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A career as an Internet marketer is a great choice for Internet-savvy individuals who possess an innate marketing sensibility. Internet marketers must have excellent communication skills and the ability to effectively and creatively relay information in a variety of different arenas. Good organization, analytical thinking, creativity, attention to detail, and great problem-solving abilities are also standard traits among the most successful internet marketers.
Influencer marketing: Important nodes are identified within related communities, known as influencers. This is becoming an important concept in digital targeting. It is possible to reach influencers via paid advertising, such as Facebook Advertising or Google Adwords campaigns, or through sophisticated sCRM (social customer relationship management) software, such as SAP C4C, Microsoft Dynamics, Sage CRM and Salesforce CRM. Many universities now focus, at Masters level, on engagement strategies for influencers.
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Our agency can provide both offensive and defensive ORM strategies as well as preventive ORM that includes developing new pages and social media profiles combined with consulting on continued content development. Our ORM team consists of experts from our SEO, Social Media, Content Marketing, and PR teams. At the end of the day, ORM is about getting involved in the online "conversations" and proactively addressing any potentially damaging content.
Our SEO professionals are all well-respected thought leaders in the space and have decades of combined experience and include the following credentials: Search Engine Workshop Certification, Google Analytics and Yahoo Certifications, PMP Certification, UNIX Certification, Computer Engineering degrees and MBA's. Our SEO team members are acclaimed SEO speakers and bloggers. IMI's SEO team members have been keynote presenters at Pubcon, SMX, SEMCon, Etail, and many more influential conferences.
The biggest problem that most people have when trying to learn anything to do with driving more traffic to their website or boosting their visibility across a variety of online mediums, is that they try to do the least amount of work for the greatest return. They cut corners and they take shortcuts. Because of that, they fail. Today, if you're serious about marketing anything on the web, you have to gain Google's trust.
Word of mouth communications and peer-to-peer dialogue often have a greater effect on customers, since they are not sent directly from the company and are therefore not planned. Customers are more likely to trust other customers' experiences.[22] Examples can be that social media users share food products and meal experiences highlighting certain brands and franchises. This was noted in a study on Instagram, where researchers observed that adolescent Instagram users' posted images of food-related experiences within their social networks, providing free advertising for the products.[26]
Affiliate marketing is the art of marketing products, services or information for others. It doesn't require that you ever house or warehouse a single thing. But it does require that you have an audience to market those things to online. Without that audience, whether it's through search engines like Google or social media channels like Facebook, you'll find a difficult time with affiliate marketing.
Deliver value no matter what: Regardless of who you are and what you're trying to promote, always deliver value, first and foremost. Go out of your way to help others by carefully curating information that will assist them in their journey. The more you focus on delivering value, the quicker you'll reach that proverbial tipping point when it comes to exploding your fans or followers.
While many people attempt to understand and wrap their minds around the internet marketing industry as a whole, there are others out there that have truly mastered the field. Now, if you're asking yourself what the term internet marketing actually means, it simply boils down to a number of marketing activities that can be done online. This includes things like affiliate marketing, email marketing, social media marketing, blogging, paid marketing, search engine optimization and so on.
Guys at Think Traffic are really honest. They don't tell you that building a successful and profitable blog is all unicorns and rainbows. Corbett and Caleb don't try to sugarcoat the fact that it takes a lot of hard work and often a lot of time to earn money online, but if you're comitted to it, they are willing to show you how to do it right. I think this honesty is one of the reasons why Think Traffic is so successful.
The Marketing Communication master's concentration prompts you to analyze consumer behavior, conduct market research, and engage the power of brands and messages in order to develop powerful digital marketing strategies. Evaluate various tactics, measure their effectiveness, and explore the intricacies of working with or in complex, multi-functional teams to execute compelling marketing campaigns.
With the rise of platforms such as Yelp or TripAdvisor, digital word-of-mouth has become a major concern for marketers. Online reviews, including brand mentions posted on social networks, are more influential now than ever, with the majority of consumers trusting them to ensure they make informed buying decisions. Consequentially, reviews are the cornerstone of online reputation management — a legitimate facet of digital marketing — and all fear the negative review.
Corbett is an experienced entrepreneur himself. Prior to Think Traffic, he has founded and ran a venture-backed startup in Sillicon Valley, as well as worked as a consultant for Fortune 500. His first blog, www.corbettbarr.com, attracted over 500,000 visitors in it's first year. Now, Corbett runs a small publishing company caleed Insanely Useful Media, which is the business behind Think Traffic, Expert Enough, Traffic School and How To Start A Blog That Matters. He also advises high profile bloggers, including Leo Babauta of Zen Habits and Adam Baker of Man Vs. Debt.
He is the co-founder of Neil Patel Digital. The Wall Street Journal calls him a top influencer on the web, Forbes says he is one of the top 10 marketers, and Entrepreneur Magazine says he created one of the 100 most brilliant companies. Neil is a New York Times bestselling author and was recognized as a top 100 entrepreneur under the age of 30 by President Obama and a top 100 entrepreneur under the age of 35 by the United Nations.
Okay, obviously, this is not something that I can link you to, but Danny runs great webinars. You know those webinars that are basically just very long sales pitches and nothing more? Well, that's not the case with Danny, because in his webinars he shares very useful insights on online marketing. I really try not to miss those. You have to be subscribed to Danny's e-mail list to know when something is coming up, though.
Fine-tune your digital marketing strategy with a well-chosen technology stack. Learn about the roles and benefits of each "layer" in the stack—marketing and advertising, digital experience and clickstream measurement, back office functions, and analysis—and the technology that will help you drive engagement, measure results, increase sales, and improve customer relationships.
Our SEM team has been managing paid search since its inception and is driven solely by analytics and financial data. Our core focus is to expand our clients' campaigns, drive quality traffic that will foster conversions and increase revenue, while decreasing the cost per acquisition. IMI's PPC team members are recognized thought leaders, active bloggers and speakers and major tradeshows, and care deeply about each and every client. We manage our client's budgets as if it was our own, tracking every dollar and optimizing towards very specific milestones and metrics.
People love stories and can relate to them. A blog is a more serious business, but I have often felt that Matthew used the power of storytelling amply on his blog. By creating a video series of Tiered Link building tutorials, he made people come back for more. For more months than I can count these tutorials were the most shared and visited items on his blog.
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Keeping up with the latest trends is a must for any business, but ignoring technology trends in the digital world is the matter of staying in business. Unfortunately, those trends (while easy enough to find mentioned online) are rarely explained well. There seems to be this mistaken idea that anyone who has an interest or need in the practice will just magically get the jargon. As we all know, that is one superpower that doesn't exist in the real world.
I'm not a super social person. Some people are just wired that way and find social media a great medium to extend their personalities. However, I have found social media incredibly valuable. Regarding business, it has sent a lot of traffic and provides a way to find like-minded individuals. It also serves as a very strategic tool to invite people to join the site and experience our "subscriber only" email content.
Once you understand how everything works, and your expectations are set the right way, decide what you want to do. Do you want to become an affiliate marketer? Do you want to be a network marketer? Do you want to become a blogger and sell your own products? Squeeze pages, which are glorified sales pages that attract people and direct their attention towards a single action of providing their email address, are created in a variety of methods. The better they are, the more likely they'll convert.
And CamFind is a visual search mobile app, which enables users to search for anything from their mobile phones simply by snapping a picture and this app will tell you what it is. Instead of typing queries into a search engine, you can directly search through images to find similar images, price comparisons, local shopping results, etc. You can also take a picture of a movie poster and CamFind will show you movie information, trailers, showtimes, and local theaters.
Email marketing is the practice of nurturing leads and driving sales through email communications with your customers. Like social media, the goal is to remind users that you're here and your product is waiting. Unlike social media, however, you can be a lot more aggressive with your sales techniques, as people expect that email marketing will contain offers, product announcements and calls to action.
The new digital era has enabled brands to selectively target their customers that may potentially be interested in their brand or based on previous browsing interests. Businesses can now use social media to select the age range, location, gender and interests of whom they would like their targeted post to be seen by. Furthermore, based on a customer's recent search history they can be 'followed' on the internet so they see advertisements from similar brands, products and services,[38] This allows businesses to target the specific customers that they know and feel will most benefit from their product or service, something that had limited capabilities up until the digital era.
One of his readers in Costa Rica Yeison began a blog mytanfeet.com which is entirely about Costa Rica. In less than 6 weeks this guy who could not write English properly had his blog featured on two newspapers and earned $350. Over 90% of bloggers don't make a cent. Currently, it does over $1000 every month. And they have gone on to launch one of the first multilingual marketing blogs yeisonkim.com.
Digital marketing methods such as search engine optimization (SEO), search engine marketing (SEM), content marketing, influencer marketing, content automation, campaign marketing, data-driven marketing,[6] e-commerce marketing, social media marketing, social media optimization, e-mail direct marketing, display advertising, e–books, and optical disks and games are becoming more common in our advancing technology. In fact, digital marketing now extends to non-Internet channels that provide digital media, such as mobile phones (SMS and MMS), callback, and on-hold mobile ring tones.[7] In essence, this extension to non-Internet channels helps to differentiate digital marketing from online marketing, another catch-all term for the marketing methods mentioned above, which strictly occur online.
However, some of the world's top-earning blogs gross millions of dollars per month on autopilot. It's a great source of passive income and if you know what you're doing, you could earn a substantial living from it. You don't need millions of visitors per month to rake in the cash, but you do need to connect with your audience and have clarity in your voice.
I've taken a few awesome courses and certifications through HubSpot Academy, including an inbound marketing certification and a content marketing certification. These classes helped me be better at my job, so I started making a list of other classes I could take to learn more skills. When I finished the list, I realized that you, dear readers, might have similar skill gaps, so I wanted to share it in a blog post.
Constant Contact's Social Media Quickstarter emphasizes opportunities to integrate email with social media marketing, to maximize the impact of both channels. In a series of step-by-step lessons, learners can study digital marketing tactics for Facebook, Twitter, LinkedIn, Pinterest, Instagram, Google+, YouTube, blogging, and online listings and reviews sites. The way the courses are structured makes them perfect for beginner-level marketers, with components such as glossaries and how-to guides, combined with practical examples of the lessons at hand in action.
Internet Marketing Inc. is one of the fastest growing full service Internet marketing agencies in the country with offices in San Diego, and Las Vegas. We specialize in providing results driven integrated online marketing solutions for medium-sized and enterprise brands across the globe. Companies come to us because our team of well-respected industry experts has the talent and creativity to provide your business with a more sophisticated data-driven approach to digital marketing strategy. IMI works with some clients through IMI Ventures, and their first product is VitaCup.
Have you heard of the digital skills gap? By 2020, it is projected that there will be 150,000 digital jobs available, but not enough digital marketing professionals to fill them. For those learning digital marketing, this offers a unique competitive advantage: You're gearing yourself up for a career where demand exceeds supply. This is always a good move.
The University of Illinois at Urbana-Champaign is a world leader in research, teaching and public engagement, distinguished by the breadth of its programs, broad academic excellence, and internationally renowned faculty and alumni. Illinois serves the world by creating knowledge, preparing students for lives of impact, and finding solutions to critical societal needs.
I'm a web developer, programmer, blogger and SEO expert from Glasgow, Scotland, with over 15 years experience in the industry. When I'm not writing about marketing and SEO you'll find me strumming the guitar in my band or listening to Revolver on repeat. Follow me on twitter, connect with me on google+ and add us on facebook to keep up with all the latest trends in SEO and online marketing.
As digital marketing continues to grow and develop, brands take great advantage of using technology and the Internet as a successful way to communicate with its clients and allows them to increase the reach of who they can interact with and how they go about doing so,.[2] There are however disadvantages that are not commonly looked into due to how much a business relies on it. It is important for marketers to take into consideration both advantages and disadvantages of digital marketing when considering their marketing strategy and business goals.
A great way to learn how to be an internet marketer is to explore available online resources. Because digital marketing has quickly revolutionized the marketing world, there arose a need for easily accessible online resources to ensure those already in marketing could learn how to adapt to new digital platforms. One form of online resources are massive open online courses, or MOOCs. MOOCs are a great way to learn the same type of educational information covered in degree programs but with the freedom to only take necessary subjects. Because of the way the internet and technology rapidly changed the marketing world, many MOOCs cover marketing, specifically digital marketing. Other online resources to learn about digital marketing include one of many great marketing blogs or articles, like our own 12 Essential Terms for Online Advertising. For the existing marketing professional looking to gain a little more knowledge about internet marketing, there are many online resources to help learn the basic fundamentals.


