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This Teacher of the Year lesson plan also includes:
- Rubric
- Worksheet
- Join to access all included materials
Now is the time to identify the great teachers in your school! Discuss the characteristics of persuasive writing and analyze an example. Then, each pupil chooses a teacher who they feel should be named teacher of the year. They plan and write a paragraph to convince the class of their choice.
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subset: commoncrawl


text:
Meet UNSW's
newest sporting stars
Challenging both body and mind is a pursuit not only for Sydney Sixer's cricketer Carly Leeson, but for all UNSW's Ben Lexcen Sports Scholars.
In 1988, thanks to the support of alumni, UNSW was the first Australian university to offer sports scholarships to help students excel at both sporting and academic endeavours.
Since then, donations have continued to grow the prestigious Ben Lexcen Scholarships, which have assisted more than 160 elite student athletes.
This year four UNSW undergraduate students have begun university life with Ben Lexcen Scholarships.
Rugby back Nick Wilkinson, champion sprinter Jessica Thornton, and cricketers Carly Leeson and Declan White have joined the list of elite sporting stars who have chosen to study at UNSW.
Current UNSW students, swimmer Emily Washer, rower Sophie Jerapetritis, 3,000m steeplechase runner Georgia Winkcup and sailing's Kurt Hansen and James Colley have also been elevated to Ben Lexcen Scholars in 2017.
The scholarships recognise students not just for their outstanding sporting ability but also for their all-round qualities in leadership, community and academia.
Nick Wilkinson
Nick grew up in Cowra, a small country town in western NSW, where he went to school until year 9. He then attended St Joseph's Hunters Hill, where he made the switch from rugby league to rugby union.
"I'm training with both the Randwick Rugby Club and the NSW Waratahs under 20s."
"So I'm doing both but once the Waratahs are concluded I'll be back at Randwick full time.
Nick has just started a Commerce degree at the UNSW Business School.
"I always did quite well with those subjects at school, and it's quite a broad degree, so I'm hoping it will open up lots of opportunities," Nick says.
Nick's sporting goals are to perform consistently, particularly as he transitions from schoolboy rugby to the Waratahs under 20 squad and the Randwick Rugby club.
"I was really happy to receive the Ben Lexcen Sports scholarship.
Nick takes inspiration from Henry Hutchison and Andrew Kellaway, who were both UNSW Ben Lexcen scholars. Andrew is currently playing with the Waratahs and Henry is with the Aussie 7s.
"What they have been able to do in such a short period of time is really exciting so I'd like to try to emulate that in some way," Nick says.
Carly Leeson
The 17-year-old all-rounder hails from the north coast of NSW and was named Female Country Cricketer of the Year in both 2015 and 2016. She recently moved to Sydney and plans to live on campus during her studies.
"It's a great privilege to be awarded a UNSW Ben Lexcen Scholarship. It is a prestigious award and, especially knowing those who have been awarded it before me, it's definitely an honour," says Carly.
Carly is studying environmental management at UNSW. "I've always been interested in animal conservation, and the environment, and I'm also interested in law, so environmental management covers all those areas," she says.
Carly has had to juggle sport and study all through high school so she is well practised in starting her exam preparations early.
"It is great to know that there are people at UNSW who understand the situation and who will be there to support me," she says.
Carly became a member of the Shooting Stars squad for their tour of Sri Lanka in 2015, and she is also in the NSW Women's under 18s squad and the NSW Women's High Performance Academy.
"I'm looking to play for the NSW Breakers soon, and playing for Australia is the ultimate goal, but that is still a few years away yet," she says.
Jessica Thornton
Jessica Thornton's running career started with the under 8's at Little Athletics and took a big leap in 2014 when she attended the Youth Olympics in China, winning a gold medal. She was then selected as the first runner in the 4 x 400 m relay at the Rio Olympics.
"It was a pretty incredible experience, it was an amazing Olympics – being my first as well, the atmosphere was incredible and everyone was helpful and supportive.
"I was 18, so I was the youngest of the athletics team," she says.
Jessica takes inspiration from Australia's 400 m great Cathy Freeman, who ran in the relay at the 1990 Commonwealth Games before going on to win gold at the 2000 Sydney Olympics.
Jessica is studying a Bachelor of Life Science part-time and plans to transfer to exercise physiology. She also has a strong interest in nutrition and diet. Jessica is following in the footsteps of her brother and sister who both attended UNSW.
"It is a great honour to be a Ben Lexcen Scholar. You get to meet others who have the same problems balancing sport and study.
"I'm hoping to compete in the world championships in London in August, then the Commonwealth Games in 2018, and then to progress to another Olympics would be the main goal," she says.
Declan White
Declan White grew up in Sydney's eastern suburbs and attended Marcellin College in Randwick. The talented cricketer began by bowling and batting with his dad in the backyard.
"I started playing on Waverly cricket ground with Easts under Fives. I played junior cricket, and grade cricket when I was 14 or 15."
Declan decided to take a gap year before starting university, and played cricket in Scotland for six months.
"I knew some guys from the UNSW Cricket club who had gone over to the UK to play cricket. I tried to get a few ideas from them and then the coach of UNSW cricket club had a contact in Scotland and got in contact with them, and it went from there," Declan says.
The 19-year-old is studying Commerce and Economics at the UNSW Business School and says he was thrilled to receive the Ben Lexcen Scholarship.
"It was definitely a proud moment, receiving the scholarship.
"It really helps me with my study because you get to be a bit more flexibility – so that was a big draw card. The money and the gym membership are also nice."
"It can be stressful but it can also be a time to get away from study. It's a balance that you have to strike.
"My sporting goal is to play for NSW, otherwise I'll keep doing what I am doing but hopefully crack the baggy blues."
Previous Ben Lexcen scholars have included dual winter Olympian Scott Kneller, Rio Olympian, silver medallist Lisa Darmanin and six-time World Windsurf Champion Dr Melanie Webb.
UNSW's nine new Ben Lexcen scholars in 2017 will join the current group of 15, including NSW cricketer Georgia Redmayne, Australian Rugby 7's Henry Hutchison and Olympic skier Taylah Paige O'Neill.
The scholarship provides $7,500 worth of financial and personal support and a mentoring program for each student to provide flexibility between study and sporting commitments.
The scholarships are named after Australian yachtsman and marine architect Ben Lexcen.
Lexcen designed the winged keel for Australia II which, in 1983, became the first non-American yacht to win the prestigious America's Cup in 132 years.


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Desenvolver arte para canecas!!
Orçamento R$90-750 BRL
Bom dia, procuro uma pessoa com boas ideias e domínio em photoshop / Illustrator para desenvolver arte para canecas de porcelana, possuo um negocio de bolos caseiros onde vendemos bolos e salgados( empadão, bola salgada e sanduíche americano) as canecas teriam que ter relacionamento com a loja, as mesmas serão vendidas na loja, ao total serão 05 modelos de arte para caneca.
Obs: Segue em anexo os 05 modelos da caneca e um exemplo de caneca personalizada.
32 freelancers estão ofertando em média R$382 para esse trabalho
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In case there is ever severe weather and schools are closed, we want students to still be able to practice their brain power whether they are at school or not.
So here are some websites: (You can click on them! Nifty!)
So here are some websites: (You can click on them! Nifty!)
- Readworks (Reading comprehension)
- Student CNN (Social Studies & Science; a lot of real world relations)
- BrainPOP (Username: Gainesville & password: elephant) (Math, science, social studies, & ELA)
- iLearn (Username is the student's ID number & password is Enota1) (Math instruction & practice)
- Google Classroom (Some teachers may use Google Classroom to post up assignments or notes & the students know how to log in & which teachers use them)


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Tibetans cite a new government effort to control what news they hear.
Photo: RFA
KATHMANDU—Chinese authorities have begun to remove satellite dishes in a Tibetan-populated region of
Tibetan-language broadcasts by Radio Free Asia and Voice of America appear to be particular targets of the campaign, one source said.
"Beginning in April of this year, the local broadcasting department oin Kanlho [in Chinese, Gannan] prefecture [of Gansu province] dispatched staff to the counties to install cable lines and to pull down the satellite dishes used by local Tibetans to listen to foreign broadcasts like RFA and VOA Tibetan programs," a Tibetan woman in the Labrang area of Kanlho said.
"They also installed cable lines for listening to government-approved programs," the woman added, speaking on condition of anonymity.
"Local Tibetans were told by officials that they were carrying out the directives of central and provincial level authorities," she said.
"They distributed copies of the letters issued by the government."
A Gannan prefecture document obtained by RFA, citing State Council document #129, describes what it calls "unprecedented efforts to collect satellite dishes" to restrict access to long-distance broadcasts in Gansu province, a site of repeated Tibetan protests against Chinese rule during the past year.
Anyone failing to comply with government directives to remove the dishes would be "dealt with in accordance with law," the memo said.
Begun in 2000
Tibetan writer Woeser, in the June 15 entry of her blog "Invisible Tibet," noted efforts "as early as 2000" by China's government to block broadcasts by Radio Free Asia and Voice of America.
Hundreds of jamming towers have been built in Tibetan regions for this purpose, she wrote.
"The Chinese government is now forcing Tibetan monks to pull down satellite dishes so that they cannot listen to RFA and VOA broadcasts. In May this year, the Chinese authorities carried out the policy vigorously in Kanlho."
"In their place, the local Tibetans are forced to listen to [state-controlled] local TV programs connected through land lines," she wrote.
Originally reported by Lhumbum Tashi for RFA's Tibetan service. Tibetan service director: Jigme Ngapo. Translations by Karma Dorjee. Written in English by Richard Finney. Edited by Sarah Jackson-Han.


