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Includes some great links to printables for a Homeschool Mom's Notebook
This page has tons of wonderful, hands-on math activities. Scroll down to the bottom of page for links to more math ideas for PreK-3rd.
Art Appreciation, Free Artist Studies, and a Bit of A Book Review via The Homeschool Post.
An informative, important article about the process of art…plus some nice free resources.
So many great ideas in this post: the set-up of the work area, the art smock, and the fabric collage itself.
Glue Prints via The Chocolate Muffin Tree
A different and fun approach to print-making. Can't wait to try it!
Glue and Salt Painting via The Chocolate Muffin Tree
These are so pretty. I love the way the watercolor soaks into the salt. My girls will have a ball with this!
A really nice artist study on Paul Gaugin with free notebooking pages at Jimmie's Collage


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Zoe Saldana Thanks Boyfriend For His 'Independent Soul'
Zoe Saldana was honored on Tuesday night for her blossoming film career and when Access Hollywood caught up with the actress, she took time to thank boyfriend Keith Britton, who she usually keeps quiet about.
"I feel like the partners that stay at home… they have their lives, but they're the ones that are living with the real you," Zoe told Access Hollywood's Shaun Robinson on Tuesday at the Women In Film 2010 Crystal + Lucy Awards in Century City, Calif., when asked about her beau.
"I think that they need to be recognized, every now and then, every 10 years, just come out in public… put him on the spot and just say thank you," she said of her decade-long relationship with Keith.
The "Avatar" and "Star Trek" star said her man is very supportive of her life in the spotlight.
"He's a very independent soul. He understands what I do, but this is not what he fell in love with and that's what I love," Zoe said.
Additionally, the 31-year-old actress said her entire family keeps her in check.
"I have an amazing family that that keeps me grounded," she explained. "I come home and they're like, 'OK, drop the facade, be Zoe, go do the dishes and speak to us sincerely.'"
During the awards ceremony on Tuesday night, Zoe was honored with the 2010 Max Mara "Face of the Future" award.
Copyright 2014 by NBC Universal, Inc. All rights reserved.
This material may not be published, broadcast, rewritten or redistributed.

subset: commoncrawl


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URL: http://www.entrepreneur.com/answer/221244If you are in a commercial zone, then organize with the other businesses in the area to cross sell and promote each other as a destination. For example, in my town there is a toy shop next to a stationery store next to a craft boutique across from a restaurant and bar. They include info on each other's businesses in each of their newsletters, e-mails, by the register, etc.
Many cities also have economic development offices through the local government or chambers of commerce that might be helpful. Be creative and resourceful while talking to your customers and neighbors about the ideas you generate. If you test and learn, the traffic will grow.
Good luck,
Paige Arnof-Fenn is the founder and CEO of Mavens & Moguls, a strategic-marketing consulting firm whose clients include Fortune 500 companies as well as early stage and emerging businesses.


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"How Do I Get to Carnegie Hall?"
Posting has been a bit thin lately; lots of fun going on. But Bachtoberfest isn't over yet, and for now I'll leave you with this gem from oiseaur0uge…
Started working on Chopin Scherzo 4 yesterday. It will take time and diligence, but everything will be squarely manageable except for all those pp thirds near the end. How I will ever get those to sound like anything more graceful than an idling engine without one of its sparkplugs is beyond me.
Off to practice tons of accompaniments for an art song presentation and then a vocal masterclass, both later this week. I'm a touch out of shape from the holiday. Wish me luck… @_@
ambulavi said: Another quick question - I'm just starting piano and I tend to memorize the music without thinking and then I stare at my hands the whole time so I don't screw up. Would it be wiser to force myself to look at the music while playing (so I can get used to connecting page --> fingers) or keep memorizing?
Pianists differ pretty widely on memorization, I've noticed. There are many who will conscientiously memorize music a few bars at a time.
The process I've sort of fallen into over the years goes something like this: when I'm getting to know a piece, I'll practice it with the music for quite some time before I allow myself to even think of memorizing it. When most of the technical issues are ironed out and I'm able to do run-throughs, at some point I'll take the music away and see how much of it I can play. Almost always I really surprise myself, but often there are a few "spots" that I have to pretty carefully review.
I would say the downside to the kind of memorization you're describing (if I understand it right) is that it focuses on "muscle memory," that is, memorizing movements instead of musical ideas. A certain amount of playing from memory is always going to involve muscle memory, but relying on it can create a situation in which you might find it very difficult to regain your composure, for instance, if you had to stop in the middle of a performance.
So I'd say it's partially about connecting the page with your fingers, but mostly it's a matter of internalizing the music as music and not as physical activity, though it certainly is that, too. It helps me to spend a lot of time just sitting and studying the score, listening to it in my head. But everyone learns and works differently, so there's no right or wrong answer.
Great article with many interesting points. A summary:
Chopin is known to have strongly discouraged his students from practicing more than four hours at a time.
Working in small chunks is also good. It doesn't always jive with the modern student schedule, but it lends itself to clarity and mastery rather than mediocrity and injury. Though I don't always get to work that way at the keyboard, the results are better when I do.
As far as composing goes—which is really a different ball game—three hours is about my limit for concentrated activity. Occasionally I get in the zone and pull an all-nighter, but I have to be careful doing that. In reviewing my work the next day, I don't often like what I see.
(Source: allegroconfuoco, via fantasyofawanderer)
Source: oddquartet.
oh my gosh.
I need to tape this on my wall :}
omg i need this in poster size!
I love that the most popular thing I've ever posted (by a considerable margin) is about practice. That makes me happy. And Oddquartet is awesome, you should check them out!
from Odd Quartet.
Ah…I remember those days. They never did get me to march mellophone.
Heh, heh.
"After you've done all the work and prepared as much as you can, what the hell, you might as well go out there and have a good time."
"I try to practice with my life."


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Riding motorcycles , Cafe racers, photography and writing. The best part getting paid to do what I love. Eventually it's all aircooled
aircooledmc.weebly.com/ - 24 followers
These categories are free for everyone to enter, simply by tweeting a nomination. Choose one of the Official Categories below or make your own Community Category.
The Shorty Industry Awards recognize the best campaigns and social media leaders of 2013. Entries for the Shorty Industry Awards are now closed. Visit the Shorty Industry Awards Site.
The Shorty Awards honor the best of social media. Millions of people participate in The Shortys to recognize individuals and organizations producing great content on Twitter, Facebook, Tumblr, YouTube, Foursquare and the rest of the social web. The 6th annual ceremony will be held in New York City and livestreamed on the web on April 7, 2014.


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Solutions for Caregivers - this program provides expert assistance from a Care Advocate to members or spouses that care for an elderly relative or disabled dependent. Learn more about our Solutions for Caregivers.


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not only have i been lying about my virginity for well over a year and a half to my friends, but i had a miscarriage 3 weeks ago, and i don't have the guts to tell my boyfriend.
I'm Bi-sexual. My friends know it and I know it. I've wanted to tell my family for some time, if only they already knew.
Sometimes, I randomly think of killing myself. Not out of depression but, just because I wonder what dying feels like.
I don't understand how people in other countries could be so much nicer to me than the people in my own country, including my family. Then they wonder why I hate this country so much.
Most days, I feel like killing myself.
I want to have sex but I don't want to be called a slut and I don't want stds or to get pregnent.
I let my insecurities ruin so much in my life. It got to the point where I broke up with a guy because I knew he had a pool and I didn't like the way I looked in a swim suit..
At family gatherings, I want to stand on a table, point to my mother and scream: "That woman is not the funny, easy-going person you think she is. When no one is around she has spit on me, strangled me, slapped me, and told me to kill myself."


text: Description Facilities Map The Crystal Duvet is an exclusive boutique guest house situated in the hustling and bustling business district of Sandton. The guest house is located in Sandown residential estate, and is only few minutes' drive away from many amenities and various local attractions. Situated in close proximity you will find a number of key attractions including the Sandton Convention Centre, Village Walk Shopping Centre, Sandton City, and Nelson Mandela Square which offers a diverse range of restaurants, shops, entertainment, and vibrant nightlife. Our guest house offers rooms and suites which have been individually designed, with contemporary finishes to meet the needs of both business and leisure travellers. Whether you are overnighting for business or leisure, the Crystal Duvet offers you the luxury of a hotel and the exclusivity and privacy of a home. Type: Bed and BreakfastSleeps: 12 Check-in: 02:00 PM Check-out: 10:00 AM Reviews: 2 Airport Shuttle ServiceLaundry Facilities*Braai/BarbecueSwimming PoolWi-FiADSL InternetLanguages SpokenEnglishZulu (isiZulu)Xhosa (isiXhosa)Afrikaans* Please enquire for further details. Toggle Street View * We rely on Google's mapping service, and the location information supplied to us to show street view images. Please use street view as a guide only as we cannot guarantee its accuracy.