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I love this candid photo. What a great expression this guy has! It makes you happy just to look at him – his carefree, confident grin caught for the camera, as he walks down the street. The year is about 1941, and the place, presumably a city somewhere in Mexico. We see several others out and about, and some advertising, though the ads would be difficult to completely decipher. The back of the card indicates "Kodak Mexicana, Ltd." and the stamp box shows EKC and Sello. Playle.com identifies this stamp box as being from 1941, and we can see the clothing and hair styles fitting this general time frame. The guy on the right wears a double-breasted suit jacket. The main subject of the photo in suit and tie wears a thin mustache….But that smile!
Divided back, unused Real Photo Postcard. Mexico, circa 1941. Kodak Mexicana, Ltd. EKC with Sello stamp box.
Price: $3.00

subset: commoncrawl


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Quickpea Curry
This colorful curry is a nice change of pace for a busy weeknight. I like to substitute fresh peas for frozen when they're in season. —Beth Fleming, Downers Grove, Illinois
Total TimePrep: 15 min. Cook: 35 min.
Makes6 servings
- 1 tablespoon canola oil
- 1 medium onion, finely chopped
- 2 garlic cloves, minced
- 1 tablespoon curry powder
- 2 cans (14-1/2 ounces each) diced tomatoes, undrained
- 2 cans (15 ounces each) chickpeas or garbanzo beans, rinsed and drained
- 2 cups cubed peeled sweet potato (about 1 medium)
- 1 cup light coconut milk
- 2 teaspoons sugar
- 1/4 teaspoon crushed red pepper flakes
- 1 cup uncooked whole wheat pearl (Israeli) couscous
- 1-1/2 cups frozen peas (about 6 ounces)
- 1/4 teaspoon salt
- Chopped fresh parsley
- Plain yogurt, optional
- In a large skillet, heat oil over medium heat; saute onion and garlic with curry powder until tender, 3-4 minutes. Stir in tomatoes, chickpeas, sweet potato, coconut milk, sugar and pepper flakes; bring to a boil. Reduce heat; simmer, uncovered, until mixture is thickened and potatoes are tender, 25-30 minutes, stirring occasionally.
- Meanwhile, prepare couscous and peas separately according to package directions. Stir salt into peas.
- To serve, divide couscous among 6 bowls. Top with chickpea mixture, peas, parsley and, if desired, yogurt.
Test Kitchen tips
Nutrition Facts1 serving: 390 calories, 8g fat (2g saturated fat), 0 cholesterol, 561mg sodium, 68g carbohydrate (14g sugars, 13g fiber), 13g protein.
Originally published as Quickpea Curry in Simple & Delicious February/March 2018


