action in itself is nonetheless indicative of Eagulls' unmediated approach to their art form. Drawing influence from the likes of Public Image Ltd, Magazine and Joy Division, they're a rolling ball of anger, thrilling immediacy and wonderfully skewed guitar tones. "I never take my chorus pedal off," says Goldy of his and rhythm guitarist Liam Matthews' harmonic sound. "Liam's creating that wall of noise behind with the echo and rhythm, and I'm more the melody on the chorus and the flange, which cuts through that."
Aside from their trusty Boss pedals, Liam relies on a Squier Jaguar and Laney amp (both from the 90s), while Goldy employs a 70s Orange OR80, plus an idiosyncratic Korean Squier from the early 90s.
"The guy I bought it from had some Seymour Duncan Quarter Pounds put in," he says. "Also, he stripped all the finish off and took it to a car paint shop, so my guitar is actually Land Rover Green with metallic car paint on it! It feels heavier than any of the other Strats I've played, and I think it resonates better."
You can hear it in used on the band's self-titled recently released debut album. "I'm just eager now," says Goldy. "I'm keen to put that to bed and start writing a new album or EP, because there's nothing worse than writing a song then having to sit on it."
For more information visit the official Eagulls website, or connect with the band on Facebook or Twitter.Read more about


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Joined: 17 September 2004
Posts: 298
thank god, armaan did not win in the end coz' that wld have been really painful, especialy after what he said and the way he said it. he was too 'damn' sure that he wld win and said as much with his confident 'chandigarh... main janata hoon aap mujhe zaroor jitayenge ....' gibberish.
geeee.........k, how can he even be considered in the favourites category. Beats me, at least !
also, the fact that channel is still giving him too much promotion and jassi too in every programme/interview of hers coo............s abt her armaan sir only, reaffirms my belief that he shall remain the main lead and jassi will end up with him in the end.
Tony / diya hum logo ko mama bana rahe hain aur kuch naihn.
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it was just tv actors dancing on movie songs. also jassi acted in a serial but thats a diff story. there was daksh(from CID) and Annie(from ye meri life hai) dancing on "bindaas" from krishna cottage. There was ksh*tij(from kkusum) and kumud(also from kkusum) dancing on "meri makhna" from baghban, and also "aaja soniye" from mujhse shaadi karogi. there was nandu just talking on the mike and saying some jokes. anjali(from hum 2 hain na), and shyla(from hum 2 hain na) were hosting the show. shakti anand(crime patrol guy) danced on "tumse milke dil ka" from main hoon na. the show ended.
but in the previews, they showed ayushmaan and hamara purab dancing but that will come next week.
this aap jaisa koi program will come every week, so stay tuned.
Joined: 22 September 2004
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Posts: 125
i guess, maybe its a temporary show organized by sony just for entertainment. but i think it will come for quite a few weeks before finishing. they will show all sony tv stars then probably finish.
i saw a preview of samir(purab) dancing, hes so natural.
p.s- oh, i forgot, and kalika(from devi) danced on "sajna ve sajna" from chameli and "oodhni" from tere naam.
Joined: 12 August 2004
Posts: 125
i think next week it will be ayushmaan and purab dancing. i thought it was today n i got sad when it didnt come. but im certain its next week. he was wearing a white shirt in the preview. hes soo sweet hamara purab.
it comes on saturday at 7.00 pm for those of u in the us. i live in texas. u guys can figure out the time diff ureselves plz.thanx.
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Angad Jaisa Koi Nahin!!
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BP Comment Quick Links
|Strength of Schedule Report
May 24, 2010
Between The Numbers
Official Secrets
I've written before about why I dislike the error and its cousins, due to its subjective nature. But how much does it matter, especially over a long period of time? Is there a practical consequence to the subjectiveness of the error?
So here's what I did. I took a look at the rate of errors per balls fielded by infielders in all of a team's home games, including the visitors, from 2002 - 2009. I did the same for a team's road games. Each of those rates were then regressed to the mean, then the regressed home rate divided by the regressed road rate to produce park factors. Then I averaged all the one-year regressed park factors over the full time span, and here's what I got:
The standard deviation of the group over the eight-year time span was about four percent in either direction; in other words, teams had an error park factor of between 96 and 104 about 68% of the time.
Of course, this raises the question - how much of the difference between parks is scorers, and how much of it is actual changes in the way balls are hit at infielders? Bear in mind, for something to be an opportunity here, a fielder has to reach the ball. So the park effect would have to control how cleanly a fielder can field a ball.
Now, I have my own suspicions (and familiarity with my work would probably tell you what those suspicions are). But it's just a suspicion - I'm not sure we really know, and I'm not sure that we will ever know for certain.
But it does give one pause - or at least it should give one pause - when using errors to attribute value to players. Which is of course something we frequently do for hitters, pitchers and fielders right now. (Anyone who thinks we don't use errors for evaluating hitters, or that we shouldn't - the very act of considering an error an at-bat but not a time where he reached safely implicitly, if not explicitly, includes the error in an evaluation of a hitter's prowess.)
Colin Wyers is an author of Baseball Prospectus. Follow @cwyers
10 comments have been left for this article.
BP Comment Quick Links
The average everyday player might reach base on an error, what, 5-10 times a season. So maybe 1-2 base hits are errors or vice versa depending on the park?
May 24, 2010 09:19 AM
"I took a look at the rate of errors per balls fielded by infielders..."
May 24, 2010 09:56 AM
Probably because a) most OF errors are scored hits since the ball doesn't touch the glove, and b) the number of OF errors actually scored errors (dropped balls) is too miniscule to bother with.
May 24, 2010 11:10 AM
I should clarify that this isn't fielding percentage, but looks at all balls fielded at all. And, with the exceptions of home runs and foul balls, all batted balls have to be fielded by somebody. With the exception of infield singles and home runs (and ground rule doubles), every hit is fielded by an outfielder at some point.
May 24, 2010 11:49 AM
Dumb question: does a higher number mean more errors, or fewer errors, at a given ballpark?
May 24, 2010 11:24 AM
May 24, 2010 12:12 PM
That's interesting. I don't know if it's really bimodal or not - it could simply be a strongly right-skewed distribution that needs some smoothing. You're right that I haven't given enough data points to say for sure. I'll have to look at this a bit more and report back.
May 24, 2010 12:37 PM
I don't want to say I looked at a larger data set, but I looked at a more granular one - I figured three-year park factors for each year in the data set. (Anyone interested can get the data here.)
