Then you have failed utterly my friend.

From Nature News:

“The area in which I have failed the most is as a father,” Quiñones-Hinojosa readily admits.

Then you have failed.

None of us are perfect. We have our successes and our failures in many parts of our lives. Lord knows I do.

I do know this though.

If parenthood is where you fail “the most”, you are fucking up.

If your Chemistry-trained grad student is past 7 years, you may want to ask some questions

From the unfortunate Dunlap laboratory at Dartmouth College.

Randy Lambreghts received his B.S. in Chemistry and M.S. in Biochemistry from the University of Ghent, Belgium. His current research involves identifying novel components of the Neurospora circadian clock using classical genetic mapping as well as next-generation sequencing techniques. He enjoys travelling and plans to see all of South America after graduation.

News of our young hero [PubMed] from The Dartmouth:

A Dartmouth graduate student was arrested for the attempted manufacture of methamphetamine/amphetamine on Sunday, the Union Leader reported.

Randy Lambreghts, 28, whose graduate date is not listed in the Dartmouth Network Directory, allegedly ran a methamphetamine lab from his 3 School St. apartment, according to the Union Leader.

and from here:

After the DEA got a search warrant, a field team searched the pad, collected evidence suspected of being related to making meth, and sent it to a lab; it is still being analyzed, Giaccone said.

Lambreghts was charged Tuesday with one count of attempted manufacture of methamphetamine/amphetamine, Giaccone said. He was being held on $20,000 bail.

Lambreghts lives with two other people, but they are not expected to be charged, Giaccone added.

Lambreghts, who had been studying at the Ivy League school for about seven years, received a bachelor’s degree in chemistry and a master’s in biochemistry from the University of Ghent, in Belgium, according to a Dartmouth website.

Ugh.

UPDATE: The title has been modified to remove the inaccurate impression that Lambreghts was enrolled in a Chemistry graduate program.

Any racial disparity in NIH Centers and Program Projects?

The BigMechanisms are rare compared with R01 awards but they sure are a big deal to those Investigators who are supported by them. In some walks of academic research, your BSD-ness is practically defined by having one.

The NIH doesn’t know if the diversity problem extends to the larger mechanisms.

I will be eagerly awaiting the followup data.

Structural Aspects of Revising Your NIH Grant

A recent query to the blog emailbox echos things I occasionally see on the search traffic leading to the blog and that I deal with IRL. It asks about the more structural aspects to revising a NIH grant application that has been unsuccessful. In the most recent case it is coming from someone pretty junior who has been asked by the PI to learn how to accomplish this task. (I think that’s weird, of course, this is the PI’s job in my view but so it goes.)

One of the best starting places for getting in the proper mindset to revise a NIH grant is to think about the review process. There are a couple of key aspects that I didn’t pick up on until I was actually doing reviews and a couple that I knew but didn’t understand how to incorporate that information.

You are aware that in most cases your grant will go back to the same study section…but sometimes it will not. It will likely go back to at least one reviewer that has seen it before, but also to at least one reviewer new to the application. It is not impossible to get all three retreads or all three new, btw. The reviewers will see the summary statement from the prior review but not the application itself. This last is absolutely key.

You also have to keep in mind that any prior reviewers (and it is not impossible that members on the panel may have read your application closely even if not assigned as a reviewer) may of course remember your proposal. They may also have, illegally, retained a copy in their files to which they may refer.

With that as background, structurally speaking the revised application is duck soup. Here’s what I recommend based on my own approaches and a distilled impression from reviewing grants that I am far from alone in this approach.

At present you have a one-page “Introduction to the Revised Application” to work with. Before the shortening of the R01 application, you had three. Space is most assuredly at a premium in the present era.

You should start off with a sentence to the effect of “This is a revision of IC031666 reviewed in Panel VWXYNot in Feb of 2011 where it received a priority score of 31 and a percentile rank of 26%“.

Recall that while any reviewers who were present at the prior review know the post-discussion score range, they do not know how the mean of the panel went down, nor the all-important percentile rank. I think it a good idea to get this in their minds. Yes, yes, scores are not supposed to be benchmarked on the prior score but let me tell you this is a nearly inescapable psychology of some reviewers.

Next you will be inclined to polish the apple a little bit. Don’t. You simply don’t have room for that crap, nowadays.

