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Related quotes
"This is a crazy, crazy week. It's very hectic because lots of folks wait until the last minute to file. It's just human nature putting it off until the end."
"I voted for her because of her enthusiasm and [because] I know her from before, ... She has lots of integrity. I guess those are the most important things."
"There are lots of cops and robbers shows, but what attracted me to this part was that they've cut out all the jargon. There's no, 'Roger, Roger' or 'Over'. We simply answer the phone, 'Yeah, what do you want?'"


text: We are humbled, by FIAT's gesutre of inviting TFI, to be a part of the Inaguration of the All new 2013 FIAT Linea T-jet, which is happening in Mumbai right now. Stay tuned, for the coverage and live updates of the event. The new T-jet gets Door Visors and Boot Spoiler. The event has started moments ago. An introduction with a general statement about, the gradual reduction in the price difference between Diesel and Petrol. Growing trend towards petrol engines. C+ Segment: 51% Diesel and 49% Petrol market share as per statistics. 2013 T-Jet Engine Features: 114 PS @ 5000 RPM 207 NM @ 2200 RPM Highest torque offered in its segment. Around 30% more than the competition and more importantly at a much lower RPM. 15.7 kmpl ARAI Focus has been more on City driveability, more so importantly on Stop n Go traffic conditions. Comes in 3 Variants. Active, Dynamic and Emotion Active Feature List: ABS All 4 Disc brakes. 185mm GC Electric OVRM Auto On/Off Headlamps Rain Sensing Wipers * ABS+EBD Standard across all variants Dynamic Features List All features from Active + Blue n Me 15" Alloy Wheels Dual Airbags Emotion Features List: All Features of Dynamic + 16" Alloy Wheels 205/55 R16 tyres 190mm GC Leather Seats General Features 15000km Service Interval 3+2 yrs Warranty 57 Active Exlusive dealers 17 more coming up TOTAL 74 Exclusive Dealerships PRICING Mumbai Ex-showroom Prices Line T-jet Active : 7.87 Lakhs Line T-jet Dynamic : 8.73 Lakhs Line T-jet Emotion : 9.11 Lakhs Delhi Ex-showroom Prices Line T-jet Active : 7.6 Lakhs Line T-jet Dynamic : 8.4 Lakhs Line T-jet Emotion : 8.8 Lakhs Snippets The 1.4 Linea FIRE will not be discontinued as of yet. 2013 Line T-jet will be available across 8 Cities initially Delhi NCR Kolkata Mumbai Pune Bangalore Hyderabad Chennai Trivandrum

subset: commoncrawl


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Female entrepreneur fund 'can boost economy post-Brexit'
The co-founder of a new £10 million fund targeting Britain's female-led firms says women are key to solving the post-Brexit economic slump.
Debbie Wosskow, the chief executive and founder of home exchange platform Love Home Swap, told the Press Association that the current period of economic uncertainty was the perfect time to launch AllBright - a funding platform set to support Britain's female entrepreneurs.
"More than ever, businesses need support to weather the Brexit storm and ensure that they continue to thrive and deliver.
"And if we can fully engage women in starting those businesses, then that's great for the UK," Ms Wosskow said following the fund's launch on Monday.
She pointed to YouGov research commissioned and released by Facebook earlier this year, which showed that if every woman who was interested in running their own business was able to do so, it could inject an extra £10.1 billion into the British economy.
"It feels like it's a really important time to try and make the UK really good at this," Ms Wosskow said.
The fund - which was co-founded by Ms Wosskow and Hearst UK boss Anna Jones - aims to raise £10 million by year-end.
It already boasts backers including former Labour minister Lord Davies and Founders4Schools chair Sherry Coutu, both of which will sit on the fund's advisory board.
But Wosskow said that Allbright's angel platform stands to deploy "a lot more" than £10 million.
The angel network will be part of the fund's three-pronged support system, which will also offer a crowdfunding platform and access to "vital business resources and learning" through its AllBright Academy.
AllBright expects to fund its first batch of female-led businesses in the coming weeks.
Ms Wosskow said: "There is some exceptional female business talent in the UK just waiting to be discovered and accelerated."


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Saturday, July 20th was graduation day for Isaac. It was a very traditional ceremony dating back hundreds of years held in the beautiful Cambridge University Senate House. We watched as masters and doctoral candidates from King's College received their degrees, followed by members of Trinity College; there are 31 colleges in all and degrees were conferred in groups throughout the day, beginning with King's and Trinity.
We rode bikes into, around, and outside of town every day. Here we are in our dress clothes locking them up prior to Isaac's graduation.
Photos weren't allowed inside Senate House, another elegant Cambridge venue, this 1 completed in 1730. Isaac will receive his official diploma later but received this document at the day of graduation.
We gathered outside after the ceremony with some of Isaac's friends.
Looks like they stepped out of a Harry Potter story - Isaac, Nick, and Ben.
Silly poses - Isaac and Nick.
Leading the way to a café.
There was also a reception on 1 of the lawns at King's, a treat since generally only the fellows (professors) are allowed on the grass. Next came a really elegant luncheon at King's Hall.
Can you see the hidden doors? They lead to the fellows room.
Mariah and I went shopping for gifts and souvenirs. Here's what we got (the photo, not the hats).
This is the ornate main gate of St. John's College. We ran into Sarah, another friend of Isaac's, who attends St. John's and she offered to take us on a private tour which included climbing the narrow spiral steps to the top of St. John's Tower, the highest point in Cambridge.
Sarah had to hand over her St. John's member card to obtain the key to the tower.
Nice fit!
Nice gargoyles!
Nice views!
That is King's Chapel in the background.
(I will insert some hilarious jumping photos here when I get them from Sarah.)
Heading back down
Looks to me like Mariah and Greg are royalty.
Nick took us out for drinks before dinner,
then we headed to St. John's Chop House. We adopted Nick (Belgian by birth but raised in The Netherlands) since his parents were unable to attend.
How they served the beer
Congratulations, Isaac and friends! Happy trails!


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12 Coolest Grandmaa's You Would Have Ever Seen Around
Grandma's are usually old typical ladies who don't like to mess up things. That's at least how the world perceive them to be. But these coolest grandma's have broken all stereotypes. They seem like they have gone back to their young days and have awesome ways of handling things around them. Here are few statements which will make you believe that world is a different place now:
Courtesy: Whisper


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Wednesday 15 March 1972
It was Wednesday, under the sign of Pisces. The US president was Richard Nixon (Republican).
Famous people born on this day include Steve Danielson in Honolulu and Filip Dewulf.
In that special week of March people in US were listening to Heart Of Gold by Neil Young.
In UK Without You by Nilsson was in the top 5 hits.
Pink Flamingos, directed by John Waters, was one of the most viewed movies released in 1972
while The Winds Of War by Herman Wouk was one of the best selling books.
On TV people were watching Split Second.
If you liked videogames you were probably playing Empire or Hunt the Wumpus.
But much more happened that day: find out below..
You can also have a look at the whole 1972 or at March 15 across the years.
Old Newspapers
Have a look at the old newspapers from 15 March 1972 and get them!
TV Series
Which were the most popular TV series released in the last months ?
Which were the most popular movies released this week ?
Find out your future
Get a FREE Numerology report based on the digits of 15 March 1972!