May 24, 2010 17:39 PM
Thanks for reporting back on it! I was struck by the lack of 100's in the data in the article, but it is clear that a larger data set fills it in better. I always like reading about the reliability of the source data that is used in so many of the advanced metrics, and this was a nice look at the way errors are scored.
May 26, 2010 12:06 PM
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Just an FYI that Roy & Tyler will be appearing at the Indiana Live Casino on Thursday 3/18/2010 from 7-8pm EST signing autographs, etc! Admission is free! With this being at a Casino, I'm also guessing that you have to be 21 to enter.
The Casino is located in Shelbyville, Indiana right off of Interstate 74 about 15 miles southeast of Indianapolis.
See the link for more info: http://www.indianalivecasino.com/eve...pacers_new.pdf


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A joint program between the Washington State Patrol and Gordon Trucking hopes to help bring home some of the state's missing children using pictures and information on the side of Gordon trailers. The initiative, part of the Homeward Bound program hopes to help bring home some of the 23,000 children that are reported missing in the state every year.
The Homeward Bound program was started in 2005. Gordon Trucking currently has over 85 trucks on the road on which pictures of missing children can be seen. According to the WSP webpage dedicated to the program, "the hope is that putting pictures of missing children from Washington out to the nation that someone will recognize and help locate these missing children."
Since 2005, the Homeward Bound program has helped to recover 6 missing children. Currently there are 20 missing children featured on Gordon Trucking trailers.
Anyone with information on a missing persons case is urged to call 1-800-THE-LOST.
Next Story: Driver Reports Unsafe Truck, Gets Fired, Wins $115k Lawsuit
Source: krem, klew, washingtonstatepatrol
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Last Updated Sep 20, 2010 4:34 PM EDT
In short, a stated fee isn't always what it seems. For that matter, neither is an advisor. I recommend fee-only planners but I've found some who are so new to the business or so limited in their skills that I wouldn't go near them.
So how do you go about assessing what you're paying for advice and what the potential conflicts or trouble spots might be? Here's a rundown:
Fee-only advice. This is my choice, always. These advisors give you a price list up front, for work by the hour, by the task, or for ongoing management of your money. They don't take sales commissions, so they're not primed to push products. They sell only their planning and investment expertise.
Within this world, however, there's a lot of variation.
A fee-only planner, with a CFP designation (for Certified Financial Planner) helps you establish your priorities and goals, create budgets, set savings targets, test your insurance safety net, establish retirement savings accounts, project future retirement income, plan for taxes, and make basic investment decisions. By "basic," I mean simple asset allocation and picking no-load (no sales charge) mutual funds. That's all that most families need. You can find some of these fee-only planners through the Garrett Planning Network, the Alliance of Cambridge Advisors, or the Financial Planning Association (when you search the FPA site, click on "How Planners Charge" and check the box for "fee-only").
But some of these advisors -- especially people who have been in business for only three or four years -- might not have the knowledge or experience to analyze your investments in depth. Those with a brokerage-house background are familiar with securities, but others are still learning. They might be qualified to advise on mutual funds but not individual stocks and bonds. They might be taking clients before they've finished their CFP.
On average, you'll find more experienced planners through the National Association of Personal Financial Advisors. Some NAPFA members deal only with people of higher wealth. Others take middle-class clients, too (see what their websites say).
Even planners with good paper qualifications might not serve you well if they don't understand your life experience. For example, young planners who don't own homes are not the best guide through mortgage decisions. Someone in his or her mid-30s will think more aggressively about investments than someone in late middle age. If you're approaching retirement, you want a planner who can feel the same, cold wind of uncertainty that you do.
Fee-only planners typically charge 1 percent on accounts up to $1 million or so, and less on larger amounts. But fees have been going up, says Tom Orecchio of Modera Wealth Management and former president of NAPFA. Some firms charge 1.5 percent or more for the first $500,000.
"Advisors say they're working harder, for less money, than at any time in their career," Orecchio says. Accounts under management have declined in value, clients need more handholding, and more new products are coming to market that need evaluating. So they're charging people more.
Normally, a percentage fee applies only to money that the planner has directly under management. A few planners assess the fee on your total net worth, including your 401(k) and home equity. "That's for comprehensive financial planning," says John Sestina of John E. Sestina and Co. "We advise on everything, including whether to refinance a mortgage and how to allocate a 401(k)." He charges $5,000 for accounts up to $1 million (that's 0.05 percent, at the top) and larger fees for larger accounts. For younger clients, he offers "financial planning lite"-- $1,000 for full planning and investment services on accounts of any size, but only two or three meetings a year.
Fee-based advice. Here, you have wolves in sheep's clothing. It sounds as if they also give fee-only advice. In fact, they sell products and earn commissions. You might pay fees for some products and commissions for others. The size of the fees might depend on what else you buy. "Fee offset" means that the fee is deducted from the commission you pay. Commissions aren't always visible, so it's easy to pay more than you realize.
Brokerage house advisory accounts. You pay fees here, too. The broker provides an investment plan, developed and monitored by the firm's advisory team. You get periodic reports. Small investors, with $25,000 to $50,000, might be charged in the area of 2 percent a year. These accounts don't include packaged products such as variable annuities or unit trusts. Your broker might sell them to you on the side, earning a commission on the trade.
Skip these expensive advisory accounts if you're a long-term investor who holds mutual funds and a few stocks. You're much better off in a regular brokerage account that doesn't charge fees--or, for that matter, with a fee-only planner.
Regarding conflicts of interest, I'm always careful about the commissioned-sales world because of its fondness for selling high-cost products. But the fee-only world has potential conflicts, too. Planners who charge on an hourly basis might stretch out the time it takes to complete your job. Planners who work on retainer might pay less attention to your account, because they've got the money anyway. Planners who charge a percentage of assets have an incentive to hold on to your money -- for example, by recommending that you keep your mortgage rather than paying it off.
Always evaluate the advice, in terms of your advisor's interest as well as your own. Advice isn't always worth what you pay for it. You might do better by paying less.
More on MoneyWatch:
Have an Annuity with Lifetime Guarantees? Don't Give It Up
Should You Trust Your Broker? No, and Here's Why
Credit Card Interest Rates Rise, But That's a Good Thing


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by Dr. Edwin Berry
Congratulations to our new Secretary of Interior, Ryan Zinke. Ryan Zinke is the first Secretary of Interior from a mountain state and the first Montanan to be in a president's cabinet.
Governor Bullock has set May 25 to elect the candidate who will take Ryan Zinke's seat in Congress.
