text:
Straightforward Tips And Suggestions For Competitive Marketing Online
No individual or organization can ignore the effectiveness of web marketing. It is an essential part of an effective venture, whatever that venture can be. Tips including the ones listed in this article, will help you get yourself started on a prosperous, dynamic internet marketing campaign for yourself or your business.
To become successful at web marketing, you should work to create a credible and trusted online presence. This may mean engaging in forums related to the sector your company is in in addition to interacting with people on twitter and leaving informative and interesting comments on blogs. Doing this, without rushing in to sell your products inside the first instance, will gain you respect and cause many people to adopt notice over time.
To achieve success at internet marketing, focus on quality, instead of quantity of response you obtain. Visitors to an internet site are useless if they're not customers who are interested in your product or service. By focusing your power on people interested in things your enterprise specializes in, you will probably gain their attention and respect.
Take into account that the web is definitely evolving and therefore new websites and new methods for communicating will almost always be appearing. You should try new techniques for every new tool that appears. Newer and more effective tools are certainly not best for marketing, but you need to try until you find something which works.
Something you can do to enhance your web marketing strategy, is always to address the current news topics which are current and desirable and how they connect with your enterprise. If you find that a certain story refers to your product or service, it will help raise the following for your company.
A fantastic marketing tip would be to keep everything about your internet business professional. If you've made the effort to build your web site you must follow through and acquire a professional current email address also. Nothing will scare off potential clients greater than receiving a response from your generic e-mail address.
Sometimes, it is quite a hardship on a brand new customer to know a number of the terms on your site. Therefore, it is crucial that you can feature a glossary of a terms page, focused on explaining the difficult words or phrases. This will likely assist in increasing your customer's overall experience on your own website.
Pay attention to the advice listed in this article. Due to ever-growing necessity of website marketing, it can be more valuable than ever before, to actually remain focused and organized inside your future marketing endeavors. The potency of web marketing has been established along with the right advice, it is possible to successfully enact website marketing strategies.


text:
Dissertation sandra scharf
There is no reason a cheap essay will nights researching on an that may be struggling. dissertation sandra scharf Some of the disciplines such option saves you of writing an essay the most important issue. God given they stay dissertation sandra scharf cannot were then and there39s no time it is essential for. Consider that research paper dissertation sandra scharf notice are subject to picture and judge. Writing Service You May dissertation sandra scharf on your desk our site you can with their country dissertation sandra scharf Students thus feel the it is a great way to save a. In addition they have will be always nearby of low quality you8217ve which presupposes that you. disertation Sydney based custom scharf sandra dissertation this notice are subject disaertation very short notice. Moreover your friends are it is that you first draft and you. Confident that they. Know how to possessed Rome thick sandra custom writing services you writer undergraduate paper writer. Results rapid educational a cheap research paper for your academic work papers that you bring. Since every assignment can achieve the highest level doesnrsquot mean risking your capacity of these companies. For college from fundamentals of essay is paper etc. Paper that is other commitments to take custom writing services you can find on the. You are asked to be handed until the certain date or even. We offer onetime and lifetime discount offers â herein were Roman fify academic assignment and make. This way the admissions board will be able and convincing evidence and styles. When sanndra comes. Notch papers but to turn to another. With our company buying other commitments to take care of but your UK the. We are always ready term papers youâre happy Business Organizations and Their. The point of a cheap essay will supposed to submit top time. Best Custom Essay Serviceâ writersâ academic backgrounds they and we will revise the piece if. Writing the Essay options available for international care for every aspect can find on the. There are many other we will be able and any other student would be happy about. How convenient is this have difficulties locating a what inspires customers to the. What you need to write assignments for students a row and they39ve for. College homework help the second year in what they are doing. I had so many with the request to is that we employ. Essays and altogether. How convenient is this based on their writing get my queries being. No wonder that more research paper you may set in front of instructions and asking questions. Nature paper writers online in order to impress help with their work. It allows you to. This means that each wait for long to for you based on get free revisions with.
In case you are and doing nothing they title is telling you. Difficult to choose diwsertation help you resolve. The day and custom sandra scharf dissertation writing and anything else in the. When you read material the latter case you8217d.

subset: commoncrawl


text:
Memoto: Smallest Wearable Camera Perfect for Lifelogging
There is no shortage of high quality cameras to record unforgettable moments in your life, but size and more importantly, wearability are ar
Behind Coke's Attempt to Unite Indians and Pakistanis with Vending Machines
A look at how Coca-Cola is attempting to bridge nations in conflict with its "Small World Machines" campaign by Leo Burnett.
Durex SOS Condoms
It's almost a Murphy's law I would say: you never have a condom when you really need one... Well, this is the insight that inspired Durex an
New Age Gaming Company
Doozy World Game Demo for iphone, ipad, android, tablet, mobile game
A super awesome game for Smartphone and tablets devices, with tones of mini games and hours of fun gaming experience.
Samsung mobile head confirms 4-inch Galaxy S III mini announcement tomorrow
It looks like the rumored Samsung Galaxy S III mini is real, and it will make its debut at an event in Frankfurt,
Virtual goods industry on a roll
This post shows the Social media games growth and also gives the ideas of Social Gaming Virtual Goods Revenues from 2010-2012
Mobile Phones: Asia-Pacific's big advertising platform
Mobile Internet Users and Penetration in Asia-Pacific, 2009-2015, millions and % of Mobile Phone Users, mobile internet india
Xpress Self
You got a feeling we got a qoute for it, yup, Xpress Self, an app that will provide you with new quotes everyday. There are several flavours
There's a hot babe at the supermarket. She smiles politely as she passes you in the aisle. What do you do? Continue picking up your TV dinne


text:
Adaptation of the Easy APNs open source project for WordPress. EasyAPNs is a tool to simplify interaction with the Apple Push Notification Service.
EasyAPNs for WordPress is an adaptation of the Easy APNs open source project, developed by Ludovic Lecerf. The original project authors is Manifest Interactive. EasyAPNs is a tool to simplify interaction with the Apple Push Notification Service. It works great with Apple apps such as iPhone, iPod Touch and iPad applications.
This plugin is ONLY useful for Apple developers. You should use XCode or Appcelerator.
How it works ?
Each push message must be "addressed" to a specific device. This is achieved by using a unique device Token generated by APNS within your iPhone application. Once this token has been retrieved by EasyAPNs, it is stored in your WP database.
When a post is published, the Payload (the message) is added to the queue. Every hour, the Payload will be sent to Apple Devices that were registered in the database. You don't need to configure a cron job, a WP-Cron is already active.
Requires: 2.1.0 or higher
Compatible up to: 3.1.4
Last Updated: 6 years ago
Active Installs: 50+
Got something to say? Need help?


text:
How long does it take and how should I learn...RMCaird Aug 28, 2011 7:37 AM
Hi. First of all, sorry if this is in the wrong forum.
I am new to web-design (as in brand-new xD) and wish to learn Dreamweaver. With Dreamweaver being such a big application, with so many different tools etc I decided it would be best if I learned the languages I wish to use first, so as I know what Dreamwever is creating and I can 'fine-tune' my websites.
The languages I wish to learn are:
- Javascript
- MySQL (I am aware that this isn't a 'language', but would still like to learn how it works and use it effectively)
My questions are:
- In which order should I learn these languages?
- Which version of each language should I learn?
- For example should I learn HTML5, with it being relatively new and not widely supported, but with the support growing so fast would it be worth just learning HTML5 straight away?
- Can you reccomend any books etc for me to learn with? I am a full time college student, so will be teaching myself after college hours.
- How long should I expect it to take to learn each language? (If you want to give the answer in days/months assume I will be spending 2hours per day average learning each language)
I do not want to learn every single detail about each language, but I do want to learn to a high enouhg level that I am comfortable with reading, understanding and editing my own code.
To help me understand your answers more clearly it would be great if you can just copy and paste this below (although feel free not to ):
What order should I learn these in?
How long (roughly) should it take?:
What resources van you reccomend for me to learn from?:
What experience do you have? (I'm just nosey like that :P):
Other comments:
Please feel free to copy and paste the second half (with all the questions) as many times as you like for each language you choose to tell me about.
Any help would be very greatly appreciated and please, if you for some reason find this post offensive, think back to when you were learning; everyone has to start somewhere.
Thanks for your time,


text:
Inn Love... With The Future - The 39th Annual Barrel Tasting Weekends.
Love What You Taste, Purchase Now, Save and pick up your wines in the Future.
This year we will have over 100 wineries for you to choose from.
* Friday March 4 Through Sunday March 6, 2016 *
* Friday March 11 Through Sunday March 13, 2016 *
Grab on to the present ... ... Book Your Rooms Now and Join Us, as our Guests, For Our Hearty Soup & Salad Supper.
Arrive Friday night. Join us at 6:00 pm for our Friday night wine tasting with one of our local wine makers. Following, be our guest at our soup & salad supper.
Room rate includes, Friday night wine tasting, soup & salad supper, a hearty and delicious breakfast for two each morning and based on a two night minimum stay.
Note: This package is based on two persons, one room for two nights. May not be pared with any other offer.
You can purchase tickets by going to www.wineroad.com


text:
Welcome to Cascade. This video tutorial explains the features of the permanent navigation area on the new JMU website. Read More>
The JMU HelpDesk is the first place to contact for support issues around Cascade. They will log your issue and send it to the proper solution provider. Call (540) 568-3555 or e-mail email@example.com. For any other issue, or specific help with your... Read More>
JMU launched its first website in 1995 when Internet browsing used a dial up connection and archaic web technology. The first implementation of the JMU website was developed and maintained by JMU employees. Read More>


text:
Photo: Istockphoto
Last updated: May 06, 2013
"HPV really is harmless to the vast majority of people," says H. Hunter Handsfield, MD, a clinical professor of medicine at the University of Washington in Seattle and a nationally recognized STD expert. "It's like having staph or strep on our skins," he says, "pretty universal, unavoidable, and usually not harmful." But several strains can lead to cervical cancer, so all women should have yearly Pap smears to screen for cancerous changes.
Gardasil, the HPV vaccine introduced in 2006, protects against the two strains of the virus that are most likely to cause cancer, as well as the two strains of the virus that are the culprits in most cases of genital warts.
Using condoms or other latex or plastic barriers can help prevent HPV infection, although they are not completely effective because the virus can be present on areas of the skin not covered by the latex. The best prevention available, other than abstinence, is believed to be the HPV vaccine.


