Each week, North Wales Live pulls together its files to name and shame the criminals locked up for offences committed in and around the region.
Every one of the people named here has appeared in court.
In some of the cases, trials have been held and jurors have deliberated over the evidence.
A judge has decided their crimes are so serious that only a custodial sentence will suffice.
A man was jailed for 12 weeks after crashing a works Mercedes lorry into a bridge - when he shouldn’t have been driving it.
Kyle Twist, of Oswald Road, Llandudno Junction, pleaded guilty to failing to give a specimen of blood for alcohol analysis after the crash at Dolwen on November 11 last year.
His solicitor Andrew Hutchinson suggested a suspended sentence, but Llandudno court chairman John Rooney said the case was so serious that only immediate custody was appropriate.
Diane Williams, prosecuting, said that after the lorry belonging to a utilities company crashed into the wall, the rear of the vehicle was wedged in a stream.
A roadside breath test showed a reading of 90 for alcohol – the limit being 35.
The court heard he’d driven the lorry for his own private use on a Sunday and faced disciplinary proceedings from his company but had resigned. His solicitor said Twist was struggling to find alternative employment.
In addition to the prison sentence, Twist was banned from driving for three years and was ordered to pay £265 costs.
The chairman told him: "It was a wilful refusal to give a sample, a very high reading at the roadside and it followed a serious road traffic accident."
Stephen Lewis Nesbitt
A restaurant boss who attacked a woman with whom he was said to be obsessed still found it "impossible to believe" she was not interested in him as he was jailed for the offence, a judge said.
Prosecutor Matthew Curtis said the teenager had made it clear on several occasions that she had no romantic feelings for the defendant at all.
During his sentencing at Mold Crown Court, Judge Niclas Parry said Nesbitt still found it "impossible to believe" she was not interested in him.
Nesbitt had been described as obsessive about the woman before the offences took place.
She had deleted him as a friend on social media after he sent a naked Snapchat picture of himself in bed with his wrist partially covering his genitals, which he claimed had been sent in error.
Nesbitt was jailed for 16 weeks and was made the subject of a five-year restraining order banning him from contacting the victim.
He was also ordered to sign the sex offenders register for five years.
Billy Perks was arrested after video of the incident emerged on a mobile phone seized from a teenage girl involved in an unrelated incident.
The device also contained footage of another incident in which the 29-year-old, of no fixed address but previously of Butler Street in Shotton, had smashed a glass bottle and threatened another man with it.
Perks had initially denied the charges and a trial was due to be held at Caernarfon Crown Court. But before the judge was chosen, Perks asked for two of the charges to be put again and he admitted the offences.
Sentencing Perks, Judge Huw Rees it had been his “displeasure” to watch the videos in court.
“They show sheer loutish behaviour on your part and you should be thoroughly ashamed of yourself,” he said.
The judge also ordered Perks to be subject of a Criminal Behaviour Order and he is banned from being in Connah's Quay for five years.
A man who admitted pleasuring himself in front of a debt collector has been jailed for possessing indecent images of children .
Michael Gate, 70 of Western View, Pandy, Wrexham, had already admitted three counts of making indecent images of children when he appeared for sentencing at Mold Crown Court.
At the time the offences were committed, he was on licence after serving a seven-year sentence for sexual touching and serious sexual assaults against children between the ages of six and nine in 2010.
The court heard North Wales Police officers visited Gate on September 20 last year after concerns had been raised about his sexual behaviour.
It was apparent to the officers it had escalated.
Judge Niclas Parry sentenced Gate to two years in prison and made him the subject of a sexual harm prevention order, which means he must register any electronic device he has in future with police.
They must be owned in his own name and it must be a device with a history.
The SHPO is to run alongside his existing order to register as a sex offender.
A North Wales man nearly bankrupted a Liverpool theatre by siphoning off hundreds of thousands of pounds to splurge it on his own “frivolous” lifestyle .
Kelvin Lloyd even spent more than £10,000 on take aways from Deliveroo and Uber Eats using the money he’d stolen from the Epstein Theatre.
But while he was living it up using the £273,000 he stole to pay for holidays to the USA, expensive phones, TVs, games consoles and even top-of-the-range vacuum cleaners, the theatre’s bosses were facing financial ruin.
They had creditors turning up at their homes demanding money they were owed, and administrators had to be called in.
It was then that a number of odd payments came to light.
Initially Lloyd, 27, of Jubilee Street, Shotton, blamed “spreadsheet errors”, but did return £18,000.
But it was only when police were called in that the scale of Lloyd’s crime became clear.
He confessed to transferring £180,574, that was meant to go to creditors, into his own accounts. And he put another £92,535 from the theatre’s cash takings, banking a total of £273,109.
Jailing Lloyd for 28 months, Judge Rachel Smith said his actions had “profoundly damaged” the theatre where he had worked and had been regarded as a trustworthy and responsible employee.
A pervert who admitted watching two girls in the Philippines being sexually abused online has been locked up .
Peter Booth was jailed for seven years and four months after pleading guilty to four charges of causing or inciting the sexual exploitation of a child under 13 by paying to view the live abuse via Skype.
The 74-year-old, of St Andrew’s Avenue in Llandudno, had also admitted charges of possessing indecent images of children and distributing such images, and having extreme pornographic material of children on a laptop and a mobile phone.
Jailing him at Caernarfon Crown Court, Judge Timothy Petts said: “What you did to these girls was absolutely horrific. It was all done for your perverted pleasure.
“In addition, investigations showed you were collecting images of child abuse and sharing these with others.
“These are very serious offences and only a lengthy prison sentence can be justified.”
A man suggested he was a Nazi during an incident where he hurled racist abuse and smashed all the windows in his council flat with a hammer, a court heard .
Harry Jones, 38, of Cefn Dre in Wrexham, who was on bail for assaulting a police officer when he became involved in the affray, was jailed for 12 months at Mold Crown Court.
But a judge warned that, if he had been properly charged, the sentence would have been longer.
Jones admitted assaulting the police officer on November 17 - four days after a new act on assaulting emergency workers had been introduced.
Judge Rhys Rowlands said the new act doubled the available sentence for assaulting police officers and others.
But Jones was fortunate to have been charged under the old act because of an error either within the police or the CPS, he said.
Daniel James Dobbs and Jamie Milburn
Drug dealers from Liverpool who were placed on a North Wales housing estate to sell heroin and cocaine “stuck out like sore thumbs”, a court heard .
Daniel James Dobbs and Jamie Milburn spent four days in the Maesgeirchen area of Bangor in May last year.
They were arrested after being seen acting suspiciously by police and, while no drugs were found on them initially, CCTV footage showed Milburn dropping a package which was later recovered.
It was found to contain wraps of heroin and cocaine with a street value of about £200. Officers found the men were carrying a total of £300 cash.
Dobbs, 19, of Dorrington Walk, Liverpool, and Jamie Milburn, 20, of Beatrice Street, Bootle, admitted charges of possessing the drugs with intent to supply when they appeared at Caernarfon Crown Court .
They were jailed for two years each, after Judge Huw Rees rejected pleas by defence barristers to suspend any prison sentences.
He said: “These offences are too serious for anything other than immediate sentences of detention.”
A police officer had to swerve out of the path of a motorist driving the wrong way down the M56 while high on drugs .
Hassan Waseem was seen driving erratically, changing speeds and drifting across the road towards oncoming cars in his white BMW during the “terrifying” incident at around 4.30am on Thursday, January 10.
Other motorists called the police after spotting the car travelling in the wrong direction between Junction 11 and Junction 12 near Runcorn in Cheshire.
Officers were sent to the scene and, on arrival, Sergeant Anton Sullivan saw the vehicle driving towards him at speed with its lights on full beam.
Sgt Sullivan took evasive action, swerving onto the hard shoulder to avoid a head-on collision.
A short time later, the BMW was located parked on the hard shoulder, with Waseem sat in the driver’s seat.
Waseem was arrested at the scene and a drugs test revealed that he had a cannabis reading of 5.5µg/l – more than double the legal limit.
The 23-year-old appeared at Chester Crown Court and was sentenced to 12 months in prison.
Waseem, of Broadstone Road, Heaton Chapel, had earlier pleaded guilty to dangerous driving, drug driving, driving without insurance and possession of a class B drug.