At stake is a seat in Congress that Republicans have held for 22 years. Will this election be a slam dunk for the Republican candidate?
To be clear, I will support the Republican candidate for Congress. However, there are political forces that are far stronger than any recommendation I can make. The 200 or so Republicans who will nominate their candidate should be aware of these political forces before they make their choice.
The last election made it very clear that Montanans do not follow party lines in final elections. Donald Trump beat Hillary Clinton by 61 to 39 percent. Yet, Democrat Governor Steve Bullock beat Republican candidate Greg Gianforte by 52 to 48 percent. [Read more…]


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BP Comment Quick Links
|Strength of Schedule Report
September 24, 2010
Taking Turns
Last night, watching Madison Bumgarner mow down the Cubs from a perch in the press box, it was easy to dissociate from that bloodbath and turn my mind to happier exercises. Chiefly, I started thinking about the assorted rotation possibilities of the different playoff teams, a topic I'll be writing a bit more about next week. It's already easy to anticipate an upset in the Bronx, because the vincibility of the Yankees in a short series if Andy Pettitte isn't entirely right seems fairly obvious.
But expand that question to the other likelies: What do the Rays do with James Shields? Or the Reds, as I noted in TA today, with Bronson Arroyo? Will the temptation be to go with staff leaders, defined either in terms of workloads or experience or some more subjective criterion like charisma, and will that trump performance, or even potentially favorable matchups?
Kevin always likes to chime in that players aren't Strat cards, which is true... but at what point does a skipper abdicate his responsibility to doing his best in terms of achieving the team's best shot at success? I take the observation that the postseason is a crapshoot as a truth, but only up to a point--it shouldn't also be taken as cause to abdicate agency. A skipper is responsible for his club's success, and sometimes that has to involve telling a full-season contributor he's being skipped, or left off the post-season roster entirely. The exercise is not and cannot be a popularity contest. When Lou Piniella left Jason Marquis off the Cubs' post-season roster, for example, that wasn't a utter dismissal of Marquis' value as a contributor, as a pitcher, or as a teammate. It was a sensible operational decision.
Which is the other thing that Bumgarner's dominance got me to thinking about last night, the other half of the argument, the "soft" factor of decision-making, of treating a useful player with the dignity he might understandably expect. At what point has a pitcher "earned" his post-season starts? Storm Davis' plaintive cry over being passed over for a World Series start in the quake-punctuated '89 series wasn't just an instance of selective memory--Storm got blown over pretty badly twice in the A's fan horror show of '88, after all. It was also a comment on his having paid his dues to help generate the team's getting there in the first place. Was that selfish of him? Maybe a little, not that you can blame him, not as a matter of identifying himself as an element of the team's success, however much Davis might be something of a sabermetric punchline these days.
But bringing this back to last night's action and looking at the Giants, if or when Madison Bumgarner bumps Barry Zito for an LDS or LCS start, how should you expect Zito to react? Maybe that's the chance for Zito to play the role Bud Black did for the Royals in '85, or David Cone in 2000, the veteran starter bumped by those better and younger, but still able to serve a purpose to achieve ultimate success.
So, that said, looking at any of the playoff teams, I'm curious about other people's tacks on rotations and what you'd do if you were Dusty Baker or Joe Maddon, Bruce Bochy or Bud Black.
Christina Kahrl is an author of Baseball Prospectus.
2 comments have been left for this article.
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Adam B.
I'm a Phillies fan, so this one's easy. It's Two Roys and the Boy (or H20) unless we're up 3-0 in the LCS, in which case Blanton may get a start.
Sep 24, 2010 15:14 PM
I appreciated the reference to the role that Bud Black played in KC's success in 1985. The Royals' manager, Dick Howser, did some clever things with his pitching staff in the LCS that year, with both Black and Charlie Leibrandt serving as both starter and reliever, largely to mitigate the declining effectiveness of Dan Quisenberry. It will be interesting to see what manager Black does in this postseason, if he gets the chance.
Sep 24, 2010 16:18 PM
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As temperatures keep dropping on the East Coast, now is the time to seek out 80 degree weather and sandy beaches. One way to start is the special fare sale from Cayman Airways. Until February 8, you can book one way flights to Grand Cayman from New York (JFK) for just $174.20, which includes taxes and fees. Note, the airfare from Grand Cayman to New York one-way is $249.35, and includes two check bags and complimentary rum punch. Additional airfare to Cayman Brac and Little Cayman is only $49.25.
This deal is valid for all travel between January 29 and March 30. Book the fare sale online now.


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text: CSI: NY Season 9 Review "Late Admissions" November 17, 2012 CSI:NY, Reviews This week's "CSI: NY," entitled "Late Admissions," was one of my favorite kinds of "CSI" episodes- the ones that make no sense on the surface and only get crazier as the episode progresses. Though they'd be hard-pressed to top that one "CSI" involving cannibalistic cheerleaders, this was a pretty solid entry, nicely juxtaposed with another sort of mystery: the reason behind Lindsay's mysterious visit back home out of the blue, and why she won't talk to anyone about it. We opened with a montage of a kid doing drugs before taking his standardized tests. As he looked around the classroom, it seemed like maybe he wasn't the only one doing so. Was it some weird hazing stunt of some kind? Some sort of brain-enhancing drug, like in that movie "Limitless"? These bath salts I keep hearing about? Smarties? More importantly, would cannibalism be involved? Fingers crossed! Alas, there was no zombie activity this time out- guess I'll have to wait until Sunday's new episode of "The Walking Dead" for that. Instead, we got a kid found dead in the library. Was it Professor Plum with the candlestick? Oh wait, that was last week. Moving on… To add insult to injury, drugs were found in the kid's backpack…but not in his system, as it turned out. Further, his father was an acquaintance of Mac's, and not above taking the law into his own hands. After a few hazy moments over the last few weeks, Mac was on top of his game here- no brain farts to speak of. He was determined to get to the bottom of things, for better or worse. Eventually, the clues led to Billy, a classmate of Luke's, aka the dead boy in question. Although they were able to trace the pills- which turned out to be ADHD meds- back to Billy, there was no evidence linking him to the murder itself. In the end, it turned out to be a teacher that was the culprit, scared that the fact he knew what was going on and didn't do anything about it would ruin his career. For those keeping track at home, this is at least the third teacher somehow involved in the main crime at hand this season- and we're only on the eighth episode! Not sure what the people at "CSI: NY" have against teachers, but cut them some slack, you guys! (Sorry, I'm studying for an education degree on the side- it's hard not to take umbrage with all this teacher-themed crime…) Meanwhile, the Lindsay stuff was genuinely poignant, as it