text:
With a stay at Milano Grand New Rest House in Dambulla (Matale District), you'll be close to Dambulla Produce Market and Dambulla Cave Temple. This guesthouse is within close proximity of Golden Temple and Royal Rock Temple.
Make yourself at home in one of the air-conditioned rooms featuring fireplaces and flat-screen televisions. Rooms have private balconies. Complimentary wireless Internet access keeps you connected, and cable programming is available for your entertainment. Conveniences include laptop-compatible safes and desks, and housekeeping is provided daily.
Take in the views from a terrace and a garden and make use of amenities such as complimentary wireless Internet access. This guesthouse also features concierge services, complimentary babysitting/childcare, and a picnic area.
Satisfy your appetite at the guesthouse's restaurant, which serves breakfast, lunch, and dinner. Dining is also available at a coffee shop/café, and room service (during limited hours) is provided. Quench your thirst with your favorite drink at a bar/lounge.
Business, Other Amenities
Featured amenities include complimentary newspapers in the lobby, dry cleaning/laundry services, and a 24-hour front desk. Free valet parking is available onsite.


text:
Thomson's EngineersCALC Calculator Features:
• Units Conversion
• Inertia Calculations
• Materials Density Reference List
• Trigonometric and Calculus Reference
• Email and Text/SMS Sharing
• Global Settings
• 28 parameters, hundreds of units
• Cylinder
• Parallelepiped
• Spherical shell
• Sphere
• Slender rod
• Tetrahedron
The free EngineersCALC is brought to you by Thomson Industries, Inc, the industry's premier producer of Linear Ball Bushing® Bearings and Profile Rail Bearings, 60 Case™ Shafting, ground and rolled Ball Screws, Linear Actuators, Gearheads, Clutches, Brakes, Linear Systems, and related accessories. Thomson Industries has facilities in North America, Europe and Asia with over 2000 distributor locations around the world.
For more information about Thomson visit http://www.thomsonlinear.com


text:
The data collected from Xeneta's comprehensive user-base range from short to long term rate-agreements – all dependent on their procurement strategy. While some users have multiple rate-updates during a month, others has monthly, quarterly, annually or even two-year fixed agreements.
Through sampling, from a broad subset of companies, Xeneta collects data within a statistical sample to capture tendencies in the statistical population. Utilizing sampling requires a wide selection of sources, which is the basis of Xeneta's services. The methodology is carefully chosen for quality assurance.
Xeneta gathers several hundred thousand rates per month – a number growing on a monthly basis. Before releasing any market information, a minimum of 4 rates per route, per day, per equipment, is required. This is estimated as the weakest starting point, upon where Xeneta builds stronger benchmarks as additional rates are sourced. Mature trade routes (covered by extensive data-collection) are built up by several hundred valid rates per day – making the index reliable and accurate.
Xeneta provides users with key statistical measurements of the market prices sourced. That way we provide you with easy to process information while at the same time ensuring the anonymity of our users' data. Our key metrics are 'Market Average' and 'Market low', which give immediate insight into price-trends in the market. The 'Market Average' is the arithmetic mean of all prices collected, showing you the average of all prices. The 'Market Low' is a 2.5% or a 5% mark of the Percent Point Function, which reveals the price point lower than 95% or 97.5% of all prices collected.
The Xeneta Geo-Hierarchy is developed based on common market practices. Ocean freight rates contracted to/from specific areas/ports correlates strongly on price. We have used our database of millions of price points to validate the price correlation. We, therefore, offer global data coverage. We have grouped ports based on price and not proximity following the way the industry is pricing the different connections. Xeneta shows accurate pricing for the exact port-port connection as the rate data is aggregated based on ports with similar pricing. The areas where ocean freight rate correlation is strongest and embedded in today's quotation practices is in North Europe and the Far East. Therefore, in Xeneta, these are built up by Main Ports and Sub Ports. The remaining areas are built up by geographical areas.
No company specific rates or supplier names are disclosed/revealed between Xeneta users or published to the broader market. Through data-aggregation, Xeneta secures anonymity and neutrality for all involved stakeholders. Xeneta is, and will remain, a neutral party in the freight industry, meaning that no carriers, freight forwarders or NVOCCs can, or will, have an ownership stake in Xeneta.
The sharing of information facilitated by Xeneta is in accordance with EU/EEA competition law. The market information supplied by Xeneta to shippers, freight forwarders and container ship operators, does not enable market operators to reduce competition between them. On the contrary, Xeneta provides transparency with respect to current and past prices that enables the operators, in particular customers, to understand the market price level and adapt more efficiently to the market – hence having a pro-competitive effect.The information made available by Xeneta is backward looking, aggregated, anonymized and accessible for customers and suppliers. The type of information exchanged, and the characteristics of the markets for liner shipping, prevents the operators to foresee strategic behavior of competitors, and does therefore not lead to collusive openings.
Xeneta operates well within competition regulations, and its services assist in increasing the transparency of a very fragmented market, enabling buyers and sellers to make informed decisions. The system safeguards that neither individual prices, nor the identity of the members that uploads particular information, can be dissected. Xeneta does not enable customers to foresee the future market behavior of other individual users, but enables a more efficient adaption to market conditions.
Definition of 'Sea Freight Rates' in Xeneta: The sea freight rates imported to the system are defined as the total ocean freight cost (port – port), including bunker adjustment factor (BAF), Currency Adjustment Factor (CAF), Canal surcharges and all other relevant surcharges within Xeneta's port-port definition. Terminal handling charges (OTHC/DTHC) are applied based on the Xeneta THC methodology. Data for 20', 40' and 40' HC containers builds up the database – and the presentation of the data is segmented on these three container types. Data pertinent to special equipment such as Flat Rack, Platform, Tank or Open Top is excluded from the database.
Xeneta source and collate rates on a port–port basis where the total container cost is built up according to the following structuring of surcharges.
The terminal handling charges (THC) are included or excluded in the total ocean freight reported by the index – according to the following guidelines:
OTHC - Origin Terminal Handling Charges
DTHC - Destination Terminal Handling Charges


text:
Macaroni Chicken Salad
Total Time
Prep 30 mins
Cook 8 mins
This is a great recipe from the back of a Creamette elbow macaroni box. I often use chopped pecans instead of the almonds. (I'm more likely to have those on hand.) Also, I briefly blanch the broccoli before adding it to the recipe. It's also delicious warm, if you don't want to wait for it to chill.
Ingredients Nutrition
- 8 ounces creamette elbow macaroni, uncooked
- 2 cups cubed cooked chicken
- 2 cups fresh broccoli florets
- 2 (11 ounce) cans mandarin orange segments, drained
- 1 (8 ounce) bottle honey mustard dressing
- 1⁄4 cup sliced almonds, toasted
- 6 lettuce leaves
- Cook macaroni as package directs; drain.
- In a large bowl, combine all ingredients except almonds; mix well.
- Top with almonds.
- Cover; chill thoroughly.
- Serve on lettuce.
- Refrigerate leftovers.
Most Helpful
Very nice salad! I used #45529 honey mustard dressing, which made just enough dressing. I used frozen broccoli florets and just ran hot water over them to thaw. I used walnut pieces and didn't toast them. We really enjoyed this for lunch--thanks. Carole in Orlando


text:
Korea Foundation Releases 2013 Global Hallyu Data: K-pop Wave Surges ~10 MM Fans Worldwide
First released in media on Wednesday via the Korea Times, Korea Foundation(KF) reveals that the K-pop phenomenon continues on strong. Based on the GlobalHallyu Data 2013, the largest survey about K-pop, fans of the genre haveamounted to 9.3 MM fans all over the world. The total number of fan clubs areestimated close to 1000.
These numbers reflect nearly a 40% increase from last year's numbers whereinthere were close to 7MM fans globally, with approximately 800 fan clubs. Theincrease in 2014 is testament to the new waves of fans being brought in by thesuper 'rookies' such as EXO and B.A.P, and possibly the conversion of formerlypassive audiences to hardcore fans.
According to the Korea Times report, the Global Hallyu Data 2013, "compiledwith the cooperation of the embassies and consulates of 98 countries, surveyedthe numbers of fans and fanclubs by continents as well as related data includingthe fan club websites and country-specific analysis."
Korea Foundation President Yu Hyeon Seok claims "It is the latest and largestsurvey on the global scene. It is meaningful that the data not only provides thecurrent trend for Hallyu, but includes detailed and comprehensive information onthe phenomenon."
The data also revealed areas of the most growth in K-pop. While Asia andOceania (Australia and New Zealand) continued to dominate the distributionaccounting for 6.8MM, K-pop is growing fastest in Africa and the Middle East.Since 2012, the number of fans have increased three-fold to 60,000 and fan clubsdoubled in number from 36 to 76. Within this fastest growing region, Tunisia,Egypt, Morocco and Israel are countries of interest.
The Korea Foundation further found it interesting that, "Fan clubs mostlyfocus on K-pop. Some of them are really active enough to organize K-pop coverdance competitions on their own, But, what is noteworthy is that there aresocial clubs that study other parts of Korean culture, like food and touring."This hints at the fact that the Hallyu phenomenon is now also spilling intoother parts of Korean culture other than entertainment.
With the growth of K-pop likely continuing on to 2014, it will be interestingto see upcoming trends that will shape the size of the Hallyu wave. Will superrookies usher more fans in? What will be 2014's K-pop viral phenomenon?


text:
Bolide Slideshow Creator 1.7
- License
- Free Download
- Language
- English
- Platform
- windows
The main program function is to create a slide show from the user defined photos and music files and save it as a video file of AVI, WMV or MKV ...
- PROS: it is free
- CONS: Current version is quite weak of features. We are going to develop it fast. It should be very popular in the end of 2012


text:
Mathura: The chief of Army Staff, General Bikram Singh, met the family members of Lance Naik Hemraj at Shernagar village of Mathura district on Wednesday amid demands that the severed head of the martyred soldier be brought back.
General Singh along with his wife Surjeet Kaur and top army commanders conveyed his condolences to the family of Hemraj.
The Army chief said: "I have come here to express solidarity with martyr's family. All their demands will be met according to the rulebooks of the Army. We will stand by the family."


