Neurological Control Systems

In Section 10.12 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I provide examples of negative feedback. One of these examples analyzes how pupil size is controlled by the light impinging on the retina.

The pupil changes diameter in response to the amount of light entering the eye. This is one of the most easily studied feedback systems in the body, because it is possible to break the loop and to change the gain of the system…. [This feedback loop] has been studied extensively by Stark (see Stark 1957, 1968, 1984).

Neurological Control Systems,
by Lawrence Stark.

The 1968 reference is to Lawrence Stark’s book Neurological Control Systems: Studies in Bioengineering. In the introduction, Stark outlines his philosophy of science, which is similar to the approach in IPMB.

Science proceeds by alternate steps: formulation of an intuitive concept for a new phenomenon, incorporation of the new and other related phenomena into a mathematical structure, and finally, again, development of intuitive concepts of further phenomena utilizing the added perspective obtained with the formal elegance of the mathematical model or theory.

I like how he emphasizes the connection between mathematics and intuition.

In Neurological Control Systems, Stark describes his motivation for choosing the pupil of the eye as his model system.

The pupil was chosen for study from a host of possible examples of biological servosystems for several reasons... First, its motor mechanism, the iris, lies exposed behind the transparent cornea for possible measurement without prior dissection. This had previously been exploited for scientific and clinical researches by using high-speed motion picture cameras. Further, by employing invisible infrared photographic techniques, measurements can be made without disturbing the system, because its sensitivity is limited (by definition) to the visible spectrum. Second, the system can be disturbed or driven by changes in intensity of visible light, a form of energy fairly easy to control, and painless in its administration to the subject. The first two advantages lead to still a third: the possibility of performing experiments on awake, unanesthetized animals whose nervous system is fully intact and functional. In fact, all of the experiments to be discussed below have been performed on human subjects. Last, the system responds with a movement having only one degree of freedom, a change in pupil size, which simplifies the system equation analysis.

A photograph of Fig. 6 from Section II, Chapter 1
of Neurological Control Systems, by Lawrence Stark.

In Stark’s system you can break the feedback loop by restricting the light to a small dot at the center of the pupil, so changes in pupil area do not affect the amount of light impinging on the retina. Figure 10.34 in IPMB illustrates this point, as does Fig. 6 in Section II, Chapter 1 of Neurological Control Systems (shown at the right).

Stark goes on to analyze the transfer function (how the pupil area responds to an oscillating light intensity), oscillations induced by focusing the light on the border of the iris and pupil to increase the gain (in this case the light intensity is constant but the pupil area oscillates), random fluctuations of pupil noise (using many of the techniques discussed in Chapter 11 of IPMB), and nonlinearities in the pupil feedback loop.

After this exhaustive discussion of pupil area, Stark moves on to another feedback system: accommodation of the lens of the eye. But that’s another story.

Below, listen to Stark describe his life and work.

Listen to Lawrence Stark describe his research.

https://www.youtube.com/watch?v=Gk6jvYwGSsE

Me, Me, Me

Most of my blog posts are about the textbook Intermediate Physics for Medicine and Biology. This post, however, is all about me. IPMB makes a few appearances, but its mainly me, me, me.

OUTV Interview

I was recently featured in a Focus on Faculty interview filmed by the Oakland University TV station (OUTV). I uploaded a copy to Youtube, and you can view it here. I apologize for the hair; I was supposed to get a haircut before filming began, but I got busy. Watch for a cameo by IPMB.

OUTV interviews Brad Roth at Oakland University.
https://www.youtube.com/watch?v=IKjab7_unRA

(l-r) Daughters Kathy and Stephanie with me,
and with Auggie, Smokie, and Harvest.

Harvest

Long-time readers of this blog will remember Suki, my beloved Cocker Spaniel-Westie mix who helped explain concepts in IPMB. After her death about a year ago, my wife and I decided to get another dog. Let me introduce you to Harvest, our 65-pound Treeing Walker Coonhound. She is as lovable as Suki (though not quite as smart). We adopted her from the Making Miracles Animal Rescue. On the right is a picture of me with my daughters Kathy and Stephanie, along with Harvest and my two granddogs Auggie (the foxhound) and Smokie (the greyhound), about to start a 5k walk. We like to take them to a dog park, and as we enter yell "Release the Hounds!"

The photo of Harvest and me published
in the October 2018 issue of Physics Today.

