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Ireland's new Taoiseach (Prime Minister)-elect Enda Kenny is facing into considerable political challenges, but those who know him best in New York believe he's more than equal to the task.
Radio broadcaster and longtime Irish community leader Adrian Flannelly, a fellow Mayo man who has known Kenny personally for many years, told the Irish Voice, "Enda Kenny is a country boy from the west but he knows his stuff. For as long as I've known him he plays hard and works hard."
Flannelly believes that Kenny is a different type of politician to his predecessor Brian Cowen.
"Enda has smarts that Cowen never had. When the Irish bailout deal was negotiated it seemed like a campaign tactic for Kenny to say he planned to renegotiate it, but Enda is the type of guy who can actually do that.
"Kenny is also much more credible than the former taoiseach. He's much more practical and he has better business sense. He can argue that what was done to the country is something that we cannot afford. He will say to the EU and the IMF, 'Do you want to run the risk of defaulting, or will you give us a chance to afford what we've signed off on?'"
Prominent New York attorney and Irish American activist Brian O'Dwyer, whose father Paul was from Mayo, agrees that Kenny is the ideal candidate for the challenges currently facing Ireland.
"Frankly I think he's the perfect man for the times," O'Dwyer told the Irish Voice. "He's not flashy; he's a calm, steady consensus builder. He more like a CEO than a politician and I think that's what Ireland needs right now, a steady hand at the wheel as opposed to a career politician."
Pressure is building in Ireland for the Kenny to renegotiate the financially punishing IMF and EU bailout deals, but the question is, how will Kenny handle it?
"If he can renegotiate something on the European level and on the bailout, however slight it might be, it will instantly establish a credibility that he can take home with him," says Flannelly.
The most pressing challenge for Kenny is to achieve a level of cooperation with both the EU and the IMF, Flannelly believes. "I think that's where his strengths lie too. He believes that deal can be modified -- nothing major, perhaps a lower interest rate -- and he can then come back to the people and say we're here already."
Flannelly believes the political honeymoon that incoming governments enjoy will be shorter than usual because the Irish people are just beginning to understand the severity and the depth of what has happened to their economy.
"Most people have been living in denial. What's really going to hurt is when you have a thousand people a week looking to emigrate somewhere. We're right back to the 1980s, back to a great sense of loss and insecurity," he said.
But Flannelly believes in Kenny's ability to calmly weather the storms ahead. "I've known Enda for a long time and he doesn't get devastated by the image he has (for good or bad). He has experience within his own party and knows that some of his closest confidants will stick him in the back," he said.
"But that's in the past, it's done, it's not going to happen again. I think his election is a great move and working with his coalition partners in the Labor Party is one that makes sense."
O'Dwyer believes that the Irish people are desperate for change and the repudiation of the former government makes that clear.
O'Dwyer added, "I'm very impressed by his performance in the election, when his polls numbers increased by twenty points as people got to know him. Now he's the chairman of the board of Ireland.
There are times when you need an inspiring, flashy leader and there are times when you need a consensus builder. And it doesn't hurt that he's from Mayo."


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The Tennessee State University women's basketball team will make the trip to Kentucky to face No. 14 Louisville in the final non-conference game of the season. TSU will match-up with the Big East member on Monday, Dec. 31 at the KFC Yum Center. Tip-off is slated for 6 p.m. EST. The game will be TSU's second contest in three days.
Simone Hopes leads the team with 9.8 points and 7.0 rebounds per game while Jasmin Shuler is the second leading scorer with 9.6 ppg. Kesi Hess rounds out the top three with an average of 9.3 points per outing.
As a team, TSU is averaging 56.9 points per outing while shooting 35.8 percent from the field and 26.7 percent from beyond the arc. TSU is currently shooting only 67.8 percent from the free-throw line while committing an average of 17.3 turnovers per game.
TSU averages 36.1 rebounds, 9.9 assists and 9.7 steals per game. The Lady Tigers are under first year head coach Larry Joe Inman.
The Big East Member has won two straight including the most recent win over Wagner College, 106-32. In the victory over Wagner, Louisville posted a season-high 106 points and had nine players to score in double-figures.
Megan Deines led the way with a career-high 19 points, Jude Schimmel added career-highs with 15 points and eight steals, and Sara Hammond contributed with 14.
As a team, Louisivlle averages over 75 points per game behind a 46.5 shooting percentage. The Cardinals average 40.8 rebounds, 15.8 assists and 13.2 steals per game.
Sara Hammond (12.3 ppg and Shoni Schimmel (11.3 ppg) pace the Cardinal offense.

subset: commoncrawl


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hotorwhat necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 50 diseños de 22 diseñadores freelance.
Hot or What
We're launching a Web 2.0 ratings site this Spring to enable users and experts to rate anything (people, places, things) through our web and smart phone interface. The site is centered around rating items as "hot" or skipping them (no negative ratings).
The site's secondary focus is bringing people together for events and will include other social networking aspects popular with sites today.
Young, web- and tech-savvy individuals, ages 15-55, non-gender specific, in urban areas. The site will initially launch in metropolitan areas -- New York metropolitan area to start -- and will spread out to more suburban and rural areas throughout 2010.
The logo should feel modern, urban, young, fresh and energetic. It should imply the social aspects of rating people, places, things and be attractive to our target audience.
Logo must be printable in RGB, CMYK and Black and White, so we require variations with each submission to show how it will look on different media.
We like the idea of focusing on visual imagery of products being "hot" (flames, fire, etc.) but request your creativity to make the logo the most original and memorable for attracting and retaining users.
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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Mayor's Office
Mayor Chris Beutler today presented the Mayor's Award of Excellence for August to Equipment Operator Timothy Garrison of the Parks and Recreation Department. The monthly award recognizes City employees who consistently provide exemplary service and work that demonstrates personal commitment to the City. The award was presented at the beginning of today's City Council meeting.
Garrison has worked for Parks and Recreation since 1978 and was nominated by Southeast District Park Supervisor Matt Mittelstadt in the categories of customer relations, loss prevention and productivity. Mittelstadt wrote that Garrison's 30 years of service alone is "a testament of his loyalty and dedication," but the real measure has been in the past 15 months when Mittelstadt had multiple military commitments. Garrison assumed his duties for the much of that period.
In January, Garrison showed his planning and coordination skills by helping with budget preparation as well as managing the Southeast District. After Mittelstadt returned, Garrison was directed to oversee district mowing operations, and he developed a plan to implement the new mowing program that was established this year. Mittelstadt said Garrison met the challenge with the leadership and dedication needed to maintain a consistent mowing cycle, while dealing with the demands of the existing and new employees. By providing a safe work environment and conducting hands-on training sessions for new workers, the Southeast District reduced mowing incidents to an all-time low and reduced equipment repair down time.
Mittelstadt said Garrison's consistent oversight of the mowing crews' operation and his reinforcement of standards has resulted in improved productivity and a quality mowing operation in the Southeast District. Mittelstadt said Garrison also dealt with concerned citizens and handled all phone calls and site visits with courtesy, consideration and professionalism.
The other categories in which employees can be nominated are safety and valor. Consideration also may be given to nominations that demonstrate self-initiated accomplishments or those completed outside of the nominee's job description. All City employees are eligible for the Mayor's Award of Excellence except for elected and appointed officials.
Individuals or teams can be nominated by supervisors, peers, subordinates and the general public. Nomination forms are available at lincoln.ne.gov (keyword: personnel) or from department heads, employee bulletin boards or the Personnel Department, which oversees the awards program.
All nominations are reviewed by the Mayor's Award of Excellence Committee, which includes a representative with each union and a non-union representative appointed by the Mayor. Award winners receive a $100 U.S. savings bond, a day off with pay and a plaque. Monthly winners are eligible to receive the annual award, which comes with a $500 U.S. savings bond, two days off with pay and a plaque.


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Mario Kart Toys are Coming to a Happy Meal near You
Mario, Luigi, Toad, Yoshi and the rest of the racers of Mario Kart 8 are going to be worth every calorie of McDonald's Happy Meals with these new Kart-riding toys.
There are eight Mario Kart 8 toys coming to a McDonald's near you. As of now, restaurants are still carrying Pokemon-themed toys for their Happy Meals, and it's hard to tell whether or not Mario Kart 8 will be the next set of toys to be released for McDonald's Happy Meals after Pokemon finishes its run.
While the Luigi toy doesn't have his epic death stare, Mario, Bowser, Toad, Yoshi and Princess Peach will all be on their karts when packaged with their Happy Meals. Acting as the eighth toy of the series, there is a red visor which looks similar to Mario's iconic hat. You don't even have to buy a Happy Meal for each toy, McDonald's actually sells each one individually for $1.