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The Final Fight of Mario
The last gig of Kintana with the Expired has been amazing! We just want to thank all the crazy people that came at Blue Rose Saloon! A special thank to Extirpation and Hellstorm, that shared the stage with us, and obviously to Mario for this beatiful last gig! We all hope the best for him!


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Unique Egg Cups
1 item(s) in stock
*These conversion prices are indications only
Please re-enter your quantity
In her hometown of Bamberg, Carmen Munzinger occupies a beautiful little studio, tucked away in the winding streets of Bamberg. Her incredible, quirky ceramic work is truly unique in every sense, no two pieces are the same.
Read more about Carmen Munzinger
In her hometown of Bamberg, Carmen Munzinger occupies a beautiful little studio, tucked away in the winding streets of Bamberg. Her incredible, quirky ceramic work is truly unique in every sense, no two pieces are the same. There are egg cups, tea pots, vases and decanters, to choose from. If it can be made from clay, you'll find it at Carmen's studio. You can visit her ceramics studio and see her at work and watch as her wonderful creations come to life.
Read more about Bamberg, Germany
We decided to go to Bamberg because it sounded a bit like hamburger. That's not true but it's an amusing thought. In my opinion, Bamberg is a must see if you go to Germany. It boasts the most amazing collection of beautiful buildings, they are all incredibly old (17th and 18th century) and extremely well preserved. We spent quite a bit of time just wandering around the gorgeous streets ogling the buildings, taking a ridiculous amount of photos, and just getting lost in this stunning city.
One of the most beautiful, colourful buildings is perched on its own little island, surrounded by canals that connect the city together, meaning that you cross gorgeous old bridges to get from one side to the other. It was raining when we arrived and after a couple of hours of trudging around the town under umbrellas, the skies cleared and we climbed a flight of stairs and caught our first glance of the Domplatz (Romanesque and Gothic Cathedral) glistening in the late afternoon sunshine. This was definitely a highlight. It started raining again soon after and so we decided to shelter in a lovely little pub that we discovered. After sitting down and ordering drinks, another couple came in and sat at the booth behind ours. David felt something warm and soft on his feet and after a bit of investigation (the both of us peering into the dark underneath the table) we realised that the couple at the next booth had brought along their fluffy, black labradoodle to dinner and he was sitting under the table sniffing at David's feet! We didn't know whether to feel shocked that there was a dog at the pub or to feel sad because it made us miss our beautiful Lola. Travellers Tip: Don't be surprised to see dogs in retail shops and restaurants when you are travelling through some parts of Europe, and be prepared to have your feet sniffed while eating dinner!
Design by Design & Other
/ Build by Flint Interactive


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Before visiting the country, I knew Panama was rich in history; however, after visiting the Panama Canal and Casco Antiguo I learned so much more about the construction of the Panama Canal and details about Casco Antiguo from Fabio.
First, I did not know that the French initially started the construction of the Panama Canal that was completed by the United States in 1914. I also learned that there are three locks along the 51 mile canal: Gatun, Pedro Miguel and the Miraflores. Fabio, our guide, later told us that the amount of material that was excavated from the canal was large enough to circle the earth four times! We were lucky enough that we were able to watch two ships pass through the Miraflores locks as they continued their way to the Pacific Ocean. We learned it cost the cruise ship we saw $250,000 to pass through the locks. At first, this seemed like a lot of money to me, however passing through the canal, which takes 8-10 hours saved the cruise ship $2 million and two weeks (Unbelievable!)
Our fourth day in Panama we visited Casco Antiguo the old city. First and foremost, the view of Panama City from Casco Antiguo took my breath away. We could see the entire skyline which seemed to stretch on forever. I found it fascinating when Fabio explained that Panama is currently in the process of building smaller islands off the coast similar to those in Dubai. Fabio further explained that Casco Antiguo is going through a huge makeover, reconstructing and remodeling the old buildings in the city into lavish hotels and apartments. It was also interesting to learn that because the French occupied Casco Antiguo in the past, the architecture of the building are similar to those in France which I noticed with the various balconies. I learned that the French had a huge influence in Panama from the Canal to Casco Antiguo.
Jocelyn P.


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Buyers willing if banks are.
Despite the sensationalist reporting in some sectors of the media, there is no shortage of buyers in the current property market.
Leading indicators of market sentiment such as internet activity, enquiry level and inspection numbers all remain healthy. The challenge comes when the interested buyer approaches their respective financial institution.
The credit squeeze through the banks has been the catalyst for the current market downturn. Fortunately for those vendors prepared to sell at current market price, there are still ample buyers willing to pay a fair market price.
Interest rates remain at record lows and look set to stay that way for some time. As prices begin to show more value, buyers now face some of the best buying conditions since 2012.
Along with finance, sentiment has a huge bearing on how the property market performs.
In a boom, buyers tend to feel as though they are buying at the top of the market. In a matter of weeks, the purchase looks sound.
The credit squeeze through the banks has been the catalyst for the current market downturn.
Conversely, in a falling market, sellers feel as though they are the chump selling at the bottom of the cycle. By the time the sale settles, they are relieved they sold when they did.
The interim report from the Banking Royal Commission was released in late September. The damning evidence highlighting the banks behaviour has seen further tougher standards imposed into the marketplace.
The current softness in property prices creates an opportunity for first home buyers, investors and upgraders to take advantage the value on offer.


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MILL BAY, B.C. – Mateo Albinati scored three goals, Patrick Ostermann stopped 40 shots, and the Victoria Cougars beat the Kerry Park Islanders 4-2 on Saturday night.
Also scoring for Victoria was Foster Martin.
The Cougars, coming off an ugly loss to the Saanich Braves two nights ago, enjoyed period leads of 1-0 and 2-0.
Sampson McLean and Parker Ellis replied in a losing cause.
Victoria finished 1-for-5 on the power play and gave up a shorthanded goal. Meanwhile, the Islanders went 0-for-7 with the man advantage.
Parker Swanson made 20 saves in his debut for Kerry Park.
Elsewhere in the VIJHL: Oceanside Generals 4, Peninsula Panthers 3. Nanaimo Buccaneers 6, Comox Valley Glacier Kings 4.
Next game for the Cougars is Tuesday, November 28 versus the Peninsula Panthers.
1st star, Mateo Albinati (Goals: 3, Assists: 0)
2nd star, Patrick Ostermann (Saves: 40, Save Percentage: .952)
3rd star, Connor Bissett (Goals: 0, Assists: 0)


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Explore Liverpool with Liverpool City Walks. Take a bespoke walk with our professionally qualified Blue Badge and Green Badge guides.
Walk this way ……. to enjoy a walk along Hope Street with its two landmark cathedrals: between them you will find stunning architecture, fascinating culture and a host of hidden treasures.
Awarded 'The Great Street Award' in the 2012 Urbanism Awards,
judging it to be the best street in the country – it has it all.
Starting with the modern, circular designed Metropolitan Cathedral
to the newly refurbished Everyman Theatre winner of the 2014
Royal Institute of British Architects Awards Stirling Prize,
the world's most prestigious architecture prize, on to the
architectural gem of the Philharmonic Dining Rooms to
the former educational establishments of John, Paul and George with so much
more in between.
Beginning with the Georgian period right up to modern times there is so much history to be discovered on this walk you really can't afford not to experience it all!
Available in all weathers by arrangement 21 days in advance, subject to numbers:
email firstname.lastname@example.com to request preferred timings.
Length of walk 2hrs. Distance covered approx. 1.5miles over some cobbled walkways and level paved surfaces. There is an incline during part of the walk.
Wheelchair users will require assistance from a strong able pusher.
Toilet facilities are available in public buildings.
We walk in all weathers so recommend comfortable footwear and clothing to match the weather of our Maritime City.
Starts : Metropolitan Cathedral of Christ the King piazza at the base of the steps.
Ends : Liverpool Cathedral.
From the city centre the Cathedral is about a 10 minute walk. There are signs throughout the city centre directing visitors to the two cathedrals. Head for the Adelphi Hotel and then walk up Mount Pleasant which runs from the right of the hotel as you face it, and is the right hand of the fork, keeping to the right of the multi-storey car park.
If using satnav, input L3 5TQ or Mount Pleasant. Alternatively follow the brown tourist signs for the Cathedrals or Liverpool University.
From the city centre, the Hop on Hop off city tours visit and stop here.
Main line trains terminate at Lime Street Station. The cathedral is about a 10 minute walk from the station. Central Station is the nearest Merseyrail station to the cathedral.


text: I received a menu in the mail last week for a restaurant called Turning Point. Since then I have been seeing that phrase numerous times while reading different articles. This is validation from Spirit regarding my previous blog post regarding a change occurring. I Love the creativity of Spirit! They will practically knock you over the head with what they want you to understand! I do not know how this turning point will BE experienced, whether it is an internal turning point or an external change, but I AM open to how this calling on my heart manifests next. So indeed it appears I have reached a turning point.


