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Split level home located on .28 acres in the Village of Bolivar. Enter this home from the long covered front porch. The main floor includes a spacious living room with a bow window, a ½ bath, an eat-in kitchen with appliances, and a mud room that leads to the attached one car garage with a carport.
Beauty Shop and former Hardware Store offer 2 store fronts and 3704 sq. ft. and upstairs living quarters offer 1736 sq. ft. Thats a total of 5440 sq. ft. plus a large basement. The former hardware store has a beautiful tin ceiling and still has a working hand operated freight elevator. The Beauty shop is still in operation but both have many possibilities. Upstairs yoou will find a full 3 bedroom 2 bath home for the owner to occupy or for rental income.
Remodeled ranch home located on a quiet dead end street near the Riverwalk Plaza. Enter this home from the covered front porch into the foyer. The main floor of this home includes a spacious living room, dining area, kitchen with appliances and an eat-at counter and a door leading to the attached 1 car garage with a concrete driveway. There are two nice size bedrooms with closets and a full bath. The full basement is dry with a concrete floor. The back yard is private with shade trees and a creek.
Sellers motivated to sell.
Four bedroom home in the Village of Wellsville close to the Wellsville Middle-High School and shopping. Enter from the large covered front porch into the living room.
4 BEDROOM RANCH STYLE HOME IN THE VILLAGE OF WELLSVILLE. Enter this home to large open living area with fireplace. The main floor has a kitchen, dining area, master bedroom with bath, 3 additional bedrooms and another full bath. The finished basement has a fireplace and several other rooms that could be used for bedrooms, storage, etc. This home is located on a secluded lot and has a back deck that overlooks a wooded area.
Call us with your Property Questions at 1-585-593-3457


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rooting a cherry tree cutting
I recently got a cutting from a cherry tree (it seems to be a "shogetsu"). It was new growth and was green. I cut off the bark from the bottom inch and put rooting hormone and put it in peat. I put it in a large open ziplock (upside down) and have now added a little 1% peroxide since a little mold started growing.
I saw a few posts recommending removing leaves. This cutting has about 4 leaves on it (I removed the others). Are the leaves of any use for rooting or is it best to take them all off?
Since there are no roots on the cuttings there is no way to replace the water lost through the leaves so yes yemove all but one leaf that will supply additional suggars for root formation & not deplete the water stored in the cutting
Also do NOT remove all the bark from the bottom of the cutting just removea small portion of the bark ...say 1 tenth of the bark...
need to remove the baggie several times a day to help preven fungal growth & to replace the air inside the bag...

subset: commoncrawl


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Gasteria pics...
Hi everyone, I have taken some pics of my Gasteria plants..
Hope you like them :)
Gasteraloe 'green ice'
Gasteria Batesiana barberton form
Gasteria Batesiana
Gasteria Brachyphylla Seedlings
Gasteria brachyphylla var bayeri
Gasteria brachyphylla variegata
Gasteria brachyphylla
Gasteria ellaphieae
Gasteria Excelsa
Oh gosh! Firstly, the Gasteria brachyphylla var. bayeri has the loveliest shape--gosh, want! :) And Mr. Smokey and Schwickerdtiana are absolutely stunning. Well, and the rest too! Your 'Little Warty' has some gorgeous color, much prettier than mine. And for that matter, it has got some spectacular shape, with those pups!
Well, gotta say, I'm jealous! :) I really hardly see Gasteria around here.
These Gasterias are great! It is interesting how Gasteria brachyphylla variegata has a leaf that has such a sharp contrast on each side. The pups are cute. I agree that the Schwickerdtiana is gorgeous. I love the big pictures. You get to really see the plant detail best.
Great plants, and pics Nikki, I prefer the bigger pics myself, shows details better. I don't grow many cacti/succulents actually but I like to see what you are all growing, so keep them coming!
Gill form the UK.
Thanks everyone, Gasteria are one of my favorite succulents :)
I should correct one name Gasteria schwickerdtiana should be Gasteria schweikertiana (still can't say it anyway haha)
Im looking forward to seeing the pups get bigger then I will share them, I have been lucky to have come across many people who have shared plants with me and helped to build my collection. I will also share my plants once the babies are big enough :)
My favourite is Gasteria schweikertiana, the biggest one is beginning to twist
I love your nice big pictures, makes it easy to really see how the plants look. I just ordered some gasterias and I have never grown them before.
I would love to know what kind of soil I need to use. Can I get away with cactus mix?
I love your Little Warty. I have seen pictures of it and think its so pretty. That is one I would like to get.
Its hard to find posts in this forum just for gasterias.
Neysa in California
Hi Neysa,
No there don't seem to be many posts here of Gasterias. I too grow a few, mostly no IDs.
Cactus & Succulent soil w/ extra perlite (like 30-50%) works well for mine. If you're new to Gasterias, pls. note they are not plants for direct sun, will burn easily. Since you're in CA, I thought it best to warn you of that. They do well in light shade or under the shade of taller plants.
Here in NYC (indoors only), I put them at the edge of my west windowsills. They do well in clay or plastic, if you're new to them & likely to want to overwater, I'd say go with clay pots. Either type must have drainage holes.
Also a reminder (for succulents) when in doubt about watering them, don't water.
Welcome & Good luck!
Thanks Nikki and irate Girl for your responses. I have never heard of on2 soil so maybe we don't have that hear in So. Calif. Pirate Girl, I will get some Cactus & Succulent soil. I have a bag of perlite I could mix in with it. I see others use rocks on top. Is that for a reason or is it for decoration? I have about 5 plants that hopefully will come. I need to be ready because 4 of them are coming bare-root. I have never had any before but one day I saw some and started looking on ebay and some I fell in love with. There are some really pretty ones. I guess I will put mine on my patio. It gets some sun part of the day, I may have to have it where the sun only for a small part of the day instead. Probably need to also invest in clay pots ,cause the only ones I have are plastic.............
Thanks again for your advise.
Neysa in California
Where in SouCal are you? Depending on your area, there are lots of C&S Societies you could join to increase your knowledge of C&S, as well as more Gasterias, to name just two of the numerous attributes membership would get you.
Top dressing is used for aesthetics, to keep weeds down, and to inhibit a potted plant's soil from drying out too quickly.
This post was edited by cactusmcharris on Mon, Jan 13, 14 at 22:36
Thanks bunches the both of you. I just found out that some plants are being sent today. They will be coming from Oregon, and should be here by Friday. I will take pictures when they come so you can see who I choose. The plants from this business I only got minis.
Now, I must go get some soil so I can be ready.
I live by West Covina, California.
Whoops, here it is.
Here is a link that might be useful: LA Cactus, she get to know you
Not as beautifully staged as the first pix, but here's one of my no ID Gasterias.
I'm partial to variegates & was pleased this decided to have a pup.
Gasterias are low maintenance, rewarding plants. I find them very sculptural & handsome to look at.
That link is in San Fernando Valley, which is not near me........... but thanks for the link anyhoo.
I like the variegated plants toooooooo. I hope they will end up as easy to raise as my neglected succulents.
I like the green with the stripe Pirate Girl.
Gasteria gracilis variegata* (Mini)
I love the variegated ones, so this one stuck out It too is on its way home............bare root. Now, I for sure need to go to Home Depot and buy a bag of Cacti and succulent mix and I don't have any small pots, so will also need those tooo...........I am really excited to try these kids out.
Hope I did not bore you with all the pictures........
Neysa in California
I will have to take pictures soon of the plants since planting them. I still have to get a container for the one that came in its pot..............also have to get the batteries charged in my camera or maybe use my cell phone for pictures.
Has anyone got any nice pictures to share. I love seeing them.
Neysa in California
Caligrown and Cactusmharris, love your plants. I think the verigated are just beautiful............of course I am partial to all verigations.............thanks for sharing your pictures...............
Anyone have any updates they would like to share? Any hints on how your plants are doing this winter..........what food you like the best for your plants?
Neysa in California
I am looking for a place to get decent plastic markers so I can keep tract of my gasterias and haws.....................I found one on amazon.net
Garden Helpers H166 6-Inch Plastic Plant Labels and Plant Marker Pen, 100-Pack
by Bosmere
Price: $16.94
Everyone thinks they are nice and sturdy. But they don't like the marker pen that comes with them.................I also need to know of a type of pen besides sharpie that can write fine point and won't fade in the sun or whatever..........
