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£750,000 Guide Price
Land Commercial for sale
Berryfield, March
Residential development siten1.18ha (2.91a)nn.e. edge of town locationnoutline planning consent for up to 30 dwellingsnedge of town locationnestablished residential area
6 Bedrooms Detached House for sale
2 Greys Lane, March, PE15
(draft details) a detached grade ii listed residence having approximately 17 rooms over 3 floors. the property has a double fronted mooring, a mass of off road parking, outside storage…
Waterside Gardens, March
Executive detached property situated alongside the river nene complete with private mooring. within walking distance of the town centre the property benefits from gas central heating…
4 Bedrooms Detached House for sale
The Hollies, March
Extended improved * four double bedrooms * three reception rooms * impressive master bedroom * great size accommodation throughout * [use contact agent button] *
Wisbech Road, March
Elliswinters - a lovely, lovely house, with four bedrooms, an en-suite and two reception rooms. good quality fittings throughout and tastefully decorated, ready for you to move straight…
Creek Road, March
Four plots non estate location. land situated in a non estate location north of the town centre. outline planning permission was granted on the 2nd april 2008 for residential development…
3 Bedrooms Detached House for sale
Burn Street, March
No upward chain located in a highly sought after area on the north side of march is this three bedroom detached family home.nin need of some refurbishment, it boasts some attractive…
3 Bedrooms Detached Bungalow for sale
Ash Grove, March
A lovely detached bungalow with three double bedrooms, an en-suite shower room and a 22ft living room. the property has well maintained landscaped gardens which have been lovingly…
Acacia Grove, March
No onward chain located on the north side of march, in an area popular with families, is this impressive detached home. tastefully renovated by our current vendors, it boasts a generous…
Norwood Road, March, PE15
(draft details) a beautifully presented, extended bungalow offering three bedrooms, two en-suites, shower room, kitchen/breakfast room, lounge and off road parking. this property is…
Norwood Road, March, Cambridgeshire. PE15 8JL
Smart move are pleased to have on offer this immaculately presented three bedroom detached bungalow located in march. the property has been fully refurbished by the current owners…
2 Bedrooms Bungalow for sale
The Windsors, March
No onward chain offered with no onward chain and ready to view today, this two bedroom bungalow with a garage is nestled down a popular cul de sac on the north side of march.
3 Bedrooms Bungalow for sale
Nursery Drive, March
Comfort and convenience in one located on the north side of march in a popular cul de sac is this well maintained, three bedroom bungalow. with generous room sizes and a pleasant garden,…
4 Bedrooms Town House for sale
Riverdown, March
4 bedroom town house with accommodation including lounge, kitchen/diner, utility room, cloakroom, 2 bedrooms en-suite and family bathroom. having gas central heating, double glazing,…
2 Bedrooms Detached Bungalow for sale
Elm Close, March
A well presented and much improved detached bungalow with two double bedrooms, a refitted kitchen and a refitted shower room. this lovely home has well tended gardens, parking, double…
4 Bedrooms Detached House
The Green, March
4 Bedrooms Detached Bungalow
3 Bedrooms Semi Detached House
Alpha Street, March
3 Bedrooms Detached House
Holly Close, March
3 Bedrooms Property
Russell Avenue, March
2 Bedrooms Semi Detached Bungalow
Benwick Road, Doddington
2 Bedrooms Cottage House
Rookswood Road, March
2 Bedrooms Terraced House
Elliott Road, March
2 Bedrooms Town House
Jolley Close, Manea, Camb…
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Wirefly helps you save on cell phones and plans by offering innovative comparison tools so consumers can make educated choices. Start saving today with Wirefly!
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Test your current internet connection with our speed test and see what services your provider can handle. Find out your download speed, upload speed, latency, and more.
The ability of your customers to reach out and purchase your product or service in Hallowell, ME depends upon your choosing a reliable telephone service provider. Using the telephone remains the number one way most customers still use to get in touch with your business. Choosing the right kind of phone service for your business means contracting with a service that is affordable, dependable, and offers your business the specific features that make doing business with you as easy and convenient as possible. It's important to take the time to carefully evaluate a variety of business phone service types and providers available in the Hallowell, ME area before making a commitment. You can choose between traditional analog telephone service, or VoIP service, explained in the comparisons of business phone service providers that follow.
Voice over Internet Protocol is a newer phone service type that gives users an alternative to putting in a traditional analog phone line. VoIP has been around for about ten years now but has just recently become more mainstream. Many businesses are finding that letting go of their traditional service and choosing VoIP is really helping their business communication needs. Using VoIP service gives you quality calls just like the traditional phone lines of old, but the calls are transferred through the Internet. Therefore, you must be sure that you have a strong Internet connection before choosing this type of phone service. If you are not sure if your current connection will support VoIP, use the Wirefly Internet Speed Test to check.
The biggest difference found between PSTN and VoIP is the way that calls are carried. With PSTN service, all calls are carried through an analog signal. VoIP uses the Internet and digitizes the calls you make and receive. A perk of this service is that sending your calls through the Internet is much less expensive than the traditional way, so making and receiving calls costs a whole lot less. This is a great choice for any business that deals with a lot of international calls because the rates are much lower. You'll also find packages that allow you to make unlimited calls to certain areas for one low price, eliminating the need to worry about per minute rates.
VoIP service in Hallowell, ME will come with any type of calling feature that you could need for your business. These will include caller ID, multiple extensions, ring groups and call forwarding. You'll also have remote access to your voicemail, voicemail to email and fax to email service.
VoIP providers in the Hallowell, ME area provide plans that are meant for small and large businesses alike. You may be a small company that needs just five lines or a large corporation who will require hundreds of extensions for your employees. Either way, there will be a VoIP service that can meet your business needs.
Now that VoIP has become a favorite with business owners, a lot of carriers are ready to fight for your attention. On first glance this may make it seem hard to pick out a specific provider, but you can in fact benefit from this.
The first step is to take into account your needs in relation to a professional phone system. Think about things like how many extensions you'll require, what functions you'll have to use day by day, whether you expect to expand your company in the coming months, and what your budget is for business telephone service.
After that, you can search for plans from the numerous commercial VoIP companies in Hallowell, ME. Scope out the plans they have, how much they cost, and the company's industry standing in general. Keep in mind that functional telephone service is vital to your company's profitability, so try to select a vendor that has established itself positively in terms of dependability and customer support.
A traditional phone service carries all calls over the PSTN. This stands for public switched telephone network and is generally what most consumers think of when they think phone service providers. This system has been around for nearly 100 years and is made up of cables, telephone lines, satellites and mobile networks. This was the very first type of phone network to ever be used.
However, the PSTN actually is more expensive than VoIP, because of how old and large the PSTN infrastructure is. It requires very regular maintenance and that cost gets passed onto consumers. PSTN is analog, so it is harder sending data over longer distances.
When someone makes a long distance call to or from a Hallowell, ME business using the PSTN, the data stops at different places along its journey. The equipment that is in use is also owned by various companies, making these types of calls more expensive. While most of the infrastructure that carries and routes these calls has become digital, the "last mile' is not. The connection between the caller and the local central office is still analog.
Most Hallowell, ME businesses use a private branch exchange, or PBX, to route the calls that come through their company. The PBX is what allows the company to enjoy the different calling features, such as voicemail, caller ID, call forwarding and more.
When a company uses a traditional PSTN phone system, they must have a PBX, which can be located either at the company or at a remote location. But it doesn't matter where the PBX is located in terms of cost, as it is still very expensive to use. When you first need to set up the whole phone system, you'll be required to purchase a number of pieces of hardware. Your initial investment could cost at least $1,000, if not more. Other necessary steps, such as installation, configuration and future maintenance, will not be included in your initial purchase price. Therefore, if you need to hire a service technician to fix a problem, you will be paying at least a $100 an hour for them to come out to you.
Additionally, a traditional PBX system in Hallowell, ME may need upgraded or expanded in the future, which can be both difficult and expensive to do. Since many PBX systems don't support more than a few different phone lines, if you need more extensions in the future you will be required to pay for the hardware to install them.
A PBX system can also experience breakdowns and issues after being installed. If it does, you will again be responsible for paying for the repairs and any hardware costs that your company needs. There is also the chance that your system could become obsolete at any time, forcing you to replace it.