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The presentation layer handles data formats and code formatting. The layer's functions are normally transparent to the end user because this layer takes care of code formats and presents them to the application layer (Layer 7), where the end user can examine the data. Examples of presentation layer protocols include the following:
■ Graphics Interchange Format (GIF)
■ Joint Photographic Experts Group (JPEG)
■ American Standard Code for Information Interchange (ASCII)
■ Moving Picture Experts Group (MPEG)
■ Tagged Image File Format (TIFF)
■ Musical Instrument Digital Interface (MIDI)
■ Hypertext Markup Language (HTML)
application will be accessed end users. Examples of
■ File Transfer Protocol (FTP)
■ Simple Mail Transfer Protocol (SMTP)
Layer 7: The Application Layer
The application layer is closest to the end user, which means that the by the end user. This layer's major function is to provide services to application layer services include the following:
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For anyone interested, but too lazy - pulled from Espen Kraft's description of the video:
Anamorphic shoot at one of the most beautiful, scenic and dramatic sites you will find in Norway: The deep blue UNESCO-protected fjord Geiranger. The fjord is surrounded by majestic, snow-covered mountain peaks, wild waterfalls and lush, green vegetation. Camera: Panasonic GH2, GH3 & Go Pro Hero3 Lenses: Helios 44M with Kowa for Bell & Howell 2x anamorphic on the GH2 and a Olympus digital 12mm 2.0 on the GH3 Other equipment: Slider, Crane, tripods, ND filters Had to intercut the anamorphic shots occasionally with the Olympus lens because of setup time. The Go Pro was used to capture the shots when driving the car. Used Protune on the Go Pro, Picture profile on both the GH2 and GH3 is standard with everything turned down except for saturation. Used a Driftwood Hack on the GH2. Framerate is 24p. Added some grain in Premiere Pro in addition to extensive color correction to match up the different cameras and lenses. Still not perfect but I think it's mostly ok now. Some of the shots with the Olympus is done with ex.tele on the GH3 and have some noise I've removed with Neat to some extent. No noise on the anamorphic shots have been removed. Due to tremendous vibration on the boat it was impossible to use the anamorphic setup on the tripod and had to shoot it handheld. Had to use some warp stabilizing in premiere pro on those shots hence some "heatwave" artifacts from time to time. The same goes for the Go Pro shots done handheld out through the open window from the car while I was driving. Still a little wobbly, but the image of the MB 190SL HAD to go into this short imo. The aspect ratio of 3:55 is not to everyone's liking, but I like it more and more. Music: Blackmill
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Chromebooks are the new textbooks: More NJ schools assign laptops
Schools across New Jersey are learning they can't ignore the digital age.
Even if the process takes years, several districts and schools have been making efforts to provide most, or even all, of their students with an electronic device like a laptop or tablet in order to enhance the learning experience and prepare students for a technology-driven world on the other side.
These decisions are made at the local level, and statistics are not tracked statewide, but according to Larry Cocco with the Office of Educational Technology within the state Department of Education, the number of computers and other devices in the classroom has been increasing over the past few years.
"The push to get more technology in schools, and get students more familiar with digital learning and the digital world, is one that all educators are taking very seriously," Cocco told New Jersey 101.5.
Cocco said part of that push is due to assessments such as PARCC that require online access.
With help from the state, Cocco said, more than 99 percent of PARCC-takers last year were using a device to answer the questions.
In Freehold Township, every student from third to eighth grade is provided with a Chromebook laptop, and sixth-through-eighth graders are allowed to take the devices home with them. In fact, they need to in order to get their work done.
"They're on the computer to function the way we do in the real world with our email, word processing, spreadsheets, Google drawing, presentations," said Ali Ryan, an educational technology coordinator within the district. "It's an integral part of their homework lives."
The devices were phased in slowly across the district, grade by grade, to make sure teachers were properly trained on the equipment.
"We're preparing kids for jobs that don't exist yet," said Superintendent Ross Kasun. "Most traditional schools, I think, are preparing kids for our past and not for their future."


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Great location in the heart of Kakaako. Walking distance to Ala Moana Shopping Center, Wal-Mart, Target with easy access to freeway access to the east and the west side. The building has amenities galore! Heated swimming pool, theater, tennis court, putting green, children's play area, and many guest parking. The first showing will be on Wednesday, Open House on July 11 from 9:30-11:30 AM
Listing courtesy of Keller Williams Honolulu. Selling Office: List Sotheby's Int'l Realty.
Based on information from the Multiple Listing Service of Hicentral MLS, Ltd. Listings last updated on . Information is deemed reliable but not guaranteed. Copyright: 2020 by HiCentral MLS, Ltd. IDX information is provided exclusively for consumers' personal, non-commercial use. It may not be used for any purpose other than to identify prospective properties consumers may be interested in purchasing.


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IRS Office of Professional Responsibility webinar Jan. 17
January 5, 2018
Authored by: Keith Kehrer
Topic: The Office of Professional Responsibility: What you need to Know about Practicing before the IRS (rebroadcast)
Date: Wednesday January 17, 2018
Times: 2:00 p.m. Eastern; 1:00 p.m. Central; Noon Mountain; 11:00 a.m. Pacific
Duration: Two hours
Webinar featuring OPR Director Stephen Whitlock with live Q&A at the end of the presentation
Topics include:
- Regulations governing tax practice before the IRS (Circular 230, Rev. 6/2014)
- Due diligence obligations of tax professionals
- Overview of other key Circular 230 provisions
- Practitioner responsibilities to their clients and to the tax administration system
- Best practices for all tax professionals
- Office of Professional Responsibility policies and procedures
Earn two CE credits in ethics
To receive a certificate of completion and CE credit, you must:
- View the live presentation on 1/17/18 for at least 100 minutes from the start of the program.
- To confirm your attendance and receive your certificate of completion, view the presentation while signed-in using the same email address used to register; you will not receive credit by watching this webinar on someone else's computer.
- Groups cannot register with one email address and receive separate certificates; each person must register separately.
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While some of the elite few travel to exotic places to train during the off season, getting pampered and living under extremely controlled environments, the rest of us make do with what we have. For me, that means training whenever I can, early morning, late at night, lunch hour, in the cold, the dark, wet and sometimes freezing (actually I prefer frozen to wet, it's not as cold). I do the best I can do with what I have to work with.
The elite do it because it's their job, I do it because I love to race and I love the feeling of being fit.
My "off season" is over, my first race of 2009 is Saturday at the first round of the Knoxiecross Cyclocross series in Knoxville. Round 2 is on Sunday then rounds 3 and 4 are in February. I will miss the last two rounds at the end of February because I am going to Florida for the 12 Hours of Santos. Then in March, there is a couple of road races that I will be doing leading up to the start of the "racing" part of my year and the 6 Hours of Warrior Creek and the Cohutta 100, both in April.
These races this winter are all training races and very little priority is given to them. I will be trying some new stuff out and different strategies, especially at Santos and basically trying to get fit for the important races this summer.


