Straight from NASA. Water has been found on Mars.
Thursday, July 31, 2008
The head of a prominent cancer research institute issued an unprecedented warning to his faculty and staff Wednesday: Limit cell phone use because of the possible risk of cancer.Now this is something many of us have heard before - cell phones cause cancer - but how true is it? Is this warning warranted, or is Dr. Herberman yelling fire in the proverbial theatre? Since the data this is being based on is unpublished, it's impossible for me to comment on. However, studies on cell phones and cancer have been done, so we can look at the data we have so far.
The warning from Dr. Ronald B. Herberman, director of the University of Pittsburgh Cancer Institute, is contrary to numerous studies that don't find a link between cancer and cell phone use, and a public lack of worry by the U.S. Food and Drug Administration.
Several years ago, the US Food and Drug Administration consumer magazine had a piece explaining some of the difficulties in getting an answer to the phone-cancer question. The article included a very brief summary of studies that had been done (as well as some commentary by cancer researchers). The conclusion there was that there is very little to no risk of brain cancer from cell phone use. However, the intervening 8 years has been ample time for further studies to be done. A quick pubmed search shows numerous animal studies that show no increase in cell death or proliferation in mice exposed to non-ionizing radiation of the same frequency used by mobile phones. Many of the human studies (retrospective studies, for example here and here) are also negative, but they aren't exclusively so. While meta-analysis is not ideal for answering this type of question (see here for a brief discussion, particularly Bayman's commentary there), so far this year at least two meta-analyses have been done on the issue. This study found no overall increase of brain tumors (though they note in a subset of the cases included in the analysis that there is a potential elevated risk with long term cell-phone use). Similarly, this analysis is more assertive in its conclusions, claiming "a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period" (while their data show that shorter term use is not associated with increased brain cancers).
So what's the answer? Is there a risk to cell-phone use? The literature seems to indicated that in the short term, no, probably not. Long term (>10 years) usage starts to tilt things towards the positive, although not in a huge way (the studies mentioned above indicate that the increased risk is relatively small). As is usually the case with these situations, the answer will probably bounce back and forth for awhile until a definitive study is done to put the question to rest
This brings us back to the renewed warnings issued last week. Given that the potential risks are small (but not negligible) and associated only with long term exposure, the question becomes what was the proper way to deal with the unpublished data from the University of Pittsburgh Cancer Institute? Again, it's difficult to say without seeing the data in question, but given the information we have so far it's hard to imagine a definitive, home-run conclusion (Herberman, who issued the warning, says as much in the news article). Should he have waited for peer review before sounding the alarm (would an extra few months before releasing it make a difference when talking about a 10 year latency)? Is it better to err on the side of caution? After all, he's not calling for an end to cellphone use, but rather certain precautions, particularly with children. Dr. Herberman defends himself thusly:
Herberman is basing his alarm on early unpublished data. He says it takes too long to get answers from science and he believes people should take action now - especially when it comes to children.Without seeing the unreleased data, is it enough to change your cellphone habits? For the University of Pittsburgh statement and the recommended precautions, go here.
"Really at the heart of my concern is that we shouldn't wait for a definitive study to come out, but err on the side of being safe rather than sorry later," Herberman said.
Tuesday, July 29, 2008
Posted by Kamel at 5:42 PM
Thursday, July 24, 2008
Wii Fit, for the Nintendo Wii, recently hit store shelves, touting itself as a fun fitness product claiming
By playing Wii Fit a little every day, you, your friends, and your family can work towards personal goals of better health and fitness.Perhaps the game Rock Band should take a similar tack in advertising.
A story at BBC News equates rock drummers to top athletes. These conclusions were reached by tests on Clem Burke, drummer for Blondie, who was hooked up to a heart monitor and other equipment during a performance. An hour in concert can burn up to 600 calories and tests on Burke showed his heart averaged 140-150 bpm, peaking at 190 (see this chart for Fox and Haskell's exercise zone formula). These rates, the article claims, are comparable to Premier League football (soccer) players.
I don't doubt that you can get a workout playing the drums - I've certainly broken a sweat hammering away at Rock Band (sorry, not a musician here) - but the BBC piece seems to go a bit far in it's comparison to top athletes:
"Footballers can normally expect to play 40 to 50 games a year - but in one 12 month period, Clem played 90-minute sets at 100 concerts.This quote, combined with the previous comparison to professional football players, seems to imply that drumming is more physically demanding. Instead, I would read it as going against their thesis that "rock drummers are top athletes"; that is, drumming isn't nearly as strenuous as professional sports.