Wirefly offers great deals on a large selection of smartphones, cell phones, tablets, mobile hotspots, and other wireless devices for the nation's most popular carriers. Use Wirefly's innovative cell phone and plan comparison tools to ensure you are getting the best deal on the market. Shop with confidence knowing that Wirefly wants to help you find the best prices on cell phones, cell phone plans, TV, and Internet service.


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Learn about this topic in these articles:
presence of iron deposits
...as iron formations. In short, the organisms produced the oxygen and the iron formations accepted it. Iron formations can be found in the earliest sediments (those deposited 3.8 billion years ago) at
Isua in West Greenland, and thus this process must have been operative by this time. Iron formations dating to early Precambrian time (4.6 billion to 541 million years ago) are so...


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Diederik Cuckoo Chrysococcyx caprius |
Home | Alphabetical | Maps | Taxonomic | Links/Resources |
The Diederik cuckoo parasitizes several weaver (especially the Village Weaver) and bishop species. Note the completely barred underwing in flight (upper, Rubondo, 3-13; 2nd row left, Kitulo NP, 3-11, both courtesy of Paul Oliver) and the red eye in the male, brown eye in the female. The 2nd row right photo is of a juvenile (Lengijavi, 1-12). The 3rd row immature was at Nanja Dam, 6-06). The left lower bird (courtesy of Owen Evans) was trapped and died in the tubular entrance of a weaver's nest. The right lower adult male was seen at Shambarai (1-13); click it to see several enlargements. |
Last page Next Alphabetical Next Taxonomic |
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text: Jason J Sergi is a "Speculative Fiction" author with many interests and many future projects in the works. He lives and writes within the frigid hills and vales of New England. According to his calculations, he will need 300+ years to finish every project he plans to write and intends to reach that goal, somehow, someway, and hopes that his readers will join him for every step of the journey. Visit his webpage at: jjsergi.blogspot.com


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Browse over 100 articles to help you manage your child's symptoms.
Browse our library of information about various medical conditions.
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We are proud to offer the latest state-of-the-art technology to assist with our patients, and we will continually strive to improve care for our patients by utilizing the most advanced technologies. Our facility includes:


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Discussions |
Academic Rigor |
Dorm Life |
Food and Dining |
Bang for the buck |
Clubs and Activities |
Campus Safety |
Having only taken 3 quarters of classes so far, I have mainly completed General Education classes. While getting adjusted with the school and learning how to work out selecting classes and registering, I just got into a major class in the Spring quarter. However GE classes are not a bad thing at all! In fact they give you an incredible opportunity to find out interests you may have beyond your intended major. I was able to explore such fields as Astronomy, Psychology, and Spanish while adding units to my graduation requirement. The GE options are abundant when you learn how...
To find more tips for prospective students, what to do for fun and whether this school is great for a particular type of student read the 190 reviews for Cal Poly
Curious about something that isn't answered here? Feel free to ask Cal Poly a question
i am so so so excited to become a part of the mustang family in less than a month and a half!!! so happy i got in and decided this school. i absolutely fell in love with the campus from the first second i saw it.
Read Morethe school was beautiful and i fell in love with the campus. the engineering tour was super cool. the surrounding area was nice too.
Read Morethe most welcoming, beautiful campus. all the students seemed like they were happy to be at slo and were even happier to tell you all about the school. it is in the best location with some of the best people.
Read Moreone of the most beautiful and friendly campuses i have ever been on. everyone here including the staff is very open and spirited and truly believes in the "learn by doing" philosophy of the school. i am so excited to start here in the fall!
Read Morei just committed to cal poly slo and i am so excited! the campus is so beautiful, surrounded by rolling green hills and right by the beach. the whole school has such a friendly and happy atmosphere. i love it!
Read MoreThe best education, in the best location with amazing weather and amazing people. For what you're getting compared to most of the UC schools, Cal Poly is cheap.
Read MoreGreat school! Like anyplace, it is what you make of it. And, it's not just for engineering and agriculture.
Read MoreCal Poly is well known throughout CA as a strong engineering and business school. There is an incredible abundance of cool classes and activities, both on campus and in the town of SLO. Something to note is that many majors are impacted (such as engineering), so getting your necessary classes can be a challenge.
Read MoreLooks like a great university. It is a very well organized campus with nice people running around everywhere. The learn by doing motto is great especially for a Architecture focused mind.
Read More


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Tag: tourism
The famous Heroes' Square: now and then
Posted by Fanni Grajzel | Feb 11, 2017 | Special Hungary | 0
The airports of Hungary: records in 2016 and new f...
Posted by Fanni Grajzel | Feb 3, 2017 | Business | 0
Budapest's growing popularity among tourists...
Posted by Fanni Grajzel | Jan 2, 2017 | Culture | 0
This year's Christmas Market in Budapest is ...
Posted by Fanni Grajzel | Nov 15, 2016 | Society | 0
5 Hungarian baths to cheer you up when the weather...
Posted by Fanni Grajzel | Sep 25, 2016 | Culture | 0
Here are the plans for the reconstruction of the Chain Bridge and the Castle Hill Tunnel
The reconstruction project is estimated to begin later this year
Read MoreBeauty of Matthias Church praised by The Huffington Post
Mar 29, 2017 | Special Hungary | 0
Get mesmerised by the Matthias Church 🙂
Read MoreA new national memorial site to visit in Hungary
Have you been to the beautiful Esztergom? 🙂
Read MoreDirect flight to be launched between Tunisia, Hungary
Lets go to Tunisia 🙂
#tunisia #tunis #budapest
Debrecen among the top ten touristic recommendations of Lonely Planet
Debrecen, "in the doorstep of the great plain"
Read More11 reasons to love Budapest in spring
Mar 25, 2017 | Special Hungary | 0
Gotta love Budapest in springtime 🙂
Read MoreBudapest bucket list – Best things to do in spring
Mar 23, 2017 | Special Hungary | 0
Embrace spring in Budapest 🙂
Read MoreFINA – Budapest2017: Synchronised swimming in Budapest – "wonderful sight for the viewers" – VIDEO
FINA – Budapest2017 – Amazing places in Budapest 🙂
Read MoreSpring has come, Budapest's public bike fleet is back in full force
In spring, more and more users hop on public bikes 🙂
Read MoreFifteen Hungarian restaurants join French cuisine programme
2,000 restaurants preparing a French menu in 150 countries around the world
Read MoreNew Hungarian start-up to appear in hotel and catering trade
Would you try boxhotels? New Hungarian development with good promises
Read MoreSecrets about Hungarian AirBnb revealed
Is AirBnb declining? Details revealed
Read MoreSecrets of Budapest: Citadel, the symbol of the 1848-49 revolution's defeat
Mar 19, 2017 | Special Hungary | 0
The story of the Citadel 🙂
Read MoreTelegraph's 25 amazing things about Hungary
Mar 18, 2017 | Special Hungary | 0
Which is your favourite point from the list?
Read MoreArboretum to burst into flower in Hungary
Thousands of beautiful snowdrops covers the territory of the Hungarian arboretum at Alcsút
Read MoreOutstanding touristic developments start in Hungary
Long-term touristic developments to be launched in Hungary
Read MoreMore and more popular thermal baths in Budapest
Amazing baths in Budapest!
Some 1.5 million visitors bathed at the Széchenyi
Downtown Market – Gastro and gourmet market in the heart of Budapest
Mar 16, 2017 | Special Hungary | 0
A must-visit market in the heart of Budapest 🙂
Read MoreBudapest Airport wins fourth Skytrax Award in a row
Skytrax: Budapest Airport is the best airport in the region
Hungary national stand wins award at ITB Berlin travel trade show
The Hungarian national stand at the ITB Berlin travel trade show has taken a top prize
Read MoreRecent Posts
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Sci fi/Fantasy image by
Lilleah Westhe is from last year and actually i despise the bowl, it was not what i had planned. this poor dragon got beheaded just before he was supposed to be fired to make the clay hard. it was vandalisim because it was no accident that his head was cleanly cut, his horns gone and his legs and tail busted off, that and my sculpture of the Eagle Rider was also touched and this proved it was no accident as you can never gorge the eyes out of the eagles head by accident (not to mention broke the guys arms and wings off and scratched up the beak!) i cried needless to say and did not let the 'god damn cheesy weasles', as my teacher put it, get the best of me and i fixed them both it took forever and i had to put the dragon in a bowl because his head would not stay on but its here for all of you to see.
