text:
Option 2 (Better): Use Buffering, Preferably Asynchronous
One typical strategy for dealing with high-latency operations is to introduce buffering. The most basic kind of buffering is synchronous buffering; for example, we could do all the work synchronously inside the calls to
write, but have most calls to
write only add the data to an internal queue, so that
write only actually writes anything to the file itself every N-th time, or if more than a second has elapsed (perhaps using a timer event to trigger occasional extra empty calls to
write just to ensure flushing occurs), or using some other heuristic.
But this column is about effective concurrency, so let's talk about asynchronous buffering. Besides, it's better in this case because it gets much more of the work off the caller's thread.
A better approach in this case is to use a buffer in the form of a work queue that feeds a dedicated worker thread. The caller writes into the queue, and the worker thread takes items off the queue and actually performs the writing. Example 2 illustrates the technique:
// Example 2: Asynchronous buffering // // The log file, and a queue and private worker thread that // protects it message_queue<string> bufferQueue; // Private worker thread mainline File logFile = …; while( str = bufferQueue.pop() ) { // receive (async) // If the queue is empty, pop blocks until something is available. // Now, just do the actual write (now on the private thread). logFile.write( str ); } // Each caller assembles the data they don't want interleaved // with other output and just puts it into the buffer/queue string temp = …; temp.append( … ); temp.append( … ); bufferQueue.push( temp ); // send (async)
Note that in this approach the individual calls to
send on multiple threads are thread-safe, but they can interleave with each other. Therefore, a caller who wants to send several items that should stay together can't just get away with making several individual calls to
send, but has to assemble them into an indivisible unit and send that all in one go, as shown above. This wasn't a problem in Option 1, because the indivisible unit of work was already explicit in the Example 1(a) and 1(b) calling code while the lock was held, no other thread could get access to the file and so no other calls could interleave.
Another minor drawback is that we have to manage an extra thread, including that we have to account for its termination; somehow, the private thread has to know when to go away, and Example 2 leaves that part as an exercise for the reader. I call this issue "minor" because the extra complexity isn't much, and termination is easy to deal with in a number of ways (note that Option 1 had a similar termination issue, too, to make sure it destroyed the file object), but I mention it for completeness if you use a strategy like Example 2, don't forget to join with those background helper threads at the end of the program!
But enough about minor drawbacks, because Option 2 delivers major advantages in the area of performance. Instead of waiting for an entire write operation to complete, possibly incurring high-latency accesses and all the trimmings, now the caller only has to wait for a simple and fast
message_queue.push operation. By never executing any part of the actual write on the caller's thread, callers will never have to wait for each other for any significant amount of time even if two try to write at the same instant. By thus eliminating throttling, we eliminate both performance issues we had with Option 1: We get much better concurrency among callers, and we eliminate the scalability problem inherent in the mutex-based design.
Guideline: Prefer to make high-contention and/or high-latency shared state, notably I/O, be asynchronous and therefore inherently buffered. It's just good encapsulation to hide the private state behind a public interface.
Oh, but wait don't modern languages have something called "classes" to let us express this kind of encapsulation? Indeed they do, which brings us to Option 3…


text:
Brunch at the Spotted Pig: Deep-Fried Eggs, Burgers, and More
The Spotted Pig
314 West 11th Street, New York NY 10014 (at Greenwich St; map); (212) 620-0393; thespottedpig.com
Service: Reasonably friendly and efficient
Setting: A good-looking (and nearly always packed) West Village pub
Must-Haves: Fried Duck Egg and Ramps, Gingerbread Pancakes
Drinks: Check out our post »
Cost: $15 brunch entrees
Grade: A-
Perhaps it's because we've so often found ourselves at The Spotted Pig well after midnight that it's never occurred to us as a destination for brunch the next morning. (Even though we're the kind of people who often start dreaming about meals a day before.) But once we were struck by the idea of a Spotted Pig brunch, we couldn't get it out of our heads. For a weekend day's kickoff meal, we usually want (or, well, need) something fatty and salty and gut-satisfyingly delicious, and that's just the kind of food the Spotted Pig excels at.
Of course, we weren't the only ones to hit upon this idea—a line had already formed out the door when we showed up last Saturday morning at the stroke of eleven. But what we tried of their brunch offerings was more than enough to justify a wait.
Counter Culture coffee ($5) is thick and dark and refilled from French presses throughout the meal, a brew made for anyone needing a powerful kick into consciousness. They've also got a long drink menu, as well as their usual roster of beers and wines; of the drinks, we enjoyed a grapefruit-vodka Salty Dog ($11) and the Pig's Bloody Mary ($12). (For more on the drinks, check our our post)
While a number of dishes from lunch and dinner service show up on the brunch menu (we saw hardly a table without their famous Roquefort-topped burger, a fine meal if ever there were one), there are a number of brunch exclusives, too. On the sweeter side, the gingerbread pancakes ($16) were deeply spiced but light in texture, moist and fluffy with nice, crisp edges. Three to a plate, with a light vanilla cream, candied almonds, and a blizzard of powdered sugar, they constitute an brunch plate that one could actually finish.
The Dutch Baby ($15), like a crisp-edged, eggy crepe, is another sweet dish that's not overwhelmingly so; atop it lie two thick slices of the Spotted Pig's housemade bacon. It's thick and chewy, not shatter-thin, with a smokiness that builds the longer you chew it. Ending up covered in maple syrup from the pancake, its sweet-meaty bite is the best part of the dish.
Eggs poached or fried (or poached, then fried) dominate the rest of the brunch dishes. Deep Fried Poached Eggs with Chorizo Stew ($16) sounded like the sort of borderline-excessive dish the Spotted Pig does best. On the plate, the thick chunks of chorizo were drowned in a sweet sea of cooked-down onions and sherry vinegar; though that savory-sweet-tangy balance was appealing at first, it was a little too greasy to stay appealing for more than a few bites. Though the panko-coated deep-fried eggs were done right, they didn't stay crunchy long in a sea of chorizo oil; they weren't the star of the dish, and the fry didn't do much other than add novelty. Criticisms aside, it's still a plenty tasty plate of food, that some of our number would order again.
Simpler and lighter, the fried duck egg with ramps and anchovy dressing ($16) was a knockout plate of food—and not only because ramps get us so excited this time of year. They're done extraordinarily well here, the slender greens amply salted and oiled and picking up a good char, the duck egg runny and molten, all topped off with an anchovy-butter emulsion; even the bread is perfectly suited, it too salted and charred and olive-oiled. It reminds us that the Spotted Pig can make vegetable dishes just as indulgent-seeming as its fattier, meatier ones.
In the more traditional camp, the Two Poached Eggs with Roast Pork Hash ($16) was a bit less porky than we'd expected, but we have no complaints: the potatoes were soft and buttery, with tons of crispy charred bits, incredibly tasty with a runny egg oozing over the top. Again, it's straightforward food, but done right.
While we preferred some dishes to others, there's really nothing we've tried from this brunch menu that we wouldn't eat again. (There are even dishes we'd consider forgoing the burger for.) It's not a cheap brunch, particularly once you factor in double-digit cocktails and $5 coffee, but it's across-the-board delicious enough to be totally recommendable, particularly when considering the number of profoundly mediocre $15 egg dishes out there in the West Village. Perhaps it's not an every-weekend destination, but we're just happy to find that the Spotted Pig is as good a place to kill a hangover as it is to create one.
All products linked here have been independently selected by our editors. We may earn a commission on purchases, as described in our affiliate policy.

subset: commoncrawl


text:
Do you eat tempeh? Me neither. But now I'm going to. I bought some tempeh on a whim today and decided to cook it and eat it for dinner. Alex was sad, then he was happy. It turned out that this is delicious. Tempeh doesn't taste like much, but is firm and holds sauce well.
Tempeh is full of protein, and a little easier to digest than tofu, I hear. The kind I bought had some veggies snuck into it, carrots and peppers. Look how healthy, I am, ma! I served this over brown rice with some kale on the side. Then Alex ate a bunch of gross kim chee. I don't like kim chee.
Teriyaki tempeh
This is the same sauce I used for sesame tofu a while ago - next time I would double the sauce.
1 pack of tempeh, about 8 oz
1 T oil


text:
by Megan
Plush Peahen Costume Photo 6 of 9
Rate this costume:
10 votes
|3 comments · add a comment
|Costume type:
|Costumes for Women
This homemade costume for women entered our 2012 Halloween Costume Contest.
A word from Ambree, the 'Plush Peahen' costume creator:
Intro: I had a blast making my Plush Homemade Peahen. Knowing I could make it as huge and dramatic as I wanted was really exciting. It was pretty simple to make. After ordering the materials... Read more »
Similar costumes:


text:
2019 Camry Owners Manual - The 2019 Toyota Camry is just a mid-size, front-wheel-drive sedan that produces a compelling reason to consider a car. 12 months removed from a major overhaul that gave this sedan sportier looks and more standard features, the 2019 Toyota Camry remains a crowd favorite in a shrinking segment. The 2019 Toyota Camry features a Manufacturer's Suggested Retail Price (MSRP) of $24,765, including destination charge. Just for $505 more, we recommend the better-equipped LE model. Pricing & Release Date. That represents a $200 increase versus the previous year. The XLE and XSE will be rising $325, starting at $29,845 and $30,395, respectively. Prices at top of the end of the spectrum are now actually going down. MSRPs for the XLE V6 and XSE V6 have already been lowered $500, and will become at $34,970 and $35,520.
Virtually very little is recognized about the Toyota Camry 2019, but maybe simply because Toyota has not yet unveiled for some time the specifics of an entirely 2019 Toyota Camry AWD. The Camry has been available since 1982, it's about 35 years aged, and during that point it moved from getting a car that no person truly wished, for one thing, a fairly more … properly, just far better. So, with the sizeable level of changes for the 2020 model year, what must we notice for 2019? Perform not assume that this changes, for the reason that this next model is virtually new; It even features a new Camry logo design/badge. The principal competitors of the automobile are Nissan Altima, Honda Accord, KIA Optima.
2019 Toyota Camry Engine
The 2019 Toyota Camry has a selection of three powertrains. Most buyers may well be more than pleased with the conventional 2.5-liter 4-chamber engine that provides a good mixture of execution and mileage. Those trying to find stacks of smooth power can settle on Toyota's 3.5-liter V6 engine, yet you should have to wander up to an XLE or XSE trim. The 2019 Toyota Camry Hybrid joins a 2.5-liter 4-chamber engine with an electric motor.
That model wins up to 40 mpg joined – a lot, yet in the meantime a couple underneath that of the newest Accord Hybrid. All Camry models are front-wheel drive. Fuel models are of a refined 6-speed programmed transmission, while the hybrid Camry uses an electronically controlled reliably calculate programmed transmission, which has a tendency to meander under expanding speed.
In one another condition, the power gets ready is completely imperceptible. Moves rise and fall in engine speed and lively downshifts are smooth, skirting on barely noticeable. Bustle, vibration, and remorselessness are Lexus-bore, aside from crisis stops, when the transmission shudders a bit. Whenever you do need to stop, the pedal provides a fair, solid feeling from expressway rates to no speed.
Regardless of the V6's thirst besting that of the four-banger, the six reliably returned 30 mpg on Michigan roadways, where the conventional activity speed runs 80 to 85 mph. In the town, the mileage dropped to sub-20, and everything touched base at the midpoint of out to around 24 mpg, which can be not extremely shabby for a V6.
2019 Toyota Camry Interior
The 2019 Toyota Camry sports a bold and stylish design and distinguishing it from the prevailing model is easy at all. The brand new model is now lower and comes with a different rear bumper. It comes in several enticing colors like ruby flare pearl, midnight black metallic, celestial silver metallic, blue crush metallic, galactic aqua mica etc. It is sold in trims like L, LE, SE, XLE, XSE and some trims also get hybrid versions. Based on trim the wheel size also varies. The XSE trim comes with the quad-tip dual exhaust. The brand new TNGA platform contributes to improved visual oomph and better fuel economy.
The cabin of upcoming 2019 Toyota Camry is sleek and touches of craftsmanship are evident in the trims. The cabin is a tad smaller than the prevailing model but most people won't feel the difference easily. However, the hybrid versions offer more cargo space than fuel driven trims, as it is. The inclusion of a big touchscreen for controlling the infotainment system is commendable. In some trims, you are able to choose for a 10-inch head-up display.
2019 Toyota Camry AWD Engine
We assume that 2019 Toyota Camry AWD will maintain the fairly recently up-to-date 2.5-liter 4-cylinder petroleum engine, however, there's a gossip that the hybrid engine is current. Toyota Camry 2019 comes with a new system with lately produced bodywork. The car even runs on the great drivetrain revival. Evidently, the engine will select 2 sorts. The real V-6 engine is often modified by new turbo-4. The present many-banger could very well function as go-to the enter into a regular remedy. For the much more a volume of pipe, it should ought to generate 2.-liter turbo for 235 steeds and also 258 lb-feet of torque. When as when compared to the supply engine, the automobile raises petroleum intake to near 15 to 20 percentage. Moreover, additionally, there's a design with light in weight products, making the auto keep to help expand improve by 30Per cent to gasoline intake quickly.
2019 Camry AWD Release Date and Price
Producers like to obtain the car the year before the model year: a 2020 model would see the display room in 2017, for instance. We assume Toyota to complete specifically the exact same matches the 2019 Toyota Camry AWD, but as you might find a whole lot fewer that which you should scream, they are likely to not hurry. Most likely due to the fact Toyota failed to truly give specifics in regards to the 2019 Camry, in addition, it held extremely calm about the price, which suggests they are able to transform features nearer to release. All we realize at this point is that the recent Camry begins with only below $ 24,000. Provided the technologies and only a little of the cost of living, it's straightforward the 2019 Camry coming in the display room for approximately $ 25,000.


text:
Hamza Yusuf (Mark Hanson)
Hamza Yusuf started life as Mark Hanson in Walla Walla, Washington, USA. The son of two US academics of a Catholic and Greek Orthodox background, he seemed destined not for Islamic scholarship, but for Greek Orthodox priesthood until a near-death experience in a car accident, and reading the Quran, diverted his attentions towards Islam.
It was this sudden confrontation with his own mortality that Yusuf has described as being the defining moment that gave " someone who was introspective, perspective." Although, numerous factors interplay in any individual's conversion, it was this vista in particular, that opened up a path of enquiry and reflection that ultimately led to his conversion to Islam in 1977, a few months before his 18th birthday. His brush with death had sparked an intrigue into the afterlife, causing him to study various traditions' views on death. Islam, he found, offered the most detailed account of all.
Furthermore, he found that many of his own values only served to harmonise with Islamic belief. His father, a Humanities Professor and his mother a Berkeley graduate, were fairly active in the civil rights movements enabling a strong awareness of social struggle and justice in the young Mark. "As a westerner, the child of civil rights and anti-war activists, I embraced Islam not in abandonment of my core values, drawn almost entirely from the progressive tradition, but as an affirmation of them."
Simultaneously, the arguments put forward in the Quran drew parallels with many of his own musings. From a young age, he was very much aware of being a product of his environment. The Quran prompted reflection on his perception of life, reality, and religion. Just as his parents were Christian, he had been raised as one, yet the Quran offers many parables of those following the religion of their forefathers without question. The Quran prompted him to look beyond what many take for granted.
After his conversion he left for England where he embarked on private study which was to instill a desire to learn the tradition from its source. It was during this time, in which he was beginning to learn Arabic, that he met Sheikh Abdullah Ali Mahmood of Sharjah who was in England at the time. This meeting was to prove pivotal in Yusuf's life providing him the opportunity to further his studies in the United Arab Emirates.
Yusuf spent some four years in the UAE, where he became a Muadhin (caller to Prayer) and Imam at a local mosque. It was also during this time that he met various West African scholars who kindled an interest in studying traditional Islam as is still being taught in West Africa today. These scholars did much in the way of his personal tuition before his aspirations of studying in West Africa were finally realised.
His journey of reflection, prompted by a fateful car accident, took him to many parts of the Middle East over a ten-year period where he received numerous teaching licenses, or ijazas, from the some of the greatest remaining scholars of traditional Islam. Having travelled to the UAE, Madinah, Algeria, Morocco, and West Africa he eventually returned to the US where he took degrees in nursing and religious studies from Imperial Valley College and San Jose State University, respectively.
He has since travelled to numerous countries around the world giving talks on various topics on Islam, with his video and audio recordings selling by the thousands. His ability to move many to tears, both of laughter and humility, have ensured his popularity with many, but only someone who speaks from the heart will have any lasting impact upon it-and it is in this aspect that he has left his greatest impression. His talks have inspired confidence in many young Muslims disillusioned with the West and further disillusioned by other Muslims insisting on a suffocating interpretation of Islam. He advocates a refreshing tolerance that counteracts the cancerous intolerance crippling the Muslim community, and promotes a sincerity and purification of the heart that will necessarily permeate and purify societies. For those who have attended the short courses, organised by traditional learning institutes in the West, in which he is one of many teachers, it is to bear witness to this possibility. In meeting the teachers of sacred knowledge who have come from all walks of life to teach students living in the West, is to witness the greatness of Islam itself in its inherent ability to dignify and elevate all who embody its teachings regardless of race, rank or background. For Islam truly is an invitation to all mankind.
For more information on Deen Intensive Courses click here.
For more information on the Zaytuna Institute founded by Hamza Yusuf and Dr Hesham Alalusi click here.