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Colby Bird
Fitzroy Gallery
"Rules: consistent dimensions, accurate Kodak Color Control Patch colorways, precise professional framing, careful art handling, correct installation, proper contextualization, sale of work." Whether the last of these itemslisted, along with a set of "mediating actions," by Colby Bird as critical to his recent exhibition "Clyde Glenn Burns"was realized may remain forever known only to the artist, his dealer, and their actual or prospective collectors. I can report, however, that every other condition was met. Yet Bird's second solo outing here was far from the dry classic-Conceptual exercise that this deadpan prose poem might have led one to expect; it was, in fact, highly crafted, even sensual.
The show, named for "an elderly handyman in Valley Mills, Texas" who exerted an unspecified influence over the artist, consisted of three bodies of work. Entries from Bird's "
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EASL guidelines compared to other international guidelines
1. Introduction
An estimated 400 million people are chronically infected with hepatitis B virus (HBV), worldwide, and over 500,000 chronic hepatitis B (CHB) patients die annually because of cirrhosis and hepatocellular carcinoma (HCC) [1,2]. Clinical care for patients with CHB has advanced considerably during the last decades as a result of growing knowledge about the mechanisms of disease, diagnostic procedures and advances in therapeutic options.
Since the introduction of interferon alpha as first antiviral therapy at the end of the 1980s, management of CHB has dramatically evolved due to the availability of direct antivirals which greatly increased the therapeutic options, thus permitting treatment of patients previously excluded from IFN treatment. In particular, new oral antivirals have been developed and used in clinical practice, leading to a substantial improvement in antiviral efficacy, mainly due to their increased potency and higher barrier to resistance. On the other hand, the expanding molecular and clinical knowledge of HBV infection and evolution of therapy have made the management of CHB patients much more complex. Therefore, within the recent past, several guidelines have been issued by many organizations and professional expert panels in order to better define diagnostic criteria and improve therapeutic decisions.
This chapter focuses on the current management of chronic hepatitis B patients and reviews up-to-date studies and concepts regarding antiviral treatment.
2. Pre-therapeutic assessment
Chronic HBV infection is not necessarily accompanied by progressive liver disease requiring antiviral therapy. Therefore, as a first step, an accurate evaluation of all HBsAg-positive carriers is required in order to identify: a) the phase of infection, b) the subjects with chronic liver damage, c) the stage of liver disease, d) the concurrent causes of liver disease, and e) patients requiring treatment.
The natural history of chronic HBV infection can be divided into five, not necessarily sequential, phases (Figure 1). Firstly, the (i) immune-tolerant phase is characterized by high levels of serum HBV DNA, HBeAg positivity, normal ALT levels, and mild or absent liver necroinflammation. In patients who remain in the immune-tolerant phase, disease progression is minimal [3]. After a variable time depending on the age at acquisition of HBV infection, immune-tolerance to the virus is lost and the immune system mounts an attack on the infected hepatocytes, thus entering into the (ii) immune-reactive phase.This phase is characterized by fluctuating, but progressively decreasing, HBV-DNA levels, elevated ALT and hepatic necroinflammation (HBeAg-positive CHB). A prolonged immune-reactive phase with multiple ALT flares may result in progressive liver fibrosis, leading to cirrhosis. An important outcome of the immune-reactive phase is the seroconversion from HBeAg to anti-HBe, thus marking the transition to the (iii) immune-control phase, characterized by low (<2000 IU/ml) or undetectable serum HBV DNA, normal ALT levels, and disappearance of liver necroinflammation (inactive carrier state). The estimated annual incidence of spontaneous HBeAg seroconversion is 2%-15%, depending on factors such as age, ALT levels, and HBV genotype [2]. In a minority of patients, despite HBe seroconversion, reactivation of HBV replication may occur due to the selection of HBeAg defective HBV mutants. This (iv) reactivation phase is characterized by positivity for anti-HBe antibodies, fluctuating HBV DNA and ALT levels and a high risk of progression to severe hepatic fibrosis (HBeAg-negative CHB). In patients with periodic ALT flares and normalization, HBV-DNA levels can fall below the inactive carrier cut-off (2000 IU/ml), making differential diagnosis between active CHB and the inactive carrier status problematic. Therefore, to warrant an accurate differential diagnosis, it is mandatory to monitor serum HBV-DNA by sensitive and quantitative polymerase chain reaction (PCR) assays and ALT levels over a period of at least 1 year. A recent study, however, demonstrated that a single-point combined quantification of HBV-DNA (<2000 IU/ml) and HBsAg (<1000 IU/mL) permits to identify inactive HBV genotype D carriers with a very high diagnostic accuracy which is comparable to that of 1-year monthly monitoring [4]. In the (V) "HBsAg-negative phase" after HBsAg loss, low-level HBV replication may persist with detectable HBV DNA in the liver [5]. In patients with "occult" HBV infection the persistence of an efficient HBV immunological control has been demonstrated [6], and it is now well known that immunosuppression may lead to HBV reactivation in these patients.
On the basis of the serological and virological profile, three distinct HBsAg carrier types can be identified, each characterized by a distinct natural course, prognosis, and treatment indications: 1) immune tolerant carrier, 2) inactive carrier, 3) carrier with CHB (HBeAg-positive and HBeAg-negative CHB). In both tolerant and inactive HBV carriers, treatment is not indicated, but an appropriate longitudinal follow-up is crucial. Immunotolerant patients should be subjected to ALT measurements every 3-6 months and should be tested for the presence of HBeAg every 6 months. In the inactive carriers, ALT and HBV DNA levels should be assessed every 3 months during the first year, and then every 6 months [7-9]. Patients with serum HBV DNA <2000 IU/ml and levels of HBsAg less than 1000 IU/ml, may require less frequent monitoring due to a very low probability of disease reactivation [7].
In the HBsAg carriers with CHB, the diagnostic work-up must be continued and the severity of liver disease should be assessed by laboratory tests, and hepatic ultrasound examination. A liver biopsy would be useful for determining the grade of necroinflammation and stage of fibrosis. Prognosis and management of CHB greatly depend on the stage and progression of liver fibrosis and thus the risk of developing cirrhosis. In addition, liver biopsy may help to clarify diagnosis when ALT and HBV DNA levels are discordant and to exclude other coexistent causes of liver disease (e.g. fatty liver or alcoholic liver disease).
Liver biopsy has traditionally been considered the "gold standard" to measure fibrosis. However, liver biopsy is an invasive procedure which can be painful, and carries a small risk of complications; it is also costly and prone to sampling errors. To provide a reliable estimation of grading and staging of liver disease, liver biopsy specimens should be at least 20-25 mm long and/or containing more than 11 complete portal tracts [10]. Recently, non-invasive methods, including serum markers and transient elastography, are being increasingly utilized to assess liver fibrosis [10]. Transient elastography (FibroScan) is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis. It has demonstrated a high diagnostic accuracy for the detection of cirrhosis, but transient elastography might be inaccurate in discriminating between the different stages of intermediate fibrosis (F1 vs F2), F2 being considered the threshold for initiating antiviral therapy. Moreover, stiffness measurement may be influenced by potential confounding factors such as additional space-occupying tissue abnormalities (e.g. oedema and inflammation, cholestasis).
Lastly, in the diagnostic work-up of CHB, the presence of other possible liver damaging cofactors (co-infections with HDV, HCV and HIV, co-morbidities including alcoholism, autoimmune or metabolic liver disease) which would increase the risk of progression to cirrhosis or HCC should be assessed [11].
3. Treatment indications
Candidates for treatment are the HBsAg carriers with CHB and, consequently, those with active viral replication, increased ALT levels and evidence of liver disease at liver biopsy or other non-invasive methods.
According to the 2012 HBV guidelines of the European Association for the Study of the Liver (EASL), patients should be considered for treatment when they present HBV DNA levels above 2000 IU/ml, serum ALT levels above the upper limit of normal (ULN) and a liver biopsy showing moderate to severe necroinflammation and/or at least moderate fibrosis using a standardized score system. The comparison between EASL guidelines and American Association for the Study of Liver Diseases (AASLD) guidelines and Asian Pacific Association for the Study of the Liver (APASL) guidelines can be found in Table 1.
However, patients with compensated or decompensated cirrhosis and detectable HBV DNA should be considered for treatment, independent of ALT levels. Moreover, treatment indications should also take into account the patient's age, health status, family history of HCC or cirrhosis and extrahepatic manifestations.
4. Goal of therapy and end-points
The ultimate goal of CHB therapy is the prevention of cirrhosis, hepatic decompensation and/or HCC [7-9]. This goal can be achieved if HBV replication can be suppressed in a sustained manner, thus leading to biochemical remission, HBe seroconversion in HBeAg-positive patients, histological improvement and prevention of cirrhosis and its complications. Several studies have demonstrated that undetectable or low levels of HBV DNA are associated with a lower risk to develop cirrhosis [12-14].
Loss of HBsAg from serum with or without seroconversion to anti-HBs is considered the ideal end-point of therapy, as it is associated with remission of chronic hepatitis B activity and an improved long-term outcome [11]. The loss of HBsAg, however, is infrequently achieved with currently available anti-HBV agents. Hence, a more realistic end-point is the induction of a sustained or maintained virological response. It must be emphasized that a complete eradication of HBV infection is impossible to achieve due to the persistence of the so-called covalently-closed-circular DNA (cccDNA), the transcriptionally active HBV mini-cromosome in the nucleus of infected hepatocytes; that is to say, that an HBV infected patient can be "cured" but the HBV infection cannot be eradicated and continues to persist as an occult infection.
5. Anti-HBV drugs
Two different types of drugs have been approved for the treatment of CHB: conventional interferon alpha (IFN) and its pegylated form (Peg-IFN), and 5 nucleoside/nucleotide analogues (NAs) (Figure 2). Currently, IFN has been replaced by Peg-IFN due to the more convenient administration (once weekly). There are two pegylated-IFN formulations: Peg-IFN alpha-2a and Peg-IFN alpha-2b which have shown similar efficacy in clinical trials, but only the former is globally licensed for treatment of CHB, while Peg-IFN alpha-2b has been approved in only a few countries. Among the nucleoside analogues with anti-HBV activity, emtricitabine is not licensed for HBV treatment in most European countries and its combination with tenofovir in one tablet (Truvada) has been licensed only for treatment of human HIV infection.
6. Peg-interferon
Peg-IFN is a cytochine with a dual antiviral and immunomodulatory activity and is administered by subcutaneous injections. After binding with receptors located on the surface of several different cells, it induces the activation of at least 40 cellular genes, encoding for several antiviral proteins. Peg-IFN suppresses HBV virion budding, HBV entry and synthesis of the nucleocapsid; moreover, this cytochine enhances the interaction between the antigen-presenting cells and CD4, and between CD8 and infected hepatocytes. Therefore, Peg-IFN has the potential for an immune-mediated control of HBV infection, thus providing the opportunity to obtain a sustained virological response after treatment discontinuation, and the possibility of inducing HBsAg loss in patients who achieve and maintain undetectable HBV DNA. IFN-based treatment, however, is often complicated by the occurrence of side effects, such as influenza-like symptoms, fatigue, neutropenia, thrombocytopenia, and depression, which sometimes require dose modification and cause premature cessation of treatment [15]. Moreover, Peg-IFN is contraindicated in patients with decompensated HBV-related cirrhosis or autoimmune disease, in patients with uncontrolled severe depression or psychosis, in patients receiving immunosuppressive therapy or chemotherapy, and in female patients during pregnancy [7].
7. Nucleoside/nucleotide analogues
NAs are oral direct antiviral agents which specifically inhibit the viral polymerase/reverse transcriptase, an enzyme with a crucial role in the HBV life cycle. As a result, NAs block the production of new virions and progressively reduce serum HBV DNA to undetectable levels, but they have little or no effect on the cccDNA present in the nucleous of the infected hepatocytes. The persistence of the intrahepatic cccDNA determines the reactivation of HBV replication after stopping NA treatment and therefore justifies the need for a long-term (potentially life-long) therapy for a sustained viral replication control.
After lamivudine (LAM), the first nucleoside analogue approved for the treatment of CHB, another two nucleosides, telbivudine (LdT) and entecavir (ETV), and two nucleotide analogues, adefovir (ADV) and tenofovir (TDF) have become gradually available in recent years. NAs are characterized by a different antiviral potency and drug-resistance pattern. Entecavir and tenofovir are the two most potent analogues with a high barrier to resistance development. Resistance rates in NA-naïve patients treated with monotherapy are shown in Figure 3.
The main advantages and disadvantages of Peg-IFN and NAs in the treatment of CHB are shown in the following Table 2.
8. Treatment strategies
There are two different therapeutic strategies for both HBeAg-positive and HBeAg-negative CHB patients: short-term or "curative" treatment and long-term or "suppressive" treatment (Figure 4). The first strategy aims to obtain a sustained suppression of viral replication off-treatment by inducing an immune controll status of HBV infection. The immune control status corresponds to the profile of an inactive carrier: normal ALT levels coupled with HBV DNA <2000 IU/ml and anti-HBe positivity. This strategy is IFN-based (Peg-IFN administered for 48 weeks); a finite treatment with NA is possible only in HBeAg-positive patients. The second strategy aims to obtain a rapid and long-term maintained viral suppression (HBV DNA <10-15 IU/ml). This strategy is exclusively based on NAs.
9. First-line monotherapy
Peg-IFN, entecavir or tenofovir are recommended as first-line monotherapy by all major guidelines in patients with CHB or compensated cirrhosis [7-9]. The choice of first-line monotherapy should be based on several factors including host, virus and drug related factors (Figure 5). The most favourable candidates for Peg-IFN are those with low HBV DNA levels, high ALT and HBV genotype A or B rather than C or D, and those without advanced disease. Peg-IFN alpha-2a is administered as subcutaneous injections at the dose of 180 μg once weekly for 48 weeks.
Entecavir or tenofovir are the only therapeutic options in patients with decompensated liver disease, in patients undergoing immunosuppressive treatment, in patients with controindications or unwilling to receive Peg-IFN. The licensed entecavir dose for patients with decompensated cirrhosis is 1 mg (instead of 0.5 mg for patients with CHB or compensated liver disease) once daily. Tenofovir is administered orally at dosage of 245 mg/die.
For oral antiviral agents, in HBeAg-positive patients, treatment can be discontinued after a 12 month-consolidation therapy from documented HBeAg seroconversion with undetectable HBV DNA. Close monitoring for relapse is required following therapy discontinuation. In HBeAg-negative patients, long-term treatment is necessary and can be stopped when confirmed HBsAg loss occurs [7,8].
As Peg-IFN can achieve a sustained off-therapy response in only a minority of cases, and a proportion of patients cannot tolerate or present controindications to IFN or do not wish to be treated with Peg-IFN, long-term treatment with NAs is the most commonly used treatment strategy.
10. Virological and non-virological monitoring
During Peg-IFN therapy, full blood counts and serum ALT levels should be monitored monthly and TSH should be assessed every 3 months. All patients should be monitored for safety throughout the 12 months of treatment. Serum HBV DNA levels should be assessed by real-time PCR at 3, 6, 12 months during treatment and at 6 and 12 months post-treatment. Quantitative determination of serum HBsAg levels should be checked after 3 months of therapy in order to identify patients with a low probability of response in whom IFN therapy discontinuation should be considered [7]. In HBeAg-positive patients, HBeAg and anti-HBe should be tested every 6 months. Lastly, in all responder patients, HBsAg should be checked at 12-month intervals [7].
In patients treated with NAs, HBV DNA levels should be monitored at month-3 to ascertain virological response, and thereafter, every 3-6 months. In patients treated with ETV or TDF, the frequency of DNA measurements may be decreased once patient compliance and treatment efficacy are confirmed. In HBeAg-positive patients, HBeAg and anti-HBe should be tested every 6 months. HBsAg should be checked at intervals of 12 months in all patients with undetectable HBV DNA by real-time PCR [7].
All NAs are cleared by the kidneys, therefore all patients should be tested for serum creatinine levels and estimated creatinine clearance at baseline to identify the need for dose adjustments. As the nephrotoxic potential damage seems to be higher for nucleotide analogues, it is recommended for patients treated with ADV or TDF renal monitoring, including serum phosphate levels every three months during the first year and every 6 months thereafter. In patients at high renal risk or in those who develop clearance creatinine <60 ml/min or serum phosphate <2 mg/dl, a closer renal monitoring is required [7].
11. IFN-based therapy: Update
Published data have demonstrated that in patients with HBeAg-positive CHB, Peg-IFN achieves a more than 30% HBeAg seroconversion rate after one year of treatment [7]. In a registration trial, Peg-IFN alpha-2a provided a sustained immune control which increased post-therapy; in fact, the HBeAg seroconversion rate continued to increase from 27% at the end of treatment to 32% during the six months after discontinuing treatment, and to 42% after 1 year post-treatment [16,17]. Moreover, the seroconversion remained stable over time in >80% of Peg-IFN alpha-2b treated patients achieving this end-point at the end of therapy [18]. Peg-IFN also determined HBsAg seroconversion in up to 30% of patients with a long-term follow-up [19].
In patients with HBeAg-negative CHB, Peg-IFN alpha-2a demonstrated a sustained immune control (HBV DNA <2000 IU/ml) in 31% of patients after 1-year post-treatment. Among these, 88% maintained this response up to 5-year follow-up, and remarkably 28% achieved HBsAg clearance after 5-years post-treatment [20].
Thus, Peg-IFN treatment remains an attractive therapeutic option, since it provides higher rates of off-therapy immune control, including HBsAg clearance, when compared with NAs. However, IFN is effective in only a minority of patients (20-30%), has a poor tolerability and significant costs. Therefore, the improvement of Peg-IFN efficacy is a major challenge. Several attempts have been made to optimize the cost-effectiveness of IFN-based therapy, including combination therapy, duration of therapy, pre-treatment predictors of response, and on-treatment predictors of response. De novo combination therapy with NAs, did not improve sustained response in either HBeAg-positive or HBeAg-negative patients [16,21-23]. Regarding duration of therapy, the NEPTUNE study conducted in patients with HBeAg-positive CHB reported that dose and duration are important because the highest sustained response was obtained with 180 µg and 48 weeks compared to 90 µg and 24 weeks [24]. A recent study has demonstrated that extended treatment with Peg-IFN alpha-2a to 96 weeks was well-tolerated and improved the rates of sustained virological response (29% vs 12%) in HBeAg-negative genotype D patients when compared to the current standard of care of 48 weeks. In addition, after 1-year post-treatment, HBsAg clearance (6%) was observed only in the extended therapy group [25].
There have been many attempts to identify pretreatment predictors of response, resulting in the identification of high ALT levels, low HBV DNA, and virus genotype as significant predictors [7-9]. When combining data from the two largest clinical trials regarding HBeAg-positive CHB patients [16,26], Buster et al. found that the best candidates for a sustained response to Peg-IFN were genotype A patients with high levels of ALT (ALT≥2xULN) or low levels of HBV DNA (<9 log10 copies/ml), and genotypes B and C patients who have both high levels of ALT and low HBV DNA. Genotype D patients have a low chance of sustained response [19]. However, these factors cannot accurately predict response at the individual level; furthermore, ALT and HBV DNA levels are time-dependent and thus their use in clinical practice is difficult.
To obtain additional insight into the individual patient's probability of achieving response to Peg-IFN, the presence of precore and basal core promoter mutants before treatment has been correlated to the serological and virological response in HBeAg-positive CHB patients [27]. Data from this study demonstrated that the presence of a wild-type virus at baseline was an independent predictor of response to Peg-IFN and can assist in improving patient selection for this treatment option [27]. Lastly, the role of IL28B polymorphisms, clearly indicated as a baseline host factor predictor of response in patients with chronic hepatitis C, has been also investigated in CHB patients. Studies in HBeAg-positive patients provided conflicting results, while, in the only study carried out in HBeAg-negative genotype D patients, the rs12979860 genotype in the IL28B locus independently predicted both virological and serological responses [28-31]. Therefore, further studies are necessary to define the role of IL28B polymorphisms as a baseline factor to improve pretreatment patient selection.
A promising approach to improve the cost-effectiveness of Peg-IFN therapy is a response-guided treatment, based on HBsAg kinetics which permit early identification of either responders, for whom continuation of treatment to week 48 could be beneficial, or non-responders who should discontinue IFN treatment.
Two stopping rules at week 12 have been proposed for HBeAg-positive patients: 1) no HBsAg decline, 2) HBsAg levels >20 000 IU/ml [24,32,33]. The negative predictive value (NPV) for a sustained response ranged from 82% to 100%, depending on prevalence of HBV genotypes in the various studies. In HBeAg-negative genotype D patients, no HBsAg decline and <2 log copies/ml HBV DNA decline at week 12 has been proposed as a stopping rule and independently validated with a 100% NPV [34,35]. Overall, therapy with Peg-IFN could be discontinued at week 12 in the 20% of primary non-responders, who are therefore candidates for suppressive therapy with NAs.
12. NA-based therapy: Update
Entecavir and tenofovir are the third-generation NAs recommended as first line therapy for CHB NA-naïve patients by all international guidelines. In registration trials, both antivirals demonstrated a long-lasting efficacy (viral suppression in more than 95% of patients over 5 years) associated with prevention of developing cirrhosis and to a greater extent, with fibrosis regression [36-40]. Moreover, these studies reported a minimal risk of drug resistance (1.2% with ETV after six years and 0% with TDF after 5 years) and a favourable safety profile [39-43]. However, as registration trials are conducted under standardized conditions in well-selected and compliant patients, long-term efficacy and safety of ETV and TDF remain to be confirmed in real-life patients who generally have a more complex clinical profile as they are usually older with a higher prevalence of cirrhosis and comorbidities treated with several concomitant medications.
13. Entecavir in real-life practice
Currently, 2,736 CHB naïve patients have been treated with ETV monotherapy in six real-life studies and 4-year efficacy and safety data are available for two of these. In a multicenter Italian study, 418 consecutive NA-naïve patients initiating treatment with ETV 0.5 mg/die were enrolled. In this cohort, at baseline patients were older (median age 58 years), were predominately infected with HBV genotype D (90%), presented a diagnosis of cirrhosis in 49% and concomitant disease in 56%. Viral suppression was achieved in 100% of patients over 48 months of therapy, independent of HBeAg status. Only one patient with a partial virological response at week 48 developed resistance at year 3 of treatment with a cumulative rate of 0.2%. In HBeAg-positive patients, the 4-year cumulative probability of HBeAg seroconversion and HBsAg loss were 56% and 21%, respectively. However, despite persistent suppression of viral replication, HCC developed in cirrhotic patients at 2.5% yearly rates, making continuous surveillance for liver cancer mandatory [44].
A cohort from Hong Kong included 222 NA-naïve patients who demonstrated a 96% 4-year cumulative rate of virological response [45]. Only one patient developed resistance, corresponding to a 0.6% cumulative resistance rate up to year-4.
The safety profile of ETV in real-life studies has been excellent, as there have been no reports of drug-related adverse reactions, discontinuation, or renal toxicity [44-46].
In the VIRGIL multicenter study including 243 consecutive NA-naïve patients receiving ETV monotherapy, the cumulative probability of achieving a virological response at week 144 was 90% in HBeAg-positive patients and 99% in HBeAg-negative patients [47]. In this cohort, 81% of patients with partial virological response at 48 weeks reached a virological response during prolonged ETV monotherapy and no patient developed ETV resistance. When stratifying patients according to their viral load at week 48, 95% of patients with HBV DNA<1000 IU/ml and 57% of patients with HBV DNA>1000 IU/ml achieved a virological response without treatment adaptation during the prolonged treatment period beyond week 48. Therefore, the authors concluded that no treatment adaptation is needed in the majority of NA-naïve patients treated with ETV and obtaining partial virological response, particularly in those with HBV DNA <1000 IU/mL at week 48. In addition, data from the Virgil cohort demonstrated that in cirrhotic patients, virological response to ETV is associated with a lower probability of developing a clinical event and disease progression [48].
14. Tenofovir in real-life practice
A total of 1,203 CHB patients, including both NA-naïve and experienced, were treated with TDF monotherapy in real-life. In the multicenter European cohort study, 302 consecutive NA-naïve patients receiving tenofovir (245mg/die) were retrospectively and prospectively followed for a median period of 28 months. At baseline, median age was 55 years, 35% of patients had cirrhosis, and concomitant diseases were present in 43% [49]. By month 36, virological response was reached in 86% of HBeAg-positive patients and 98% of HBeAg-negative patients. No patient developed drug resistance and, in HBeAg-positive patients, cumulative probability of HBeAg seroconversion at 30 month was 33%. Most partial virological responders at week 48 achieved undetectable HBV DNA during additional treatment. Data from this European cohort confirmed the safety profile of TDF reported in the registration studies. Discontinuation therapy was reported in 9 patients (3%) including renal-related adverse events in two. The TDF dose was reduced in ten patients (3%) because of a decline in the estimated glomerular filtration rate [49].
15. Antiviral treatment failure
All patients receiving NA-therapy for CHB should be closely monitored for virologic response defined as undetectable HBV DNA by a sensitive PCR assay. Failure of antiviral therapy may be due to several reasons and three types of treatment failure can be identified: 1) Primary Non Response; 2) Partial Virologic Response; 3) Virologic Breakthrough [50] (Figure 6).
Primary non response is defined as less than 1 log10 IU/ml decrease in HBV DNA level from baseline after 3 months of therapy; the cause might be attributed to lack of compliance or to reduced drug susceptibility in a particular individual. Primary non response seems to be more frequent with Adefovir than with other NAs because of sub-optimal antiviral efficacy. When a primary non response is identified antiviral treatment should be modified to prevent disease progression and drug resistant development. In a compliant patient HBV genotyping for the identification of possible resistant mutations should be performed and a switch to a more potent NA is recommended [7].
Partial virological response is defined as a decrease in HBV DNA of more than 1 log10 IU/ml, but detectable HBV DNA after 24 weeks of therapy in compliant patients treated with low genetic barrier NAs (LAM, LdT) and after 48 weeks in patients receiving ADV.
Several studies demonstrated that in patients with persisting viremia after 24 weeks of LAM therapy or 48 weeks of ADV therapy, there is a greater risk of resistance development with further treatment, compared to patients with undetectable HBV DNA. Therefore, an alternative treatment should be considered in these patients before emergence of genotypic resistance and a change to a more potent drug (entecavir or tenofovir) without cross-resistance is recommended [7]. With the more potent and high genetic barrier drugs, such as ETV and TDF, it has been shown that the rate of viral suppression continues to increase even after one year of treatment, without evidence of drug-resistance [7]. These data suggest that a modification of therapy is not necessary in patients with partial virological response under entecavir or tenofovir, especially in those with declining serum HBV DNA levels. However, in patients with persisting low viremia or when HBV DNA levels do not continue to decline, treatment should be adapted (switching or adding the other drug) in order to maximize viral suppression and prevent long-term resistance [7].
Virological breakthrough is defined as a confirmed increase in HBV DNA level of more than 1 log10 IU/ml compared to the lowest value (nadir) achieved during treatment. In all patients with a virological breakthrough, treatment compliance should be assessed. In compliant patients, virological breakthrough is related to the selection of HBV drug-resistant mutants [50].
16. Antiviral drug-resistance
Antiviral drug-resistance is defined as the reduced susceptibility of a virus to the inhibitory effect of a drug due to adaptive mutations selected under the selective pressure of antiviral therapy. In CHB patients treated with NAs, antiviral drug-resistance is due to mutations within the Polymerase gene of HBV, thus resulting in amino acid substitutions within the polymerase/reverse transcriptase, target of all NAs. These amino acid changes reduce the affinity of the enzyme for the antiviral drug, in favor of natural substrates. Moreover, the resistance-associated mutations selected by a particular NA confer at least some degree of cross-resistance to other members of its structural group but may also diminish the sensitivity to NAs from a different chemical group, thus limiting future treatment options (Figure 7).
Development of antiviral drug-resistance is a complex and multistep phenomenon. Figure 8 shows the chronology of events.
Initially, during antiviral therapy, there is the emergence of mutants containing the primary mutations which are known to confer resistance to the antiviral drug (genotypic resistance). If treatment is continued, resistant mutants are selected under the selective pressure of the drug, and over time become the dominant viral species, producing the progressive increase in serum HBV DNA levels. The virological breakthrough is then followed by a biochemical breakthrough, defined as elevation in serum alanine aminotransferase, after achieving normalization. The time span between virological and biochemical breakthrough may vary from weeks to years.
Development of antiviral drug-resistance has important clinical implications, as it provokes the loss of clinical benefits due to treatment. The selection of drug-resistant mutants was one of the most important concerns with the first and second generation NAs, especially with LAM (Figure 3). Currently, the availability of most potent antivirals with a high barrier to resistance, such as entecavir and tenofovir, significantly reduced the rates of resistance. Consequently, the correct choice of a first-line monotherapy provides the best chance of preventing treatment failure and drug resistance.
In clinical practice, the early identification of the virologic breakthrough permits an effective timely rescue therapy, before the biochemical breakthrough, thus avoiding disease progression, decompensation in patients with advanced cirrhosis, and accumulation of secondary mutations which may improve viral fitness and may become the basis for cross-resistance with other NAs.
In all patients with a virological breakthrough, genotypic resistance testing should be performed to confirm genotypic resistance and to determine the pattern of mutations. There are two commercially available methods for detection of resistance mutations: a direct PCR-based sequencing, which detects all mutations present in a resistant mutant if it is present in ≥20% of the viral quasispecies, and a hybridization-based genotyping method, which can detect only known nucleotide mutations, but is more sensitive, allowing for detection of mutants when they constitute 5% or more of the total viral population.
The management of treatment failure has changed significantly in recent years, due to the availability of potent antivirals. An appropriate rescue therapy should be initiated with the most effective antiviral drug without cross-resistance to reduce the risk of selecting multiple drug-resistant viral strains. The add-on strategy is the therapeutic approach recommended by guidelines, in order to prevent the emergence of multi-drug resistant strains and raise the resistance barrier. However, with the availability of more potent drugs, such as entecavir and tenofovir, there is a trend to recommend a switch to a complementary drug having a high barrier to resistance. Both options are considered in the recent EASL guidelines [7]. Recommendations for treatment adaptation in CHB-resistant patients are showed in Table 3. The switch strategy does not apply to patients who have been exposed to multiple monotherapies; these patients should be treated with add-on strategies in order to minimize the risk of subsequent treatment failure.
17. Summary and conclusions
Chronic hepatitis B remains a serious clinical problem because of its worldwide distribution and potential progression of liver damage. Over the last decades, treatment of CHB has greatly advanced due to the availability of safe and effective drugs and guidelines have been developed. Both Peg-IFN and two NAs, entecavir and tenofovir, can currently be indicated as first-line therapies for CHB.
Peg-IFN treatment is a short-term treatment strategy which provides a significant off-treatment sustained responses, including loss of HBsAg. However, as Peg-IFN is effective in 20-30% of patients, it should, therefore, be considered only for patients with an elevated possibility of response based on pre-treatment and on-treatment factors. In particular quantitative HBV-DNA and HBsAg may be suitable to early identify patients who are unlikely to benefit from Peg-IFN early during the treatment course, thereby avoiding unnecessary treatment. Nevertheless, despite this individualised and response-guided approach, increasing the cost-effectiveness of Peg-IFN therapy remains a clinical challenge. Combining Peg-IFN with NA appears to be the most appealing approach to increase the efficacy of antiviral therapy and new trials on a combination of Peg-IFN with ETV or TDF are required.
Currently, nucleos(t)ides analogues represent the treatment option used in the majority of CHB patients due to their potent antiviral effect, oral administration (one oral tablet daily) and optimum tolerance. In registration trials, entecavir and tenofovir, third-generation potent antivirals with a high barrier to resistance, showed long-term HBV-DNA suppression, low rise of resistance, potential reversion of fibrosis and no progression to cirrhosis, and lower risk of adverse clinical events in cirrhotic patients, except for HCC development. Real life studies have confirmed the long-term efficacy and safety of these two first-line NAs. However, NAs require a long-term, perhaps indefinite, treatment thus raising several concerns: patient's commitment to lifelong treatment, adherence, long-term safety, drug resistance in the long-term and costs. Combination of IFN and NAs might achieve an antiviral synergy and provide new opportunities to increase HBsAg clearance rates and shorten treatment duration. New studies exploring different strategies of combining Peg-IFN with ETV or TDF are required to further improve the treatment of chronic hepatitis B.