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Aetna considers adalimumab (Humira) medically necessary for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adults 18 years of age or older with moderate to severely active rheumatoid arthritis. According to the Food and Drug Administration (FDA)-approved product labeling, adalimumab can be used alone or in combination with methotrexate or in combination with non-biologic disease-modifying anti-rheumatic drugs (DMARDs).
Aetna considers adalimumab medically necessary for reducing signs and symptoms of active arthritis in adults with moderate to severely active psoriatic arthritis who meet criteria set forth in CPB 0658 - Psoriasis and Psoriatic Arthritis: Biological Therapies.
Aetna considers adalimumab medically necessary for reducing signs and symptoms of members with active ankylosing spondylitis who have an inadequate response to 2 or more NSAIDs.
Aetna considers adalimumab medically necessary in adults with active Crohn's disease, or in children and adolescents with active Crohn's disease who do not respond to infliximab or develop infusion reactions to infliximab, where active Crohn's disease is manifested by:
When Crohn's disease has remained active despite treatment with either 6-mercaptopurine, azathioprine, or corticosteroids.
Aetna considers adalimumab medically necessary for reducing signs and symptoms of moderate to severely active polyarticular juvenile idiopathic arthritis (juvenile rheumatoid arthritis) in persons 4 years of age and older.
Aetna considers adalimumab medically necessary for treatment of adults with moderate to severe chronic plaque psoriasis according to the criteria set forth in CPB 0658 - Psoriasis: Biological Therapies.
Aetna considers adalimumab necessary for the treatment of active ulcerative colitis in persons who meet either of the following criteria:
Aetna considers adalimumab experimental and investigational for all other indications, including any of the following conditions, because the safety and effectiveness of adalimumab for these conditions has not been established:
See also CPB 0315 - Enbrel (Etanercept), CPB 0341 - Remicade (infliximab), and CPB 0595 - Kineret (Anakinra).
Adalimumab (Humira) (Abbott Laboratories, North Chicago, IL) is a recombinant human IgG1 monoclonal antibody that acts by inhibiting tumor necrosis factor alpha, an inflammatory protein that, when produced in excess, plays a key role in the inflammatory responses of some autoimmune diseases. Adalimumab has been approved by the U.S. Food and Drug Administration (FDA) for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, plaque psoriasis, and juvenile idiopathic arthritis.
Adalimumab has been approved by the FDA for reducing signs and symptoms and inhibiting the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis. Adalimumab can be used alone or in combination with methotrexate or other non-biolgic disease modifying anti-rheumatic drugs (DMARDs). The efficacy and safety of adalimumab were assessed in 5 randomized, double-blind studies in 2,869 subjects aged 18 years and older with active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria. All subjects had at least 6 tender and 9 swollen joints. Humira was administered subcutaneously in combination with methotrexate or as monotherapy or with other DMARDs. Two studies involved 815 patients who had failed to respond to DMARDS; 1 study involved 619 patients who had an inadequate response to methotrexate. One study assessed 636 patients who were either DMARD-naive or were permitted to remain on their pre-existing rheumatologic therapy. One study evaluated 799 patients with moderately to severely active rheumatoid arthritis of less than 3 years duration who were methotrexate naïve. In all 5 studies, adalimumab showed significantly greater improvement than placebo in standardized indices of disability and health outcomes from baseline to the end of study. One of the 5 studies also examined the effect adalimumab on inhibition of disease progression, as detected by X-ray results. Subjects treated with adalimumab and methotrexate showed significantly less radiological progression of disease than subjects treated with methotrexate alone. Subjects treated with adalimumab and methotrexate showed significantly less radiological progression of disease than subjects treated with methotrexate alone.
According to guidelines from the ACR (Saag et al, 2008), patients with early rheumatology with low or moderate disease activity (in study) were not considered candidates for biologic therapy. The use of anti-tumor necrosis factor (TNF) agent in combination with methotrexate was recommended if high disease activity was present for less than 3 months with features of a poor prognosis.
Adverse events from adalimumab include upper respiratory infection, sinusitis, flu syndrome, nausea, and abdominal pain. Cases of tuberculosis and invasive fungal infections have rarely been observed in patients receiving adalimumab.
The recommended dose of adalimumab for adult patients with rheumatoid arthritis is 40 mg administered every other week as a subcutaneous injection.
The FDA has approved adalimumab for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis. The FDA-approved product labeling for Humira states that adalimumab can be used alone or in combination with methotrexate or with DMARDs. The FDA approval of Humira was based on 2 multi-center randomized controlled clinical studies evaluating the safety and efficacy of adalimumab compared with placebo in 413 patients with moderate to severely active psoriatic arthritis (greater than 3 swollen and greater than 3 tender joints) who have had an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDS). In 1 study (Mease et al, 2005), 313 patients with moderately to severely active psoriatic arthritis and a history of inadequate response to NSAIDS were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study participants had the following forms of psoriatic arthritis: (i) distal interphalangeal (DIP) involvement (n = 23); (ii) polyarticular arthritis (absence of rheumatoid nodules and presence of psoriasis) (n = 210); (iii) arthritis mutilans (n = 1); (iv) asymmetric psoriatic arthritis (n = 77); or (v) ankylosing spondylitis-like (n = 2). Patients on methotrexate therapy (158 of 313 patients) at enrollment (stable dose of less than or equal to 30 mg/week for greater than 1 month) could continue methotrexate at the same dose. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the ACR 20 % improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 25. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3 % of body surface area. At week 12, 58 % of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14 % of the placebo-treated patients (23 of 162) (p < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (p < 0.001). Similar responses were seen in patients with each of the subtypes of psoriatic arthritis, although few patients were enrolled with the arthritis mutilans and ankylosing spondylitis-like subtypes. Responses were similar in patients who were or were not receiving concomitant methotrexate therapy at baseline. Patients with psoriatic involvement of at least 3 % body surface area (BSA) were evaluated for Psoriatic Area and Severity Index (PASI) responses. Among the 69 adalimumab-treated patients evaluated for PASI responses, 59 % achieved a 75 % PASI improvement response and 42 % achieved a 90 % PASI improvement response at 24 weeks, compared with 1 % of the 69 placebo-treated patients evaluated (p < 0.001). The investigators reported that disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo.
Similar results were seen in an additional, 12-week study in 100 patients with moderate to severe psoriatic arthritis who had suboptimal response to DMARD therapy as manifested by greater than or equal to 3 tender joints and greater than or equal to 3 swollen joints at enrollment.
The manufacturer reported that the rates of adverse events and serious adverse events in clinical trials of adalimumab for psoriatic arthritis submitted for FDA approval were comparable with clinical trials of adalimumab in rheumatoid arthritis. Among patients taking adalimumab, the most common adverse events (those affecting at least 5 % of patients) were upper respiratory infection, nasopharyngitis, injection site reaction, headache and hypertension. The safety profile of adalimumab in these clinical trials was similar to that observed in the clinical trials of adalimumab for rheumatoid arthritis that were submitted for FDA approval. The FDA-approved product labeling states that the safety and efficacy of adalimumab in pediatric patients has not been established.
The recommended dose of adalimumab for psoriatic arthritis is 40 mg every-other-week by subcutaneous injection, which is also the usual dose used for adalimumab in the treatment of moderate to severe rheumatoid arthritis.
Ankylosing spondylitis (AS) is a form of arthritis known as spondyloarthritis, which is a group of closely linked rheumatic diseases that can cause pain in the spine and joints as well as ligaments and tendons. Ankylosing spondylitis is an autoimmune disorder in which TNF-alpha has been suggested to play a role in its pathogenesis. A chronic disease, AS primarily affects the spine causing back stiffness and potential deformity over time. Wendling and Toussirot (2004) noted that anti-TNF represents a major therapeutic advancement in the treatment of AS. De Keyser and associates (2006) stated that AS is the prototype disease within the spondyloarthropathies, a group of diseases presenting mainly with spondylitis, pauci-articular peripheral arthritis and enthesiopathy. Non-steroidal anti-inflammatory drugs are the classical cornerstone of medical therapy in these patients; no real DMARD was available, until recently. Tumor necrosis factor-alpha blocking agents (monoclonal antibodies or soluble receptors) are the first representative drugs, of which the indication has recently been expanded to encompass also patients with AS. In a 52-week open-label study (n = 15, mean age of 40 years with a range of 19 to 55 years), Haibel and colleagues (2006) reported that adalimumab treatment of active AS resulted in a clear improvement in clinical (reduction of spinal symptom) as well as MRI outcome measurements, similar to that observed with other TNF-alpha blocking agents.
On July 31, 2006, the FDA granted a supplemental indication for adalimumab -- for reducing signs and symptoms in patients with active AS. This indication was approved by the European Commission in June 2006. The recommended dosage of adalimumab for AS is 40 mg (subcutaneous injection) every other week. The approval of adalimumab for the treatment of patients with active AS is based on data from the ATLAS (Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS) trial (n = 315), which was a randomized, placebo-controlled, double-blind, phase III study conducted in Europe and the United States of patients with AS who had failed to respond to NSAIDs or DMARDs. Results at 12 weeks showed that 58 % of patients receiving adalimumab achieved and sustained a minimum 20 % reduction in pain and inflammation, as measured via the Assessment in AS (ASAS) International Working Group criteria for evaluating function, pain, patient global assessment, and inflammation. At week 24, 42 % of adalimumab-treated patients versus 16 % of those receiving placebo achieved a reduction of 50 % or more in disease activity, as evaluated using a patient-assessed composite index for pain, stiffness, and fatigue (Bath AS Disease Activity Index [BASDAI]). Moreover, approximately 1 of 5 patients achieved partial remission, defined as a value of less than 20 on a 0 to 100 scale in each of the 4 ASAS domains.
ATLAS also explored the impact of adalimumab on enthesitis, a primary pathology in AS that is characterized by inflammation of the ligaments attachment to the bone. At week 24, the mean change in the enthesitis symptom score as indexed by Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in patients treated with adalimumab showed significant reduction. MASES is an index that assesses enthesitis in certain locations, such as the rib cage, lower back, and Achilles tendons.
The British Society for Rheumatology (BSR, 2006) has stated that "there is evidence to support the use of adalimumab as a treatment for adult patients with active AS, who have had an inadequate response to non-steroidal anti-inflammatory drugs and conform to the current BSR guideline for the use of anti-TNF-? drugs in AS." The BSR statement notes that "[w]hilst there have not been any direct comparisons between anti-TNF-α drugs in AS, adalimumab appears to be as effective as any other licensed agents."
Adalimumab has also been shown in clinical trials to be effective for moderate to severe Crohn's disease. Colombel et al (2007) reported on the results of a controlled clinical trial, which demonstrated that adalimumab was effective in maintenance of response and remission in patients with moderate to severe Crohn's disease. In this clinical study, patients received open-label induction therapy with adalimumab 80 mg at study initiation followed by 40 mg 2 weeks later. Four weeks following study initiation, patients who responded to adalimumab were stratified by response (decrease in Crohn's Disease Activity Index greater than or equal to 70 points from baseline) and randomized to 3 treatment groups: (i) placebo, (ii) adalimumab 40 mg every other week, or (iii) adalimumab 40 mg weekly. Patients were followed for 56 weeks. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score less than 150) at weeks 26 and 56. The investigators reported that the percentage of randomized responders in remission was significantly greater in the groups receiving adalimumab weekly and every other week compared to the placebo group at week 26 (47 %, 40 %, and 17 %, respectively; p < 0.001) and at week 56 (41 %, 36 %, and 12 %, respectively; p < 0.001). There were no significant differences in efficacy between adalimumab administered weekly and every other week. The investigators noted that adalimumab was well-tolerated; more patients receiving placebo discontinued treatment because of an adverse event (13.4 %) than those receiving adalimumab (4.7 % and 6.9 % in the adalimumab weekly and every other week groups, respectively). The investigators concluded that, among patients who responded to adalimumab, both weekly and every other week adalimumab was significantly more effective than placebo in maintaining remission in moderate to severe Crohn's disease through 56 weeks.
Hanauer et al (2006) reported that adalimumab was shown in a controlled clinical trial to be superior to placebo for induction of remission in patients with moderate to severe Crohn's disease. A total of 299 patients with moderate to severe Crohn's disease naive to anti-TNF therapy were randomized to receive subcutaneous injections at study initiation and 2 weeks later with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission (defined as a Crohn's Disease Activity Index score less than 150 points) at 4 weeks after study initiation among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups. The investigators found that the rates of remission at the 4th week in the adalimumab 40 mg/20 mg, 80 mg/40 mg, and 160 mg/80 mg groups were 18 % (p = 0.36), 24 % (p = 0.06), and 36 % (p = 0.001), respectively, and 12 % in the placebo group. The investigators reported that adalimumab was well-tolerated, noting that adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients. The investigators concluded that adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy. The investigators stated that the optimal induction dosing regimen for adalimumab in this study was 160 mg at initiation of therapy followed by 80 mg 2 weeks later.
Colombel et al (2009) compared outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with re-initiation of adalimumab (in the event of clinical deterioration) for patients with moderate-to-severe Crohn's disease who participated in the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM). In the CHARM trial, all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2, respectively. In total, 778 patients were randomized at week 4 to one of three groups: (i) placebo after initial induction doses (followed by re-initiation of adalimumab therapy); (ii) continuous maintenance treatment with adalimumab 40 mg every other week (e.o.w.); and (iii) continuous maintenance treatment with adalimumab 40 mg every week. At/after week 12, patients receiving placebo with flare or non-response could re-initiate open-label adalimumab 40 mg e.o.w., and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w. Patients in all groups could switch to weekly therapy with continued flare/non-response. In the previously published primary analysis, results for only those patients who had responded at week 4 (decrease in Crohn's Disease Activity Index (CDAI) of greater than or equal to 70 points, referred to as "randomized responders") and remained on blinded therapy were analyzed. In this analysis, data from all randomized patients were analyzed based on original randomized treatment using an intention-to-treat analysis, regardless of whether they subsequently switched to open-label therapy. Disease activity, clinical remission, number of flares, Inflammatory Bowel Disease Questionnaire (IBDQ) score, number of Crohn's disease-related surgeries, and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups. Results for all outcome measures were superior for both continuous groups compared with the induction only/re-initiation group. On the basis of median CDAI and IBDQ results, patients in both continuous treatment groups achieved statistically significantly greater improvements versus the induction only/re-initiation group (p < 0.05). At week 56, a significantly greater percentage of patients who had received continuous adalimumab (51 % for e.o.w. and 49 % for weekly) were in clinical remission versus the induction only/re-initiation group (38 %, p < 0.05). Continuous adalimumab therapy was also associated with fewer flares and fewer Crohn's disease-related surgeries (p < 0.05). Patients in both continuous adalimumab groups had significantly lower risks of Crohn's disease-related and all-cause hospitalizations than did patients in the induction only/re-initiation group (p < 0.05). The authors concluded that for patients with active Crohn's disease, continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by re-initiation of adalimumab with clinical deterioration for maintenance of clinical remission, improved quality-of life outcomes, reduced flares, and a decrease in number of surgeries and risk of hospitalization.
Adalimumab has been approved by the FDA for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients 4 years of age and older. In the United States, JIA is commonly referred to as juvenile rheumatoid arthritis (JRA). JIA is the most common chronic rheumatic disease in children with onset before age 16. Typical symptoms include stiffness when awakening, limping, and joint swelling. Any joint can be affected and inflammation may limit the mobility of the affected joints. Polyarticular JIA is a form of arthritis affecting 5 or more joints, usually in a symmetrical fashion. While it was once believed that most children eventually outgrow JIA, it is now known that between 25 and 70 % of children with JIA will still have active disease into adulthood.
The approval of adalimumab for JIA was based on the results of a 48-week study and a subsequent open-label extension evaluating the efficacy and safety of adalimumab in children with JIA. The 48-week phase III study included 171 children (4 to 17 years of age) with polyarticular JIA. In the first part of this study, 2 groups of children -- those taking methotrexate (MTX) and those not taking MTX -- received open-label adalimumab (up to a maximum of 40 mg) every other week for 16 weeks. Patient responses were measured using the American College of Rheumatology Pediatric (ACR Pedi) 30 score, which represents a 30 % or greater improvement in JIA signs and symptoms. Children who showed a positive clinical response (n = 133) entered the second part of the study and were randomized to receive adalimumab or placebo for an additional 32 weeks or until disease flare. A flare was defined as a worsening of 30 % or more in at least 3 of the 6 ACR Pedi response variables, a minimum of 2 active joints, and no more than 1 indicator improving by 30 % . In the second part of this study, significantly fewer children receiving adalimumab demonstrated disease flare compared to children on placebo, both without MTX (43 % versus 71 %) and with MTX (37 % versus 65 %). Additionally, more children treated with adalimumab continued to show ACR Pedi 30/50/70 responses at week 48 compared to placebo. At the conclusion of the 48-week study or at the time of disease flare during the double-blind phase, children could enter the open-label extension period. Efficacy and safety were assessed at routine intervals throughout the study. ACR Pedi responses were maintained for up to 2 years in children who received adalimumab throughout the study. Upon initiation of treatment with adalimumab, the most common adverse reactions that occurred were injection site pain and injection site reaction (19 % and 16 %, respectively). In general, adverse reactions in children were similar in frequency and type to those seen in adult patients. Severe adverse reactions reported in the clinical trial in JIA included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia and appendicitis. Serious infections were observed in 4 % of children within approximately 2 years of initiation of treatment with adalimumab and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. Recommended dosing in JIA is based upon weight. For children 15 kg (33 lbs) to less than 30 kg (66 lbs), recommended dose is 20 mg by injection every other week. For children 30 kg (66 lbs) and greater, recommended dose is 40 mg by injection every other week.
Adalimumab has been approved by the FDA for the treatment for adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. According to the FDA-approved labeling, adalimumab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Chronic plaque psoriasis is an autoimmune disease characterized by inflammed, scaly skin lesions known as plaques, which may crack and bleed. While psoriasis can occur in people of all ages, it typically appears in patients between the ages of 15 and 35 years. Approximately 25 % of persons with chronic plaque psoriasis exhibit moderate to severe disease. Up to 30 % of psoriasis patients develop psoriatic arthritis. Treatment may include topical agents, phototherapy or oral or injectable medications.