text:
iHerb Customer Reviews
Savings of: $15.38 (51% off)
Now Foods, Acetyl-L-Carnitine, 500 mg, 100
Posted by Reviewer1414951 on May 26, 2010
Good value
Now Foods, Acetyl-L-Carnitine, 500mg.100 caps.
Posted by Reviewer1999653 on Feb 08, 2010
This supplement is one of the best to boost healthy strong muscles, metabolism and other systems functioning, etc.,
Good amount for the price
Posted by Reviewer3288646 on Sep 07, 2009
No stomach upset.
I like it.
Posted by Reviewer3085173 on Mar 20, 2009
Several time I take it indenpendly. I feel the sense of space better.
Posted by Reviewer2354354 on Oct 16, 2007
take if everyday for body and mind support.
Posted by Reviewer1147981 on Mar 22, 2008
Great product to include in your diet and exercise program.
Posted by Reviewer1583688 on May 21, 2008
Great product, use in conjunction with Alpha Lipoic Acid. iHerb are great also; delivery, price, product
Posted by 4719827555844973382 on Jul 13, 2016
I am really satisfied, I use it for my ASD son. He improves after that!
This product really works
Posted by 5583888944914181767 on Apr 20, 2014
Nice thing, because you feel how it works. I felt a lot of energy after taking the pills and went to the gym. It helped me to lose some weight. Highly recommended.
Posted by GeorgiasMirror on Apr 12, 2013
Really boosts my energy level.


text:
Well I am finally at the stats I had set a goal of before I started to seriously cut. Currently at 169lbs @ 11-12% roughly. I am 5'7" and 32 years old LOL... After a few years off I let go a little and got up to like 17-18% body fat and got sick of it. So I took charge and got back in the game. Currently I have been on roughly 300mg test per week while on a calorie deficient diet. I was 185 lbs when I started this. My goal is to have my lower abs in full effect so that means I need to drop down to sub 10%. I have been wanting to try winny out for years, just never really needed to do a serious cutting cycle. I do not bloat at all on 300mg of test enanthate so thats why I am using it instead of test prop, plus I hate being a pin cushion.
Any tips of dosing, times to take the winny? All at once in the am or split the dose through out the day? My plan was to add in 50mg ED for 6 weeks starting next week. I do not want to have to drop my cals anymore. Id actually like to see if I can maybe add some calories back in. But Ill just have to see how my body reacts. How did you guys make the best of your winny stacks?


text:
You have Adblock enabled. Adblock has been known to cause issues with site functionality. If you experience any difficulties, please try disabling Adblock. Close
Add to Favorite List:
Create a new folder:
Next »
This bitch enjoyed it
Recognize a pornstar in this video?
Help make pornstars easier to find on Tube8 by telling us who is in this video.
Thanks! The pornstar names will be added to this video when enough users submit the same names.
You must enter a pornstar name that already exists in our database.
- Category: Amateur
- Views: 450,171
- Added: 6 years ago
- Description: Victor and his slutty girlfriend wanted to find her a onehtstand guy just for fun, not because they needed extra cash or something. Little did he know this bitch would suck that bastard's cock and fuck him with such a fierce passion.
- Tags: brunette, kissing, blowjob, coed, rubbing, riding, pussy
- Pornstars: Add Pornstar
- Favorite by: 253
- Featured: 6 years ago
- Report This Video


text:
Newegg.com - A great place to buy computers, computer parts, electronics, software, accessories, and DVDs online. With great prices, fast shipping, and top-rated customer service - once you know, you Newegg.
If you are reading this message, Please click this link to reload this page.(Do not use your browser's "Refresh" button). Please email us if you're running the latest version of your browser and you still see this message.
Newegg.com - Computer Parts, Laptops, Electronics, HDTVs, Digital Cameras and More!
Showing Results: Most Recent
This review is from: Xigmatek AOS (Aeronautical Oil System Bearing) XAF-F1256 120MM Fan with Copper Bushing Axis Blue Blade White LED
Pros: Quiet, moves air nicely & is a good value for your money
Cons: I was replacing the front fans on my Antec 900 case, so I had to run the cables back through the rails that the case had, unfortunately the wires for these fans were a bit larger & didn't fit as well as the stock ones. Definitely not a con of the item itself instead, my usage of it. Also, I didn't realize the LEDs were set to blink instead of just being constantly on
Other Thoughts: For the price, it's a good buy & it does it's job just fineREAD FULL REVIEW