Does anyone have a place where they buy theirs from?
Neysa in Calfornia


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Make a Difference – Help Save The World From Brian Williams Style Journalism
Get Involved… Voting is a Must, But Not Enough!
The 2014 Mid-Terms were a sign that Americans are ready for a change and 2016 will define the future of America. So get involved! No more recycles... No more Clintons or Bushs! It is time for some new blood in Washington, D.C.
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Category Archives: Common Sense
Forum: Is America In Decline? Why Or Why Not?
Every week on Monday morning , the Council and our invited guests weigh in at the The Watchers Forum, short takes on a major issue of the day, the culture, or daily living. This week's question: Is America In Decline? … Continue reading
Bloomberg News By Marion Algier – Ask Marion Video: Mia Love Full CPAC Speech Video: Carly Fiorina CPAC 2015 Full Speech Bashes Hillary in CPAC Speech Video: Chris Christie CPAC 2015 Ingraham Grills Christie on His Low 2016 Polling … Continue reading
Posted in Americana, Common Sense, Conservatives, Elections, Events, Leadership, News and politics, Patriotism, Politics Tagged Ben Carson, Bobby Jindal, Conservativsm, CPAC, CPAC schedule, CPAC speeches, Election 2016, Hannity, Palin, PTSD, Sarah Palin, speeches, Ted Cruz, veterans 10 Comments
Joni Ernst GOP Response to SOTU 2015
Video: Watch Joni Ernst deliver the Republican response to the 2015 State of the Union address
Posted in Americana, Changing Winds, Common Sense, Get Involved, Leadership, News, News and politics, Patriotism, Politics, Solutions, Success, You Be the Judge Tagged GOP, Joni Ernst, SOTU, speeches, State of the Union Leave a comment
Governor Jindal – We Need Muslim Leaders to Stand Up and Denounce These Radical Islamists
Video: Gov Jindal: "We need Muslim leaders to stand up and denounce these Radical Islamists" US Must Arm Muslims Fighting Extremists 'To the Teeth' Says Judge Pirro as World Leaders, Sans Obama and Kerry, Gather in Paris – Updated
Posted in Common Sense, Leadership, Politics, Religion, Wisdom, You Be the Judge Tagged Bobby Jindal, fanatics, Islam, Muslims, radical Islam 1 Comment
Trey Gowdy Gave a Speech for the Ages Leaving the Democrats Floored
Take the time to listen to this short speech. Video: Rep Gowdy's Floor Speech on Stopping President Obama's Executive Action on Immigration Sheriff Joe's case against amnesty on fast track House-Passed Immigration Plan Gets Bitter Response at GOP Hershey Retreat
How Japan deals with Islam
This is very interesting and if you think that Japan is being too harsh on Islam, just think of what Islam has done to those that don't convert to their way of life… And remember what happened in Paris. Ask … Continue reading
Posted in Books, Choices, Common Sense, Freedom, Knowledge Is Power, Leadership, Religion, Solutions, Stand Up, Strength, Wake Up, You Be the Judge Tagged common sense, Islam, Islamic terrorists, Japan, Muslims, religion, survival Leave a comment
US Must Arm Muslims Fighting Extremists 'To the Teeth' Says Judge Pirro as World Leaders, Sans Obama and Kerry, Gather in Paris – Updated
Video: US Must Arm Muslims Fighting Extremists 'To the Teeth' – 01-10-15 By Marion Algier – Ask Marion On Saturday night, Fox News' Judge Jeanine Pirro of "Justice with Judge Jeanine" opened her show with "The US should arm Muslims … Continue reading
Posted in Alerts, Common Sense, Dumbing Down of America, Events, Freedom, Get Involved, History, Knowledge Is Power, Leadership, News, News and politics, Politics, Religion, Solutions, Stand Up, Wake Up, You Be the Judge Tagged Allen West, Beck, Egypt, extremists, Fox News, ISIS, Islam, John Kerry, Judge Jeanine Pirro, Middle East, Muslim Brotherhood, Obama, Palin, vetting our candidates, Wake Up 17 Comments


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If you have an account you can simply login by entering your information in the login area to the right or at the top of the page.
Or register for an account so you start contributing your thoughts and ideas to the vaporizer community. People just like you are what make HerbalVaporizerReview.org the web's most trusted Vaporizer Review site.
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"PAIN(T) FREE" is an independent documentary about graffiti art in Bangkok/Thailand, local and residential artists, who put their skills into making those blank walls a little bit more beautiful and colorful. One of the old graffiti writers MISTER BOWS Badblood and new MATT DIAMOND transforming their neighborhood!
Painting the wall seems like a challenging hobby, though you start to appreciate the effort when people stop by, smile and cheer you up! Or maybe it's just Bangkok:D
Artist: MISTER BOWS Badblood/ MATT DIAMOND
Produced: BEZoCEAN
Music: THE UNDERACHIEVERS- Herb Shuttles
more info: bezocean.com
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One had best be careful before opening up one of these barrels…
the Apple Tree of Selilion holds the secret of life and death
30 Minor Curses
The Headsman is drawn to areas where great injustices have occurred. ... He is absolutely cold and emotionless. The only mercy he knows is swift death.
This item provides the user access to other realms in a small package.
Lutazum is an immense (32' at the top of it's shell) tortoise which walks on huge 2' thick legs. It is dark green with speckles and looks about with suprising intelligance. On top of its shell are strapped leather containers of all description.
Demontrumpets, as illuded to by the name, are not normal plants, but are plants who hold their origin in the Abyss. Perhaps brought by summoned demons, perhaps created by a dark god for some purpose, perhaps simple plants mutated by an artifact of great evil.
"MINE!!!!" thundered the demon as he caught site of the chests of gold coins. With a gesture of his hand the chests rose, sundering the enchantments which held them down and drew them towards him.
A vast city nearly built in ages past by a long-lost race of giants. Now the vast stone structure contains no less then three seperate kingdoms.
Thaumatrium (Yellow,Black & White)
Never buy your potions from the Discount Dealer…
A fine suit of armour that provides protection, but from what?
This weapon lets you reach out and poke someone…
The Grinder was instituted as a capital punishment for the worst murderers and criminals.
In these gloves was placed a seed of the power used to create the world.
You find a patch of edible funghi. They taste well and all, no ill effects. UNLESS you consume some beverage, even 3 (three) days after eating it. Then you become really sick with pains, vomiting, all the fancy stuff. As a gift or good meal, it could be a cruel joke or to make sure the heroes spend their time focused on the mission. And the fine soup you had in the inn yesterday could have some in.
(Inspired through a real-world fungus. Was really used to cure alcoholism.)


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Create a free account to check out faster, store multiple shipping addresses, view and track your orders in your account, and much more.
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Let's be frank: your feet are in tough condition. Between the flip flops and walking around barefoot, you've amassed quite the collection of callouses and scaly areas. Lucky for you, this thick salve can handle even the most neglected feet. Apply it regularly and you'll be ready to play footsie in no time.
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Tag Archives: RHEL
RHEL 5.3 excessive file handles
As per my previous post here. I'd like to share some conclusions and how they came about. A scheduled reboot was performed and the nagios agent and scripts got corrected. However this wasn't the issue, which was sort of determined … Continue reading
Tagged Events, Linux, RHEL, Technology Leave a comment


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Rabbi Zach's dog is possessed, so naturally he finds a Kabbalah witch on Craigslist to do the exorcism.
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Flight departure days
1. Flight G31937: Aracaju - Rio de Janeiro, AJU - GIG, 2h 35m
Gol Transportes Aereos domestic flight G31937 departs from airport Aracaju, Santa Maria (AJU), Brazil on Saturday, 18 July at 10:45 / 10:45 am. The flight arrives to «Terminal 1» of airport Rio de Janeiro, Galeao (GIG), Brazil on Saturday, 18 July at 13:20 / 1:20 pm. Flight duration is 2h 35m.
