Healthiculture - Why Anti-inflammatories Don't Work For Fibromyalgia?
Why Anti-inflammatories Don't Work For Fibromyalgia?
Anti-inflammatory drugs are usually the very first medication doctors prescribe to fibromyalgia patients to help alleviate their pain. It is also what many fibromyalgia patients would turn to during early years of their condition. However, it wouldn't take long for many to realize that this class of drugs are not effective for fibromyalgia.
Most over the counter painkillers such as Ibuprofen (Advil), Naproxen (Aleve) fall under the class of non-steroidal anti-inflammatories (NSAIDs) analgesics. As the name suggest, NSAIDs drugs reduce pain caused by inflammation which can result from an infection, an injury or an illness.
Inflammation is often misunderstood or misused. Most people use the word inflammation and infection interchangeably causing a misconception of the meaning of an inflammation. While infection is the cause of an attack of foreign substance such as bacteria or virus on body cells, inflammation, on the other hand, is a defensive process initiated by our body in response to harmful stimuli and our body's attempt to heal itself. Inflammation can cause swelling, redness, hotness and pain.
Under normal circumstances, inflammation is a benign, however, it can become malignant when our body is not able to control it, leading to chronic inflammation which are seen in illness like asthma, chronic sinusitis, rheumatoid arthritis, Crohn's disease etc.
So why exactly do anti-inflammatories not work for fibromyalgia?
Is Your Bra Causing You More Pain?
Emily is a certified physiotherapist which has a burning passion for. She has helped many fibromyalgia patients manage and control their chronic pain problems. Her other passion is writing, she writes about pain issues during her free time.


Howdy friends, As ICAI took exams of CA Final in May 2017 and the result of CA Final also declared. Indeed, many students who applied for the verification of answer sheet have shared some certified copies on Facebook to share.
Download below CA Final May 2017 Auditing & Professional Ethics Certified Copies in PDF.
CA Final May 2017 Adv. Auditing & Pro. Ethics certified copies are available for download from below given link.
We will also upload other subjects certified copies here very soon. Subscribe to our free updates and keep checking our site for free certified copies to download. You can share with your friends who may need this certified copies.
This is best website to get daily free downloads and good information.


text:
Breckenridge je město ve střední části Colorada, ve Spojených státech amerických. Leží v okrese Summit County, přibližně 100 km jihozápadně od Denveru. Město bylo založeno roku 1859. Okolo 250 původních budov ve městě je zapsáno v Národním registru historických míst (National Register of Historic Places).
Breckenridge má rozlohu 15,5 km2 a žije zde okolo 4 500 obyvatel.

Historie
Město bylo založeno jako jedno z prvních v Coloradu, kde se těžilo zlato. Ve 40. letech 20. století byla těžba ukončena, což vedlo k odchodu velkého počtu obyvatel. Na počátku 60. letech zde byl otevřen jeden z prvních velkých resortů sjezdového lyžování. Od té doby město žije především z turistického ruchu.

Geografie
Breckenbridge leží v údolí obklopeném horami pohoří Mosquito Range, respektive jeho severního výběžku nazývaného Tenmile Range. Některé vrcholy hor mají nadmořskou výšku vyšší než 4 000 metrů. Mosquito Range je součástí Jižních Skalnatých hor. Lesy v okolí jsou součástí Arapaho National Forest.

Podnebí
Breckenridge má subpolární podnebí. Léta jsou mírná až teplá, zimy velmi chladné se sněhem. Srážky se vyskytují v průběhu celého roku, kulminují v červenci a srpnu. Celkový roční úhrn srážek je 515 mm.

Reference

Externí odkazy

Města v Coloradu

redpajama_set_name: RedPajamaWikipedia


Trustchain is specifically designed for storing identity and creating trust. Trustchain provides full control, real privacy, and strong security.
Self-sovereign identity puts people in charge their own digital identities. With our self-sovereign identity solution individuals are freed from profit-driven entities, such as Facebook, to give them an identifier. You now create your own identity, legally own it and control it along with what information is shared with whom under what conditions. Ownership creates control, transparency and helps build trust. We created a fully functional prototype of a self-sovereign identity. Strong identity is directly build inside Trustchain. Our approach containts vital improvements upon previous work, it does not require a smart contract, governance foundation or other complexity.
We put your digital identity in your smartphone. We have created an "identity wallet" or "digital passport" for your smartphone. What you keep in our "important drawer" at home is under your full control, such as passports, birth certificates, utility bills. We aim to offer the same control, privacy and security on your smartphone. Our open source based infrastructure centers on people and enables a whole new ecosystem to flourish.
The Netherlands is the first country in the world to experiment with self-sovereign identity. The state should provide a digital identity infrastructure as a principle of constitutional law. Delft University of Technology and the government are ready to conduct the first small-scale tests with real citizens. This technology is not yet ready to be widely available. In 2018 citizens in selected municipalities can request this new blockchain-based identity. It does not require a plastic card, just your smartphone. We envision that one day this technology can be used for opening a bank account, boarding your flight, or creating a startup. However, that remains the future. This is applying the latest technology for security: the blockchain. Scientists at Delft University of Technology have been studying ledger technology and blockchains for over 10 years. Our IETF Internet Standard draft of Trustchain will be used for this trial.
The provider of the paper-based passport is using biometrics to authenticate people and establish trust. That is the hard condition of the government of our Kingdom to recognize our open source self-sovereign identity, it needs biometric authentication. We developed an open API between our open source work and the biometrics. We developed alternatives for traditional biometrics. It provides security based on laws of physics. You can't easily replace fingerprints or facial features once they are compromised. Our biometrics solution takes a fingerprint of hardware you buy. This is much less invasive and in the future could be put inside smartphones. It would make every smartphone in the world unique and impossible to clone. We have developed the first software-based physical unclonable function (PUF device) which is fully open source.
Scientific details of this work can be found here, "Deployment of a Blockchain-Based Self-Sovereign Identity". This work has been accepted for publication at IEEE Blockchain.
Below is a demo of our integration with DigiD, MijnOverheid and GitHub. You can read more about this implementation on https://tlswitness.org/.
TU Delft is home to the largest European research groups on blockchain technology. Our work combines running code with novel approaches to broaden and strengthen the cybercurrency field. We aim to provide a secure, scalable, cybercurrency without forks and without the need for confirmations.


Give us your parameters and our Chemists will design a recipe to fit your needs. RRT can adjust its process criteria & ingredients to mesh smoothly with your other compound components.
RRT's Unique Patented Thermo-Chemical Process lends itself to batch production from as little as 2,000 pounds to millions of pounds - it combines a Boutique with a Super Store!!
Reliable Rubber Technologies' rigid Quality Control ensures consistency from batch to batch as demanded by its Customers.


text:
De La Hoya hinting Canelo vs. Golovkin 3 coming soon
November 4th, 2018 - Comments Closed
By Dan Ambrose: Golden Boy Promotions CEO Oscar De La Hoya dropped a big hint on this weekend about a trilogy fight between Saul Canelo Alvarez and Gennady Golovkin taking place soon by showing a photo of the two fighters, and saying on social media, 'Great fights are good for boxing." With Canelo signed with DAZN for the next five years as part of an 11-fight deal, it's imperative that good fights like Canelo-GGG3 take place sooner rather than later.
Some fans think the controversial decisions that impacted Golovkin's career has hurt boxing in a major way, making the fans distrust the judging and seeing certain fighters getting special treatment when they face guys they can't beat based on their own talent. It looks bad that 48 out of 50 ringside boxing media saw GGG winning the rematch against Canelo last September. This comes after Golovkin was seen as a clear winner in the first fight against Alvarez in 2017.
Canelo needs to fight Golovkin (38-1-1, 34 KOs) in a third fight to clear up the controversy of the first two fights, both of which resulted in controversial decisions at the the T-Mobile Arena in Las Vegas, Nevada.
The boxing public is less than excited about Canelo's upcoming December 15 against WBA 'regular' super middleweight champion Rocky Fielding (27-1, 15 KOs), which makes it even more important than ever that Golden Boy Promotions sets up with the trilogy fight with Alvarez and Triple G. The boxing fans don't want to see Canelo fighting obscure champions they've never heard of and don't care about. To bring in the subscribers on DAZN,
Great fights are good for boxing 🥊 #Goldenboyforboxing pic.twitter.com/lRN0suCEfi
— Oscar De La Hoya (@OscarDeLaHoya) November 4, 2018
It's important that De La Hoya makes the Canelo vs. Golovkin3 fight before Alvarez suffers another suffer and the boxing public loses interest in a third fight between him and GGG. Now that Canelo is the World Boxing Council middleweight champion, there's tremendous pressure on him and the WBC to make the fight against interim WBC 160 lb champion Jermall Charlo (27-0, 21 KOs). Charlo and Daniel Jacobs are both fighters that have the size, speed, power and talent to beat the short 5'8″ Canelo. That makes it extremely important that De La Hoya and Golden Boy matches Canelo against Golovkin while they still can. After Canelo loses again, it's going to cause the fan interest in that fight to fizzle out. As it is, there's a good chance that the fans aren't as interested in seeing a third fight due to the controversial decisions in the firt two fights between Canelo and Golovkin. When fans lose faith in the process and feel that the system of scoring the fights are flawed, then they won't want to continue to invest their time in watching the bouts.
NEWS: Eddie Hearn wants Dmitry Bivol to challenge Canelo Alvarez at 168 for undisputed in September in "ideal world"
The sooner De La Hoya makes the Canelo-GGG3 fight the better it will be for Canelo and Golden Boy Promotions, since the boxing public thinks that Golovkin was robbed twice in the first two fights. Canelo needs to prove that he can beat Golovkin in a non-controversial way with judging that makes sense to the fans. The fans think Golovkin won the first fight against Canelo by an 8 rounds to 4 score last year in September 2017. In their rematch on September 15 of this year, the fans overwhelmingly saw Golovkin winning a close decision. Some fans saw the fight as a draw, but only a small percentage felt that Canelo deserved a win. That's bad for Golden Boy that the boxing public saw Canelo losing again to Golovkin, reason being that it entirely invalidates the victory for the Mexican star, making him look like a pampered fighter, who only wins fights due to him competing in Las Vegas.
Golovkin landed more shots than Canelo in both fights, and made sure that he kept the Mexican star in the center of the ring in the rematch. Golovkin didn't allow Canelo to fight against the ropes and run like in the first fight. Although much was made about Canelo backing Golovkin up during the rematch, the fact is GGG only backed up to the center of the ring. At no time did Golovkin back up against the ropes, which means that he intentionally backed up against Alvarez so that he could keep the action in the center of the ring. Golovkin didn't want to have to chase Canelo for 12 rounds, and he knew that if the Golden Boy star fought against the ropes, he would be running all night long in big circles. The only fighter that was against the ropes in the Canelo-GGG2 rematch was Canelo. Golovkin didn't back up against the ropes.
NEWS: Dmitry Bivol to fight in late April or early May, undecided on Canelo rematch at 168
The rumors are that after Canelo faces – and beats the over-matched Fielding – on December 15, he's going to fight new IBF middleweight champion Daniel 'The Miracle Man' Jacobs (35-2, 29 KOs) on May 4, 2019 on the Mexican holiday Cinco de Mayo in Las Vegas. That's a fight that Jacobs and his promoter Eddie Hearn of Matchroom Boxing USA/DAZN are both calling for. Hearn is sounding so confident that the Jacobs vs. Canelo fight will be taking place that he's talking about the fight night and day. If the Canelo-Jacobs fight does get made in 2019, it would help De La Hoya fulfill his goal of wanting to bring great fights to DAZN. Obviously, De La Hoya has more than just Canelo to help make good fights for DAZN. He also has good fighters in his Golden Boy stable like super featherweight contender Ryan Garcia and David Lemieux. Those fighters will be be matched against good opposition. Lemieux is fighting Tureano Johnson on the undercard of Canelo-Fielding on December 15.
Canelo was popped on a drug test by VADA last February in testing positive for clenbuterol. This led to a six-month suspension for the Golden Boy star. That obviously looked bad for boxing to see one of the biggest stars in the sport testing positive for a banned substance.
NEWS: Dmitry Bivol could face Joshua Buatsi next says Eddie Hearn
A lot of boxing fan think Canelo should have five losses on his resume from his 2 fights against GGG, and his matches against Floyd Mayweather Jr., Austin Trout and Erislandy Lara. With all that, it's in Canelo's best interest to fight only the best from this point on in his career, and focus on fighting in venues that are considered neutral and not ones where there's a history of him receiving controversial decisions.
« Nonito Donaire revitalizes career beating Ryan Burnett
Bellew: I'll find a way to defeat the monster [Usyk] »
More boxing news on: Canelo vs. Golovkin 3, DAZN ,Canelo Alvarez, Gennady Golovkin, Oscar De La Hoya
Boxing News 24 » De La Hoya hinting Canelo vs. Golovkin 3 coming soon