The less-obvious no-no is that you will be inclined to reiterate some of the more glowing and approving comments made by the reviewers. I used to do this…

“We are gratified that Reviewer #2 found the PI’s laboratory ‘uniquely qualified’ for the studies and Reviewer #1 thought the Approach was elegant and ideal for…”

…and got smacked down for it by a senior colleague who had study section experience. This is where your understanding that the reviewer has the summary statement right on her desk next to your revised application comes in handy. They can read the good bits and heck, they might have written those themselves. Cut to the chase.

I shouldn’t have to mention this but also resist the urge to talk schmack about the prior review(ers). This doesn’t go well.

The rest is, structurally speaking, quite simple. It should be a listing of the most-important and/or most-consistent criticisms, one by one, with your reply underneath. I like to set quoted material in italics and then answer in plain font. You can do this with a line in the margin (meh) or with font face (yuk) but I like italics better. I also edit this down to a few phrases that communicate the point and combine the same criticism from multiple reviewers if applicable- gotta save space. Remember, they have the summary statement.

Identifying which are the most critical comments is up to the Investigators and it is very hard to set general principles or advice here. Obviously you’d be best off if you can reply to anything that looks like a knock on your prior version but space is limited. Having more-experienced colleagues read your summary statement and draft Intro can be helpful here.

Likewise, the content of your response is going to be up to the criticism, your proposal and your situation in general. My generic advice is to give them something. Throw the reviewer a bone, even if you can’t deliver the response they probably want to see. Never, ever totally stiff a comment by saying there is no way in hell you are going to do it. That is a surefire way to another crappy score.

Where possible it is nice to point the reviewer to where you made the discussed changes. A few parenthetical references to “see Innovation” or “Specific Aim 2” goes a long ways here.

Try as hard as you can not to blow off a criticism that seems important. If it shows up in the Resume of Discussion you’d damn well better have a response. Ditto if your conversation with your PO after the review revealed a major issue of discussion.

Then you end (or possibly end the first paragraph before you get into the point-by-point) with the comment that major changes in the proposal are indicated by a line in the margin (I find this the most readable) or italics or altered font or something. If there really is wholesale revision, you can say this and omit the indication of revised bits. But in most cases you are going to have a few key passages and design features, perhaps some new data, and you want to draw the reviewer’s eye to what is new. Remember, that she does not have access to the prior version of the proposal…and may not have ever seen it before anyway.

These changed bits will hopefully correlate directly with the items you have listed in your point-by-point and indeed with other criticisms that have not made the cut for the one page Intro to the Revised Application.

The quality of your response to the prior criticism is a major factor in review. You do not want the reviewer in any doubt as to just what you have changed. Fortunately, the structural part is relatively easy.

It is only the content of your revision that should have you sweating bullets.

On the perceptions of well intentioned people regarding the NIH’s little diversity whoopsie

BikeMonkey Guest PostBelieve you me, it does not escape my attention that instead of working on my grant that is due in approx one month’s time, I am talking about the Ginther et al report. No, I am not obligated to say jack squatte about it. These little distractions are optional. As is the mentoring “tax” that the senior author of that report, Raynard Kington, discussed. Likewise participation in the well-intentioned “enhance the diversity” efforts of our Universities and professional societies. Yet…here we are.
The DM has been taking a few whacks at what appears to be the reasonably well-intentioned musings of one Michael Eisen. I am fascinated by the latter’s defensive comment:

But I’m shocked at how many people leapt to the immediate conclusion that the peer review system penalizes applications from black PIs when we know that black scientists face all sorts of other obstacles that both discourage them from entering the field in the first place and make it more difficult for them once they are here. I just felt it was pretty naive on the NIHs part to expect anything different – as if they thought the things they were doing to promote the careers of black scientists had actually solved all the problems they face. And then to look at the data and cry racism is just making the problem even worse by both discouraging black scientists from joining the field and making it harder for them to recruit people once there here.

“leapt to the immediate conclusion“. “cry racism“. Yes, perhaps I should reconsider the “well-intentioned” bit. These are stock in trade phrasings of anti-affirmative action people.

Your Grant in Review: Productivity on Prior Awards

A commenter named ES over at writedit’s blog asked:

I am wondering if I can conduct unfunded research projects using my current RO1 support since I have more experience and more publications on these unfunded projects. In contrast, testing our hypothesis proposed in my funded RO1 is practically not promising. If I decided to do something else which was not originally proposed in my funded RO1, how can I renew my funded RO1 or submit the report down the road.

and expands upon the theme:

the issue here is that my unfunded and funded project are total irrelevant. It is almost impossible to convert my unfunded project to something which is even close to the funded project. Can I do whatever Science takes me to with the unfunded project, and submit the unfunded project as new applications later, instead of renewal of my RO1? Will this cause a bad record for my academic career?