Aracaju, Santa Maria (AJU)
10:45 am
10:45 am
Jul 18
Gol Transportes Aereos
2h 35m
Rio de Janeiro, Galeao (GIG)
1:20 pm
1:20 pm
Jul 18
Terminal 1
Gol Transportes Aereos G3 1937 alternative and return flights
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John Lithgow Celebrity Watchlist
Photos | Credits | Biography | Video Clips
Prior to becoming a leading man on the sitcom 3rd Rock From the Sun, this veteran actor had spent the previous two decades as a stage and screen supporting player. The son of a well-known theater producer, Lithgow earned a Tony Award for his 1973 Broadway… (more)
Birth Name: John Arthur Lithgow
Birth Place: Rochester, NY
Birthday: October 19, 1945, Libra
Profession: Actor
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Richard Dreyfuss portrays a private eye involved in political intrigue and murder. Susan Anspach, Bonnie Bedelia. Sam: John Lithgow. Alora: Ofelia Medina. Eppis: F. Murray Abraham. Directed by Jeremy Paul Kagan.
Supremely entertaining adaptation of the Broadway hit about the ups and downs of a 1960s girl group. Beyoncé Knowles, Jamie Foxx. Jennifer Hudson won a Best Supporting Actress Oscar as a member of the trio who is replaced as lead singer. Eddie Murphy got (more…)
Three small-time marijuana farmers become entangled in murder, greed and lust when their boss is slain by an unknown assailant. Billy Bob Thornton, Hank Azaria. Lucy: Kelly Lynch. Danny: Jon Bon Jovi. Harlan: Ryan Phillippe. Directed by Stephen Gyllenhaal (more…)
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March 31, 2015
Reilly Lecture: Advances in siRNA and Protein Delivery Through Smart Polymers
Engineering the molecular design of intelligent biomaterials by controlling structure, recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. Recent developments in siRNA and protein delivery have been directed towards the preparation of targeted formulations for protein delivery to specific sites, use of environmentally-responsive polymers to achieve pH- or temperature-triggered delivery, usually in modulated mode, and improvement of the behavior of their mucoadhesive behavior and cell recognition. We address design and synthesis characteristics of novel crosslinked networks capable of protein release as well as artificial molecular structures capable of specific molecular recognition of biological molecules. Molecular imprinting and microimprinting techniques, which create stereo-specific three-dimensional binding cavities based on a biological compound of interest can lead to preparation of biomimetic materials for intelligent drug delivery, drug targeting, and tissue engineering. We have been successful in synthesizing novel glucose- and protein-binding molecules based on non-covalent directed interactions formed via molecular imprinting techniques within aqueous media. We have also developed structurally superior materials to serve as effective carriers for siRNA delivery to combat Crohn's disease and ulcerative colitis.>Full Description
April 1, 2015
Reilly Lecture: Nanotechnology and Bioengineering in an Evolving Chemical Engineering World
Nanotechnology and Bioengineering, have evolved out of chemical engineering because of the need to address important societal problems. Emphasis in such areas has led to the solution of complex chemical engineering problems that required non-newtonian flows, non-ideal thermodynamics, multicomponent systems, macromolecular analysis and diagnostic/intelligent responsive systems. The introduction of these fields brought up also an emphasis on translational research, product engineering, development of devices/systems and processes and an associated emphasis on applications and commercialization. An unfortunate result of these changes was a shift of Chemical Engineering from fundamentals to applied sciences. I examine the underlying reasons for this shift, with emphasis on changes in societal needs in the 1970s to translational research that started in the late 1980s. I examine the impact of these changes on ChE education, including the academic shift towards applied sciences and the de-emphasis of fundamentals. We address new educational and research directions that will provide a corrective path towards convergence in Chemical Engineering.>Full Description


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#58|Feb. 18, 2012|Penguins at Flyers|1:00 p.m. ET
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Location: Northwest Florida
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Originally Posted by
Lavy has lost the room... it's unacceptable to play 30 minutes a game and expect to win.
Did he "lose" the room last game ? They certainly seemed to listen to him last game after he lit em up in the room ? I think the REAL problem is pretty simple actually.....Our goal tending duo has ZERO confidence at the moment, which can really be something that can haunt them for some time.....And we certainly had plenty of chances to score more goals in the 2nd especially..Bryz is certainly gripping and for the life of me i will NEVER understand the positioning BOTH our goalies use on bad angle shots....The whole top of the net is open when they crouch down so low on really crazy angles....I have no idea why that nonsense is taught by MANY goalie coaches these days..When i watch the NHL hi lights each night on the NHL channels "on the fly" i see a lot of goals scored on crazy angles these days.....And our goalies are leading the pack in that category.......
Having said that, sometimes you gotta reach rock bottom before you can start your way back up the "confidence" ladder....I am hoping that will be the case with our goalies and defense etc...Just gotta keep on working it out and playing through it,,,I certainly am not ready to "blow up" the team as some suggest.I see Homer making another move this week etc....
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HIV Risk After Pool Water
Here's a taste of what TheBody.com has to offer on this topic:
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Stopping the Spread of HIV...infection, you should take steps to prevent getting infected. People recently infected (within the past 2 or 3 months) are most likely to transmit HIV to others. This is when their viral load is the highest. In general, the risk of transmission is higher with higher viral loads. This fact sheet provides an overview of HIV prevention, and refers you to other fact sheets for more details on specific topics. Sexual Activity You can avoid any...
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test2Dr. Bob,Although it might sound strange, I enjoy skinny dipping in the Lake. I usually do it where there are no people around so I don't freak anyone out...plus I am really not that well hung!!. Is there any risk of catching hiv or hepatitis in...
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University of Cincinnati, College of Medicineasdfasdf Read more »
test2Dr. Bob,Although it might sound strange, I enjoy skinny dipping in the Lake. I usually do it where there are no people around so I don't freak anyone out...plus I am really not that well hung!!. Is there any risk of catching hiv or hepatitis in...
Response from Judith Feinberg, M.D.
University of Cincinnati, College of Medicinedfsdv Read more »
HOW WELL DOES THE HIV VIRUS TRANSMIT AT SWIMMING POOL?Hi Dr Bob I have one quick question regarding how well does the HIV virus survive in chlorine water. I went to the indoor swimming pool other day and I didn't notice this when I walked in but there was blood on the ground foot print maybe someone...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Hi,The only way you could contract HIV in that pool would be by having unsafe sex with an HIV-positive hunky lifeguard.Dr. Bob Read more »
"the blood pool" workplace HIV exposureHi Doc, you are truly the best. Keep up the great work.I keep trying to convince a friend that their exposure risk was zero, maybe he will listen to you. He has fallen into a depression because of this, and is terrified of HIV. This happened two...
Response from Robert J. Frascino, M.D.
The Robert James Frascino AIDS Foundation...Hello,Your friend's HIV risk is nonexistent. If he remains worried, let alone terrified and depressed, he should get an HIV rapid test at the three-month Read more »
2009 H1N1 Flu (Swine Flu) and You...hospitalized as a result of 2009 H1N1 have had one or more "higher risk" medical conditions. Young children are also at high risk of serious complications from 2009 H1N1, just as they are from seasonal flu. And while people 65 and older are ... Read more »
How HIV Is Spread...having sex) Not sharing needles Masturbation Abstention from sex Please see the sections on Reducing the Risk of Getting HIV from Sexual Activities and from Injection Drug Use for additional information. Ways in Which... Read more »
HIV-Positive Nevada Man Files Complaint After Mobile Home Park Prohibits Him From Using Pool...lives, after the park earlier this year sent him a letter saying that state law prohibits him from using the park's swimming pool because he is HIV-positive, the Las Vegas Review-Journal reports. Hutchison and Steffen, the law firm... Read more »
Oral Sex: What's the Real Risk for HIV?...activity, people have reportedlybecome infected with HIV in this way. A number of studies have tried todetermine the exact level of risk of oral sex, but it can be difficult to getaccurate information from study participants. Since oral sex is... Read more »
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Desperately seeking answers
Posted by scared_stiff_to, 5 Replies...off it and it did not expose any blood nor ooze any liquid - another scab never formed. I wrote this incident off as a low-risk exposure, and vowed never to put myself at such risk again. Soon after I met a lovely woman who I know has tested... Read more »
Penis Glans and the risk of contracting HIV
Posted by dopey33, 3 Replies...penis, it ran to the glans of my penis. NEVER did the cum enter the tip of my penis. I immediately washed my penis with warm water and dry it up. I am concern because online it talks about how you can get HIV if any contaminated fluids goes as... Read more »
Chronic Tonsil Cheese
Posted by brent4861, 10 Replies...throat isn't sore and I was surprised. I went online to google.com to search and found out that kids get this and people with AIDS. This isn't able to be affected by antibiotic at all times cause it hides or something like that. I called my... Read more »
Posted by Anonymous, 3 Replies...A user in the other section said she sat on a needle and got HIV, its very possible and it has happened before, my question is has anyone ever heard of this happening ? and do they know anyone Read more »
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Oil painting. I really admire her work, so I'm doing an upload spree. I didn't get a chance to write down the names of the paintings, or the dimensions.
anthony_cudahy, rudisillart, and 39 other people added this photo to their favorites.
oh i love her work
Peter, a Young English Girl
I am always moved by this painting. One of my favourites. I am happy to have introduced you to someone you have really grown to admire :-)


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The plight of Guantanamo detainees is in jeopardy of being eclipsed and rationalized by Osama bin Laden's death.