dealt with the crime she herself was at the center of as a child. Barely escaping with her life, she had to watch in horror as her sister and friends were killed in cold blood- an experience that directly led to her becoming a CSI. It turned out that her hidden agenda was that she was there to bear witness to the killer's death sentence being carried out. Strong stuff, to be sure. While they've alluded to these events before on the show, it was illuminating to get things from Lindsay's point-of-view and see flashbacks of her sister and friends and their hopes and dreams, all of which they had no idea were about to be taken away. It was confronting these buried memories that allowed Lindsay to make her peace with everything that happened, as well as to solidify what she'd always known: they got the right guy, and he was finally paying the price. In the end, he confessed- not that she needed verification. You don't forget things like that, ever. I'm really digging all these character-driven touches they're emphasizing this season. When they picked "CSI: NY" over "CSI: Miami" to keep, I was a little disappointed, as I leaned towards the latter in my preference, but I must say, the former has really stepped up their game this season. Sure the main crimes have been a mixed bag, but the character stuff is golden, and when you've got a cast this good, that accounts for a lot of good will in viewers. As anyone will tell you that watches some of the more formulaic shows out there, it's not so much about the plot; it's how our beloved cast at hand handles it. And "CSI: NY" is doing it right. Now if we could just get them to lay off the teachers! What did you think? Did you find Lindsay's back-story as touching as I did? Are you digging the details of our team that are unfolding each week? Or do you prefer the more stunt-driven plotlines, a la last week's "Clue"-themed episode? Let me know in the comments! Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Google+ (Opens in new window)Click to share on Tumblr (Opens in new window)Click to share on Pocket (Opens in new window) Sumflow >Was it Professor Plum with the candlestick?< No it was the Professor with the coffee cup. Lindsay's back story was more interesting than the front story. Did she wait 16 years to come forward and nail the guy? Was the connection between the front and rear stories, about the guilt of not coming forward? The implications are that teachers know more than they are telling. CSI Miami had gotten a little weird. Once NY got Sela Ward, Miami did not have a chance, even if it did have higher ratings. Mark Trammell LOL on the first comment…right you are. Agreed on the Lindsay story. As far as it goes, they've alluded to it before, so no, she didn't wait this long to come forward to nail the guy- she was simply having trouble coming to terms with his denying everything up until practically the very end. She was there for his execution, plain & simple, and was still convinced he was the culprit, even thought he claimed otherwise. However, at the end, he finally admitted & apologized for what he'd done, confirming what Lindsay knew all along. He'd simple been trying to cast doubt in her mind to no avail, but she held strong. I do think you're right about the whole "guilt" thing being the connection between the two, in a way. Lindsay felt guilty bc she survived & hid away while her family/friends were being killed, while guilt over knowing what was going on with drugs in his school is what made the kid come forward- and what ended up getting him killed, sadly. In this case, it was lack of remorse on the teacher's behalf- and the killer Lindsay confronted as well- that also connected the two, I think .


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blend. I was a bit skeptical; I am not a big fan of Stash's Peppermint, and thought that I would just not like mint teas period.
Well, apparently, I just don't like pure mint teas. This tea actually is not pure Spearmint – which is, by the way, just delicious – but accented by yummy, subtle black tea to make a tea that even cold doesn't fall into the category of toothpaste backwash. As others have stated, this tea tastes best cold, which differentiates it from Stash's mint tea.
Spearmint + black tea = delicious dessert tea that pairs perfectly with cheesecake or chocolate anything.


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Playing in a facility the size of the arena would be daunting to about anyone. It's certainly different from playing in the Monte Vista High School gym. And playing against the three-time defending state champs for Interscholastic Federation Division I would give one pause, especially when you consider that its lineup consists of girls who are 6 feet 4 inches, 6 feet 2, and 6 feet 1.
But if the Lady Mustangs were in any way daunted by the size of the stadium or their opponents on Saturday it certainly didn't show in the way they played. Coming in off their Northern California Sectional win, the MVHS basketball team dug in and played with a feral intensity.
Coach Ron Hirschman instructed his team to maintain its zone defense against the Jackrabbits, closing down the middle and forcing the Long Beach team to shoot from the outside. This strategy limited the opponent's scoring and allowed the quicker Monte Vista players to snag rebounds and start the ball back upcourt.
Team standout Niveen Rasheed had the unenviable task of moving the ball toward their basket against a very aggressive and determined full court press put on by the Jackrabbits. Pitting speed against speed, Rasheed executed phenomenal dribbling skills in foxing her way around opponents in order to pass the ball off to waiting teammates.
The solid zone defense coupled with the quick upcourt movement took the Long Beach team by surprise and allowed Monte Vista to jump out to a quick lead. By the end of the first quarter the score stood 8-6 in favor of MVHS.
The second quarter followed suit, but problems began to emerge as fouls were called against the Mustangs, allowing the Jackrabbits to notch more points. Rasheed racked up two fouls by midway through the second quarter and Coach Hirschman began to substitute her out more frequently in order to keep her from drawing further fouls.
However with only nine seconds left in the half and sensing a chance to get one more basket before the buzzer he substituted her back in for one last drive. Tragedy struck when the play ended with yet another foul levied against Rasheed. Going into the half the Mustangs were down 19-17.
In the second half, Monte Vista was forced to play a more defensive game, cycling Rasheed in and out to preserve her primarily for offense. With only two fouls left before she would be out of the game, Hirschman couldn't afford to let his key player stay in the game.
At the same time, the Jackrabbits emerged from the half energized and hungry, piling on the pressure and forcing the Mustangs to fight for every inch. The tactic forced risky shots and caused more frequent turnovers, which allowed the Long Beach team to steal away with the game. Even a pair of 3-pointers fired in from the outside by Dani Rabago were not enough to stop the hemorrhaging as the Jackrabbits gained momentum. By the end of the third quarter the score stood at 37-25.
Hirschman was forced to keep Rasheed in for longer periods of time, trying to build up momentum of his own. To some degree it worked as the Jackrabbits were slowed for a time, but with three minutes left in the game she picked up her fifth and final foul. Obviously upset, she stepped off the court for the final time having accounted for 16 points. Tired but determined, the team pushed for a run they hoped would offset the huge point deficit.
Unfortunately, the Long Beach team was on a roll and continued to force turnovers and make baskets so that when the final buzzer sounded the score was 57-33.