There was also a related query from Saheli in that thread:

2. Should the renewal reflect a substantial continuity to the current grant?
3. What the ingredients of a successful renewal?

The question from ES led to some startlingly bad advice.

Polling Returns Without Review

Child Protection

Civil society such as the one in the US, where I live, takes a custodial interest in children.

It is not unerring, but then what is? The goal, however, is to recognize that while parents are responsible for their own children, sometimes this goes wrong. Parents can be bad parents and therefore society has a mechanism for intervention on the side of the child’s welfare.

We also force parents to put their children in carseats which may* provide only marginally improved protection in rare case scenarios.

These, and many other societal steps assert that at some point the child has independent rights that must come into consideration. Alongside, or perhaps even before, those of the parent.

I am a fairly staunch supporter of abortion being the decision of the mother into a fairly late stage. And I am a big believer in the slippery slope argument that you can’t give the right wing wackaloons a micron on this issue. I do not by any means think this custodial obligation of a civil society starts at conception. Not by a long shot.

But FFS, the day of birth is one place I’m full willing to let the slippery slope in support of right wing wackaloonery start.

How about you?
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*see those freakonomics guy’s claim.

Home Birther Logic. or “Logic” actually

Riddle me this.

For background, Isis the Scientist started some shit by posting

Your Home Birth is Not a Feminist Statement

which sounds totally noncontroversial right from the start. But since it reviewed some data on home birth suggesting up to 37% of planned home births result in emergency hospital visits and noting as much as a 0.3% uptick in the neonatal death rate, well, the home birth fans went shitnutz.

One can only hope that this homebirth person who had one kid die, one need resuscitation and still can’t understand why anyone would think she’s high risk is rare. Very rare.

Kate Clancy, for whom I have a great deal of respect on most issues, has a somewhat reasonable post up on the motivations for home birther fanaticism.

And these motivations are key, I agree. Because these motivations are driving otherwise reasonable people into a frenzy of woo based illogic that is really something to see.

There is one particular bit of thinking that I cannot for the life of me grasp. I’m going to pick on this post from homebirthercurious Dr.B

Hospitals are clearly equipped for dealing with the worst case scenarios. But it also seems that they are big fans of unnecessary interventions.

but really it pops up everywhere. Such as on the Twitts:

Given that it’s kinda a one way trip, how does one determine this? RT @DrSnit: @drisis I don’t see your blog about unnecessary c-sections

and

absent evidence of convenience scheduling, you simply have no idea what the “unnecessary” rate actually IS. No way to tell. @DrSnit

Right? RIGHT??????

In birthing, the only way to know if a procedure was “unnecessary” or “necessary” is to either do it or not do it and figure out if the bad consequence is prevented, ameliorated or unaffected. And unfortunately you only get one try for each case study. Which means that you cannot actually know for sure for any particular case whether the procedures were in fact “necessary”.

Amirite?

Please explain to me, homebirther fans who wield the “unnecessary intervention” cudgel, exactly how you can determine which procedures were and were not necessary in advance. Because I am missing your logic here.

Look, science-based and/or evidence-based medicine recognizes that in the cases that are interesting*, there is rarely such a thing as a clear cut 100% accurate prediction of the future. What there is are probability distributions. If the kid’s heart rate slows down by such and such, the damn cord is wrapped around it’s neck X% of the time. Or, when the kid is in breech, Y% of the time the delivery ain’t going well.

Which always leaves some percentage of the time that everything is going to be fine and dandy.

Between fine-and-dandy land and 100% of births, however, you are playing with the health, well-being and even viability of a new human being. And this, mind you, is just for the stuff we can actually detect with high confidence is an adverse effect on the child. Dying is a pretty good one there, also hypoxia induced brain damage.

We do not know, however, if there are more subtle effects. Maybe you knock 5 pts off the kid’s IQ because you insist on laboring too long for “the experience”. Maybe you bathe that little wackaloon in hormonal responses that produce a raft of a subtle effects on development? Or maybe the child’s innate stress responses set a different stage. Who knows? Me, I’m betting on the side of smooth deliveries. Relatively rapid appearance of the kid once the laboring commences is my preference.

