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Key Details
Property Type: Single Family Home
Purchase Type: For Sale
ListingStatus: Active
Price per Sqft: $148
Lot Size: 0.276 Acres
Year Built: 2000
MLS Listing ID: 1337832
Financing: Cash,Conventional,FHA,Texas Vet,VA
Subdivision: Berry Creek Sec 11 Ph 03
Full Baths: 2
Half Baths: 1
Special Sale: None
Construction Status: Resale
Property Description
NO HOA but monthly Mandatory Deed Fee of apprx $160 applies to club memberships. One story home with ENORMOUS family room, completely open to the spacious island kitchen. Private office is perfect to work from home. Over-sized garage will hold your golf cart. Wall of windows across the back of the home brings in tremendous light and provides lovely views across the patio and yard and private land behind you. Large private master suite with luxurious master bath and huge closet.
State: TX
County: Williamson
Community: Georgetown
Area: Gtw
Direction: I35 to Hwy 195. West on Berry Creek Drive , through entrance to Berry Creek Country Club, stay on Berry Creek Drive. Right on Champions Drive. House is on the Left.
Region: Georgetown
Dining Room: Breakfast Area,Formal Dining Room
Num of Dining: 2
Num of Living: 2
Kitchen: Breakfast Area,Breakfast Bar,Center Island,Granite/Marble Counters,Open to Family Room
Master Description: Double Vanity,Garden Tub,Separate Shower,Walk-In Closet
Main Level Bedrooms: 3
Dining Room: Breakfast Area,Formal Dining Room
Kitchen: Breakfast Area,Breakfast Bar,Center Island,Granite/Marble Counters,Open to Family Room
Interior Features: Built-in Book Cases,Ceiling-High,French Doors,Indoor Utilities,In-Law Plan,Smoke Detector,Walk-In Closet,Window Treatments
Laundry: Dryer Connection - Electric,Utility/Laundry Room,Washer Connections
Heating: Central Heat
Cooling: Central Air
Flooring: Carpet,Tile - Hard
Fireplaces Number: 1
Fireplaces Type: Family Room
Steps: No Exterior Steps,No Interior Steps
Appliance: Built-In Oven(s),Cook Top Electric,Dishwasher,Disposal,Microwave Oven,Single Oven
Master on Main: Yes
Exterior Feature: Gutters Partial,Patio-Uncovered
Fence: Wood,Wrought Iron
Utilities Available: Electricity on Property
Amenities Available: Club House,Golf Course Private,Pool-Community
View: Woods
Roof Type: Composition Shingle
Lot Description: Interior,Level
Building Description: All Sides Masonry
Faces: North
Story: 1
Unit Features: Single level Floor Plan
Foundation: Slab
Sewer: City on Property
Water: City
Elementary Schools: Raye Mccoy
Middle Schools: Charles A Forbes
High Schools: Georgetown
School District: Georgetown Isd
Restrictions: Deed Restrictions
Tax Amount: $8,659
Tax Year: 2019
Tax ID: 2013001103C028
SqFt Source: Tax Record
Tax Rate: 2.28803
Restrictions: Deed Restrictions
Listing Provided By RE/MAX 1
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Lot 6697 (Sandafayre #5298, 22nd October 2019)
INDIAN FEUDATORY STATES - SIRMOOR 1894-99. ATTRACTIVE COLLECTION with a degree of specialization, includes many perforation variants & shades. We see a perf 15 x 15 "Indian Elephant" complete fine mint set (SG 22/29) with additional shades of 1 anna blue & 2a rose, used examples of 3p, 6p, 1a, 2a, 8a & 1 rupee, perf 15 x 14½ mint 2a, 3a, 4a & 8a, used 3p & 2a, perf 14½ x 15 mint 3p, 6p, 1a, 4a & 8a, used 3a, 4a & 8a, perf 14½ x 14½ set mint (less 6p) & used 3p, 6p, 1a, 2a, 3a & 1 rupee, perf 14 x 14 mint 3p, 6p & 1a, used 3p, compound perf mint 3p & 6p, a selection or re-entries, 1899 Raja set mint and again used. A delightful semi specialized collection. (60+ stamps)
Time left to bid: 7 days, 4 hours and 38 minutes
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IN OUR MAIL BID SALES (Sandafayre, Hunters, Kwik-Bid and Express) You can bid directly from each lot, simply add your maximum bid into the "Bid" field and decide if you want to add a bid boost percentage in case you are being beaten and then click "Place Bid". Your current bids can be found from the drop-down menu beneath your name at the top of the screen.
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IN OUR PUBLIC AUCTION (Cheshire Stamp Auctions, once every 3 months) you can leave bids for our auctioneer to manage on your behalf (traditionally called "Commissions Bids") by bidding from this website up to 30 minutes before the public auction begins (please remember, our buyers premium is 20% which is higher than in our Mail Bid Sales). You can also watch the auction and bid live online from our bidding platform which goes live 30 minutes before the auction but please make sure you are registered and logged in. After 30 minutes before the auction the option to make bids will be suspended and instead you will be enabled to view the live auction and bid if you wish. It doesn't take 5 minutes to get registered with us, just go to the "My Account" link at the top of the screen > "Sign in / Register" > "Create My Account". Unlike most auctions we do not charge any additional fee for online bidding.
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Auction: Sandafayre #5298, 22nd October 2019
Highlights from our 5298 auction include:
Plus hundreds of Commonwealth lots, Great Britain lots, European lots – All countries in the world from Aden to Zululand! There are also some great sorter lots and collections.
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SANTA CLARA, Cuba — Fidel Castro and Hugo Chávez faced each other on giant posters above the boxing rings at Amistad Arena, suggesting a friendly round of socialist sparring between eternal comrades.
A third presidential aura hovered over the Cuban national championships during the weekend — that of President Obama, who has ordered the restoration of diplomatic relations between Cuba and the United States.
The prospect of better ties between the countries, not to mention future Olympic medals, created an optimistic mood as Cuba's top fighters were escorted to the ring by women in short skirts and high heels and the booming stadium anthem "We Will Rock You."
"Not only sports, but almost everything in life is going to be better," said Julio César la Cruz, 25, a two-time world light-heavyweight champion, whose sentiment was repeated often here among boxers and officials.
In sporting terms, much more is in play in Cuba than the possibility of its terrific baseball players gaining unrestricted access to the major leagues.
Cuba is seeking to maintain its pre-eminence as a regional athletic power despite decades of erosion caused by the American trade embargo and the collapse of the Soviet Union and the Eastern bloc, formerly the island nation's primary sporting benefactors.
The 15 medals won by Cuba at the 2012 London Olympics were its fewest at a Summer Games since 1976 (not counting the 1984 and 1988 events, which it boycotted). Its stadiums are decaying, and some equipment is sorely lacking, something officials attributed to an inability to buy on credit.
Seeking much-needed hard currency, and to dam a flood of defections by elite athletes over the years, Cuba has also embraced a concept that was once anathema to its revolutionary ideal: professional sports, barred by Castro in 1961.
Today, Cuba's top Olympic-caliber fighters can earn $8,000 to $12,000 in a month, according to the president of the country's boxing federation.