redpajama_set_name: RedPajamaCommonCrawl


text:
Why GPS Insight
Looking to Switch?
Why Switch to GPS Insight?
CEO / Owner
CFO / Accounting
Safety / Risk
GPS Insight Press Releases
GPS Insight Ranked on Deloitte Technology Fast 500 for Third Consecutive Year
GPS Insight ranked 478 on Deloitte's Technology Fast 500™, a ranking of the 500 fastest growing technology, media, telecommunications, life sciences and clean technology companies in North America.
Live Webinar: How to Introduce GPS to Your Employees
GPS Insight will be hosting a webinar on Wednesday, November 13th at 10am PST, titled "How to Introduce GPS Tracking to Your Employees".
GPS Insight Moves Headquarters to Landmark Building in Scottsdale, AZ
GPS Insight, a technology leader in GPS fleet tracking software, moved their headquarters to the top floor of the iconic Henkel Building in Scottsdale, AZ on October 1st, 2013.
GPS Insight Selected as a Finalist for ASU Spirit of Enterprise Awards
GPS Insight was named a finalist in the 17th annual Spirit of Enterprise Awards from the W.P. Carey School of Business at Arizona State University.
GPS Insight Ranked on the 2013 Inc. 5000 for the Fourth Consecutive Year
Inc. magazine ranked GPS Insight number 3,294 with three-year sales growth of 97% on its seventh annual Inc. 5000, an exclusive ranking of the nation's fastest-growing private companies.
NuBilt Uses GPS Fleet Tracking Solution to Ensure Quick Emergency Response
GPS Insight allows NuBilt to take full control of their fleet. They are now able to keep the cost of fuel down, monitor driver behavior and location, and dispatch their team more efficiently than ever before.
GPS Insight Wins Silver in Best in Biz Awards 2013 International
GPS Insight has been named the silver winner in the Enterprise Product of the Year category for the Best in Biz Awards 2013 International.
GPS Insight Named American Technology Award Winner
GPS Insight was named the winner in the Software category for the American Technology Awards for the second time. GPS Insight was named the winner for the same award in 2011 as well.
GPS Insight Named as American Technology Awards Finalist
GPS Insight has been named a finalist in the software category for the 2013 TechAmerica Foundation American Technology Awards (ATAs). GPS Insight was honored to win the award in 2011 and hopes to win again this year.
DVIR
© 2020 GPS Insight


text:
On What... Life
Art is about Legacy
On What it Means to Live an Artful Life
A love note, an authentic dish cooked with care, and a beautiful story, art is something that an artist is communicating with the people close to him, close to the heart.
Art is an expression to carry forward the legacy of who you are to those who love you.
What Does it Mean to Live a Healthy Life?
This is one of the central questions that our community is working to answer. For my part, I started asking this question when I decided that exercising and eating healthy, while important, is a painfully limited view of what it means to live a healthy life.
The act of creating things is one of the best ways to avoid living a short, unimportant life. You get to contribute something to the world around you.
Creating new experiences hel...
Too often, however, we take for granted the opportunity that our health gives us to live a life that's true to us.
To accomplish the things we dream about, we are required to be makers, explorers, and creators. We are required to move and become active participants in life.
Human beings are the most social creatures on planet earth. So, you're not really living a healthy life if it doesn't involve others.
The people you connect with will have a huge influence on you: Those who have already walked through the fire can help you do the same. And those who haven't will make it seem impossible for you to do so.
The Art of Mindful Communication
huffpost.com
I like to think of the way we speak with one another as the "Art of Communication." There are courses taught on this subject, but it seems to be geared towards strengthening public speaking and writing skills, which is great if you're going into public speaking.
Talking to another person mindfully should be because you're wanting to "connect" with whomever you're speaking with from a place that is present, kind and respectful.
We have the oppo...
Bring out the "best of yourself"
Make a conscious effort to bring out the best in someone else through your communication.
This makes communicating less "me-centric," which is talking to hear yourself talk, or talking "at" someone rather than "with" them, or being more interested in wanting to "capture" their attention for some kind of pay off.
Consider communication as an empty canvas to paint with words, think of all of the wonderful and beautiful things you can say to another person.
It's helpful to know that what we say to someone else, might not be what we would want said to us.
Is It Even Possible to Define What Art Is, Exactly?
thoughtco.com
There are many things that contribute to the definition of art. Explore the history, philosophy, value, and meaning of visual art.
Defining Art
Art does not have a universal definition, though it is generally believed that it is an intentional and conscious creation of something that requires imagination and skill.
It can ...
Defining Art Through History
From the 11th century until the end of the 17th century, the definition of art was anything that was done with expertise, with the result of knowledge and practice.
The Romantic period of the 18th century, beauty became the main criteria for defining good art. Nature, spirituality and free expression were sought after and well received.
The 19th Century started the Avant-garde art movement, with art becoming real, modern, futuristic and surreal. Whatever the definitions, the originality of art stands out as a time-tested measure, with new genres and manifestations like performance art, digital art, and electronic art.
Philosophy of Art
Art as Representation or Mimesis. Representation of art as an imitation or copying became the mainstream meaning of art in Greece. Plato first developed the idea of art as "mimesis," which, in Greek, means copying or imitation. How immaculately it replicated the original subject became the measure of its value.
Art as Expression of Emotional content. Dramatic, sublime and heartfelt art becomes a way to express oneself during the Romantic movement , with audience response becoming key to the valuation of the content. The emotions that were felt when the art was witnessed became its barometer for success.
Art as Form. Formal qualities of art became influential in the 18th century, with the principles of art and design, like balance, rhythm, harmony and unity became as important as the content of the work of art.


text:
Compromise Bill Would Allow 4.0% Alcohol By Weight Beer In Grocery Stores
By Nicole Nixon • Mar 13, 2019
iStock.com / TrongNguyen
A push to raise the limit on beer in grocery stores is back at the State Capitol after legislation hit some turbulence last week.
The compromise, unveiled Wednesday, would raise the cap on beer sold in grocery and convenience stores — and on tap — from 3.2 percent alcohol by weight to 4.0 percent.
Sen. Jerry Stevenson, the legislative lead for the alcohol bills, was pushing for 4.8 percent. But a House committee gutted Stevenson's bill last week, shelving the proposed cap for a task force to study whether the change is really necessary.
Demand for 3.2 percent beer has fallen in recent years as states including Colorado and Oklahoma have allowed stronger brews in grocery stores. That has led big manufacturers to stop making some products.
Stevenson said going to a limit of 4.0 percent would keep about 88 percent of product labels on store shelves in Utah.
"It's not certainly where we wanted to go, but I think we can get there eventually. It might take years" to get to 4.8 percent, the Layton Republican said.
The new version of the bill would keep the task force, though its makeup would be tweaked slightly.
Response to the new proposal is mixed. The Church of Jesus Christ of Latter-day Saints had opposed the 4.8 percent limit, but its lobbyist said the Church will not object to the new compromise.
"We believe the proposed compromise represents a significant improvement over the original bill," the Church's chief lobbyist Marty Stephens said in a statement. "Although we still have concerns, we do not oppose the compromise bill as drafted and look forward to reviewing the results of the interim study group."
Kate Bradshaw with the Responsible Beer Choice Coalition acknowledged that big alcohol changes are difficult to get through the Legislature and called the compromise a "baby step."
"It's a compromise. We feel the glass is half full but it's not all the way full," she said.
Bradshaw's group had threatened a ballot initiative to put stronger beer and wine in grocery stores if lawmakers did not pass Stevenson's original bill. If the new version passes, a ballot initiative would be off the table "for at least right now," she said.
"It's expensive and it takes a lot of time. The earliest you could start for a 2020 ballot initiative would be April of 2019" — just one month from now, Bradshaw said.
The Utah Brewers Guild, a group of local breweries, opposed Stevenson's original bill. Citing mixed support from its members, the guild will remain neutral on the new version.
The Guild is not taking a position on the new 4% ABW limit deal because some brewers are for it and some brewers do not support it. All of these voices are valid. We don't always agree with each other on everything, but the Utah craft beer community is a family. #utpol #utleg
— Utah Brewers Guild (@UtahBrewers) March 13, 2019
#utpol
Update: House Committee Pours Cold Water On Beer Bill, Proposes Task Force Instead
By Nicole Nixon • Mar 6, 2019
Austen Diamond for KUER
Updated 3:30 p.m. MST 3/6/19
A bill to raise the alcohol limit of beer sold in grocery and convenience stores from 3.2 percent alcohol by weight to 4.8 percent met stiff resistance in a House committee Wednesday morning and was changed substantially before getting the green light.