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text:
Democracy is a vision of hope that has never been well implemented in any mass society. Americans should learn the lessons inherent in the missteps of other societies struggling against internal factions that attempt to use democracy in order to destroy it.
Democracy, if civil liberties are not taken to be an inherent part, is a concept with little meaning and less value. If Stalin’sThis conflict between democracy and theocracy is increasingly becoming the central issue in Israeli politics and, with the militarists who advocate a garrison state deepening their alliance with the theocrats, threatens to become a fight to the death for the future of
were “democratic” just because the law required everyone to vote, with 100% happening to vote for him, then “democracy” would be just another political rip-off. Therefore, I take the term “democracy” to incorporate civil liberties. That said, a democracy and a theocracy can only overlap if exactly 100% of the population desires a religious state; should even one person choose another path, then either the democracy will become a dictatorship or the theocracy must be abandoned. USSR
One recent piece of evidence that theocratic forces are winning this battle for control of Israel is the bill just approved by a Knesset committee to give the “orthodox rabbinate” [Alana Newhouse, “The Diaspora Need Not Apply,” New York Times,
authority over who is legally considered a Jew in
, a fundamental question in a theocracy because the answer defines who is a citizen. Israel
Going hand-in-hand with the above example of rising Israeli theocracy is the recent Israeli cabinet approval of a law that would require illegal residents aspiring to citizenship to swear allegiance to a “Jewish democratic state.” [“Israeli ‘Loyalty Oath’ Approved” MWC
Israeli legal affairs editor for the newspaper Yediot and retired judge Boaz Okon published on June 22 his own list:
- A school that began segregating students on ethnic lines with the support of the community;
- A Knesset member is humiliated by her peers for joining the
- Apartheid on the streets of
has become institutionalized; Hebron
- Punishment of Arabs is harsher than punishment of Israelis;
- The extraction of false confessions from minorities by police are not investigated;
- Illegal wiretapping by the government is not investigated.
This is only part of the judge’s list, which he summarizes as “growing evidence of the lack of the spirit of freedom and the emergence of apartheid and fascism.” [Didi Remez, “Yediot’s Legal Affairs Editor on ‘the Emergence of Apartheid and Fascism’ in
,” Coteret.com Israel 6/23/2010.]
Writing in Haaretz a few months ago, Carlo Strenger, Chair of the Clinical Graduate Program at
, put it this way: Tel Aviv University
In this time of rising anxiety
's political echelon has taken a number of steps toward undermining Israel 's sometimes flawed but always vibrant democracy. The Knesset's shameful passing of Yisrael Beiteinu's so-called Nakba Law in a first reading is a dangerous precedent: Once freedom of expression starts to be curtailed, a state enters a slippery slope and nobody can know where it ends. The Israel Defense Forces' declaring Bil'in a closed military area is an active step against political freedom and a way to undercut decisions taken by Israel 's Supreme Court. [Muzzling Israel ’s Left Only Harms Its Democracy, Haaretz Israel 4/2/10.]
One can easily imagine where this is headed: in the future, lifelong Jewish Israeli citizens who dare to oppose government policies will find a rabbinate court stripping them of their “Jewishness” and the government stripping them of their citizenship and themselves being fined the cost of a one-way flight to somewhere else.
When the privilege of enjoying democratic rights is reserved for a subset of the population, say, whites, or males, or the rich, then the society is already set on a slippery slope down to authoritarianism. After all, if “the poor” or those lacking blue eyes can rightfully be excluded, then why not you…or, indeed, everyone except “the leader?”
is now clinging to this slippery slope and losing its grip. Israel
All is of course not lost. The U.S., with its 18th century democracy for rich white men, managed to climb some ways up this slope but at the cost of the Civil War, which cracked open the door not just for blacks but for Indians and white women as well. So the course can be reversed, but slipping down the slope is far easier than crawling back up.
Those Israelis so fond of talking about existential threats should think about the contradiction between democracy and theocracy before it becomes the real existential threat facing
. But that is the business of Israelis. For Americans, the issue is different: having been taught a lesson about the dangers of external violent fundamentalism, it is now time for Americans to learn about the dangers of internal fundamentalists who pursue their anti-democratic goals by democratic means. Israel
When democracy is reduced to democratic processes without a secure foundation in popular responsibility to defend civil liberties, then democracy becomes a dangerous tool in the hands of extremists subtle enough to conceal their penchant for force. The first lesson for Americans is that this danger exists in the
as well, although for Americans, it may be easier to perceive it by looking overseas. In both Israel and Iran today, the contending forces are particularly clear, but Israel is the country Americans should be watching the most closely, both because it is still a relatively open society and because many Americans pursuing a special agenda are pleased to insist loudly that Israelis “share American values.” If Israel is to be taken as a model for or a reflection of American values, then we owe it to ourselves to make sure we know exactly what values Israelis today believe in. U.S.
The initial version of this article, entitled "Israeli Theocracy," was published by Media With Conscience on

domain: politics


November 22, 2014
CARSON CITY, Nev. (AP) - Legislative money panels have voted unanimously to restore pay cuts imposed on state workers but to keep unpaid furloughs.
The actions Friday by the Assembly Ways and Means and Senate Finance committees comes as lawmakers are putting the finishing touches on the budget in the final days of the 2013 session.
Republican Gov. Brian Sandoval had proposed keeping the pay cuts, but reducing the number of furlough days from six to three in the upcoming fiscal year and eliminating them beginning July 1, 2014.
The committees' actions, if adopted in the final budget, would cost $32 million over the biennium.
Republicans agreed conditionally to restore the 2.5 percent pay cuts but say they'll oppose it if takes money away from public schools.
Copyright 2014 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or firstname.lastname@example.org.


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text:
2005 Ducati Monster 620 with less than 2200 miles on it for $6050 Services all done at GP motorcycle in San Diego. This bike is pretty much stock except for a custom frame sliders, eliminator silence plate and 14 tooth c/s sprocket. This bike is a unique offering in the world of motorcycles, welcoming to beginners, and yet able to deliver a level of performance that can also thrill advanced riders.
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domain: hobby


text:
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domain: artistic


text:
Find a copy online
Links to this item
Find a copy in the library
Finding libraries that hold this item...
|Material Type:||Online system or service, Internet resource|
|Document Type:||Internet Resource, Computer File|
|All Authors / Contributors:||
Charles Johnson; Daniel Defoe
|Notes:||Charles Johnson is believed to be a pseudonym.
Sometimes attributed to Daniel Defoe (Hutchins, Moore, Novak). Attribution disputed by Furbank and Owens, Defoe de-attributions.
First edition entitled 'A general history of the robberies and murders of the most notorious pyrates, . '.
Reproduction of original from the British Library.
|Description:||1 online resource (, 17-427,  pages, plates)|
|Other Titles:||General history of the robberies and murders of the most notorious pyrates
Eighteenth Century Collections Online (list of titles)

domain: library


text:
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All artistic items, products, compilations or collections are manufactured directly from the original art work by a high quality German scanner. Authentication of works includes ink stamp, signature and artist impressed paper signature embedded into the works by the artist himself for full authentication. You will have a piece of art that last a life time and can be passed down from generation to generation. Your digital or hard copy images that are of excellent quality can be made from the foundations of digitalization, framing, imaging, designing, creation and professional reproduction to print.
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text:
A recent survey conducted by Telenav reveals some trends and habits of the smartphone user. The survey looks at habits of smartphone users, asks what they would give up for their device, and examines the various different smartphone platforms. Of interest, iPhone users are most likely to checkin to a business (23%), Blackberry users are most likely to spend more than $1 for an app, while Android device users seem to feel their device reflects their sense of style.
Some findings of interest:
- iPhone users were twice as likely than Android users to have spent more than $40 on apps for their current phone.
- Nearly half of Android users said their phone reflects their overall sense of style—more than iPhone users (35%). 43% of BlackBerry users felt their phones reflected their overall sense of style.
- While a strong majority of iPhone users (83%) thought other iPhone users would make the best romantic partners, and a strong majority of Android users (70%) selected other Android users, only 48% of BlackBerry users thought other BlackBerry users would make for the best romantic partners.

domain: news


text:
World National AIDS Day
COLUMBUS, Miss. (WCBI)-December 1st marks the 23rd Anniversary of World AIDS Day.
Approximately 34 million people now live with HIV and AIDS and 1.2 million of them live in the United States.
“Getting to Zero”, is the theme for this year’s World AIDS Day. It is a campaign that is helping in the fight against AIDS. Throughout the United States many will recognize Saturday’s awareness in different ways. For some Columbus organizations, it was all about making an imprint for generations.
By planting a magnolia tree many hope it will bring awareness to HIV and AIDS. As well as supporting those who live with the virus everyday. And remember those who have passed away.
“This is an epidemic that we are experiencing and the more people who know their status the better,” says Whitney Washington.
“There are so many people out there that are victims of the illness and they don’t know,” says Monique Montgomery.
Kimberly Washington, an active member in The Columbus Lowndes chapter of Delta Sigma Theta, felt honored when asked to help spread awareness. She hopes other students her age will do the same and get involved.
“I’m a college student and maybe younger people who see me and see what we are trying do,” says Washington.
“Today they just challenged every chapter in the nation of Delta Sigma Theta sorority to take an active movement and not just be a monument,” says Montgomery.
The AIDS virus has no descrimination and can affect anyone. Learning about the disease and the proper preventions can go a long way in the fight against AIDS.
The Sally Kate Winters family hosted today’s event. The magnolia tree that is planted at the River walk was donated by the city of Columbus.
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text:
Marshall Co. Fiscal Court Sets Final Workshop for Alcohol Ordinance
After Marshall County voters approved countywide liquor sales last month, city and county governments are trying to finalize their alcohol ordinances so that sales can begin.
Assistant county attorney Jason Darnell says there have been three sticking points thus far in discussions regarding the county ordinance – the regulatory license fee which he says is basically a sales tax, the sale of alcohol on Sundays and the distance between liquor stores and schools and churches. Darnell says the fiscal court is currently discussing a distance between 500 and 1,000 feet.
"I want to emphasize that regardless of what the number is, it’s going to be a case-by-case determination,” Darnell said. “So in other words, if somebody applies for a package liquor store and it’s 900 feet from a school, that’s not going to automatically disqualify them from getting it.”
Darnell said the issue of Sunday sales is still being debated and will be a close vote for the fiscal court. He said the ordinance, which will cover unincorporated areas like Draffenville and Aurora, needs to be in place by October 4 because that’s the day the county officially goes wet and can begin capitalizing on licensing permit revenue.
“It’s a two-step process to be licensed," Darnell said. "Number one, you have to apply for the local permit first before you apply for the state and if we don’t have ours in place, then they’d just apply directly to the state and we’d risk losing out on that revenue.”
The fiscal court will hold a final workshop on the ordinance Thursday, September 10, before its second reading and a vote in late September. The cities of Benton and Calvert City are also in the process of creating their own ordinances.