Issues / Human Rights
The protests in Syria are encouraging, but Bashar al-Assad will pull out all the stops before he leaves voluntarily.
Nobel laureate Muhammad Yunus lost his appeal to continue as chief of the pioneering microcredit institution he founded.
Ironically, relaxing the rules for a troubled young Guantanamo detainee facilitated his suicide.
Without an Arab Voltaire it is difficult to see how the Arab world can escape the cycle of authoritarianism.
When it comes to protests in the United Arab Emirates, the United States has looked the other way.
Despite bin Laden's death, the rallying cause for jihad still holds: U.S. support for Israel is as strong now as ever.
The point-blank shooting of Osama bin Laden raises questions.
The grievances expressed in bin Laden's manifestoes can still replenish the ranks of jihadis.
Jihadists see a window of opportunity in Libya.


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Page 1
Morphological predictors of BRCA1 germline mutations in
young women with breast cancer
MC Southey1, SJ Ramus2, JG Dowty3, LD Smith1, AA Tesoriero1, EEM Wong1, GS Dite3, MA Jenkins3,
GB Byrnes4, I Winship5,6, K-A Phillips7,8, GG Giles1,9and JL Hopper*,3
1Department of Pathology, Genetic Epidemiology Laboratory, Victoria, Carlton, Australia;2Department of Gynaecological Oncology, UCL EGA Institute for
Women's Health, University College London, London, UK;3Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic
Epidemiology, School of Population Health, The University of Melbourne, Carlton, Victoria, Australia;4The International Agency for Research on Cancer,
Lyon, France;5Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia;6Department of Genetics,
Royal Melbourne Hospital, Parkville, Victoria, Australia;7Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Victoria, East
Melbourne, Australia;8Department of Medicine, St Vincent's Hospital, Victoria, East Melbourne, Australia;9Cancer Epidemiology Centre, The Cancer
Council Victoria, Victoria, Carlton, Australia
BACKGROUND: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical
management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer
morphology and hormone receptor status data.
METHODS: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years
for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review,
and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using
multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified
RESULTS: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting
for family history and ER and PR status (Po0.0001). From the most parsimonious multivariate model, the odds ratio for being a
carrier were: 9.7 (95% confidence interval: 2.6–47.0) for trabecular growth pattern (P¼0.001); 7.8 (2.7–25.7) for mitotic index over
50 mitoses per 10 high-powered field (P¼0.0003); and 2.7 (1.3–5.9) for each first-degree relative with breast cancer diagnosed
before age 60 years (P¼0.01).The area under the ROC curve was 0.87 (0.83–0.90).
CONCLUSION: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost
all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history.
British Journal of Cancer (2011) 104, 903–909. doi:10.1038/bjc.2011.41
Published online 22 February 2011
& 2011 Cancer Research UK
Keywords: BRCA1; early-onset breast cancer; tumour morphology
About 5–10% of young women diagnosed with breast cancer carry
germline mutations in BRCA1 (Newman et al, 1998; Southey et al,
1999; Malone et al, 2000; Ozcelik et al, 2003). Knowing a woman's
BRCA1 mutation status soon after the time of diagnosis is
important because it could inform her immediate treatment
choices, particularly with regard to breast conservation therapy
vs mastectomy (Pierce et al, 2010), and perhaps in the future, her
use of targeted therapies, such as Poly (ADP-ribose) polymerase
inhibitors (Goodwin et al, 2007; Fong et al, 2009). Her mutation
status is also important for her female relatives because a
substantial proportion of these women will carry the same
mutation and so will therefore be at high risk of breast and
ovarian cancer (Antoniou et al, 2003) and will have different
preventive and screening options than the general population.
What is the best approach to identify the BRCA1 mutation
carriers among young women with newly diagnosed breast cancer,
in terms of timeliness, sensitivity, specificity? Family history is
difficult to collect well, especially in a busy clinical setting, in the
context of a young woman newly diagnosed with breast cancer.
In addition, the woman might not know her family cancer history
details and gathering the relevant data and ensuring its accuracy
might involve other family members, a process that can be time
consuming. Even when accurately reported, well collected and
verified cancer family history is often uninformative, unless
extreme, as it is neither sensitive nor specific to BRCA1 mutation
status. The areas under the receiver operator characteristic (ROC)
curves for algorithms based on family history alone, such as
BRCAPRO and BOADICEA, are at most 0.7–0.8 (e.g., Antoniou
et al, 2008b). The odds of being a carrier increases on average by
only a few fold for each first-degree relative with breast cancer
(Ozcelik et al, 2003; Apicella et al, 2007) and given that the
mutation frequency in the general population is about 1 in 600
(Antoniou et al, 2008a), it can be seen that family history must be
extreme before the probability of being a carrier exceeds a nominal
Received 20 August 2010; revised 4 January 2011; accepted 26 January
2011; published online 22 February 2011
*Correspondence: Professor JL Hopper;
E-mail: firstname.lastname@example.com
British Journal of Cancer (2011) 104, 903–909
& 2011 Cancer Research UK All rights reserved 0007– 0920/11
Clinical Studies
Page 2
and historic testing threshold of 10% (Burke et al, 1997), let alone
the newer UK benchmark of 20% (National Institute for Clinical
Excellence, 2004). Even for the women with apparently strong
family histories being tested by cancer genetics services, the great
majority (470%) are found to be non-carriers (Parmigiani et al,
2007; Antoniou et al, 2008b). Further, large proportions of the
women who have been tested have had low a priori probability of
being a carrier. For example, in a high-risk setting in the United
States 440% of those tested were below the 10% threshold based
on BRCAPRO (Parmigiani et al, 2007), and similar figures have
been observed in the United Kingdom (Antoniou et al, 2008b).
It has been known for some time that there are particular
morphological and histopathological features evident on tumour
review that are more common in cancers arising in BRCA1
mutation carriers (Lakhani et al, 1998). These features have been
identified by studying carriers across a wide range of ages at
diagnosis who were ascertained because of their strong family
cancer history. Lack of ER and PR expression have also been
reported to improve prediction of BRCA1 mutation status based
on family history (Lakhani et al, 2002; James et al, 2006; Mavaddat
et al, 2010). To date, no validated algorithm appears to have been
developed based on all of these predictive features, let alone using
a population-based series of early-onset breast cancers.
Our aim was to devise a practical strategy that could be applied at
the time of diagnosis for identifying, with high sensitivity and
specificity, those young women with early-onset breast cancer who
have the highest probability of carrying a germline mutation in
BRCA1. We used morphological and immunohistochemical data that
could be routinely collected at diagnosis, as well as data on family
history of breast cancer in first- and second-degree relatives.
Australian Breast Cancer Family Registry
The Australian Breast Cancer Family Registry (ABCFR) includes a
population-based, case–control–family study of breast cancer, in
which cases and controls (probands) and their relatives were
administered the same questionnaires, carried out in Melbourne
and Sydney, Australia (Hopper et al, 1994, 1999; McCredie et al, 1998).
