More Recent Comments

Tuesday, March 03, 2009

Octo-mom: could it happen in Canada?

 
The short answer is .... no.

The University of Toronto Bulletin publishes an interview with fertility expert Robert Casper [Octo-mom: could it happen here?"
Q. The woman in California who gave birth to octuplets was single. Is this common?

Yes. While couples (both heterosexual and same-sex) comprise the majority of IVF patients, we see many single women using donated sperm as well. We don’t discriminate.

Q. The California woman was implanted with six embryos using in-vitro fertilization. Could something like this happen in Canada?

In Canada no reproductive infertility specialist would be putting back that many embryos.
There’s no law in Canada—it’s up to the doctor and the patient to decide. Our guidelines are to transfer up to two embryos in women under 35, up to three for women between 35 and 39 and up to five for women 40 and older. The reason that the number of embryos goes up as you get older is that there are more and more chromosomal abnormalities that accumulate in the eggs as a woman ages. By the time a woman is 40, for example, 90 per cent or more of her eggs have a chromosomal abnormality that would be incompatible with a live birth. So the idea of putting more embryos in an older patient is to try and ensure that there’s one healthy normal embryo that will actually implant.

Q. So, in a nutshell, this is pretty much unheard of?

To put six embryos in someone who is 33 is way, way outside what it is considered to be normal standard of care.

Q. Any thoughts on what the doctor was thinking?

I have no idea what was happening in that clinic. It sounded like they didn’t have much experience. They put a lot of embryos in to increase her chances—I don’t think they were counting on the fact that she was so fertile or thinking about the fact that she had six previous children.

Q. Are women counseled psychologically before receiving IVF? This woman had six other kids – should her doctor have discouraged her from trying to have more?

Psychological counseling is mandatory—a standard of care in Canada—for women using donor sperm. However, we wouldn’t turn away a woman who has six children and wants another—it’s her decision if she wants to have another child. But at 33, we would encourage that she have only one embryo put back, especially, as with the case with this woman, she has proven very high fertility.


Monday, March 02, 2009

Monday's Molecule #110

 
Identify all three molecules shown here. Be as specific as possible.

There's are several possible Noble Laureates associated with these molecules. I'm looking for the one(s) who got the first prize. There's a special connection to Sandwalk, can you guess what it is?

The first person to identify the molecule and the Nobel Laureate wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are seven ineligible candidates for this week's reward: David Schuller of Cornell University, Nova Syed of the University of Toronto, Dima Klenchin of the University of Wisconsin and undergraduate Alex Ling of the University of Toronto, and James Fraser of the University of California, Berkeley, Guy Plunket III from the University of Wisconsin, and Deb McKay of Toronto.

David, and Dima have offered to donate their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch to the first undergraduate student who can accept a free lunch. Please indicate in your email message whether you are an undergraduate and whether you came make it for your free lunch (with a friend).

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

Comments will be blocked for 24 hours.


Bacteria in Your Mouth

 
A paper examining the diverstiy of human salivary bacteria has recently appeared in the journal Genome Research (Nasidze et al. 2009).

The authors looked at 120 individuals from different locations all over the world. They extracted DNA from their saliva and isolated small fragments of DNA copied from a highly variable region of 16S ribosomal RNA. On average, they sequenced 120 different DNA fragments from each individual. After eliminating artifacts they were left with 14,115 fragments.

The DNA sequences were compared with a large database of bacterial sequences in order to identify the bacterial species present in the mouths of each person. In most cases it was possible to positively identify the genus although they did find 196 sequences that were not in the database. These are probably unknown species of bacteria.

ResearchBlogging.orgThere were 101 different types of bacteria (genera). Each person has between six and thirty different species of bacteria in their mouth. There are about 45 different genera in each location (e.g. Bolivia, Congo, China, California, Germany, etc.).

Some genera were seen only once while others are quite common. The most common ones are listed below.

Actinomyces: Actinomyces are rod-shaped, gram positive bacteria that can survive under both aerobic (oxygen) and anaerobic conditions. Such bacteria are called facultative anaerobes. A. naeslundii forms dental placque by adhering to the surface of your teeth.