domain: law


text:
1/28/2015 | W. Basketball
Ohio State eyes its third three-game winning streak of the season on Thursday when it travels to Madison, Wisc., to take on the Badgers in the only regular season meeting between the two teams. Tip-off is set for 9 p.m. ET from the Kohl Center.
1/26/2015 | W. Basketball
For the second time this season, Ohio State guard Kelsey Mitchell has swept the B1G Weekly awards as she was named the B1G Player and Freshman of the Week on Monday.
1/25/2015 | W. Basketball
Ohio State freshman Kelsey Mitchell scored 31 of her Mackey Arena record 37 points after halftime to lead to the Buckeyes to a 79-71 overtime victory over Purdue Sunday afternoon.
1/23/2015 | W. Basketball
Ohio State will take its show on the road as its starts a two-game road trip on Sunday in West Lafayette, Ind., against the Purdue Boilermakers. Tip-off is set for 2 p.m. from Mackey Arena.
11/24/2014 | W. Basketball
Returning for an unprecedented fifth season is Courtside with Marty Bannister! The play-by-play voice of the Ohio State women's basketball team for the past 12 years will be keeping a blog once again throughout the season to provide fans with insight on the team and give his take on the Buckeyes, the Big Ten and the rest of the college...
1/19/2015 | W. Basketball
Ohio State freshman point guard Kelsey Mitchell averaged 28.5 points per game in the Buckeyes two games last week and was named the Big Ten Freshman of the Week on Monday.
1/18/2015 | W. Basketball
Ohio State got 21 points from freshman Kelsey Mitchell and a double-double from fellow freshman Alexa Hart to outlast Penn State 69-60 on Sunday afternoon at Value City Arena.


text:
With fall in full swing and snow adorning the mountain tops, I turn to a classic dish for a little winter comfort: Campbell’s Tomato Soup. First introduced in 1895, the can would don its familiar red and white label in 1898 after an executive attended the annual Cornell-Penn football game and “was impressed by Cornell’s new red and white uniforms,” according to Campbell’s website.
Stubbornly consistent, very little has changed about the soup over the century it’s been available. As such, it makes for an unusual, albeit informative, way to measure a current problem: inflation.
For the first 76 years of its existence, until late 1973, consumers paid $0.07 to $0.12 per can thanks to government price controls on food. As of January 2020, the average advertised sale price was $0.85 per can, resulting in an approximate inflation rate of about 4.3% per year over 46 years (from when the controls were lifted.) Today the average price rings in at $1.18 per can. Do the math, and that means the average price has increased at a 17.8% rate over the past two years alone.
This shouldn’t be surprising to anyone. Prices have been on the rise across the board. Inflation has become a household word and the boogieman everyone is trying to stop. Who or what’s to blame? It depends on your news source: Democrats, Republicans, OPEC, COVID, Federal Reserve (Fed), suppliers, consumers, the person who owns your local bakery… you name it. As if these individual entities have a lever in their office that directly controls the prices of goods and services. I find the image of the corner baker maniacally laughing while raising the price of croissants, thinking, “That’ll get ’em!” both humorous and completely inaccurate.
The reality is no one wants to raise prices, least of all the businesses that serve you. The higher the croissant price, the fewer sold alongside a cup of morning coffee. But the cost of flour, sugar, energy for the oven, and labor has gone up, so what’s the baker to do? Their sole purpose as a business is to provide value to their customers and generate a profit. When costs go up, prices go up. It’s a simple balancing act. Can anyone fault a business owner for raising prices because of increased costs?
Yet, consumer spending remains high. Anyone who’s traveled lately is familiar with the long lines at DIA or the difficulty in finding some of the goods we all still want. Personally, I assume most things I order are going to take at least two weeks more to arrive than anticipated. With consumers adapting to higher prices, I believe it’s unlikely we’ll see significantly lower prices soon. Inflation is “sticky.”
Last week’s Consumer Price Index reading was a welcome shift in what had been continuous increases month over month and year over year. The September number was +8.2%, meaning that for the same basket of goods and services, prices had risen by 8.2% over the past year. However, this month saw that number “drop” to +7.7%, the lowest annual increase since January, according to CNBC. Some believe this is a sign that perhaps inflation has peaked and might trend toward more reasonable, long-term levels. They think this might give the Fed enough data to slow down the rate at which they’ve been increasing interest rates. I hope this is the case, but “hope” isn’t a financial strategy.
Even if inflation has peaked, goods and services are still +7.7% higher than a year ago, at which time they were already much higher than the year before. If companies and consumers continue to adapt to higher prices, all we’ve done is hit a new price plateau. By raising the cost of money (interest rates), the Fed has seemingly applied enough “brake” to slow us down momentarily. Unfortunately, continuing to raise the price of money puts us at an ever-increasing risk of a longer and deeper recession. I don’t believe that method of fighting inflation works.
For many years, consumers got drunk on the idea of cheap money. Cash is trash was a popular saying. While the Fed kept interest rates near 0% for too long, swinging the pendulum to the other extreme is unlikely to fix the problem.
Instead, I believe we need to increase our productivity to lower prices. Readers also know of our inflation analogy of apples: If the economy is ten apples, and there are $10 in the economy, the price per apple is $1. When the government printed and pushed 40% more dollars into the economy over the past two years, that $10 increased the money supply to $14, but the economy still produced the same ten apples. The price per apple is now $1.40. Now, that’s inflation! Raising interest rates or the cost of money will not cause the price per apple to fall but growing more apples will. If we grow 14 apples and have $14 in the economy, the price per apple will fall to $1. The solution is to increase productivity, produce more goods and services, de-regulate, lower the friction between business and people, and incentivize growth. That is the solution.
The definition of entrepreneurship is taking some raw material or product and creatively adapting it to a new, higher-valued level. There are so many opportunities in our economy. Innovators wake up every day thinking about how to do things faster, easier, better, and cheaper to raise value for consumers and businesses. Our way out of inflation is not by making it more complicated or expensive to do business but rather by tearing down the barriers that make starting and growing a business so difficult.
The opinions voiced in this material are for general information only.
The economic forecasts set forth in this material may not develop as predicted and there can be no guarantee that strategies promoted will be successful.
Securities offered through LPL Financial, Member FINRA/SIPC.
https://prosperion.us/wp-content/uploads/2020/02/campbells-soup.png6671000Steve Boorenhttps://prosperion.us/wp-content/uploads/2017/02/whitelogosized.pngSteve Booren2022-11-20 13:13:312022-11-29 14:53:53Growing Our Way Out of Inflation
A few weeks ago I attended the retirement party of someone I’ve called a dear friend for over 49 years. Long ago, we were both young financial advisors chasing similar career paths. We even migrated to independent businesses around the same time. His retirement prompted me to reflect with gratitude on all my opportunities and […]

domain: economics


When Andrew Burke learned he had won the lottery last month, he knew he was about to win it again.
Burke was at the Fas Gas in Calmar, Alta., where he regularly buys lottery tickets, when he asked the clerk to check his ticket.
She did, and the counter staff erupted.
“The owner walked in and said, ‘Have you broken my machine, Andrew?’ ” Burke told CBC News.
“I said, ‘I don’t know. What’s up, bud?’
“He said, ‘You’ve won $2.5 million.’ I said, ‘You’d better check that other ticket, because that’s a winner as well.’ “
Burke accidentally bought two tickets for the Sept. 16 LOTTO 6/49 draw using the same numbers. So in effect, he split the draw’s top prize of $5 million, which he would have won regardless, with himself.
“Two people won the lottery,” he said. “It just happens both of them are me.”
‘I just won five million bucks’
Once Burke returned home, he called his wife, Christine, asking her to pick up some takeout for dinner on her way home.
When she arrived, he sat her down.
“I have something to tell you,” he said.
She assumed immediately he had quit his job.
“I said, ‘Do you remember when we got married what your father said in his speech? He said, ‘I always wanted my daughter to marry a millionaire. I got the next best thing, a man who spends money like a millionaire.’
“She said, ‘You haven’t.’
“I said, ‘Yes. I just won five million bucks.’ “
Burke said he’s taking the win in stride.
“I’m 63 years old with two replacement knees and a bad back,” he said.
“I always wanted a Porsche 911. But the problem with that is, I can’t get in one. And if I did get in one, I couldn’t get out of one.”
All he’s ever wanted from a lottery win is to keep his home in the town 22 kilometres southwest of Edmonton, restore his Land Rover and retire — which he did four days after his win, Burke said.
“That’s it. Fix the house the way we want it and live comfortably for the rest of our lives.”