It is a component of the international Breast Cancer Family Registry
(John et al, 2004; Neuhausen et al, 2008). The study was approved by
the ethics committees of The University of Melbourne and The Cancer
Councils of Victoria and New South Wales. All participants provided
written informed consent for participation in the study.
Family history data
For each family, a pedigree was constructed by interviewing the
proband and all participating relatives, covering all known first-
and second-degree adult relatives of the proband, their vital
statuses, cancer histories, dates of birth and, if appropriate, dates
of death and/or diagnosis. Consequently, reports of cancer in
relatives came from multiple sources within the family, so that the
pedigree information for each person was based on a self-report or
report(s) from first-degree relatives and rarely was only on a
report from a second-degree relative. Attempts were made to verify
cancer reports using cancer registries, death certificates and other
medical records (Dite et al, 2003). For probands, a strong family
history was defined as having two or more first- or second-degree
relatives diagnosed with breast or ovarian cancer (including male
breast cancer) on the same side of the pedigree.
Tumour retrieval, pathology review and morphology score
We attempted to retrieve archival blocks for the first primary
invasive breast tumours of all 856 probands diagnosed before the
age of 40 years. A total of 452 tumours (53%) were retrieved and
included material from 16 surgical biopsies, 7 spot/needle localisa-
tions, 309 lumpectomy/quadrantectomies, 167 mastectomies and
442 axillary dissections. The mean age at diagnosis for these
retrieved cases was 35 years, as it was for the 856 probands.
Histological type was recorded for 442 (98%) of the reviewed cases,
the majority of the tumours were infiltrating ductal carcinomas
(NOS) (83%). Atypical medullary (5%), classical medullary (1%),
pleomorphic lobular (4%), classical lobular (2%) and other very rare
histological types (tubular, cribiform, mucinous, secretory, meta-
plastic and alveolar lobular, 4%) made up the remainder.
These were scored for morphology features by a pathologist blind
to the mutation status as described by Armes et al (1998) and
Longacre et al (2006). Briefly, the tumours were typed into primary
pattern and secondary pattern using the World Health Organisation
breast carcinoma classification with minor modifications as des-
cribed by Page et al (1987). Tumour grade was scored using the
modified system of Bloom and Richardson by assessing mitotic rate,
tubular differentiation and nuclear pleomorphism (Page et al, 1987).
We then selected nine features that have been reported
to be associated with BRCA1 germline mutation status (Eisinger
et al, 1996; Breast Cancer Linkage Consortium, 1997; Jo ´hannsson
et al, 1997; Armes et al, 1998; Lakhani et al, 1998):
(1) Very high mitotic index defined here (see justification
below) as 450 mitoses per 10 high-powered fields (h.p.f.).
The mitotic index of each tumour was scored as: number of
mitoses per 10 h.p.f.
(2) High nuclear grade (score of 3 for nuclear pleomorphism
according to Elston (1987), which is scored as: (1) bland,
(2) intermediate or (3) malignant (high)).
(3) Little or no tubule formation (score of 3 for tubule formation
(o10%)) according to Elston (1987), which is scored as: (1)
475%, (2) 10–75% and (3) o10%).
(4) Trabecular growth pattern. Primary and secondary growth
patterns are scored as: (1) acinar (organoid), (2) lobular,
(3) trabecular and (4) tubular. Primary trabecular growth
pattern was scored according to Ridolfi criteria for medullary
cancers requiring 475% of the tumour to have a trabecular
growth pattern (Ridolfi et al, 1977).
(5) Pushing margin, defined here as a continuous front of cells
observed in 450% of the tumour circumference and scored
as: (1) yes and (2) no.
(6) Circumscribed growth pattern scored as: (1) yes and (2) no.
(7) Syncytial growth pattern 475% scored as: (1) yes or (2) no.
(8) Necrosis scored as: absent or present; and
(9) Moderate or intense lymphocytic infiltrate, scored as:
(1) absent/minimal, (2) moderate or (3) intense.
We generated a morphology score for each tumour by adding up
the number of the following features that were present; high
mitotic index, high nuclear grade, little or no tubule formation,
trabecular growth pattern, pushing margin, circumscribed growth
pattern, syncytial growth pattern, necrosis and a moderate or
intense lymphocytic infiltrate, so that the score ranged from 0 to 9.
ER and PR status had been collected by the ABCFR for 402
(89%) of the 452 reviewed breast cancer cases. This information
was collected from the state cancer registries (58%), diagnostic
pathology reports (29%) and from immunohistochemical staining
of tumour tissues (13%; Armes et al, 1998) as described in
McCredie et al (1998).
BRCA1 mutation screening
For 788 (92%) of the probands, and for all 455 of the reviewed
cases, previous BRCA1 mutation screening included:
(1) Protein truncation testing covering exon 11 of BRCA1
(Hopper et al, 1999).
Morphological predictors of BRCA1 germline mutations
MC Southey et al
British Journal of Cancer (2011) 104(6), 903–909
& 2011 Cancer Research UK
Clinical Studies
Page 3
(2) Manual sequencing of the coding and flanking intronic
regions of BRCA1 for: (i) a random sample of 91 probands
(Southey et al, 1999), (ii) 63 probands with a strong family
history of breast and/or ovarian cancer, (iii) 6 probands whose
mothers had two primary breast cancers and (iv) 9 probands
who had at least two or first- or second-degree relatives
(maternal and paternal) with breast or ovarian cancer.
(3) Large genomic alteration screening of BRCA1 using multiplex
ligation-dependent probe amplification (MLPA) as previously
described (Smith et al, 2007) for groups (ii), (iii) and (iv)
in (2) above.
(4) Testing for the two Ashkenazi founder mutations in BRCA1,
185delAG and 5238insC for all (Leong et al, 2000; Dite et al,
2003; Apicella et al, 2007).
(5) Testing for the duplication of exon 13 in BRCA1 for 641 probands
as described previously (Puget et al, 1999; Leong et al, 2000).
Definition of pathogenicity for BRCA1 sequence variants was
consistent with the policy of the Breast Cancer Information Core
database (http://research.nhgri.nih.gov/bic/) and Neuhausen et al
(2008). The above testing identified 39 pathogenic mutation
carriers. The breast cancers arising in 29 (74%) of these carriers
were retrieved and reviewed.
Statistical analysis
Associations between features were assessed by dichotomising
and calculating corresponding odds ratios (ORs). Associations
between the outcome, mutation status and potential predictors
were estimated using simple and multiple logistic regression. The
best fitting model was defined to be the one with the lowest
Bayesian information criterion (BIC) (Schwarz, 1978) using
observations with no missing data for any variable (N¼400).
P-values were based on the likelihood ratio test unless otherwise
indicated and all calculations were performed using R version 2.7.2
(R Development Core Team, 2010).
The performance of the best fitting model was assessed using the
same data set on which the model was fitted using a five-fold stratified
cross-validation approach, as recommended by Kohavi (1995).
The predicted probability that a woman carries a BRCA1
mutation according to the best fitting model was calculated in the
standard way as f(xTb) where f is the logistic function given by
f(L)¼exp(L)/(1+exp(L)), b is the column matrix of maximum
likelihood estimates, and x is the relevant part of the woman's
column matrix of covariates. Asymptotic likelihood theory implies
that b is normally distributed and allows estimation of its
variance–covariance matrix S so it follows that xTb is normally
distributed with variance s2¼xTSx. A 95% confidence interval
(CI) for the predicted carrier probability, f(xTb), was obtained by
applying f to the limits, xTb±1.96s, for the predicted log-odds.
A total of 29 (6%) of the 452 probands whose tumours had
undergone pathology review were found to be BRCA1 mutation
carriers. The odds of being a carrier depended strongly on the
morphology score, increasing on average by 80% (95% CI: 40–
240%) with each additional feature after adjusting for family
history and ER and PR status (P for trend o0.0001). Figure 1A
shows that mutation carriers tended to have higher morphology
scores than non-carriers; of the carriers, 27 (93%) had a
morphology score of 5 or more compared with 25% of all
probands. Figure 1B shows that, when restricted to probands with
a strong family history, the distribution of the morphology score
was bimodal. All 10 carriers with a strong family history also had a
morphology score of 5 or more, and these carriers comprised 48%
of all probands with a strong family history and a morphology
score of 5 or more.