Wish him/her..
Historical Events
Which were the important events of 15 March 1972 ?
- International Day Against Police Brutality
- Turkey buzzards return to Hinckley, Ohio.
- Blessed Arnicus of Averbode
- For corporations in the United States that use the calendar year as their fiscal year, the date on which the corporation must file its corporate income tax return
- Constitution Day in Belarus
- National holiday in Hungary celebrating the 1848 Revolution. (See also Public holidays in Hungary)
- World Consumer Rights Day [2]
- In Japan, Hounen Matsuri
- Saint Clemens Maria Hofbauer (died 1820)
- Saint Lucretia
- Saint Luise of Marillac
- In the Roman calendar, the Ides of March.
Famous Birthdays:
- Steve Danielson in Honolulu: Hawaii, USA; field hockey defender (Olympics-1996).
- Filip Dewulf: in Belgium; tennis star.
- Casey Cristin: Mizell; Miss South Carolina-USA (1997).
- David Rhodes: WLAF wide receiver (Rhein Fire).
- Oliver Gibson: NFL defensive tackle (Pittsburgh Steelers).
- Constantin : Liechtenstein royalty, the third son of Prince Hans-Adam II and Princess Marie. He married civilly in Vaduz on 14 May 1999 and religiously in Číčov, Slovakia, on 18 July 1999 Countess Marie Gabriele Franziska Kálnoky de Kőröspatak. They have three children.
- Mike Tomlin: American football coach
- Mark Hoppus: American musician (+44 and blink-182)
- Ben Hunt-Davis: English rower
- Darren Dunstan: Canadian stage and voice actor and voice director
- Holger Stromberg: German chef
Famous Deaths:
- Aleksandr Ivanovich Laktionov: Russian painter (Born 1910).
- NASA selects three-part configuration for Space Shuttle.
- Danish airliner hits mountain in Sheikdom of Oman killing 112.
- Assassination attempt on Governor George Wallace of Alabama.
Featured Contents
Would you like to write an original contribution on a topic related to this specific date and get featured on Takemeback.to ? Send us your proposal!
Music Charts
Which were the top hits in that special week of March 1972 ?
Top #10 songs in the USA
- Neil Young - Heart Of Gold
- America - A Horse With No Name
- Robert John - The Lion Sleeps Tonight (Wimoweh) (Mbube)
- Nilsson - Without You
- Bread - Everything I Own
- Paul Simon - Mother And Child Reunion
- Climax - Precious And Few
- Cher - The Way Of Love
- Donny Osmond - Puppy Love
- The Osmonds - Down By The Lazy River
Search For Your Ancestors
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...and if 15 March 1972 was your Birth Date then Join our Birthday Club!
Make this date unforgettable
Genealogy: find out your family heritage
Magazine Covers
What news were making the headlines those days in March 1972?
- Time: Uncle Sam with empty pockets
- SportsIllustrated: Sports Illustrated: no.8271
- Life: Marlon Brando
Which were the most popular books released in the last weeks ?
Remember when
What videogames would you be playing back in the days ?


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Inviato: Gio Ago 10, 2017 9:50 am
Oggetto: nike internationalist uk
Alright sneakerheads, it looks like Yeezy
nike internationalist uk
season will be coming around again next month with the release of the Solar Red-inspired Nike Air Foamposite Pro. Set to touch down on April 19, this highly anticipated yet highly criticized release has garnered quite a bit of attention since we first previewed it. Equipped with a black base, carbon fiber detailing and glow in the dark sole, will you be looking to cop these when they drop? Or do you think Nike is running the whole Yeezy look into the ground? Check out another look after the jump and be sure to sound off in the comments section below.
What do you get when you bring together a talented customizer, a pair of Air Yeezy s and a Oregon Ducks theme? The Nike Air Yeezy Oregon Ducks custom by JBF. Utilizing green and yellow, the uppers on
nike internationalist mens sale
the Air Yeezy Oregon Ducks features snake skin making them even more unique. JBF also has slapped the infamous O on the tongue. Last but not least horse hair has been placed on the strap and above the midsole. If you re interested in picking up the Oregon
nike internationalist women cheap
Ducks Air Yeezy custom head on over to JBF and drop him a line.
A new colorway of the Asics Gel Sight is scheduled to release this weekend in a color shade that is ideal for the Summer. Utilizing a suede and leather upper, grey suede dominates the majority of the shoe while white leather overlays can be seen on the branding stripes, midfoot, ankle and heel. Adding a slight touch of contrast is Blush Pink on the heel counter that runs down to a portion of the midsole. Lastly we see a white midsole and white
nike internationalist for sale
rubber outsole. Pick up your pristine Asics Gel Sight in Whisper Pink this weekend at select Asics retailers for $140.
Aside from its upcoming collaboration with fellow Japanese label, monkey time, the Asics Gel Sight is introduced in another colorway for S/S 2016. Dubbed, Whisper Pink, the low-top sneaker incorporates a variety of neutral tones across its suede and leather composition. A slightly biege/off-white hue is utilized for the suede component, while white is prominent on the leather overlays, particularly its distinctive formstripes on the side panels and heel counter. Blush pink adorns the rear section and portion of its midsole unit to coordinate with its respective theme, as a white rubber sole and matching laces finishes off the design. Retailing for a price tag of $140, you can purchase a pair at select Asics retailers on Saturday, June 11th.
We haven t seen an awful lot of the New Balance 997 lately, but with Fall season quickly approaching the premium runner brand is beginning to shelve out their season-inspired colorways. One of the newer NB 997 models that has surfaced is this Merlot colorway that uses a rich
nike internationalist mid online
and buttery suede throughout the majority of the upper. Contrasting the dark hits of burgundy are grey hits of mesh on the toe and around the ankle. Additional contrasting touches of black also make their way onto the eyelets, around the toe and on the heel counter. If you think the sneaker still didn t have enough color, New Balance decided to add orange on the branding on the tongue, heel and side panels. So if you re on the hunt for a fresh runner this Fall, look for this
nike air max 2015 mens black
Merlot New Balance 997 at select NB retailers now.
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Professionally Optimized Content
Edgar Allan SEO prides itself on our SEO writing service, SEO content, local SEO, small business SEO, unique content, and improving organic search results. Writing niche content is usually a difficult task, but with an Edgar Allan SEO writer, you can worry, nevermore.
The philosophy of SEO is similar to Poe's "Philosophy of Composition" in that the length should be short and concise, yet focus heavily on the keywords at hand. Secondly, the method should follow a pattern of selecting the most optimal path and target for the keywords used in your content. And thirdly, our SEO "Unity of Effect" is having a clear and concise conclusion of how the content is to be optimized and maintained to improve organic results in search engines.


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Click here to make an online transaction through our secure VCS gateway.
Gift of the Givers has begun its response to the recent storms in Cape Town and surrounds.
Gift of the Givers begins in Maitland with the distribution of 200 Shoprite-Checkers blankets to residents of informal shelters which have flooded and were damaged during the storm.Total Project Value: R16 300.00.
Gift of the Givers responded to 136 fire victims in 6th Avenue Kensington with:
Total Project Value: R37 415.95.
Read more
Gift of the Givers responds to calls for assistance to the community of Uitsig where 38 informal dwellings were destroyed by a fire that displaced 150 people.Gift of the Givers distributed 150 blankets and 80 mattresses to the fire victims.