Vonceil Farr, 92, of Morgantown, passed away Tuesday, June 26, 2018, at the Madison.
Friends and family will be received at Wesley United Methodist Church, in Morgantown, from 10-11 a.m., on Saturday, July 7, with the funeral service to follow with the Rev. Dr. Randall Flanagan officiating. Interment will follow at Beverly Hills Memorial Gardens in Westover.
A full obituary will appear in a future edition of the Dominion Post.


text:
Peacekeeping Missions
Canadian soldiers on a peacekeeping mission, Haiti, 2013.
Canada's role in the development of peacekeeping during the 20th century led to the establishment of Canada as a prominent world power. Canada's commitment to multilateralism has been closely related to peacekeeping efforts. Canadian Nobel Peace Prize laureate Lester B. Pearson is considered to be the father of modern United Nations Peacekeeping. Prior to Canada's role in the Suez Canal Crisis, Canada was viewed by many as insignificant in issues of the world's traditional powers. Canada's successful role in the conflict gave Canada credibility and established it as a nation fighting for the common good of all the world's nations and not just their allies.
More than 125,000 Canadian Armed Forces members have served in dozens of international peace missions to more than 35 countries over the past six decades. Approximately 130 Canadians have died in these efforts and many more have suffered physical and mental injury.
In 1988, the prestigious Nobel Peace Prize was collectively awarded to the world's peacekeepers, including thousands of Canadians, who served in UN missions during that year. This honour inspired Canada to create the Canadian Peacekeeping Service Medal. Tens of thousands of serving Canadian Armed Forces members and Veterans proudly wear this medal.
Peacekeeping Fatalities by Nationality and Mission United Nations Peacekeeping
List of Canadian Peacekeeping Missions Wikipedia
Peace Support Operations (1954-present) Government of Canada
Tags: Peacekeeping
Next item South African War
Previous item Battle of Panjwaii
Gunner V.C. Northey, 5th Battery, 2nd Light Anti-Aircraft Regiment, Regiment of Canadian Artillery (R.C.A.), Campobasso, Italy, 29 October 1943.
E. W. H. Chichester, 1918
W. S. Newsam, 1917
G. H. Pike, 1917
P. D. Corkery, 1944
J. R. Inglis, 1917
O. Lein, 1919
R. F. Matthews, 1943
J. Kendzierski, 1945
J. H. Vanbuskirk, 1947


Cross reacts with plasmin, but not with HGF1/MSP or HGF/SF.
Full length protein. Human Plasminogen.
Our Abpromise guarantee covers the use of ab20230 in the following tested applications.
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.
Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.
Present in plasma and many other extracellular fluids. It is synthesized in the liver.
Defects in PLG are a cause of susceptibility to thrombosis (THR) [MIM:188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation.
Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.
Belongs to the peptidase S1 family. Plasminogen subfamily.
Kringle domains mediate interaction with CSPG4.
N-linked glycan contains N-acetyllactosamine and sialic acid. O-linked glycans consist of Gal-GalNAc disaccharide modified with up to 2 sialic acid residues (microheterogeneity).
In the presence of the inhibitor, the activation involves only cleavage after Arg-580, yielding two chains held together by two disulfide bonds. In the absence of the inhibitor, the activation involves additionally the removal of the activation peptide.
Secreted. Locates to the cell surface where it is proteolytically cleaved to produce the active plasmin. Interaction with HRG tethers it to the cell surface.
ab20230 has not yet been referenced specifically in any publications.
Publishing research using ab20230? Please let us know so that we can cite the reference in this datasheet.
There are currently no Customer reviews or Questions for ab20230.


Tom Bancroft is a drummer, composer, bandleader and educator. Trained as a medical doctor Tom now makes a living from music. He has played with musicians ranging from Sun Ra and Martyn Bennett to Geri Allen and Bill Wells.
He leads occasional big band Orchestro Interrupto, group Trio Red,and the non-jazz electronic/experimental group Vincent – with Japanese avant grade pianist Satoko Fujii, as well as being a long term member of Trio AAB and a founder member of the Pathhead Music Collective. In 2007 he won the BBC Jazz Award for Innovation and a Herald Angel award for his kids music show Kidsamonium and in 2004 won the Creative Scotland Award. He has devised/produced a range of events like; Clandemonium – a 2000 strong jazz flash mob; Heidland – a fictional multi-media recreation of Pathhead in 5 spaces in Edinburgh's Dancebase; and Multi Story Karma Park – the multi media jazz big band, dance, and video show that first introduced Martyn Bennett to Michael Marra. He has also composed music for dance, film, radio, and TV.
After running Scottish jazz record company Caber Music for 7 years, he now runs the music education company ABC Creative Music (www.abccreativemusic.com) with his twin brother Phil. The company produces music creativity education resources for mainstream schools and has over 7000 teachers signed up to use lessons teaching creativity and improvisation to young children.


text:
Rubén Plaza ist der Name folgender Personen:

* Rubén Plaza (Fußballspieler) (1959–2012), uruguayischer Fußballspieler
 Rubén Plaza (Radsportler) (* 1980), spanischer Radrennfahrer


text:
Category Archives: New Video
Category "New Video"
Nick Cannon – Young & Gettin It (Freestyle)
Freestyles, New Music, New VideoBy Smithalar November 9, 2012 Leave a comment
@NickCannon turns on the autotune as he decides to hop on Meek's "Young & Gettin' It".
LL Cool J Announces Authentic Hip Hop Release Date
Interviews, Music News, New VideoBy Smithalar November 9, 2012 Leave a comment
@LLCoolJ plans on bringing back Authentic Hip Hop in his upcoming 14th album and whilst chatting with Craig Ferguson, he revealed that the album will drop in February next year, and more specifically, the 12th.
Kendrick Lamar Performs In East London, England
New Video, PerformancesBy Smithalar November 9, 2012 Leave a comment
@KendrickLamar crossed the pond yesterday to perform some tracks from his recent album good kid, m.A.A.d city at the Rough Trade store in London before signing some copies of his album for fans. Check out "m.A.A.d City", "Backseat Freestyle" and "Bitch, Don't Kill My Vibe" below.
French Montana And Future Work On New Music
New Video, WebisodeBy Smithalar November 9, 2012 Leave a comment
@1future joins @FrenchMontana in the studio as the pair work on some new music that may very well find its way on to Mac And Cheese 3.
VIDEO: Azealia Banks – Fierce
DAILY DOSE, Music Video, New VideoBy DDot Omen November 9, 2012 Leave a comment
Azealia Banks down right fierce like Street Fighter moves. Check out this new visual aid for the song off her Fantasea mixtape, brought to you by ASOS.
VIDEO: Mac Miller – One Last Thing (Blue Slide Park Anniversary Edition)
Mac Miller opens up the vault and takes a drip down memory lane in this video whilst slouched in a bath tub. This visual aid celebrates the one year anniversary of his debut album, Blue Slide Park. Something to hold you over until his sophomore project "Watching Movies With The Sound Off" drops. via SC.
B.o.B Debuts "Alright" Off Fuck 'Em We Ball Mixtape
DAILY DOSE, New Music, New VideoBy DDot Omen November 9, 2012 Leave a comment
Last night B.o.B connected to his ustream account for a broadcast. The ATLien kicked it with his fans announced the mixtape will be dropping November 15th on Datpiff. Before signing off he played a new song produced by homie Osinachi called 'Alright'. Watch the clip below or listen to the rip of the song below.
VIDEO: Big Boi Reveals Features On Vicious Lies & Dangerous Rumors
DAILY DOSE, Hip-Hop News, Interviews, New VideoBy DDot Omen November 9, 2012 Leave a comment
Big Boi sat down with 106 KMEL to discuss his upcoming album, Vicious Lies and Dangerous Rumors which will be in stores December 11th. According to the active rhyming half of Outkast, he's managed to recruit Ludacris, B.o.B, A$AP Rocky, T.I., Kelly Rowland and more. via HHNM
VIDEO: Keyshia Cole – Trust & Believe
Check out @KeyshiaCole new video from her Woman to Woman album, in stores on November 19th. Watch it below.
VIDEO: Ben Baller Says Jay-Z Reference For "Still D.R.E." Exists
DAILY DOSE, Hip-Hop News, Interviews, New VideoBy DDot Omen November 8, 2012 2 Comments
Ben Baller appeared on Shade 45 with DJ Whoo Kid to talk about his jewelry empire that he's built around most of your favorite rappers (that can afford it). The most interesting thing here is Ben recalling his days hanging with Dr. Dre and Aftermath in their early stages, specifically that he has Jay-Z's referenced…
23456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109110111112113114115116117118119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263264265266267268269270271272273274275276277278279280281282283284285286287288289290291292293294295296297298299300301302303304305306307308309310311312313314315316317318319320321322323324325326327328329330331332333334335336337338339340341342343344345346347348349350351352353354355356357358359360361362363364365366367368369370371372373374375376377378379380381382383384385386387388389390391392393394395396397398399400401402403404405406407408409410411412413414415416417418419420421422423424425426427428429430431432433434435436437438439440441442443444445446447448449450451452453454455456457458459460461462463464465466467468469470471472473474475476477478479480481482483484485486487488489490491492493494495496497498499500501502503504505506507508509510511512513514515516517518519520521522523524525526527528529530531532533534535536537538539540541542543544545546547548549550551552553554555556557558559560561562563564565566567568569570571572573574575576577578579580581582583584585586587588589590591592593594595596597598599600601602603604605606607608609610611612613614615616617618619620621622623624625626627628629630
636637638639640641642643644645646647648649650651652653654655656657658659660661662663664665666667668669670671672673674675676677678679680681682683684685686687688689690691692693694695696697698699700701702703704705706707708709710711712713714715716717718719720721722723724725726727728729730731732733734735736737738739740741742743744745746747748749750751752753754755756757758759760761762763764765766767768769770771772773774775776777778779780781782783784785786787788789790791792793794795796797798799800801802803804805806807808809810811812813814815816817818819820821822823824825826827828829830831832833834835836837838839840841842843844845846847848849850851852853854855856857858859860861862863864865866867868869870871872873874875876877878879880881882883884885886887888889890891892893894895896897898899900901902903904905906907908909910911912913914915916917918919920921922923924925926927928929930931932933934935936937938939940941942943944945946947948949950951952953954955956957958959960961962963964965966967968