"Footballer [sic] find playing a Champions League game once every two weeks a drain, but these guys are doing it every day when they are on tour.
Enjoy your drumming, and feel good knowing that you're burning some calories, but if you're planning on leaving your pick-up soccer league to go pro there are probably better ways to get in shape.
Any thoughts from drummers out there?
Don't mess with Garson. Turns out that while I was correct when using the modern tuning of equal temperment, back in the day of musical geniuses like Bach, instrument tuning was not so crude and was specific to the key in which it was being played. Intervals in musical scales are defined by frequency ratios, and they aren't always so pretty. C# is not Dflat according to that definition.
Ken has done some fine research on this subject in order to point out my infiroirity. Equal temperment is used so that an instrument like the piano can be played in any key. However, from a great summary on the history of tuning and temperment:
* Our first written instructions for setting equal temperament come from Giovanni
Maria Lanfranco in 1533:
* "The 5ths are tuned so flat that the ear is not well pleased with them; and the
3rds are as sharp as can be endured."
Equal temperament has had its share of critics. Very few composers or organists
preferred equal temperament until the French Romantic school.
* In 1879, William Pole wrote in his book The Philosophy of Music, "The modern
practice of tuning all organs to equal temperament has been a fearful detriment to
their quality of tone. Under the old tuning, an organ made harmonious and
attractive music. Now, the harsh 3rds give it a cacophonous and repulsive effect."
So is there a audible difference to those of us who aren't musical geniuses or Ken Garson?
Check out this youtube link of a guy playing the same piece in using different temperments.
I think I can tell the difference but maybe the guy is just playing it better.
A computer simulation would probably be best.
Wednesday, July 23, 2008
Posted by rob at 4:05 PM
In a bit of a stretch in an otherwise amazing film, Batman: The Dark Knight, the caped crusader uses cellphone signals to enable his own echolocation technology. It was fitting since bats use echolocation for navigation and prey location. I don't have any idea how feasible something like this would be although I would suspect highly impossible.
I just found some interesting things about echolocation.
FoxP2 is a gene that the bayblab has discussed previously, and has sequence variation and patterns of expression linked to human speech defects, the evolution of language, and vocal learning in animals. An interesting paper shows that bats have a great variation in the FoxP2 and the authors speculate this is due to selection for echolocation.
Also found some information that humans are capable of limited echolocation. Here is a older story about Ben Underwood who from what I have read is basically a bat. Here is a 'documentary' on Ben.
Tuesday, July 22, 2008
Normal flies sleep away almost half of each day (tell that to the ones in my kitchen). However, flies lacking Sleepless get by on 2 or fewer daily hours of sleep.
The mutation – in a gene that controls how brain cells fire and now dubbed Sleepless – suggests that, at the most basic level, sleep is caused by a slowdown in certain neurons.As if the fatigue that comes after a sleepless night isn't enough, the authors point out that the mutant flies also have shortened lifespans and impaired co-ordination, underscoring the importance of a good night's rest. Somehow that won't help me sleep any easier.
An inability to control these neurons might spell a restless night for animals besides flies
The research was published in Science.
Saturday, July 19, 2008
Posted by rob at 11:54 AM
It's free to watch, but will only be online until midnight, Sunday July 20th.
Friday, July 18, 2008
Wednesday, July 16, 2008
Does anybody out there know of a good explanation or theory on the origins of clapping?
Posted by The Doc at 11:02 AM
Contributors should not only describe the research involved but also put it in a broader historical/scientific context: why is the work in question important/groundbreaking/revolutionary/nifty? [...] Entries profiling an important person or concept in the history of science are also acceptable.The inaugural edition has gone up at A Blog Around the Clock and it's a doozy - dozens of entries profiling work as far back as 1543 and covering diverse areas from medical case studies to classic physics to ... Dungeons and Dragons? Check it out.