Gift of the Givers distributed 1000 cans of juice and biscuits to the firemen and rescue teams who battled all day and night to douse the fire in Durban.
Total Project Value: R15 000.00
Total Project Value: R60 000.00.
Read more


text:
FOXBOROUGH, Mass. – Patriots coach Bill Belichick talked in detail about the evaluation process the team undertakes on each player before signing or drafting them, a practice that has been called into question in the wake of Aaron Hernandez's murder charge.
"As far as the whole process goes, I can tell you that we look at every player's history from the moment we start discussing it, going back to his family, where he grew up, what his lifestyle was like, high school, college experiences -- we evaluate his performance, his intelligence, his work ethic, his motivation, his maturity, his improvement, and we try to project that into our organization on a going-forward basis," Belichick explained Wednesday. "It combines a player's personal history, but it also has to project what we think, and how we think, he will be in our environment. Obviously this process is far from perfect, but it's one that we've used from 2000 until today. Unfortunately, this most recent situation with the charges that are involved is not a good one on that record.
"We'll continue to evaluate the way we do things and the way we evaluate our players," continued Belichick, who wore a blue Patriots pullover for the news conference and handed his visor to an assistant before approaching the podium. "We do it on a regular basis -- not just at the beginning when they come in. Personally, I'm challenged by decisions that affect the team on a daily basis, and I'm not perfect on that either. But I always try to do what I think is best for the football team.
"We spent a considerable amount of time evaluating our current players and educating them on not only football, but many other life experiences and off-field subjects. We stress high character, and we stress making good decisions. We'll continue to do this, and we'll work to do a better job of it as we go forward.
"We'll learn from this terrible experience we've had, and we'll become a better team from the lessons that we've learned. We have so many players on this team that work hard, that do the right thing, that set a great example of being a professional and being a solid representative of this team and this community."
Belichick said they evaluate every potential Patriot on an individual basis, a process for which he is the ultimate decision-maker.
"As the coach of the team, I'm primarily responsible for the people we bring into the football operation," he said. "Our players are generally highly motivated and gifted athletes that come from very different backgrounds. They've met many challenges along the way and have done things to get here -- sometimes they've made bad or immature decisions. But we try to look at every single situation on a case by case basis and try to do what's best for the football team and what's best for the franchise. Most of those decisions have worked out, but some don't."


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Quaint small town or bustling metropolitan city? Sault Ste. Marie is a bit of both. The "Soo" (as locals call it here) is a safe, friendly, community offering you a diverse experience to enhance your classroom learning. This spectacular border city has four seasons of outdoor adventure for all interests. Travel and fun are minutes away across the International bridge connecting to Sault, Michigan. With 75,000 people, we are small enough to be friendly, and large enough to be FUN!
The blend of professional and whimsical student and seeker comes to make this coffee, hockey, and pasta-loving town uniquely eclectic with a penchant for self-reinventing every few months. Drop into a Tim's to talk to the locals about just about any topic, and you'll come away with enough to write an award-winning short story or intriguing novel.
You'll hear how the city has a large and vibrant Italian contingent, but don't overlook the other cultural influences from European countries like Finland and Portugal, plus the growing number of Indian and Argentinian foreign nationals arriving to work at Essar Steel and Tenaris.
We have all the amenities and city-life attractions, and the most awe-inspiring scenic views and adventure recreation in the province. The breath-taking views found immediately north, east and west of town on the Great Lakes is what most people remember most about Sault Ste. Marie and area. With a large number of public beaches on beautiful pristine lakes that can be accessed for free, Sault Ste. Marie often has a lasting impact on those who travel this way, and sometimes those who have camped here in their youth find their way back here to study and work because of the stunning views found in nature.


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MOVIE SYNOPSIS [ General Audiences ] With a great performance of Gwendolyn Cheatham. (see full cast), this film directed by Vitaliy Versace was premiered in cinema in 2014. The feature film "All of Her" was produced in USA. You can watch All of Her online on TV cable or theaters with original audio in English at different dates. This film premiered in theaters in 2014.
Rating: 5 by 18 users./
Runtime: 90 minutes
Gwendolyn Cheatham ., Brian Abruzzi, Pierre Alati, Jen Bramlett, Cristee Brianas, Brian Briggs, Kristyn Cheatham, Nicholas Costello, Scott Deyling, Raymond Didpolite, Terrance Esarco, Michael Gamino, Gary Gansel, Kathleen Garcia and Victor Garcia.
Drama, Romantic.
90-minute film (full movie) directed by Vitaliy Versace.
The original audio of All of Her has dialogues in Dolby Digital, it was produced in USA.
It premiered in cinemas or television in 2014.
Screenplay written by Dave Matheny.
Vlad Opara.
Linda Weaver, George Anton, Vitaliy Pysmennyy, Raelynn Ibrahim, Vitaliy Versace, Paul Summers and Paul Gustovich.
This film was produced and / or financed by VersaceEntertainment.
Echo Bridge Home Entertainment.
Without commercial breaks, the full movie All of Her has a duration of 90 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in EnglishDolby Digital in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, All of Her in FULLTV Movies.


text:
Bon Courage Hillside Red 2012
The Cabernet Sauvignon grapes were carefully handpicked and selected from terroir specific vineyards to produce a premium quality wine. The grapes were picked at optimum ripeness to ensure soft round tannins and subtle ripe black fruit on the palate and rich, spicy flavours and smokiness on the nose. The use of oak maturation adds complexity and an extra dimension. Excellent to enjoy with food, this wine calls for good quality meat dishes, including steak, stews and roast. Excellent ageing potential.
20% off for any mixed 12
60% Cabernet Sauvignon, 40% Shiraz
Shiraz fermentation took place for 8-10 days on the skins.After the grapes were cold soaked for 2 days, yeast wasadded. Cabernet Sauvignon juice was separated from theskins and left to ferment dry in stainless steel tanks for 3 days.The wine was then oak matured in 2nd and 3rd fill French Oakbarrels for 12 months.


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Annual vaccination is the primary strategy for preventing complications of influenza virus infections. Antiviral medications with activity against influenza viruses are useful adjuncts in the prevention of influenza, and effective when used early in the course of illness for treatment. Four influenza antiviral agents are licensed in the United States: amantadine, rimantadine, zanamivir, and oseltamivir. Influenza A virus resistance to amantadine and rimantadine can emerge rapidly during treatment. Because antiviral testing results indicated high levels of resistance (413—416), neither amantadine nor rimantadine should be used for the treatment or chemoprophylaxis of influenza A in the United States during the 2007—08 influenza season. Surveillance demonstrating that susceptibility to these antiviral medications has been reestablished among circulating influenza A viruses will be needed before amantadine or rimantadine can be used for the treatment or chemoprophylaxis of influenza A. Oseltamivir or zanamivir can be prescribed if antiviral chemoprophylaxis or treatment of influenza is indicated. Oseltamivir is licensed for treatment of influenza in persons aged >1 year, and zanamivir is licensed for treating influenza in persons aged >7 years. Oseltamivir and zanamivir can be used for chemoprophylaxis of influenza; oseltamivir is licensed for use as chemoprophylaxis in persons aged >1 year, and zanamivir is licensed for use in persons aged >5 years.