The presence of ERα is the basis for treating breast cancer patients with targeted molecular therapies that block estrogen stimulation of breast cancer cell division. To select patients for the above therapies, currently, the ERα presence in breast cancer tissues is determined in clinical laboratories by microscopically scoring the slides subjected to immunohistochemistry (IHC). This method is not quantitative, highly subjective and requires large amount of tumor tissue, therefore, cannot be applied to sterotactic and ultrasound guided biopsy samples. To circumvent these problems, we previously developed quantitative real-time PCR based molecular assay that can be applied to determine mRNA copies of ERα in picogram amounts of total RNA from tumor samples. However, it is not known how the mRNA copy numbers correlate to IHC positive and negative status.
In the current study we determined the copy numbers of ERα mRNA by Q RTPCR in breast cancer tissues that were graded as ERα-positive and negative by 1) IHC and 2) functional estrogen binding assay and statistically analyzed the data.
We demonstrate here that ERα mRNA copy numbers are not significantly different in tissues that are graded as positive by IHC and ligand binding assays. We establish here a cut of value of 5 × 106 copies per 1010 mRNA copies of GAPDH with an Odds Radio of 39.4, Sensitivity of 0.81 and Specificity of 0.90 in breast cancer tissues that are negative for ERα protein by IHC and estrogen binding assays. ROC analysis of the data gave an area of 0.8967 under the curve.
We expect that the cut off values determined here will be highly significant for applying molecular assay in the place of IHC in clinical laboratories for evaluating the presence of ERα for prognostic and therapeutic purposes.
Breast cancer is the most diagnosed and the second leading cause of cancer deaths for women in the United States striking about 300,000 and killing about 40,000 women a year . A substantial body of epidemiological, experimental and clinical evidence indicated that unopposed stimulation of breast epithelial cells by the natural hormone, estrogen, plays a major role in the progression of breast cancers . Because endogenous estrogens directly promote the growth of breast cancer cells, estrogen deprivation either by inhibiting its biosynthesis (aromatase inhibitors) or blocking estrogen-mediated gene transcription (tamoxifen) through its high affinity receptor, the estrogen receptor alpha (ERα), are the primary lines of therapy for breast cancer patients. In most cases, the efficacy of the above treatments has correlated with the presence of ERα in the tumor tissues. Currently, only those patients who express ERα in their tumors are chosen for aromatase inhibitor or tamoxifen therapies. In addition to being a therapeutic target, ERα was also shown to be the most important factor to predict breast cancer prognosis. The patients who express ERα in their tumors have an overall longer cancer-free survival and lower recurrence rates than patients who do not express this receptor .
To predict prognosis and identify patients for the above two anti-estrogen therapies, every breast cancer tissue is currently screened for the presence of ERα before a treatment regimen is selected for any breast cancer patient. The presence of ERα in breast tumors was originally determined in clinical labs by estrogen binding assay for about 20 years. However, when the tumors were detected at comparatively smaller sizes and highly specific monoclonal antibodies were developed that could detect ERα both in the fresh frozen as well as formalin fixed paraffin-embedded tissues, the clinical labs switched to immunohistochemistry (IHC) from estrogen binding assay for determining the presence of ERα. Currently ERα is determined in the clinical laboratories from rough estimates yielded by microscopically scoring the slides subjected to IHC technique using antibodies against the N-terminal A/B region of ERα. Although this procedure is used for over ten years, it has several limitations including not quantitative, highly subjective, variations due to antibody preparations, variations from one clinical lab to other and comparatively large sample size requirement.
In recent times, due to increased awareness and substantially improved screening methods, breast cancers are detected at very early stages and excised, in a large majority of cases, by stereotactic and ultrasound guided techniques. In these cases the limited amount of tumor tissue that remains after histological testing restricts determining ERα status for prognostic and therapeutic purposes by IHC. In many cases, ERα status is not determined due to insufficient amount of tumor tissue. For these reasons there is an urgent need to switch to a procedure that can detect ERα in a very small amount of tumor tissue obtained by the above methods. There is a general consensus that ERα mRNA quantification is a more suited technique for detecting its presence in tumor tissues. Several PCR based approaches have been described for detecting the presence of ERα in breast cancer tissues [4, 5]. We recently developed a highly sensitive real-time PCR based quantitative molecular assay that can detect and quantify as low as 50–100 copies of ERα mRNA from as small as 40 picograms of total RNA from breast cancer tissues. Because quantitative real-time PCR is a high through-put method, it could be automated to apply in clinical laboratories. However, it is not known how the ERα mRNA copy numbers correlate to ERα positivity and negativity by IHC assay. Establishing a cut off value in IHC negative tissues is required for the application of molecular assay in the place of IHC assay. To determine the cut off value, we have profiled ERα mRNA copy numbers in breast cancer tissues which have been graded as ERα positive and negative by IHC and estrogen binding assays. We demonstrate here that ERα mRNA copy numbers are not significantly different in tissues that were graded as positive by IHC and ligand binding assays. However, ERα positive tissues, either by IHC or estrogen binding assays, express significantly higher mRNA copy numbers than the negative tissues. We have determined the cut off values of ERα mRNA copy numbers by molecular assay that correlate to ERα negativity by both IHC and ligand binding assays using CART program (Classification And Regression Tree). We expect that the cut off values determined here will be highly significant for applying molecular assay in the place of IHC in clinical laboratories for determining the ERα status for prognostic and therapeutic purposes.
All the primers used in the current study were synthesized by Gibco-BRL Life Technologies. TaqMan Universal PCR Master Mix (Cat # 4304437) was from Applied Biosystems. 5'FAM and 3'TAMARA labeled oligonucleotide probes were synthesized by Applied Biosystems and available from previous studies. PCR quality water and Tris-EDTA buffer were from BioWhittaker.
Breast cancer tissues with known ERα status by IHC and ligand binding assay were available from previous studies [6–9]. Briefly, the tumor samples were collected from either biopsy or mastectomies immediately after surgery and stored at -80°C until use. Fresh tumor tissue samples for ERα quantification were routinely harvested immediately adjacent to the histologic/diagnostic sections and considered to be representative of the tissue used for diagnosis. All the samples were examined by a pathologist and tissues containing > 80% cancer cells were excised and used for ERα mRNA quantification. The ERα-status for the samples used in this study was determined either by IHC using monoclonal antibodies against NH2-terminal portion of the molecule at Oncotech Laboratories, Irwine, CA, or by ligand binding assay as described . The tumor tissues were considered positive for ERα by IHC if > 5% of cancer cells showed positive nuclear staining. The tumor tissues that were diagnosed as ERα positive by estrogen binding assay had > 3 fmol of ER/mg of total tissue extract. A total of 70 samples positive by IHC, 33 positive by estrogen binding assay, 43 negative by IHC and 20 negative by estrogen binding assay were included in the current study (Tables 1, 2, 3 and 4 respectively). The tumor tissues were processed to isolate total RNA and cDNAs prepared as previously described [6–9]. Howard University Institutional Review Board granted the ethical approval of Tumor collection procedures for the study.
* These samples were collected at the time when the practice was to grade the samples as just Positive or Negative but no numerical scorings were given.
Absolute quantification of ERα transcript copy numbers was achieved by quantitative real-time PCR in ABI Prism GeneAmp 7900 HT Sequence Detection System as described previously (9). Briefly, a typical real-time PCR reaction mixture contained cDNA prepared from reverse transcription of 0.5 – 5 nanograms of tumor tissue total RNA, 0.04 micromolar each of sense and anti-sense primers, 0.05 micromolar 5'FAM and 3'TAMARA labeled oligonucleotide probe and 1 × Taqman Universal PCR Mix in a total volume of 25 μl. PCR conditions were initial hold at 50°C for two minutes, followed by denaturation for ten minutes at 95°C, and denaturation for 15 seconds at 95°C in the subsequent cycles and annealing and extension for 1 min at 60°C for 40 cycles. The ERα mRNA copy numbers in tumor tissues were determined in comparison with a standard graph constructed simultaneously using 102, 103, 104, 105, 106, 107, 108, and 109 copies of reverse transcribed cRNA of ERα. All the samples were amplified in triplicate and real-time PCRs were repeated four times. The ERα mRNA copy numbers in tumor tissues were normalized to mRNA copy numbers of the house keeping gene, glyceraldehyde 3- phosphate dehydrogenase (GAPDH). GAPDH copy numbers were determined as previously described [11, 12]. The sense, and anti-sense primers and probe for quantifying the mRNA copy numbers of ERα were 5' caagcccgctcatgatcaa 3' (position, exon 4, bp 1110–1128), 5'ctgatcatggagggtcaaatccac3' (position, exon 5, bp 1358–1338) and FAM 5'agaacagcctggccttgtccctg3'TAMARA (position, exon 4, bp 1140–1162) respectively. The sense and anti-sense primers and probe for quantifying GAPDH mRNA copy numbers were 5'ttccagg agcgag atccct3' (position, bp 304–322), 5'ggctgttgtcatacttctcatgg3' (position, bp 483–505) and FAM 5' tgctggcgctgagtacgtcgtg3' TAMARA (position, bp 342–363) respectively. Primer positions of ERα and GAPDH nucleotide sequences were as described [13, 14].