Tuesday, July 15, 2008
Once mature, S. tellinii needs to return to water to complete its life cycle. To do this, the Gordian worm infects the cricket’s mind, and forces it to commit suicide. Little is known about how the worm achieves this, but French scientists recently reported that the expression of certain proteins in the infected cricket’s brain were altered, namely those involved in neurotransmitter function and geotactic behaviour. The partly-digested and now zombified cricket seeks out water, and once there, throws itself in, and drowns. The adult Gordian worm then burrows out of the cricket carcass, swimming away to find a mate. So uninterested is the Gordian worm in the non-parasitic stage of its life cycle that it doesn’t even have a mouth - it will live on the reserves built up whilst inside the host and then die. Each female Gordian worm can lay up to 10 million eggs. Bad news for crickets, good news for zombie fans.
Here is a video that is making it's way through the intertubes, of the suicide and emergence from the cricket of this creepy parasite.
Posted by rob at 2:34 PM
Monday, July 14, 2008
Popular Science has a breakdown of the physics:
"If, as the narrator informs us, the car achieves a takeoff speed of 280 mph, then using the equations of projectile motion, we can easily calculate that without air resistance (estimating a launch angle of about 30 degrees) the maximum distance the car could achieve is around 1500 meters, or just short of a mile. (I'll leave it to those of you with a little physics background to confirm this is true.) However, at speeds of this magnitude, air resistance will have a major effect on the flight of the car. The force of air resistance is proportional to the square of the velocity, so if you double the speed you quadruple the air resistance. Incorporating the effect of air drag into the calculations we find that Kenny won't even make it a quarter of a mile before falling ignominiously into the river."
Ooo. A little harsh. Come on guys, hind-sight's 20-20 right? Anyway, check out the video and judge Kenny's physics for yourself:
Further reading: For those unfamiliar with the psychology of the male Canadien and/or interested in further exploring Canadian anthropology through the miracle of YouTube Video, see also The Best Of Ron Hextall, Canadiens vs Nordiques 'Good Friday brawl' 1984, The Never-Ending Bench Clearing Brawl of Canada vs Russia 1987 at the World Juniors, the seminal National Film Board of Canada mockumentary "FUBAR", and Canadian television favorite "The Trailer Park Boys".
Sunday, July 13, 2008
- Edward O. Wilson
I concur. I can't think of anything that works better. It's also helpful to avoid repeating them...(sooner being better than later).
I heard recently someone declare, on CBC radios 'crosscountry checkup' (mp3 of that program on the proposed carbon tax), that a meat eating bicycle commuter produces more carbon emissions than a vegetarian SUV commuter. Turns out its not quite true according to this calculation investigating the exact same claim. However it is quite shocking how energy intensive a omnivorous diet actually is in this day of industrialized agriculture. Basically a full vegan diet saves about 1.5 tonnes of carbon emissions, while an SUV can produce over 3 tonnes of carbon emissions. So it's actually close enough that it depends on how long your commute actually is. I guess this leaves the question, could you do both? Probably not since vegetarians are so notoriously physically weak. I have yet to see one on UFC.
BTW check out how great a site New Zealand has for consumer information about choosing a good vehicle with safety, fuel economy and emissions as criteria. Compare this to the only equivalent Canadian site I could find.
Friday, July 11, 2008
Posted by Kamel at 3:22 PM
Story: "An elderly female comes to the Emergency Department complaining: "I got the green vines in my virginity." The patient reports a two-week history of a vine growing from her vagina. On physical examination it is discovered that she does indeed have a vine growing out of her vagina, about six inches in length. A pelvic exam reveals a mass which is easily removed from the vaginal vault, vine still attached. Upon extraction, the patient reports that her uterus had been falling out and that she "put a potato in there to hold it up" and subsequently forgot about it."
Bayblab verdict: The story seems to have many variants on the web, so there may be a lot of embellishment. I have no doubt that someone out there has used a potato as a home remedy for prolapsed uterus. I have seen some weird stuff when i was hanging out in OB/Gyn but I'm not sure anything could germinate in the acidic environment of the vagina ~pH 4.0 . Perhaps we could test whether a potato would grow at that pH.
Thursday, July 10, 2008
Dr. Forsmann pioneered the technique of cardiac catheterization, a process by which a cable is inserted through an artery or vein into the heart. Conventional wisdom was that this would be certainly fatal, and Dr. Forsmann was forbidden from trying the technique by his department head. He decided to try the technique on himself. When his assistant protested, he tied them to a table, in order to prevent an alarm being raised. He then gouged his own arm, placed a urinary catheter (designed for something quite different) into one of the veins he located, pushed it up his arm and into his heart.