During the 2007—08 influenza season, influenza A (H1N1) viruses with a mutation that confers resistance to oseltamivir were identified in the United States and other countries. As of June 27, 2008, in the United States, 111 (7.6%) of 1,464 influenza A viruses tested, and none of 305 influenza B viruses tested have been found to be resistant to oseltamivir. All of the resistant viruses identified in the United States and elsewhere are influenza A (H1N1) viruses. Of 1020 influenza A (H1N1) viruses isolated from patients in the United States, 111 (10.9%) exhibited a specific genetic mutation that confers oseltamivir resistance (417). Influenza A (H1N1) virus strains that are resistant to oseltamivir remain sensitive to zanamivir. Neuraminidase inhibitor medications continue to be the recommended agents for treatment and chemoprophylaxis of influenza in the United States. However, clinicians should be alert to changes in antiviral recommendations that might occur as additional antiviral resistance data becomes available during the 2008—09 influenza season (http://www.cdc.gov/flu/professionals/antivirals/index.htm).
Role of Laboratory Diagnosis
Influenza surveillance information and diagnostic testing can aid clinical judgment and help guide treatment decisions. However, only 69% of practitioners in one recent survey indicated that they test patients for influenza during the influenza season (418). The accuracy of clinical diagnosis of influenza on the basis of symptoms alone is limited because symptoms from illness caused by other pathogens can overlap considerably with influenza (26,39,40) (see Clinical Signs and Symptoms of Influenza).
Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunofluorescence assays (419). As with any diagnostic test, results should be evaluated in the context of other clinical and epidemiologic information available to health-care providers. Sensitivity and specificity of any test for influenza can vary by the laboratory that performs the test, the type of test used, the type of specimen tested, the quality of the specimen, and the timing of specimen collection in relation to illness onset. Among respiratory specimens for viral isolation or rapid detection of influenza viruses, nasopharyngeal and nasal specimens have higher yields than throat swab specimens (420). In addition, positive influenza tests have been reported up to 7 days after receipt of LAIV (421).
Commercial rapid diagnostic tests are available that can detect influenza viruses within 30 minutes (422,423). Certain tests are licensed for use in any outpatient setting, whereas others must be used in a moderately complex clinical laboratory. These rapid tests differ in the types of influenza viruses they can detect and whether they can distinguish between influenza types. Different tests can detect 1) only influenza A viruses; 2) both influenza A and B viruses, but not distinguish between the two types; or 3) both influenza A and B and distinguish between the two. None of the rapid influenza diagnostic tests specifically identifies any influenza A virus subtypes.
The types of specimens acceptable for use (i.e., throat, nasopharyngeal, or nasal aspirates, swabs, or washes) also vary by test, but all perform best when collected as close to illness onset as possible. The specificity and, in particular, the sensitivity of rapid tests are lower than for viral culture and vary by test (419,422—424). Rapid tests for influenza have high specificity (>90%), but are only moderately sensitive (<70%). A recent study found sensitivity to be as low as 42% in clinical practice (425). Rapid tests appear to have higher sensitivity when used in young children, compared with adults, possibly because young children with influenza typically shed higher concentrations of influenza viruses than adults (426). Since RT-PCR has high sensitivity to detect influenza virus infection compared to viral culture, rapid tests have lower sensitivity than viral culture when compared to RT-PCR.
The limitations of rapid diagnostic tests must be understood in order to properly interpret results. Positive rapid influenza test results are generally reliable when community influenza activity is high and are useful in deciding whether to initiate antiviral treatment. Negative rapid test results are less helpful in making treatment decisions for individual patients when influenza activity in a community is high. Because of the lower sensitivity of the rapid tests, physicians should consider confirming negative tests with viral culture or other means because of the possibility of false-negative rapid test results, especially during periods of peak community influenza activity. The positive predictive value of rapid tests will be lower during periods of low influenza activity, and clinicians should consider the positive and negative predictive values of the test in the context of the level of influenza activity in their community when interpreting results (424). When local influenza activity is high, persons with severe respiratory symptoms or persons with acute respiratory illness who are at higher risk for influenza complications should still be considered for influenza antiviral treatment despite a negative rapid influenza test unless illness can be attributed to another cause. However, because certain bacterial infections can produce symptoms similar to influenza, if bacterial infections are suspected, they should be considered and treated appropriately. In addition, secondary invasive bacterial infections can be a severe complication of influenza. Package inserts and the laboratory performing the test should be consulted for more details regarding use of rapid diagnostic tests. Additional updated information concerning diagnostic testing is available at http://www.cdc.gov/flu/professionals/labdiagnosis.htm.
Despite the availability of rapid diagnostic tests, clinical specimens collected in virus surveillance systems for viral culture are critical for surveillance purposes. Only culture isolates of influenza viruses can provide specific information regarding circulating strains and subtypes of influenza viruses and data on antiviral resistance. This information is needed to compare current circulating influenza strains with vaccine strains, to guide decisions regarding influenza treatment and chemoprophylaxis, and to formulate vaccine for the coming year. Virus isolates also are needed to monitor antiviral resistance and the emergence of novel human influenza A virus subtypes that might pose a pandemic threat. Influenza surveillance by state and local health departments and CDC can provide information regarding the circulation of influenza viruses in the community, which can help inform decisions about the likelihood that a compatible clinical syndrome is indeed influenza.
Antiviral Agents for Influenza
Zanamivir and oseltamivir are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses. The two medications differ in pharmacokinetics, adverse events, routes of administration, approved age groups, dosages, and costs. An overview of the indications, use, administration, and known primary adverse events of these medications is presented in the following sections. Package inserts should be consulted for additional information. Detailed information about amantadine and rimantadine (adamantanes) is available in previous ACIP influenza recommendations (427).
Indications for Use of Antivirals
Initiation of antiviral treatment within 2 days of illness onset is recommended, although the benefit of treatment is greater as the time after illness onset is reduced. Certain persons have a high priority for treatment (Box 3); however, treatment does not need to be limited to these persons. In clinical trials conducted in outpatient settings, the benefit of antiviral treatment for uncomplicated influenza was minimal unless treatment was initiated within 48 hours after illness onset. However, no data are available on the benefit for severe influenza when antiviral treatment is initiated >2 days after illness onset. The recommended duration of treatment with either zanamivir or oseltamivir is 5 days.
Evidence for the efficacy of these antiviral drugs is based primarily on studies of outpatients with uncomplicated influenza. When administered within 2 days of illness onset to otherwise healthy children or adults, zanamivir or oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day compared with placebo (143,428—442). Minimal or no benefit was reported when antiviral treatment is initiated >2 days after onset of uncomplicated influenza. Data on whether viral shedding is reduced are inconsistent. The duration of viral shedding was reduced in one study that employed experimental infection; however, other studies have not demonstrated reduction in the duration of viral shedding. A recent review that examined neuraminidase inhibitor effect on reducing ILI concluded that neuraminidase inhibitors were not effective in the control of seasonal influenza (443). However, lower or no effectiveness using a nonspecific (compared with laboratory-confirmed influenza) clinical endpoint such as ILI would be expected (444).