"If it was possible to go to the U.S. to train and compete and come back freely, I think 100 percent of the Cuban team would come back," said Robeisy Ramírez, the 2012 Olympic flyweight champion, who turned 21 Saturday.
The United States also has its reasons to facilitate athletic relations with Cuba. For one thing, the United States Olympic Committee plans to bid for the 2024 Summer Games and will be seeking as many friends as possible to bolster an American city's chances.
Coaches at American universities have also begun to consider the potential of reciprocal trips to train and compete in Cuba. They may also offer athletic scholarships to Cuban athletes in sports like track and field, wrestling and baseball.
"Any time we get a young person in the country for educational purposes, it can't hurt relations," said Pat Henry, a prominent track and field coach at Texas A&M who has won 35 indoor and outdoor N.C.A.A. titles there and at Louisiana State. "That's the way you effect change."
In Olympic-related sports like boxing, wrestling, and track and field, and to a lesser extent soccer, elite athletes from the United States and Cuba already compete and travel regularly between the two countries. These exchanges seem certain to increase. And in sports in which Cuba has an advantage, American officials will no doubt seek to import Cuban coaches and expertise.
About 1,500 Cuban coaches are working in more than 70 countries, in effect rented out for cold cash.
"I've tried to get one of their top coaches and athletes here as one of my assistants for years," said Steve Fraser, a 1984 Olympic champion in Greco-Roman wrestling and the head coach of the national team for 18 years, who is now the chief fund-raiser for USA Wrestling. "It has been impossible. I'm hoping that will loosen up."
Efforts underway by the United States Commerce Department to lift export barriers on construction and sports equipment will be welcomed in Cuba. At some provincial stadiums in the Cuban baseball league, balls can become so scarce that games stop while children retrieve home runs and fouls and return them to the umpires, said Robert Huish, an assistant professor of international development studies at Dalhousie University in Halifax, Nova Scotia, who studies Cuban sports.
Rain can leave the wrestling mats soaked at the Greco-Roman training center, said Fraser, who travels here yearly. When the United States played a soccer match in Havana in 2008 while qualifying for the 2010 World Cup, a downpour left the field looking "like a cow pasture," said Don Garber, the commissioner of Major League Soccer.
"Sport is the victim of limitations of the embargo," said Tomás Herrera Martínez, the director of international relations for Cuba's sports ministry and a bronze medalist in basketball at the 1972 Munich Olympics. "Sport is one of the main rights of the people, but sometimes there have not been enough resources."
Baseball is Cuba's most popular sport, but it has been dropped for now from the Olympics. Boxing, with its numerous weight classes, has long been the country's most reliable producer of gold medals; Cuba has won 34.
Teófilo Stevenson, a heavyweight who won three golds from 1972 to 1980, once gave a short and loyal explanation about why he would not leave Cuba for the riches of professional boxing.
"What is a million dollars worth compared to the love of eight million Cubans?" said Stevenson, who died in 2012.
International isolation and the disappearance of mandatory amateurism from the Olympics have given Cuba a more pragmatic approach to professionalism.
Last year, Cuban officials announced that athletes could turn professional and compete in foreign leagues. They keep 80 percent of their earnings, officials said. In exchange, the athletes agree to compete for Cuba in important domestic and international competitions.
Frederich Cepeda, an aging outfielder, signed a $1.5 million contract in April with the Yomiuri Giants of Japan with mixed results. He batted .194 in 52 games and finished the most recent season on the club's farm team.
In June, another Cuban outfielder, Alfredo Despaigne, was permanently barred from playing in the Mexican League for using a false Dominican passport for reasons that were not clearly explained.
The same month, though, Cuba won a country-versus-country competition called the World Series of Boxing, which brought a first-place prize of $500,000. The share for Ramírez, the Olympic champion, was a $5,000 bonus, and $400 more for each victory in the tournament, his mother said.
As an Olympic gold medalist, Cuban officials said, Ramírez is entitled to $300 a month for life. (The average monthly salary in Cuba is about $20.) He has also been provided with a home and a car, a white Chinese-made model that sat in the parking lot at the championships.
With Ramírez's earnings, including a minimum of $1,000 a month for being a part of the national team, he said, he bought a television and a refrigerator for his mother and lavished attention on his year-old daughter.
"The way of life is better," Ramírez said. "It helps so much."
Asked if increased pay seemed to have made Cuba's boxers less likely to defect, Alberto Puig, the president of Cuba's boxing federation, smiled and said: "It's true. They have a good life."
Ramírez, who will seek to repeat as Olympic champion at the 2016 Games in Rio de Janeiro, has yet to visit the United States. There are three places he would like to visit, he said, listing Miami first, then New York and Las Vegas.
Vegas, of course.
"A great boxing town," Ramírez said.


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Coroner Officially Releases Identity of Homeless Man Killed by LAPD
Coroner's officials on Thursday released the identity of a homeless man who was shot and killed by Los Angeles police officers Sunday on skid row.
Charley Leundeu Keunang, 43, had been living under a stolen identity belonging to a French man, said Ed Winter, spokesman of the Los Angeles County coroner's office. Authorities believed he was a Cameroonian.
But coroner's investigators finally obtained his true identity from federal investigators and were able to track down his family, who are living on the East Coast, he said. They positively identified him.
"It was tough … We tracked him though," Winter said.
Click here to read the full story at LATimes.com.


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Our maids will strive to provide excellent service on every visit. See below for basic services offered. For special needs or customized cleaning services, please contact us.
All Rooms
- Dust - Furniture, shelves, light dusting of blinds and shutters, windows, ceiling fans and decor
- No more Cobwebs - Your maids will remove them all in each room
- Floors - Vacuum/Mop all floors, carpets, rugs and stairs
- Glass - Dust and Clean all glass surfaces
- Trash - Empty trash in all rooms
- Handles - Clean and disinfect all knobs and door handles, switches and outlets.
- Stairs & Hallways - Sweep, mop & vacuum stairs, hallways, entrance and rails
- Beds - Change Linens, make beds. Dust under the beds if possible.
- Walls & Baseboard - Attempt to remove visible stains. Dust all baseboards.
- Doors & Doorways - Dust all doors and doorways. Attempt to remove any visible stains.
- Ceiling Fans - Dust all reachable ceiling fans
- Windows & Blinds - Lightly dust windows and blinds
- Appliances - Clean, dry and shine all exteriors
- Sink - Clean, scrub and sanitize. Wash dishes.
- Stove - Clean stove drip pans, burner grates, and control knobs.
- Counter Tops - Wash and sanitize countertops\
- Cabinets - Wipe cabinets fronts, leave a light polish
- Microwave - Clean microwave oven inside and out, including turntable
- Refrigerator - Clean, dry and shine exterior. Clean most magnets on fridge.
- Sink & Counter Top - Clean, dry and shine all exteriors
- Shower & Tub - Clean, scrub and sanitize. Wash dishes.
- Toilets - Clean stove drip pans, burner grates, and control knobs.
- Mirrors & Fixtures - Wash and sanitize countertops
- Cabinets - Wipe cabinets fronts, leave a light polish
Additional Items
Your Checklist: Every customer has different needs. That is why with Friendly Maids you have the freedom to customize your service to fit your individual needs. At the time of your booking, please let our office know what items you'd like done by your maid. If there is anything not listed, just add it.