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Ekandjo, Doeseb Call for Professionalism and More Sponsors
Although the Namibia Premier League (NPL) receives an annual grant of N$16 million from MTC, Tim Ekandjo, MTC's chief human capital and corporate affairs officer is still not yet convinced that the NPL leadership has done enough to professionalise the league despite limited funds.
Speaking at the MTCNPL Awards ceremony in Windhoek at the weekend, Ekandjo announced that the Namibian football premiership is currently the 5th best sponsored league in Africa with a yearly investment of N$16 million, which sees the league winners take home N$1 million.
"Johnny Doeseb, the NPL chairman, you have now effectively been at the helm of the league for the past seven years. We would like to thank you for your contribution and that of your entire leadership team for the strides local football has made. Our next collective vision must be to attach a professional status to the game as we cannot continue maintaining the current status quo with this amount of investment, which is indeed significant," said Ekandjo
"We are well aware that the league needs in excess of N$20 million per annum to reach its full potential, but we also understand that MTC alone cannot carry this joy, not burden. The NPL leadership therefore desperately needs to seek more sponsors to join MTC. But I'm with the Brave Warriors' recent accomplishment – the future of Namibian football is bright and promising and as a sponsor we can see the promised land, although we might not reach that promised land with you."
In conclusion, Ekandjo said: "We must thank and recognize those who paved the way to our recent Cosafa Cup victory. The likes of former president Muinjo and his administration, companies like The Namibian for the annual Namibian Newspaper Cup, corporates like Biest Namibia for the Biest Cup, Standard Bank for the Standard Bank Super Cup, Metropolitan for the Metropolitan Summer Cup and Skorpion for the Skorpion Zinc Cup – these are all tournaments that concentrate on grassroots development of the game and we must therefore salute and encourage them to re-double their efforts because development is key to further success."
In his short speech, NPL chairman Johnny 'JJD' Doeseb recognised MTC's unwavering support towards the development of Namibian football and urged more sponsors to come on board and assist the NPL in taking Namibian football to greater heights – and hopefully achieve professional status.
"Going into the new season, we want to ensure all clubs plying their trade in the NPL put special emphasis on young structures within their respective clubs. Clubs must move out of their comfort zones and start going the extra mile to secure sponsors. We speak of youth empowerment, but yet we fail to recognise the potential that football, and sport in general, has to develop and empower the youth," said Doeseb.
Source : New Era