Data are limited about the effectiveness of zanamivir and oseltamivir in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases), or for preventing influenza among persons at high risk for serious complications of influenza. In a study that combined data from 10 clinical trials, the risk for pneumonia among those participants with laboratory-confirmed influenza receiving oseltamivir was approximately 50% lower than among those persons receiving a placebo and 34% lower among patients at risk for complications (p<0.05 for both comparisons) (445). Although a similar significant reduction also was determined for hospital admissions among the overall group, the 50% reduction in hospitalizations reported in the small subset of high-risk participants was not statistically significant. One randomized controlled trial documented a decreased incidence of otitis media among children treated with oseltamivir (437). Another randomized controlled study conducted among influenza-infected children with asthma demonstrated significantly greater improvement in lung function and fewer asthma exacerbations among oseltamivir-treated children compared with those who received placebo but did not determine a difference in symptom duration (446). Inadequate data exist regarding the efficacy of any of the influenza antiviral drugs for use among children aged <1 year, and none are FDA-licensed for use in this age group.
Two observational studies suggest that oseltamivir reduces severe clinical outcomes in patients hospitalized with influenza. A large prospective observational study assessed clinical outcomes among 327 hospitalized adults with laboratory-confirmed influenza whose health-care provider chose to use oseltamivir treatment compared to untreated influenza patients. The average age of adults in this study was 77 years, and 71% began treatment >48 hours after illness onset. In the multivariate analysis, oseltamivir treatment was associated with a significantly decreased risk for death within 15 days of hospitalization (odds ratio = 0.21; CI = 0.06—0.80). Benefit was observed even among those starting treatment >48 hours after symptom onset. However, oseltamivir treatment did not significantly reduce the duration of hospitalization or 30 day mortality after hospitalization. An additional 185 hospitalized children with laboratory confirmed influenza were identified during this study, but none received antiviral treatment and no assessment of outcomes based on receipt of antiviral treatment could be made (95). A retrospective cohort study of 99 hospitalized persons with laboratory-confirmed influenza administered who received oseltamivir that was conducted in Hong Kong reported that persons who received oseltamivir treatment >48 hours from illness onset had a median length of stay of 6 days compared to 4 days for persons who received oseltamivir within 48 hours of symptom onset (p<0.0001) (447). However, additional data on the impact of antiviral treatment on severe outcomes are needed.
More clinical data are available concerning the efficacy of zanamivir and oseltamivir for treatment of influenza A virus infection than for treatment of influenza B virus infection. Data from human clinical studies have indicated that zanamivir and oseltamivir have activity against influenza B viruses (437,448—451). However, an observational study among Japanese children with culture-confirmed influenza and treated with oseltamivir demonstrated that children with influenza A virus infection resolved fever and stopped shedding virus more quickly than children with influenza B, suggesting that oseltamivir might be less effective for the treatment of influenza B (452).
The Infectious Diseases Society of America and the American Thoracic Society have recommended that persons with community-acquired pneumonia and laboratory-confirmed influenza should receive either oseltamivir or zanamivir if treatment can be initiated within 48 hours of symptom onset. Patients who present >48 hours after illness onset are potential candidates for treatment if they have influenza pneumonia or to reduce viral shedding while hospitalized (453). The American Academy of Pediatrics recommends antiviral treatment of any child with influenza who is also at high risk of influenza complications, regardless of vaccination status, and any otherwise healthy child with moderate-to-severe influenza infection who might benefit from the decrease in duration of clinical symptoms documented to occur with therapy (454).
Chemoprophylactic drugs are not a substitute for vaccination, although they are critical adjuncts in preventing and controlling influenza. Certain persons are at higher priority for chemoprophylaxis (Box 4); however, chemoprophylaxis does not need to be limited to these persons. In community studies of healthy adults, both oseltamivir and zanamivir had similar efficacy in preventing febrile, laboratory-confirmed influenza illness (efficacy: zanamivir, 84%; oseltamivir, 82%) (455,456). Both antiviral agents also have prevented influenza illness among persons administered chemoprophylaxis after a household member had influenza diagnosed (efficacy: zanamivir, 72%—82%; oseltamivir, 68%—89%) (455—459). Studies have demonstrated moderate to excellent efficacy for prevention of influenza among patients in institutional settings (460—465). For example, a 6-week study of oseltamivir chemoprophylaxis among nursing home residents demonstrated a 92% reduction in influenza illness (464). A 4-week study among community-dwelling persons at higher risk for influenza complications (median age: 60 years) demonstrated that zanamivir had an 83% effectiveness in preventing symptomatic laboratory-confirmed influenza (465). The efficacy of antiviral agents in preventing influenza among severely immunocompromised persons is unknown. A small nonrandomized study conducted in a stem cell transplant unit suggested that oseltamivir can prevent progression to pneumonia among influenza-infected patients (466).
When determining the timing and duration for administering influenza antiviral medications for chemoprophylaxis, factors related to cost, compliance, and potential adverse events should be considered. To be maximally effective as chemoprophylaxis, the drug must be taken each day for the duration of influenza activity in the community. Additional clinical guidelines on the use of antiviral medications to prevent influenza are available (453,454).
Persons at High Risk Who Are Vaccinated After Influenza Activity Has Begun
Development of antibodies in adults after vaccination takes approximately 2 weeks (369,370). Therefore, when influenza vaccine is administered after influenza activity in a community has begun, chemoprophylaxis should be considered for persons at higher risk for influenza complications during the time from vaccination until immunity has developed. Children aged <9 years who receive influenza vaccination for the first time might require as much as 6 weeks of chemoprophylaxis (i.e., chemoprophylaxis until 2 weeks after the second dose when immunity after vaccination would be expected). Persons at higher risk for complications of influenza still can benefit from vaccination after community influenza activity has begun because influenza viruses might still be circulating at the time vaccine-induced immunity is achieved.
Persons Who Provide Care to Those at High Risk
To reduce the spread of virus to persons at high risk, chemoprophylaxis during peak influenza activity can be considered for unvaccinated persons who have frequent contact with persons at high risk. Persons with frequent contact might include employees of hospitals, clinics, and chronic-care facilities, household members, visiting nurses, and volunteer workers. If an outbreak is caused by a strain of influenza that might not be covered by the vaccine, chemoprophylaxis can be considered for all such persons, regardless of their vaccination status.
Persons Who Have Immune Deficiencies
Chemoprophylaxis can be considered for persons at high risk who are more likely to have an inadequate antibody response to influenza vaccine. This category includes persons infected with HIV, particularly those with advanced HIV disease. No published data are available concerning possible efficacy of chemoprophylaxis among persons with HIV infection or interactions with other drugs used to manage HIV infection. Such patients should be monitored closely if chemoprophylaxis is administered.
Other Persons
Chemoprophylaxis throughout the influenza season or during increases in influenza activity within the community might be appropriate for persons at high risk for whom vaccination is contraindicated, or for whom vaccination is likely to be ineffective. Health-care providers and patients should make decisions regarding whether to begin chemoprophylaxis and how long to continue it on an individual basis.