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STEP Perspective
Evaluating Treatment Option and Health Care Providers:
by Jeffrey Shouten, MD, Jon Hubert, DDS & Brian Coppedge
HIV/AIDS treatment has entered a new era of optimism as well as a period of daunting complexity. For the first time "eradication" of HIV is being seriously discussed. Almost a dozen anti-HIV drugs are available and many more are in the pipeline. Despite the enthusiasm over advances reported at the XI International Conference on AIDS in Vancouver, people infected with HIV face a significant challenge in making decisions about multiple drug combinations, interpreting viral load tests, as well as issues about how their choices today will effect treatment options tomorrow. If treatment questions seem complex, add to the mix the task of negotiating a rapidly changing U.S. health care system.
Be As Informed As PossibleNow, more than ever, it is essential to have as much knowledge as possible about HIV treatment options. Even expert panels of researchers have difficulty in making recommendations in today's environment of multiple treatment regiment and rapidly evolving research data. A recent review of AIDS information newsletters demonstrates the range of opinions to be found regarding treatment choices. For a person newly infected with HIV, one doctor recommended no treatment, while another recommended a six drug combination. How can a reader make sense of such a wide disparity in recommendations? How could one person, perhaps consulting these two doctors for recommendations, make a decision? The tremendous value of newsletters lies in the explanation and discussion of the background issues and the context of each approach. The six drug combination was used in a research setting, testing a very aggressive approach for people newly infected with HIV. The " no treatment" approach was discussed by a conservative doctor working in a urban clinic who wanted more research done and was concerned about compliance and medical coverage issues.
When treatment strategies are reported on television, in newspapers, or discussed by friends, often the background information is left out. Reliable treatment newsletters provide information based on interviews and surveys of leading researchers, reports from scientific journal articles and analysis by authors experienced in HIV/AIDS treatment issues. The information in these newsletter is reviewed and cross checked by a number of different people to insure accuracy and reduce bias.
Treatment journals (see end of this article) are an extremely valuable source of state of the art information covering various options as well as putting these options in perspective. They can provide a lifeline for people living in small communities or who otherwise have limited access to up to the date treatment. They also provide information which can be taken to a doctor to help with treatment discussions.
Finding the Right Health Care Provider (HCP)In today's world of PPO's, HMO's, provider lists and other manifestations of managed care, finding a HCP can be a challenge. In some managed care situations HCP choice is restricted, change is difficult and cost constraints limit treatment choices. However, the single most important factor in choosing a HCP is his or her level of clinical experience in treating people with HIV and AIDS. A recently published study conducted at a health care maintenance organization in Seattle found that the level of experience of primary care physicians in the treatment of HIV/AIDS was significantly associated with the survival of their patients. The study was conducted by Kitahata et al, and was report in the New England Journal of Medicine, March, 14, 1996. The study looked at 403 adult males diagnosed between 1984 and 1994 and cared for by 125 primary care physicians. The researchers rated the physicians based on their experience caring for people living with HIV/AIDS during their medical training and the cumulative number of patients with AIDS they had cared for in their individual practices. The median survival of people who had physicians with the least experience was 14 months, as compared to 26 months for patients who had physicians with the most experience. The authors controlled for CD4 count, severity of illness and year of diagnosis. For physicians who saw 5 or more AIDS patients the survival rate improved significantly
The bottom line in insuring the best treatment possible is the combination of an educated client and a knowledgeable and experienced health care provider. It is essential that a HCP has a good understanding of current treatment guidelines as well as a reasonable amount of clinical experience with HIV/AIDS clients. AIDS/HIV Care Access Project (ACAP) is a non-profit organization in Seattle that can provide physicians referrals for people living with HIV/AIDS. They can be reached at: 190 Queen Anne Ave. N (Third Floor), Seattle, WA 98109 206/284-9277
Treatment GuidelinesThe table below outlines basic treatment guidelines as recommended by health care professionals who treat a large number of HIV-positive people, recommendations published by the International AIDS Society, and recommendations made by local and national university-based AIDS experts. As with any general guidelines, each person's unique situation must be factored into any treatment plan. Considerations include drug tolerance, drug interactions, and the person's overall health, including energy level, weight loss, or other symptoms. Another very important consideration is the rate of change of CD4 cells and viral load. Any treatment plan should take into consideration future therapy as well.
Two measurements of viral load a couple of weeks apart are recommended for a baseline for all HIV-positive persons. Subsequently, viral load should be measured about 4 times per year. Additionally, viral load measurements should be obtained 4-8 weeks after initiating a new therapy to assess its efficacy.
Therapy RecommendationsViral Load Non-detectable, CD4 greater than 500 - OBSERVATION
Viral Load Non-detectable, CD4 200-500 - DOUBLE THERAPY
Viral Load Non-detectable, CD4 less than 200 - TRIPLE THERAPY
Viral Load up to 5-10,000 , OBSERVATION OR DOUBLE/TRIPLE THERAPY
Viral Load greater than 5-10,000, CD4 greater than 500, DOUBLE OR TRIPLE THERAPY
Note: Double therapy means a combination of 2 drugs, usually two nucleoside reverse transcriptase inhibitors (AZT, 3TC, ddI, ddC, and d4T). Triple therapy means a combination of 2 nucleoside reverse transcriptase inhibitors and a protease inhibitor (saquinavir, ritonavir, or indinavir) or a non-nucleoside reverse transcriptase inhibitor ( delavirdine or nevirapine). Alternatively, an effective combination of 2 drugs may be 2 protease inhibitors, such as saquinavir and ritonavir. (See STEP Perspective, Summer 1996; Vol. 8, No. 2 for a complete discussion of combination therapy.)
Guidelines for Prevention of Opportunistic InfectionsFollowing is a list of common Opportunistic Infections (OI's) and whether or not preventative therapy is recommended:
Pneumocystis pneumonia (PCP), DEFINITELY BENEFICIAL IF CD4 less than 200
Toxoplasmosis, MAY BE BENEFICIAL IF CD4 less than 100 AND Toxo Antibody Positive
CMV, DEFINITELY BENEFICIAL IF CD4 less than 50
Cryptococcus, MAY BE BENEFICIAL IF CD4 less than 100
Mycobacterium Avium Complex, DEFINITELY BENEFICIAL IF CD4 less than 100
Note: Preventative therapy (prophylaxis) for PCP is definitely of benefit to all HIV-positive persons with CD4 values below 200, and some health care providers recommend preventative therapy even in some people with slightly higher CD4 counts. While some studies have shown a benefit for preventative therapy for the other infections in the table above, problems with side-effects, drug interactions, and resistance have resulted in selective use of drugs to prevent these infections. An HIV-infected person with low CD4 counts, (less than 100), should discuss the use of drug therapy to prevent these infections with their health care provider on an individual basis. CMV infection in the eye can cause permanent, irreversible vision loss, even when treated. Therefore, many health care providers recommend that all HIV-infected persons with CD4 counts below 100 be examined regularly for evidence of early CMV infection in the eye (retinitis). Early treatment may prevent vision loss. Screening cannot be done by a quick look into the eye, but requires drops to dilate the eye and a careful examination by a trained professional (fundoscopy). Prophylactic therapy for opportunistic infections should not be discontinued if low CD4 counts increase significantly on antiretroviral therapy. Apparently, the risk of an OI is not significantly decreased when CD4 cell counts increase on antiretroviral therapy.
Self-AdvocacyIn a perfect world, all health care providers would be well-informed and the best and most effective treatment would be offered to all persons who are HIV-positive. However, this is not always the case, and clients must take action and insist that their health care provider and health plan provide them with the opportunity to receive the best possible care. Survival may depend upon it! Sometimes, health care providers are not well-informed about the latest developments concerning protease inhibitors or viral load testing. Other times, the health care plan or health maintenance organization (HMO) may not allow health care providers access to the newest, or best drug, or laboratory tests that he or she wants to prescribe. In either case, each person must become an activist and a treatment advocate on their own behalf.
The first option for a client is to discuss their care with their health care provider and provide him or her with literature supporting any requests, such as the treatment guidelines outlined above. If this approach does not resolve the problem, then the next option is to request to talk to a patient care representative. Most HMO's and clinics have an ombudsman or patient care representative with whom concerns can be addressed, within the group or clinic, if a health care provider has not been responsive.
If the client is still not able to access the care they feel is in their best interest, then a few other options are still available. HMO and some clinics have a restricted formulary, which means that they control the drugs they provide to their members. However, often times these organizations have a mechanism whereby an individual health care provider can prescribe a non-formulary drug. So if a health care provider refuses to administer a drug that has been requested because it is not on the formulary, they should be asked if there is any mechanism whereby approval may be obtained for him or her to prescribe a non-formulary drug.
HMOs and managed care plans often erect "gate-keepers" to limit access to test or drugs, but there are usually appeals or approval processes built in to allow for individual exceptions. Ask your health care provider what mechanisms are available in your HMO or health care plan to make an exception to these rules. Also, most HMOs allow members to switch health care providers if they are not satisfied with their current HCP, although this will not resolve institutional problems.
Lastly, some people have found that the only way to advocate for change within an HMO or managed care group is to form an advocacy group of members within that particular HMO or managed care plan. The most successful of these group have lobbied for changes with the Kaiser-Permanente HMO in California. One person cannot advocate for change as effectively as a group. STEP can assist in forming an advocacy group within health care plans or clinics. If, the above recommendations have been followed, and still not achieved the desired outcome, call STEP and they will attempt to coordinate and facilitate the formation of a consumer advocacy group within a particular health care plan or clinic.
What To Expect When You Are Involved In a Drug Trial Or Research ProjectDrug trials provide the opportunity to start on new or unapproved drugs well before they are available to the general public. Remember: trials are developed and designed to evaluate the effectiveness of a particular treatment and its potential toxicity. Before deciding to take part in a trial special consideration to the possible pro's and con's of each trial should be considered.
In most trials, one arm (group of people who receive identical treatment) includes the unapproved drug and the other arm is a drug or drugs previously shown to have some benefit. Trials may contain several arms which study drugs at different dosage levels. This allows the researchers to compare the results of the new treatment to treatments which have already been approved for use by the Food and Drug Administration (FDA). Currently, many trials compare combinations that include protease inhibitors to combinations of non-protease inhibiting drugs that have already been shown to inhibit HIV replication. People have to decide if they are willing to risk being assigned to an arm that may contain drugs that are not as effective as the ones currently available through their health care provider.
Many health care plans have been slow to offer the viral HIV RNA test. These tests are generally agreed to be the most important test to track the progression of HIV. One way to get a free viral load test is to join a drug trial. Most trails will run these tests because they are the best tool to evaluate the efficacy of the new drugs. Before joining a trial, find out if the researchers will release viral RNA results to clients; also see if the tests will be released in a timely manner, or whether they wait until the end of the trial to release the HIV RNA results. If trials don't provide access to a viral load test, or if the trial is not going to release the results frequently, it may be better not to join the trial.
Some trials may ask participants to stop taking particular medication or may ask them not to start taking other medication. Always find out before starting a trial what restrictions will be place on participants. People who are even slightly uncomfortable with the requirements of the trial, should consult their health care provider before joining. Once in a trial, people should try to be as compliant with trial protocols as possible. If severe side effects appear, the investigators should be notified, and the option to withdraw from the trial should be considered. Trials can provide excellent opportunities for people to access drugs and tests that they would not otherwise have access to. Careful examination of the trial protocols and consultation with a health care provider are crucial when considering new drug trails.
The trial investigators can be contacted directly at:
University of Washington AIDS Clinical Trials Unit
Novum Inc.
Advanced Research Management
Bastyr University
Gay Men's Health Crisis
AIDS Treatment News - available here at The Body
Positive Living
STEP Perspective - available here at The Body
About the Authors
Jeffrey Schouten is a general surgeon and co-chair of STEP's Scientific Review Committee.
Brian Coppedge is the Treatment Information Specialist at STEP.
Jon Hubert is a member of STEP's Scientific Review Committee and is a member of the Board of Directors.
Recent Development In The Treatment And Prevention Of Disseminated Mycobacterium Avium Complex (MAC)by Jeffrey Shouten, MD, Jon Hubert, DDS and Stan Whittemore, MD
Disseminated Mycobacterium avium complex (DMAC) is the third most common opportunistic disease in people with AIDS, ultimately infecting 30-50% of the patients with very low CD4+ counts, and significantly reducing the length and quality of life. MAC is a group of closely related bacteria that grow in water even chlorinated water as hot as 125 degrees F), soil, house dust, and some animals. However, it does not appear that the MAC organisms in the environment are the exact same as those in the infected people, thus there are no recommendations for avoiding exposure. People with CD4 cell counts below 75 who have had a previous AIDS-defining opportunistic infection are at greatest risk for developing DMAC. Symptoms of DMAC include high fever, weight loss, fatigue, diarrhea, poor appetite, night sweats, and anemia (low red blood cell counts). The diagnosis of DMAC is usually made by finding the bacteria present in blood or bone marrow cultures. Prevention of DMAC and the treatment of people with active infection has been very difficult primarily due to drug side effects and resistance. 23% of people on 500m mg of clarithromycin twice daily and about 50% of people using multi-drug regiments have dose limiting drug reactions. 46% of patients receiving clarithromycin alone developed resistance at a median of 16 weeks. Treatment with combinations of 2-4 drugs have serious side effects, often as a result of their complex drug interactions. This article will focus on a few recent favorable reports concerning both the prevention (prophylaxis) and treatment of DMAC.
Two studies were reported in the New England Journal of Medicine on August 8, 1996 evaluating drug therapy to prevent MAC infection in HIV-infected people with less than 100 CD4+ cells. The first study was a randomized trial in which one half of the participants received an antibiotic, clarithromycin (500 mg twice a day), and one half of the participants received a placebo. After about ten months, MAC infection developed in only six percent of the participants who received the clarithromycin, compared to 16% of the participants who received the placebo ( a 69% risk reduction). 50% of the infections occurred in people with CD 4+ counts in the 0-9 range, and all the infections occurred in people with less than 50 CD4+ cells. In the ten month follow-up period, 32% of the clarithromycin treatment group, and 41% of the placebo group died ( a 26% reduction in mortality). One danger of using a drug to prevent an infection is that people who subsequently develop the infection may have a drug resistant infection, which could be more difficult to treat. In this study, 11 of the 19 people who developed DMAC in the clarithromycin group were resistant to the antibiotic, vs. none in the placebo group. Over the course of the study, the death rate was significantly lower in the group which received clarithromycin ( 32% versus 41%).
The second study compared other antibiotics to prevent MAC. Participants received either azithromycin (1200 mg weekly), rifabutin ( 300 mg daily), or both drugs. All the participants were on either 400 mg fluconazole once a week, or 200 mg daily as well. After one year, the rate of MAC infection was 15.3% with rifabutin, 7.6% with azithromycin, and 2.8% with both drugs. In the group treated with azithromycin who subsequently developed MAC, 11% had azithromycin resistance. Even though the best results were observed in the group which received both drugs, side effects limited tolerance in that group significantly. The most common side effects were gastrointestinal symptoms. However, overall, 23% in the combination group, 16% on rifabutin, and 13% on azithromycin had dose limiting toxic effects. A major advantage of azithromycin is that it only needs to be taken once a week. Once a week azithromycin has been shown to reduce the risk of MAC by 60% when compared to a placebo (19.1% one year rate of DMAC vs. 8.2% with 1200 mg of azithromycin once weekly).There are no data evaluating the concomitant use of azithromycin and protease inhibitors.
What, then, is the preferred choice for the prevention of DMAC? Moreover, when should such prophylactic therapy be initiated? A national panel has recommended considering antimicrobial prophylaxis against M. avium when CD4 lymphocyte count falls below 75 in people who have had opportunistic diseases. Choosing a regimen requires balancing efficacy against tolerability, cost, the potential for drug interaction, and the dangers of resistance to the drug. Administering these drugs together with other medications used to treat people with advanced AIDS has substantial pharmacokinetic implications. Serum levels of both clarithromycin and rifabutin increase when they are taken with fluconazole; HIV-protease inhibitors increase the metabolism of clarithromycin and decrease that of rifabutin. Azithromycin has been less well studied, but has not been reported to interact in these ways. The resistance to clarithromycin and azithromycin is a worrisome development, because resistance to one of the two brings with it resistance to the other, so that people with disease due to resistant organisms have limited options for treatment. The above study by Pierce et al. indicates that the benefit in terms of prevention outweighs the risk of drug-resistant regimens as azithromycin and rifabutin in individuals with CD4 counts less than 10, who have up to a 40% risk of acquiring MAC over the course of one year.