The FDA approval of adalimumab for chronic plaque psoriasis was based on 2 pivotal trials, REVEAL and CHAMPION, showing that approximately 3 out of 4 patients achieved 75 % clearance or better at week 16 of treatment versus placebo. Both studies evaluated the efficacy and safety of HUMIRA in clearing skin in moderate to severe adult plaque psoriasis patients versus placebo. In addition, CHAMPION compared a biologic medication to methotrexate, a standard systemic treatment for psoriasis. In each trial, reduction in disease activity was determined by the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). In REVEAL, a 52-week trial, the short-term and sustained clinical efficacy and safety of adalimumab were evaluated in 1,212 patients with moderate to severe chronic plaque psoriasis. Patients experienced a significant reduction in the signs and symptoms of their disease at 16 weeks when treated with adalimumab. Specifically, 71 % of patients receiving adalimumab achieved PASI 75 compared to 7 % of patients receiving placebo at week 16. At week 16, 62 % of adalimumab-treated patients achieved a PGA score of clear or minimal compared to 4 % of placebo-treated patients. In CHAMPION, a 16-week study evaluating 271 psoriasis patients, adalimumab-treated patients experienced a significant reduction in the signs and symptoms of their disease compared with methotrexate or placebo-treated patients. Seventy-eight percent of patients treated with adalimumab (n = 99) achieved a PASI 75 response, compared to 19 % of patients treated with placebo (n = 48). Seventy-one percent of patients treated with adalimumab achieved a PGA score of clear or minimal at 16 weeks of treatment, compared with 10 % of placebo-treated patients. The safety profile of adalimumab in the plaque psoriasis clinical trials was reported to be similar to that seen in adalimumab clinical trials for rheumatoid arthritis. The most commonly reported adverse events in adalimumab psoriasis trials were upper respiratory tract infection, nasopharyngitis (inflammation of the nose and pharynx), headache, sinusitis and arthralgia. In clinical studies of plaque psoriasis, patients are treated with an initial 80-mg dose of adalimumab (2 40-mg injections) followed by 1 adalimumab injection (40 mg) 1 week later. After that, a maintenance dose of 40 mg was administered every other week.
Adalimumab has not been proven to be effective for ulcerative colitis (UC). In an open-label study, Peyrin-Biroulet et al (2007) assessed the effectiveness of adalimumab induction therapy in patients with UC who previously responded to infliximab and then lost response or became intolerant. A total of 10 patients with UC were enrolled in a 4-week trial. Patients received a loading dose of 160 mg adalimumab at week 0 followed by 80 mg at week 2. The primary outcome measure was clinical improvement at week 4, as defined by a decrease in clinical activity index (CAI) of more than 4. Four of 10 patients (40 %) benefited from subsequent adalimumab therapy; 1 patient achieved remission (CAI less than 4) and 3 had clinical improvement at week 4; 6 patients had no response (60 %); 2 of 6 (33.3 %) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/ml at baseline to 3.85 mg/ml at week 4, excluding 2 patients who underwent colectomy after 2 infusions of adalimumab. Among the 6 patients with severe colitis (CAI greater than 12) at baseline, none achieved remission and only 1 patient had clinical improvement at week 4. The authors concluded that the small advantage of adalimumab in patients with mild to moderate UC and lost response or intolerance to infliximab needs to be confirmed in randomized, double-blind, placebo-controlled trials. Furthermore, in a Cochrane review on TNF-alpha blocking agents for induction of remission in UC, Lawson et al (2006) did not mention the use of adalimumab.
Fiorino et al (2011) summarized available data on the safety and effectiveness profile of adalimumab in patients with UC. The authors concluded that adalimumab may be effective and well-tolerated in UC. Moreover, they stated that its effectiveness in maintaining clinical remission needs to be confirmed in a randomized controlled trial.
In a pilot study (n = 12), Magnano et al (2007) examined if adalimumab can safely improve symptoms of erosive/inflammatory osteoarthritis (EOA). Patients greater than 45 years of age with EOA of the hands defined by greater than or equal to 2 tender and greater than or equal to 2 swollen joints (distal inter-phalangeal, proximal inter-phalangeal, first carpo-metacarpal) despite NSAID therapy were eligible. Patients were excluded for autoimmune arthritis, recent disease modifying anti-rheumatic drug use, prior use of anti-TNF therapy, infection, malignancy, or poorly controlled medical conditions. All patients received adalimumab 40 mg every other week for 12 weeks. Safety was assessed 4 weeks after the final dose. Primary endpoints included safety and ACR response. Patients were predominantly female with a mean age of 60 years and 12 years of arthritis. All subjects completed the study and safety follow-up. Adverse events were mild without necessitating discontinuation of study drug. After 12 weeks, there was a statistically significant improvement in the number of swollen joints compared to baseline (p < 0.01). One patient achieved an ACR20 response and 42 % achieved an OMERACT-OARSI response. Although these investigators detected no statistically significant improvement in the number of tender joints, grip strength, disability, pain, or global disease assessments, trends suggested modest improvement in all efficacy measures. The authors concluded that the findings of this small open-label study of patients with EOA demonstrated that adalimumab was well-tolerated. Treatment with adalimumab for 3 months did not significantly improve the signs and symptoms of EOA and most patients did not achieve an ACR20. Trends suggested improvement and individual patients had some benefit. Factors limiting interpretation of this study include the lack of a control group, outcomes chosen, number of patients treated, and the duration of treatment.
Cutaneous sarcoidosis may be a chronic disease with important morbidity requiring aggressive therapy. The effectiveness of different anti-TNF-alpha treatments in refractory cutaneous and systemic sarcoidosis has been reported previously. Thielen et al (2009) reported the first patient with chronic cutaneous sarcoidosis who responded to dose escalation of anti-TNF-alpha agents that have been ineffective at the standard dosage, illustrating that the optimal dosing regimen has still to be defined for this indication before considering difficult-to-treat patients as non-responders. This case report also illustrated that the fusion protein etanercept, even used at a high dosage, may be less effective for the treatment of cutaneous sarcoidosis than the monoclonal antibodies infliximab and adalimumab.
Patel (2009) stated that sarcoidosis is an inflammatory disorder characterized by the presence of non-caseating granulomas in affected organs. The presence of CD4-positive T lymphocytes and macrophages in affected organs suggests an ongoing immune response. Systemic corticosteroids remain the mainstay of treatment, but therapy is often limited by adverse effects. This is the first report of the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. The patient was a 42-year old African-American man with a medical history significant for hypertension and diabetes mellitus presented with anemia and thrombocytopenia of 2-month duration. He underwent physical examination, bone marrow aspiration and biopsy, chest X-ray, acid-fast bacilli stain, computed tomography with contrast, and additional laboratory tests; and was diagnosed with systemic sarcoidosis with splenomegaly and bone marrow involvement. Drug therapy included prednisone, which had to be discontinued owing to adverse effects, and adalimumab. The author concluded that this is the first report describing the use of adalimumab in a patient with systemic sarcoidosis with bone marrow involvement. Tumor necrosis factor antagonism with adalimumab was effective and well-tolerated in this patient and may be considered as a treatment option for similar cases.
Antoniu (2010) noted that sarcoidosis is a granulomatous disease with various organ manifestations in which TNF-alpha has been demonstrated to play a major pathogenic role. Conventional therapies are not always able to minimize TNF-alpha-driven inflammation and other approaches should be used. The author reviewed TNF-alpha roles in sarcoid inflammation and granuloma formation based on the literature published in the last 20 years and the therapies able to target it specifically or non-specifically in sarcoidosis were discussed. In some subsets of sarcoidosis with more rapid progession and/or therapeutic refractoriness TNF-alpha plays a more prominent role in disease pathogenesis, and its blockade might represent an appropriate therapeutic approach.
In a multi-center, double-blind, randomized, controlled trial, Genevay and colleagues (2010) evaluated the effectiveness of adalimumab in patients with radicular pain due to lumbar disc herniation. Patients with acute (less than 12 weeks) and severe (Oswestry Disability index greater than 50) radicular leg pain and imaging-confirmed lumbar disc herniation were randomized to receive as adjuvant therapy either 2 subcutaneous injections of adalimumab (40 mg) at 7-day interval or matching placebo. The primary outcome was leg pain, which was recorded every day for 10 days and at 6 weeks and 6 months based on a visual analog scale (0 to 100). Of the 265 patients screened, 61 were enrolled (adalimumab = 31) and 4 were lost to follow-up. Over time, the evolution of leg pain was more favorable in the adalimumab group than in the placebo group (p < 0.001). However, the effect size was relatively small and at last follow-up the difference was 13.8 (95 % confidence interval: -11.5 to 39.0). In the adalimumab group, twice as many patients fulfilled the criteria for "responders" and for "low residual disease impact" (p < 0.05) and fewer surgical discectomies were performed (6 versus 13, p = 0.04). The authors concluded that the addition of a short course of adalimumab to the treatment regimen of patients suffering from acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures. Limitations of this study include small sample sizes, inability to determine the sufficient dose and best route of administration for TNF-alpha inhibitors in radiculopathy because of disk herniation, or to identify subgroups of patients most likely to respond to this treatment. More studies are needed to ascertain the adequate dose and the best route of administration of TNF-alpha inhibitors, elucidating the effective therapeutic role of TNF-alpha inhibitors in this disease and determining the dosage, times and route of administration, as well as evaluating the possible occurrence of harmful events, as serious infections or adverse cardiovascular events, as seen in patients with rheumatoid arthritis treated with biological drugs.
The FDA-approved product labeling for Humira includes a black box warning about the risk of serious infections with adalimumab. The labeling states that patients treated with Humira are at increased risk of developing serious infections that may lead to hospitalizations or death. Most patients who developed these infections were taking concomitant immunosuppresents such as methotrexate or corticosteroids. The labeling states that Humira should be discontinued if a patient develops a serious infection or sepsis.
The labeling states that tuberculosis (TB), invasive fungal infections, and other opportunistic infections, have been observed in patients receiving adallimumab. The labeling notes that some of these infections have been fatal.
Active TB including reactivation of latent TB has been reported in patients taking Humira. Patients with TB have frequently presented with disseminated or extra-pulmonary disease. Anti-TB treatment of patients with latent TB infection reduces the risk of re-activation in patients receiving adalimumab. However, active TB has developed in patients receiving adalimumab whose screening for latent TB infection was negative. The labeling recommends that patients should be evaluated for TB risk factors and be tested for latent TB prior to initiationg adalimumab and during therapy. According to the product labeling, when TB skin testing is performed, an induration size of 5 mm or greater should be considered positive, even if the patient was previously vaccinated with Bacille Calmette-Guerin (BCG). Treatment of latent TB should be initiated prior to therapy with adalimumab. The labeling recommends that physicians should monitor patients receiving adalimumab for signs and symptoms of active TB, including patients who tested negative for latent TB.
Invasive fungal infections, including histoplasmosis, coccidiodomyocosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis, have been reported in patients taking Humira. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. The labeling states that empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral and other infections due to opportunistic infections have been reported. The labeling recommends that the risks and benefits of treatment with Humira should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Humira, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
The labeling states that cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Humira has not been formally studied in patients with CHF; however, in clinical studies in CHF of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. The labeling recommends to exercise caution when using Humira in patients who have heart failure, and to monitor patients with heart failure carefully.
Tato and colleagues (2005) noted that treatment of patients with Takayasu's arteritis remains a demanding challenge to clinicians. In many patients, the course of the disease is characterized by frequent relapses and disease progression under conventional treatment with glucocorticoids and cytotoxic drugs. These researchers presented the case of a young woman with severe cerebrovascular and aortic involvement, who experienced disease progression in spite of more than 2 years of treatment with high doses of prednisone, methotrexate and cyclophosphamide. In this patient, treatment with adalimumab achieved clinical remission and allowed tapering of prednisone within a few months. The present case, as well as previous reports on the use of infliximab in giant cell and Takayasu's arteries, suggested that TNFalpha-blockade may be a new, promising treatment for glucocorticoid-refractory large-vessel vasculitis.
Ramos-Casals et al (2008) stated that in 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS project, a multi-center study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases (SAD). The information source is a periodic surveillance of reported cases by a MEDLINE search (last update before this writing: December 31, 2007). The analysis included a total of 19 SAD and 6 biological agents. By December 31, 2007, the Registry included 1,370 patients with SAD who had been treated with biological agents (562 received infliximab, 463 rituximab, 285 etanercept, 42 anakinra, and 18 adalimumab). Systemic autoimmune diseases included Sjogren syndrome (SS; 215 cases), Wegener granulomatosis (261 cases), sarcoidosis (219 cases), systemic lupus erythematosus (SLE; 172 cases), Behçet disease (173 cases), adult-onset Still disease (118 cases), cryoglobulinemia (88 cases), and other diseases (80 cases). The higher rate of therapeutic response was found for the use of rituximab in patients with SLE (90 %), SS (91 %), anti-phospholipid syndrome (92 %), and cryoglobulinemia (87 %); infliximab in sarcoidosis (99 %), adult-onset Still disease (90 %), and polychondritis (86 %); and etanercept in Behçet disease (96 %). Results from controlled trials showed lack of efficacy for the use of infliximab in SS and etanercept in SS, Wegener granulomatosis, and sarcoidosis. In addition, an excess of side effects (greater than 50 % of reported cases) was observed for the use of infliximab in inflammatory myopathies and sarcoidosis, and for the use of etanercept in polymyositis. Sufficient data are not yet available to evaluate fully the safety and effectiveness of adalimumab and anakinra in patients with SAD. The authors concluded that current scientific evidence on the use of biological therapies in patients with SAD is mainly based on uncontrolled, observational data. The best results have been observed in the use of rituximab for SS, SLE, and cryoglobulinemia; infliximab for sarcoidosis and adult-onset Still disease; and etanercept for Behçet disease. Lack of efficacy was demonstrated for infliximab and etanercept in SS, for etanercept in Wegener granulomatosis and sarcoidosis, and for TNF in SS. They stated that future controlled trials are needed to confirm the potential use of biological therapies in patients with SAD.
Androudi et al (2010) evaluated the safety and effectiveness of intra-vitreal adalimumab injections on refractory cystoid macular edema (CME) secondary to non-infectious uveitis. A total of 8 consecutive patients with controlled uveitis and chronic, refractory CME who had failed steroid treatment were included in this study. Intra-vitreal adalimumab injections were given monthly for 3 months. Main outcome measure was mean change in central retinal thickness (CRT) on optical coherence tomography (OCT); secondary objective was the mean change in best-corrected visual acuity (BCVA). Five of the 8 patients completed the 6-month follow-up. For all 5 patients, the changes in BCVA from baseline to 3 months were not statistically significant (p = 0.070). Similarly, the change in BCVA from baseline to 6 months was not statistically significant (p = 1.0). The mean CRT at baseline was 692 microm. The changes from baseline to 3 months were not statistically significant (p = 0.466); the changes from baseline to 6 months were also not statistically significant (p = 0.808). These researchers did not observe any ocular or systemic adverse effects. The authors concluded that intra-vitreal adalimumab showed no efficacy in improving BCVA or reducing CRT in patients with chronic uveitic macular edema. Furthermore, Neri et al (2011) stated that adalimumab is a promising drug for the treatment of uveitis, although further studies are needed on its application in uveitis.
Hyams et al (2012) evaluated the safety and effectiveness of adalimumab double-blind maintenance dosing regimens following open-label induction for pediatric patients with moderate-to-severe Crohn's disease (CD). These investigators studied 192 patients with Pediatric Crohn's Disease Activity Index (PCDAI) scores greater than 30 for whom conventional treatment was unsuccessful. Patients received open-label induction therapy with subcutaneous adalimumab at weeks 0 and 2 (160 mg and 80 mg, or 80 mg and 40 mg, for body weight [BW] greater than or equal to 40 kg or less than 40kg). At week 4, 188 patients were assigned to groups based on achievement of clinical response (defined as PCDAI decrease less than or equal to 15 points from baseline, 155/188 [82.4 %]) and prior exposure to infliximab (82/188, 43.6 %). Groups were given double-blind maintenance therapy with adalimumab at high (40 mg or 20 mg for BW greater than or equal to 40 kg or less than 40 kg; n = 93) or low doses (20 mg or 10 mg for BW greater than or equal to 40 kg or less than 40 kg; n = 95), every other week for 48 weeks. Clinical remission (PCDAI less than or equal to 10) at week 26 (the primary endpoint) was compared between groups using the Cochran-Mantel-Haenszel test, adjusting for strata, with non-responder imputation. Adverse events were monitored to evaluate safety; 152/188 patients (80.9 %) completed all 26 weeks of the study. At week 26, 63 patients (33.5 %) were in clinical remission, with no significant difference between high- and low-dose groups (36/93, 38.7 % versus 27/95, 28.4 %; p = 0.075). No new safety signals were detected. The authors concluded that adalimumab induced and maintained clinical remission of children with CD, with a safety profile comparable to of adult patients with CD. More children that received high than low dose were in remission at week 26, but the difference between dose groups was not statistically significant.
In a prospective case series, Díaz-Llopis et al (2012) evaluated adalimumab therapy in refractory uveitis. A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated inthis study. Patients received a 40-mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). Main outcome measure were degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), VA (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (OCT). There were 61 men and 70 women (mean age of 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82 % of patients and in the vitreous cavity in 59 % of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (p < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (p < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3 %) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3 %). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (p < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] versus 5.40 [4.43]; p < 0.001). Six months after the initiation of the study, 111 patients (85 %) were able to reduce at least 50 % of their baseline immunosuppression load. Only 9 patients (6.9 %) had severe relapses during the 6 months of follow-up. The authors concluded that adalimumab seems to be well-tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Moreover, they stated that further controlled studies of adalimumab for uveitis are needed.
On September 28, 2012, the FDA approved adalimumab for the treatment of moderate-to-severe ulcerative colitis in adults. The approval was based on findings of 2 clinical studies showing the safety and effectiveness of adalimumab for ulcerative colitis. A total of 908 patients who had never been treated with a TNF-blocker, or who lost response to or were intolerant to TNF-blockers participated in the studies. All patients enrolled in the studies had a Mayo score of 6 to 12 and an endoscopy subscore of 2 to 3. Patients were randomly assigned to take adalimumab or a placebo. The studies were designed to measure the percentage of patients whose Mayo score decreased to 2 or less with no individual subscore of more than 1 after 8 weeks of treatment. Patients who obtained such reductions in the Mayo score were determined to have achieved clinical remission. Results from both studies showed 16.5 % to 18.5 % of patients treated with adalimumab achieved clinical remission compared with 9.2 % to 9.3 % of patients receiving placebo. Additionally, in the 2nd study, 8.5 % of patients treated with adalimumab sustained clinical remission compared with 4.1 % of patients treated with placebo. The effectiveness of adalimumab has not been established in patients with ulcerative colitis who have lost response to or were intolerant to TNF blockers.
The FDA-approved dosing regimen for adalimumab for ulcerative colitis begins with an initial dose of 160 milligrams, a 2nd dose 2 weeks later of 80 mg, and a maintenance dose of 40 mg every other week, thereafter. The drug should only continue to be used in patients who have shown evidence of clinical remission by 8 weeks of therapy.
Adalimumab has been used successfully in children and adolescents with Crohn's disease who do not respond or develop infusion reactions to infliximab. A randomized controlled trial (Hyams, et al., 2012) comparing two doses of adalimumab in 188 patients with refractory moderate-to-severe pediatric Crohn's disease found comparable rates of remission with the two dosing regimens, occurring in about one-third of subjects at six months. In a retrospective series of 115 persons with refractory pediatric Crohn's disease treated with adalimumab (Rosh, et al., 2009), 70 percent had a clinical response at one year.
Information about the Psoriasis Area and Severity Index (PASI) and the Physicians' Global Assessment (PGA) is available from the following reference (Feldman and Kruger, 2005): http://ard.bmj.com/cgi/content/full/64/suppl_2/ii65.
Hyams JS, Griffiths A, Markowitz J, et al. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012;143(2):365-374.