DOPETHRONE are a band from Montreal, Quebec, Canada. Active since 2008, this DIY band is known for their abrasive mix of sludge, stoner and doom with lyrics based in murder, cannabis and sleazy drug abuse. Although some people think they are named after the Electric Wizard album, they hold no dedication to the Electric Wizard sound, leaving many to believe it is simply a nod at the titanic gods themselves.
HIGH FIGHTER formed in the summer of 2014 in Hamburg, Germany. This band is a volatile cocktail of heavy as hell riffs, add a dose of the blues and these deadly schizophrenic vocals, and HIGH FIGHTER offer something different to the Sludge, Stoner, Doom & Metal Scene.


text:
Following up his acclaimed study of the Six-Day War, historian Oren analyzes America's 200-plus-year involvement in the Middle East, from battling Barbary pirates to toppling Saddam Hussein. Dietz, one of AudioFilemagazine's Best Voices of the Century, with a measured, leisurely reading style, turns in another solid performance. Dietz comes from the classic school of readers, sounding like an action movie-trailer narrator in a more contemplative mood. His almost brusque masculine swagger is highly appropriate for Oren's tale of American misadventure in the Middle East, compounded in equal parts of the three titular components. Counterintuitively for so long an audiobook, Dietz's tortoise-like performance adds to, rather than detracts from, Oren's prose, with Dietz's careful pace giving Oren's carefully researched tome an added measure of dignified wisdom. Available as a Norton hardcover (Reviews, Nov. 20, 2006). (June)Copyright 2007 Reed Business Information
Power, Faith and Fantasy: America in the Middle East, 1776 to the Presentby Michael B. Oren, Norman Dietz
From the first cannonballs fired by American warships at North African pirates to the conquest of Falluja by the Marines, and from the early American explorers who probed the sources of the Nile to the diplomats who strove for
This is the first comprehensive history of America's involvement in the Middle East from George Washington to George W. Bush.
From the first cannonballs fired by American warships at North African pirates to the conquest of Falluja by the Marines, and from the early American explorers who probed the sources of the Nile to the diplomats who strove for Arab-Israeli peace, the United States has been dramatically involved in the Middle East. For well over two centuries, American statesmen, merchants, and missionaries, both men and women, have had a profound impact on the shaping of this crucial region. Yet their story has never been told—until now.
Drawing on thousands of government documents and personal letters, this book reconstructs the diverse and remarkable ways in which Americans have interacted with this alluring yet often hostile land stretching from Morocco to Iran and from the Persian Gulf to the Bosporus. Covering over 230 years of history, Power, Faith, and Fantasy is an indispensable work for anyone interested in understanding the roots of America's Middle East involvement today.
"This is a wonderfully rich and thought-provoking history." —Library Journal Starred Review
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Norman Dietz, a writer, an actor, and a solo performer, has recorded over 150 audiobooks, many of which have earned him awards from AudioFile magazine, the ALA, and Publishers Weekly. Additionally, AudioFile named Norman one of the Best Voices of the Century.
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domain: geography