Once M. avium disease occurs, antimycobacterial therapy with a combination of drugs is required. The optimal therapeutic regiment remains to be determined. Current regiments to treat MAC usually include 2-3 drug combinations due to the rapid development of resistance if only a single antibiotic is used. A study of ethambutol (15 mg/kg) added to clarithromycin showed prompt improvement in symptoms and reduction in MAC levels in the blood within several months, and was highly effective in preventing the emergence of resistance to the macrolides. The three drug combination of rifabutin (600 mg daily ), ethambutol ( 15 mg per kg daily), and clarithromycin (1000 mg twice daily) was compared to the four drug combination of rifampin (600 mg daily), ethambutol ( 15 mg per kg daily), clofazimine (100 mg daily ), and ciprofloxacin ( 750 mg twice daily) in a recently published study. A total of 229 individuals with active MAC infection, confirmed by blood culture, were randomized to one of the two regiments.
The study found that people treated with the three drug regimen had a greater chance of removing the bacteria from the blood more rapidly (69% vs. 29%), and their survival rates were better than people treated with the four drug regimen ( 8.6 months vs. 5.2 months). The accompanying editorial, cited above, noted that an earlier study showed that the dose of clarithromycin used in this study ( 1000 mg twice daily) was associated with a decreased survival compared to a lower dose of 500 mg twice daily, and the dose of rifabutin had to be lowered because of a 38% incidence of uveitis (inflammation in the eye). However, it was noted that the treatment of MAC infection once present is inferior to primary prevention. Even though the median survival was around seven months, 20% of the participants in Chaisson's study died in the first 12 weeks of treatment. Other drugs available for use in combination therapy for M. avium disease include, clofazimine, rifampin, ciprofloxacin, and amikacin. Clofazimine, when given with clarithromycin, neither prevents the emergence of resistance to clarithromycin nor prolongs survival. Indeed, recent studies have shown that there was significantly higher mortality when this drug was used in combination with clarithromycin and ethambutol. Rifampin offers on therapeutic advantage over rifabutin and appears to have more potential for drug interactions. Ciprofloxacin is poorly tolerated and has marginal in vitro activity, whereas amikacin adds little to oral regimens. For those persons intolerant to the multi-drug therapies, or who do not respond well to the therapy, steroid administration can reduce symptoms dramatically. Dorman and Sax showed that the addition of 4 mg/day of dexamethasone to their small group of participants who were worsening after a mean of 30.5 days of anti-mycobacterial treatment, had rapid improvement in symptoms. The duration of this benefit varied from a minimum of three months to a maximum of seven months. There was no apparent worsening of baseline prevalent opportunistic infections. Wormser et al. showed that a dose of two mg dexamethasone, in addition to the anti-mycobacterial therapy for people who had progressive weight loss and persistent fever, and an improved sense of well-being.
One of the most potentially serious toxicities of rifabutin is an inflammation in the eye called uveitis. This condition began to show up when rifabutin was used at very high doses (1200+ mg), and when combined with clarithromycin and fluconazole (with rifabutin doses in the 600 mg range). This has occurred in non-HIV patients infected with MAC as well, but only in conjunction with clarithromycin or fluconazole. Before this condition was well known, a group of opthamologists treated the affected people with intensive topical corticosteroid therapy, and were able to continue rifabutin, sometimes without a dose reduction. This condition developed at a range of 51 to 393 days (median, 79 days) after starting rifabutin, clarithromycin and fluconazole. The interaction of these drugs has been discussed above, showing marked elevations of rifabutin levels when combined with either of these other two drugs. These authors felt it was potentially safe to continue rifabutin at lower doses under close supervision if the clinical situation indicated the need. Horsburgh, in his editorial in the New England Journal of Medicine, states that "there is now strong evidence that primary prophylaxis against M. avium disease has a substantial clinical benefit, and such prophylaxis should be considered the standard of care." The question remains: when to begin therapy, but it appears that azithromycin has the least toxic effects and least drug interactions and equal efficacy. Chaisson suggests that treatment of DMAC initially should be with clarithromycin 500 mg twice daily (or azithromycin 600 mg daily) plus ethambutol 15 mg/kg/daily (maximum 1000 mg) with or without rifabutin (300-450 mg daily). In people who may have antibiotic resistant disease, the three drug combination should be used. Treatment of relapsed disease due to resistance is difficult, as there are no additional agents with proven activity. One option is to add two new agents such as amikacin and ciprofloxacin, though the efficacy of such maneuvers is unknown.
About The Authors
Jeffrey Schouten is a general surgeon and co-chair of STEP's Scientific Review Committee.
Stan Whittmore is on STEP's Scientific Review Committee and is a member of the Board of Directors.
New Recommendations On Health Care Workers Exposure To HIVby Jane Woodward, Pharm.D.
Human Immunodeficiency Virus (HIV) has always drawn vast media attention and study, probably due to its lethality and agility in evading the immune system. Recently, there has been an explosion of knowledge about the dynamics of its life cycle, especially in measuring the velocity and magnitude of its replication. Although frightening, this knowledge has also come at a time when new ways of treating the infection have emerged which have given new hope to people infected with HIV and those responsible for their care.
Health care workers who administer care to people living with HIV are highly trained in universal precautions and procedures to prevent possible transmission of the virus. When an unfortunate contact with blood or body fluid occurs, the risk of seroconversion is low but decidedly present. In the most risky esposures, there has always been interest in finding something to offer these affected workers, either to prevent transmission or possibly eradicate infection once it occurs. Knowledge of the viral life cycle and highly aggressive, potent antiretroviral regiments have completely altered our perceptions of how to treat these exposures.
New Findings in Viral DynamicsOne of the most important advances in HIV/AIDS care is the ability to measure the amount of viral particles in the blood stream. More commonly known as "viral load,"the measurement gives a more complete picture of immune system. At high viral levels, it is a sensitive marker of those who are at risk to progress rapidly to AIDS. Viral measurements have also given us a better idea of the velocity of replication and the damage that can occur to the immune system when replication is allowed to continue unchecked. It has now been estimated that the half life of an infected CD4 cell that is rapidly producing viral particles is about 1.6 days and for a free virion in plasma it is 0.3 days. Thus, the number of virions produced daily is at least 10.3 x 109. It is estimated that up to two billion immune cells are destroyed daily (Science).
Protease inhibitors are a new class of drugs designed to block viral replication. They work late in the life cycle and thus are effective in newly and chronically infected cells. When used in combination with nucleoside analogs such as zidovudine (AZT) and lamivudine (3TC) it is possible to block viral replication within the bloodstream. When this occurs viral levels decline rapidly - an initial lag is followed by exponential decay. This phase of decay is due to clearance of free virions and productively infected cells. The half life of this phase is estimated at 2.1 days. Once the plasma is cleared of infecting virus, a second elimination phase begins that is due to the drugs' effect on macrophages and latently infected CD4 cells. This is a much slower phase with the average cell life span of 13.3 days. In theory, administering potent antiretroviral medications over an extended period of time would allow all compartments to burn out cells that have been infected with HIV (XI Int AIDS Conf (ThB930 Ho, David).
While these are exciting theories, there are many questions left to be answered. It is not known how long these potent antiretroviral regimens would have to be administered to completely clear virus particles and infected cells. It has been estimated that at least 1.5-3 years will be required (XI Int AIDS Conf (ThB930 Ho, David). Antiretroviral regimens have always lost their efficacy over time. The reasons for this are unknown, but considerable evidence has pointed to development of resistance. Thus, there is some skepticism that these regimens will remain effective or will be tolerated for the time required to eradicate the virus. Previous regiments were never able to completely stop replication in the bloodstream and thus, viral replication occurred in the presence of the drug, driving resistance mutations. Completely stopping replication may result in resistance being avoided altogether. However, even if the regimen was successful, it is unknown if the immune system would be able to recover.
Post Exposure Prophylaxis (PEP)Theories on viral dynamics and aggressive antiretroviral regiments both play a role in the decision of how to treat someone exposed to HIV in the health care setting. Potent antiretroviral drugs, if introduced early after exposure, could theoretically block the first cycle of replication, preventing infection of multiple cells lines. It has also been hypothesized that they may also be used to eradicate infection, again, if introduced soon enough after exposure. Even if they do not completely eradicate the virus, they could potentially alter the natural history of the disease by lowering the set point of initial viremia after infection has occurred ( Gerberding NEJM 1995).
What is the Risk?Needlestick exposures are thought to be the most risky, yet seroconversion rates are only 0.2-0.3%. Factors which increase the risk of seroconversion are deep injuries, devices visibly contaminated with blood, procedures involving a needle placed directly in a vein or artery and advanced AIDS in the source patient (probably indicative of high viral load or syncytium inducing virus) (MMWR 1995). Injuries with hollow core needles and injuries that do not occur through gloved skin are thought to be more risky as well.
Mucocutaneous exposures resulting in seroconversion have never occurred in studies, but the risk has been estimated at 0.08% ( XI Int AIDS Conf 1996 TuC120). Higher risk is associated with large volumes of blood, prolonged duration of contact and a potential portal of entry such as non-intact skin (Gerberding NEJM 1995). Host defense may also play a role since evidence of cellular immune response has been found in exposed but uninfected health care workers. Treatment of HIV exposure has been hampered with concern over lack of efficacy of available treatments and also high toxicity rates. Zidovudine (AZT) is the only antiretroviral agent formally studied for this indication and there have been well documented failures despite early administration. The Center for Disease Control (CDC) surveillance data found AZT used in 31% of exposures overall and 31% of patients did not complete the course. Adverse events occurred in 75% of those treated. Failure of AZT occurred in at least nine cases, although five failures had exposures greater than a needle stick ( Annals of Int Med 1993;118(12) 913-19). Failure can occur because of inadequate control of replication, timing, lack of penetration into target tissues, compliance with the regimen and resistance.
Interest in post exposure prophylaxis was renewed recently with the results of a study reported in 1995 (MMWR 1995). A case-control study was reported of 31 workers who seroconverted after occupational percutaneous exposure to HIV. Results found a significant reduction in seroconversion in those who took AZT early after exposure. Taking AZT reduced the risk 79% (MMWR Dec 22, 1995 vol 44 no 50:929-933). Although a prospective, placebo-controlled trial would have given more reliable results, such a study is not feasible at this time, (given the very low seroconversion rate and the participants' understandable hesitation at being randomized to the placebo arm).
Although AZT alone has proven efficacy in reducing the risk of seroconversion after exposure to HIV, failures have kept investigators searching for better regimens. As previously discussed, potent combinations of antiretrovirals that include protease inhibitors afford much better control of viral replication and will probably be more effective at preventing seroconversion. Using the knowledge of viral dynamics and the properties of these medications, the United States Public Health Service (USPHS) has published new recommendations for post exposure prophylaxis (see table 1). If possible, these drugs should be started within 1-2 hours of exposure, preferably as soon as possible, and continued for four weeks. The University of Washington and Harborview Medical Centers have adopted these recommendations and are prepared to provide these medications quickly following accidental exposure.
Careful evaluation of the severity of the exposure is necessary, as these medications are not innocuous. There is not much information of the incidence of adverse events in people not already infected with HIV, but considerable toxicity does occur. Zidovudine, when used for this indication, is hampered by nausea (61%), vomiting (15%), fatigue (49%), abdominal pain (15%), headache (12%), myalgias (12%), anemia (12%) and neutropenia (8%) (Int Con AIDS TuC122). All serious exposures should receive three medications - zidovudine (ZDV or AZT), lamivudine (3TC) and the protease inhibitor indinavir (IDV). Please see table 2 for details regarding dose, adverse reactions and possible drug interactions. Changes may be made to this regimen on a case-by-case basis, particularly if the source patient is known to be taking any of these medications. Some providers may elect to use a loading dose (high initial dose) to achieve therapeutic drug levels as quickly as possible. It is unknown whether a loading dose will offer additional prophylactic benefit, but will possibly cause more transient side effects. Compliance with the medication regimen is of paramount importance. Resistance can develop quickly if the regimen is not adhered to, and efficacy may compromised.
Prophylaxis Following Risky BehaviorsIt has become a concern that antiretroviral medications are being used by some people following potential exposure to HIV, especially following unsafe sex and needle sharing. This "morning after" use of these medications is fraught with problems. If these drugs are not taken in combination, very soon after exposure, at correct dosages, and at least for four weeks, incomplete viral suppression will occur, thus potentially breeding resistance. AZT alone will not prevent HIV infection when used in this setting. These medications are anything but innocuous, and require frequent monitoring by someone well-versed in HIV care to avoid toxicities that may be irreversible. "Morning after" therapy should not be used in place of well-accepted methods to prevent HIV transmission.
About The Author
Jane Woodward, Pharm.D, is a pharmacist currently in practice at the University of Washington.
Dietary Consideration And Protease InhibitorsBy Brad S. Lichtenstein, ND
Drug therapy is becoming increasingly more complex every day. New combinations offer a great deal of promise, yet it is important to remember that these drugs are still in their infancy. More needs to be learned before we have all the answers. The new protease inhibitors are a case in point. The drug ritonavir (Norvir or ABT - 538) has been studied for its numerous drug interactions due to its effects on the liver.
One of the key roles of the liver is detoxification. Detoxification is the process of neutralizing and eliminating toxins from the body. External sources of toxins include smoke, fumes, pesticides, drugs, pathogenic microorganisms, food additives and dyes, and excessive hormones found in animal products. Oddly, our body generates its own source of internal toxins during the detoxification process. For this reason, maximum liver function must be maintained in order to prevent destruction of liver cells (hepatocytes) and other bodily tissues. The liver deals with toxins in a variety of ways. In the healthy, optimally functioning liver, approximately two liters ( half a gallon) of blood flow through it each minute before returning to general circulation. While in the liver the hepatocytes filter out toxins and bacteria. Special liver cells, called Kupffer cells, engulf foreign particles (bacteria and toxins), ingest them, and remove them from the bloodstream. This filtration is the first step in the detoxification process.
The second step occurs during the liver's daily production of bile. Bile is necessary for digestion and absorption of all fats. This includes the fat soluble vitamins, vitamins A, K, E, and O. Without bile, deficiencies in the fat soluble antioxidants (vitamins A, K, E and 0) would ensue. For detoxification purposes, toxins in the liver bind to bile to be excreted from the body. Fiber, from the diet, is necessary in order for this toxic bile to be excreted through the feces. If bile, or fiber for that matter, is not present, these toxins will become reabsorbed in the intestines and re-enter the bloodstream, allowing them another chance at destruction. The last step in the detoxification process involves a series of enzyme systems which help remove chemicals from the bloodstream by neutralizing them. The two pathways required in this operation are known as the Phase I and Phase II detoxification systems. Phase I directly alters the structure of chemical compounds. This initial phase involves a series of enzymes collectively known as the mixed function oxidase system (MFOS0, which includes approximately 100 different enzymes perform the following role during Phase I detoxification:
When this last step occurs, a new chemical intermediate is formed that is more toxic than the original substance. Smoking is an example of this process. When the chemicals from tobacco or charcoaled foods (polycyclic hydrocarbons) are taken into the body, they are not carcinogenic until they pass through Phase I detoxification. The intermediates formed during this process are more chemically toxic than the original substance. On an unfortunate note, every time the Phase I system is invoked, free radicals are generated which can, in turn, produce more free radicals and result in serious injury and stress to the body. Therefore, despite the perceived benefits of Phase I detoxification, activation of the system is not always desired, as we will discuss below.