After the game, Hirschman congratulated the Long Beach squad for its victory, but said he was very proud of the effort put forth by his team.
"That is a great team we played tonight, but I think you saw tonight what our kids are made of. I'm so proud of these 12 individuals. They showed tonight that they can play with any team out there," he stated.
Hirschman said that the first half went exactly according to the gameplan with one exception: "I had us up by 20," he joked. Then he added, "We played them to a standstill and we were still down by 2. That's the kind of team Poly has."
The coach said he felt the game could have been different if he hadn't put Rasheed back in for that critical nine seconds where she got her third foul.
"It changed the whole aspect of the game. We had to protect her as much as we could. It meant we had to play more defensively than offensively."
Rasheed said having to regulate her play made it harder for her to be effective on the floor.
"I had to get in, get a point, then get out again. I didn't get momentum," she explained.
The Princeton-bound senior said that even though her team lost she was glad they made it all the way to the CIF finals.
"We didn't want the season to end," she said. "As a senior it's a great way to end your season ... at the state championship."
While the Division I championship was the culmination of the season, Hirschman said his team has just had a phenomenal year in general.
"These kids are a true team. That's one of the reasons they got this far. They have a friendship, a unity that's there both on the floor and off," he said.
The Lady Mustangs had a 29-3 season and Hirschman said there was one game in particular that showed him just how much potential they had.
"It was the first time we played Carondelet and we beat them," he stated. "They brought their 'A game' every night."
One of the most high pressure games came for the team when they were 23-2 and starting the North Coast Section playoffs.
"We were having such a strong season. If we went out there and laid an egg and lost in those two games, that would have been it for us," he said.
The end of the season also means a significant shift in the status quo for the Lady Mustangs as four of the team's starters graduate this year and move on.
"Every year you always lose something special. You don't just replace these four kids. You don't replace Niveen Rasheed," he said.
"But we will just keep putting the best team out that we can," he added. "These kids have a great work ethic, they enjoy what they do, and we'll just see where that takes us next year."


text: The Elk River-Zimmerman boys stayed unbeaten wit a 3-2 win over the Anoka Tornadoes at home Saturday evening. Senior forward Mitch Kierstad knocked in two goals, Nick McCormack made two assists, and goalie Anders Franke stopped 31 shots. Andrew Zerban scored the other goal. The Elks (3-0) will play at Centennial on Tuesday evening.


text:
Give us a call to get our secret deals 1-800-468-3578
Property Location
With a stay at Hotel Route-Inn Natori in Natori, you'll be within the vicinity of Sendai Gymnasium and Museum of the Forest of Depths of the Earth. This hotel is within the vicinity of Sendai City Jomon Site Park and Dainenji Temple.
Make yourself at home in one of the 207 guestrooms featuring refrigerators. Complimentary wired Internet access is available to keep you connected. Bathrooms have complimentary toiletries and hair dryers. Conveniences include phones and coffee/tea makers.
Enjoy a satisfying meal at a restaurant serving guests of Hotel Route-Inn Natori.
Business, Other Amenities
Featured amenities include complimentary wired Internet access and laundry facilities.


text:
Scuttlebutt (Dubstep)
Credits & Info
- Uploaded
- Jun 2, 2012 | 9:21 PM EDT
- File Info
- Song
- 3 min 56 sec
- Score
- 4.53 / 5.00
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Please contact me if you would like to use this in a project. We can discuss the details.
- Score:
- Rated 4.53 / 5 stars
- Plays & Downloads:
- 2,878 Plays | 247 Downloads
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- Genres:
- Electronic - Dubstep
- house
- sample
- electro
- dubstep
Author Comments
Rated 5 / 5 stars
Wow!!!! Well done on actually getting ME to like a dubstep song!!!
I honestly don't really like dubstep, but I really liked this!!!
Awesome job!!!
Rated 5 / 5 stars
I love u this is going on my mp3
Rated 4 / 5 stars
Not bad mate needs a touch of mastering. Flow is good and bass is decent. Good vocal qoutes too.
The mastering is your issue hear. Check out my post in the audio fourm it might help you out.
http://www.newgrounds.com/bbs/topic/1 309374
Rated 4.5 / 5 stars
The wubs could use a but more bass but otherwise it's an awesome track.
Yeah I know what you mean, actually tried to squeeze in more bass without overlapping, I'll do a better mastering job on my next dubstep track:)
Rated 5 / 5 stars
xDD As soon as i submitted my audio piece on the 2nd, I saw your song there. I clicked on it and immediately 5-starred it. I saw this again today and felt compelled to comment, so here I am~
Glad to see that it's getting an audience. Keep up the good work. Wish i could compose as good as you >.<;;
Seriously? Thank you so much. That warms me to hear :)


text:
Here are the characters
Name: Marissa (make up the last name)
Eyes: Blue/Grey
Hair: Blonde
Personality: Quiet, thoguthful, gets along with mostly anyone
Looks: average build, braces, and dresses VERY casually. Like jeans and t-shirts
Scars: none
(Created by MMullins16)
Name: Michelle
Eyes: Brown
Hair: Brown
Personality: Strongwilled,Brave, Clever, A Leader
Looks: Dark skin,skinny
Scars: none
(Created by playful52)
Name: Sapphire Green
Eyes: Light Blue
Hair: A light blond, gold color
Personality: She is a sweet, carefree girl looking for adventure. But she never expected to get stranded, and now she has no idea what to do or how to get off the island.. D:
Looks: Average height, hopelessly skinny and very light skin, almost pale.
Scars: One on her wrist from a bike accident a few years ago, that never really went away…
(Created by Music4Ever22)
Name: Sky Gold
Eyes: Sky blue
Hair: golden blond
Personality: energetic with some smarts
Looks: medium weight, light skin tone, average height, plaid skirt with black tights under, and a blue shirt
Scars: none
(created by skygold)
Name: Joshua (Josh-U-Ah)
Eyes: Electric blue
Hair: So dark brown, that it looks almost black
Personality: He's a little mean, and likes to make fun of everyone. He demands peers call him Josh, and he's pretty much a bully..But when he gets on the island, things get tough for him, when he refuses to help… (Just some ideas)
Looks: He's a little taller than average, maybe 5'7, but he's not a giant either. He has very olive skin, almost black as well. (Trying not to be racist here. xD )
Scars: He has many all over his body from fights, including one over his eyebrow, almost on it from a huge fight that included a black eye. He doesn't like to talk about it though, any anyone who tries to bring it up will get bullied…
(Created by Music4Ever22) (HE HAS BIG ROLE)
name: Renneth
eyes: bright green
hair: kind of sandy brown, a dark shade though
personality: he likes music, always singing songs by bands no one has heard of (genre= indie rock hence my profile name. 100 Monkeys) he's nice and very helpful.