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Prediction Houston FC - Brazos Valley Cavalry
Houston FC VS Brazos Valley Cavalry
United States Usl League Two
Date match: 07/09/2019 Tuesday
United States Usl League Two
Date match: 07/09/2019 Tuesday
Under you found the prediction processed by our proprietary software and reviewed manually by our editors of the football match Houston FC-Brazos Valley Cavalry, match of the championship United States Usl League Two. Even stats, standings, news and information on the football league United States Usl League Two and on teams Houston FC and Brazos Valley Cavalry.The prediction 1x2 or under/over or goal/nogoal, with odds of bookmakers comes complete with the correct score. With this, we always try to provide gratis all the tools you need to bet responsibly and we hope winning!
Prediction Houston FC-Brazos Valley Cavalry: 2 (Odd )
Prediction Gol/NoGol Houston FC-Brazos Valley Cavalry: NoGol
Prediction Under/Over 2.5gol Houston FC-Brazos Valley Cavalry: Over (Odd )
Prediction correct score: 0 - 4
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|07/09/2019 Houston FC - Brazos Valley Cavalry 0-3 (United States Usl League Two)
06/21/2019 Brazos Valley Cavalry - Houston FC 4-0 (United States Usl League Two)


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Born in London, UK to Zimbabwean and English parents, Stephen studied the violin and piano at the Guildhall School of Music and Drama, and film composition with Amit Sen. Stephen began his professional music career with the Reggae Philharmonic Orchestra and has since earned an enviable reputation playing, arranging, orchestrating and conducting successful and ground-breaking projects both in the UK and internationally.
During Stephen's career, he has enjoyed collaborating with many of the industry's finest artist's, lending his skills to the creation of many iconic recordings and award-winning projects. His dynamic combination of skills and experience has been an invaluable contribution to the creative process of many prestigious producers and artists including Nitin Sawhney, Maxi Priest, Robert Miles, Mick Jagger, Annie Lennox, Take That and The Script.
Stephen specialises in music projects that bridge different genres and cultures. His unique heritage heralds a deep understanding and empathy of a diverse range of musical styles. Stephen is the Founding member, Director and Lead violinist of the Urban Soul Orchestra.
Classic Ibiza concert at Capesthorne Hall, Cheshire, Saturday 29th June 2019
Classic Ibiza concert at Ragley Hall, Warwickshire, Saturday 6th July 2019 SOLD OUT
Classic Ibiza concert at Weston Park, Shropshire, Saturday 13th July 2019
Classic Ibiza concert at Harewood House, West Yorkshire, Saturday 20th July 2019
Classic Ibiza concert at Bowood House, Wiltshire, Saturday 3rd August 2019 SOLD OUT
Classic Ibiza concert at Blickling Estate, Norfolk, Friday 9th August 2019
Classic Ibiza concert at Windsor, Berkshire, Saturday 10th August 2019 (Summertime Live)
Classic Ibiza concert at Lingfield Park Racecourse, Friday 16th August 2019 (Summertime Live)
Classic Ibiza concert at Hatfield House, Herts, Saturday 1st September 2019
Classic Ibiza concert at Brighton Racecourse, Saturday 7th September 2019 (Summertime Live)
Classic Ibiza concert at Hoglands Park, Southampton 27th September 2019 (Summertime Live)
For More information and to purchase tickets see here: www.classicibiza.co.uk & www.summertimelive.co.uk


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One Reason Why Kidney Transplants Fail
WEDNESDAY, Aug. 15, 2018 (HealthDay News) — Scottish scientists say they've found new clues to why some kidney transplants fail. It has to do with the amount of "wear and tear" a transplanted kidney has and how that affects its work in the recipient, the new study says. It was known that the age of…Details


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History and overview
The Chilean government ceded a significant parcel of land in downtown Santiago to the municipality, in 1848, and an 1853 decree by President Manuel Montt Torres provided for the construction of a municipal theater in his nation's capital, by then a rapidly-growing city. French Chilean architect Claudio Brunet des Baines was commissioned for its design, and its construction was entrusted to another French Chilean, civil engineer Felipe Charme de l´Isle. Brunet des Baines created a French Neoclassical exterior for the theater, though his 1855 death left the supervision of the design to his countryman, Lucien Henault and to the latter's assistant, Manuel Aldunate. The new team also benefited from a collaboration with Charles Garnier, the architect of the Opéra National de Paris.
The Municipal Theater was inaugurated in September 17, 1857, with the opera Ernani by Giuseppe Verdi, performed by an Italian company brought in specially for the occasion. The theater, at the time, had a capacity for 1,800 spectators, and included distinctive interior details such as a teardrop crystal chandelier. A December 8, 1870, performance by opera deva Carola Patti was followed by a massive fire, however, that practically destroyed the building. A quick response by both the local government and Chilean high society resulted in the theater's prompt reconstruction, designed by Henault and completed on July 16, 1873. Its reinauguration was accompanied by a performance of Verdi's La forza del destino.
The theater went through a devastating 1906 earthquake, suffering the loss of most of its interior, and a second, serious fire in 1927 - though it recovered quickly on both occasions. Following these reconstructions, the theater's capacity would be of 1,500 spectators (in the main hall), though its interior became more opulent. It was modernized further in 1952 and 1959, and numerous cultural institutions were created for the theater during that era. The Symphony Orchestra was established in 1955, the Cultural Corporation of Santiago was formed to administer the center in 1957, the Santiago Ballet in 1959, and the Philharmonic Chorus, in 1962.
The Municipal Theater was declared a National Monument, in 1974. Renowned Chilean pianist Claudio Arrau, who had left his homeland in 1941, returned for a visit in 1984, on which occasion the Claudio Arrau Salon, seating 250 spectators, was inaugurated. The stage curtain, installed in 1926, was replaced in 1995 with funds raised by offering donors a piece of the older curtain as a keepsake. The institution continues to maintain an active repertoire, and some of its most illustrious recent international guest performers and conductors have included: names in ballet such as Julio Bocca, Mikhail Baryshnikov, the Bolshoi Ballet and the Mariinsky Ballet; pianists Claudio Arrau and Arthur Rubinstein, as well as conductors Vladimir Ashkenazy and Daniel Barenboim; violinists Mischa Elman, Jascha Heifetz, Yehudi Menuhin, Gil Shaham and Isaac Stern; and stage performers such as Plácido Domingo, Dame Kiri Te Kanawa, Vivien Leigh, Luciano Pavarotti and Tito Schipa.
Its Music Director is currently Jan Latham-Koenig, a British conductor who has led numerous European orchestras and Opera companies.


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Wedding caterers have an important role to play—making sure the food and drink are top notch on your big day! Whether you'd prefer a casual buffet-style meal or a formal plated dinner, wedding caterers will create a delicious menu your guests won't soon forget. Be sure to read reviews on WeddingWire of wedding caterers in Peoria before booking!