text:
Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer. In order to establish a robust and clinically applicable gene expression-based measure of CIN, we assessed the ability of four qPCR quantified genes selected from the 70-gene Chromosomal Instability (CIN70) expression signature to stratify outcome in patients with grade 2 breast cancer.
AURKA, FOXM1, TOP2A and TPX2 (CIN4), were selected from the CIN70 signature due to their high level of correlation with histological grade and mean CIN70 signature expression in silico. We assessed the ability of CIN4 to stratify outcome in an independent cohort of patients diagnosed between 1999 and 2002. 185 formalin-fixed, paraffin-embedded (FFPE) samples were included in the qPCR measurement of CIN4 expression. In parallel, ploidy status of tumors was assessed by flow cytometry. We investigated whether the categorical CIN4 score derived from the CIN4 signature was correlated with recurrence-free survival (RFS) and ploidy status in this cohort.
We observed a significant association of tumor proliferation, defined by Ki67 and mitotic index (MI), with both CIN4 expression and aneuploidy. The CIN4 score stratified grade 2 carcinomas into good and poor prognostic cohorts (mean RFS: 83.8±4.9 and 69.4±8.2 months, respectively, p = 0.016) and its predictive power was confirmed by multivariate analysis outperforming MI and Ki67 expression.
Citation: Szász AM, Li Q, Eklund AC, Sztupinszki Z, Rowan A, Tőkés A-M, et al. (2013) The CIN4 Chromosomal Instability qPCR Classifier Defines Tumor Aneuploidy and Stratifies Outcome in Grade 2 Breast Cancer. PLoS ONE 8(2): e56707. https://doi.org/10.1371/journal.pone.0056707
Editor: Aedín C. Culhane, Harvard School of Public Health, United States of America
Received: February 11, 2012; Accepted: January 16, 2013; Published: February 26, 2013
Copyright: © 2013 Sza´sz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Legacy of Szőllős András Péterné, Egeszsegugyi Tudomanyos Tanacs (ETT)-029/2009, ETT-088/2009, Tarsadalmi Megujulas Operativ Program(TaMOP)-4.2.1.B-09/1/KMR2010-0001 and the TaMOP-4.2.2/B-10/1-2010-0013 grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Chromosomal instability (CIN) is a key determinant of biological behavior of breast cancer , yet remains challenging to determine using high throughput methodologies . We and others have shown that CIN may play a role in determining response to taxane treatment in ovarian cancer  and intrinsic multidrug resistance in colon cancer  and it also appears to be an important determinant of breast cancer prognosis , . While direct determination of CIN by counting centromeres in a sufficient number of breast cancer cells or measuring DNA index is possible , it is technically challenging and time-consuming , . Consequently, a simple measure of CIN, based on for example qPCR measurement of a handful of genes, would greatly facilitate its introduction into general oncological practice. Therefore, we decided to investigate whether a clinically implementable a qPCR-based gene expression based CIN measure could be created. The ability of such signatures to reflect CGH based genomic instability has been previously demonstrated .
The potential utility of a gene expression based measure of CIN is further emphasized by its complex relationship with histological grade . It has been known for many years that grade 2 tumors classified by the Nottingham grading system display heterogeneous characteristics in terms of clinical outcome , . It has also been shown that relatively simple gene expression based methods were able to stratify grade 2 cases into low risk and high risk patients in a robust fashion . Genes intimately involved with CIN prominently featured in such gene expression signatures, but it has become clear recently that quantifying ploidy has improved prognostic potential than stratifying intermediate histological grade in terms of clinical outcome. The vast majority of hormone receptor negative cases (ER-/PgR-/HER2-) fall into histological grade 3 category , but even within those, the level of CIN may define subgroups of patients with distinct clinical outcomes . Therefore in this study, we determined a minimal gene set that seems to capture the information contained in the previously published CIN70 signature, tested its correlation with directly quantified CIN and verified its ability to stratify grade 2 breast carcinomas according to good and poor clinical outcome in routine formalin-fixed, paraffin-embedded (FFPE) pathological samples. We compared the predictive power of the resulting signature to mitotic index and Ki67 expression.
Materials and Methods
In silico selection of CIN genes for expression analysis
All microarray data sets used in this analysis were normalized by robust multi-array average (RMA) . Probe sets to represent each gene in the various signatures (CIN70 , NKI70 , 21-gene Recurrence Score (DX21) , intrinsic subtype , Ivshina's molecular grade , Ma's 5-gene HOXB13∶IL17BR ratio (Ma5) , Sotiriou's Genomic Grade Index (GGI) ) analyzed were selected by Jetset as described previously . If no reliable probe set was found for a given gene that was excluded from further analysis. The data sets are displayed in Table S1.
Focusing on histological grade, we evaluated 185 invasive breast carcinomas consisting of 63 grade 1, 62 grade 2 and 60 grade 3 FFPE tissue samples regardless of other pathological features from the Buda MÁV Hospital (1999–2002), diagnosed and graded by a single pathologist (J.K.). Recurrence-free survival (RFS) time was defined either by loco-regional relapse or the appearance of a distant metastasis, and whichever shorter if both applicable. The study was a retrospective analysis. General written consent was obtained from all patients at time of surgery. The samples were anonymised for the study. The study was approved by the Ethical Committee of the Semmelweis University (IKEB #7/2008 and #7-1/2008).
In line with bioinformatics, the clinicopathological properties of the selected 185 breast cancer patients were analyzed. The mean age of patients was 58.8±12.8 years (59.9±11.8 years, 59.2±13.0 years, 56.5±13.7 years in grade 1, 2 and 3 tumor groups, respectively). Among the histological types, invasive ductal carcinoma was the most common overall (65.9%), but less frequent types of cancer were also included in the analysis (8.1%): 1 papillary, 1 tubular, 1 micropapillary and 3 mucinous carcinomas in the grade 1 group; 1 micropapillary and 1 mucionous in grade 2; and 4 with medullary features, 2 metaplastic and 1 micropapillary carcinomas in grade 3 cancers. Tumor size, frequency of vascular invasion, presence of necrosis, Nottingham Prognostic Index (NPI) and number of relapses showed an increase, while ER, PgR expression and RFS decreased with higher grade (Table 1). When characterizing tumors according to immunophenotype, expression of ER, PgR and Her2 were evaluated and fluorescence in situ hybridisation (FISH) was performed to assess Her2 amplification. ER and PgR expressing tumors with lower than 20% Ki67 expression were considered as Luminal A (LumA). For ER or PgR and Her2 positive tumors and ER and PgR expressing tumors with more than 20% Ki67 index, Luminal B subtype (LumB) was assigned . Her2 expressing and/or Her2 amplified and ER and PgR negative tumors were considered as the Her2 subgroup (none were treated with trastuzumab at that time). Triple negative breast cancers (TNBC) were ER, PgR, Her2 negative tumors with no Her2 amplification. The disease free survival of patients in the different grade- and immunophenotype groups were plotted on Kaplan-Meier graphs (Figure S1).
RNA purification and qPCR
Five to ten 5 µm thick sections were used from each case for RNA purification after assessment of cellularity on HE stained slides (minimum of 70% tumor cell content was required). RNA was extracted with Qiagen FFPE RNeasy kit according to the manufacturer's protocol (Qiagen, Venlo, The Netherlands). High Capacity RNA-to-cDNA kit was used to reverse transcribe 1000 ng of RNA (Applied Biosystems, Foster City, CA, USA). The Eppendorf epMotion 5070 robotic system was used to transfer samples and reagents to 384-well full-skirted white plates (Eppendorf, Hamburg, Germany). The qPCR was performed in duplicates with Taqman® Assays (Table S2) in Gene Expression Master Mix (all from Applied Biosystems) according to the manufacturer's protocol. The reactions were run in Roche LightCycler 480 real-time PCR system (Roche Diagnostics, Mannheim, Germany). The CIN4 signature resulting from the qPCR measurement was assessed based on the average expression of the four genes (AURKA, FOXM1, TOP2A, TPX2) normalized to the average expression of the three control genes. In order to find robust internal reference control genes for clinical evaluation of CIN4 by qPCR in formalin-fixed tumor tissue, we chose three known housekeeping genes which bare consistently low variance in the microarray profiles of all breast cancer datasets as normalizing genes: B4GALT3, SLC9A3R2  and PUM1 .
Flow cytometry was performed for the analysis of ploidy. Briefly, a 50 µm section was cut from all the FFPE blocks. A scroll of tissue was placed in a microcentrifuge tube and xylene was added to remove the paraffin wax. The tissue was then serially re-hydrated through 100%, 95%, 70% and 50% ethanol for 5 minutes respectively at room temperature. The tissue was washed twice with distilled water. A suspension of nuclei was made by incubating the tissue in a 0.5% pepsin solution (Sigma-Aldrich, Dorset, UK) prepared in 0.9% saline at pH 1.5. Incubation was carried out at 37°C for 30 minutes. The nuclei were washed once with PBS, stained with propidium-iodine and analyzed using the Calibur 1 FACS mashine and CellQuest software (Beckman Coulter, Buckinghamshire, UK). DNA index was assigned as follows: diploids were ‘1.0’, a tumor with a DNA index greater than 1.10 was classified as aneuploid .
The assignment of each patient into two cohorts using the CIN4 expression signature was performed in the R statistical environment (R, version 2.10.1) using the package Prediction Analysis for Microarrays (PAM, version 2.19) as described previously . By performing a soft thresholding to produce a shrunken centroid, which allows the weighting and ranking of genes with high predictive potential, PAM is capable to classify the samples into two cohorts. After this assignment, Kaplan-Meier curves were used to plot the efficiency of the prediction on recurrence-free survival. Chi-squared test was performed to test relation of qPCR and FACS assigned cohorts and clinicopathological variables grouped into categorical variables. Continuous variables were compared with student's t-test. Regression models and Cox multivariate regression analysis was performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA) and R (version 2.10.1, Vienna, Austria). We used two-sided tests and set a significance level of 0.05 for accepting the test p-values.
CIN4 signature derived from in silico ranking of CIN70 genes also reflects histological grade
In order to select a more limited set of genes that optimally reflect the CIN70 signature we retrieved expression profiles for the CIN70 signature genes from 10 publicly available breast cancer datasets .
The CIN70 genes were then ranked by Pearson's correlation coefficients to the CIN score (mean CIN70 expression) within these breast cancer microarray cohorts [supplementary references]. In order to derive a clinically applicable qPCR expression signature for use in FFPE tissue, containing fewer genes with equivalent information reflecting mean CIN70 expression , Correlation with grade was not used in selecting the PCR quantified CIN genes, those were selected purely based on their highest average correlation coefficients to tumor CIN score. These four genes (AURKA, FOXM1, TOP2A, TPX2) were termed the CIN4 signature.
For 5 of the 10 breast cancer microarray cohorts histological grade was also available. The above listed 4 genes were also highly correlated with histological grade (Pearson correlation coefficient above 0.7).
Next, we assessed the association individually on data sets between the mean-expression level of CIN4 and clinical outcome across the same 10 cohorts containing expression data from 1928 breast cancers. We observed significant discriminative power (p<0.05, for all) by CIN4 for the stratification of good from poor clinical outcome in all of the breast cancer cohorts [supplementary references]. Therefore, the expression of CIN4 appears almost as efficient at predicting cancer outcome as the extended CIN25 and CIN70 signatures. We were able to compare the performance in silico of the CIN4 signature to a number of previously published predictors of outcome such as CIN25, CIN70 , Ki67, Ivshina's molecular grade , Ma5 , GGI , DX21  and NKI70  in 3 datasets (GIS , JBI , JBI1 , ). CIN4 performed almost as well as CIN25. The univariate model based on which the meta analysis performed clearly suggested the HR of CIN4 is slightly better than the other predictors (Figure S2a), however, we wanted to know if CIN4 classification adds any predictive power to existing classifiers (predictorX). In another analysis, testing the additive power from CIN4 to a given predictor we determined the following model: survival = CIN4+predictorX+CIN4:predictorX. If CIN4 adds any predictive power, the benefit is represented by a significant interaction (CIN4:predictorX). However, we did find that even though CIN4 has a higher HR in the univariate model it does not add significant predictive power to other signatures (Figure S2b).
Identification of control genes in datasets and their variability in the tissue samples
B4GALT3, SLC9A3R2 and PUM1 were previously chosen based on their low variability in gene expression datasets described previously , . The three genes showed low variation between the investigated samples as well (Table S3).
CIN4 stratifies outcome in grade 2 tumors in a cohort of 185 breast cancers
Expression of CIN4 was assessed in a retrospective cohort of 185 patients for which we had FFPE primary breast cancer samples available from Buda MÁV hospital, treated between 1999 and 2002 (Table 1). Kaplan-Meier curves of the pathological evaluation of Ki67 expression and mitotic index performances on prognosis are shown in Figure S3.
In order to define a threshold for CIN4 expression for distinct outcome groups, we trained the PAM algorithm using the continuous CIN4 gene expression signature to discriminate clinical outcome of 63 patients with grade 1 breast cancer compared to the poorer outcome associated with 60 grade 3 breast cancers from within this cohort of 185 patients. Using this CIN4 expression threshold that best distinguished grade 1 compared to grade 3 breast cancers, the PAM defined CIN4 score was established, and we assessed the ability of this CIN4 score to stratify cancer outcome in the remaining 62 patients with grade 2 breast cancer from this 185 patient cohort.
Using this threshold, the CIN4 score was able to stratify patients with grade 2 breast cancers into good (44 patients) and poor (18 patients) prognostic groups (mean, relapse-free survival: 83.8 months [95%CI: 73.6–94.2] and 69.4 months [95%CI: 55.1–90.6], respectively [p = 0.016], HR = 2.155[1.007–4.612]) (Figure 1A).