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Do you think �influencer marketing� is just a fashionable phrase? Not so. Influencer marketing can equal big business�and big money. This guide will show you how using influencers to contribute to your product marketing can supercharge your campaigns and help you reach a bigger, more relevant audience than ever before. In this report, we'll explore:
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One of the biggest sources of traffic to my little blog is from people who are searching for more information about Onnit's three different lines of specialty kettlebells, the Primal Bells, Zombie Bells, and its newest line, the Legend Bells. While the first two series have been completely released, the newest Legend Bells line is just beginning. The first in the series was the Werewolf Legend Bell and the word on the street is that the Legend Bells will be a line of famous monsters. The next likely release in the Legend Bells line will be a Bigfoot Legend Bell, but that isn't 100 percent confirmed just yet.
Because the appeal of the Primal, Zombie, and Legend Bells is the appearance of the kettlebells, I decided to dedicate a single blog post to outline each of the bells in each of the lines. Below you'll find 360 degree views of each of the bells so you can see just how well they're sculpted and how they look from all sides and angles.
Each of these specialty kettlebells features enlarged handles for increased grip strength and they're crafted with chip-resistant iron. They've all been custom sculpted for Onnit and all are 3D scanned to ensure perfect balance. This means that when you're using one of the specialty kettlebells for exercising, they'll perform just as well as a normal kettlebell would but they look infinitely more badass. Of course, if you want to keep them as artistic sculptures to display, you can do that too!
Since the Primal Bells were the first line of specialty kettlebells that Onnit introduced, let's start with those:
The Chimp Primal Bell was the first specialty kettlebell released by Onnit. It weighs in at one pood, which is 36 lbs. for those of you who aren't familiar with archaic weight measurements.
The next release in the Onnit Primal Bell line was the Gorilla kettlebell. It's the heaviest of the bunch, weighing in at a hefty two poods, or 72 lbs.
The Onnit Orangutan Primal Bell
The strangest looking of the Primal Bell bunch is the Orangutan Primal Bell with it's wide face weighing in at 1.5 poods, or 54 lbs.
The last in the Primal Bell line was the Howler Primal Bell, and it was also the lightest of the bunch, weighing in at a scant half pood, or 18 lbs.
Around Halloween last year Onnit introduced the Zombie Bells. If I remember correctly, it dropped all of these at once rather than releasing them slowly one by one. Unfortunately these are no longer available and Onnit didn't post any 360 degree views of these bad boys. I believe that now that they're all sold out, they won't be made again. So if you didn't buy one in time, you're out of luck I'm afraid.
From left to right we have the Mega Dead Zombie Bell weighing 72 lbs. followed by the Ghostface Thrilla tipping the scales at 54 lbs. followed by the Staple Head Zombie Bell weighing 36 lbs. and finally the Brain Goblin is the smallest of the bunch weighing 18 lbs.
Joe Rogan has a fascination with large hairy monsters, and if you're a religious listener of his podcast The Joe Rogan Experience, you probably already know this. He has a giant life-size replica of a werewolf in his podcast studio, and he went looking for Bigfoot in his television series Joe Rogan Questions Everything. What the other two Legend Bells will be I do not know, but I'm sure they will be just as awesome as the other Onnit specialty kettlebells.
The Onnit Werewolf Legend Bell
The first in the Legend Bell line doesn't seem to follow the weight pattern set by the other two kettlebell lines. The Werewolf Legend Bell weighs in at 28kg, or 62 lbs. I'm not exactly sure why Onnit chooses to weigh some in poods, all in pounds, and then the Legend Bells in kilograms. Not that it matters, but it's just something that I noticed.
And there we have it guys! A complete guide to the different sizes and weights of the specialty kettlebells along with 360 degree views of each of the ones that are still for sale. For those of you who glossed over the words in the rest of the blog post but you're reading this summary, the Primal Bells are all currently available and can be purchased as a bundle for a discounted price. The Zombie Bells are sold out and as far as I know will not be made available again. The Legend Bells line is just starting and it's unknown how many kettlebells will be made available in this line, nor is it known if this is a limited edition like the Zombie Bells.


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Julie works closely with the executive director and staff to continue the great work CRWA does and to take on the many issues the river and watershed residents face from climate change. As Director of Projects, she also manages CRWA's science program and serves as project manager for CRWA's Smart Sewering, Twinning and Climate Change Adaptation projects. Julie provides support for CRWA's advocacy work, analyzing CRWA's research and data to inform organizational focus and reviewing project or permit applications. Julie often presents CRWA's work at conferences, with local officials or committees, and at public events.
Julie ran CRWA's Field Science program from 2008 to 2014. Prior to joining CRWA, Julie was an AmeriCorps volunteer with the Maryland Department of Natural Resources where she participated in water quality monitoring, and stream surveying and restoration. She also worked as a Program Educator for the New England Aquarium.
Julie has a B.A. in Mathematics from Boston College and an M.S. in Environmental Science from the University of Massachusetts, Boston. She is the proud mother of Connor and Brayden, a fitness enthusiast and marathoner, and can frequently be found running with him along the Charles.


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Choose your room
Kingsgate Hotel Abu Dhabi is centrally located in Abu Dhabi, walking distance from Abu Dhabi Commercial Bank and close to Abu Dhabi Mall. This hotel is within close proximity of Khalifa Center and Capital Garden. Take advantage of recreation opportunities such as a fitness center, or other amenities including complimentary wireless Internet access and concierge services. Featured amenities include a business center, limo/town car service, and express check-in. Event facilities at this hotel consist of conference space and meeting rooms. A roundtrip airport shuttle is provided for a surcharge (available on request), and self parking (subject to charges) is available onsite. Make yourself at home in one of the 108 air-conditioned rooms featuring refrigerators. Complimentary wireless Internet access is available to keep you connected. Private bathrooms with showers feature complimentary toiletries and hair dryers. Conveniences include phones, as well as safes and desks.
Useful information:Other names for Kingsgate Hotel Abu Dhabi by Millennium:
Kingsgate Abu Dhabi
Kingsgate By Millennium
Kingsgate Hotel