text:
Image from Art+Tech: Virtual Reality, November 2014. (Photo: Codame).
Over the past year, San Francisco and the Bay Area have come to be defined in the national sphere by the think piece. In the constant stream of articles about gentrification, the Ellis Act evictions, artist displacement, and arts non profits closing left and right in response to the city's rising population and booming tech industry, it might be surprising to note that a number of tech companies are investing increasingly in artist residency programs. In fact, two of the biggest tech companies in the region—Facebook and Autodesk—maintain active residency programs. For companies without the infrastructure for such endeavors, local art and technology non-profit CODAME offers to pair tech companies with artists for individual projects through their "Adopt An Artist" program. While there is a lot of conversation (and concern) in the Bay Area regarding the tech industry's lack of support and philanthropy for the arts, the questions seem skewed towards trying to figure out how to cater to tech wealth, rather than thinking through art's role in the tech industry itself. This text surveys corporate residency programs in the Bay Area which exemplify how artists engage with this industry, and begins to sketch out possible implications—or potential—for the art infrastructure and its relationship with tech creativity.
Autodesk's Pier 9 Artist-in-Residence program is housed in the corporation's immense facility in Pier 9 along the waterfront in downtown San Francisco. Artists apply for four-month residencies at the space, which provides access to their workshop, a stipend, and the ability to work directly with the company's engineers on their projects. The program maintains a diverse pool of applicants who range from fashion designers to chefs, architects, and technologists as well as fine artists, who have access to Autodesk's high-end equipment, materials, and software, plus training and skillshare programs. Although it is not an explicit part of the program, the focus on "makers" over "fine artists" benefits Autodesk as well. The company launched Autodesk 123D in 2009 as free 3D modeling software designed for the general consumer, and they acquired the DIY info sharing website Instructables in 2011. The AIR program began at Instructables before their purchase by Autodesk, who developed it into a much larger initiative. All AIR residents are required to post their projects to the website, so there is a direct tie into the site's content. Envisioning how people create with their tools, or their competitor's tools, in a variety of scenarios is clearly a valuable asset to the company, especially as the mainstream culture moves into a maker culture.
Autodesk Pier 9 Workshop.
Autodesk's Pier 9 AIR Program Manager Vanessa Sigurdson describes the environment at Autodesk as an "office full of artists, not an office with artists" and they aim to have active interchange between the resident artists and engineers. Former resident artists Joseph DeLappe and Adrien Segal felt that the environment was very supportive and encouraging for visiting artists, with an "anything goes" atmosphere. DeLappe created rubber stamps for In Drones We Trust, while Segal used water consumption statistics to build a canyon-like bench. Both mentioned that the workshop helped to foster the company's culture of bustling, creative energy. Sigurdson referenced the Xerox PARC artist-in-residence (PAIR) program as an important inspiration for the residency, a project that similarly brought artists and technologists together in collaboration.


text:
Yacht Haven Grande - St. Thomas
On-Site Customs & Immigration
High Speed Fueling
Full Yacht Provisioning Available
Guest & Crew Facilities
On-Site Duty-Free Shopping
Click below for Full List of Marina Amenities
From water services to yacht provisioning and more, Yacht Haven Grande has what you need and desire to restock and rejuvinate to get you back on the water.
As one of the most prominent locations on St. Thomas, Yacht Haven Grande hosts an array of events and activities for marina guests and locals.
Our trusted partners are here to ensure your needs are met, no matter where your destination lies.
Arriving to our amazing St. Thomas marina? Take a moment to check out the equally amazing weather!
Sneak a peek at our megayacht marina in St. Thomas to see how you could be spending your time in one of the best marinas in the Caribbean


text:
Sign up to hear more about Paolo Nutini!
Sign me up to discover more artists like Paolo Nutini and other offers.
By submitting my information, I agree to receive personalized updates and marketing messages about Paolo Nutini
, based on my information, interests, activities, website visits and device data and in accordance with the Privacy Policy.
I understand that I can opt-out at any time by emailing email@example.com
Would you like to leave a comment?
Log in > to the Fan Club or sign up >
Would love to have being there but got rah and Glasgow to look forward to. I have no doubt show will have been incredible. Paolo is looking fit by the way.
Great photos Awesome gig
This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies. Find out more.


text:
Fleeting Beauty
Daylillies explode in color at
Sarcoxie's Gilbert H. Wild
by Bob McEowen
The bloom of
a daylily usually opens to full glory for just one day. But the continual
burst of color from successive blooms makes late June and early July
an especially spectacular time in a garden adorned with Hemerocallis,
the botanical name for daylilies which literally translates beauty
and day.
Not only is
Gilbert H. Wild and Son of Sarcoxie the largest grower of daylilies,
iris and peonies in America but it also maintains the nations
largest daylily show garden with more than 2,800 daylilies growing within
3 acres.
Each year Wild
sells more than a million daylilies like the Stately Queen
variety on our cover through its mail order catalog, Web site
or in person at the garden. Orders are shipped to all 50 states and
40 countries.
While customers
cant pick up orders in person they can select the variety they
like and place an order for mail delivery.
In addition
to the show garden, visitors are welcome to roam the companys
360 acres of flower fields.
This years
daylily bloom is expected to peak between June 10 and July 15.
Gilbert H. Wilds
show garden is located in southwest Missouri on Highway 37, 1 mile north
of Interstate 44 exit 26.
For more
information call (417) 548-3514 or visit Wild on the Internet at www.gilbertwild.com.


text:
Globalstar offers a suite of solutions tailored to meet the needs of all of our customers. Whether you are running a small fishing charter business or a fleet of trucks moving cross country, Globalstar has a solution for you.
"Besides my automatic life raft, my GSP-1700 is probably the most important piece of safety equipment I carry on my charter boat."
- Capt Barry Gibson
Read More
Learn More
Globalstar connects you to the people and information that matter most from over 120 countries around the world.
Monday - Friday, 24h CST
877 452 5782
985 327 7500
Chat support is only available in English.
Mon - Fri 8AM - 5PM US CST
Chat support only available with Chrome, Edge, Firefox and Opera.
Your feedback helps us deliver useful products and solutions that meet your needs.
Provide Your Feedback
Globalstar service works well beyond terrestrial networks to provide peace of mind to the multitude of companies, workers and outdoor enthusiasts who work and play beyond the limits of intermittent or unavailable cellular coverage.
"We look forward to working with Symmetry and its customers to provide our voice, data and location services and technology using Globalstar's satellite technology."
Streamline South Africa's latest IOT solution makes use of the brand new ST100 IOT Board from Globalstar. This embeddable device brings a low cost, reliable, complete one -way data module to the IoT market. Simply add power, set the configuration and place in a mechanical housing for a working device suited for any market.
Read More »
You are leaving globalstar.com and entering a website that Globalstar does not control. Globalstar has provided this link for your convenience, but does not endorse and is not responsible for the content, links, privacy, policy or security policy of this website.


text:
ADANA Area Rug By Michelle Parascandolo
Anchor your room with this beautifully printed, low pile, jacquard woven rug. Ideal for high traffic areas and occasional spills. From contemporary to traditional motifs, this stunning floor art is the perfect addition to any living space. Rug pad recommended.
- Heavy cotton backing
- Easy to vacuum
- Low Pile
- Easy to Clean
- Printed on Fine Jacquard weave


