Author: James Vornov

I'm an MD, PhD Neurologist who left a successful academic career on the Faculty of The Johns Hopkins Medical School to develop new treatments in Biotech and Pharma. I became fascinated with how people actually make decisions based on the science of decision theory and emerging understanding of how the brain works to make decisions. My passion now is this deep explanation of what has been the realm of philosophy, psychology and self help but is now understood as brain function. By understanding our brains, I believe we can become happier, more successful people.

Ignoring Chris Carmicheal Since I’m Not Lance

I’ve been reading Vern Gambetta’s weblog for some time now.

Functional Path Training: Variation: “The human organism is highly adaptable so it must be continually challenged with new stresses and increasingly challenging movement problems to solve.”

As a pioneer in Functional Training, he stresses that conditioning programs- endurance or strength need to be designed as preparation for the activity itself. At first, I thought this meant staying away from weight machines and using medicine balls and agility drills, but I’m beginning to think that the idea has much broader implications.

As I’ve explored some of the websites that favor high intensity interval training for general conditioning (Hillfit, The 20 Minute Fitness Solution, Mark’s Daily Apple) I’ve begun to understand that we may have been damaged by the “Aerobics Revolution” just as we have with low fat dieting.

Mark’s Daily Apple » Blog Archive » A Case Against Cardio (from a former mileage king): “Unfortunately, the popular wisdom of the past 40 years – that we would all be better off doing 45 minutes to an hour a day of intense aerobic activity – has created a generation of overtrained, underfit, immune-compromised exerholics. ”

There’s a strong emphasis on relatively low intensity, extensive training across the fitness literature. It led me for years to take long fitness rides, keeping my heart rate down. In reading Joe Friel and Brian Clarke last year, I began to get some idea of work volume and hard easy training, but in the end, my fitness over a good bit of the year was stagnant, especially when training time was short.

I now think that the problem is that the professional atheletes that these approaches have been developed for can stress themselves with very large volumes at the moderate intensities. I can squeeze in a 3 hour ride on some Sundays, but not all. And I can’t get more than about 10 hours of duration in a week. Once I’m adapted to the 3, 2, 2, 1, 1, 1 hr training week, I can’t get anywhere since I’m adapted to it. At first I thought that there would be some adaptation since more work could be done during the same time, but I’m now seeing that such gains will be limited.

As a 50 year old who’s been active for years, my limiter is no longer my 2-3 hour endurance at 60-70% of VO2 max. And I would probably gain little developing my 3-5 hour endurance even if I had the time. My limiters are strength and oxygen utilization (VO2 Max). I need to stress those systems to force adaptation and improvement in my ability to hike, run and bicycle.

Returning to Vern Gambetta, cycling through different activities that empahasize different abilities, while maintaining the overall base is likely to be the most efficient and productive means of functional conditioning. I think he presents some of these ideas in a practical way in this article: Rethinking Periodization.

Camera Theft

Sadly, Michael David Murphy has had his camera and lenses stolen. One only hopes that his blogging at 2point8 didn’t make him a target for camera theft. Certainly his film cameras won’t fetch lots of cash on the market. And there’s clearly sentimental attachment to the tools.

This is something that we have lost in the digital age. My digital cameras are expensive pieces of consumer electronics. No sense forming a long-term relationship with them.

Neurology Notes

Video: Trepanation

Retrospectacle: A Neuroscience Blog: “Trepanation is a procedure where a hole is drilled into the skull, exposing the dura mater and brain for either medical (releif of pressure) or mystical (supposed heightened consciousness)purposes. ”

Pharma Marketing

For reasons I don’t really understand, this report is getting lots of attention in the media and pharma-related weblogs. These are large businesses with shareholders expecting return on investment. They market where they believe the return will be found. The same is true of R&D and the relative rate of spend between the two.

Big Pharma Spends More On Advertising Than Research And Development, Study Finds: “A new study by two York University researchers estimates the U.S. pharmaceutical industry spends almost twice as much on promotion as it does on research and development, contrary to the industry’s claim.”

Up and Coming: Metabotropic Glutamate Receptor Modulation

It seems that since the September announcement by Lilly showing efficacy of a metabotropic glutamate receptor agonist in Schizophrenia, there’s more activity in the area than I’ve ever seen before:

Pfizer’s in:

Pfizer Inc. and Taisho Pharmaceutical Finalize Deal on Schizophrenia Drug; to Pay Initial $22M – News, Search Jobs, Events: “TS-032 is a novel mGluR (metabotropic glutamate receptor) agonist that may offer a new treatment option for central nervous system disorders. Although the characteristics of mGluR are still only partly understood, mGluR is believed to play a role in the transmission of glutamate and other substances in the brain. Abnormalities in the neurotransmission through mGluR may be one cause for symptoms related to schizophrenia as well as other CNS disorders. Data show that mGluR agonists, such as TS-032, offer potential as new treatments for schizophrenia.”

As is Merck:

Addex Pharmaceuticals : 3 January 2008 ADX63365: “Allosteric modulation company Addex Pharmaceuticals (SWX:ADXN) announced today that it has entered an exclusive worldwide license agreement with Merck & Co., Inc. (“Merck”) to develop ADX63365, an orally available drug candidate for the potential treatment of schizophrenia and other undisclosed indications. Allosteric modulators are an emerging new class of therapeutic agents. ADX63365, currently in preclinical development, is a positive allosteric modulator (PAM) that targets the metabotropic glutamate receptor 5 (mGluR5), which is believed to be important as a target for the treatment of schizophrenia and other conditions. The deal also includes mGluR5 PAM backup compounds discovered by Addex.”