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'Thoofan' audio launch
Srihari, Ram Charan Teja, Venkatesh
Ram Charan forayed into films with Telugu movie 'Chirutha' in 2007, which earned him a Filmfare (South) Best Debut award. His second release 'Magadheera' got him his second Filmfare, this time for best actor.
The actor, who has also starred in Telugu movies like 'Orange', 'Racha', 'Naayak', is just five films old and said he was surprised when director Apoorva Lakhia approached him to star in 'Zanjeer' remake.
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Is there a crafter on your gift roster?
People who craft, love to receive useful and inspiring gifts. There is no shortage of items that crafters will appreciate.
Whether you opt to contribute to their stock of supplies, add a little more weight to their toolbox, or simply provide them with a meaningful gift for inspiration, crafters will be incredibly grateful to receive a craft-related present.
Materials and Supplies
Crafters are in constant need of new materials. Most people who craft like to keep a healthy inventory of the supplies that they frequently use. Knitters stock up on yarns, scrapbookers stash paper, and beaders acquire tons of beads in every shape and size.
When money's tight and the supplies are running low, every crafter appreciates a little help in the form of a gift.
Finding items a crafter would love to receive involves nothing more than a quick trip to your own local craft supply store.
For even greater ease, try shopping online. Many online vendors will ship gifts directly to the recipient, gift-wrapped, and with a card.
For easy one-stop gift shopping, Amazon now has a dedicated section for Arts, Crafts & Sewing. If you want a subcategory like crochet, just type that into the Crafts search box and the most popular items in that category will show up on top.
Come back tomorrow for More Tips for the Crafters on Your Holiday List.
Monday, December 19, 2011
Crafters are Easy to Shop for. Here are Some Tips for the Crafters on Your Holiday List.
Is there a crafter on your gift roster?
7 comments:
- Debbie @ Work Your Art said...
I love this. Crafters are usually the type of person that already have EVERYTHING they need, because they usually stack up a lot of materials to be used in the future (yes, I'm talking about *me* also ;)).
- Eileen Bergen said...
Hi, Debbie. Well, if you're the rare crafter who doesn't have a wish list of supplies or neat new gadgets, be sure to read tomorrow's post.
I'm sure you'll find gift ideas there to suit you ;-)
Maybe it's because I'm an eclectic crafter and move from one craft to another as often as I change underwear; but I frequently don't have just what I need for my current project.
Thanks for stopping by.
- Debbie @ Work Your Art said...
Thanks Eileen, I'll be sure to stop by tomorrow to see what you've come up with. Goodies, goodies!
- Cyndi L said...
I used to spend all year filling up a big box of supplies for my daughter when she was young. I'd just buy whatever was on sale each week or so, and by Christmas time she'd have a fabulous package to dive into!
- Eileen Bergen said...
That's wonderful, Cyndi. My mother fostered my interest in arts and crafts in the same way. I'm forever grateful. I bet Dani is too.
- Cherie said...
Cyndi: that's a great idea.
Eileen: I love that you're writing about this. I try and buy some of the crafters on my list things for their hobby and they always appreciate it. There's always a wish list when you're a crafter.
- Eileen Bergen said...
I wonder if there's a job opportunity here: personal shoppers for crafters. there seem to be enough of us who would love to do it!