For exceptional catering services for your Phoenix-area wedding, trust the experienced wedding caterers of Classic Catering. With over 30 years of catering experience in the Valley of the Sun and New York, Quality has been our reputation since 1982. Each of our menus is carefully crafted by experts... (Wedding Caterers Peoria)
Let us take the worry out of planning your event. We are the Top Quality Bar Catering service in the valley. It is all we do and you can expect exceptional service and attention. Our bartenders arrive one and a half hours prior to the event start time to ensure all is ready to go. Our staff is... (Wedding Caterers Peoria)
We bring our Mobile Wood Fired Pizza Oven to your location. Please visit our website at intothefirepizza.com for additional information and to view our menu. Using our own fresh made pizza dough, we will prepare, cook onsite, and serve the pizzas buffet style so your guests can savor the different... (Wedding Caterers Peoria)
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Associate Creative Director
Nothing is more fun than meeting someone who is where you want to be in life.
Nothing is more fun than meeting someone who is where you want to be in life. I had the opportunity to meet Bryan Sedey the Associate Creative Director of the company C3. There they design toys, family, and kid programs for the hospitality and restaurant industry; such as Arby's, Sonic, Raising Canes, and more. In the following interview Mr. Sedey gives us a peek at who he is and shares some of the best advice I have heard for any creative working in the industry.
Bryan was twenty-seven when he started college at Johnson County. Before he was living in Dallas, Texas with a career as a traveling musician for fifteen years. "I played bass in a harder rock band called The Feds. So, I was on the road quite a lot and recording albums. We'd done the U.K. and the majority of the U.S.," Bryan said in the interview.
I just knew how to draw, I had done it since I was a little kid.
Kat Foster: Did you know what you wanted to do when you started school?Bryan Sedey: Yes. Our band's manager owned a design company that catered to the music industry in Dallas, where I lived. He gave me a job as an intern. I was doodling at work one day and he learned that I could illustrate. So, he put me on a limited edition silk screen poster project where I illustrated this big pink gorilla with Baby New Year sitting on his hand screaming. But, I didn't know any typography at that time or anything, I just knew how to draw, I had done it since I was a little kid. I got to see first-hand some of the stuff that they put out. I mean, it's kind of a dream. I realized that I wanted to do what my boss was doing. Not being an intern who just filled print orders and answered the phones. Luckily, I got enough exposure that I when I got tired of the touring life I thought 'now is the perfect time to go for an education in design and see what happens from there'.
KF: Why Johnson County Community College?
BS: I'm from here, originally. Johnson County was the first college that popped into my mind when I was thinking about moving back here; there really was no rhyme or reason. It turned out they had this incredible program that competes with other great schools, so I lucked out there. But, when I started I was poised to do very well, it wasn't the kind of thing where I guessed myself into the program. It was very, very clearly what I wanted to do. KF: What are qualities of a good designer? BS: Maybe not so much what qualities, but what the best practices are. Working in a team is a must. Being able to communicate and hold your own in a team meeting. Know how much to contribute and when it's time to get in there. Being dependable is a huge thing. Someone who is not married to their work and can take constructive criticism or even take negative criticism and turn that into a positive outcome is a real asset. Use the criticism and your team involvement to your benefit and make it better.
KF: What is an average workday like? Is there an average workday? That's a better question!
BS: I wouldn't say there is. In my experience where I work, an average day is busy. That's about as boring an answer as I can give you. But, the diversity of the stuff you are working on at a place like C3 is huge. One day you are developing for an app or you are designing a character set, sometimes you are coming up with games, other times it is all brainstorming together as a group to come up with ideas. At times you have to put on your headphones, find a quiet spot in the building and go to town and not be interrupted. If the juices are not flowing and you can't get past a block of some sort, you just have to get out of the building and go outside to work. Go to a coffee shop, a museum, or get inspiration from the field in a store or someplace relative to what you are doing. One great thing about C3 and probably a lot of creative companies is that they want to get the best work out of their people and know that the creative process is not always contrived. You know what I mean? There is a little more mystery to it.
KF: Do you have a dream job or client?
BS: Kind of what I'm doing is my dream job. I love doing what I'm doing. I think a dream client, the easy answer would be a client that respects and values your expertise. That doesn't mean a client who just lets you do whatever you want, it means one who will engage in valuable conversation about what you are doing and respect your expertise in it, and their feedback is constructive and useful. Sometimes you can get pigeon-holed in a project, but it is really nice to work for clients that go "We want to let you dream as big as you possibly can." That's kind of the most fun, I think, when they let you get super creative.
KF: Do you have a favorite or most memorable project or client?
BS: A few years ago I used to work at Brockton Creative Group and one of our clients was Allegiant Air. They needed a pocket folder to give to investors or to potential partners. It was one of those projects where they said, "Run with it, go! Be creative!" The only stipulation was that it was an outside, heavy stock folder with two pockets and room for a business card. So, we were able to develop a pocket folder that ended up looking exactly like a piece of luggage. They loved it and we were able to produce it. It was a really fun and probably my first big, larger scale, passion project. It's not the quantity, it's just the polish on it that someone was willing to spend the money on that to produce that and let us be who we really are with it, which is zany and weird and fun, and it totally reflected in the end product. It's something I will always be proud of. So, thank you Allegiant, because it was so cool they were so open to it.
KF: How do you work with difficult clients?
BS: I would say the best answer I could give you to that is you have to be able to efficiently communicate your idea to a difficult client. I think sometimes the difficulty may be a lack of understanding where you are coming from. When you use the term communication design, it didn't make a lick of sense to me in college, but it makes sense now, because all we are doing is communicating. Most importantly, it's knowing how to speak to their customers because, really, that's the bottom line. They want to be able to communicate with their customers. That is what they are relying on you to do. So, if you can have the research and the foresight of who they are speaking to, it is a lot easier to sell your vision to a client who has those peoples' personalities in mind.


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Report a security vulnerability to Code42
Who is this article for?
CrashPlan for Small Business, yes.
Code42 for Enterprise, yes.
Link: Product plans and features.
Code42 investigates all reports of security vulnerabilities affecting Code42 products and services. If you believe you've found a Code42 security vulnerability, we'd like to work with you to investigate it.
The Code42 security team does not provide technical support. If you need help with something other than reporting a potential security vulnerability, contact our Customer Champions for Code42 for Enterprise support or CrashPlan for Small Business support.
Information to include
To help us better understand the nature and scope of the potential vulnerability, include as much of the following information as possible:
- Type of issue (buffer overflow, SQL injection, cross-site scripting, etc.)
- Product and version that contains the issue
- Any special configuration required to reproduce the issue
- Step-by-step instructions to reproduce the issue on a fresh install
- Proof-of-concept or exploit code
- Impact of the issue, including how an attacker could exploit the issue
How to contact us
To report a potential security vulnerability, email us at firstname.lastname@example.com.
We recommend that you encrypt your message with our PGP key. To view and copy our public key, expand the following section.