Looks: jeans and t-shirts, square toed boots, he's not like a tooth pick but he's not built or fat, he's like in the middle of built and thin, he's flat stomached. ???
scars: he has no scars he's too pretty
(Created by 100Monkeys Junkie) (HE DOESN'T HAVE AS BIG A ROLE)
Stranded on Jules Island
218 2 0


text:
Footprints #1 is an independent book from writer Joey Esposito and artist Jonathan Moore that has the potential to grow into something interesting, but it's going to have to grow pretty fast to mark itself as something different from its obvious influences.
The story is as follows: Bigfoot and Yeti are two furry brothers who can't stand each other and haven't seen one another in years – until a letter from Yeti arrives at Bigfoot's apartment in New York City, prompting Mr. Foot to go on a trek to the mountains, only to discover his brother's been murdered. So this hard-boiled detective sasquatch has to pull together an old team of "cryptid" creatures – made up of other mythical creatures like the Loch Ness Monster, the Chupacabra and the Megalodon, who have no real love for him – to try and find some answers about the killer, believed to be their old enemy Motheresa (which is a pretty a clever name).
As you might surmise, it reads like a cross between Fables and B.P.R.D. with a pulp style – hardly the worst of influences to draw from, of course. Bigfoot in particular feels a lot like early Bigby Wolf – probably a little too much so – and as cool as the noir gumshoe archetype is, it's also common enough to border on trite, depending on the mood you're in when you're reading it. The fact that he's going around with his "Choop" on a leash and harassing former Nazis doesn't help with the Hellboy comparisons, either. Esposito has a fertile premise, but he'll need to hit the ground running with the next couple of issues to make it stick.
However, he might already have that necessary hook with Nessie, who looks to be headed for a fairly twisted kind of character arc. It seems she's some kind of shapeshifting spy, and her job is to "sleep with who she can for intel" much to the chagrin of her apparent mate, the Megalodon, who is relegated to the shark tank with the venerable "Aquaman is lame" motif while the others do all the legwork. Now whether or not Nessie can actually take human form or if she just shifts in size and goes around boffing other cryptid creatures for information is a big question, and it's possible this could become particularly bent if Esposito is setting up for a bunch of freaky monster nooky. Whether anybody actually wants to see that is another story, but it would certainly be different. All bets are off with small press publishing.
Even the mentally-scarring subject matter like that has its niche in comic books – read any Meatman issue of Preacher for confirmation – but it would require the artist to go for broke on the splash pages. Unfortunately, that's probably more than we can expect out of Moore at this point. His black and white work fits the book adequately, although it still feels a bit amateurish – but hey, everybody's got to start somewhere, and he's certainly got potential to grow – just like Footprints itself.
Rest assured, that's all just a tentative hypothesis. Esposito is most likely not going to turn this into a book into a cryptozoological orgy freakshow and we'll all be the better for that. It'll likely remain a flavorful murder mystery worth giving a chance to find its legs. Or feet, since it's sure got some big ones.


text:
"She'd seen it before. The new guy pushes the incumbent hard for a few months, creates problems, and then brings in someone from his old company to replace the failure. Was he there to test her and teach her, or to toss her out at the first sign of trouble?" (The Offsite)
Drawing on the leadership theories from the bestselling classic, The Leadership Challenge, Robert Thompson effortlessly incorporates Jim Kouzes and Barry Posner's time-tested concepts into a winning fable of leadership and growth. This dramatic tale of transition centers on a three-day meeting of two former rival pharmaceutical companies taking the first step towards creating a joint sales strategy.Told through the perspective of participants from both camps, they come to rely on The Five Practices that form the heart of The Leadership Challenge:
Exploring the dynamics of a company offsite with humor and insight, Thompson addresses the fears and concerns many participants have, especially around 360-degree feedback, the key component of The Leadership Challenge model and workshops. An invaluable audio book for anyone planning to attend (or produce) a leadership training retreat, The Offsite also provides a succinct introduction to The Leadership Challenge for professionals, at all levels, who want to hone their leadership skills.
©2008 Robert H. Thompson (P)2012 Gildan Media, LLC
"The Leadership Challenge is one of my all-time favorite books. The Offsite goes one step further by showing how great ideas can be put into practice. We can all lead from the heart. The Offsite shows how - it's a wonderful audio book." (Marshall Goldsmith, author of What Got You Here Won't Get You There)
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3 bedroom terraced house for saleHaverhill Road, Balham, SW12
Under Offer £630,000
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The Netherlands saw an unexplained increase in campylobacteriosis incidence between 2003 and 2011, following a period of continuous decrease. We conducted an ecological study and found a statistical association between campylobacteriosis incidence and the annual number of prescriptions for proton pump inhibitors (PPIs), controlling for the patient's age, fresh and frozen chicken purchases (with or without correction for campylobacter prevalence in fresh poultry meat). The effect of PPIs was larger in the young than in the elderly. However, the counterfactual population-attributable fraction for PPIs was largest for the elderly (ca 45% in 2011) and increased at population level from 8% in 2004 to 27% in 2011. Using the regression model and updated covariate values, we predicted a trend break for 2012, largely due to a decreased number of PPI prescriptions, that was subsequently confirmed by surveillance data. Although causality was not shown, the biological mechanism, age effect and trend-break prediction suggest a substantial impact of PPI use on campylobacteriosis incidence in the Netherlands. We chose the ecological study design to pilot whether it is worthwhile to further pursue the effect of PPI on campylobacteriosis and other gastrointestinal pathogens in prospective cohort studies. We now provide strong arguments to do so.
Gastric acid is a first barrier against exogenous bacteria. The acid is secreted by parietal cells to maintain a median gastric pH of around 1.4 [1]. This level is generally sufficiently low to inactivate bacteria when the passage time is short (i.e. when the bacterial adaptive acid-tolerance response has not started), whereas pH levels >4 substantially increase their probability of survival [2,3]. Proton pump inhibitors (PPIs) are used to increase gastric pH in patients requiring, for example, treatment of gastro-oesophageal reflux disease and treatment or prevention of gastric and duodenal ulcers (e.g. co-prescribed with analgesics such as nonsteroidal anti-inflammatory drugs). PPI use is therefore hypothesised to facilitate gastrointestinal infections and has been reported repeatedly in case–control studies as a risk factor for Campylobacter and Salmonella infections with odds ratios between 3.5 and 12, suggesting a substantially increased risk [4]. The estimated attributable fraction for PPI use in campylobacteriosis cases was estimated at 8% in a Dutch case–control study [5].