text:
You often hear people lament the cost of painting a car, but done in a way that's not always accurate. The actual painting part of the process is really just the tip of the iceberg. For the most part, what really sets a show-worthy paintjob apart from the budget spray-and-pray deal from Mr. Scheib is the amount of time perfecting the body before it goes into the spray booth and the time spent polishing the paint to perfection afterwards. Having a painter who can expertly wield the spray gun is important, but what is done before and after has a huge effect on the final product.
Color sanding, if done correctly, can turn a good paintjob into an amazing one. The general idea is to smooth out the tiny waves and bumps in the clearcoat (commonly referred to as orange peel) and get rid of minute imperfections in the finish. Specialized high-grit papers are used that range from 400-grit all the way to super-fine 3,000-grit varieties. Depending on the desired final result, the process can take anywhere from 20 to 60 hours to complete.
This is definitely an area where "practice makes perfect," and if you're new to this you might want to spray a few test panels to practice on first. For some professional guidance on how it's done, we cruised over to Best of Show Coach Works in Escondido, California, to watch Jon Lindstrom work over project Track Rat, our '68 Camaro, which was recently covered in Axalta paint. As you can tell by the gray hair, Jon has been doing this quite a while and he's learned there's no shortcut to achieving a show-winning finish.
01. This is what we're trying to get rid of: the finish-killing bumps known as "orange peel," and the ridge at the edges of the red stripes. How much orange peel is present, along with how many coats of clear were put on the car, determines the grit of paper you should start with.
02. Best of Show's Jon Lindstrom never starts with anything more aggressive than 600-grit paper, and in this case he chose to start with 1,000-grit. The idea is to replace the coarse scratches from leveling the paint's surface with finer and finer scratches that can eventually be hidden with polish. It's a tedious, time-consuming process, but the results can make or break a paintjob.
03. You can see that Jon was careful not to sand the sharp edge on the top of the fender lip. Areas like this can easily be "burned through" since there's less clear on these peaks due to how the clear flows when wet. Some guys use pinstriping tape to protect the edges from being accidentally hit with the sanding block, but Jon is skilled enough to know how to stay away from it.
04. After some time with Meguiar's 1,000-grit paper and a 3M hard pad, it's easy to see how the finish is going from lumpy to smooth. Soon, the orange peel will be history.
05. Jon used to go from 800- to 1,200-grit, but after talking with Mike Pennington at Meguiar's, they decided to add an extra step and go over the car with 1,000-grit paper. The reason is that the 1,200 doesn't always remove every 800-grit scratch, and the extra step makes the buffing process far easier.
06. At this point the side of the fender was done with 1,200-grit, and the result was an evenly "scratched" surface. Again, it's a process of patience and staying consistent with the pressure applied to the paper.
07. Jon then moved on to Meguiar's 2,000-grit paper. When sanding over graphics, he used a 3M hard pad, but other areas of the car necessitated a softer pad sourced from Meguiar's. The uniform grit of the Nikken silicon-carbide paper from Meguiar's doesn't tend to load up quickly, which means it lasts longer. Did we mention that water, lots of water, with a touch of Ivory dish soap is the key?
08. Once the panel has been gone over with the 2,000-grit, Jon gets busy with some Buflex 2,500- (green) and then 3,000- (black) grit paper and a soft foam pad. Some shops start the buffing process after the 2,000-grit, but Jon feels that using the finer grits pays off big in the final finish. The Buflex paper is hard to find, but is made by Kovax out of Tokyo, Japan (www.kovax.com or www.eagleabrasives.com). It runs over a dollar a sheet, but given how much a typical paintjob costs, there's no point in pinching pennies.
09. It's finally time to address that edge we avoided earlier. For this, Jon used 1,200-grit Meguiar's Unigrit paper followed by the ultra-fine Buflex paper. No pad, just his hand and lots of slightly soapy water. Patience is the key since horizontal ridges like this typically have less clear on them compared to flat surfaces.
10. With the sanding done, it was time to start the buff and polish stage. This is done in three stages using progressively finer materials. For this we used Meguiar's Pro Speed Compound (PN 100) followed by 3M machine polish (PN 06064), and finally 3M Ultrafine polish (PN 06068).
11. We were trying out 3M's new line of quick-change pads, and they necessitated us having this quick-release adapter (PN 05752). At over $30, it isn't cheap, but it really did make swapping pads a snap.
12. First up was a 100-percent wool compounding pad from 3M (PN 05753). The compound used here is Meguiar's Pro Speed 100 since it's designed to remove scratches from 1,200-grit and finer paper. The key was not to overload the pad with compound and to take care not to burn through the paint. Speed comes with practice, so if you're new to this, Jon advises you go slow and get a feel for the process.
13. At this point the scratches were gone, but now we had even finer swirls. To get rid of these, Jon switched to a 3M foam polishing pad (PN 05707) and their machine polish (PN 06064).
14. The final step in perfecting the finish was a few passes with the 3M 5708 pad along with their Ultrafine polish (PN 06068). Like the wool and polishing pads, this was double sided thanks to the design of the quick-release adapter. Being able to utilize both sides meant we could get double the life out of each pad.
15. Jon then cleaned the panel with Meguiar's Final Inspection spray detailer. This cleaned the panel without leaving behind a residue so that Jon could look for any spots he missed. It's also perfect for cleaning up the panels between the different polishing compounds.
16. And here is the result of all the time and effort: a mirror-like shine that sets a high-dollar paintjob apart from a squirt and scuff deal. In all, Jon will have over 40 hours of cuttin' and buffin' on Project Track Rat just so we can look good flinging it around various tracks.
17. The effect of the Anvil Auto carbon fiber under the layers of polished clear is spectacular out in the sunshine. Most of the cost with a quality color sand and buff falls on the labor side of the ledger, but expect to shell out around $300 for materials.


text:
BANGOR, Maine — The Rev. Seamus Griesbach learned from a parishioner early Monday morning that Pope Benedict XVI had announced his resignation effective Feb. 28.
"I received a text message at 6:30 this morning that said, 'Rise and shine, the pope resigned,'" the Catholic priest assigned to St. Paul the Apostle Parish, which is made up of churches in Bangor, Brewer, Hampden and Winterport, said Monday afternoon.
"It's not entirely unforeseen but I don't think anyone expected it," he said of the pontiff's decision.
Lay Catholics in Maine also said they were surprised but not shocked by the pope's announcement. Although there was no consensus on what direction a new pope should take, they agreed that the selection of a new pontiff most likely will delay the appointment of a new bishop in Maine.
Catholics in the Pine Tree State have been without a spiritual leader since August when Bishop Richard J. Malone became head of the Roman Catholic Diocese of Buffalo, N.Y. Malone remains the apostolic administrator of the Maine diocese but is not often in the state.
"Nothing will happen before a new pope is in place," the Rev. Thomas Worcester, a history professor at the College of the Holy Cross in Worcester, Mass., said in a telephone interview. Worcester teaches a class on the history of the papacy and authored "The Papacy since 1500: From Italian Prince to Universal Pastor."
"There will be no new bishops appointed until the new pope has been in place a little while," the Jesuit priest predicted.
Dave Guthro, spokesman for the Roman Catholic Diocese of Portland, agreed.
"In reality, this development likely delays the process [of a new bishop being appointed]," he said in an email accompanying Malone's reaction to the resignation.
The bishop urged Maine Catholics to pray for the pope. He also said he was surprised by the resignation announcement.
"When I met with the pope in November 2011 at the Vatican, he did seem rather frail," Malone said. "I wish to express my gratitude for his faithful ministry as Successor of St. Peter, his life of scholarship and his faithful leadership of the Catholic church. One of the hallmarks of Pope Benedict XVI is his humility and pastoral concern in putting the good of the church first in his discernment. I cherish the pectoral cross he gave to me and other bishops who met with him during our [2011] visit."
Brett Baber who attends St. John Catholic Church and is a member of the Knights of Columbus, a fraternal Catholic organization, said he hoped a new pope would not implement major changes.
"My expectation is that they will select someone with deep faith in God and Christ who will likely carry on the values that have been demonstrated by the church since Vatican II," Baber of Veazie said. "I don't expect to see a new pope make many doctrinal changes but I would like him to be a catalyst for peace."
Sue Ewing of Portland said Benedict made the right decision.
"I am glad that he did this," she said. "I think the time probably had come."
Ewing attends Mass at Sacred Heart/St. Dominic Parish in Portland. She was active in Catholics for Marriage Equality, which supported the
referendum in November that made same-sex marriage legal in Maine in defiance of Malone.
"I hope we have a pope who will listen to the people," she said. "I think that the people are making noise and the spirit is blowing. I think the spirit is blowing through the church."
Ewing said she felt under Benedict and his bishops, the church "has not been going in the right direction. We've lost track of what we're all about and concentrated too much on rules and doctrine."
The election of a new pope will be a different experience for Griesbach than it was eight years ago. In 2005, he was a seminarian studying in Rome when Benedict was elected. He was having coffee at a cafe in Vatican City with some friends visiting from Maine when church bells rang out all over the city.
"Everybody dropped everything and headed to St. Peter's Square," he said. "Every street in the city suddenly became a one-way street. The piazza [outside St. Peter's Basilica] went from having a few hundred people to 300,000 in half an hour."
Griesbach will be in Maine tending to his flock during Lent when the next pontiff is announced.
"A holy pope, I think that's the first need of the church," the priest said. "A person who is close to God and a man of virtue, who is courageous."
For Griesbach, a courageous pope would be one who could offer hope to Catholics and non-Catholics that there is a place for the faithful in the United States and Europe, where the secularization of society has caused a dramatic decrease in the number of Catholics attending Mass and taking part in other sacraments.
"We're living through a time of cultural upheaval in the West where being Christian in our foundations is under serious challenge," the priest said. "The church in Europe and the U.S. faces some serious challenges and that will require a real steady hand. You have to be able to not lose hope in the face of that."
Griesbach said a pope who can offer that hope is what the church really needs in the 21st century.
Success. Please wait for the page to reload. If the page does not reload within 5 seconds, please refresh the page.
Enter your email and password to access comments.
Invalid username/password.
Please check your email to confirm and complete your registration.
Use the form below to reset your password. When you've submitted your account email, we will send an email with a reset code.
Randolph woman spends night in FedEx truck after getting stuck in northern Franklin County
Maine-born boxer Amelia Moore pushed through pandemic to continue Olympic training
Sister's book offers a glimpse into Sara Gideon's past
Cruise lines say they'll test all passengers, crew as they plan to resume sailing
Maine, union officials issue warning on failure to pass federal COVID-19 aid package


text:
A man who collapsed and died Monday near the Greenbelt jogging trail in Hermosa Beach has been identified as producer and director Jeffrey Ian Pollack, 54, of Manhattan Beach.
Pollack was the producer of television's "The Fresh Prince of Bel-Air" and was the writer and director of the 1994 basketball drama "Above the Rim."
Hermosa Beach Police Acting Capt. Tom Thompson said there appeared to be no foul play and it is believed he died of a heart attack or other natural causes.
"A lady saw him there a little before 6:23 (a.m.) and walked into the station to report there was a man down," Thompson said Thursday.
He was wearing jogging attire and had earphones and an iPod. Thompson said Pollack was already dead when the woman jogger spotted him lying next to a tree near 31st Street off to the side of the Hermosa Valley Greenbelt, a popular 3.5-mile-long trail surrounded by lush vegetation near the ocean.
A spokesman for the Los Angeles County Coronor's Office said Thursday that the cause of death has been deferred pending a number of tests.
"There are a lot of people on the greenbelt early in the morning," Thompson said, adding that the man may not have been noticed since he was not on the trail itself.
Pollack, reportedly an avid runner and softball player, also directed the films "Booty Call" and the 1999 comedy "Lost & Found." His iPod, according to one published account, was playing songs by the Eagles when police arrived.
Pollack was born in 1959 in Manhattan Beach and graduated from the University of Southern California Film School in the early 1980s.
He worked with Jeff Beacher, the creator of the Beacher's Madhouse variety shows performed at the Roosevelt Hotel in Hollywood.
"He was my best friend and partner for a decade," Beacher was quoted in a statement published by CNN. "He was my brother and father in one. Words can't describe how I feel right now."