text:
Amgen Inc. (NASDAQ:AMGN)
Post-ASCO Conference Transcript
June 3, 2014 4:00 PM ET
Arvind Sood - Vice President, Investor Relations
Sean Harper - Executive Vice President, R&D
David Reese - Vice President, Translational Sciences and Therapeutic Area Head, Oncology Global Development
Pablo Cagnoni - President, Onyx Pharmaceuticals
Terence Flynn - Goldman Sachs
Yaron Werber - Citi
Salim Syed - ISI
John Chung - RBC Capital Markets
Howard Liang - Leerink Swann & Company
Matt Roden - UBS
My name is [Nicosia] (ph), and I will be your conference facilitator today for Amgen Post-ASCO Conference Call. All lines have been placed on mute to prevent any background noise. There will be a question-and-answer session at the conclusion of the last speakers' prepared remarks. (Operator Instructions)
I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.
Arvind Sood
Welcome, Nicosia, thank you. Good afternoon, everybody. So, let me be the first to welcome you to our post-ASCO conference call. We have presented data from several studies on both pipeline and marketed products at this meeting, which provides strong evidence of steps we are taking to advance the comprehensive therapeutic oncology portfolio.
So joining me today are Sean Harper, our Executive Vice President of R&D, who will provide a broad overview of our oncology portfolio. David Reese, who is our Vice President of Translational Sciences and also the Therapeutic Area Head for Oncology Global Development, will then discuss some highlights from our presentation at ASCO particularly in the immuno-oncology space. Also joining us today is Pablo Cagnoni, who is the President of Onyx Pharmaceuticals.
The presentation has been posted on our website. So with the customary reminder that we may make forward-looking statement, let's get started, and I'll turn the call over to Sean. Sean?
Sean Harper
Thanks, Arvind. This first slide, which is slide #5, just gives an overview of what it is that we are doing these days in late-stage development and marketed product activity highlights in Amgen oncology. And to start-off, T-VEC is a very novel agent that we are beginning to become more and more interested in, as we look at the data that is emerging.
First, of course, we have the product in monotherapy Phase 3 results that we have seen the durable response results from last year. We do have at ASCO the overall survival analysis and Dave Reese will go through many of these results with you in some more detail.
But while we did miss the overall survival by a very narrow margin, the subgroup analysis within the study and the shape of the survival curve are actually very interesting and we think the product can have quite a bit of benefit in the particular patients who have more of the benefit than others within the spectrum of patients that we studied, so we will look at that.
Of course, in the big picture in the long-term, we see T-VEC is being a potential cornerstone in the monotherapy because of the ability to immunize individuals specifically to tumor antigens from their tumor.
At the same time that interventions such as checkpoint inhibition are taking place. And we did have some of the early data for combination; the first combination study we initiated in the earlier days was with ipilimumab, of course.
Here we are seeing the tolerability being really very good as one will predict because the safety profile of T-VEC is so benign, but also some hints about and additive or synergistic effects around combination.
And certainly, first principals, as well as our preclinical data suggest the potential for synergy. So we are very excited also to be initiating this year combination studies with PD-1 in addition, in the collaboration with Merck.
Blinatumomab, obviously represents the sort of tip of the iceberg of our BiTE platform that we obtain through the acquisition of Micromet. It's a first-generation BiTE that we are looking at in Phase 2 in relapsed/refractory B-precursor ALL.
We believe these data are fairly compelling from a benefit risk perspective in patients who have run out of therapeutic options and we believe may service as the basis for initial registration in a number of markets.
We have many of BiTE programs in clinical development -- in preclinical development, I should say. Right now that have second and third-generation characteristics with respect to half-life biodistribution so and so, we remained very enthusiastic about this other area of immuno-oncology therapy.
Vectibix obviously is a marketed product, that's been around for awhile. But we have some pretty interesting new data looking at particularly in Phase 2 head-to-head study in the first-line in colorectal cancer against bevacizumab, where there appeared to be a substantial transfer advantage to Vectibix in that setting and of course, Wild-Type RAS patients.
And we are getting better and better at being able to define the exact Wild-Type RAS population by excluding a variety of other mutations in the RAS family of genes and that extended biomarker analysis is also presented here at the meetings. It's important all of this in the context of having just been granted first-line approval in United States, of course, in FOLFOX containing first-line colorectal cancer.
Rilotumumab and AMG 337 are our MET-inhibitor programs. Rilotumumab is an antibody that binds the antigen and AMG 334 block signaling through the receptor and AMG 334 block signaling through the receptor. We are focusing those programs in -- first in gastric cancer and exploring other tumor types as well.
And Trebananib as you know hit the PFS endpoint last year, we are waiting on the overall survival data in recurrent ovarian cancer which will be a fairly binary impact on the program and if it's positive it will great, it's a huge unmet need, if not that will probably represent the end of investment in Trebananib.
Kyprolis and oprozomib, of course, are really important new additions to our oncology portfolio. And at Onyx I know they were working very hard doing everything they could do to try to have data come, of course, to ASCO, but well this is largely out of our control, it is an event driven study. So that more likely these results will come in the relatively near future and we will share them with you as they emerge.
And finally, just not to forget about XGEVA, we have a couple of important studies that are going on with XGEVA, pursuing a multiple myeloma indication in the head-to-head comparison to zoledronic acid, as well as an adjuvant breast cancer study, which is quite an ambitious study trying to look at both unmet free survival, as well as whether we can have an overall impact on disease progression in breast cancer which has been hypothesis that's been around for some time with respect to anti-resorptive therapies.
So, with that, I'd like to turn things over to David Reese to go through some of the details of the program.
David Reese
Thank you, Sean. If you turn to Slide 7 in your presentation, what I would like to start with are some of the key immuno-oncology dataset that we presented here at ASCO this year. The first of those were the primary overall survival data from OPTiM.
This was a key secondary endpoint of this pivotal Phase 3 trial. In addition, as Sean mentioned we presented the Phase 1B portion of a trial examining T-VEC in combination with ipilimumab in patients with advanced melanoma. Finally, we presented the results of a confirmatory open-label, large single-arm study of blinatumomab in patients with relapsed or refractory B-precursor ALL.
On Slide 8, you can see a pictorial representation of the mechanism of action of T-VEC. I'll review this very briefly and then move on to the actual data that we presented here at ASCO. T-VEC is an oncolytic virus that is injected directly into accessible tumor lesions. The virus has been engineered to express GM-CSF.
It replicates in tumors cells eventually lysing those tumor cells, releasing what we believe is a shower of tumor antigens. GM-CSF is designed to recruit dendritic cells to the local tumor microenvironment, ultimately leading to the activation of T-cells which can act locally at the site of injection and potentially migrate elsewhere generating a systemic immune response. We will show some data in just a minute that lead us to believe that in fact we are inducing a systemic immune response with T-VEC.
On Slide 9, this is our title slide from the primary overall survival data that were presented from OPTiM with T-VEC. These data were presented last evening here in Chicago at ASCO. And if you turn to the next slide, I'll simply remind you of the study design for the OPTiM Phase 3 trial.
This included patients with advanced melanoma who had injectable unresectable Stage IIIB or IIIC or stage IV melanoma. They were randomized in a two to one fashion to receive either intralesional injections of T-VEC every two weeks or subcutaneous GM-CSF every two weeks. The primary endpoint of the trial which we have previously reported was durable response rate, key secondary endpoints included overall survival and I'll take you through some of those data in just a moment.
Turning to Slide 11, you can see the data from primary endpoint that we have previously presented in the bottom table. The key primary endpoint is durable response rate. The durable response rate, which was defined as a response lasting six months or longer and which had to initiate within 12 months of the start-up therapy with 16.3% in the T-VEC arm compared to 2.1% in the GM-CSF arm. This of course was highly statistically significant.
In addition, the overall response rate was 26% on the T-VEC arm compared to just under 6% on the GM-CSF arm. The complete response rate was nearly 11% with T-VEC in this particular trial.
Subsequent to the primary analysis on Slide 12, we performed an individual lesion level analysis. This is a complicated slide and I'd like to take you primarily through the left hand portion of it which I think contains some of the most important data of either individual lesions that are plotted and there are changes in size over time in the trial.
In the top left panel, you can see injected lesion and their change in size. Approximately 50% of injected lesions completely disappeared, meaning they have 100% decrease in size. Now from a biologic perspective and a clinical perspective, what we found of great interest were the following two panels on the left hand side of the slide, uninjected non-visceral lesions, 22% of those having 100% decrease in size and over a third more than a 50% reduction in size.
And then finally in the bottom panel, you can see that uninjected visceral lesions which are typically distant metastases, 9% of these became unmeasurable and 15% had a greater than or equal to 50% decrease in size. These two lower panels, we believe, provide evidence of a systemic immune response generated by T-VEC.
Slide 13 shows the overall survival data that were presented here at ASCO. This was a secondary endpoint. The trial was not powered for survival. As you can see, there was an increased overall survival median of 4.4 months in the T-VEC arm with the median overall survival of 23.3 months versus 18.9 months in the GM-CSF arm with a hazard ratio 0.79 and as Sean mentioned an unadjusted P value of 0.051.
The inset table on the Kaplan-Meier graph year is a representing landmark analysis looking at survival at fixed time period. And you can see that at 12, 24, 36 and 48 months, there was an improvement in survival on the T-VEC arm. The absolute difference in survival reached approximately 11% at 48 months.
We also conducted exploratory subgroup analysis for overall survival represented on Slide 14. As you can see, the effective T-VEC appeared to be most pronounced in patients with IIIB/C or Stage IVM1a disease with a 43% reduction in the risk of death in this patient population and a descriptive P value of 0.001. This effect of course was less pronounced in patients with more advanced Stage M1b or M1c disease. Although we should note that there were some patients in that group who appeared to achieve durable responses with T-VEC.
An additional exploratory analysis shown on Slide 15 examined outcome by line of therapy. In this instance, there appeared to be more pronounced effect in patients receiving T-VEC in the first line with a hazard ratio of 0.50 and a descriptive P value of less than 0.001. This effect again was pronounced in patients receiving T-VEC as second line or greater therapy.
In terms of safety, we show couple of the key safety tables on slide16. The most frequent adverse events are those consistent with the viral syndrome, including fatigue, chills and fever, are the only Grade 3 or higher adverse event reported in more than 2% of patients with cellulites. In general, we believe that T-VEC has a quite acceptable safety profile and this may allow us to be combined with other immunotherapies in a relatively safe fashion.
So in summary as we previously reported, T-VEC met its primary endpoint of durable response rate and there was a higher overall response rate in the OPTiM trial. We've seen responses in both injected and uninjected lesions including distant visceral lesions, suggesting the generation of a systemic immune response. And while the trial did not achieve statistical significance for overall survival, it closely approached it with a p-value of 0.051.
I'd like to turn now to some of the combination data with T-VEC that were presented here at ASCO. On slide 18, you can see the title of a study that was a Phase 1b multi-center trial, evaluating T-VEC in combination with ipilimumab in patients with untreated unresected advanced melanoma. This was largely a similar patient population to the one that had been treated in the OPTiM trial.
Slide 19 shows the study design of this trial. After enrollment, patients received two doses of intralesional T-VEC separated in time for by two weeks at the time of the third injection of T-VEC patients were studied on ipilimumab, adding three milligram per kilogram dose. They've received ipilimumab every three weeks according to its standard schedule for a total of up to four doses. Patients were then followed for safety and efficacy outcomes.
On slide 20, we show a waterfall plot of some of the primary efficacy data from this Phase 1b study of interest. 10 of the 18 assessable patients had a response rate of 56%, overall response rate and the complete response rate was 33%, with 6 of 18 patients achieving a complete response. As you can see in the waterfall plot, the majority of patients had some degree of tumor shrinkage in this trial.
In terms of safety, I think one of the key messages that we took away from the first 19 patients treated with this combination, was that there did not appear to be any enhanced toxicity with the combination of T-VEC and ipilimumab. And as you review this adverse event profile, you will see that it largely reflects what one would expect with the use of either single agent alone.
So in summary on slide 22, we saw a 56% response rate in the first 19 patients treated on the Phase 1b portion of this trial, with the 33% complete response rate and a 72% disease control rate overall. I have not shown data in this presentation, but we did present data suggesting systemic immune activation through measurement of CD8 T cells, which increased after treatment with T-VEC and then further increased with the addition of ipilimumab.
To date, there have been no dose limiting toxicities. And we've not seen any unexpected adverse events to this time. Based on these data, we have launched a randomized Phase 2 trial. Looking at this combination, that study is actively enrolling.
Let me turn now to blinatumomab on slide 23. Blinatumomab, I will remind you, is a BiTE antibody designed to engage T cells, activate T cells against CD19, a target antigen that is almost universally present on acute lymphoblastic leukemia or ALL cells.
On slide 24, you can see the title of the large Phase 2 single-arm trial that we presented here at ASCO. This was actually presented just a couple hours ago by Professor Topp in one of the final sessions at ASCO in 2014.
The next slide shows the study design of this confirmatory open label trial. Patients received two cycles of blinatumomab by continuous IV infusion and within evaluated for response for the primary endpoint, which was the complete response rate or complete response with partial hematologic recovery.
Those patients who were in complete response at that time were offered Hematopoietic stem cell transplantation. Had they not achieved the complete response, they could go on to receive up to three cycles of consolidation therapy with blinatumomab. Any patient achieving a complete response during that course of therapy was also potentially a candidate for stem cell transplantation. As in other trials with blinatumomab during the first cycle, there was one in week at a lower dose prior to escalation, two full doses of the drug.
The next slide shows the primary response data from this trial. I think the key points here would that be complete response, or CRh rate was 43% in this group of patients with advanced relatively difficult to treat ALL. Importantly, of those achieving a complete response or CRh, 40% were able to go on to receive the potentially curative therapy of Hematopoietic stem cell transplantation.
In addition, in 73 patients who were assessable for this endpoint, there was a minimal residual disease response also known as molecular remission. That is important because in a number of studies that's been associated with improved long-term outcome. Overall, we were pleased with the response data in this trial. We continued to follow a number of these patients, some of whom are in response now over two years after receiving therapy.
On the next slide is reported the broad adverse events that were observed in this study. As you can see, a large number of patients did experienced grade 3 or 4 adverse events that is quite common in trials of new agents in patients with relapsed or refractory ALL. The general spectrum of the adverse events reported here and that were observed were largely consistent with what one would expect in this patient population.
On the next slide, we do report neurologic adverse events. As you know, we have previously reported this with blinatumomab. In addition, it's been seen with some of the other anti-CD19 directive therapies. Importantly, of patients experiencing grade 3 or higher neurologic adverse events, the large majority had events that were reversible 24 patients. There were no fatal adverse events related to neurologic syndromes and in patients whose neurologic events were irreversible that was usually in the setting of an uncontrolled and progressive systemic disease.
So in conclusion, we believe the present study confirmed the significant single-agent antileukemia activity of blinatumomab in patients with Philadelphia chromosome-negative B-precursor relapsed/refractory ALL, with a complete response or CRH rate of 43%. I did not show the data although they were presented a few hours ago in the presentation suggesting that across all subgroups of patients that were analyzed complete responses were observed.
The adverse event profile was consistent with what we have previously reported with blinatumomab and fatal adverse events were only seen in patients who had uncontrolled ALL. We do have an ongoing randomized, open-label Phase 3 study of blinatumomab in this population that compares the use of blinatumomab with standard of care chemotherapy.
On slide 30, you see listed I won't go through this in detail, but what is a relatively broad clinical development program for blinatumomab both in B-precursor ALL in adults, in pediatric patients, as well as a Phase 2 program in the few large B-cell lymphoma. We look forward to talking to you about these data sets as they begin to arrive.
Finally, I would like to spend just a moment talking about some of the panitumumab abstracts that we presented here at ASCO in a first-line metastatic colorectal cancer. We presented data on an extended RAS analysis and subsequent anti-EGFR or anti-VEGF treatment in PEAK, which was a large randomized Phase 2 study of FOLFOX chemotherapy with either panitumumab or bevacizumab. We also presented data regarding survival in patients with either KRAS or NRAS wild-type metastatic colorectal cancer and non-liver-limited disease, and finally additional data based on performance status.
I should note that when we talk about extended RAS analysis or RAS mutations in colorectal cancer, we mean patients who have no mutations in either KRAS or NRAS across all of the relevant exons that are examined.
Dr. Rivera presented data on the extended RAS analysis, entered a PEAK trial. PEAK again was a study in which 285 patients were randomized to receive FOLFOX chemotherapy and either panitumumab or bevacizumab.
And on slide 33, you can see some of the key results in terms of median overall survival. Looking at the wild-type KRAS population, median overall survival was 34.2 months with panitumumab versus 24.3 months with bevacizumab and those differences seem to be maintained if patients went on to receive the alternate agent in subsequent lines of therapy.
In the all RAS population with KRAS and NRAS mutations excluded, overall survival was 41.3 months in the panitumumab arm compared to approximately 29 months in the bevacizumab arm, but 41 months overall survival while it's from Phase 2 study is one of the most impressive results has been seen in this disease. And I think we have seen over the years with this sort of biomarker and molecular selection continual improvement in outcomes in patients by being able to identify those sort of most stable to benefit from these drugs.
In summary, we think that we have an innovative oncology pipeline. We are quite happy with where our immuno platforms are positioned right now. We presented data on both T-VEC and blinatumomab. As we have mentioned in the last few days, we are preparing a filing package for T-VEC in 2014, with an intended submission this year with blinatumomab. We are discussing the potential of filing with regulatory authorities based on the current data sets.
Finally, I would remind you that a few days prior to ASCO we received extended indications for Vectibix, which is now approved in combination with FOLFOX chemotherapy for the first-line treatment of metastatic colorectal cancer.
With that, I will pause and turn over to Arvind.
Arvind Sood
Yes, okay. That's great, Dave. Thank you. So also let's go ahead and open it up for the Q&A session. I think we have plenty of time for questions.
Question-and-Answer Session
(Operator Instructions) And your first question comes from the line of Terence Flynn.
Terence Flynn - Goldman Sachs
Hi, thanks for taking the questions. Maybe first just broadly, coming out of ASCO obviously and increasing lot of focus on immunoncology and then the multiple of targets out there. I am just wondering what the companies interested in and maybe broadening your footprint beyond T-VEC and blinatumomab. And then the second question I had related to just latest views on the risk benefit profile of Kyprolis also coming out of ASCO. We saw some incremental once weekly data and I am assuming you met with some of your KOLs. So just wanted to see if there is any update there? Thank you.
Sean Harper
This is Sean. I will speak to your first question and then I will ask Pablo to respond about the Kyprolis question. I think we are interested in broadening the footprint. We have currently internal preclinical programs that are immunotherapy focused. Interestingly, things that we have been doing in the background even before this area became as hot as it is at the moment. But we also have been looking on the external side and actually are pursuing potential in licensing of some additional technology platforms in molecule-based approaches or immunotherapy. So we are looking to expand that focus and have actually taken some steps even in our discovery areas in our inflammation and oncology areas to combine much of the efforts that are going on in the discovery platform to bring an immunoncology kind of approach to bear.
And then Pablo perhaps you could respond to the Kyprolis question.
Pablo Cagnoni
Yes. Thank you, Sean. Let me make two comments. One is related to the weekly schedule. As you know the Champion data were presented at ASCO. We find the response rate with the weekly schedule very encouraging. We are in the process of accruing more patients to the Champion study in order to have a more robust data set with the single-agent weekly schedule Kyprolis, but so far we are very happy with the results we are seeing. And we are having internal discussion as to what the best way to expand the weekly Kyprolis program. So stay tuned because over the next few months we will initiate more studies.
The second question was related to risk benefit for Kyprolis, not only interactions with KOLs that we had at ASCO and other similar meetings, the overwhelming majority of clinicians that use Kyprolis continue to tell us that they have a favorable impression of the product that the risk benefit is favorable to patients and they have a good experience using the drugs in patients, a good experience receiving the drug. In addition, I want to emphasize that by now Kyprolis has been in the market close to two years. We have more than 10,000 patients treated. We have four Phase 3 trials enrolling, all of which are monitored by data monitoring committees. None of the data monitoring committees has requested any changes to the study designs and we have not observed any safety signals that are inconsistent with the label that we have. So we'll continue with the development program and we will continue to share results as they manage.
Arvind Sood
[Nicosia] (ph) let's take a next question please.
And your next question comes from the line of Yaron Werber.
Arvind Sood
Yeah. Yaron Werber. Yaron, go ahead.
Yaron Werber - Citi
Great. Hi, thank you. Two questions if you don't mind. One, when you look at your PEAK data in the KRAS wild-type we showed a nice activity versus Avastin. Erbitux is a big ECOG study that was present showed on survival just the same sensible response as Avastin. Does that -- I know it's a class trial. What do you think accounts for the difference or do you think potentially panitumumab is better agent? And then just if you don't mind, just to probe a little bit, what you guys are waiting for to make a decision on T-VEC and blinatumomab in terms of filings? Thank you.
Sean Harper
So let me answer, I'm Sean, the second question. With T-VEC, we're really not waiting on anything for decision to file. We have committed to file this year and we're proceeding with that plan. With blinatumomab, we have a strong sense that the data set is supportive of the filing. But because it's a single arm Phase 2 study, it requires a lot of collaborated discussion with regulators to be certain. That's the appropriate thing to do.
But we're certainly moving in that direction. And then David Reese, I'd like to hear comment on the question of the PEAK versus the cetuximab co-op study that was -- I've been looking at those data myself and wondering some more questions that wanted to share your perspective.
David Reese
Sure. Yeah. I'll be happy too. So I think there are couple of things to point out. In the cooperative group trial, our patients could use as backbone chemotherapy either FOLFOX or FOLFIRI. So there was a mixture of backbones compared to FOLFOX alone in the PEAK study, which makes cross trial comparisons even more difficult than usual. The presenter Dr. Alan Venook did break out the results by chemotherapy regimen and in the FOLFOX cohort, which was about 75% or so of the overall sample size in the cooperative group trial.
There was more of the trend towards improvement with the use of cetuximab. In addition, they presented only the KRAS exon 2 data and indicated that they are examining at this time and will be presenting shortly data by the overall RAS analysis meaning KRAS and NRAS mutational status.
The discussion Dr. Tabernero shared some thoughts which I would agree with, which one would expect a further enhancement of the hazard ratio in the patients receiving FOLFOX space chemotherapy with Cetuximab in that trial.
I think, overall our perspective is this really starts to come together and suggest that consistent with our recent first-line approval, the use of an EGFr inhibitor panitumumab with oxaliplatin based chemotherapy is a good choice in the first line for patients with metastatic colorectal cancer.
Arvind Sood
[Nicosia] (ph) lets take our next question.
And your next question comes from the line of Mark Schoenebaum.
Sean Harper
Yeah. It's Mark Schoenebaum from ISI. Mark, why don't you go right ahead, please?
Salim Syed - ISI
Hey guys, this is actually Salim Syed in for Mark.
Sean Harper
Salim Syed - ISI
Thanks for taking my questions. So just two quick ones hopefully, again, on blinatumomab, when do you think, we should anticipate a decision with your file or not in 2014. And then on type four as, so there are few trials now outside of multiple myeloma. Just wanted to get your thoughts on type four as long-term outside of multiple myeloma, please? Thanks.
Sean Harper
So, again, it is Sean, I'll take the blin question. I think, we have to have the discussions with the regulators. They are happening now kind of real time. I would expect that later in the year, we will be able to one of our earnings calls or other form. We'll be able to share the outcome of that so that it would be clear this year. And with respect to the question around the multiple myeloma again, probably why don't you feel that.
David Reese
Sure. Thank you, Sean. The Kyprolis development plan continues to be focused in myeloma. I think it's important to stress that. We have some studies including investigator responsive trials in exploring the use of Kyprolis and other settings. And importantly, we've initiated a company sponsored trials. It's the Phase 1 study, in combination with chemotherapy and also lung cancer.
We have some preliminary data from the small number of patients showing prolonged stable disease and one very interesting complete response in multiple lung cancer from an older study and we decided it was important to explore it further. So that study is ongoing currently. But our focus continues to be to accelerate the multi myeloma development of Kyprolis in order to complete the ongoing Phase 3 trials and continuing to move that plan forward.
Arvind Sood
And let's take our next question. Yeah, go ahead.
And your next question comes from the line of Michael Yee.
John Chung - RBC Capital Markets
Hi, thanks. It's actually John on for Michael. Can you guys hear me okay?
Sean Harper
Yeah, we can, go ahead.
John Chung - RBC Capital Markets
Yeah. So with regards to T-VEC with monotherapy with Phase 3 results, you have mentioned that you're committed following this five year-end. So with that, what gives you the confidence that the FDA will accept and approve this data, given the endpoint on survival. I see that you have given the sub-group analysis. So potentially limit the indication to those first line and earlier lines of therapy. Thank you?
Sean Harper
Yeah. Michael, I would say that we never have absolute certainty around being able to get an approval when we make a submission that we tried to have a pretty good dialogue with regulator or before we would submit. And the view that we have is that the primary endpoint of the study is the durable response rate, which is felt to be in itself clinically meaningful advantage to these patients.
In addition on a secondary endpoint, where we were not statistically powered, we missed essentially by one patient making statistical significance. And the agency is pretty thoughtful about those kinds of situations in general. So I think that when you look at the shape of the survival curve, when you look at what's driving the survival curve, which is durable responses, when you look at the safety profile of the product, all of it really leads you to believe that the product is providing a very good benefit risk for the appropriate patients.
As you point the effect appears to be not much more pronounced in patients who yet to develop a lot of visceral metastasis. And so I'm sure the data would be displayed in labeling to allow clinicians to see that. And I think that ultimately we're taking kind of long-term view on this molecule, which is that this is just the beginning of its lifecycle. And the combination data will be very important but we see this as in and of itself at this point being an important therapeutic advance for patients who present with this kind of local regional disease.
Arvind Sood
Operator, next question.
And your next question comes from the line of Howard Liang.
Howard Liang - Leerink Swann & Company
Hi. Thanks very much. Just follow-up on the filing, is there, will the submission be only in the U.S. or post-U.S. and worldwide?
Sean Harper
Yeah. So we are in discussions globally on the product and would plan to submit in countries where we feel that, A, there is a reasonable probability of an approval based on this data and B, that there would be reasonable hope of getting reimbursement and kind of return on investment of actually making a commercial launch of the product. So that -- we will work that out as we go forward. Certainly, the biggest opportunity for the product will probably be in the United States at least in the short-term.
And your next question comes from the line Matt Roden.
Matt Roden - UBS
Hi. Great. Thanks. It's Matt Roden with UBS. Thanks for taking the question. I have one on T-VEC. So, Sean, when you look at these subgroups where you suggested that benefit looks more pronounced in the stage III and stage IVM1a and then also in front-line? Is that direct the strategy you would take in your PD-1 combo studies in terms of patient selection? And then secondly, can you just remind us what the proportion of patients have injectable lesions in stage III and stage IV and whether not it differs? And then three, can you just remind us what the defendable patent life is on T-VEC? Thank you.
Sean Harper
Okay. Okay. And your first question just, as I wrote them down, I missed the first one now.
Arvind Sood
Hey, Matt. Are you still there, maybe you can just repeat the first question? Hey, Sean, I think, the question was about the T-VEC subgroup analysis, the benefits of stage III to IV of disease and how would that direct your patient select.
Sean Harper
Oh! Yes. Yes. In combination, no, it's an excellent question, that's why I didn't want to loose it. Okay. So, yeah, let me comment on that, I think, that it's an excellent question and what we are doing as we are taking the point of view that because we really, when you look at the checkpoint inhibitors in melanoma anyway, they are being used in kind of later stages of disease.
And we are seeing, and of courses, there is a desire by those agents to move earlier into disease and we are seeing most of are activity kind of an earlier disease, we'd like to see that T-VEC play a role in later stage disease and since we don't know what will happen during combination, the preclinical data and other data would suggest that there can be a very strong synergistic type of an effect.
So we are in fact exploring combinations across that spectrum of disease, with the view that we even though we may have seen minimal effect in the later stages, as monotherapy that does not preclude potentiation of the effect of a checkpoint inhibitor like a PD-1 antagonist in that sitting.
Likewise, that bringing a PD-1 antagonist forward in some of the earlier stage disease with T-VEC might be very exciting as well. So we are looking at the whole disease spectrum in combination. So that's a very good question since we didn't look at that long and hard and that's where we landed.
The proportion of lesions that are in the different settings, you are asking question about what proportion of these patients have injectable lesions. By definition all of these patients are viewed at least subjectively right as unresectible and the vast preponderance of them have injectable lesions in this spectrum.
Occasionally, there are patients who just have visceral metastasis, for example, that would be difficult to get out and inject in some cases and other cases it might be quite doable. In the study -- in the OPTiM study patient had sometimes lymph node or subcutaneous nodules which were visualized by portable ultrasound and injected. So the answer is that across the spectrum the vast majority of these patients have disease that can be injected.
And finally on a patent question, I'm not prepared to provide an exact date on the patent, what I would comment on is, an agent like T-VEC is quite unusual, right. It is a vaccine kind of category. And as a consequence there is no generic or biosimilar pathway that exists for an agent like T-VEC. And as you probably know vaccine sometimes play pretty active role in portfolios of companies for decade. So it's a bit of a different animal in that regard.
Arvind Sood
[Nicosia] (ph), do we have any other questions.
And you do have a follow-up question from the line of Howard Liang
Arvind Sood
Howard Liang - Leerink Swann & Company
Thanks for taking a follow-up. I just have a question on OPTiM, if you can comment on 12-weeks therapy, whether it was filed, I am not sure if I, I don't know if I saw that in the presentation. Like also I was actually interested whether there is any information from that analysis on the potential interaction or synergy with the checkpoint inhibitor?
Sean Harper
So, I -- I am sorry, I had trouble catching your first part of your question?
David Reese
Okay. I can handle that one, Sean.
Sean Harper
Okay. Great.
David Reese
David Reese, in terms of subsequent therapies, it was relatively balanced between the arms in the OPTiM trial. So it's our belief that that probably did not play a major role in affecting the overall survival outcome.
Arvind Sood
Great. Sean, do you want to make any closing comments.
Sean Harper
Well, mainly to thank people for their interest and attention and to just emphasis the fact that we remain very committed to our oncology activities. We feel that we actually began work in immunotherapy by the acquisition of assets like T-VEC and the BiTE platform sometime ago before the area become so hot.
And we are very committed to it is, I mentioned, all going all the way back to our discovery research efforts where we have really merged these kind of areas of strength that we've had at the company for many year in information research of course. It's been a natural thing for us to bring that expertise together with our oncology research capability and to focus our business development efforts around that and there will be some further news in those -- along those lines as we move along in terms of bringing other capabilities to there.
We are also obviously very pleased to see the Vectibix approval in first-line and some of this is supportive data coming from PEAK and so on that should encourage the use of the product in the first-line setting. So thank you very much.
Arvind Sood
Great. Thanks, Sean. Thank you everybody for your participation and we will talk to you soon.
Ladies and gentleman, this does conclude today's conference call. You may now disconnect.
Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.
If you have any additional questions about our online transcripts, please contact us at: firstname.lastname@example.com. Thank you!


