Archive for the 'Uncategorized' category

Rep Harris proposal shows why NIH should actually look at the data

Oct 10 2014 Published by under Uncategorized

A Rockey post that I originally missed last spring tells us that the median age of first R01 for Early Stage Investigator (ESI) applicants is 39. This is of comfort to my longstanding inability to match the 42 year old number with my experience- I, of course, mentally ignore a key part of the NI distribution from which that median derives.
Continue Reading »

29 responses so far

Thought of the day: Scientific genius

Oct 07 2014 Published by under Uncategorized

One does not demonstrate "genius" by being the first over the line to answer a question that a whole bunch of other people know is the question and are likewise pursuing. Particularly when the thing that lets you "win" is access to some particular datum that someone else just doesn't happen to have right now.

Genius is more credibly associated with answering questions that no other scientist even realizes is the key question yet.

10 responses so far

Chin up, grantseekers!

Sep 22 2014 Published by under Uncategorized

I'm in the middle of a slightly unusual grant reviewing task. It's weird in several ways but all you need to know is that all of the proposals were previously scored VERY highly. As in highly enough to get funded, highly.

 

You might imagine that these proposals would all be kick ass wonders of grant preparation, supportive preliminary data, innovation, slick and seamless plans of attack and all that jazz.

 

If you have been paying attention to my continued assertions about what happens in regular study section you will not be surprised in the least to learn that this is not so.

 

These suckers have warts all over them. Some of them, in my view as just one reviewer, are pretty terrible on many of the usual dimensions.

 

Just goes to show you.

36 responses so far

Open Post-Pub Peer Review of Cheaters

Sep 22 2014 Published by under Uncategorized

There is an interesting story over at retraction watch.

Last month, PubPeer announced that a scientist had threatened to sue the site for defamation. At the time, all PubPeer would say was that the “prospective plaintiff” is a US researcher” who was “aggrieved at the treatment his papers are getting on our site.”

Today, PubPeer revealed the that the prospective plaintiff was Fazlul Sarkar, a distinguished professor of pathology at Wayne State University in Detroit. Sarkar’s attorney, Nicholas Roumel, tells us that Sarkar had a job offer from the University of Mississippi, which rescinded it after seeing comments about his work on PubPeer.

The part that interests me is, as you might predict, that the offending "comments" at PubPeer detail retractions, suspicious figures and basically edge right up to calling Sarkar a cheater. A data faker. A fraud.

If it is indeed the case that this guy had a job offer at a different University and it was revoked, we may finally be seeing a clear success of post-publication review.

One of the thornier problems involved with nailing a data faker is the twin whammy of Universities having no skin in the game once a data faker has departed their employment and a general fear of being sued for defamation if data faking cannot be proved.

There was a prior case detailed on this blog in which a pair of scientists hop-skipped-and-jumped across three Universities until eventually disappearing. There is a fair bit of high quality rumoring that they finally got busted for data fakery.

There are other cases, even in the ORI findings, where a given scientists seems to have a short tenure at a given University and moves quickly along. Eventually, the person is busted and it may become clear that some of the fraudulent work stretches back to a prior appointment.

What one wonders is how many times a scientific fraud departs his or her University before an investigation can come to a conclusion? Gets out of Dodge before the posse arrives.  Given the usual lengthy process of investigation, she or he would know long before any finding can be made public that the heat was coming. Long enough to search out a faculty appointment elsewhere. Perhaps at a lower-profile institution that cannot believe their good fortune that such a high-flier wants to work there (and bring all that grant money!).

 

Maybe this is a case where the University got wind of the cheating before they hired the guy. Thanks to publicly available comments on his suspicious data.

6 responses so far

Driverless automobiles

Sep 09 2014 Published by under Uncategorized

Driverless cars will not be accepted until most people who remember Windows95 are dead.

16 responses so far

The good old days of science

Sep 04 2014 Published by under Uncategorized

49 responses so far

Guest Post: Gender Sensitivity in Neuroscience is a Work in Progress

This is a guest post from someone who wishes to remain anonymous.

 


 

This week, the Society for Neuroscience opened its website allowing attendees to book their hotels for their annual meeting. The timing was couldn’t have been worse for the Vanderbilt neuroscience community given that on Monday, a former graduate student of the program leveled a disturbing series of accusations against neuroscientist Aurelio Galli. At least 10 of the 60+ alleged events of harassment occurred at SfN meetings. The year before the defendant claims she was subject to harassment, The Society for Neuroscience named Vanderbilt their ‘Neuroscience Training Program of the Year’.