Published More than a year ago
Category Fantasy
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Dynacom offers a complete line of scalable accounting software, from this Free Startup Edition to higher-end multi-users, customizable SQL editions. Over 250, 000 users worldwide cannot be wrong! Its Startup Edition is available free of charge. Unlike other manufacturers offering free trials, Dynacom Free Startup Edition is forever free. Even online support is free. Dynacom understands that small business owners need to cut costs in order to grow, and in an effort to help them achieve that, the Startup Edition is available for free. As their business grows, and so do their requirements, savvy managers will certainly look at Dynacom products and services for eventual upgrades. How would you like to be printing and emailing your first invoice within the next five minutes? Dynacom Startup Edition is so easy to use, you will be up and running in no time. Free and completely functional, you will be able to process an unlimited number of transactions and use it for an unlimited time. The program is so easy to use that you may not ever need the wide range of free support services, but they will be available to you. An ideal choice for freelancers and new businesses, Dynacom Startup Edition provides all the tools you need to manage efficiently sales, cash flow, receivables, taxes, etc. It also has built-in affiliation program, just in case you would like to promote the free version too! Gain unmatched control of your business today, for free. Register now to win a Dell computer.
Simple, easy to use, award winning accounting programs. Includes Payroll, General Ledger, Accounts Payable, Accounts Receivable and Invoicing, Budgeting, and Label Printing. Author: Jerry Medlin - Shareware Hall of Fame
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Checking, budgeting, credit card tracking plus graphs and tables let you manage your money and shows where your money is going. Credit card tracking shows balances, payments, and history and clearly shows all your credit card debt.
Construction Job Cost Tracking and Reporting System for Excel. Designed for contractors, builders, remodelers, construction professionals. Tracks construction costs tied to user-defined cost categories, computes accurate forecasts, reports variances
Teach your bank statements to reconcile themselves and reduce your accounting data entry up to 80%. Import and export transactions to your favorite accounting package, including Quicken MS Money, or even Excel.
PbxTools PhoneJournal is a call accounting software designed for small and medium offices that can help reducing the phone bill and give real-time information about outgoing and incoming calls inside the company.
Creates and prints Invoices. can be used by any type of company. Items can be saved and will appear on later invoices from a drop down list. Labor, shipping, and additional charges or credits can be added. Taxe/ discount are automtically calculated
Contact Book and Daily Notes. Can be used at home or for business. Keeps track of all kinds of contacts (personal, business).
PO manager software provides multiuser solution to maintain products, material and other purchases via purchase order. Application maintains company, vendor and supplier records and creates invoices of sold, purchased and returned items details.


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Coding! | |
Event Type: Educational Programs Age Group(s): Tweens, Teens Date: 3/2/2017 Start Time: 6:00 PM End Time: 7:00 PM Description: Advanced Coding! Please register for this event even if you were already in the "Scratch" coding classes.
Library: Selby Library
(Click for a map to Selby Library.)
Location: Youth Program Room Registration Ends: 3/1/2017 at 8:00 PM Presenter: Education Foundation of Sarasota Status: Closed |
Please Note | |


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Full profile →'">
The author is a Forbes contributor. The opinions expressed are those of the writer.
With nearly 770,000 YouTube channel subscribers, 761,000 Instagram followers and 376,000 likes Dr. Sandra Lee's social media brand, Dr. Pimple Popper, has high visibility.
For those who are unfamiliar with the @DrPimplePopper accounts, Dr. Lee, a dermatologist, records and uploads videos of herself removing whiteheads, blackheads and cysts from her patients' skin.
I spoke to Dr. Lee about her brand and how she's monetized her social media presence in the obscure 'popping' market:
Have you noticeably gotten more business from new patients who come because of your social media brand?
SL: Yes, definitely.
For example, I've done some TV stuff for the last five years and some of the shows will go all around the world, and certainly all around the country. I don't get approached for those appearances.
I get approached for Dr. Pimple Popper all the time. It's crazy. 'Popping' is a phenomenon that has hit younger generations, and that generation is the one that's out there. I just think the exposure from social media is stratospheric in comparison to your exposure on a TV talk show, it's like way more. It's amazing.
But, yes. I've had people come from London, and I've had people come from Saudi Arabia and from across the country. People have come from Canada for their cysts.
Have you found a way to monetize your videos?
SL: Yes, that's why I do my YouTube channel. You can monetize your videos and it's sort of win-win-win situation. It's good for my patients that have blackheads, because insurance doesn't cover the removal. So, many dermatologists we won't remove them, they say, "You have a blackhead there but don't worry about it." But now, I'll do the extractions for free if my patients let me videotape and use the video. Of course, I make them anonymous and remove anything identifying.
Literally, they all say yes. A lot of these people really want these things to be removed. They're benign and they're not anything that needs to be removed medically, which is why insurance won't pay. So my patients win, because they get the blackheads removed for free.
I win, because I get to take it out and put the video on YouTube. At least I get some sort of payment for that, as opposed to me doing it totally for free.
And all of these people who love popping videos win because they get to watch it on YouTube. There's some kind of obsessive quality, because when you watch it sucks you in. I don't exactly know what it is either, but you do get addicted to it. I see that all the time. People say, "This is so gross yet oddly satisfying. This is so nasty that I cant stop watching."
Have you had any issues with your YouTube platform?
SL: There's a fine line you have to walk with YouTube. Most YouTube channels are for entertainment, and I'm doing mine for education. But, if you're doing something like these popping videos for entertainment they might be taken off. It has to be medically educational. That's mostly been helpful for me me because I am an educator and dermatologist.
I think I might be starting something new on YouTube where it's going to become more acceptable to have content like this. I think I might be becoming one of the pioneers, so to speak, of this. In the past, some of my videos were just taken off. They were considered 'gory, disgusting and for shock value.'
I fought back. I was like, "That's not what this is. I'm a dermatologist. This is what I do." I'm not doing this for shock value. Honestly, it was insulting that they leave videos on of people getting shot or even porn and they would take my content down.
It's an ongoing fight.


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Innovations on display at Mid-America Trucking Show David Kolman May 14, 2012 No Comments This year's Mid-America Trucking Show (MATS) featured 1,070 exhibitors in 1.2 million square feet of exhibit space. Read More
2012 truck roundup Latest models designed for power, green options David Kolman November 14, 2011 No Comments Completed annually, Beverage Industry's medium- and heavy-duty truck roundup, which consists of Classes 4 through 8, is a compilation of vehicle offerings suited to beverage industry applications. Highlighted as follows is an overview of model year 2012 trucks and selected vehicle specifications.Read More


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Clay Pipe Engineering Manual c1946 Clay Prod.Assoc.
Click thumbnails for expanded view.
Hardcover that is flexibile, 159pgs, Contents; Few words on clay pipe, estimating sanitary flow, hydraulics of sewers and drains, sewer and drain layout, pipe strength and trench loads, laying and construciton of appurtenances, ASTM specifications and standards, clay filter block specs, vitrified clay lineer plates, house swere and drain connections, designing municipal storm sewers and drains, general drainage, roadway drainage, airport drainage, railroad track drainage, commanly used constants and tables, some wear to page edges, creasing of cover, Overall Good Condition! [Box 4665] - [Item 120955]
Crown Antiques & Collectibles
- Pittsburg, Pennsylvania
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- Description
Deep Basket Closet Pull-Out - Oil Rubbed Bronze. Patent-pending design installs easily in 32mm applications, and basket removal and re-installation is easy with Bayonet Mounting System which rests on top of the slides.Standard Dimensions: 18"W x 20"D x 11"H
Finish: Oil Rubbed Bronze
Contains: oil rubbed bronze wire basket, full extension slides, and instructions.
Notes: 100lb. Weight rated slides - Additional Info
Additional Information
Manufacturer Rev A Shelf SKU CB-182011ORB-1 mpn CB-182011ORB-1 UPC 090713007519 Excess Item No Usually Ships In 3 to 4 Days Install Type No Type Storage Pull Out Base Cabinet Size No Minimum Cabinet Opening No Material Steel Finish Oil Rubbed Bronze - Shipping Details
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Seven migrant workers are upset after large building company Buildtech made them redundant less than half-way through their three-year contract to work in the rebuild.
Relief at leaving their abandoned street has ended with more stress for a red-zone elderly couple.