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Thurs 10 May 2007
Armada Hotel
Speaker: Aaron Sim
Like PowerUp – Rule the Stock Market Workshop, those who have registered before the workshop/seminar starts would get a reminder from the organizer about the date, time and venue. This is an attentive feature to ensure you turn up.
Actually, we were supposed to be at another seminar at PBD but we got this sms reminder and somehow, our brain only remembered this. On the way, after I had boarded into LRT to Asia Jaya only I suddenly remembered – we had discussed about which 1 to go and Thurs would be at PBD, Sat this Smart Traders. I kept smsing Nat about this on the way but she didn't understand!
Luckily, we both had the same wired thinking – we reached Armada Hotel at about the same time.
Aaron Sim, the CEO of Wealth Mentors, didn't end his words with "Yeah?" but he always asked questions when the answers were apparent in the presentation slides, like "So what is the next step?"
And the audiences had to participate by giving answers listed on the presentation slides. I felt maybe Aaron had been a primary school teacher? It reminded me of trainers drilling soldiers. In a softer way, of course.
He automatically added, "Thank you," after someone answered the obvious answer.
Wealth Mentors – Mirriam MacWilliams & Aaron Sim
It's tough to be a speaker. You have to convey your sincerity and to some point, be spontaneous.
The points presented were simple and easy to understand because I had known about Call and Put Options explained in the first workshop I had attended by PowerUp. Aaron showed a lot of testimonials from ex-students – in fact, there were 3 of them available to answer questions. He also showed how chief trainer, Mirriam MacWilliams made millions in the US stock market. Wow. All the time there, I visualized myself trading in stock options and get millions of $$$. I could work still, just to pass time and learn different things but I could go to vacations, buy exotic food and gorgeous clothes, open lots of different businesses… Wooo!
You have to know when to buy – it doesn't have to be at the top or bottom, somewhere around the middle can still enable money making. Provided you know what action and option to take and when.
The course is worth almost RM11K. There was a discount thrown in but not much. Reason being using RM11K in this course is much more useful than losing RM11K in the stock market. Ahh.. I looked at Nat and Nat looked at me. *a bit roll eyes* When we are super rich. Other courses are not as expensive as this but I guess Miriam has excellent track record and she's from the US (currency exchange over also *3+).
// Update 14 May 2007
Received an sms from Wealth Mentors that the discount for the course still stands, for 3 days. From when – the date I went for seminar?
If you are a subscriber of the site and included your email during the seminar, you'll get to see Channel NewsAsia video clips of interview with Miriam sent to your email. Actually you can view them at Wealth Mentors – Media Room. The Media Room has Newspapers & Magazines, TV & Radio Interviews.
// EOU (End of Update)