A) The 4-gene signature based, PAM designated CIN4 score showing discrimination between grade 2 good and poor prognostic groups plotted on Kaplan-Meier curve in the validation group (p = 0.017): 45 cases (38 ER+, 7 ER−) in low CIN4 score group and 17 cases (10 ER+, 7 ER−) in high CIN4 score group. B) The CIN4 score performing in ER+ tumors only: 38 cases in low CIN4 score group and 10 cases in high CIN4 score group (p = 0.009).
Performance of the components of the CIN4 signature/score regardless of immunophenotype
For the identified genes that have been previously described to be of prognostic value, we have evaluated the prognostic power of AURKA, FOXM1, TOP2A, and TPX2 separately. Although, in public breast cancer datasets (grade 2, follow-up: 10 years, n = 497, split at median) all the genes showed strong predictive potential (AURKA: p = 0.047, HR = 1.33[1.00–1.78]; FOXM1: p<0.001, HR = 1.69[1.26–2.27]; TOP2A: p<0.001, HR = 1.68[1.26–2.25]; TPX2: p<0.001, HR = 1.64[1.23–2.18] for relapse-free survival (Figure S4), the data generated by qPCR was unable to distinguish prognostic subgroups for AURKA, FOXM1, and TPX2 at 10, 25, 75, 90 percentiles, median or average expression in our limited number of patients (Table S4). While TOP2A was already able to split prognostic subgroups at 25 percentile and median expression by itself (Table S4). The gain in performance is presented in the same table when considering all the four (CIN4) genes simultaneously.
Performance of CIN4 in ER positive breast tumors
We assessed the performance of the CIN4 score in ER+/HER2− tumors classified by immunohistochemistry. This cohort was also stratified into good and poor prognostic groups with reasonable confidence (p = 0.009, HR = 2.269[1.117–5.486], Figure 1B), suggesting that the CIN4 score-defined group with poor outcome is not driven by the worse outcome of the HER2+ subgroup diagnosed and treated before the introduction of trastuzumab. Other subtypes were under-represented and comparison could not be made in the herein investigated cohort.
CIN4 expression signature reflects aneuploidy directly quantified by FACS analysis
We assessed tumor DNA index through flow cytometry, classifying cancers into aneuploid and diploid categories according to standard threshold (threshold = 1.10 ). We evaluated the relationship of DNA index and the CIN4 expression by regression analysis. The variables showed a significant relationship between CIN4 expression and increasing DNA index (p = 0.036, Figure 2A). From Fig. 2A, a substantial proportion of tumors with high CIN4 scores have a normal DNA ploidy (diploid cases: 44 below, 48 above mean expression of CIN4 signature; aneuploid cases: 34 below, 50 above mean expression of CIN4 signanture). In this cohort, aneuploid tumors defined by flow cytometry were relatively enriched within the grade 3 tumor group (Figure 2B). As expected, when all breast tumors were considered, ploidy status correlated with histological grade (p = 0.004).
A) Regression curve showing relation of CIN4 expression signature and DNA index (p = 0.036). B) Bar graph showing numbers of diploid and aneuploid cases grouped according to histological grade: grade 3 tumors are relatively enriched in aneuploid cancers.
CIN4 expression signature and DNA index correlates with clinicopathological variables
Using regression analysis, considering all 185 patients, the CIN4 expression signature was significantly correlated with mitotic index (p = 0.001, Figure 3A) and Ki67 expression (p = 0.005, Figure 3C), suggesting that proliferation is correlated with tumor aneuploidy (p = 0.014, p = 0.023, respectively; Figure 3B and D). The Nottingham Prognostic Index (Figure 3E and F) or tumor size (Figure 3G and H) showed a trend only towards correlation with CIN4 signature or with DNA index.
Relation of CIN4 and DNA index to A) and B) mitotic index, C) and D) Ki67 expression, E) and F) Nottingham Prognostic Index and G) and H) tumor size displayed with regression curves (coefficients and p-values on graphs).
Estrogen and progesterone receptor expression as measured by IHC inversely correlated with CIN4 expression (p = 0.012, p = 0.017, respectively, Figure S5A and S5B). HER2 expression and HER2/C17 FISH counts correlated with CIN4 expression (p = 0.001, p = 0.013, respectively, Figure S5C and S5D), indicating that ER negativity and HER2 positivity are associated with higher CIN4 expression. The data derived from a qPCR assessment of CIN4 mRNA expression from FFPE breast cancers, confirms that the expression of this signature appears to be relatively enriched within ER negative and HER2 positive breast cancers (Figure S6).
CIN4 outperforms known clinical clinicopathological parameters in multivariate outcome models
CIN4 score and clinicopathological variables were tested for their correlation in grade 2 cancers (Table S5). Cox multivariate regression analysis was then performed in grade 2 breast carcinomas: in multiple models CIN4 outperformed clinicopathological variables including hormone receptor status, tumor size, NPI, mitotic index and Ki67 index, although, when considering concordance indices the models' quality is only modest (Table 2).
In this study, we developed a 4 gene-based measure of CIN applicable to FFPE material demonstrating clinical utility as a fairly robust marker of breast cancer prognosis. Aneuploidy determined by FACS-based DNA index correlated with the CIN4 signature, indicating that the CIN4 signature may in fact serve as a surrogate method to determine tumor aneuploidy status.
These data derived from a qPCR assessment of CIN4 mRNA expression from FFPE breast cancers, seems to confirm our previous analysis from microarray expression datasets , that CIN signature expression appears to be relatively enriched within ER negative breast cancers as well.
Directly or indirectly quantifying CIN in human tumor biopsies may hold significant potential for clinical practice , , , , . The aim of the current work has been to establish such a gene expression based indirect measure and validate its utility in an already existing retrospective FFPE cohort. In multivariate regression analysis the CIN4 signature confers prognostic power in comparisons across grade 2 cancers specifically. ER status and vascular invasion showed predictive power, while the CIN4 score seems to outperform mitotic index and Ki67 expression in multivariate analysis.
The CIN4 signature performed comparably to previously published gene signatures in similar cohorts. For example, the previously published Genomic Grade Index was further simplified and converted into a qPCR-based test from formalin-fixed, paraffin-embedded tissues , . It examines the expression of 4 genes, CDC2, CDC20, KPNA2 and MYBL2 and its utility has been demonstrated to predict outcome following tamoxifen treatment. A 5-gene assay was also developed quantifying the expression of CHDH, HOXB13, IL17BR, MIB1 and MKI67 to identify a subgroup of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy . Considering the previously published correlation between Genomic Grade Index and CIN , , it is reassuring to see that both CIN4 and the 4-gene Genomic Grade Index signature yield similar results , , indicating that replacing histological grade 2 with gene expression based low and high risk cases could be considered in prospective studies.
Interestingly, in the study we identified a group of samples with a diploid DNA index which have a wide range of CIN scores. There might be several explanations behind this phenomenon including tumor heterogeneity or the presence of yet unknown other compensatory mechanisms . Clearly, a substantial proportion of tumors with high CIN4 scores have a normal DNA ploidy, indicating that the CIN4 score likely reflects factors in addition to DNA copy number. In these cases, it is possible that highly proliferative cells, although with relatively stable genomes, may have high levels of the genes comprising the signature
While establishing a qPCR-based simple test to improve histological classification is an important clinical goal, – following further validation – the CIN4 signature as a quantifier of CIN is expected to serve as a potential marker of other clinical characteristics as well. Most prominently, the putative role of CIN in determining taxane response would suggest that the predictive role of CIN4 should be tested in the neoadjuvant setting when comparing response to therapy with or without taxanes in the treatment of hormone receptor negative breast cancer.
Kaplan-Meier plot showing the disease-free survival of the different grade and immunophenotype groups in the validation cohort, respectively.
In silico comparison of the performance of CIN4 vs. CIN25, CIN70, Ki67, genetic grade, HOXB13:IL17BR index, Genomic Grade Index, the 21-gene recurrence score and NKI70 in the GIS, JBI and JBI1 datasets , ,  (A), and assessing the additive power of CIN4 (B).
Kaplan-Meier curves of Ki67 and mitotic index performances in the tissue samples of grade 2 breast tumors.
Individual prognostic performance of AURKA, FOXM1, TOP2A and TPX2 in breast cancer datasets as compared to CIN4 signature (groups split at median expression).
Correlation of CIN4 and markers used in the determination of immunophenotype. CIN4 and A) ER, B) PR, and C) HER2 expression, and D) HER2/chromosome 17 score determined by FISH.
CIN4 expression in ER-negative and ER-positive tumors.
The public datasets analysed in the study and their supplementary references.
The probes used for the qPCR evaluation in the study.
Expression of control genes in the breast cancer tissue samples according to grade.
Performance of the individual components of CIN4 in tissue samples of grade 2 breast tumors.
The authors thank Márta Jäckel MD, PhD for providing the tissue blocks, the assistance of Erzsébet Azumah, Csilla Jaczó, Magdolna Pekár, and Erika Samodai in tissue handling. Distinguished thanks to Miklós Szendrői MD, PhD, DSc for both his personal and professional support to this project. Financial support: Legacy of Szőllős András Péterné, ETT-029/2009, ETT-088/2009, MKOT-GSK-2010, TÁMOP-4.2.1.B-09/1/KMR-2010-0001 and the TÁMOP-4.2.2/B-10/1-2010-0013 grant. B.G. was supported by the OTKA PD 83154 grant. C.S. was supported by the Breast Cancer Research Foundation (BCRF).
Conceived and designed the experiments: AMS JK CS ZoS. Performed the experiments: AMS AE QL ZsS AT AR BS. Analyzed the data: AMS ZsS BG JK CS. Contributed reagents/materials/analysis tools: AK MS. Wrote the paper: AMS JK QL CS AE ZoS.
- 1. Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z (2006) A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38: 1043–1048.
- 2. Habermann JK, Doering J, Hautaniemi S, Roblick UJ, Bündgen NK, et al. (2009) The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome. Int J Cancer 124: 1552–1564.
- 3. Swanton C, Nicke B, Schuett M, Eklund AC, Ng C, et al. (2009) Chromosomal instability determines taxane response. Proc Natl Acad Sci U S A 106: 8671–8676.
- 4. Lee AJX, Endesfelder D, Rowan AJ, Walther A, Birkbak NJ, et al. (2011) Chromosomal Instability Confers Intrinsic Multidrug Resistance. Cancer Research 71: 1858–1870.
- 5. Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, et al. (2011) Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. Cancer Res 71: 3447–3452.
- 6. Roylance R, Endesfelder D, Gorman P, Burrell RA, Sander J, et al. (2011) Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 20: 2183–2194.
- 7. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643–649.
- 8. Nakamura H, Saji H, Idiris A, Kawasaki N, Hosaka M, et al. (2003) Chromosomal Instability Detected by Fluorescence in Situ Hybridization in Surgical Specimens of Non-Small Cell Lung Cancer Is Associated with Poor Survival. Clin Cancer Res 9: 2294–2299.
- 9. Fiegler H, Geigl JB, Langer S, Rigler D, Porter K, et al. (2007) High resolution array-CGH analysis of single cells. Nucl Acids Res 35: e15.
- 10. Ellsworth R, Hooke J, Love B, Kane J, Patney H, et al. (2008) Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors. Breast Cancer Research and Treatment 107: 259–265.
- 11. Ivshina AV, George J, Senko O, Mow B, Putti TC, et al. (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66: 10292–10301.
- 12. Dalton LW, Pinder SE, Elston CE, Ellis IO, Page DL, et al. (2000) Histologic Grading of Breast Cancer: Linkage of Patient Outcome with Level of Pathologist Agreement. Mod Pathol 13: 730–735.
- 13. Toussaint J, Sieuwerts A, Haibe-Kains B, Desmedt C, Rouas G, et al. (2009) Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues. BMC Genomics 10: 424.
- 14. Reis-Filho JS, Tutt ANJ (2008) Triple negative tumours: a critical review. Histopathology 52: 108–118.
- 15. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264.
- 16. Van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AAM, et al. (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347: 1999–2009.
- 17. Paik S, Shak S, Tang G, Kim C, Baker J, et al. (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351: 2817–2826.
- 18. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. (2000) Molecular portraits of human breast tumours. Nature 406: 747–752.
- 19. Ma XJ, Salunga R, Dahiya S, Wang W, Carney E, et al. (2008) A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res 14: 2601–2608.
- 20. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, et al. (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98: 262–272.
- 21. Li Q, Birkbak NJ, Gyorffy B, Szallasi Z, Eklund AC (2011) Jetset: selecting the optimal microarray probe set to represent a gene. BMC Bioinformatics 12: 474.
- 22. Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Viale G, et al. (2004) Minimal and small size invasive breast cancer with no axillary lymph node involvement: the need for tailored adjuvant therapies. Ann Oncol 15: 1633–1639.
- 23. Eisenberg E, Levanon EY (2003) Human housekeeping genes are compact. Trends in Genetics 19: 362–365.
- 24. Szabo A, Perou C, Karaca M, Perreard L, Quackenbush J, et al. (2004) Statistical modeling for selecting housekeeper genes. Genome Biol 5: R59.
- 25. Chassevent As, Jourdan M-L, Romain S, Descotes Fo, Colonna M, et al. (2001) S-Phase Fraction and DNA Ploidy in 633 T1T2 Breast Cancers. Clin Cancer Res 7: 909–917.
- 26. Tibshirani R, Hastie T, Narasimhan B, Chu G (2002) Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A 99: 6567–6572.
- 27. Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, et al. (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25: 1239–1246.
- 28. McClelland SE, Burrell RA, Swanton C (2009) Chromosomal instability: A composite phenotype that influences sensitivity to chemotherapy. Cell Cycle 8: 3262–3266.
- 29. Bakhoum SF, Danilova OV, Kaur P, Levy NB, Compton DA (2011) Chromosomal Instability Substantiates Poor Prognosis in Patients with Diffuse Large B-cell Lymphoma. Clin Cancer Res 17: 7704–7711.
- 30. Heselmeyer-Haddad K, Chaudhri N, Stoltzfus P, Cheng JC, Wilber K, et al. (2002) Detection of Chromosomal Aneuploidies and Gene Copy Number Changes in Fine Needle Aspirates Is a Specific, Sensitive, and Objective Genetic Test for the Diagnosis of Breast Cancer. Cancer Res 62: 2365–2369.
- 31. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, et al. (2012) Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing. N Engl J Med 366: 883–892.