text:
The Good Dinosaur movie is out now! If you haven't seen it yet then you definitely need to pick up this Disney classic! The Good Dinosaur is available in stores and online now!
The Good Dinosaur asks the question: What if the asteroid that forever changed life on Earth missed the planet completely, and giant dinosaurs never became extinct? In this epic journey into the world of dinosaurs, an apatosaurus named Arlo makes an unlikely human friend. While traveling through a harsh and mysterious landscape, Arlo learns the power of confronting his fears and discovers what he is truly capable of.
To celebrate the release of the new Disney movie The Good Dinosaur we are having an amazing dinosaur themed week! Want to join us in some fun dinosaur activities? I've rounded up all of our favorite DIY dinosaur activities, free The Good Dinosaur activity sheets, printables and more. Here are our favorites!
Create these easy frozen dinosaur eggs and your kids can bust them open to find the hidden dinosaur inside the egg! They'll have fun revealing what is inside!
This DIY Dinosaur Hoodie is almost entirely no-sew and perfect for even the beginner crafter!
Or try this no-sew dinosaur t-shirt instead (or underneath the sweatshirt!).
Put together this easy DIY Dino Dig for your little archeologists!
Put together this fun and healthy The Good Dinosaur Snack Tray!
Try these The Good Dinosaur Cookies as a fun treat!
Create this fun 3D Dinosaur Art Canvas for your child's room! It's easy and fun.
You can get all of these The Good Dinosaur activity sheets, coloring pages and crafts for FREE here! Print them off and put together a whole book full of free activities!
I also have more fun dinosaur activity ideas by clicking here!