 

In a 20 million dollar harassment suit filled in Nashville, sordid details were laid out of alcohol fueled harassment both in the lab and at the Society for Neuroscience’s annual meetings in 2012 and 2013. The student, a recovering alcoholic, alleges she was subjected to unwelcome and embarrassing commentary from Galli about her perceived lesbianism, her sex life and her looks both in lab as well as in front of male professors.

 

Vanderbilt fired back saying they had investigated the claims and would vigorously defend themselves.  The medical center director and the chancellor were named as defendants, as were Mark Wallace, the head of the Vanderbilt Brain Institute and National Academy member and Chair of the Department of Molecular Biology and Physiology, Roger Cone. Wallace and Cone were included for their failure to act on the student’s claims and protect her career.

 

For those outside the field, the neuroscience community seems to be holding down opposite poles in gender and racial equality. The leadership of both the Journal of Neuroscience and the Society are enviably gender balanced in the last decade. SfN was one of the first national societies to initiate meaningful career-long mentorship for women and minorities. Thanks in part to this commitment, women constitute 50% of most neuroscience graduate training programs. The national attrition of women from academic science is also evident in Vanderbilt’s neuroscience program which has an all male leadership and > 30% of its training faculty as women. The vast majority of these female faculty members are assistant professors.

 

Sending a female graduate student from a heavily male influenced neuroscience graduate program to SfN would present many sources of potential conflict. The first SfN meeting the student claims she was harassed at was in New Orleans, a city proud of its tradition of asking women to show their breasts for beads.

 

The female graduate student alleges that at SfN, her PI required her to attend a cocktail party on a boat where senior male scientists “became intoxicated and were allowed to make romantic and sexual advances on the students”. <I’ll insert my editorial opinion that news does not surprise me especially in light of the report this week from Kate Clancy that the majority of women in her survey of field scientists say they have been harassed with more than 20% reporting that they have been assaulted.>

 

Why would anyone attend boat party or any other kind of party where alcohol is flowing freely and fun is a much more clear objective than science?   For many trainees, this is often the only chance they have to spend time talking to well-published PIs. Presumably, at a party like this, senior investigators would be amenable to laid back conversations with trainees providing a rare chance to judge the character of potential future mentors.

 

These parties are the products of the bygone era of much larger gatherings held a decade or more ago by men who were SfN officers and investigators. Hosts had ample institutional ‘slush’ funds and open bar was the norm. The fabled parties hosted by former Emory Psychiatry chairman Charlie Nemeroff were more or less the height of partying for many members.

 

While at Emory, Nemeroff managed to get millions in personal wealth by consulting for drug companies while also studying those drugs using funding for his lab from NIMH. This income presumably enabled him to host these lavish events. Nemeroff’s parties would often devolve into factions that went skinny-dipping, participated in drinking contests and unwelcome ass grabbing, and yes, accomplished some important networking.

 

From the Venderbuilt lawsuit, “networking” was the reported benefit Galli touted as a reason for the trainee to attend the boat party. Indeed, Galli trained at Emory from 1993-1995 while Nemeroff was there, so these kinds of parties probably did help him advance his career. The expectation that a female recovering alcoholic would likewise benefit underscores a clear cultural clash that needs to be addressed by both the Vanderbilt community and the Society for Neuroscience.

31 responses so far

Science

Jun 24 2014 Published by under Uncategorized

Cool result! Yay!

Control verification fails inexplicably. Ugh. How can this be?

Running obvious other control....works. So first control was valid, meaning the negative result was also valid.

Scrutinizes data......AHA!

Actually explains the design flaw in our first control! YAY!

New experiment planned.

12 responses so far

Will a dual sigma receptor antagonist / dopamine transporter inhibitor treat stimulant abuse?

This post covers a platform presentation in symposium 222. Molecular Basis of Addiction: Neurocognitive Deficits and Memory (Mon, Apr 28, 9:55 AM - 12:10 PM) at the 2014 Experimental Biology meeting.