domain: literature


text: Learning all he knows under the esteemed tutelage of Silvia Venturini Fendi and Karl Lagerfeld, Italian talent, Marco De Vincenzo spent 13 years at world-class fashion house, Fendi before launching his eponymous label in 2009. Synonymous with boundary-pushing reverie and astute and impeccable craftsmanship, De Vincenzo continually demonstrates a deep understanding of fine materials. Defined by dazzling, rainbow hues, glittery finishes, boxy silhouettes and opulent embellishment, Marco De Vincenzo is the go-to for refined, striking styles. Step-up your cold-weather repertoire with Marco De Vincenzo coats. These fabulous, standout styles will work hard to cement your catwalk-inspired sensibility.


text:
Benefits of Quickstep Capture (Signature)
The main benefits of Quickstep Capture (Signature) flooring include:
- Excellent strength and durability - the planks measure 9mm thick, providing incredible strength and stability underfoot. The surface is protected with Scratchguard technology, keeping it safe from daily wear and tear. For reassurance, the manufacturer provides a 25-year warranty on domestic installations.
- Easy installation and maintenance - the planks are fitted with Quickstep's patented Uniclic system. This means they click together for a fast, easy fit. You should be able to fit the floor yourself, minimising the cost of installation. In terms of maintenance, you can hoover or give the floor a daily sweep, followed by a weekly mop.
- Waterproof - Quickstep Capture (Signature) flooring is equipped with Hydroseal technology. Hydroseal provides a waterproof design. You won't need to worry about spills or stains, making it an excellent choice for family homes.
- Beautiful, realistic designs - there are 18 beautiful designs to choose from in this range. From traditional oak to warm walnut designs, each features an unprecedented amount of detail.
- Underfloor heating compatible - it is important to read through the guidelines provided by the manufacturer prior to installation. This will help you to ensure that your system is suitable.
One of the best things about the Quickstep Capture (Signature) laminate range is that it can be installed in any room including:
- Children's playroom
Quickstep Capture (Signature) Laminate Wood Effects
Within the Capture (Signature) Quickstep laminate range, there are striking effects to choose from. Most of the floors feature an oak effect design, though more exotic options such as walnut are also available. Let's look at the main wood effects included brushed oak, white, grey, natural varnished oak, and painted oak.
Whether you are looking for a traditional effect, or something more contemporary, the Quickstep Capture (Signature) laminate range has something to suit any interior. Shop the full collection now to see which design is right for you.
If you need help choosing a Quickstep effect, use our Room Visualiser Tool.

domain: design


text:
Sit in the Sun:
The other day I picked my first broccoli and went home and had it for tea. It was absolutely wonderful. I thought to myself’ how did I grow this, it taste so good’
However I came to the understanding that we do not grow anything.
Growing does not have to be difficult ( unless, you want it to be ).
Put the plant in, feed/water/keep weed and pest free and then
So many books have been written about it, but why; it is very simple.
Growing something, teaches us the wisdom of ripening in our lives, if you will let it.
How does an apple ripen: it just sits in the sun and that is just what we should do. We strive, but to what end!
In the northern hemisphere the days are growing shorter—we have fewer and fewer hours of daylight. We may have to seek out the sun’s rays more intentionally. In moderation, sunlight strengthens the immune system, enhances emotional health, and synchronizes biorhythms. Make like a plant: Find some time where you can simply bask in sunshine, exposing your skin and soul to the light freely given, only waiting to be received.


Iris yellow spot (IYS) disease, caused by Iris yellow spot virus (IYSV), results in irregular and diamond-shaped, chlorotic, and necrotic lesions on the leaves and seedstalks of onions (Allium cepa L.). These lesions reduce leaf photosynthetic area and ultimately reduce onion bulb size and yield from larger bulb classes. IYSV is vectored by onion thrips (Thrips tabaci L.) that are difficult to control under certain environmental conditions. Currently, no onion cultivar is resistant to the disease symptoms, virus, and/or thrips. Twenty-one cultivars and 17 germplasm lines were evaluated in the field for IYS disease severity and thrips densities at multiple times during the season as well as leaf color, waxiness, and axil openness of these entries. Plants were grown under conditions that favored thrips populations (high temperatures, low moisture, and no insecticidal spray applications), IYSV presence and distribution, and IYS development. Plants of New Mexico State University (NMSU) 07-10-1 had fewer thrips than several entries later in the season in both 2009 and 2010. Several entries exhibited a lower number of thrips per plant early or later in the season; however, these results were not consistent across years and were not associated with a particular foliage characteristic. Lighter leaf color and/or a lesser amount of epicuticular wax did not always result in the fewest number of thrips per plant as has been reported in the literature. Plants of NMSU 09-58 tended to exhibit fewer and less severe IYS symptoms early in the season as compared with plants of other entries.
Christopher S. Cramer, Neel Kamal and Narinder Singh
Christopher S. Cramer, Narinder Singh, Neel Kamal and Hanu R. Pappu
Iris yellow spot is an economically important disease of onion that reduces bulb size and yield and is difficult to control. The disease is spread by Thrips tabaci (onion thrips) and disease symptoms are exacerbated by hot, dry climatic conditions that also favor rapid thrips multiplication and make control programs less effective. Currently, no onion cultivar is resistant to the disease and/or thrips. Certain onion foliar characteristics have shown nonpreferential feeding activity by thrips and may be the first step in developing Iris yellow spot (IYS)-tolerant onion cultivars. Seventy-five onion PI accessions from the U.S. germplasm collection were evaluated for leaf color, waxiness (bloom), and axil pattern; thrips number per plant; and IYS disease severity under conditions that favored thrips and disease buildup. Plants of PI 289689 were less attractive to thrips and had a lower number of thrips per plant than plants of most other accessions. These plants were rated as having light green to green-colored foliage and a relatively low amount of epicuticular leaf wax. Plants of PIs 239633 and 546192 generally exhibited less severe IYS disease symptoms than those of other accessions. Individual plants, that exhibited less leaf area exhibiting IYS disease symptoms, were selected at bulb maturity from 22 different accessions with PI 546140 producing the largest number of selected bulbs. Physiological plant development, environmental conditions, and tolerance to plant stress may influence the degree of disease symptom expression. Further work that examines the role of plant maturity and host plant tolerance to stress with respect to disease expression is needed.