PGP key
-----BEGIN PGP PUBLIC KEY BLOCK----- Version: GnuPG v2 mQENBFwvjOABCACbMCul+1FZiLZ+ugwzwCy4DvQFzbh4RxoGPMAh5JYqPBXT0VMA iF9itJwbMNPMAP0j/IlarbCqTpnAs/1pupIqn8Ex5LWPHxkMATJxeSsp5CUeTv9u 4yL+MDdTBIe19lHZ1aJzqwnM/h9/7Jvtx2K6PrNCIGNU6JjJOwqwc48+OAd/KOUg GyPekXxOoSD3N3W85p4fxZdBy5HjIYumjLFNOS1AJu35aVL/yDEMP0WrnTNB2qD1 h5MB54btuj4CdhM5Q1Rcz+vjeYK10nTge4gtTqLyL0DIZ2d1VorCP8nxkz51bwmi C9MmVYNuF/KiFzjx3D7XzJ3nLkXAignOC+13ABEBAAG0HUNvZGU0MiBCdWdzIDxi dWdzQGNvZGU0Mi5jb20+iQE3BBMBCAAhBQJcL4zgAhsDBQsJCAcCBhUICQoLAgQW AgMBAh4BAheAAAoJEJWOka7v4rbDLEYH/RsFfznbev2LHaVqg8o9/3GawLknMUo+ fWEKDYU4J0kHInFxftIMUxmg4EhFWd0klM0cAFyljUIiETr+EN0v9tAqymy/wskL TPR0UzZRS3zFcUC5fuhIelgHev05vgYl7kfqUgbMhkMj0MxHJpNByqLJveOzJNmk JEm5MVlJwSZT1oa0GugBKbYlbbxnmCmeSB3eiKxk6SUPnpMvUi+HNdO3+kFTnTNv +GGXl40OvPKvAwC5cm1duvezjebKZ8/m/wizR23ixiEYoB37qgSxI7GzpIwkvu/K Krxeg3Zpc6hPVZg7xichGAM5WvEki3CXIxb9iCxQKuB573ncnbLulfi5AQ0EXC+M 4AEIANDfiA1evoC1tKWAC5vxsBe4Nf7fpQ7jSj2q0CQJRECeJFnkXj0u/D8DFIsC 9wN/tmrPOGlAsww3nvNAitYw/UgMufjuU5SHn0mCt6JVjcW2VtVJpjsr59uCfbqR ybJ8EBRrZFH+hDrvcYUICABSlkgtgAHt62MSPkIhnm99L+BxFybzuEtmgy+gvMU9 ieT8JlOBPt59yExTowkgFoi5qa4Zvzm8VmrZOeOnNmh9Arks3kxbRx68NXNW7n0M 4hWFZrSzUHWK6qixhlijkTOHE+2nN3AvolB6evEd1xlhxs4ah/R7lr9k+6axuVnz AV8oF5Fi5e14YtapSnQ0NA2e3CEAEQEAAYkBHwQYAQgACQUCXC+M4AIbDAAKCRCV jpGu7+K2w9eQB/9z6uHm2Z7Irwm0l1EwRxrj1kkEg7zMbwWEiQ70R7V1ulRbl/BM EfxBttqQJCab3Am0coKV6RQ1fCKgkY5zQoemfkCzKomKM6aeYFa8+TpzCcjx8Ars 16GoOorvSTGlLFTtcXFLjg46LkgeKvixnEee1dZysgcDPHe4ph0M1A5uXlz+PemJ /+xtloFox/dQdqbHuWAMlfTjF8LkOQFBrZNXrCNpsr1Jb+kihqDURKZT7Ihm/B5E ejJR7uF4Zt/zyqNd/SuAEMnmLhjDR/rBoui4Ww/4cb/NpUdR0g4shhpHKfIzwAGO qsJBlqr76mv0w2WitncOH8yvr+3WZaFSwYoJ =H//V -----END PGP PUBLIC KEY BLOCK-----
What happens after I contact Code42?
When Code42 receives a vulnerability report, we triage it to determine if we should open a more in-depth investigation.
If we confirm that a report has identified a security vulnerability, Code42 takes the following steps:
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- Once Code42 customers have had time to remedy the security vulnerability, we publish a security advisory to the public in the following locations:
- The Code42 support site: Code42 security advisories
- The Mitre Common Vulnerabilities and Exposures (CVE) list
If you want to be notified when Code42 identifies a security vulnerability, sign up for email notifications.


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Study Group Radio: Process Party explicit
Mark all (un)played …
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Manage series 1281591
By Zack Soto and Study Group Comics. Discovered by Player FM and our community — copyright is owned by the publisher, not Player FM, and audio is streamed directly from their servers. Hit the Subscribe button to track updates in Player FM, or paste the feed URL into other podcast apps.
Study Group Comics has a podcast! Join cartoonists Zack Soto (Secret Voice, Power Button) & Mike Dawson (Rules For Dating My Daughter, Troop 142) as they discuss their own creative processes, comic art, family life, the nuts & bolts of being a working creative, and a ton of other stuff. Each episode finds a new guest from the world of comic books & graphic novels joining Mike & Zack for an in depth conversation, with occasional guest segments from their pals around the world.
264 episodes


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Get extra marks for reading books you enjoy
Their familiarity with the Hogwarts School of Witchcraft and Wizardry or who killed Roger Ackroyd will soon help students gain credit points at school.
As part of its effort to take academics beyond rote learning, the Central Board of Secondary Education (CBSE) will introduce a new reading project that will award points for reading popular fiction. This is expected to encourage students to read books for the fun of it and not because they will be marked for it.
A CBSE circular sent last month asked schools to break free from binding reading to weekly library periods and encourage students to visit the library as and when they want to.
The project will be part of Continuous and Comprehensive Evaluation in 10,000 CBSE-affiliated schools and will require students to read at least one popular writer each term.
Students will be evaluated through innovative methods such as group discussions, creating graphic novels and storytelling. They won't be asked to write book reports as this may make them lose interest altogether.
"We've suggested activities such as literary fests, creating graphic novels, critical evaluation of the plot and interaction with the author," said a CBSE official, unwilling to be named as he isn't authorized to speak to the media. "We believe these will help the child fall in love with reading again."


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I have a 16 year old jack Russell/staffy cross, who is totally blind but very agile and good in the house. She loves a daily walk around the lake and is a wonderful companion. House is 3 bedroom 1930 Californian bungalow. 2 bath. Good back yard with small veggie garden and yard. Lawns are done by maintanence person.
100 metres to walking path on lake, close to shops, train and 15 minutes to beaches.
Sorry, this assignment has been closed.
© 2019 The House Sitters - Privacy


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OSU Prime 2015 — photo 16 of 62: The low angle of the newly-risen sun combined with the rough texture of the stone walls of the recently-renovated Joyce Collin Furman Hall create a dramatic pattern of light and shadow. Oregon State University, February 2015. Camera used: Olympus OM-D E-M5 with Olympus 12mm f/2.0 prime lens.
For further details about the story behind this photo, see the related article Oregon State University Prime.


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Elle magazine collected five women who are satisfied with themselves and their figure.Laysan Utiasheva Anfisa Chekhov, Svetlana Bondarchuk, Jan Lebedev and Natalia Rogozin told how they learned to accept themselves as they are, and how they keep themselves in shape.
Laysan Utiasheva
I love myself any: and lean and plump.Even when I have recovered eight kilograms, I liked everything in itself: the feet and hands, and the ass and breasts.In summer, always wear short dresses - I like to please others.
must be able to keep yourself in shape.Every woman should be something like "the discipline of the body."For example, when walking, I always try to involve themselves in the stomach, and if you sit at work or writing a text, be sure to do warm-up on the calves and thighs.The body immediately comes into shape, and I feel quite differently.I know that my figure is individual and the second such in this world.Never in itself did not refuse - if I want something to eat, I eat, but I know the measure.