The body deals with the intermediates of Phase I by shuttling them to Phase II. In Phase II, another group of enzymes, the conjugating enzymes, are involved. Not only do these enzymes conjugate (attach particles) to the intermediates, (which inactivates them in order to be safely excreted in urine or bile), but they may also conjugate chemicals which never passed through Phase I. In order to deal effectively with toxins, the Phase II system must be kept working properly. If Phase I is working well, yet Phase II is not, build up and the Phase I induced, chemically altered, toxic intermediates will have no means of being removed from the body. They will continue to circulate in the blood stream causing more damage. Ritonavir affects the liver's ability to perform optimally. Ritonavir affects the MFOS by keeping the cP450 enzymes busy and unavailable. In other words, ritonavir inactivates the cP450 enzymes. As a result, many drug interactions can occur when taking this protease inhibitor. First, the liver's ability to clear drugs such as antihistamines and benzodiazepine antidepressants can pose life-threatening complications when taken in conjunction with ritonavir. The majority of drugs taken orally undergo a process known as the "first pass effects." This process occurs when the drug enters the bloodstream and goes to the liver to be metabolized, or inactivated, by the cP450 enzymes. The dosages for oral medications take this into consideration. Since ritonavir ties up the enzymes essential for this to occur, chemicals and drugs are unable to be metabolized properly. Therefore, they stay in the bloodstream longer and at higher concentrations. What was once a standard dose now becomes a toxic one, since they are not fully inactivated by the liver.
Second, ritonavir affects the liver's ability to activate many chemicals and drugs in order for them to be converted into substances the body can use. This is the reason why many drugs lose their effectiveness in conjunction with ritonavir; oral birth control pills are an example of this. Since these drugs need to be converted by the c P540 enzymes, an increased dose is necessary in order to obtain the desired effects.
Diet and food can play a role in influencing the liver and the Phase I and Phase II detoxification systems. Although no studies exist as of this date regarding the interaction between food and ritonavir, much has been written describing the role of diet and lifestyle on basic drug metabolism. Once again, we find that common sense and basic nutrition cannot be overlooked when the goal is to stimulate the body's natural ability to stay healthy and maintain a strong functioning immune system.
The goal for healing with food is to ensure that Phase II detoxification is working properly. Although the cP450 system (Phase I) is inactivated by ritonavir, attempts at activating these enzymes is not necessarily the objective. By activating these enzymes, we decrease the effectiveness and concentration of ritonavir in the body. This is seen in tobacco smoke. Tobacco and other smoked products contain chemicals (nitrosamines) which must be activated by the cP540 enzymes in order for their toxic and carcinogenic effects to take place in the body, i.e., they must be converted to toxic intermediates. These nitrosamines activate the cP450 enzymes. The same thing occurs with charcoaled food which yields polycyclic hydrocarbons. Theses hydrocarbons are produced by incomplete combustion when drippings contact hot coals and are redeposited on the foods. Hydrocarbons activate cP450 enzymes as well. Studies show that those who smoke have an 18% reduction in their blood levels of ritonavir. This is due to the fact that activated cP450 enzymes begin clearing ritonavir from the body. Alcohol also increases the cP450 activity and may have the same effects on blood levels of this drug as does tobacco. Stimulating cP450 enzymes has another hazard; activating Phase I detoxification without an intact Phase II can result in an increase in circulating toxic intermediates which can be life-threatening.
In addition to these effects, both smoking and alcohol consumption lead to deficiencies in nutrients essential for virtually all enzymatic pathways in the body, especially Phase II detoxification. The consequences of such deficiencies can be more problematic for maintaining a healthy immune system and functioning liver that the actual activation of cP450 enzymes. Therefore, as a rule, avoidance of tobacco, alcohol and charcoaled foods is advisable. If cooking with charcoal, tightly wrap foods in aluminum foil in order to prevent the formation of hydrocarbons.
As mentioned above, adequate nutrition is paramount. In order for the Phase II detoxification to perform optimally, it must have all the basic building blocks. The proper vitamins and minerals must be available; without them, detoxification cannot occur. Vitamin deficiencies can lead to an increased conversion of procarcinogenic substances to toxins and carcinogens by the cP450 system, and an increased level of circulating toxic intermediates from Phase I. Providing the body with the essential nutrients, either through supplementation, or diet, helps restore balance. All the B vitamins, (thiamin, riboflavin, niacin, pantothenic acid pyridoxine, folic acid and cobalamin), are needed at some level for the Phase II system to function properly. Emphasis should be given to these nutrients of the antioxidant family as well, namely vitamin C and E, beta carotene and selenium. Both vitamin C and E can block the formation of nitrosamines which can prevent activation of cP450 enzymes and inhibit tumor formation. Furthermore, when levels of selenium and B vitamins decrease, glutathione decreases. Glutathione is a major antioxidant in both of the Phase I and Phase II systems. Stores of glutathione must be maintained to prevent free radical damage and ensure adequate detoxification. The amino acid N-acetylcysteine (NAC) can protect glutathione levels from dropping in the body. NAC supplementation has been studied for its ability to successfully treat and prevent liver toxicity by such drugs as acetaminophen (Tylenol). All in all, supplementation with a good multivitamin is a start and can ensue the body with B vitamins, antioxidants and NAC is warranted when taking ritonavir. However, supplementation does not preclude the fundamental necessity for proper diet. Like the effects of tobacco and alcohol, methylxanthines, such as caffeine, theophylline, and cola induce the cP450 enzymes of Phase I. Rather than further stimulate this system, it would be best to decrease consumption of foods containing theses substance. Such foods would include coffee, black teas, chocolate, and sodas. As with all parts of our lives, balance is the key; complete avoidance to the point of fanaticism is not necessary. If you are taking a protease inhibitor, rather than continue to stress the liver, allow it time to balance and recharge. Although these protease inhibitors are extremely potent, becoming obsessed with everything you do (including everything you eat and drink) does not promote healing and wellness. If you find yourself drinking many cups of coffee per day, explore your need for coffee. If you find yourself addicted to the caffeine, now would be and excellent time to do something about it. This does not mean coffee can never be consumed again. It simply suggests that moderation, without addiction, is key.
Cruciferous vegetables, such as broccoli, cabbage, and brussel sprouts, contain a chemical known as indole-3-carbinol which is a potent activator of Phase I and Phase II detoxification. While diets high in these vegetables have anti-tumor producing effects, they induce cP450 enzymes. Remember activation of Phase I is problematic with out Phase II. Since cruciferous vegetables do both, simply be cautious. Even though your mother may have had good motives, feel comforted in knowing that it is not always beneficial to eat your brussel sprouts! So what to eat or drink? One class of chemical compounds, flavonoids, phenolic compounds abundant in fruits and vegetable, have potent action on Phase I and Phase II systems. Not all flavonoids are the same. Flavonoids containing multiple hydroxyl groups appear to be more effective inhibitors. Fruits such as lemons, limes, and grapefruits possess the highest amounts of these polyhydroxylated flavonoids, while tangerines and oranges do not. Ingestion of lemons, limes, and grapefruits inactivate Phase I even more. Since ritonavir is already performing this action, there is no need to provoke the situation any further. Oranges and tangerines, on the other hand , activate Phase I, which we do not want to do either. As a rule, avoidance of citrus fruits and juices is wise. The inhibition of Phase I detoxification is the reason why people are told to take their saquinivir (invirase) with an 8 once glass of grapefruit juice. If the cP450 enzymes are inactivated, then the drug (saquinivir) will not be cleared from the system as readily. Ritonavir's inhibition of cP450 enzymes is the rationale behind taking both of these protease inhibitors simultaneously. Ritonavir will increase circulating saquinivir in the bloodstream. Unfortunately, without an understanding of proper dosage, this combination can be lethal. Studies are being conducted to determine the levels and concentration necessary for these two drugs to be taken together.
Consuming the following foods daily would be helpful to ensure proper Phase II detoxification; foods high in glutathione, sulfur containing amino acids, protein, and vitamins, especially B and C. Glutathione rich foods include asparagus, walnuts and avocados. Foods high in sulfur containing amino acids include red peppers, onions and garlic, and cruciferous vegetables (to be eaten moderately). Some foods with B vitamins are yeast, whole grains, animal products and beans. Vitamin C are peppers and cabbage. Again, supplementation is useful to ensure no deficiencies are occurring. Yet, supplementation should never be used as a means of ignoring healthy eating habits.
Included in a healthy diet for the liver would be herbs and vegetables that are known to stimulate liver detoxification and cleansing. Such vegetables that are known to stimulate liver detoxification and cleansing. Such vegetables are beets, artichokes, radishes, carrots and baby dandelion greens. As a rule of thumb, dark leafy green and yellow vegetables have healing properties for the liver and should be consumed often. Licorice root contains the chemical compound glycyrrthitinic acid which accords protection for the liver. Licorice prevents destruction of the liver cells by toxins, decreases the production of free radicals and helps restore balance to the adrenal glands (helping those suffering from fatigue due to over exertion and stress). This herb can be added to the diet through teas made from the fresh root. A word of warning: Licorice root should not be used by those with pre-existing condition of hypertension as glycyrrhitinic acid is known to exacerbate this condition. Glycyrrhitinic acid does not raise the blood pressure of those individuals with normal levels. Deglycyrrhinated licorice root (DGL), however, does not provide the benefits for the liver listed above, and therefore should not be used with these goals in mind. The herb milk thistle (silybum marianum) contains the chemical silymarin which has been studied for its many healthy effects of the liver. Milk thistle is known to prevent liver cell destruction, enhance liver function, inhibit free radical damage in the liver, inhibit synthesis of inflammatory chemicals (prostaglandins) and promote protein synthesis of new liver cells. Studies have demonstrated milk thistle's ability to prevent liver necrosis (destruction of liver cells) from toxic chemicals, such as carbon tetrachloride, when administered intravenously. On the whole, adding milk thistle to your daily regime can have a major effect in preserving your liver cells and minimizing the toxic effects of many medications in addition to ritonavir. Milk thistle can be found in capsules as well as the seeds. If using capsules or tincture, look for standardized extract with at least 70% silymarin content. When using the seeds, these can be soaked in water or apple juice overnight, then crushed or blended in order to be consumed.
Drug therapy, regardless of its benefits, can be harsh on the body, especially the liver. Taking steps towards healing requires an examination of our behaviors, including our eating habits. Avoiding known carcinogens and stimulators of the MFOS, (smoking, alcohol, and charcoal foods), will only promote our well-being and health. The choices we make in our diets can positively affect our liver. Supplementation with antioxidants and B vitamins supports Phase II detoxification system. Adequate fiber in the diet ensures that toxins in the bile are removed effectively. As a basic rule, a diet high in fresh vegetables and fruits (particularly yellow-green vegetables and fruits),and whole grains has a protective affect on the liver. The goal is balance.
About The Author
Dr. Brad S. Lichtenstein is a licensed naturopathic physician in private practice in Seattle and is a member of STEP's Scientific Review Committee.
Anderson, K. E. and Kappas, A. Dietary Regulation of Cytochrome P450. 1991. Annual Review Nutrition, 11: 141-167.
ICAAC Update
by Brian Coppedge
The 36th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held September 15-18, 1996 in New Orleans. Following so closely after the XI International AIDS Conference, there was speculation that very little new information about HIV/AIDS would be presented in New Orleans; this proved not to be true. New information about the clinical benefits of lamivudine (3TC), the use of ritonavir and saquinavir in combination, and information about a promising new protease inhibitor were all presented at ICAAC.
Clinical Benefit of 3TC StudiedDr. Julio Montaner of Saint Paul's Hospital in Vancouver B.C. presented results of the CAESAR (Canada, Australia, Europe and South Africa) study which sought to compare the efficacy and safety of adding 3TC, 3TC plus Loviride, (an experimental non-nucleoside reverse transcriptase inhibitor under development in Europe but not yet available in the US), or a placebo to the participants current antiretroviral regimen. The CAESAR trial was a large trial of 1800 participants with CD4 counts between 25 and 250. All trial participants were already receiving either zidovudine (AZT) monotherapy, or AZT plus didanosine (ddI), AZT plus zalcitabine (ddC). Trial participants were separated into three separate arms. After 52 weeks of the trial all participants were offered open-label 3TC plus Loviride.
The study was stopped and unblinded following a Data Safety Monitoring Board analysis on July 5, 1996, because the trial data showed a significant difference between the three arms and it was determined no further data would change the results. The rate of disease progression to an AIDS-defining illness was: 17% for the placebo arm; 9% for the 3TC group, and 8% for the 3TC plus loviride group. Death rates in the trial were: 4.6% for the placebo arm: 2.4% for the 3TC arm, and 2.7% for the 3TC plus loviride group. This study determined that adding 3TC to these existing treatments led to a 54% reduction in AIDS-defining illnesses, and a 53% reduction in the risk of death for the trial participants. Adding 3TC to already existing combination therapy did not appear to increase toxicity and seemed to be well-tolerated by the participants. The addition of loviride did not appear to add any benefit to the 3TC enhanced treatments. The purpose of this trial was not to measure the clinical benefit of loviride. Further trials are necessary to evaluate loviride's efficacy.
Ritonavir and Saquinavir in CombinationIn Vancouver, early data (only six weeks on trial) was presented that hinted to the possible advantages of using ritonavir and saquinavir in combination. The two protease inhibitors are being studied in combination because ritonavir can increase the blood levels of saquinavir up to 40 times. Additionally they have different toxicity's, and may have different resistance mutation patterns.
The study was an uncontrolled, open-label study which allowed participants to know which therapy they were receiving. Participants had CD4 counts between 100 and 500 and none were allowed to have taken any protease inhibitors previously. In addition, to be included in the trial, people had to discontinue all antiretroviral therapy for at least two weeks before starting on the new combination. The study divided the 136 volunteers into four arms: 400 mg ritonavir plus 400 mg saquinavir twice daily; 600 mg ritonavir plus 400 mg saquinavir twice daily; 400 mg of ritonavir plus 400 mg of saquinavir three times a day; 600 mg of ritonavir plus 600 mg of saquinavir twice daily.
After 12 weeks, the first two arms had a combined median reduction in viral load of 2.97 logs (a 99.9% reduction) and CD4 increase of 95. 75% of the participants in the first two arms saw their viral loads decrease to undetectable level ( below 200 copies). This same group of participants had been reported as having a 2.4 log (99.6%) drop after six weeks of the combination therapy. Only four people from these two arms had to discontinue therapy because of side effects ( one in the first arm and three in the second).
The third and fourth arms of the trial (which used high dosages) were started only after the initial lower dosage trials proved to be safe. After 6 weeks of the higher dosages, the median viral load dropped by 2.14 logs (99.3) and the median CD4 counts increased by 75 cells. The arm which received 400 mg of both ritonavir and saquinavir three times a day was not well-tolerated; eight of the participants in this arm had to discontinue treatment due to adverse side effects. The arm with 600 mg of ritonavir plus 600 mg of saquinavir was well tolerated and none of the participants in this arm had to discontinue therapy.
141W94 (Glaxo Wellcome): A New Protease InhibitorGlaxo Wellcome is developing a new protease inhibitor, 141W94, which it has licensed from the biotech firm Vertex. The initial study was aimed at determining the safety and maximal antiviral activity of different dosages of 141W94. This new drug seems quite promising for a few reasons: Initial data shows that it is synergistic with reverse transcriptase inhibitors, it is water soluble and therefore quite well-absorbed into the blood system, and in animals models, higher levels of the drug were seen in brain tissue than in the blood.
Antiretroviral activity was seen in the trial which was relatively small, enrolling 42 people in four separate arms. Participants CD4 counts ranged from 150 to 400 cells/ mm3 and had a median viral load of 483,000 viral copies/ml. Each arm consisted of about ten people who received either 300 mg of 141W94 twice a day, 300 mg three times a day, 900 mg twice a day or 1,200 mg twice a day. The study offered 141W94 monotherapy only, and none of the participants were allowed to have taken any protease inhibitors previously. The highest dose group saw a median increase in CD4 counts of 110 cells and a decrease in viral load of 1.95 log. The 900 mg group had a median CD4 increase of only 35 cells, had a decrease in viral load of 1.69 logs. The results of the lower dose arms were not quite as impressive. Volunteers taking 300 mg of 141W94 twice a day experienced only a .53 log reduction in viral load and an increase of 64 CD4 cells. Those who took 300 mg three times a day had CD4 increases of 84 cells and a viral load reduction of 1 log. 141W94 was generally well-tolerated, although about 10% of the participants reported side effects which included, headaches, loose stools and nausea.
Information presented at ICAAC continues to provide encouragement for people living with HIV/AIDS. The CAESAR study results confirm the clinical benefits of adding 3TC to existing antiretroviral treatments, ritonavir and saquinavir appear to be another strong combination that can be used to slow the replication of the virus and 141W94 is just one of many anticipated new protease inhibitors in development. Although the news from New Orleans was not as dramatic as that from Vancouver, important new information was made available.
Brian Coppedge is the Treatment Information Specialist for STEP.