Several European countries such as the Netherlands, Norway and the United Kingdom, experienced decreasing campylobacteriosis incidence rates from 2001 onwards, but faced a subsequent increase starting between 2003 and 2008. Simultaneously, other European countries, such as Denmark and Iceland, did not observe such an increase. In these countries, measures to reduce exposure of consumers to chicken meat are thought to have contributed to the favourable trends [6,7]. The decreasing incidence in the Netherlands, based on culture-positive campylobacteriosis cases, continued until 2003, followed by an increasing trend until 2011. This increase cannot be explained by improved detection methods and/or changes in testing regime, (data not shown). Furthermore, Campylobacter contamination of chicken fillets at retail, a recognised risk factor for Campylobacter infection, showed a decreasing trend between 2002 and 2011 in the Netherlands [8]. Anecdotal reports suggested that the use of PPIs in the Netherlands had increased in the years before 2011. We therefore hypothesise that the increase in campylobacteriosis cases in the Netherlands is, at least in part, related to increased PPI use. To study this hypothesis we related national trends in PPI prescriptions to the annual number of reported campylobacteriosis cases between 2004 and 2011, while controlling for age and chicken consumption. We then estimated the proportional incidence that was potentially related to PPI use.
Data and analysis
Data on PPI prescriptions were collected at Anatomical Therapeutic Chemical (ATC) level 5 (according to the World Health Organization (WHO) classification for medicine) from annual reports of the Foundation for Pharmaceutical Statistics (SFK) in the Netherlands (available in Dutch at www.sfk.nl) covering 95% of Dutch pharmacies. These reports cover drugs prescribed by general practitioners and physicians, and exclude over-the-counter sales. Data were available for the two most frequently prescribed PPIs: omeprazole and pantoprazole. For the former, prescription data were available for the whole study period. For the latter, prescription counts were available from 2005 onwards. The number for 2004 was estimated by dividing the available annual sales revenue for the drug (which was available) by the unit price calculated for 2005. Given the similar mode of action of the two drugs, the prescription numbers for both PPIs were aggregated. The age distribution of patients receiving PPI prescriptions was not available from the annual reports. Age-stratified data were available at ATC-4 level from Statistics Netherlands [9] for the period 2006 to 2011, covering more generally use of medicine to suppress peptic ulcers and gastro-oesophageal reflux (ATC-code A02B). These data reflected medicine refunded by 10 (groups of) health insurance companies covering >90% of the Dutch population.
Four age groups were considered: 0–25, 26–50, 51–70 and ≥71 years. Data on national sales of fresh and frozen chicken were provided by the Product Boards for Livestock, Meat and Eggs and used as a proxy for consumption. To indicate exposure, sales of fresh chicken were multiplied with the annual prevalence of campylobacter in fresh chicken meat as estimated from monitoring at retail [8]. Sales data were stratified for the consumers' age based on the population size per age group. The population size per age group per year was obtained from Statistics Netherlands [10]. Annual incidences for reported campylobacteriosis cases, including the cases' age, were obtained for the period 2004 to 2012 from national laboratory surveillance data covering 52% of the Dutch population [11].
Negative binomial regression was used to relate reported campylobacter case numbers per age group (dependent variable) to the independent variables PPI prescriptions, age and chicken consumption (fresh and frozen). The age-stratified population size was used as offset. Data from 2004 to 2011 were used; not all data were available for earlier years. Backward elimination of variables was done until all remaining factors were significantly associated with campylobacteriosis cases at the 95% confidence level. Two-way and three-way interaction terms were subsequently examined for statistical significance at the same level.
The excess incidence due to PPI prescriptions expressed as population-attributable fraction (PAF) was estimated by counterfactual assessment [12]. The regression parameters and their covariance were used to estimate the number of campylobacteriosis cases per age group per year, setting the number of PPI prescriptions to zero. The difference was divided by the estimated number of cases based on the collected data to obtain the PAF.
Data for 2012 for the independent variables of the final model (i.e. PPI per capita, chicken purchases and population counts per age group) were used to predict the number of campylobacteriosis cases for 2012 using the regression parameters and their covariance. This number was subsequently compared to the case numbers reported for 2012 to the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu; RIVM) through the laboratory surveillance.
The number of prescribed PPI in the Netherlands has increased since 2004 (Figure 1), especially in the older age groups. Campylobacteriosis incidence has increased since 2003 (Figure 1).
Figure 1. Annual number of prescribed proton pump inhibitors at pharmacies and annual incidence of reported and estimated (with the regression model) campylobacteriosis cases, the Netherlands, 2004–2012
The trend and yearly fluctuations in the number of campylobacteriosis cases were explained statistically by PPI prescriptions (p<0.0001), age (p<0.0001), the interaction between age and PPI prescriptions (p<0.04), and consumption of frozen chicken meat (preventive factor; p=0.003) (Table).
Table. Negative binomial regression analysis for association of factors with the reported campylobacteriosis incidence, the Netherlands, 2004–2011
Consumption of fresh chicken adjusted for Campylobacter contamination at retail was not significantly associated with the campylobacteriosis incidence (p=0.19). The effect of PPI prescriptions was largest for the younger age groups and gradually decreased for older ages (Figure 2). The estimated counterfactual attributable proportion for PPI prescriptions was 8% (95% confidence interval (CI): 0–16) in 2004 and increased continuously to 27% (95% CI: 30–34) in 2011. The estimated proportion differed by age group: 12% (95% CI: 5–19) for the youngest group, 24% (95% CI: 15–32) for ages 26–50 years, 45% (95% CI: 39–51) for ages 51–70 years and 41% (95% CI: 34–48) for the oldest age group. That the attributable proportion for the elderly was higher despite the lower effect size per PPI prescription compared with the young, results from the larger number of prescriptions in the older groups.
Figure 2. Effect of the number of prescribed proton pump inhibitors per capita per age group on the campylobacteriosis incidence, the Netherlands, 2004–2011
The number of prescribed PPI declined in 2012 compared with 2011, most likely because of changes in refunding policies. In total our model predicted 8,400 (95% CI: 7,600–9,100) cases of campylobacteriosis in 2012, a mean decrease of 230 cases from 2011. In accordance with the prediction, the number of reported campylobacteriosis cases decreased by approximately 320 to 8,200 in 2012.