Antiviral Drug-Resistant Strains of Influenza
Oseltamivir and Zanamivir (Neuraminidase Inhibitors)
Among 2,287 isolates obtained from multiple countries during 1999—2002 as part of a global viral surveillance system, eight (0.3%) had a more than ten fold decrease in susceptibility to oseltamivir, and two (25%) of these eight also were resistant to zanamivir (467). In Japan, where more oseltamivir is used than in any other country, resistance to oseltamivir was identified in three (0.4%) A (H3N2) viruses in 2003—04, no A (H3N2) viruses in 2004—05, and no A (H3N2) viruses in 2005—06 influenza seasons. In 2005—06, four (2.2%) A (H1N1) viruses were identified to have oseltamivir resistance with a specific genetic marker (468). Neuraminidase inhibitor resistance remained low in the United States through the 2006—07 influenza season (CDC, unpublished data, 2007).
In 2007—08, increased resistance to oseltamivir was reported among A (H1N1) viruses in many countries (469,470). Persons infected with oseltamivir resistant A (H1N1) viruses had not previously received oseltamivir treatment and were not known to have been exposed to a person undergoing oseltamivir treatment (469,470). In the United States, approximately 10% of influenza A (H1N1) viruses, no A (H3N2) viruses, and no influenza B viruses were resistant to oseltamivir during the 2007—08 influenza season, and the overall percentage of influenza A and B viruses resistant to oseltamivir in the United States was <5%. No viruses resistant to zanamivir were identified (417). Oseltamivir or zanamivir continue to be the antiviral agents recommended for the prevention and treatment of influenza (418). Although recommendations for use of antiviral medications have not changed, enhanced surveillance for detection of oseltamivir-resistant viruses is ongoing and will enable continued monitoring of changing trends over time.
Development of viral resistance to zanamivir or oseltamivir during treatment has also been identified but does not appear to be frequent (450,471—474). One limited study reported that oseltamivir-resistant influenza A viruses were isolated from nine (18%) of 50 Japanese children during treatment with oseltamivir (475). Transmission of neuraminidase inhibitor-resistant influenza B viruses acquired from persons treated with oseltamivir is rare but has been documented (476). No isolates with reduced susceptibility to zanamivir have been reported from clinical trials, although the number of post-treatment isolates tested is limited (451,477). Only one clinical isolate with reduced susceptibility to zanamivir, obtained from an immunocompromised child on prolonged therapy, has been reported (451). Prolonged shedding of oseltamivir- or zanamivir-resistant virus by severely immunocompromised patients, even after cessation of oseltamivir treatment, has been reported (478,479).
Amantadine and Rimantadine (Adamantanes)
Adamantane resistance among circulating influenza A viruses increased rapidly worldwide over the past several years, and these medications are no longer recommended for influenza prevention or treatment, although in some limited circumstances use of adamantanes in combination with a neuraminidase inhibitor medication might be considered (see Prevention and Treatment of Influenza when Oseltamivir Resistance is Suspected). The proportion of influenza A viral isolates submitted from throughout the world to the World Health Organization Collaborating Center for Surveillance, Epidemiology, and Control of Influenza at CDC that were adamantane-resistant increased from 0.4% during 1994—1995 to 12.3% during 2003—2004 (480). During the 2005—06 influenza season, CDC determined that 193 (92%) of 209 influenza A (H3N2) viruses isolated from patients in 26 states demonstrated a change at amino acid 31 in the M2 gene that confers resistance to adamantanes (413,414). Preliminary data from the 2007—08 influenza season indicates that resistance to adamantanes remains high among influenza A isolates, with approximately 99% of tested influenza A(H3N2) isolates and approximately 10% of influenza A(H1N1) isolates resistant to adamantanes (CDC, unpublished data, 2008). Amantadine or rimantidine should not be used alone for the treatment or prevention of influenza in the United States until evidence of susceptibility to these antiviral medications has been reestablished among circulating influenza A viruses. Adamantanes are not effective in the prevention or treatment of influenza B virus infections.
Prevention and Treatment of Influenza when Oseltamivir Resistance is Suspected
Testing for antiviral resistance in influenza viruses is not available in clinical settings. Because the proportion of influenza viruses that are resistant to oseltamivir remains <5% in the United States, oseltamivir or zanamivir remain the medications recommended for prevention and treatment of influenza. Influenza caused by oseltamivir-resistant viruses appears to be indistinguishable from illness caused by oseltamivir-sensitive viruses (469). When local viral surveillance data indicates that oseltamivir-resistant viruses are widespread in the community, clinicians have several options. Consultation with local health authorities to aid in decision-making is recommended as a first step. Persons who are candidates for receiving chemoprophylaxis as part of an outbreak known to be caused by oseltamivir-resistant viruses or who are being treated for influenza illness in communities where oseltamivir-resistant viruses are known to be circulating widely can receive zanamivir. However, zanamivir is not licensed for chemoprophylaxis indications in children aged <5 years, and is not licensed for treatment in children aged <7 years (451). In addition, zanamivir is not recommended for use in persons with chronic cardiopulmonary conditions, and can be difficult to administer to critically ill patients because of the inhalation mechanism of delivery. In these circumstances, a combination of oseltamivir and either rimantadine or amantadine can be considered, because influenza A (H1N1) viruses characterized to date that were resistant to oseltamivir have usually been susceptible to adamantane medications (CDC, unpublished data, 2008). However, adamantanes should not be used for chemoprophylaxis or treatment of influenza A unless they are part of a regimen that also includes a neuraminidase inhibitor, because viral surveillance data has documented that adamantane resistance among influenza A viruses is common. Influenza B viruses are not sensitive to adamantane drugs.
Control of Influenza Outbreaks in Institutions
Use of antiviral drugs for treatment and chemoprophylaxis of influenza is a key component of influenza outbreak control in institutions. In addition to antiviral medications, other outbreak-control measures include instituting droplet precautions and establishing cohorts of patients with confirmed or suspected influenza, re-offering influenza vaccinations to unvaccinated staff and patients, restricting staff movement between wards or buildings, and restricting contact between ill staff or visitors and patients (481—483). Both adamantanes and neuraminidase inhibitors have been successfully used to control outbreaks caused by antiviral susceptible strains when antivirals are combined with other infection control measures. (460,462,464,484—488).
When confirmed or suspected outbreaks of influenza occur in institutions that house persons at high risk, chemoprophylaxis with a neuraminidase inhibitor medication should be started as early as possible to reduce the spread of the virus (489,490). In these situations, having preapproved orders from physicians or plans to obtain orders for antiviral medications on short notice can substantially expedite administration of antiviral medications. Specimens should be collected from ill cases for viral culture to assess antiviral resistance and provide data on the outbreak viruses. Chemoprophylaxis should be administered to all eligible residents, regardless of whether they received influenza vaccinations during the previous fall, and should continue for a minimum of 2 weeks. If surveillance indicates that new cases continue to occur, chemoprophylaxis should be continued until approximately 7—10 days after illness onset in the last patient (489). Chemoprophylaxis also can be offered to unvaccinated staff members who provide care to persons at high risk. Chemoprophylaxis should be considered for all employees, regardless of their vaccination status, if indications exist that the outbreak is caused by a strain of influenza virus that is not well-matched by the vaccine. Such indications might include multiple documented breakthrough influenza-virus infections among vaccinated persons, studies indicating low vaccine effectiveness, or circulation in the surrounding community of suspected index case(s) of strains not contained in the vaccine.