Harvest is already famous. She was featured in the October 2018 issue of Physics Today. The magazine had a selfie contest that Harvest and I entered. Unfortunately, in the magazine our location is listed incorrectly; we are actually in our home in Rochester Hills, Michigan. To the left is the selfie that appeared in Physics Today.

Harvest with the IPMB Ideal Bookshelf.

Live Action IPMB Ideal Bookshelf

The logo for the Intermediate Physics for Medicine and Biology Facebook page is a drawing of the IPMB Ideal Bookshelf. You know how Disney often makes live-action movies out of previous animated shows? (Dumbo is the most recent example.) I’ve done the same thing. Below is a photograph of the “live-action” version of IPMB's My Ideal Bookshelf. Harvest helped me with the filming, so on the right I include a photo of her on the set.

The IPMB Ideal Bookshelf, consisting of books cited in Intermediate Physics for Medicine and Biology.

How to Get Published

Below is a video (divided into two parts) of Michael Sevilla (Distinguished Professor of Chemistry at Oakland University) and me talking to a group of graduate students about how to publish their research. Enjoy!

Part 1 of a discussion about Academic Publishing: How to Get Published in a Peer Review Journal, held Nov. 15, 2013 at Oakland University and hosted by the graduate student group Grad Connection. The host is then-graduate student George Corser, and the guests are Brad Roth and Michael Sevilla.

Part 2.

Kerma

Radiation Therapy Physics,
by Hendee, Ibbott, and Hendee.

In Section 15.15 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I define the kerma. It’s measured in the same units as absorbed dose: J/kg, or gray. What’s the difference between the two? Kerma indicates the energy transferred to charged particles, while dose indicates the energy imparted to (or absorbed by) the tissue. Kerma is more closely related to the number of photons in the tissue, but absorbed dose is more closely related to biological damage. In Radiation Therapy Physics, Hendee, Ibbott and Hendee distinguish between kerma and dose.

The kerma (an acronym for kinetic energy released in matter) is the sum of the initial kinetic energies of all IP [ion pairs] liberated in a volume element of matter, divided by the mass of the matter in the volume element. The absorbed dose is the energy actually absorbed per unit mass in the volume element. If ion pairs escape the volume element without depositing all of their energy, and if they are not compensated by ion pairs originating outside the volume element but depositing energy within it (electron equilibrium), the kerma exceeds the absorbed dose. The kerma also is greater than the absorbed dose when energy is radiated from the volume element as bremsstrahlung or characteristic radiation. Under conditions in which electron equilibrium is achieved and the radiative energy loss is negligible, the kerma and absorbed dose are identical. The output of x-ray tubes is sometimes described in terms of air kerma expressed as the energy released per unit mass of air.

Figure 15.32 of IPMB plots the energy transferred and the energy imparted in 2-cm-thick slices versus depth when a 10 MeV photon beam is incident on water, calculated using Russ’s program MacDose.

Figure 15.32 of IPMB. A plot of energy transferred and energy imparted
for a simulation using 40,000 photons of energy 10 MeV.

If we divide both energies by the mass of the slice and average over many simulations, we get plots of the absorbed dose (dashed curve) and the kerma (solid curve). Hendee et al. provide a similar plot in their Figure 5-7.

The difference between kerma and absorbed dose is useful in explaining the skin-sparing effect of high-energy photons such as multi-MV x rays used in radiation therapy. As shown in Figure 5-7, the kerma is greatest at the surface of irradiated tissue because the photon intensity is highest at the surface and causes the greatest number of interactions with the medium. The photon intensity diminishes gradually as the photons interact on their way through the medium. The electrons set into motion during the photon interactions at the surface travel several millimeters in depth before their energy is completely dissipated… These electrons add to the ionization produced by photon interactions occurring at greater depths. Hence, the absorbed dose increases over the first few millimeters below the surface to reach the greatest dose at the depth of maximum dose (d_max) several millimeters below the surface [d_max is about 0.05 m in Fig. 15.32 of IPMB]. This buildup of absorbed dose over the first few millimeters below the skin is responsible for the clinically important skin-sparing effect of high-energy x and γ rays. Beyond d_max, the absorbed dose also decreases gradually as the photons are attenuated. At depths greater than d_max, the kerma curve falls below that for absorbed dose because kerma reflects the photon intensity at each depth, whereas absorbed dose reflects in part the photon intensity at shallower depths that sets electrons into motion that penetrate to the depth.

Medical Imaging Physics,
by Hendee and Ritenour.