Cantabrians will have to wait four to six more weeks to get three new restaurant bars following delays in the completion of the Strange's building.
A Christchurch family are distressed and fear for their health after their earthquake repairs may have exposed them to asbestos.
The Press is on the hunt to find Canterbury's Hottest Tradie from the thousands of men and women now working in the region's construction, demolition and associated industries.
Labour wants to ramp up mental health services in Canterbury to help people deal with the ongoing health impacts of the earthquakes and their aftermath.Labour's health spokeswoman Annette King today pledged to double the number...
Police are investigating after a Christchurch firm went bust leaving homeowners and creditors left out of pocket.
The man behind a Christchurch building firm which went bust, owing hundreds of thousands of dollars, has apologised to homeowners and other creditors left out of pocket.
Christchurch's YMCA is planning to build a $6 million swimming pool and squash facility, a theatre and an art venue on its Hereford St site.
The man behind a company that left a Canterbury homeowner hundreds of thousands of dollars out of pocket started another firm.
Canterbury economic activity is at its highest level, with construction starting to roll, a bank survey says.
The findings of an investigation into the psychological effects of survivors of the 2010 and 2011 Christchurch earthquakes will be presented in Paris by Christchurch University researchers next month.
They said it of Robert Sarkies' film, Out of the Blue, which dramatised the story of the Aramoana Massacre. They said it of Peter Sharp's mini-series Erebus: The Aftermath.
International and local interests are considering turning Christchurch's badly damaged former Forsyth Barr building into a hotel, as the city gears up for next year's Cricket World Cup.
A new drama series set during the 2011 Christchurch earthquake comes with a health warning while broadcaster TV3 is fielding complaints before it even goes to air.
Canterbury University researchers say the quakes are having long-term effects on health and well-being.
For many people in Canterbury, the earthquakes of September 2010, February 2011 and later had little or no effect. Their homes were not damaged, their incomes not affected and their families emerged unscathed.
A project aimed at greening the Christchurch residential red zone has been launched.
Lee Germon CEO of Canterbury Cricket talks to Lesley Murdoch on the All Sport Breakfast Canterbury about the change of name and playing colours to the Canterbury T20 cricket team.
Christchurch mayor Lianne Dalziel will speak at a World Bank project in London about learning from crisis.
A Labour government would build 100 ''high-quality, modular'' houses in Christchurch in its first four months, and have a further 300 Kiwibuild homes ready within six months.
A Labour-led Government would build 400 homes in Christchurch within its first six months of office.
Labour's Housing Spokesperson Phil Twyford talks to Newstalk ZB's Chris Lynch about the housing announcement today
Hundreds of builders are in Hamilton for the Certified Builders Conference and Expo.
Nigel Ross wants his building back.
Christchurch earthquake victims will have died in vain if building safety improvement laws are not fast-tracked, Mayor Lianne Dalziel says.
They let their insurance policy lapse just prior to the earthquakes, so they walked away from their $500,000 property with just $80,000.
The Christchurch rebuild has attracted many tradies, but wages are not keeping up with high living costs.
A Christchurch landlord has been convicted on 34 charges involving false claims to the Earthquake Commission for emergency quake repairs.
A quake-damaged house will go under the hammer with a $1 dollar reserve today as part of a charity auction.
A new report on mitigating rockfall risk on the Port Hills confirms it is feasible in five areas but not financially viable.
A Christchurch pilot stressed by aftershocks completed an unsafe landing in fog where he first saw the runway when he was just 30 metres above it.
An Air NZ captain says stress from the Christchurch quakes is partly to blame for failing to follow procedure.
Plans for a gleaming glass building returning hundreds of workers to central Christchurch have been hailed as a major boost for the city.
Contact Energy has been billing a Christchurch couple for a house that does not exist.
New Christchurch has come a big step closer.
Construction is starting on the new retail building in August.
NBR Journalist Chris Hutching talks to Newstalk ZB's Chris Lynch about what he thinks about the expected rate rise for the city
It's great to meet positive people; their energy and enthusiasm rubs off. That is especially the case in Christchurch, a city where it is far too easy to get weighed down by seemingly intractable problems, of which there are many.
Christchurch risks becoming a "doughnut city" with an empty hole in the middle if more is not done to encourage businesses and residents back into the city centre, a visiting housing consultant says.
Claimant Ali Jones and her family had hoped their next move would be to their rebuilt home, but instead it is to another rental in another suburb.
Construction on Christchurch's new $53 million bus interchange is a step closer after contractors took control of the site today.
Officials gearing up for International Accreditation New Zealand's (Ianz) audit of the Christchurch City Council's building control unit are confident they are on track to regain accreditation.
Labour will commit nearly $25 million for full buyout offers across the red zone if it gains power at the election.
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text: Peter:I think the bigger question here is does his 1099 reflect the proper code for early (I assume) distribution. If it doesn't say 3 (I think -- it's explained on the back of the form) there will be a 10% penalty + taxes if none were taken out at the time of withdrawal.I've gone through this. It can get messy if not done correctly.Regards,DWSz


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Doctor insights on:
Long Term Effects Of Klonopin
What are the short- long-term effects of taking klonopin, doxepin, wellbutrion, seroquel, (quetiapine) armour thyroid, pravastatin, xanex, alcohol, marijuana?
Confusion: Mental status changes can take place. Be sure to generate a list of all meds and herbals and street drugs to distribute to all of your physicians to make sure that no medication dosing takes place without all informed. ...Read more
See 1 more doctor answerClonazepam (Definition)
Klonopin (clonazepam) belongs to a class of medications called benzodiazepines. They are also referred to as sedative-hypnotics & anxiolytics. These medications are used for a variety of indications to include anxiety, insomnia, muscle spasm, seizure, & alcohol withdrawal. All benzodiazepines including Clonazepam are potentially habit forming. Alcohol should be ...Read more
In 05 diagnosed w/hypomania bipolar - topamax (topiramate) 400mg wellbutrin ER 150 nuvigil 250 mg klonopin .5 mg. Long term effects of these meds?
Too many: Too many for me to list. You need to ask for printouts from your pharmacist. ...Read more
I have been on 1mg of clonazepam for 3 weeks. Doctor says it would be beneficial to stay on it at same dose for 3 months. Any long term effects?
Benzodiazepines: clonazepam is one of a class of meds called benzodiazepines. These medications can be very addictive and tolerance leads to same dose not being as effective. For this reason they are not recommended for long term use. 1 mg is a relatively low dose, but may require taper and difficult to get off of. There are other options. You may want to request a psychiatric consult ...Read more
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I don't intend on taking anxiety/ depr. Meds long term. Side effects concern me. Will i be ok? Is klonopin and Paxil (paroxetine) very strong compared to others?
You should be fine: Make sure that you are also in psychotherapy, that you get plenty of exercise. Make sure that you keep a strong social support network. Never stop your medications without discussing your physician's plans for you and also make sure you understand that you need to come off of them that they are tapered extremely slowly. Both clonopin and Paxil (paroxetine) must be tapered very slowly. ...Read more
Started 0.5mg of klonopin (clonazepam) for anxiety & mainly chronic motor tics. What kind of side effects can I expect from this med? & can it be taken long term?
Not best long-term: Klonopin not usually the best long-term treatment for anxiety, at least not as initial choice. Zoloft (sertraline) is better choice for chronic anxiety. Klonopin could be used as-needed while waiting for zoloft (sertraline) to take effect-- other non-addictive medications could be tried first for the chronic motor tics. Klonopin is addictive if taken on regular basis; causes drowsiness; can cause depression long term. ...Read more
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Is long term use of klonopin (clonazepam) bad for you? I only take .5 twice a day but i'm worried it'll have a permanent effect. I've been taking it 6 months
Context is all: If you've been placed on klonipin thoughtfully, alternatives have been considered (by you and doc), the possible long term loss of efficacy examined -- no, it is extremely unlikely you will have any irreversible effects from this reasonable dose. ...Read more
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Is long term low dose klonopin (clonazepam) use safe? I have been really anxious the past couple of weeks and have been taking .25mg daily (sometimes .5mg)
Usually with: Benzo's for anxiety, patients are evaluated for side effects, tolerance to the drug, etc , at least every three months. There may be a risk of addiction depending on multiple factors. Safety profile is good if not mixed with alcohol, other sedating medications, or controlled substances. Please discuss w/your prescriber re: other meds that you're taking. Good luck! ...Read more
Is klonopin (clonazepam) addictive? I am having great success on it and would like to stay on it long term. Is this typical or is it only for short term use?