The current study was set up as an ecological study to generate hypotheses based on data that were available at an aggregate level. Ecological associations often fail to reflect the biological effect on the individual, and the aggregation of data undermines the control of confounding [13]. Proper data to analyse causal associations were, however, not available. Collecting such data would have required extensive time and funding, which we did not have at the time of our study. We therefore chose the approach of an ecological study to examine whether it is worthwhile to pursue studies on the effect of PPI on campylobacteriosis further. As such, we are unable to conclude on causality between PPI prescriptions and Campylobacter infections. Nevertheless, a number of arguments favour a causal association. Firstly, the biological rationale for the observed effect is plausible: gastric acid secretion is impaired structurally by PPI use, leading to an increased gastric pH that favours pathogen survival. Secondly, the age modification of the PPI effect can be explained biologically. Gastric acid secretion in the elderly appears to be impaired compared with younger individuals due to e.g. atrophic gastritis [14,15], resulting in a slower return to baseline levels after pH-level disruption [16], and probably in an increased probability of pathogen passage to the intestines [17]. The effect of PPI prescriptions on this probability may therefore be smaller than in younger age groups. Thirdly, the model predictions for 2012, based on covariate data for 2012, suggested a trend break, which was confirmed by surveillance data. Lastly, the current study estimated that 8% of the reported campylobacteriosis cases in 2004 were caused by PPI prescriptions. Our estimate for 2004 is similar to the estimated population-attributable fraction for PPI use of 8% in an independent case–control study on Campylobacter in the Netherlands that was based on data collected in 2003 at the individual level [5].
The findings in the current study are similar to those obtained by Strachan et al. [18] for Scotland. These authors found a consistent association between reported campylobacteriosis cases and PPI use between 1990 and 2011. The attributable fraction was largest for those aged over 65 years, reaching more than 30% in the period 2007 to 2011, which is comparable to our average estimate of ca 35% in that period. Brophy et al. [19] recently showed an increased risk of PPI use for acquiring campylobacteriosis (hazard ratio 1.5) at individual level. However, they also showed that this risk was low compared to the demographic profile of individuals observed in the cohort. The authors concluded that there was no evidence that PPI use led to an increase in diagnosed infections, but rather that these other factors did. The cohort in Brophy et al. [19] comprised mainly persons from our two oldest age groups (average age: 58 years), the age groups for which we estimated the effect of PPI use to be smaller compared with younger ages. Mimicking their calculation methodology by dividing our counterfactual incidence rate (i.e. no PPI prescription) among those older than 50 years by the reported rate, we obtained similar hazard ratios ranging from 1.3 to 1.7 depending on the year. In our study, it was the combination of the volume of PPI prescriptions per age group and the increased risk, albeit smaller in the elderly, that resulted in the estimated impact of PPI use on campylobacteriosis incidence at population level. In addition, the sudden trend break in 2012 at population level in the Netherlands is not easily explained completely by a change in factors related to the demographic profile of those being prescribed PPIs, as these factors are generally not as dynamic as drug use. Thus, our data do not conflict with the results from Brophy et al. [19], but support the hypothesis that PPI use results in an increased campylobacteriosis risk at population level.
The change in purchases of fresh chicken fillet during the study period, corrected or not for the prevalence of Campylobacter contamination in retail stores, was not associated with reported campylobacteriosis case numbers. However, changes in the consumption of frozen chicken were related to the increasing number of campylobacteriosis cases. No statistical correlation existed between purchases of fresh vs frozen meat at population level (data not shown), suggesting that an increase in purchases of frozen chicken was not associated with a decrease in purchase of fresh chicken fillet. Freezing of chicken fillet has been suggested to reduce contamination levels, and hence the risk of infection, in other studies [20], and this effect may also have influenced our findings. Alternatively, increases in the consumption of frozen chicken may represent a reduction in other risk-increasing food-related exposures, as suggested previously [5]. The fact that the consumption of fresh chicken fillet was not associated with the incidence of campylobacteriosis may be due to several factors modulate the representativeness of chicken fillet purchases as proxy for chicken fillet as risk factor. These include variations in the numbers of Campylobacter on individual fillets or changes in antigenic types that limit the protective effects of acquired immunity. Chicken fillet consumption was associated with increased campylobacteriosis risk in a previous study in the Netherlands [5].
Annual reports of the SFK are based on records for PPIs prescribed by general practitioners and physicians and dispensed by pharmacies. PPIs that are obtained over the counter in the Netherlands are not included in these reports. If the proportion obtained over the counter was negligible, or the ratio was similar in all study years, then the effect of disregarding the use of non-prescribed PPIs on our estimates was probably minimal. This proportion may, however, be sensitive to changes in refund policies of health insurance companies. For instance, refund policies changed in 2012, which is likely to have caused an abrupt decrease in PPIs prescribed at pharmacies. This may have led to an increase in over-the-counter sales, but data to examine such changes were unavailable.
In conclusion, we found a potential association between increasing PPI prescriptions and increasing campylobacteriosis incidence. The effect of PPI prescriptions on incidence was age-dependent and largest for the youngest age group, but the oldest age group contributed most to the overall incidence because they had the largest share of PPI prescriptions. In addition to the beneficial health effects of PPIs, this ecological study suggests a substantial impact of PPI use on the campylobacteriosis incidence in the Netherlands. Comparison with other countries with a different history of PPI prescriptions and campylobacteriosis trends may add to the understanding of the role of these drugs in the incidence at population level. Furthermore, a risk-benefit analysis, based on a prospective, individual-based study design, could provide insight in the net health benefit of PPI use and could inform a review of current prescription guidelines. Such a study should also include gastrointestinal pathogens other than Campylobacter spp. for which a similar effect can be expected [4]. While waiting for such results to become available, however, critical evaluation of current prescription policies is indicated. Furthermore, our study suggests that PPI users should be added to the susceptible groups targeted for specific food safety information and stresses the need for effective food safety management in the light of an increasing number of vulnerable consumers.
The authors thank Riny Janssen (RIVM) for stimulating discussions on this topic.
Conflict of interest
None declared.
Authors' contributions
WvP, MB, and AHH conceived the study and evaluated study results. MB conducted the data search and data analysis. WvP provided surveillance data. MK and MW provided data and evaluated the study results. MB drafted the first version of the manuscript and all authors contributed to its finalisation.
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