William Hendee, the lead author of Radiation Therapy Physics, is a giant in medical physics. He was the editor of the journal Medical Physics from 2005 to 2013. In addition to Radiation Therapy Physics, he wrote another textbook, with E. Russell Ritenour, about Medical Imaging Physics. These two books are at a level similar to IPMB, but with less mathematics and a narrower focus, overlapping our Chapters 13-18. A fourth edition of Radiation Therapy Physics is out, with a new title: Hendee‘s Radiation Therapy Physics.

Robert Lagemann's engraved copy of
The Handbook of Chemistry and Physics,
which I inherited when I become the
Robert T. Lagemann Assistant Professor
of Living State Physics at Vanderbilt.

My connection to Hendee is that—according to an interview for the American Society for Radiation Oncology—he worked for a couple years as a graduate student at Vanderbilt University with Robert Lagemann. I knew Lagemann when I was a graduate student at Vanderbilt twenty years after Hendee was there, and I served as the Robert T. Lagemann Assistant Professor of Living State Physics at Vanderbilt from 1995 to 1998.

Listen to Hendee discuss medical physics in his own words.

Interview with William Hendee, in which he reflects on the history of the 
Radiological Society of North American, its influence on his career, 
radiology's progress, and improved patient care.

https://www.youtube.com/watch?v=Me06HwRQNvc

Two textbooks by William Hendee, along with
Intermediate Physics for Medicine and Biology.

 

Power Lines and Cancer FAQ

The Power Lines and Cancer FAQ,
by John Moulder.

In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I wrote

An excellent discussion of the all aspects of the problem [whether radiofrequency and power-line electromagnetic fields cause cancer] is available at a frequently updated website, Powerlines and Cancer FAQ [Moulder (Web)].

Then we quoted from the website extensively

Moulder (Web, question 20A) says…

The reference was to

Moulder, J. E. (Web). Power Lines and Cancer: Frequently Asked Questions, www.mcw.edu/gcrc/cop/powerlines-cancer-FAQ/toc.html.

In the 5th edition of IPMB, the story became

John Moulder, the author of a web site about power lines and cancer that unfortunately no longer exists, said…

Yet, I wonder... Nothing disappears from the internet. After a few minutes of googling, I found the entire website saved as a pdf, available at large.stanford.edu/publications/crime/references/moulder/moulder.pdf or https://www.nrc.gov/docs/ML1126/ML112660019.pdf. You can also download it from the IPMB website, or just click here. It begins with a brief summary.

Questions and answers on the connection between power lines, electrical occupations and cancer; includes discussion of the biophysics of interactions, summaries of the laboratory and human studies, information on standards, and a bibliography.

The question-and-answer format includes cross-references to other questions (e.g., “Q12” or “Q27J”). References are listed in the bibliography (e.g., “B12”). Below, I reproduce the first question.

1) Is there a concern about power lines and cancer?

The concern about power lines and cancer comes largely from studies of people living near power lines (see Q12) and people working in “electrical” occupations (see Q15). Some of these studies appear to show a weak association between exposure to power-frequency magnetic fields and the incidence of some cancers. However:

• the more recent epidemiological studies show little evidence that either power lines or “electrical occupations” are associated with an increase in cancer (see Q19); 

• laboratory studies have shown little evidence of a link between power-frequency fields and cancer (see Q16); 

• an extensive series of studies have shown that life-time exposure of animals to power-frequency magnetic fields does not cause cancer (see Q16B); 

• a connection between power line fields and cancer is physically implausible (see Q18).

The International Commission on Non-Ionizing Radiation Protection (2001):

“In the absence of evidence from cellular or animal studies, and given the methodological uncertainties and in many cases inconsistencies of the existing epidemiologic literature, there is no chronic disease for which an etiological [causal] relation to [power-frequency fields] can be regarded as established.” (See B12)

The International Agency for Research on Cancer (2001):

“There is limited evidence in humans for the carcinogenicity of extremely low-frequency magnetic fields in relation to childhood leukaemia.... There is inadequate evidence in humans for the carcinogenicity of extremely low-frequency magnetic fields in relation to all other cancers [and] there is inadequate evidence in humans for the carcinogenicity of extremely low-frequency electric fields.” (see Q27J)

The U.S. National Institutes of Health (2002):

“The overall scientific evidence for human health risk from [exposure to power-frequency fields] is weak. No consistent pattern of biological effects from exposure to [power-frequency fields] has emerged from laboratory studies with animals or with cells. However, epidemiological studies... had shown a fairly consistent pattern that associated potential [exposure to power-frequency fields] with a small increased risk of leukemia in children and chronic lymphocytic leukemia in adults... For both childhood and adult leukemias interpretation of the epidemiological findings has been difficult due to the absence of supporting laboratory evidence or a scientific explanation linking [exposure to power-frequency fields] with leukemia.” (see Q27G).