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By Joe R
| Season 4 | Episode 12 | Aired on 12.13.2009
Joe R is sorry he was so hard on Rita this season and hopes Julie Benz's next gig is a lil' more badass. He can be reached for lavish praise and nothing but at email@example.com.
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brainwashedbyvogue asked: Your hair is so....KICK ASS! OMG! LOL I'm sure you get that often. I saw your interview on curlynikki.com, and I have to say that you're an inspiration (corny)! I'm transitions currently (14 mos. & 10 to go). I can't wait until I can get my hair like yours, so pretty! :D
:) No matter how many times I get it, it's still new, and Thank you so much! You'll get there soon!


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- Sam Ash Gift Guides
- Hot Deals
- Guitars
- Bass
- Accessories
- Live Sound
- Keyboards
- Microphones & Wireless
- Recording
- DJ & Lighting
- Drums
- Books/DVDs
- Band/Orchestra
(4 reviews)
Strukture SK1X-BK Single Brace Keyboard Stand
Keith McMillen Instruments K705 12 Step Foot Controller
Boss FC-300 MIDI Foot Controller
Voodoo Lab Ground Control Pro MIDI Foot Controller
To automatically re-order this item before you run out, select the recurring order option during checkout.
Keith McMillen Instruments' SoftStep 2 is the world's most powerful MIDI foot controller.SoftStep 2 is USB powered and compatible with any music software. Each pad detects foot pressure and directional movements, for a myriad of control possibilities.
|Pads & Triggers
|4.2 x 17.5 x 1 inches (WxHxD)
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|SoftStep 2
One year parts and labor warranty