Enterobacter: Enterobacter species belong to the γ-proteobacteria group of gram negative bacteria. They are facultative anaerobes. Enterobacter are related to Escherichia coli—no examples of E. coli were found in this study.

Fusobacterium: These are gram negative, anaerobic, bacteria that are normal inhabitants of the oral cavity. They cause periodontal disease under some (unknown?) circumstances .

Granulicatella: The Granulicatella species belong to the phylum Firmicutes. They are gram positive bacteria related to Streptococcus.

Haemophilus: These species belong to the γ-proteobacteria as well. They are rod-shaped, gram negative bacteria related to E. coli.

Leptotrichia: The Leptotrichia species are long, filamentous, gram negative, anaerobic, bacteria in the Bacteroides group.

Neisseria: Neissria is a genus in the β-proteobacteria group. They are usually small, aerobic, bacteria. N. gonorrhoeae causes gonorrhea and N. meningitidis causes meningitis but most of the species in your mouth are harmless.

Porphyromonas: These are gram negative, anaerobic, members of the Bacteriodes group. P. gingivalis is normally harmless but it can cause periodontal disease.

Prevotella: Prevotella species are gram negative, rod-shaped, anaerobic, bacteria closely related to Bacteriodes. They are among the most common bacteria in the intestines of sheep and cattle where they aid digestion.

Rothia: These gram negative bacteria belong to the phylum Actinobacteria. They are related to micrococcus.

Serratia: These are motile, rod-shaped, gram negative bacteria. S. marcescens grows in bathrooms where it is often found on tile grout. The bacteria produce a characteristic red pigment and that's why contaminated areas appear pink.

Streptococcus: Streptococcus species are small, gram negative, nonmotile, and round. They are mostly facultative anaerobes. Individual bacteria associate in long chains. It is the most common genus in mouth cultures.

Vellionella: These common species are gram negative, anaerobic cocci.

There are problems with bacterial phylogeny, especially with a classification that relies exclusively on the sequences of ribosomal RNA [Bacteria Phylogeny: Facing Up to the Problems]. Reliable trees can be constructed using concatenated sequences and these trees (see below) reveal that the main groups of bacteria diverged from each other billions of years ago.



(You can see a high resolution image here.)

Note that the Firmicutes (red) are on the same branch as Actinobacteria (olive green) but these two groups are still as distantly related as dogs and dandelions. The α-proteobacteria (orange) are also very distantly related. The diversity of bacterial species in your mouth is truly remarkable.

Stoneking's group was interested in the differences between humans and especially between groups living in different parts of the world. Stoneking was one of the original authors on the Mitochondrial Eve paper so I suspect he was looking for bacterial markers that he could use to trace human ancestry.

Unfortunately, there isn't much difference between individuals or between groups from different parts of the world. The most significant geographical variation is between the samples from the Congo and everyone else. People in the Congo have a higher percentage of Enterobacteria. The only other significant difference is that there tend to be fewer Prevotella in people from Louisiana.

The somewhat surprising conclusion is that diet, culture, and environment don't seem to play much of a role in the diversity of the human salivary microbiome.


Nasidze, I., Li, J., Quinque, D., Tang, K., and Stoneking, M. (200() Global diversity in the human salivary microbiome. Genome Res. Published in Advance February 27, 2009, [doi:10.1101/gr.084616.108] [Genome Research]

I. Nasidze, J. Li, D. Quinque, K. Tang, M. Stoneking (2009). Global diversity in the human salivary microbiome Genome Research DOI: 10.1101/gr.084616.108

When Chiropractors Get Angry ....

 
Gary Goodyear is Canada's Minister of State (Science and Technology). He's also a chiropractor.

Last week he met with two representatives of the Canadian Association of University Teachers (CAUT). CAUT has a long history of lobbying in favor of increased funding for university research. Apparently the meeting didn't go well [Researchers fear 'stagnation' under Tories].
The screaming erupted last Wednesday afternoon, just down the street from Parliament Hill, in the offices of a Conservative cabinet minister.

Two officials with Canadian Association of University Teachers sat on one side of a boardroom table and on the other sat Gary Goodyear, Minister of Science and Technology, his policy adviser Wesley Moore and a civil servant ready to take notes.