text:
Up until now, Alexa users usually have to use the skill name when invoking a third party skill. For instance, "Alexa, ask 21 Dayz what my goals are for today?" In this example, "21 Dayz" is the skill name. If a user tried to ask "Alexa, what are my goals for today," without it, they would typically get "Sorry, I don't know that one".
Now with the new CanFulfillIntentRequest type, you can include your skill in a pool of possible skills that can handle name-free skill interactions. This new request type is backward-compatible and can work with your existing skill with some minor tweaks, specifically handling the CanFulfillIntentRequest type similar to how you handle the other request types. For example, say you have a simple switch statement like…
switch (req.type) {
case "LaunchRequest":
processLaunchRequest(req); break;
case "IntentRequest":
processIntentRequest(req); break;
case "SessionEndedRequest":
processSessionEndedRequest(req); break;
In this case (pun intended), you add another case for "CanFulfillIntentRequest" for example…
switch (req.type) {
case "LaunchRequest":
launchRequest(req); break;
case "CanFulfillIntentRequest":
canFulfillIntentRequest(req); break;
case "IntentRequest":
intentRequest(req); break;
case "SessionEndedRequest":
sessionEndedRequest(req); break;
Or if you are using the Alexa Skills Kit SDK, then you can implement the "onCanFulfillIntent" interface. Whichever route you take, in your function, in our case here, we do something like the following…
function canFulfillIntentRequest (req) {
var intentName = req.intent.name;
var slots = req.intent.slots;
//TODO: validate if your skill can handle
//this intent name and any provided slots here
return {
version: "1.0",
sessionAttributes": {...},
response": {
canFulfillIntent: {
canFulfill: "<YES, NO or MAYBE>",
canFulfillSlotsResponse: {
canUnderstand: "<YES, NO or MAYBE>",
canFulfill: "<YES or NO>"
Basically what's happening in the code sample above is, first, Alexa sends an HTTP post request to your endpoint with the request type set to "CanFulfillIntentRequest". This request includes an intent name and possibly some slots as well. In your canFulfillIntentRequest function, we want to validate if we can indeed handle the intent name and any slots provided but we do not, and this is very important, do not execute the actual intent! All we want to do is make sure we can indeed handle it then respond back to Alexa with either YES or NO specified for the "canFulfill" property as well as set "canFulfill" to YES or NO for all slots under "canFulfillSlotsResponse". The reason why we do not want to execute the actual intent is because Alexa will send out multiple "CanFulfillIntentRequest" to multiple third-party skills (currently 2 skills at a time) and will pick one skill after it's collected the canFulfillIntentResponse back. So imagine if all those skills kicked off a pizza ordering process or turned off lights for example, not good. Only the chosen skill should execute the actual intent.
As for the other property in "canFulfillSlotsResponse" called "canUnderstand", you set this to YES if your skill has a perfect match or high-confidence match. Set to NO if it can't match the value. Pretty straight forward.
Call me… MAYBE?
Here's an interesting one, instead of YES or NO on some of those "canFulfill" and "canUnderstand" properties (I bet you were wondering why not true or false right?), you can also specify "MAYBE".
Setting MAYBE on "canUnderstand" basically let's Alexa know that your skill has a partial match instead of an exact match as in the case of partial or fuzzy search results. As for "canFulfill" at the "canFulfillIntent" level, MAYBE instructs Alexa that your skill has might be able to process the request. This could be due to some slots being set to YES and others to MAYBE or if you need to prompt for account linking or fulfill required slots or some other multi-turn conversation requirement.
What Else?
If you are using the latest ASK CLI tools for your skills, check out the Quick Start Guide to get started.
To learn more about the specification, check out the "Name-Free Interaction for Alexa Skills" page.
Lastly, if you haven't already, read the official Beta announcement here.
Once the feature is out of public beta, I'll circle back and update this post with any relevant updates.
If you have any questions, feel free to reach out to me anytime or any one of the Alexa Champions or Evangelists in Slack.
Happy coding!


text:
Server Sales Declined a Smidge in Late 2012, but Will Grow a Bit This Year
Much as people talk constantly about the booming future for the construction of data centers and thus for the potential of sales of the gear that goes in them, the market reality is that on a global basis, fewer servers were sold in late 2012 than in the same period in 2011.
The latest market data from research firm Gartner found worldwide server sales declined by 0.2 percent, even as revenue from sales of those servers increased by more than 5 percent. For the full year though, sales increased by 1.5 percent on a unit basis, while revenue declined slightly.
Budget worries caused many companies to hold back on replacing older x86 machines, Gartner said, especially in the enterprise and in some mid-tier data centers. That no doubt factored into some worries around Intel's outlook when it reported Q4 earnings last month. The only ones really buying were big players like Google, Facebook and China's Baidu. Sales of RISC-based machines running Unix, as well as specialized hardware like Hewlett-Packard's Itanium servers, were also weak.
IBM made the most on a revenue basis, clocking in sales worth north of $5 billion, while HP sold the most on a unit basis, with a little less than 664,000 units.
On a regional basis, North America saw unit shipments grow 5.5 percent, followed by Asia/Pacific at 3.4 percent, and Latin America, which was essentially flat.
Europe, on the other hand, declined substantially, and that's where a lot of the pain was. As sovereign debt and economic concerns continued to take much of the oxygen out of the room in those countries, server sales declined by more than 10 percent on a unit basis, Gartner said. Most companies there saw their unit sales decline except for Japan's Fujitsu and Cisco Systems. In Cisco's case, its unit sales grew by nearly 20 percent, but that was off a low base relative to the other vendors. By comparison, Cisco sold about 14,000 servers in the region, versus HP which sold nearly 248,000.
Looking ahead to the rest of 2013, Gartner said to expect modest growth, offset a little by a boost in the use of virtualization, which allows one physical machine to run as if it's many virtual machines. Virtualization logically tends to eat into the overall volume of machines needed. Simply put, where you once needed two or four or eight servers, it's pretty likely you can now, given the improvement in processing power plus virtualization, replace them with one or two or three.
Here's the worldwide breakdown for the top five vendors in the quarter, revenue first.


text:
'European Football Weekends is a perennial source of pleasure' The Guardian
Wednesday, 17 November 2010
FC United of Manchester
7 comments:
Great piece.
I'm really looking forward to this game.
The biggest issue for me though is which end to get tickets for. Having read this article, I think I now know.
- 18 November 2010 at 01:11
- armchair fan of fans united said...
FCUM has mirrored the past plight of Brighton & Hove Albion, in a way..
previous owners sold the stadium for a fat profit, without anywhere to go.. years in the wilderness (aka groundsharing at Gillingham), at another decade at the stadium of trees (withdean porta loo cum athletic track cum stadium..), we are on the up, top of the league, and well on the way to the promised land that is FALMER!
good luck from a fellow fan of football. as it should be. we want proper pies, not prawn sandwiches!
c/o the unwashed lot at
- 18 November 2010 at 01:18
Excellent unbiased & personal view of the FCUM experience. Credit to the reporter who obviously "gets it" This article has been very well received on the FC United forum. Hopefully the writer can make it to future games.
Back to Grass Roots.
- 18 November 2010 at 08:26
- Damon said...
You have to take your yellow and green hat off to these chaps for all the sterling work. My one qualm is that so much of the noise/passion is directed at Glazer & the actual United that you have to wonder what will sustain that noise and passion when Glazer ultimately fecks off?
One thing that struck me and saddened me about the Rochdale game was that the beef with the Glazers overshadowed the achievements by the ACTUAL FCUM players on the pitch, which was a shame.
Other than that, cracking article too, Huddo.
Damon, therealfacup
- 18 November 2010 at 11:44
Good post. Oddly even as a Gooner I have a soft spot for FCUM. David v Goliath I suppose.
Good luck to them I say.
- 18 November 2010 at 12:08
- The General said...
Good luck to them...The principals and ethics of the club are to be admired in the current climate. If more clubs are like FCUM, AFC and Lewes in the future football will have a bright future. However, I doubt we will ever see the boom-and0-bust cycles we see today.
- 18 November 2010 at 19:20
Great article. Kudos to you, sir.
I bought my first Man United season ticket this year (having wanted one for as long as I can remember), but am now a recently converted and active member of the anti-Glazer cause. So yes, I feel incredibly guilty and hypocritical about having my season ticket.
I could go on and on about the intracices and contrasting views and opinions of the FC United movement all evening, but with each article I read about them I feel myself becoming more and more respectful and wanting of them.
But I can't see Berbatov at FC United. That's a big one. He's a beautiful player to watch. When he controls the ball, that's where babies come from.
- 18 November 2010 at 20:42


text: Helo, I have a big problem with spam assasin settings. I am using ISPConfig 3, installed same as in manual "Perfect server Centos" I have mailbox [email protected] and its alias [email protected] When I receive spam to [email protected], it is correctly signed as spam. BUT when I receive the same spam to [email protected], it jumps to Incoming mail folder, with no sign of spam. I've looked over the log and the mail is scanned, signed as spam, but then when it moves to incoming mail folder the sign disappears and mail is magically clear I have mailbox full of not signed spam, I need to solve this. Can anyone help me please? Thank you very much.