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Fitness part deux
Hi there, Tech Savvy fans! Thanks for joining us again. As promised, this week continues our review streak. This week we are going to take a look at another great fitness tracking accessory, the UP by Jawbone. On loan from my friends at Verizon Wireless, the UP was designed to work with smartphones and devices like my HTC DNA and the iPad.
Step it UP
Jawbone, long-time smartphone accessories makers, has a history of making high quality products for affordable prices. Typically they are known for their Bluetooth headsets, their headsets are synonymous with high quality, durable, user friendly headsets and they continue to produce those. With the UP, they stepped out of their comfort zone and created a state of the art fitness tracker for everyday use.
The UP is a wrist worn device, which sets it apart from other devices new on the market, like my FitBit. Unlike a watch, the UP doesn't have a clasp. Instead it relies on a pre-formed shape that uses pressure to hold it onto your wrist. Made of a rubberized vinyl material it's pretty comfortable to wear, and it weighs hardly anything.
The UP tracks your steps walked, your sleep patterns and can also track your food and beverage intake. The device itself only tracks your steps and sleep. It uses accelerometer technology to gauge your step count and by holding in the button you activate or deactivate the sleep timer. For the rest of the information you enter that into the partner app that is available for free from the Android Market and the App Store.
After using it for a couple of weeks, I can honestly say I really enjoy the device. It had easy to follow instructions, seemed to track well and was easy to access. It was also interesting to me to compare it to the results that I got from my FitBit, just to see if they were accurate. I'm happy to say the both devices tracked similarly and neither had large discrepancies from the other.
Some things I like about the UP...
One of the main things I like about the UP was that I could wear it on my wrist. With my FitBit, I have to put it on the edge of my pocket and it tends to get caught on stuff and I worry that if it fell off I might not notice. With the UP I can always tell if I've got it on me. Another feature I liked is the lack of display on the tracker. I know, it sounds weird, right? If I am tracking my steps wouldn't I want to see how many steps I've taken? Yes, but at the same time I find that I obsess over my FitBit and I'm constantly checking how many steps I've taken that day and the UP eliminates that issue. Another feature that may appeal to some users is that the UP syncs with your device just by plugging it into the headphone jack. There are actually a couple benefits to this, not having to worry about pairing via Bluetooth and that you can sync it anytime you like.
Some of the things I'm not a huge fan of...
Ironically one of the main things I like about the UP is also one of the things I dislike about it. Although it is convenient to have it wrist worn, because it doesn't latch like a watch it makes it easy to catch on my coat, shirts, things I walk past. Now, that being said, it did not dislodge easily and for folks without an 8 month old that grabs onto anything within reach, you're probably fine.
Another aspect I took into account was the app itself. And it's not to say that the UP's app wasn't done well but my FitBit app was much more robust and was able to track more with the device itself — like calories burned, flights of stairs, etc.
Overall, the UP is a great product. It seems accurate, it's easy to use and it has a great set of features. I see it as something for someone looking into the fitness tracking habit, or for those that really don't want to deal with a clip on product. It worked great with my 4G LTE, Verizon powered, smartphone and it was a nice check to see if the FitBit was tracking with the same consistency.
Bottom line: if you can't bring yourself to get something as small as a FitBit, you don't like relying on Bluetooth, or if you just like being able to update on the go directly to your smartphone, the UP is a great choice. Check one out if you have a chance, and check our website in the coming week and I'll be posting a video so you can see a little of what I'm talking about here.
I read an article the other day about how, in anticipation of Google Glass, some lawmakers are already looking at preemptive bans on using them while driving. The head worn Glass is supposed to be a peripheral device that will place a screen in front of the user's eye and allow them to see text messages, emails and video without having to use their device. Preliminary specs set Glass at having 16 GB of internal storage, a 5 MP camera and all the features of a second tier phone (think the models from a couple years ago).
You may have seen media reports of Glass in action on the fashion runways, or at certain A-list Hollywood parties and it is slated for release to the general public near the end of 2013. This has folks worried it will take distracted driving to a whole new level — cat videos causing 10-car pileups on the interstate and imagine the tragedy of actually being a first hand witness to a car accident with the occupants of that vehicle?
I'm not saying I'm perfect, or even acceptable at eliminating my driver induced distractions when I drive but it's time that people start using some common sense. Time and again it's been shown that using devices, like smartphones, is just as distracting as driving while eating and even while driving drunk. There are a plethora of apps and programs available now that eliminate a lot of the distractions from your smartphone while you're in the car, and we all need to start using them. There are also shortcuts you can use to take the challenge of remembering. NFC can be used to activate programs now when you step into your vehicle, and there are apps that will automatically reply with texts while you are driving.
We need to start making a conscious effort to be better drivers and start paying better attention to our driving and less to our devices. We shouldn't need laws for things that should be common sense. Especially with this wonderful, wintery, spring we're having so far. Stay safe out there!