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Hiler Industries president speaks to congress on importance of foundries. (Washington Alert).
Jack Hiler, president, Hiler Industries, and a former congressman from Indiana, spoke on the value of the foundry industry to the U.S. economy and the challenges this industry faces today. Hiler discussed the differences between the domestic competition the foundry industry faced 25 years ago and the international struggle U.S. foundries are now mired in. He cited the drastic difference in foundry labor salaries between the U.S. ($15/hr) and China ($0.42/hr) as one item contributing to today's unlevel playing field. While the metalcasting industry is producing a higher-quality product than ever before, Hiler said, prices still have hit unprecedented lows because the industry is forced to compete on the playing field of these offshore sources. Hiler also explained that the financial burden of government-imposed regulations for health care and the environment continue to have a detrimental effect on manufacturing. Hiler said that with each new regulation comes hidden costs to the manufacturing industry, and wit h each new cost, more firms are moving their labor offshore.
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SMO.net Online News
The news here is primarily concerned with the happenings of the Shawn Olson Creative Arts website, but sometimes roams to areas beyond the scope of this site. "SMO News" relates specifically to upgrades and changes to this site and its features.
Latest Articles
New Artistic Network
News relating to the Artistic Network, a website that I launched for artists around the world.
John Dewey Online
Information about my John Dewey projects.
Web Color Tool
Information regarding my RGB Color tool.
GoodGuest System
Information on the release of my GoodGuest system, an anti-spam guestbook website.
Creative Arts Newsletter 2003
The official Creative Arts Newsletter series.
Website Traffic Milestones
News snippets from various traffic milestones on my site.
Webonizer Goes Live
Information relating to the Webonizer Content Management System that I've been building for several years.


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Hair and Skin Perfections;
2 Essex Street,
Wash Common,
May 29, 2019
COURSE OF 10 FACIALS SAVE £100 Throughout July and August 2019 purchase a course of 10 CACI, 1 hour, facials for £340, saving £100
November 22, 2018
Gifts Vouchers Available Stuck for what to get someone for Christmas? At Hair and Skin Perfections we have a wide range of styling and treatments for you to choose from. Contact us for more details 01635Read more
All rights are reserved ©2019 Hair and skin perfections; website by Dizzy Web Design


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There are some people who need to have colonoscopy (e.g. first degree relative with colon cancer, Inflammatory Bowel Disease, etc. – see resources below) and there are some other tests out there (e.g. virtual colonoscopy, flexible sigmoidoscopy) but for most of us the first option is FOBT – aka Fecal Occult Blood Test aka Mailing Your Poo.
Have a look at this helpful how-to movie from U of T explaining the details of the FOBT test.
Here is the bigger picture from the Ontario Ministry of Health and Long Term Care.
And below are some more great resources to help you understand your options:
Choosing Wisely: Colonoscopy Patient Resources
New York Times: Giving Patients Choices in Colon Cancer Screening
Journal of the American Medical Association: Adherence to Colorectal Cancer Screening – A Randomized Clinical Trial of Competing Strategies
USA Centre for Disease Control Infographic: Colorectal Screening


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I guess many people view of artists are of strange obsessive creatures, often with a taste in big floppy hats, flowing scarfs and spattered smocks!! well think again.
Mind you,
I think the strange bit is pretty damm accurate!! at least my better half would agree with that. But when it comes to hats we artists need a whole range of differing styles because we need to be proficient in a variety of trades. This last few weeks for example has seen little painting done in the Fraz studio, granted a short break down to the South of France was partly to blame. Poor man I hear you say! but hey, someone has to drink their wine and eat our seafood.
Funnily enough, I actually met an artist while there, who did indeed wear the floppy hat, cravat and smock, all carefully co-ordinated to match up with his long flowing blonde hair which he proudly flicked over his shoulder from time to time (lucky BA#%*^D).
Anyway as explained in my last post Read it Here, I have gone over to painting on rigid panels which prompted the creation of the Handy Fraz Drying Rack.
Then a little more thought about my panels (I should not read in bed, very dangerous) and their framing options prompted a design modification.
So the last week or so has seen me strengthing my panels with timber batons at the back, not only will this prevent warping as the paint and atmospheric conditions dry the panels out. But they provide options to attach hooks or screws when framing. As you can see in the photos they look pretty good and I was very pleased with them
BUT, you guessed it......
they would no longer fit in the damm drying rack I was so proud of.... so I had to go back and build a bigger stronger version 2 Drying Rack. Painting.. when will I find the time?


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? Hendo and Mignolet are finally back in the fold (Gallery)
- LFC skipper and our third choice (?) keeper Simon Mignolet are back at Melwood to get off with the pre-season fine Sunday morning
Liverpool duo are finally back on club duty following their participation in the World Cup finals for England and Belgium respectively.
Henderson and Mignolet trained with their teammates as the Reds get ready for the start of exciting and promising 2018-19 campaign.
WATCH ALSO: Alisson joins Liverpool to become the most EXPENSIVE goalkeeper ever
Source: Liverpool FC


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Do you have trouble drifting off to sleep? It might be time to look at your bedtime routine. Get started here:… https://t.co/ApnFQ59pzT
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All GP Practices are required to declare the mean earnings (e.g. average pay) for GPs working to deliver NHS services to patients at each practice.
The average pay for GPs working in Linkway Medical Practice in the last financial year was £60,575 before tax and National Insurance.
This is for 2 full time GPs; 1 Part time GP; 2 full time salaried GPs and one part time salaried GP.


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Brian Torchin: Habits to Avoid in your Workplace
When Brian Torchin finished his studies, his next move was getting a job. In the processing of sending applications and attending interviews, the medical student made some shocking discoveries. The job seekers were mostly ruining their reputation in the first days of employment. Years later, when Brian Torchin started his prestigious staffing company, he vowed … Read moreBrian Torchin: Habits to Avoid in your Workplace