This last part is MY version of birth woo. I’d rather not take chances.

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*i.e., debatable.

Racial Disparity in NIH Grants: Solutions from Your Humble Narrator

A comment by Halophile on a prior post asks:

I’m honestly interested in how a hypothetical NIH Director DrugMonkey would handle the situation.

This was in response to my expressed skepticism that putting together an advisory panel was the right solution. Especially when they are tasked with:

Its charge will focus on five key transition points in the pipeline: (i) entry into graduate degree programs; (ii) the transition from graduate degree to post-doctoral fellowship; (iii) the appointment from a post-doctoral position to the first independent scientific position; (iv) the award of the first independent research grant from NIH or equivalent in industry; and (v) award of tenure in an academic position or equivalent in an industrial setting. The Committee will provide concrete recommendations to the NIH Director on ways to improve the retention of underrepresented minorities, persons with disabilities, and persons from disadvantaged backgrounds through these critical periods.

These are age-old concerns of academia and the solutions are not at all simple. And the obvious stuff comes up over and over again. With little success*. I am making the leap here that the primary motivation of this new panel is a response to the recent revelation that African-American Principal Investigators who apply to the NIH for research grant funding are having poorer outcomes than are white PIs. Correspondingly I think they should be focusing on the proximal problem and not letting themselves get distracted into the larger problem. Yes, even if the proximal issue is a death-of-a-thousand-cuts type of dealio. Yes.

My take with respect to the NIH response is as follows.

i) and ii) are things the NIH is supposedly already doing and tracking with their NRSA programs, MARC training grants and assorted other topics. So first, this is being taken care of elsewhere in the institution. Second, it is pretty damn far away from the prize and you would have to start with a hypothesis that somehow the good African-American scientists are being disproportionately shelled out at grad school and postdoctoral transitions. Thus, those that make it through to apply for grants are only the mediocre ones and this relationship differs for white scientists. I think this is a low probability hypothesis. Move on.

iii) is certainly a concern, particularly with the recent focus of the NIH on transition, creation of the K99/R00 mechanism and general worry about “the next generation”. At this point I’m doing the facepalm and thinking “yeaaah, that should have been an obvious component of this K99/R00 flurry but damn I bet it wasn’t.” However. Much like my response to items i and ii, this is still a bit distant from the grant outcome issue that has been revealed.

iv and v are where the money is. This is where the NIH needs to focus. The fate of existing junior and not-so-junior faculty particularly where it comes to winning grant support from the NIH. Stop getting distracted with “tenure” though, except where you can identify that clearly with disparity in NIH grant awards, the need for African-American investigators to submit more times for a given award, etc.

I am dismayed that the charge is not to delve further into the causes of disparate grant review outcome. To go right at the proximal problem, now, with great dispatch and figure out how to fix it. As soon as possible. Why? Because this news has an immediate and discouraging effect on our current trainees! Not to mention the PIs…

Now, maybe further data mining has already been conducted or is in the works but we don’t know that. Tabak and Collins referred to some preliminary analyses that may or may not go beyond what Ginther et al reported. Here’s what I would commission from the CSR data miners.

-Outcomes for black versus white applicants on a study section by study section basis.

-Participation of African-American and white reviewers on each panel; heck throw in the same racial/ethnic breakdowns used by Ginther while we’re at it.

-Outcomes on a IC by IC basis as well.

These are important bits of information. Is there any relationship with particular scientific domains, review panels or review panel makeups? That would recommend one set of fixes. If not, we’d have to move on to other considerations.

Next up…..um, why not actually talk to the applicants? Supplementary Table 2 of Ginther says there were only 2,942 applications with Black PIs from 2000-2006, 285 awards. I think the 16 member panel could make a serious dent in interviewing this population of investigators. A couple of emails and badabing! What do they think has been helpful and detrimental to their successes and failures as applicants? Where do they point the finger? I’m not saying they will have the same viewpoint or even necessarily be correct (with respect to the broader problem) but for goodness sake this is a place to generate some hypotheses, is it not?

Finally, I come to the most immediate response of all. Programmatic alterations in funding priority. This disparity is a bias in the system, like it or not. Not dissimilar to the bias against new investigators that has been a repeated topic of my blogging. Familiar, in fact, to an older (yet sadly ongoing) discussion of bias against female investigators.