CAUT, a lobby group that represents 65,000 staff at 121 colleges and universities, had planned to raise concerns over the government's handling of research funding. But within moments, it became clear they wouldn't get very far.

“The minister was very angry,” said David Robinson, associate executive director of CAUT. “He was raising his voice and pointing his finger … He said everyone loves their [federal budget] and we said, ‘A lot of our members don't love it'… and he said, ‘That's because you're lying to them, misleading them.'”

The talks, Mr. Robinson said, went from bad to worse. In 15 years on the job, he “never had a meeting like that.”

Mr. Goodyear agrees. “I, too, have never had a meeting like that. It was a unique experience and one I don't care to repeat.”
I don't know what could possibly have gone wrong. Perhaps it was something that Mr. Goodyear said?
Mr. Goodyear said he has met university presidents, deans of research, and researchers themselves and believes government critics are few. “You're going to see that one person who didn't get what they wanted,” he said. But “eight out of 10 folks I talk to get it … they are very positive.”

Mr. Goodyear, a chiropractor from Cambridge, Ont., said the government has been steadily investing in science and technology since 2006, with a new emphasis on commercialization and that it has designed an overall strategy to ensure Canada remains a world leader in research.

“We have done everything right,” he said.
Or maybe it had something to with the change in science policy since the Conservatives took over in 2006?
After years of double-digit budget increases in the early 2000s, government contributions in recent years to NSERC, SSHRC and CIHR have barely kept pace with inflation – and last year they underwent a government-mandated strategic review to reduce their spending.

So while the Barack Obama administration in Washington has added $10-billion (U.S.) to finance basic research in the United States, the three agencies that back basic research in Canada must cut spending by $148-million over the next three years.

CIHR, for example, Canada's main funding body for medical research, has to find about $35-million in savings by 2012, and $28-million of that is by eliminating a program that provided grants to research teams.
In any case, it ended badly ...
CAUT, however, is less confident. It was the position of researchers fretting for the future the lobby group hoped to represent at last week's meeting with Mr. Goodyear.

They had barely begun to state their case, Mr. Robinson said, when the minister accused them of twisting facts.

When CAUT staff said the Conservatives have a spotty record on science and noted they abolished the office of the national science adviser, Mr. Robinson said, the minister's assistant screamed at them to shut up.

“Then the minister said, ‘You've burned all your bridges with us!' and they stormed out.

“In all the meetings I've been in like this, I've never been shouted at and told to shut up,” Mr. Robinson said. The civil servant who escorted them to the elevator suggested it would not even be a good idea to return to the minister's office to collect their coats, he said. Instead, she retrieved them.
This meeting is more extreme than most but it confirms an impression I had when I used to go up to Ottawa for those lobbying weeks in March. When dealing with the Conservatives, the only workable strategy is to vote them out of office as quickly as possible.

Trying to reason with them doesn't work.


Liberal Party Policy Development Workshop

 
Here's where I'll be this evening.
WHEN:
Monday, March 2, 2009
7:30 - 10:00 PM

WHERE:
Mississauga Central Library
Meeting Room #3, second floor

PRICE:
Cost: $5 (to recover room and refreshment costs)

CONTACT:
For more information, please contact
Sharon McCarthy 905 828 5786
Omar Alghabra 416 564 5468

NOTES:
The Mississauga-Erindale Federal Liberal Riding Association is organizing an informative and engaging workshop on policy development and promotion. The workshop will be facilitated and presented by Maryanne Kampouris, Vice President, Policy, Liberal Party of Canada (Ontario)

The session will discuss policy development process touching upon different components, including Party structure, Policy Structure, role of the riding association, role of the policy committee with practical ideas on how to engage constituents in 'ideas' or policy discussions.

The session will include practical discussion on how riding associations can proceed in engaging their members and their constituents in this process.

The purpose of this workshop is to empower Liberals and educate them on how to convert their policy ideas into real resolutions that can make a difference, and how to promote and advocate for their policy ideas.
Does anyone have any suggestions? How can the Liberal riding associations engage voters and make them care about defeating Stephen Harper and the Conservatives?

We should probably start with hiring a proofreader for press releases but is there anything else?


Can We Win in Afghanistan?