Table 1 shows that some characteristics of family history were
associated with mutations status, but no family history feature
alone was highly sensitive (maximum 41%) and all had low
positive predictive values (o0.25%).
Table 1 also shows that, in contrast to family history features,
most morphological features studied were individually predictive
of BRCA1 mutation status, with four having smaller P-values
than even the most significant family history feature. In general,
the morphological features had high sensitivities (all but
three475%) and specificities (all but threeX65%). Moderate or
intense lymphocytic infiltrate, nuclear grade and little or no tubule
formation had high sensitivities but low specificities while
syncytial growth pattern, pushing margins and circumscribed
growth pattern had high specificities but low sensitivities.
The predictive features with crude OR410 were: trabecular growth
pattern, high mitotic index, and necrosis (sensitivityX79%,
specificityX65%, positive predictive value 0.14–0.32).
Of the 452 tumours reviewed, 154 had mitotic indices between
0 and 9/10 h.p.f. and of these 1 (1%) was a BRCA1 mutation
carrier, 115 had mitotic indices between 10 and 19/10 h.p.f and of
these 1 (1%) was a BRCA1 mutation carrier, 111 had indices
between 20 and 49/10 h.p.f. and of these 2 (2%) were BRCA1
mutation carriers and 72 had mitotic indices of 50 or more/10
h.p.f. (range 0–292/10 h.p.f.) and of these 25 (35%) were BRCA1
mutation carriers. A total of 74 tumours were scored to have
primary trabecular growth pattern and 36 were scored to have a
secondary trabecular growth pattern (all these 36 tumours were
scored to have a primary acinar growth pattern).
ER and PR statuses were both individually predictive of
mutation status, but while they had high sensitivities they did
not have high specificities and alone their positive predictive
values were each only 0.13. Being negative for both ER and PR was
Number of tumours
Number of tumours
BRCA1 mutation carrier
27/29 BRCA1 carriers
27carriers/107 tumours
BRCA1 mutation carrier
8/8 BRCA1 carriers
8 carriers /18 tumours
Figure 1
early-onset breast cancer with a strong family history (B).
Morphology scores of all early-onset breast cancer (A) and
Morphological predictors of BRCA1 germline mutations
MC Southey et al
British Journal of Cancer (2011) 104(6), 903–909
& 2011 Cancer Research UK
Clinical Studies
Page 4
associated with an OR of 5.3 (95% CI: 2.3–13.0), sensitivity of 70%,
specificity of 67% and positive and negative predictive values of 13
and 97%, respectively.
Figure 2 shows that the features within each of the three
categories (family history, morphology and immunohistochemis-
try) were strongly associated with each other. The morphology
features and ER and PR status were generally associated with each
other but not with the family history features.
When models containing multiple features were considered, the
best fitting model (as judged by BIC) included just three features.
These features and their jointly estimated ORs (95% CI, Wald
P-value) were: trabecular growth pattern, OR¼9.7 (2.6–47.0;
P¼0.001); high mitotic index, OR¼7.8 (2.7–25.7; P¼0.0003);
and number of first-degree relatives with breast cancer diagnosed
before the age of 60 years, OR for each relative¼2.7 (1.3–5.9;
P¼0.01). The area under the ROC curve for this model was 0.87
(95% CI: 0.83 to 0.90). The OR estimates for the two morphology
features were negatively correlated with each other (r¼?0.44) but
neither was correlated with the OR estimate for family history
(r¼?0.04 and 0.09).
Table 2 shows cross-validation estimates of the areas under the
ROC curves for models that included the most predictive features
from one or more of the three categories of morphology,
immunohistochemistry (comprising ER and PR receptor status)
and family history. It is apparent from Table 2 that the
morphology features have the greatest impact on the area under
the ROC curve, and that models that include the morphology
features are not improved by the addition of family history
variables or ER and PR status.
Under the best fitting model, the probability that a woman
diagnosed with breast cancer before age 40 years carries a BRCA1
mutation is exp(L)/[1þexp(L)] where the log-odds L is given by
the formula L¼?5.1544þ2.0539 xþ2.2750 yþ0.9784 z and: x is
1 if the woman's tumour has high mitotic index and 0 otherwise; y
is 1 if the woman's tumour has a trabecular growth pattern and 0
otherwise; and z is the number of the woman's first-degree
relatives who have been diagnosed with breast cancer before the
age of 60 years. A list of predicted probabilities for various values
of x, y and z are given in Table 3.
Table 1
OR with 95% CI and corresponding statistical significance (P), and the NPV, PPV, sensitivity (proportion of carriers with the feature) and specificity
(proportion of non-carriers without the feature)
For each feature potentially predictive of BRCA1 mutation status, the number (frequency in brackets) overall and by BRCA1 mutation status, the
BRCA1 carriers
BRCA1 non-carriers
Family history
One or more first-degree relatives with breast cancer o60years
One or more first- or second-degree relatives with ovarian cancer
Strong family history
One or more first-degree relatives with breast cancer X60years
One or more second-degree relatives with breast cancer
12 (41%)
2 (7%)
10 (34%)
2 (7%)
9 (31%)
48 (11%)
6 (1%)
61 (14%)
19 (4%)
126 (30%)
5.6 (2.5–12)
5.2 (0.74–24)
3.1 (1.3–7)
1.6 (0.24–5.9)
1.1 (0.45–2.4)
Morphological features
Trabecular growth pattern
High mitotic index
Circumscribed growth pattern
Moderate or intense lymphocytic infiltrate
Syncytial growth pattern
Malignant nuclear grade
Pushing margins (4 50%)
Little or no tubule formation
26 (90%)
23 (79%)
25 (86%)
18 (62%)
28 (97%)
8 (28%)
28 (97%)
2 (7%)
25 (86%)
84 (20%)
48 (11%)
148 (35%)
75 (18%)
339 (80%)
28 (7%)
361 (85%)
14 (3%)
319 (75%)
35 (12–150)
30 (12–85)
12 (4.5–40)
7.7 (3.5–17)
7.2 (1.5–130)
5.4 (2.1–13)
5 (1–91)
2.2 (0.33–8.3)
2.1 (0.79–7.2)
ER and PR status
ER negative
PR negative
23 (85%)
19 (70%)
153 (41%)
125 (33%)
8.3 (3.1–29)
4.7 (2.1–12)
Abbreviations: CI¼confidence interval; ER¼estrogen receptor; NPV¼ negative predictive value; OR¼odds ratio; PPV¼positive predictive value; PR¼progesterone
Figure 2
Each row and column corresponds to a feature (in the same order as in
Table 1) and the shading represents different levels of odds ratios (ORs), as
indicated in the figure. Odds ratios that were o1 were shaded the same
as their reciprocals.
Levels of association between the features listed in Table 1.
Table 2
logistic regression models whose predictors were restricted to one or
more of the categories of explanatory features given in the table 1
Cross-validation estimates of areas under the ROC curves from
No family history or ER or PR status
Family history alone
ER and PR receptor status alone
Family history and ER and PR status
—0.88 (0.85–0.91)
0.87 (0.83–0.90)
0.88 (0.85–0.91)
0.87 (0.83–0.90)
0.65 (0.61–0.70)
0.73 (0.68–0.77)
0.76 (0.71–0.79)
Abbreviations: ER¼estrogen receptor; PR¼progesterone receptor; ROC¼recei-
ver operating characteristic.
Morphological predictors of BRCA1 germline mutations
MC Southey et al
British Journal of Cancer (2011) 104(6), 903–909
& 2011 Cancer Research UK
Clinical Studies
Page 5
The fit of the best model was not improved by more than could
be attributed to chance by the addition of either ER and/or PR
receptor status. After adjusting for the three variables in the best
fitting model, the ORs (95% CI) associated with negative ER and
PR receptor statuses were 1.8 (0.5–7.1) and 1.5 (0.6–4.4),
respectively (both P¼0.3).
Of the 58 probands whose tumours had both high mitotic index
and trabecular growth pattern, 21 (36%) were BRCA1 mutation
carriers. Of the 332 probands who had neither of these
morphological features, only one (0.3%) was a carrier. Of the
123 who had one or both features, 28 were carriers, and this was
associated with OR¼98 (95% CI: 20–1750), sensitivity¼97%,
specificity¼78% and positive predictive value¼23%.