text:
You are here: Home > Prescription(RX) Drugs > V > Vytorin (Lake Erie Medical Dba Quality Care Products Llc)
ezetimibe and
simvastatin tablet
----------Vytorin 10/20 mg
VYTORIN contains ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and simvastatin, an HMG-CoA reductase inhibitor.
The chemical name of ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The empirical formula is C24H21F2NO3 and its molecular weight is 409.4.
Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is:
Simvastatin, an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMGCoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C25H38O5 and its molecular weight is 418.57.
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol. Its structural formula is:
YTORIN is available for oral use as tablets containing 10 mg of ezetimibe, and 10 mg of simvastatin (VYTORIN 10/10), 20 mg of simvastatin (VYTORIN 10/20), 40 mg of simvastatin (VYTORIN 10/40), or 80 mg of simvastatin (VYTORIN 10/80). Each tablet contains the following inactive ingredients: butylated hydroxyanisole NF, citric acid monohydrate USP, croscarmellose sodium NF, hypromellose USP, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, and propyl gallate NF.
[See Clinical Pharmacology (12.3).]
VYTORIN7.1 CYP3A4 Interactions
The risk of myopathy is increased by reducing the elimination of the simvastatin component of VYTORIN. Hence when VYTORIN is used with an inhibitor of CYP3A4 (e.g., as listed below), elevated plasma levels of HMG-CoA reductase inhibitory activity can increase the risk of myopathy and rhabdomyolysis, particularly with higher doses of VYTORIN. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).]
Itraconazole, ketoconazole, and other antifungal azoles
Macrolide antibiotics erythromycin, clarithromycin, and the ketolide antibiotic telithromycin
HIV protease inhibitors
Antidepressant nefazodone
Grapefruit juice in large quantities (>1 quart daily)
Concomitant use of these drugs and any medication labeled as having a strong inhibitory effect on CYP3A4 should be avoided unless the benefits of combined therapy outweigh the increased risk. If treatment with itraconazole, ketoconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with VYTORIN should be suspended during the course of treatment.7.2 Lipid-Lowering Drugs That Can Cause Myopathy When Given Alone
The risk of myopathy is increased by gemfibrozil and to a lesser extent by other fibrates [see Warnings and Precautions (5.1)].7.3 Amiodarone, Verapamil, or Diltiazem
The risk of myopathy/rhabdomyolysis is increased by concomitant administration of amiodarone, verapamil, or diltiazem with higher doses of VYTORIN [see Warnings and Precautions (5.1)].7.4 Niacin
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. In particular, caution should be used when treating Chinese patients with VYTORIN coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive VYTORIN 10/80 mg coadministered with lipid-modifying doses of niacin-containing products. [See Warnings and Precautions (5.1).]7.5 Cholestyramine
Concomitant cholestyramine administration decreased the mean AUC of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding VYTORIN to cholestyramine may be reduced by this interaction.7.6 Cyclosporine or Danazol
The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol particularly with higher doses of VYTORIN [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].
Caution should be exercised when using VYTORIN and cyclosporine concomitantly due to increased exposure to both ezetimibe and cyclosporine [see Dosage and Administration (2.7)]. Cyclosporine concentrations should be monitored in patients receiving VYTORIN and cyclosporine [see Clinical Pharmacology (12.3)].
The degree of increase in ezetimibe exposure may be greater in patients with severe renal impairment. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided by ezetimibe. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3).]7.7 Digoxin
In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in plasma digoxin concentrations. Patients taking digoxin should be monitored appropriately when VYTORIN is initiated.7.8 Fibrates
The safety and effectiveness of VYTORIN administered with fibrates have not been established.
Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile [see Animal Toxicology and/or Pharmacology (13.2)]. Coadministration of VYTORIN with fibrates is not recommended until use in patients is studied. [See Warnings and Precautions (5.1).]7.9 Coumarin Anticoagulants
Simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in a normal volunteer study and in a hypercholesterolemic patient study, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting VYTORIN and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of VYTORIN is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
Concomitant administration of ezetimibe (10 mg once daily) had no significant effect on bioavailability of warfarin and prothrombin time in a study of twelve healthy adult males. There have been post-marketing reports of increased INR in patients who had ezetimibe added to warfarin. Most of these patients were also on other medications.
The effect of VYTORIN on the prothrombin time has not been studied.
13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal carcinogenicity or fertility studies have been conducted with the combination of ezetimibe and simvastatin. The combination of ezetimibe with simvastatin did not show evidence of mutagenicity in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with ezetimibe and simvastatin with or without metabolic activation. There was no evidence of genotoxicity at doses up to 600 mg/kg with the combination of ezetimibe and simvastatin (1:1) in the in vivo mouse micronucleus test.
A 104-week dietary carcinogenicity study with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). A 104-week dietary carcinogenicity study with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). There were no statistically significant increases in tumor incidences in drug-treated rats or mice.
No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation. In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test.
In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe).
In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively, (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day.
In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).
In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC).
A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80-mg daily dose.
No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
There was decreased fertility in male rats treated with simvastatin for 34 weeks at 25 mg/kg body weight (4 times the maximum human exposure level, based on AUC, in patients receiving 80 mg/day); however, this effect was not observed during a subsequent fertility study in which simvastatin was administered at this same dose level to male rats for 11 weeks (the entire cycle of spermatogenesis including epididymal maturation). No microscopic changes were observed in the testes of rats from either study. At 180 mg/kg/day, (which produces exposure levels 22 times higher than those in humans taking 80 mg/day based on surface area, mg/m2), seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. In dogs, there was drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation at 10 mg/kg/day (approximately 2 times the human exposure, based on AUC, at 80 mg/day). The clinical significance of these findings is unclear.13.2 Animal Toxicology and/or Pharmacology
CNS Toxicity
Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.
A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.
CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.
There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).
The hypocholesterolemic effect of ezetimibe was evaluated in cholesterol-fed Rhesus monkeys, dogs, rats, and mouse models of human cholesterol metabolism. Ezetimibe was found to have an ED50 value of 0.5 μg/kg/day for inhibiting the rise in plasma cholesterol levels in monkeys. The ED50 values in dogs, rats, and mice were 7, 30, and 700 μg/kg/day, respectively. These results are consistent with ezetimibe being a potent cholesterol absorption inhibitor.
In a rat model, where the glucuronide metabolite of ezetimibe (ezetimibe-glucuronide) was administered intraduodenally, the metabolite was as potent as ezetimibe in inhibiting the absorption of cholesterol, suggesting that the glucuronide metabolite had activity similar to the parent drug.
In 1-month studies in dogs given ezetimibe (0.03 to 300 mg/kg/day), the concentration of cholesterol in gallbladder bile increased ~2- to 4-fold. However, a dose of 300 mg/kg/day administered to dogs for one year did not result in gallstone formation or any other adverse hepatobiliary effects. In a 14-day study in mice given ezetimibe (0.3 to 5 mg/kg/day) and fed a low-fat or cholesterol-rich diet, the concentration of cholesterol in gallbladder bile was either unaffected or reduced to normal levels, respectively.
A series of acute preclinical studies was performed to determine the selectivity of ezetimibe for inhibiting cholesterol absorption. Ezetimibe inhibited the absorption of 14C-cholesterol with no effect on the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinyl estradiol, or the fat-soluble vitamins A and D.
In 4- to 12-week toxicity studies in mice, ezetimibe did not induce cytochrome P450 drug-metabolizing enzymes. In toxicity studies, a pharmacokinetic interaction of ezetimibe with statins (parents or their active hydroxy acid metabolites) was seen in rats, dogs, and rabbits.
Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate.1.1 Primary Hyperlipidemia
VYTORIN is indicated for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia.1.2 Homozygous Familial Hypercholesterolemia (HoFH)
VYTORIN is indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.1.3 Limitations of Use
No incremental benefit of VYTORIN on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. VYTORIN has not been studied in Fredrickson type I, III, IV, and V dyslipidemias.
Hypersensitivity to any component of this medication [see Adverse Reactions (6.2)].
Active liver disease or unexplained persistent elevations in hepatic transaminase levels [see Warnings and Precautions (5.2)].
Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins), such as simvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, VYTORIN may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of VYTORIN use during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. VYTORIN should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, VYTORIN should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
Nursing mothers. It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require VYTORIN treatment should not breast-feed their infants [see Use in Specific Populations (8.3)].
The following serious adverse reactions are discussed in greater detail in other sections of the label:
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.In the VYTORIN (ezetimibe/simvastatin) placebo-controlled clinical trials database of 1420 patients (age range 20-83 years, 52% women, 87% Caucasians, 3% Blacks, 5% Hispanics, 3% Asians) with a median treatment duration of 27 weeks, 5% of patients on VYTORIN and 2.2% of patients on placebo discontinued due to adverse reactions.
The most common adverse reactions in the group treated with VYTORIN that led to treatment discontinuation and occurred at a rate greater than placebo were:
The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) in controlled clinical trials were: headache (5.8%), increased ALT (3.7%), myalgia (3.6%), upper respiratory tract infection (3.6%), and diarrhea (2.8%).
VYTORIN has been evaluated for safety in more than 10,189 patients in clinical trials.
Table 2 summarizes the frequency of clinical adverse reactions reported in ≥2% of patients treated with VYTORIN (n=1420) and at an incidence greater than placebo, regardless of causality assessment, from four placebo-controlled trials.
Other adverse reactions reported with ezetimibe in placebo-controlled studies, regardless of causality assessment: Musculoskeletal system disorders: arthralgia; Infections and infestations: sinusitis; Body as a whole – general disorders: fatigue.
Other adverse reactions reported with simvastatin in placebo-controlled clinical studies, regardless of causality assessment: Cardiac disorders: atrial fibrillation; Ear and labyrinth disorders: vertigo; Gastrointestinal disorders: abdominal pain, constipation, dyspepsia, flatulence, gastritis; Skin and subcutaneous tissue disorders: eczema, rash; Endocrine disorders: diabetes mellitus; Infections and infestations: bronchitis, sinusitis, urinary tract infections; Body as a whole – general disorders: asthenia, edema/swelling; Psychiatric disorders: insomnia.
Laboratory Tests
Marked persistent increases of hepatic serum transaminases have been noted [see Warnings and Precautions (5.2)]. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have been reported. About 5% of patients taking simvastatin had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK [see Warnings and Precautions (5.1)].6.2 Post-Marketing Experience
Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported in post-marketing experience for VYTORIN or ezetimibe or simvastatin: pruritus; alopecia; erythema multiforme; a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails); dizziness; muscle cramps; myalgia; arthralgia; pancreatitis; memory impairment; paresthesia; peripheral neuropathy; vomiting; nausea; anemia; erectile dysfunction; interstitial lung disease; myopathy/rhabdomyolysis [see Warnings and Precautions (5.1)]; hepatitis/jaundice; hepatic failure; depression; cholelithiasis; cholecystitis; thrombocytopenia; elevations in liver transaminases; elevated creatine phosphokinase.
In addition, an apparent hypersensitivity syndrome has been reported rarely that has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
No specific treatment of overdosage with VYTORIN can be recommended. In the event of an overdose, symptomatic and supportive measures should be employed.
In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hyperlipidemia for up to 56 days, was generally well tolerated.
A few cases of overdosage have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious.
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.
A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.
The dialyzability of simvastatin and its metabolites in man is not known at present.
2 DOSAGE AND ADMINISTRATION2.1 Recommended Dosing
The dosage range is 10/10 mg/day through 10/80 mg/day. The recommended usual starting dose is 10/20 mg/day. VYTORIN should be taken as a single daily dose in the evening, with or without food. Initiation of therapy with 10/10 mg/day may be considered for patients requiring less aggressive LDL-C reductions. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10/40 mg/day. After initiation or titration of VYTORIN, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed.2.2 Patients with Homozygous Familial Hypercholesterolemia
The recommended dosage for patients with homozygous familial hypercholesterolemia is VYTORIN 10/40 mg/day or 10/80 mg/day in the evening. VYTORIN should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.2.3 Patients with Hepatic Impairment
No dosage adjustment is necessary in patients with mild hepatic impairment [see Warnings and Precautions (5.3)].2.4 Patients with Renal Impairment
No dosage adjustment is necessary in patients with mild or moderate renal impairment. However, for patients with severe renal insufficiency, VYTORIN should not be started unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Caution should be exercised when VYTORIN is administered to these patients, and they should be closely monitored [see Warnings and Precautions (5.1); Clinical Pharmacology (12.3)].2.5 Geriatric Patients
No dosage adjustment is necessary in geriatric patients [see Clinical Pharmacology (12.3)].2.6 Chinese Patients Taking Lipid-Modifying Doses (≥1 g/day Niacin) of Niacin-Containing Products
Because of an increased risk for myopathy, caution should be used when treating Chinese patients with VYTORIN coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive VYTORIN 10/80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients. [See Warnings and Precautions (5.1).]2.7 Coadministration with Other Drugs
[See Warnings and Precautions (5.1) and Drug Interactions (7).]
Bile Acid Sequestrants
Dosing of VYTORIN should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant [see Drug Interactions (7.5)].
Cyclosporine or Danazol
Caution should be exercised when initiating VYTORIN in the setting of cyclosporine. In patients taking cyclosporine or danazol, VYTORIN should not be started unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. The dose of VYTORIN should not exceed 10/10 mg/day [see Drug Interactions (7.6)].
Amiodarone or Verapamil
In patients taking amiodarone or verapamil concomitantly with VYTORIN, the dose should not exceed 10/20 mg/day [see Warnings and Precautions (5.1) and Drug Interactions (7.3)].
The dose of VYTORIN should not exceed 10/40 mg/day [see Warnings and Precautions (5.1), Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
Other Concomitant Lipid-Lowering Therapy
The safety and effectiveness of VYTORIN administered with fibrates have not been established. Therefore, the combination of VYTORIN and fibrates should be avoided [see Warnings and Precautions (5.1) and Drug Interactions (7.2 and 7.8)].
There is an increased risk of myopathy when simvastatin is used concomitantly with fibrates (especially gemfibrozil). Combination therapy with gemfibrozil should be avoided because of an increase in simvastatin exposure with concomitant use. [See Warnings and Precautions (5.1) and Drug Interactions (7.2 and 7.8).]
No. 3873 — Tablets VYTORIN 10/10 are white to off-white capsule-shaped tablets with code "311" on one side.
They are supplied as follows:
NDC 66582-311-31 bottles of 30
NDC 66582-311-54 bottles of 90
NDC 66582-311-82 bottles of 1000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-311-87 bottles of 10,000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-311-28 unit dose packages of 100.
No. 3874 — Tablets VYTORIN 10/20 are white to off-white capsule-shaped tablets with code "312" on one side.
They are supplied as follows:
NDC 66582-312-31 bottles of 30
NDC 66582-312-54 bottles of 90
NDC 66582-312-82 bottles of 1000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-312-87 bottles of 10,000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-312-28 unit dose packages of 100.
No. 3875 — Tablets VYTORIN 10/40 are white to off-white capsule-shaped tablets with code "313" on one side.
They are supplied as follows:
NDC 66582-313-31 bottles of 30
NDC 66582-313-54 bottles of 90
NDC 66582-313-74 bottles of 500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-313-86 bottles of 5000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-313-52 unit dose packages of 50.
No. 3876 — Tablets VYTORIN 10/80 are white to off-white capsule-shaped tablets with code "315" on one side.
They are supplied as follows:
NDC 66582-315-31 bottles of 30
NDC 66582-315-54 bottles of 90
NDC 66582-315-74 bottles of 500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-315-66 bottles of 2500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)
NDC 66582-315-52 unit dose packages of 50.
Store at 20-25°C (68-77°F). [See USP Controlled Room Temperature.] Keep container tightly closed.
Storage of 10,000, 5000, and 2500 count bottles
Store bottle of 10,000 VYTORIN 10/10 and 10/20, 5000 VYTORIN 10/40, and 2500 VYTORIN 10/80 capsule-shaped tablets at 20-25°C (68-77°F). [See USP Controlled Room Temperature.] Store in original container until time of use. When product container is subdivided, repackage into a tightly-closed, light-resistant container. Entire contents must be repackaged immediately upon opening.
[See FDA-Approved Patient Labeling (17.5).]
Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.
Patients should be advised about substances they should not take concomitantly with VYTORIN [see Warnings and Precautions (5.1)]. Patients should also be advised to inform other physicians prescribing a new medication that they are taking VYTORIN.17.1 Muscle Pain
All patients starting therapy with VYTORIN should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. The risk of this occurring is increased when taking certain types of medication or consuming larger quantities of grapefruit juice. They should discuss all medication, both prescription and over the counter, with their healthcare professional.17.2 Liver Enzymes
It is recommended that liver function tests be performed before the initiation of VYTORIN, and thereafter when clinically indicated. Patients titrated to the 10/80-mg dose should receive an additional test prior to titration, 3 months after titration to the 10/80-mg dose, and periodically thereafter (e.g., semiannually) for the first year of treatment.17.3 Pregnancy
Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using VYTORIN. Discuss future pregnancy plans with your patients, and discuss when to stop taking VYTORIN if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking VYTORIN and call their healthcare professional.17.4 Breast-feeding
Women who are breast-feeding should be advised to not use
VYTORIN. Patients who have a lipid disorder and are breast-feeding should be
advised to discuss the options with their healthcare professional.
(ezetimibe/simvastatin) Tablets
Read this information carefully before you start taking VYTORIN. Review this information each time you refill your prescription for VYTORIN as there may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about VYTORIN, ask your doctor. Only your doctor can determine if VYTORIN is right for you.
What is VYTORIN?
VYTORIN contains two cholesterol-lowering medications, ezetimibe and simvastatin, available as a tablet in four strengths:
VYTORIN is a medicine used to lower levels of total cholesterol, LDL (bad) cholesterol, and fatty substances called triglycerides in the blood. In addition, VYTORIN raises levels of HDL (good) cholesterol. VYTORIN is for patients who cannot control their cholesterol levels by diet and exercise alone. You should stay on a cholesterol-lowering diet while taking this medicine.
VYTORIN works to reduce your cholesterol in two ways. It reduces the cholesterol absorbed in your digestive tract, as well as the cholesterol your body makes by itself. VYTORIN does not help you lose weight. VYTORIN has not been shown to reduce heart attacks or strokes more than simvastatin alone.
For more information about cholesterol, see the section called "What should I know about high cholesterol?"
Who should not take VYTORIN?
Do not take VYTORIN:
VYTORIN has not been studied in children under 10 years of age.
What should I tell my doctor before and while taking VYTORIN?
Tell your doctor right away if you experience unexplained muscle pain, tenderness, or weakness. This is because on rare occasions, muscle problems can be serious, including muscle breakdown resulting in kidney damage.
The risk of muscle breakdown is greater at higher doses of VYTORIN.
The risk of muscle breakdown is greater in patients with kidney problems.
Taking VYTORIN with certain substances can increase the risk of muscle problems. It is particularly important to tell your doctor if you are taking any of the following:
Tell your doctor if you are taking niacin or a niacin-containing product, as this may increase your risk of muscle problems, especially if you are Chinese.
It is also important to tell your doctor if you are taking coumarin anticoagulants (drugs that prevent blood clots, such as warfarin).
Tell your doctor about any prescription and nonprescription medicines you are taking or plan to take, including natural or herbal remedies.
Tell your doctor about all your medical conditions including allergies.
Tell your doctor if you:
Tell other doctors prescribing a new medication that you are taking VYTORIN.
How should I take VYTORIN?
Your doctor has prescribed your dose of VYTORIN. The available doses of
VYTORIN are 10/10, 10/20, 10/40, and 10/80. The usual daily starting dose is
What should I do in case of an overdose?
Contact your doctor immediately.
What are the possible side effects of VYTORIN?
See your doctor regularly to check your cholesterol level and to check for side effects. Your doctor may do blood tests to check your liver before you start taking VYTORIN and during treatment.
In clinical studies patients reported the following common side effects while taking VYTORIN: headache, muscle pain, and diarrhea (see What should I tell my doctor before and while taking VYTORIN?).
The following side effects have been reported in general use with VYTORIN or with ezetimibe or simvastatin tablets (tablets that contain the active ingredients of VYTORIN):
Tell your doctor if you are having these or any other medical problems while on VYTORIN. This is not a complete list of side effects. For a complete list, ask your doctor or pharmacist.
What should I know about high cholesterol?
Cholesterol is a type of fat found in your blood. Cholesterol comes from two sources. It is produced by your body and it comes from the food you eat. Your total cholesterol is made up of both LDL and HDL cholesterol.
LDL cholesterol is called "bad" cholesterol because it can build up in the wall of your arteries and form plaque. Over time, plaque build-up can cause a narrowing of the arteries. This narrowing can slow or block blood flow to your heart, brain, and other organs. High LDL cholesterol is a major cause of heart disease and one of the causes for stroke.
HDL cholesterol is called "good" cholesterol because it keeps the bad cholesterol from building up in the arteries.
Triglycerides also are fats found in your body.
General Information about VYTORIN
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use VYTORIN for a condition for which it was not prescribed. Do not give VYTORIN to other people, even if they have the same condition you have. It may harm them.
This summarizes the most important information about VYTORIN. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about VYTORIN that is written for health professionals. For additional information, visit the following web site: vytorin.com.
Inactive ingredients:
Butylated hydroxyanisole NF, citric acid monohydrate USP, croscarmellose sodium NF, hypromellose USP, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, and propyl gallate NF.
Manufactured for:
Revised: 11/2010 Lake Erie Medical DBA Quality Care Products LLC
Reproduced with permission of U.S. National Library of Medicine
Copyright © 2020
Drugsdb.eu by Dionisios Fentas || Terms of Use
|Prescription(RX) Drugs
|Over-the-counter (OTC) Drugs
|Homeopathic Drugs
|Animal Drugs