In addition to use in nursing homes, chemoprophylaxis also can be considered for controlling influenza outbreaks in other closed or semiclosed settings (e.g., dormitories, correctional facilities, or other settings in which persons live in close proximity). To limit the potential transmission of drug-resistant virus during outbreaks in institutions, whether in chronic or acute-care settings or other closed settings, measures should be taken to reduce contact between persons taking antiviral drugs for treatment and other persons, including those taking chemoprophylaxis.
Dosage recommendations vary by age group and medical conditions (Table 4).
Zanamivir is licensed for treatment of adults with uncomplicated acute illness caused by influenza A or B virus, and for chemoprophylaxis of influenza among adults. Zanamivir is not recommended for persons with underlying airways disease (e.g., asthma or chronic obstructive pulmonary diseases).
Oseltamivir is licensed for treatment of adults with uncomplicated acute illness caused by influenza A or B virus and for chemoprophylaxis of influenza among adults. Dosages and schedules for adults are listed (Table 4).
Zanamivir is licensed for treatment of influenza among children aged >7 years. The recommended dosage of zanamivir for treatment of influenza is 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily (approximately 12 hours apart). Zanamivir is licensed for chemoprophylaxis of influenza among children aged >5 years; the chemoprophylaxis dosage of zanamivir for children aged >5 years is 10 mg (2 inhalations) once a day.
Oseltamivir is licensed for treatment and chemoprophylaxis among children aged >1 year. Recommended treatment dosages vary by the weight of the child: 30 mg twice a day for children who weigh <15 kg, 45 mg twice a day for children who weigh >15—23 kg, 60 mg twice a day for those who weigh >23—40 kg, and 75 mg twice a day for those who weigh >40 kg. Dosages for chemoprophylaxis are the same for each weight group, but doses are administered only once per day rather than twice.
Persons Aged >65 Years
No reduction in dosage for oseltamivir or zanamivir is recommended on the basis of age alone.
Persons with Impaired Renal Function
Limited data are available regarding the safety and efficacy of zanamivir for patients with impaired renal function. Among patients with renal failure who were administered a single intravenous dose of zanamivir, decreases in renal clearance, increases in half-life, and increased systemic exposure to zanamivir were reported (450). However, a limited number of healthy volunteers who were administered high doses of intravenous zanamivir tolerated systemic levels of zanamivir that were substantially higher than those resulting from administration of zanamivir by oral inhalation at the recommended dose (491,492). On the basis of these considerations, the manufacturer recommends no dose adjustment for inhaled zanamivir for a 5-day course of treatment for patients with either mild-to-moderate or severe impairment in renal function (451).
Serum concentrations of oseltamivir carboxylate, the active metabolite of oseltamivir, increase with declining renal function (450). For patients with creatinine clearance of 10—30 mL per minute (450), a reduction of the treatment dosage of oseltamivir to 75 mg once daily and in the chemoprophylaxis dosage to 75 mg every other day is recommended. No treatment or chemoprophylaxis dosing recommendations are available for patients undergoing routine renal dialysis treatment.
Persons with Liver Disease
Use of zanamivir or oseltamivir has not been studied among persons with hepatic dysfunction.
Persons with Seizure Disorders
Seizure events have been reported during postmarketing use of zanamivir and oseltamivir, although no epidemiologic studies have reported any increased risk for seizures with either zanamivir or oseltamivir use.
Persons with Immunosuppression
A recent retrospective case-control study demonstrated that oseltamivir was safe and well tolerated when used during the control of an influenza outbreak among hematopoietic stem cell transplant recipients living in a residential facility (493).
Oseltamivir is administered orally in capsule or oral suspension form. Zanamivir is available as a dry powder that is self-administered via oral inhalation by using a plastic device included in the package with the medication. Patients should be instructed about the correct use of this device.
In studies of healthy volunteers, approximately 7%—21% of the orally inhaled zanamivir dose reached the lungs, and 70%—87% was deposited in the oropharynx (451,494). Approximately 4%—17% of the total amount of orally inhaled zanamivir is absorbed systemically. Systemically absorbed zanamivir has a half-life of 2.5—5.1 hours and is excreted unchanged in the urine. Unabsorbed drug is excreted in the feces (451,465).
Approximately 80% of orally administered oseltamivir is absorbed systemically (495). Absorbed oseltamivir is metabolized to oseltamivir carboxylate, the active neuraminidase inhibitor, primarily by hepatic esterases. Oseltamivir carboxylate has a half-life of 6—10 hours and is excreted in the urine by glomerular filtration and tubular secretion via the anionic pathway (450,496). Unmetabolized oseltamivir also is excreted in the urine by glomerular filtration and tubular secretion (468).
Adverse Events
When considering use of influenza antiviral medications (i.e., choice of antiviral drug, dosage, and duration of therapy), clinicians must consider the patient's age, weight, and renal function (Table 4); presence of other medical conditions; indications for use (i.e., chemoprophylaxis or therapy); and the potential for interaction with other medications.
Limited data are available about the safety or efficacy of zanamivir for persons with underlying respiratory disease or for persons with complications of acute influenza, and zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease (497). In a study of zanamivir treatment of ILI among persons with asthma or chronic obstructive pulmonary disease in which study medication was administered after use of a B2-agonist, 13% of patients receiving zanamivir and 14% of patients who received placebo (inhaled powdered lactose vehicle) experienced a >20% decline in forced expiratory volume in 1 second (FEV1) after treatment (451,498). However, in a phase-I study of persons with mild or moderate asthma who did not have ILI, one of 13 patients experienced bronchospasm after administration of zanamivir (451). In addition, during postmarketing surveillance, cases of respiratory function deterioration after inhalation of zanamivir have been reported. Because of the risk for serious adverse events and because efficacy has not been demonstrated among this population, zanamivir is not recommended for treatment for patients with underlying airway disease (451). Allergic reactions, including oropharyngeal or facial edema, also have been reported during postmarketing surveillance (451,498).
In clinical treatment studies of persons with uncomplicated influenza, the frequencies of adverse events were similar for persons receiving inhaled zanamivir and for those receiving placebo (i.e., inhaled lactose vehicle alone) (428—432,498). The most common adverse events reported by both groups were diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections. Each of these symptoms was reported by <5% of persons in the clinical treatment studies combined (451). Zanamivir does not impair the immunologic response to TIV (499).
Nausea and vomiting were reported more frequently among adults receiving oseltamivir for treatment (nausea without vomiting, approximately 10%; vomiting, approximately 9%) than among persons receiving placebo (nausea without vomiting, approximately 6%; vomiting, approximately 3%) (434,435,450,500). Among children treated with oseltamivir, 14% had vomiting, compared with 8.5% of placebo recipients. Overall, 1% discontinued the drug secondary to this side effect (437), and a limited number of adults who were enrolled in clinical treatment trials of oseltamivir discontinued treatment because of these symptoms (450). Similar types and rates of adverse events were reported in studies of oseltamivir chemoprophylaxis (450). Nausea and vomiting might be less severe if oseltamivir is taken with food (450). No published studies have assessed whether oseltamivir impairs the immunologic response to TIV.
Transient neuropsychiatric events (self-injury or delirium) have been reported postmarketing among persons taking oseltamivir; the majority of reports were among adolescents and adults living in Japan (501). FDA advises that persons receiving oseltamivir be monitored closely for abnormal behavior (450).