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BSEB 12th Commerce Result
2019/2020 www.Biharboard.net
Download Bihar board Result
2019/2020 Check Result Name Roll no wise 12th Commerce Result BSEB 10+2 result.
The Bihar School Examination Board is established for holding and conducting an examination at the end of the Secondary School stage, for prescribing course of studies for such examination and for carrying out such other objects and duties as may be considered necessary for the purpose as stated in the Act, Rules and Regulations of the Board.BSEB 12th Commerce Result
Bihar School Examination Board Recently Published the Result of 12th Science Class On 16.05.
2019/2020. Passing percentage this year is recorded at 91.87 compared to 91.36 of last year where 3,32,650 have managed to clear the examinations out of total students appeared in the Science stream exams.
Bihar Board 12th Commerce Result will be Declared Very Soon. So keep watching it @ www.biharboard.net.
How To Download Bihar Board 12th Commerce Result
All of the Students who are Waiting for the latest Result of Bihar Board 12th Commerce Result they can Download their Result by the Visiting of Official website Of Bihar Board www.biharboard.net. OR www.indiaresults.com.


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PLAINVIEW – Like any typical afternoon in Wayland Baptist University's Hutcherson Center, the Flying Queens basketball team is hard at work. The Queens rotate in and out of defensive drills as the coach pushes them to improve their positioning and footwork.
Back-and-forth they go, taking turns trying to break down their teammate's defense, then rotating to the defensive side of the ball to try and stop the next Queen in line. Nothing flashy, just hard work.
Suddenly Nikki Wallace stops. She steps out of line and hurries over to a recruit who is working out with the team. As the drill continues she pulls the recruit aside to explain the technique. As the drill rotates back to Wallace's side of the floor, coach waits a moment while his point guard finishes making her point. Wallace quickly jumps back in line and the drills commence.
While the break in action momentarily disrupted the rhythm of the drill, you won't hear head coach Will Flemons complaining. In fact, that type of leadership is what he expects out of the junior business major from Haskell.
"The point guard is one of the hardest positions on the floor to play," Flemons said. "(Nikki) has to be an extension of the coach. If the offense is not running smoothly, we turn to her first, before we do anything else."
Wallace was thrust into the starting point guard position last year when the team's leading scorer, Cassie Birkenfeld, was lost for the season due to a knee injury. Wallace filled in nicely and has grown into her leadership role. In a season that has already seen its share of ups and downs for the Queens (3-3), the quiet, unassuming point guard is the one player Flemons has been able to count on night in and night out.
"Right now, Nikki is kind of our constant," Flemons said. "She has been playing great defense. She has really done a great job of getting us in our offense. She is running our primary and secondary systems and doing a ton of good things."
At 5-6, Wallace is the smallest player on the Queens' roster, but she is carrying a tremendous load. Not only has she shouldered the responsibility of the team and maintained her high academic standards, but Wallace has faced some personal trials this year.
Wallace said she was raised in a strong Christian home with a family that is close and cares for each other. Earlier this year, her sister suffered a miscarriage at five months pregnant. Then, a cousin died while on a family vacation from complications of an enlarged heart and a few months ago, Wallace's aunt passed away after suffering a stroke.
"It's been a hard year," said Wallace, who missed an annual family gathering while on a road trip with the Queens. She said every year between Thanksgiving and Christmas her family gathers for a joint holiday celebration at her grandparents' house. Although she missed the gathering this year, she said it was hard on her family.
Still, the young woman has held herself together and met each complication and challenge head on.
"I've tried to stay with it," she said. "Just keep playing and keep my grades up. I've been doing as much as I can, working hard and praying. That's all I can do."
Wallace's hard work is paying off on the court. She is averaging nearly seven points, three rebounds and more than five assists a game. She has a 2-to-1 assist to turnover ratio and she has stolen the ball 10 times in the team's first six games. Still, Flemons wants to see more from her.
"I would love for her to be more vocal," Flemons said. "She does everything good, but I need her to step up and be more vocal because everybody on the team respects her."
It's a criticism the soft-spoken Wallace has heard before.
"(Coach Flemons) tells me that every single day," Wallace said. "My high school coach (Melynn Hunt) always told me that. I never said a word.
"But I'm trying …" Wallace grinned. "I've gotten better in practice. Every once in awhile I try to work with somebody, or I'll tell everybody to work hard … I'm trying."
Wallace has whole-heartedly accepted her role as a leader and is excited about what the remainder of the season holds for her team. Although the Queens are young, Wallace said they have the potential to be better than last year's squad that finished 18-11 overall and 11-7 in the Sooner Athletic Conference, earning a trip to the NAIA national tournament.
"I think we have better athletes this year," Wallace said. "We have better team communication on and off the court. Last year that really bothered us. We play a lot better as a team this year than we did last year."
Wayland opens its tough conference schedule on Jan. 3 when the Queens travel to Lubbock to take on rival Lubbock Christian University at 6 p.m. in the Rip Griffin Center. It's one game that Wallace is looking forward to.
"We are pretty big rivals," she said. "We will not lose to LCU, I can promise you that ... even if they have to drag me off the floor."
Wallace said the early part of the season has been kind of "rocky" as the Queens try to work new players into the system, and with the loss of junior Rachel Smith to injury last week, things will have to change even more. But she is ready for the challenge and she knows much of the team's success or failure will fall on her.
"It's pressure on your shoulder, but somebody has to do it," Wallace grinned. "I like it … I love it!"