 
It's seems like only a few years ago (March 6, 2006) when Prime Minister Stephen Harper said this ...
A debate on whether Canadian troops should be in Afghanistan would put the troops in danger, and any attempt to pull them back would be a betrayal, says Prime Minister Stephen Harper.

Harper, speaking after a cabinet meeting on Tuesday, stressed that the previous Liberal government committed the troops to their Afghan mission, which has proved deadly in recent weeks, and that the Conservatives will honour the commitment.

"I'm saying that Canadians don't cut and run at the first sign of trouble," he told reporters. "That's the nature of this country, and when we send troops into the field, I expect Canadians to support those troops." He repeatedly rejected the idea of a debate and said his government will not make decisions based on opinion polls.

"I understand the frustrations," he said. "Perhaps the previous government should have had a vote on the deployment, but that was not their decision. The decision was taken and we can't change our opinion when the troops are in danger."

He did not say why a debate in Canada would put soldiers at risk in Afghanistan, but he stressed it is "a very dangerous mission. "It's not the intention of this government to question the particular commitment when our troops are in danger," he said. "Such a debate or such a lack of strength by any of the political parties in Canada will merely weaken the resolve of our troops and will even put our troops in even more danger."
At the time, the issue was all about "supporting the troops." The danger, according to Harper, was in raising the possibility that our soldiers might have died in vain. That's unacceptable to many Canadians. Unacceptable, perhaps, but is it true?

Here's what Prime Minister Stephen Harper said yesterday, according to The Canadian Press [Western forces alone can't beat Afghan insurgents: Harper].
Western forces alone can never defeat the Taliban insurgency in Afghanistan and President Barack Obama better realize that in shaping his strategy there, says Prime Minister Stephen Harper.

In an interview aired Sunday on the U.S. cable news network CNN, Harper said he's "delighted" the president is sending more troops to the country in the short term.

Many of them will be deployed in the Kandahar region, where more than 2,000 Canadian soldiers already on the ground can use the help.

But in the longer run, said Harper, it's the government in Kabul that will have to run its own country and be responsible for its own security.

"We're not going to win this war just by staying," he told interviewer Fareed Zakaria.

"Quite frankly, we are not going to ever defeat the insurgency. Afghanistan has probably had - my reading of Afghanistan history (is) it's probably had an insurgency forever of some kind."

"What has to happen in Afghanistan is we have to have an Afghan government that is capable of managing that insurgency."

Asked if the current administration of President Hamid Karzai has the legitimacy to do that, Harper replied: "There is no doubt that governance in Afghanistan has to improve, and has to improve, and has to improve, much more quickly than we've seen."

Harper has repeatedly stated he's sticking to a commitment to pull Canadian combat forces out of Afghanistan by the end of 2011, although Canada would likely maintain a more limited presence focusing on development and reconstruction.

Obama said on his recent visit to Ottawa he didn't press the prime minister to change his mind. But if the U.S. leader did ask him to stay, Harper said Sunday, he'd want to know more about the long-term goals and the ultimate end date for the mission.

"Over the long haul, if President Obama wants anybody to do more, I would ask very hard questions about what is your strategy for success and for an eventual departure."

The comments are not a radical departure from Harper's past observations but he has rarely been so blunt in assessing the situation.
It's true that right now Canada is committed to withdrawal in 2011, so, in that sense, these comments don't represent a shift in policy.

However, Harper's current "bluntness" does make some of his earlier comments look hypocritical. If he really knew his history, as he now claims, then he has known all along that foreign troops can't impose an unpopular government on the people of Afghanistan. In other words, he knew that Canadian troops would die in a hopeless cause.

And why is Harper "delighted" that more US soldiers are about to die in Afghanistan in the same hopeless cause?

Now we need to hear from Michael Ignatieff, the leader of the Liberal Party. Can he be as honest with the Canadian people as Harper was yesterday? I hope he can.


[Thanks to The Galloping Beaver and Canadian Cynic]

Gasoline Temperature Maps

 
I recently posted about problems with the Alberta oil sands and the impact on carbon emissions and the environment [The Problem with the Alberta Oil Sands].

I noted that Alberta had received lots of money from the oil companies and suggested that the provincial government was well-positioned to take the lead in developing cleaner methods of extracting oil. I specifically said that the province had "plenty of room to manoeuvre."