Wilcoxon-rank-sum test and standard two-sample t-test were used to determine whether the mRNA copy numbers were significantly different in breast cancer tissues that were 1) ERα-positive and ERα-negative by IHC, 2) ERα-positive and ERα-negative by estrogen binding assays, 3) ERα positive by IHC and estrogen binding assays, and 4) ERα-negative by IHC and estrogen binding assays. Test results were considered significant if P ≤ 0. 05. To determine the cut-off value/maximum level of mRNA copy numbers in the samples which were negative by IHC and estrogen binding assays, we used CART (Classification Regression Tree) [15, 16] program. The data consisting of 103 ERα positive and 63 ERα negative samples which had a predictive variable, mRNA copy numbers, were partitioned into two groups using CART program. This program determines the best cut-off value copy numbers in the sense that the OR (Odds Ratio, ERα positive to ERα negative in our case) of the two groups (with copy number greater than the cut-off value in one group and less or equal to the cut-off value in the other) is maximized. Receiver Operating Characteristic (ROC) analysis was performed to determine the sensitivity and specificity of the RNA based molecular assay. The ROC curves were generated by connecting all the points determined by the copy numbers in all the samples in an increasing order. Since data on IHC grading as percent positive cells were available on some of the samples, the correlation between the IHC grading and the mRNA copy number was determined both in the original scale and in logarithmic transformations scale using S-PLUS software.
We have undertaken the current study to determine ERα mRNA copy numbers in breast cancer tissues that were positive and negative by two conventional methods of assaying ERα protein, IHC and estrogen binding. The rational for undertaking this study is that once we establish a threshold value in IHC negative tissues, then the molecular assay could be applied in clinical laboratories in the place of currently used IHC assay for determining the status of ERα for prognostic and therapeutic purposes. Our rational for establishing a cut off value is that any patient who expresses above the cut off level could be selected as a candidate for anti-estrogen therapies and could be considered to have good prognosis.
We first profiled ERα mRNA copy numbers in 70 samples positive by IHC, 43 negative by IHC, 33 positive by estrogen binding assay and 20 negative by estrogen binding assay. The data are presented in Tables 1, 3, 2 and 4 respectively. A box plot drawn for the copy numbers (logarithm base 2 scale) in the four groups (positive and negative by IHC and by estrogen binding assay) using S-PLUS software is shown in Figure 1.
A Box plot drawn for the ERα mRNA copy numbers (logarithm base 2 scale) in the four groups (positive and negative by IHC and by estrogen binding assay) using S-PLUS software is shown.
We next compared the quantitative data on mRNA copy numbers among samples as described below. 1) We tested whether the two conventional assays, the IHC and estrogen binding assays, correlate in terms of mRNA copy numbers in 70 and 33 positive tissues (Tables 1 and 2 respectively) using Wilcoxon-rank-sum test and standard two-sample t-tests. By these two tests, we did not find significant differences in the ERα mRNA copy numbers in samples that were ERα positive by IHC and estrogen binding assays (p > 0.28 by both tests). 2) We also compared the mRNA copy numbers in 43 samples negative by IHC with 20 samples negative by estrogen binding assay and did not find significant differences (Tables 3 and 4 respectively) (p > 0.25 by the above two tests). However, 3) we found significant differences in mRNA copy numbers in the breast tumors that were IHC positive from those which were IHC negative (Tables 1 and 3 respectively) (p = 1.3e-6 by standard two-sample t-test and p = 2.7e-18 by Wilcoxon-rank-sum test). And 4) we also found significant differences in the samples that were positive and negative by estrogen binding assay (Tables 2 and 4 respectively) (p = 7.6e-3 by standard two-sample t-test and p = 3.6e-7 by Wilcoxon-rank-sum test).
After establishing that ERα-positive tissues express significantly higher levels of mRNA copy numbers compared to negative tumor samples, we next determined the maximum level of expression in ERα-negative samples using CART program. By using this program, we found the maximum level of expression of mRNA copy numbers/cut-off value to be 5 × 106 per 1010copies of GAPDH mRNA. Of the total 106 positive (70 by IHC and 33 by estrogen binding assay) samples in our study, 83 samples showed higher level of expression than 5 × 106 copies per 1010 copies of GAPDH. It is possible that the samples that showed less than the above cut off value copy numbers could be due to false positivity by the above methods. In a total of 63 negative samples (43 by IHC and 20 by estrogen binding assay) only 6 samples showed higher expression than 5 × 106 copies per 1010GAPDH copies. It is also possible that the samples that showed higher than the cut off copy numbers could be false negative. The OR (Odds Ratio) in the two groups is about 39.4, an extremely high OR value. The counts of the ERα-positive (80, 23) and ERα-negative (6, 66) in the two groups produce a chi-square value of 88.2544 with 1 degree of freedom, which is consistent with our T-test and Wilcoxon-rank-sum test results.
We applied the above cut off value and determined the Sensitivity (percentage of samples that showed higher copy numbers than the cut off value of 5 × 106 copies per 1010 GAPDH copies in IHC positive tissues) and Specificity (percentage of samples that showed less than 5 × 106 copies per 1010 GAPDH copies in IHC negative tissues) and the values obtained were 0.81 and 0.90 respectively. We also determined Receiver Operating Characteristics using S-PLUS software and the ROC curve generated is shown in Figure 2. The area under the ROC curve, 0.89675, shows that the molecular assay clearly distinguishes the positives by IHC or estrogen binding from the negative tissues.
Receiver Operating Characteristic curve drawn using the data on ERα mRNA copy numbers is shown.
Since we have the grading score as percent positive cells for about 50 samples (Table 1), we tested if a correlation exits between the percent positive cells by IHC and the mRNA copy numbers using S-PLUS software. We obtained a correlation coefficient of 0.02. When we used the logarithmic transformations scale, we obtained a correlation coefficient of 0.037. These results indicated that there is no correlation between the percent positive cells and the level of ERα mRNA copy numbers. These observations could be due to qualitative nature of IHC assay. The IHC data only show the number of positive cells but not quantitative to determine the level of ERα expression. The molecular assay based on RNA is quantitative to determine the level of ERα expression.
Previously ERα mRNA levels in immunohistochemically positive and negative tissues were evaluated in breast cancer tissues by several groups using conventional RT PCR. Cullen et al  determined mRNA levels by conventional PCR in 107 breast cancer tissues. They reported that ERα mRNA was more frequently detected in ERα protein positive tissues than ERα protein negative tissues. Jarzabek et al  studied ERα mRNA levels and protein levels in 41 primary breast cancer tissues. They reported the presence of ERα mRNA in all the tissues, where as the protein was present only in 70% of tumor tissues by Western blotting and 67% showed positive by immunohistochemistry. They concluded that lack of ERα protein is not due to lack of ERα gene expression or methylation of its promoter, but may be due to post-transcriptional or post-translational mechanisms. Alkarain et al  reported the presence of ERα mRNA in immunohistochemically ERα-negative tissues. However, none of the above studies has evaluated the threshold levels of ERα mRNA levels in immunohistochemically negative tissues or those negative by ligand binding assays. Our quantitative analysis of ERα mRNA copy numbers demonstrate that breast cancer tissues that are negative by both IHC and ligand binding express significant levels of ERα mRNA. The reasons why the mRNA is not translated to detectable protein are not clear. Our previous studies on ERβ mRNA copy numbers  in breast cancer tissues have shown that at the 5 × 106 copies per 1010 mRNA copies of GAPDH levels ERβ protein is translated. It is possible that either ERα mRNA is not translated or the translated protein is degraded to undetectable levels in these tissues.
The results and the analysis presented above clearly demonstrate that the ERα positive tissues by IHC or estrogen binding assay express significantly higher mRNA copy numbers than 5 × 106 copies per 1010 GAPDH copies. An extremely high Odds Ratio, high sensitivity and specificity demonstrate that the molecular assay could be used in the place of currently used IHC in the clinical laboratories. Based on our data above any patient who has more than 5 × 106 copies per 1010 GAPDH copies in her tumor tissue could be considered positive for ERα, could be selected for anti-estrogen therapies and considered to have good prognosis. However, the above described approach has some limitations in that it needs to be verified on a defined set of biopsy samples and with reference to another house keeping gene. Therefore, the results should be interpreted with caution and undoubtedly will require confirmation by a larger prospective multi-centered clinical study with a more accurate design to bring the technology to the clinic. The current study is a first step in that direction. We expect that the cost effective, extremely sensitive, high though-put molecular assay which requires only a few cancer cells could be an assay of choice to replace IHC in clinical labs for determining ERα status in breast cancer tissues once established in a multi-centered prospective clinical study.
Odds Ratio and ROC, Receiver Operating Characteristics.
This work was supported by a grant from the Susan G. Komen Breast Cancer Foundation (POP34206), a grant from the National Cancer Institute (R33 CA88347) under Innovative Molecular Analysis Technologies (IMAT) program, and a grant from DOD, BCRP (idea award, DAMD17-02-1-0409) to I. Poola. Q.Y was supported by an RCMI grant from the National Institutes of Health (2G12RR003048). We are thankful to Dr. George Bonney for advising on CART program and Dr. Jessy Abraham and Alecia Saunders for their assistance in sample preparations.
I. P conceived the study, participated in the design of the study, performed the real-time PCR quantifications of ERalph mRNA copy numbers and drafted the manuscript. Q.Y participated in performing the statistical analysis of the data. Both authors read and approved the final manuscript.