text:
. Rate of physisorption increases with
A: decrease in temperature
B: increase in temperature
C: decrease in pressure
D: decrease in surface area
- The process of physisorption is exothermic in nature.
- Therefore, according to LeChatliers principle, it decreases with increasing temperature.
- This means that physioabsorption occurs more easily at low temperatures.
The correct option is A: decrease in temperature

domain: chemistry


text:
|Battlefield 4 zoom on Box art|
EA CFO Blake Jorgensen said that Battlefield 4 looked "stunning" on a Playstation 4. So Awesome.
Battlefield 4 Beta to be released by DICE in the Fall of 2013. According to GamingBlend, the beta will include "guaranteed access" to Medal of Honor: Warfighter pre-order customers.
Gamestop employees did get to see a preview of Battlefield 4. Gamestop, Inc. tweeted in late Feb. 2013: "Got to see Battlefield 4 today and all I can say is WOW! Thanks @EA for the sneak peek Can't wait for you all to see it. ^CEO #BF4"
The full picture (below) of the game was released on March 16, 2013.Various gaming outlets speculate if the storyline will incorporate a soldier and armored vehicles advancing through a city.
Gaming source Kotaku.com tried to use Photoshop to gain more information based on the full release photo. Writer Stephen Totilo speculates that a skyline of Shanghai is seen in the picture. This can be read here.
The official EA announcement for Battlefield 4 will be on March 26, 2013.
|Battlefield 4 Full picture released by GamingBlend|
"Battlefield 4: First Image Confirms Modern Setting." GamingBlend.com
Original DICE spoiler about upcoming Battlefield 4:
Battlefield fans –
The team at DICE is hard at work on the next entry in the Battlefield series, and to ensure access to the exclusive Battlefield 4 beta, shooter fans can pre-order Medal of Honor Warfighter today. While there is no further Battlefield 4 news at this point – remember, if you don't see it published here, it's just rumor and speculation – we did want to take this opportunity to share a few thoughts on the state of the Battlefield franchise.
We are extremely proud of Battlefield 3, and with millions of fans out there, we're happy you're enjoying it too. When we launched the game, we introduced unparalleled levels of in-game destruction, all-out vehicle warfare and redefined online gameplay. Even with billions of bullets fired and millions of games played, we know the Battlefield 3 story is still just the beginning. As ever, we are humbled by the community's response to the game, and couldn't be happier with the feedback we have received to Battlefield 3 Premium. With the Back to Karkand and Close Quarters expansion packs already out, Armored Kill around the corner, and End Game and Aftermath still on the horizon, we're looking forward to many more hours of gameplay with you, and can't wait to see the stories you will tell through Battlelog and player created videos.
But we're not ready to talk about Battlefield 4 yet - in the meantime, we hope you will continue to enjoy Battlefield 3 and all the Battlefield 3 Premium content still to come. We invite you to check out Danger Close Studio's Medal of Honor Warfighter, which is also powered by the Frostbite 2 engine and the free social network, Battlelog. Don't forget that pre-ordering Medal of Honor Warfighter Limited Edition (at no extra cost) guarantees access to the exclusive Battlefield 4 Beta.
See you on the battlefield!

domain: entertainment


text:
Director David Fincher talks the music of Mank with composers Trent Reznor and Atticus Ross.
Opening photo by
Trent Reznor and Atticus Ross have written a dozen film and television scores together. Not just partners in Nine Inch Nails, they have won multiple awards for music in visual media: an Oscar and a Golden Globe for The Social Network, a Grammy for The Girl with the Dragon Tattoo, an Emmy for Watchmen. But they had never tackled a project quite like Mank.Director David Fincher, whose films The Social Network, The Girl with the Dragon Tattoo, and Gone Girl Reznor and Ross also scored, came to the duo with a period piece set between 1930 and 1940 and shot in black and white, the story of Hollywood screenwriter Herman “Mank” Mankiewicz (played by Gary Oldman).Reznor and Ross’s previous scores had been created with synthesizers, samplers, and sequencers in their Los Angeles studios, where they recorded all of the music themselves. Mank required something different: a more traditionally orchestral score, with swing-jazz and dance-band elements appropriate to the era. It was an arena in which neither Reznor nor Ross had any prior experience.So they listened to the popular music of the 30s and 40s and, intriguingly, the early film scores of Bernard Herrmann, the longtime Orson Welles collaborator. His music for Citizen Kane proved inspirational in terms of the style of orchestral writing that frames Mank.Ultimately, they created more than 90 minutes of original music, played by the equivalent of a 70-piece orchestra and big band. Because of the pandemic raging through the summer and fall of 2020, all of the musicians performed individually in their home studios and were mixed together into a seamless whole.“It was an incredibly intoxicating, inspiring environment,” Reznor says of working with Fincher. “We felt like artists, not artisans, being challenged to try to make something awesome.”We talked to the musicians and the director about creating the music for Mank.
Hand-drawn score by Conrad Pope
Jon Burlingame: What role did you envision music playing in your film?
David Fincher: I initially went to Trent and Atticus basically to say that I didn’t know whether this needed to be symphonic and tipping its hat to Bernard Herrmann, or if it should be synthesizers. I just dropped it in their laps and said, “You guys are much better at this than I am. What should we be doing?” They made 45, 50 minutes’ worth of music and sent it over. Within seconds of hearing it I wrote them and said that we wanted to use it all.
At this point did you prepare a team that would help you realize your ideas orchestrally and in terms of the big band? Or did you write the material and then worry about how to record it later?
TR: We developed a new technique. Usually, it’s the two of us in the studio and when we finish, it’s done. This, we endlessly tweaked back and forth with David. There is also no recording stage in our typical process because we’ve already played the final music ourselves. We did fully orchestrate the entire film with samples and programming, but in the meantime we looked to who would be the right arrangers to translate that into actual people playing it.
What about the source music, the various band pieces heard in the background? You could have licensed songs from the era, but you actually wrote a lot of that.
TR: David had described in detail a scene with music that would be playing while Mank is on the film set. It needed to feel a little stuffy and not cool. It was the music playing on a turntable while the dialogue’s taking place. That’s incredibly rich and it’s a great creative seed. What would that sound like? We wrote a number of pieces as we started gaining confidence that we could actually do this, and then part of it was just studying the music of the era and trying things and having fun with it.
on Netflix now.


Latest Tax Stamp and Traceability Developments in Nepal
Nepal has been using excise stamps (hereinafter referred to as tax stamps) for more than two decades now, with the stamps effectively contributing to government tax revenue. Indeed, every year, the Nepalese government generates 57 billion Nepalese rupees ($477 million) from excise duty, value-added tax, and health hazard tax imposed on cigarettes and alcohol.
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Last week's brokering of an $8-billion transit plan on the city council floor should cause all of the Greater Toronto Area's taxpayers to feel nervous. It's exactly why Metrolinx, the regional transit planning agency, was created – and it's why we need it now more than ever.
Indeed, Metrolinx was the response to years of advocacy by organizations such as the Toronto Board of Trade, specifically warning of such situations. When the Ontario government created and passed the Metrolinx Act in 2006, it tasked the agency to "develop and adopt a transportation plan for the regional transportation area, and plan, co-ordinate and set priorities for its implementation."
Specifically, the act directs Metrolinx with the mandate to "ensure the efficient and cost-effective resolution of matters of shared concern respecting transportation," including "the optimal use and location of transportation infrastructure."
But last week's events raise the question of whether Metrolinx has been given the authority to exercise its mandate. Six years after the act was passed, why is the provincial government looking to Toronto City Council to clarify the province's own position? We can only interpret that Metrolinx has not been given the authority we thought it had.
Signalling that key decisions are largely at a council's discretion is the reason why decisions and plans have gone back and forth. Cabinets and councils come and go. Nothing will get built if every new one sends progress in a different direction.
To be sure, Metrolinx must balance the democratic process with the need to depoliticize decision-making over the spending of limited resources. But the province must allow the agency to do what it was supposed to.
Furthermore, the province has its hands on the purse strings. It must enable Metrolinx to exert more influence on how those dollars are spent. It can't simply give Toronto, or any other GTA municipality, a blank slate for spending billions of dollars in provincial money.
Our transit challenges are much larger than going back and forth on decisions to bury or not to bury a particular route. This becomes even more critical when you consider the next major challenge.
As the province moves forward to finance and build the rest of the Big Move – a massive undertaking that will take at least 25 years – it must ensure that its transportation planning body has the weight to fulfill its assignment. Indeed, Metrolinx must play the lead role in advancing the full $50-billion regional transportation plan.
So long as transit planning remains politics as usual, progress will continue to be slow. Avoiding these politics is also why the Toronto Board of Trade will decline to participate in the city's advisory panel on the Sheppard line. Metrolinx should lead the analysis on what transit needs to be built, where it should be built and when.
In doing so, the agency must propose the best business-case supported solutions to our region's transportation challenges, then forcefully voice its expert-based point of view.
Now is the time for Queen's Park to reaffirm the intentions behind Metrolinx's creation. Give it the assurance it can lead so we can get on with financing and building the regional transportation plan.
Carol Wilding is president and CEO of the Toronto Board of Trade.