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'5G is about enhanced mobile broadband, requiring much greater throughput than 3G or 4G.'
According the latest study by GSM Alliance, there would be 670 million 5G subscribers (excluding IoT connections) in Asia Pacific by 2025, or 60 per cent of all 5G connections by then. Frost & Sullivan estimates that 5G service revenue in Asia-Pacific will reach US$4.50 billion by 2022. Some say that Asia Pacific is leading in the race of 5G compared to other parts of the world, with South Korea working towards early deployment of 5G for the PyeongChang Winter Olympics next year, and the Japanese providers have the opportunity to showcase full-fledged 5G at the 2020 Olympics in Tokyo. With no doubt, operators in Asia are actively conducting research and development on 5G. It is said that Asia Pacific operators accounted for four of the six fastest pre-standard 5G lab tests announced to date.
Navin Vohra, Vice President of Wireless Sales at CommScope discusses the progress of 5G development in Asia and how businesses in the region can reap the benefits of 5G. The following is an interview by The Fast Mode with Navin on his views on the topic.
The Fast Mode: Do you think Asia is leading in 5G deployment compared to the rest of the world? Why?
Navin Vohra: We are already seeing a large number of 5G trials and proof of concepts being trialed in the region, along with a sizeable number of advanced 4G deployments and IoT deployments. China, for example, is already planning 5G trials in over 100 cities. According to a report from Viavi Solutions, four out of six of the world's fastest pre-standard 5G lab tests were from APAC based operators.
In addition, the upcoming Pyeongchang 2018 Winter Olympic Games in South Korea and the 2020 Olympic Games in Japan present a huge opportunity for operators in both countries to enhance networks to support these high-profile international events, through showcasing 5G deployments - highlighting that they are one step ahead. Quite recently, Nikkei reported that NTT Docomo, KDDI and SoftBank Group were expected to invest a combined US$45.7 billion to rollout 5G services in Tokyo and other areas ahead of the 2020 summer Olympics in Tokyo.
The Fast Mode: What are the challenges that Asia is facing in rolling out 5G?
Navin Vohra: 5G is about enhanced mobile broadband, requiring much greater throughput than 3G or 4G. The vision for 5G also includes ultra-low latency speeds to enable futuristic applications. But implementing 5G also has its challenges – it will require exploiting millimeter wave frequency bands, which has been formidable so far.
One of the more pressing challenges facing operators looking to introduce 5G is matching their infrastructure to meet 5G requirements. 5G is a "network of networks" and part of the 5G vision is how to make 2G, 3G and 4G, Wi-Fi, Bluetooth and the wireline protocols all work together in a seamless network of networks.
If 5G is really going to deliver super-fast speeds, wireless networks will require more base stations in a given area —increasing the density of the network itself. Such "densification," as it is known in the industry, adds complexity to the network because it increases the number of cell borders, where interference becomes a problem and handoffs introduce the possibility of dropped connections.
The Fast Mode: How does 5G reshape the way that Asian businesses operate in the future? Navin Vohra: The wireless industry has coalesced around three primary use cases for 5G: enhanced mobile broadband, the Internet of Things (IoT) and ultra-low latency applications. 5G envisions super-fast data rates for each user, massive machine-to-machine communications in which billions of devices send short bursts of information to other systems, and futuristic applications like autonomous cars and augmented reality. Using IoT in a work environment can enable companies to realize cost savings and greater efficiencies that validate their investments. Key areas for IoT investment in the workplace are lighting and space utilization.
Lighting The LED lighting revolution created a way for organizations to immediately reduce their power bills. In some cases, those savings are being re-invested in a high density sensor network deployed throughout the building, operating on a common platform. For instance, the approach of adding one sensor per light fixture enables users to optimize energy savings based on dimming, daylight harvesting and tailored occupancy. But such an approach can be utilized to do even more.
Space Utilization The sensor network can be leveraged to provide insight about how spaces are being used. Tracking utilization of conference rooms or collaboration spaces enables organizations to quickly learn how to best optimize their spaces; for example, is there too little or too much space deployed? Sensors also make it possible for individualized adjustments to lighting, space monitoring for finding empty spots to gather, and real time temperature monitoring. Customizable user experiences, improved workplace well-being and increased productivity are the goals.
And More Collecting space and resource usage data over time enables organizations to utilize deep learning to better understand and predict behavior. The next evolution of using IoT technology will involve predictive analytics; for example, the intelligent building will know that John Smith scheduled a 10:00 a.m. meeting in conference room 101, so it will start cooling the room in advance, knowing the room will be more than 80 percent occupied and most of the attendees like cooler areas. Such IoT networks will also interact with the audio/visual equipment in the room to automatically set the lights, start the video equipment and dial participants as needed without human interaction.
The Fast Mode: When do you foresee 5G can be truly commercialized in Asia?
Navin Vohra: The first phase of 3GPP 5G standards is targeted for release before the end of 2017 by 3GPP, and 5G should be fully defined by the end of 2019. The first implementations of 5G will utilize the LTE control channel and core, and will focus on enhancing mobile broadband. It's believed that the 2018 Winter Olympic Games in South Korea will offer the first large-scale taste of 5G, with commercial 5G deployments following by 2020. The standards will continue to evolve even after the technology has landed in the market.
The Fast Mode: What are your recommendations for operators in APAC in order to achieve success in supporting future 5G services?
Navin Vohra: We all know that 5G is coming and that means wireless networks need to lay the foundations for it. To better serve their customers, operators are preparing for the 5G world by deploying more fiber.
There are two steps that every operator should follow when evolving their network:
• Oversize the fiber cables they deploy today to cater for fiber needs of the future
• Utilize plug-and-play connectivity solutions to allow for simple and flexible connection of devices to their network
When we talk about 5G being a network of networks, one of those networks is LTE. Today's evolved LTE network is going to be a cornerstone in 5G's network of networks. LTE will be the workhorse of the wireless industry for many years to come. We're going to see incremental improvements in LTE capabilities on the way to 5G, and 4G, 5G and Wi-Fi will all coexist—along with some earlier wireless air-interfaces depending on the region. Mobile network operators (MNOs) will use slices of different networks to address different applications and provide connectivity resources to them.
To service Internet of Things (IoT) use cases for 5G such as augmented driving and the tactile Internet, cloud-computing capabilities are needed at the edge of the mobile network. Mobile Edge Computing (MEC) architecture is being integrated into the 5G vision. MEC involves many smaller data centers distributed closer to the cell sites, forming an edge cloud where intelligence can be placed closer to devices and machines. MNOs will need the ability to turn up data centers in a short amount of time with high-density, high-speed solutions that are easy to install and quick to deploy.
As always, MNOs need to design and deploy network equipment for optimal performance. On a general level, this means increased efficiency throughout the converged network—from spectrum efficiency to implementation of virtualized load-balancing, and from space-efficient small cells to energy-efficient backhaul.
Like the journeys to 3G and 4G, the quality of the RF path will be critical in the arrival of 5G. The level of noise and interference in a wireless network strongly determines the data throughput. To this end, operators must focus on ensuring a clean RF path as they densify, virtualize and optimize their networks. The bridge to 5G will include the evolution of LTE, and 5G will only succeed in applications where it can offer significant advantages over LTE.