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WebMD Answers
A common ovulation problem that affects about 5% to 10% of women in their reproductive years is polycystic ovary syndrome (PCOS). PCOS is a hormonal imbalance that can make the ovaries stop working normally. In most cases, the ovaries become enlarged and appear covered with tiny, fluid-filled cysts. Symptoms include:
This answer should not be considered medical advice...This answer should not be considered medical advice and should not take the place of a doctor's visit. Please see the bottom of the page for more information or visit our Terms and Conditions.


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$765—$995 1—2 bed 255 Sonoma Way, Woodland CA, 95695
from $765 1—2 bed
255 Sonoma Way, Woodland, 95695
Commute to Downtown Woodland
The rent at Courtside Village Apartments ranges from $765 for a one bedroom to a $995 two bedroom. Apartments in this building are about as expensive as the Woodland average. This is a pet-friendly apartment.
This apartment is in Woodland. Nearby parks include Harris Park, Davis Estates Park and Bemmerly Park.
Courtside Village Apartments has a Walk Score of 72 out of 100. This location is Very Walkable so most errands can be accomplished on foot.
Nearby schools include Rhoda Maxwell Elementary School, Dan Jacobs School and Midtown Community School.
The closest grocery stores are Raley's, Seminis Inc and Nugget Markets Pharmacy.
Nearby coffee shops include Starbucks, Dutch Brothers Coffee and Sweetie's Cafe. There are 10 restaurants within a 15 minute walk including Golden Dragon Restaurant, Brown's Corner Bar & Grill and Judy's Grinder.
Courtside Village Apartments is near Harris Park, Bemmerly Park and John Ferns Park.
Welcome to Courtside Village. We are conveniently located near the Westgate Shopping Center where Raleys is located. We have two sparkling swimming pools, a sauna and a bubblie spa for your summer enjoyment. We have five laundry rooms spaced out throughout the community, one assigned cover parking space for each apartment home and on site management and maintenance to take of your needs in a timely fashion.
All of our apartment homes have all your major kitchen appliances; dishwashers, garbage disposals, self cleaning ovens, two door frost free refrigerators, central air/heat, ceiling fans in the dining rooms and mini blinds throughout. We pay all water, garbage and sewage. We are located right off W. Court on either Sonoma Way or Ashley Ave. Please call for an appointment today.
Pets allowed:
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Woodland, California, 95695
Most errands can be accomplished on foot.
A few nearby public transportation options.
Explore how far you can travel by car, bus, bike and foot from Courtside Village Apartments.
Courtside Village Apartments has some transit which means a few nearby public transportation options. Car sharing is available from RelayRides.
Bus lines:
210 West Woodland Local
0.1 mi
211 West Woodland Local
0.1 mi
215 Cache Creek Shuttle
0.3 mi
242 Woodland/Davis Commute
0.4 mi
45 Woodland Express
0.4 mi
Car shares:
View all Woodland apartments on a map.
Popular apartment searches include pool, fireplace and fitness. View all Woodland apartments and rentals.
Courtside Village Apartments is in the city of Woodland, CA. Woodland has an average Walk Score of 44 and has 55,468 residents.Learn More About Woodland