text:
Proclamation and Policy
This essay is written from a very USA-centric perspective. Though I hope the more general conclusions are more widely applicable, I admit that the examples used are provincial in the extreme.
There are dozens of ways to explain philosophically the key divides of modern politics: left- vs. right-wingers, libertarians vs. authoritarians, rich vs. poor, old vs. young, and so on. I'm sure a half-dozen more such classifications sprang to mind when you began to read that list. However, I've become convinced that there is another key philosophical difference about the role of law that underlies much of modern political debate, and is nevertheless poorly understood. For the purposes of this essay, I will describe this debate as that of "proclamation vs. policy." The "proclamation" perspective holds that the purpose of the law is to announce or express the moral views of society, while the "policy" perspective holds that law should be used to change the material conditions of society, including through indirect means. The unacknowledged difference between these two perspectives leads to proposed laws being justified in terms that their opponents find literally incomprehensible, causing confused political discourse. Likewise, the under-examination of this distinction leads to thoughtless, unjustified radicalism on this question. Even a cursory exploration of these two sides of the law can help clarify numerous legislative debates, past and contemporary, while allowing citizens to more clearly understand their own views and values.
Before exploring how the tension between proclamation and policy underlies contemporary USian political debates that express themselves in quite different terms, I'm going to explore the two perspectives at greater length, using a handful of unequivocal examples.
The "proclamation" model holds that the law represents an expression of moral values. Among the most lauded examples of the "proclamation" model of law [1] was the USA's Emancipation Proclamation. The Emancipation Proclamation marked an official declaration of the Union's position on slavery: unequivocally against. It was able to fulfill this goal without, in fact, freeing many slaves. Though it ultimately took several more years of military action and a Constitutional Amendment to end slavery in the USA as an institution, the Emancipation Proclamation is still understood as the key moment in the process of emancipation, because it articulated the Union's moral stance against slavery so incontestably. The most extreme form of proclamation-type law can be found in legislative proclamations without enforceable terms; for example, those designating a particular day a "National Day of Prayer" or a day to commemorate some particular cause.
Conversely, the "policy" model holds that the aim of the law is to change conditions as they actually apply; to address problems and improve the state.[2] It is hard to find an independent, ideal example of legislative work of this form—as policy cannot be considered in isolation, and it does not tend to attract much notice. Thus, we can consider the example of a field rather than a particular law. Traffic law is a useful example for an initial approach. It involves a great number of small decisions which must be made, by the legislature or regulatory bodies. Few, if any, such decisions can be resolved by appeal to prior moral principle. There is no known way to derive, a priori, which side of the road cars should drive on. Decisions cannot be made in isolation. Policymakers must consider whether the impact of their rules improves or worsens conditions on the road, rather than assuming their rulings work toward the desired effect, because policy rulings often work indirectly toward their aims. Policy is inevitably a technical field, often boring those who do not have a personal interest in the matter under consideration. It can be accused of social engineering; in the case of traffic rules it does often reduce down to actual civil engineering, managing the timing of stoplights and the number of lanes a highway can support. However, it is clear that policy decisions make a real difference in the lives of citizens.
When put this way, each perspective on law seems to have its place. It would be foolish for legislators to declaim on the moral principle of a speed limit of only 55 miles per hour without reference to its consequences, or try to cite the great principles of democracy in service of alternate-side-of-the-street parking exemptions. It would have been inhumane for Lincoln to have sought to address slavery with, say, an "emancipation tax credit," or other such policy incentive. There are realms where there is a broad consensus that the legislature should be acting in the interest of policy,[3] and others where it is clear that a moral proclamation is called for.
Furthermore, there are places where laws can serve both sorts of purpose simultaneously. Consider, for example, laws against perjury. At first glance, they might seem to be a proclamation. Certainly they oppose lying, and lying to a judge, both considered moral offenses. Laws against perjury could be justified on purely moral grounds: our society opposes such dishonesty. However, when considered in context of the other laws and rules of criminal procedure, laws against perjury clearly have a policy justification as well. By punishing dishonesty in court, they encourage honesty and promote the efficient operation of the justice system. Even if there was no moral reason not to lie to a judge, perjury laws could still be justified entirely on policy grounds. So laws need not adhere just to one perspective or another. Indeed, some of the most widely supported laws fit both: they are independent moral claims, and simultaneously promote the efficient functioning of society.
Conflict on this matter arises, however, in areas where there is debate over what role the law should play, and different perspectives—proclamation or policy—would yield different pieces of legislation. These areas encompass many of the most heated debates of modern politics. Furthermore, they entail a meaningful "dialogue gap:" a hidden difference in premises that undermines substantive dialogue about the matter under debate. Given that the democratic process seeks not only to produce majoritarian laws, but to allow for thoughtful reflection on legislative decisions, such failures to communicate are a real problem for our democracy.
Take, for example, the question of the War on Drugs. Proponents of decriminalization are liable to cite an array of studies suggesting that decriminalization of drugs has no significant effect on rates of usage.[4] Those who favor criminalization certainly have their own studies to retort with. However, fascinatingly, they often don't. Instead, pro-Drug War rhetoric often parallels Steven Levitt's depiction of "the daughter test."[5] In describing the rationale for some of his political positions, Levitt writes "[if ] I wouldn't want my daughter to do it, then I don't mind the government passing a law against it. I wouldn't want my daughter to be a cocaine addict . . . [so] I don't mind those activities being illegal." From a policy perspective, there is a crucial gap in this logic. If criminalization of drugs does not affect their rate of use, then cocaine's illegality does nothing to prevent Mr. Levitt's daughter from becoming an addict. However, from a proclamation perspective, Levitt's logic makes perfect sense. Levitt opposes the prospect of his daughter using cocaine. He would like the government to endorse this moral perspective, regardless of its impact on outcomes. Levitt believes that "it would probably be more economically efficient to legalize drugs and prostitution subject to heavy regulation/taxation," but his opposition remains.
Similar debates can be found on a range of other issues. I personally encountered one such question when talking with a pro-life friend. (I myself am pro-choice.) I made the argument that legal abortion keeps the procedure safe while not actually increasing its frequency, and that, on the other hand, the pro-life movement fails to endorse policies that would actually decrease the incidence of abortion. He granted this claim, more or less, but held that it was still important to outlaw abortion as a statement of what is right and wrong. Policy-relevant information will not affect the legislative preferences of someone thinking in proclamation terms.
This contention between proclamation and policy does not simply apply to the range of "social issues" that Levitt identifies—abortion, drugs, gambling—but is spreading to realms once firmly in the policy camp. The most notable examples are tax policy and healthcare. Taxes have been unpopular in America for a long time. Few people like to simply turn over their money, and in America, Justice Holmes's awareness that by "paying taxes [one is] buy[ing] civilization" is not a common one. There have been anti-tax protests for much of American history. However, these have mostly complained about an onerous tax burden. Such protests can be self-centered, and infused with moralizing rhetoric. However, the position that tax laws should represent the moral views on tax in general, or express a moral opposition to them, is a comparatively recent one.[6] For example, President Bush said in his 2000 acceptance speech that "On principle, no one in America should have to pay more than a third of their income to the federal government." The notion of an a priori, "in principle" maximum marginal tax rate represents the encroachment of proclamation perspective upon the realm of tax policy. So does the Tea Party rhetoric. The Tea Party relied strongly on equating the problem of taxation without representation with taxation more generally, painting a categorical opposition to taxation as a moral stance.
Likewise, a similar shift occurred on healthcare. Liberal commentators noted throughout the 2009 and 2010, Republican elected officials decried reforms that they had supported in the early 90s. Mitt Romney spoke out against, and continues to oppose, a federal policy more rightist than the one he instituted as governor of Massachusetts. Jonathan Chait has argued that this shift represents more than a change in the Overton window.[7] Instead, Chait says, the ferocity and character of the Republican attacks on health care reform demonstrate that the Republican party is not interested in improving health care outcomes. Rather, they are ideologically committed to smaller government, regardless of the outcome.[8] Proclamation has overtaken policy.
Another area of relevance is the prevalence of accusations of the "nanny state." (For those unfamiliar with the term, it is used to convey the contemptuous belief that the government is meddling over-protectively in the affairs of its citizens.) Such accusations often confused me, but they follow simply if one realizes the accusers understand policy laws in proclamation terms. Consider laws against trans fats in restaurants. A policy thinker would argue that these laws simply represent a way to improve the life of individuals, like any industry or trade standard. Furthermore, they are decided upon by the government, and thus, indirectly, by society at large—quite a different process than the quasi-parental authority of a nanny. However, when one imagines laws against trans fats as proclamation, immediately the image of the government as a nagging parent begins to make sense. To a policy thinker, laws against trans fats need not entail any judgement of individual food choices. They simply work to reshape the environment so that individuals are more likely to make better choices. To a proclamation thinker, a law against trans fats necessarily implies that individuals were bad or wrong for choosing them in the past. The law cannot be written without scolding the citizenry.
The examples used thus far have aligned leftists with policy and rightists with proclamation. This connection, however, is not a necessary one. It is, instead, a consequence of the different sorts of rhetoric and philosophy espoused by the modern USA left and right—Democrats and Republicans might be an even better description. Of course it would have been possible to have a health care debate where one side insisted on universal care as a moral right, and the other wanted a more complex system of incentives because they had concluded it would have superior outcomes. However, such was not the debate that took place.
It is also important to note that over the course of this essay, the modern promoters of proclamation have lauded a model where women are the appropriate objects of implicitly male state protection and even paternalism (the "daughter test," administered by fathers), and now derided a model where a female-identified state acts protectively toward its citizenry (the "nanny state"). Something undoubtedly sexist is afoot here. Unfortunately, I confess that I can't explain it quickly, and I'm sure this subpoint could grow to exceed the full essay, so I'm forced to simply give three possible explanations. Hopefully we'll hash them out in the comments.
First, it's possible that the modern (USA) identification of proclamation with the rightist/conservative/anti-feminist axis had lead to a situation where proclamation-style thinkers are likely to be sexist, and thus articulate their philosophical commitments with sexist vocabulary. That would account for the fact that feminist and anti-oppression movements have also been able to use the language of proclamation, though its primary contemporary representatives are rightist. Second, it's possible that the sweeping moral and emotional claims of proclamation are susceptible to being expressed with sexist language in a way that policy claims are not susceptible. It's hard to imagine a sexist way of articulating the introduction of an extra tax bracket, for example. One would probably be forced to recast it as a simple moral action first, i.e., rewrite it as proclamation. Third, it's possible that I, as a feminist, am particularly struck by rhetoric that offends my egalitarian sensibilities, and so when I sat down to write an essay to explicate rhetoric I found disconcerting, I was drawn toward the sexist examples. I'm not sure which, if any, of those explanations are accurate.
All of examples laid out above show that the tension between proclamation and policy is a key one in the political debates of the modern USA. However, it is not explicitly argued. Political debates presume to be about the good at which laws are aimed, not what it means for a law to serve a particular end. Thus, the first step to resolving the tension is recognizing this gap. When one side of a political debate is making a policy case, and the other is making a proclamation case, neither can hope to persuade the other. We have to first establish why the matter under discussion is appropriately the target of one or the other (or some fusion of the two), and then much of the rest of the policy case falls into place.
Another important takeaway is to resist the unjustified expansion of one field into another. Politicians may desire to recast a policy issue as ripe for proclamation—as in the case of Bush's quote above, this move reduces complexity and allows a disinterested member of the public to take a strong stand on the issue. However, it leads to poorly constructed laws, with bad outcomes, and radicalizes a debate in which nuance is key. Policy in place of proclamation is a quieter evil, but still risky. For example, those who want to encroach upon worker protections or social security argue that they should be considered solely as instruments of economic policy. This attempts to change the terms of the debate from moral to practical. In each case, such transformations of the terms of debate can go unnoticed, but they can undermine sensible government work, and the meaningful but complex rights of the citizens of the welfare state.
Finally, in the case of the USA, it is important for each political party to regain a more complete voice on the matter. The two primary political parties are horribly unbalanced. The Democrats have renounced strong, leftist moral arguments. This deprives the American moral landscape of real advocacy for the poor, for equality, and for communal action. The Republicans have renounced policy thinking, leading to the recent failure to, for example, offer any real alternative to the Obama health care reform. The pre-midterm mantra of "repeal and replace" was entirely vacuous. There was no replacement in the offing, because Republicans were unable to formulate a complex policy response to a difficult practical problem.
I'm a strong leftist, and I've no doubt that this has colored my interpretation of the current political situation. But I'm willing to acknowledge that I'm probably wrong about at least some of the important decisions my nation faces. When one major current of politics has stepped out of morality, and the other has stepped out of careful policy thought, our decisions are impoverished. That has to change, and the first step is recognizing the real significance of the distinction between proclamation and policy.
--Erl
Notes and links:
[1] and, in fact, the one that inspired its name. ↩
[2] for the purposes of this article, the policy model is agnostic about both the set of persons and things which constitute the target of the state's assistance, or even what constitutes improvement. Similarly, the proclamation model is agnostic about which moral principles to espouse. This indifference to the actual content of policy or proclamation is deliberate. It serves to isolate the matter under discussion. Still, when this model is applied to contemporary political debate, there are differences in the visions of the good, which sometimes correspond clearly to the question of proclamation vs. policy. This complicates the conclusions of this essay, but, I hope, does not eliminate them. ↩
[3] aside from anarchists or strong libertarians. When one's political philosophy is opposed to state action in general, every single item of policy constitutes a proclamation of state power, to be opposed. That said, I personally find it hard to maintain the image of a philosophically consistent anarchist legislator, so it is reasonable to disregard this perspective for the purposes of this essay. ↩
[4] Were this an academic paper, I would like to a number of studies which are behind paywalls. For the purposes of this piece Wikipedia provides a good summary of the literature, Arguments for and against drug prohibition. ↩
[5] This essay will address the considerable sexism implicit in the formulation and popularization of this test further on. ↩
[6] I believe. I'd be fascinated to be proved wrong. However, given that American history seems to be a tale of the broadening of the tax base, sometimes with substantial popular approval (e.g. the 16th Amendment), I don't think I will be. ↩
[7] The "Overton Window" describes the set of policies that are considered reasonable, live options within a particular context, primarily political discourse. The Overton Window shifts when the range of policies considered moves in one direction or another. For example, in the USA the current debate over the marginal income tax rate considers rates of 36% or 39%, and though a generation ago the rate of 90% was in force, no serious politician proposes it now. ↩
[8] Romney, Empiricism, And Conservative Dogma ↩ >
Jul 25, 2011 10:58:00 AM | Erl, guest posts