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Category Archives: Blog
Cement vs Concrete: The hard facts
They're two similar words describing wet stuff that's mixed up, poured out and allowed to harden into durable shapes and forms. We've heard them used interchangeably. But are they? Is there a difference between cement and concrete? You bet there is!
Cement is a binding agent made of finely powdered limestone and other ingredients which, when mixed with water, forms a powerful binding agent that hardens to near rock-like consistency. It was discovered by Englishman Joseph Aspdin three centuries ago. Aspdin found that mixing these ingredients and heating them to approximately 2,700 degrees Fahrenheit created a product which, when mixed with gypsum and ground into a powder, would harden when mixed with water.
Concrete is merely a mixture of Aspdin's product – cement – with aggregated stone, sand and other materials that allow it to be used in masonry, flooring, countertops and other useful materials. So while you can have cement without concrete, you can't have concrete without cement. Make sense?
Typically, concrete contains about 10 to 15 percent cement. The amount of gypsum in the cement mixture affects the setting time of the concrete (the amount of time it takes the concrete to harden), and additional products can be added to the mixture to control cracking and chipping. Also, the amount of aggregate has an effect – the more stone and other materials used results in stronger concrete.
Here are two more interesting facts: The amount of water needed to set cement is not set in stone, so cement can actually be poured, and will harden, underwater. Also, since cement and concrete utilize raw materials that are abundant worldwide, they do not use up our precious resources – and the more that's produced, the less raw resources need to be used in the future, since both products are easily recycled.
At Sunworks Etc., we utilize a technique called Glass Fiber Reinforcement Concrete (GFRC). What's great about this is we can cast larger pieces with less weight. It also makes curves far are more achievable – and even large floor-to-ceiling pieces can be realized.
Central PA Garden Expo: Mission Accomplished
This year's Pennsylvania Garden Expo was an amazing experience for us. I wish we could thank each and every one of you in person for coming out and supporting SunWorks Etc.!
This year's Expo featured more than 200 vendors, outdoor living displays, classes and workshops. I know this isn't actually true, but it seemed like everyone was coming to see us! There weren't five consecutive minutes of downtime for us during the entire three-day Expo!
Decorative concrete is becoming more widely used in flooring, countertops and other parts of the home, and Expo visitors certainly were interested in learning more about its durability, good looks and nearly limitless design options. (At one point, our small planters were so popular, we had to go back into production to make more!)
Of course, we were very excited to see our beautiful pieces of art. But honestly, the opportunity to educate people about the beauty, simplicity and versatility of decorative concrete – that was why we attended the Expo. That was the real mission we assigned ourselves.
Based on your overwhelming response, I can only say this.
Mission accomplished.
See us at the Garden Show - A sure cure for Cabin Fever!
Shopping for new countertops? Seeking unique ideas for paving that outdoor area? Longing for a dramatic change to that kitchen or foyer? Come out and see us at the 2014 Pennsylvania Garden Expo, to be held Friday through Sunday, February 21-23 at the Pennsylvania Farm Show Complex in Harrisburg.
We'll be in booths 812 and 814, just down the aisle from the second entrance to the show, which is the largest and longest-running event of its kind in Central Pennsylvania. The annual expo features vendors, presentations and ideas from flowers to fencing, bollards to bricks and nearly anything else you can imagine involving horticulture, interior and exterior decorating, and more.
What a great time to check out what we have to offer you at SunWorks, etc. Decorative concrete is becoming more widely used in flooring, countertops and other parts of the home as consumers discover its durability, good looks and nearly limitless design options. We'll have experts on hand who can discuss your particular project and provide ideas and helpful advice.
The garden show features nearly 200 vendors, outdoor living displays, classes and hands-on workshops. Whether your project is a small, do-it-yourself task or a complete home remodeling, landscape architects and other experts will be there to answer your questions.
Show hours are 10 a.m. to 8 p.m. Friday and Saturday, and 10 a.m. to 5 p.m. Sunday. You can purchase tickets online for $10 each on the show's website, www.pagardenexpo.org. Tickets will be $13 at the door. For more information about SunWorks, etc., visit our website at www.sunworksetc.com.