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PREP YEAR IN REVIEW: Small-Schools Softball Coach of the Year Dan Wiedman of Marquette Catholic
Greg Shashack / The Telegraph
ALTON – The 2018 Telegraph Small-Schools Softball Coach of the Year award is certainly not the first for Marquette Catholic's Dan Wiedman.
But with no state championship to show from a career blessed with pitchers like Alexis Silkwood and Meghan Schorman, Wiedman wonders, in jest, if he may be unworthy.
"To have two D-I pitchers who both pitched in the SEC – maybe the strongest college softball conference in the country – kind of makes you wonder," Wiedman said with a laugh.
Silkwood hurled the Explorers to three state trophies before setting a career wins record at Mississippi State. And with Kentucky-bound Schorman cast in the ace role for her third and final season at Marquette, the Explorers set a program record for victories in a 36-2 season that ended with a Class 2A sectional title-game loss to Williamsville. Wiedman shares coach of the year honors with Calhoun's Duane Sievers.
"Record-wise, obviously with the school record for wins at 36-2, winning the regional and beating a lot of the really good teams that we played this year, that was great," Wiedman said. "But there is still a little bit of sting from losing that sectional game."
Marquette figured a drop to Class 2A for the first time since the multiplier that came from the Silkwood era's success bumped it to 3A would provide a less treacherous postseason path. It got them through the regional, but an uncleared hurdle came in the sectional.
"There's just good teams all across the state and you never know when you're going to run into one of them," said Wiedman, whose team finished the regular season ranked No. 2 in the Class 2A state coaches poll.
Wiedman saluted Williamsville, which then beat top-ranked St. Joe-Ogden in the super-sectional on its way to a third-place finish at state. "We've got a good ballclub and we got beat by a good ballclub," Wiedman said after the loss the Bullets. "That's basically what it boiled down to."
The season included a milestone victory for Wiedman, who got career win No. 500 with a 7-2 triumph over Springfield SHG on April 12 in Springfield. The Explorers would break at 18-0 before a 7-0 defeat to Pinckneyville. They would string together another 18-game winning streak before state dreams were ended with the sectional loss at Gillespie.
"Williamsville's a very good team, but we had a good team too with an outstanding pitcher," Wiedman said. "It's tough when you get an opportunity like that to let it slip away. … Seems like you remember the losses more than you remember the wins."
The Explorers also had a difficult time shaking the memory of a season-ending injury to catcher Grace Frost on May 2 at Moore Park. Schorman threw a no-hitter to beat Collinsville 7-0, but the broken thumb suffered by its four-year starting catcher staggered Marquette.
The Explorers would win 11 in a row without Frost, but they were never really the same.
"We still played good ball after Grace Frost got hurt," Wiedman said. "But it just seemed like the last few weeks of the season, because of that injury, we spent a lot our time just trying to develop players at new positions that they were going to be playing. I wish we would have had more time to spend on some things like hitting and other stuff."
Marquette needed a dramatic three-run home run by Grace Frost in the sixth inning to beat Southwestern 3-2 in the championship game of the Marquette Regional. "I told our coaches, if our top of the order doesn't get things going here," Wiedman recalled of the late comeback, "we're toast."
That was the fifth one-run game the Explorers played in 2018 and they won all five. Much of that toughness came from the example set by a group of seven seniors. Four of those — Schorman, Frost, Morris and Tess Eberlin — were starters as freshmen.
But with Taylor Whitehead (10-0, 0.23 ERA) inheriting the No. 1 pitcher's role, the Explorers expect to remain a factor in 2019 with a promising crop of incoming freshman.
"We had a lot of seniors that are going to be hard to replace," said Wiedman, who offered high praise for assistant coaches Gaudio, Mary Rivera, Jeff Gaines, Rob Frost, Greg Gutierrez and Maddie Youngblood. "We've got some good ballplayers coming in, but 14-year-olds compared to 18-year-olds is a big difference."


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One by one, they showed up at the Kronemeyer household.
Players. Coaches. Teammates. Classmates. Friends. Family.
It was nearly eight months ago but the Kronemeyers remember every second of the day vividly. It was a day that altered the lives of everyone in the family and everyone at Calvary Schools of Holland.
At 5:15 a.m. on June 18, Harald Kronemeyer and his wife Nancy were awoken by a knock on the door where a police officer delivered the shattering news that their daughter Marissa, 18, had died in a car crash.
"I don't know how to describe that. I still have nightmares about it every once in awhile. It is every parent's nightmare. It is something I wouldn't wish on my worst enemies," Harald said. "It is hard for me to put into words. It has been very overwhelming. By noon I had 20 kids in my house. We were put at Calvary for a reason. That certainly shined through."
People from Calvary, where Marissa attended and her younger brother Lucas currently attends, knew what the family needed and showed up at their house to show their support. Marissa's older siblings Ben and Makayla also went to Calvary.
"It was just shock. It was 5 in the morning. I was the last one to be woken up and I came downstairs and everyone was crying and I was super confused. It took a few hours to process it. Your cousins walk in, your grandma walks in and every time you see someone, you have to do the same thing over and over. They cry it out with you and you get composed, then someone else comes in," Lucas said. "The day it happened, pretty much the entire senior class was at my house. That is not going to happen for most people."
"When it first happened, the first thing we wanted to do is be with friends," Marissa's brother Ben said. "We are a very social family and people visiting was good for us. There were 15-20 people in our house. I love that the family and friends came to visit. Me and Lucas have to be busy to keep our minds off of things."
After that first day, the Kronemeyers kept their minds off of things on the court, where they share their biggest bond. Harald is the Calvary varsity basketball coach. Lucas is a senior and Ben is an assistant coach.
"It is that constant thing that you have. At first, playing basketball was a way to get away from everything," Lucas said. "One of the first things I did after it happened was shot hoops in my driveway. It is something we can always do together to have fun."
Basketball has been a passion of Harald for decades.
"For me, I have always loved basketball. I played in the 80s at Holland Christian and played rec leagues for 20 years. I have always loved the sport. To coach it now is a really special thing," he said.
But Harald wasn't sure he could do it this year.
"This year, I needed those kids more than they needed me. I wasn't so sure after Marissa was killed if I could coach again. I didn't know if I could mentally do it. I haven't as good an X's and O's coach as I have been," Harald said. "After the first summer scrimmage, I knew I had to coach. It was something I could do to put the accident out of my mind and focus on the kids.
"It is always special to have your kids work with you. Especially this year, it has been healing for me. I love watching them play and we just enjoy our time together."
Together, they also found a way to honor Marissa with a personal and constant reminder — tattoos.
"I got the idea from a family friend who had a sibling die. I thought that was a cool idea.
I actually had my art teacher, who was also Marissa's art teacher, draw it first then brought it to the tattoo artist," Lucas said.
Lucas has his on his left arm, making the name Marissa visible to everyone when he is on the basketball court.
"I don't notice it every time I take off my warm-ups, but when I go out to play a game it is a reminder that there are more important things than a basketball game," he said.
Ben got one on his side.
"I got a tattoo of her dream car with her name in it. And a cross with a he is greater than I in it on my arm," Ben said.
Harald has one, too.
They don't need the constant reminders, but sometimes they will catch a glimpse of her name on the tattoo and will think of a fond memory of Marissa.
The first thing that comes to mind is the same for the entire family.
"We had a very sarcastic relationship," Ben said. "She was the one I would always joke around with at home."
"Marissa and I were a lot alike. We had similar sarcastic humor. We tried to zing each other all the time," Harald said.
"Her sarcastic humor. She had some of the best one-liners and funny comments to every situation. Very rarely was she super serious," Lucas said. "I am kind of the same way so I do think of those comments and think it is exactly what she would say."
Now the brothers joke more with each other.
"Lucas talks to me more. That is a big step for him," Ben said. "He was kind of the type to hibernate. We definitely hang out more now."
They hang out more on the court, too.
But the family's resiliency couldn't have been achieved without the community, Harald said.
"If it wasn't for our church and family here, I don't know if we could have handled it," he said. "The Holland community, too. I can't tell you how many notes and texts I got from so many people, some I knew from way back. Holland is just a great place to live."
The family is healing, but knows life will never be the same.
"There isn't a day that goes by that I don't mourn for my daughter. Very seldom is she not on my mind. I know that is going to get less as time goes on but it is still pretty raw," Harald said. "My kids are everything, and I hope they know that."
— Follow this reporter on Twitter @DanDAddona.