Benzodiazapines: One of the issues with Klonopin (clonazepam) is that tolerance can develop. I try to use Klonopin (clonazepam) as a bridging medication. In other words, i often use it until the effects of another medication (such as a selective serotonin reuptake inhibitor ) kick in. ...Read more
Is blepharospasm from long term use(11 years @ 2 - 4 mg/day) of klonopin (clonazepam) reversible?
Why?: Why? why? why? That's a very long time on the drug. Please consider CBT therapy to deal w/ the problem more safely. That said, why do you think it caused the eye issue? It's actually used to help w/ that condition. Here's info: http://www.blepharospasm.org/ There's no cure, but there's help. Your medications need to be evaluated and therapy will help. ...Read more
I know both of these are considered bad long term drugs but what is so different from taking klonopin (clonazepam) long-term than xanex XR long-term?
Agree: I am not sure there is much difference. ...Read more
Klonopin (Definition)
Klonopin is a long-acting benzodiazepine which is a kind of sleep-inducing drug (anti-anxiety drug, psychiatric drug) and a blood pressure drug which is a ...Read more
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Sci fi/Fantasy image by
Ian SimmonsThis was a painting produced for the 2005 British Fantasy Society Calendar, which had the theme of the Arthurian Legend of Gawain and the Green Knight. This was painted in acrylics over an ink wash ground on canvas board. I used a technique of applying an initial, loose ink wash, then masking off the lightest areas of the picture with gum arabic and applying a slightly darker ink wash. The next lightest tonal areas were then masked and a darker wash applied. This process was repeated 4 times. The resulting tonal image was then painted into with acrylics.
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Mutations in the CYP1B1, MYOC, OPTN, and WDR36 genes result in glaucoma. Given its expression in the optic nerve, it is likely a mutation in the OPTC gene is also involved in initiating glaucoma. This study was designed to evaluate the involvement of the CYP1B1, MYOC, OPTN, and OPTC genes in the etiology of adult-onset primary open-angle glaucoma… (More)
- Wei Qin, Vineeta Bajaj, Izabela Malinowska, Xin Lu, Laura MacConaill, Chin-Lee Wu +1 other
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Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC) and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive… (More)
Genomic imprinting is an epigenetic chromosomal modification in the gametes or zygotes that results in a non-random monoallelic expression of specific autosomal genes depending upon their parent of origin. Approximately 44 human genes have been reported to be imprinted. A majority of them are clustered, including some on chromosome segment… (More)
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Joachim Loew - A host of stars were photographed on the red carpet as they arrived to the Bild 'Place to B' Party in Berlin, Germany - Saturday 7th February 2015 (2 Pictures)
Joachim Loew
Photo credit: Brian Dowling
Joachim Loew
Photo credit: Brian Dowling
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The 'Iron Man' star will play the doctor who can talk to the animals.
The show will return to CBS for seasons 11 and 12.
30 year old Mvula said Sony only told her she was being dropped in a 'seven-line' e-mail.
From Bono to Michael Fassbender, here are some of Ireland's best loved celebrities on St. Patrick's Day.


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TENDENCY AND COINCIDENCE CLASS 9 28 JULY 2014 DANIEL TYNAN – 12 th Floor Wentworth Chambers
Tendency and Coincidence
What is this type of evidence? Conduct of the defendant Proves tendency to act in a particular way Proves improbability of 2 or more events See Odgers' examples
Dangers this type of evidence Reasoning prejudice – Over-estimating the probative value Moral prejudice – Jury fails to give the accused the benefit of reasonable doubt – Outraged by conduct and desire to punish – Jury confusion and misuse of evidence – See Pfennig at [72]
"psychological studies of decision-making show that where there are gaps in available information decision-makers fill them with reference to preconceptions and stereotypes." (Fiske and Taylor, Social Cognition, 2 nd ed, 1991) Bostock study - jurors more likely to convict with recent similar conviction
Can the risks associated (with the evidence be cured by judicial direction?
Makin v A-G(NSW) [1894] AC 57
What was the evidence the subject of the appeal ? -Evidence of finding the 12 other bodies in backyards -Evidence from 5 mothers - they had entrusted the Makins with their baby and had never seen it again
"It is undoubtedly not competent for the prosecution to adduce evidence tending to show that the accused has been guilty of criminal acts other than those covered by the indictment, for the purpose of leading to the conclusion that the accused is a person likely from his criminal conduct or character to have committed the offence for which he is being tried. On the other hand, the mere fact that the evidence adduced tends to show the commission of other crimes does not render it inadmissible if it be relevant to an issue before the jury, and it may be so relevant if it bears upon the question whether the acts alleged to constitute the crime charged in the indictment were designed or accidental, or to rebut a defence which would otherwise be open to the accused. " Lord Herschell
Australian position re admissibility EA jurisdictions – ss97, 98, 101 Common law – test in Pfennig
Pfennig v R (1994) HC What was the evidence the subject of the appeal? Common law test for admissibility of this evidence is
Mason CJ, Deane and Dawson JJ " Because propensity evidence is a special class of circumstantial evidence, its probative force is to be gauged in the light of its character as such. But because it has a prejudicial capacity of a high order, the trial judge must apply the same test as a jury must apply in dealing with circumstantial evidence and ask whether there is a rational view of the evidence that is consistent with the innocence of the accused. Here "rational" must be taken to mean "reasonable" and the trial judge must ask himself or herself the question in the context of the prosecution case; that is to say, he or she must regard the evidence as a step in the proof of that case. Only if there is no such view can one safely conclude that the probative force of the evidence outweighs its prejudicial effect. And, unless the tension between probative force and prejudicial effect is governed by such a principle, striking the balance will continue to resemble the exercise of a discretion rather than the application of a principle." at [60]
McHugh J Why does McHugh J criticise the common law test for the admissibility of similar fact evidence? What is McHugh J's approach to the admissibility of H's evidence?
The Evidence Act Sections 94 – 101
94 Application (1) This Part does not apply to evidence that relates only to the credibility of a witness. (2) This Part does not apply so far as a proceeding relates to bail or sentencing. (3) This Part does not apply to evidence of: (a) the character, reputation or conduct of a person, or (b) a tendency that a person has or had, if that character, reputation, conduct or tendency is a fact in issue.
97 The tendency rule (1) Evidence of the character, reputation or conduct of a person, or a tendency that a person has or had, is not admissible to prove that a person has or had a tendency (whether because of the person's character or otherwise) to act in a particular way, or to have a particular state of mind unless: (a) the party seeking to adduce the evidence gave reasonable notice in writing to each other party of the party's intention to adduce the evidence, and (b) the court thinks that the evidence will, either by itself or having regard to other evidence adduced or to be adduced by the party seeking to adduce the evidence, have significant probative value.
"significant probative value" More than mere relevance but something less than a 'substantial' degree of relevance (R v Lockyer) Important (R v Lock) Of consequence (R v Lock)
What factors will determine SPV? Number of occasions of conduct Time gap(s) btwn them Degree of similarity of conduct Degree of similarity of circumstances
98 The coincidence rule (1) Evidence that 2 or more events occurred is not admissible to prove that a person did a particular act or had a particular state of mind on the basis that, having regard to any similarities in the events or the circumstances in which they occurred, or any similarities in both the events and the circumstances in which they occurred, it is improbable that the events occurred coincidentally unless: (a) the party seeking to adduce the evidence gave reasonable notice in writing to each other party of the party's intention to adduce the evidence, and (b) the court thinks that the evidence will, either by itself or having regard to other evidence adduced or to be adduced by the party seeking to adduce the evidence, have significant probative value.
101 Further restrictions on tendency evidence and coincidence evidence adduced by prosecution (1) This section only applies in a criminal proceeding and so applies in addition to sections 97 and 98. (2) Tendency evidence about a defendant, or coincidence evidence about a defendant, that is adduced by the prosecution cannot be used against the defendant unless the probative value of the evidence substantially outweighs any prejudicial effect it may have on the defendant. (3) This section does not apply to tendency evidence that the prosecution adduces to explain or contradict tendency evidence adduced by the defendant. (4) This section does not apply to coincidence evidence that the prosecution adduces to explain or contradict coincidence evidence adduced by the defendant.