803.3/D382 - Preclinical efficacy of the dual sigma receptor antagonist dopamine uptake inhibitor, CM699, as a medication for stimulant abuse

Johnathan Katz of the NIDA Intramural Research program presented an overview of the data and findings that led up to the creation of a new molecule (CM699) that functions a both a dopamine transporter (DAT) inhibitor and a sigma receptor antagonist. As a bit of background, NIDA has spent a tremendous amount of effort trying to use dopamine transporter inhibitors as agonist therapy for stimulant abuse. The theory of agonist therapy is familiar from the nicotine patch and methadone. The outline is that if you have a drug which mimics the abused drug in effect but has different time-course of effect, you may be able to blunt the acute high of the preferred drug and/or method of use. The nicotine patch supplies the identical drug but in a more sustained, slower and less-peaky manner. Methadone is relatively long acting at endogenous opioid receptors, apparently providing relief without the acute euphoric high. A similar strategy has governed attempts to identify compounds which would confer protection against stimulant abuse.

Since the acute reinforcing effect of stimulants such as cocaine and methamphetamine is mediated through the DAT, this was the target of considerable NIDA effort over decades. It has not been a successful effort.

First off, Katz pointed out that calling sigma a "receptor" is bit of a misnomer as it functions as an intracelluar chaperone protein. This molecule hangs out in association with the endoplasmic reticulum but under ligand activation can migrate to modulate the function of membrane bound proteins. One of those is apparently the dopamine transporter.

Another background consideration for the presentation is that cocaine, as Katz noted, blocks the DAT but also has some sigma affinity. The significance of this agonist activity was not made entirely clear in the talk and we should keep in mind that any antagonism of the sigma receptor will also likely remove the sigma-mediated effects of cocaine. This part was not well explicated in the talk.

At any rate, sigma antagonist compounds block the effects of cocaine. Katz described data indicating that the acute locomotor stimulant effect of cocaine can be prevented and that sigma antagonists can attenuate lethality from an otherwise toxic dose of cocaine.

An initial study from Remi Martin-Fardon, however, found that one sigma antagonist (BD1047) did not reduce cocaine self-administration. Katz then tested several additional sigma antagonists to rigorously determine that no, sigma antagonist compounds by themselves did not reduce cocaine self-administration, even cross a wide range of cocaine doses.

Katz next presented data to remind us that the DAT inhibitor methylphenidate (aka Ritalin) not only fails to reduce cocaine self-administration but that it can increase the self-administration of lower per-infusion doses of cocaine.

However, the combination of methylphenidate with any of several sigma antagonists produced an "insurmountable antagonism" of cocaine self-administration. Meaning that across a wide range of per-infusion doses of cocaine, the rats now failed to self-administer. Importantly, these combinations had no effect on food maintained operant responding, no effect on self administration of opioids or direct dopamine D1 or D2 like receptor agonists but did work to suppress methamphetamine self-administration. This indicates the effect is specific to DAT mediated reinforcing effects.

This all led up to the creation of a compound (CM699) that had the ability to both antagonize sigma receptors and to inhibit the DAT. It was found to blunt the dopamine response to acute cocaine, as measured with intracerebral microdialysis. Furthermore, this single compound produced the "insurmountable antagonism" of cocaine self-administration that had been found for the two-drug combinations.

The talk ended with a proposal that the mechanism of action is that sigma antagonism depletes cholesterol from the membrane which promotes an inward-facing conformation of the DAT.

Obviously, Katz is optimistic that this combined-action CM699 compound proves the concept for a stimulant abuse treatment medication. The half-life of this particular compound was only about 4 and a half hours, thus their immediate goal is to get a longer acting compound which both antagonizes sigma and blocks the dopamine transporter. Nevertheless, the chance that it can completely remove the rewarding properties of cocaine supports the idea that combined activity at DAT and sigma is the route to effective agonist therapy for stimulant abuse.

No responses yet

Full disclosure to the higher education consumer

Jan 31 2014 Published by under Uncategorized

An article in Slate makes the case, a bit excitedly, that popular college/University ranking entities should present the ratio of permanent to temporary faculty more prominently. I agree wholeheartedly that this is information the consumer needs to know. The relative adjunctification is highly pertinent to the quality of education on offer.

The simple ratio of teaching bodies is not enough, though it is probably the only thing Deans and Presidents are willing to report.

Ideally the percentage of student contact hours, including labs and sections, would be reported by tenure track status of the instructor.

29 responses so far

« Newer posts Older posts »