One commenter noted that the provincial government doesn't have as much money as we think. But that wasn't the entire point. I was also referring to the fact that provincial income taxes are lower in Alberta and the province does not have a sales tax.

I was thinking about gasoline prices as well. Here's a map of current gas prices across Canada from GasBuddy.com. Most of the differences are due to taxes. Notice anything peculiar about Alberta—the province that's being accused of so much pollution? I think there's room to manoeuvre if it's serious about climate change.


Here's the USA map for comparison.



A typical US price is $2 per (US) gallon. The current Canadian dollar is equivalent to about 0.8 US dollars and there are 3.79 litres per US gallon. This means that a typical US gas price of $2.00/gal is equivalent to 53¢(US)/liter or 66¢(CDN)/liter.

A typical price for Canadian gas is about 86¢(CDN)/liter so the USA is selling gasoline for 20% less than Canada. I think this is mostly due to lower taxes.

I don't know what the current price of gasoline is in Europe but I suspect it's much more.


Come Ride an "Atheist" Streetcar on the Streets of Toronto!

 
The Canadian Atheist Bus Campaign is throwing a party on Friday night. Meet for food and drinks at the Centre for Inquiry on Beverly St. then take a one hour ride on a TTC streetcar bearing the atheist ad [Toronto Streetcar Party Tickets Now on Sale!].
A party in the downtown Toronto area on a streetcar and at the Centre for Inquiry building. Ticket holders will receive one ride on a streetcar around various landmarks in the downtown Toronto area and also have a chance to mingle, talk, and party with other atheists, secularists, and humanists at the Centre for Inquiry. Drinks and food will be available for purchase.
This is your chance to meet and thank the organizers who raised the money and got the ads on the buses (and streetcars). Buy a ticket and help support the cause in other Canadian cities.


Free Speech in Ottawa

 
Some of you might recognize these people in spite of their attempts to disguise themselves!1

They are protesting the decision by OC Transpo in Ottawa (Canada) to ban the atheist ads on city buses. Apparently it's okay to run Christian ads but the atheist ad is "too controversial."

The Humanist Association of Ottawa wants you to show up at Ottawa City Hall on Wednesday March 11 when the city council is scheduled to vote on a motion to overrule OC Transpo and allow the ads [Protest the bigots at City Hall]. Several members of council are sympathetic and the first vote last month was a tie. It only takes one more council member to get the ads on the buses.

Atheist Bus Ottawa has put up a petition that you can sign. Do it now!


1. To find out who they are you have to sign the petition and see who else has signed!

Playing Chess with Pigeons

 
It's the blogiversary of Troy Britain's blog Playing Chess with Pigeons. Today it is one year old.

Congratulations Troy! Check out today's posting to see the cake [It’s Playing Chess with Pigeons 1st Birthday!]. Look in the right sidebar to see where the title of the blog comes from. It's really clever—I'd love to quote it here but if I do that you might not want to read it in situ and that would be a shame.


Sunday, March 01, 2009

Massimo Pigliucci vs Jonathan Wells

 
Greg Laden found this old video of a moderated discussion between Massimo Pigliucci and Jonathan Wells [Massimo Pigliucci v Jonathan Wells on evolution and intelligent design...].

It's actually pretty good. If you don't pay close attention, you might even mistake Jonathan Wells for someone intelligent.




When Atheism Is the Norm

 
The Friendly Atheist has posted an interesting comment on what's it's like to live in Denmark or Sweden [What Happens When Atheism is the Norm Instead of the Exception?].

His comments are based on a recent article in The New York Times that discussed that topic [Scandanavian Nonbelievers, Which Is Not to Say Atheists].
Anyone who has paid attention knows that Denmark and Sweden are among the least religious nations in the world. Polls asking about belief in God, the importance of religion in people’s lives, belief in life after death or church attendance consistently bear this out.

It is also well known that in various rankings of nations by life expectancy, child welfare, literacy, schooling, economic equality, standard of living and competitiveness, Denmark and Sweden stand in the first tier.

Well documented though they may be, these two sets of facts run up against the assumption of many Americans that a society where religion is minimal would be, in Mr. Zuckerman’s words, “rampant with immorality, full of evil and teeming with depravity.”