R v Ellis (2003) NSWCCA Application of s 101
95 Use of evidence for other purposes (1) Evidence that under this Part is not admissible to prove a particular matter must not be used to prove that matter even if it is relevant for another purpose. (2) Evidence that under this Part cannot be used against a party to prove a particular matter must not be used against the party to prove that matter even if it is relevant for another purpose.
Phillips v R (2006) 158 A Crim R 431 Jacara v Perpetual Trustees WA (2000) 106 FCR 51
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On Eternal Patrol - Lost Submariners of World War II
Rank/Rate Electrician's Mate, Third Class Service Number 337 27 75 Birth Date November 15, 1921 From Champaign, Illinois Decorations Purple Heart Submarine USS Kete (SS-369) Loss Date March 20, 1945 Location Between 29-38N 130-02E and Midway Circumstances Lost at sea, cause unknown Remarks Elmer was born in Nashville, Tennessee. Photo and information courtesy of Paul Wittmer.
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The project team consists of representatives from Worcestershire LEA, The University of Worcester, Warriors Study Centre and our Principle Community Partners npower as well as a host of other contributors such as Slick Systems.
Warriors Study Centre Staff, Warriors Community Staff and the Operations team supported the children's learning by discussing issues that face the club in its on going mission to be one of the leading rugby stadia facilities in Europe. The climax of the week was the presentation evening where participants were judged on their submission by a panel of expert judges who identified the best all round design for innovation, appearance and environmentally conscious design.
'This project is one of a kind and it is down to the hard work and dedication of Janet Lodge the LEA Science Consultant and the Warriors Study Centre Manager Glynn who have coordinated a team of internal and external partners to deliver a unique and invigorating project with real tangible outcomes' Ryder added the success of this project has given the Warriors a taste of running this type of ground breaking project and it is sure to become a much more regular occurrence,' commented Tom Ryder, Warriors Community Manager.
The final submitted designs and recommendations for the North Stand will be taken seriously when planning the East Stand development and the proposed on going development of the North Stand. Charlie Little Warriors General Manager, discussed the value of this type of project for the Warriors 'the results of the npowering Easter school have provided us with some real challenges with our developments to ensure they meet the high levels of environmentally conscious developments that the extremely talented young people have produced.'
Congratulations were passed on by eight of the Warriors Stars, who presented the awards and watched in anticipation at some potential designs for the ever changing face of Sixways Stadium.


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Liberalism and Imperialism
Liberalism and Imperialism
Unit(s): 3.0 | Level(s): Graduate | Term(s): Winter | Offered?: Yes |
This course examines the historical and conceptual relationship between liberal political theory and modern imperialism. It explores the tension between liberalism's universalistic commitments to equality, political inclusiveness and individual rights and the forms of exclusion and domination accompanying the modern era in which those ideals developed. The course treats a broad range of thinkers from the early modern, Enlightenment, late modern and contemporary period to consider (a) how theories grounding universal human rights and political equality were made compatible with imperial and colonial domination, and (b) how this might impact on evaluation of the liberalisms that we inherit from them.
Assistant Professor


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Ronald StantonSergeant First Class243RD ASHC, 10TH CAB, 1 AVN BDE Army Of The United States 21 October 1946 - 04 October 1978 Massillon, OH Panel 40W Line 008 |
The database page for Ronald Stanton
Ronald Stanton was missing in action since his disappearance in October, 1968. After 33 years, he and his crewmates have come home. I "adopted" him while he was in MIA status and I would like to know more about him. Please e-mail me if you knew him. Thank you!
Five men of the 243rd Assault Support Helicopter Company, 10th Combat Aviation Battalion, died when their CH-47A (hull number 66-19053) went down.
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Prayer of the Day for Friday, August 8
Prayer to Our Lady, Mother of Mercy
Blessed Virgin Mary, who can worthily repay you with praise and thanks for having rescued a fallen world by your generous consent! Receive our gratitude, and by your prayers obtain the pardon of our sins. Take our prayers into the sanctuary of heaven and enable them to make our peace with God.
Holy Mary, help the miserable, strengthen the discouraged, comfort the sorrowful, pray for your people, plead for the clergy, intercede for all women consecrated to God. May all who venerate you feel now your help and protection. Be ready to help us when we pray, and bring back to us the answers to our prayers. Make it your continual concern to pray for the people of God, foryou were blessed by God and were made worthy to bear the Redeemer of the world, who lives and reigns forever. Amen.
Saint Augustine of Hippo
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Monday, May 3, 2010
Endorsements in Republican Primaries
There are lots of people running for the Republican nomination for federal office, but there are few quality candidates from which to choose. It is almost by default that we offer these as the best of the lot.
John Boozman for U.S. Senate. He is more sane than Jim Holt or Gilbert Baker, one of whom might make a run-off with Boozman. We know that Boozman votes and talks the right wing party line, but he seldom goes beyond those marching orders to make up stuff to get attention. He is a tool of Walmart and the monied interests, and he cares not for the average voter in Arkansas. In other words, a typical Republican.
Cecile Bledsoe for Congress, 3rd District. Again, all of the Republican candidates swallow the party line and can be counted to vote as the Whip tells them. Bledsoe would be better than Steve Womack or Gunner DeLay, because she is a nice person and generally unoffensive. Womack or DeLay would be sure to embarrass us with their loose lips as well as their voting records, so we go for the safer alternative.
15 comments:
- AnonymousMay 3, 2010 at 12:18 PM
The GOP of Arkansas is endorsing candidates? That's what you make it look like.
ReplyDelete You-ins is passing up a prince of a fellow and a good Faubus-loving candidate, my main man, Conrad Reynolds.
Who has your back? Click here.
.- AnonymousMay 4, 2010 at 4:00 PM
General Skotch is going to surprise you folks, because the T.E.A. Party voters know that Bailout Boozman and Tobacco Tax Bledsoe will be just more of the same that got us in this mess.
ReplyDelete - LibertasMay 4, 2010 at 6:37 PM
The Arkansas Times has been following the early voting turnout by county and party. After the second day, Republican ballots outnumber Democratic ballots in five counties: Benton, Baxter, Boone, Searcy, and Sebastian.
The link is at:
http://www.arktimes.com/blogs/arkansasblog/earlyvotingtuesday.pdf - another booze haterMay 4, 2010 at 11:21 PM
what the hell has Don Marr got to do with this post?
ReplyDelete The one time I voted in the Republican primary in LR, what did I do? I can't remember whether I voted for T. Robinson just to vote against him in the general election or I voted for Sheffield Nelson to get T R out of the mix.
Whatever, I won't do it this time. Got to put a true democrat in the Senate NOW.
We'll work on keeping Halter on the right track once he has the nomination.
Need to have Lioneld lecture Halter on being a servant of the people before we elect him. No Republican has that attitude and Blanche hasn't mentioned it in her campaign.- fool me twiceMay 5, 2010 at 2:35 PM
Aubrey, did Boozman and Lincoln ever follow through on those promises to get funding for expansion of the Fayetteville National Cemetery?
ReplyDelete Indeed. Courtney Henry sure went down on the religious right.
Wait! That didn't come out right.
Arkansas Times is endorsing Judge John Fogleman.
click on eLwood.
I'm endorsing and supporting Judge Tim Fox, mainly because he had the good sense to throw out the testimony of long stroke George Rekers in the Arkansas homosexual banning law.
"George Rekers, an anti-gay Baptist minister said to be an expert in "conversion therapy" -- "curing" gayness. He is also a founder, with James Dobson, of the Family Research Council, sort of the home church for Arkansas's anti-gay Family Council"
Ark Times, May 4 click here
Hooray for Circuit Judge Tim Fox! Let send him to the Supreme Court.
.Boozman is clearly the pick of the litter among the GOP field. He's not as smart as his late brother Faye, but he got his head whacked a lot playing football in the old days. He's a nice guy, good ol' boy and apparently honest, but he's never had an innovative or original idea that I know of. He will win easily and I'll support him against Halter, but moderates like me will pick Blanche and she'll win in the fall if she survives the Progressive money machine in the primary.