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Karndean Designflooring
Inspired and inspiring; full of charm and character, our premium Art Select collection brings the natural beauty of wood and stone flooring to life in your home. Through meticulous attention to detail and careful selection of some of the most beautiful natural timbers and stone floors, Art Select includes our most intricate designs and realistic embosses.
View the latest news and events from Karndean Designflooring USA or search the news archives for previous updates.
22 August 2014
Karndean Designflooring is pleased to announce it has been named to the Pittsburgh Business Times Top 100 Fastest Growing Companies for 2014.
The Pittsburgh 100 recognizes the fastest-growing private companies in western Pennsylvania. Karndean ranked #4 within the Retail/Wholesale/Distribution category. This is the second straight year that Karndean has received recognition in the Pittsburgh 100.
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|Pen Refills & Inks
|Erasers Etc
|Pencil Cases & Bags
|New Arrivals
Reviews Written by mon...
|1 to 10 (of 12 ) 1 2
Hands-down BEST BALLPOINT..., May 29, 2013
Hands-down BEST BALLPOINT ever!!! I love Uni Jetstream pens but with the Alpha Gel grip, ultimate pen to have. I had couple of Uni Alpha Gel HD Ballpoint Pens the original and thin, but they don't compare to this one. Jetstream's ink is smooth and dark, so no need to press down hard. The ink glides... And the grip is soft so my fingers are not tired. Although the price is up there, it's worth every $. Highly recommend.
This pen writes smooth..., May 29, 2013
This pen writes smooth but there's blotting like the other reviewers shared. For the price, this pen is better than your typically ballpoint pen. The point is fine, so it's nice.
This is the BEST ballpoint..., May 5, 2012
This is the BEST ballpoint pen! I converted from gel-ink pen to ballpoint pen. Jetstream Ballpoint pen is so smooth that I feel like it's a gel ink pen. I use this pen for writing checks, helps prevent check fraud. I have 2 pens so far and will get more... I wish they have blue ink.
It's thick and writes..., May 5, 2012
It's thick and writes well. Average pen, but the color of the body is unique. So I can find it under piles of paper.
I didn't give GOOD rating..., May 5, 2012
I didn't give GOOD rating because of the price. It's a nice roller ink pen and the blue color is dark enough that I don't have to press hard. However, it's no different than the Pentel or Pilot (cheaper) pens. If you're looking for a decent liquid rollerpoint pen, get uni-ball® Vision™ Exact™ Liquid Ink Rollerball Pens. This one has rubber-grip and it's cheaper.
I stock on new pens that..., May 5, 2012
I stock on new pens that write smoothly and don't skip. This one does both and it looks simple. I don't own a Moleskine notebook, instead I carry around post-its.. I like this pen for office. It's black and no one else has one.. yet..
This pen writes smooth,..., May 5, 2012
This pen writes smooth, vivid blue color, and it has rubber grip. I like this pen and for the price it's a steal. I write a lot due to constant reminder notes for myself. Pen's light and I carry it with me. I am planning to restock before it's sold out.
I don't like this on..., March 28, 2010
I don't like this one.
The rubber grip is nice...., March 28, 2010
The rubber grip is nice. But wished I could say the same about it's ink.
I like this pen. It writes..., March 28, 2010
I like this pen. It writes smooth and the ink is dark, so you don't have to press hard. Only if they had blue ink refills.


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Recent Stories
- Google award recognises Lancaster academic's focus on eye tracking research
- Sustainable green alternatives to fertilisers could boost food and energy security
- Lancaster spin-out company adapts crime-fighting tech to the marketing world
- Lancaster University cyber security course is certified by UK's national intelligence agency
- Lucky heather earns its name in carbon study
- New postgraduate courses to help stem the tide of flood devastation in the UK
- Cyber-crime costs region's businesses almost £107 million a year - a new report reveals
- Businesses offered chance to explore one of Europe's top environmental research centres
- A dream come true for former mechanic
- Career success for First Class Engineering graduate
Lancaster Emeritus Professor Wins Prestigious Physics Prize
Professor David Lyth (Lancaster University physics) has won the 2012 Hoyle medal and prize from the Institute of Physics for his contributions to particle cosmology, in particular to the origin of the structure of the Universe.
The citation reads as follows:
One of the central planks of modern cosmology is the idea of inflation. Inflationary cosmology postulates a period of accelerated expansion during the Universe's earliest stages. Originally introduced by Guth in order to explain the initial conditions for the hot big bang model, it has subsequently played a much more important role in providing a possible explanation for the origin of structures in the Universe, such as galaxies, galaxy clusters and cosmic microwave background anisotropies.
David Lyth has been responsible for many of the key advances in the theory of inflation, and has devised many of the analytical tools that are now widely used by the theoretical cosmology community. His work is always characterised by an incisive clarity. Although mathematically sophisticated, it always maintains contact with observation.
The methods he developed have become the standard language for those who compare observational data obtained by the Cosmic Background Explorer (COBE) and the Wilkinson Microwave Anisotropy Probe (WMAP) with the predictions of inflationary theory. While much work on inflation has been purely phenomenological, David has linked cosmology with fundamental physics, particularly extensions of the Standard Model.
In 2000, together with Andrew Liddle, he published a textbook on cosmological inflation and large-scale structure that has become the standard reference and an essential resource for everyone in the field. They followed this up in 2009 with the first graduate-level textbook devoted specifically to the primordial density perturbation. Both books exemplify David's dedication to accurate scholarship and his ability to make complex concepts accessible.
Tue 03 July 2012
Latest News
Google award recognises Lancaster academic's focus on eye tracking research
Computing giant Google has recognised research at Lancaster University to develop eye-tracking technology.
Story supplied by LU Press Office
Thu 18 September 2014
Sustainable green alternatives to fertilisers could boost food and energy security
Lancaster University scientists are leading research looking at formulating sustainable fertilisers from renewable energy waste.
Story supplied by LU Press Office
Thu 14 August 2014
Lancaster spin-out company adapts crime-fighting tech to the marketing world
A company established at Lancaster University to commercialise crime-fighting technology is set to revolutionise the marketing industry.
Story supplied by LU Press Office
Fri 08 August 2014
Lancaster University cyber security course is certified by UK's national intelligence agency
A Lancaster University course that is helping to produce the crime fighters of the digital age has received a seal of approval by the UK's national security and intelligence agency - GCHQ.
Story supplied by LU Press Office
Thu 07 August 2014


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Universal Fit
Yamaha EPH-100SL Inner-Ear Headphone
"This is my second pair of EPH-100s. I purchased my first pair in the beginning of 2012 some while after they became a FOTM here on Head-fi. Strangely enough I would have thought that they would have increased in price with the popularity these have, but I got the second pair for $15 less than the first pair I bought. The first pair survived a lot of hours of music at work, but the housings were..." --daerron
T-Peos H-300 - 3 Way Hybrid
" I must admit It's been quite a journey with the company T-PEOS since I tried their H-100 going way back to October - 2012. Since then I've heard most of T-PEOS mid tier line up including H-200 hybrid released around March - 2013 which grabbed quite the attention on Head-Fi and probably for good reason as it scored notably high in some reviews other than mine. I..." --H20Fidelity
T-Peos H-200
"Shin-woo Tech who recently changed their name to T-PEOS has brought us a new product inherit of their H-100 last year. Their new Triple Hybrid called H-200 has been redesigned from the ground up, undergone extensive tuning before finally reaching the hands of selected reviewers on Headi-Fi. I was excited to hear this release was finally underway wanting to hear what changes had been made, also..." --H20Fidelity
T-Peos D-300
Budget dynamic IEM from T-PEOS
T-Peos D-200
Friendly to any genre, easy on the ears. The D-200 series by T-PEOS boasts of lightweight cables that are flat and thin for optimal comfort. For extra convenience, there's also a click button mic to pick up your calls with, or to play and pause your music. There's a look for everyone.
T-Peos H-100
Hybrid Earphone H-100KG Balanced Armature & 8mm Dynamic Driver Specification Driver Unit : Balanced Armature & 8mm Dynamic Driver Impedance : 60 ohms / 1KHz Sensitivity : 100db / 1Khz Frequency Response : 20Hz ~ 20KHz Power : 3mW (normal) Connector : 3.5mm / 3pole / 24K...


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Twitter is the popular social networking site that allows users all over the world to share their ideas and thoughts in the micro blogging web site. Many people use micro blogging websites to promote their business or products.
You can create an account and start blogging on a selected topic and you can even tweet your thoughts on someone else tweet. If you do not have Internet access from your mobile phone no problem you can tweet via text SMS and receive tweets from your account on your mobile phone via free SMS service. All you have to do is just register your mobile phone number with Twitter to enable sending and receiving tweets.


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Hampton Inn & Suites North Conway offers free WiFi in every guest room, a handy handy lap desk and our clean and fresh Hampton bed®.
We have limited availability of pet-friendly rooms in standard queen and standard king room types only.
Our promise to you includes a clean, comfortable hotel room. In fact, we have 97 of them! If you're traveling with your family, you may opt for a room with two beds. Or, if you're here by yourself on business, why not book a room with a plush, king-sized bed so you can stretch out and relax?
Looking for some extra room to stretch out and relax? Our suites are spacious, comfortable and convenient. Check out our various options below.
We've designed our accessible hotel rooms to make our guests with disabilities - as well as friends and family who accompany them - more comfortable. Click on the links below for more information. The corresponding photo may not reflect the specific accessible room type or room feature.


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Police are appealing for witnesses to a robbery that happened in Whittington Moor, Chesterfield.
At about 12.20pm on Wednesday October 2 a 24-year-old woman was walking through the underpass on Sheffield Road when a man, who was walking from the Brimington direction, bumped into her and asked for her mobile phone and cash.
She gave him a small amount of cash and ran off towards Whittington Moor. She wasn't injured.
The suspect was white, in his mid 20s, 5' 7" tall and of medium build. He was wearing a red waterproof coat, with the hood up, and dark trousers or jeans.
Anyone who witnessed the robbery or has any information that would help the investigation should ring the police on 101 or call Crimestoppers anonymously on 0800 555 111.
Do you need a quick answer to a general question? Then we recommend you visit the national Ask The Police web site.