The NIH has responded quite directly in the most recent case of new investigators by putting a finger on the scale to rebalance outcomes. The less established investigators are still getting crappier scores from review panels (and maybe even worse), but the NIH is choosing to pick them up out of the review order in recognition that poorer review outcome is a bug in the system.

This is no different. So my clearest answer to the question raised by Halophile is that I’d put out the word, informally if I had to**, that I was expecting the IC heads to fix the problem pronto. To examine their portfolios of scores in each round to make sure they were prioritizing*** black PI apps in their above-payline pickups.
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*Sorry but I am exhausted by us majority white institution folks fruitlessly pointing the finger at the supply chain below us. It dilutes the blame and gives a handy out when you fail to improve. There are two methods, only, that work. They are related to each other. The pull side, “attractiveness” of a career, a University, a training program, etc, solves itself as a self-fulfilling prophesy. When women, gays, the poor and minorities inhabit specific roles in society, that makes them more imaginable to subsequent generations. Make the job “look” diverse and dismantle any real hurdles that exist and you are most of the way over the hump. How to get there? I am on record as a big fan of creating overt, visible diversity by any means necessary. This brings me to the second method- money. Making your graduate program, postdoctoral environment or faculty ranks more diverse is simple- outbid the competition for the limited resource.

**think, rightwing anti-affirmative action political bigots

***By way of disclaimer, yes, this would theoretically benefit people who’s careers are of direct personal and professional interest of mine.

NIH Director empanels working group on diversity

The initial response to the dismal news about black-white disparity in grant scores and funding is…create an advisory panel.

I have seen this reaction before and indeed served on such panels at the local institutional level.

I am not hopeful.

They have a boatload of people listed on the roster already. Going by the stats on the number of African-American PIs, this panel could easily interview each and every one of them. And make a damn good start on all the unsuccessful ones too.

I suggest they start there.

Rather than the usual hot air that never goes anywhere…

Racial Disparity in NIH Grants: Priority Scores

Unless you have been hiding under a rock, my NIH-focused Reader, you will have heard of the explosive findings of Ginther et al (2011) who reported on an analysis of racial and ethnic disparity in the review and funding of NIH grant applications.
There is a lot to discuss about these findings. A LOT. Well beyond the scope of one or even six blog posts. Commentary from the Office of Extramural Research, the NIMH and the Chronicle of Higher Education are worthwhile reads and there is a bit on National Public Radio as well. Blogger Bashir suggests* that these data prove that if you are African-American you have to be twice as good to succeed.
I’m going to jump right into some grant review geekery. I’m sure you are shocked.

Shared authorship hilariousity

I just noticed something.

Did you see the commentary from Tabak and Collins on the racial disparity in NIH grant awards?

Lawrence A. Tabak*,
Francis S. Collins*

*These authors contributed equally to this work.

This is unbelievable. It is a TWO PERSON COMMENTARY!!

Collins is the bloody director of the NIH. He needs authorship credit spelled out? Seriously?

Pseudonymous blogging at Science Blogs is over.

I have just been informed that ScienceBlogs will no longer be hosting anonymous or pseudonymous bloggers. In case you are interested, despite extensive communication from many of us as to why we blog under pseudonyms, I have not been given any rationale or reason for this move. Particularly, no rationale or reason that responds to the many valid points raised by the pseudonymous folks.
This is, as they say, not unexpected. It is pretty clear that when corporate flacks ask you for your opinion in response to their reflexive stance they are not in fact going to be influenced. So I do hope none of my colleagues are surprised by this. Disappointed, as am I, but not surprised.
I am not certain when the drop-dead date will occur but you will no doubt be able to find me blogging elsewhere.

Active metabolites of JWH-018 may contribute to effects of K2/Spice, etc.

A recent paper from Brents et al. (PubMed) presents the data that we’ve been hearing about for the past several months. I think leigh of the Neurodynamics blog (see posts on THC and cannabimimetic/JWH-018 pharmacology), may have been the first to report seeing these data at a meeting and then I ran across them at CPDD this past June.
As many of you are fully aware by now, the past couple years has witnessed the emergence of broad popular use of “synthetic marijuana” or cannabimimetic products. They have been retailed widely as small (usually 3g) packets of various plant materials sprayed with a growing list of synthetic drugs which all seem to have full agonist properties at the endocannabinoid 1 receptor subtype (CB₁). A series created by J. W. Huffman have been commonly reported, thus you will see reference to the compounds themselves, JWH-018, JWH-073, JWH-081, etc.