Anfisa Chekhov
Every woman should hang himself in his room mirror from floor to ceiling, and every day to look at him over bare.It may seem strange and even cause rejection, but eventually you get used to it and gradually begin to love yourself.[...] All we have in mind.It is not necessary to invent an image, you need to find the courage to be yourself.
I have long been involved in fitness, but then I realized: do not do what you do not like, and began to go to the lessons of choreography.After class, I feel completely different.By the way, for 10 years, as the abandoned jeans and pants and wear only skirts and dresses.
Svetlana Bondarchuk
important for women to be able to care for themselves and accept themselves for what is, rejoice that nature gave you.I have a "comfortable weight," I try to adhere to.I remember a few years ago I went with a friend to rest there and recovered several kilograms.Not to say that it was ugly, just that I was very uncomfortable.
I do several times a week Pilates - they teach feel my body, every muscle, which is very important.Torturing myself diets - not for me.And I really love wearing dresses - they make any woman beautiful.
Yana Lebedeva
need to mind in choosing clothes.There are things that are not obvious to me, and it does not matter that in this case they may be trendy.Also, much depends on the age and skills to present themselves.
I treat myself quite critical, so I try to keep myself in shape.Go swimming, I go for a massage.It helps.I do not understand how you can all the time to diet!For example, I have found for themselves an excellent alternative: a few times a week to arrange fasting days currently.
Natalia Rogozin
Let's just say I'm in harmony with each other.And on some specific parts of the body you should ask the person to whom I'm cute.
I can not afford to relax even for a moment.I had the story, when the pre-fight weigh-in for the first time in my life I was not included in your weight.It was not in me, but in the new fashionable bathing suit that I bought the day before: he had a heavy attachment in the form of rings, which gave the advantage to 200 grams.Swimsuit had to be removed, and everything fell into place: I weighed, as always, exactly 76 kilos and 204 grams.
Photo source: Slava Filippov / Elle
Articles Source: Elle, spletnik.ru


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US troops abandoned equipment and weapons after they came under fire from ISIS fighters, the Pentagon acknowledged Tuesday.
The Pentagon had previously indicated that photos of the military items paraded by ISIS on the Internet this weekend were likely American and lost during recent operations in Afghanistan.
On Tuesday, Brig.-Gen. Charles Cleveland, chief spokesman for the US-led anti-ISIS coalition, said US troops came under "effective enemy fire" in eastern Afghanistan on July 25.
This forced them to abandon their position and led to some of their equipment being captured and displayed in the ISIS photos distributed by ISIS, according to Cleveland.
The photos depict ammunition, fabric packs and possibly a shoulder-fired rocket launcher of the type used by US forces.
US troops, including Special Operations Forces, had been in combat against ISIS in their stronghold in Afghanistan's Nangarhar Province for several days when the incident occurred in July.
Wounded troops had already been moved from the area at the time the equipment was left.
But as a result of the incoming fire, the collection point "was moved to a safer location," in the course of which "some equipment was left behind," Cleveland said in an emailed statement.
"For understandable reasons, the lives of the soldiers were not put at risk to recover the equipment," he continued. "Neither US positions or personnel were overrun."
It is not clear why the US was not able to repel the incoming fire.
For many years, the Taliban have scoured the battlefield for US military gear and weapons, so it's not known for certain what US military unit all the items displayed came from. But a coalition official said that some of the equipment shown "is used" by Special Operations.
The fighting in Nangahar against ISIS has resulted in injuries to several US troops.
Three US soldiers suffered minor wounds in the last few days when an improvised explosive device struck their convoy while they were on patrol near Jalalabad. A NATO Resolute Support mission spokesperson told CNN that the soldiers suffered minor injuries.
In the same group of recently released photos, ISIS displayed the military identification card of US Army specialist Ryan Jay Larson, claiming they had captured him. US commanders were able to quickly determine Ryan had lost his card during the firefight on July 25 but was with his unit at all times.


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Article Text
Aims To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders.
Methods This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed.
Results Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3).
Conclusions Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis.
- IgG4-related disease (IgG4-RD)
- orbital inflammatory disorders (OID)
- IgG4
- IgG2
Statistics from Altmetric.com
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition of unknown aetiology, with consistent histological changes (defined by the IgG4-RD consensus criteria) in different organs and typical clinical and radiological features.1–3 The precise role of IgG4 in this disease is unknown,1–4 and theories suggest that IgG4 may be a biomarker or an epiphenomenon.5–7
During our tertiary ophthalmic pathology practices in the UK and Singapore, we had independently observed serum IgG2 elevation in patients with IgG4-positive biopsies. The primary aim of this study was to determine if significant serum and tissue IgG2 differences existed between orbital IgG4-RD and non-IgG4 orbital inflammatory disorders (OID).
Materials and methods
This is a descriptive retrospective study of 69 cases of orbital biopsies from January 2002 to March 2016 performed with an institutional review board approval from the Royal Hallamshire Hospital, Sheffield, UK, and Singapore General Hospital, Ophthalmic Pathology Service. The H&E slides of these cases were reviewed, and immunohistochemistry (IHC) was performed for tissue IgG, IgG4 and IgG2 plasma cells. The antibodies included IgG (Dako, rabbit polyclonal antibody #IR512, 1:1000), IgG2 (Abcam, Singapore, rabbit monoclonal antibody #EPR4418, 1:2000) and IgG4 (The Binding Site Group, mouse monoclonal antibody #HP6025). Using previously published techniques,8 IHC was performed with single and dual staining for IgG4 (Leica Bond Polymer Refine kit) (diaminobenzidine) and IgG2 (Leica Bond Polymer Refine Red kit alkaline phosphatase chromogen).
Using the 2012 published IgG4-RD histological consensus criteria,3 the presence of storiform fibrosis, lymphoplasmacytic infiltrate and obliterative phlebitis was determined.3 Inflammation was categorised as 'sclerosing' if 50% or more of the biopsy was occupied by fibrosis. Elevated tissue IgG4 was defined as IgG4:IgG ratio >40% and averaged tissue IgG4 plasma cells >50 cells/high-power field (hpf, 40×, field diameter of 0.55 mm) assessed in areas of greatest density of IgG4 plasma cells, over 3 hpf. However typically, the number of IgG4-positive plasma cells seen in the lacrimal gland is >100, in keeping with the consensus criteria findings.3 Similarly, the absolute tissue IgG2-positive plasma cells were counted on consecutive histological sections. The ratio of IgG2:IgG and IgG2:IgG4 was determined.
IgG subclass serology and extraorbital IgG4-RD status was established from retrieved clinical records, and cases were divided into the following groups:
Group 1: orbital IgG4-RD was defined as orbital IgG4-RD with/without systemic involvement and with/without raised serum IgG4. The exclusion criteria were evidence of autoimmune disorders (thyroid eye disease, Sjogren's disease, granulomatosis with polyangiitis (GPA) and other specific autoimmune diseases).
Group 2: idiopathic orbital inflammation was defined as non-IgG4 OID with non-specific histological features (with similar exclusion criteria as group 1).
Group 3: autoimmune orbital conditions such as thyroid eye disease, Sjogren's disease, GPA and other defined autoimmune diseases.