The U.K. National Radiological Protection Board (2004):

“The epidemiological evidence indicates that exposure to power-frequency magnetic fields above 0.4 microT [4 milliG] is associated with a small absolute raised risk of leukaemia in children... However, the epidemiological evidence is not strong enough to justify a firm conclusion that [power-frequency magnetic] fields cause leukemia in children. There is little evidence to suggest... that cancer risks of other types, in children and adults, might arise from exposure to [power-frequency magnetic] fields... The results of epidemiological studies, taken individually or as collectively reviewed by expert groups, cannot be used as a basis for derivation of quantitative restrictions on exposure to [power-frequency magnetic] fields.” (see Q27H)

Overall, most scientists consider that the evidence that power line fields cause or contribute to cancer is weak to nonexistent.

The document answers 35 questions, which together provide a detailed analysis of the controversy through 2006. How I wish the FAQ was up-to-date.

The final question is

35) Who wrote this FAQ?

This FAQ document originated in the early 1990's as a USENET FAQ in sci.med.physics. The USENET FAQ was maintained by Dr. John Moulder, Professor of Radiation Oncology, Radiology and Pharmacology/Toxicology at the Medical College of Wisconsin. Dr. Moulder has taught, lectured and written on the biological effects of non-ionizing radiation and electromagnetic fields since the late 1970’s.

The USENET FAQ was converted to html in 1997 by Bob Mueller and Dennis Taylor of the General Clinical Research Center at the Medical College of Wisconsin. The FAQ was expanded and updated to serve as a teaching aid at the Medical College of Wisconsin. The web server and web management was provided by the General Clinical Research Center at the Medical College of Wisconsin. The development and maintenance of this document was not supported by any person, agency, group or corporation outside the Medical College of Wisconsin.

In August 2005, Dr. Moulder became Director of the NIH-funded Medical College of Wisconsin Center for Medical Countermeasures Against Radiological Terrorism. This new job does not leave him the time required to keep these FAQs up-to-date. When the FAQs had become more than two years out-of-date they were discontinued. There is no version more up-to-date that this PDF version....

Parts of this FAQ were derived from the following peer-reviewed publications:

• JE Moulder and KR Foster: Biological effects of power-frequency fields as they relate to carcinogenesis. Proc Soc Exp Med Biol 209:309–324, 1995. 

• JE Moulder: Biological studies of power-frequency fields and carcinogenesis. IEEE Eng Med Biol 15 (July/Aug):31–49, 1996. 

• KR Foster, LS Erdreich, JE Moulder: Weak electromagnetic fields and cancer in the context of risk assessment. Proc IEEE, 85:733–746, 1997. 

• JE Moulder: Power-frequency fields and cancer. Crit Rev Biomed Eng 26:1–116, 1998. 

• JE Moulder: Une approache biomédicale: le point de vue d'un chercheur en cancérologie. In: J Lambrozo, I Le Bis (Eds), Champs Électriques et Magnétique de Très Basse Fréquency: Electricité de France, 1998. 

• JE Moulder KR Foster: Is there a link between exposure to power-frequency electric fields and cancer? IEEE Eng Med Biol 18(2):109–116, 1999. 

• JE Moulder: The Electric and Magnetic Fields Research and Public Information Dissemination (EMF-RAPID) Program. Radiat Res 153:613–616, 2000. 

• JE Moulder: The controversy over powerlines and cancer, III Jornadas sobre Líneas Eléctricas y Medio Ambiente, Red Eléctrica de España, Madrid, 2000, pp. 159–168.

Dr. Moulder maintained similar “FAQ” documents on “Mobile (Cell) Phone Base Antennas and Human Health” and “Static EM Fields and Cancer”.

I discovered a version of the static fields FAQ at https://stason.org/TULARC/health/static-fields-cancer/index.html. I have not found the cell phone FAQ; maybe things can disappear from the internet after all. If you find it, let me know (roth@oakland.edu).

I like the Power Line FAQ’s poetic closing lines.

Public controversy about electricity and health will continue

until:

future research shows conclusively that the fields are hazardous,

or

until the public learns that science cannot guarantee absolute safety,

or

until the public and media gets bored by the subject. 

Neither of the first two outcomes are particularly likely, 

But the third may happen.