Of the 156 (34%) probands who had one or more of the three
features high mitotic index, trabecular growth pattern and one or
more first-degree relatives diagnosed with breast cancer before the
age of 60 years, 28 (18%) were carriers. Of the 70 probands who
had two or more of these three features, 24 (34%) were carriers.
Our study has shown that, by considering just two tumour
morphological features that could potentially be reported at the
time of diagnostic pathology, and one aspect of family history of
breast cancer, it is feasible to establish a simple way to identify
those young women with breast cancer who are most likely to
carry a BRCA1 germline mutation. Even if not supplemented by
the information on family history, a trabecular growth pattern and
a high mitotic index high were strong indicators of a woman's
BRCA1 mutation status. Moreover, knowing ER and PR status did
not improve the model predictions once the two morphology
features and a family history variable were taken into account. In
the context of breast cancers arising in young women, we found
that any BRCA1 predictive value of these two measures appears to
be subsumed by the two key morphological features. It would be
of interest to know if this applied to breast cancers in women with
later age at diagnosis.
For our population-based sample of women with early-onset
breast cancer, if BRCA1 screening had been restricted to those with
a strong family history then we would have screened 71 cases and
found 10 carriers (14%). If instead we had screened those with a
high mitotic index, we would still have screened 71 cases but found
23 carriers (32%), more than twice as many. If we also screened
those with a trabecular growth pattern, we would have screened a
further 53 cases and found another 5 carriers (10%). Therefore,
screening those with high mitotic index and/or trabecular growth
pattern would have found 28 BRCA1 mutation carriers in 124
women screened (24%) and missed only one carrier. Screening
only one-quarter of early-onset cases based on just these two
morphology features would have been sufficient to identify almost
all carriers, without any reference to family history.
Table 2 shows the area under the ROC curve (AUC), an omnibus
measure of a model's predictive power. Knowing family history in
addition to the morphology features made no improvement in the
AUC. The AUC based on family history alone was less than that
based on ER and PR, and when used together was still less than the
AUC based on the two key morphology features alone. In terms of
predictive strength, the traditional indicators – measures of family
history – were weaker than most of the morphological features.
Our family history data are likely to be no less accurate and
complete than family history data collected in a clinical setting.
This work has also identified a fascinating group of early-onset
breast cancers that share the morphological features of early-onset
breast cancers that carry identifiable BRCA1 mutations. These are
the cancers, illustrated in Figure 1A, that have a morphology score
of 5 or more but, despite extensive testing, are from women for
whom we have not been able to identify germline BRCA1
mutations. We performed further BRCA1 mutation screening on
DNA samples from the women whose tumours had mitotic indices
over 50 per 10 h.p.f. and a trabecular growth pattern and who
were not already known to carry a mutation in BRCA1 (n¼37).
(The mutation testing that had been performed on DNA from these
women was varied because of the previous mutation testing
strategy described above in the methods). A further two BRCA1
mutations, BRCA1 del1A-23 and BRCA1 delexon20, were identified
by MLPA testing. The woman with the BRCA1 del1A-23 mutation
had breast cancer diagnosed at the age of 33 years and a paternal
grandmother with breast cancer diagnosed at age 71 years
(verified). The women with the BRCA1 delexon20 mutation had a
breast cancer diagnosed at the age of 31 at recruitment, and
subsequently another at age 35 years, and had an unverified report of
breast cancer in a paternal grandmother (age at diagnosis unknown).
Using tumours from multiple-case breast cancer families with on
average later age at onset than in our series, Lakhani et al (1998 and
2002) carried out similar studies to ours to try to identify BRCA1
mutation carriers on the basis of pathology and immunohistochem-
istry. The ORs for prediction they found were somewhat lower than
we observed for early-onset cases. This might be due to a potential
change in morphological features associated with BRCA1 germline
mutations in postmenopausal women that could be due to non-
germline factors, such as oestrogens and methylation (both known to
have a changing role with increasing age).
From our data and model fit, we have calculated the predicted
probability of carrying a germline BRCA1 mutation based on the
two morphology features and family history: see Table 3. It can be
seen that 15% of our sample had predicted probabilities 410%
(68 women in 7 categories). On the other hand, for the group of
women who had none of the three predictive features, comprising
66% of our sample (299 women), the predicted probability was
Table 3The predicted probability that a woman carries a BRCA1 mutation according to the best fitting logistic regression model
growth pattern
High mitotic
Number of first-degree relatives diagnosed
with breast cancer before age 60 yearsn (%)
Predicted percent probability of
carrying a BRCA1 mutation (95% CI)
299 (65.7%)
29 (6.4%)
4 (0.9%)
11 (2.4%)
2 (0.4%)
0 (0%)
42 (9.2%)
9 (2%)
1 (0.2%)
43 (9.5%)
11 (2.4%)
2 (0.4%)
1% (0–2%)
2% (0–5%)
4% (1–18%)
4% (1–16%)
11% (2–36%)
24% (4–69%)
5% (2–14%)
13% (5–31%)
28% (8–65%)
30% (19–44%)
54% (36–71%)
76% (44–92%)
Abbreviation: CI¼confidence interval.
Morphological predictors of BRCA1 germline mutations
MC Southey et al
British Journal of Cancer (2011) 104(6), 903–909
& 2011 Cancer Research UK
Clinical Studies
Page 6
only 1%. This information could be clinically useful in helping
decide where limited resources for counselling and mutation
testing for BRCA1 carriers in women with early-onset breast cancer
might best be directed.
Therefore, our data suggest that is possible to institute a
pathology-based and more sensitive and specific method for
prioritising women with early-onset breast cancer for BRCA1
mutation testing, similar to that which already applies to colorectal
cancer and the DNA mismatch repair genes (Boland et al, 1998;
Vasen et al, 1999; Southey et al, 2005; Lenz, 2005; Mead et al,
2007). We intend to undertake an independent study to further
improve our algorithms, and we encourage others to try to validate
and extend this approach, especially to later-onset disease.
Pathology review, with attention to a few specific morphological
features of invasive breast cancers, can identify almost all BRCA1
germline mutation carriers among women with early-onset breast
cancer without taking into account family history.
The Australian Breast Cancer Family Registry was supported by
the National Health and Medical Research Council of Australia, the
New South Wales Cancer Council, the Victorian Health Promotion
Foundation (Australia) and the National Cancer Institute, National
Institutes of Health under RFA-CA-06–503 and through coopera-
tive agreements with members of the Breast Cancer Family
Registry (CFR) and PIs. The University of Melbourne (U01
CA69638) contributed data to this study. The content of this
paper does not necessarily reflect the views or the policies of the
National Cancer Institute or any of the collaborating centres in the
CFR, nor does mention of trade names, commercial products or
organisations imply endorsement by the US Government or the
CFR. We extend our thanks to the many women and their families
who generously participated in the Australian Breast Cancer
Family Registry and consented to us accessing their pathology
material. We also thank the many study staff who made this work
possible, the study Pathologists, Jane Armes, Deon Venter, Elena
Provenzano, Sarbar Napaki and Beena Kumar, who worked to
review and score the material presented in the study and Veronika
Gazdik and Simon Royce for their expert technical support. JLH is
a National Health and Medical Research Council Australia Fellow.
MCS is a National Health and Medical Research Council Senior
Research Fellow. JLH and MCS are both group leaders of the
Victoria Breast Cancer Research Consortium. KAP is the Cancer
Council Victoria Dr John Colebatch Clinical Research Fellow.
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Morphological predictors of BRCA1 germline mutations
MC Southey et al
British Journal of Cancer (2011) 104(6), 903–909
& 2011 Cancer Research UK
Clinical Studies


text:
ADE is pleased to welcome District Wellness Coordinator, Rachel Hurshman, for a special professional development event on Local Wellness Policies. Please join us on March, 2015 at the Desert Willow Conference Center in Phoenix, AZ. You may register here: www.surveymonkey.com/s/LWPRegistration
Local Wellness Policy: Professional Development Event
Stanfield Elementary School achieves Arizona's first and only Gold of Distinction HealthierUS School Challenge (HUSSC) Award!