In the Congressional race,
Bledsoe is nice, friendly and able to work and play with others much better than Womack. However, she showed during a recent debate that she does not fully understand the issues. Womack is being criticized by the GOP because he admits he likes Gov. Beebe abd did not publicly support Asa Hutchinson against Beebe, but I commend him for that and agree. He's a hard ass who speaks plainly, but that's what we need now to fix this horrible crisis caused by out-of-control government deficit spending.dude, government spending did not create this crisis. Extreme recklessness in the private sphere created this crisis. the administration of the 8 years before the current, 15 month old administration did alot to help of course, by allowing those folks greater access with less regulation, but the cause of this crisis is not "government spending" just because that's a comfortable scapegoat.


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I finally thought of a new icon and theme design. I am calling this theme "Vaporize". Its based off of the color cyan that is used in ics and jelly bean on android. I am now complete with this theme and it is posted in the go launcher section of this site. Get it now, this theme is hot!!
Sunday, January 6, 2013
Finally though of a new theme design
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Special Issue: Proceedings of the 5th Paris Hepatitis Conference. International Conference of the Management of Patients with Viral Hepatitis: Special Edition Hepatitis C
Genotype 2 (HCV-2) accounts for 8% of the patients with chronic hepatitis C virus in Europe. Because of the favourable response to interferon (IFN)-based treatment, this group is considered an 'easy-to-treat' genotype along with HCV-3. However, experimental and clinical data suggest possible differences between HCV-2 and -3. Recently, subtle differences in treatment efficacy have also been shown in response-guided treatment studies. In these studies, the duration of pegylated interferon (PEG-IFN) and ribavirin (RBV) treatment was tailored according to treatment response. Although SVR rates were similar between HCV-2 and HCV-3 patients after a rapid virological response (RVR), in the absence of RVR, the rates were lower in HCV-3 than in HCV-2. The triple combination treatment, including direct-acting antivirals (DAA) that will be commercialized in the coming months might increase SVR rates in this particular subgroup of patients. According to existing results, telaprevir might be beneficial in HCV-2 but not in HCV-3 patients. A nucleotide analogue polymerase inhibitor, PSI-7977 by Pharmasett has been shown to be active against both. The role of the IL28B polymorphism as a predictor of response to the current standard of care (SoC), PEG-IFN and RBV treatment is the subject of debate, but this mainly seems to be because of the small size of the samples in the studies performed so far. Existing results suggest that the genetic evaluation of IL28B may be useful in patients with HCV-2 for predicting response in patients without RVR.
Epidemiological background
Epidemiological background
In the European countries, the most frequent HCV genotype is genotype 1 followed by genotypes 3, then 2 (Table 1). Despite these epidemiological differences, HCV-2 and -3 are usually analysed together on the basis of similar favourable responses to IFN treatment. Studies exploring a reduction in treatment duration have recently highlighted potential differences between these two genotypes. A mean prevalence of 8.2% has been reported in Europe for genotype 2, ranging from a prevalence of 0.9% in Turkey to 27% in Italy [1]. In 1997, genotype 2 was observed in 38% of the HCV chronic infected patients referred to our centre [2]. Although the corresponding prevalence of genotype 3 in that study was less than 5%, a wave of genotype 3 infection is currently also increasing the proportion of HCV-3 infected patients in Italy [3]. The HCV-2 is observed in 3% and 9% of HCV patients, in Spain and in France respectively. Outside of Europe, a high frequency of HCV-2 has been reported in some Southern African and Asian areas where it accounts for 30% of chronic HCV infection overall [4].
*Click On Table 1. To Enlarge
Table 1. Hepatitis C virus genotypes frequency by country
*Click On Table 1. To Enlarge
Table 1. Hepatitis C virus genotypes frequency by country
HCV genotype 2 treatment: PEG-IFN and ribavirin combination
These results are supported by those of a recent meta-analysis evaluating six trials of standard or shortened treatment. Sensitivity analysis by genotype showed that an SVR was achieved by 84% of HCV-2 rapid responders with no significant differences between standard or shortened duration when weight-based dosages of RBV were used for 16 weeks. The corresponding rate in patients with HCV-3 was 81%, but the difference between short and standard duration was greater perhaps because of the use of fixed doses of RBV [22].
The combination of PEG-IFN and RBV has been shown to be very successful in patients with genotype 2. The AASLD guidelines [5] advise treating HCV-2 and -3 patients for 24 weeks with combination treatment, including PEG-IFN alpha-2a or alpha-2b and a fixed dose of 800 mg of RBV [6]. With this treatment, more than 80% achieve SVR. However, because experimental and clinical data suggest possible differences between HCV-2 and -3 [7, 8, 9], it may be worthwhile to focus on response rates by genotype for the future scenario of the treatment of hepatitis C.
One trial by Zeuzem and the large 'real-world' WIN-R study reported a 9% difference between HCV-2 and -3 genotypes in SVR rates in favour of HCV-2 after 24 weeks of treatment [10, 11]. Recently, REDD 2/3 another 'real-world' study analysed HCV-2 and -3 separately in an evaluation of both a lower dose of PEG-IFN alpha-2b and a reduced duration of treatment [12]. This study reported somewhat higher rates of relapse in patients with HCV-3 than in those with HCV-2 after 24 weeks of PEG-IFN alpha-2b and weight-based RBV [12].
To reduce the costs and spare the side effects of combination treatment, several studies have investigated the effectiveness of treatment for less than 24 weeks after an RVR. Several studies in Europe and one study from Taiwan [13] have shown that a course of treatment with PEG-IFN and weight-based RBV for 12–16 weeks was not less effective or was cost-effective compared to the standard of 24 weeks [13, 14, 15, 16, 17]. However, one larger multicenter study, using a fixed dosage of RBV did not demonstrate that the two treatments were not less effective [18]. Based on the analysis of results in the literature, the updated European guidelines conclude that HCV-2 and -3 can be treated for 12–16 weeks when HCV RNA is undetectable after 4 weeks of treatment, as long as there is no advanced liver disease or obesity and RBV is weight-based [19]. The guidelines suggest that a short course of treatment may be slightly less effective in patients with HCV-3.
In a meta-analysis evaluating customized treatment of patients with HCV-2 and -3 in four studies, including 957 patients for whom separate data are available for both genotypes, we showed that SVR rates in HCV-3 patients with RVR were similar to those of HCV-2 patients [20]. The difference between the two genotypes is the probability of SVR in patients without RVR. In the absence of RVR [20], EASL guidelines advise 24 or 48 weeks of treatment depending on whether the patient is HCV RNA-negative or if there is a greater than 2 log10 decline in HCV RNA at week 12 respectively. However, the recommended schedule for HCV-2 and HCV-3 patients is the same [19].
Rapid virological response, SVR and relapse rates for HCV-2 patients in studies on short treatment duration with separate analysis of HCV-2 and -3 are shown in Table 2. Patients with HCV-2 infection had extremely high RVR rates ranging from 68 to 87%. No significant differences were observed in the SVR rate after 12 or 24 weeks of treatment once RVR was achieved (Table 2). After 24 weeks of treatment, the risk of relapse in patients with HCV-2 is low and the increased risk as a result of a short treatment course appears to be clinically irrelevant. Indeed, only the Accelerate study reported relapse rates increase of more than 12% in the short treatment arm when compared with the standard duration. The analysis by Diago [21] took into account only the subgroup of patients with RVR. This result may be explained by a high proportion of patients with advanced liver disease were enrolled in the short treatment arm; 28% of patients who received 16 weeks of PEG-IFN plus fixed 800 mg doses of RBV had bridging fibrosis or cirrhosis [18].
*Click On Table To Enlarge
Table 2. Response rates in HCV-2 patients enrolled in studies on short or standard treatment duration
*Click On Table To Enlarge
Table 2. Response rates in HCV-2 patients enrolled in studies on short or standard treatment duration
These results are supported by those of a recent meta-analysis evaluating six trials of standard or shortened treatment. Sensitivity analysis by genotype showed that an SVR was achieved by 84% of HCV-2 rapid responders with no significant differences between standard or shortened duration when weight-based dosages of RBV were used for 16 weeks. The corresponding rate in patients with HCV-3 was 81%, but the difference between short and standard duration was greater perhaps because of the use of fixed doses of RBV [22].
Table 3 reports the SVR rates in patients without RVR by genotype, in studies with data on 24 weeks of treatment. Unlike in HCV-3 patients, the SVR in HCV-2 patients who do not achieve RVR is above 60%. Increasing the SVR rate in patients without RVR is still an unresolved issue.
