Apparently the $100 spike boyz have been busy bees over the past year. To recap:

As I stumbled back deep into the UU section (the end) of the afternoon SfN poster session in search of coffee, I noticed a bit of a crowd surrounding a poster board, in rapt attention. As I approached they started laughing and clapping. This is unusual. There is rarely a crowd back in the History / Teaching (and now Ethics) section of the poster sessions.
I decided to investigate.


Spike-Prototypes400.jpgTheir submitted abstract lays out the goal of the study:

We here present a self-imposed engineering challenge. If we have a standard PC laptop and a cricket caught in the back yard, can we record a spike (action potential) for under $100 using components purchased solely from local neighborhood hardware stores and Radioshack?

YouTube and podcast (part of Neuropod podcast).
So, what do these gents have on tap for this year?

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Just a brief note in follow up to a prior post on a death alleged to be from Ecstasy. The CourierMail is now reporting that the autopsy on Rosie Bebendorf attributes the death to MDMA.

But in establishing her death from MDMA (ecstasy) toxicity, an autopsy report received by Ms Bebendorf’s parents highlights two injection marks on her arm.
“The needle marks on the crook of the right elbow, which were fresh – a few hours old – could be the site where the drug was administered,” a government pathologist states.

Interesting. Very interesting indeed. Especially given all of the initial reporting characterized her as having “taken two Ecstasy tablets”. And then there is this odd note:

[Ms Bebendorf’s mother Gerry] believed it was “very unlikely (Rosie) injected herself” with the fatal dose of ecstasy, although she had known for some time that her daughter took speed intravenously.

So the autopsy concludes MDMA at fault. Presumably due to levels of MDMA judged to be high enough and no other drug levels seeming to be of threatening levels on the tox panels? Ahh, who knows. Still a frustrating lack of detail. The parents seem quite keen to go on record with the media quotes in a keep-others-off-MDMA mode, perhaps they would be kind enough to release the whole report.
The route of administration thing is interesting to contemplate. First because of the parents’ tone, as quoted, of poor little lamb daughter led astray by evil boyfriend. Those always ring hollow to me, as do the claims that it was the first time the kid ever did any drugs. Second because of the resulting questions about the pharmacokinetic profile when MDMA was injected rather than ingested. And then we get into possible nonMDMA contributors to the toxicity…

So in case you missed it, since it occurred on a very bloggy timescale, our good blog friend DamnedGoodTechnician was outed at work. Leading to much unpleasantness with some people above her in the management chain at MassivePharma. DGT then decided to pull the blog.
This event led to much thinking on the risks of overly-personal or overly-detailed blogstylings here and there. Hit the posts and read through the comments if you want a full flavor.
Prof in Training (and here)
Prof-Like Substance
Odyssey
Dr. Isis’s Rules for Pseud Blogging
Ambivalent Academic
Now, as it turns out, DGT has returned to blogging. From appearances DGT’s job is safe, it is just a matter of damaged relationships with the bosses.
I hate to be the wet blanket but it is well worth thinking about.

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See, now this is the problem with trying to make complex scientific points relatively simple. They never are. Biology and physiology are complicated and thus we end up minimizing or overlooking important aspects at times. Luckily in the blogosphere someone is usually all over it.
Abel Pharmboy responded to my recent post on a paper comparing MDMA pharmacokinetics between humans and one of the animal models which has generated the most specific and controversial data as a real pharmacologist should:

Getting back to other differences even within a given species is that the initial, non-conjugative metabolism of MDMA is mediated by CYP2D6, a notoriously polymorphic enzyme. In humans, there are significant interethnic differences in 2D6 activity: ~75 allelic variations that are grouped into four phenotypes: poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). (nice free full-text review, albeit in the oncology setting, by CYP clinical pharm guru David Flockhart and colleagues.)
So, if there is toxicity in humans, it is important to consider whether the parent MDMA or any number of its metabolites are neurotoxic and whether there are correlations of toxicity with individuals any of the four phenotypes. As if that is not complicated enough, the methylenedioxy group (the MD of MDMA) is notorious for mechanism-based inhibition of P450 activities and I’m having trouble thinking of whether this would be have more or less influence on a poor or ultra-rapid metabolizing individual.

Hammer meet head of nail.