Stanfield Elementary School achieves Arizona's first and only Gold of Distinction HealthierUS School Challenge Award!
Principal Dr. Chris Lineberry arrived at Stanfield Elementary School District with a personal mission to pursue and achieve USDA's prestigious HealthierUS School Challenge (HUSSC) award for school excellence in nutrition and physical activity promotion. Not only had he seen the academic rewards of including nutrition and physical activity in previous schools, but he had also personally benefitted from such healthy lifestyle changes after a serious life-changing event. Superintendent, Dr. Melissa Sadorf, was in complete agreement that going for USDA's top honors, the "Gold of Distinction" HUSSC award, was the best strategy for Stanfield and students.
Fortunately, Director of Dining Services, Verta Bedwell, Jessica Krug RD, and PE teacher, Yvette Hernandez were already working on the HUSSC application, and Stanfield was well on its way to meet all criteria. They all worked diligently to achieve staff buy-in, excellent meals, strong nutrition policy, and exemplary physical education. They provide 180 minutes per week of physical education for elementary students and 285 minutes per week in middle school, to qualify for Gold of Distinction honors!
Presentation of the HUSSC plaque and banner will take place at their February 12th School Board meeting, followed in the spring by a school-wide celebration of their Gold of Distinction HealthierUS School Challenge Award! The district will also receive $2000 as part of this 4 year award. ADE congratulates Stanfield Elementary in attaining the top honors, leading the way as Arizona's first!
For information on how your school can achieve the new streamlined HUSSC: Smarter Lunchroom (HUSSC: SL) criteria, contact Gayle McCartney (602) 364-3177 and visit www.fns.usda.gov/hussc .


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Brave Cowboy
Brave Cowboy (Paperback)
By Edward Abbey
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The Brave Cowboy
Jack Burnes is a loner at odds with modern civilization. A man out of time, he rides a feisty chestnut mare across the New West -- a once beautiful land smothered beneanth airstrips and superhighways. And he lives by a personal code of ethics that sets him on a collision course with the keepers of law and order. Now he has stepped over the line by breaking one too many of society's rulus. The hounds of justice are hot in his trail. But Burnes would rather die than spend even a single night behind bars. And they have to catch him first.
About the Author
Edward Abbey spent most of his life in the American Southwest. The author of numerous works of fiction and nonfiction, including the much celebrated Desert Solitaire, which decried the waste of America's wilderness, Abbey was one of the country's foremost defenders of the natural environment. He died in 1989.


text: WOW Be here. August 15-23 A week long event filled with opportunities to become a part of campus, get involved, meet other Cougs, and have fun before classes start. Saturday, August 15 and Sunday, August 16 (Move-In/Relationship Building) Faculty, staff and current students will help welcome new students and their families and assist in the move-in process. Residence Life will host community programs and Student Involvement and University Recreation will facilitate relationship and connection building events. University departments and groups may also host experiential activities and workshops students will pre-register for. Monday, August 17 (Academic Foundations) The Office of Undergraduate Education and Health and Wellness services will host academic success sessions and academic support workshops aimed at preparing students and fostering an environment of intellectual engagement. The Compton Union Building will host a student job fair and the Office of Diversity Education will partner with New Student Programs on a diversity education event. Tuesday, August 18 (Coug Connections Day) Coug Connections will focus on helping students foster connections and build a support system based on their various values and social identities. This is inclusive of social relationships and connections to university resources, faculty and staff. These connection and introduction programs will take place throughout the day with a carnival focused broadly on being a Coug rounding out the events. Wednesday, August 19 Academic Colleges will host kickoff events to showcase what it means to be a member of each college and to foster excitement for the semester and years ahead. Colleges will also share services and resources for their students and involvement and leadership opportunities. Residence Life will sponsor a healthy relationships and consent speaker in the early evening and the Light Up the Night dance will cap off the days events. Thursday, August 20 (wsYOU Conference) The wsYOU Conference will focus on creating interactive sessions and experiential opportunities aimed at the developmental needs of first year students in transition. Staff and students can submit conference proposals. A concert sponsored by the Compton Union Building will be the signature evening event. Friday, August 21 (Celebration of Scholars) Following past tradition, University Convocation will kick-off the day and be followed by the All-campus Picnic featuring a campus and community fair. The Lentil Festival and Stimson Hall's Green M & M Dance will be the evening entertainment. Saturday, August 22 and Sunday, August 23 (Community Engagement and Connections) Saturday will be a mainly social and community event day featuring the Lentil Parade, Lentil Festival concerts and the Welcome Back Up All Night. There will also be another opportunity for university departments and groups may also host experiential activities and workshops students will pre-register for. Sunday will feature University Recreation's annual Backyard Bash, Conexion, and a Transfer social and welcome event. The complete WOW 2015 schedule will be available in early June. Please check back from more information! Required Programs All incoming students are required to complete the following workshops and activites during the Week of Welcome. Students living in the residence halls will be assigned workshop times when they check into their residence hall. All other students need to sign up on their own using the links below. Student who do not complete these sessions will have a hold placed on their account preventing them from registering for classes for future semesters. Booze, Sex, and Reality Checks Two requirements for incoming First Year and Transfer students (under the age of 21) during WOW: In person Booze, Sex, & Reality Checks workshop Personalized feedback survey on alcohol use (E-CHUG) Visit adcaps.wsu.edu/realitychecks for more information. Green Dot Workshop All incoming freshman and transfer students (post-baccalaureates, part-time, and non-degree seeking students excluded) are required to attend this mandatory workshop. Green Dot is a research-informed, theory-driven violence prevention curriculum designed to enhance bystander skills around recognizing gender-based violence (partner violence, sexual violence, and stalking) and intervening in potentially dangerous situations. The Green Dot workshop during Week of Welcome will introduce the basic elements of the program – recognizing and responding to situations that could be high risk for violence. Visit hws.wsu.edu/WOWgreendot for more information.


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Texas A&M's Johnny Manziel Drops Out of Heisman Trophy Race
After a 34-10 loss to LSU on Saturday night Texas A&M quarterback Johnny Manziel has much to think about, with questions abounding regarding if – and really when – he will announce an intention to enter the 2014 NFL Draft. But while this will provide food for thought for the near future, one thing that the quarterback can cross off his wish list is winning the Heisman Trophy, as his performance on Saturday afternoon was absolutely awful.
Throughout the game Manziel was constantly hassled by LSU defenders, who made it their mission to hit the quarterback as many times as possible. This strategy worked to great success, as after cutting off the run game of Texas A&M they were able to get to the quarterback and subsequently block all of his passing lanes. For the night he completed 16 of 41 passes for 224 yards, one touchdown and two interceptions, which was by far his worst game of the 2013 season.
On the whole of the season, Manziel has thrown for 3537 passing yards, 32 touchdowns and 13 interceptions, while running for an additional 665 yards and 8 touchdowns on the ground. This has contributed for 62.5 percent of the team's offensive touchdowns, 69.1 percent of Texas A&M's total offense and has made the quarterback the undoubted most valuable player in college football.
Unfortunately, the Heisman Trophy is not decided solely on personal statistics, but also relies heavily on the success of a player's team. For Manziel this will be a key stumbling block, as the loss on Saturday dropped Texas A&M to 8-3 in 2013 and effectively ended any chances of appearing in a BCS Bowl.
When this is compared to the three main competitors for the Heisman Trophy– Jameis Winston, AJ McCarron and Bryce Petty – there simply is no comparison. Winston, Petty, and McCarron are all but locks to play in BCS Bowls this season – two of the three will most likely play in the National Championship game – and therefore have a huge part of their resume filled that Manziel will be missing.
After considering the fact that only five out of the last 43 winners of the Heisman Trophy have lost three games or more, it becomes clear that their is little chance Manziel wins the award in 2013. When it is also considered that his statistical output does not significantly stand out from that of his competitors for the award, it is shown that these slim chances drop down to no chance, and that the quarterback is better off wishing he gets drafted high in the 2014 NFL Draft.
Tyler Leli is a Washington Capitals writer for Rant Sports. Follow him on Twitter, "Like" him on Facebook or join his network on Google.
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