Statistical analysis
Kruskal-Wallis test was used to compare serum and tissue IgG, IgG2 and IgG4 and their ratios among the three groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic tests and to identify potential cut-offs to differentiate among the groups. Youden's index was used to identify the optimal cut-off point.
A total of 69 (38 Singapore cases; 31 UK cases) orbital biopsies were reviewed, with a total of 43 cases in group 1, 12 cases in group 2 and 14 cases in group 3. Patient demographics and results are summarised in tables 1 and 2. All the biopsies and serology were performed prior to corticosteroid therapy, except for patient 15 who received low-dose oral corticosteroid for treatment of acute tubulointerstitial nephritis secondary to IgG4-RD (diagnosed on renal biopsy prior to referral for a long-standing asymptomatic lacrimal gland swelling).
The mean age of presentation in group 2 (38.1±14.7 SD years, p=0.01) was significantly younger than group 1 (57.1±13.9 SD years) and group 3 (53.5±19.1 SD years). No difference was seen between groups 1 and 3.
Racial and sex distribution
A significantly higher percentage of Asians (Chinese, Indian and Malays) in group 1 was seen in contrast to the significantly higher percentage of Caucasians in group 2 (p=0.009). There was no significant difference in the racial distribution between group 1 and group 3.
There was no statistically significant differences in gender across all three groups (p=0.052) despite a slight male predominance (60% male:40% female distribution) in group 1 in contrast to the 60% and 80% female predominance in groups 2 and 3, respectively.
Patterns of inflammation
Chronic inflammation was present in all the cases (figure 1A–C,E). Group 1 was characterised by the presence of lymphoplasmacytic aggregates with reactive germinal centre formation, as described in the consensus criteria (figure 1A). Eosinophils were variable and present in group 1 and group 3 (figure 1C). Some cases in group 3 also contained neutrophils (figure 1E), a feature absent in groups 1 and 2. Xanthogranulomatous inflammation (figure 1F) was seen in 3 of 43 cases in group 1. Granulomas were present in group 2 (1/12 cases) and group 3 (5/14 cases) only.
Pattern of fibrosis
Storiform fibrosis was not seen in groups 2 and 3, and only focally present in group 1 (figure 1D). When present fibrosis was predominantly hyaline, with sclerosing inflammation (>50% of biopsy) more common in group 1 (10/43) than groups 2 and 3 (4/26).
Other accompanying histological features
Obliterative phlebitis was absent in all 71 cases, but perivenular inflammation (figure 1D) was seen in group 1 only. Vasculitis with/without necrosis was identified only in 6/14 cases from group 3.
Serum subclass elevation: both serum IgG2 and IgG4 are significantly elevated in IgG4-RD
Both mean IgG2 and IgG4 serology were found to be significantly elevated in group 1 (tables 1 and 2, IgG2, p=0.002; IgG4, p=0.028) when compared with groups 2 and 3.
In group 1, serological data were available for 47% (20/43) of patients. Of these, 45% (9/20) had elevated serum IgG2 subclass alone compared with the 25% (5/20) with IgG4 subclass alone. Twenty per cent (4/20) had both serum IgG2 and IgG4 subclasses elevation. Only one patient had raised serum IgG3 alone. Of note, 89% (8/9) of patients with IgG2 subclass elevation also had systemic IgG4 involvement, in contrast to only 60% (3/5) of patients with IgG4 subclass elevation and with systemic IgG4-RD involvement.
In group 2, serological data were available for 67% (8/12) of patients. None of these patients had elevated IgG2 subclass elevation. Only one patient showed elevated IgG4 serology alone and only one had elevated IgG3 serology alone.
In group 3, serological data were available for 36% (5/14) of patients. No patients had elevation of any of the IgG subclasses.
Tissue IgG2-positive plasma cells are present alongside IgG4-positive plasma cells: distribution and extent (figure 1, table 3)
In group 1, plasma cells expressing IgG2 were clearly detected in the tissues (figure 1I). These IgG2 plasma cells were admixed with IgG4 plasma cells and were without co-expression of IgG2 and IgG4 (figure 1G–J). IgG2 plasma cells were also detected in groups 2 and 3 (table 3 for mean IgG, IgG2 and IgG4 tissue counts). Tissue IgG2 plasma cells (IgG2, p=0.045) were significantly elevated when group 1 was compared with groups 2 and 3. Tissue IgG4 plasma cell count was significantly elevated in group 1 when compared with group 2 (Bonferroni adjusted, p<0.0001), but no significant difference between groups 1 and 3 was detected (Bonferroni adjusted, p=0.072).
IgG2:IgG and IgG4:IgG percentages (table 3)
IgG2:IgG percentages between all three groups did not show any statistically significant difference (p=0.334). In contrast, IgG4:IgG percentage was significantly elevated between groups 1 and 2 (Bonferroni adjusted, p<0.001) and between groups 2 and 3 (Bonferroni adjusted, p=0.020), but no difference was seen between group 1 and group 3 (Bonferroni adjusted, p=0.127).
IgG2:IgG4 ratios
In group 1, three patients (table 1; cases 15, 27 and 32) had IgG2:IgG4 ratios approaching unity with the tissue IgG4 plasma cells. In groups 2 and 3, 11/26 (42%) patients had an IgG2:IgG4 ratio >1, whereas in group 1, 100% showed an IgG2:IgG4 ratio <1. When IgG2:IgG4 ratio was compared between groups 1 and 3 (autoimmune disorders), the mean IgG2:IgG4 ratio was significantly lower (p=0.01) in group 1 (table 3). Similarly the IgG2:IgG4 ratio was also significantly lower (p<0.0001) in group 1 when it was compared with group 2 (idiopathic orbital inflammation).
ROC curve analysis for serum IgG2 and tissue IgG2 plasma cells
As serum IgG2 and tissue IgG2 plasma counts were found to be statistically significant between group 1 and both groups 2 and 3, the ROC curve/area under curve (AUC) was used to identify potential cut-offs to differentiate between the groups (table 4). A serum IgG2 cut-off >5.3 g/L was found to give a sensitivity and specificity of 80% and 91.7%, respectively, for differentiating between group 1 and groups 2 and 3, with an accuracy of 0.90.
Our results confirmed our observational impression and confirmed a higher percentage (65%, 13/20) of orbital IgG4 cases with serum IgG2 elevation in comparison with none in the idiopathic orbital inflammatory and autoimmune cases (0/13 cases). The statistical analysis revealed a significant twofold elevation of serum IgG2 in orbital IgG4-RD cases when compared with idiopathic non-IgG4-RD, autoimmune disorders. Being a retrospective study, not all serological data were available either due to lack of availability (at time of diagnosis), or even when suggested by pathologists was not carried out (lack of availability and cost constraints). Despite this limitation, ROC/AUC statistical analysis suggests serum IgG2 to be a useful surrogate serum marker for IgG4-RD, with an accuracy equal to serum IgG4 (table 4). Although further retrospective and prospective studies will be required to validate this, serum IgG2 may be particularly useful in 30%–40% IgG4-seronegative patients.