To seal the deal, he then walked up a flight of stairs (holding the catheter in place) to the x-ray department, and ordered an x-ray of his chest, to prove the location of the catheter.
He was subsequently fired. And fired again from his next position. Having become disillusioned with cardiology, and having now practiced with the urinary catheter, he changed specialties to urology, and became a country doctor.
He was awarded the Nobel prize in 1956.
Posted by The Doc at 11:50 AM
Fourteen years after the local transmission of measles was halted in the United Kingdom (UK), the disease has once again become endemic, according to the Health Protection Agency (HPA), the public health body of England and Wales. In an update on measles cases in its weekly bulletin last week, the agency stated that, as a result of almost a decade of low mumps-measles-rubella (MMR) vaccination coverage across the UK, ‘the number of children susceptible to measles is now sufficient to support the continuous spread of measles’Current vaccination rates in the UK are well below the 95% desired to maintain herd immunity. Of over 50 lab-confirmed measles cases in Scotland so far this year (there have been 461 in England and Wales), only 2 of them were imported from overseas.
Measles is no longer endemic to Canada and the USA, but remains endemic in many other countries. If the current anti-vaccination movement continues to flourish, how long will it be before it returns to our shores?
[via Respectful Insolence]
Wednesday, July 09, 2008
1-Mathematical formulae make up the VERIFICATION LANGUAGE of science. Formulae are the only reliable way to test a theory. Every scientific theory has a formula, except the Theory of Evolution. Darwinists have never been able to derive a working Evolution Formula because Evolution theory does not work.
2-Darwinists claim we evolved from the simplest form of bacterial life to ever more complex forms of life. The most basic bacteria had less than 500 genes; man has over 22 thousand. In order for bacteria to evolve into man, organisms would have to be able to add genes. But there is no genetic mechanism that adds a gene. (Mutations change an existing gene but never add a gene.) This means there is no mechanism for Darwinian Evolution and this is a fatal flaw in the Theory of Evolution.
3-The Theory of Evolution in a nutshell is "Survival of the fittest." But most mammals and birds give birth to helpless babies - instead of strong and fit ones. Neither Darwinism nor Neo-Darwinism can explain infantile helplessness. Every baby that is born contradicts Evolution Theory and this is a fatal flaw.
Check out their promotional page about abolishing pipetting slavery :).
"Pipetting all those well-plates, baby, sends your thumbs into overdrive
And spending long nights in the lab makes it hard for your love to thrive
What you need is automation, girl, something easy as 1 2 3
So put down that pipette, honey, I got something that will set you free
And it’s called epMotion (whisper: ‘cause you deserve something really great)
Girl you need epMotion (whisper: yeah girl it’s time to automate)
It’s got to be epMotion (whisper: no more pipetting late at night)
Only for you epMotion (whisper: girl this time we got it right)
Saves you money
Well, well, well
And it’s called epMotion (whisper: ‘cause you deserve something really great)
Girl you need epMotion (whisper: yeah girl it’s time to automate)
It’s got to be epMotion (whisper: no more pipetting late at night)
Only for you epMotion (whisper: girl this time we got it right)"
I ride my bicycle into the lab everyday in the summer here in Ottawa. Today I was passed by another cyclist which, as always, instigated an understanding between the passer and myself that we were racing. This guy was dressed in nice shoes and a shirt and I think he even had a tie on. Thing is he was riding a power assisted bicycle, available from Canadian Tire. He was fast and not sweating nearly as much as myself on a fast road bike. I would have thought that these bikes were for geezers and out of shape nerds but I was really impressed. The website has good reviews of the bike and it is only $500, and parking would be free at work. If these bike could make a longer bicycle commute more comfortable these things might really be a viable alternative to a car for a larger number of commuters.
I can't wait to race him again.
Posted by rob at 11:26 AM
Tuesday, July 08, 2008
It turns out the normally progressive State of California is taking those concerns seriously, and recently sent cease and desist orders to 23andMe and 12 other personal genetics companies.
The basis of the order was two-fold. First, the State requires that all such companies must be certified by both the state and federal governments, with the idea being to safeguard privacy and protect consumers from charlatans who might turn around and sell that data to the highest bidder.