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One of the fondest arguments of the MDMA/Ecstasy fan is that the doses used in animal studies are so large as to invalidate predictions or inferences about human health concerns. This most usually comes up in the long standing literature demonstrating lasting reductions in markers for serotonergic neuron function associated with MDMA. In such studies, doses of 5-10 mg/kg (monkeys) or 10-20 mg/kg (rats) are reasonably common; the regimen is often twice per day for 4 days in a row. The chronicity is debatable and indeed shorter regimens can produce significant effects, but that is a topic for another day because the complaints focus on the individual dose levels as well.
But this argument also arises when trying to figure out why three teens have died after consuming Ecstasy tablets, particularly when a medical doctor issues an opinion that it is unlikely to be 3,4-methylenedioxymethamphetamine which is at fault.
It breaks down to “Oh, c’mon! Nobody takes 5 or 10 mg/kg of Ecstasy”. The defense is based on a Pharmacology 101 concept that mg of drug per kg of bodyweight is very rough in estimating realistic drug exposure across species. Better to use a complex scaling equation, based on empirical data, that takes into account species-typical differences in drug distribution and metabolism. I overviewed the initial foofraw over the dose-scaling argument that has been subsequently used repeatedly by Ricaurte in defense of his dose selection. Although I also buy the notion that dose-scaling based on species size (mass to surface area, more or less) is important and meaningful… there are caveats to keep in mind.

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We’re just shy of two years past the NIH RFI on evaluating the strengths and weaknesses of the granting system. We’ve seen some changes and I thought it a decent time to revisit a post I had on what I saw as the key strengths to the system. This post went up 10 July 2007.


Instead of only addressing the core values of the peer review system (that must be retained or enhanced), as requested in the recent RFI from the NIH, I thought I’d highlight the core values of the NIH-funded research system as a whole. This seems a good exercise particularly since many of my posts trend toward critique. It strikes me that many of my criticisms of the NIH arise from a failure of the system to live up to the ideals to a sufficient degree. This is a VeryGoodThing, much better than being in the position of criticizing intentional behavior. So I recognize that these strengths are not perfectly realized. It is, however, important that these are the ideals and goals of the system.

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BikeMonkey Post
PhysioProf has a bit up over at his place complaining about the Challenge grant payout odds. I was whinging about the extra grant load that we are about to get and was reminded of something. I got an interesting little email from the head of NIDA the other day.

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Hey peeps, do me a favor would you? Hunt around on your University’s website for the Human Subjects office or Institutional Review Board website. Find the email contact for the IRB coordinator or, failing that, the chair. Dash them off a note and ask if posting a simple internet poll such as you see on blogs now and again would require IRB consideration? Is a matter of explicit exemption or is something that they cannot conceive of why you would be asking and of course it doesn’t require consideration.
If you get a ruling either summarize in the comments (I guess I’d prefer no explicit details as to where unless said IRB person says it is okay) or drop me an email.
thxkbai!

More Ecstasy users dead, this time in Edmonton.

Cassie, 14, and friend Ashley were at a Rock ‘n’ Ride Dance Party at West Edmonton Mall on April 24. They took some ecstasy but got so sick they had to be taken to hospital.
Her friend recovered, but Cassie died over the weekend.

Dammit! Did I mention I’m the parent of a nonzero number of mini-women? Dammit, dammit, DAMMIT!
and… it gets worse.

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The Journal of Neurophysiology is reporting an analysis of peer review outcome for a sample of manuscripts submitted for review in the first half of 2007. Major kudos to them for being concerned enough to conduct such a self-analysis.

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Carnival #3 of Scientia Pro Publica is up over at Bob O’Hara’s joint. It has lots of tasty reading about the swine flu so it is sure to enthrall. Go read.

source

I’ve *realized that a greatly overlooked topic around these parts is the panic felt by the **N-th year graduate student who is finally sighting down the barrel on the thesis defense date. This poor individual is in high gear, finishing experiments, making papers out of data, thinking s/he’d better finally write a dissertation and, finally, facing the biggest hurdle of graduate education- getting all of the committee members in the same room at the same time.
And then somebody throws out a casual mentoring thought: “You know, most postdoctoral training slots are arranged a year in advance“.
AIEEEE!!!!!

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Our good blog friend Dr. Isis of On Becoming a Domestic and Laboratory Goddess has recently launched a “Letters to Our Daughters” project to solicit advice from women researchers to those who are following. The first entry is one from Pascale Lane, M.D. on being assertive… and the inevitable epithet of “bitch”.
You may also have noticed the latest iterations of vigorous discussion over the role of observations about personal attractiveness in the work setting.
These issues raise their ugly heads everywhere….including the discussion over the merger of NIAAA with NIDA. NIDA, of course, is headed (2003-present) by

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