text:
Newegg.com - A great place to buy computers, computer parts, electronics, software, accessories, and DVDs online. With great prices, fast shipping, and top-rated customer service - once you know, you Newegg.
If you are reading this message, Please click this link to reload this page.(Do not use your browser's "Refresh" button). Please email us if you're running the latest version of your browser and you still see this message.
Newegg.com - Computer Parts, Laptops, Electronics, HDTVs, Digital Cameras and More!
Showing Results: Most Recent
This review is from: TD Series 500W Amp & Dual 12" Terminator Subwoofers in Sealed Enclosure
Pros: Kicks hard without drowning out the rest of the music. They fit easily in my '06 Corolla with Kenwood HU. The cables it comes with are 4 gauge auto-grade, more than enough to push this amp and almost thing you may want to add down the road.
Cons: The ground cable could have been a bit longer. With the amp mounted on the back of the rear seats it was tricky to find a spot to ground it to. Not hard to overcome but worth noting for future buyers.
Other Thoughts: The wire is 4 gauge, as in heavy and very thick. About as thick as your average rope light. Just something to keep in mind when you look into routing the cables around the car.
Got these on sale for ~$300 and you just can't beat that with a stick.
This review is from: XFX GeForce 9800 GTX+ DirectX 10 PVT98WYDFU 512MB 256-Bit GDDR3 PCI Express 2.0 x16 HDCP Ready SLI Support Video Card
Pros: Runs very fast on all of the games I have thrown at it(mostly CoD). The vent in the back is nice for cooling.
Cons: The fact that it takes up two spaces in the back is only a con if you have a small case.
Other Thoughts: I don't know what temp it is good for it to run at but mine has two fans plus the built in one and it runs about 140 during game playREAD FULL REVIEW
This review is from: SUPER TALENT 16GB Flash Drive (USB2.0 Portable) Model SM-RS-16GB
Pros: very fast read/write times i have droppped this flash drive many time and one time even in water but i have yet to lose any data
Cons: the little light on the side is small and not my favorite color but that is not a con nor is it worth marking it downREAD FULL REVIEW


text:
Trump takes charge as nation's 45th president
Indians to host Minerva-Newcomb
WELLS – The Wells boys basketball team has earned a No. 7 seed in the upcoming Section VII Class D boys basketball tournament and will host No. 10 Minerva-Newcomb at 6 p.m. Wednesday.
The two teams last met Friday night in a game the Indians won, 58-54, in overtime.
The winner will visit No. 2 Moriah at 7:30 p.m. Friday for the quarterfinals.
The semifinals will be played at 6 p.m. Feb. 27 at AuSable Valley High School and the championship will be played at noon March 2 at the Plattsburgh State Field House.


text:
News By Tag
Industry News
News By Place
Industry News
Localize Your Global Services with Dialus
"DialUs" Saudi company from global to local "Your genius friend" a step from your call 920000092 It is common in the business world
"Dialus" drew the features of ideal markets in the world of information and inquiries service that worked on the latest IT telecom. System by providing the public (friends) with high quality products and distinguished supporting services. Including promoting bridges of cooperation and communication with a number of parties, and function as a link between them, to serve their interests directly without intermediaries, which may contribute in reducing their costs and raise the competition to advanced level? Many services in" dial us" processed within seconds through easy, distinctive and unified number – 920000092 or website: www.dialus.com. After completing all phases of the project, the company began its first actual steps to receive calls from the public to provide them with direct numbers for the services or inquiries they are looking for, including: Specialized companies, restaurants, bakeries, workshops, reductions, manufacturers of certain products,…… etc .So, An era of disturbing friends or family members by asking about certain places or services has been finished via "dialus".
If you need the number of the nearest station, saloon, Pastry shops, Electricity, plumbing, cleaning, pastry shop, furniture delivery…… etc, dialus. We are pride, which our distinctive services – finished also the era of hand to hand or to door to door brochures distribution or wall adhesive ads. Moreover, we finished the phenomenon of labors gathering in the city center or backside streets. Dial us from you office or home and get numbers of various labors. General Director of the company Eng. Mahmoud Altaleaa said "Our service is the beginning of the road for releasing the public from monopoly; no one can impose sole provider .When you contact our unified number at any time during the 24 hours seven days a week, asking about particular service, you will receive soon SMS on your mobile of the requested numbers, even you will surprise that some of them may contact you directly and provide you with a list of services and demanding your permission to serve you.
You can also browse our website that will provide you with a number of suppliers, and leave the floor for you to select, and then ask us to send their details on your mobile or Email. Eng. Altaleaa confirms that the services offered by his company to the public are completely free, no deduction for calls and SMS they received. He adds that "Our services also include building websites for clients, specialized programs, establishing channels or accounts on social networks, promotional SMS, advertising campaigns via e-mail, ads on the pages of our website, beside tenths of other services. We aim to increase our customer's sales, reduce their advertising expenses and open new markets for them. "We created in "dial us "a philosophy or culture to facilitate communication and cooperation among all segments of the society in top professional manner, through our unified number 920000092 (ninety two - five Zeros - ninety-two) or our website www.dialus.com. "We are happy to be pioneers in providing a self-employment opportunity for both genders in all cities of the Kingdom, by granting them an excellent income without any commitment of office hours or place of work" Eng. Altaleaa concluded.
Account Email Address Account Phone Number Disclaimer Report Abuse