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Second treatise of government As essay concerning the true original extent & end of civil government English
By: Locke John.Material type: BookSeries: English literature Classics fiction. Publisher: New delhi Watchmaker 2011Edition: Reprint.Description: 127p Paperback.ISBN: 9781603864107.Subject(s): Literature English -- IndiaDDC classification: 810 LOJ S
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World War II hero to parachute again in Holland
COLUMBIA, S.C. -- You have seen Columbia's T. Moffatt Burriss before. But he looked like Robert Redford.
On Sept. 17, 1944, Burriss, a battle-hardened 24-year-old in the 82nd Airborne Division, jumped into Holland in the largest airborne invasion in the history of warfare — World War II's Operation Market-Garden.
So prominent was Burriss' role in the operation — which liberated parts of Holland but ultimately failed to reach Germany — that Redford played him in the movie "A Bridge Too Far."
Burriss will return to Holland this week. On Friday, four days shy of his 90th birthday, he will jump once again to commemorate the operation's 65th anniversary.
Burriss, who also jumped at 75 for the 50th anniversary commemoration, chuckled when asked if he was nervous.
"No. Not at all. If I was nervous, I wouldn't do it," he said. "It'll be fun. A renewed experience for me."
Burriss will be jumping with a group of Dutch World War II re-enactors called Pathfinder Holland. The one disappointment, Burriss said, is the group would only let him jump tandem — strapped to a female jumper.
"I would rather go solo," he growled.
Friday's jump is part of a three-day commemoration in Nijmegen, Holland. Burriss and a 28-person entourage will attend, including three sons and a daughter and three of their spouses, seven grandchildren, eight friends, an ETV film crew and a newspaper reporter.
During the festivities, he and other veterans of the operation will be honored by Queen Beatrix of the Netherlands.
"It's great," Burriss said. "I don't recall getting the royal treatment before."
Burriss is scheduled to speak after the award presentation.
"For the queen to come here (to Nijmegen) to celebrate this is pretty remarkable," said Anton van Ensbergen, one of the Pathfinders and an organizer of the event. "But Moffatt can only talk for 2½ minutes. I worry about that.
"I've heard him talk before."
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Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers.
Lamins as multifunctional proteins
Study of the nuclear lamina is becoming increasingly popular, due to the discovery of the numerous and complex roles of lamins in normal and diseased cells. Mutations in LMNA, the gene encoding A-type lamins, lead to a wide range of degenerative diseases termed laminopathies [1]. Lamins are type V intermediate filament proteins that bind together to form a filamentous meshwork encompassing the nucleoplasmic side of the nuclear envelope. Three genes are known to encode lamin proteins in human somatic cells: A-type lamins (A, AΔ10 and C) are alternatively spliced products of LMNA [2,3], and B-type lamins are encoded by LMNB1 (lamin B1) [4] and LMNB2 (lamin B2) [5]. B-type lamins are essential for cell survival [6]. Lamins B1 and B2 are expressed in most cells, although lamin B2 is more ubiquitous than lamin B1 [7]. A-type lamins, however, are normally only expressed in differentiated cells [7].
Lamins play a role in a myriad of cell processes implicated in tumour progression, such as control of nuclear architecture, regulation of gene expression, apoptosis, senescence and chromatin organization and segregation [1]. Therefore the effects of alterations on lamin expression or localization in tumour cells are particularly complex.
Lamins as diagnostic biomarkers
Numerous studies have tried to elucidate the relationship between lamin expression and cancer subtype by investigating the changes in lamin expression in malignant cells and tissue sections. Expression levels of lamins are often but not always variable in tumours.
As B-type lamins are necessary for cell survival [6], at least one B-type lamin is always present in a malignant cell. Variable expression levels are present in some tumour subtypes: expression is usually found to be reduced [8,9], but increased lamin B1 expression has also been shown in prostate cancer and in HCC (hepatocellular carcinoma) [10–12]. The presence of B-type lamins in most normal and tumour cells renders them poor diagnostic biomarkers for many cancer subtypes. However, lamin B1 has the potential to be used as a diagnostic biomarker to detect HCC from an early stage, as it is overexpressed in early and late stage HCC when compared with non-malignant controls (P<0.0001). Lamin B1 mRNA was present in plasma of HCC patients and was found to detect early stage HCCs with a sensitivity of 76% and a specificity of 82% [12].
As with B-type lamins, there is no simple overall pattern of A-type lamin expression in cancer and frequently no consistent patterns are observed between cancer subtypes. Many studies show lamin A/C to be down-regulated in tumour cells [8,9,13], but expression is also frequently positive or up-regulated [8,14,15]. Often expression levels can vary dramatically even within cancer subtypes; for example, in colorectal and BCCs (basal cell carcinomas), A-type lamin expression can be positive [13,14,16], reduced [9,13] or negative [9,13,16] in tumour tissue.
The presence of variable A-type lamin expression in most tumour subtypes suggests that, in most cases, A-type lamins may not be useful as diagnostic biomarkers. Nevertheless, cell-type-specific lamin A expression may be valuable as a diagnostic biomarker for detecting some cancers such as skin cancer. In non-cancerous skin, lamin A is not expressed in basal layers of the epidermis. However, in the apparently normal epidermis covering SCC (squamous cell carcinoma) and BCC, lamin A was found to be present in the basal layer [14].
Lamin A/C has been shown to aberrantly localize to the cytoplasm in some lung carcinomas, colon adenomas and adenocarcinomas, pancreatic and gastric cancers [8,9,16], whereas lamin B1 was localized to the cytoplasm in colon and lung cancers [9]. Lamin C was localized to the nucleolus in BCC and adrenal cortex carcinoma [13,14,17]. A number of studies have shown that lamins are present in the nucleoplasm in addition to the nuclear envelope in non-tumour cells [18–20]. Therefore the detection of lamins in the cytoplasm is more likely to function as a diagnostic marker than the detection of lamin C in the nucleolus.
Lamins as markers of tumour characteristics
Proliferating epithelial cells contain low levels of A-type lamins [7] and overexpression of A-type lamin expression has been shown to inhibit cell proliferation [21]. However, data on the relationship between A-type lamins and proliferation in cancer cells are currently inconclusive. In BCC, highly proliferative cells were negative for expression of lamin A, whereas slow-growing tumours were negative for expression of lamin C [13]. Ki67 and lamin A/C expression were found to be mutually exclusive in approx. 80% of Hodgkin's disease cells [22]. However, co-expression of lamin A and Ki67 was found in 56% of proliferating SCC cells and in 62% of proliferating BCC tumour cells [14]. It appears that too little is known about the patterns of A-type lamin expression in proliferating tumour cells for it to be used as a marker for cell proliferation.
In non-cancerous tissue, A-type lamins are generally only expressed in differentiated cells [7,23] and lamin B1 has been shown to be reduced in some differentiated cells [7,24]. The link between B-type lamin expression and differentiation appears to vary with tumour subtype. B-type lamins were expressed in TGCTs (testicular germ cell tumours) regardless of the degree of differentiation [24], whereas well-differentiated SCCs showed reduced expression of lamins B1 and B2 compared with poorly differentiated tumours [25]. The presence of A-type lamins is often used to demarcate differentiated tumour cells. Down-regulation of A-type lamins in poorly differentiated tumours has been shown in many tumour subtypes such as SCC [25] and gastric carcinoma [26]. A study of TGCTs [24] showed that differentiated non-seminomas were positive for lamins A/C, only lamin C was expressed in EC (embryonal carcinoma), and poorly differentiated seminomas were negative for lamins A/C. It is understood that, in general, the poorer the differentiation of tumour cells, the worse the prognosis. More work needs to be carried out to assess the potential for expression of lamin A/C to act as a prognostic biomarker by using large patient cohorts to assess survival and the absolute degree of correlation of expression and differentiation status.