2019 is going to be a big year for Clodewerks. I am digging in and working hard on my solo set and at least one release all under the Clodewerks moniker. After 7(!) years of relative quiet from me as a solo artist, I thought it would be a good idea to revisit my brand as a whole. I thought that my logo especially needed an update.
My friend David Mellor designed the old logo for me in college. It had a silhouette of a grinning face with a fedora type hat and a pointy goatee style beard on top of a gold record. Needless to say a lot has changed since the creation of that logo.
When my full bearded, ballcapped self was thinking of a new logo and brand, there were a lot of decisions to make. I am generally a minimalist, so I liked the idea of something simple. The core of what I do is combining my trumpet with electronic sounds. The logo had to reflect that duality in some capacity.
I gravitated towards the cw single character immediately, but I had trouble getting it to look right. I played around with the idea on paper. I learned about the enso circle, and thought my regular cw doodling was a very similar practice. I leaned into that aesthetic, and came up with the creation you see before me today.


text:
Comic Reviews: The Punisher, Loki: Agent of Asgard, and Wolverine!
February 5, 2014 Jonwahizzle
This week you get not one, not two, but THREE books reviewed!Punisher heads to LA, Loki breaks into Avengers Tower, and Wolverine's healing factor is BROKEN!!!
Frank Castle is back, and my god, he kicks so much ass. From Black Widow and Who Is Jake Ellis writer Nathan Edmondson and artist Mitch Gerards, The Punisher #1 finds Mr. Castle moving to Los Angeles on the hunt for more scumbags. What follows is a fantastic debut issue that brings the Punisher roaring back into the Marvel universe.
Edmondson's script hits all the notes you'd want a Punisher story to hit. You want Frank blowing up bad guys? Boom, you got it. Frank interrogating scumbags for info on other, bigger scumbags? This issue has it. Frank drinking coffee? Yep, that's in here as well. The issue follows Frank's first steps in taking out the trash in the City of Angels, and Edmondson clearly has a strong grip on what makes The Punisher tick. There's an excellent noir feel to this comic that is perfect for the character, and at times I was expecting to hear some bad ass 70's action music to kick in. Edmondson's Punisher is extremely calculating and brutal, but he's also pretty funny at times, which is strange to see. I for one welcome this take though, and Frank's interplay with the local diner cook and a female beat cop is a lot of fun, and they make great supporting characters for him.
I've never seen Mitch Gerards' art before, but I really love his work in this issue. Gerards showcases the extremely brutal ways that Punisher takes out his enemies in grand fashion, and you can feel the grime and sweat in Los Angeles in his work, and it works in perfect union with Edmondson's script. His Frank Castle is intimidating, but not a gigantic hulk of a man like some past depictions have shown him, which is nice to see.
Punisher #1 is an awesome debut issue that will please long time fans of Frank Castle and new ones alike. There are plenty of brutal moments here, and the opening action scene with Frank is one of the coolest comic moments I've seen this year. While it's hard to believe a guy like Frank Castle serves a purpose in the regular Marvel universe, it seems like Edmondson and Gerards are making a compelling case for keeping him in the same world as other heroes like Iron Man, Captain America, and the Hulk. If you're looking for a gritty crime comic, The Punisher is the one to get.
Loki: Agent of Asgard #1
Capitalizing of the Loki craze, Marvel has finally given the god of mischief his own book. No, he doesn't look or sound like Tom Hiddleston, but Al Ewing and Lee Garbett's opening issue has some okay moments. However, it tries too hard to appeal to people who have watched The Avengers multiple times, and not those who have been long time fans of the character.
This is really the only problem I have with the issue. The multiple references to Joss Whedon's superhero classic really bog down the story, which finds Loki breaking into Avengers tower to try and free Thor from the control of an evil demon. While in Avengers tower, who does he come across? If you guessed Hawkeye, Black Widow, Thor, Hulk, Captain America, and Iron Man, you've won this week's no prize. Loki causes the Hulk to attack his teammates, gets placed in a holding cell that looks very similar to the one he was in in the movie, and there's even two panels that are the exact scenes from Avengers when the team confronts Loki after his attack on New York has failed. It tries so hard, that it's almost sad. At least the art from Lee Garbett looks nice.
While I get the intention of referencing the most popular superhero movie of all time, it just doesn't work for me. I'm hoping this won't be the theme of every issue, because the idea of Loki being used to help Asgard is really cool, and has a lot of potential. But if this is what we'll be getting for next issue, I think I'll be sitting this one out.
Wolverine #1
Wolverine has lost his healing factor, but he's found his dark side. Picking up from writer Paul Cornell's previous Wolverine series, the All-New Wolverine #1 finds Logan teaming up with a team of super villains, but more importantly, it has the mighty Ryan Stegman on art, which is the real reason to pick up this issue.
That's not to say that Cornell's story isn't good. It's fine, and actually does a very good job for someone like me who decided to pass on Wolvie's last series. There are a few weird questions that arise from Logan's situation though, like the fact that he's not using his claws, and instead using a gauntlet mechanism. Also, I'm pretty sure the last time he lost his healing factor his body was in danger of admantium poisoning, so unless that's been ret conned, it's completely brushed aside. Much of the issue follows Logan going through a mission with his new super villain team, while his boss, "The Offer", tries to pitch Logan to a new client. That's really all there is to this issue, other than a flashback with Storm and Logan that doesn't tell us anything new.
Ryan Stegman's art is pretty excellent in this issue. If there was any doubt that he's a new force to be reckoned with, just look at the splash page showing Wolverine slashing into some goons. The only real complaint I have is Stegman's depiction of mask less Logan. For some reason, his hair gets flattened to the back, and takes on the look of Lilandra from the Shi'ar. It's pretty weird, but hopefully it's fixed in later issues.
Wolverine #1 doesn't give us many answers for Logan's sudden change from hero to villain. Really, the only revelation is why he's now using a gun. Hopefully we won't be waiting too long to find out why Wolverine's doing what he's doing now. However, next issue sees Ryan Stegman drawing Wolverine squaring off with the Superior Spider-Man, which gives me more than enough reasons to pick up it up.
Jonwahizzle is a jack of all trades: educator, comic book slinger for Jetpack Comics, and member of Another Let Down. Follow him on twitter and check out his blog, The Collective: Examples of Nerdery for more!
The Top 10 Times David Letterman Got Too Real
5 Ways Shin Megami Tensei X Fire Emblem Looks Like Henry's Perfect Game
Homer And Marge Explain They Aren't Breaking Up, So Relax
Laser Time – 1-900-LAZR-TIME
Cape Crisis #79 – A Super Bowl of conversation
3 thoughts on "Comic Reviews: The Punisher, Loki: Agent of Asgard, and Wolverine!"
paragon_shepard says:
I too am getting sick of the movie pandering that takes place in some select avengers comics.
That said I am loving the down to earth stories being told in wade's daredevil and now Edmonson's Punisher.
laserclock says:
Why no Ms. Marvel review? Ah well. Maybe next time.
Jonwahizzle says:
Sorry man, I'm on a budget for these things. Maybe next week!
Rare Replay – Let's Do This!
The Greatest Movie Commentaries of All-Time – Laser Time #381
Neighbors [Blu-ray]
Super Mario 3D World - Nintendo Wii U
Masters of the Universe (25th Anniversary) [Blu-ray]
The Spectacular Spider-Man: The Complete Series [Blu-ray]
Moon Knight, Vol. 1
Simpsons Comics Extravaganza (Simpsons Comics Compilations)