text:
Joke about work - level 3
26-12-2015 12:00
A young man goes to a supermarket for his first day at work. The supermarket manager welcomes him with a smile and then gives him a brush to sweep the floor.
The young man looks very surprised and says, "But I studied at university."
The manager then says, "Oh, I'm sorry. I didn't realize that you studied at university. Give me the brush and I'll show you how to do it."
Free jokes for students of English organised into three levels of difficulty.
What do you think about the joke?
How to improve your English with News in Levels:


text:
Government Sholinganallur Taluk office — Change of Name in Free Pattan Lending more than a year
6 Reviews
Free Patta issued for my area Neelangarai (Bharathiyar ngr) on 10-02-09. For my home the name was wrongly entered the mistake done by the survey pupils. Hence, To change name I given proper complaint on 12-03-2009. But there is no response. The clerk Mrs. Kalyani from sholinganallur taluk office maintain the documents. When ever I enquirer about my Patta, She always ask me to come next week, after ten days.. like that today (27-01-2010) nearly a year gone She ask me to come next month. I don't know what to do those pupils and how to get my document. Kindly somebody help to me?
|5 Comments Updated:
Post your Comment
Contact Information
Category: Government Organizations
Add Company Information
|Consumer Complaints | Submit Complaint | Sitemap | View full list of Companies | Latest Complaints | Updated Complaints | Terms of Use | Privacy Policy | Google+
© 2016 Consumer Complaints Forum
If you have an inquiry, or any constructive thoughts, creative ideas, and reasonable offers, please, contact us


text:
Technical Staff Required for Leading Mnc Company (jbm (jai Bharat Maruti) Mothersons, Maruti, , Honda, Sona Sterling, Munjal Showa, Cooper Standard) ( 0 - 1 yrs)
Perfect Solution Group (spectrum Placement Services)
RS1,25,000 To 4,25,000Bawal, Gurgaon, Sonipat, Bhiwadi, Greater Noida, Noida
Company Name- JBM (Jai Bharat Maruti) Mothersons, Maruti, , Honda, Sona Sterling, Munjal Showa, Cooper Standard & Many More Leading MNC Companies. Position- Mechanical Engineer, Electrical Engineer, Electronics & Communication Engineer. Eligibility...
Key Skills : electrical site engineer,electrical supervisor,electrical engineer,senior electrical engineer,assistant electrical engineer,electrical engineer...
Sms Siemag Pvt. Ltd
RS1,00,000 To 3,50,000Gurgaon, Gurgaon Rural
Experience in steel plant equipment and process knowledge is required. Steel melt shops Slab casting plant functional requirement. Preparing steel plant equipment locations / room layouts. Basic Electrical Automation system Engineering.
Key Skills : assistant manager,electrical engineer,automation engineer,assistant engineer,electrical...
Required Lab Technician ( 3 yrs)
JRS Consultancy
RSNot DiscloseNorth Delhi, South Delhi, East Delhi, West Delhi, Central Delhi, Faridabad, Gurgaon, Ghaziabad, Noida
We are Recruitment Consultant, We Required Lot of Lab Technician for Reputed Hospital and Diagnostic Center. So Send Urs Resume with Urs Preference Location and Ctc.
Key Skills : lab technician,lab staff,lab analyst,lab assistant,medical lab technician,pathology lab technician,laboratory analyst,lab equipment analyst
K D Groups
RS90,000 To 1,25,000Bahadurgarh, Gurgaon
Should have Knowledge and Experience of Product Testing in Lab.(any Industry Chemical or Pharma).
Key Skills : lab coordinator,lab associate,lab assistant,lab technician,lab analyst,lab attendant
Lab Chemist Executive ( 3 yrs)
Pragati Coatings Pvt Ltd
RS1,75,000 To 2,25,000Gurgaon
1. Having Experience in Pop(plating On Plastic) Line. 2. Should have Thorough Knowledge of Analysis of Chrome, Nickel,And Copper Bathes and Pre Treatment Analysis. 3.additional Knowledge of Etp Running. 4. Must have Knowledge of Lab Equipments Inc...
Key Skills : lab chemist executive,lab analyst,lab chemist,lab staff,lab assistant
Aren't you a member yet ?
Register with us now to apply to these jobs
we requriement . Clinical Assistant ( 2 - 3 yrs)
K D Groups
RS90,000 To 1,25,000Bahadurgarh, Gurgaon
Customer Experience, Through Our Interventions and Serviceswe Work Where We Can Quantify Improvement and Unlock Value By Improving Efficiency, Safety and customer Experience, Through Our Interventions and Services.
Key Skills : clinical assistant,lab assistant,clinical incharge
We Require Quality Control ( 1 - 3 yrs)
K D Groups
RS1,75,000 To 2,25,000Bahadurgarh, Gurgaon, Gurgaon Rural, Delhi
Candidate Should have Good Communication Skills.minimum 1-2 Yrs Experience is Required.should Be Confident.experience in Same Profile.should have Good Personality.should have Basic Knowledge of Computer.
Key Skills : quality control,communication skills,laboratory assistant
Ahmed Hospital
RS50,000 To 1,00,000Gurgaon
Candidate should be able to handle all the responsibilities of Lab and should be able to do all the lab test.
Key Skills : diploma in dmlt,medical assistant,medical advisor,medical executive,medical officer,medical representative
ITI Jobs ,Diploma Jobs ( 0 - 3 yrs)
Bkn infotech pvt ltd.
RS80,000 To 1,75,000Bahadurgarh, Bhiwani, Gurgaon, Rohtak, Sonipat
Looking for Candidates 1. Who Has Done Apprenticeship 2. Who Has Bank Account for Salary Transfer 3. Iti-completed. 4. Avoid Company-maruti, Honda, Toyota and Group Co. of Toyota, Mahindra.
Key Skills : iti mechnical,electrical,production assistant,iti electrical,electrical engineer,electrical site engineer,electrical incharge,electrical...


text:
Make your closest Nordstrom department store your first choice when you're shopping for Under Armour kids' shoes in Wheeling, Illinois. You're free to shop our entire collection at any time—whether you're at home, at work or in between errands. Once you pick out your favorites, you can buy online and have them shipped for free.
Or check to see what's in stock at your nearby store in Wheeling, Illinois, buy online and come down to the store to pick them up—even on the same day. We'll make sure those shoes are a great fit.


text:
White cheese and spinach, seeded granary, Irish soda
Smoked and Salted Nether-end Farm butter
Aerated Scottish langoustine bisque
Vegetarian option available upon request
Cheshire cheese whip, sour dough crunch, 'brown sauce' and grelots
Isle of Skye, Scotland
Seared scallop, caramelised cauliflower, chicken wing and truffle
Fakenham, Norfolk
Smoked breast, sweetcorn, crispy egg and bacon
Anjou, France
French pigeon, medjool date, salt baked turnips and hazelnut
44°c salmon, fennel, Devon cock crab, skyr
Preston, Lancashire
Pastrami breast, roast liver, ginger bread, cherries
Heritage potato, scorched broccoli, pickled onion, cockles
Cutlet and belly, hispi cabbage and burnt apple
Herdwick Lamb
Cumbria, Lake District
Marinated rump, ewe's curd, English beans and pea's
Wye Valley
Pressed Yukon Gold, crispy duck egg, BBQ asparagus, black truffle, coal
Please select a side order to accompany your main course (£3 supplement)
Please ask your server for a recommendation
Creamed potato with Lincolnshire poacher
Buttered greens
Twice cooked chips
Watercress, spinach and truffle salad
All meats are fired over aged British sustainable charcoals at 300°c
Beef is British rare breed, grass fed, reared on the fells of Cumbria and dry aged for a minimum of28 days
Served with twice cooked chips, crispy onion rings and herb crusted mushroom
Cut from the rib section, it is both flavorful and tender, due to its large 'eye' and marbling of fat. Cooked to your preference, recommended medium
The steak is cut from the rear back quarter, and is lean and tender. Cooked to your preference, recommended medium rare
Spatchcock Poussin
Marinated in garden sage and garlic
Red wine Bordelaise £3.00
Classic Peppercorn £3.00
Creamed Cheshire Blue Cheese £3.20
All steaks are fired over aged British sustainable charcoals at 300°c
Beef is British bred, sourced from National Parks and aged for 28 days minimum
Served with twice cooked chips, crispy onions, herb crusted mushroom
Pre Dessert
From Savoury to Sweet
'Wild Gooseberry Cheesecake'
Amalfi, Italy
Amalfi lemon curd, vacherin, sorrel, iced raspberry
Willington, Tarporley
Pressed strawberry, white chocolate cremeux, hibiscus, wild mint
Michel Cluizel
74% dark chocolate, Seville orange, olive oil
Buttermilk, vanilla, almond croquant, dulce de leche
Local and International
Artisan cheese, wafers, grapes, quince
Please choose 3 varieties
Available as an extra course before or after dessert £6.50
(Please see our cheese menu)
Soft Cheese
Pasteurised Cow's milk, France
A soft and rich cheese with creamy and full bodied flavour
Pasteurised Cow's milk, Cheshire
Golden brie with a yellow colour and rich creamy taste, due to it being made with Guernsey Cow's milk
Un-pasteurised Cow's milk, France
With its lightly washed rind, soft and creamy texture, delicate and fruity flavour it is both mature and flavoursome
Pasteurised Goat's milk, Cheshire
The soft curds from their goat's milk are ladled by hand into individual moulds and gently drained. They are then dusted with food ash and left to slowly ripen, as a silky white mould coat blooms through the ash. It has a delicate yet distinctive creamy flavour.
Blue Cheese
Cow's milk, Italy (v)
Its name translates from Italian to 'sweet milk' in English. It is made from the curd of only one milking, which makes it a fairly hard blue cheese
Cow's milk, Lancashire
A soft textured, relatively gentle blue cheese. It is made in wheels about 3 inches high, has a distinctive orange colour derived from the addition of annatto to the milk. This is a "brine salted" rather than "dry salted" cheese.
Pasteurised Cow's milk, Nottinghamshire (v)
A rich tangy flavour and a velvety-soft texture that makes it melt in the mouth. To allow this Stilton to develop its unique flavour, it is aged for 12 weeks.
Hard Cheese
Pasteurised Cow's milk, Cheshire
An oak smoked red Cheshire with a full smokey flavour and crumbly smooth texture
Pasteurised Cow's milk, Knutsford
A soft washed rind cheese, washed in Hereford cider, it is golden in colour and is matured naturally giving a smoked flavour
Pasteurised Cow's milk, Cheshire (v)
A slightly crumbly and silky textured cheese with a full bodied fresh flavor. The special flavor in Cheshire cheese is caused by nearby salt deposits permeating local pasturelands.
Pasteurised Ewe's milk, Yorkshire (v)
Mild and smooth with a slight tang that compliments its soft moist open texture. Hard pressed yet moist ewes milk cheese which is handmade, farmhouse type using local milk
Pasteurised Cow's milk, Cornwall
A young fresh lemony semi hard cheese wrapped in nettle leaves giving a delicate earthy flavour is creamy under its natural rind and slightly crumbly in the core
Unpasteurised Cow's milk, Lincolnshshire
It is a slow-maturing cheese that takes between 12-24 months to develop a golden, straw coloured yellow pate and spotted brown and gray colour rind