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Nice Needs No Filter – Pink Shirt Day 2018
This year's shirt says it all – Nice Needs No Filter.
Pink Shirt Day, now a global movement, was started back in 2007 by two boys attending a Nova Scotia high school. After witnessing the bullying of a new student for wearing a pink shirt to school, the boys rallied dozens of classmates to wear pink in solidarity of the bullied student. The movement has gained traction over the years, with worldwide support and participation. Last year alone, people in almost 180 countries shared their support of Pink Shirt Day through social media posts and donations.
The focus for this years movement is Cyberbullying, something that we are no stranger to here at TransLink. Sadly, online bullying can come in many forms, from spreading rumours, threats, and just overall harassment. This year, we rallied our troops internally to show our support of anti-bullying. We stand with Pink Shirt Day and encourage others to choose kindness first, and encourage those online to combat cyberbullying by thinking twice before posting something negative and remembering that Nice Needs No Filter. Read more »


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A weighted sensory blanket engineered to be 10% of your body weight to naturally reduce stress and increase relaxation.
- The weighted inner layer and the duvet cover are sold separately.
- 100% Cotton fabric, breathable and more natural, was sewn into small pieces which will make sure the pellets evenly distributed throughout of the blanket.
- Weighted Idea blanket(48"x78", 15 lbs) is suitable for 100-150 lbs or 55"-85" height person.
- Filled with safe, Non-toxic Hypo-allergenic plastic poly pellets for weight, engineered to be 10% of your body weight to naturally reduce stress and increase relaxation.
- Each of our blanket is well made with our own factory, which gives you the best quality at the good price. Any questions, please feel free to contact us before or after sale. We will do our best to satisfy you. In the meantime, we provide a service of unconditional refunding or changing the item within 30 days since the receipt of it. Finally, wish you are happy and healthy every day!


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Barter economy FTW!!
I have two Bokashi bins, which I fill about every six weeks, and I love them. I think they're great for inner city living...until you have to empty them every six weeks.
I have got a kind of (dying and waiting for replanting in Spring) garden out the back, but I really don't have enough room for burying the Bokashi compost. What to do, what to do?
I went into the Watershed a few months ago to find out if there was a compost sharing community or something around Newtown, and there didn't seem to be one running. However, one of the women working at the Watershed offered to take the compost off my hands for her garden. I jumped at the chance and she came and picked up that lot soon afterwards.
This week I had reached the limit of fullness in the bins, and she was happy to come around again to pick up the compost, and she offered to give me some gifts from her garden. To my surprise and joy, this bounty greeted me when I got home this evening:
There are little hot chillies (which I used in tonight's iteration of Spicy Lentil Soup)
A green and gorgeous tangle of herbs, including coriander (already consumed tonight!), basil, oregano and mint
I'm assuming these are Asian greens - they look shiny and well tasty!
A beautiful big bunch of rhubarb - I'm going to make breakfast rhubarb crumble with this! Yum!
And finally plump purple wondrous smelling lavender - I'm drying this out and will put it into my clothes drawer, mmmmm!
I'm feeling very blessed and lucky at the moment - some wonderful things are happening in my life - and finding these gifts on my doorstep today really gave me a joyful feeling of community, and that is a wonderful way to feel!!


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This elegant building, Real Gabinete Português de Leitura, is home to the largest and most valuable Portuguese literature collection outside of Portugal. Constructed between 1880 and 1887, it holds more than 350,000 volumes, bringing together rare books from the 16th, 17th and 18th centuries. Its incredible architectural beauty and its rich collection transport the visitor back to the 19th century. The reading room was built in a 'neomanuelino' style that evokes the exuberant Gothic Renaissance style from the Portuguese Discovery period. The façade, inspired by the Jeronimos Monastery in Lisbon, was carved in limestone in Lisbon and brought to Rio by ship. The statues and medallions sculptured in the entrance portray distinguished Portuguese men, including Pedro Álvares Cabral, Luís de Camões and Vasco da Gama, as the eternal guardians of human knowledge and discovery.
Real Gabinete Português de Leitura, Rua Luís de Camões 30, Centro, Rio de Janeiro, Brazil, +55 21 2221 3138
This museum is located in the Niterói, and was designed by the architect Oscar Niemeyer in 1996. The MAC has become one of most iconic monuments of the city due to the boldness of its contemporary features, which make it resemble a chalice or a flying saucer. The MAC Niterói presents bare concrete in a round, smooth and futuristic shape. Located on top of Boa Viagem Lookout, on Niterói's seafront, the museum enables visitors to enjoy panoramic views from the courtyard, as well as from the inside, through its huge glass windows that divide the building into two strips. MAC Niterói primarily displays contemporary artworks, and has the second largest collection of contemporary art in Brazil.
MAC Niterói, Mirante da Boa Viagem, S/N, Boa Viagem, Niterói, Rio de Janeiro, Brazil, +55 21 2620 2400
Opening in 1909, this theater is now the leading playhouse in Brazil, and is one of the most important in South America. The Teatro Municipal hosts all the major international and Brazilian artists, from dancers to musicians. Its architecture and decoration is impressive. The façade features large marble columns and is notable for its stone staircase, stained glass windows and the three domes on the roof. The interior of the theater is as luxurious as the façade. In the entrance hall are two bronze statues that represent dance and poetry. In the foyer, several masterpieces stand out; the three precious stained glass windows that Fuerstein and Fugel created in Stuttgart and the dome painted by Eliseu Visconti. Moreover, the magnificent ceilings, the Venetian mosaic floors and the marble countertops make this building a work of art.
Teatro Municipal do Rio de Janeiro, Praça Marechal Floriano, S/Nº, Centro, Rio de Janeiro, Brazil, +55 21 2332 9191
Built between 1964 and 1979, this cathedral is dedicated to Saint Sebastian, the patron saint of Rio de Janeiro. The main door is composed of 48 bronze plaques with bas-reliefs that cover topics related to faith. The cathedral's beauty lies in its interior, where four vividly colored rectilinear stained glass windows span 64 meters from floor to ceiling over the walls in the four cardinal points. This gives the church beautiful natural lighting and a mystical atmosphere. In the basement, the Sacred Art Museum has a collection of sculptures, murals, artwork, and fonts used to baptize the members of the Portuguese royal family.
Catedral Metropolitana de São Sebastião do Rio de Janeiro, Avenida Republica do Chile, 245, Centro, Rio de Janeiro, Brazil, +55 21 2240 2669
Vista Chinesa is a monument that stands 780 meters high and is located in the Tijuca Forest, at the ascent of the Alto da Boa Vista. Although built in 1903, its name dates back to the nineteenth century, during the reign of D. João VI, when Chinese people who came to cultivate tea in Brazil inhabited the area and finally established themselves in the country. Famous for its oriental style gazebo with spectacular views of the city, it has won an award in China as the best example of a Chinese gazebo outside of the homeland.
Vista Chinesa, Parque Nacional da Tijuca, Estrada da Vista Chinesa, Alto da Boa Vista, Rio de Janeiro, Brazil
Founded in 1590 by monks coming from Bahia in the north, the Benedictine monastery of Rio de Janeiro was built upon the request of the inhabitants of the newly founded city of São Sebastião (which would later become Rio). A fine example of early colonial architecture, this is a place of silence, peace, prayer and work. Here you can enjoy calming Gregorian chants, sung by the monks in Sunday Masses at 10am. In their repertoire are pieces from the fifth to the 12th century, an adaptation of Apassionata Sonata by Beethoven, and an indigenous composition entitled Ave Maria – Maria Atuaximbagê, from a tribe located in the Xingu Park and adapted by Don Placido Lopes de Oliveira, musical director of the choir.
Mosteiro de São Bento, Rua Dom Gerardo, 68, Centro, Rio de Janeiro, Brazil, +55 21 2206 8100
This gorgeous confectionery was founded in 1894 and is part of the historical and artistic heritage of Rio de Janeiro due to its long-standing presence, architecture and decoration. A portrait of the belle époque in Rio, the Confeitaria Colombo still retains much of the art nouveau style of the early 20th century. Its glamorous salons, with Belgian crystal mirrors, frames, rosewood showcases and Italian marble counter-tops, all remain intact. The place has a glorious past, having been a meeting point for intellectuals, poets, artists, politicians and heads of state, such as King Albert of Belgium in 1922 and Queen Elizabeth II of England in 1968.
Confeitaria Colombo, Rua Gonçalves Dias, 32, Centro, Rio de Janeiro, Brazil, +55 21 2505 1500
This building is the first church that was built in Rio de Janeiro, and dates back to 1630. It went through a series of reforms to reach its current state in 1898. It was built on the site of a chapel, founded in 1610 by Antônio de Palmas and his wife as a means of showing gratitude to God for having survived a shipwreck. The neoclassical interior is covered in marble and features colorful stained glass windows, stunning paintings that are distributed on the roof of the aisles and the dome, and doors richly worked in cast bronze.
Igreja Nossa Senhora de Candelária, Praça Pio X, S/N°, Centro, Rio de Janeiro, Brazil, +55 21 2233 2324
This museum, dedicated to fine arts, opened in 1938 and was built to house artworks brought by D. João VI of Portugal in 1808. It currently houses over 16,000 pieces and is one of the most important cultural institutions in Brazil, being particularly abundant in 19th century paintings and sculptures. The main façade is inspired by the French Renaissance, with gables, colonnades and terracotta reliefs representing the great civilizations of times gone by. The rear façade is a perfect example of neoclassicism, with ornamental reliefs crafted by Edward Cadwell Spruce. Materials such as marble and mosaics, plaster, crystals and French pottery were used for its interior decor.
Museu de Belas Artes in Rio de Janeiro, Av. Rio Branco, 199, Centro, Rio de Janeiro, Brazil, +55 21 2219 8474
The Palácio do Catete was built in 1858 and is a prime example of neoclassical architecture in Brazil. It has a pink granite and marble façade and portals framed by white marble. Bronze eagles feature on the front of the building. Inside, the hall's main feature is a sequence of six marble columns leading to the main staircase. The rooms exhibit antique French and Brazilian furniture, numerous paintings on the walls and ceiling, as well as sculptures, chandeliers and porcelain from the 19th and 20th centuries. The Palácio do Catete is part of a magnificently landscaped park with reflecting pools, lakes, caves and bridges.
Palácio do Catete, Rua do Catete, 153, Catete, Rio de Janeiro, Brazil