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A fractured clavicle in the newborn is a broken collar bone in a baby that was just delivered.
Alternative Names
Fractured collar bone – newborn
A fracture of a newborn's collar bone (clavicle) can occur during a difficult vaginal delivery.
The baby will not move the painful, injured arm. Instead, the baby will hold it still against the side of the body. Lifting the baby under the arms causes the child pain. Sometimes the fracture can be felt with the fingers, but usually the problem cannot be seen or felt.
Within a few weeks, a hard lump may develop where the bone is healing. This lump may be the only sign that the newborn had a broken collar bone.
Exams and Tests
A chest x-ray will show whether or not there is a broken bone.
Generally, there is no treatment other than lifting the child gently to prevent discomfort. Occasionally, the arm on the affected side may be immobilized, most often by simply pinning the sleeve to the clothes.
Outlook (Prognosis)
Full recovery occurs without treatment.
Possible Complications
There are usually no complications. Because infants heal well, it may be impossible (even by x-ray) to tell that a fracture occurred.
When to Contact a Medical Professional
Call for an appointment with your health care provider if your baby acts uncomfortable when you lift him or her.


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The Genetics of CF
The Genetics of Cystic FibrosisCystic fibrosis (CF) is a genetic disease. This means that CF is inherited. A child will be born with CF only if two CF genes are inherited - one from the mother and one from the father. A person who has only one CF gene is healthy and said to be a "carrier" of the disease. A carrier has an increased chance of having a child with CF. This type of inheritance is called "autosomal recessive." Autosomal means that the gene is on one of the first 22 pairs of chromosomes which do not determine gender, so that the disease equally affects males and females. "Recessive" means that two copies of the gene, one inherited from each parent, are necessary to have the condition. Once parents have had a child with CF, there is a one in four, or 25 percent, chance with each subsequent pregnancy for another child to be born with CF. This means that there is a three out of four, or 75 percent chance, for another child to not have CF.
The birth of a child with CF is often a total surprise to a family, since most of the time there is no previous family history of CF. Many autosomal recessive conditions occur this way. Since both parents are healthy, they had no prior knowledge that they carried the gene, nor that they passed the gene to the pregnancy at the same time.
Genes are founds on structures in the cells of our body called "chromosomes." There are normally 46 total, or 23 pairs of chromosomes in each cell of our body. The seventh pair of chromosomes contains a gene called the CFTR (cystic fibrosis transmembrane regulator) gene. Mutations or errors in this gene are what cause CF. This gene is quite large and complex. Over 1,000 different mutations in this gene have been found which cause CF.
The risk for having a mutation in the gene for CF depends on your ethnic background (for persons without a family history of CF):
Testing for the CF gene can be done from a small blood sample or from a "cheek swab," which is a brush rubbed against the inside of your cheek to obtain cells for testing. Laboratories generally test for the most common mutations, and most labs test for anywhere from 30 to 100 total mutations. The detection rate depends on the person's ethnic background. In general, the detection rate for the Caucasian population is around 90 percent, 97 percent or more for the Ashkenazi population, 57 percent for Hispanics, 75 percent for African-Americans, and 30 percent for Asians. The detection rate differs because CF is more common in certain geographical areas and certain populations of the world. The diagnosis is confirmed by another test call the sweat chloride test.
There are many people with CF whose mutations have not been identified. In other words, all of the genetic errors that cause the disease have not been discovered. Because not all mutations are detectable, a person can still be a CF carrier even if no mutations were found by carrier testing.
Testing for the CF gene is recommended for anyone who has a family member with the disease, or whose partner is a known carrier of CF or affected with CF.
Click here for a handout on the Genetics of Cystic Fibrosis from the CF Foundation.