Future therapies
Recently approved DAA inhibitors of HCV replication are expected to provide a major step forward in the treatment of HCV infection. Several small molecules, mainly inhibitors of HCV NS3/4A protease and NS5B polymerase are in the process of being commercialized in Europe.
Although DAA will improve virological response rates in patients with genotype 1, the development of small molecules effective against HCV genotypes other than one is in earlier stages [23]. Telaprevir, the first agent to directly target viral replication, has been shown to be active against HCV-2, but not against HCV-3. Telaprevir is a powerful oral protease inhibitor [24, 25] that can increase the SVR in genotype 1 HCV by about 30% compared to standard PEG-IFN/RBV. The activity of telaprevir was investigated in patients with HCV-2 and HCV-3 in the C209 study. The combination of telaprevir plus PEG-FN alpha-2a and RBV was evaluated in five patients with HCV-2 and compared to telaprevir alone in nine patients and to PEG-IFN and RBV in an additional nine patients in the control group. The triple combination therapy resulted in SVR rates of 100% which is remarkable considering the 89% rate observed in patients receiving standard PEG-IFN/RBV [26]. Conversely, telaprevir monotherapy had little or no activity in patients infected with HCV-3. In that study, telaprevir was administered as monotherapy or in combination with PEG-IFN for only 2 weeks, while the overall duration of treatment was 24 weeks in each arm. It should be noted that the histological diagnosis of cirrhosis was an exclusion criteria in this study.
Other NS3/4A protease inhibitors, nucleoside and non-nucleoside reverse replicase inhibitors as well as NS5A inhibitors have shown to have antiviral activity against HCV-2. One of the most promising drugs so far is PSI-7977, a nucleotide analogue polymerase inhibitor [27]. In the Proton study, an open label study, the drug was evaluated in 15 patients infected with HCV-2 and in 10 infected with HCV-3 as well as in a larger group of patients with HCV-1 infection [28]. That study, whose results were presented at the last EASL meeting, reported an RVR of 96% after the triple combination of 400 mg of PSI-7977 plus PEG-IFN/RBV. Twenty-four HCV-2 and -3 patients who completed the 12 weeks of treatment achieved SVR (96%). Patients with cirrhosis were excluded. The Electron study, an ongoing study, is currently evaluating this triple combination in an IFN sparing regimen strategy of only 8 weeks of triple combination treatment.
The role of IL28B to modify treatment strategies
The role of IL28B to modify treatment strategies
The recent identification of a single nucleotide polymorphism (SNP) upstream from the IL28B gene associated with a response to IFN-based treatment is a landmark observation [29, 30, 31]. Genotype 1 patients with IL28B CC genotype had higher response rates compared to those with the rs12979860 TT alleles. Previous data proposed that interferon stimulated genes (ISGs) are up-regulated in non-responders prior to treatment [32, 33]. Genetic variation of the IL28B gene may explain the pre-activation of interferon stimulated genes (ISGs) in non-responder patients to IFN-based treatment, because the subjects with the unfavourable IL28B TT genotype have higher levels of activation of ISGs in the liver [34].
Distribution of CC genotypes in patients with HCV genotype 2
Distribution of CC genotypes in patients with HCV genotype 2
Numerous studies have investigated IL28B in patients with HCV-2 and -3 analysing both genotypes together. Separate analyses of the frequency of IL28B in patients with HCV-2 and -3 infections have only been performed in two studies, one by Sarrazin, and other by ours [35, 36] (Table 4). In both cases, the rs12979860 SNP was investigated [35].
Sarrazin et al. evaluated 378 patients with HCV-1, 77 with HCV-2 and 190 with HCV-3 [35]. They showed that the frequency of the CC genotype in patients with genotype 1 was 33.9%, whereas in patients with HCV-2 and HCV-3, it was 42.7%. When HCV-2 and -3 were analysed separately, the CC genotype was observed in 51.9% of those with HCV-2 compared to 38.9% of patients with HCV-3. When these frequencies were compared to those in the general population (49%), the difference between patients with HCV genotype 1 and healthy controls was high and statistically significant (P < 0.001). The difference in frequency between HCV-2 and the normal population was not statistically significant (P = 0.116). The frequency of the CC genotype in HCV-1 was significantly lower than that in HCV-2 patients (P = 0.045). No difference was observed in the frequency of CC between HCV-1 and -3 patients (P = 0.43).
Our group performed a study on the IL28B polymorphism in a cohort of 268 patients with HCV-2 (n = 215) (Table 4) and HCV-3 (n = 55) who were previously randomized in a multicenter-controlled trial to a treatment of variable or standard duration [36]. The favourable IL28B CC genotype was present in 37% of patients. When this group was compared to a cohort of HCV-1 patients in the same geographical area, the frequency of the CC genotype was slightly higher (37% vs 29% respectively). In the general population, the IL28B CC genotype was detected in 42% of cases. As in the study by Sarrazin, we observed a lower frequency of the CC genotype in patients with HCV-1 compared to the general population, but the difference was not significant. Differences between HCV-2 and control patients were not identified.
It is unclear if these variations in distribution are an effect of the functional mechanisms that lead to the development of chronic HCV infection, as previously suggested [37]. A prospective study in a large cohort of patients, including different HCV genotypes and subtypes in the presence of a specific IL28 genotype is required to clarify this issue.
SVR response in patients with HCV genotype 2 by IL28B
SVR response in patients with HCV genotype 2 by IL28B
Several independent genome-wide association studies (GWAS) reported SNPs near the IL28B (IFN-λ3) locus that displayed association with treatment response, mainly in genotype 1 infected patients. Furthermore, in a mono-centric cohort of genotype 4 infected patients from three different ethnic groups (Egyptian, European and Sub-Saharan African), IL28Brs12979860 CC genotype was associated with a higher sustained virological response [38].
In contrast, available data on the predictive role of the IL28B polymorphism on SVR are conflicting for patients with HCV-2 and -3 infections. Some studies have failed to demonstrate any clear association between the IL28B polymorphism and SVR in patients with HCV-2 or -3 infection [39, 40]. Others have reported a positive association between the favourable rs12979860 CC or rs8099917 TT genotype, respectively, with RVR, but not SVR [41], suggesting an increased rate of relapse in this subset of patients. Finally, two European studies, including ours, examining HCV-2 and HCV-3 together, have shown that CC is associated with SVR [35, 36].
In our study, the association was largely driven by the subgroup of patients who did not achieve RVR [36]. Indeed, we observed that the IL28B CC genotype selects those who will respond to treatment among non-RVR patients. In contrast, the SVR rates in patients without RVR and with the TT genotype were negligible.
The CC genotype was not associated with RVR in the standard treatment arm or in patients who achieved RVR and were therefore treated for only 12 months. This lack of association may be a consequence of the rate of RVR observed in the different series of HCV-2 patients studied so far; larger numbers of patients would probably equalize the different results. In our cohort, CC genotype was an independent baseline predictor of SVR.
Our results suggest that IL28B may play a role in some patients, particularly those who do not achieve RVR, as defined by undetectable HCV RNA in serum after 4 weeks of treatment with an assay of sensitivity ≤ 50 IU/ml.
No association was found between RVR and IL28B genotype in the study by Sarrazin et al. evaluating 58 patients with HCV-2 and 147 with HCV-3 infection treated with PEG or standard IFN [35]. However the authors found an overall association with SVR, and with SVR in RVR patients, in particular. The main limitation of this study was the heterogeneity of previous treatment regimens, including IFN monotherapy. This may explain why the association with SVR was not statistically significant.
One difference between American patients and the HCV-2 patients evaluated in Sarrazin's and our study was that an intermediate degree of IFN sensitivity was observed in patients with the CT genotype.
Patients infected with genotype 2 HCV are an 'easy-to-treat' population. As a result of the very high successful response rate and the possibility of shortening the duration of treatment in nearly all patients who achieve an RVR in the absence of cirrhosis, treatment of HCV-2 with a standard combination of PEG-IFN/RBV may be continued.
The DAA potentially active against HCV-2 should be explored to increase the SVR response rates in the subgroup of patients without RVR whose SVR rates remain unsatisfactory, with the combination of PEG-IFN/RBV. In patients without RVR, IL28B might be a useful predictor of SVR after PEG-IFN/RBV combination treatment.
Conflicts of interest
Conflicts of interest