Which is why he insists at some length that what he and his wife and children experienced was quite the opposite: “a society — a markedly irreligious society — that was, above all, moral, stable, humane and deeply good.”
This is a very important issue. You should read the article by Peter Steinfels and the posting by Hemant Mehta. I often encounter otherwise intelligent people who try to tell me that religion is here to stay—it will never disappear. Those people really need to get out more. We already have societies today where religion, and belief in God, are minority views.

As you might imagine, there won't be too many attempts to teach creationism in Danish and Swedish schools. That's not because their courts are good at keeping religion out of the schools, it's because the hearts and minds of the people have changed. Rationalism is winning over superstition.

It could happen in America. I think it is happening.


The Problem with the Alberta Oil Sands

 

This month's issue of National Geographic has a lengthy article on the Alberta oil sands [The Canadian Oil Boom].
The U.S. imports more oil from Canada than from any other nation, about 19 percent of its total foreign supply, and around half of that now comes from the oil sands. Anything that reduces our dependence on Middle Eastern oil, many Americans would say, is a good thing. But clawing and cooking a barrel of crude from the oil sands emits as much as three times more carbon dioxide than letting one gush from the ground in Saudi Arabia. The oil sands are still a tiny part of the world's carbon problem—they account for less than a tenth of one percent of global CO2 emissions—but to many environmentalists they are the thin end of the wedge, the first step along a path that could lead to other, even dirtier sources of oil: producing it from oil shale or coal. "Oil sands represent a decision point for North America and the world," says Simon Dyer of the Pembina Institute, a moderate and widely respected Canadian environmental group. "Are we going to get serious about alternative energy, or are we going to go down the unconventional-oil track? The fact that we're willing to move four tons of earth for a single barrel really shows that the world is running out of easy oil."
Canadians know there's a problem but politicians are very reluctant to address it. Albertans have been very vocal in playing the victim card in Canadian politics. They have successfully convinced people that the province was hard done by in the past when the evil citizens of Ontario and Quebec tried to deprive them of their right to keep all the oil money for themselves, instead of sharing it with less fortunate Canadians.

Today, any attempt by the Federal government to impose restrictions on Alberta will be viewed as an act of war.

There's an obvious solution. The government of Alberta has amassed a fortune in oil revenues. Even in these tough economic times, it still has plenty of room to manoeuvre.

Wouldn't it be wonderful if the provincial government took steps to reduce green house gas emissions and develop greener ways of extracting oil? Wouldn't it be wonderful if they took the lead in recognizing there's a problem and start to deal with it? There's some evidence that the Alberta government might be headed in that direction [National Geographic oilsands portrayal "fair": environment minister].

Of course they'd have to abandon the whining about Alberta being a victim of the East. In the long run, that may be very hard to do.


[Photo Credit: Peter Essick, National Geographic]

Saturday, February 28, 2009

United Kingdom Protects Science Budget

 
From NatureNews: Brown pledges to protect science during downturn.
British Prime Minister Gordon Brown said he would not let science "become a victim of the recession" in a speech today at the University of Oxford.

Speaking to an invited audience, Brown said he would defend investment in science by maintaining the ring fence around the science budget, so that it cannot be raided to prop up other areas competing for public funds such as the health service and industry.

He signalled his aim for Britain to move away from an economy "heavily centred" on financial services and towards one focused on science.

....

Responding to Brown's speech, Nick Dusic, director of the Campaign for Science & Engineering in the UK (CaSE), a London-based lobby group says, "The prime minister is absolutely right that now is the time to show the world the UK is the place to do science. Unfortunately he needed to go further today in his commitments because other countries are raising the bar by making science and engineering central to their economic recovery."

Dusic added that just maintaining current spending commitments will mean that Britain loses ground against countries, like the United States, that are giving science a huge boost within their stimulus packages.
Meanwhile, Stephen Harper and the Conservative Party are cutting the budgets of the major granting agencies in Canada.

How stupid is that?


Have You Been Scammed by Nigerians? Get Compensation!!!

 

Jim Lippard alerts us to the Best Nigerian 419 scam ever.

I think he might be right, but the competition isn't that tough.