Vincent Versace’s Flickr Group

The Three at the Side of the Road

Great news for those who have been learning digital methods from Vincent Versace’s “Welcome to Oz”. There’s now a Flickr group dedicated to the book. Vincent is participating a bit and left a very nice comment on one of my recent images:

The Sky Reflected on Flickr – Photo Sharing!: “Nice use of form and shape. Good gesture too. The only thing I’d say to consider is toning down the hot spot that rides the top edge on the right. if that were pulled down just a bit, the wonderful texture and use of light and contrast of the center leaf would stand out even more. There are several ways to do this. If you’re interested in how I would suggest to do this please send me an e-mail. But this is a really nice image.”

This image was captured last night during a walk around the neighborhood in late afternoon. It was taken in the grove of trees right across the street from my house. As I’ve worked through the techniques in Oz, I see that many of the manipulations across time and space that are done depend on the camera being on a tripod. While I sometimes use one, I prefer a more spontaneous way of working with a handheld camera. It may be worth some experimentation if I can correct some of the exposure and focusing problems that I run into with my current style.

The Noble Wounded Tree



The Noble Wounded Tree, originally uploaded by jjvornov.

Sometimes documenting the suburban landscape is like street photography in that one violates personal space. However, it’s not the bubble we cloak ourselves in when on a busy city street, but rather the privacy expected in the suburban neighborhood.

I am continually struck by the beauty that surrounds us wherever we are. There is a world there to enjoy.

Dynamic Composition



The Move, originally uploaded by jjvornov.

Early on in my photography, influenced I think by abstract expressionism, I tried hard to create formal compositions that were themselves the subject. At some point I decided that this lack of a “subject” was limiting the images and I began more consciously to create an image a subject.

As I’ve been working through Vincent Versace’s “Welcome to Oz” and thinking more in terms of light and modeling, I hope I can move into something more dynamic and worthy of a more than a quick look.

This morning I was looking over my son’s shoulder at the illustrations in a story book and noting the multiple centers of interest that the illustrator had created in telling a story in a single image.

Sol Snyder on Seeking God in the Brain

It seems to be Guilford Pharmaceuticals day here. Sol Snyder, scientific founder of Guilford has this wonderful piece in the New England Journal:

NEJM — Seeking God in the Brain — Efforts to Localize Higher Brain Functions: “In seeking a general relationship between religious states, poetry, and music, Trimble ascribes all three to the right, nondominant side of the brain. He assumes that integration of the activity of the right-sided emotional brain with that of the left-sided analytic brain gives rise to the greatest intellectual achievements in the arts. I suspect that major advances in science, too, are the product of more than pure reason — in the finest scientists I have encountered, I have always detected a notable creative, artistic flair. ”

Can we be better scientists by practicing art? The specificity principle of general adaptation would suggest that scientists would be best practicing science like art.

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease — The NINDS NET-PD Investigators 68 (1): 20 — Neurology

On the subject of Guilford Pharmaceutical drugs that I’ve worked on, the second NIND NET-PD trial has been published, a futility design that included GPI-1485.

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease — The NINDS NET-PD Investigators 68 (1): 20 — Neurology: “Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. ”

This trial was independently conducted by NINDS. We supplied the drug. Their results in untreated patients were consistent with our own 2 year long study of patients who were already on dopamine agonist monotherapy. There are important lessons to be learned from these studies about the challenges of designing studies to test disease modifying drugs in Parkinson’s Disease and other neurodegenerative diseases.

Aetna to End Payment for a Drug in Colonoscopies – New York Times

Of interest:

Aetna to End Payment for a Drug in Colonoscopies – New York Times: “Aetna, one of the nation’s largest private health plan managers, is the latest insurer to clamp down on the use of a powerful anesthetic during an increasingly common form of colon cancer screening.”

This insurer’s reaction to the use of anesthesiologists to administer propofol for colonoscopy is of interest to me because of my work with AQUAVAN over the years. At Guilford Pharmaceuticals (and then MGI Pharma after their acquisiton of Guilford) I directed the first in man study of AQUAVAN and worked on trials on and off through the recent NDA filing. AQUAVAN, as a prodrug of propofol, is not expected to require the same FDA mandate for administration by an anesthesiolgist that propofol does.

AQUAVAN is a prodrug of propofol, extending its action enough to make it a better sedative and a less powerful anesthetic. It’s an interesting, perhaps unique example of how making a drug worse for one use makes it more suitable for another.

This Times article doesn’t mention the alternatives like AQUAVAN or midazolam, but with pressures like this on physicians from insurers and pressures from patients for comfort during procedures, I expect that AQUAVAN will find its niche as a sedative for procedures. Eisai is now in the process of acquiring MGI, so AQUAVAN’s future now rests with them.

Nikon P5000 Again

The Patch of Sun

It’s actually hard for me to believe how much mental energy I’ve devoted to deciding whether or not to capture images with the Nikon P5000 compact digital. On the one hand I can have it everywhere, all the time. On the other hand, the image quality just doesn’t compare to either the Leica / chromogenic BW film system or the Nikon D300. On the other hand, I’m less serious with the P5000. I don’t evaluate exposure or work subjects the way I do with the serious cameras.

When issues are so undecidable, I tend to believe that the goals are unclear. These various image capture systems result in entirely different results for which I have not set relative values. The single dimension that they vary on is portability, Decision theory would dictate that I chose based on that dimension and accept the varied results as the outcome of deciding on the basis of whether I can carry the kit.