text:
MenuStrip 3.5
Old versionsSee all
Take control of your menu bar! MenuStrip allows you to create your very own custom menus that appear in the menu bar or as a control strip placed anywhere on the screen. Add applications, files, or folders to any number of customizable menus. Always have your most frequently used items easily within reach.
• Create your own fully customizable drop-down menus with your most commonly used applications, files, and folders.
• Add shortcuts in the menu bar for all of your favorite applications.
• Quicklaunch applications and open files simply by typing their name! No more searching through your hard drive to find where you put that important file.
• Launch, hide, or quit groups of applications at once using fully-customizeable "Action Buttons".
• Hide background clutter. With the 'Auto-Hide' feature enabled, as you switch between applications all background apps will hide out of the way letting you focus on what you need to do.
Got screen? Use it!
Chances are if you are using a Cinema Display, or other large monitor, you have plenty of empty space up in your menu bar. Well why let all that valuable screen space go to waste? You paid good money for those pixels! MenuStrip can let you put all that empty space to good use. Create your own menus to sit alongside the standard system menus, or use that space for shortcuts to your most commonly used applications and files. Either way, by using MenuStrip you're maximizing your big-screen investment.
Small screen? No problem.
Have a MacBook with a smaller screen or have too much stuff in your menu bar already? That's fine, MenuStrip can help out there too. Instead of taking up more space in your cramped menu bar, MenuStrip can display in a small control strip that sits underneath your existing menu bar or anywhere else on the screen. The control strip can also be set to auto-hide; basically it will hide out of view when not needed and then slide onto the screen when you want to access it. This will help you make the most out of your valuable screen real-estate.
- Custom Menus: Create custom menus with your favorite applications, folders, or files.
- QuickLauncher: Launch applications or open files by simply typing their name.
- Application Switcher: App Switcher menu with Hide Desktop / Auto-Hide feature
- Action Buttons: create customizable menu buttons which perform multiple custom actions (launching, hiding, quitting application or opening specified files with the push of a button)
- Alarm Clock and Calendar
- Control Strip: place your menus anywhere on the screen
Why MenuStrip?
It simply works better. While there are other menu bar utilities available for Mac OS X, nothing comes close to the integration of features, customizability, value, and ease of use that MenuStrip has. Why buy four or five different tiny $15+ applications when MenuStrip can do it all in one great package? Integration and ease of use has been a priority from the very start.