Use During Pregnancy
Oseltamivir and zanamivir are both "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, these two drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers' package inserts should be consulted (450,451). However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to such women.
Drug Interactions
Clinical data are limited regarding drug interactions with zanamivir. However, no known drug interactions have been reported, and no clinically critical drug interactions have been predicted on the basis of in vitro and animal study data (450,451,502).
Limited clinical data are available regarding drug interactions with oseltamivir. Because oseltamivir and oseltamivir carboxylate are excreted in the urine by glomerular filtration and tubular secretion via the anionic pathway, a potential exists for interaction with other agents excreted by this pathway. For example, coadministration of oseltamivir and probenecid resulted in reduced clearance of oseltamivir carboxylate by approximately 50% and a corresponding approximate twofold increase in the plasma levels of oseltamivir carboxylate (468).
No published data are available concerning the safety or efficacy of using combinations of any of these influenza antiviral drugs. Package inserts should be consulted for more detailed information about potential drug interactions.
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Bling up your bike and support Chase Trails
There is no trail building this coming Sunday as we are having a meeting with the Forestry guys to plan out what we'll be doing over the coming months and what support the FC can give us.
Normal service will resume the following Sunday.
This Sunday saw us finish the rock ramp feature we started a couple of weeks ago. The two routes down the slope offer a drop-off to a rocky landing or an easier rock ramp – both look good. They also ride well – we do have to test ride our efforts just to make sure they work as expected.
Young Phil ("Crash Test") turned up just in time with a rather muddy
The top launch pad gained a sump and drainage pipe to prevent the area flooding in poor weather – that's five corners that we've improved drainage so no more swimming pools. We'll be looking at applying this technique to other corners on our trails.
At the other end of the trail, the guys helped out by three new volunteers started resurfacing the trail after the Rollers. This section is very sandy and suffers during wet weather so a mixture of grit stone and quarry material was worked in and wackered flat. Further along, a "French drain" was dug along the inside edge of the second berm to drain water from the trail and into a sump hole. For the technically minded, a French drain is a shallow trench filled with fist sized stones to prevent the sides collapsing and snagging wayward wheels.


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Release Notes: This release adds support for SQLite and IPTC Metadata (found in some Photoshop images). A new logging plugin, major speed improvements, a new permissions framework, and dozens of other enhancements and fixes were done.
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If you or someone you know has cancer, there are places you can go to, and people you can turn to, who will give you support and advice.
If you are a patient, you may have been assigned a clinical nurse specialist (CNS) who will be involved in co-ordinating your care. You will be given their contact details so that you can get in touch with the CNS at any point during your treatment to ask for advice about your care.
Check the Borders, Dumfries and Galloway, Fife and Lothian pages (Lothian Support Centres and Lothian Support Groups) to find out about support groups and services in your local area.
Macmillan Cancer Support Helpline - Macmillan's team of experts can answer any questions you have, offer support, or simply listen if you want to chat. Call free on 0808 808 0000 (Monday to Friday, 9am-8pm).
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Submit News
Verizon Looking to Buyout Vodafone's Verizon Wireless Stake for a Cool $100B+
Jason Mick
April 25, 2013 10:00 AM
Recipient E-mail
Sender E-mail
Pending bid is Verizon Communications' second attempt to purchase Vodafone's stake
You might notice that whenever we report on news about Verizon Wireless we mention the Vodafone Group Plc. (
). That's because while America's top wireless carrier shares the name of its majority (55 percent) owner Verizon Communications Inc. (
), the UK-based Vodafone Group owns 45 percent of it.
I. Verizon Communications Aims to Complete Massive Buyout
new report
suggests that may change with a brewing offer by Verizon Communications to buy out Vodafone's stake. Experts predict the offer may reach well above $100B USD. These experts say a 50-50 mix of cash ($50B USD cash) and stock (roughly 965m shares of VZ at current prices). The company is reportedly confident it can raise the cash for the deal via bank financing.
The prospective deal is boosted by Verizon's high share prices. Shares of Verizon Communications have risen 20 percent this year as it
has performed well
as rivals struggled.
A "top 40 Vodafone investor" is quote anonymously by the report stating, "I'd be delighted with $135 billion, but there's absolutely no way it will be $100 billion. The guidance I have had from someone close to the company is that they are looking at $125-130 billion."
Verizon Communications is willing to pay
a lot
for Vodafone's VZW stake.
[Image Source: Julie Jacobson/AP]
The report claims to have definitive knowledge that Verizon Communications has hired banking and legal advisors to craft the bid. Vodafone is reportedly wary of taking a $20B USD capital gains tax hit on the buyout, so Verizon Communications may have to structure the deal in a tricky manner. Sources say that Verizon's hired team estimates they could trim the tax hit to around $5B USD.
Verizon Communications reportedly is willing to arrange the deal in private with Vodafone executives, but if they don't bite it's also willing to take the deal public -- directly to Vodafone shareholders.
The deal will likely be discussed at Verizon's board meeting, which is to be held next week.
II. Gotta Know When to Hold Them, Know When to Fold Them
A top 15 shareholder told
anonymously that they expect the company to give the lion's share of the sale directly to shareholders and not to horde it. He or she comments, "I don't really see this as a surprise. The talk about this deal has been quite intense recently. They should look to return a large amount to shareholders, retaining a relatively small amount for deleveraging and bolt-on deals. I don't think shareholders would be pleased with Vodafone viewing any disposal proceeds as an acquisition war chest."
The Verizon Wireless stake is estimated to account for 75 percent of Vodafone's net worth, as Verizon Wireless has soared as king of the U.S. market, even as Vodafone's European units have struggled.
Vittorio Colao, Vodafone's CEO, has expressed wariness about selling his company's crown jewels. He faces a tough decision. If he holds on to the stake longer he could get Verizon Communications to offer a bigger buyout and could also buy time for his European holdings to stabilize.
Vodafone's chief faces a tough decision on whether to sell or hold out.
[Image Source: Sarah Lee/The Guardian]
On the other hand, completed or pending consolidations -- namely the buyout of Sprint Nextel Corp. (S) by either
Japanese carrier Softbank
Corp. (
) or
American satellite television firm
Dish Network
Corp. (
), plus Deutsche Telekom AG's (
approved bid
partially acquire MetroPCS
Communications Inc. (
) and merge it with the T-Mobile USA -- may make the market more competitive. If Verizon loses subscribers or even is viewed as having a weakening grip on the market, its value could slide.
Verizon Communications was created in 2000 by the merger of Bell Atlantic Mobile and GTE Wireless. That merger ported a deal with Vodafone by Bell to invest $49.5B USD along with $40.5B USD from Vodafone to create a wireless network.
Four years later, Verizon Communications almost succeeded in buying out Vodafone's stake. The deal was driven by Vodafone's bid to buy AT&T Wireless, a deal that would have forced it to divest from the Verizon Wireless stake. Vodafone was hoping to rebrand AT&T Wireless as a "Vodafone" unit introducing its brand in the U.S. market.
But Cingular beat out Vodafone's bid. The collapse of that deal also sunk the prospective stake sale in Verizon Wireless. Now, almost a decade later, that sale may finally be on the eve of completion.
"It looks like the iPhone 4 might be their Vista, and I'm okay with that." -- Microsoft COO Kevin Turner
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