I know I could find the answer by harnessing the Google power but it's more fun asking y'all!
Are dies interchangeable with other manufacturer's presses? My brother gave me all of his reloading stuff which included a Lee "hand press". I ordered Lee 30-06 dies before even opening the box he sent the stuff to me in as I knew he only had 9mm and 5.56 dies. Can I use them with say a Hornady or Dillon press?
I've barely started reading up on reloading and don't plan on going elbow deep for awhile though I want to make sure I don't buy anything I'll have to return later on.
Yeah I think the major manufacture dies are interchangeable.
Standard threads on nearly all dies will be the now standard 7/8-14 thread, that is a diameter of 7/8", with 14 threads per inch.
There is some variance in .50 BMG dies, with some manufacturers using 1-1/4- 12 and some making their dies 1-1/2- 12 thread.
And you may occasionally find some old Lyman or Ponsness Warren dies with 7/8-9 threads.


Many small firms view legal billing as a means to an end, yet struggle to get paid. This is underscored by recent studies that show law firm billing realization rates are declining, hitting a 10-year all-time low in October 2015 and continuing to decline into 2017, according to a 2015 and 2017 Georgetown Law Center and Thomson Reuters Peer Monitor Report on the State of the Legal Market. When you're a small-firm attorney responsible for performing substantive work in addition to management functions, low realization rates can be particularly devastating. With only so many hours in a day, putting in more billable time just isn't a realistic option. It's time to start working smarter, not harder.
Smarter starts with understanding changes in the legal marketplace. It's a buyer's market. Clients are demanding predictability with respect to fees and that attorneys use cost-effective business practices. They are also no longer willing to pay for firm inefficiencies, including unnecessary time spent on administrative work or processes that a computer could handle in a fraction of the time.
A highly efficient firm will attract and sustain clients, achieve high realization rates, and enjoy a growing bottom line.
A focus on firm processes and procedures is key to becoming a highly efficient firm. When it comes to combating low realization rates, billing should not be viewed merely as a means to an end but as an important procedure worthy of management resources and attention.
Accomplish this by reviewing the eight legal billing best practices and procedures below. Then update the procedures accordingly for your firm, memorialize them, and train everyone in your firm on the new procedures.
Have a system for selecting clients that starts with client intake and an interview. Develop a grading system to vet potential clients. List your criteria for your A, B, C, and D client, and use this criteria to guide your selection process.
As soon as you spot a D client, it's time to end the interview.
In this scenario, because they use technology and are more efficient in their work output, Firm B can double the revenue of Firm A.
Whether you bill by the hour or use a flat rate, make it a practice to collect money up front. Review your jurisdiction-specific rules to determine whether you must first deposit this into your IOLTA account or whether it can go directly into your operating account. When a client is willing to pay you up front, it demonstrates an ability to pay and invest in the case.
Again, clients like predictability; thus, if you can bill with some regularity, you'll have an easier time collecting money owed. Whatever you do, don't let too much time pass between when you complete work and when you send out the bill. The more time that passes, the less likely the client will be to pay. This goes for collections as well. The probability of receiving payment diminishes the longer an account goes unpaid.
To make this easy, you can track everything from unbilled time to aging client receivables in a convenient financial performance data dashboard within a law practice management system.
It should go without saying that to get paid what you are owed, you must track and record your time. If you are billing at the traditional rate, failing to record your time for a mere six minutes per day can result in thousands of dollars lost over the course of a year.
Too many attorneys attempt to reconstruct their time at the end of the day or even worse at the end of the week. Contemporaneous timekeeping is a must. The most effective way to track your time contemporaneously with your work is by using time and billing software within a law practice management system, such as Firm Central, that allows you to start and stop a timer, add time manually, and convert it directly to invoices without double entry.
Tracking your time contemporaneously will also lead to more complete and accurate time records. When tracking your time, be sure to include all relevant data about your work. When it comes time to bill, you'll use that information to demonstrate value to your client, thus increasing the likelihood of payment.
Clients like their attorneys to treat them as though they are the number-one priority. If you don't give them the attention they need, they will be less likely to pay. You should implement processes to send out regular reports regarding the status of your client matters and the good work you are doing to help demonstrate your value and make your clients feel comfortable paying your fee. Technology can help here. Use your law practice management system to set up reoccurring tasks or calendar notifications, or use your client portal to share information with the click of a button.
If a client stops paying you, have a procedure to assess and effectuate withdrawal – as dictated by your state's ethics and court rules. Refer back to the client expectations delineated in your written fee agreement to help assess the situation. If you plan to depart from a case involving potential litigation, seek and acquire leave of the court prior to terminating the client relationship.
As a last resort (and I can't emphasize this enough), you can hire a collections agency or sue your client for fees owed. Before you take those measures, be sure to have, and follow, a firm collections policy that details how you track client payments and handle nonpayment. When embarking upon these measures of last resort, be sure to weigh all the risks and associated costs.
You should make it a practice to report and analyze that data on a regular basis to determine where you can make improvements.
Most lawyers I know went to law school to become lawyers and not business managers. But, the reality is that in a small-firm setting, every attorney and staff person must make a contribution to the business side of the practice. If you use these best practices to review, revise, and supplement your own legal-billing procedures, you will be well on your way to a more efficient and effective law practice. This, in turn, will allow you spend more time on the substantive side of practice, increase your bottom line, and maybe even allow you to take a vacation once in a while.
Heidi Alexander is director and law practice advisor for the Massachusetts Law Office Management Assistance Program and deputy director of Lawyers Concerned for Lawyers, a nonprofit lawyer assistance program.
In a small law firm, it is a constant struggle to balance the practice of law with managing the business. Get three tips to help you find balance and feel like a real lawyer again.
Are you happy with your law firm's legal billing process? If you still track time on paper or in spreadsheets, it is time to consider a new approach.


text:
Cette page concerne des événements qui se sont produits durant l'année 2023 du calendrier grégorien au Mexique

2021 au Mexique — 2022 au Mexique — 2023 au Mexique — 2024 au Mexique — 2025 au Mexique

 2021 par pays en Amérique — 2022 par pays en Amérique — 2023 par pays en Amérique — 2024 par pays en Amérique — 2025 par pays en Amérique

Éphémérides
 x.

Toujours en cours
 Andrés Manuel López Obrador est Président des États-Unis mexicains et son gouvernement est en place depuis décembre 2018.
 La Guerre de la Drogue est toujours en cours depuis 2006, et elle s'intensifie depuis 2016 provoquant chaque année plus de morts.
 Le Mexique est toujours touché par la crise migratoire en Amérique centrale depuis 2017.
 Le Mexique est toujours l'un des pays les plus touchés au monde par la pandémie de covid-19.

Événements

Janvier
 5 janvier : arrestation de Ovidio Guzmán López dans le cadre de la guerre de la drogue au Mexique à Culiacán. L'opération de capture s'achève sur un bilan total de 10 militaires et un policier morts, 19 membres du cartel de Sinaloa abattus, 35 militaires, 17 policiers et un garçon de 14 ans sont blessés, 21 sicaires prisonniers.

Février
 x

Mars
 x

Avril
 x

Mai
 x

Juin
 x

Juillet
 x

Août
 x

Septembre
 x

Octobre
 x

Novembre
 x

Décembre
 x

Voir aussi

Articles connexes

Articles sur l'année 2023 au Mexique
 Pandémie de Covid-19 au Mexique

L'année sportive 2023 au Mexique
 Tournoi d'ouverture du championnat du Mexique de football 2023
 Tournoi de clôture du championnat du Mexique de football 2023
 Grand Prix automobile de Mexico 2023
 Tournoi de tennis du Mexique (ATP 2023)
 Tournoi de tennis de Cabo San Lucas (ATP 2023)
 Tournoi de tennis de Guadalajara (WTA 2023)

L'année 2023 dans le reste du monde
 L'année 2023 dans le monde
 2023 par pays en Amérique, 2023 au Canada, 2023 au Québec, 2023 aux États-Unis
 2023 en Europe, 2023 dans l'Union européenne, 2023 en Belgique, 2023 en France, 2023 en Italie, 2023 en Suisse
 2023 en Afrique • 2023 par pays en Asie • 2023 par pays en Océanie
 2023 aux Nations unies
 Décès en 2023

Liens externes

Notes et références

Mexique