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The Seven Cries of Today's Teens
- Friday, April 25, 2003
Your teenager is crying out and desperately wants you to hear, so you can respond and make a new connection. What are these cries? According to author Timothy Smith, today's teens are crying out with seven specific needs: to be trusted, to be loved, to be safe, to have purpose, to be heard, to be valued and to be supported. Read on as he explains further.
A Cry For Trust
Millennials have a fairly clear idea of why they want in the future, but the don't know how to get there or who will help them. Most are open to a closer relationship with their parents, or a mentor, or both. They aren't as cynical as their Gen X brothers and sisters. They are willing to trust someone, but they aren't sure what that looks like. After all, trust is a critical element of marriage, and these are children of divorce. They are open to giving trust a chance, but they are looking for models of trust. They are ambitious enough to succeed, but they are confused about the meaning, purpose, and direction of life. They need trusted guides who know the way, but for many, no adults are around to protect them or show them the way.
A Cry For Love
We discovered that many teens do not feel loved even though their parents say I love you or give them hugs on a regular basis. In order to feel loved, they need to experience love in their love key (see pages 52-69 for a comprehensive explanation of love keys). Some of this does not seem logical to parents - and that is the point. Successfully relating to teenagers is not logic-based. You can't always think your way out of a problem with your teenager or reason your way into a close relationship. Sometimes with millennials, you are better to feel your way.
A Cry For Security
Immediately after the terrorist attacks of September 11, 2001, I counseled many teens who were rattled by the trauma of what they saw on TV. In some cases, teens were more stressed than younger children. This could be because teens often believe the myth that they are immortal. When they saw reality TV of planes crashing into towers and people jumping from burning buildings, their I-will-always-be-safe world crumbled.
In spite of the recent terrorism and school shootings, most teens feel safe. Teens are looking for borders. Borders protect our teens and allow them to be relatively carefree as they pass through their last stage of childhood. Teenagers are frightened to live in a culture that doesn't protect them, hurries them into adulthood and adult-sized problems, and doesn't equip them to handle adult problems.
A Cry For Purpose
Our teens need to believe that life is meaningful and has a purpose. When teens feel that their lives are purposeful, they feel more capable and equipped to take on the demands of adolescence. Purposed is developed as teens discover the Three D's of Purpose:
Design - God made each of us according to His master plan.
Destiny - We discover our purpose in relationship to God.
Duty - Our purpose is further developed as we discover what we can offer in
service to God and others.
One cause of the lack of purpose is that many teens do not take time to reflect. Their active schedules and the clamor of the media crowd out time for serious reflection. As a result, teens make decisions with a mosaic morality - a little of this combined with a little of that. Millennials desire meaning and morals, but they don't often have the time, energy, and examples to build an integrated moral base. Since they make decisions based on ever-changing criteria, they are often disappointed with the results.
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text: Posted Online: Jan. 08, 2013, 5:41 pm Desyl Bloom Comment on this story Photo: Desyl L. Bloom Desyl L. Bloom, 98, formerly of Moline, died Monday, Jan. 7, 2013, in Rock Island Nursing and Rehab Center, Rock Island. Services are 10:30 a.m. Thursday in the Celebration of Life Chapel at Trimble Funeral and Cremation Center, Moline, with the Rev. Stacie Fidlar officiating. Burial is at Andover Cemetery. Visitation is one hour before the services. Memorials may be made to St. John's Lutheran Church, Rock Island, or American Cancer Society. The former Desyl Luella Swanson was born Aug. 24, 1914, in Lynn Center, to Carl W. and Antelia Peterson Swanson. She married Robert D. Bloom on June 21, 1941, in Andover. He died Dec. 23, 2004. She worked at Deere and Company and Desaulniers Printing during World War II. She was a member of St. John's Lutheran Church and the Ageless Group at the church and enjoyed bowling in earlier years. Desyl is survived by a sister-in-law, Marion Swanson, Silvis, and many nieces and nephews and their families. She was preceded in death by her husband; sisters, June Hultgren and Irene Youngberg; and brothers, Glenn and Sherman Swanson. Remembrances and condolences may be shared with the family at www.TrimbleFuneralHomes.com.


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wave flow yoga
| Yoga Classes in Arugam bay
|wave flow yoga Website
|Stardust beach hotel, Arugam bay, Arugam bay
|Yoga Style: dynamic flow, acuyoga, vinyasa, corework
|Send Message
Since 2001, Kevin and Yael have been teaching together yoga. they run combined yoga and surfing retreats, and offer acupressure and reflex points training to people from all around the world. The classes they teach offering something more then just the physical postures; physical skills and achievement are of relatively minor importance, and awareness and self-observation are central and really the heart of there yoga practice.
WAVE FLOW YOGA & BODYWORKS, SEASON 2012 ARUGAM BAY, SRI LANKA Join us for a weekend of yoga, meditation, massage, culture and nature in peacefull Arugam bay. Indulge in four relaxing days away from the pressures of daily life. Devote a full weekend to yourself and your yoga practice. Enjoy spectacular view of the Ocean, surfing , and plenty of wilderness to explore. 4 days retreats & Workshops
June 7-10, 2012 June 14-17, 2012 June 21-24, 2012 July 5-8, 2012 July 12-15, 2012 July 19-22, 2012 Aug' 2-5, 2012 Aug' 9-12, 2012 Aug' 16-19, 2012 Daily Morning & Evening Classes overlooking the beach, including: ~ Wave flow yoga classes ~ Breathing techniqs ~ Guided Meditation ~Yoga Core works ~ Innovative Acuyoga & Thai yoga workshops ~Customized Body treatments
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Sri Lanka Yoga Retreats
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Jan 7, 2013
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Live from Qualcomm's CES 2013 keynote
"Dogs with GPS collars. Runners with heart rate monitors. So much mobile. It's everywhere. 'We're calling them Gen M now.'"
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If you want to see what hilariously fucking awkward tech companies spend money on, read this and enjoy the madness.
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Need to get my dog his GPS collar. I also need some runner heart monitors. So much stuff!
- businesstechriffle reblogged this from thisistheverge and added:
What will the next generation be?
- psl reblogged this from thisistheverge and added:
hmm, I wonder if the whole "Gen" thing should be left to posterity to determine? We don't know what the future will hold...
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The Verge is the definitive source for the latest in technology news, reviews, and up-to-the-minute scoops.


text:
Porter Park decided to go with defense for the Bills with CB Mike Jenkins from South Florida.
This could pan out well for the Bills if Jenkins doesn't stay out late at "da club", McGahee said there is nothing to do in Buffalo, which might be good for Jenkins.
Now those damn Donkeys are on the the clock — that means you Paradise (sorry, my hatred for the Denver Broncos sometimes just comes out). Wasn't it hard signing up for the Broncos in a Chiefs fans mock draft?
Watch this clip of Mike Jenkins while we wait on the pick:
Next Chiefs Game View full schedule »
Monday, Sep 2929 Sep7:30New England PatriotsBuy Tickets
Tags: Bills Broncos Chiefs Mike Jenkins Paradise Porter Park


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Each year Portland Opera To Go takes an opera on the road, sharing the power of opera, music, and theater with schools and communities throughout Oregon and SW Washington. It's not necessarily the easiest thing in the world, as you might imagine. But it's one of the most rewarding . . . for us and for the thousands upon thousands of students who get to experience live opera, many for the first time.
And this blog will give you a first-hand view from the performers themselves of what it's like when Opera hits the road!
Here's a link to more information on the tour and the program.
Life on the road is exciting, rewarding, and challenging!
We though we would share some of those moments with you in photos. Enjoy!
The Hampton Opera Center | 211 SE Caruthers St, Portland, OR 97214 | Main 503-241-1407 | Box Office 503-241-1802
2013/14 Opera Season | Privacy Policy | Employment | Auditions | Rentals | Resident Artist Program | website by Level OS


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HANFORD, WA. - The U.S. Department of Energy will pay $15,000 to improve waste management practices in central Hanford.The state Department of Ecology and the Department of Energy have signed an Agreed Order to make the improvements. The agreement will also better comply with the Department of Ecology's requirements on how to handle dangerous waste at three Hanford facilities that manage hazardous and radioactive waste.
The three facilities are the Central Waste Complex (CWC), Waste Receiving and Processing Facility (WRAP), and T Plant.
DOE agreed to a total stipulated penalty of $261,000 and will pay the $15,000 immediately. The Department of Ecology will also suspend the balance while DOE makes changes according to the agreed schedule.
The Agreed Order requires DOE to make a number of changes in how the agency manages mixed wastes at the three facilities. The changes include:
"DOE is responsible for ensuring the safe storage of waste and compliance with the dangerous waste regulations," said Ecology Nuclear Waste Program manager Jane Hedges. "DOE cooperated with Ecology staff to identify fixes for the violations and concerns, and has agreed to a schedule to implement the changes."The Ecology Department first found violations of state Dangerous Waste Regulations for Waste Management Units during two inspections at WRAP and CTC in July 2011 and February 2012.DOE has agreed to address concerns identified at these facilities, as well as T Plant, which is operated together with CWC and WRAP.