Secondly, California law requires that genetic tests be ordered by the patient's doctor. Here, presumably the motivation is make sure someone (the doctor) is going to help properly interpret the results.
[T]he site still provides some probabilities of getting certain diseases. And while none of these sites are going to offer any life-shattering information (e.g. “You will die before you hit 30″), many health care professionals worry that any amount of genetic information could be misinterpreted. What happens when a patient finds out they have a lower-than-average risk of heart failure that leads them to neglect regular checkups? Then again, it’s my information - shouldn’t I be free to (mis)interpret it as I see fit?23andMe feels they are acting withing current law, and are continuing business as usual, at the risk of a fine of up to $3000 per day.
Is this a case of an over-protective nanny state, or a legitimate consumer protection issue?
Monday, July 07, 2008
This is kind of older news but I ran into a video of a presentation by 23andme to a tech audience at Google (I think). If you aren't aware 23andme is a personal genome analyzing company. Basically they analyze the SNPs in your genome and give you all the associations with those SNPs. For instance they will tell you your ancestry and what SNPs that you have are associated with particular diseases. There are some pretty interesting questions and an interesting look at the interface of how a costumer of 23andme's services would 'surf their genome.'
I guess that I could have also just found out all this stuff on the 23andme website.
I was actually impressed with what they do. Integration with Facebook ect. The security of the data that they collect was stressed, which would be important to me if I was a customer. Also I liked the point that personalized genetics and medicine has been moving too slow and they might be the solution to this. They also plan to share anonymous data for drug reactions and efficacies based on SNPs. This would probably be very valuable information assuming they get lots of customers.
This perhaps is the big problem with 23andme. The only SNPs looked at and the only genomic data collected at a statistically significant amount will be from customers who can afford the US$1000 price tag. Somehow I don't think my genetic relationship to African goat herders is going to be properly analyzed.
Saturday, July 05, 2008
Scientists are trained to recognize that correlation is not causation, that no conclusions should be drawn simply on the basis of correlation between X and Y (it could just be a coincidence). Instead, you must understand the underlying mechanisms that connect the two. Once you have a model, you can connect the data sets with confidence. Data without a model is just noise. But faced with massive data, this approach to science — hypothesize, model, test — is becoming obsolete.The argument, it seems, is one of induction on steroids: with so many data points, creating a model isn't necessary because the data are predictive with computational pattern finding, statistical analyses. "With enough data, the numbers," he writes, "speak for themselves."
To illustrate this point, Anderson uses Google as an example. Google's algorithm doesn't care why one page is higher ranked than another, all that matters is that the math says it is. This, of course, is a red herring. Google's algorithm is the model and their continued dominance in search is the successful test. As a technology company, they probably don't care what makes a page relevant, as long as their model continues to reflect what people are looking for.
A more relevant example used in the article is Craig Venter. Lamenting that our knowledge of biology and biochemistry is becoming too complex to be able to model and predict, Anderson points to Venter's ocean and air sequencing projects as an example of science without hypotheses.
If the words "discover a new species" call to mind Darwin and drawings of finches, you may be stuck in the old way of doing science. Venter can tell you almost nothing about the species he found. He doesn't know what they look like, how they live, or much of anything else about their morphology. He doesn't even have their entire genome. All he has is a statistical blip — a unique sequence that, being unlike any other sequence in the database, must represent a new species.There's no doubt that Venter has made some major contributions to biology (and while he's pretty badass, I don't know if anybody considers him the greatest scientist who ever lived, as some do Darwin), but is his work really done without the scientific method? Of course not. Whatever genomes he sequences will be aligned and annotated, gene functions will be hypothesized all based on current theory. The massive amounts of data can be used to test evolutionary hypotheses; they can be used to generate hypotheses.
This sequence may correlate with other sequences that resemble those of species we do know more about. In that case, Venter can make some guesses about the animals — that they convert sunlight into energy in a particular way, or that they descended from a common ancestor. But besides that, he has no better model of this species than Google has of your MySpace page. It's just data. By analyzing it with Google-quality computing resources, though, Venter has advanced biology more than anyone else of his generation.