The presence of tissue IgG2-positive plasma cells could be clearly demonstrated by IHC (figure 1). The IgG2 plasma cells were admixed with the IgG4 plasma cells in every case examined, suggesting a common inciting stimulus. It was beyond the scope of our study to determine if our findings represented the emergence of two distinct IgG2 and IgG4 plasma cell populations or one undergoing subclass switch from IgG2 to IgG4 or vice versa, although the lack of plasma cells co-expressing IgG2 and IgG4 subclasses appears to favour the former. The increased tissue IgG2-positive cells (IgG2 >50 cells/hpf, p=0.023) in orbital IgG4-RD when compared with idiopathic non-IgG4-RD and autoimmune disorders imply that IgG2 is not a passive player in IgG4-RD. Since this study was completed, we have also observed IgG2 plasma cells outnumbering IgG4-positive plasma cells in non-orbital IgG4-RD, supporting the possibility of IgG2-positive plasma cells being a central player in this fibroinflammatory process and perhaps with a more systemic influence (similar to the elevated serum IgG2 observation).
Serum IgG2 is the second most abundant subclass of IgG in the serum and is usually formed as an immune response to bacterial capsular polysaccharide antigens.9–11 The IgG2 subclass is therefore an important defence mechanism against bacterial infections, such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis, and its deficiency is associated with increased susceptibility to such infections leading to chronic sinopulmonary infections.10 11 In contrast to IgG2, IgG4 is the least abundant subclass found in the serum. Similar to IgG2 deficiencies, its deficiency is also associated with chronic sinopulmonary infections.11 12 Thus, both these IgG subclasses appear to share potential common aetiologies.
Currently, the role of IgG2 serum elevation in IgG4-RD is not known. In orbital IgG4 inflammation, we noted 89% with elevated serum IgG2 also had evidence of multiorgan involvement by IgG4-RD and of this group, suggesting that serum IgG2 may be a biomarker of multifocal organ involvement by IgG4-RD. In addition, many of these were of South East Asian (SEA) ethnicity suggesting a possible genetic background to this possibly heightened response in SEA patients. However, given the small numbers in our study, this postulation will require further confirmation.
Others have reported that the IgG subclass undergoes temporal class switching in an ordered fashion from IgG3 to IgG1 to IgG2 to IgG4, with IgG2 and IgG4 being the later formed IgG subclasses.13 Immunoglobulins undergo affinity maturation during an immune response via class switching by somatic hypermutations and class switch recombination.13 The latter allows for the immunoglobulin constant region to switch to one of the four IgG subclasses. On the other hand, increased somatic hypermutations in the immunoglobulin variable regions have been shown in germinal centres to effect the sequential IgG subclass class switching.13 Although our study is purely observational, our serum IgG2 findings where the majority of the IgG4-RD cases show serum IgG2 without IgG4 serum elevation appear to corroborate this temporal IgG programmed class switching. This suggests that serum IgG2 may rise prior to serum IgG4, and perhaps our lack of IgG4 serum detection reflects a later class switch. The lack of statistically significant elevation of IgG1 and IgG3 among our three groups, while acknowledging the limitations of the dataset, is consistent with the idea that IgG1 and IgG3 class switch to IgG2 and IgG4, and suggests that IgG1 and IgG3 are unlikely to have a significant contributory role in IgG4-RD or orbital idiopathic and autoimmune disorders.
Published data on IgG4-RD have shown little correlation between serum and tissue IgG4 plasma cell counts.4 14 15 Our study also found a wide range of tissue IgG2 plasma cells with no distinct correlation with serum IgG2 similar to IgG4 subclass findings in IgG4-RD, suggesting that both tissue IgG4 and IgG2 subclass plasma cells in IgG4-RD may be a tissue response to a possible common inciting agent, perhaps with a serum IgG4 and IgG2 elevation representing a spillover response. Although this needs to be clarified, it is an interesting hypothesis for consideration.
Current literature has reported significant IgG4-positive plasma cells in a wide variety of autoimmune and lymphoproliferative conditions.16–20 Similarly, in our study, comparing IgG4 plasma cell counts between IgG4-RD and autoimmune disorders showed no significant differences (p=0.072), emphasising the need to exclude autoimmune causes before diagnosing IgG4-RD.
In our study, we noted that IgG2-positive plasma cells were also present in non-IgG4-RD OID and autoimmune conditions, suggesting that, just like IgG4, IgG2 plasma cells are not specific to IgG4-RD. This strengthens the notion that the two are linked in a common pathogenesis, yet emphasises that interpretation of IgG2-positive plasma cells in tissue biopsies must be approached with the same level of discernment as for IgG4-positive plasma cells to avoid overinterpretation. It is also interesting to note that a higher IgG2:IgG4 ratio was seen in the orbital autoimmune disorders, which usually have a more aggressive clinical course than orbital IgG4 and idiopathic orbital inflammation. Together with the presence of a higher percentage of elevated serum IgG2 in orbital IgG4 with systemic involvement, these findings again highlight the possibility that IgG2 may be associated with a more chronic and/or systemic disease process that is worthy of future larger scale studies for validation.
This study has several limitations, the first and most obvious being the absence of serological data for reasons as previously discussed. Second, the smaller size of groups 2 and 3 and the different numbers across all three groups limit our study despite our attempts to adjust for this in the statistical analysis. However, there are several qualitative and semi-quantitative observations of note that are worth pursuing in larger studies to clarify the significance of IgG2.
In summary, our study describes a significant association of serum and tissue IgG2 subclass with IgG4 orbital inflammation. Although future studies are required to define their role, we have postulated on its potential role in the pathogenesis of IgG4-RD, which leads to the question on what IgG4-RD actually is. Would an alternative terminology of 'IgG subclass disease' (with documentation of the proportion of IgG2 and IgG4 plasma cells within the biopsy) be a more accurate and better reflection of the histology and IHC findings? When the percentage of IgG2 and IgG4 expressing plasma cells is added for each patient with orbital IgG4-RD, 58% (25/43) have a total of IgG2+IgG4 plasma cells >90%, compared with 0/12 for idiopathic OID and only 36% (5/14) in orbital autoimmune, suggesting that a composite IgG2 and IgG4 subclass score may represent a useful parameter in further studies for determining its significance.
The authors thank the oculoplastic and orbital surgeons from the UK (Dr Sachin Salvi, Dr Zanna Currie, Dr Jennifer Tan and Dr Omar Hadid) and from Singapore (A/Professor Seah Lay Leng, Dr Choo Chai Teck, Dr Audrey Looi, Dr Morgan Yang and Dr Livia Teo) for the biopsies and clinical information.
Contributors ASYC and HM conceived the idea of the paper and are joint first authors.
ASYC, HM, MF, SYS, IR, LD and IAJ helped collate the clinical and histological data.
MHH and NJG performed the immunohistochemistry and technical aspects.
SSL performed the statistical analysis.
All authors reviewed and commented on the paper.
Funding This research was funded by the Singapore National Eye Centre, Health Research Endowment Fund (HREF) Grant R1210/16/2015.
Competing interests None declared.
Ethics approval Institutional Review Board from Royal Hallamshire Hospital and Singapore General Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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July 3, 2019
Another solid day of weather…and fishing
Caught loads of fluke today,,,guys who were dialed in had a limit…some even 2 or 3 more maybe helping out some who had the shorty curse…..and some did have the curse and caught just shorts….they did do best with the jigs today
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