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The second part of the first session of the Ad Hoc Working Group on the Durban Platform for Enhanced Action (ADP 1-2) was held in conjunction with the eighteenth session of the Conference of the Parties at the Qatar National Convention Centre in Doha, Qatar.
The conclusions adopted by the ADP at the second part of its first session are contained in the report on the session.
Decision 2/CP.18 (Advancing the Durban Platform)
Reflections on the Doha session and the year ahead. Note by the Co-Chairs of the ADP
ADP Roundtables under Workstreams 1 and 2
The Co-Chairs of the ADP continued the rich exchange that was initiated in the roundtable setting in Bangkok, with the aim of building upon and advancing the discussions under both workstreams. They focused the discussions on the topics specified in paragraphs 4 and 8 of their "reflection note" issued on 5 October. The Co-Chairs have issued summaries of the roundtables under both workstream.
Summary of the roundtable under workstream 1
Summary of the roundtable under workstream 2
View the webcasts here
Special Event
The ADP Co-Chairs convened a Special Event on Saturday, 1 December 2012, from 1:00-3:00 pm, to further engage observers in the work of the ADP by providing an opportunity for them to present their substantive ideas and engage in an in-depth discussion.
Presentation by Mr. Pan
Presentation by Mr. Bodansky
Presentation by Mr. Höhne
Presentation by Mr. Karmali
The Co-Chairs have prepared a summary of the Special Event.
Summary of the ADP Co-Chairs' special event
Follow this link to view the webcast.
All documentation relevant to the session including in-session documents is available on the PaperSmart portal.


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ESA assessing the situation to bring the Artemis satellite back into the right orbit
Ground controllers are evaluating possibilities to recover the mission of the Artemis telecommunications satellite, one of two spacecraft launched by a European Ariane 5 vehicle on Thursday, 12 July 2001 at 18:58 local time in Kourou, French Guiana , 23:58 (CEST), but that was left stranded in a lower than expected orbit due to a malfunction in the upper stage of the Ariane 5 launcher.
Analysis of the situation is continuing as the spacecraft has been put into a safe sun-pointing condition by ground controllers. The solar panels were partially deployed during the night and are powering the satellite correctly, as planned for the nominal mission. The satellite is fully under control and is being monitored via different ground stations all over the world. Artemis can remain in this safe condition for as long as it is needed to allow ground controllers to evaluate the best way to rescue the mission.
"Our ground controllers were ready for such an eventuality," said Gotthard Oppenhäuser, ESA Artemis Project Manager, speaking from the launch site in Kourou. "The team is well practised in reacting to all sorts of potential problems and we are confident that a good technical solution to the problem will be eventually found.
Thanks to the availability of the ion propulsion system for position–keeping manoeuvres, most of the chemical fuel on board the satellite can be used to raise its orbit to the right altitude. Experts are working out a strategy to make the best use of the available fuel".
The multi-purpose Artemis satellite – the precursor to new and advanced satellite communication services – is the most advanced telecommunications satellite yet developed by ESA.
A press conference is scheduled to be held in Kourou on Friday, 13 July at 10:00 Kourou time, 15:00 CEST.
For further information, please contact:
Franco Bonacina
ESA Communication Department
Media Relations Office
Tel: 0033 594 33 49 10


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Place the pStyle so the widest part is between your legs and centered under your urethra. Tilt the open end slightly down, relax, and pee. When finished peeing, pull the pStyle forward with a firm upward motion to remove any remaining drops.
The slick plastic of the pStyle sheds liquid easily. If available, wash the pStyle with soap and water, otherwise simply rinse. If neither is possible shake the pStyle vigorously – this removes most of the urine.
Read all our Frequently Asked Questions >>
The pStyle and the DivaCup are sold by The pStyle Company.


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M&S Collection
Wedge Heel Ankle BootsT02/5940A
M&S says
Our vegan wedge heel boots have been designed to be free of animal traces, while offering fabulous Insolia® technology for all-day comfort. These ladies' boots have a smooth and elegant design, with a lovely buckle accent and a secure and straightforward side zip fastening.
Product Details
Item details
- Heel Height for Ladies Size 4 Shoe: 74mm
- Product Style: Ankle boots
- Regular fit
- Zip fastening
- Insolia®
Care and Composition
- Upper: Textile
- Lining and Sock: Textile & other materials
- Outsole: Other materials
Returns & Refunds
35 days to return
You may return unused products within 35 days of purchase with a valid parcel summary document. Your items don't need to be in the original box or bag as long as they're securely packaged.
How to return
It's easy to return items to us in the UK. No need to purchase postage stamps from the post office. Simply print the returns label, attach it to the top of your parcel and insert the returns note in the parcel. We will automatically deduct the cost of return from your refund.
Free returns when you pay with PayPal Learn more
To print the returns label and return, simply click here.
Delivery Options
Standard Delivery: FREE over FR.100 (otherwise Fr.7), 4-5 working days. All duties and taxes included.
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We'd like your feedback
As a valued customer we would love to hear what you think of our website, and how we could improve our service to you? It only takes 3 minutes to participate.


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Fhaconline necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 70 diseños de 24 diseñadores freelance.
Fallbrook Heating and Air Conditioning
Fallbrook Heating and Air Conditioning Inc (FHAC) was started in 1972 by Ralph Wilson and his father. Together they provided the kind of home-town service you would expect from a local service based business, hence the name Fallbrook Heating and Air Conditioning.
We have over 36 years experience in the HVAC industry that allows us to draw upon decades of excellent service and thousands of satisfied customers in your area. We are a family owned and operated business and are now in our third generation of ownership.
Our audience are from 30-75 and are of a smal town mentality. They like using local business for all of their needs and are willing to pay a little more to help out the community.
They are mostly republican and are laid back on religion. Fallbrook is located in San Diego county in California and has beautiful weather year round.
Avocados are our claim to fame with us being the avocado capital of the world.
Here is our objective, our current logo does not portrait that we are a heating and air conditioning company at a glance.
We want people to know from our logo we are a heating and air conditioning company, but also keep our name in the logo to keep the established branding we have in Fallbrook.
You can use the acronym for Fallbrook Heating and Air Conditioning (FHAC) or the entire name itself, just as long as it is in the logo.
Our current logo is here: http://www.fhaconline.com
Here are more requirements for the logo:
1. Please do not use any cartoons or cheesy drawings.
2. It should be VERY PROFESSIONAL, this is a service based business and we go into peoples homes, this logo may be on our shirts, it has to look sharp.
3. DO NOT use stock images or clip art, must be of your own creation.
4. Please be creative with this, it should say to the customer: "This looks like cutting-edge, professional company that has been in business since 1972 and I'd love to have them come to my home!"
Stick with blues and reds.
Green may be doable too if done right.
Files we require:
Illustrator (.ai) CMYK
Layered Photoshop File (.psd) RGB
No JPG necessary.
Thank you for taking the time on this project, we appreciate your effort very much!
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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Build 17841 will be deployed to the PTR realms soon.
New Icons
Item Changes
Timeless Isle weapons were upgraded from 476 to 489 (example).
Strings Changes
Originally Posted by MMO-Champion
- BLIZZARD_STORE_CONFIRMATION_SERVICES - Services purchased will be accessible at the character select screen when processing has been completed.
- BLIZZARD_STORE_CONFIRMATION_SERVICES_EUR - Services purchased will be accessible at the character select screen when processing has been completed. |HurlIndex:21|h|cff006995Change your payment method|r|h
- BLIZZARD_STORE_CONFIRMATION_SERVICES_TEST - Services purchased here will use the Test Currency. You will not actually be charged.
- CHARACTER_UPGRADE_COMPLETE_LABEL - Character Boost Complete!
- FIXEDFUNCTION_UNSUPPORTED - This video card will not be supported in future versions of World of Warcraft. Please see http://nydus.battle.net/WoW/enUS/lau...on-unsupported for more information.
- CHARACTER_UPGRADE_PROFESSION_BOOST - Now notes that First Aid also receives a boost: Level 60+ characters will also receive a skill level boost to their primary professions and First Aid.
Spell Changes
Originally Posted by MMO-ChampionMounts
- Dread Raven Summons and dismisses an
Imperial Quilen. This mount changes depending on your Riding skill and location. Account wide. 1.5 sec cast.
Item Set Bonuses
- Fortitude Increases PvP Resilience by
Rogue (Forums, Talent Calculator)
- Nerve Strike A successful Kidney Shot or Cheap Shot also reduces the damage dealt by the target by 50% and healing done by the target by 10% for 6 sec after the effect fades. Rogue - LvL 30 Talent.
Warrior (Forums, Talent Calculator)
- Charge Charge to an enemy,
stunningit for 1.5 sec. Generates 20 Rage. 8-25 yd range. Instant. 20 sec cooldown. (Warbringer will become a 3 second stun in a future build - Source)