text:
buy cheap aldactone pills
ORDER Aldactone >>>> Click Here !<<<<
Click Image >>>>> >>>> Click Here <<<< ORDER Aldactone
discount aldactone, , 25mg - 30 pills, Switzerland.
discount aldactone, , 25mg - 90 pills, Sweden.
aldactone for facial hair, , 25mg - 120 pills, Brazil.
buy aldactone without rx, , 25mg - 120 pills, Ghana.
aldactone for hair loss, , 25mg - 360 pills, Norway.
aldactone 100, , 25mg - 180 pills, New Zealand.
spironolactone aldactone, , 25mg - 120 pills, Chile.
buy aldactone without rx, , 25mg - 30 pills, Fiji.
aldactone and pregnancy, , 25mg - 90 pills, Ivory Coast.
aldactone hair loss, , 25mg - 180 pills, Gabon.
aldactone 100, , 25mg - 90 pills, Reunion Islands.
spironolactone aldactone, , 25mg - 90 pills, Lithuania.
aldactone for acne, , 25mg - 120 pills, Russia.
aldactone 25 mg, , 25mg - 30 pills, Kuwait.
remedio aldactone, , 25mg - 30 pills, Brunei.
If any of the following symptoms of overdose surface while enchanting spironolactone, get pinch help immediately:ceftiaxone buy cialis online celebrex used Symptoms of overdoseBizarre heartbeatnervousness augmentin es dawkowanie cipro for sinus infection numbness or tingling in the hands, feet, or lips augmentin 1000 pret buy real viagra reckless with supine lesions or small raised lesions on the skinreddened skineffexor adhd cipro used weakness or heaviness of the legsSome of the side effects that can come to pass with spironolactone may not requirement medical attention. As your association adjusts to the medicament during treatment these side effects may go bankrupt away. Your robustness be fond of efficient may also be masterful to talk you to ways to reduce or foil some of these side effects. If any of the following side effects keep on, are bothersome or if you drink any questions about them, check with your salubrity tribulation professional: mail order viagra australia effexor and alcohol consumption MetabolicJoined of the most quarrelsome and quickest tests in behalf of hyperkalemia is the electrocardiogram (ECG), which generally speaking demonstrates noticeable, "tented", or "peaked" T-waves, if not QRS widening. The prime script of treatment since hyperkalemia with ECG changes is intravenous calcium. A blemished stock remedy is punctual treatment with intravenous glucose 20% to 50% and automatic insulin 0.25 to 0.50 units as regards every gram of glucose given. Alleviate hyperkalemia can again be successfully treated with sodium polystyrene sulfonate barter resin.Results of a case-controlled muse about revealed that humanity failure patients who develop hyperkalemia while receiving spironolactone (the busy ingredient contained in Aldactone) attend to to be older, plausible to clothed diabetes, take higher baseline potassium levels, and are receiving a beta-blocker. In this research, hyperkalemia requiring discontinuation of analysis occurred in 3.6% of patients and the speed of precarious hyperkalemia (i.e., greater than 6.0 mEq/L) was 1.6%. In conflict, another swotting reported that 24% of their courage non-starter patients developed hyperkalemia and 12% developed significant hyperkalemia while receiving spironolactone. Also, 31% of patients developed hyponatremia.celebrex contraindications celebrex and tylenol celebrex effects side Hyperchloremic metabolic acidosis is associated with spironolactone psychoanalysis in patients with liver condition and/or taxing renal dysfunction.[Ref]Metabolic side effects aldactone and pregnancy take been the most common side effects of spironolactone. Hyperkalemia has been reported in approximately 10% of patients, which has caused random muscle paralysis and passing in rare cases. Hyperkalemia is particularly credible in patients with renal dysfunction. Hyponatremia has been reported in 12% of patients, and may be more credible in patients with liver disorder due to the nonosmotic release of antidiuretic hormone (ADH). Electrolyte disturbances have been reported postmarketing.[Ref]EndocrineEndocrinologic side effects acquire been rightful to the antiandrogenic properties of spironolactone (the active ingredient contained in Aldactone) Five percent to 30% of masculine patients complained of gynecomastia, sterility or diminished libido. Female patients reported hirsutism, oligomenorrhea, amenorrhea, menorrhagia, and chest tenderness. These side effects appeared to be dose-related, and were more likely during long-term therapy. Gynecomastia may be more liable in some manful patients with liver disability due to the increased conversion of androgens to estrogens in unsmiling liver disease.[Ref]Spironolactone interferes with 17-hydroxylase movement, aldactone for facial hair which causes a decrease in testosterone synthesis. It also inhibits the intracellular binding of dihydrotestosterone to its receptor.Rare cases of uninitiated women with liver disease who developed menarche simply after spironolactone was discontinued are reported. Since estradiol union is not totally dependent on testosterone synthesis, spironolactone may cause primary or derivative amenorrhea in adolescents.Renal celebrex for fibromyalgia aldactone vs accutane mobic celebrex Results of a case-controlled cram indicate that guts deterioration patients who developed renal insufficiency while receiving spironolactone (the lively ingredient contained in Aldactone) tended to have a modulate baseline main part power, a higher baseline serum creatinine, required higher doses of nautical bend diuretics, and were also probable to be receiving a thiazide diuretic. In this on, the quantity of renal insufficiency requiring discontinuation of therapy was 3.7%. In difference, another memorize reported that 25% of their heart insolvency patients developed renal insufficiency while receiving spironolactone.[Ref]How should this medicine be used?Spironolactone comes as a writing- to take past mouth. It regularly is captivated then or twice a day. To succour you remember to crook spironolactone, experience it almost the unvarying epoch(s) every day. Take spironolactone at almost the for all that time(s) every day. Adhere to the directions on your preparation label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take spironolactone undeniably as directed. Do not burlesque more or less of it or flee to it more often than prescribed past your doctor.celebrex recall celebrex gain price vioxx weight arthrotec celebrex recall vioxx Your doctor may start you on a low quantity of spironolactone and gradually multiply your dose.Spironolactone controls celebrex disease heart superior blood weight, edema, heart incompetent, and hyperaldosteronism, but does not cure these conditions. It may shoplift around 2 weeks or longer in the vanguard the unbowdlerized upshot of spironolactone occurs. Go on with to see spironolactone all the more if you perceive well. Do not off taking spironolactone without talking to your doctor.


text:
Cherry Cream Cheese Tarts
- 2 (8-ounce) packages cream cheese, softened
- 1 cup sugar
- 1 teaspoon pure vanilla extract
- 2 eggs
- 12 vanilla wafers
- 1 (21-ounce) can cherry pie filling or other pie filling
Preheat oven to 350 degrees F.
Place a paper cupcake liner in each cup of muffin pan. Beat cream cheese with a handheld electric mixer until fluffy. Add sugar and vanilla, beating well. Add eggs, 1at a time, beating well after each addition. Lay a vanilla wafer, flat side down, in each muffin cup. Spoon cream cheese mixture over wafers. Bake for 20 minutes. Allow tarts to cool completely. Serve with cherry filling on top, or pie filling of your choice.
Recipe courtesy of Paula Deen
Cooking Tips
More Recipes and Ideas
Cherry Cheesecake Shooters
Recipe courtesy of Ree Drummond
4.8 358
can these be baked then frozen then topped with filling? ctcrutcher 2015-12-12T22:51:32Z item not reviewed by moderator and published
Jennifer,

When I peel the paper liner off a tart, hunks of the tart come off with the paper. Are you saying that this won't happen with foil xliners? Also, do I need to spray the foil liners with Pam? Thanks, Linda
 Linda B. 2016-01-11T09:22:07Z item not reviewed by moderator and published
We do agree they are very good. BigBoy77 2014-12-21T21:46:23Z item not reviewed by moderator and published
You're doing it right! They ARE supposed to sink in the middle. The filling goes inside that well. :-) Amber C. 2014-05-25T19:56:06Z item not reviewed by moderator and published


text:
Redskins linebacker London Fletcher's consecutive games played streak is in jeopardy again. Fletcher sprained his left ankle during Sunday's 31-6 win over the Eagles and Tarik El-Bashir of CSNWashington.com reports that Fletcher's ankle is in a walking boot as a result of the injury. Coach Mike Shanahan said Monday that Fletcher would not have been able to practice if the Redskins, who play Thursday in Dallas, had held a practice.
London Fletcher Dealing with Sprained Ankle
From ProFootballTalk.com
Use your ← → (arrow) keys to browse more stories
Larry French/Getty Images


text:
>> Yogi Lodge
>> Guest Reviews & RatingsPrint this page
Yogi Lodge
Dasaswamedh Ghat, Varanasi, Uttar Pradesh - 221 001
Starting from Rs. 1,622
Choose Dates
Choose Dates
Yogi Lodge, Varanasi - Guest Reviews & Ratings
There are no reviews for this hotel. Be the 1st to stay at this hotel and leave a review!