Lamins as prognostic biomarkers
Little is known about the link between lamin B expression in cancers and prognosis, although it has been shown in one study that an increase in lamin B in prostate cancer strongly correlates with the Gleason score (P=0.001), which is a predictor of prognosis [10].
Much more work has been carried out into the relationship between A-type lamins and cancer prognosis. Some studies point to a lack of lamin A/C expression as being a sign of poor prognosis. CpG island promoter hypermethylation, which silences LMNA and leads to loss of lamin A/C expression in nodal diffuse large B-cell lymphoma, has been correlated with a decrease in overall survival (P=0.0005) [27]. Moreover, a recent study has revealed that patients with gastric carcinoma cells containing down-regulated lamin A/C expression have poorer prognosis compared with those expressing lamin A/C (P=0.034) and that lamin A/C expression is an independent prognostic factor [26]. However, Willis et al. [16] unexpectedly discovered that patients with CRC (colorectal cancer) tumours expressing lamin A/C were almost twice as likely to die from the cancer compared with clinicopathologically identical patients with tumours showing negative expression of lamin A/C (P=0.005). A-type lamins are therefore potential biomarkers of poor prognosis in CRC.
It has been suggested that the poorer prognosis of CRC patients with lamin A expressing tumours may be linked to the discovery that lamin A is a marker of colonic stem cells [16] as cancer cells with characteristics of stem cells may be more aggressive [28]. The presence of CSCs (cancer stem cells) has been reported in several subtypes of cancer, such as breast [29], colon [28] and brain [30]. The CSC model describes a hierarchical system in which only a small population of cancer cells, namely the CSCs, are able to initiate and maintain tumour growth. This contrasts with the stochastic theory in which every cancer cell is capable of initiating a tumour [31]. CSCs maintain their aggressive properties as they are capable of self-renewal and differentiation [31].
However, lamin A may not be a universal marker of stem cells. In TGCTs, expression of lamin C but not lamin A indicates the presence of EC cells, the stem cells of non-seminomas. Determining the percentage of EC cells present in non-seminomas has been proposed as a potential prognostic marker for TGCTs [24].
These results demonstrate once more the complex role of lamins in cancer, and that the use of A-type lamins as prognostic biomarkers may depend greatly on the subtype of cancer involved.
A-type lamins and cell motility
A potential mechanism by which the expression of lamin A leads to poor prognosis of CRC patients has been elucidated. Willis et al. [16] found that expression of lamin A promotes increased cell motility. In wounding assays, wound closure was seven times faster in cells transfected with GFP (green fluorescent protein)–lamin A compared with control cells transfected with GFP alone. Lamin A was shown to control a pathway in which up-regulated expression of T plastin, an actin bundling protein, led to down-regulated expression of the cell adhesion molecule E-cadherin, resulting in increased cell motility [16]. Loss of E-cadherin and expression of plastins are often hallmarks of tumours, correlating with invasive and metastatic behaviour [32,33]. These results may reveal a function of lamin A as a regulator of a pathway involving actin dynamics, cell adhesion and cell motility.
It has been recently discovered that the cytoskeleton is connected to the nucleus through LINC (linker of nucleoskeleton and cytoskeleton) complexes, formed through binding of KASH (Klarsicht/ANC-1/Syne homology) domain proteins such as nesprins to SUN (Sad1 and UNC-84 homology) domain proteins [34]. The nucleoplasmic regions of human SUN domain proteins bind to A-type lamins [35,36] and nesprins have been shown to bind to actin microfilaments [37], plectin [38], emerin [39] and A-type lamins [39,40]. This provides a pathway by which signals can travel from the outside of the cell to the nucleus. Lamin A expression may therefore control the reorganization of the cytoskeleton through its association with LINC complexes, causing alterations in cell migration. The increase in cell motility may be a cause of the poorer prognosis of CRC patients with lamin A-positive tumours.
Once again, however, it appears that the link between A-type lamins and cell motility is not the same in all cell types. Green tea extract has been shown to induce up-regulation of lamin A/C expression in lung cancer A549 cells leading to a decrease in cell motility [41].
Cancer is a vastly complex and heterogeneous disease, and lamins exhibit a multitude of functions within a cell; therefore expression levels of lamins vary greatly depending on the subtype and characteristics of tumour cells.
Research into the use of lamins as cancer biomarkers is still at an early stage and none are yet being used clinically. A- and B-type lamins have limited use as diagnostic biomarkers in many cancers, due to their variable expression patterns between and within cancer subtypes and the presence of at least one B-type lamin in every tumour and normal cell. However, they can function as diagnostic biomarkers in some cancers: B-type lamins can detect early stage HCC [12], lamin A can detect the presence of skin cancer [14] and the mislocalization of lamins to the cytoplasm can be indicative of a number of different cancers [8,9,16].
Lamins have the potential to be used as prognostic biomarkers because the factors analysed in the present review, namely differentiation state, proliferative capacity and cell motility, can all be used to determine tumour aggressiveness [42]. In some cancers, A-type lamins appear to act as tumour suppressors. Many tumour subtypes and poorly differentiated cells exhibit down-regulation of lamin A/C expression [8,9,13,16,25,26] and loss of lamin A/C correlates with poor prognosis in large B-cell lymphoma and gastric cancer [26,27]. Conversely, in CRC, tumour cells expressing lamin A/C are indicative of poor prognosis and cells expressing lamin A are more motile and stem-cell-like [16].
It is well known that differentiated tumour cells express A-type lamins, but it is also interesting to note that the pattern of expression of A-type lamins has also been shown to define stem cells in TGCT (presence of lamin C) [24] and normal colon (presence of lamin A) [16]. It is thought that A-type lamins play a role in the control of stem cell self-renewal and differentiation. Progerin, a truncated form of lamin A, activates downstream effectors of the Notch signalling pathway in human mesenchymal stem cells [43] and mutated lamin A inhibits differentiation of muscle stem cells [44,45]. As stem-cell-like cancer cells are likely to be more aggressive, A-type lamin expression has the potential to be used as a marker of stem cells and hence as a prognostic biomarker in certain cancer subtypes. It would be of merit to further research patterns of lamin expression in CSCs to investigate if any trends can be identified.
Many of the studies discussed in the present review appear to give conflicting results. This can in some cases be explained by a lack of statistical significance caused by small sample sizes or methodological differences. However, an important conclusion is simply that the nature of the relationship between lamins and cancer is extremely complex. It is important to carry out more large-scale clinical studies to truly assess the potential of lamins as cancer biomarkers. Unravelling the complex nature of lamin function and the mechanisms that control its expression in cancer could have great benefits for the detection and analysis of tumours and the management of cancer patients.
Nuclear Envelope Disease and Chromatin Organization 2009: Independent Meeting held at College of St Hild and St Bede, University of Durham, Durham, U.K., 22–23 April 2009. Organized and Edited by Chris Hutchison (Durham, U.K.).
This work was supported by a grant from the J.G.W. Patterson Foundation and funds from the James Cook University Hospital.


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11 Sep 2017
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