Imagine in the future, with all this wealth of personal genomic information available, somebody did the kind of pattern finding and statistical analyses the WIRED piece suggests, and finds a novel mutation that is the cause of some disease. This tells us nothing about human biology or the etiolgy of the disease. This doesn't suggest intervention or treatment. Without the scientific method - hypothesis forming and testing - this is little more than trivia.
Science is a way of knowing; a way of exploring our world and learning about it. It's the way we test ideas, answer questions and advance technologies. Chris Anderson seems to see it as bookkeeping; simply cataloguing observations. He's certainly correct that the 'Petabyte Age' offers "huge amounts of data, along with the statistical tools to crunch these numbers" and this will undoubtedly be a powerful tool and invaluable resource. To say it marks the end of the scientific method is absurd. If anything, the vastness of data will provide new observations and new ideas, which is the beginning of the process, not the end. The rumours of its death have been greatly exaggerated.
UPDATE: Good Math, Bad Math writes about the WIRED piece and large scale data analysis.
Friday, July 04, 2008
First we start with a "blogging on peer review" post over at OMICS OMICS! In it, Dr. Robinson looks at a recent paper in nature which suggest a common target in multiple myeloma: IRF4. IRF4 is a transcription factor which regulates amongst other things the powerful oncogene MYC and has been known to be translocated in some myelomas. The author notes:
"An interesting further bit of work targeted various identified IRF4 targets and showed these knockdowns to be lethal to myeloma cell lines. Hence it is suggested that IRF4 ablation in myeloma would lead to tumor cell death by many routes. Mice heterozygous for IRF4 deletion are viable, suggesting that IRF4 could be targeted safely."
While this is an exiting new finding in the field, Dr Robinson astutely points out that transcription factors are generally poor therapeutic targets...
Our next story comes from Cancer and Your Genes and examines how genomics can predict prostate cancer survival. As tools become more readily available and cheaper, the dream of personalised medicine is to use personal gene profile and compare it against large epidemiological databases to extract useful information for treatment. The paper discussed by Dr. Mealiffe appeared in the Journal of Clinical Oncology and paves the way by looking at 600 father-son pairs afflicted with prostate cancer:
"they were able to show that sons of fathers with shorter survival from prostate cancer tended to survive for a shorter period as well. Likewise, sons of fathers who survived for a longer period of time after the diagnosis tended to survive for a longer period of time as well."
Next we learn about neurofibromatosis, a type of famillial cancer which affects nervous tissues, often in young patients. Highlight in Health discusses some of the mutations underlying the disease in the NF1 and NF2 tumour suppressors and other topics covered at a recent conference in Florida.
"The conference was attended by over 200 researchers from around the world This year’s theme — Genes to Complications to Treatments — highlighted the progress being made in NF research and clinical care, as well as the research programs of the Children’s Tumor Foundation. Last year’s NF Conference focused on models, mechanisms and therapeutic targets. "
A great blog post on peer-reviewed research over at Hematopoiesis explains what systemic instigation is, and what are the roles of hematopoietic stem cells, and osteopontin in this process:
"To summarize - some tumors can do kind of magic (on systemic level, - through release some factors into the blood) with bone marrow, progenitor populations in particular; this magic is called “instigation”; functionally perturbed bone marrow cells leave their niches and are mobilized into stroma of tumor-responder, that causes its growth and metastases."
Rob also wants to plug his paper which has to do with engineering viruses to kill cancer cells or something like that. Congratulations Rob, I guess we should develop an icon for blogging on self-reviewed research :
Thursday, July 03, 2008
This is such a massively broad topic but I ran across a review of the literature on why we sleep in PLoS Biology. Check out the above table of the leading reasons why we need to sleep and the pros and cons of that arguement. Previously I had thought that it known that sleep was necessary for learning and thus just plain necessary, but it turns out that it is just one of three leading theories. The most convincing to me according to the review is the theory that we require sleep to restore some key macromolecules. The article also contains many other interesting aspects of sleep research including some conjecture on why evolution favoured sleep as such a prevalent behavior, but I didn't understand much of it.
"Rosemary's speech is perfectly clear, unlike most stroke victims who have damage to speech-motor areas of the brain," says Humphreys. "You wouldn't guess that the speech changes are the result of a stroke. Most people meeting her for the first time assume she is from out East. What we are seeing in this case is a change in some of the very precise mechanisms of speech-motor planning in the brain's circuitry."