text:
My husband is a busy man. He loves to read, and even though he reads non-fiction quite steadily, he does feel he has to have a little 'down time' to enjoy some fiction. After seeing 61 Hours on book lists and in airport bookstores, I thought I would pick this one up for him – he loves action/thrillers. Well, he never got to reading it yet, … too busy, so I decided to give it a try myself. Action/thriller is usually not my genre of choice, so take a seat ladies and gentleman, you are in for a ride!
61 hours counting down, one chapter at a time…I found the plot good, and the scene and story well set up, but the action was a bit lacking, until the very end. It wasn't nearly as scary as I had expected and I actually had the culprit in mind long before Reacher did!
Having said that, the character of Jack Reacher is totally intriguing and I would read another Lee Child book, just to catch a glimpse of this nomad in another situation, somewhere, somehow. Reacher is observant in a detailed Sherlock Holmes sort of way. As an ex-military cop he is smart and decisive, but also a wanderer, a drifter, and a large loner of a man. Jack Reacher is a maverick, but does not go looking for trouble. Trouble seems to find him. He carries nothing with him, not even clothes, which he just buys new every three days or so. He gets involved and becomes the hero for no other reason than to do good, and then he moves on. Very slick, like his website. I've never seen a website so smooth.
This severely dates me, but the Jack Reacher character made me think of the theme song for The Littlest Hobo. Sorry Jack (and Lee)! I couldn't resist.